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  Table of Contents    
CASE REPORT  
Year : 2018  |  Volume : 61  |  Issue : 4  |  Page : 596-599
Malignant Sertoli cell tumor of the testis masquerading as seminoma with bone metastasis


1 Department of Medical Oncology, Rajiv Gandhi Cancer Institute and Research Centre, New Delhi, India
2 Department of Research, Rajiv Gandhi Cancer Institute and Research Centre, New Delhi, India
3 Department of Surgical Oncology, Rajiv Gandhi Cancer Institute and Research Centre, New Delhi, India

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Date of Web Publication10-Oct-2018
 

   Abstract 


Sex cord–stromal tumors of the testes are rare malignancies as compared to germ cell tumors. Pure Sertoli cell tumors are still rare representing <1% of testicular cancers and the malignant forms are too rare. Furthermore, the occurrence of metastasis in such cases is extremely rare with <30 cases reported in literature so far to the best of our knowledge. We present herein a case of malignant Sertoli cell tumor in a 48-year-old male who was initially misdiagnosed as seminoma based on histology and clinical presentation. Four months later, he presented with symptoms due to bony metastasis and found to have widespread metastatic disease which is a very rare presentation of Sertoli cell tumors. Diagnosis of sex cord–stromal tumor requires high index of suspicion as these tumors are most of the times misdiagnosed as germ cell tumors due to their rare incidence and atypical presentation leading to mismanagement. Timely diagnosis at an early stage can provide therapeutic benefit due to lack of well-defined treatment options at advanced stages.

Keywords: Seminoma, Sertoli cell tumor, sex cord–stromal tumor

How to cite this article:
Agrawal CR, Babu Koyyala VP, Talwar V, Tayal J, Poonia DR. Malignant Sertoli cell tumor of the testis masquerading as seminoma with bone metastasis. Indian J Pathol Microbiol 2018;61:596-9

How to cite this URL:
Agrawal CR, Babu Koyyala VP, Talwar V, Tayal J, Poonia DR. Malignant Sertoli cell tumor of the testis masquerading as seminoma with bone metastasis. Indian J Pathol Microbiol [serial online] 2018 [cited 2018 Dec 15];61:596-9. Available from: http://www.ijpmonline.org/text.asp?2018/61/4/596/242991





   Introduction Top


Sex cord–stromal tumors (SCTs) are very rare tumors of the testes. Whatever knowledge about their management we owe is on the basis of case reports and small series only. We herein report a 48-year-old patient, who was initially misdiagnosed as seminoma and presented with diffuse metastatic disease finally being diagnosed as Sertoli cell tumor of the testis. This case highlights the importance of keeping high index of suspicion, especially when age of presentation does not match with typical age-wise distribution of germ cell tumor, and early diagnosis is important as further treatment options are blurred lacking definitive strong evidence.


   Case Report Top


A 48-year-old nondiabetic, nonhypertensive male patient, who initially presented at a peripheral center in Nepal with painless progressive swelling of the left testis, was diagnosed and was treated as a case of stage IB seminoma and underwent left high inguinal orchiectomy at the same place. The diagnosis of seminoma was made on the basis of histopathological examination and normal serum tumor markers, and the patient was kept on surveillance only with serial monitoring.

After 4 months of treatment completion, he presented to our center for the second opinion due to recent onset back pain and abdominal pain. However, there was no history of precocious puberty or decreased libido, and physical examination was unremarkable; there was no evidence of gynecomastia. Investigations revealed D12 vertebral collapse with thecal compression along with marrow changes in multiple vertebral levels suggestive of metastasis on magnetic resonance imaging spine [[Figure 1] Panel d]. Computed tomography chest and abdomen [[Figure 1] Panel a-c] revealed multiple space-occupying lesions (SOLs) in the liver, left adrenal nodule with enhancing soft-tissue lesion (Panel A), subcentimetric retrocaval nodes, left para-aortic node (Panel B), and bilateral lung nodules with mediastinal lymphadenopathy (Panel C). The review of histopathological slides and blocks at our center was repeated. The tumor morphology revealed an encapsulated neoplasm with cells arranged in solid nests with clear cytoplasm and oval nuclei containing vesicular chromatin and conspicuous nucleoli [Figure 2]a and [Figure 2]b. There was brisk mitosis (5–6/10 high-power field [HPF]) with no evidence of necrosis or intratubular germ cell neoplasm. On immunohistochemistry, tumor cells expressed focal positivity for CK, CD56, and calretinin and were negative for placental alkaline phosphatase, sal-like protein 4, inhibin, CD117, and CD30 [Figure 2]c. The final histomorphologic diagnosis was confirmed to be Sertoli cell tumor of the testes – not otherwise specified (NOS) on the basis of histopathology and immunohistochemical (IHC) combined.
Figure 1: Contrast-enhanced computed tomography chest and abdomen showing multiple hypodense liver lesions with the left adrenal nodule, left para-aortic nodule, bilateral lung nodules (Panel a-c), and magnetic resonance imaging spine showing multiple spinal metastases (Panel d)

