Abstract
Sertoli cell tumours are very rare testicular tumours accounting for 0.4-1.5% of all testicular neoplasms. In the current report, we present a case of sclerosing Sertoli cell tumour. The histology and clinical features were compared to those of other Sertoli cell tumour subtypes in order to assess if the different subtypes really represent distinct clinical and prognostic entities. The current literature was also reviewed. Only 20 cases of sclerosing Sertoli cell tumours have been encountered. Our case, a 38-year-old man represents the 21st case. Distinction among Sertoli cell tumours is important not only histologically; sclerosing Sertoli cell tumours have a distinct clinical behaviour and prognosis, different from those of classic and large-cell calcifying Sertoli cell tumours. Pathologists and urologists should know and understand all the types of Sertoli cell tumours in order to be able to choose the correct therapeutical approach when they encounter these tumours.
Testicular sclerosing Sertoli cell tumor (SSCT) is a very rare tumour. To date, only 20 SSCTs have been reported (1-11). We, herein, report an additional case of SSCT (the third in Italy) in a 38-year-old man treated with conservative surgery. The current urological and pathological literature was reviewed. Single case reports, as well as clinical series of Sertoli cell tumours were analysed.
Case Report
A 38-year-old white male was referred to our Institution in November 2010 with a painful nodule of his right hemi-scrotum. Previous cryptorchidism and testicular traumas were not reported and the family history was negative for neoplasms. At physical examination, the gonad revealed a small hard well-demarcated nodule. No physical signs of endocrine imbalance (i.e. gynecomastia) were observed. Ultrasonography (US) revealed a small didymal dishomogeneous, hypervascular nodule (5 mm maximum diameter) at the upper third; the remaining right gonad along with the entire left gonad was normal (Figure 1). Serum tumour markers α-fetoprotein, β-human chorionic gonadotropin, placental alkaline phosphates (PALP) and lactic dehydrogenase were all in the normal range. A surgical testicular exploration was performed; the nodule was enucleated and sent to a pathologist for frozen examination. A small, hard, well-demarcated whitish nodule was bisected and frozen sections were examined by the pathologist, who was unable to establish a clear diagnosis. The urologist favoured a conservative treatment. The tumour specimen was routinely processed. For light microscopy, 4-μm tissue sections from the paraffin-embedded specimen were routinely mounted and stained with haematoxylin and eosin. Immunohistochemistry was performed using reagents from the Ventana automatic immunostainer™ for the antibodies against cytokeratins (MNF116, AE1/AE3, CK8/18, CK14 and CK5 and 6), epithelial membrane antigen (EMA), inhibin, calretinin, PALP, and also CD117, CD34, vimentin and smooth muscle actin.
Definitive pathological diagnosis revealed a SSCT-6 mm in diameter. Histologically, the tumour presented a tubular growth pattern with round to oval cells having pale and vacuolated cytoplasm and regular nuclei, all of which were embedded in an abundant fibrotic connective stroma (Figure 2A). No mitoses were present.
Immunohistochemistry was negative for cytokeratins (MNF116, AE1/AE3, CK8/18, CK14, CK5 and 6) EMA, calretinin, smooth muscle actin, PALP, CD117, CD34, and also inhibin (with positive control of intratubular Sertoli cell proliferation) (Figure 2B). Only staining for vimentin was positive. Clinically, the US performed after surgery was normal. The patient had no evidence of local recurrence at three months (Figure 3). Follow-up US is to be performed every six months.
Discussion
SSCT of the testis is a very rare tumour which was described for the first time in 1991 by Zukerberg (11). To date 20 SSCTs have been reported (1-11). The 21st case is presented here.
Primary testicular tumours originate from germ cells in 95% of cases and only 5% arise from sex cord stromal cells. According to the WHO classification (12), stromal testicular tumours are classified as Leydig, Sertoli, Sertoli-Leydig, granulosa, and mixed cell tumours. Sertoli cell tumours are very rare, accounting for fewer than 1% of all testicular tumours. Sertoli cell tumours are currently divided into three histological subtypes with different features and prognosis: a) classic tumors; b) large cell calcifying tumors; c) sclerosing tumors (12).
