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Year : 2016  |  Volume : 59  |  Issue : 3  |  Page : 351-354
Primary thymic mediastinal seminoma with florid granulomatous reaction

1 Department of Pathology and Laboratory Science, Armed Forces Medical College, Command Hospital, Pune, Maharashtra, India
2 Department of Pathology and Laboratory Science, Command Hospital, Pune, Maharashtra, India
3 Department of Radiodiagnosis and Imaging, Armed Forces Medical College, Command Hospital, Pune, Maharashtra, India

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Date of Web Publication10-Aug-2016


Primary mediastinal seminomas are rare tumors. Morphologically, they can be associated with secondary changes in the form of thymic remnants, cystic change, epithelioid granulomas, abundant fibrosis, and syncytiotrophoblast like cells. Ours was an interesting case where a 17-year-old adolescent male presented with anterior mediastinal mass. Fine needle aspiration and trucut biopsy of the mass favored tuberculosis; however, he did not respond to antituberculosis treatment regime. He was subjected to video-assisted thoracoscopic surgery and the histopathological examination along with supportive immunohistochemistry of the mass revealed scattered seminoma cells which were being masked by extensive granulomatous reaction. The aim of this article is to report a case of primary mediastinal thymic seminoma in a young male associated with extensive granulomatous reaction masking the neoplastic population of cells leading to erroneous diagnosis on small biopsy.

Keywords: Extragonadal germ cell tumor, mediastinal mass, mediastinal seminoma

How to cite this article:
Gupta D, Rath A, Rathi KR, Singh G. Primary thymic mediastinal seminoma with florid granulomatous reaction. Indian J Pathol Microbiol 2016;59:351-4

How to cite this URL:
Gupta D, Rath A, Rathi KR, Singh G. Primary thymic mediastinal seminoma with florid granulomatous reaction. Indian J Pathol Microbiol [serial online] 2016 [cited 2022 Jan 26];59:351-4. Available from: https://www.ijpmonline.org/text.asp?2016/59/3/351/188113

   Introduction Top

Germ cell tumors (GCTs) occur primarily in the gonads; however, they have a predilection to arise from midline structures such as mediastinum, retroperitoneum, pineal gland, and sacral region forming a group designated as extragonal GCTs.[1] Anterior mediastinum is the most common site for primary extragonadal GCTs. Primary mediastinal seminoma is usually located in the anterior mediastinum and affects young male. It constitutes 25% of all extragonadal GCTs.[2] Seminoma is the second most common type of GCT of the mediastinum after mature teratoma.[3] The diagnosis can be made on needle biopsy alone unless the tumor is masked by secondary changes in the form of florid granulomatous reaction as was seen in our case. We hereby report an interesting case of anterior mediastinal tumor associated with exuberant granulomatous reaction in a young male leading to delay in diagnosis.

   Case Report Top

A 17-year-old young male presented with chest pain, unquantified weight loss, and low-grade fever of 1-month duration. He did not have any history of cough, dyspnea, syncope, and palpitations. He did not have a history of any testicular neoplasm. General physical and systemic examination were within normal limits. On admission, the vital parameters were as follows: Body temperature - 99.8 F, pulse rate - 88/min, and blood pressure - 110/70 mmHg. There was no lymphadenopathy, no pallor, or raised jugular venous pressure. Baseline hematological and biochemical parameters were normal. His erythrocyte sedimentation rate was mildly raised to 22 mm/h (normal range 1–20 mm/h).

X-ray chest done (posterioranterior view) [Figure 1]a showed a mediastinal contour abnormality in the region of the pulmonary bay. Computed tomography (CT) scan [Figure 1]b done on subsequent day revealed heterogeneously enhancing lobulated well-defined mass in the anterior mediastinum closely abutting the aorta and pulmonary artery without any obvious invasion. The mass measured maximum of 6 cm in the longest dimension and did not show any calcification. There were no focal lesions noted in both lungs. Ultrasound-guided fine needle aspiration cytology (FNAC) of the mass was planned along with needle biopsy. Leishman and Giemsa stained slides of mediastinal mass FNAC revealed epithelioid cell granulomas in a background of mature lymphocytes. Hemotoxylin and eosin (H and E) section of trucut biopsy also showed numerous coalescing, nonnecrotizing granulomas. Special stain Ziehl–Neelsen done on the aspiration and biopsy slides were both negative for acid-fast bacilli. No neoplastic cell population was noted on the small biopsy. Based on histomorphological and clinical findings, a differential of tuberculosis or sarcoidosis was considered. His serum lactate dehydrogenase was 550 U/L (normal range is 200–400 IU/L), serum calcium, and serum angiotensin-converting enzyme levels were within normal limits. The patient was started on antitubercular (ATT) treatment emperically. The patient received antitubercular treatment (ATT) for nearly 4 months; however, he did not show any clinical improvement. A radiological evaluation with contrast enhanced CT (CECT) of the chest, revealed a well-defined heterogeneously enhancing mass lesion with multiple nonenhancing areas in the prevascular space of anterior mediastinum, measuring 46 mm × 36 mm × 62 mm in size. Posteriorly and laterally, the mass was surrounded by the anterior segment of the left upper lobe of the lung and anteriorly, it was abutting the anterior chest wall. Few subsegmental patchy areas of consolidation and adjacent ground glass opacities were also noted in the subpleural location of anterior, lateral, and posterior basal segments of left lower lobe and medial basal segment of the right lower lobe of lungs. Because the persistence of mass in the mediastinum with no regression, he was reevaluated clinically for alternate possibilities as well. His serum beta-human chorionic gonadotropin was 1.48 mIU/mL (normal <5.00 mIU/mL) and serum alpha-fetoprotein (AFP) was 1.00 ng/mL (normal <10.00 ng/mL). The ultrasound of the scrotum was unremarkable.
Figure 1: (a) Frontal chest radiograph showing a mildly lobulated mediastinal mass at the region of pulmonary bay. (b) Contrast enhanced computed tomography chest shows a heterogenous well-defined mass in the anterior mediastinum, not invading the great vessels

