Abstract

We report a case of testicular granulosa cell tumor of the adult type in a 48-year-old man. Microscopically, the tumor consisted of round to ovoid cells with grooved nuclei that were arranged in several patterns, including microfollicular, macrofollicular, insular, trabecular, gyriform, solid, and pseudosarcomatous. These cells demonstrated strong immunopositivity with MIC2 (O13) antibody, vimentin, and smooth muscle actin and focal positivity with cytokeratin. Although this type of sex cord–stromal tumor is relatively common in the ovaries, it is still extremely unusual in the testis, and it probably represents the rarest type of testicular sex cord–stromal tumor.

Granulosa cell tumors are divided into 2 types, adult and juvenile, and both types represent a distinct group of the so-called sex cord–stromal tumors of the gonads. Testicular granulosa cell tumor of the adult type is a very rare tumor, and to date, only a small number of cases have been reported. We report an additional case of adult-type granulosa cell tumor and emphasize certain aspects of its clinical behavior, as well as the immunophenotyping characteristics of this tumor.

REPORT OF A CASE

A 48-year-old man presented with right scrotal swelling that had been present for 3 years and that had significantly increased in size in the 2 months prior to admission. The swelling was associated with pain. The patient was known to have brucellosis, which responded to medical treatment. There was no history of other systemic illnesses, sexually transmitted diseases, urinary symptoms, discharge, or weight loss. He has 2 sons and 3 daughters.

On physical examination, the patient was found to have right scrotal swelling encroaching on the epididymis and testis. This swelling measured roughly 5 cm in maximum dimension and was characterized by an irregular lobulated surface, hard consistency, absence of cough impulse, and the ability to get above it by manual examination. Initial laboratory workup showed normal blood counts, liver function tests, kidney function tests, electrocardiogram, and chest radiography. α-Fetoprotein and β-human chorionic gonadotropin values were within the accepted ranges. Antibodies against Brucella abortus and Brucella melitensis were negative. Ultrasonography showed a right testicular mass measuring 5.3 × 3.2 cm in longitudinal axis and 4.2 × 2.5 cm in transverse axis. This mass had a homogeneous appearance with central calcification. Left scrotal examination revealed normal testis and unremarkable adnexa. The radiological impression was testicular tuberculosis. The patient was put on antituberculosis treatment but showed no response; therefore, surgical exploration was undertaken. Six months after initial presentation, a right orchidectomy through a right groin incision was performed. A hard testicular mass was identified, and the operative impression was an inflammatory mass, most probably tuberculosis; however, malignancy could not be ruled out. The patient had an uneventful postoperative course and is doing well 7 months after surgery.

PATHOLOGIC FEATURES

Gross Findings

The specimen consisted of testis with attached epididymis and spermatic cord. The upper pole of the testis was occupied by an ovoid, well-defined mass that measured 5.0 × 4.0 × 4.0 cm. The mass was partially encapsulated and came in direct contact with the tunica albuginea. The cut surface was homogeneous, beige, firm, and fleshy (Figure 1). There was no evidence of necrosis or hemorrhage; however, an area of ossification (2 cm in diameter) was evident. A central round nodule with a yellow surface and firm consistency (2.5 cm in diameter) was also present. The mass did not infiltrate the adjacent testicular tissue. The gross appearance of the epididymis and spermatic cord was unremarkable.

Figure 1.

Sagital section of the testis showing a lobulated and well-encapsulated tumor with beige and finely granular cut surface.Figure 2. A, Photomicrography shows characteristic granulosa cells forming sheets and microfollicles (Call-Exner bodies). B, Ovoid nuclei with obvious intranuclear inclusions (coffee-bean nuclei) (hematoxylin-eosin, original magnifications ×100 [A] and ×400 [B])

Figure 1.

Sagital section of the testis showing a lobulated and well-encapsulated tumor with beige and finely granular cut surface.Figure 2. A, Photomicrography shows characteristic granulosa cells forming sheets and microfollicles (Call-Exner bodies). B, Ovoid nuclei with obvious intranuclear inclusions (coffee-bean nuclei) (hematoxylin-eosin, original magnifications ×100 [A] and ×400 [B])

Microscopic Findings

Histologic examination of several sections from the tumor revealed granulosa cells that grew in a wide variety of patterns, which were very commonly admixed. These patterns included gyriform, macrofollicular, insular, trabecular, solid, pseudosarcomatous, and microfollicular (Figure 2, A). The microfollicular pattern was characterized by the presence of numerous cavities simulating Call-Exner bodies. These cavities contained eosinophilic fluid and sometimes hyalinized basement membrane material. The microfollicles were separated by well-differentiated granulosa cells that contained scant cytoplasm and pale, angular, or oval, often grooved nuclei arranged haphazardly in relation to one another and to the follicles (Figure 2, B). Rare theca cells were seen scattered in between the neoplastic granulosa cells. Few mitotic figures were seen, but no abnormal forms could be detected. Necrosis was not evident in the sections examined. The central, round, yellow nodule consisted of interlacing bundles of spindle cells with cigar-shaped nuclei that contained similar grooves, but which were not as prominent as other areas, and eosinophilic cytoplasm. Mitotic figures in this spindle cell area were more numerous than the adjacent conventional patterns of granulosa cells. The area of ossification noted in the gross description consisted of several layers of osteoid material with immature calcification; this osteoid material was rimmed by cells that had features similar to the granulosa cells.

