GYN Cytology Flashcards
Cells such as these were found in the gynecologic sample of a 42-year-old woman (SurePath, left and right, medium magnification). The most likely diagnosis is:
(a) Repair
(b) Squamous metaplasia
(c) Squamous cell carcinoma
(d) Hyperkeratosis
(e) Endocervical cells
a) Repair
These cells show enlarged hypochromatic nuclei with prominent nucleoli in almost every cell. Also note the cohesive nature of this sheet of cells. These are features of classic repair found in a gynecologic sample. Squamous metaplasia is not a consideration due to the prominent nucleoli in most cells. The cells are neither hyperchromatic nor a loose group nor syncytial which would be expected in squamous cell carcinoma. Hyperkeratosis is made up of anucleated squamous cells and these cells have their nuclei. These cells are squamous in origin and not endocervical.
These cells (ThinPrep, medium magnification, right and left) are indicative of which of the following:
(a) Acute inflammation
(b) Endocervical cell component
(c) Chronic follicular cervicitis
(d) Lymphoma
(e) Small cell carcinoma of the cervix
(c) Chronic follicular cervicitis
These are groups of somewhat variably sized lymphocytes, caught up in a matrix of proteinaceous debris. The population of cells seems to be reactive rather than neoplastic and there is a tingible body macrophage (lower end of group, right). This is consistent with chronic follicular cervicitis. Acute inflammation would be made up of neutrophils, not lymphs. These cells do not have endocervical morphology. Their nuclei are smaller than those of the intermediate cells. Although they are lymphoid in origin, they are not malignant, lacking nucleoli, pleomorphism, and nuclear protrusions. Finally, these cells are not consistent with small cell carcinoma of the cervix, which would have a greater variation in size, and would be unlikely to have tingible body macrophages accompanying them
These cells were found in the gynecologic sample of a 32-year-old female (conventional, right and left, medium magnification). These cells are most consistent with which of the following:
(a) Repair
(b) Herpes
(c) Cytomegalovirus
(d) HGSIL
(e) Adenovirus
(b) Herpes
These multinucleated cells are displaying the classic signs of herpes: molding of the nuclei, margination of the chromatin, and multinucleation. Repair does not have multinucleation as displayed here or the “ground-glass” nuclei. CMV can have “viral”-looking nuclei, but is almost always seen with only a single nucleus and a very large nuclear inclusion. These can also have cytoplasmic inclusions in a minority of cases. Although the N:C ratio might suggest a HGSIL, the nuclei are not coarsely granular but are smudgy and consistent with viral infection. Finally, adenovirus usually affects with columnar cells of the endocervix and displays perinuclear halos, which are not seen in these cells
The most significant clinical history when treating a patient with these types of cells (SurePath, medium magnification, right and left) is which of the following:
(a)
Previous history of HGSIL
(b)
Second trimester pregnancy
(c)
Postmenopausal
(d)
Day 6 of a normal menstrual cycle
(e)
IUD placement
(b) Second trimester pregnancy
A woman who contracts herpes during her pregnancy is at risk to deliver an infant with several serious problems which can even include death from viral encephalitis or brain damage. As a precaution, these women are often advised to deliver by C-section, avoiding possible transmission to the infant during delivery. A previous history of HGSIL, postmenopausal status, day 6 of a normal menstrual cycle, or history of IUD placement would not be as clinically important as pregnancy with this diagnosis.
The findings illustrated here (conventional, medium, left; ThinPrep, high, right) are most consistent with a patient with a clinical history of which of the following?
(a)
Postradiation
(b)
Adenovirus
(c)
Repair
(d)
IUD wearer
(e)
Herpes
(d) IUD wearer
The cells on the left are vacuolated metaplastic cells, consistent with IUD effect. The image on the right is consistent with Actinomyces, which can be found in women wearing an IUD or any other foreign device, such as a forgotten diaphragm or a pessary. Although radiation may cause vacuolization, Actinomyces is not associated with it. There are no perinuclear halos consistent with adenovirus infection. The cells lack the nucleoli and the cytoplasmic streaming associated with repair. Also, they do not display the multinucleation, margination, and molding of the nuclei consistent with herpes.
A risk factor for this finding (ThinPrep, high, right and left) is:
(a)
Previous history of herpes simplex
(b)
Pregnancy
(c)
Previous history of HGSIL
(d)
HPV infection
(e)
IUD use
(b) Pregnancy
These images are consistent with the morphology of Candida: eosinophilic pseudohyphae with oval-shaped budding. Risk factors for Candida include pregnancy, use of antibiotics, and diabetes. None of the other choices are a risk factor for Candida
his pattern seen in a ThinPrep sample from a 29-year-old woman (ThinPrep, medium, left; ThinPrep, high, right) is most often seen in which of the following days of the cycle?
(a)
Days 1–6
(b)
Days 7–11
(c)
Days 12–16
(d)
Days 17–21
(e)
Days 22–28
(e) Days 22–28
The last days of the menstrual cycle (days 22–28) are the most likely to reveal this pattern of cytolysis in which the normal lactobacilli digest the glycogen present in the generally intermediate cell pattern. This causes lysis of the cells, release of naked nuclei, and the presence of cellular debris in the background. These three features are seen in these images
This appearance of this slide (ThinPrep, medium, left; high, upper and lower right) is most likely due to:
(a)
Melanin
(b)
Hemosiderin
(c)
Glycogen
(d)
Lipofuscin
(e)
Trapping of air under the coverslip
e) Trapping of air under the coverslip
This brownish granular appearance on the surface of the cells is known as “cornflake artifact” and is caused by allowing the film of xylene on the surface of the slide to evaporate prior to applying the mounting media and the coverslip. This allows air to be trapped between the top surface of the cells and the coverslip, resulting in this artifact. Rapid application of the mounting media and the coverslip, and coverslipping the slides one by one as they are removed from the xylene (rather than trying to remove several slides at a time and “batch” them), will help to avoid this artifact. The other choices are all pigments rather than trapped air and would be distributed in the cytoplasm, rather than just appearing centrally in the cell.
The structure on the left, combined with the finding on the right of small safety pin-shaped inclusions within histiocytes, is most compatible with a diagnosis of which of the following (conventional, medium, left; medium, lower right; oil, inset upper right)?
(a)
Tuberculosis
(b)
Sarcoidosis
(c)
Chlamydia
(d)
Granuloma inguinale
(e)
Coccidioides immitis
(d) Granuloma inguinale
The image on the left is consistent with a granuloma, with palisading epithelioid histiocytes and chronic inflammatory cells. The presence of the small, closed safety pin organisms within histiocytes on the right is consistent with Donovan bodies. These organisms (Klebsiella granulomatis) are the causative agent of granuloma inguinale, a sexually transmitted disease that leads to ulcerative nodules. The closed safety pin appearance is best seen with air-dried or formalin-fixed material. Tuberculosis and sarcoidosis may both have granulomas; however, mycobacteria are small and very difficult to identify without special stains for TB, and there is no identifiable causative agent for sarcoidosis. Chlamydia is too difficult to reliably identify on gynecologic material without ancillary testing and it does not cause granulomas. Coccidioides immitis would have the typical “marbles in a bag” appearance of organisms within the double-walled outer structure.
Several groups of cells such as these with abundant cytoplasm, nucleoli, and finely granular chromatin patterns were found in the gynecologic sample from a 28-year-old woman on her postpartum checkup (conventional, medium, right and left). These cells are most consistent with a diagnosis of:
(a)
LGSIL
(b)
HGSIL
(c)
Squamous cell carcinoma
(d)
Choriocarcinoma
(e)
Repair
(e) Repair
These images are most consistent with a reparative process having prominent nucleoli in most cells, a cohesive “streaming” cellular pattern, and a finely granular chromatin pattern. LGSIL would tend to have more hyperchromatic chromatin and show either an increased N:C ratio or large perinuclear halos as are found in HPV infection. HGSIL would have even more hyperchromasia and significant increase in N:C ratio. Additionally, in cases consistent with a biopsy diagnosis of CIS, a “salt and pepper” coarse chromatin pattern may be present and there may be syncytial groups in evidence in the cytology. Squamous cell carcinoma would additionally have a tumor diathesis of blood, fibrin, and cellular necrosis. Choriocarcinoma would show evidence of multinucleation, as well as other features of malignancy such as necrosis, macronucleoli, and coarse chromatin pattern.
The next immediate step in the appropriate follow-up and treatment of this patient (ThinPrep, medium, right and left) should be which of the following?
(a)
High-risk HPV testing
(b)
Colposcopically directed biopsy of cervix
(c)
Repeat Pap in 4 weeks
(d)
Repeat Pap in 1 year
(e)
Hysterectomy
d) Repeat Pap in 1 year
These images are consistent with a diagnosis of chronic follicular cervicitis in a ThinPrep slide. Note the lymphocytes of various degrees of maturity. Often in liquid-based preparations, the lymphocytes seem to be caught up in a proteinaceous matrix. Tingible body macrophages may be seen as well but they are not a necessary component for the diagnosis. This condition may be found at any time but it often occurs in postmenopausal women, due to decreased protection of the epithelium because of the onset of atrophy. Other than being an indication of a chronic inflammatory process, this diagnosis does not require any special follow-up other than a routine Pap. Thus, the Pap should be repeated in 1 year. The other follow-up recommendations are too extensive for this diagnosis. One key to this diagnosis is in recognizing that the small dark cells are of lymphoid origin and are not HGSIL, small cell carcinoma of the cervix, or other neoplastic entities.
hese findings (conventional, medium, right and left) are most consistent with a diagnosis of which of the following?
(a)
Repair
(b)
Endocervical adenocarcinoma
(c)
HGSIL
(d)
HPV
(e)
Herpe
(e) Herpes
These images show the multinucleation, margination of the chromatin, and molding of adjacent nuclei that are characteristic of infection with herpes simplex. The image on the right also shows eosinophilic inclusions in the nucleus. These intranuclear inclusions are also present on the left, but are not as distinctly seen. The molding of the nuclei as well as the multinucleation and ground-glass nuclei excludes all of the other choices from consideration.
he perinuclear halo in the cell near the center of the image is most likely caused by which of the following (SurePath, medium)?
(a)
HPV
(b)
Candida
(c)
Trichomonas
(d)
Nonspecific inflammatory cell changes
(e)
Herpes
(c) Trichomonas
The small, ill-defined perinuclear halo is most consistent with infection by either Candida or Trichomonas. The Trichomonas organisms can be seen in several places in the image, including just underneath the cell with the arrow. HPV has much larger, well-defined halos. Although Candida can also cause a similar-appearing perinuclear halo, there are no Candida organisms present in the image. Nonspecific inflammatory cell changes can also produce a perinuclear halo, but there are no accompanying neutrophils. Herpes does not usually produce this change.
his gynecologic sample was taken from a 59-year-old female (SurePath, medium). The small pinkish cell in the middle of the image is most likely representative of which of the following?
(a)
Parakeratosis
(b)
Hyperkeratosis
(c)
HPV effect
(d)
Degenerated parabasal cell
(e)
LGSIL
d) Degenerated parabasal cell
Occasional eosinophilic cells may be present in atrophic slides. The cells are usually small and rounded with dense cytoplasm and they represent degenerated parabasal cells. These should be distinguished from parakeratotic cells (which have thinner cytoplasm, orangeophilia, and a polygonal shape). Hyperkeratotic cells are normal in size and orange to yellow, have thin transparent cytoplasm, and lack a nucleus. Although dyskeratotic cells of HPV might resemble this cell, in DK the nucleus is larger and appears smudgy, and the N:C ratio is larger than is seen here. LGSIL would also have an increased N:C ratio higher than the cell seen here.
This finding is most consistent with which of the following (SurePath, medium)?
(a)
Actinomyces
(b)
Mucin strands
(c)
IUD effect
(d)
Candida
(e)
Leptothrix
(d) Candida
These strands are uniform in size, are parallel, and have areas of fainter staining alongside areas where the stain is of a more usual uniformity. They seem to protrude out from the cell cluster. These are features consistent with a diagnosis of Candida. Actinomyces is not a fungus but a higher-order bacterium. It is associated with colonies of coccobacilli out of which a “starburst” arrangement of the organisms can be seen. It is usually associated with IUD use or the presence of other “foreign” objects such as pessaries, forgotten tampons, or diaphragms. Mucin strands can be differentiated from Candida in that they are not uniformly parallel and they vary in width as well. IUD effect is most often associated with the presence of highly vacuolated metaplastic cells in small clusters. These cells from the endocervix are reactive and thought to exhibit these characteristics due to the presence of the endocervical string which is used to verify placement of the IUD. The cells often are clustered with other more normal-looking metaplastic cells, and this can help to distinguish them from neoplastic cells. Leptothrix is almost always present only with Trichomonas vaginalis, and trichomonads are not seen. Also, Leptothrix has a tendency to have looping or curving long tendrils, whereas the pseudohyphae of Candida are straighter and they are broader in width as well.
The most likely clinical history for this patient, given the appearance of this sample (SurePath, medium power), is which of the following?
(a)
Day 2, 18-year-old nonpregnant woman
(b)
Day 13, 29-year-old nonpregnant woman
(c)
Day 28, 32-year-old nonpregnant woman
(d)
Second trimester, 33-year-old pregnant woman, normal pregnancy
(e)
64-year-old postmenopausal woman, no hormone use
(e) 64-year-old postmenopausal woman, no hormone use
This slide is showing a typical hormonal pattern of atrophy, which would be most consistent with a 64-year-old woman who is not taking hormone replacement therapy. The group of small cells in the center is most likely endocervical in origin, due to their honeycomb pattern. The other squamous cells are consistent with mostly parabasal and lower intermediate cells, and no cells suggestive of superficial cells are seen, indicating a relative lack of estrogen. Choice “a,” day 2, would likely show a bloody background, endometrial cells, and cellular debris associated with menses. Choice “b,” day 13, would likely show the effects of a high estrogen level and would be composed of a much higher proportion of superficial cells, with no parabasal cells. Choice “c,” day 28, would show mostly intermediate cells, and there may be evidence of cytolysis: cell debris, Doderlein bacilli, and naked nuclei. Choice “d,” second trimester, normal pregnancy, would most likely be made up of almost 100 % intermediate cells, since the cell pattern during pregnancy is mainly influenced by progesterone. Only the sample of a postmenopausal woman would provide the atrophic cell pattern seen here. Other causes of atrophy during childbearing years include postpartum, death of the fetus in utero, and surgical castration without hormone replacement.
Cells such as these were found in the gynecologic sample from a 64-year-old patient who had received a hysterectomy and radiation therapy for squamous cell carcinoma (SurePath, medium power; inset, high power). The most likely diagnosis of these cells is:
(a)
Repair
(b)
Recurrent squamous cell carcinoma
(c)
Radiation effect
(d)
Mixed Müllerian tumor
(e)
Endometrial adenocarcinoma
(c) Radiation effect
Many of the cells in the lower power image are greatly enlarged when compared to the normal cells in the field. Additionally, (lower power image and inset) there is a great deal of cytoplasmic vacuolization present in some of these cells as well as bizarre shapes and elongated cytoplasm. Although the nuclei are somewhat enlarged, there is not a marked increase in the N:C ratio. The background appears clean. These are all features of radiation effect. Repair would not usually display the vacuolization and cytomegaly present. Also, repair usually has macronucleoli which are not evident in this image. Squamous cell carcinoma, recurrent, is not displayed in this image. A recurrent carcinoma would have cells with hyperchromasia, coarse chromatin, nucleoli, and increased N:C ratio and would present in a background of tumor diathesis. Cytomegaly and vacuolization are not characteristic for recurrent squamous cell carcinoma. Mixed Müllerian tumor and endometrial adenocarcinoma are very unlikely in a woman who has had a hysterectomy and no history of these tumors previously. Also, features of malignancy (prominent nucleoli, tumor diathesis, etc.) are not present in this sample
The cellular material in the center of this image (SurePath, medium) from a 26-year-old patient is most likely:
(a)
Endometrial cells
(b)
Endocervical cells
(c)
Colonic adenocarcinoma
(d)
Fibroblasts
(e)
Granuloma
(b) Endocervical cells
These endocervical cells are displaying themselves in a typical palisading arrangement (picket fence), although they appear to be in a somewhat unusual 3-D arrangement, perhaps due to an endocervical polyp. But the cells are clearly elongated with eccentric nuclei typical for normal endocervical cells. There is no apparent nuclear or cytoplasmic pleomorphism and the background of the slide appears quite clean. This is most consistent with an interpretation of normal endocervical cells. Endometrial cells are more cuboidal than tall columnar. Additionally, they occur either as pools of single cells, as double-walled endometrial cell balls in exodus (days 4–10), or in 3-D arrangements. Although colonic adenocarcinoma may occur as tall columnar cells, these cells lack the nucleoli, the nuclear pleomorphism, and the distorted architecture that metastatic adenocarcinoma may have.
Metastatic extrauterine adenocarcinomas usually have a clean background on cytology and relatively few abnormal cells, but the exception is a direct invasion of a colonic adenocarcinoma to the vagina or cervix. In the case of direct extension, the background may be quite bloody and dirty, the carcinoma may appear as tall columnar cells, and there may be large numbers of carcinoma cells present. These factors may cause a differential diagnostic problem with endocervical adenocarcinoma. Fibroblasts would not be as cohesive as these cells. Although a granuloma is composed of epithelioid histiocytes which may show evidence of palisading around the outer edge of the group, the cells depicted in the image are too cohesive and exhibit eccentric nuclei, more typical of normal endocervical cells. Additionally, there is no evidence of chronic inflammation (multinucleated histiocytes, lymphs, etc.) seen.
These findings (left, high, ThinPrep; right, medium, ThinPrep) may be associated with which clinical history?
(a)
Vaginal pessary use
(b)
Condom use
(c)
Oral contraception
(d)
Coexisting HPV infection
(e)
Radiation effect
(a) Vaginal pessary use
These images are consistent with an interpretation of Actinomyces, a higher-order bacterium that is often associated with IUD use. Additionally, other “foreign” devices such as a pessary, forgotten tampon, or diaphragm have also been associated with this finding. Note the radiating “starburst” appearance of the thin organisms. The background may show a number of neutrophils, as seen on the right. None of the other choices, condom use, oral contraception, coexisting HPV infection, and radiation therapy, have been associated with Actinomyces.
This finding from a gynecologic sample (conventional, high magnification) is most likely which of the following?
(a)
Psammoma body
(b)
Cholesterol crystal
(c)
Vegetable contaminant
(d)
Ova of Enterobius vermicularis
(e)
Suture contaminant
d) Ova of Enterobius vermicularis
This finding is consistent with an interpretation of an ovum from the pinworm, Enterobius vermicularis. Distinguishing features of this ovum include a large oval size (about 55–25 μm), a double-walled appearance, and a flattening of one end of the ovum so that it does not resemble a perfect oval. These usually stain deep pink to red, with a darker area in the central area where the embryonic worm is located. Psammoma bodies are also reddish but are usually more round, have a concentric appearance, and will sometimes appear “cracked,” as if one pushed down on a hard-shelled round candy and the outer shell cracked open. Cholesterol crystals are typically rectangular in shape. Vegetable contaminants have a variety of appearances but the flattened oval is specific for pinworm ova. Suture material can sometimes be found in gynecologic samples either postpartum or after gynecologic surgery. It appears as rectangular shapes of variable lengths but a uniform width. Pinworm ova as well as vegetable contaminants are most often found as GI contamination due to poor hygiene. However, rarely pinworm ova might be due to a true gynecologic infection.
