Gyn Flashcards
3 features of endometrial polyps?
Polypoid shape, altered (often fibrous) stroma, thick-walled blood vessels.
Uterine leiomyomas. Threshold mitoses #s to upgrade to a leiomyosarcoma?
> 5 if atypical-appearing, >10 for usual-appearing, >15 if secretory phase.
Compare and contrast the following characteristics for endocervical microglandular hyperplasia (MGH) and well-differentiated endometrioid adenocarcinoma (EC): age, background, glandular architecture, cytoplasm, nuclei, and mitotic activity.
Age is reproductive for MGH and perimenopausal or postmenopausal for EC. Background is endocervix for MGH and benign or hyperplastic endometrium for EC. Glandular architecture is complex for both MGH and EC. Cytoplasm is mucinous with subnuclear vacuoles for MGH and endometrioid and/or mucinous for EC. Nuclei are bland for MGH and atypical for EC. Mitotic activity is absent or rare for MGH and present for EC.
Compare and contrast the following characteristics for reactive epithelial atypia of the fallopian tube (REA) and serous carcinoma in situ of the fallopian tube (CIS): associated conditions, type of surgery, nuclear atypia, nuclear/cytoplasmic ratio, cilia, and mitotic activity.
Associated conditions are inflammation (sometimes) for REA and BRCA mutation for CIS. Type of surgery is salpingectomy was part of surgery for other reasons for REA and prophylactic salpingo-oophorectomy for CIS. Nuclear atypia is mild to moderate (can be focally severe) for REA and severe for CIS. Nuclear/cytoplasmic ratio is maintained in REA and increased in CIS. Cilia are present in REA and absent in CIS. Mitotic activity is absent in REA and present in CIS.
Cytotrophoblasts and syncytiotrophoblasts predominantly produce ___, while intermediate trophoblasts express large amounts of ___.
Cytotrophoblasts and syncytiotrophoblasts predominantly produce hCG, while intermediate trophoblasts express large amounts of hPL.
Diagnosis of conventional (spindle) leiomyosarcoma of the uterus is established when any 2 of the following 3 criteria are present:
- Diffuse moderate to marked cytologic atypia. 2. Mitotic rate of 10 or more mitoses per 10 HPFs. 3. Tumor cell necrosis.
Diagnosis of myxoid leiomyosarcoma of the uterus is established when 1 of what 2 criteria are found?
- Severe cytologic atypia and/or tumor cell necrosis with any mitotic index, or 2. 2 or more mitoses per 10 HPFs in the absence of atypia or tumor cell necrosis.
Diagnosis of epithelioid leiomyosarcoma of the uterus is established when 1 of what 2 criteria are found?
- Any degree of cytologic atypia and 5 or more mitoses per 10 HPFs in the absence of tumor cell necrosis, or 2. 5 or more mitoses per 10 HPFs and tumor cell necrosis with any degree of cytologic atypia.
Placental mesenchymal dysplasia.
~1/4 of cases are associated with Beckwith-Wiedemann syndrome. Can also have a completely normal fetus or a growth-restricted fetus. There is increased maternal serum AFP, and normal to slightly elevated bHCG. Large placenta with dilated and tortuous chorionic plate vessels. Can have chorangiomas and cystic vesicles. Absence of: trophoblastic proliferation, stromal trophoblastic inclusions, scalloping of villous surface. Most cases are diploid.
Squamous lesions of the ovary.
Squamous elements are most commonly identified in the ovary as part of a mature cystic teratoma (or dermoid cyst). The mature cystic teratoma is both the most common ovarian tumor and the most common benign ovarian tumor. Although the squamous elements in these tumors are benign the vast majority of the time, squamous cell carcinoma can arise from them, and is the most common malignant component arising from a mature teratoma. Although only 1-2% of mature teratomas harbor a malignant component, up to 80% of those will be of squamous derivation. Metaplasia is likely the next most common cause of squamous differentiation in the ovary. The most frequently encountered nonteratomatous primary tumors showing squamous differentiation are ovarian endometrioid adenocarcinoma of the ovary and the Brenner tumor. Metastases are another common source of squamous elements in the ovary; endometrial endometrioid adenocarcinoma and squamous cell carcinoma of the cervix are 2 likely sources of metastatic ovarian squamous components. Vary rarely, squamous elements are identified in the absence of any of the above senarios; there have been a few cases of de novo squamous cell carcinoma of the ovary, some associated with endometriosis, as well as a few cases of pure epidermoid cysts without teratomatous features. In squamous cell carcinomas that are less differentiated, other epithelioid lesions may enter the DDx, such as epithelioid mesothelioma and epithelioid sarcoma.
Which are the HPV low risk and high risk genotypes? Which are the most common subtypes found in invasive squamous cell carcinoma and adenocarcinoma of the cervix?
