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Flashcards in Cytology Deck (45):
1

Ciliocytophthoria is classically seen in what infection?

Adenovirus infection in the respiratory system. Ciliocytophthoria are decapitated ciliated columnar cells, where only the terminal bar and cilia are seen.

2

In the 2001 Bethesda system for Paps, are smears without endocervical cells considered unsatisfactory? When is an endocervical component considered to be present?

No, but the absence of an endocervical or transformation zone component is mentioned as a quality indicator. The absence does not imply that a repeat Pap is necessary, but that physicians are expected to use their judgement and to consider repeating the Pap is the patient is at high risk for cervical cancer. An endocervical component is considered to be present if 10 or more endocervical or squamous metaplastic cells, either isolated or in groups, are present.

3

In the Bethesda system for reporting thyroid FNA interpretations, list the diagnostic categories and corresponding % risk of malignancy and usual management.

-Insufficient for diagnosis (nondiagnostic, unsatisfactory), 1-4%, repeat FNA with US guidance. -Benign, 0-3%, follow clinically. -Atypical cells of undetermined significance, 5-15%, repeat FNA. -Suspicious for a follicular neoplasm, 15-30%, lobectomy. -Suspicious for a Hurthle cell neoplasm, 15-45%, lobectomy. -Suspicious for malignancy (suspicious for... papillary carcinoma, medullary carcinoma, lymphoma, metastatic tumor, or other), 60-75%, lobectomy or thyroidectomy. -Malignant, 97-99%, thyroidectomy.

4

What are the 2001 Bethesda criteria for ASC-H?

There are 2 patterns seen and different criteria for each. "Atypical (Immature) Metaplasia" (small cells with high N/C): Cells usually occur singly or in small fragments of less than 10 cells; occasionally, in conventional smears, cells may "stream" in mucus. Cells are the size of metaplastic cells with nuclei that are about 1.5 to 2.5 times larger than normal. N/C may approximate that of HSIL. In considering a possible interpretation of ASC-H or HSIL, nuclear abnormalities such as hyperchromasia, chromatin irregularity, and abnormal nuclear shapes with focal irregularity favor an interpretation of HSIL. "Crowded Sheet Pattern": A microbiopsy of crowded cells containing nuclei that may show loss of polarity or are difficult to visualize. Dense cytoplasm, polygonal cell shape, and fragments with sharp linear edges generally favor squamous over glandular (endocervical) differentiation.

5

What are the 2001 Bethesda criteria for HSIL?

Cytologic changes affect cells that are smaller and less "mature" than the cells in LSIL. Cells occur singly, in sheets, or in syncytial-like aggregates. Hyperchromatic clusters should be carefully assessed. Overall cell size is variable, and ranges from cells that are similar in size to those observed in LSIL to quite small basal-type cells. Nuclear hyperchromasia is accompanied by variations in nuclear size and shape. Degree of nuclear enlargement is more variable than that seen in LSIL (Some HSIL cells have the same degree of nuclear enlargement as in LSIL, but the cytoplasmic area is decreased, leading to a marked increase in the N/C. Other cells have very high N/C, but the actual size of the nuclei may be considerably smaller than that of LSIL). Chromatin may be fine or coarsely granular and evenly distributed. Contour of the nuclear membrane is quite irregular and frequently demonstrates prominent indentations or grooves. Nucleoli are generally absent, but may occasionally be seen, particularly when HSIL extends into endocervical gland spaces. Appearance of cytoplasm is variable; it can appear "immature," lacy, and delicate or densely metaplastic; occasionally the cytoplasm is "mature" and densely keratinized (keratinizing HSIL).

6

What are the 2001 Bethesda criteria for ASC-US?

Nuclei are approximately 2.5 to 3 times the area of the nucleus of a normal intermediate squamous cell (approximately 35 square micrometers). Slightly increased N/C. Minimal nuclear hyperchromasia and irregularity in chromatin distribution or nuclear shape. Nuclear abnormalities associated with dense orangeophilic cytoplasm ("atypical parakeratosis").

7

What are the 2001 Bethesda criteria for LSIL?