These findings in the gynecologic sample from a 27-year-old woman (conventional, right and left, high magnification) most likely represent which of the following?
(a)
Candida and Trichomonas
(b)
Actinomyces and IUD effect
(c)
Leptothrix and Trichomonas
(d)
Aspergillus and Entamoeba histolytica
(e)
Lactobacillus and Giardia lamblia
(c) Leptothrix and Trichomonas
The image on the left represents the curving, looping forms consistent with Leptothrix, and the organisms on the right and in the inset are consistent with Trichomonas vaginalis. Leptothrix is almost always found with Trichomonas but Trichomonas can often be found without Leptothrix. If Leptothrix is identified, one should then search for the Trichomonas which does need to be treated. Candida is thicker than Leptothrix, which rules out “a” as a choice. The strands of Actinomyces are quite slender and are usually found in a “starburst” arrangement. Also, they do not curve as Leptothrix usually does. Aspergillus is much thicker than Leptothrix branches at a 45° angle. Giardia lamblia is normally found in the GI system and is caught by drinking contaminated water. Although it is a flagellated parasite, it does not coexist with Leptothrix, as does Trichomonas. Giardia also does not inhabit the gynecologic system. Thus, the best answer is c.
This finding in a gynecologic sample (ThinPrep, high) would be reported as which of the following using the 2001 Bethesda System terminology?
(a)
Gardnerella vaginalis
(b)
Shift in vaginal flora suggestive of bacterial vaginosis
(c)
Coccobacilli
(d)
Lactobacilli consistent with Doderlein bacilli
(e)
Bacteria morphologically consistent with Actinomyces
(b) Shift in vaginal flora suggestive of bacterial vaginosis
The Bethesda System 2001 uses the above terminology for describing the pattern previously described as “clue cells.” In this condition, the normal bacterial flora of the gynecologic sample is altered from the usual Doderlein bacilli to a proliferation of coccobacilli, which often coat the squamous cells and give rise to this appearance. While this appearance was previously often associated with Gardnerella vaginalis, now the diagnostic terminology is more general and covers both cocci and bacilli. As noted the specific diagnosis of Gardnerella is no longer used in TBS, so choice a is eliminated. Choice c is also not used in TBS. The appearance of these clue cells is not consistent with Doderlein bacilli or with Actinomyces
This image is from the conventional smear of a 28-year-old woman (conventional, high magnification). The cells seen here are most consistent with which of the following?
(a)
Normal endometrial cells during exodus
(b)
Endocervical cells
(c)
Inflammatory cell balls
(d)
HGSIL
(a) Normal endometrial cells during exodus
These cells are showing the typical “double-walled” appearance of endometrial cells as they appear in large cell balls during days 5–10 of the menstrual cycle. This time period, termed “exodus,” shows both epithelial and stromal endometrial cells commonly. Endocervical cells occur in a two-dimensional group with honeycomb or picket fence arrangements, rather than the three-dimensional arrangements seen here. These cells are in a ball; however a close inspection reveals that they are too large for neutrophils or other elements of inflammation. Finally, although HGSIL cells might be this small with a high N:C ratio, the cells are more glandular in appearance, without the dark clumpy chromatin typical of HGSIL. The typical cell ball arrangement and the young age of the patient also exclude an endometrial adenocarcinoma from serious consideration.
These squamous cells have prominent eosinophilic inclusions (vulvar scrape, conventional, medium). The most likely clinical presentation in this patient is:
(a)
Postcoital bleeding
(b)
Dome-shaped nodules with umbilicated margins
(c)
Widespread reddish rash
(d)
Draining groin lymph nodes
b) Dome-shaped nodules with umbilicated margins
This slide displays the typical appearance of molluscum contagiosum. These cells show large eosinophilic inclusions in the cells. The dermatologic symptoms include numerous raised lesions which have raised outer edges and a central depression. This disease is highly contagious and can occur in children. Postcoital bleeding, widespread reddish rash, and draining groin lymph nodes are not symptoms of this disease.
These small safety pin-shaped inclusions found within the macrophages are called by which of the following (conventional, left, high magnification; right upper, low magnification; right lower, oil immersion):
(a)
Schaumann bodies
(b)
Donovan bodies
(c)
Histoplasma capsulatum
(d)
Torulopsis glabrata
(e)
Coccidioides immitis
(b) Donovan bodies
These small safety pin-shaped organisms are ingested into the macrophages. The “safety pin” appearance is more easily seen in Giemsa-stained material. These organisms, Klebsiella granulomatis, are the causative agent of granuloma inguinale, also known as donovanosis. The organisms are also known as Donovan bodies. Schaumann bodies are calcified bodies within multinucleated giant cells, most often associated with sarcoidosis; Histoplasma capsulatum might be confused with the Donovan bodies as they both are seen within macrophages, but Donovan bodies have the unique closed safety pin appearance. Torulopsis is larger than these organisms and is more reminiscent of the size and shape of spores ofCandida albicans. Coccidioides immitis usually is found within an outer structure, giving a “bag of marbles” appearance.
The three elements seen here, naked nuclei, lactobacilli, and cytoplasmic debris, are consistent with a diagnosis of which of the following (conventional, left, low magnification; right, conventional, high magnification)?
(a)
Cytolysis
(b)
Tumor diathesis
(c)
Shift in vaginal flora suggestive of bacterial vaginosis
(d)
Degenerative changes consistent with atrophy
(a) Cytolysis
Cytolysis is a common feature of slides obtained during the latter part of the menstrual cycle, days 25–28. Superficial cells, which are more resistant to the lysing action of the Doderlein bacilli than intermediate cells, are seldom seen this late in the cycle. The intermediate cells tend to lyse, releasing naked nuclei and cytoplasmic debris into a background of abundant Doderlein bacilli. Tumor diathesis contains cytoplasmic debris as well as old and new blood and fibrin. Additionally, of course, there will also be malignant cells present. Shift in vaginal flora will not have Doderlein bacilli, the normal bacteria present in the gynecologic tract. Degenerative changes consistent with atrophy would not show these naked nuclei, abundant Doderlein bacilli, and cytoplasmic debris.
These findings (ThinPrep, medium magnification, left; ThinPrep, medium magnification, right) are indicative of which of the following?
(a)
Acute inflammatory response
(b)
Lymphoma
(c)
ALL
(d)
Chronic follicular cervicitis
(e)
Small cell carcinoma of the cervix
(d) Chronic follicular cervicitis
These images show cells consistent with a diagnosis of chronic follicular cervicitis, a condition which is more common in women with long-standing inflammatory conditions, such as in atrophic, postmenopausal women. In this condition, a “pool” of lymphocytes of all ranges of maturation is seen. Sometimes, tingible body macrophages with ingested nuclear debris from lymphocytes are also seen (right image). On liquid-based slides, the lymphs are often found within a matrix of proteinaceous material (left image). Although not terribly significant in terms of patient treatment, it is important to be able to differentiate this condition from other more serious conditions. Neutrophils are not a significant feature of these images so acute inflammation is not a good choice. Although some of the lymphocytes are immature, most are more mature and do not show clefting, nucleoli, or other features of lymphoma. ALL is also not a consideration, for these same reasons. Finally, small cell carcinoma of the cervix would show cells which are molding and which display significant nuclear abnormalities in small cells of neuroendocrine or squamous origin.
This finding from the cervical sample of a 42-year-old female (conventional, medium magnification, right and left) is most consistent with:
(a)
Enterobius vermicularis
(b)
Schistosoma haematobium
(c)
Vegetable contaminant
(d)
Lubricant artifact
(b) Schistosoma haematobium
These images display several ova consistent with Schistosoma haematobium as well as an actual miracidium. These ova are approximately 150 μm by 50 μm and have a uniformly shaped oval structure which tapers to a point on one end. These ova are from flukes which utilize freshwater snails as a vector. The free-swimming organisms may penetrate the skin after swimming or bathing in infected water. The common location for ova to be found is in the bladder, where constant inflammation due to the ova is associated with squamous cell carcinoma of the bladder. Enterobius vermicularis, the pinworm ova, is a much more frequent finding due to cross contamination from the GI tract, where these parasites usually reside. Its ova can be distinguished as they are not uniformly oval, but have one flattened end. These structures are quite uniform in size and shape and do not contain nuclei, as would vegetable cells. Lubricant artifact also might be a differential, especially if it contained plant cells which simulated the ova. However, the miracidium is conclusive for Schistosoma infection.
This finding in the conventional smear of a 45-year-old woman (conventional, medium magnification) is consistent with which of the following?
(a)
Squamous metaplasia
(b)
Endocervical cells
(c)
Endometrial cells
(d)
HGSIL
b) Endocervical cells
These cells in this honeycomb-type arrangement are consistent with endocervical cells. Note the uniformity of the size and shape of the cells and the columnar appearance at the edge of the group in the upper edge of the image. These cells are too small for squamous metaplastic cells, which are somewhat more polygonal and have more abundant cytoplasm. Endometrial cells would have less cytoplasm and would tend to occur in three-dimensional groups, such as cell balls. HGSIL cells would be much less uniform, have squamous-appearing cytoplasm, and have darker coarser chromatin. They would also tend to occur with dysplastic cells and not be found in this regular honeycomb pattern
This finding is from the gynecologic sample of a 27-year-old female (ThinPrep, high magnification). It is most likely to be found with which of the following?
(a)
HPV changes
(b)
Adenovirus
(c)
Leptothrix
(d)
Molluscum contagiosum
(e)
Actinomyces
(c) Leptothrix
This image shows a “ball” of Trichomonas organisms. They show the eccentric nucleus and ill-defined cytoplasm of these organisms. Flagella are usually lost in processing but can occasionally be seen. Leptothrix vaginalis is a Gram-positive anaerobic bacterium that is almost always found with Trichomonas vaginalis. The finding of Leptothrix should institute a thorough search for Trichomonas. HPV changes,
This image is from the gynecologic sample of a 24-year-old female (conventional, high magnification). The curving structures noted are most likely:
(a)
Actinomyces
(b)
Doderlein bacilli
(c)
Flagella from Trichomonas
(d)
Leptothrix
(e)
Aspergillus
(d) Leptothrix
The curving structures in the image are consistent with Leptothrix. These organisms are usually associated with Trichomonas, although Trichomonas often occurs in the absence of Leptothrix. These Gram-positive anaerobic bacteria are usually rather long and can curve without breaking, unlike Actinomyces and Doderlein bacilli which are usually much shorter and do not curve. The flagella from Trichomonas are seldom seen and, in any case, are much shorter than the organisms seen here. Aspergillus is a thicker fungus with septate hyphae which branches at a 45° angle.
These images are from a 32-year-old female G1P1 (conventional slide, left, medium magnification; right upper, high magnification; right lower, medium magnification). This is most likely which of the following?
(a)
Actinomyces
(b)
Aspergillus
(c)
IUD effect
(d)
Trichomonas and Leptothrix
(e)
Cytolysis
(a) Actinomyces
These images illustrate the appearance of Actinomyces in a gynecologic sample. The organisms are associated with the use of an IUD or other foreign device such as a pessary. They occur as starburst-shaped rods emerging from a colony of associated coccobacilli. The structures often appear almost “fuzzy” looking. Often there is an accompanying inflammatory exudate with this finding. Aspergillus is a fungal organism and several times wider than the thin bacteria of Actinomyces. While Actinomyces often occurs in the presence of an IUD, the finding of “IUD effect” is reserved for cases in which there is cytoplasmic vacuolization and a reactive appearance to the metaplastic cells of the endocervical canal, probably due to irritation by the IUD string. Trichomonas and Leptothrix are not identified on this sample. Cytolysis is the physiologic lysing of intermediate cell cytoplasm due to the action of Doderlein bacilli. It is recognized by cell debris, naked nuclei, and abundant short Doderlein bacilli in the background of the slide.
A conventional Pap smear was done on a 32-year-old female and many fields such as the one illustrated were seen (conventional, medium magnification). The most likely diagnosis for this case is which of the following?
(a)
Trichomonas vaginalis
(b)
Doderlein bacilli
(c)
Actinomyces
(d)
Candida species
(e)
Shift in vaginal flora suggestive of bacterial vaginosis
(e) Shift in vaginal flora suggestive of bacterial vaginosis
This image shows many coccobacilli coating the surfaces of the squamous cells. These cells are sometimes referred to as “clue cells.” In the most recent Bethesda System terminology, the term “shift in vaginal flora…” indicates that the bacteria encountered on the slide are not the normal Doderlein bacilli and that this finding suggests bacterial vaginosis. Trichomonas are not identified on the slide. Doderlein bacilli do not usually coat the squamous cells and coccoid forms are not seen. Actinomyces are found in colonies with accompanying bacteria and they show a starburst appearance. Finally, Candida species are fungi, not bacteria, and are thus wider than the organisms seen here.
This finding in a 32-year-old non-gravid female would be most consistent with a diagnosis of which of the following (conventional, medium magnification)?
(a)
HPV
(b)
LGSIL
(c)
Hyperkeratosis
(d)
Parakeratosis
(e)
Shift in vaginal flora suggestive of bacterial vaginosis
(c) Hyperkeratosis
The finding of a number of plaques or abundant single cells without nuclei is consistent with a diagnosis of hyperkeratosis. This finding can overlie an abnormality such as LGSIL or HGSIL, especially if the lesion is keratinized. The cells are usually pink to orange staining and often show a “ghost” nucleus, a pale area where the nucleus previously was located. Although hyperkeratosis might coexist with HPV, it is not a diagnostic feature to look for. HPV changes usually show a clear large perinuclear halo and some abnormality in the nucleus (hyperchromasia, smudginess, multinucleation, increase in N:C ratio). LGSIL also would include the diagnostic features of HPV as well as any cells which had an N:C ratio of at least one-third the diameter of the cell. Parakeratosis is another benign proliferative change, as is hyperkeratosis. In parakeratosis the abnormal cells appear similar to superficial squamous cells, but are much smaller in overall size. PK cells are about one-tenth the size of normal squamous cells and they have a small, pyknotic nucleus.
This overall pattern is most consistent with which day of the menstrual cycle (ThinPrep, low magnification)?
(a)
Days 0–5
(b)
Days 6–11
(c)
Days 12–16
(d)
Days 17–21
(e)
Days 22–28
(c) Days 12–16
The image shows almost all of the squamous cells to be superficial cells. This is most highly correlated with a very high level of estrogen in the patient. The highest level of estrogen occurs about days 12–16 in the menstrual cycle, peaking just prior to ovulation. The other days of the cycle would have a different appearance. Days 0–5 would be during or just after menstruation and the slide would be bloody, have endometrial cell balls present, and have more intermediate cells and fewer superficial ones. Days 6–11 would coincide with the proliferative phase of the cycle in which the newly shed endometrium is built back up to a proper thickness for implantation after ovulation. Days 17–21 are postovulatory as the estrogen level falls and progesterone levels increase. This is associated with a decline in the number of superficial cells and a relative increase in the number of intermediate cells. During days 22–28, the progesterone levels are high and the pattern is mostly intermediate with cytolysis often occurring in the background. Thus, an estimate of days 12–16 is the best answer. However, it should be noted that hormonal levels vary between women and various patterns may be seen as a number of factors affect these average trends.
Most of the cells seen in this image (conventional, high magnification) are:
(a)
Lymphocytes
(b)
Plasma cells
(c)
Histiocytes
(d)
Polymorphonuclear leukocytes
(e)
Eosinophils
(d) Polymorphonuclear leukocytes
These inflammatory cells are mainly polymorphonuclear leukocytes, the most common type of inflammatory cell seen in gynecologic samples. In fact, it is rare that a few of these “polys” do not appear in the slide. If they are very numerous, they may interfere with optimally viewing the slide and the diagnosis may change to “unsatisfactory for evaluation due to obscuring inflammation.” Lymphocytes are small and round and have very little cytoplasm. This contrasts with the three to four lobes seen in the polys. Plasma cells usually have a round, eccentrically placed nucleus with a markedly coarse chromatin pattern. Histiocytes are larger with abundant frothy cytoplasm and bean-shaped nuclei. Eosinophils are associated with allergic responses or parasitic infections. They have two nuclei in cytoplasm with eosinophilic granules.
The yellowish material seen in the cytoplasm of these elongated cells is most likely (ThinPrep, medium magnification):
(a)
Glycogen
(b)
Mucin
(c)
Lipofuscin
(d)
Melanin
(e)
Hemosiderin
(b) Mucin
These cells are endocervical cells, tall columnar cells which produce mucin for the endocervix. The yellowish material seen at one end of the cell is ready to be expelled into endocervical canal. Glycogen is produced by squamous cells at certain times but not mucin. Lipofuscin is a “wear and tear” pigment that is occasionally found, but not usually in a gynecologic sample. It is not usually this color. Melanin is usually not found on normal Pap smears, but if present, it appears as golden yellow to brown pigment in the cytoplasm of the melanocytes. Hemosiderin may sometimes become ingested into the cytoplasm of histiocytes if bleeding is taking place. However, the only material that is consistent with the type of cells and the setting is mucin.
These cellwere frequently found in the gynecologic sample of a 48-year-old woman (ThinPrep, medium magnification). The most likely diagnosis of these cells is:
(a)
Normal superficial and intermediate cells
(b)
Squamous metaplasia
(c)
Inflammatory cell changes
(d)
Hyperkeratosis
(e)
Pseudoparakeratosis
(d) Hyperkeratosis
These orangeophilic cells have lost their nucleus, and with the information that many of these were seen in the sample, an interpretation of hyperkeratosis can be made. One can note the pale central area where the nucleus was previously located. This is sometimes referred to as a “ghost” nucleus. Hyperkeratosis is a benign proliferative change and can be found in a number of situations such as coexisting LGSIL or HGSIL, uterine descensus, or post hysterectomy. Due to the lack of nuclei in a number of cells, the diagnosis of hyperkeratosis (HK) is appropriate. If, however, the cells were rare, anucleated squamous cells on a slide might represent contamination from the handling of the slide (fingertip cells). Squamous metaplasia would have denser, more immature cytoplasm and the cells would have nuclei. Inflammatory cell changes may have a faint, ill-defined halo near the nucleus, but the nucleus is maintained, unlike this case. Finally, pseudoparakeratosis (also known as microglandular hyperplasia) is made up of degenerated endocervical columnar cells which are quite small, have lost their columnar appearance, stain orange, and show small, dark degenerated nuclei. These cells in the image do not have nuclei and they are too big and polygonal to suggest pseudoparakeratosis.
Many cells such as these were found in the gynecologic sample from a 62-year-old woman with no history of hormone use or previous abnormality (conventional, low magnification). The most likely diagnosis of these cells is:
(a)
Squamous metaplasia
(b)
Parakeratosis
(c)
Atrophy
(d)
Keratinizing LGSIL
(c) Atrophy
Most of the normal-appearing blue cells in this image are parabasal cells, reflective of the lack of estrogen normally present in a postmenopausal woman. The small rounded orange cells with dense cytoplasm are commonly found in atrophic slides. They are thought to be degenerated immature forms of parabasal cells. Squamous metaplasia would have a different N:C ratio than these cells and would usually stain blue, indicative of the immaturity of its cytoplasm. Although parakeratosis (PK) is the primary differential for these cells, PK has smaller, more condensed pyknotic nuclei and a thinner more transparent polygonal cytoplasm. They have been described as miniature superficial cells and that is an apt description. A keratinizing LGSIL would show the typical perinuclear halo consistent with HPV infection and/or cells with hyperchromatic nuclei and orange staining cytoplasm and an increase in N:C ratio. These features are not present in this image
Cells such as these were seen in the Pap sample (ThinPrep, medium magnification) from a 49-year-old woman, status post hysterectomy and radiation for squamous cell carcinoma of the cervix 10 years ago. The correct interpretation of these cells is most likely:
(a)
Repair
(b)
Recurrent squamous cell carcinoma
(c)
Normal superficial and intermediate cells
(d)
Radiation effect
(e)
Atypical endocervical cells
(d) Radiation effect
The atypical cells in this image have enlarged, multiple nuclei and vacuolated cytoplasm and, despite being larger than the normal cells in the image, have a more or less normal N:C ratio. These features are characteristic of radiation effect, which can be seen in samples many years after radiation therapy is completed. Repair would have prominent nucleoli, pale chromatin, and streaming cytoplasm. It does not usually have the multinucleation and cytoplasmic vacuolization noted here. Recurrent SCCA would have hyperchromatic enlarged nuclei with an increased N:C ratio and nucleoli. The cells are much too large in comparison to the normal cells in the background and cannot be classified as normal cells. Finally, the atypical cells seem to be squamous in origin and display polygonal, sharply defined cytoplasm, rather than the columnar, vacuolated cytoplasm of endocervical cells.
Cells such as these were seen occasionally in a ThinPrep slide (medium magnification) from a 28-year-old female, G0P0. The smaller, more rounded cells are most consistent with which of the following?
(a)
Squamous metaplasia
(b)
Atrophy
(c)
Inflammatory cell changes
(d)
LGSIL
(e)
Navicular cells
(a) Squamous metaplasia
The smaller rounded cells in this image are consistent with squamous metaplasia. This is one of the most common benign proliferative changes seen in gynecologic samples. Morphologically they cannot be distinguished from parabasal cells, but using the patient’s age, expected level of hormone production, and the occurrence of the cells on the slide can usually help to distinguish between them. True parabasal cells are reflective of a reduced hormonal status, and if that is the case, the cells are evenly distributed over the slide. If the cells are squamous metaplasia, however, most of the slide is normal intermediate and superficial cells and occasional areas contain squamous metaplasia, as seen in this image. Atrophy therefore is not a good choice for this patient as the age and occurrence of the cells does not fit. Inflammatory cell changes would include polychromasia, small ill-defined perinuclear halos, and inflammation in the background. LGSIL would have cells of normal size but with larger, more hyperchromatic nuclei and with an increase N:C ratio. Navicular cells are boat-shaped intermediate cells with glycogen found in pregnant patients. Thus, the best answer is a
These cells were found in the gynecologic sample from a 48-year-old female (SurePath, medium magnification, left and right). The most likely interpretation of these cells is:
(a)
Endocervical adenocarcinoma
(b)
Endometrial adenocarcinoma
(c)
Endocervical AIS
(d)
HGSIL
(e)
Repair
(e) Repair
This image shows cells with nucleoli, streaming cytoplasm, and a cohesive arrangement. Additionally, the nuclei are hypochromatic with finely granular chromatin. These are features which best describe repair. Endocervical adenocarcinoma would have larger nucleoli and coarser chromatin and would occur in glandular groupings with tall columnar cells. Endometrial adenocarcinoma is usually a three-dimensional group with enlargement of the nuclei, nucleoli, and powdery chromatin. AIS of the endocervix would have cytoplasmic feathering, elongated nuclei with coarse chromatin, but usually rare nucleoli, unlike the frequent nucleoli present here. HGSIL should display cells with hyperchromatic enlarged nuclei, coarse chromatin, and increased N:C ratio. Thus, the best choice is repair.
The most likely interpretation for cells such as these found in the gynecologic sample (ThinPrep, medium magnification) from a 39-year-old woman would be:
(a)
Chronic follicular cervicitis
(b)
Poly balls suggestive of Trichomonas
(c)
Small cell carcinoma of the cervix
(d)
HGSIL
(e)
Suggestive of lymphoma
(a) Chronic follicular cervicitis
This image shows a variety of mature and immature lymphocytes caught up in proteinaceous debris. This appearance in liquid-based preparations is common, contrasting with the “pool” of a single population of lymphs as is seen on conventional slides. Note the slight irregularities in the nuclear size and shape, indicating the presence of both mature and immature lymphs. Trichomonas may form balls of organisms but will not stain this dark purple color and instead will stain gray to lavender with an eccentric ill-defined nucleus. Small cell carcinoma of the cervix would have larger cells with hyperchromatic nuclei and small amounts of cytoplasm. This is also true of HGSIL. Detecting the lymphocytic nature of the cells of chronic follicular cervicitis is an important first step in reaching the correct diagnosis. Careful inspection of these cells will show that although the cells are lymphocytes, they do not have the irregular chromatin, nucleoli, and nuclear clefts or protrusions common in lymphoma.
The most likely interpretation of these cells is (ThinPrep, medium magnification):
(a)
Adenovirus
(b)
CMV
(c)
Herpes
(d)
HGSIL
(e)
LGSIL
(c) Herpes
These cells show the common features found in herpes infection: multinucleation; smudgy, ground-glass chromatin pattern; and molding of the nuclei. The image on the left also shows the eosinophilic inclusion bodies which may be found in herpes. Adenovirus only occurs in endocervical cells and it is not multinucleated. CMV usually has only one nucleus and has a very large basophilic intranuclear inclusion which gives an owl-eye appearance to the slide. HGSIL would not feature the marked smudgy ground-glass chromatin and molding featured on this slide, and LGSIL would not have the intranuclear inclusions, molding, and multinucleation seen here
This patient is status post hysterectomy and therapy for squamous cell carcinoma of the cervix 5 years ago (SurePath, medium magnification, right and left). A number of cells with cytomegaly, cytoplasmic vacuolization, and bizarre shapes such as these were found on the slide. The most likely interpretation is:
(a)
Inflammatory cell changes
(b)
Radiation effect
(c)
Repair
(d)
LGSIL
(e)
Recurrent squamous cell carcinoma
(b) Radiation effect
The cells in these images are consistent with the effects of radiation therapy. We can see cytomegaly, vacuolization, bizarre shapes, and an increase in nuclear size with a corresponding increase in cytoplasmic area, leading to a mostly normal N:C ratio. Note that these changes can be seen for years or even decades after cessation of therapy. The changes seen are not consistent with inflammatory cell changes which usually have small perinuclear halos, polychromasia, and an abundance of neutrophils. Repair is also not a good choice as there are no nucleoli, streaming cytoplasm, and maintained polarity to suggest this diagnosis. This degree of cytomegaly is usually only seen in patients after radiation therapy or certain types of chemotherapy or with vitamin B12 deficiency. LGSIL would have a higher N:C ratio. Recurrent squamous cell carcinoma would generally have much smaller cells with a markedly higher N:C ratio, hyperchromasia, nucleoli, and a dirty background.
Many clusters of cells such as these were found in the gynecologic sample (ThinPrep, medium magnification) from a 27-year-old woman in her second trimester of a normal pregnancy. The squamous cells with the “moth-eaten” appearance to the cytoplasm are a clue to look carefully for which of the following likely organisms?
(a)
CMV
(b)
Herpes
(c)
Actinomyces
(d)
Candida
(e)
Chlamydia
(d) Candida
The “moth-eaten” appearance in the cytoplasm should lead one to carefully search the slide for the appearance of Candida. The patient’s history of pregnancy also suggests that Candida may be the cause of this inflammatory cell change. Although Trichomonas may also give this appearance, it was not one of the choices given. Neither CMV nor herpes will give the appearance seen here. Actinomyces would display as fuzzy-looking colonies of bacteria with a starburst configuration. Chlamydia would appear as small vacuoles with tiny organisms within the vacuoles. Thus the best answer is d.
his appearance in a gynecologic sample processed on a ThinPrep slide (low magnification) gives an important clue in searching for organisms, cytolysis, atrophy, or possible cancer. This appearance is called:
(a)
Busy background
(b)
Tumor diathesis
(c)
Increased stain intensity
(d)
Endometrial cell balls
(e)
Estrogen effect
(a) Busy background
A background such as this is very suggestive of an infection with either Candida or Trichomonas. This “busy” background on ThinPrep slides can be identified at low power and can instigate a search for the true cause. Common causes of a busy background are Trichomonas or Candida infection, atrophy, cytolysis, or tumor diathesis. In addition to the observation that there are too many “things” in the background (too busy), one can note a single pseudohyphae in the center of the field, which leads to a diagnosis of Candida. A tumor diathesis should have an identifiable blood and/or cellular necrosis aspect to the slide. An increase in the intensity of the stain can go along with either Candida or Trichomonas infection but this is not observed here. Endometrial cell balls are usually seen during exodus (days 7–10 of the cycle) but they are not noted here. Estrogen effect is not usually associated with a particular organism, although it might coexist with an infection. The fungal hyphae noted here is the best clue to the diagnosis of Candida
This gynecologic sample (conventional, low magnification) would be most consistent with which of the following clinical histories?
(a)
17-year-old patient, day 5
(b)
25-year-old patient, third trimester of a normal pregnancy
(c)
32-year-old patient with testicular feminization
(d)
69-year-old patient with no exogenous hormone use
(d) 69-year-old patient with no exogenous hormone use
This low-power view shows the type of hormonal pattern that would likely be seen in a postmenopausal woman not taking any exogenous hormone replacement therapy. This atrophic pattern is mainly made up of lower intermediate to parabasal type cells, reflective of the decreased estrogen status of the patient. Maturation indices for these patients usually range from MI: 100/0/0 to MI: 50/50/0. A 17-year-old patient on day 5 would be expected to show copious blood, endometrial cell balls, other debris, and a maturation index which had more intermediate cells than superficial cells, but no parabasal cells. A 25-year-old patient in the third trimester of a normal pregnancy should normally have all intermediate cells in the smear. Small variations may occur immediate prior to delivery. A 32-year-old patient with testicular feminization would have a high estrogen level with a maturation index approaching nearly 100 % superficial cells.
This sample is from the gynecologic smear of a 32-year-old female (conventional, low magnification, left; high magnification, right inset). The best interpretation of these findings is:
(a)
Doderlein bacilli and Trichomonas
(b)
Actinomyces and shift in vaginal flora suggestive of bacterial vaginosis
(c)
Candida and Trichomonas
(d)
Entamoeba histolytica and Doderlein bacilli
(e)
Leptothrix and Trichomonas
(e) Leptothrix and Trichomonas
This image shows the long curving slender organisms consistent with Leptothrix. These organisms usually occur with Trichomonas; however, Trichomonas may often occur without Leptothrix. The Trichomonas organisms may be better seen in the higher power view in the lower left. We see an eccentric nucleus in a small grayish pear-shaped organism. These organisms have multiple flagella, but they are often lost in processing and are seldom identified on Pap-stained material. Doderlein are not seen in this image as the long, curving nature of the Leptothrix is not consistent with the appearance of Doderlein bacilli. Neither Actinomyces nor shift in vaginal flora is consistent with the images. Actinomyces is arranged in a starburst type of pattern in a colony of bacteria. Candida and Trichomonas seldom occur together and the Candida organisms will be several times greater in width than the Leptothrix. Entamoeba histolytica is a parasite of the GI tract and also has two distinct nuclei rather than the one seen in Trichomonas
Small, pink to orange cells such as these were found throughout the gynecologic sample from a 42-year-old female (ThinPrep, right and left, medium magnification). The best diagnosis is:
(a)
Normal squamous cells
(b)
Parakeratotic cells
(c)
Hyperkeratosis
(d)
Squamous cell carcinoma
(e)
Repair
(b) Parakeratotic cells
Parakeratosis is a benign proliferative reaction made up of miniature superficial squamous cells. The cells are quite small and polygonal, usually stain pink to orange, and have small pyknotic nuclei. They occur on the surface of the epithelium and may occur with hyperkeratosis. Their presence has been associated with more serious lesions, especially keratinizing LGSIL. The cells are too small to be normal squamous cells. These cells do have nuclei so they are not hyperkeratosis. There is not a high enough N:C ratio to be considered for squamous cell carcinoma. These cells do not have the nucleoli and streaming cytoplasm consistent with repair. Thus, the best answer is parakeratosis.
In the Bethesda System 2001, cells such as these found in the ThinPrep slide (right and left, medium magnification) of a 36-year-old woman would be interpreted as:
(a)
ASC-US
(b)
ASC-H
(c)
LGSIL
(d)
HGSIL
(e)
Glycogenated squamous cells
(c) LGSIL
These cells have prominent large distinct perinuclear halos, consistent infection with HPV. This finding is classified by the 2001 Bethesda System as consistent with LGSIL. ASC-US might be considered if only a few of these cells were present or if the HPV changes were questionable. However, the changes seen here are unequivocal for HPV infection. ASC-H might be considered if only a few cells with N:C ratios suggestive of a HGSIL were seen. These cells do not have a high enough N:C ratio for an ASC-H diagnosis. Likewise, a diagnosis of HGSIL is ruled out due to the lack of a sufficiently high N:C ratio. Finally, glycogenated squamous cells would have yellowish material surrounding the nucleus and would not show the nuclear abnormalities (binucleation, hyperchromasia, smudgy chromatin) seen here
Large numbers of cells with this appearance were seen on the ThinPrep (medium magnification) slide from a 32-year-old woman. This appearance is consistent with infection with:
(a)
Herpes simplex
(b)
CMV
(c)
HPV
(d)
HIV
(e)
HBV
(c) HPV
The large distinct perinuclear halos in cells which contain nuclei with some type of abnormality such as binucleation, hyperchromasia, or smudgy chromatin are consistent with infection by HPV. We now know that HPV infection is the cause of virtually all squamous cell carcinomas of the uterine cervix as well as most of the several stages of noninvasive neoplasia of squamous epithelium. Other viral infections (e.g., herpes) were at one time considered as possible precursors, but unequivocal proof has been obtained through molecular techniques that HPV infection is the cause of both LGSIL and HGSIL, as well as most squamous cancers of the cervix. Herpes has features of multinucleation, molding, and ground-glass chromatin, which are not seen in this image. CMV is characterized by large “owl-eye” nuclear inclusions in cells which generally have only one nucleus. Cytoplasmic inclusions may occasionally also occur. Neither HIV nor HBV has specific morphologic changes that can be seen with a light microscope.
This finding from a 29-year-old woman (ThinPrep, high magnification) is consistent with which of the following interpretations?
(a)
Hemosiderin-laden macrophages
(b)
LGSIL
(c)
HGSIL
(d)
Endocervical cells
(e)
Lower uterine sampling
(d) Endocervical cells
These cells are displaying the typical appearance of endocervical cells: tall columnar cell shape, eccentric nuclei, and picket fence arrangement. Hemosiderin-laden macrophages would contain hemosiderin pigment and show the typical finely vacuolated cytoplasm and single lying arrangement of macrophages. These cells are clearly columnar in configuration and so both LGSIL and HGSIL which occur in squamous epithelium would be eliminated. Lower uterine sampling might be a consideration but the image does not show the high cellularity, tubular structures, and hyperchromatic nuclei typical of lower uterine segment samples.
everal groups such as this were found in the ThinPrep sample (medium magnification) from a 34-year-old woman. The most likely interpretation is that these cells represent:
(a)
AGUS, endocervical origin
(b)
AGUS, endometrial origin
(c)
Repair
(d)
LGSIL
(e)
HGSIL
c) Repair
These cells are showing nucleoli in nearly every cell, streaming of the cytoplasm, and generally a fine, even chromatin pattern. Along with the clean background seen in this image, these cells are typical for repair. AGUS of endocervical origin should have much greater irregularity of the chromatin pattern and should not show the streaming of the cytoplasm seen especially in the right-hand image. AGUS of the endometrium should show enlarged endometrial cells in three-dimensional groups. Small nucleoli may also be seen in AGUS of the endometrium. Neither LGSIL nor HGSIL should have so many prominent nucleoli. Additionally, they should have increased N:C ratio, hyperchromatic nuclei, and irregular chromatin pattern.
Recommended cervical screening guidelines (American Cancer Society) allow for cessation of screening if the patient has no previous abnormal history and if:
(a)
She is older than 55 years
(b)
She is older than 70 years
(c)
She has a history of DES exposure
(d)
She is receiving corticosteroid therapy
(b) She is older than 70 years
Choice a is not recommended by the ACS and choices c and d are contraindications for cessation of cervical cancer screening. Choice b is correct.
The appropriate administration of prophylactic HPV vaccines:
(a)
Must take place before initiation of sexual activity
(b)
Has 2 doses
(c)
Will successfully treat an HPV infection
(d)
Will eliminate the need for Pap testing by 2017
(e)
Will eliminate the risk of clear cell adenocarcinoma in DES exposed women
(a) Must take place before initiation of sexual activity
The protective effect of the three dose prophylactic HPV vaccines occurs prior to exposure to HPV, and therefore, girls and young women ages 9–26 are targeted as recipients. The vaccine will not treat or eradicate a current HPV infection nor is it effective against clear cell adenocarcinoma caused by DES exposure. Decades will pass before all women are able to take advantage of the vaccine, and the need for continued Pap testing will continue into the future, far beyond 2017. Choice a is correct.
Which of the following may interfere with the optimum Pap test sampling of the uterine cervix?
(a)
Use of cytobrush
(b)
Application of fixative after 90 seconds
(c)
Taking the sample after day 14 of the cycle
(d)
Use of 95 % ethyl alcohol as a fixative
b) Application of fixative after 90 seconds
Delay in the application of fixative to the gynecologic slide will result in air-drying artifact and may interfere with the diagnostic accuracy of the specimen. The use of the cytobrush, restricting collection of the sample to the latter half of the cycle, and the use of 95 % ethyl alcohol as a fixative all have a beneficial effect on the accuracy of the slide. The correct answer is b.
Which of the following is NOT a Bethesda System criteria for “unsatisfactory for evaluation”?
