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Year : 2015  |  Volume : 58  |  Issue : 1  |  Page : 55-58
Calcifying/ossifying synovial sarcoma: A clinicopathologic and molecular study of 5 cases


1 Department of Pathology and Microbiology, Section of Histopathology, Aga Khan University Hospital, Karachi, Pakistan
2 Department of Pathology and Laboratory Medicine, Mount Sinai Hospital, Toronto, Ontario, Canada

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Date of Web Publication11-Feb-2015
 

   Abstract 

Background: Synovial sarcoma (SS) is a soft tissue sarcoma with a generally aggressive behavior. Calcifying/ossifying SS is a rare variant associated with a favorable prognosis. Aim: The aim was to report clinicopathological features and molecular analysis of 5 cases of calcifying/ossifying SS. Materials and Methods: Record of 370 cases of SS reported in the section of Histopathology, of a tertiary care Hospital, between 2002 and 2011 were retrieved. Five cases exhibiting extensive calcification and ossification were identified. Immunohistochemistry was performed using Flex technique. Molecular analysis of these 5 cases was performed later at the collaborative Hospital abroad, by reverse transcription polymerase chain reaction. Results and Conclusions: The ages of the patients ranged from 13 to 44 years (mean age 27 years; female to male ratio 1.6:1). The duration of symptoms ranged from 5 months to 5 years. Histologically, 4 were monophasic, and 1 was biphasic. Three cases exhibited extensive calcification and two extensive ossification. Immunohistochemical stain (epithelial membrane antigen was positive in all 5 cases, CKAE1/AE3 (3/4), Bcl2 (4/4), S100 (4/4), CK7 (2/2), CD99 (1/3) and vimentin (2/2). Intact RNA was obtained from 3 cases, all of which were positive for the SYT/SSX fusion transcript. Follow-up was available in 4 cases and ranged from 19 months to 85 months (mean 50 months). Local recurrence was seen in 2 cases. In conclusions, we report clinicopathologic features of 5 cases of calcifying/ossifying SS. The duration of symptoms and mean age of patients is similar to the literature. A slight female predominance was seen in contrast to a male predominance described in the literature. The clinical course of our cases validates the favorable prognosis of this rare type of SS.

Keywords: Calcifying, favorable prognosis, ossifying, synovial sarcoma

How to cite this article:
Din NU, Hopkins A, Memon A, Ahmad Z, Ahmed R. Calcifying/ossifying synovial sarcoma: A clinicopathologic and molecular study of 5 cases . Indian J Pathol Microbiol 2015;58:55-8

How to cite this URL:
Din NU, Hopkins A, Memon A, Ahmad Z, Ahmed R. Calcifying/ossifying synovial sarcoma: A clinicopathologic and molecular study of 5 cases . Indian J Pathol Microbiol [serial online] 2015 [cited 2019 Mar 25];58:55-8. Available from: http://www.ijpmonline.org/text.asp?2015/58/1/55/151188



   Introduction Top


Synovial sarcoma (SS) is a distinct soft tissue sarcoma mainly involving the extremities and especially occurring around large joints of young adults and children. Histologically, three subtypes are described: Monophasic (purely fibrous or epithelial), biphasic and poorly differentiated. [1] Approximately, 30% cases of SS exhibit punctate or stippled calcifications which are detectable radiologically or histologically. [2] However, extensive diffuse calcification or ossification is rare, and if present the lesion is termed calcifying/ossifying SS. To the best of our knowledge, only 47 cases have been published in the literature. [2],[3],[4],[5],[6],[7],[8],[9],[10],[11],[12],[13],[14] Herein, we report clinicopathological features of 5 cases of calcifying/ossifying SS.


   Materials and Methods Top


A total of 2012 soft tissue sarcomas were reported in a tertiary hospital between 2002 and 2011. SS comprised of 370 cases (18%) after undifferentiated sarcoma. Five cases with extensive calcification and ossification were identified. Blocks and slides of these 5 cases were retrieved, and slides were reviewed. Immunohistochemical studies were performed with the Flex technique using the following antibodies: Epithelial membrane antigen (EMA), CKAE1/AE3, cytokeratin 7, CD99, Bcl 2, S100, CD34, Alpha smooth muscle actin, Desmin and vimentin.

Molecular analysis was done by reverse transcription polymerase chain reaction (RT-PCR) method by using RNA obtained from paraffin-embedded tumor. Due to specimen decalcification, fragmentation of the RNA was not surprisingly observed in several cases. This was demonstrated by the absence of amplification for the housekeeping gene control in four of the 5 cases tested. However, two of these cases were positive for the shorter SYT/SSX fusion product, confirming the partial fragmentation of the specimen RNA.