Cells occur singly and in sheets. Cytologic changes are usually confined to cells with "mature" or superficial-type cytoplasm. Overall cell size is large, with fairly abundant "mature" well-defined cytoplasm. Nuclear enlargement more than three times the area of normal intermediate nuclei results in a slightly increased N/C. Variable degrees of nuclear hyperchromasia are accompanied by variations in nuclear size, number, and shape. Binucleation and multinucleation are common. Chromatin is often uniformly distributed, but coarsely granular; alternatively, the chromatin may appear smudged or densely opaque. Nucleoli are generally absent or inconspicuous if present. Contour of nuclear membranes is often slightly irregular, but may be smooth. Cells have distinct cytoplasmic borders. Perinuclear cavitation ("koilocytosis"), consisting of a sharply delineated clear perinuclear zone and a peripheral rim of densely stained cytoplasm, is a characteristic feature but is not required for the interpretation of LSIL; alternatively, the cytoplasm may appear dense and orangeophilic (keratinized). Cells with cytoplasmic perinuclear cavitation or dense orangeophilia must also show nuclear abnormalities to be diagnostic of LSIL; perinuclear halos in the absence of nuclear abnormalities do not qualify for the interpretation of LSIL.

8

What are the past and current categories of specimen adequacy for Paps in the Bethesda system?

1988: satisfactory, less than optimal, unsatisfactory
1991: satisfactory, satisfactory but limited by..., unsatisfactory
2001: satisfactory, unsatisfactory

9

What are the past and current requirements for an adequate squamous component in Paps in the Bethesda system?

1988 and 1991: well-preserved and well-visualized squamous epithelial cells should cover more than 10% of the slide surface.
2001: minimum estimated number of squamous cells of 5000 for liquid-based and 8000-12,000 for conventional preparation method.

10

Mediastinal germinoma/seminoma. What does it look like on FNA?

Germinomas occur exclusively in males. The typical aspirate from a geminoma grossly appears slimy or viscous. Microscopically, smears are usually fairly cellular, containing large, round or polygonal, poorly cohesive cells with a moderate amount of pale cytoplasm with distinct cell membranes. The cells have relatively round nuclei and prominent nucleoli. The background typically has a characteristic "tigroid" appearance on Diff-Quik-stained smears that corresponds to the viscous appearance of the aspirate. The granular background is likely composed of cytoplasmic remnants. Lymphocytes are usually present, and granulomas and syncytiotrophoblast-like multinucleated giant cells may also be observed.

11

How does medullary thyroid carcinoma appear on FNA?

FNA biopsy yields neoplastic neuroendocrine cells and amyloid in variable proportions. The cellularity of the smears is usually inversely proportional to the amount of amyloid produced by the tumor. The neoplastic cells are dispersed or form loose clusters, rarely forming microfollicles or papillae. MTC is a great mimicker. The tumor cells may have spindly, plasmacytoid, polygonal, hurthloid or giant cells appearances; may demonstrate mild pleomorphism; and may be bi- or multinucleated. The nuclei often have a "salt-and-pepper" or "speckled" chromatin pattern on Pap stain. Nucleoli may be seen, but are usually inconspicuous. Intranuclear cytoplasmic inclusions are frequently identified, and are morphologically identical to those seen in papillary thryoid cancer. Mitotic figures are present in 15% of cases. On Diff-Quik staining, red cytoplasmic granules, corresponding to neurosecretory granules containing calcitonin, may be seen.

12

What is seen on FNAs in Hashimoto thyroiditis?

Smears from Hashimoto's thyroiditis show a polymorphous lymphoplasmacytic infiltrate with germinal center formation. Lymphoid tangles, lymphohistiocytic aggregates, tingible body macrophages, and background lymphoglandular bodies may be the overwhelming findings on the smears. Multinucleated histiocytes may be seen. Oncocytic (Hurthle cell) metaplasia is usually prominent. Hurthle cells are epithelial cells with abundant, finely granular cytoplasm and enlarged, variably sized, typically round nuclei that may display prominent nucleoli.

13

How does Warthin's tumor appear on FNA?

