Intratubular Malignant Germ Cells Research Articles

Genetic and histopathological analysis of transverse testicular ectopia without persistent M\xfcllerian duct syndrome: two case reports

BackgroundTransverse testicular ectopia (TTE) is a rare anomaly in which both testes descend through a single inguinal canal into the same hemiscrotum. Although almost 20–50% of patients with TTE exhibit persistent Müllerian duct syndrome (PMDS) and many genetic analyses have been performed, no reports have described the genes contributing to TTE without PMDS. Here, we report two cases of TTE without PMDS using immunohistochemical staining and genetic analysis.Case presentationTwo Asian patients with TTE without PMDS were subjected to orchiopexy. We performed testicular biopsies during operation and obtained blood samples before the operation. Testicular tissues were stained for c-kit, placental alkaline phosphatase (PLAP), and undifferentiated embryonic cell transcription factor 1 (UTF1) to evaluate the presence of intratubular malignant germ cells. Additionally, we performed polymerase chain reaction-based direct sequencing to identify single nucleotide polymorphisms in genes associated with regression of the Müllerian duct and testicular descent (that is, anti-Müllerian hormone [AMH], AMH receptor 2 [AMHR2], insulin-like 3 [INSL3], and relaxin family peptide receptor 2 [RXFP2]). The three-dimensional structures of proteins were predicted using SWISS-MODEL. In immunohistochemical analysis, c-kit and UTF1 were positive, whereas PLAP was negative in three testicular tissue samples from the two patients. These features were also detected on the unaffected side. In variant analysis, common missense variants in the AMH gene (g.365G>T; c.165G>T; p.Ser49Ile [rs10407022]) were observed. All variants in INSL3 and RXFP2 genes were intronic or silent.ConclusionsBecause UTF1, a specific marker of spermatogonial stem cell activity, was expressed in both the affected and unaffected sides in the testicular tissues of two patients, the risk of malignancy may be high in these patients. Although the etiology of TTE without PMDS remains unclear, our variant analysis results were consistent with previous reports, and variants in the AMH gene (rs10407022) may contribute to the specific phenotype of TTE without PMDS.

Immunohistochemical heterogeneity of type 1 blood group antigen expressions in testicular germ cell tumors.

The immunohistochemical expression of type 1 blood group antigens (type 1 BGAs) was analyzed for 30 cases of testicular germ cell tumors (TGCTs), using monoclonal antibodies against DU-PAN-2, CA19-9, Lewis(a) (Le(a)), and Lewis(b) (Le(b)). DU-PAN-2 was expressed very frequently in all of the embryonal carcinomas (ECs). CA19-9 expression was demonstrated in 53% of ECs, but the number of positive cells was generally smaller than that for DU-PAN-2. CA19-9-negative ECs tended to show a higher number of DU-PAN-2-positive cells compared to CA19-9-positive ECs, and ECs in which DU-PAN-2 was more strongly expressed showed a relatively frequent expression of CA19-9. In 36% of seminomas and 56% of yolk sac tumors (YSTs), DU-PAN-2 was weakly expressed, and the positive cells were few in number. Little or no expression of CA19-9 was demonstrated in seminomas and YSTs. Regarding Le(a) and Le(b), the expressions were found to be limited to teratomas at a frequency of 57% and 86%, respectively, with the exception of one EC positive for Lea and one YST positive for Leb. Eighty-six percent of teratomas showed expressions of DU-PAN-2 and CA19-9. DU-PAN-2 was also seen in some intratubular malignant germ cells. The antibodies used were all negative for choriocarcinomas, syncytiotrophoblastic giant cells, and normal testicular tissues. The antigen expressions were predominantly observed on the surface of tumor cells developing luminal structures. In conclusion, although CA19-9 was relatively specific for ECs, it should be emphasized that ECs were rather characteristic of extensive DU-PAN-2 expression. Particularly in CA19-9-negative ECs, a combined analysis of DU-PAN-2 and CA19-9 would be helpful in confirming the histopathologic diagnosis of TGCTs. The clinical significance of DU-PAN-2 in ECs as a tumor marker remains to be clarified. Le(a) and Le(b) expressions were thought to be related to the differentiation or maturation rather than to the malignant transformation in TGCTs.

Testicular Sparing Surgery for Prepubertal Teratoma of the Testis: A Clinical and Pathological Study

We report on 5 patients 14 months to 6½ years old with prepubertal teratoma of the testis treated by testicular sparing tumor enucleation. All 5 patients had no evidence of recurrence at a mean followup of 96 months. Recognizing that this is not accepted therapy for testis tumors, 17 orchiectomy specimens containing teratoma from children were histologically analyzed in cooperation with the Armed Forces Institute of Pathology Tumor Registry. All patients were prepubertal at orchiectomy (3 months to 8 years old) and all are well with a mean followup of 174 months. Histological examination revealed no foci of teratoma separate from the main tumor in any specimens. Immunohistochemical studies with placental alkaline phosphatase, a marker for malignant germ cells, were done to detect carcinoma in situ in the seminiferous tubules of these testes. This test did not reveal any intratubular malignant germ cells (carcinoma in situ). Based on our clinical experience with testicular sparing tumor enucleation, the histological findings on Armed Forces Institute of Pathology review demonstrating no associated carcinoma in situ and the universally benign behavior of prepubertal testicular teratomas, we recommend a testicular sparing operation rather than orchiectomy for testicular teratoma in prepubertal patients.

Placental alkaline phosphatase immunohistochemistry of intratubular malignant germ cells and associated testicular germ cell tumors.

Two hundred three testicular germ cell tumors were studied immunohistochemically for the presence of placental alkaline phosphatase (PLAP). Special emphasis was placed on the pattern and incidence of positive staining of intratubular malignant germ cells (ITMGCs) adjacent to tumors. 99% of cases with adjacent ITMGCs showed a positive staining reaction in some or all IT-MGCs present. Other germ cell elements showed at least a focal positive staining reaction in the following proportions: seminomas, 96%; embryonal carcinomas, 96%; yolk sac tumors, 25%; mature teratomas, 5%; immature teratomas, 4%; choriocarcinomas, 45%; and syncytiotrophoblasts, 43%. The staining pattern for seminomas tended to be diffuse, whereas for embryonal carcinomas the staining pattern was more focal. Yolk sac tumors stained inconsistently for PLAP and a positive reaction was limited to a small percentage of cells. Syncytiotrophoblasts, singly or in choriocarcinomas, also showed variable positivity. These results corroborate the fact that PLAP is a sensitive marker for ITMGC, seminoma, and embryonal carcinoma.

Intratubular Malignant Germ Cells (Carcinoma in SITU) Accompanying Invasive Testicular Germ Cell Tumors

We examined 111 radical orchiectomy specimens from patients with germ cell tumors of the testis treated between 1971 and 1981 for the presence of intratubular malignant germ cells (so-called carcinoma in situ) in adjacent testicular tissue. Of the specimens 12 were unevaluable because the entire specimen was tumor, while 36 of 44 cases of pure seminoma (82 per cent) and 41 of 55 mixed or nonseminomatous tumors (75 per cent) had intratubular malignant germ cells. Of the 22 cases without intratubular malignant germ cells 10 had severe atypia that suggested an earlier or borderline stage of development. These data support the contention that germ cell tumors originate as intratubular neoplasms or so-called carcinoma in situ in the seminiferous tubules.