(a)
Lack of patient identification
(b)
Insufficient squamous component
(c)
Absence of endocervical or transformation zone component
(d)
Obscuring elements covering over 75 % of the epithelial cells
(e)
Less than 5,000 squamous cells on a liquid-based preparation
(c) Absence of endocervical or transformation zone component
The addition of a determination of adequacy in the Bethesda System beginning in 1988 was an important advancement in Pap test reporting. In 2001, the lack of transformation zone component was changed from being “unsatisfactory” to a comment under “quality indicator.” The other choices are all appropriate choices to designate a case as “unsatisfactory.”
A patient with a history of uterine descensus is most likely to display which of the following on the Pap:
(a)
Hyperkeratosis and parakeratosis
(b)
Candida and leptothrix
(c)
LGSIL and dyskeratocytes
(d)
Repair and Trichomonas
a) Hyperkeratosis and parakeratosis
Uterine prolapse (or “descensus”) can be the cause of areas of leukoplakia seen on the cervix or vaginal wall. However, hyperkeratosis and especially parakeratosis may also overlie a more serious lesion such as HGSIL and large white plaques should be removed gently by the clinician using gauze prior to taking the sample. Choice “b” would be of an infectious nature and descensus does not cause this, choice “c” would indicate HPV infection, and choice “d” would also not be associated with prolapse of the uterus. Choice a is correct.
In combination with host cell genes p53 and pRB, the two most important HPV genes which lead to the development of squamous cell carcinoma of the cervix are:
(a)
L1 and L2
(b)
E1 and E2
(c)
E4 and E5
(d)
E6 and E7
d) E6 and E7
E6 binds to the p53 gene and transforms it from a proto-oncogene into an oncogene blocking the normal process of apoptosis (cell death). E7 binds to the pRB gene and halts its usual tumor suppressor function of regulation of the cell cycle which leads to unregulated cellular proliferation. The loss of the two normal gene functions thus leads to an unregulated proliferation of cells which do not die. These two HPV genetic factors seem to be the most important in the multiple changes that lead to squamous cell carcinoma. D is the correct answer.
The most common HPV subtype found in squamous cell carcinoma of the cervix is:
(a)
HPV 6
(b)
HPV 11
(c)
HPV 16
(d)
HPV 18
(c) HPV 16
HPV 16 is the most common HPV subtype found both in squamous carcinoma as well as in the precursor lesions of LGSIL and HGSIL.
A diagnosis of ASCUS is most often made in the presence of:
(a)
Rare cells with high N/C ratios
(b)
Rare cells with morphologic changes short of LGSIL
(c)
Moderate numbers of spindled, keratinizing cells
(d)
Moderate numbers of cells with nucleoli, enlarged pale nuclei, and streaming cytoplasm
(e)
Very small, discohesive dark cells with high N/C ratios
(b) Rare cells with morphologic changes short of LGSIL
Although ASCUS is one of the most common abnormalities seen on gynecologic samples, its description, criteria, and reproducibility have all been areas of study and diagnostic controversy. The newest 2001 Bethesda system subdivided the category of “atypical cells” into ASCUS, “atypical cells of undetermined significance” or ASC-H, “atypical cells, cannot exclude HSIL.” The quantity, degree of morphologic change, clinical history, and maturity of the cytoplasm all should be evaluated in reaching this decision. However, most cytologists agree that a diagnosis of ASCUS generally means the finding of cells which do not quite meet either the morphologic degree of change or the number of abnormal cells found in a LGSIL, or both. However, they also do not meet guidelines for normal cells. This is a significant lesion, however, and 10–20 % of ASCUS cytology samples are found to contain HGSIL on biopsy. About 30–40 % of cases contain high-risk HPV when tested with molecular diagnostic tests. Thus, these patients should be properly followed up, tested for high-risk HPV, and further followed with colposcopy if high-risk HPV positive. The criteria of rare cells with high N/C ratios better describes a diagnosis of ASC-H. Moderate numbers of spindled keratinized cells would more likely lead to a diagnosis of at least LGSIL, if not HGSIL. Cells with streaming cytoplasm and nucleoli with pale chromatin are most consistent with repair, and very small, dark, high N/C ratio cells would be unlikely to be diagnosed as ASCUS. The correct answer is b
The correct immediate treatment for a patient with a diagnosis of ASC-H is:
(a)
Repeat Pap in 6 months
(b)
Repeat Pap in 12 months
(c)
Testing for high-risk HPV
(d)
Colposcopically directed biopsy
(e)
LEEP procedure
d) Colposcopically directed biopsy
ASC-H is a significant diagnosis with a high rate of biopsy-proven HGSIL (50 %). Therefore, according to the suggested follow-up protocol of the ASCCP (2007), the appropriate follow-up for these patients is an immediate colposcopically directed biopsy (Choice D). These patients, of course, should not have HPV testing as their first therapeutic choice, as it would not be cost-effective (84 % positivity), nor repeat Pap test. A LEEP procedure is not recommended without first obtaining biopsy confirmed evidence of HGSIL or worse disease.
These images were from a cervical/vaginal smear on a 36-year-old woman (conventional, low and high magnification). The cellular material is most consistent with:
(a)
Endocervical cells
(b)
HGSIL
(c)
Repair
(d)
Squamous cell carcinoma
(e)
Endocervical adenocarcinoma
(c) Repair
These cells are most consistent with repair. They have preserved polarity, streaming cytoplasm, nucleoli in nearly 100 % of the cells, hypochromatic finely granular chromatin pattern, and a clean background. Although there are some red blood cells visible in the background, a true tumor diathesis is made up of old and fresh blood, necrotic cellular debris, and often fibrin strands. In liquid-based preparations (LBP) the tumor diathesis is often found clinging to the groups of malignant cells. Endocervical cells would occur in a more honeycomb architectural arrangement and have less polygonal cytoplasm. HGSIL is not a consideration due to the presence of prominent nucleoli, lack of hyperchromasia, and lack of irregular chromatin pattern. Also the nuclear/cytoplasmic ratio (N/C ratio) is not as markedly uniformly increased as in HGSIL. Endocervical adenocarcinoma is not a consideration because these cells appear as flat, ribbon-like sheets, and not in syncytial-like arrangements or loose strips. These cells are also polygonal, indicating squamous origin, rather than endocervical columnar cells with eccentric nuclei. Also, endocervical adenocarcinoma usually has a pronounced tumor diathesis
Several clusters of cells such as these were found on the cervical/vaginal smear of a 56-year-old woman (ThinPrep, medium and high magnification). These cellular groups are most consistent with a diagnosis of:
(a)
Small cell carcinoma of the cervix
(b)
Endometrial adenocarcinoma
(c)
Chronic follicular cervicitis
(d)
HGSIL (CIS)
(e)
Normal endometrial cells
(c) Chronic follicular cervicitis
These cells are fairly hyperchromatic and seem to be occurring in a “pool” which contains both very small round cells as well as slightly larger cells. Nucleoli are inconspicuous to absent, and there seems to be a proteinaceous matrix in which these cells reside. The clue to this diagnosis is the presence of the very small, perfectly round cells which are mature lymphocytes. These cells are too small to represent small cell carcinoma of the cervix, endometrial adenocarcinoma, or HGSIL (even if CIS) (Compare their size with the squamous cell nuclei in the image.). Although some of the larger, more immature lymphocytes might overlap these categories in their size range, the smaller ones do not. Also note that these cells are non-cohesive. Although tingible body macrophages can often be seen with chronic follicular cervicitis, they are not a requirement to make this diagnosis. This condition commonly occurs with Chlamydia infection and is more often seen in postmenopausal women, although it can occur at any age. Normal endometrial cells also are slightly larger than these cells. The perfect roundness of the mature lymphocytes precludes consideration of normal endometrial cells.
Cells such as these were seen in moderate numbers throughout the slide from a 26-year-old woman (Sure Path, medium and high magnification). The most likely diagnosis is:
(a)
Syncytiotrophoblast
(b)
Glycogen-filled cells consistent with pregnancy
(c)
Multinucleated histiocytes
(d)
LGSIL
(e)
HGSI
(d) LGSIL
These cells are characteristic of those with HPV infection. Note the large, perinuclear halos with sharply defined edges. Additionally, HPV infected cells have nuclear abnormalities of some type. These may include enlargement, hyperchromasia, smudgy chromatin, and bi- or multinucleation. Syncytiotrophoblasts usually have many more nuclei and have a more vacuolated appearance to the cytoplasm, since they arise from placental tissue. Additionally, the nuclei are often bland and similar in their staining, size, and shape. Glycogen-filled cells have yellow granular material in the cytoplasm and do not have the nuclear irregularities seen in HPV. Multinucleated histiocytes also have bland, uniform appearing nuclei without hyperchromasia, smudginess, or enlargement. Additionally, they often contain frothy finely vacuolated cytoplasm, unlike these cells which have hard, sharp-edged cytoplasm of squamous origin. HGSIL cells would be expected to have a much higher nuclear/cytoplasmic ratio than is seen here. Thus, these cells are consistent with HPV infection and the best diagnosis is LGSIL.
This 67-year-old patient had a cervical smear processed by ThinPrep, and the slide had this appearance over the entire surface (medium and low magnification). Which of the following is the most appropriate diagnosis?
(a)
Unsatisfactory due to obscuring blood
(b)
Quality indicator: thick, shift in vaginal flora, NILM
(c)
Quality indicator: obscuring blood, HGSIL, cannot rule out invasion
(d)
Shift in vaginal flora, LGSIL
c) Quality indicator: obscuring blood, HGSIL, cannot rule out invasion
A diagnosis of “unsatisfactory” is unacceptable as there are clearly abnormal cells in the slide. Any abnormality, even if accompanied by a qualifying adequacy factor, must be diagnosed and not read out as “unsatisfactory.” Although the blood appears granular in the background, it should be recognized as such and not diagnosed as bacteria. Additionally, the abnormal N/C ratio of the cells precludes a NILM diagnosis. The high nuclear/cytoplasmic ratios are inconsistent with a diagnosis of LGSIL. Of these choices, “HGSIL, cannot rule out invasion” is the best choice. The groups seem to include “clinging tumor diathesis” as well as abnormal cells. Tumor diathesis on liquid-based preparations will often appear as seen on this slide and will contain fresh and old blood, as well as necrotic debris from degenerating and dying cells. Before an “unsatisfactory” diagnosis is rendered, the slide should be carefully screened even when there are obscuring factors such as blood to rule out the presence of abnormal cells.
This slide from a 32-year-old female contained several cellular groups as seen in these two photomicrographs (SurePath, medium and high magnification). The best cytologic diagnosis of this case would be:
(a)
LGSIL
(b)
HR HPV 16 or 18+
(c)
HGSIL
(d)
Repair
(a) LGSIL
These cells are consistent with infection by HPV. They show large, clear halos, and some type of nuclear irregularity (enlargement, wrinkling of the nuclear membrane, and hyperchromasia). Although infection with HR HPV 16 or 18 might be present, it is impossible to diagnose on cytology what specific type of HPV is causing the cellular abnormality. A molecular diagnostic test would be required. The cells depicted do not show the increased N/C ratio consistent with HGSIL. Also, they do not have the cytoplasmic ribboning, prominent nucleoli, and hypochromasia typical of repair
A 49-year-old female was found to have numerous groups of cells on her SurePath slide resembling those seen here (medium and high magnification). A clean background was noted and in other areas of the slide, some pleomorphic cells in tadpole shapes were noted. Some of the cells were noted to have deeply eosinophilic or orangeophilic cytoplasm. The most likely diagnosis is:
(a)
Repair
(b)
LGSIL
(c)
HGSIL
(d)
Endocervical AIS
c) HGSIL
This slide most likely represents HGSIL, probably of keratinizing type. The slide shows cells with a high N/C ratio and deeply eosinophilic cytoplasm (suggestive of abnormal keratinization). Additional history given indicates a clean background, numerous abnormal cells, and occasional pleomorphism. These features are characteristic of HGSIL, keratinizing type. In cases in which the pleomorphic cells make up greater than 10 % of the abnormal cells, a keratinizing squamous cell carcinoma should be considered. The differential diagnosis should not include LGSIL, due to the very high N/C ratio present. Also, indications of pleomorphism are most often seen in higher grade lesions rather than LGSIL. The lack of nucleoli and ribboning excludes repair. Endocervical AIS might be considered due to the clean background and cytoplasmic eosinophilia; however, the pleomorphism, abnormal keratinization, and polygonal appearance of these cells should exclude this from consideration
This patient is a 76-year-old female with a moderate number of clusters of cells such as these on her slide (ThinPrep, medium magnification). The most likely diagnosis is:
(a)
Squamous cell carcinoma
(b)
Endocervical adenocarcinoma
(c)
Endometrial adenocarcinoma
(d)
LGSIL
(c) Endometrial adenocarcinoma
The most likely diagnosis of this case is endometrial adenocarcinoma. The cells are seen in clusters rather than sheets or syncytial groups. They have a distinctly three-dimensional appearance. The background seems to contain delicate wisps of tumor diathesis. Conventional slides often will have a watery, bluish, granular tumor diathesis. Liquid-based slides often have a “stringy” diathesis and some “clinging” tumor diathesis. However, the blatantly bloody tumor diathesis of endocervical adenocarcinoma or squamous cell carcinoma is not present. Additionally the cells are not markedly hyperchromatic, as would be expected with a squamous cell carcinoma and to a somewhat lesser degree, endocervical adenocarcinoma. The cytoplasm is finely vacuolated, frothy, and the nuclei are considerably enlarged from the standard size of a normal intermediate cell nucleus. Nucleoli can be observed in the right hand panel. LGSIL is not a consideration since these cells have a glandular configuration and cytoplasmic appearance rather than the sharply defined cytoplasm of cells of squamous origin.
A 59-year-old female has numerous cells with this appearance on a Thin Prep cervical/vaginal slide (medium magnification). The most likely diagnosis is:
(a)
Squamous metaplasia
(b)
Endocervical AIS
(c)
LGSIL
(d)
HGSIL
(e)
Squamous cell carcinoma
(d) HGSIL
These images show cells in sheet arrangements with high nuclear/cytoplasmic ratios. The nuclei are hyperchromatic and some of them are very angular or irregularly shaped. Note for example in the left panel, in the upper left corner, the nucleus which is crescent-shaped, the one a little lower which is shaped almost like a triangle, and the several which are spindle-shaped. Normal nuclei should be round to oval and this degree of angularity is quite abnormal. Also note the anisonucleosis present in the groups, as well as the indication of abnormal keratinization in the left panel. The background appears clean. While there are some normal squamous metaplastic cells present, the abnormal cells are larger, with higher N/C ratios and more hyperchromasia. Endocervical AIS is not a consideration as these cells are not glandular or columnar in shape and do not have the palisading common in AIS. The N/C ratio is too high for LGSIL. There are no classic features for squamous cell carcinoma such as nucleoli, dirty background, highly pleomorphic cells, and extremely high N/C ratio or syncytial groups.
A 49-year-old woman had a cervical/vaginal sample processed by the ThinPrep method which showed cells such as seen in these images (medium magnification). Blood or other debris was not noted in the background. The most likely diagnosis is:
(a)
Squamous metaplasia
(b)
ASCUS
(c)
LGSIL
(d)
HGSIL
(e)
Squamous cell carcinoma
(d) HGSIL
These cells have a high N/C ratio, irregular nuclear shapes, hyperchromasia, and some nuclear grooves and wrinkling. Their arrangement seems to be sheet-like with some cells approaching a syncytial arrangement. This is most consistent with HGSIL. The cells are too large with too high an N/C ratio to be squamous metaplasia. Compare the abnormal cells with the normal squamous cells present in the image. The N/C ratio is too high for the consideration of ASCUS or LGSIL as a diagnosis. The cells also lack nucleoli and do not appear to have any clinging tumor diathesis in the background. Thus, squamous cell carcinoma is not a consideration.
A 64-year-old woman had a history of irregular spotting for the last 4 months. Cellular material such as seen in this image was abundant in the SurePath slide (medium magnification). The most likely diagnosis is:
(a)
Repair
(b)
LGSIL
(c)
HGSIL
(d)
Squamous cell carcinoma
(e)
Adenocarcinoma, NOS
(d) Squamous cell carcinoma
These cells show hyperchromasia, irregular chromatin patterns, anisonucleosis, clinging tumor diathesis, and indications of abnormal keratinization. The chaotic, haphazard arrangement of the cells is also an indication of malignancy. Repair would have much less hyperchromasia and a more finely granular, uniform chromatin pattern. Also, this case lacks the ribbon-like arrangements frequent in repair. The consideration of LGSIL or HGSIL is highly unlikely due to the very high N/C ratio present in these cells and the dirty background. Nucleoli are also present in this image and would be highly unlikely in premalignant lesions. While an adenocarcinoma might be considered due to the patient’s age and history, the cells themselves have sharp-edged distinct cytoplasm and polygonal shapes, indicating their squamous origin. The cells also lack a two dimensional picket fence arrangement (as would be seen in endocervical adenocarcinoma) or a three-dimensional cluster or papillary grouping (as would be seen in endometrial adenocarcinoma).
This woman’s cervical/vaginal ThinPrep slide (medium magnification) showed many cells similar to those seen in these images. The best diagnosis is:
(a)
NILM
(b)
ASCUS, Trichomonas
(c)
LGSIL, Trichomonas
(d)
Reactive atypia, Trichomonas
(d) Reactive atypia, Trichomonas
There are at least four trichomonads in the left panel, right lower edge, as well as several that can be observed in the right panel. These flagellated amoeba are probably among the most commonly seen infectious agents in Pap smears. The flagella are seldom observed, although since the advent of liquid-based preparations, they can more often occasionally be seen. There are several common patterns of staining and morphology observed with a Trichomonas infection. One commonly seen pattern is an extreme inflammatory reaction with many polymorphonuclear leukocytes, sometimes in wreaths and ball formations in the background. Another common pattern is as seen here, in which, paradoxically, there is virtually no background of polys at all. These slides also often display an unusually bright, intense staining reaction, as seen here. Also, the presence of the Trichomonas causes a slight edema of the nuclei, which is seen as very slight nuclear enlargement in the slide. Also, some cytoplasmic irregularities may be seen, including a “moth-eaten” appearance, or some small indistinctly edged perinuclear halos (seen on the right). One should be careful not to overcall these as evidence of LGSIL. Additionally, the very slight nuclear enlargement is insufficient for a diagnosis of either ASCUS or LGSIL. The Trichomonas should be reported so that the clinician can properly treat the patient for the infection
This slide was prepared by the SurePath methodology (medium magnification) from the cervical/vaginal material of a 26-year-old patient. The best diagnosis is:
(a)
NILM
(b)
ASCUS, Candida
(c)
LGSIL, Candida
(d)
NILM, contaminant fungi
(e)
NILM, reactive atypia, Candida
e) NILM, reactive atypia, Candida
The right panel shows the typical appearance of Candida in a cervical/vaginal sample. Note the pseudohyphae and somewhat irregular staining showing the septate growth pattern of the fungal organisms. Candida is associated with pregnancy, diabetes, and immunosuppression. Note also the small, ill-defined perinuclear halos in the cell group on the left. These are reactive changes caused by the Candida infection. While slight nuclear enlargement can be seen, it is most consistent with one and one-half to two times the size of a normal intermediate cell nucleus. The nuclei that are visible have maintained a normal N/C ratio and do not appear to have nuclear irregularities. This excludes both ASCUS and LGSIL as diagnostic possibilities. Thus, since the right panel shows typical features of Candida species, the best answer is e.
