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CASE REPORT  
Year : 2011  |  Volume : 54  |  Issue : 2  |  Page : 384-387
Poorly differentiated monophasic synovial sarcoma of the mediastinum


Division of Histopathology, King Saud University, King Khalid University Hospital, Riyadh, Kingdom of Saudi Arabia

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Date of Web Publication27-May-2011
 

   Abstract 

Poorly differentiated synovial sarcoma is a diagnostically challenging neoplasm. Most commonly they occur in the soft tissue of the extremities and are rare in the mediastinum. They can be indistinguishable from other "round cell tumors" based on the morphology alone or at times by immunohistochemical studies. Here in, we report an extremely rare case of metastatic poorly differentiated monophasic synovial sarcoma of the mediastinum without a known primary in a 30-year-old man. The imaging studies on admission showed 10 × 9.5 cm anterior mediastinal mass with multiple nodules in the lung and pleura along with multiple enlarged mediastinal and axillary lymph nodes. Histopathologic and immunohistochemical analysis supported the diagnosis of poorly differentiated synovial sarcoma, which was further confirmed by molecular genetic analysis.

Keywords: Immunohistochemistry, mediastinum, synovial sarcoma

How to cite this article:
Arafah M, Zaidi SN. Poorly differentiated monophasic synovial sarcoma of the mediastinum. Indian J Pathol Microbiol 2011;54:384-7

How to cite this URL:
Arafah M, Zaidi SN. Poorly differentiated monophasic synovial sarcoma of the mediastinum. Indian J Pathol Microbiol [serial online] 2011 [cited 2020 Feb 17];54:384-7. Available from: http://www.ijpmonline.org/text.asp?2011/54/2/384/81650



   Introduction Top


Synovial sarcoma was initially described by Simon [1] in 1865 and was termed as synovial sarcoma in 1938 by Sabrazes et al.[2] due to its resemblance to the developing synovial tissue under the light microscope. However, it has no demonstrable connection or relationship with the synovium. [3] It is a distinctive soft tissue tumor that displays epithelial differentiation. It is more prevalent in adolescent and young adults, 15-40 years of age. Males are affected more than females, with an average male:female ratio of 1.2:1. [4]

Classical synovial sarcoma has a biphasic pattern and is composed of sheets of spindle cells and sharply segregated epithelial cells forming gland-like areas in varying proportions. The poorly differentiated synovial sarcoma represents a form of tumor that can occur in either monophasic or biphasic forms and is often diagnostically challenging. The diagnosis of synovial sarcoma has been facilitated by the inclusion of molecular biological techniques in pathology and the recent incorporation of cytogenetics in the oncologic examination.

To date, synovial sarcoma has been found to occur in several unusual locations, including head and neck, skin, blood vessels, abdominal wall, prostate, nerves, pleural cavity, and kidney. The occurrence of poorly differentiated synovial sarcoma in the mediastinum is rare, but recently the occurrence of this tumor is being increasingly recognized. [5] Here we report further a case of a patient with poorly differentiated monophasic synovial sarcoma of the mediastinum who presented clinically with shortness of breath and progressive weight loss.


   Case Report Top


A 30-year-old man presented to the emergency room complaining of shortness of breath that started suddenly and was progressively increasing in severity, with nonproductive cough for one month, and progressive weight loss. His chest examination showed signs of massive pleural effusion. He was an exsmoker and his past medical history was unremarkable. The radiographic studies showed a large heterogenous mass with multiple cystic degenerating areas measuring 10 × 9.5 cm in the anterior mediastinum with massive right-sided pleural effusion. In addition, there were multiple pulmonary and pleural soft tissue deposits, largest measuring 3.4 cm and multiple enlarged right axillary and mediastinal lymph nodes showing a heterogenous enhancement [Figure 1]. The computerized tomography (CT) scan of the abdomen was unremarkable; with no evidence of metastasis. Thoracocentesis was performed to examine pleural effusion, which was hemorrhagic, serous, and exudative with numerous lymphocytes in the background. No malignant cell was seen.
Figure 1: Contrast-enhanced CT scan demonstrates large anterior mediastinal mass representing a neoplastic lesion with multiple areas of cystic degeneration

