Case of the Month ...

Fig 1

Case History

A 28 year old male presented with worsening abdominal and back pain. Physical examination was unremarkable. A computerized tomography scan demonstrated an 8 x 6.5 cm left-sided, heterogeneous retroperitoneal mass above the level of the aortic bifurcation and below the left renal vein (Figure 1). The mass was well circumscribed and central areas of necrosis were noted. A small amount of pelvic ascites was also seen. Laboratory findings revealed an alpha- fetoprotein level of 22,576 ng/ml. A CT guided fine-needle aspiration biopsy of this retroperitoneal mass was performed.

Diagnosis & Discussion
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Cytologic Findings: The smears were cellular and revealed cohesive sheets of tumor cells, some forming papillary groupings with tumor cells surrounding capillaries. In addition, a necrotic background with tumor diathesis was appreciated (Figure2, nodified Giemsa stain). The tumor cells were round to polygonal in shape with increased nuclear to cytoplasmic ratios, moderately pleomorphic nuclei and a moderate amount of basophilic cytoplasm (Figure 3, modified Giemsa stain). Intranuclear and intracytoplasmic vacuoles were seen. An Ultra-Fast Papanicolaou (UFP) stain revealed enlarged nuclei with multiple prominent nucleoli (Figure 4). A helpful cytologic feature was the presence of abundant metachromatic basement membrane-like material in the background (Figure 5, arrow, modified Giemsa stain).


Histologic Findings: A cell block preparation of the aspiration biopsy revealed predominantly microcystic areas (Figure 6, hematoxylin and eosin stain) with a focal solid pattern (Figure 7). A Schiller Duval’s body, a pseudorosette pattern composed of tumor cells surrounding capillaries (Figure 6, arrow, Figure 8, hematoxylin and eosin) was readily identified. Immunohistochemical stains showed strong positivity for AFP (Figure 9), CAM 5.2, AE1/AE3; and negativity for HCG, CD30, PLAP, CK 7, CK 20, EMA, and Vimentin. The patient subsequently underwent a testicular ultrasound that revealed a 3 x 4 x 4 mm left testicular mass and a left radical orchiectomy was performed. An 8 x 5 x 4 cm well-circumscribed, tan-firm mass was identified grossly (Figure10). Histologically, a mature teratoma with cysts lined by glandular epithelium of the small intestinal type and stroma were seen (Figure 11). He subsequently received chemotherapy with a decrease of his AFP level to 3,000 ng/ml.

Discussion: Carcinoma of the testis is the most common malignancy in men aged 15 to 35 years, with an estimated 8980 new cases and 360 deaths expected in 2004. Primary extragonadal germ cell tumors in the retroperitoneum are uncommon and a careful examination of the testis is indicated for detection of a primary testicular tumor (1). Image guided aspiration biopsy has been shown to be useful in the diagnosis of retroperitoneal germ cell tumors (2).

