Joshua J. X. Li

Keratinization in atypical glandular cell clusters as a cytological clue to endometrioid carcinoma on cervical cytology

AbstractIntroductionSpecific diagnosis of endometrial carcinomas on cervical cytology is difficult with few useful cytomorphological clues reported. This study reviews a cohort of cervical cytology to investigate the presence of keratinization in atypical glandular cells (AGC), an undescribed cytomorphological clue for identifying endometrial endometrioid carcinomas on cervical cytology.MethodsCervical cytology slides from patients with a histologic diagnosis of endometrial endometrioid carcinoma were reviewed for the presence of keratinization associated with AGCs. Corresponding histology slides were reviewed for tumour grading and degree of squamous differentiation.ResultsIn total, 42 cases of cervical cytology specimens from 41 patients were retrieved, including 7 (16.7%) with keratinization associated with AGCs seen and 35 (83.3%) without. Comparison of histologic grading did not demonstrate an association with the presence of keratinization on cytology (p = 0.565). Corresponding histology slides were available for 37 cases. Cytologic and histologic keratinization were associated statistically (p = 0.002). Frank keratinization was seen on histologic slides of five cases, with four also showing cytologic keratinization. Area of squamous differentiation, including squamous morule formation, did not correlate with keratinization on cytologic preparation (p = 0.185).ConclusionHistologic and cytologic keratinization are observed in endometrioid endometrial carcinomas. Such is reflected in cervical cytology by the presence of orangeophilic, rigid and acellular fragments within or associated with AGC clusters. Keratinization, when identified with AGCs, should be regarded as a cytologic clue suggestive of an endometroid carcinoma of endometrial origin.

Detection rates and factors affecting thereof in endometrial hyperplasia, endometrial carcinoma, and cervical glandular lesions on cervical smear

AbstractIntroductionEndometrial lesions are morphologically diverse and uncommon on cervical smears, with its detection rate and associated diagnostic categories uncharacterized. In this study, cervical smears matched to histologically proven endometrial hyperplasias and carcinomas were reviewed and compared with cervical in‐situ‐carcinomas/carcinomas, aiming to detail the diagnostic performance of cervical smears for upper tract and glandular lesions.MethodsPathology reports of cervical smears, hysterectomies, endometrial and cervical biopsies from 1995 to 2021 were retrieved. Diagnoses of cervical smears were matched to endometrial hyperplasias and carcinomas, or cervical carcinomas and reviewed.ResultsTotally 832 cervical smears (272 cervical carcinomas, 312 endometrial carcinomas, and 248 hyperplasias) were included. Considering all cytologic glandular diagnosis as positive, the detection rate of cervical adenocarcinoma‐in‐situ was the highest (64.3%), followed by cervical adenocarcinoma (63.8%), endometrial carcinoma (31.7%), and hyperplasia (with atypia–8.5%; without atypia–2.3%) (p < 0.001). Endometrial hyperplasia was most often diagnosed as atypical squamous cells of undetermined significance (ASCUS) (5.0%) or atypical glandular cells, not otherwise specified (3.6%) without indication of endometrial origin. For endometrial carcinomas, higher FIGO grading and endocervical involvement were associated with higher detection rates across all diagnostic categories (p = 0.002–0.028). High FIGO grade was associated with suspicious/favor neoplastic (C4) (31.1%vs10.3%, p < 0.001) and carcinoma (C5) (17.8% vs. 5.6%, p = 0.005) categories, but not for all glandular diagnoses combined (33.3% vs. 31.0%, p = 0.761).ConclusionDetection rates for endometrial lesions are lower than cervical lesions but not insignificant. Endometrial hyperplasia should be recognized as a differential of human papilloma virus‐negative ASCUS and prompt consideration of investigation of the upper genital tract.

Smear detected cervicovaginal melanoma following negative screening—a cautionary tale of rapidly developing malignancy of the lower female genital tract

Cervicovaginal melanoma is a rare and aggressive neoplasm detectable by Pap smear. Non‐HPV‐related lesions, such as melanoma, can be rapidly progressive and unsuspected. Awareness of uncommon but clinically significant lesions on Pap smear is important.

Trichoblastic Carcinosarcoma Arising From the Vagina: A Case Report With Comprehensive Immunophenotypic Analysis

A 54-year-old woman presented with abdominal pain. Magnetic resonance imaging revealed an upper vaginal mass with no pelvic side wall involvement, nodal, or distant metastasis. Radical hysterectomy was performed. Histology showed trichoblastic carcinoma with hair follicle structures and malignant sarcomatous and carcinomatous components. Hair follicular differentiation was confirmed by positivity to hair follicle markers (Bcl-2, TLE1, CD56/NCAM, and TDAG51) and presence of CD10-positive trichogenic stroma. The tumor involved the vaginal muscularis only (FIGO [International Federation of Gynecology and Obstetrics] stage I) and was excised with clear margins. The patient remained disease free at 3-month follow-up. This is the first case of cutaneous-type carcinosarcoma reported in the vagina, highlighting the difference in histology, immunophenotype, and behavior compared with gynecologic carcinosarcomas.

Digital image analysis of gland-to-stroma ratio by CD10 objectively differentiates between low-grade endometrioid carcinoma and atypical hyperplasia on endometrial biopsy

Distinguishing between endometrial atypical hyperplasia/endometrial intraepithelial neoplasia (EAH/EIN) and grade 1 endometrial endometrioid carcinoma (EEC) requires the evaluation of gland-to-stromal ratio, presence of stromal invasion, extent of epithelial proliferation and nuclear alterations. In small biopsies, stromal invasion may not always be sampled, so other features become more important. However, assessing of some of these features may be subjective. Digital analysis improves diagnostic uniformity, and when combined with CD10 immunostain, it can potentially become a useful objective parameter. Endometrial biopsies with a diagnosis of EAH/EIN or EEC matched were retrieved with subsequent hysterectomy for reference diagnosis. CD10 immunohistochemistry was applied to the biopsies, followed by scanning and annotation. Pixel-accurate stromal percentages were deduced from digitised whole-slide images from a test cohort. An optimal stromal percentage cut-off, thus gland-to-stroma ratio, was extrapolated from the receiver operating characteristic curve. A separate cohort was used to validate the diagnostic performance of the determined gland-to-stroma cut-off. Seventy endometrial biopsies were included in the test cohort, comprising 48 grade 1 EECs and 22 EAH/EINs. The mean stromal percentage was 15.69% for EEC and 33.65% for EAH/EIN (all endometrial tissue annotated/analysed) and 14.77% for EEC and 31.88% for EAH/EIN (only lesional tissue annotated/analysed). The corresponding gland-to-stroma ratio was 5:1 for EEC and 2:1 for EAH/EIN. The areas under curve were 0.758 (p=0.001) (all endometrial tissue) and 0.761 (p=0.001) (only lesional tissue), (p=0.001). In the validation cohort, a cut-off of 30% CD10-stained stroma (7:3 gland-to-stroma ratio) was superior in diagnostic performance than the H&E diagnosis (p=0.042). Evaluation of gland-to-stroma ratio using CD10 immunostain and digital image analysis is a robust and objective method for distinguishing between grade 1 EEC and EAH/EIN in small biopsies. A cut-off >7:3 is highly indicative of EEC.