Spermatozytäre Tumoren – Eine Optimierung des diagnostischen Prozesses
Spermatocytic Tumors – An optimization of the diagnostic process
by Valerie Unterkircher
Date of Examination:2024-10-30
Date of issue:2024-10-11
Advisor:PD Dr. Felix Bremmer
Referee:PD Dr. Felix Bremmer
Referee:PD Dr. Silke Kaulfuß
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Abstract
English
Spermatocytic tumors are among the gonadal germ cell tumors, which in turn make up the largest proportion of testicular tumors. Spermatocytic tumors are known as tumors of the older man. However, around 30% of patients are diagnosed in their fourth decade. These tumors are usually indolent; rare cases of metastasis or sarcomatous transformation have also been described, which have a poor prognosis because spermatocytic tumors are largely unresponsive to chemotherapy. Spermatocytic tumors are extremely rare (0.9/million). Morphological differentiation is not always easy and there are no established immunohistochemical markers for diagnosis, so these tumors are usually diagnosed by excluding other tumors. According to the guidelines, patients who are incorrectly diagnosed with a seminoma or non-seminoma, particularly yolk sac tumor or choriocarcinoma, instead of a spermatocytic tumor, could receive chemotherapy that they actually do not need. The case collective included those tumor entities that represent an important differential diagnosis for spermatocytic tumors: seminomas, primary testicular lymphomas, yolk sac tumors and choriocarcinomas. Yolk sac tumors and choriocarcinomas represent a relevant differential diagnosis in the case of negative OCT3/4 immunostaining. In contrast to type 2 germ cell tumors, which typically show chromosomal changes in the form of an isochrosome 12p, spermatocytic tumors characteristically show chromosomal changes on the 9th chromosome. An important gene that is of great importance for spermatogenesis and is also located on chromosome 9 is DMRT1. Two other proteins that have been described in the literature in connection with spermatocytic tumors are SSX-2 and SAGE1, which come from the group of chromosome X-encoded cancer/testis antigens (CT-X antigens). They are expressed in the testis during germ cell development as part of the OCT3/4 downregulation. For my work, I put together a panel of immunohistochemical antibodies and included DMRT1, SAGE1, SSX-2, SALL4, OCT3/4, CD117, D2-40, Glypican3, CD45, OCT2 PLAP and Vimentin. For the molecular pathological investigations, a probe was also selected for the FiSH that binds to a region on the 9th chromosome. SALL 4 differentiates germ cell tumors from non-germ cell tumors, OCT3/4 differentiates seminomas and embryonic carcinomas from non-seminomas such as yolk sac tumors or spermatocytic tumors. CD117 and D2-40 show variable staining and do not allow a reliable distinction between seminoma and spermatocytic tumor. Glypican3 is a marker for yolk sac tumors, with variable staining in spermatocytic tumors. SAGE1 and SSX-2 indicate spermatocytic tumors. DMRT1 only shows constant, strong staining in spermatocytic tumors, but only weakly focally in seminoma. CD45 and OCT2 indicate lymphoma because staining only occurs in lymphocytes. PLAP is stained in seminoma, and vimentin in seminoma and lymphoma. The FiSH probe signals were counted for a defined number of cells and analyzed to see how many cell nuclei had more than 2 probe signals. 88% of spermatocytic tumors were classified as polysomic, 13.3% of seminomas, and the remaining tumor entities as not polysomic at all. This work showed that DMRT1, as well as SAGE1 and SSX-2, are reliable immunohistochemical markers for spermatocytic tumors and can be used to differentiate them from seminomas and testicular lymphomas. Chromosome 9 amplification was confirmed with FiSH and can therefore be used to aid in diagnosis.
Keywords: spermatocytic tumor; DMRT1; SSX-2; SAGE 1