The decisive role of molecular pathology in presumed somatic metastases of type II testicular germ cell tumors: report of 2 cases

Abstract

Background: Molecular diagnostics can be decisive in the differential diagnosis between a somatic metastasis of type II testicular germ cell tumor (TGCT) or a second primary carcinoma. This is in line with recent recommendations from the International Society of Urological Pathology, based on an international survey which showed that molecular testing is currently only performed by a minority of urological pathologists. Case presentations: This case report illustrates the necessity of molecular testing in two patients with a history of type II TGCT and a metastatic (retro) peritoneal carcinoma years later. The genetic hallmark of type II TGCT, chromosome 12p gain, was studied by fluorescence in situ hybridization and whole genome methylation profiling in case 1, and by single nucleotide polymorphism (SNP)-array in case 2. Next generation sequencing (NGS) was used to further explore clonality between the primary TGCT and peritoneal metastasis in case 2. In case 1, chromosome 12p gain was found in the primary type II TGCT and in the acinar cell carcinoma of the metastatic malignancy. In case 2, SNP array showed 12p gain in the epithelial component of the primary teratomatous TGCT but not in the peritoneal adenocarcinoma. Furthermore, NGS showed no mutations in the primary teratomatous TGCT but a KRAS and GNAS mutation in the peritoneal adenocarcinoma, suggestive of an appendicular origin. Conclusions: Without the molecular data, both cases would have been regarded as a metastatic TGCT with development of somatic-type malignancy, which appeared a wrong diagnosis for case 2. These cases demonstrate the importance of molecular methods as an adjunct in today's pathology practice.

Independent primary cutaneous and mammary apocrine carcinomas with neuroendocrine differentiation: Report of a case and literature review

“…In contrast, SNP microarray revealed a distinct pattern of chromosomal copy number alterations between the tumors, providing no evidence of relatedness. This technology uses hybridization probes at SNP sites throughout the genome to interrogate for sites of copy number alterations, and has been used in a research setting to distinguish primary vs metastatic tumors at other anatomical sites, including breast and ovarian adenocarcinomas, 28 head/neck and esophageal squamous cell carcinomas, 29 and germ cell tumors, 30 as well as in patients with multiple cutaneous melanomas 31 . In two related tumors, one would ordinarily expect a degree of overlap in copy number alterations, while independent primary neoplasms would show distinct patterns.…”

Primary hepatic mixed germ cell tumor in an adult

“…The patient in this report showed no notable medical history and no other tumor sites were identified after extensive preoperative imaging studies. Applying either isochromosome 12p or 12p overrepresentation by fluorescence in situ hybridization (FISH) may be helpful for diagnosing germ cell tumors [ 9 , 10 ], but it is difficult to conduct FISH testing in most hospitals. Therefore, the primary hepatic mixed GCT in this case was diagnosed based on the clinicopathologic features and the IHC staining results.…”