Most of them are cystic, feel "doughy" upon palpation, and yield cloudy fluid on FNA. Smears are hypocellular, but scattered flat sheets of oncocytic cells and lymphocytes are likely to be found. Corpora amylacea and mast cells may be seen. Aspiration of more peripheral solid regions of the lesion may yield more cells. Oncocytic metaplasia is common in elderly males. Therefore, identification of all three components - oncocytic cells, lymphocytes, and cyst contents - is important for diagnosis.

14

How does pleomorphic adenoma/benign mixed tumor appear on FNA?

BMTs present as painless, slowly growing masses, and are the most common type of salivary gland tumor, especially in the parotid. Aspirates of BMT contain a combination of myxoid matrix, sheets and clusters of epithelial cells, and mesenchymal cells. The mesenchymal cells are of myoepithelial origin and are spindle shaped. "Hyaline cells" are modified myoepithelial cells which appear plasmacytoid with dense, glassy cytoplasm. They tend to present singly and may also be embedded within the fibrillary chondromyxoid stroma. Their presence is quite characteristic of BMT. Electron microscopy demonstrates that intermediate prekeratin filaments account for the dense, glassy appearance of the cytoplasm of hyaline cells. The chondromyxoid stroma is believed to be produced by myoepithelial cells. Tyrosine-rich crystals with radiating, flower-shaped or "daisy head" appearances stain orangeophilic on Pap stain and are not pathognomonic but, when present, support the diagnosis of BMT. They are detectable in less than 10% of BMTs. BMTs may show considerable epithelial atypia, but the atypia is limited and focal. If an aspirate contains features of BMT, but with readily identifiable, highly atypical epithelial cells, high mitotic activity, atypical mitotic figures and necrosis, malignant transformation should be suspected.

15

Breast carcinoma has a few characteristic patterns in fluid cytology, one of which is the presence of large morules (also called proliferation spheres or "cannonballs"). Describe.

"Cannonballs" are large, tightly cohesive balls of relatively uniform, neoplastic epithelial cells. Very few single malignant epithelial cells may be present. The borders of the cell groups are smooth - so-called "community" borders. In contrast, malignant cell clusters in mesothelioma are more commonly "knobby." Although cannonballs are suggestive of breast origin, they may also be seen in carcinomas from other sites (e.g., ovary, lung, GI tract).

16

How do you distinguish fibroadenoma from phyllodes tumor on breast FNA?

FAs characteristically appear at age 20-30, while phyllodes tumors appear at age 40-50. Aspirates of phyllodes tumors typically contain the same triad of features as FAs, and the epithelial component is usually indistinguishable from FA. The main differentiating diagnostic feature is the stromal component: large, highly cellular, stromal fragments; single, intact mesenchymal cells; stromal cell atypia; and mitotic activity in stromal cells favors phyllodes tumor.

17

How do you distinguish fibroadenoma from papillary neoplasms in the breast on FNA?

Papillary neoplasms, including benign papillomas and invasive and noninvasive papillary carcinomas, may clinically mimic FAs. A subareolar location and nipple discharge favor a papillary neoplasm. FNAs from papillary neoplasms may be similar to those of FAs. However, 3D clusters containing fibrovascular cores are a feature of papillary neoplasms and not of FAs. In addition, the stromal component is usually sparse or absent in papillary neoplasms. Tall, columnar, epithelial cells are characteristic of papillary neoplasms, but may be seen in FAs as well.

18

Candida ___ consists of small, uniform, round budding yeast forms surrounded by clear halos on Pap stain. Unlike other Candida species, it does not form pseudohyphae in vivo or in culture.

Candida (previously Torulopsis) glabrata consists of small, uniform, round budding yeast forms surrounded by clear halos on Pap stain. Unlike other Candida species, it does not form pseudohyphae in vivo or in culture.

19

The 2 liquid-based cytology Pap tests used today are ThinPrep (Hologic) and SurePath (BD Diagnostics-TriPath). For each, give: FDA approval year, fixative, mechanism of test, and diameter of the resulting circle of cells on the slide.

ThinPrep: 1996. Methanol-based solution (PreservCyt). Using a vacuum, cell are trapped on a filter and then transferred to a glass slide. 20 mm. SurePath: 1999. Ethanol-based solution (CytoRich). Using density centrifugation, cells sediment on a coated slide. 13 mm.

