Diagnosis 2: Metastatic germ cell tumor showing mature teratoma (cartilage and cysts lined by intestinal epithelium) (subcarinal lymph node and right lower lobe lung nodule)

Testicular Germ Cell Tumors and Metastases

Introduction: These tumors show the spectrum of differentiation of germ cells of the seminiferous tubules. Tumors may show one type of differentiation or combinations of different types. Similar tumors arise in the mediastinum from aberrant totipotential cells. All are characterized by an abnormality of chromosome 12--either a deletion in the long arm or an isochromosome with 2 short arms [1]. They have been classified as follows.

Classification of Testicular Germ Cell Tumors [1]

Seminoma--30-40% of testicular tumors

Non-seminomatous germ cell tumor (NSGCT)*--patterns resemble embryonal development

*When combinations exist, each component should be listed and quantified.

Clinical features: These tumors are rare but constitute the most common tumor in men between ages 25 and 29. Seminoma has a peak incidence at age 40; NSGCT peaks at age 30. Risk factors include cryptorchism. Patients present with a testicular mass; metastases to the retroperitoneum, lung, or mediastinum; or gynecomastia. Tumor spreads lymphogenously to retroperitoneal and mediastinal nodes and the left supraclavicular node (Virchow node). Hematogenous metastases usually go to lungs, liver, brain, or bones. Therapy consists of orchiectomy and high ligation of the spermatic cord. Treatment for seminomas includes additional radiation to the retroperitoneum. For NSGCT, therapy may include retroperitoneal lymphadenectomy, radiation ± chemotherapy, and excision of metastases [1].

Prognosis: Poor prognostic features of stage I disease include extension of tumor through the testicular capsule, Leydig cell hyperplasia away from tumor, and vascular invasion. Treatment of stage I (no metastases) or II (metastases to nodes only) seminoma results in cure in 95% of cases. Treatment of NSGCT (except choriocarcinoma) results in cure in 60-95% of cases depending on stage [1-3]. Choriocarcinoma is a fatal disease [1].

Monitoring the patient: ß-human chorionic gonadotropin and/or alpha-fetoprotein serum levels are elevated in about 75% of patients with NSGCT, drop with treatment, and usually, but not always, rise with recurrence [2]. A 2-y disease-free interval indicates cure in about 90% of patients [1].

Histopathology of other germ cell tumors


NSGCT--Embryonal carcinoma: Patterns consist of sheets, papillae, or glands. Cells have increased N/C ratios, nuclear and cellular pleomorphism, large and multiple nucleoli, and nuclear crowding. Hemorrhage and necrosis are common [1].

Immature and mature teratomas: Tumors are usually multicystic. They show varied types of differentiation along 2 or more germ lines. Nerve, cartilage, and epithelium are the most frequent tissues seen. If all components are well-differentiated and benign-appearing, the tumor is designated mature. If some or all are not, it is designated immature [1].

Teratoma with malignant transformation: Non-germ cell malignant components may arise in primary or metastatic germ cell tumors. These may be sarcomas or carcinomas. However, marked atypia of epithelial or stromal cells post-chemotherapy is not diagnosed as malignant unless invasion or large areas of atypical cells are present. Further, despite atypia of chondroid elements, patients rarely die of chondrosarcoma; in contrast, death from rhabdomyosarcoma has been reported [4].

Choriocarcinoma: These largely hemorrhagic and necrotic tumors are composed of syncytiotrophoblastic and cytotrophoblastic cells mixed together [1].

Yolk sac tumor (endodermal sinus tumor): This pattern occurs in up to 80% of NSGCT. It has four characteristic features: 1) the Schiller-Duval body, which is characterized by a ring of epithelial cells around a small, central vessel, 2) hyaline cytoplasmic or extracellular droplets, 3) microcysts, and 4) solid areas [1].

Histology of metastases in lung: Following treatment, metastases can be completely necrotic or fibrotic, can have an appearance similar to the primary tumor, or can show a different type of differentiation (although presence of a pattern in the metastasis that was not seen in the primary tumor may be a result of incomplete sampling of the primary tumor). Metastases often show a pattern of mature teratoma even though the primary is predominantly of another type. Typical components of metastases of mature teratoma are cysts lined by gastrointestinal-type epithelium or by non-keratinizing squamous epithelium, and foci of smooth muscle, lymphoid tissue, cartilage, or striated muscle. Some metastases with cartilage and epithelium can resemble benign hamartomas of the lung. Others can be mistaken for primary pulmonary teratomas if the history of primary testicular tumor is not known [5].

Resection of metastases: The histologic appearance of metastases resected after chemotherapy predicts prognosis and guides further therapy. If metastases contain only mature tissues or necrotic tumor, no further therapy is required. Prognosis is good. Presence of undifferentiated tumor, carcinoma, or sarcoma indicates the need for further therapy; prognosis is guarded [3,4,6,7]. Interestingly, the DNA content of mature teratoma in metastases is similar to that of the primary tumor. Also, a histologic marker of proliferating cells (proliferative cellular nuclear antigen) often labels the epithelial cells at a high rate. Further, alpha-fetoprotein, ß-hCG, and CEA are found in fluids of the tumor cysts but not in the serum. These features of the metastatic tumors suggest that growth and malignant potential are still present and that these mature metastases, which do not respond to chemotherapy [6], should be removed, especially when enlarging [3,8]. Possible causes of the maturation of tumor in the metastases include 1) death of undifferentiated malignant cells leaving mature cells, 2) induction of maturation by therapy, or 3) natural progression of the disease [9].


1. Rosai J. Ackerman's Surgical Pathology: Chapter 18, Male reproductive system. 8th ed., Chicago,Mosby Co. 1996, 1265-1295.

2. Ulbright T, Roth L. A pathologic analysis of lesions following modern chemotherapy for metastatic germ-cell tumors. Pathol Annu 1990; 25 (Pt 1):313-340.

3. Debono D, Heilman D, Einhorn L, Donohue J. Decision analysis for avoiding postchemotherapy surgery in patients with disseminated nonseminomatous germ cell tumors. J Clin Oncol 1997; 15:1455-1464.

4. Ulbright T, Loehrer P, Roth L, Einhorn L, Williams S, Clark S. The development of non-germ cell malignancies within germ cell tumors. A clinicopathologic study of 11 cases. Cancer 1984; 54:1824-1833.

5. Moran C, Travis W, Carter D, Koss M. Metastatic mature teratoma in lung following testicular embryonal carcinoma and teratocarcinoma. Arch Pathol Lab Med 1993; 117:641-644.

6. Panicek D, Toner G, Heelan R, Bosl G. Nonseminomatous germ cell tumors: enlarging masses despite chemotherapy. Radiology 1990; 175:499-502.

7. Madden M, Goldstraw P, Corrin B. Effect of chemotherapy on the histological appearances of testicular teratoma metastatic to the lung: correlation with patient survival. J Clin Pathol 1984; 37:1212-1214.

8. Sella A, El Naggar A, Ro J, Dexeus F, Amato R, Lee J, Finn L, et al. Evidence of malignant features in histologically mature teratoma. J Urol 1991; 146:1025-1028.

9. Hong W, Wittes R, Hajdu S, Cvitkovic E, Whitmore W, Golbey R. The evolution of mature teratoma from malignant testicular tumors. Cancer 1977; 40:2987-2992.

Clinical summary

Comments: mw6825@itsa.ucsf.edu

Table of Contents

Last revised 5/10/97

Copyright 1997 Martha L. Warnock. All rights reserved.