Low risk genotypes: 6, 11, 42, 44. High risk genotypes: 16, 18, 31, 33, 45, 58. HPV 16 is the most common subtype found in cervical squamous cell carcinoma. HPV 16 and 18 are detected with equal prevalence in most subtypes of cervical adenocarcinoma (HPV 18 is more common in cervical AIS).
What HPV types (in order of frequency) are seen mostly commonly in the following lesions? Plantar wart, common wart, flat (juvenile) wart, oral squamous papilloma, oral focal epithelial hyperplasia (Heck disease), epidermodysplasia verruciformis, laryngeal papillomas, condyloma acuminatum, cervical LSIL, cervical HSIL, cervical AIS and invasive cervical adenocarcinoma.
Plantar wart: 1, 2. Common wart: 2, 1, 4, (HPV 7 in fish and meat handlers). Flat (juvenile) wart: 3, 10. Oral squamous papilloma: 6, 11. Oral focal epithelial hyperplasia (Heck disease): 13, 32. Epidermodysplasia verruciformis: 2, 3, 10, 5, 8. Laryngeal papillomas: 6, 11. Condyloma acuminatum: 6, 11. Cervical LSIL: 6, 11. Cervical HSIL: 16, 18, 31, 33, 35. Cervical AIS: 18. Invasive cervical adenocarcinoma: HPV 16 and 18 are detected with equal prevalence in most subtypes of cervical adenocarcinoma.
Peritoneal ovarian tumor implants. What types are there?
The two major types are noninvasive and invasive. The noninvasive type is further subdivided into epithelial and desmoplastic subtypes. The epithelial noninvasive implants may be exophytic or buried within invaginations beneath the peritoneal surface; they are characterized by a papillary pattern of growth, mild to moderate aypia, and lack of inflammation or stromal reaction. In desmoplastic noninvasive implants, the epithelial component is more irregular, the cells have a more abundant acidophilic cytoplasm, and there is inflammation (oocasionally severe) and a brisk stromal reaction with a granulation tissue-like appearance. Invasive implants show haphazard destructive infiltration of the stroma. As a general rule, psammoma bodies are less numerous than in noninvasive implants. The nuclear atypia is not necessarily more pronounced. Some implants of either noninvasive or invasive types are composed of papillary cores within clear spaces lined by mesothelial cells or tumor cells, resulting in a glomeruloid appearance.
Lynch syndrome has mutations in what genes?
The hallmark of Lynch syndrome is a genetic mutation in one of the family of DNA mismatch repair (MMR) protein genes (MLH1, MLH3, MSH2, MSH6, PMS2). These proteins function to repair errors in replication of DNA at short repetitive sequences (microsatellites). Lynch syndrome is associated with a high risk of colon and endometrial cancers, as well as increased risk of urothelial, small bowel, hepatobiliary, and pancreatic cancer. Further, 10-15% of sporadic colon, endometrial, and gastric tumors may harbor a somatic, non-germline MMR mutation or loss of expression.
Immunostains for endometrial stromal sarcoma.
ESS is CD10 positive, but other mesenchymal tumors such as smooth muscle tumors (highly cellular leiomyoma, leiomyosarcoma), adenosarcoma, and MMMT can be CD10 positive. Also, CD10 expression can be reduced in endometrial stromal sarcomas with variant histologic features (fibrosis, myxoid change, etc.). Therefore, CD10 is best used with a panel of other stains. Most of the tumors also express vimentin, ER, PR, WT1 (nuclear), bcl-2, and SMA; some express keratin and KIT. There can be scattered staining for desmin in some cases (in areas besides those of smooth muscle differentiation); so, like CD10, it should be used in a panel. Caldesmon is another smooth muscle marker expected to be negative in most ESS and is often included in diagnostic panels. Areas of sex cord differentiation may express inhibin, calretinin, melan-A, CD56, and CD99. EMA, DOG1, and CD34 should be negative in ESTs.
The spectrum of gestational trophoblastic disease (GTD) includes what entities?
The spectrum of gestational trophoblastic disease (GTD) includes hydatidiform molar pregnancies (complete hydatidiform mole, partial hydatidiform mole, and invasive mole), as well as non-molar lesions (placental site nodule, epithelioid trophoblastic tumor, placental site trophoblastic tumor and choriocarcinoma).
What immunostain is useful to distinguish complete hydatidiform mole from partial hydatidiform mole?
Since complete hydatidiform moles are paternally derived, paternally imprinted genes that are normally expressed exclusively from maternally derived chromosomes should be absent. Studies have shown that p57KIP2, a paternally imprinted, maternally expressed gene, is useful in confirming the diagnosis of a complete mole, as the villous mesenchymal cells and villous cytotrophoblast of CHM are negative for this marker. PHM are p57KIP2 positive.
