Microscopic description and IHC:

The excised supraclavicular lymph node is partially replaced by a highly pleomorphic tumor with large areas of necrosis, apoptosis and mitoses. The tumor cells are somewhat cohesive with moderate amounts of amphophilic cytoplasm and indistinct cell membranes.

Immunohistochemical stains are positive for OCT3/4, SALL4, AE1/3, PLAP, Glypican3, CK7, and CD30; negative for CD117, SOX10 and CD45. Beta-HCG is strongly and diffusely positive, however is interpreted as non-specific staining. OCT3/4, CD30, Glypican3, and CK7 demonstrate a dual population with differential staining. The immunoprofile and differential pattern of staining is consistent with embryonal carcinoma with a second component of choriocarcinoma.

Discussion:

Germ cell tumors comprise a morphologically heterogeneous but histogenetically related population of tumors. Normally classified based on cytomophology; however, overlapping and poor tissue preservation are commonly found (1). These tumors in general are divided into seminomatous and non-seminomatous germ cell tumors; the former including seminomas and the latter comprised by embryonal carcinoma, yolk sac tumor, trophoblastic tumors, teratomas and non-seminomatous germ cell tumors with more than one histologic type (mixed germ cell tumor and regressed germ cell tumor). Appropriate classification is essential since biological behavior and therapeutic options vary accordingly. For example, a stage I non-seminomatous tumor with embryonal carcinoma predominance requires additional therapy after orchiectomy since it may indicate a high risk for treatment failure and metastasis (2).

Immunohistochemistry plays an important role in classification:

  • OCT3/4: positive in embryonal carcinoma and seminoma
  • CD117: positive in seminoma (negative in chorioCA and EC)
  • CD30: positive in embryonal (negative in most other GCTs)
  • Glypican3: positive in yolk sac tumor, teratoma and choriocarcinoma (negative in seminoma and most EC) beta-HCG and human placental lactogen: positive in choriocarcinoma (along with yolk sac and immature teratoma)

According to the proposed ISUP Recommendations, a reasonable initial germ Cell Tumor Subtyping panel is: OCT3/4, CD117, CD30 & GPC3.

This panel may be reduced depending on the light microscopic differential, for instance omitting OCT4 & GPC3 if the question by morphology is limited to seminoma versus embryonal carcinoma.

References:

Gopalan A, Dhall D, Olgac S, Fine SW, Korkola JE, Houldsworth J, et al. Testicular mixed germ cell tumors: a morphological and immunohistochemical study using stem cell markers, OCT3/4, SOX2 and GDF3, with emphasis on morphologically difficult-to-classify areas. Mod Pathol Off J U S Can Acad Pathol Inc. 2009 Aug;22(8):1066–74.

Heidenreich A, Knüchel-Clarke R, Pfister D. [Importance of pathology for therapy planning of testicular germ cell tumors]. Pathol. 2014 May;35(3):266–73.

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