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BOSNIAN-TURKISH CYTOPATHOLOGY

SCHOOL June 18-19, 2016

Sarajevo

Case Discussions

Prof Dr Sıtkı Tuzlalı

Tuzlalı Pathology Laboratory

• 60 year old woman

• Routine gynecologic control

• LBC

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• Endometrial thickening

• Probe curretage

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• Endometrioid carcinoma FIGO Grade I

ENDOMETRIAL CELLS - Benign-appearing

• Normal finding in reproductive age

• Common in menses and proliferative phase

• Considered as abnormal in postmenapusal women

• Postmenapusal? (unclear, unknown to us)

• Bethesda 2001: Report end cells in w ≥ 40 y

• It is not feasible for a screening test to detect every malignancy

• Cervical cytology is primarly a screening test for squamous lesions

• 2014 Bethesda: Report ‘benign appearing endometrial cells’ in w ≥ 45 y

• Histologic assesment is done only if the patient is menapousal (ASCCP)

ENDOMETRIAL CELLS

• Small, ball-like clusters, rarely isolated

• Cytoplasm is scant, often vacuolated

• Cell borders are ill-defined

• Nuclei are small (intermediate squamous cell nucleus)

• Nuclei are dark, chromatin is not easily discernible (overlapping)

• Nucleoli are inconspicous

• Karyorrhexis is often present

• No mitoses

• Double-contoured , three dimensional clusters

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ATYPICAL ENDOMETRIAL CELLS

• CATEGORY:

• Epithelial cell abnormality

ATYPICAL ENDOMETRIAL CELLS

• Distinction between benign and atypical:

• Primarily on the increased nuclear size

• Not further qualified as neoplastic

• Comment: IUD, polyp etc…

• Small groups, usually 5-10 cells

• Nucleai are slightly enlarged compared to normal endometrial cells

• Mild hyperchromasia

• Chromatin heterogeneity

• Occasional small nucleoli

• Scant cytoplasm, with occasional vacuoles

• Cell borders are ill-defined

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• Polyp, IUD, hyperplasia, endometritis or carcinoma

• In LB preparations cells may be significantly pleomorphic than is seen in CSs

Atypical Endometrial cells

• Small groups with usually 5 to 10 cells

• Nuclei are slightly enlarged compared to normal endometrial cells

• Mild hyperchromasia

• Small nucleoli may be present

• Scant cytoplasm is occasionally vacuolated.

• Cell borders are ill defined.

Atypical Endometrial cells

Atypical endometrial cells can be seen in various entities like polip, chronic

endometritis, hyperplasia, IUD or carcinoma.

hyperplasia

polip

ENDOMETRIAL ADENOCARCINOMA

• Single cells or small, tight clusters

• Well-dif tm: Nuclei may be only slightly enlarged than non-neoplastic end. cells

• Variation in nuclear size, loss of nuclear polarity

• Moderate hyperchromasia, irregular chromatin distribution

• Small to prominent nucleoli

• Cytoplasm is scant, cyanophilic, often vacuolated

• Cells may have intracytoplasmic neutrophils (bag of polys)

• Watery tumor diathesis is variably present (more common in CS)

• Gr 1 tumors: Few abnormal cells with minimal cytologic atypia

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Feature Endocervical Ca Endometrial Ca Extrauterine Ca

Cellularity Hypocellular Low cellularity usually Rare cells (unless direct extension)

Pattern Strips, rosettes, sheets w feathering, single malignant cells

Small clusters, rarely papillae, single cells

Varies depending upon primary and mode of spread

Diathesis Visible, types vary Variable, watery or subtle or absent

Usually absent unless direct spread

Cell shape Oval, columnar, pleomorphic,

Round, irregular, usually smaller

Variable

Nuclei Oval, elongated, pleomorphic, vesicular

Round, irregular in higher grade

Variable

Cytoplasm Mucin + Degenerative vacuoles Variable

SIL or SCC Present in > 50% Absent Absent

High-risk HPV Positive in most Negative Negative

p16 Block positive Pattchy/focal except in high grade/serous

Variable, depends on type

The Bethesda System for Reporting Cervical Cytology, Third ed. eds Ritu Nayar, David C Wilbur, Springer, 2015

Celar cell endometrial adenoCa

Mimickers of Endometrial Adenocarcinoma

• Hyperplasia

• Arias Stella reaction and pregnancy

• Endometrial ve endocervical polips

• Cervical small cell carcinoma

• RİA changes

• Fixation and staining artefacts

• Radiation changes

• Postmenopousal atrophy and naked nuclei

Adenocarcinoma out of uterus

• Background is clean and cell morphology of adenocarcinoma cells is entirely different from cervix and uterus

• It can be considered as metastasis in the presence of the tumor diatesis associated with different cell morphology

• Papillary structures and psammoma bodies might suggest ovarian primary.

• Clinical history, previous PAP test results, cytomorphology and convinient IHC panel are the basic tools for the final diagnose.

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COLON CA

Thanks to Dr. Volker Schneider

• 56 y old woman

• RT for cervical carcinoma

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2014

• 56 y old w

• RT for cervix Ca in 1999

• We have her smears with such cells since 2007

• No gross/ colposcopic lesion

• NED

RADIATION-ASSOCIATED CHANGES

• Cell size is markedly increased without a substantial increase in N/C ratio

• Bizarre cell shapes may occur

• Nuclei may vary in size and shape

• Some cell groups have both enlarged and normal-sized nuclei

• Binucleation and multinucleation common

• Mild hyperchromasia may be present

• Degenerative changes including nuclear pallor, wrinkling or smudging of chromatin, nuclear vacuolization

• Porminent single or multiple nucleoli may be seen if co-existing repair is present

• Cytoplasmic vacuolization and/or cytoplasmic polychromasia and intracytoplasmiz PNL

• Acute radiation changes (degenerated blood, bizarre cell forms, cellular debris) generally resolve within 6 mo following therapy

• Sometimes chronic radiation changes persist indefinitely

• These are cytomegaly, karyomegaly without N/C alteration, mild hyperchromasia, neutrophil engulfment, persisting polychromasia

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• Of these, 508 smears were from patients who had undergone hysterectomy for a gynecological malignancy.

• Review of this vaginal cytology material revealed 17 posthysterectomy patients whose smears contained BGCs.

• All the patients had a history of gynecological malignancy and had radiation therapy.

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• Radiation might give rise to a metaplastic process in which basal cells of squamous epithelium of the vagina transform into glandular cells.

• Most probably this process is independent of radiation dosage

• Irreversible

• The possibility of encountering glandular cells in posthysterectomy smears is higher than expected, if the mucin stains have been used for the microscopic examination.