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A video-assisted thoracoscopic surgery was planned, and the mediastinal mass was completely excised and submitted for histological examination.

On gross examination, the mass was globular, firm and congested and it measured 9 cm × 5 cm × 4 cm. Cut surface showed multiple gray, white nodules largest measuring 6 cm × 5 cm × 3 cm [Figure 2].
Figure 2: Gross specimen shows nonencapsulated multinodular tan-brown ovoid mediastinal mass with slightly irregular to sharp peripheral margins; the cut surface is solid and rubbery firm in consistency

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Microscopic examination of the hematoxylin and eosin (H and E) sections from the mass showed nodular lymphoid aggregates separated by fibrous bands. The periphery of these nodules showed normal thymic tissue connoting the origin of this mass. There was effacement of thymic parenchyma in the nodules by numerous coalescing noncaseating granulomas composed of epithelioid histiocytes and scattered multinucleated giant cells [Figure 3]a.
Figure 3: (a) Microscopic examination of the mediastinal mass (×10) shows florid discrete to confluent granulomas. (b) Higher magnification shows tumor cells interspersed and rimming these granulomas. The malignant cells appear to be of large polyhedral shape with abundant thin cytoplasm and round to oval vesicular nucleus with coarse clumped chromatin encircling clear areas in nucleoplasm, prominent nuclear membrane, and skein-like prominent nucleolus. (c) Immunostaining with CD117 shows strong membranous positivity in the seminoma cells

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On higher magnification, we found small clusters of malignant cells interspersed between and rimming the granulomas. These malignant cells appeared to be of large polyhedral shape with abundant thin cytoplasm and round to oval vesicular nucleus with coarse clumped chromatin encircling clear areas in the nucleoplasm, prominent nuclear membrane, and skein-like prominent nucleolus [Figure 3]b. The mitotic activity was 1–2/10 hpf, and there was no necrosis seen. The tumor cells showed periodic acid Schiff cytoplasmic positivity and on immunostaining were strongly positive for CD117, placental alkaline phosphatase (PLAP) and D2-40, weakly positive for pan-cytokeratin and negative for leukocyte common antigen, CD20, CD3, CD5, AFP, epithelial membrane antigen, CD15, CD30, ALK, human melanoma black-45, and CD68 [Figure 3]c.

We have used PLAP, CD117, and D240 positivity and a large number of negative markers to confirm seminoma and exclude other pathological entities showing similar morphological features. Although Oct3/4 nuclear positivity and SOX2 negativity are more specific for seminoma, we were unable to perform these as these markers are not available at our center.

Based on these histomorphological and immunohistochemical features, a definite diagnosis of primary thymic mediastinal seminoma was given.

Our patient received chemotherapy comprising bleomycin, etoposide, and cisplatin (BEP; bleomycin 18 U/m 2 intravenously, etoposide 100 mg/m 2 intravenously, cisplatin 20 mg/m 2 intravenously) 3 weekly for three cycles.

The patient tolerated the chemotherapy well and is presently asymptomatic 1 year after completion of his therapy. He is on out patient department (OPD) follow-up at the malignant disease and treatment center (MDTC) of our tertiary care hospital.

   Discussion Top

The most common tumors found in the anterior mediatinal compartment are of thymic, lymphatic or germ cell origin. More rarely masses associated with aberrant thyroid or parathyroid are found. GCTs of the mediastinum can be benign (mature teratoma) or malignant including seminomas, and nonseminomatous GCTs such as embryonal carcinoma, immature teratoma, yolk sac tumor, choriocarcinoma, or mixed GCTs.

Some debate exists between the origin of seminomatous and nonseminomatous GCTs. According to one theory, they develop from extragonadal yolk sac germinal cells whose normal migration along urogenital ridge to gonads was halted in the mediastinum.[4] Another theory suggests that they originate in the thymus due to its maldevelopment. Mediastinal seminoma is often associated with the thymus as was seen in our case and has been reported by Knapp et al.[5]

Primary mediastinal seminoma is rare but well-defined disease which commonly affects young men.[6] The diagnosis should be considered after exclusion of primary testicular tumor. The patients present with dyspnea, cough, fever, weight loss, and rarely superior vena cava syndrome.[7] In most cases, these are detected incidentally, the patients being asymptomatic.