Classic Sertoli cell tumours affects any age (age range= 14 to 90 years) and it is usually unilateral. Systemic symptoms are encountered in 11-25% of cases due to estrogen production (feminisation) (13). Malignant classic Sertoli cell tumour with distant or lymph nodes metastasis represents approximately 10-12% of all cases.
Large-cell calcifying tumour generally affects patients younger than 20 years. It can present with multifocal (28%) and bilateral (40%) nodules, and is frequently (36%) associated with extragonadal signs and symptoms (virilization and precocious puberty), or complex syndromes (14). It can metastasize in up to 4-6% of cases.
SSCT generally affects patients in the third and fourth decade of life (age range=18 to 80 years). All cases reported are presented as a unilateral lesion (1-11). Unlike the two previously described subtypes, no extragonadal signs and symptoms due to hormone production or concomitant syndromes have been recorded (10-11). SSCT is thought to be a benign tumour. No malignant cases have been reported at the present time. At US SSCTs usually present as a well-demarcated nodule with heterogeneous density, indistinguishable from other types of testicular tumours. Macroscopically, SSCTs are generally described to be a small, well-demarcated painless lesion with firm consistency and a yellow-whitish colour. Histologically, all tumours contain Sertoli cells, which can be arranged in well-formed tubules, cords or irregular aggregates. SSCTs are characterized by extensive hypocellular, collagenous stroma separating the clusters of Sertoli cells. Differential diagnosis of SSCTs mainly includes Leydig cell tumours, carcinoid tumours and adenomatoid tumours (as in the present case).
When the overall histological features of SSCT and Leydig cell tumours are evaluated, their distinction is generally straightforward, despite some overlap in the patterns. Tubule formation is always present (at least focally) in SSCTs; additionally, SSCTs lack crystals of Reinke, which are present in 30-40% of testicular Leydig cell tumours. When the differential diagnosis is difficult, inhibin immunohistochemical stain may be of diagnostic value, with it being less consistently expressed in SSCT: a lack of inhibin staining (as in our case) argues strongly against the diagnosis of Leydig cell tumours.
Ultrasonography revealed a small hypoechoic nodule at the upper third of the right testis.
The cord-like pattern of SSCT may simulate carcinoid tumour, but the latter is generally associated with teratomatous elements and is always immunoreactive for chromogranin and other endocrine markers.
As in the present case, the tubular growth pattern and presence of intracytoplasmatic lipid vacuoles of SSCT may suggest an adenomatoid tumour, but the primary testicular location of the tumour (even if peripheral), immunohistochemical negativity for EMA, calretinin, and cytokeratins and the presence of intratubular Sertoli cell proliferation in the surrounding parenchyma helped in the differential diagnosis.
Conclusion
The identification of Sertoli cell tumours and their classification into different histological subtypes are needed now more than ever. In fact, as reported in current literature, the different subtypes have distinct clinical behaviours and prognoses (2, 5-6, 9-12, 13, 17-9). Understanding the types of Sertoli cell tumours helps pathologists and urologists to choose the correct therapeutical approach, as in our case, in which an organ-sparing approach was preferred. Currently, it is highly recommended to proceed with an organ-sparing approach for all small intraparenchymal testicular lesions until final histology is available. Secondary orchiectomy can be performed if the final pathology reveals a non stromal tumour. Nevertheless, recommendations for appropriate follow-up of Sertoli cell tumours cannot be given due to their rarity and the lack of follow-up data for most reported cases (20).
A: Histology of sclerosing Sertoli cell tumour. Tumour growth pattern demostrating tubules and cords separated by abundant connective stroma (left) (haematoxylin and eosin; ×10) and small to medium-size Sertoli neoplastic cells (right) (haematoxylin and eosin; ×40). B: Immunohistochemistry for inhibin showing positive intratubular Sertoli cell proliferation (intermingling neoplastic cells are negative) (×20).
Ultrasonography performed three months later after surgery: no evidence of recurrence.
Acknowledgements
The Authors thank to Dr. Maurizio Colecchia (National Tumour Institute, Milan, Italy) for his second opinion regarding histological diagnosis.
- Received July 31, 2012.
- Revision received September 28, 2012.
- Accepted October 1, 2012.
- Copyright© 2012 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved
