Endometrioid Squamous Proliferations of the Endometrium Express Alpha-Methylacyl-CoA Racemase (P504s)

Squamous morular metaplasia is closely associated with endometrioid proliferative lesions such as endometrial intraepithelial neoplasia, whereas endometrioid adenocarcinoma may also demonstrate squamous differentiation (morular or nonmorular). Alpha-methylacyl-CoA racemase (AMACR; P504s) is an immunohistochemistry marker expressed in many tumors, including prostate adenocarcinoma, renal cell carcinoma, and in a subset of gynecologic carcinomas, predominantly of clear cell histology. In small biopsy samples, the distinction between cervical high-grade squamous intraepithelial lesions (HSILs) involving endocervical glands from endometrioid squamous proliferations can be challenging, given their anatomic vicinity and some degree of morphologic overlap. Following the observation of AMACR positivity by immunohistochemistry within squamous morules in an index case, 35 endometrial samples containing squamous morular metaplasia (25) and nonmorular squamous metaplasia (10), and 32 cases of cervical HSIL involving endocervical glands were stained with AMACR. The endometrial cohort consisted of 2 benign anovulatory endometrium, 7 endometrial polyps, 7 endometrial intraepithelial neoplasia, 4 atypical polypoid adenomyomas, and 15 endometrioid adenocarcinomas. Positive cases were scored as diffuse (≥50%) or focal (<50%). AMACR staining was present in 96.7% of endometrial squamous lesions, including 14 (93.3%) of endometrioid carcinomas, and in all cases of endometrial intraepithelial neoplasia, endometrial polyps, atypical polypoid adenomyomas, and anovulatory endometrium with squamous morular metaplasia or nonmorular squamous metaplasia. In comparison, only 2 cases (5.8%) of cervical HSIL demonstrated positivity for AMACR. In conclusion, AMACR can reliably differentiate the cervical versus endometrial origin of squamous lesions in small biopsy specimens.