The diagnosis in this patient was metastatic yolk sac tumor to the retroperitoneal lymph nodes from a mature teratoma of the testis. The finding of histologic discrepancies between the primary tumor of the testis and the metastases has been described (3). The differential diagnosis of a retroperitoneal mass of unknown primary includes germ cell tumor, poorly differentiated carcinoma, lymphoma, melanoma, and sarcoma. Among the germ cell tumors, it is important to distinguish a seminomatous germ cell tumor from a non-seminomatous germ cell tumor because of the high radiosensitivity of seminomas. On aspiration biopsy, smears from seminomas show a biphasic pattern composed of dyscohesive, round to ovoid shaped large cells with abundant eosinophlic, granular cytoplasm with variably prominent vacuoles and one to several nucleoli admixed with smaller lymphoid cells. The cytoplasm of the tumor cells is delicate and often dispersed in the background of the smears leading to the classically described tigroid pattern. Seminomas are positive for anti-placental alkaline phosphatase (PLAP), vimentin, and OCT4 (4); but usually negative for cytokeratin, AFP, CEA, CD30, and EMA. The non-seminomatous tumors include embryonal carcinoma, yolk sac tumor, choriocarcinoma, and teratoma. The smears of embryonal carcinoma show cohesive sheets of tumor cells forming solid, papillary or glandular patterns. The tumor cells have ill-defined cell borders, high nuclear to cytoplasmic ratios and light basophilic granular cytoplasm. The nuclei are irregular with coarse chromatin and usually contain multiple nucleoli. Some of the clusters may contain delicate branching capillaries. The background in embryonal carcinoma is usually necrotic with scattered inflammatory cells. Immunostaining for Ki-1 (CD30) is helpful as embryonal carcinomas are positive and yolk sac tumors are commonly negative. Yolk sac tumors show cells arranged in cohesive sheets, papillary groupings or acinar arrangements (5). The tumor cells are moderately pleomorphic with enlarged hyperchromatic ovoid nuclei with coarse chromatin and a moderate amount of cytoplasm (5). Vacuoles can be noted in the cytoplasm and nucleus. Globular or linear deposits of metachromatic intercellular material may also be present in some cases, corresponding to the basement membrane-like material encountered in histologic sections (6). Intracytoplasmic hyaline globules, positive for PAS and diastase resistant, are also described (7). Immunohistochemically, yolk sac tumors are positive for alpha feto-protein. Choriocarcinomas consist of two cell types: the syncytiotrophoblast and the cytotrophoblast. Syncytiotrophoblasts are characterized cytologically by large multinucleated neoplastic cells, with abundant basophilic and vacuolated cytoplasm that contains multiple hyperchromatic, irregularly shaped nuclei. The cytotrophoblast shows well defined cell borders with a pleomorphic nucleus and scanty eosinophilic cytoplasm. Staining for human chorionic gonadotrophin is most useful with the syncytiotrophoblastic component positive in the majority of cases. Focal PLAP positivity is seen in roughly 50% of cases and unlike seminomas, embryonal carcinomas and yolk sac tumor a significant proportion (46%) satin with epithelial membrane antigen, mainly in syncytiotrophoblastic cells (8). Teratomas are composed of a mixture of cell types, including elongated epithelioid cells, mesenchymal cells and many large, naked amorphous nuclei with a homogeneous chromatin pattern. Mature appearing ganglion cells, fragments of bone and glandular or squamous epithelial cells can also be seen.

As seen in this case and noted above, metastatic involvement with discrepant histologic diagnoses may be seen with a mature teratoma in the testis and a metastasis showing a nonteratomatous component. One hypothesis suggests this to be due to the development of a precursor component in the testes that metastasizes but later differentiates in the testis to form a teratoma. At the metastatic site, the precursors remain unchanged leading to histologic discrepancies (9). Other studies suggest that a mature teratoma may undergo transformation into other malignant germ cells elements at distant sites (10).


  1. Scholz M, Zehender M, Thalmann GN, Borner M, Thoni H, Studer UE. Extragonadal retroperitoneal germ cell tumor: evidence of origin in the testis. Ann Oncology 13:121-4, 2002.
  2. Ustun M, Heilo A, Fossa S, Aass N, Berner. Ultrasound-guided fine needle cytology of retroperitoneal masses in patients with malignant germ cell tumours: diagnosis and therapeutic impact. European Urology. 42:221-8, 2002.
  3. Dixon FJ, Moore RA. Testicular tumors: a clinicopathologic study. Cancer 6:427-454, 1953.
  4. Cheng L. Establishing a germ cell origin for metastatic tumors using OCT4 immunohistochemistry. Cancer 101:2006-10, 2004.
  5. Afroz N, Khan N, Chana RS. Cytodiagnosis of yolk sac tunor. Indian Journal of Pediatrics 71:939-942, 2004.
  6. Yang GCH, Hwang SJ, Yee HT. Fine-needle aspiration cytology of unusual germ cell tumors of the mediastinum: Atypical Seminoma and Parietal Yolk Sac Tumor. Diagnostic Cytopathology 27:69-74, 2001.
  7. Dominguez-Franjo P, Vargas J, Rodriguez-Peralto JL et al. Fine needle aspiration biopsy findings in endodermal sinus tumors. A report of four cases with cytologic, immunocytochemical and ultrastructural findings. Acta Cytologica 1993;37:209-215.
  8. Niehans GA, Manivel JC, Copland GT, Scheithauer BW, Wick MR. Immunohistochemistry of germ cell and trophoblastic neoplasma. Cancer. 62: 1113-1123, 1988.
  9. Ulbright TM, Amin MB, Young RH. Germ cell tumors: Nonseminomatous. Atlas of Tumor Pathology, 3 rd series, Fascicle 25. Washington, D.C.:Armed Forces Institute of Pathology, 1997.
  10. Heidenreich A, Moul JW, McLeod DG, Mostofi FK, Engelmann UH. The role of retroperitoneal lymphadenectomy in mature teratoma of the testis. Journal of Urology. 157:160-3, 1997.

Acknowledgement: This case is contributed by Drs. Hua Chen, Aylin Simsir, and Joan Cangiarella from New York University , New York , NY.

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