Cytopathology Flashcards
What disease causes bullet shaped nuclei that can be seen in both cytology specimens and oral mucosa biopsies?
Pemphigus vulgaris
On a pap test, how many cells are considered adequate on a liquid based pap and on a conventional pap?
Liquid based smears >4,000 cells
Conventional 5,000-7,000
According to Fang Fan: Liquid based 5,000 cells and conventional 8,000-12,000
*this is according to 2001–I think the first answer is from 2007
What condition do you see LOTS of superficial cells in a pap smear?
When do you see lots of intermediate cells?
Lots of parabasal cells?
lots of superficial cells in high estrogen states (ie preovulation, tumors, cirrhosis)
lots of intermediate cells in high progesterone states (secretory phase, also lactating and newborn girls who get all progesterone from mom)
atrophy has lots of parabasal cells as well as right before menses (low hormone states)
During HPV, what is associated with intergration of the HPV genome into host genome?
Disruption of E1 and E2 regions of the virus genome which inactivates E2 region. E2 inhibits E6 and E7 so without that you get increased E6 and E7 expression
E6 binds to p53 and E7 binds RB
leads to transformation of LSIL into a high grade lesion
Small cell carcinoma of the cervix is caused by what HPV type?
HPV 18
usually will have a background of HSIL
What is the risk of LSIL progressing to CIN2 or worse within two years?
20-30%
With HSIL on pap smear, chances of HG lesion present?
>80%
With ASC-H on pap smear, chances of high grade lesion being present?
40%
Management of:
>25yo with ASCUS and positive HPV?
colposcopy
Management of:
>25yo and ASCUS with negative HPV?
cotesting PAP and HPV in 3 years
If HPV not performed, repeat PAP at 1 year
How do HPV vaccines work?
virus like particles that mimic L1 capsid proteins
Which HPV gene is responsible for increasing p16?
E7
E7–>RB–>frees E2F–>cell proliferation
also E7–>cyclinA and cyclinE–>increased p16 (INK4A)
What are the work limits on primary pap smear screening?
no more than 100/8 hour shift (without automation)
pro-rate 12.5/hour for part time workers
Secondary reviews are NOT regulated
Imaged slide counts as half a slide
What are the rules regarding the ‘88 CLIA QC regulations of paps?
10% random re-screen of all negative results and review of biopsy correlation for HSIL or higher lesions
What are two exits for stopping pap screenings on woman?
1) >65 yo with 3 consecutive negative paps
2) women with hysterectomy for benign lesions without history of cervical dysplasia in 10 years
If woman has history of CIN2 or 3, she can exit with one above criteria and at least 20 years of follow up
If history of cervical cancer, endometrial cancer or DES exposure-screen until life limiting condition is present
Does the absence of endocervical cells or transformation zone alone require a new PAP smear earlier than usual?
NO!
This was new in 2012
What percentage of positive HPV and ASCUS have CIN2 or higher on biopsy?
25-30%
What is the mechanism of alveolar proteinosis?
Not exactly certain but most think it is some type of macrophage defect
What is the term for detached cilia seen in a bronchial specimen (arrow) and what is this associated with?
Ciliocytophthoria and is associated with ADENOVIRUS
What can look exactly like adenoCA in a bronchial specimen but will have cilia? What is this associated with?
Creola body
Assoc with asthma
What morphology do carcinoid tumors in the lung have that are found in the periphery of the lung?
Spindled morphology
What two gene re-arrangements does papillary thyroid carcinoma have?
ret and trk oncogene rearrangement
What mutation is found in anaplastic thyroid carcinoma?
p53
What thyroid carcinoma is CEA positive?
Medullary thyroid carcinoma
What is a tricky breast lesion that is hard to pick up on cytology but on test they will show you a bland arrow shaped group of epithelial cells?
Tubular carcinoma
What crystal is shown here and what are these structures compared to?
Triple phosphate crystals in urine and they are compared to coffin lids
Form in alkaline urine related to urea splitting organisms (P mirabils) and may cause staghorn calculi (>75% of staghorn calculi are struvite)
What urine crystals is shown?
Cysteine crystals (6 sided hexagon)
seen in the setting of inherited disease characterized by defective renal and intestinal dibasic amino acid transport affecting cystine, ornithine, lysine and arginine (COLA)
What urine crystal is shown?
Tyrosine crystal
seen in tyrosinosis, hyperbilirubinemia and liver disease
What process is shown in this urine cytology specimen?
Cystitis glandularis
*will show you columnar cells
In urovision, what do the different colors represent?