20

What are the differences in primary screening systems and interactive screening systems for automated Pap test screenings? Give examples of each system.

Primary screening systems classify cells without human interaction. Example: BD FocalPoint Slide Profiler (BD Diagnostics-TriPath), formerly called the AutoPap system, was FDA approved for both conventional smears and BD SurePath Pap tests. This system is not approved for high risk Paps. Glass slides get scanned, during which a computer assigns scores for selected fields of view, and given a final score (ranked from 0-1.0) based upon the likelihood of a slide containing a significant epithelial abnormality. Negative slides require no further review, can be reported as negative and archived. Slides ranked with a potential abnormality require human review. Interactive screening systems guide cytotechnologists to cells on a slide for their review. Examples: ThinPrep Imaging System (Hologic) and BD FocalPoint GS (Guided Screening) Imaging System (BD Diagnostics-TriPath). The cytotechnologist's attention is driven to significant cellular fields of interest using automated X-Y axis relocation. The final interpretation relies on the diagnostic acumen of the human reviewer.

21

Numerical criteria for squamous cellularity on LBC Pap tests were developed that take into account the objective, eyepiece field number (FN), and cell circle diameter. Cellularity is typically estimated by evaluating the number of cells seen when moving across the diameter of at least 10 microscopic fields, intentionally including spots/holes where there are no cells. What is the average number of cells per field required to achieve a minimum of 5000 cells (using an eyepiece field number of FN20 or FN22) for ThinPrep and SurePath?

ThinPrep (20 mm prep diameter): 3-4 cells using 40x objective. SurePath (13 mm prep diameter): 8-9 cells using 40x objective.

22

What features can be used to help differentiate endocervical vs endometrial adenocarcinoma on Pap smears?

Endocervical lesions will typically present more cells. Endocervical adenoCA cells and nuclei are typically larger. Nucleoli are more common and larger in endocervical adenoCA. Endocervical AIS and adenoCA cells typically retain their columnar configuration, consistent with direct sampling, whereas endometrial groups tend to round up, consistent with spontaneous exfoliation. As endometrial adenoCAs become higher grade, differential features are less helpful in rendering a definitive distinction.

23

What are Liesegang rings?

Liesegang rings are laminated ring-like structures that are sometimes found in benign cysts, abscesses, and areas of old hemorrhage. They have been confused with parasites (especially eggs), algae, calcifications, and psammoma bodies. They are best seen with Pap, H&E, trichrome, AFB, and Gram stains, which accentuate the concentrically laminated morphology. Liesegang rings are composed of organic substances most likely formed by period precipitation from a supersaturated solution within cystic fluid.

24

Warthin's tumor (papillary cystadenoma lymphomatosum and adenolymphoma) is the second most common benign neoplasm of salivary glands. What does it arise from?

It arises from ducts trapped during embryologic development of lymph nodes in the parotid glands. This may explain why Warthin's tumor almost always occurs in or around the parotid gland.

25

On breast FNA, what lesions may show bland epithelial cells in a mucinous background, or even mucus alone?

Colloid carcinoma. Benign papillomas. Fibroadenoma with myxoid degeneration. Mucocele-like lesions.

26

What is seen on FNA of a branchial cleft cyst?

These cysts usually arise in the lateral neck, anterior to the sternocleidomastoid muscle. FNA shows turbid material composed of proteinaceous material; histiocytes; and nucleated and anucleated squamous cells, which may be sparse or numerous. Multinucleated giant cells and epithelioid histiocytes, indicating a granulomatous reaction, may also be present. Inflamed lesions may come to clinical attention because of a sudden increase in size. FNAs of inflamed branchial cleft cysts show inflammatory cells, and squamous cells may display significant cytologic atypia.

27

What is seen on FNA of parathyroid cysts?

Aspirates of parathyroid cysts characteristically yield thin, clear, watery fluid. Epithelial cells are typically sparse, relatively uniform and bland, resembling thyroid follicular cells. Immunocytochemical staining for PTH and analysis of cyst fluid for PTH may be diagnostically helpful.

