ThinPrep® Pap Test Diagnostic Challenges and Differential

ThinPrep® Characteristics
Wet Fixation
enhanced cytoplasmic and nuclear detail
variability in nuclear staining
Cell Size
proportionately smaller
single cells more prominent
cells may round up in solution e.g.. adenocarcinoma
Smear Pattern
Cellular material not pulled out in mucous
Mechanical artifacts eliminated
Specimen Background
Cellular debris may appear clumped

Differential Diagnoses
Endocervical Adenocarcinoma vs. Poorly Differentiated Squamous Cell Carcinoma (SCC)
Endocervical Adenocarcinoma vs. Endometrial Adenocarcinoma
Endometrial Adenocarcinoma vs. Small Cell Squamous Carcinoma
Adenocarcinoma-in-situ vs. Tubal Metaplasia
HSIL vs. Single Endometrial Cells
HSIL vs. Immature Squamous Metaplasia
Poorly Differentiated Squamous Cell Carcinoma vs. Repair

Poorly Differentiated Squamous Cell Carcinoma vs. Endocervical Adenocarcinoma
Poorly Differentiated SCC
2D sheets and single cells
Ragged group edges
Dense, homogenous cytoplasm
Pleomorphism, irregular nuclear shapes and sizes
Irregular chromatin clumping
Nucleoli variable in shape, size, number and position
Endocervical Adenocarcinoma
3D cell groupings
Common group borders
Delicate, foamy cytoplasm
Enlarged nuclei, commonly round/oval
Parachromatin clearing
Round, central, single or multiple macronucleoli

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Endocervical Adenocarcinoma vs. Endometrial Adenocarcinoma
Endocervical Adenocarcinoma
Abundant abnormal material
directly scraped
Well preserved material
Cells and cell groupings generally larger in size
Abundant, foamy cytoplasm, occasionally columnar shaped
AIS precursor with endocervical architecture may be seen
Endometrial Adenocarcinoma
Isolated abnormal groups
cell shedding
Variable preservation of cells
Cells and cell groupings generally smaller in size
Scant, cyanophilic cytoplasm with occasional conspicuous vacuoles
Mature hormonal pattern, watery transudate may be seen

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Endometrial Adenocarcinoma vs. Small Cell SCC
Endometrial Adenocarcinoma
Isolated abnormal groups
cell shedding
Occasional clusters, fewer single cells
Scant, vacuolated cytoplasm
Eccentrically located nuclei
Parachromatin clearing
Round, central, single or multiple macronucleoli
Small Cell SCC
Abundant abnormal material
directly scraped
++ Single cells, clusters
Dense, homogenous cytoplasm
Centrally located nuclei
Irregular chromatin clumping
Prominent, irregular nucleoli

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Adenocarcinoma In Situ vs. Tubal Metaplasia
Adenocarcinoma In Situ
Crowded sheets & strips
Feathering & pseudostratification
Relative hyperchromasia
Uniformly stippled chromatin
Nuclear size and shape variation
Block-like nucleoli
Mitoses and apoptotic bodies
Tubal Metaplasia
Cilia and/or terminal bars reliably identified
Crowding without overlap, lacking depth of focus
Evenly distributed chromatin
Cytoplasm dense and cuboidal
Nucleoli absent
Nuclear membrane irregularities and thickening absent
Occasional elongate nuclear forms

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HSIL vs. Endometrial Cells
HSIL
Sheets, syncitia; thick plaques rather than 3D ball-like clusters
Hyperchromasia
Irregular nuclear membranes
Single cells have centrally located nuclei
Dense homogenous cytoplasm
Endometrial Cells
3D ball-like clusters and small, single cells
Relative hyperchromasia
Regular nuclear membranes
Single cells with eccentrically located nuclei
Scant basophilic cytoplasm with cytoplasmic “blebs”

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HSIL vs. Immature Squamous Metaplasia
HSIL
Single cells, clusters, and thickened plaques
Variable hyperchromasia
Irregular nuclear membranes
Coarse clumped chromatin
Variation in nuclear size within a cluster
Immature Squamous Metaplasia
Single cells & cobblestone sheets
Normochromatic
Regular nuclear membranes
Evenly distributed chromatin with pinpoint chromocenters
Nuclear size & shape consistent

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Repair vs. Poorly Differentiated SCC
Poorly Differentiated SCC
Poorly cohesive sheets and single cells
Irregular nuclear shapes & sizes
Thickened nuclear membranes
Irregular chromatin clumping
Nucleoli variable in shape, size, number and position
Some nuclei display nucleoli, some nuclei do not
Repair (typical)
Cohesive sheets
Significant nuclear size variation but typically round/oval in shape
Thin, well defined nuclear membranes
More open chromatin pattern with minimal variability
Centrally located macronucleoli with smooth, round contours
Virtually all nuclei display nucleoli

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