The tumor seemed to infiltrate the tunica albuginea and the rete testis, as well as the root of the epididymis.

Immunohistochemistry

Immunohistochemical studies were undertaken with formalin-fixed, paraffin-embedded material. The avidin-biotin immunoperoxidase method was used. A panel of antibodies was applied (Dako A/S, Glostrup, Denmark). There was strong and diffuse membranous positivity with MIC2 (O13-Ewing sarcoma marker) in the spindle cell area, ossified area, and in the conventional granulosa cell tumor area. In addition, staining with smooth muscle actin and vimentin showed strong and diffuse positivity in all 3 of these areas. Cytokeratin positivity was variable, but was more intense in the conventional area. Reactions for desmin, epithelial membrane antigen, S100 protein, and leukocyte common antigen were negative.

COMMENT

The term sex cord–stromal tumors refers to neoplasms containing epithelial elements of sex cord origin (Sertoli and granulosa cells) admixed with elements of mesenchymal origin (Leydig and theca-lutein cells) in varying combinations and degrees of differentiation. These tumors involve the gonads in both sexes; however, their testicular involvement is relatively uncommon and accounts for less than 4% of all testicular tumors.1 The rarest of these tumors is the adult type of granulosa cell tumor. To date, only 19 cases of adult granulosa cell tumor of the testis have been reported in the English literature (Table). In 1952, Laskowski2 reported the first case of an adult granulosa cell tumor in a 20-year-old patient. Since then, few case reports and short series have been published.3–12 The most comprehensive of these studies was reported by Jimenez-Quintero et al.12 These authors reviewed 7 cases of adult granulosa cell tumor and concluded that this group of tumors represents a rare and slow-growing tumor that can potentially cause distant metastasis, which might take place several years after initial presentation. This characteristic clearly warrants long-term follow-up.12 

Summary of Reported Cases of Testicular Granulosa Cell Tumor of the Adult Type*

Summary of Reported Cases of Testicular Granulosa Cell Tumor of the Adult Type*
Summary of Reported Cases of Testicular Granulosa Cell Tumor of the Adult Type*

The current case is unique because of the following features: first, the duration of the presentation of the mass was relatively long. Second, the tumor showed dual differentiation into a classic granulosa cell component with different patterns and a central component in which there was mesenchymal differentiation into smooth muscle and osteoid components. One can argue that this spindle cell component is truly another pattern of granulosa cell tumor (pseudosarcomatous pattern) or it might represent a fibrothecomatous component, taking into consideration that most granulosa cell tumors have at least some theca cells focally. Such dual differentiation has been described previously.12 

The third feature is the expression of MIC2 (O13) antibody by immunohistochemistry. Loo et al13 performed a comprehensive study of the immunohistochemical labeling of granulosa cell tumors and other sex cord–stromal tumors. They found that 69% of granulosa cell tumors and 67% of Sertoli-Leydig tumors expressed the MIC2 (O13) antibody in a membranous fashion, while less than 25% of the carcinomas and 0% of other sex cord–stromal tumors expressed MIC2 (O13) antibody.13 In addition, Loo et al found that granulosa cell tumors react positively with vimentin and smooth muscle actin, but have a variable reaction with cytokeratin, which is consistent with the findings in the current case.

Another argument is that since this mass has a focal heterogeneous area with some stromal changes, why not consider it a sex cord–stromal tumor, unclassified? Our response to this question is that the majority of the tumor (>80%) consisted of unequivocal granulosa cells with the usual patterns seen in classic adult-type granulosa cell tumor. Even in the areas that looked heterogeneous, we noted significant numbers of granulosa cells with the classic nuclear grooves. In addition, O13 staining was diffusely positive in all of the tumor areas, including the area that looked heterogeneous. Finally, the term sex cord–stromal tumor, unclassified includes a group of neoplasms in which a predominant pattern of testicular or ovarian differentiation is not clearly recognizable,14 which is not true of the findings in the current case.

In summary, adult granulosa cell tumor is considered a very rare testicular tumor. It does have the potential to metastasize, even a long time after the initial presentation, and it is usually associated with a long survival period.11,12 By immunophenotyping, membranous staining with MIC2 (O13) is helpful in differentiating this tumor from other gonadal tumors.

Acknowledgments

We thank David G. Bostwick, MD, and F. K. Mostofi, MD, for their insights.

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