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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
Author(s) -
Nogales Francisco F,
Prat Jaime,
Schuldt Maolly,
CruzViruel Nelly,
Kaur Baljeet,
D'Angelo Emanuela,
MatiasGuiu Xavier,
Vidal August,
McCluggage W Glenn,
Oosterhuis J Wolter
Publication year - 2018
Publication title -
histopathology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.626
H-Index - 124
eISSN - 1365-2559
pISSN - 0309-0167
DOI - 10.1111/his.13426
Subject(s) - biology , cytokeratin , pathology , germ cell , clear cell , stem cell , population , somatic cell , clear cell carcinoma , immunohistochemistry , yolk sac , stem cell marker , ovary , cancer stem cell , carcinoma , medicine , immunology , endocrinology , embryo , microbiology and biotechnology , genetics , environmental health , gene
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: HNF 1‐β, napsin‐A, cytokeratin 7 ( CK 7), PAX 8, EMA , AFP , SALL 4, villin, glypican‐3 ( GPC ‐3), GATA 3, HepPar‐1, OCT 4, CDX 2, CD 30 and SOX 2. HNF 1‐β, CK 7, EMA and GPC ‐3 were often expressed in both components. Other markers had higher specificity for each cellular lineage; napsin‐A and PAX 8 were expressed only in CCC , while SALL 4, villin, AFP and HepPar‐1 were positive in the glandular YST component but negative in the clear cell component. OCT 4 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 OCT 4‐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.