CASE OF THE WEEK
Editors: Francesca Khani (Frk9007@med.cornell.edu) and Mahmut Akgul (akgulm@amc.edu)
2022-02/January 10
Contributors: Maria F Arisi and Li Li
A man in his 30’s presented with 3 days of abdominal pain, nausea, and vomiting. CT imaging revealed a 14 cm ill-defined right retroperitoneal mass, a 2 cm left pulmonary nodule, and a 10 cm right testicular mass. Serum alpha-fetoprotein (AFP) was elevated, and beta-HCG and LDH were normal. He underwent biopsy of the retroperitoneal mass.
Quiz
What is the correct diagnosis?
a. Seminoma
b. Hepatoid Teratoma
c. Metastatic mixed germ cell tumor
d. Metastatic hepatocellular carcinoma
e. Urothelial carcinoma
1. c
Metastatic mixed germ cell tumor
This young man presented with a quickly growing mass in the retroperitoneum and testicle, and elevated alpha-fetoprotein. A small biopsy of the mass showed multiple histologic patterns, including microcystic, solid and focal hepatoid-like cytology patterns with intracytoplasmic eosinophilic (hyaline) globules (Figure 1A and B). Perivascular growth pattern, but without Schiller-Duval bodies, was identified (Figure 1C). The biopsy also showed an area of glandular elements with primitive cell features (Figure 1D).
Most of the tumor components were positive for AFP (not shown), glypican-3, GATA3, and CDX2 (Figure 2A-C), but negative for OCT3/4. The morphologic and immunophenotypic features support the diagnosis of yolk sac tumor (YST). The small portion of the tumor with glandular features stained with OCT3/4, CD30, (Figure 2E-F), and CK7 (not shown) consistent with embryonal carcinoma (EC). The diagnosis in this case is therefore a metastatic mixed germ cell tumor consisting of cytokeratin AE1/AE3 positive YST and EC components. Endometrioid-like YST can mimic embryonal carcinoma, but the immunostaining pattern does not support this diagnosis.
Seminoma occurs in young patients and is the most common testicular germ cell tumor. Seminoma typically shows pale and glycogen-filled cells. While this patient’s tumor had some positive OCT3/4 staining, it is inconsistent with seminoma component due to negative c-Kit staining (not shown). The hemorrhagic area was also negative for hCG immunostaining (not shown) and no elevated serum beta-HCG was detected; therefore, no choriocarcinoma is present in this mixed germ cell tumor.
There is no teratoma and/or somatic malignancy component identified due to the limitation of submitted tissue. Accurate evaluation is needed in the primary site (testicle) and metastatic tumor especially if the patient underwent chemotherapy before the surgical resection. Somatic malignancy from teratoma or other mixed germ cell tumor component is commonly seen in the metastatic mixed germ cell tumor with post-chemotherapy.
The solid tumor component had hepatocyte like cytology with intercellular eosinophilic globules, and on immunostain was positive for CK7, glypican 3, and AFP, but negative for hepatocyte differentiation marker (HepPart-1 and Arginase-1), and without CK19+ ductule and bile canalicular-like structures. This supports the diagnosis of YST but not hepatoid YST. Hepatocellular carcinoma (HCC) could be on the differential. However, unlike HCC, this mass had no Mallory-Denk bodies and was negative for HepPar-1 and Arginase-1. Additionally, the overall clinical picture and young patient age was inconsistent with metastatic HCC. Rare hepatoid teratoma is a potential mimicker of a hepatoid YST, but morphology and immunostains do not support this entity.
Lastly, the transcriptional factor GATA3 nuclear staining is not specific for urothelial carcinoma, and it can be seen in YST and other germ cell tumor components. Negative p63 staining (not shown), and lack of the morphology of urothelial carcinoma was again inconsistent with this diagnosis.
In summary, this patient had a metastatic mixed testicular germ cell tumor with YST and embryonal carcinoma components. The hepatoid cytology features of YST introduced interesting differentials. Additional workup of this patient’s lung nodule, testicular mass and metastatic mixed germ cell tumor would be warranted to classify the testicular tumor and for accurate clinical staging.
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Maria F Arisi
Thomas Jefferson University
maria.arisi@jefferson.edu
Li Li
Thomas Jefferson University
li.li@jefferson.edu
@lili_PathMSH
Testis
mixed germ cell tumor, yolk sac tumor, embryonal carcinoma