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.

Pseudomyxoma-type Invasion in Gastrointestinal Adenocarcinomas of Endometrium and Cervix: A Report of 2 Cases.

This paper presents a clinicopathologic and immunohistochemical report of 2 gastrointestinal-type tumors, one in the endometrium and the other in the cervix. Both showed extensive invasion into the pelvic structures with acellular mucin, identical to pseudomyxoma but in the absence of appendiceal or ovarian tumors. Case 1 was an 81-yr-old female with a Stage III endometrial gastrointestinal-type adenocarcinoma who had had an endometrial polyp with intestinal metaplasia 4 years previously. Case 2 was a 68-yr-old female with Stage IIIB endocervical gastrointestinal-type adenocarcinoma. Both were associated with a pseudomyxoma type of invasion, which in the endometrial case was transmural through the myometrium, and in the cervical case involved parametria, pelvic floor, and lymph nodes. Immunohistochemically, both tumors had a gastrointestinal phenotype coexpressing cytokeratins 7 and 20, CDX2, villin, MUC2, MUC5AC, and MUC6 and were negative for human papillomavirus, analyzed by real-time polymerase chain reaction. The first case exemplifies intestinal endometrial metaplasia as a precursor lesion of the rare gastrointestinal type of adenocarcinoma and also proves its progression into carcinoma. The second case exemplifies the highly aggressive nature of cervical invasion forming mucin lakes. Extensive pseudomyxoma in the uterus and cervix was associated with high clinical stages with marked lymphovascular invasion and lymph node metastases.

Endometrial stromal nodule of the vaginal wall with a review of vulvovaginal endometrial stromal neoplasms.

•It is reported the first endometrial stromal nodule (ESN) in the vagina.•This is an excepcionall ESN because it was not associated with endometriosis•It was successfully treated by local resection.•Primary vulvovaginal endometrial stromal neoplasms are rare (only 5 reported).

Ovarian Small Cell Carcinoma of Pulmonary Type Arising in Mature Cystic Teratomas With Metastases to the Contralateral Ovary.

A bilateral small cell ovarian carcinoma pulmonary-type (SCCOPT), arising in bilateral mature cystic teratomas (MCTs) presented as stage IIIB in a 37-year-old woman. Microscopically, tumor nests were related to the dermoid protuberance and expressed pancytokeratin, EMA, CD56, chromogranin A, NSE, synaptophysin, and SOX2. SALL4 was also focally positive. CDX2, TTF1, PAX8, CK7, CK20, and several neuroendocrine gut hormones were negative. Serum NSE was elevated. This case represents a SCCOPT arising in an MCT in the right ovary with metastasis to the left one also containing a synchronous MCT. Surface implants and lymphovascular invasion suggested metastasis from the right ovarian SCCOPT and excluded a metastatic origin from usual locations of small cell carcinoma (SCC). SCCOPT is morphologically identical to SCC elsewhere, even sharing NSE serum elevation. Although the tumor was closely related to teratomatous mature tissues, a complex immunohistochemical panel failed to provide a tissue of origin.

Ovarian strumal carcinoid containing appendiceal-type mucinous tumor patterns presenting as pseudomyxoma peritonei.

We report for the first time a case of ovarian strumal carcinoid containing both trabecular carcinoid and mucinous glands lined by both goblet and neuroendocrine cells and a low-grade mucinous neoplasm that presented clinically as pseudomyxoma peritonei in the absence of appendiceal lesion in a 58-yr-old woman. Histologically, there were both a tall columnar cell epithelial component lacking neuroendocrine cells, showing the scalloped contours and subepithelial clefts of low-grade appendiceal-type neoplasms and a mixed goblet cell neuroendocrine element. Characteristically, both reproduced appendiceal neoplastic phenotypes in a teratoid fashion. In addition, we present previously unreported oncocytic and mucinous changes in the thyroideal components of strumal carcinoid. This case represents a rare instance of pseudomyxoma peritonei of primary ovarian origin and is an example of multiple somatic teratoid endodermal differentiations of the different sections of the embryonal gut: foregut represented by thyroid, midgut by both mucinous appendiceal components, and hindgut by trabecular carcinoid.

Ovarian paraganglioma.

A rare case of ovarian paraganglioma was incidentally found as a 1.2-cm intraovarian mass in a 68-year-old hypertensive female operated for an endometrial carcinoma. Histologically, it was arranged in characteristic Zellballen composed of polygonal clear cells with a granular cytoplasm that expressed diffusely CAM5.2 cytokeratin, chromogranin, neuron-specific enolase, synaptophysin, and CD56, while S-100 protein was only present in sustentacular cells. We analyzed differential diagnoses with other rare ovarian tumors such as Sertoli cell tumor, with which it may share an immunophenotype expressing cytokeratins, S-100, and other neural markers, and extra-axial ependymoma, which invariably expresses diffusely GFAP, that may be positive only in the sustentacular cells of paraganglioma. However, on simple hematoxylin-eosin inspection, ovarian paraganglioma displays characteristic Zellballen clusters and cells with a granular cytoplasm but lacks the distinctive Sertoli cell tubules and the characteristic rosettes and fibrillary cytoplasm of ependymoma. Pathologists should be aware of the unusual locations of paraganglioma.

Papillary ependymoma of the endometrium.

AIMS: To report an exceptional case of papillary ependymoma occurring in the endometrium. METHODS AND RESULTS: A clinicopathological study was performed regarding a case of papillary ependymoma occurring in the endometrial cavity of a 61-year-old patient who had presented with a solid-type, stage III anaplastic ependymoma of the ovary, treated with cytoreductive surgery that included total abdominal hysterectomy. The uterus was enlarged and showed a dilated cavity, with broadly implanted papillary excrescences without myometrial invasion that were covered by tall, cylindrical cells. These cells had glial fibrillary acidic protein-expressing cytoplasm that was also positive for cytokeratins 7, 8, 18, and 34ß-E12, epithelial membrane antigen, S100 protein, vimentin, and oestrogen and progesterone receptors. CONCLUSIONS: Pathogenetically, the presence of this uterine ependymoma could represent either an example of multicentricity or a phenomenon of transtubal implantation of the ovarian tumour. Exceptionally, papillary ependymoma can occur in the endometrium, and may prompt differential diagnoses with other papillary endometrial tumours. Pathologists should consider this rare possibility in the differential diagnosis of papillary ovarian and endometrial lesions.