Persistent trophoblastic disease occurs in approximately __% of women with a prior complete hydatidiform mole, and in __% of women with a partial hydatidiform mole.
Persistent trophoblastic disease occurs in approximately 20% of women with a prior CHM. Persistent trophoblastic disease may represent persistent mole with no myometrial invasion, an invasive mole, or a choriocarcinoma (occurring in approximately 2 – 3% of women with prior CHM). Persistent trophoblastic disease is treated with chemotherapy with a cure rate approaching 100%. PHM are rarely associated with persistent trophoblastic disease.
How does a hydropic abortus differ from a complete hydatidiform mole?
Hydropic abortus differs from CHM as (1) it typically is not associated with a markedly elevated ß-HCG level, (2) the volume of tissue removed is typically much less than that with CHM, (3) the villi appear swollen but lack true cistern formation, (4) the villi typically have a degenerative appearance in keeping with early embryonic demise, (5) the trophoblastic proliferation has a polar distribution with the formation of trophoblastic columns at one end of the villous and (6) are p57KIP2 positive.
Twin-twin transfusion syndrome (TTTS) is a serious condition that affects __% to __% of twin pregnancies with monochorionic diamniotic placentation.
Twin-twin transfusion syndrome (TTTS) is a serious condition that affects 10% to 15% of twin pregnancies with monochorionic diamniotic placentation. It occurs due to intrauterine blood transfusion from one twin (donor) to another twin (recipient) through placental vascular anastomoses from shared placental cotyledons. This results in increased fetal and neonatal mortality, premature delivery and neurologic complications in the surviving twin(s).
Juvenile granulosa cell tumor comprises __% of granulosa cell tumors as a whole, and represents __% of ovarian tumors in patients younger than 20 years of age. __% of JGCTs present in patients less than 30 years of age, with an average age of __ years at presentation.
Juvenile granulosa cell tumor comprises 5-15% of granulosa cell tumors as a whole, and represents 10% of ovarian tumors in patients younger than 20 years of age. 97% of JGCTs present in patients less than 30 years of age, with an average age of 13 years at presentation. These tumors frequently produce estrogen and are associated with isosexual pseudoprecocity in most prepubertal patients. JGCTs presenting after puberty may be detected secondary to abdominal swelling, pain, a pelvis mass or menstrual irregularities.
Histologic appearance of juvenile granulosa cell tumor.
JGCTs are composed of a nodular to diffuse proliferation of granulosa cells, with a fibrothecomatous stroma that can be myxoid or edematous. Characteristic follicular spaces are found within the nodules or scattered in the solid areas. The folicular spaces vary in shape from round to irregular and in size from small to macrofollicular, but microfollicles (Call-Exner bodies) are rare. Eosinophilic or basophilic fluid is present in the spaces, and the fluid is mucicarmine positive in two-thirds of the cases. The granulosa cells of JGCT are generally larger than those of AGCT and often have luteinized, moderate to abundant, pale or eosinophilic cytoplasm. The nuclei are round or oval and hyperchromatic; grooves are rarely present. Most of the tumors have at least some foci or moderate to marked nuclear atypia. Mitotic activity is variable, ranging from 1 to 32 per 10 HPF, with a median of 6-8 per 10 HPF. Theca cells can be seen in JGCTs. They may surround nodules of granulosa cells or intermix with them in solid areas.
Stains for juvenile granulosa cell tumor.
Reticulin staining demonstrates fibers around groups and nodules of granulosa cells, and fibers that surround individual theca cells. JGCT is characteristically positive for inhibin and/or calretinin. Vimentin, keratin, and CD56 are positive in most cases, and WT-1 (nuclear) and S-100 are also frequently expressed. In contrast to other sex cord-stromal tumors, focal staining for EMA (<25% of tumor cells in most cases) can be seen in 25-50% of JGCTs. Most cases are positive for SMA, but desmin is negative.
What entities are in the differential diagnosis of juvenile granulosa cell tumor, and how can they be distinguished?
The diffuse and nodular pattern with follicular spaces, round to oval hyperchromatic nuclei without grooves, and frequent luteinized cells distinguish JGCT from the adult counterpart. Because of the luteinization, JGCTs may be mistaken for thecomas. Thecomas, however, lack the follicular spaces and generally the mitotic activity seen in JGCTs; the reticulin fiber pattern is also different in these tumors. Because of the young age of most patients with JGCT, germ cell tumors, such as yolk sac tumor or dysgerminoma, may be considered. However, follicular spaces and inhibin expression are not features of those tumors. Small cell carcinoma of the hypercalcemic type is also characteristically seen in young patients and has follicle-like spaces, but it lacks the estrogenic manifestations, theca cells, and inhibin expression of JGCT. The luteinized cells with pale to clear cytoplasm in some JGCTs may resemble clear cell carcinoma. But clear cell carcinoma is rare in patients of the age that is typical for JGCT; additionally, clear cell carcinoma lacks inhibin expression and is diffusely positive for EMA.
