RETRACTED ARTICLE: Cervical adenosquamous carcinoma: detailed analysis of morphology, immunohistochemical profile, and clinical outcomes in 59 cases

Abstract

Although 2014 World Health Organization criteria require unequivocal glandular and squamous differentiation for a diagnosis of cervical adenosquamous carcinoma, in practice, adenosquamous carcinoma diagnoses are often made in tumors that lack unequivocal squamous and/or glandular differentiation. Considering the ambiguous etiologic, morphological, and clinical features and outcomes associated with adenosquamous carcinomas, we sought to redefine these tumors. We reviewed slides from 59 initially diagnosed adenosquamous carcinomas (including glassy cell carcinoma and related lesions) to confirm an adenosquamous carcinoma diagnosis only in the presence of unequivocal malignant glandular and squamous differentiation. Select cases underwent immunohistochemical profiling as well as human papillomavirus (HPV) testing by in situ hybridization. Of the 59 cases originally classified as adenosquamous carcinomas, 34 retained their adenosquamous carcinoma diagnosis, 9 were reclassified as pure invasive stratified mucin-producing carcinomas, 10 as invasive stratified mucin-producing carcinomas with other components (such as HPV-associated mucinous, usual-type, or adenosquamous carcinomas), and 4 as HPV-associated usual or mucinous adenocarcinomas with benign-appearing squamous metaplasia. Two glassy cell carcinomas were reclassified as poorly differentiated usual-type carcinomas based on morphology and immunophenotype. There were significant immunophenotypic differences between adenosquamous carcinomas and pure invasive stratified mucin-producing carcinomas with regard to HPV (p < 0.0001), PAX8 (p = 0.038; more in adenosquamous carcinoma), p40 (p < 0.0001; more in adenosquamous carcinoma), p63 (p = 0.0018; more in adenosquamous carcinoma) and MUC6 (p < 0.0001; less in adenosquamous carcinoma), HNF-1beta (p = 0.0023), vimentin (p = 0.0003), p53 (p = 0.0004), and CK7 (p = 0.0002) expression. Survival outcomes were similar between all groups. Adenosquamous carcinomas should be diagnosed only in the presence of unequivocal malignant glandular and squamous differentiation. The two putative glassy cell carcinomas studied did not meet our criteria for adenosquamous carcinoma, and categorizing them as such should be reconsidered.

Figure 1.

Distribution of endocervical adenocarcinomas, adenosquamous carcinomas, and mimickers after microscopic evaluation.

Figure 2.. Adenosquamous carcinoma.

A: Malignant glandular and squamous differentiation is present; B: Poorly differentiated squamous component; C: p63 expression; D: p40 expression; E: Positive high-risk human papillomavirus in situ hybridization; F: Block-like p16 expression

Figure 3.. Invasive stratified mucin-producing carcinoma.

A: Invasive nests of cells with stratified mucinous cells surrounded by a palisade; B: p63 expression in the peripheral palisade; C: Block-like p16 expression

Figure 4.

Invasive stratified mucin-producing carcinoma combined with usual-type adenocarcinoma

Figure 5.

Usual-type adenocarcinoma with benign-appearing squamous differentiation

Figure 6.

Glassy cell carcinoma (A) with positive high-risk human papillomavirus in situ hybridization (B)

Figure 7.

Analysis of overall survival between cervical adenosquamous carcinomas, adenosquamous carcinomas with invasive stratified mucin-producing carcinomas components, invasive stratified mucin-producing carcinomas, and usual-type human papillomavirus HPV-associated adenocarcinomas

Figure 8.

Analysis of disease-free survival between adenosquamous carcinomas, adenosquamous carcinomas with invasive stratified mucin-producing carcinoma components, invasive stratified mucin-producing carcinomas, and usual-type human papillomavirus HPV-associated adenocarcinomas