Several groups of cells such as these were found in the cervical/vaginal slide (ThinPrep, medium magnification) of a 38-year-old woman with no previous history. The most likely diagnosis is:
(a)
Normal endometrial cells
(b)
Normal endocervical cells
(c)
Squamous metaplasia
(d)
ASC-H
(e)
HGSIL
(e) HGSIL
These cells are quite small with very high N/C ratios. Careful examination may be required to arrive at the correct interpretation. These cells seem to contain sharp-edged, crisp cytoplasmic borders, and the largest of these cells (top section of the left panel) clearly shows their squamous origin. They have a somewhat polygonal shape with a central nucleus. This eliminates normal endocervical cells which have eccentric nuclei. The cytoplasm in normal endometrial cells would be less well-defined, finely vacuolated, and the cells tend to occur in 3D groups or loose clusters. Also, endometrial cell nuclei are less uniformly round to oval and often show reniform or irregularly shaped nuclei. The N/C ratio is too high and they are too hyperchromatic for squamous metaplastic cells. While ASC-H is a morphologic consideration, the history given and the several images would indicate that these abnormal cells are sufficiently abundant in number to qualify for a diagnosis of HGSIL. When the abnormal cells are quite few in number, care must be taken to locate and properly diagnose cells with this morphology as ASC-H, as these cases were found to have CIN2 or worse in 30–40 % of patients in the ALTS trial.
Numerous cells similar to those seen in these images were seen in the SurePath preparation of a 59-year-old female (high magnification). The most likely diagnosis is:
(a)
Repair
(b)
Endocervical adenocarcinoma
(c)
Reactive atypia
(d)
Tubal metaplasia
(e)
Squamous cell carcinoma
(e) Squamous cell carcinoma
These cells have the characteristic appearance of squamous cell carcinoma. Pleomorphism, abnormal keratinization, and extremely hyperchromatic, irregular nuclei are noted. Note also the dense, very sharp-edged cytoplasm. Nucleoli are not well observed in this sample, probably due to the extreme hyperchromasia often present in cells originating from a keratinizing type of squamous cell carcinoma. These types of carcinoma may have a relatively cleaner background than either non-keratinizing or small cell squamous cell carcinoma due to their often exophytic growth pattern. However, some evidence of clinging tumor diathesis may be seen, especially in the panel on the left. Differentiating between a HGSIL lesion and an invasive keratinizing squamous cell carcinoma may thus present difficulties. The best procedure is to determine the approximate percentage of abnormal cells which display pleomorphism. If it is greater than 10 %, an invasive keratinizing squamous cell carcinoma should be considered.
Cells such as these were found in the cervical sample from a 29-year-old female (ThinPrep, high and medium magnification). The most likely diagnosis is:
(a)
NILM, reactive atypia
(b)
ASCUS
(c)
LGSIL
(d)
Radiation effect
(c) LGSIL
These cells have the characteristic features of cells derived from HPV infection. These koilocytes have large, clear, distinctly defined perinuclear halos, along with nuclear abnormalities. Nuclear abnormalities may include enlargement (from slight up to one-third the diameter of the cell), smudginess, bi- and multinucleation, and hyperchromasia. Even in cells without appreciable nuclear enlargement, if one of the other nuclear abnormalities is present along with the clear, large halo, they can be designated as koilocytes and a diagnosis of LGSIL is appropriate. Small, ill-defined perinuclear halos accompany reactive atypia, such as is seen in Trichomonas or Candida infections. These HPV halos are much bigger, take up more of the cytoplasm of the cell, and some of them have thickened dense cytoplasm at the edge of the halo. If the halos were not characteristic for HPV and/or the nuclear abnormalities were absent, ASCUS might be a consideration. However, that is not the case in this image. Radiation does not produce these typical koilocytotic changes, although it may produce some vacuolization in the cytoplasm. Usually this is accompanied by an enlargement of both the nucleus and the cytoplasm so that very large cells, with multiple or enlarged nuclei may be found. The key is that the N/C ratio is usually maintained within the normal range. Polychromasia, finely granular chromatin, and bizarre cell shapes may also occur in post radiation therapy.
Many cells such as these were seen in the cervical material of a 32-year-old woman. The material was processed by ThinPrep (low and medium magnification). The best immediate next step in the follow-up of this patient would be:
(a)
Send remaining material for HR HPV testing
(b)
Send remaining material for LR and HR HPV testing
(c)
Perform a p16 molecular test on the remaining material
(d)
Send patient for colposcopically directed biopsy
(e)
Repeat Pap in 12 months
(d) Send patient for colposcopically directed biopsy
These cells are koilocytes and are pathognomic of HPV infection. The clear, large perinuclear halos, abnormalities in the nuclei, and thickening of the cytoplasmic rim around the halo are classic for a diagnosis of LGSIL. The best follow-up for LGSIL patients was evaluated in the ALTS trial which determined that high-risk HPV testing (HR HPV) was positive so often (87 %) in LGSIL patients that it was not cost-effective to perform. Low-risk HPV (LR HPV) is never indicated for any reason in the cytology laboratory. A p16 molecular test would also not be cost-effective in the follow-up of this patient. The prescribed follow-up would be colposcopically directed biopsy. It must be remembered that even LGSIL has a biopsy correlation of CIN2 or above in 15–25 % of patients. Therefore, a repeat Pap in 1 year may allow up to a quarter of patients with cytologically diagnosed LGSIL to progress to even more serious lesions without proper timely care. Thus, an immediate colposcopically biopsy is the best follow-up.
A number of cells such as those illustrated here were found in the gynecologic sample of a 44-year-old female (ThinPrep, medium magnification). The best diagnosis is:
(a)
Endocervical AIS
(b)
Normal endometrial cells
(c)
LGSIL
(d)
HGSIL
(e)
Squamous cell carcinoma
(d) HGSIL
These images show cells that have high N/C ratios, hyperchromatic irregular chromatin, moderate anisonucleosis, an absence of nucleoli, and a clean background. Compare their size with the normal appearing cells in the left panel. The nuclei are darker, have irregular areas of clearing and clumping in the chromatin, and some cells have nuclear rim thickening. They appear to have squamous type cytoplasm, rather than glandular cytoplasm such as AIS or normal endometrial cells might have. The cytoplasm appears polygonal, and the nuclei are central. The edges of the cytoplasm seem sharp and distinctly bordered. Also, the N/C ratio is quite marked, excluding a LGSIL from consideration. On the other hand, the background appears clean and no nucleoli are noted. The absence of these features helps to rule out a diagnosis of squamous cell carcinoma.
A 52-year-old female with a past history of Chlamydia infection presents with no clinical complaints. These cells were discovered on her conventional Pap smear (high magnification). The most likely diagnosis is:
(a)
Leukemia
(b)
Severe acute inflammation
(c)
Small cell carcinoma of the cervix
(d)
Chronic follicular cervicitis
d) Chronic follicular cervicitis
The key to this diagnosis is in noticing the very small, round lymphocytes within this “pool” of lymphs of a range of maturation. Some of the more immature lymphs have much larger, hypochromatic nuclei and nucleoli, consistent with the histologic appearance of follicular groups of lymphs below the epithelium. Note how there is no molding of the nuclei, consistent with the non-cohesive nature of lymphocytes. Also, this group of lymphocytes is relatively “pure” without many other types of inflammatory cells. The only exception to this is the occasional presence of tingible body macrophages (TBM), histiocytes with lymphocytic nuclear material ingested in the cytoplasm. Although finding a TBM is not required for this diagnosis, it can help to confirm an initial suspicion. Patients with Chlamydia and postmenopausal patients are often found to have chronic follicular cervicitis. Although these are lymphocytes and a few of them are immature, the patient has a diverse population with all levels of maturation included. Leukemia would generally have only one immature type of lymph present. Acute inflammatory cells are not noted. The final possibility, small cell carcinoma of the cervix, is ruled out due to the presence of the very small, perfectly round mature lymphs. These are smaller than even the nuclei of small cell carcinoma. Also, small cell carcinoma and leukemia/lymphoma would have a more uniform appearance than the variety of lymphoid maturation apparent here.
A 36 year-old female demonstrated many cells such as these in a conventional Pap smear (high magnification). The background appeared clean. The most likely diagnosis is:
(a)
LGSIL
(b)
HGSIL
(c)
Squamous cell carcinoma
(d)
Endometrial adenocarcinoma
(b) HGSIL
These cells have hyperchromatic chromatin, very high N/C ratios, irregular chromatin pattern, anisonucleosis, and squamous appearing, hard-edged cytoplasm. These features are consistent with a HGSIL. LGSIL can be excluded because these cells have too high N/C ratio for LGSIL. Squamous cell carcinoma is not a consideration due to the lack of nucleoli, absence of syncytial groupings, and clean background. Finally, endometrial adenocarcinoma is more likely to have delicate, frothy scant cytoplasm, prominent nucleoli, and three-dimensional groupings
This 36-year-old patient is seen for her first prenatal care at 8 months gestation. Several clusters of cells such as these were seen on the conventional Pap (medium and high magnification). The most likely diagnosis and appropriate follow-up is:
(a)
Syncytiotrophoblasts, schedule a D and C for incomplete miscarriage
(b)
Multinucleated histiocytes, no follow-up needed
(c)
Herpes simplex, plan for Cesarean section at delivery
(d)
HGSIL, schedule colposcopically directed biopsy after delivery
(c) Herpes simplex, plan for Cesarean section at delivery
These cells have the typical configuration of herpes, multinucleation, molding of the nuclei, and “ground glass” chromatin. As seen here, the nuclei may be somewhat pale and powdery due to the viral infection. Sometimes, eosinophilic intranuclear inclusions can also be seen. Margination of the chromatin resulting in a thickened nuclear rim may be present. Herpes is a very significant finding in a woman towards the end of her pregnancy. If the woman is having a recurrent infection, she may already have developed antibodies and passed them on to the fetus, in which case the fetus is more likely to be protected. However, if the status is unknown and the infection occurs after week 36, the infant has a 33 % chance of developing an infection with quite serious sequelae including demise. Therefore, in this case, a Cesarean section is recommended to prevent the delivery through the infected birth canal. Syncytiotrophoblasts are occasionally seen in threatened or post abortion. However, trophoblastic cells, although multinucleated, have bland, regular nuclei without the characteristic molding and ground glass appearance of herpes. Multinucleated histiocytes may also be seen in pregnant women, but they have foamy cytoplasm and uniform bland finely granulated chromatin in the nuclei. HGSIL is not a consideration as these nuclei are not hyperchromatic and HGSIL would have distinct, irregular chromatin, unlike the powdery, ground glass pattern seen here
his 58-year-old patient presented with a history of occasional spotting and back pain. She did not have a Pap in the last 8 years (conventional, high magnification). The most likely diagnosis with its accompanying risk factor is:
(a)
Squamous cell carcinoma, HPV subtype 16 or 18 infection
(b)
Endometrial adenocarcinoma, obesity
(c)
Endocervical adenocarcinoma, HPV subtype 16 or 18
(d)
Ovarian adenocarcinoma, herpes simplex infection
(a) Squamous cell carcinoma, HPV subtype 16 or 18 infection
These cells are most consistent with squamous cell carcinoma. They display very hyperchromatic nuclei, with some that are even opaque. Pleomorphism is noted. There is evidence of abnormal keratinization with the cytoplasm of some cells staining deeply pink to orange. The arrangement of cells is single or in syncytial groups. The N/C ratio is extremely high and the nuclear shapes are spindle, triangular, or round to oval. Nucleoli may be seen if the hyperchromasia of the nuclei allows for it. Endometrial adenocarcinoma might be a consideration due to the patient’s age, but the distinct squamous-like edges of the cytoplasm would not be consistent with this diagnosis. Endocervical adenocarcinoma might be considered due to the deep eosinophilia of the cytoplasm; however in this case, the cytoplasm lacks the granularity and glandular appearance of endocervical adenocarcinoma. Ovarian adenocarcinoma is not a consideration due to the lack of clustering, glandular cytoplasmic appearance, or prominent nucleoli.
A 32-year-old woman has a past history of an abnormal Pap smear and current clinical history of postcoital spotting. Many groups of cells with the cellular morphology displayed are noted in the conventional slide (low and high magnification). Nucleoli are inconspicuous or absent. The most likely diagnosis is:
(a)
Squamous cell carcinoma
(b)
HGSIL (CIS)
(c)
Endocervical adenocarcinoma
(d)
Endocervical adenocarcinoma in situ
(d) Endocervical adenocarcinoma in situ
The key to this diagnosis lies in the ability to distinguish a syncytial group from a glandular 2D endocervical type of architecture. Note in the left panel, how the nuclei are parallel to one another on the left side of the group. Also note the crowded parallel, pseudopalisading of the nuclei at the top of the group in the right panel. This is typical feathering of the endocervical nuclei in which the nuclei are so crowded within the cluster that the nuclei protrude outward, like the feathers of a bird’s wing. Hyperchromatic crowded groups such as these should always be examined carefully to detect the architectural characteristics of the cells. Squamous cell carcinoma is excluded since this is not a syncytial grouping of cells and since nucleoli are not conspicuous. Likewise, the organized arrangement of pseudopalisading nuclei with feathering visible at the edges helps to rule out CIS. Endocervical adenocarcinoma is a consideration due to the 2D arrangement of the cells; however, these usually have very conspicuous macronucleoli or multiple nucleoli present.
Cells of this type were identified within the conventional Pap smear of a 19-year-old woman (medium magnification). The most likely diagnosis is:
(a)
Reactive inflammatory cell changes
(b)
ASCUS
(c)
LGSIL
(d)
HGSIL
(c) LGSIL
These cells have large, distinct perinuclear halos and have coexisting nuclear abnormalities consistent with a diagnosis of LGSIL. These changes are caused by HPV infection and morphologic evidence of this infection is indicated by the sharp thickened cytoplasmic edge of the halo, the increase in nuclear size or bi-nucleation, and the increase in hyperchromasia of some of the nuclei. Although not clearly seen here, the nuclei are sometimes also seen as smudgy, without crisp chromatin particles. Reactive cellular changes may also sometimes show perinuclear halos in cases with Trichomonas or Candida. However, those halos are smaller, have ill-defined edges, and should not be confused with the clear, large halos seen here. The abnormal cells seen here are also clearly caused by HPV infection, so a diagnosis of ASCUS is less precise than is possible with these cells. If cells have questionable cavitations suggestive of HPV, and no clear koilocytes can be found, then ASCUS may be an acceptable diagnosis. Finally, HGSIL is not an appropriate diagnosis for these cells as the nuclear/cytoplasmic ratio is not high enough
(SurePath, low magnification left and upper right, high magnification on the lower right). The anatomic site of origin of these cells is most likely:
(a)
In the endometrium
(b)
In the endocervical glands
(c)
In the fallopian tubes
(d)
From the squamocolumnar junction
(d) From the squamocolumnar junction
These cells are quite abnormal and indications of a tumor diathesis are seen in the background. The “stringy” appearance of the old blood and cellular debris is common on liquid-based preparations. Clinging tumor diathesis can also be found in these types of preparations. Note the evidence of keratinization in the upper right hand panel. Combined with the elongated spindle-like appearance of the cytoplasm and the nuclei, this case is most consistent with a squamous carcinoma. Thus, the endometrium, the glands of the endocervix, and the fallopian tube are unlikely anatomic sites for this type of cancer. The squamocolumnar junction is the most common site of origin for squamous cell carcinoma of the cervix.
A relatively small number of cells such as these were found in the ThinPrep slide (medium magnification except right middle panel which is high magnification) from a 41-year-old woman. The most appropriate diagnosis and follow-up for this case is:
(a)
Reactive endocervical cells, NILM, repeat Pap in 1 year
(b)
ASCUS, HR HPV testing
(c)
ASC-H, HR HPV testing
(d)
ASC-H, immediate colposcopically directed biopsy
(d) ASC-H, immediate colposcopically directed biopsy
These cells have a very high N/C ratio, irregular nuclear outlines, hyperchromasia, and the information that relatively few of these cells were found in the ThinPrep sample. This presentation is most consistent with a diagnosis of ASC-H. The most recent guidelines for treatment from the ASCCP (2009) indicate that immediate colposcopically directed biopsy is the most cost-effective treatment for these patients. HR HPV testing for these patients is not cost-effective since they have at least a 70 % positivity rate. Additionally, this is a very significant diagnosis since at least 50 % of these cases are found to have CIN 2 or worse on biopsy. This compares to the 60–70 % CIN 2 or higher biopsy rate found with HGSIL. Thus, these lesions are quite significant on follow-up. The hyperchromasia and N/C ratio is much higher than would be found in reactive cells. The N/C ratio is also too high for a diagnosis of ASCUS. ASC-H is the correct cytologic diagnosis and, as stated above, the correct follow-up should be immediate colposcopically directed biopsy
A 36-year-old female in the fourth month of pregnancy presents to the gynecologist with clinical symptoms of irritation and vaginal discharge. The cytologic presentation is seen in these three images (ThinPrep, medium left panel and right lower panel, high upper right panel). The most likely diagnosis is:
(a)
Candida
(b)
Syncytiotrophoblasts
(c)
Repair
(d)
CMV
(a) Candida
These panels show Candida organisms with pinkish hyphae which have light and dark staining. These organisms often pierce the squamous cells and create a “string of pearls” effect with the fungus being the “string” and the squamous cells being the “pearls.” Pregnancy, diabetes, and antibiotic use are common risk factors for Candida. Syncytiotrophoblasts are a very uncommon finding and are seen as multinucleated cells, often in “tadpole” like shapes. They represent placental tissue and may accompany a threatened spontaneous abortion. Reparative cells usually have streaming cytoplasm, prominent nucleoli in nearly 100 % of the cells, and pale, bland chromatin. The panel in the lower right is probably inflammatory cell changes that may accompany Candida infection. CMV should have a prominent “owl’s eye” large inclusion body within the nucleus. CMV may also have cytoplasmic inclusions as well.
