Isolated morular squamous metaplasia in endometrial biopsies and curettings: is there a role for repeated sampling?

Endometrial atypical hyperplasia and low-grade endometrioid carcinoma are often associated with morular squamous metaplasia. Limited evidence suggests that the finding of isolated morular squamous metaplasia without concomitant glandular neoplasia in biopsies is associated with a 6.5% risk of endometrial cancer in subsequent samples and warrants close follow-up. However, its prognostic value has not been clearly determined.

The Massachusetts General Hospital pathology database was queried to identify endometrial samples with a diagnosis of 'adenoacanthosis', 'morular metaplasia', 'squamous metaplasia' or 'morular squamous metaplasia' between 2012 and 2024. Cases associated with endometrioid carcinoma, non-atypical or atypical hyperplasia, atypical polypoid adenomyoma and gland crowding insufficient for diagnosis of atypical hyperplasia were excluded. Clinicopathologic data were collected. Outcomes were categorized as regression, persistence and progression to carcinoma. Of 32,800 endometrial samples reported during the study period, isolated morular squamous metaplasia was diagnosed in 57 (0.17%), including 42 (73.7%) biopsies and 15 (26.3%) curettings. The median patient age was 45 (21-70) years. Histologic follow-up (at least one follow-up sample) was available in 22 patients (median 30 months, 1-120) and included endometrial biopsy, curettage or hysterectomy. Of these 22 patients, a single follow-up biopsy was performed in 9 (40.9%), a single curettage in 1 (4.5%), hysterectomy in 6 (27.3%), a single biopsy followed by hysterectomy in 2 (9.1%), multiple biopsies in 3 (13.6%) and a curettage followed by multiple biopsies and hysterectomy in 1 (4.5%). The median number of follow-up samples was 2 (2-9) per patient. Histologically, the follow-up samples were unremarkable (regression) in most patients (19/22, 86.4%), 2 (9.1%, aged 49 and 57 years) were diagnosed with grade 1 endometrioid carcinoma in subsequent hysterectomies, and 1 (4.5%, age 62) had persistent squamous morular metaplasia (follow-up 69 months). In 15 patients with clinical follow-up but no further pathology sampling, none had clinical symptoms at their last visit (100% clinical regression). Thus, the overall rate of endometrioid carcinoma was 5.4% (2/37).

Isolated squamous morular metaplasia without associated glandular neoplasia is a rare finding, reported only in 0.17% of endometrial samples. The risk of subsequent endometrioid neoplasia appears to be low (5.4%), although the possibility of undersampled atypical hyperplasia/endometrioid carcinoma cannot be completely ruled out without additional sampling. Persistent squamous morular metaplasia is relatively uncommon (4.5%) and may not lead to the subsequent diagnosis of endometrial cancer, questioning the utility of numerous repeat samplings in patients without progression after one repeat sample.