Red=Ch3
Green=Ch7
Yellow=Ch9p21
Blue=Ch17
FAV BQ!
What is being shown here in this urine cytology?
Seminal vesicle!
They love to show this–big ugly cell with pigment but it’s benign
What type of melanoma likes to mets to liver and is c-kit positive?
Ocular melanoma!
BUZZ WORD
If they say a there is a pancreatic lesion and they see ampullary mucorrhea on examine, what should you think of?
IPMN!
Pancreatic mucinous cystic neoplasms stains?
positive for:
DUPAN2, MUC1, MUC2, stroma is ER+, PR+, inhibin+
MUST KNOW!!
Which pancreatic endocrine tumor:
1) is always benign
2) is benign if part of MEN1 but otherwise is malignant
3) DEFINITELY malignant and presents with skin rash
4) has lots of psammoma bodies and is associated with NF1
5) always malignant
1) insulinomas
2) gastinomas
3) glucagonomas (acinar cell CA also present with skin rash)
4) somatostatinomas
5) ACTH and parathormone producing tumors
Which pancreatic cancer looks identifical to acinic cell CA of the salivary gland (naked nuclei in background) and can be functional (secreting amylase, lipase or elastase)? What are it’s clinical associations?
Acinar Cell Carcinoma
Associated with florid fat necrosis, polyarthralgias, eosinophilia, skin manifestations
What fungus shown produces the crystals shown and what are these made of?
Aspergillus NIGER produces calcium oxalate crystals!
What is shown in this photo of a pap smear?
Enterobius vermicularis (pinworms)
What is shown in this pap smear?
Leptothrix
*usually indicates presence of Trichomonas
What is shown in this pap smear?
Cocklebur
Cockleburs are associated with IUD, oral contraceptive use, and second half of pregnancy. They are related to cellular regeneration and composed of nonimmune glycoprotein, lipid, and calcium. Cytologically they are identified as golden refractile orange crystalline rays surrounded by histiocytes. They have no clinical significance.
What is shown in this pap smear?
Carpet beetle
contaminant usually from tampon
1) medullary thyroid carcinoma is associated with which mutation?
2) papillary thyroid carcinoma is associated with which point mutation and which translocation?
3) follicular thyroid neoplasms are associated with which point mutation and which translocation?
1) RET point mutation
2) BRAF point mutation and RET/PTC translocation
3) RAS point mutation and t(2;3) (q13:p25) which is the PAX8/PPARy (gamma) fusion gene
What is the translocation associated with low-grade mucoepidermoid carcinomas?
t(11;19) which fuse the MECT1 and MAML2 genes
*these are the most common malignant salivary gland tumors in adults and children, rarely they can occur in the mandibular bone, are the most frequent cause of false negative results on fine needle aspirate and the oncocytic variant is notorious for mimicking other oncocytic tumors
What special stain highlights the capsule of cryptococcus?
Mucicarmine and Alcian blue
What is the risk of malignancy on thyroid FNAs for the following lesions:
1) FLUS
2) Suspicious for follicular neoplasm
3) Suspicious for malignancy
4) Malignant
1) 5-15%
2) 15-30%
3) 60-75%
4) 97-99%
The structure seen here is seen in a degenerated urothelial cell in a voided urine sample, what does it represent?
Melamed-Wolinska bodies
This round eosinophilic inclusion is commonly senn in degenerated urothelial cells, especially in voided urine specimens. The pathogenesis of this structure is unclear and it has no diagnostic significance when seen in bladder specimens. When seen in cells of extra urinary bladder cytology specimens, their presence may suggest a urothelial origin of the cells. Don’t confuse with Michaelia-Gutman bodies which are BASOPHILIC (seen below) round lamellated intracellular or extracellular bodies seen in malakoplakia
What urine crystal is shown?
Uric Acid Crystals
*key is different sizes and shapes
What urine crystal is shown?
Calcium Oxalate Crystals
“envelopes”
The most common kind of kidney stone!
In decreasing order: calcium oxalate>calcium phosphate>struvite (triple phosphate)>urate>cystine
What is the most common tumor that arises in a urethral diverticulum and can be seen in urine cytology specimens?
Adenocarcinoma
What is a caveat to remember when looking at a urine sample from higher in the urinary tract (ie ureter washing)?
Benign urothelial cells from higher in the urinary tract can show MUCH more atypia than from lower down in the tract. Caution should be taken when interpreting such specimens. Comparison between bilateral upper tract specimens is very helpful.
What is shown in this pap smear?
IUD effect
Glandular cells singly or in groups with prominent
cytoplasmic vacuolation in a clean background.
