Testicular Mass in an Adult

Specimen Type:

Testis

History:

A 45 year old was found to have an asymptomatic, firm, nontender mass in his right testis during annual physical examination. No lymphadenopathy was noted. Chest x-ray and computerized tomographic scans of the abdomen and pelvis were negative for metastatic disease. Serum alpha-fetoprotein (AFP) and beta-human chorionic gonadotropin (b-HCG) were not raised. Radical orchiectomy was performed.

Pathologic Features:

The cut surface shows a well-circumscribed, pink-tan, fleshy mass measuring 3.0 cm in diameter (Fig. 2.1). It has a central hemorrhagic area with a soft, gelatinous consistency.

The touch preparation made from the freshly sectioned tumor surface shows many cell types (Fig. 2.2). The predominant cell type is intermediate-size containing amphophilic cytoplasm and a round nucleus with filamentous chromatin and inconspicuous or punctate nucleoli. The small cells are lymphocyte-like with scant cytoplasm and round nuclei with dense chromatin. Occasional larger cells, some with multiple nuclei, and granular or filamentous chromatin are also seen in the background. In tissue sections, the tumor cells are arranged in diffuse sheets (Fig. 2.3, Fig. 2.4). Apoptotic cells and mitotic figures are frequent. Many seminoferous tubules around the periphery of the tumor are completely filled with tumor cells with no evidence of spermatogenesis (Fig. 2.5).

Differential Diagnosis:

The differential diagnostic considerations include seminoma (Fig. 2.6), spermatocytic seminoma (Fig. 2.7), lymphoma (Fig. 2.8), embryonal carcinoma (Fig. 2.9), and metastases (Fig. 2.10).

Diagnosis:

Spermatocytic Seminoma

Key Features:

  • Testicular tumor of older men
  • Not reported in children, cryptorchid testis, or extra-testicular sites
  • Contains 3 cell types: abundant intermediate-size cells and scant numbers of small lymphocyte-like and larger cells
  • Does not show elevation of AFP or b-HCG
  • Does not show intratubular germ cell neoplasia; however, may show intratubular spermatocytic seminoma
  • Anaplastic variant may be confused with solid pattern of embryonal carcinoma
  • Microcystic areas resembling yolk sac tumor occasionally present
  • Focal PLAP reactivity and dot-like reactivity for low-molecular weight keratins (CAM5.2 & CK 18) seen in a small percentage of cases
  • Only 1 credible documented case of metastases reported
  • Sarcomatous transformation (spindle cell sarcoma or rhabdomyosarcoma) seen in rare cases is associated with poor prognosis

Spermatocytic seminoma is an uncommon neoplasm comprising about 5% of testicular seminomas (2). It usually arises in older men with the mean age at diagnosis of 53.6 years (range 25 to 87 years) and has not been reported in prepubertal children or adolescents (3). It lacks an ovarian homologue and does not arise in cryptorchid testis, extra-testicular sites, or in association with other germ cell tumors. Clinically, most cases are asymptomatic and the tumor may be present for years before detection. Some tumors may attain huge dimensions due to slow but relentless growth. Less than 10% of cases are bilateral with synchronous or metachronous involvement. Occasionally, the tumor is multifocal within the testis.

Anaplastic variant of Spermatocytic Seminoma: An anaplastic variant has been recently described (4). In addition to the same three cell types, this variant shows cells with large vesicular nuclei and macronucleoli, multinucleated tumor giant cells, a high mitotic index, abnormal mitotic figures, blood vessel invasion, invasion of tunica albuginea, and necrosis. Many of these features cause diagnostic confusion with embryonal carcinoma with solid growth pattern. A lack of diffuse immunoreactivity for PLAP and epithelial markers would support the diagnosis of anaplastic spermatocytic seminoma. These anaplastic changes probably represent dedifferentiation but do not seem to alter the biological behavior of the neoplasm. The prognosis of spermatocytic seminoma is excellent, with radical orchiectomy resulting in cure in most cases. The rare exceptions to this outcome are discussed below. Post-operative prophylactic radiation or chemotherpay do not offer any additional benefit and are not routinely recommended.

Metastatic potential of Spermatocytic Seminoma: There are only four reported cases of spermatocytic seminoma with metastases. Two of these were part of the original series of 6 cases reported by Masson (5). The patients reportedly succumbed to metastatic disease. However, autopsy was not done, there are no illustrations of the primary tumor or metastases in record, and the original slides are unavailable for review (2). The third case was reported by Schoborg et al in a 61 year old man who had enlarged para-aortic lymph nodes by lymphangiography, consistent with metastatic disease, at the time of orchiectomy (6). He died of widespread metastases 8 months later inspite of radiation and chemotherapy. The diagnosis of metastates in the published illustration of the lymph node biopsy has been challenged on the grounds that it shows a highly pleomorphic neoplasm that has no resemblance to the primary tumor (3). However, anaplastic changes have been described in spermatocytic seminoma (7). It is conceivable that the anaplastic change in the primary tumor in the case described by Schoborg et al was focal and overlooked and it became more prominent in the nodal metastates. The most well-documented and the only credible case of spermatocytic seminoma with metastases is that reported by Matoska et al (8). A 50 year old man with spermatocytic seminoma presented with ipsilateral retroperitoneal lymph node metastases 18 months after orchiectomy. He received radiation and combination chemotherapy but died of therapy-related complications 7 months later. The nodal metastases showed typical features of a spermatocytic seminoma. In view of this case, all spermatocytic seminomas are best regarded as potentially capable of metastases.

