Germ cell tumour growth patterns originating from clear cell carcinomas of the ovary and endometrium: a comparative immunohistochemical study favouring their origin from somatic stem cells.

AIMS: To report a series of 11 ovarian and one endometrial neoplasm in elderly patients with mixed clear cell tumour and germ cell tumour (GCT) components, to compare their immunohistochemical profiles and demonstrate a putative stem cell population. METHODS AND RESULTS: The clear cell tumours included 11 clear cell carcinomas (CCC) and one borderline clear cell tumour, while the GCT always included glandular yolk sac tumour (YST). In four cases, there were also foci of teratoma with immature neuroepithelial and endodermal tissues and undifferentiated areas showing true embryoids. To distinguish between the clear cell and YST components, the following antibodies were used: HNF1-ß, napsin-A, cytokeratin 7 (CK7), PAX8, EMA, AFP, SALL4, villin, glypican-3 (GPC-3), GATA3, HepPar-1, OCT4, CDX2, CD30 and SOX2. HNF1-ß, CK7, EMA and GPC-3 were often expressed in both components. Other markers had higher specificity for each cellular lineage; napsin-A and PAX8 were expressed only in CCC, while SALL4, villin, AFP and HepPar-1 were positive in the glandular YST component but negative in the clear cell component. OCT4 expression occurred in six of 10 cases and consistently in teratoma (four of four). CONCLUSIONS: There is considerable immunophenotypical overlap between the two components in these mixed neoplasms, and a panel of markers should be used to facilitate the distinction. We propose that OCT4-expressing somatic cancer cells differentiate into GCT and represent spontaneously induced pluripotent stem cells, possibly conditioned by age-related epigenetic factors. These neoplasms have features of prepubertal type GCT showing lack of 12p gain, preponderance of YST and coexistence with immature neuroectoderm. However, there may also be undifferentiated stem cell areas with embryoid bodies, of the type seen in postpubertal testicular GCT, but lacking a complete embryonal carcinoma immunophenotype.

Endometrial Changes in Surgical Specimens of Perimenopausal Patients Treated With Ulipristal Acetate for Uterine Leiomyomas.

Ulipristal acetate (UPA) is used to treat leiomyomas, and its effect on the endometrium has been studied in biopsy material. Reversible histologic modifications were found, named progesterone receptor modulators-associated endometrial changes (PAEC). However, hysterectomies from patients treated with UPA have not been analyzed. For the first time, we examined surgical specimens from 100 leiomyoma-treated patients for UPA-related endometrial changes. We analyzed the distribution of lesions, involution after treatment, and the relationship between type and extent of lesions and dosage. Clinically, 72 patients were treated with 1 cycle of UPA; 23 patients with 2 cycles, and 5 with 3 cycles. A total of 66 patients underwent surgery in the first 4 wk after treatment, 24 were operated between 5 and 12 wk after discontinuation of UPA, and 10 after more than 12 wk after the last cycle, up to a maximum of 32 wk. Histologically normal endometria were found in 41 cases and PAEC in 59 cases. PAEC consisted of irregular, cystic glands showing a flattened secretory-like epithelium with vacuolation, coexisting mitoses and apoptosis, and were found focally within cyclic endometria in 51 cases. Only in 8 cases did diffuse PAEC involve the whole endometrium, transforming it into a thick spongy cushion. PAEC also occurred in adenomyosis. There was no relationship between dosage and type and extent of lesions. Diffuse PAEC, which usually presents differential diagnoses with hyperplasia, occurred in only 8 cases, being only present during the first 4 wk after discontinuation of treatment and was independent of the number of cycles administered.

Adenocarcinoma of the Lung Metastatic to the Ovary With a Signet Ring Cell Component.

A nonsmoker 45-year-old woman, presented with a solid right ovarian mass. Microscopic examination revealed heterogeneous histology with tubular formations and extensive signet ring cell component that resembled the usual appearance of metastatic gastric carcinoma to the ovary. Moreover, the histology also showed solid nests of cells with a microvacuolated basophilic cytoplasm similar to those found in adenosquamous cervical carcinoma of glassy cell type. However, analysis of the patient's past history revealed a lung adenocarcinoma, diagnosed 4 years before, which prompted an immunohistochemical differential diagnosis, showing a strong expression for TTF-1 and Napsin A. A cervical primary was excluded taking into account both macroscopic findings and the negative expression of PAX8 and absence of human papillomavirus-related marker p16. This confirmed the pulmonary origin of ovarian tumor despite its heterogeneous morphology. This is the first reported case of ovarian metastatic lung adenocarcinoma, with a signet ring cell component and solid nests, mimicking both metastatic gastric carcinoma and adenosquamous carcinoma of glassy cell type.