Occasional single epithelial cells with high N/C ratio (d/d HSIL).
Calcifications resembling psammoma bodies may be present.
What are the stains which stain adenocarcinomas and mesotheliomas (to differentiate in a pleural fluid)?
Usual practice is to pick 2 stains for each entity:
Mesothelioma stains: Calretinin, CK 5/6, WT-1, D2-40, EMA
Adenocarcinoma stains: Ber-EP4, MOC-31, TTF-1 (lung), Napsin (lung), EMA, Leu-M1, B72.3, Mucin, monoclonal CEA
Most common cause of eosinophilic pleural effusion?
Eosinophils in pleural effusion, most common cause is hemothorax / pneumothorax/ thoracocentesis
Other causes – drug reactions, parasitic infections, pulmonary infarctions
1/3 cases - idiopathic
Plasma cells seen in a CSF should make you think about what three things?
Multiple sclerosis
Neurosyphillis
Multiple myeloma
What is shown in this cytology specimen?
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Pollen
Colorful bodies with cell wall and spikes
What is are the most frequent tumors seen in pleural effusions in childhood?
Most common is hematopoietic malignancy followed by neuroblastoma and Wilms
What are the most common metastatic tumors seen in pleural effusions in men and in women?
- Men – lung >lymphoma/leukemia >mesothelioma >GI >GU >miscellaneous (11% unknown primary)
- Women – breast >lung >female genital tract >lymphoma/leukemia >GI >miscellaneous (9% unknown primary)
Shown is a metastatic testicular tumor. What are the cells in the right mid portion of the photo and what is the significance?
The cells are epithelioid histiocytes indicative of granulomatous inflammation, present in a seminoma. Granulomatous inflammation is seen in 50-60% of primary or metastatic seminomas and is a clue to the diagnosis. Occasionally it may obscure the tumor cells leading to the erroneous diagnosis of granulomatous inflammation, or in the testis, granulomatous orchitis. Most seminomatous tumor cells, but not histiocytes, are positive for c-Kit. Syncytiotrophoblastic giant cells are present in 4-7% of these tumors although hCG immunostaining may reveal their presence in 20-25% of seminomas. Syncytiotrophoblastic giant cells sometimes show prominent intracytoplasmic lacunae. The presence of granulomatous inflammation does not predict prognosis; mitotic activity in seminomas is usually high (>3/HPF) and does not accurately predict prognosis.
Although pancreatic mets aer unlikely, what is the most common cause of a metastatic tumor to the pancreas?
Metastatic clear cell renal cell carcinoma
What are three stains that will stain a chordoma (including a recently described one)?
EMA, S-100, and brachyury
PRISE Q: What stain is positive in renal oncocytoma but negative in chromophobe?
The question shows pics of stains revealing that the cells are strongly positive for S100-A1 while negative for CK7 and CAIX. S100-A1 immunohistochemistry can be helpful in distinguishing oncocytomas from chromophobe renal cell carcinomas; S100-A1 is usually positive in the former but not the latter
PRISE Q: In 2012, what stain was shown to be the most sensitive and specific for IDing SCC?
p40 (shown to be better than p63)
PRISE Q: Approximately what percent of thyroid nodules, with a preoperative fine-needle aspirate interpreted as “Follicular Neoplasm/Suspicious for a Follicular Neoplasm,” prove to be hyperplastic proliferations in nodular goiter rather than actual neoplasms on surgical resection?
According to previous studies summarized by The Bethesda System of Reporting Thyroid Cytopathology, a significant proportion of thyroid nodules, previously diagnosed as “Follicular Neoplasm/Suspicious for Follicular Neoplasm” turn out to not actually be neoplasms (i.e., follicular adenoma, follicular carcinoma, and follicular variant of papillary thyroid carcinoma). Specifically up to 35% cases of cases turn out to be hyperplastic nodules in nodular goiter.
What are the lab findings of transudates and exudates from pleural effusions (ie what causes each one and what are the lab findings)?
Transudates: result from imbalance of hydrostatic and oncotic pressure as occuring in congestive heart failure, cirrhosis and nephrotic syndrome. Typically they will have low specific gravity, low fluid protein level and low LDH level
Exudates: result from injury to the mesothelium as occurring in inflammation and malignancy. They will have the opposite findings of high specific gravity, high fluid protein and high LDH level
This cell is seen in a pleural effusion. What is this cell called and what does it indicate?