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The CT-guided percutaneous needle biopsy was performed, which on gross consisted of five linear fragments, each measuring 1.2 cm in maximum length. Histologically, the tumor was composed of densely packed round to epithelioid cells with scant vacuolated cytoplasm, irregular nuclei with clumped chromatin, and inconspicuous nucleoli with frequent mitoses (more than 6/10 high power field) [Figure 2]. The differential diagnosis included primitive neuroectodermal tumor, poorly differentiated sarcoma, thymoma, malignant mesothelioma, lymphoma, solitary fibrous tumor, fibrosarcoma, and germ cell tumor. Immunohistochemical stains [Table 1] revealed strong positivity for vimentin [Figure 3], Bcl-2 [Figure 4] and focal positivity for CD99, CK, EMA, CK-7 and CK-19. The immunohistochemical markers for lymphoma: CD45, CD-20, CD-31, CD-5, CD-30, Tdt, and CD-43; and for germ cell tumor: PLAP, Alfa-fetoprotein, and human chorionic gonadotropin (HCG) were negative. Other stains including, CD 34, CD-31, factor VIII, Ber-EP4, S-100 protein MPO, desmin, CK-117, synaptophysin, smooth muscle antigen, and p63 were all negative.
Figure 2: Histology shows densely packed round to epithelioid cells with scant vacuolated cytoplasm and irregular nuclei (H and E, ×400)

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Figure 3: Immunohistochemically, the tumor cells were diffusely positive for vimentin (IHC, ×400)

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Figure 4: Immunohistochemically, the tumor cells were diffusely positive for Bcl-2 (IHC, ×400)

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Table 1: Immunohistochemistry: source and dilution

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We resorted to molecular studies for the confirmation of the diagnosis. Fluorescent in situ hybridization (FISH) analysis revealed translocation of chromosome (X; 18) (p11.1; q11.2) [Figure 5], which confirmed the diagnosis of synovial sarcoma. The presence of a large mass in the anterior mediastinum, multiple nodules in the pleura and lung, multiple enlarged mediastinal lymph nodes, with the histologic picture of undifferentiated small cells, the immunohistochemistry and molecular study favoring synovial sarcoma, the final diagnosis of metastatic poorly differentiated monophasic synovial sarcoma was rendered. However, we were not able to identify the primary tumor, even after exhaustive metastatic workup. The patient is alive 6 months after his diagnosis and has received 3 cycles of ifosfamide-based chemotherapy. On repeat CT, there is interval regression of anterior mediastinal mass with necrosis, necrotic pleuropulmonary nodules and mediastinal lymph nodes.
Figure 5: Detection of the t(X;18) (SYT/SSX) translocation by FISH, RT-PCR, and sequencing. (a) FISH with a break-apart probe for the rearrangement of the SYT gene shows one fused signal and one separate red and green signal per nucleus indicating the presence of a t(X;18) translocation. (b) Agarose gel electrophoresis of SYT/SSX and β-actin RT-PCRs. Lane 1: patient's sample; lane 2: positive control; and lane 3: negative control. (c) Junction site of SYT-SSX1 fusion transcripts was demonstrated by sequence analysis of the RT-PCR fragment (forward and reverse strand sequencing)

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   Discussion Top


The mediastinum is a unique anatomic area containing several structures and pleuripotent cells that allow for the development of a range of tumors. In a study conducted by Burt et al, [5] of the total of 3149 soft tissue sarcomas reviewed in different sites, primary mediastinal sarcoma represented 1.4% of these. The more common primary sarcoma of the mediastinum was malignant peripheral nerve sheath tumor (26%), spindle cell sarcoma (15%), leiomyosarcoma (9%), and liposarcoma (9%). Synovial sarcoma accounted for only 2% of all sarcomas of the mediastinum.

Synovial sarcoma in general is named for their histologic pattern based on the prominence of either epithelioid or spindled cell types. They are divided into four histologic cell types: biphasic, monophasic fibrous, monophasic epithelial, and poorly differentiated. Our case showed predominantly round to epithelioid cells with nuclear features similar to other small round cell tumors. Based on the morphology, our first differential diagnosis was primitive neuroectodermal tumor/Ewing's sarcoma. Ancillary immunohistochemical and molecular genetic techniques helped to reach the final diagnosis.

