A malignant germ cell tumor morphologically represented by cells similar to primordial germ cells/gonocytes.
Seminoma comprises 40–50% of all GCTs. About 10% of seminoma patients have a history of criptorchidism and higher proportions have been noted in patients with immunodeficiency disorders.
It occurs commonly between the age of 25–50, with a peak incidence at about 34 years. Seminoma is virtually nonexistent before puberty and it is rare in adolescence (1%) with the exception of children who have a disorder of sex development; seminoma is rare in men older than 70 years (Berney et al. 2008).
Most patients present with a testicular mass, while 3% of seminomas present with symptoms related to metastatic localization as lower back pain caused by retroperitoneal lymphnode involvement. Other lymphnodal metastases could occur to the mediastinal and cervical lymphnodes; visceral metastases typically occur in the liver and lungs, and the bone is sometimes affected by seminomatous spread.
Among GCTs, seminomatous forms had the highest survival rate (98%). Survival is consistently lower for patients aged 65 years or more than for younger patients. Patients with clinical stage I disease who are managed by surveillance protocols, adjuvant radiation, or single-agent chemotherapy achieve a 95–98% overall 5-year survival rate. Predictors of relapse include primary tumor size >3 cm, rete testis, hilar tissue and epididymal involvement, and possibly vascular invasion, but the need for predictive factors of recurrence is still debated. The disease specific survival of patients with advanced stage disease with cisplatin-based chemotherapy is 83%. An adverse prognostic finding in the advanced stage is the occurrence of nonpulmonary visceral metastases.
Seminoma is positive for all markers of embryonic stem cells: PLAP, OCT 3/4, NANOG, CD117 (c-kit), and AP-2γ as well as the transcription factor SALL4. Others markers are the membrane glycoprotein of podocytes podoplanin (D2-40) and SOX 17 (Ye and Ulbright 2012). Cytokeratin AE1/AE3 immunoreactivity varies (20–36%), but it is often negative or stains only a minority of tumor cells (Cheville et al. 2000).
Most patients with seminoma have no known genetic abnormalities. In bilateral cases, mutation of KIT may be the initiating event. It is believed that the failure of gonocytes to switch off expression of OCT 3/4 is an early event in the pathway to GCNIS: Coexpression of OCT 3/4 and testis specific Y-encoded protein (TSPY) and the concomitant expression of KIT ligand, possibly drives neoplastic transformation of maturation-delayed gonocytes to overt GCNIS. The default progression of GCNIS is via intratubular seminoma into invasive seminoma. Like all GCTs, also seminoma shows gain of isochromosome i(12p). Many gain and losses of chromosomes have been reported.
Embryonal Carcinoma (ECA)
ECA in solid pattern of growth shows a marked cellular pleomorphism, nuclear crowding with overlapping and indistinct cell borders, irregularly shaped nucleoli, frequent mitoses, but the main differential features are the immunohistochemical stainings: seminoma is positive for KIT, podoplanin, and SOX 17 and negative for CD30 and SOX 2 that are positive in ECA.
Yolk Sac Tumor (YST), Solid Pattern
YST generally shows Schiller-Duval bodies and frequently solid pattern is admixed with other patterns of growth. YSTs are strongly positive for pancytokeratin and OCT 3/4 negative, but the most specific marker is glypican-3. AFP is sometimes only focally expressed.
The multiplicity of cytological tumor appearance in ST together with lack of lymphocytic infiltration or granulomatous reaction, and the absence of GCNIS are main histopathological differences. ST is negative for PAS, lacks germ cell tumor markers, while SALL 4 and c-kit may be positive.
Malignant Sertoli Cell Tumor (MSCT)
MSCT usually lack fibrous septa with lymphoplasmacytic reaction. SF-1 and α-inhibin positivity and negativity for SALL 4 allow the differential diagnosis with seminoma.
Monophasic Choriocarcinoma (MC)
It is extremely rare, more frequently associated with hemorrhage. MC is OCT 3/4 negative, positive for hCG and human placental lactogen.
Malignant Lymphoma (ML)
ML shows predominant interstitial pattern of tumor cells between tubules. Germ cell markers are negative; CD45 and B or T-cell markers (depending on type) are positive.
References and Further Reading
- Berney, D. M., Warren, A. Y., Verma, M., Kudahetti, S., Robson, J. M., Williams, M. W., Neal, D. E., Powles, T., Shamash, J., & Oliver, R. T. (2008). Malignant germ cell tumours in the elderly: A histopathological review of 50 cases in men aged 60 years or over. Modern Pathology, 21(1), 54–59.CrossRefGoogle Scholar