Brenner tumors are neoplasms of urothelial (transitional cell) differentiation that are favored to be derived from ___. They constitute ___% of all ovarian tumors. Patients present in middle age with unilateral slow-growing adnexal masses which are often found incidentally. Brenner tumors may be associated with symptoms of hyperestrinism. Approximately 20% of cases are also associated with other lesions such as ___.
Brenner tumors are neoplasms of urothelial (transitional cell) differentiation that are favored to be derived from ovarian surface epithelium. They constitute 1-2% of all ovarian tumors. Patients present in middle age with unilateral slow-growing adnexal masses which are often found incidentally. Brenner tumors may be associated with symptoms of hyperestrinism. Approximately 20% of cases are also associated with other lesions such as serous of mucinous cystadenomas of the ovary, benign cystic teratoma or struma ovarii, and urothelial carcinoma of the bladder.
Under the WHO classification, Brenner tumors are classified into what 3 subtypes?
Benign, borderline, and malignant. Transitional cell carcinomas of the ovary lack a benign or borderline Brenner tumor component.
Stains for Brenner tumor vs. transitional cell carcinoma of the ovary?
Brenner tumors are generally positive for keratins, EMA, CEA, CK7, and glycogen. Evidence of urothelial differentiation in Brenner tumors is seen with reactivity for uroplakin III, thrombomodulin, and CK20. Brenner tumors are generally negative for p16 and p53. In contrast, TCC of the ovary rarely expresses the aforementioned urothelial markers. Reactivity for ER, WT-1, CA125, p16, and p53 has been observed in TCC of the ovary.
The principal differential diagnosis of mesenchymal dysplasia, both clinically and pathologically, is partial hydatidiform mole due to the similar cystic changes and the admixture of normal and abnormal villi. How can they be distinguished?
Unlike partial hydatidiform mole, mesenchymal dysplasia shows no trophoblast hyperplasia, stromal trophoblastic inclusions, or scalloping of the villous surface. The fetus associated with partial molar pregnancy is often small and malformed, unlike the more normal fetus associated with mesenchymal dysplasia. DNA ploidy may also help in distinguishing these entities, as partial hydatidiform molar pregnancy is typically triploid, whereas mesenchymal dysplasia is typically diploid.
Are the lymphocytes seen in seminoma/dysgerminoma B-cells or T-cells?
T-cells.
Approximately __% of ovarian clear cell carcinomas have a mixed component of endometrioid carcinoma.
Approximately 20% of ovarian clear cell carcinomas have a mixed component of endometrioid carcinoma, perhaps related to the common association with endometriosis.
From the LAST (Lower Anogenital Squamous Terminology Standardization) Project, when is p16 staining recommended?
The LAST Project recognized p16 as a biomarker for E6/E7 oncogene activation in all HPV-related precancerous squamous lesions of the LAT. Briefly, p16 staining is recommended whenever there is: Differential diagnosis between precancer (HSIL) and precancer mimics. Disagreement in interpretation of precancer. High risk for missing precancer (high-risk cytology with negative/LSIL biopsy findings). H&E morphologic pattern of -IN2 (This recommendation has proved to reduce the equivocal and poorly reproducible -IN2 diagnostic category. Positive p16 staining supports classifying -IN2 as definitive HSIL). Staining for p16 is not recommended for biopsies that are negative or show unequivocal LSIL or HSIL (-IN3).
Positive p16 staining is defined as ___.
Positive p16 staining is defined as ___.
What is the difference between a D&C and a D&E?
Dilation and curettage is performed in the first trimester, as the pregnancy is easily evacuated using mechanical cervical dilation and suction curettage. The resulting specimen is fragmented placental tissue and, depending on the gestational age and indications for the procedure, there may be small portions of the embryo/fetus identified. In the second trimester, dilation and evacuation is performed because the procedure requires greater cervical dilation and advanced surgical skills for removal of tissue (the fetal tissue is larger and bony tissue is more calcified). D&Es begin with 1-2 days of cervical preparation to obtain adequate cervical dilation. The procedure may be performed with any level of anesthesia. The placental and fetal tissue is evacuated using a combination of suction and extraction forceps in multiple passes. The resulting specimen is fragmented placental and fetal tissue. The federal Partial Birth Abortion Act of 2003 bans a procedure known as “intact D&E” or “dilation and extraction,” which involves greater cervical dilation, delivery of the fetus to the level of the cranium, and decopression of the cranium to allow passage through the cervix.
Undifferentiated endometrial carcinoma.