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Figure 2: Photomicrograph at low power (×10) showing closely packed tumor cells in solid nests (Panel a), at high-power (×40 showing) tumor cells with clear cytoplasm, vesicular chromatin, and round-to-oval nuclei (Panel b), and immunohistochemical at high power (×40) showing diffuse positivity for calretinin (Panel c)

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The patient underwent percutaneous kyphoplasty of involved D11, D12, and L1 vertebrae. Histopathology of vertebral tissue and fine-needle aspiration cytology from hepatic SOL both were suggestive of metastatic deposits with poorly differentiated tumor consistent with metastasis from sex cord–stromal tumor. Other routine investigations such as complete blood cell count; blood chemistry, liver function tests, and urine analysis including serum tumor markers were within normal limits while alkaline phosphatase was raised significantly. The case was discussed in multidisciplinary clinic, and the patient was advised on paclitaxel- and carboplatin-based palliative chemotherapy and zoledronic acid every 3 weekly in view of bony metastasis. However, the advanced nature of illness and palliative intent of the therapy were explained to the patient.

Sertoli cell tumors of the testis are an uncommon entity with most of the cases being benign. Such a widespread metastatic presentation is very rare with <30 cases reported in literature to the best of our knowledge, and bony metastasis is further very uncommon site. Due to the rarity of situation, well-defined guidelines and principles of treatment for such masquerader are lacking and need further large-scale studies.


   Discussion Top


SCTs are the rare testicular tumor subset representing only 4% of all testicular tumors. Leydig cell tumor is the most common testicular sex cord–stromal tumor while Sertoli cell tumor is further rare comprising only 0.4%–1.5%.[1] Most of the sex cord–stromal tumor have a benign clinical course, with 10%–20% of these having chance to behave aggressively. Malignant SCTs are rare entities, but once they occthey arry a poor prognosis due to early occurrence of metastasis.

Sertoli cells are epithelial derived from gonadal stroma that provides structural support to spermatogenic cells of the testis. Sertoli cell tumor can occur in all age groups but are most common in adult males; the average age at diagnosis being 45 years.[2] The molecular mechanisms involved in histogenesis of SCTs are unclear. Recently, reports from immunohistochemical assay and mutational analysis of exon 3 of the CTNNB1 gene by direct sequencing have shown mutation in beta-catenin, a protein involved in WNT signaling pathway. Sertoli cells of normal testis express beta-catenin and SOX-9 (a transcription factor) while the mutated SCTs show nuclear immunopositivity for beta-catenin along with cyclin D1.[3] Their typical presentation is with slowly enlarging unilateral testicular mass. There are no known risk factors, and unlike germ cell tumor, there is no definite proven association with cryptorchidism. These tumors do not exhibit specific ultrasonographic characteristics but appear as well-defined hypoechoic lesions.[4] Therefore, these tumors are most of the time diagnosed incidentally and sometimes misdiagnosed as seminoma due to very close resemblance.

Various variants of Sertoli cell tumor have been described in literature, main four among them are large cell calcifying (LCCSCT), sclerosing, sex cord with annular tubules, and tumors that are NOS. The most common type is large cell calcifying Sertoli cell tumor, first described in 1980, exhibits diffuse intratabular and extratubular calcification, and has been known to exhibit virilization and extragonadal manifestations. LCCSCTs occur with a frequency of 0.4%–1.5% among testicular tumors.[5] They are sporadic in 60% of the reported cases, but in the remaining cases, they are linked to multiple neoplasia syndromes such as Peutz–Jeghers syndrome and Carney complex.[6] The second variety, a sclerosing Sertoli cell tumor, was first described by Zuckerberg et al., in 1991.[5] This subtype, distinguished by extensive hypocellular, collagenous stroma separating clusters of Sertoli cells, is the least reported one and has questionable malignant potential with only one reported tumor showing evidence of malignant features pathologically but with no evidence of metastasis.[7] The tumor subtype without any such specific features is classified as “NOS.”

It is important to accurately document the clinical manifestations and pathologic features of these tumors, especially those that are malignant. Around 12% of these are malignant, and features associated with malignancy are as follows:[8]

  1. Large size (>5 cm)
  2. Vascular invasion
  3. Marked nuclear pleomorphism
  4. Tumor necrosis
  5. Mitotic index >5/10 HPF.


Although pathological features suggestive of malignancy are mentioned, the designation of malignancy in Sertoli cell tumor can be made certainty only in the presence of metastasis owing to their benign nature most of the times. The first and most common site of metastatic disease of patients with sex cord–stromal tumors is the retroperitoneal lymph nodes, and according to the literature, about 10%–12% of these tumors have evidence of metastasis.[9] Considering previous literature review, even higher numbers of metastatic cases were reported in past series. Dilworth et al. reported 20% metastatic disease in series of Sertoli cell tumors while Bertram reported similar numbers in Leydig cell tumors.[10] In a review of metastasizing Sertoli cell tumors of the testis by Lindegaard Madsen and Mørck Hultberg, of the total 19 cases, only 3 cases involved the bones, while the rest metastasised to the lymph nodes. Nevertheless, metastasis to the lung, brain, skin, and disseminated disease were also reported.[11]

The immunohistochemical profile of these tumors includes positivity with calretinin, SF1, CD99, melan-A, and WT-1. The tumors are also often positive for chromogranin, synaptophysin, cytokeratin AE1/AE3, S100, and vimentin. Epithelial membrane antigen shows variable positivity while inhibin positivity is seen in about 50% of tumors and 60%–70% cases shows nuclear positivity for beta-catenin. Most cases show SOX-9 nuclear expression.[12] Microscopy and IHC are definite ways of diagnosis, especially when it is confused with seminoma.