28

The CAP makes recommendations for the minimum requirements for the retention of laboratory records and materials. They meet or exceed the regulatory requirements specified in the Clinical Laboratory Improvement Amendments of 1988 (CLIA 88). For cytology, how long must the following be kept: slides, FNA slides, reports?

Slides (includes unsatisfactory, negative, suspicious, and positive) - 5 yrs. FNA slides - 10 yrs. Reports - 10 yrs.

29

Cells from primary CNS tumors are infrequently present in CSF specimens. Exceptions to this include what 3 malignancies?

Medulloblastomas, intracranial neuroblastomas, and retinoblastomas, which commonly shed cells into the CSF. Malignant cells appear relatively monotonous, with hyperchromatic nuclei, scanty cytoplasm and often prominent nucleoli.

30

What is Mollaret's meningitis?

Mollaret's meningitis is a form of recurrent benign aseptic/lymphocytic meningitis, an uncommon illness characterized by greater than three episodes of fever and meningismus lasting two to five days, followed by spontaneous resolution. The most common etiologic agent in Mollaret's meningitis is HSV, especially HSV-2, although some patients do not have evidence of genital lesions at the time of presentation. Also, noninfectious etiologies for Mollaret's meningitis have also been proposed (intracranial epidermoid cyst or other cystic abnormalities in the brain with intermittent leakage causing meningeal irritation).

31

Mollaret's meningitis is a form of recurrent benign aseptic/lymphocytic meningitis, an uncommon illness characterized by greater than three episodes of fever and meningismus lasting two to five days, followed by spontaneous resolution. What is the etiology?

The most common etiologic agent in Mollaret's meningitis is HSV, especially HSV-2, although some patients do not have evidence of genital lesions at the time of presentation. Also, noninfectious etiologies for Mollaret's meningitis have also been proposed (intracranial epidermoid cyst or other cystic abnormalities in the brain with intermittent leakage causing meningeal irritation).

32

What is seen on CSF cytology in Mollaret's meningitis?

Cytologic findings are nonspecific, but there is often a markedly increased cellularity with pleocytosis, and marked predominance of monocytes. So-called "Mollaret cells," monocytes with deep nuclear clefts that impart a footprint-like appearance to the nucleus, are seen within the first 24 hours of the onset of symptoms. They are characteristic of but not specific for MM; they can be seen in other diseases like sarcoidois and Behcet disease. The background shows mostly small mature lymphocytes, but plasma cells and neutrophils can be seen as well.

33

Calcium oxalate crystals in lung specimiens are a useful clue to the presence of what fungus?

Oxalic acid is a fermentation by-product of Aspergillus, and the precipitation of calcium oxalate crystals in alkaline tissue environments infected by the fungus is a recognized phenomenon. The crystals are themselves potent agents of tissue destruction, causing extensive necrosis. Oxalate deposition is most commonly associated with A. niger, but it has been observed in association with other Aspergillus species, including A. fumigatus and A. flavus. Visualization of oxalate crystals in respiratory tract cytological specimens has been described as a reliable marker for the presence of Aspergillus infection and may precede the appearance of positive fungal culture results or radiographic identification of an aspergilloma by 1 year. The typical appearance of calcium oxalate crystals is that of birefringent needlelike crystals in rosette, wheat-sheaf, or fanlike arrangements; they are nonstaining and difficult to identify by ordinary light microscopy. Of greatest diagnostic value is the observation of both oxalate crystals and typical fungal elements in a single specimen.

34

What are the 3 most common metastatic tumors associated with granuloma formation in lymph nodes?

Squamous cell carcinoma, seminoma, and thymoma.

35

Ewing's sarcoma/PNET cells have scanty cytoplasm that can be finely vacuolated. What is in the vacuoles?

Glycogen. So the cytoplasm will be PAS+ diastase sensitive.

36

Follicular cervicitis, AKA lymphofollicular cervicitis, pseudolymphoma, or chronic cervicitis. What is seen on Pap smear? What usually causes it?

