Encyclopedia of Pathology

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

Embryonal Carcinoma

  • Maurizio ColecchiaEmail author
  • Alessia Bertolotti
Living reference work entry
DOI: https://doi.org/10.1007/978-3-319-28845-1_3745-1



Embryonal carcinoma (ECA) is a highly malignant tumor composed of tumor cells with ovoid to columnar profiles, clear to granular or amphophilic cytoplasm, and markedly pleomorphic nuclei resembling primitive cells that retain the ability to differentiate toward somatic or extraembryonic structures.

Clinical Features

  • Incidence

    The pure form of embryonal carcinoma accounts for only 2–10% of GCTs, but ECA is very frequent (87%) in mixed neoplasms, being after seminoma the most prevalent testicular GCT.

  • Age

    It occurs a decade before seminoma and the mean patient age at diagnosis is 25–32 years. ECA is rare in childhood apart from a disorder of sex development and after age 50.

  • Site

    Most patients present with a testicular mass; almost 10% of patients have metastases as presenting symptoms, occurring in the retroperitoneal lymphnodes.

  • Treatment

    Different protocols are applied and chemotherapy alone or in association with lymphadenectomy is performed after orchiectomy in metastatic setting (Albers et al. 2015).

  • Outcome

    Pure ECA behaves more aggressively than mixed GCTs; nevertheless, it can be cured with modern therapy protocols. In mixed GCTs, the metastases are directly proportional to the percentage of ECA in mixed GCTs (Rodriguez et al. 1986). Twenty percent have supradiaphragmatic lymph node and/or visceral metastases, and hematogeneous spread to the lungs or other sites may occur.


ECA is mostly smaller and not as well circumscribed as seminomas. The cut surface is soft, grayish, and focally hemorrhagic or necrotic.


ECA grows as a true epithelial neoplasm more commonly in solid sheet with or without clefting or in a papillary or adenomatous formation resembling adenocarcinoma. Less frequently observed morphologic patterns include nested, micropapillary (lacking fibrovascular cores), anastomosing glandular, pseudopapillary, sieve-like glandular, and blastocyst-like (Kao et al. 2014). Combinations of two or more patterns are common findings. It is frequent in the solid sheet to find darkly staining, degenerate-appearing cells that show the tendency to “apply” themselves to adjacent cells (“appliqué pattern”) (Fig. 1). Intratubular ECA form comedo structures with central necrosis as in breast cancer. Sometimes extensive tumor necrosis imparts a pseudopapillary appearance. Lymphocytes are observed, but a granulomatous reaction is rare. The tumor cells are very polymorphous and can have a polygonal, cuboid, or columnar shape. The color of the cytoplasm changes from clear to eosinophilic, amphiphilic, or basophilic (Fig. 2). The nuclei have coarse chromatin and large nucleoli. As in seminoma, also in ECA, the presence of scattered syncytiotrophoblastic giant cells is a frequent finding (Fig. 3) and elevated levels of the β-subunit of human chorionic gonadotropin is associated with syncytiotrophoblasts elements. The presence of cells having clear cytoplasm, prominent nucleoli, and distinct cell membranes are other features in common with seminoma (Fig. 4). Neoplastic immature teratomatous-type stroma may be seen between foci of ECA. It is recommended to report the presence or absence of lymphovascular invasion as important predictive factor of recurrence, and in stage S1 and S2 lymphovascular invasion is the most important prognostic factor (Albers et al. 2015); tumor emboli of mixed non-seminomas in vessels are, with rare exceptions, composed of ECA cells.
Fig. 1

Embryonal carcinoma appliqué pattern. Smudged cells “apply” themselves to adjacent cells in this peculiar pattern of growth

Fig. 2

Embryonal carcinoma. Undifferentiated cells that have overlapping nuclei and scant cytoplasm with glandular pattern in a sieve-like pattern

Fig. 3

Embryonal carcinoma with scattered giant cells

Fig. 4

Embryonal carcinoma with some cells having clear cytoplasm, prominent nucleoli, and distinct cell membranes resembling seminoma cells


The tumoral cells in ECA show strong positive reaction to cytokeratins, CD 30, SOX2, and OCT 3/4, and are negative for CD 117, SOX17 with only focal positivity for PLAP, AFP, and beta HCG in syncytiotrophoblastic giant cells. CD 30 immunoreactivity may be lost after chemotherapy (Berney et al. 2000), while in multiple-relapse/chemoresistant cases the persistence of CD 30 expression is associated with a significantly poorer prognosis and it is an independent prognostic factor for survival (Giannatempo et al. 2013).

Molecular Features

ECAs are triploid or hypotriploid tumors. Cytogenetic analysis shows unspecific anomalies, but i(12p) and increased copy numbers of 12p are present in most cases. There is a correlation between the aggressiveness of the tumor and the number of isochromosome copies.

Differential Diagnosis

Many other germ cell tumor histotypes may be confused and for this reason we address to the specific entities for a detailed description. Any confusion with seminoma for the therapeutic consequences is strongly discouraged: in such cases, the use of immunohistochemical markers (CD 30 and SOX2 positivity in ECA, CD 117, and SOX 17 in seminoma) is recommended. ECA may be confounded with large B cell-lymphoma, especially if it is CD 30 positive.

References and Further Reading

  1. Albers, P., Albrecht, W., Algaba, F., Bokemeyer, C., Cohn-Cedermark, G., Fizazi, K., Horwich, A., Laguna, M. P., Nicolai, N., Oldenburg, J., & European Association of Urology. (2015). Guidelines on testicular cancer: 2015 update. European Urology, 68(6), 1054–1068.CrossRefGoogle Scholar
  2. Berney, D. M., Shamash, J., Pieroni, K., & Oliver, R. T. (2000). Loss of CD30 expression in metastatic embryonal carcinoma: The effects of chemotherapy? Histopathology, 39(4), 382–385.CrossRefGoogle Scholar
  3. Giannatempo, P., Paolini, B., Miceli, R., Raggi, D., Nicolai, N., Farè, E., Catanzaro, M., Biasoni, D., Torelli, T., Stagni, S., Piva, L., Mariani, L., Salvioni, R., Colecchia, M., Gianni, A. M., & Necchi, A. (2013). Persistent CD30 expression by embryonal carcinoma in the treatment time course: Prognostic significance of a worthwhile target for personalized treatment. Journal of Urology, 190(5), 1919–1924.CrossRefGoogle Scholar
  4. Kao, C. S., Ulbright, T. M., Young, R. H., & Idrees, M. T. (2014). Testicular embryonal carcinoma: A morphologic study of 180 cases highlighting unusual and unemphasized aspects. The American Journal of Surgical Pathology, 38(5), 689–697.CrossRefGoogle Scholar
  5. Rodriguez, P. N., Hafez, G. R., & Messing, E. M. (1986). Nonseminomatous germ cell tumor of the testicle: Does extensive staging of the primary tumor predict the likelihood of metastatic disease? Journal of Urology, 136(3), 604–608.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