Radical inguinal orchidectomy is the hallmark treatment while retroperitoneal lymph node dissection and adjuvant radiation therapy can improve survival in localized disease.[13] In patients with limited metastatic disease, there might be some clinical benefit with metastasectomy because the responses to chemotherapy and radiotherapy are very low. Drug regimens used for germ cell tumors such as bleomycin, etoposide, and platinum and vinblastine, ifosfamide, and cisplatin are relatively ineffective with transient responses while utility of newer drugs, tyrosine kinase inhibitors, taxanes, and gemcitabine is unknown; hence, the prognosis of widespread metastatic disease remains dismal.[9]


   Conclusion Top


The rare tumors of testes are difficult to diagnose due to their resemblance to seminoma of the testes; however, poor response to chemotherapy in cases of metastatic disease leads to dismal outcome. Newer agents in treatment and validated treatment protocols for such fatal metastatic tumors need larger studies.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.

Informed Consent and Privacy

A general informed consent was taken from the patient regarding sharing of clinical data for research purpose. All the patients' information in the manuscript is anonymised and only de-identified data is used.



 
   References Top

1.
Ulbright TM, Amin MB, Young RH. Tumors of the testis, adnexa, spermatic cord, and scrotum. Amer Regist Pathol 1999; 25:149-60.   Back to cited text no. 1
    
2.
Huddart R, Hazell S, Horwich A. Rare tumors of the testis and paratesticular tissues: Textbook of Uncommon Cancer. New Jersey USA; 2012. p. 77-96.  Back to cited text no. 2
    
3.
Perrone F, Bertolotti A, Montemurro G, Paolini B, Pierotti MA, Colecchia M, et al. Frequent mutation and nuclear localization of β-catenin in sertoli cell tumors of the testis. Am J Surg Pathol 2014;38:66-71.  Back to cited text no. 3
    
4.
Kühn AL, Scortegagna E, Nowitzki KM, Kim YH. Ultrasonography of the scrotum in adults. Ultrasonography 2016;35:180-97.  Back to cited text no. 4
    
5.
Giglio M, Medica M, De Rose AF, Germinale F, Ravetti JL, Carmignani G, et al. Testicular sertoli cell tumours and relative sub-types. Analysis of clinical and prognostic features. Urol Int 2003;70:205-10.  Back to cited text no. 5
    
6.
Halat SK, Ponsky LE, MacLennan GT. Large cell calcifying sertoli cell tumor of testis. J Urol 2007;177:2338.  Back to cited text no. 6
    
7.
Coleman S, Barazani Y, Roma AA, Sabanegh E Jr. Testicular sclerosing sertoli cell tumor: A case report and review of the literature. Rev Urol 2014;16:191-3.  Back to cited text no. 7
    
8.
Shanks JH, Iczkowski KA. Non-germ cell tumours of the testis. Curr Diagn Pathol 2002;8:83-93.  Back to cited text no. 8
    
9.
Mosharafa AA, Foster RS, Bihrle R, Koch MO, Ulbright TM, Einhorn LH, et al. Does retroperitoneal lymph node dissection have a curative role for patients with sex cord-stromal testicular tumors? Cancer 2003;98:753-7.  Back to cited text no. 9
    
10.
Dilworth JP, Farrow GM, Oesterling JE. Non-germ cell tumors of testis. Urology 1991;37:399-417.  Back to cited text no. 10
    
11.
Lindegaard Madsen E, Mørck Hultberg B. Metastasizing sertoli cell tumours of the human testis – a report of two cases and a review of the literature. Acta Oncol 1990;29:946-9.  Back to cited text no. 11
    
12.
Idrees MT, Ulbright TM, Oliva E, Young RH, Montironi R, Egevad L, et al. The world health organization 2016 classification of testicular non-germ cell tumours: A review and update from the international society of urological pathology testis consultation panel. Histopathology 2017;70:513-21.  Back to cited text no. 12
    
13.
Sia SF, Dublin N, Nurul B, Wong KT. Malignant sertoli cell tumour: An uncommon testicular tumour. J Univ Malaya Med Cent 2006;9:18-21.  Back to cited text no. 13
    

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Correspondence Address:
Chaturbhuj Ramanand Agrawal
Department of Medical Oncology, Rajiv Gandhi Cancer Institute and Research Centre, New Delhi
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/IJPM.IJPM_492_17

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