   Results Top


Clinical and gross features

The duration of swelling ranged from 5 months to 5 years. Three tumors were located in the lower thigh and two in the sole of the foot. Three patients were females while two were males. The age at diagnosis ranged from 13 to 44 years (mean 27 years). Radiological examination showed heavily calcified mass in the involved areas [Figure 1]a and b]. The size of the resected tumor fragments varies in size from 3 to 7 cm (mean 5 cm).
Figure 1: X-ray images of calcifying synovial sarcoma. Calcified mass in soft tissue of distal thigh (a) and plantar surface of foot (b)


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Histological findings

Histologically, 4 cases were monophasic, and one was biphasic type. The monophasic tumors were composed of fascicles of spindle cells with uniform oval to spindle nuclei without prominent nucleoli. Mitotic figures ranged from 1 to 3 mitosis/10 HPFs. In 3 cases, extensive coarse calcifications were seen through the tumor with little ossification [[Figure 2]a]. Two cases showed an extensive ossification with focal calcification [[Figure 2]b]. Focal concentric psammomatous type calcification was also seen in 1 case. Intervening hyalinization was seen in all cases.
Figure 2: (a) Extensively calcifying synovial sarcoma (H and E, ×100) (b) extensively ossified synovial sarcoma (H and E, ×200) (c) epithelial membrane antigen positivity in monophasic variant of synovial sarcoma. (d) Reverse transcription polymerase chain reaction detection of transcriptions of SYT-SSX fusion genes (2, 4, 6, 8 and 10 PGK housekeeping gene; 3, 5, 7, 9 and 11 SYT/SSX on test cases; 12 positive control; 14 and 16 negative control)


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The one biphasic tumor had extensive coarse calcification throughout the tumor with intervening fascicles of mesenchymal spindle cells with focal epithelial clusters. Rare round concentric calcifications were also noted. Intervening hyalinization and mitotic figures of 2 mitosis/10 HPFs were noted.

Immunohistochemical stain results were showed positivity for EMA [[Figure 2]c], CKAE1/AE3, Bcl2, S100, CK7, vimentin and CD99. CD34, Alpha smooth muscle actin and desmin were negative in tumors cells.

Molecular analysis of t(x, 18) results showed positivity in 3 out of 5 cases [[Figure 2]d]. Intact RNA could not be obtained from the other 2 specimens, rendering molecular analysis inconclusive.

Treatment and follow-up

All patients underwent surgical resection of the tumor. No additional treatment was given. Follow-up was available in 4 patients and ranged from 19 months to 85 months (mean 50 months). Two patients experienced recurrence at 51 and 58 months, respectively. A second recurrence was noted in one patient, but the patient refused further resection or adjuvant therapy. Histologically, both recurrent tumors were monophasic, one was extensively calcified, while other was extensively ossified. All the four patients are alive and free of metastatic disease.


   Discussion Top


Synovial sarcoma is a high-grade, fourth most common soft tissue sarcoma accounting for 5-10% of soft tissue sarcomas. [15] In spite of the better therapeutic modalities, the 5 and 10 years survival rates vary from 25.2-62.5% to 11.2-30%, respectively. [2],[3],[4],[5],[6],[7],[8],[9],[10],[11],[12],[13],[14],[15],[16]

Synovial sarcoma with extensive calcification and ossification is very rare and to the best of our knowledge, only 47 cases have been reported to date. [2],[3],[4],[5],[6],[7],[8],[9],[10],[11],[12],[13],[14] It is associated with a better prognosis as shown by Varela-Duran and Enzinger. [2] They reported 32 cases of calcifying SS with a 5 years survival rate of 82% [Table 1]. The reported cases showed a male predominance with a male to female ratio of 1.6:1 [29 males, 18 females; [Table 1]. A slight female predominance was seen in our study. Majority of the cases involved lower limb (33/47), followed by upper limb (10/47). These tumors present as painless or painful masses and duration of symptoms has ranged from 1 month [2] to 10 years [6] [Table 1]. Histologically, majority (42/47) of reported cases in the literature were biphasic, and only 5 were monophasic [Table 1]. In our study, 4 were monophasic, and only 1 was biphasic. The follow-up of published cases ranged from 6 months to 25 years [Table 1]. Metastases were seen in 11 patients, and local recurrence was noted in 10 cases. Six patients were reported to have died of disease. No metastases were seen in our patients and two developed local recurrence.
Table 1: Reported cases of calcifying/ossifying synovial sarcoma


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Calcifying/ossifying SS may be confused radiologically and histologically with various benign and malignant lesions. These include myositis ossificans, extrakeletal or parosteal osteosarcoma and extraskeletal chondroma. Calcifying/ossifying SS should always be kept in mind and excluded by immunohistochemistry and molecular studies.

