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 1
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Endometrial thickening Probe curretage 3
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 ENDOMETRIAL CELLS 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) 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 4
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 5
Atypical Endometrial cells Polyp, IUD, hyperplasia, endometritis or carcinoma In LB preparations cells may be significantly pleomorphic than is seen in CSs 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 ENDOMETRIAL ADENOCARCINOMA polip hyperplasia 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 Atypical endometrial cells can be seen in various entities like polip, chronic endometritis, hyperplasia, IUD or carcinoma. 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 6
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 Diathesis Visible, types vary Variable, watery or subtle or absent Cell shape Nuclei Oval, columnar, pleomorphic, Oval, elongated, pleomorphic, vesicular Round, irregular, usually smaller Round, irregular in higher grade Varies depending upon primary and mode of spread Usually absent unless direct spread Variable 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 Adenocarcinoma out of uterus 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 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. 7
COLON CA Thanks to Dr. Volker Schneider 56 y old woman RT for cervical carcinoma 8
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2014 RADIATION-ASSOCIATED CHANGES 56 y old w RT for cervix Ca in 1999 We have her smears with such cells since 2007 No gross/ colposcopic lesion NED 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 normalsized 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 10
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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. 12
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. 13