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Shown is a “LE cell” which is seen in pleural effusions from patient’s with lupus pleuritis. An LE cell is a macrophage or neutrophil that contains a large basophilic glassy cytoplasmic inclusion called a hemotoxylin body.
What are the different types of pleural effusions and what are they associated with?
Lymphocytic effusions are seen in malignancy, tuberculosis and s/p CABG.
Effusions from renal failure or congestive heart failure will show reactive mesothelial cells but no lymphocytes.
Rheumatoid pleuritis is characterized by granular debris and macrophages in the fluid.
Lupus pleuritis may have characteristic LE cells.
What is the most common tumor that causes malignant peritoneal effusion in men?
Lymphoma/leukemia followed by gastrointestinal cancer and pancreatic cancer
Cytogenetic analysis is considered highly sensitive and specific for IDing mesothelioma in pleural effusions. What is the most common chromosomal aberration found?
Mesotheliomas are characterized by clonal chromosomal deletions which commonly involve 1p, 3p, 6q, 9p and 22q
What is a mutation in CDKN2A aka p16(INK4a) associated with?
Familial and sporadic melanomas
From pathology outlines also:
Cervix: overexpressed in squamous intraepithelial lesions, particularly HG SIL (97% of biopsies)
ALL (pediatric): homozygous deletions noted in 80% of cases with 9p21 abnormalities
T-ALL: deleted in 80% of all cases (even with normal #9)
Esophageal carcinoma: high frequency of abnormalities
Lymphoma: p16 gene methylation present in 60% of pulmonary MALT lymphomas; may be early event; methylation also associated with Hodgkin’s lymphoma, plaque phase of mycosis fungoides, monoclonal gammopathy of unknown significance
Melanoma: abnormalities in 50% of sporadic cases
Pancreatic carcinoma: high frequency of abnormalities
Squamous cell carcinoma, cutaneous: mutations present
What is Meig’s Syndrome?
asites, pleural effusion and benign ovarian fibroma
In AIDS patients who have a neutrophilic CSF fluid, what is the most likely reason?
CMV infection somewhere
Eosinophils in CSF are associated with what?
Ventriculoperitoneal shunts most likely but also associated with parasitic infections and Rocky Mountain Spotted Fever
What is shown in the image from a CSF fluid and what does it represent?
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Mollaret cell
Mollaret meningitis or idiopathic recurrent meningitis is a rare form of aseptic meningitis characterized by recurring attacks of fever, headache and neck stiffness. CSF findings are non-specific but often times marked by monocytosis. Mollaret cells are monocytes with deep nuclear clefts and the nucleus has a footprint like appearance. Mollaret cells can be seen in Mollaret meningitis, sarcoidosis or Behcet disease
All of the following are part of CLIA ‘88 EXCEPT:
- Prospective rescreening of 10% negative PAP smears
- Five year retrospective review of all negative PAPs from women with newly diagnosed HSIL
- Correlation of cytologic-histologic findings
- Implementation of Pap Proficiency Test
- Pathologists review of all abnormal PAPs
Prospective rescreening of 10% negative PAP smears
This was part of CLIA ‘67
All other choices are from CLIA ‘88
What are the rules regarding the PAP Proficiency Test?
It is administered every year on site. Each participant evaluates 10 GYN slides and they are allowed to choose which type of PAP slides they are accustomed to. Pathologists who ordinarily review prescreened slides are allowed to examine a prescreened set that have been dotted by a cytotech.
According to CAP, what are the minimum retention times for:
1) GYN specimens
2) NON-GYN specimens
3) FNAs
4) Cell blocks
5) Cytopathology reports
1) 5 years
2) 5 years
3) 10 years
4) 10 years
5) 10 years
What is the recommended maximum ASC diagnoses % and ratio?
ASC diagnosis should not exceed 5% preferably, for labs serving high risk populations, the ASC:SIL ratio should not exceed 3:1
What percentage of ASCUS cases have CIN2 or above on biopsy?
What percentage of ASC-H?
What percentage of LSIL?
ASCUS: 10-20%
ASC-H: 40%
LSIL: 18%
What are the most common tumors associated with granuloma formation in lymph nodes?
Seminoma, thymoma and squamous cell carcinoma
What type of pleural effusion is this?
TB effusion
Lymphocytes with few or absent mesothelial cells
In a pap smear with HSIL, which feature is MOST suggestive of microinvasion?
Nucleoli
What kind of crystals are shown here which resemble broken panes of glass?
Cholesterol crystals
What is this seen in a sputum?
Strongyloides
What percentage of LSIL will progress to HSIL?
10%
Two thirds of patients with LSIL will regress
What is this?
Osteoclast