More than 90% of SS cases are associated with a reciprocal nonrandom translocation t(x; 18) (p11.2; q11.2). Three out of five (60%) of our cases were positive for SYT-SSX fusion transcript detected by RT-PCR method. Molecular analysis of the remaining 2 cases was inconclusive due to RNA fragmentation, likely caused by specimen decalcification. Out of the two inconclusive cases, one recurred 51 months after diagnosis, while the other patient was lost to follow-up.


   Conclusion Top


We report clinicopathologic features of 5 cases of calcifying/ossifying SS. The duration of symptoms and mean age of patients is similar to that described in the literature. A slight female predominance was seen in contrast to a male predominance described in the literature. The mean follow-up was 50 months and recurrence was noted in 2 cases. The clinical course of our cases validates the favorable prognosis reported for this rare type of SS.

 
   References Top

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Suurmeijer AJ, de Bruijn D, Van Kessel AG, Miettinen MM. Synovial sarcoma. In: Fletcher CD, Bridge JA, Hogendorn PC, Mertens F, editors. World Health Organization Classification of Tumours of Soft Tissue and Bone. Lyon, France: IARC Press; 2013. p. 213-5.  Back to cited text no. 1
    
2.
Varela-Duran J, Enzinger FM. Calcifying synovial sarcoma. Cancer 1982;50:345-52.  Back to cited text no. 2
    
3.
Genest P, Kim TH, Katsarkas A, Jothy S. Calcified synovial sarcoma of the oropharynx. Br J Radiol 1983;56:580-2.  Back to cited text no. 3
    
4.
Louis DS, Hankin FM, Braunstein EM, Verklin RM Jr. Calcifying synovial sarcoma. J Hand Surg Br 1986;11:475-7.  Back to cited text no. 4
    
5.
Milchgrub S, Ghandur-Mnaymneh L, Dorfman HD, Albores-Saavedra J. Synovial sarcoma with extensive osteoid and bone formation. Am J Surg Pathol 1993;17:357-63.  Back to cited text no. 5
    
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Maxwell JR, Yao L, Eckardt JJ, Doberneck SA. Case report 878: Densely calcifying synovial sarcoma of the hip metastatic to the lungs. Skeletal Radiol 1994;23:673-5.  Back to cited text no. 6
    
7.
Cho MB, Lee TJ, Kim MK, Park YW, Song KY. Calcifying synovial sarcoma. Korean J Pathol 1995;29:536-9.  Back to cited text no. 7
    
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Ishida T, Iijima T, Moriyama S, Nakamura C, Kitagawa T, Machinami R. Intra-articular calcifying synovial sarcoma mimicking synovial chondromatosis. Skeletal Radiol 1996;25:766-9.  Back to cited text no. 8
    
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Sánchez Reyes JM, Alcaraz Mexia M, Quiñones Tapia D, Aramburu JA. Extensively calcified synovial sarcoma. Skeletal Radiol 1997; 26:671-3.  Back to cited text no. 9
    
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Winnepenninckx V, De Vos R, Debiec-Rychter M, Samson I, Brys P, Hagemeijer A, et al. Calcifying/ossifying synovial sarcoma shows t(X;18) with SSX2 involvement and mitochondrial calcifications. Histopathology 2001;38:141-5.  Back to cited text no. 10
    
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Hara S, Hatori M, Hosaka M, Komatsu T, Tsuchiya T, Kimura N. Synovial sarcoma with massive ossification: A case report. Ups J Med Sci 2003;108:151-8.  Back to cited text no. 11
    
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Shukla PN, Pathy S, Sen S, Purohit A, Julka PK, Rath GK. Primary orbital calcified synovial sarcoma: A case report. Orbit 2003;22:299-303.  Back to cited text no. 12
    
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Hisaoka M, Matsuyama A, Shimajiri S, Akiba J, Kusano H, Hiraoka K, et al. Ossifying synovial sarcoma. Pathol Res Pract 2009;205:195-8.  Back to cited text no. 13
    
14.
Tam HT, Ng WH, Wong KC, Griffit JF. Heavily mineralized malignant synovial sarcoma mimicking a benign extraskeletal chondroma. J Hong Kong Coll Radiol 2010;12:174-7.  Back to cited text no. 14
    
15.
Goldblum JR, Folpe AL, Weiss SW, editors. Enzinger and Weiss's Soft Tissue Tumors. 6 th ed. Philadelphia PA: Elsevier Saunders; 2013. p. 1052-70.  Back to cited text no. 15
    
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Cagle LA, Mirra JM, Storm FK, Roe DJ, Eilber FR. Histologic features relating to prognosis in synovial sarcoma. Cancer 1987;59:1810-4.  Back to cited text no. 16
    

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Correspondence Address:
Dr. Nasir Ud Din
Department of Pathology and Microbiology, Aga Khan University Hospital, Stadium Road, PO 3500, Karachi
Pakistan
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/0377-4929.151188

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