Identify two infectious organisms in these panels (ThinPrep, medium magnification, left two panels and right upper panel, high magnification, bottom right and center):
(a)
Herpes, Candida
(b)
Actinomyces, Trichomonas
(c)
CMV, cytolysis
(d)
Actinomyces, Candida
(b) Actinomyces, Trichomonas
The organism present in the upper left hand corner shows the typical characteristics of Trichomonas: pear-shaped, indistinct vacuolated cytoplasm, and an eccentric nucleus. Under extremely favorable conditions, the flagella of these organisms are sometimes preserved, but this is rare. The lower middle panel shows these organisms alongside some squamous cells. Actinomyces is a higher-order bacteria that forms colonies with starburst-like filaments protruding from a background of small coccoid-like bacteria. It is often found in women wearing IUDs. Herpes must have “ground glass” chromatin appearance and these images do not show this; Candida does not show the starburst arrangement seen here. CMV is not represented on the slide as owl-eye inclusions are not seen. Cytolysis is also not an organism and the bacteria
A number of cells such as these were found on the gynecologic sample from a 48-year-old female (ThinPrep, medium magnification). High-risk HPV subtyping was also performed. The most likely results from the HPV test are:
(a)
HPV subtype 6 positive
(b)
HPV subtype 11 positive
(c)
HPV subtype 16 positive
(d)
HPV subtype 40 positive
(c) HPV subtype 16 positive
The cells have the morphologic configuration of HGSIL with high N/C ratios, hyperchromatic nuclei, and squamous appearing cytoplasm. Although HR HPV typing should not be performed on HGSIL cases as it is not cost-effective, the results from subtype specific testing can be predicted in this case because the only high-risk subtype in the choices given is subtype 16. The other choices (6, 11, and 40) are low-risk subtypes and would not have been detected in a high-risk HPV molecular test. 6, 11, and 40 might coexist with 16 but are rarely found in cancer. HPV 16 is the most common viral subtype to infect the cervix and may be associated with a range of lesions from koilocytotic atypia, LGSIL, HGSIL, and on to squamous cell carcinoma. HPV types 16, 18, 45, and 31 (in that order) make up about 80 % of the high-risk HPV types found in cervical squamous cell carcinoma.
These cells were found in the gynecologic sample of a 28-year-old woman. The most likely diagnosis is:
(a)
Folic acid deficiency, NILM
(b)
Squamous metaplasia, NILM
(c)
Herpes, NILM
(d)
Reactive endocervical cells, NILM
(e)
HGSIL
(e) HGSIL
These cells have a very high N/C ratio as well as hyperchromasia. Note also the angularity of some of the nuclei. This is rare in the absence of neoplasia. These cells are most consistent with a high-grade lesion. Folic acid deficiency has cytomegaly without an increase in N/C ratio. The N/C ratio is also too high for normal squamous metaplasia. Herpes would have multinucleation, hypochromasia, and “ground glass” nuclei. Reactive endocervical cells would have a more elongated cytoplasm with small nucleoli present. Also, the characteristic endocervical pattern of picket fence or honeycomb arrangement is not seen.
A 29-year-old patient displayed a number of these cells on her gynecologic sample (ThinPrep, medium magnification). The best diagnosis would be:
(a)
Endometrial cells, NILM
(b)
Chronic follicular cervicitis, NILM
(c)
Squamous metaplasia, NILM
(d)
HGSIL
(d) HGSIL
Although these nuclei are rather small (2–2½× a normal intermediate cell nucleus), the N/C ratio is markedly increased. They are hyperchromatic and show some nuclei with abnormal shapes (arrowhead, tadpole). They are arranged in a sheet or syncytial arrangement. Compare the sizes carefully with the surrounding normal cells. Endometrial cells would be smaller (same size as an intermediate cell nucleus) with an even higher N/C ratio in the case of epithelial or deep endometrial cells. Chronic follicular cervicitis would have a more varied size range from the perfectly round normal lymphocytes to the larger, more immature lymphs making up the lymphocytic infiltrate
Which of the following statements is true about the lesion depicted here (ThinPrep, high magnification)?
(a)
>80 % of LGSIL contains HR HPV subtypes
(b)
Almost all CIN 3 lesions contain high-risk HPV subtypes.
(c)
Pregnant patients frequently display glycogen in the perinuclear area of the cell.
(d)
All patients with this lesion should receive HR HPV testing.
(a) >80 % of LGSIL contains HR HPV subtypes
These cellular changes are pathognomonic of HPV infection, (LGSIL). Note the large, clear, sharp-edged perinuclear halos, as well as some nuclear abnormality such as bi-nucleation, increase in nuclear size, or hyperchromatic, smudgy nuclei. Interestingly, although “low-risk” HPV subtypes are commonly associated with lower-grade lesions such as genital warts and LGSIL, more than 80 % of LGSILs contain “high-risk” HPV subtypes. This contrasts with CIN 3 lesions in which virtually all of the cases contain HR HPV. So although the statement is true, the lesion depicted is not HGSIL. Perinuclear glycogen in the cells of pregnant patients might briefly resemble the findings here, but a more thorough examination will rule this out, mainly due to the absence of the typical yellow glycogen deposits. Finally, as was determined in the ALTS trial, the majority of these cases are HR HPV positive, so performing molecular diagnostics on them is not cost-effective and they should go to immediate colposcopically directed biopsy. However, all of these would be smaller than the cells seen here. Also, the centrally placed nucleus and the squamous appearance of the small amounts of cytoplasm are more consistent with HGSIL than follicular cervicitis. These cells have too high an N/C ratio for squamous metaplasia, as well as too much hyperchromasia for a benign protective process.
A 32-year-old woman with no previous abnormal history occasionally displayed the following cells in her gynecologic sample (ThinPrep, medium magnification). She was G2P1 and in the fifth month of her pregnancy. The most likely diagnosis is:
(a)
LGSIL
(b)
Radiation effect
(c)
Folic acid deficiency
(d)
IUD effec
(c) Folic acid deficiency
The cytomegaly seen here in these multinucleated cells is most likely due to a deficiency in one of the B vitamins, folic acid. This vitamin is utilized in DNA synthesis and a deficiency in this vitamin can mimic changes seen in radiation therapy. This change is reversible with folic acid therapy. Low levels of folic acid during early pregnancy have been associated with increased fetal risk of spina bifida, a neural tube defect. This patient’s lack of previous abnormal history and relatively young age makes radiation effect unlikely. LGSIL is unlikely since the N/C ratio is not significantly increased, the cells are few, and they are quite large in comparison to normal cells. Also, due to the patient’s pregnant status, IUD effect is not a tenable diagnosis. IUD effect is seen as vacuolization of metaplastic or endocervical cells.
These cells were uniformly present in the gynecologic sample of a 65-year-old woman (conventional, low and medium magnification). The orange small cells are most likely:
(a)
Degenerated parabasal cells
(b)
Parakeratosis
(c)
Squamous metaplasia
(d)
HGSIL
(a) Degenerated parabasal cells
Small, pink to orange-staining cells may frequently be seen in samples from postmenopausal women who have an atrophic pattern. Note that there are also very small cells with bluish cytoplasm present as well. These changes are due to the failure of the cells to fully mature due to lack of estrogen. A key to this diagnosis is the age of the patient as well as the background pattern of marked atrophy. Although the cells are staining pink to orange, this does not indicate abnormal keratinization as might be seen with parakeratosis. The overall hormonal pattern of the slide also indicates atrophy rather than squamous metaplasia, which also usually does not stain orange. The N/C ratio in these cells and their lack of an abnormal chromatin pattern rules out a HGSIL, although atrophic slides should be screened carefully for any evidence of neoplasia
Cells such as these were found in a 65-year-old woman with a history of squamous cell carcinoma of the cervix, hysterectomy, and radiation (conventional, medium magnification). They are most likely:
(a)
Endocervical repair
(b)
Radiation effect
(c)
Herpes
(d)
Recurrent squamous cell carcinoma
(b) Radiation effect
These cells are showing marked enlargement, multinucleation, vacuolization of the cytoplasm, small nucleoli, and an N/C ratio that is not markedly increased. The bizarre shapes of the cytoplasm are also characteristic of radiation effect. Poly engulfment and polychromasia may also be seen occasionally. These are not endocervical repair because the cells are not streaming, with pale chromatin and prominent nucleoli in every cell, nor do they appear to have derived from endocervical epithelium, which in this case would not be present due to the hysterectomy. Although multinucleated, the nuclei are not ground glass nor molding as in herpes. Finally, the cells do not show the high N/C ratio, the abnormal chromatin pattern, and the loose syncytial arrangement that would be present in recurrent squamous cell carcinoma.
A 69-year-old patient with no history of previous abnormal cytology and no history of hormone replacement therapy displayed findings such as these on her Thin Prep slide (low and high magnification). The most likely cause of the blue to violet rounded structures (arrows) is:
(a)
Degenerated parabasal cells
(b)
AGUS – endometrial
(c)
ASCUS
(d)
Pollen contaminant
(a) Degenerated parabasal cells
These structures are relatively commonly found in postmenopausal patients with severely atrophic patterns, such as this patient. These “blue blobs” are thought to be very degenerated parabasal cells and remnants of the nuclei can sometimes be seen. The background in these patients often appears “busy” on liquid-based preparations and granularity of the background debris may give a false impression of tumor diathesis. However, the crisp chromatin pattern of neoplasia is not seen and the structures are not naked enlarged nuclei but are parabasal cells which have degenerated. Compare their overall size and shape with the other parabasal cells in the panels. The structure is too large to be of endometrial origin and lacks identifiable glandular cytoplasm. ASCUS is also a poor choice again due to the lack of identifiable cytoplasm. Pollen is usually better preserved, stains deep red to yellow, and varies in size and shape depending on the plant from which it is derived. It is important to recognize this common artifact to avoid overcalling.
Many cells such as these were found in the Thin Prep slide (medium magnification) of a 29-year-old woman. What other types of cells are the most likely to also be seen on this slide?
(a)
Squamous cells with small, ill-defined perinuclear halos
(b)
Endocervical cells with hyperdistended vacuoles
(c)
Parabasal cells with autolytic atrophy
(d)
Mature squamous cells with large, well-defined perinuclear halos
(d) Mature squamous cells with large, well-defined perinuclear halos
These small cells show the dense, rounded, orange cytoplasm typical for dyskeratocytes. Note also the enlarged, smudgy, hyperchromatic nuclei consistent with HPV infection. Thus, these cells would most likely be accompanied by koilocytes with large, well-defined perinuclear halos. Small ill-defined perinuclear halos are consistent with inflammatory changes caused by Trichomonas or Candida and they are not associated with dyskeratocytes. Endocervical cells with hyperdistended vacuoles are also not associated with dyskeratocytes. The slide seems to show a normal hormonal pattern and thus these cells are not the small orange parabasal cells sometimes seen in a background of extreme atrophy. Additionally, these cells have denser cytoplasm and have larger, darker nuclei than those found in atrophic slides.
The large clear areas in these cells are most likely due to (ThinPrep, medium magnification):
(a)
Effects of chemotherapy
(b)
Effects of radiation
(c)
Inflammatory cell changes
(d)
Effects of HPV infection
(e)
Hyper-vacuolization
(d) Effects of HPV infection
The large clear halos in these cells are evidence of infection by human papillomavirus (HPV). These cells, koilocytes, should have both the large clear halos seen here but also often have some abnormality of the nucleus: smudginess, hyperchromasia, increased N/C ratio, irregular chromatin, etc. Chemotherapy or radiation both lead to cytomegaly without increased N/C ratio and that is not seen here. Inflammation (Trichomonas or Candida) may cause perinuclear halos, but the halos are much smaller, more ill-defined on the inner edges, and there is not a significant increase in the N/C ratio. Also inflammatory perinuclear halos are not associated with a nuclear abnormality such as those listed above. These cells are clearly squamous cells with sharp-edged cytoplasm, and in the absence of radiation or other causes, squamous cells seldom show any vacuolization in the cytoplasm.
A 46-year-old woman had several clusters and scattered cells such as these on the slide (ThinPrep, medium and high magnification). The most appropriate diagnosis in this case would be:
(a)
Squamous metaplasia
(b)
LGSIL
(c)
HGSIL
(d)
Repair
(c) HGSIL
These cells show rounded, dense, immature cytoplasm with enlarged nuclei. These nuclei show a generally finely granular, evenly distributed chromatin pattern and a high N/C ratio. Hyperchromasia is also noted. Hyperchromasia may be less pronounced in liquid-based preparations than in conventional slides. Compare the overall cell size and nuclear size with the normal squamous metaplastic cell in the upper left panel. A LGSIL would likely have a lower N/C ratio and be less likely to show the nuclear abnormalities seen here. Especially note the irregular nuclear outlines and signs of clefting and grooving of the nuclei. These nuclear abnormalities are less likely to be seen in LGSIL than in HGSIL. Repair is not a
Many cells such as these were found in the conventional slide of a 52-year-old woman (high and medium magnification in inset). The most likely diagnosis for this case is:
(a)
Endometrial cells
(b)
Adenocarcinoma of endometrial origin
(c)
HGSIL
(d)
Squamous cell carcinoma
(e)
Adenocarcinoma of the endocervix
(d) Squamous cell carcinoma
This slide shows extensive blood, cellular debris, and necrosis in the background. The cells are small, but larger than the intermediate cell nuclei in the background. Additionally the nuclei have marked clearing and clumping of the chromatin, extremely high N/C ratios, hyperchromasia, and nucleoli can be identified. The cells appear to occur singly, in loose clusters or syncytial groups. These are all criteria for cervical carcinoma with small cell morphology. Benign endometrial cells are excluded by the presence of nucleoli and the dirty background. Also, benign endometrial cells should not be larger than the intermediate cell nuclei. Adenocarcinoma of the endometrium, although a consideration, is excluded by the marked irregularity of the chromatin, and the squamous appearance of the cytoplasm as seen in the lower right hand corner of the slide. Usually, endometrial adenocarcinoma has a more powdery, paler chromatin than the “salt and pepper” clearing and clumping observed in this slide. Also, one would expect somewhat more prominent nucleoli. The dirty background and presence of nucleoli exclude a HGSIL from consideration. Finally, adenocarcinoma of the endocervix would generally display multiple, prominent macronucleoli and architecture loosely resembling the picket fence or honeycomb arrangements seen in normal endocervical cells. Also, one would expect more abundant cytoplasm and eccentrically placed nuclei for endocervical adenocarcinoma.
In order to determine the severity of the abnormality seen in these cells (ThinPrep, high magnification), one should most carefully observe which of the following?
(a)
Whether there are koilocytes on the slide
(b)
The irregularity of the nuclear membranes
(c)
The color of the cytoplasm
(d)
The appearance of the background
(e)
The color of the nuclei
(b) The irregularity of the nuclear membranes
At first glance, these cells might lead one towards a diagnosis of LGSIL, based solely on the N/C ratio. However, the nuclear membrane irregularities, as well as nuclear clefting, grooves, and hyperchromasia are markedly abnormal. One should carefully search the remainder of the slide for other evidence of HGSIL, including cells with markedly increased N/C ratios, such as is observed in the lower right hand corner of the slide. Usually LGSIL will have smooth nuclear borders, without clefting or nuclear grooves. Numbers of abnormal cells will also be a consideration, as well as the morphology. Usually HGSIL will show higher numbers of abnormal cells than LGSIL. In the case of rare cells with HGSIL morphology, ASC-H may be a consideration. The color of the nuclei or the cytoplasm generally is not a significant consideration in determining the severity of the lesion. The appearance of the background is usually only a criteria to assist when deciding between an invasive carcinoma and a CIS-type HGSIL. Since these cells do not show morphologic changes severe enough to consider that differential, the background is not an important consideration in this case.
A number of cells such as these were found in the gynecologic sample of a 47-year-old woman (ThinPrep, medium magnification). The most likely diagnosis is:
(a)
ASCUS
(b)
LGSIL
(c)
HGSIL
(d)
Squamous cell carcinoma
c) HGSIL
The most likely diagnosis is HGSIL. These cells show hyperchromasia, high N/C ratios, angular nuclear shapes, and evidence of clefting of the nuclei. Usually LGSIL cells have smooth nuclear borders and less irregularity of the sizes and shapes of the nuclei, as well as a lower N/C ratio than seen here. The finding of arrowhead, spindle, or non-isodiametric angular nuclei is an important feature, along with high N/C ratios, to diagnosis HGSIL. The N/C ratio here is much higher than would be expected in a case of ASCUS. The absence of a dirty background and nucleoli excludes squamous cell carcinoma from consideration.
Cells such as these were found in the gynecologic sample of a 32-year-old female (ThinPrep, high magnification). Clinical history from the patient included a previous “abnormal” Papanicolaou test result about 3 years earlier, G3P3, and LMP 7 days ago. The most likely diagnosis of these cells is:
(a)
Histiocytes
(b)
HGSIL (CIS)
(c)
Endometrial cells
(d)
Atrophy
(e)
Chronic follicular cerviciti
(c) Endometrial cells
These cells are displaying the typical pattern seen in normal endometrial cells during days 6–10 of the menstrual cycle. The cells may appear in a double walled structure called an endometrial cell ball (lower right hand corner). This is made up of endometrial epithelial cells and endometrial stromal cells. The cluster of cells in the upper right hand corner is typical for epithelial endometrial cells. A few single stromal cells are noted to the left of the cell ball, showing more abundant foamy cytoplasm than is usually seen in the epithelial cells. While a single small histiocyte is nearly identical in appearance to a single stromal endometrial cell, the three-dimensional clusters of cells seen indicate their epithelial origins. HGSIL is not a consideration since the displayed nuclei are uniform in size and staining, having bland, finely granular chromatin, and no hyperchromasia. Although the N/C ratio is high, these nuclei are the same size as an intermediate cell nucleus. HGSIL nuclei would be larger, more hyperchromatic, and have more irregular chromatin. Atrophy would be unusual in this age group, unless induced by surgical castration or immediate postpartum. Also, there is evidence of estrogen effect in the superficial and intermediate cells present. Chronic follicular cervicitis is ruled out by the cohesive nature of these cells, compared to mature and immature lymphs seen in follicular cervicitis. Follicular cervicitis lymphs are non-cohesive in appearance.
The best differential diagnosis for a case with a number of cells (ThinPrep, medium) such as these would be between:
(a)
NILM and ASCUS
(b)
ASCUS and LGSIL
(c)
LGSIL and HGSIL
(d)
HGSIL and SCCA
(b) ASCUS and LGSIL
A is most likely incorrect since these cells do have some type of morphologic abnormality as seen by the bi-nucleation, Thus, ASCUS vs. NILM is not a good choice. B is a better answer, since there is some nuclear atypia with a slight increase in the N/C ratio. There is also some indication of large perinuclear halos, although perhaps not classic for koilocytes in this field. A search of the remainder of the slide should be made to see if unequivocal koilocytes might be found. If they are not, and if the N/C ratio does not increase more than is seen here, a diagnosis of ASCUS might be appropriate. LGSIL vs. HGSIL is not an appropriate choice because the N/C ratio is not significantly enlarged, as it would be in either of those lesions. The same holds true for HGSIL vs. SCCA. The morphology is not supportive of either of those diagnoses.
A 56-year-old patient displayed cells such as these on her routine Pap smear (ThinPrep, medium and high magnification). The background contained small amounts of lysed blood, but no inflammation or organisms. The cells occurred in sheets such as these. The most likely diagnosis is:
(a)
Atrophy
(b)
Repair
(c)
Squamous metaplasia
(d)
LGSIL
(b) Repair
These cells have enlarged nuclei, streaming cytoplasm, nucleoli in most of the cells, and a bloody but not dirty background. The cells seem to maintain their polarity and the chromatin pattern is bland and not remarkable. Note the distinct cell borders and the cohesive sheet-like arrangement. The cells seem to have too much cytoplasm to be atrophy and atrophy does not usually contain nucleoli. Although some of the cells resemble squamous metaplasia, streaming cytoplasm and nucleoli are not found in squamous metaplasia. Also the nuclei are too variable for the usual appearance of squamous metaplasia. LGSIL does not have nucleoli and should have a more uniformly increased N/C ratio than is seen here.
