Encyclopedia of Pathology

Living Edition
| Editors: J.H.J.M. van Krieken


  • Maurizio ColecchiaEmail author
  • Alessia Bertolotti
Living reference work entry
DOI: https://doi.org/10.1007/978-3-319-28845-1_3796-1



A malignant germ cell tumor morphologically represented by cells similar to primordial germ cells/gonocytes.

Clinical Features

  • Incidence

    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.

  • Age

    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).

  • Site

    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.

  • Treatment


  • Outcome

    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.


Small seminomas are homogeneous, well-circumscribed tumors generally bulging above the testicular parenchyma as a lobulated, solid whitish or tan or pale-yellow nodule without a capsule (Fig. 1). Large seminomas cause marked testicular enlargement, showing small necrotic areas and small dot-like hemorrhages, while large hemorrhagic, firm, or cystic areas are strongly suggestive of a non seminomatous component in mixed tumors.
Fig. 1

Seminoma. A lobulated pale yellow tumor bulges above the cut surface of the testis (hemisection on the left)


The typical microscopic pattern of seminoma shows lobules which are separated by thin fibrous septa (Fig. 2). The cells resemble immature spermatogonia and are rather monomorphous. The cytoplasm is rich in glycogen and appears water-clear in formalin fixed material (Fig. 3), a large regular nucleus contains one or more large nucleoli and finely granular chromatin. In seminomatous cells, evenly spaced non overlapping nuclei in most cases contribute to a diffuse pattern of growth interrupted by fibrous septa with lymphocytic infiltrate (Fig. 4). Intertubular growth is common at the periphery of the tumor but it is infrequently predominant (Fig. 5) (Henley et al. 2004). The amount of lymphatic infiltration varies from some few lymphocytes to heavy infiltration and formation of lymphoid follicles. Furthermore, in about one-third of seminomas, epithelioid granulomas also develop. In these noncaseating granulomatous reactions epithelioid cells and Langhans or not-specific giant cells may also be seen. Occasionally, the granulomatous reaction is so extensive that it masks tumoral cells (Fig. 6), but their presence may be confirmed by OCT 3/4 or PLAP positivity. Beside the classical morphology, there are some variants that are not been listed in the WHO classification because of the absence of prognostic or therapeutic importance: among others corded growth, microcystic, tubular-like pattern and signet-ring change are reported (Ulbright and Young 2005). In pseudoglandular and tubular seminoma, tumoral cells form small gland-like clefts. Accumulations of edematous fluid in interstitial tissue give the tumor a microcystic or cribriform appearance: with the pseudoglandular pattern these features simulate the gland formation in yolk sac tumor. Nearly 7–10% of tumors contain admixed syncytiotrophoblast cells, mostly close to vessels. Probably a more extensive use of antibodies against human chorionic gonadotropin (hCG) could detect positive cells in more than 20% of seminomas, occurring also in mononucleated cells. While serum alpha fetoprotein (AFP) elevations are sporadically reported in pure seminomas, serum human chorionic gonadotropin is increased in the 10–20% of tumors presenting syncytiotrophoblast cells. The presence of hCG cells should not be confused with true choriocarcinomas. Small hemorrhages are frequently associated with the syncytiotrophoblastic elements (Fig. 7). The formerly anaplastic or atypical seminomas have not been reported in the recent WHO classification. High-proliferative activity measured by counting mitoses or cells positive for proliferation markers (Ki 67) does not, however, negatively influence the course of the disease.
Fig. 2

Seminoma. Multinodular pattern of growth with fibrous septa

Fig. 3

Seminoma. The tumor cells have abundant clear cytoplasm, well-defined cytoplasmic borders, nuclei with prominent nucleoli

Fig. 4

Seminoma. Diffuse sheet-like pattern of growth

Fig. 5

Seminoma. Intertubular growth of tumor cells

Fig. 6

Seminoma. An extensive granulomatous reaction in a seminoma masks many of the neoplastic cells

Fig. 7

Seminoma with syncytiotrophoblast cells some with mulberry-like nuclei


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).

Molecular Features

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.

Differential Diagnosis

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.

Spermatocytic Tumor

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

  1. 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
  2. Cheville, J. C., Rao, S., Iczkowski, K. A., Lohse, C. M., & Pankratz, V. S. (2000). Cytokeratin expression in seminoma of the human testis. The American Journal of Clinical Pathology, 113(4), 583–588.CrossRefGoogle Scholar
  3. Henley, J. D., Young, R. H., Wade, C. L., & Ulbright, T. M. (2004). Seminomas with exclusive intertubular growth: A report of 12 clinically and grossly inconspicuous tumors. The American Journal of Surgical Pathology, 28(9), 1163–1168.CrossRefGoogle Scholar
  4. Ulbright, T. M., & Young, R. H. (2005). Seminoma with tubular, microcystic, and related patterns: A study of 28 cases of unusual morphologic variants that often cause confusion with yolk sac tumor. The American Journal of Surgical Pathology, 29(4), 500–505.CrossRefGoogle Scholar
  5. Ye, H., & Ulbright, T. M. (2012). Difficult differential diagnoses in testicular pathology. Archives of Pathology & Laboratory Medicine, 136(4), 435–446.CrossRefGoogle Scholar

Copyright information

© Springer Nature Switzerland AG 2019

Authors and Affiliations

  1. 1.Uropathology Unit, Department of PathologyFondazione IRCCS Istituto Nazionale dei Tumori di MilanoMilanItaly
  2. 2.Department of PathologyFondazione IRCCS Istituto Nazionale dei Tumori di MilanoMilanItaly