UEC is a relatively uncommon neoplasm thought to have a higher prevalence than had previously been thought, as many cases of UEC were either reported as endometrioid endometrial carcinoma FIGO grade 3, or as HG sarcomas or carcinosarcomas. UEC, compared to endometrioid adenocarcinoma FIGO grade 3 (the main differential diagnosis), carries a much worse prognosis. Involvement of and origin from the LUS is a frequent finding. Microscopically, it is defined as a tumor composed of medium or large-sized cells with complete absence of glandular differentiation and with absent or minimal (<10-20% of tumor cells.
How can undifferentiated/dedifferentiated endometrial carcinoma be distinguished from endometrial adenocarcinoma FIGO grade 3? Comment on mean age at presentation, high stage (stage III/IV) %, growth pattern, glands, cords and trabeculae, cohesive growth, component demarcation, rhabdoid cells, myxoid matrix, IHC for panCK, IHC for EMA, and IHC for ER/PR.
Undifferentiated/dedifferentiated endometrial carcinoma: 55, 45%, diffuse patternless sheets, absent, vague, dyshesive cells, sharp demarcation, may be present, may be present, patchy/focal, patchy/focal, focal in 12% of cases. Endometrial adenocarcinoma FIGO grade 3: 68, 30%, solid and glandular, present (1-49% of tumor area), well demarcated, cohesive squamoidlike, intermingled components, absent, absent, diffuse, diffuse, diffuse in 60% of cases.
Why does a normal placenta show heterogeneous maturation?
A normal placenta shows heterogeneous maturation because better-oxygenated centers of cotyledons (placentones) are less mature (larger chorionic villi with less syncytial knots) than are their peripheral parts, where the less-oxygenized blood returns toward the uterus. The accelerated heterogeneous hypermaturity is a sensitive feature of uteroplacental malperfusion. Homogeneous placental maturation is always abnormal, the placentas being either hypomature or hypermature.
How can decreased extracellular matrix of chorionic villi be distinguished from villous edema?
The extracellular matrix of chorionic villi can be decreased and the villous cores as pale as the intervillous space. Such a finding has to be distinguished from villous edema, where, in addition, a split artifact between the trophoblastic shell and the villous core is, at least focally, present. An increased extracellular matrix of chorionic villi, produced in excess by villous fibroblasts in response to intravillous hypoxia associated with intervillous hyperoxemia, manifests as intense eosinophilia of villous cores.
In what clinical situations are preuterine hypoxic, uterine hypoxic, and postuterine hypoxic patterns of chronic hypoxic placental injury seen, and what are the histologic features?
Preuterine hypoxic pattern is seen in maternal anemia, pregnancy at high altitudes, air pollution, maternal smoking, and multifetal pregnancy. Histologic features are: Homogeneously, diffusely hypomature villi. Diffusely increased (including diffuse or incipient chorangiosis) villous vascularity. Increased (b/c of tangential cutting) nonapoptotic, syncytial knotting; increased villous cytotrophoblasts and Hofbauer cells; and extracellular matrix of chorionic villi are diffusely present. Uterine hypoxic pattern is seen in late onset fetal growth restriction and preeclampsia. Heterogeneously hypermature villi. Same additional histologic patterns as in preuterine hypoxic pattern, but only focally present; lesions associated with increased extravillous trophoblasts; decidual arteriolopathy. Postuterine hypoxic pattern is seen with retained stillbirth and early onset fetal growth restriction and preeclampsia. Homogeneously hypermature villi. Diffusely increased apoptotic (smudgy) syncytial knotting; decreased villous cytotrophoblasts and Hofbauer cells; increased extracellular matrix of chorionic villi (terminal villous hypoplasia).
What is the histologic evolution of villous infarction in the placenta?
Agglutination of villi –> vascular congestion –> intravillous hemorrhage –> coagulative necrosis –> acute inflammatory response –> fibrin deposition, fibrosis, calcification. Villous infarction is the most frequently (or readily) diagnosed placental lesion; it starts to develop 2-4 hours to 4 days after an aucte hypoxic event. Once intravillous stromal hemorrhage (red infarction) occurs, the sequence is irreversible. The time frame of these sequential changes in humans has not been determined. Villous infarctions have diagnostic limitations b/c they occur not infrequently in otherwise uncomplicated pregnancies, indicating a substantial placental reserve. Only infarctions in a central/paracentral location and occupying >5-20% of the placental parenchyma are regarded as diagnostically significant.
Peutz-Jeghers (hamartomatous) polyps overview.
Peutz-Jeghers polyps (hamartomatous polyps) are supported by broad bands of muscularis mucosa smooth muscle, which is thicker centrally, and resembles a Christmas tree at low power. The polyp has superficial columnar and goblet cells, but Paneth and endocrine cells at its base. Peutz-Jeghers polyps are large, pedunculated polyps of the gut almost always seen in association with Peutz-Jeghers syndrome. This rare autosomal dominant disorder is usually diagnosed at ages 20-30, with hamartomatous polyps in the small bowel (100%), stomach and colon (25%), and associated adenomatous lesions that may give rise to adenocarcinoma of the stomach, large or small bowel; adenoma malignum of the cervix, ovarian mucinous tumors, and carcinoma of the breast, lung and pancreas. The syndrome is also associated with sex-cord tumor with annular tubules (almost all patients) and melanotic pigmentation of the digits, genitalia, lips, oral mucosa, palms and soles. Peutz-Jeghers syndrome is caused by mutations in STK11/LKB1, a serine threonine kinase that may play a role in cell polarity.