Several clusters of cells such as these were found in the ThinPrep Pap (high magnification) of a 38-year-old female. The most likely diagnosis is:
(a)
Endometrial cells
(b)
Reactive endocervical cells
(c)
HGSIL
(d)
Carcinoma with small cell morphology of the cervix
a) Endometrial cells
These cells are in a three-dimensional loose cluster. The nuclei are the same size as the nearby intermediate cell nucleus. Also note the bean-shaped nuclei visible within the cluster. These are indicative of endometrial origin. Additionally, the cytoplasm is fluffy or lacy appearing, indicating the glandular nature of these cells. Reactive endocervical cells are glandular but are larger in overall size, have an eccentric nucleus, and often show reactive, small nucleoli. None of these characteristics are seen in the group seen here. HGSIL would have larger cells with clearly squamous type cytoplasm. Also, the N/C ratio would be much increased over these cells, and hyperchromasia and irregular or clumpy chromatin could be observed in HGSIL. Carcinoma with small cell morphology of the cervix may have clearly squamous type cytoplasm, hyperchromasia, clumpy chromatin, and a markedly dirty background consistent with the biologic aggressiveness of the tumor. The bean-shaped nuclei of endometrial cells are not found in small cell carcinoma cells.
These cells were found in the Pap smear (SurePath, medium magnification) of a 62 year-old female with a history of squamous cell carcinoma of the cervix. She has been treated by hysterectomy and radiation completed 5 months ago. The most likely diagnosis is:
(a)
Atrophy
(b)
Post-radiation dysplasia
(c)
Radiation effect
(d)
Recurrent squamous cell carcinoma
The key to this diagnosis is the presence of a couple of normal cells within the field. These two cells (one parabasal and one intermediate) are much smaller than the other cells displaying cytomegaly, nuclear and cytoplasmic vacuoles, ingested polys, and no significant increase in the N/C ratio. These cells are much too large and have too much cytoplasm to qualify for a diagnosis of atrophy. Post radiation dysplasia should display cytomegaly and other changes of radiation effect with a significant increase in the N/C ratio. A diagnosis of post radiation dysplasia within 3 years of treatment gives the patient a higher risk of having recurrent carcinoma. These cells do not have high N/C ratios, hyperchromasia, nucleoli, dirty background, or other signs of recurrent squamous cell carcinoma. Usually the persistent or recurrent tumor cells do not show effects of radiation therapy and they may be rather small.
A number of cells such as these were found in the gynecologic sample (ThinPrep, medium magnification) of a 48-year-old woman. The most likely diagnosis is:
(a)
ASCUS
(b)
LGSIL
(c)
HGSIL
(d)
Squamous cell carcinoma
(c) HGSIL
These cells are hyperchromatic with high N/C ratios. They appear in sheets or clusters of cells with syncytial arrangement. ASCUS is not the best choice since these cells have a much higher N/C ratio than the relatively lower N/C ratio prevalent in ASCUS. Also the N/C ratio is higher than it would be in LGSIL. HGSIL would have this scanty amount of cytoplasm and a large, hyperchromatic nuclei which take up over 80–90 % of the cell. The background is clean and the nuclei do not show nucleoli as it would if it represented cancer. Therefore, the best diagnosis for this case would be HGSIL.
This patient is a 24-year-old patient in for a routine checkup after placement of an intrauterine device 4 months ago. Several clusters of cells such as these were seen on the slide (ThinPrep, high magnification). The most likely diagnosis is:
(a)
Clear cell adenocarcinoma associated with DES exposure in utero
(b)
Multinucleated histiocytes
(c)
Endocervical AIS
(d)
IUD effect
(e)
Squamous cell carcinoma
(d) IUD effect
The key to this diagnosis is the presence of highly vacuolated cells of probable metaplastic and/or endocervical origin. These cells become irritated by the presence of the endocervical string on the IUD and react by becoming vacuolated. Clear cell adenocarcinoma of the vagina was associated with intrauterine exposure to DES during the mother’s pregnancy. This resulted in vaginal adenosis and occasional clear cell adenocarcinoma of the vagina in women in their teens and early adulthood. The cells of clear cell adenocarcinoma, however, are obviously malignant, with abundant cytoplasm, macronucleoli, and a dirty background. DES was prescribed from 1945 to 1971 and the risk of clear cell adenocarcinoma was about 1/2,000 women. Since the youngest of these women are now approaching 40, this diagnosis is becoming more and more unlikely. The cytoplasm of these cells is too dense for histiocytes and these are multiple cells, rather than two multinucleated cells. Endocervical AIS is composed of crowded, tall columnar cells with feathering and elongated nuclei and clumpy chromatin. The cells here have excessively glandular appearing cytoplasm to consider a squamous malignancy. Also a squamous cancer would have nucleoli, clumpy chromatin, hyperchromasia and a dirty background.
Many cells such as these were found in the conventional slide (high magnification) from a 58-year-old woman. The most likely origin of these cells is:
(a)
Internal endocervical os
(b)
Endocervical glands
(c)
External endocervical os
(d)
Ectocervix
(d) Ectocervix
These cells show evidence of abnormal keratinization, shown by the intensely orange staining of the cytoplasm of the squamous cells. Note also the pleomorphic shapes, the dark, opaque nuclei, and the overall squamous appearance of the cytoplasm. Keratinizing squamous cell carcinoma is most likely to originate on the ectocervix of the patient and is often associated with hyperkeratosis or parakeratosis. Nucleoli may be difficult to discern due to the intensely dark nuclei. Also, as these keratinizing lesions are often exophytic in their growth pattern, the background may not have as much tumor diathesis as non-keratinizing or small cell types of cervical carcinoma. The internal endocervical os would not be a good choice for the location of the origin of this squamous cell carcinoma. Endocervical glands would also not be a likely source for these cells. External endocervical os might have some involvement with a tumor such as this, but the most likely anatomic location is the ectocervix
Cytoplasmic vacuolization and perinuclear halos were seen in the ThinPrep slide (medium magnification) of a 30-year-old woman. The most likely causative agent in this case is:
(a)
HPV 18
(b)
HPV 11
(c)
Gardnerella vaginalis
(d)
Trichomonas vaginalis
(d) Trichomonas vaginalis
There are about four to five trichomonas organisms in this field. These are protozoa which are pear- to oval-shaped with a faint elongated eccentrically located nucleus. Infection with Trichomonas and Candida may cause the small ill-defined perinuclear halos and the so-called “tissue paper” cells with cytoplasmic vacuolization. The organisms range in size from about 8–30 μm. These cells may have a somewhat “moth-eaten” appearance on ThinPrep. The halos produced by either HPV 18 or HPV 11 would be larger and the nuclei would be enlarged, smudgy, or have other abnormalities. The changes seen with Gardnerella vaginalis are the appearance of “clue cells” and background bacteria in the slide.
Several cells such as these were found in the gynecologic sample from a 56-year-old patient (ThinPrep, high magnification). Most of the cells had a single nucleus and this one had two nuclei. All of the nuclei were pale and had a single large eosinophilic structure as seen in this image. The most appropriate diagnosis is:
(a)
Endometrial adenocarcinoma
(b)
Repair
(c)
Herpes simplex
(d)
Cytomegalovirus
(d) Cytomegalovirus
Cytomegalovirus (CMV) is often described as having an “owl’s eye” appearance due to the relatively large intranuclear inclusion body found within a pale appearing nucleus. CMV is distinguished from herpes simplex infection in that the cells of herpes are usually more abundant in the slide, are usually multinucleated, show evidence of nuclear molding, and have “ground glass” chromatin. Although CMV has similar chromatin, it is most usually found as cells with one single nucleus, and it has a quite large eosinophilic or basophilic inclusion body. CMV may also have blue cytoplasmic inclusions (25 %) unlike herpes. Note also that in this unusual case with two nuclei, they overlap one another and do not display the nuclear molding seen in herpes. Repair will also have pale nuclei but crisp chromatin particles will be visible, unlike the “ground glass” chromatin seen in virally infected cells. Also, repair should have streaming cytoplasm and occur in cohesive ribbons, rather than single cells. Finally, these cells do not display the delicate foamy cytoplasm and powdery, irregular chromatin characteristic of endometrial adenocarcinoma.
A 38-year-old woman presented with mouth and vaginal ulcers of 14 months duration. She reported painful swallowing and a 40 lb weight loss over this period. Many cells such as these were found in groups and clusters within the gynecologic sample processed by SurePath (high magnification). Given this clinical history and the appearance of these cells, the most appropriate diagnosis is:
(a)
Repair
(b)
Herpes simplex
(c)
CMV
(d)
Pemphigus vulgaris
(d) Pemphigus vulgaris
This rare autoimmune disease was often fatal before the advent of corticosteroid treatment. Clinically the patient suffers from blistering, ulceration, and loss of mucosal and skin tissues, due to a loss of the desmosomes which anchor the cells to one another. The cytologic presentation shows groups and single cells with a prominent, eosinophilic bar-shaped nucleolus. The nuclei are round with pale chromatin. The cells do not show the cohesive streaming characteristics of repair. The nuclei are not “ground glass” as in herpes and the cells are not multinucleated. Also, the nuclei are not smudgy and pale, as they appear in CMV. Additionally, the nucleolus is not as large in relation to the size of the nucleus as the inclusion body is in CMV. This very painful disease may also cause blistering on the epidermis and both the loss of fluids and difficulties in swallowing may lead to significant weight loss, as in this patient. Thus, this clinical history and the appearance of the cells lead to the diagnosis of pemphigus.
This image is from a Pap smear of a 41-year-old female with a history of squamous cell carcinoma. What is the most likely diagnosis?
(a)
Neoplastic, recurrence of squamous cell carcinoma
(b)
Neoplastic, glandular
(c)
Infectious
(d)
Reactive
This Pap smear is from patient who had squamous cell carcinoma treated with hysterectomy and radiation therapy. The smear shows cytomorphological changes consistent with radiation/treatment changes. One of the most common causes of repair is radiation. The cytomorphology of radiation effects include cellular enlargements (cytomegalic cells) which do not have a significant increase in nuclear/cytoplasmic ratio. The cells, often polychromatic and sometimes having bizarre shapes, may continue for decades after the cessation of radiation therapy. A postradiation dysplasia should be differentiated from repair or radiation effect by the increase in nuclear/cytoplasmic ratio. This finding puts the patient at increased risk for recurrent carcinoma within 3 years of treatment. Recurrent squamous cell carcinoma should have a markedly increased N/C ratio, hyperchromasia, and marked pleomorphic nuclei, and may have nucleoli. A tumor diathesis in the background should be present as well as irregular chromatin patterns. The uniform, streaming cytoplasm; clean background, hypochromatic, finely granular nuclei; numerous PMNs; and absence of single cells can also assist with this differential.
Which of the epithelial cell abnormality categories is most applicable to this case?
(a)
Squamous cell carcinoma
(b)
Adenocarcinoma
(c)
Adenocarcinoma in situ (AIS)
(d)
High-grade squamous intraepithelial lesion (HSIL)
(c) Adenocarcinoma in situ (AIS)
The cells are glandular origin and lack the uniformity of nuclear spacing within well-defined, orderly cytoplasmic borders typical of benign groups. This AIS case shows acinar three-dimensional groups with feathering of peripheral nuclei. The atypical cells show columnar morphology with rosette-like arrangements. The cells have enlarged oval nuclei, nuclear hyperchromasia, and granular, evenly distributed chromatin with a clean background. There is no patchy or clinging necrosis seen. Small inconspicuous nucleoli are also present. Few single atypical cells are also noted in this case. The histological follow-up of this case shows endocervical adenocarcinoma in situ.
Which of the epithelial cell abnormality categories is most applicable to this case?
(a)
Squamous cell carcinoma
(b)
Adenocarcinoma
(c)
Adenocarcinoma in situ (AIS)
(d)
High-grade squamous intraepithelial lesion (HSIL)
(d) High-grade squamous intraepithelial lesion (HSIL)
These cells show rounded, dense, immature cytoplasm with enlarged nuclei. They appear in clusters of cells with syncytial arrangement. These nuclei show a generally finely granular, evenly distributed chromatin pattern and a high N/C ratio. HGSIL would have this scanty amount of cytoplasm and a large, hyperchromatic nuclei which take up over 80–90 % of the cell. Compare the overall cell size and nuclear size with the normal intermediate squamous cells. Especially note the irregular nuclear outlines and signs of clefting and grooving of the nuclei. The background is clean, and the nuclei do not show nucleoli as it would if it represented cancer. These abnormal cells have dense cytoplasm and central nuclei; therefore, they are not glandular origin. Therefore, the best diagnosis for this case would be HGSIL.
This liquid-based Pap test is from a 32-year-old postpartum woman who had abnormal Pap test during her pregnancy (epithelial cell abnormality—ASC). Which of the categories is most applicable to this case?
(a)
Squamous cell carcinoma
(b)
Adenocarcinoma
(c)
High-grade squamous intraepithelial lesion (HSIL)
(d)
Negative for intraepithelial lesion or malignancy (NILM)
(d) Negative for intraepithelial lesion or malignancy (NILM)
This is Arias-Stella reaction (ASR) in Pap Test. The effect was first described in 1954 by Javier Arias Stella. It is a benign cellular proliferative change in Müllerian epithelium due to pregnancy-related hormone levels (hyperprogestational states). The most common epithelium is endometrial, but it can be seen also in endocervical gland’s tubal epithelium. The morphology consists of loosely cohesive cell groups of markedly enlarged glandular cells with abundant clear cytoplasm, eccentric nuclei, nuclear enlargement, prominent nucleoli, prominent nuclear grooves, and inclusions. Binucleation and abundant cytoplasm are also seen. The morphology of ASR on both cytological and histological preparations is a known diagnostic pitfall and a source of false-positive diagnoses due to its resemblance to adenocarcinoma. Some features such as a relative preservation of nuclear/cytoplasmic ratio, fine chromatin pattern, clean background, cohesiveness of the cells, and the presence of nuclear grooves and inclusions are helpful for accurate diagnosis. There are no single cells and tumor diathesis as it would if it represented cancer. AIS shows tightly crowded sheets of glandular cells with overlapping stratified, enlarged, coarsely hyperchromatic nuclei, and “ragged-edged” borders.
This Pap test is from a 62-year-old woman. Which of the categories is most applicable to this case?
(a)
Squamous cell carcinoma
(b)
Adenocarcinoma
(c)
High-grade squamous intraepithelial lesion (HSIL)
(d)
Negative for intraepithelial lesion or malignancy (NILM)
(b) Adenocarcinoma
This is a case of serous adenocarcinoma of ovarian origin. Cervical serous adenocarcinoma is a rare variant of cervical adenocarcinoma that is similar morphologically to the ovarian or endometrial adenocarcinomas but occurs in bimodal age pattern, with one peak occurring before age 40 and another after age 65. Serous adenocarcinomas are considered high-grade malignant cells and grow in a complex papillary or budding pattern. The nuclei are large, pleomorphic, bizarre, and have macronucleoli. The background is usually bloody and necrotic, and neutrophils may be numerous. Psammoma bodies are uncommon in the cytologic specimens. This tumor is aggressive and has a poor prognosis.
This image is from ThinPrep Pap Test from a 42-year-old female. What is the most likely diagnosis?
(a)
Squamous cell carcinoma
(b)
Adenocarcinoma in situ
(c)
Adenocarcinoma with clear cell morphology
(d)
Repair
(c) Adenocarcinoma with clear cell morphology
This is a case of clear cell carcinoma. The malignant cells are abundant and have apical “hobnail” nuclei, prominent nucleoli, and clear cytoplasm. In Pap test, they are seen singly or in sheets, clusters, or, occasionally, papillae with abundant, delicate, finely granular to vacuolated, glycogen-rich cytoplasm. In occasional cases, the cells may have abundant oxyphilic cytoplasm. Intracytoplasmic mucin can also be present in some cells, resulting in signet-ring morphology. Nuclei are large, pale, round, and irregular, with prominent nucleoli. Naked nuclei are common, owing to the delicate striped cytoplasm, similar to that described in other glycogen-rich tumors such as seminoma and Ewing sarcoma.
This image is from a conventional Pap smear. What is the most likely diagnosis?
(a)
Endocervical adenocarcinoma in situ
(b)
Carcinoma
(c)
Follicular cervicitis
(d)
Repair
This image is from a conventional Pap smear. What is the most likely diagnosis?
(a)
Endocervical adenocarcinoma in situ
(b)
Carcinoma
(c)
Follicular cervicitis
(d)
Repair
The origin of these cells is most likely:
(a)
Endocervical
(b)
Endometrial
(c)
Internal cervical os
(d)
Vagina
(b) Endometrial
These are shed endometrial cells (left) and endometrial stromal cells (right). The key features of benign endometrial cells include tight or loose cell clusters, vacuolated cytoplasm, smudged or apoptotic nuclei, and nuclei with size of intermediate squamous cells. However, in LBC, enhanced nuclear detail may confuse benign endometrial cells with a low-grade endometrial adenocarcinoma. If endometrial cells are out of cycle in a woman age 40 years or older, it should be reported, due to presence of very low risk of endometrial adenocarcinoma. However, review of the published literature shows an exceedingly low rate of significant lesions in anyone less than 40 years of age, and since cytologists may lack clinical information on menstrual dates/menopausal status, hormone therapy/tamoxifen, abnormal bleeding, and other endometrial carcinoma risk factors, the TBS 2001 created a new category “Other” to report the presence of benign-appearing endometrial cells in women aged 40 years or older. This category should include only exfoliated, intact endometrial cells. These exfoliated groups of endometrial cells may be of epithelial and/or stromal origin, and the morphological distinction of these two cell types is sometimes not possible. Directly sampled lower uterine segment or abraded stromal cells/histiocytes, when present alone, should not be reported under this category. Atypical endometrial cells should be reported as an epithelial glandular cell abnormality.
This image is from a conventional Pap smear from a 61-year-old female with a history of vaginal bleeding and previous diagnosis of AS-H. What is the most likely diagnosis?