Our patient presented with a history of chest pain, weight loss, and low-grade fever.

The histomorphological features are usually indistinguishable from its gonadal counterpart. There are few case reports of mediastinal seminoma accompanied by secondary changes which may conceal the actual diagnosis as was seen in our case. These changes include reactive follicular hyperplasia, large cysts, epithelioid granulomas, and fibrosis.[8] Our case was a diagnostic dilemma on microscopic examination as there were only focal areas showing neoplastic cells which were being masked by inflammatory cells along with florid granulomatous reaction.

Mediastinal seminomas need to be differentiated from metastatic melanoma, thymoma, thymic carcinoma, Hodgkin disease, and anaplastic large cell lymphoma by use of ancillary techniques like immunohistochemistry (IHC), especially if the morphology of the original tumor is getting obscured.

Many of these entities have also been reported with exuberant granulomatous reaction.[9] The complete panel of antibodies was used for IHC to discern the phenotype of the neoplastic cells. The diagnosis of the present case was established after IHC showed tumor cells to be strongly positive for PLAP, CD117, and D2-40. D2-40 gives diffuse membrane positivity in pure seminoma as well as positive staining in embryonal carcinoma hence embryonal carcinoma cannot be excluded by this marker. Besides D2-40 is not specific marker for Germinoma as it shares expression in mesothelial cells, lymphatic endothelium, and its neoplasm. D2-40 is also positive in adenxal tumors of the skin, adrenal cortical tumors, synovial sarcoma, embryonal carcinoma, etc., thus limiting its utility as a differential diagnostic marker in germ cell tumors as compared to Oct3/4 plus SOX2. However, PLAP is variably positive only in seminoma and was a good marker for differential diagnosis in our case. Oct3/4 and SOX2 markers were unavailable at our center.

Metastasis in mediastinal seminomas is known to occur. Only 30–40% of patients are found to have localized disease. The most common behavior is an invasion into lungs and other intrathoracic structures. In our case, repeat CECT showed some opacities in bilateral lungs. Treatment includes a combination of surgery and chemo-radiotherapy. Small tumors can be attempted for complete resection and postoperative radiotherapy of 40–45 Gy is curative. Cisplatin-based chemotherapy is known to induce complete response in patients with seminoma.[10] Our patient responded to surgery along with chemotherapy and is presently on OPD follow-up at MDTC. This case highlights the importance of obtaining an adequate biopsy specimen. As some mediastinal masses such as lymphoma are not treated surgically, a diagnosis is often attempted on needle core or minimally invasive biopsies. These small biopsies may not be representative of the true lesion and depict only the peripheral secondary changes as was seen in our case.

   Conclusion Top

Thus, being a treatable tumor with a good prognosis early and correct diagnosis of mediastinal seminoma is of paramount importance. Secondary changes should not act as a deterrent in diagnosis and one should be vigilant enough while reporting on a small biopsy. A high index of suspicion by an astute pathologist and awareness of the secondary changes which can mask the primary lesion can help to clinch the diagnosis early.

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Conflicts of interest

There are no conflicts of interest.

   References Top

Dubashi B, Cyriac S, Tenali SG. Clinicopathological analysis and outcome of primary mediastinal malignancies – A report of 91 cases from a single institute. Ann Thorac Med 2009;4:140-2.  Back to cited text no. 1
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Khan FY, Al Ani A, Allaithy MS, Al-Bozom IA. A young male with shortness of breath. Ann Thorac Med 2008;3:28-30.  Back to cited text no. 3
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Knapp RH, Hurt RD, Payne WS, Farrow GM, Lewis BD, Hahn RG, et al. Malignant germ cell tumors of the mediastinum. J Thorac Cardiovasc Surg 1985;89:82-9.  Back to cited text no. 5
Weidner N. Germ-cell tumors of the mediastinum. Semin Diagn Pathol 1999;16:42-50.  Back to cited text no. 6
Bokemeyer C, Nichols CR, Droz JP, Schmoll HJ, Horwich A, Gerl A, et al. Extragonadal germ cell tumors of the mediastinum and retroperitoneum: Results from an international analysis. J Clin Oncol 2002;20:1864-73.  Back to cited text no. 7
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Al-Maghrabi JA, Sawan AS, Kanaan HD. Hodgkin's lymphoma with exuberant granulomatous reaction. Saudi Med J 2006;27:1905-7.  Back to cited text no. 9
Liu TZ, Zhang DS, Liang Y, Zhou NN, Gao HF, Liu KJ, et al. Treatment strategies and prognostic factors of patients with primary germ cell tumors in the mediastinum. J Cancer Res Clin Oncol 2011;137:1607-12.  Back to cited text no. 10

Correspondence Address:
Dr. Devika Gupta
Department of Pathology and Laboratory Science, Armed Forces Medical College, Command Hospital, Pune - 411 040, Maharashtra
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/0377-4929.188113

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