Steroid cells tumors of the ovary are divided into what 3 groups?
Steroid cell tumors of the ovary, which are composed of hormone producing cells, are divided into three groups: 1) stromal luteoma, 2) Leydig cell tumor and 3) steroid cell tumor, NOS. Steroid cell tumors in general are uncommon, representing only 0.1% of all ovarian neoplasms; however, within this category of tumors, steroid cell tumor, NOS is most frequent, representing approximately 60% of all ovarian steroid cell tumors.
Steroid cell tumor, NOS of the ovary overview.
Steroid cell tumor, NOS can occur over a wide age range; however most patients tend to be younger than those with the other types of ovarian steroid cell tumors with an average age of 43 years at presentation. Approximately 50% of patients present with virilization and hirsutism. A minority will present with estrogenic manifestations or occasionally Cushing syndrome due to cortisol production by tumor cells. The vast majority of tumors are unilateral and they are typically well circumscribed, lobulated or multinodular solid yellow to orange to brown tumors that may occasionally exhibit hemorrhage and/or necrosis. These tumors have an average size of 8.4 cm. Histologically, most show a diffuse pattern of growth, but they may also have a clustered or corded growth pattern as evident in this case. There is typically little intervening stroma, but there is often a rich vascular network of thin compressed capillaries. The tumor cells have moderate amounts of granular eosinophilic or vacuolated cytoplasm with distinct cell borders and centrally placed round and regular nuclei with conspicuous nucleoli. Cytologic atypia is uncommon and mitotic activity is usually low (<2 per 10 high power fields). Occasionally, hemorrhage and necrosis can be present. Tumor cells are positive for inhibin and calretinin, but are usually negative for keratin.
By definition, the granulosa cells must make up at least 10% of the tumor for a diagnosis of AGCT; otherwise it is classified as a ___.
By definition, the granulosa cells must make up at least 10% of the tumor for a diagnosis of AGCT; otherwise it is classified as a fibroma, or fibrothecoma, with a minor sex cord element.
In contrast to distinct reticulum fibers surrounding large groups of granulosa cells in adult granulosa cell tumor, thecomas and fibromas have ___.
In contrast to distinct reticulum fibers surrounding large groups of granulosa cells in AGCT, thecomas and fibromas have small fibers surrounding many individual cells.
In the ovary, how do you differentiate a cystic follicle from a follicular cyst, a cystic corpus luteum from a corpus luteum cyst, and a surface epithelial inclusion cyst from a serous cystadenoma?
Cystic follicle is a cyst smaller than 3 cm lined by an inner layer of granulosa cells and an outer layer of theca interna cells; if 3 cm or larger then it is called a follicular cyst. If the lining granulosa and theca cells show extensive luteinization, it is called a cystic corpus luteum when smaller than 3 cm or corpus luteum cyst when 3 cm or larger. A surface epithelial inclusion is a cyst smaller than 1 cm lined by a single layer of ovarian surface epithelium; if 1 cm or larger then it is called a serous cystadenoma.
How can pregnancy affect the Lewis phenotype Le (a-b+)?
Some Le (a−b+) women can transiently become phenotypically Le (b−), with the development of anti-Leb, during pregnancy.
In women with Lynch syndrome, is the incidence of endometrial cancer or colorectal cancer greater?
Endometrial cancer. Lynch syndrome accounts for ~2-3% of CRC and 2.3% of EC, with an overall risk of developing CRC of 68% and EC of 62% in Lynch patients. However, when looking at the two genders separately, the risk of CRC for men is 83% versus 48% for women. Therefore, women with Lynch syndrome are at a substantially greater risk of developing EC than CRC.
What are the most common benign and most common malignant vulvar adnexal lesions?
Most common benign: hidradenoma papilliferum. Most common malignant: extramammary Paget disease.
What are some epithelial cysts that can be seen in the vulva?
Vulvar epithelial cysts are derived from a variety of resident structures. Those thought to arise from remnants of urogenital sinus include urogenital sinus cysts, major (Bartholin gland) and minor vestibular gland cysts, paraurethral (Skene gland) cysts, Wolffian-like duct cyst, and cysts of canal of Nuck. Cysts derived from the overlying epidermis, hair follicles, and apocrine glands include epidermoid cysts, pilar or trichilemmal cysts, dermoid cysts, and hidrocystomas. Less-common entities include steatocystomas and cysts of anogenital mammary-like glands (previously reported as milk cysts of the supernumerary mammary glands).