(a)
Adenocarcinoma
(b)
Squamous cell carcinoma
(c)
Small cell carcinoma
(d)
Persistent of AS-H
(a) Adenocarcinoma
This is a case of endometrial adenocarcinoma in conventional Pap smear. Endometrial cancer cells are typically identified in Pap tests because they spontaneously exfoliate and move through the endocervical mucus to be picked up by the sampling device of Pap test. Because the mucus acts like a liquid suspension, the cells and cell groupings will round up and form three-dimensional clusters. Endometrial cancers in Pap smears will have fewer cells than will endocervical cancers. Endocervical carcinoma is usually highly cellular because it is collected by direct sampling. Nuclei will enlarge, become more irregular, and show nucleoli and abnormal chromatin patterns, often with a background of watery or granular diathesis pattern. This diathesis is distinctive to endometrial tumors because it does not contain the necrotic gritty breakdown material seen in the background of tumors that directly invade the lower genital tract. The cells may be associated with foamy histiocytes and with epithelial cells with large vacuoles containing neutrophils (so-called oxyphil cells)
This image is from a repeated Pap smear of a 39-year-old female with a history of previous diagnosis of AS-US and positive HP testing. What is the most likely diagnosis?
(a)
Endocervical adenocarcinoma
(b)
Endocervical adenocarcinoma in situ
(c)
Endometrial adenocarcinoma
(d)
Squamous cell carcinoma
(a) Endocervical adenocarcinoma
The number of malignant cells in endocervical cancer is large as compared to endometrial cancer, due to direct sampling by the sampling devices. These tumor cells often present with mixed “in situ” morphology, as wells as evidence of invasion including tumor diathesis and single cell configurations. The tumor cells are typically in two-dimensional sheets because of their lack of opportunity to “round up” as would be noted in exfoliated samples or in endometrial adenocarcinoma. The nuclei are large (two to three times the size of normal endocervical cells) and have irregular hyperchromatic chromatin, prominent nucleoli, and irregular nuclear contour. The cytoplasm ranges from abundant to scant and may retain a columnar appearance in well-differentiated cases and can show many of the architectural features of in situ adenocarcinoma. This includes honeycombed group configuration, pseudostratified strips of cells, and rosette formation. Invasive endocervical adenocarcinoma always shows a diathesis background pattern which will consist of clumped and clinging granular material in liquid-based specimens and diffuse granular breakdown material in conventional slides.
his image is from a Pap smear from a 51-year-old female with no previous Pap history and unknown HPV status. What is the most likely diagnosis?
(a)
Endocervical adenocarcinoma
(b)
Endocervical adenocarcinoma in situ
(c)
Squamous cell carcinoma
(d)
AS-US
(c) Squamous cell carcinoma
This is a case of invasive squamous cell carcinoma (SCC). Squamous cell carcinoma comes in two morphologic variants, keratinizing and nonkeratinizing. The Bethesda System (TBS) does not subdivide squamous cell carcinoma into these categories, but the cytomorphologic features are somewhat different. Nonkeratinizing variant shows cells with immature cytoplasm, high nuclear/cytoplasmic ratios, and nuclei with prominent nucleoli, irregular chromatin distribution, and irregular nuclear membranes. These cells may be seen in loose or syncytial groups or as single cells. Associated features may include a tumor diathesis composed of necrotic debris, old blood, and inflammation in conventional smear or clinging necrosis in liquid-based preparations. Keratinizing SCC displays all of the cellular characteristics of keratinizing HSIL with the addition of variable numbers of cells demonstrating nucleoli or the addition of a tumor diathesis. Features include marked cellular variation with tadpole, spindle, and caudate shapes (more seen in left image), dense eosinophilic cytoplasm, and markedly hyperchromatic, often opaque nuclei with high N/C ratios. Cells may be single or in loose or even thick groups.
This image is from a Pap smear of a 30-year-old female. What is the most likely diagnosis?
(a)
Neoplastic, squamous origin
(b)
Neoplastic, glandular
(c)
Benign, reactive, infectious
(d)
Dysplastic
(c) Benign, reactive, infectious
This is a case showing tubal metaplasia. Tubal metaplasia is a benign, nonneoplastic replacement of the normal endocervical (or endometrial) epithelium with ciliated cells characteristic of the fallopian tube. Tubal metaplasia is common, particularly after age 35, and can be identified histologically in 30–90 % of cervices. Tubal metaplasia usually occurs high in the endocervical canal and can be sampled owing to widespread use of the endocervical brush. It may present challenges in Pap test interpretation because it mimics glandular abnormalities such as adenocarcinoma in situ (AIS). Tubal metaplasia may show crowded sheets or 3-dimensional clusters or may occur as single cells. The cells are columnar with uniform, dense, cyanophilic, or vacuolated cytoplasm. They are usually smaller than normal endocervical cells but can have larger nuclei. The nuclei are round and display finely granular dark chromatin with small or no nucleoli. Mitosis can be seen. The background is usually clean. Tubal metaplasia shares features of glandular neoplasia, presenting as hyperchromatic crowded groups with columnar glandular morphology showing enlarged, pleomorphic nuclei and high N/C ratios. However, the cell groups are more orderly in tubal metaplasia, and the nuclear contour is usually round to oval and more uniform, whereas it is less orderly and with more elongated or irregular nuclei in AIS.
This image is from a repeated Pap smear of a 42-year- old female with a history of breast carcinoma. What is the most likely diagnosis?
(a)
Endocervical adenocarcinoma
(b)
Endocervical adenocarcinoma in situ
(c)
Metastatic adenocarcinoma
(d)
Benign endometrial cells in woman >40 years old
(c) Metastatic adenocarcinoma
This is a case of metastatic breast ductal adenocarcinoma. The diagnosis of metastatic extragenital malignancy to the cervix on a Pap test is rare and challenging often due to the absence of clinical data referring to a previous history of malignancy. In such cases, misinterpretation of these neoplastic elements as primary neoplasms of the cervix can occur. Women with secondary malignancies involving the lower genital tract may present with abnormal vaginal bleeding, ascites, or a rectovaginal fistula. Most patients have a known history of malignancy, the majority of which are poorly differentiated adenocarcinoma or another high-grade malignancy. Approximately 50 % of extrauterine malignancies are from ovarian and fallopian tube malignancies and 50 % from non-gynecological sites.
The most common non-gynecological extrauterine sites are gastrointestinal, breast, pancreas, lung, bladder, and kidney. Extrauterine malignancies in Pap tests are often characterized by a clean background with no diathesis, and the presence of tumor cells that look like them may be “floaters.” Therefore, when an obvious malignancy seen in a Pap test is associated with a clean background or when the morphology is unusual, an extrauterine neoplasm should always be suspected. Most metastatic adenocarcinomas, although classifiable as malignant, often cannot be definitively identified by site of origin on cytologic grounds alone. Clinical findings of an extrauterine malignancy, correlation with the histology of the original tumor (if available), and immunostains are usually necessary to confirm the diagnosis.
This image is from a Pap smear of a 47-year-old female with a history of colonic carcinoma. What is the most likely diagnosis?
(a)
Endocervical adenocarcinoma
(b)
Endocervical adenocarcinoma in situ
(c)
Squamous cell carcinoma
(d)
Metastatic colonic adenocarcinoma
(d) Metastatic colonic adenocarcinoma
This is a case of metastatic colonic adenocarcinoma. The diagnosis of metastatic extragenital malignancy to the cervix on a Pap test is rare and challenging often due to the absence of clinical data referring to a previous history of malignancy. In such cases, misinterpretation of these neoplastic elements as primary neoplasms of the cervix can occur. Women with secondary malignancies involving the lower genital tract may present with abnormal vaginal bleeding, ascites, or a rectovaginal fistula. Most patients have a known history of malignancy, the majority of which are poorly differentiated adenocarcinoma or another high-grade malignancy.
Approximately 50 % of extrauterine malignancies are from ovarian and fallopian tube malignancies and 50 % from non-gynecological sites.
The most common non-gynecological extrauterine sites are gastrointestinal, breast, pancreas, lung, bladder, and kidney. Extrauterine malignancies in Pap tests are often characterized by a clean background with no diathesis, unless the tumor is a direct extension such as this case. The presence of tumor cells with columnar morphology and marked necrosis is characteristic for colonic adenocarcinoma. Immunostains in some cases using CK20 and CDx2 are usually helpful to confirm the diagnosis and can be done on cell block material.
This image is from a Pap smear of a 27-year-old female. What is the most likely diagnosis?
(a)
Squamous cell carcinoma
(b)
Small cell carcinoma
(c)
High-grade squamous intraepithelial lesion (HSIL)
(d)
Follicular cervicitis
(c) High-grade squamous intraepithelial lesion (HSIL)
This is a case of HSIL with small cell morphology in syncytial-like aggregates.
The category of HSIL encompasses the older categories of moderate and severe dysplasia, CIN II, CIN III, and carcinoma in situ. The cytologic features of HSIL are characterized by cells with immature cytoplasm, abnormal nuclear features, and increased N/C ratios. The two most important differences between LSIL and HSIL are the immaturity of the cytoplasm and the high N/C ratio. The cells are present singly, in sheets, and at the high end of the spectrum may be seen in syncytial-like aggregates. The nuclei of HSIL are most often somewhat smaller than those of LSIL especially in the more severe lesions and may present as small cell morphology mimicking follicular cervicitis. The nuclear size typically ranges from two to five times the size of an intermediate cell nucleus. Of importance, the cytoplasmic area is always decreased yielding a marked increase in the nuclear to cytoplasmic ratio. The nuclei are hyperchromatic with a fine to coarsely granular, evenly distributed chromatin pattern. The nuclear membranes are wrinkled, and there is typically a significant degree of anisonucleosis. Nucleoli are generally absent.
This image is from a Pap smear of a 35-year-old female. What is the most likely diagnosis?
(a)
Neoplastic, squamous origin
(b)
Neoplastic, glandular
(c)
Infectious
(d)
Reactive
(d) Reactive
This is a case showing reparative changes in ThinPrep Pap Test. The smear shows clusters of epithelial cells with cytomorphological changes consistent with reparative changes. The cytomorphology includes no significant increase in N/C ratios. The cells are in clusters with no single cells and often polychromatic. The background is clean or inflammatory and no tumor diathesis in the background. The nuclei are relatively uniform, hypochromatic, with finely granular chromatin, and prominent nucleoli. The nuclear contour/envelope is usually smooth. The cytoplasm shows streaming-like morphology. The presence of numerous PMNs and absence of single cells can assist with this differential.
This image is from a Pap smear of a 28-year-old female. What is the most likely diagnosis?
(a)
Neoplastic, squamous origin
(b)
Neoplastic, glandular
(c)
Infectious
(d)
Benign/reactive
These are benign endocervical cells showing cytoplasmic mucus vacuoles. The endocervix does not have the classical glandular component of secretory cells that are connected to the surface by a duct lined with ductal cells. Endocervical cells are morphologically different from endometrial cells. The endocervical cells are tall columnar and have basal nuclei, delicate cytoplasm with an average N/C ratio of 30 %. They are rarely ciliated and can be seen as single or in groups (strips and sheet). They normally do not form acini, papillae, or cell balls. Cytoplasmic vacuoles in endocervical cells can occur. The nuclear size and features should help in avoiding overcalling these cells as dysplastic.
with previous Pap test of atypical glandular cells (AGC)?
(a)
Endocervical adenocarcinoma in situ (AIS) vs. invasive endocervical carcinoma
(b)
Endometrial adenocarcinoma in situ
(c)
Endometrial adenocarcinoma
(d)
Metastatic breast carcinoma
(a) Endocervical adenocarcinoma in situ (AIS) vs. invasive endocervical carcinoma
This case has features of AIS and endocervical adenocarcinoma. The follow-up surgical biopsy confirms presence of both AIS and invasive adenocarcinoma too. The average age of AIS is 35–40 years at presentation. It is a precursor to cervical invasive adenocarcinoma. There are acinar three-dimensional groups and feathering of peripheral nuclei. The atypical columnar cells show pseudostratified nuclei and rosette-like arrangement of cells. The cells display enlarged oval nuclei, nuclear hyperchromasia, and granular, evenly distributed chromatin. The oval columnar nuclei in AIS become more round in invasive adenocarcinoma. AIS usually show a clean background with no necrosis. In this case, the background shows some necrosis. Significantly pleomorphic crowded hyperchromatic nuclei with some “drunken honeycomb” morphology is seen. The cells lack the uniformity of nuclear spacing within well-defined, orderly cytoplasmic borders typical of benign groups. AIS usually shows small inconspicuous nucleoli, which is prominent, and multiple nucleoli in invasive adenocarcinoma (see right image) are also seen.
This image is from a ThinPrep Pap Test from a 34-year- old female. What is the most likely diagnosis?
(a)
Endocervical adenocarcinoma
(b)
Endocervical adenocarcinoma in situ
(c)
Squamous carcinoma
(d)
Repair
a) Endocervical adenocarcinoma
Endocervical adenocarcinoma accounts for approximately 25 % of cervical cancers in the USA. However, there is an increasing incidence in both relative and absolute frequency especially in younger women (the patient in this case is young). When endocervical adenocarcinoma is compared to endometrial cancer, endocervical cancer presents with more numerous cells due to direct sampling by the sampling devices. These tumor cells often present with mixed “in situ” morphology, as wells as evidence of invasion including tumor diathesis and single cell configurations. The tumor cells are typically in 2-dimensional sheets because of their lack of opportunity to “round up” as would be noted in exfoliated samples or in endometrial adenocarcinoma. The nuclei are large (two to three times the size of normal endocervical cells or two times the size of neutrophil) and have irregular hyperchromatic chromatin, prominent nucleoli, and irregular nuclear contour. The cytoplasm ranges from abundant to scant and may retain a columnar appearance in well-differentiated cases and can show many of the architectural features of in situ adenocarcinoma. This includes honeycombed group configuration, pseudostratified strips of cells, and rosette formation. Invasive endocervical adenocarcinoma always shows a diathesis background pattern which will consist of clumped and clinging granular material in liquid-based specimens (right side) and diffuse granular breakdown material in conventional slides.
This image is from a Pap smear of a 28-year-old female. What is the most likely diagnosis?
(a)
Neoplastic, squamous origin
(b)
Neoplastic, glandular
(c)
Dysplastic
(d)
Benign
(d) Benign
This is an endometrial cell ball/exodus. Cells from the endometrial cavity that can be detected in Pap tests include epithelial, stromal, and histiocytic cells. These cells can be shed or directly sampled from the lower uterine segment using Pap sampling devices. The most typical appearance is that of the endometrial cell ball or exodus or endometrial breakdown that contains a condensed core of stromal cells surrounded by epithelial cells with more abundant paler cytoplasm. Small nucleoli may be present. Endometrial cell balls are often most prominent in days 5–8 of the menstrual cycle. The endometrial cell ball consists of endometrial cells surrounding a stromal cell core. Endometrial epithelial cells are often packed, and the nuclear details may be difficult to appreciate. They have small, round to oval, darkly staining nuclei. Nuclear molding may be seen. Anisocytosis and apoptotic bodies (single cell necrosis) can be present. The cytoplasm is scant, and occasionally small vacuoles can be seen. The cytoplasm of the endometrial cells may engulf neutrophils. Other entities that show neutrophils within vacuolated glandular cells are microglandular hyperplasia of the cervix, endocervical polyps, and endometrial adenocarcinoma. In liquid-based preparations, endometrial cell groups appear tighter, isolated cells may be more prominent, the nuclear detail is often better preserved, and the nucleoli may be more readily visible. The nuclei may appear as bean shaped with sharper chromatin detail and visible nucleoli. The bloody background of conventional smears is less seen in liquid-based preparations, although stromal cells and histiocytes can still be s
What is the most likely diagnosis for this Pap test from a 58-year-old woman?
(a)
Adenocarcinoma
(b)
Squamous cell carcinoma
(c)
Endometrial cell, benign
(d)
Repair
(a) Adenocarcinoma
This case is endometrial adenocarcinoma with clear cell features. The cells have apical “hobnail” nuclei, prominent nucleoli, and clear or granular cytoplasm. The cells are present singly or in sheets or large clusters. They show abundant, delicate, and finely granular to vacuolated, glycogen-rich cytoplasm. Nuclei are large, pale, round to irregular, with prominent nucleoli. Naked nuclei may be present due to the delicate nature of the cytoplasm. The majority (>60 %) of clear cell carcinomas are HPV DNA negative. The round three-dimensional clustering and presence of PMNs within clusters (so-called oxyphil cells) are features that suggest endometrial origin.
The cells shown within the circles represent which of the following:
(a)
AIS
(b)
Tubal metaplasia
(c)
Benign endocervical cells
(d)
Endometrial cells
(c) Benign endocervical cells
Endocervical cells are simple columnar cells that line the endocervical canal. They are epithelial cells that maintain columnar morphology with a frothy mucus cap in the Pap test. The nuclei are round to oval, basally located, with smooth contours and evenly distributed finely granular chromatin. The nucleoli are round or may show a characteristic dot-like morphology. When endocervical cells are viewed from the side, they show a picket-fence morphology pattern. However, when viewed on end, they show a honeycombing pattern. In the honeycombing pattern, the nuclei of the cells are evenly spaced with very minimal crowding and overlapping. The cells show well-defined cytoplasmic borders with a mucus cap at different focusing points (3-D-like configuration). Endocervical cells show distinct cytoplasmic borders and may show a honeycomb or picket-fence appearance, and they may present as hyperchromatic crowded groups. However, absence of nuclear enlargement, uniform size of the nuclei, and absence of loss of polarity confirm the benign nature of the cells.
The vacuolated cells with signet-ring morphology represent which of the following:
(a)
Benign endocervical cells
(b)
Adenocarcinoma with signet-ring morphology
(c)
Tubal metaplasia
(d)
Endometrial cells
(a) Benign endocervical cells
These are endocervical cells with degenerative mucinous vacuoles. Endocervical cells are simple, columnar, mucus-producing cells that line the endocervical canal. They may present as single cells, in sheets, or in clusters. They may show mucinous vacuoles or a frothy mucus cap in the Pap test. The nuclei are relatively small, round to oval and basally located, with smooth contours and evenly distributed finely granular chromatin. The nucleoli are round or may show characteristic dot-like morphology. Signet-ring carcinoma shows nuclear enlargement, pleomorphism, and irregular nuclear contour.
This image is of a Pap smear from a 57-year-old woman. What is the most likely diagnosis?
(a)
Neoplastic, squamous origin
(b)
Neoplastic, glandular
(c)
Dysplastic
(d)
Benign, reactive, infectious
(d) Benign, reactive, infectious
This is a case of pemphigus vulgaris in a Pap test. Pemphigus vulgaris is an autoimmune disease that can be seen in the Pap test and has cytological features that may mimic adenocarcinoma or squamous cell carcinoma. It is characterized by vesiculobullous lesions of the skin and mucosal membranes with formation of suprabasal acantholytic vesicles and blisters. It has been shown that there is an autoantibody against a cadherin-like cell adhesion molecule on the surface of stratified squamous epithelial cells, resulting in erosions and ulcers. The disease can be seen in the esophagus, oral cavity, conjunctiva, larynx, urethra, vulva, and cervix. The cytological features of pemphigus vulgaris include high cellularity, extremely active nuclear chromatin (mitotic figures and large irregular nucleoli), and marked single cells and clusters mimicking malignancy. The nucleoli may show “bullet-shaped” morphology. There is a bloody or inflammatory background (more seen in conventional smears), but there is no true tumor diathesis. The liquid-based preparation will show inflammatory background only.