It has been recently suggested that vimentin, cytokeratin, and EMA in combination with CD34 negativity are the most useful and sensitive protein biomarkers for the diagnosis of monophasic fibrous synovial sarcoma and poorly differentiated synovial sarcoma. [6] In our case, immunostaining was strongly positive for EMA, vimentin, and Bcl-2 and focally for cytokeratin. The diagnosis of primitive neuroectodermal tumor was ruled out because CD99 was weak and focal. Negativity of lymphoma markers (CD 45, CD20, CD31, CD5, CD30, Tdt, and CD43) and for germ cell tumor (PLAP, alfa-fetoprotein, HCG) led to their exclusion. Negativity of S-100 protein excluded malignant peripheral nerve sheath tumor and negative smooth muscle antigen (SMA) excluded leiomyosarcoma; and p 63 was also negative, which ruled out thymoma. Solitary fibrous tumor was out because of negative CD34. Bcl-2 was positive in our case; however, it is not discriminatory as it is diffusely positive in both solitary fibrous tumor and synovial sarcoma.

Recently with the introduction of molecular and cytogenetic techniques, it has supplemented histology and immunohistochemistry and has led to a better understanding of the biology of synovial sarcoma. [7] The diagnosis in our case was confirmed by molecular detection of tX;18) by fluorescent in situ hybridization. More than 90% of patients have a t(X;18) translocation mutation, which is not associated with other sarcomas. [4] The translocation involves the SYT gene on chromosome 18 (at 18q11) and the SSX1 or SSX2 gene on the X chromosome (at Xp11) [8],[9] These genes appear to be transcription regulators, whose functions occur primarily through protein-protein interactions. Subtypes of these translocations have been shown to correlate with distinct histologic subtypes. [10]

 
   References Top

1.Simon G. Exstirpation einer sehr grossen, mit dicken Stiele angewachsenen Kneigelenkmaus mit gluklichem Erfolge. Arch Klin Chir 1865;6:573-6.  Back to cited text no. 1
    
2.Sabrazes J, Loubat E, de Grailly R, Magendie J. Synovial sarcomes. Gaz Hebd Sc Med Bordeaux 1934;55:754-62.  Back to cited text no. 2
    
3.Lazar A, Abruzzo LV, Pollock RE, Lee S, Czerniak B. Molecular diagnosis of sarcomas: Chromosomal translocations in sarcomas. Arch Pathol Lab Med 2006;130:1199-207.   Back to cited text no. 3
[PUBMED]  [FULLTEXT]  
4.Trupiano JK, Rice TW, Herzog K, Barr FG, Shipley J, Fisher C. Mediastinal synovial sarcoma: Report of two cases with molecular genetic analysis. Ann Thorac Surg 2002;73 : 628-30.  Back to cited text no. 4
    
5.Burt M, Ihde JK, Hajdu SI, Smith JW, Bains MS, Downey R. Primary sarcomas of the mediastinum: Results of therapy. J Thorac Cardiovasc Surg 1998;115:671-80.  Back to cited text no. 5
    
6.Turc-Carel C, Dal Cin P, Limon J. Involvement of chromosome X in primary cytogenetic change in human neoplasia: Nonrandom translocation in synovial sarcoma. Proc Natl Acad Sci USA 1987;84:1981-5.  Back to cited text no. 6
    
7.Rong R, Doxtader EE, Tull J, de la Roza G, Zhang S. Metastatic poorly differentiated monophasic synovial sarcoma to lung with unknown primary: A molecular genetic analysis. Int J Clin Exp Pathol 2009;3:217-21.  Back to cited text no. 7
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8.Ladanyi M. Fusions of the SYT and SSX genes in synovial sarcoma. Oncogene 2001;20:5755-62.  Back to cited text no. 8
[PUBMED]  [FULLTEXT]  
9.Fisher C. Synovial sarcoma. Ann Diagn Pathol 1998;2:401-21.  Back to cited text no. 9
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10.Schmitt T, Kasper B. New medical treatment options and strategies to assess clinical outcome in soft-tissue sarcoma. Expert Rev Anticancer Ther 2009;9:1159-67.  Back to cited text no. 10
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Correspondence Address:
Shaesta N Zaidi
Pathology Department, College of Medicine, King Khalid University Hospital, King Saud University, P.O. Box 2925, Riyadh 11461
Kingdom of Saudi Arabia
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/0377-4929.81650

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    Figures

  [Figure 1], [Figure 2], [Figure 3], [Figure 4], [Figure 5]
 
 
    Tables

  [Table 1]

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