What is extrauterine deciduosis?
Extra-uterine deciduosis (EUD) is a benign condition which can be mistaken macroscopically for malignancy and resembles peritoneal carcinomatosis. EUD can be discovered accidentally in pregnancy during caesarean sections and during pelvic surgery in women taking oral contraceptives. Deposits are found mainly on the ovary and cervix, but also on abdominal serosal surfaces of the fallopian tubes, bowel, peritoneum and vagina, as well as lungs, pleura, retroperitoneal lymph nodes and rarely skin. The decidual proliferation will be PR and vimentin positive. Most lesions do not require further treatment and spontaneously involute within 4-6 weeks of delivery.
What component of the virus is in the HPV vaccines?
The major HPV capsid protein L1.
Villin IHC stain. What is the target? In what normal and disease states is there positivity? What are some uses of the stain?
Villin is an actin binding protein present in cytoskeleton of intestinal microvilli; has critical role in maintaining brush border organization. It is relatively specific for GI epithelium with brush border microvilli or adenocarcinomas derived from them. Positive staining (normal): Digestive tract epithelium, proximal renal tubules, hepatic bile ducts. Positive staining (disease): Colonic adenocarcinoma, renal cell carcinoma, pulmonary adenocarcinomas. Negative staining: Renal distal tubules, bronchiolar epithelium, pulmonary alveolar cells, bronchial gland cells. Uses: Primary bladder adenocarcinoma (villin-, CDX2-) vs. colorectal carcinoma to bladder. Ovarian adenocarcinoma (villin-) vs. colorectal adenocarcinoma.
What is the PTEN gene? In what tumors is it often mutated?
Phosphatase and tensin homolog (PTEN) gene is on chromosome band 10q23.31. In addition to its role as a tumor suppressor, it has important roles in embryogenesis and maintenance of physiologic functions in many organ systems and is constitutively expressed in normal tissues. It is one of the most frequently inactivated genes in sporadic cancer. Sporadic mutations of PTEN occur frequently in many tumors such as glioblastoma, breast carcinoma, endometrial carcinoma, thyroid neoplasms, skin neoplasms, and advanced prostate cancer.
Primary vulvar adenocarcinomas are classified into what 3 entities?
Primary vulvar adenocarcinomas are rare, with a poorly understood histogenesis. They are classified into (a) extramammary Paget disease, (b) sweat gland carcinoma, and (c) breast-like adenocarcinoma, and are distinguished from adenocarcinoma originating in the Bartholin glands. Extramamamary Paget disease has large pale staining tumor cells, usually in the lower epidermis, in nests, glandular spaces or continuously along the basement membrane. It may be associated with urothelial carcinoma or anorectal carcinoma. Sweat gland carcinoma derives from native apocrine sweat glands, is usually ER-, PR-, and composed of glandular or papillary cords and tubules, with variable pagetoid components. Breast-like adenocarcinoma may originate from anogenital ER+, PR+ mammary like glands in the interlabial sulci, and is often accompanied by these native glands.
What are UTROSCTs?
Uterine Tumors Resembling Ovarian Sex Cord Tumors. Rare neoplasm of unknown etiology occuring usually in middle-aged women. In line with its controversial origin, the current WHO classification placed UTROSCTs in the “miscellaneous” category of tumors of the uterine corpus. A multitude of architectural patterns are described, including plexiform cords, anastomosing trabeculae, watered silk, microfollicle, macrofollicle, tubules, retiform, solid cellular islands, and diffuse pattern. Mitotic figures are infrequent and necrosis is mostly absent. This tumor has a diverse IHC profile with expression of sex cord, epithelial, and smooth muscle markers. Immunoexpression of calretinin and at least for one of the other sex cord markers is required to establish a diagnosis. Most have benign behavior, but some recur, so should be considered a tumor of low malignant potential.
Does aggressive angiomyxoma occur only in women?
No. Aggressive angiomyxoma typically occurs in the genital and pelvic regions of women of reproductive age and rarely occurs in the inguinal region, along the spermatic cord and in the scrotum of men. This neoplasm typically has infiltrating borders and shows scattered spindled and stellate shaped cells with thin and thick-walled blood vessels in a myxoid background. The spindled cells are generally positive for actins and desmin and consistently express both estrogen and progesterone receptors, but are negative for S-100.
In conjugated hyperbilirubinemia… If the step affected is transmembrane secretion of conjugated bilirubin into canaliculus (hepatocellular jaundice), the potential pathologic processes are ___. If the step affected is flow of conjugated bilirubin through canaliculi and bile ducts (cholestatic jaundice), the potential pathologic process is ___.