Variably sized lymphocytes, mature and immature, tingible body macrophages and plasma cells are seen on Pap smear, with Thin-Prep often showing clumps. Follicular cervicitis suggests, but is not pathognomonic of, chlamydial cervicitis (50-75% are associated with Chlamydia). Follicular cervicitis can also occur with noninfectious cervicitis.

37

Biopsy will reveal a high grade lesion in __ to __% of patients with LSIL.

Biopsy will reveal a high grade lesion in 20 to 30% of patients with LSIL.

38

On cytology, what is the appearance of a tuberculous effusion?

Tuberculous effusions typically appear turbid, with a yellow or silvery green metallic appearance grossly. In the later phase, an abundance of lymphocytes is present. The fibrin in the exudate traps mesothelial cells, and tuberculous pleural effusions therefore characteristically have few or no mesothelial cells. In addition, the high fibrin content of the fluid causes some of the lymphocytes to appear in clusters, and uncommon feature of lymphocytes in other conditions. Multinucleated giant cells are uncommon, although histiocytes may be evident. Because of the predominance of lymphocytes, lymphoma may enter into the differential diagnosis.

39

An adequate bronchoalveolar lavage requires more than __ macrophages per high-power field.

An adequate bronchoalveolar lavage requires more than 10 macrophages per high-power field.

40

In Pap smears, what is the appearance of tumors derived from endometrium or endocervix vs. tumors derived from fallopian tube or ovary?

Tumors cells derived from fallopian tube, ovary, and rarely, other intra-abdominal sites can occasionally be detected in cervicovaginal cytology specimens. These cells appear as atypical or neoplastic glandular cells in a clean background. They usually present as three-dimensional tubular, spherical, or papillary groups. One symptom that is quite characteristic of fallopian tube tumors is watery discharge. In contrast, tumors derived from endometrium or endocervix typically show greater numbers of neoplastic cells in a bloody or necrotic background, and evidence of a co-existing SIL may be present.

41

Pseudokoilocytes are squamous cells with perinuclear halos that are small and do not have sharply defined dense edges, and with normal nuclei. In what conditions are pseudokoilocytes seen in Pap smears?

Pseudokoilocytes can be seen in conditions such as inflammation (Trichomonas and Chlamydia), pregnancy (navicular cells), androgenic effect, and immature squamous metaplasia.

42

DDx of hyperchromatic crowded groups of small cells on Pap smears.

HCGs may represent benign epithelial cells such as endometrial cells, endocervical cells, tubal metaplastic cells, or basal cells of severe atrophy. However, malignant lesions such as carcinoma in situ, invasive squamous cell carcinoma, and invasive or in situ adenocarcinoma may also shed HCGs.

43

HPV is a nonencapsulated (single-stranded/double-stranded) (DNA/RNA) virus. Integration of viral genetic material into the host genome is the critical event in malignant transformation of the cell, which results in disruption of the viral genome E1-E2 region. Disruption of the E2 gene causes overexpression of __ and __ genes. The integration sites in the host genome as (specific/random).

HPV is a nonencapsulated double-stranded DNA virus. Integration of viral genetic material into the host genome is the critical event in malignant transformation of the cell, which results in disruption of the viral genome E1-E2 region. Disruption of the E2 gene causes overexpression of E6 and E7 genes. The integration sites in the host genome as random.

44

The corpus luteum of pregnancy and the placenta produce progesterone, resulting in a predominance of intermediate squamous cells seen on Pap smears. Navicular cells are boat-shaped intermediate cells containing abundant glycogen. Cytolysis may be marked during pregnancy. What clinical situations result in: a maturation shift towards mature squamous cells, a maturation shift towards a lower maturation, i.e., an atrophic pattern, and the presence of anucleated squames?

A maturation shift towards mature squamous cells may indicate fetal distress. A maturation shift towards a lower maturation, i.e., an atrophic pattern suggests progesterone deficiency and may indicate intrauterine fetal demise. The presence of anucleated squames may indicate rupture of fetal membranes.

45

Postpartum Pap smears show a predominantly atrophic pattern in __% of lactating and __% of nonlactating women.

Postpartum Pap smears show a predominantly atrophic pattern in 66% of lactating and 33% of nonlactating women.