Sarcomatous change in Spermatocytic Seminoma: On rare occasions, the biological behavior of this unique testicular tumor with excellent prognosis is altered by sarcomatous transformation. There are 8 cases of spermatocytic seminoma with associated sarcoma published in the English literature (9-12). In four of these cases, the tumor was confined to the testis at the time of orchiectomy. Most cases seem to present with sudden onset of pain and a rapid increase in the growth rate of a testicular mass which has been present for several years. The seminomatous and sarcomatous areas are intimately admixed, with no apparent morphologic transition between the two components. The sarcomatous elements have consisted of undifferentiated spindle cells or show rhabdomyosarcomatous differentiation. The spermatocytic seminoma component has shown the usual histological features, except for an unusually high mitotic rate and frequent atypical mitotic figures in some cases (9). No other germ cell or teratomatous elements have been identified in any case. Sarcomatous change heralds an aggressive course with extremely poor prognosis. Adjuvant chemotherapy seems to have no effect in the cases in which it has been tried. Most patients die of metastases to lungs, liver, or retroperitoneum within in a few months. Interestingly, the metastases have consisted of only sarcomatous component. The histogenesis of sarcomatous elements and their relationship to the spermatocytic seminoma has been a matter of debate. The currently held view is that sarcomatous component arises by anaplastic transformation or dedifferentiation of spermatocytic seminoma (10,11). The interpretation that sarcoma is a teratomatous component in a mixed germ cell tumor is no longer supported.

Views on the pathogenesis of Spermatocytic Seminoma: The term "Spermatocytic Seminoma" was proposed in 1946 by Masson based on the resemblance of the chromatin in intermediate and small cells to that of the primary spermatocytes and spermatogonia respectively (5). It was initially suggested that SS was composed of primary spermatocytes capable of undergoing meiosis on the basis of ultrastructural similarities between the tumor cells and spermatogenic cells (13). Subsequent studies have not confirmed these findings (14). DNA ploidy studies have now shown that the small cells are diploid or near-diploid, large cells are aneuploid, and the intermediate-sized cells range from diploid to aneuploid, indicating that each cell type has its own cell division cycle and is not involved in meiosis. Haploid cells have not been demonstrated to date in spermatocytic seminoma contradicting the original proposal that the tumor is composed of primary spermatocytes which can undergo meiosis (14,15). It is now believed that histogenesis of spermatocytic seminoma is different from that of classical seminoma and other germ cell tumors; however, the exact spermatogenic cell type, from which this tumor develops, remains unknown (3,16,17).

Since the histogenesis, clinical presentation, morphological features, and the biological behavior of spermatocytic seminoma bear no resemblance to classical seminoma, the classification of this enigmatic neoplasm alongside seminoma has been questioned (3,16). An alternative term "spermatocytoma" which drops the use of the seminoma in the name,has been proposed in a new classification of germ cell tumors but it has not been widely accepted (18,19).

Follow-up: The patient was alive with no evidence of disease 4 years after orchiectomy.

References:

  1. Cummings OW, Ulbright TM, Eble JN, et al. Spermatocytic seminoma: An immunohistochemical study. Hum Pathol 1994; 25:54-59.
  2. Talerman A. Spermatocytic seminoma: A clinicopathologic study of 22 cases. Cancer 1980; 45:2169- 76).
  3. Eble JN. Spermatocytic seminoma. Hum Pathol 1994; 25:1035-42.
  4. Albores-Saavedra J, Huffman H, Alvarado-Cabrero I, et al. Anaplastic variant of spermatocytic seminoma. Hum Pathol 1996; 27:650-55.
  5. Masson P. Etude sur le seminome. Rev Can Biol 1946; 5:361-87.
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  8. Matoska J, Ondrus D, Hornak M. Metastatic spermatocytic seminoma, a case report with light microscopic, ultrastructural, and immunohistochemical findings. Cancer 1988; 62:1197-1201.
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  11. Matoska J, Talerman A. Spermatocytic seminoma associated with rhabdomyosarcoma. Am J Clin Pathol 1990; 94:89-95.
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  15. Takahashi H, Aizawa S, Konishi E, et al. Cytofluorometric analysis of spermatocytic seminoma. Cancer 1993; 72:549-52.
  16. Muller J, Skakkebaek NE, Parkinson MC. The spermatocytic seminoma: Views on pathogenesis. Int J Androl 1987; 10:147-56.
  17. Kysela B, Matoska J. Flow cytometry analysis of ploidy and proliferation activity in classical and spermatocytic seminoma. Neoplasma 1991; 38:3-11.
  18. Grigor KM. A new classification of germ cell tumors of the testis. Eur Urol 1993; 23:93-103. 19. Skakkebaek NE, Berthelsen JG, Giwercman A, et al. Carcinoma-in-situ of the testis: A possible origin from gonocytes and precursor of all types.