In conjugated hyperbilirubinemia… If the step affected is transmembrane secretion of conjugated bilirubin into canaliculus (hepatocellular jaundice), the potential pathologic processes are Dubin-Johnson syndrome, hepatitis, endotoxin (sepsis), pregnancy (estrogen), and drugs such as estrogen and cyclosporine. If the step affected is flow of conjugated bilirubin through canaliculi and bile ducts (cholestatic jaundice), the potential pathologic process is mechanical obstruction such as from PBC, PSC, tumor, stricture, or stone.
List non-pancreatic causes of hyperamylasemia.
Diabetic ketoacidosis, peptic ulcer disease, acute cholecystitis, ectopic pregnancy, salpingitis, bowel ischemia, intestinal obstruction, renal insufficiency, salivary gland pathology, and macroamylasemia. Amylase may also be raised somewhat by the administration of opioid analgesics, due presumably to contracture of the sphincter of Oddi.
MSI testing is performed by extracting DNA from paraffin-embedded neoplastic and nonneoplastic tissue. PCR is used to amplify 5 specific microsatellite regions: ___, ___, ___, ___, ___. These regions from the tumor are compared to those from nonneoplastic tissue to assess for differences in length, indicative of MSI.
MSI testing is performed by extracting DNA from paraffin-embedded neoplastic and nonneoplastic tissue. PCR is used to amplify 5 specific microsatellite regions: BAT25, BAT26 (both of which are regions of mononucleotide repeats), D2S123, D5S346, and D17S250 (regions of dinucleotide repeats). These regions from the tumor are compared to those from nonneoplastic tissue to assess for differences in length, indicative of MSI.
What tumors are seen in patients with vHL disease?
Hemangioblastomas (CNS and retinal), pheochromocytoma, clear cell RCC, pancreatic cysts, islet cell tumors, epididymal and ovarian cystadenomas, endolymphatic sac tumors.
What tumors occur in Carney complex?
Cutaneous lentigenes (simple lentigos). Blue nevi, particularly the cellular blue nevus. Cardiac myxomas (as well as myxomas of breast, female genital tract, and skin (especially on eyelid and external ear)). Endocrine tumors including thyroid follicular adenomas, pituitary adenomas (GH-secreting), and the so-called primary pigmented nodular adrenocortical disease (a form of multinodular hyperplasia of the adrenal cortex that causes Cushing syndrome). Large-cell calcifying Sertoli cell tumor. Psammomatous melanotic schwannoma.
What are uncomplicated and complicated UTIs?
Uncomplicated UTI often refers to cases of cystitis in healthy young adult nonpregnant females without anatomic genitourinary anomalies. Some authors also include pyelonephritis in healthy young adult females, cystitis in young adult males, and cystitis in healthy postmenopausal women, Complicated UTI often refers to one arising in association with pregnancy, diabetes, stone, structural genitourinary anomalies, spinal injury, children, and males.
For the following clinical syndrome(s), give the causative agent(s) (list most common first): uterine infections following septic abortion.
C. perfringens.
CDKN1C (p57) is a paternally imprinted, maternally expressed gene, and as complete moles contain only paternal genes, they have reduced expression of the p57 protein. But what cells exactly do stain and do not stain?
The villous cytotrophoblasts and stromal cells in complete mole are negative or have only focal nuclear staining, while there is diffuse positivity in partial mole and hydropic abortus. Syncytiotrophoblastic cells are also negative for p57. It should be noted, however, that intervillous intermediate trophoblasts and decidual cells in complete mole do stain for p57.
What are causes of increased or decreased serum ceruloplasmin levels?
A falsely normal or increased ceruloplasmin may be seen in inflammatory states (ceruloplasmin is an acute phase reactant) or pregnancy. Decreased ceruloplasmin is seen with Wilson disease, hepatic failure, malnutrition, and Menke syndrome.
In what conditions/situations is transferrin increased?
Chronic inflammatory state, iron deficiency, pregnancy, estrogen therapy.
What is congenital varicella vs. perinatal varicella?
Congenital varicella is diagnosed when there is evidence of maternal varicella infection during pregnancy, skin lesions on the newborn that have a dermatomal distribution, and serologic evidence of infection in the newborn (either IgM or persistent IgG beyond 7 months). Perinatal varicella arises when maternal infection occurs within a few days of delivery
The incidence and severity of congenital varicella depend upon the timing of maternal infection. Discuss.
When a woman is infected during pregnancy, the overall incidence of congenital varicella is 1-5%. The incidence is lowest when maternal infection occurs in the 1st trimester and highest in the 3rd. In contrast, the likelihood of perinatal varicella is 50-60%.
What ovarian tumors are associated with paraendocrine hypercalcemia?
Small cell carcinoma (60%). Clear cell carcinoma (20%). Serous carcinoma, squamous cell carcinoma arising in a dermoid cyst, and dysgerminoma account for 10%.
