Case 6 -

Intra-neural Synovial Sarcoma with SYT-SSX translocation. Grade 2 histoprognostic (according to FNCLCC) DRS. L. BOCCON-GIBOD, S. BOUDJEMAA, C.ROMANA, .BENHARRATS Presented by Dr. Liliane BOCCON-GIBOD Professor of Pediatric Pathology Hôpital d'Enfants Armand Trousseau 26 av du Dr. Arnold Netter 75571 PARIS Cédex (France)

Case History: Girl aged 13 years (DOB 5/5/92). Mass present since October 2004, developed in the posterior aspect of the right arm, in the brachial biceps, adherent to ulnar nerve. In December 2005, at MRI the mass measures 39 x 20 mm and is well limited. Biopsy in February 2006. Pathology Four large fragments of the tumor are available for examination, measuring from 10 to 3 mm. Tissue is stored for molecular biology. All specimens are identical consisting in a cellular spindle cell proliferation in which the tumor cells are arranged as intersecting fascicles. Case 6 - Slide 1 Click to view with ImageScope Click to view with a Web-Based Viewer Tumor cells are uniform with central oval/spindle shaped nuclei. Cytoplasm is scanty and nuclear atypia is rare. Chromatin is thin and nucleoli are small and indistinct. Tumor necrosis and glandular component are not present. The spindle cells are not present. The spindle cells are diffusely positive for vimentin, and to a lesser extent for AE1-AE3, Kl1, EMA, CK7, CK19, CD56 and Bcl2. Cytokeratins help to highlight one small focus of glandular differentiation. Membranous immunostaining is observed with CD99. S100 is negative demarcating the tumor from the involved axonal segments that are pushed aside. The presence of a t(X;18)(SYT-SSX) translocation was assessed using RT-PCR. Diagnosis Intra-neural Synovial Sarcoma with SYT-SSX translocation. Grade 2 histoprognostic (according to FNCLCC) . Follow-up Chemotherapy with Ifosfamide and Doxorubicin began in March 2006. In May 2006 the mass measured 17 x 22 x 40 mm (versus 22 x 28 x 45 mm prior to chemotherapy). Surgery of the persisting mass is to take place in June 2006. Discussion Synovial Sarcoma (SS) are malignant mesenchymal neoplasms, most commonly arising in extremities, which occur predominantly in children and young adults. They account for approximately 10 % of all soft tissue sarcomas. Based on histological appearance, 2 major subtypes of SS can be distinguished: biphasic tumors with a mixture in varying proportions of spindle cell components and epithelial cells organized in glandular formations, and monophasic types which may be difficult to distinguish from other spindle cell sarcomas. The immunohistochemical detection of epithelial markers such as cytokeratin and EMA within both spindled and epithelial cells, is an important diagnostic help. Vimentin is positive in 100 % of cases. CD99, bcl-2 and Betacatenin are also expressed, in nearly 90 % of cases, with strong expression in half of them. However some cases may not be resolved with immunohistochemistry, especially in the differential diagnosis between a monophasic SS and a MPNST. More than 90 % of SS present with the characteristic t(X;18)(p11.2;q11.2) which creates either SYT/SSX1 or SYT/SSX2 fusion protein. The presence of this translocation (or of a variant) is an essential diagnostic tool for exclusion or confirmation of the SS diagnosis in these difficult cases. A correlation between gene fusion type and histopathology has been described: biphasic tumors tend to carry the SYT/SSX1 fusion, whereas SYT/SSX2 tends to show monophasic pattern. Intraneural Synovial Sarcoma and its differential diagnosis Synovial sarcoma most frequent localisations (> 80 %) are the peri-articular regions from the extremities usually in close association with tendon sheath, bursae or joint capsules. Synovial sarcoma arising within a peripheral nerve has been reported in 8 previous sections (Table 1). The majority of masses arising from peripheral nerves and nerve sheaths are due to benign neoplasms such as schwannomas and neurofibromas. If the mass is rapidly growing malignant peripheral nerve sheath tumor (MPNST) will be the first suggested diagnosis. It is also the main differential diagnosis for the pathologist facing a spindle cell proliferation with closely spaced, hyperchromatic, ovoid nuclei, arising in a nerve. MPNST will express nestin and NGFR (80 %) and S100 (45 %). Most important is the negativity for CK7/EMA and bcl-2 in MPNST. As always there are exceptions to this immunohistochemical pattern and for example some MPNST can be CK positive. Prognosis Older age (> 16 y) and size (> 5 cm) are clearly correlated with poorer prognosis as is residual local tumor metastases at diagnosis. Although SS is regarded as chemo-sensitive, chemotherapy is not so effective for patients with SS as for patients with RMS. Patients with initially resected tumors fare better than those where some tumor is left in place. Some data indicate that the particular subtype of translocation has prognostic significance. SYT/SSX2 translocation has been shown to be primarily associated with the monophasic histotype and better out look of survival 5 years after diagnosis. Some other studies have suggested that histological grade but not SYT/SSX fusion type in an important prognostic factor in patients with SS (Guillou, J Clin Oncol 2004). Table: Summary of nine cases of intraneural SS Cases Age Sex Nerves involved Size (cm) Type Dx by References Case 1 23 F Radial 2.0 Biphasic H Cugola [5] Case 2 16 F Median 2.5 Monophasic H,IM Rinehart [14] Case 3 16 M Radial 2.0 Biphasic H,IM O'Connell [11] Case 4 43 M Popliteal 3.5 Biphasic H,IM Spielmann [17] Case 5 16 M Median 2.0 Biphasic H,IM Chesser [3] Case 6 54 M Peroneal ? Monophasic H,IM,M Lestou [10] Case 7 43 F Facial 0.8 Biphasic H,IM,M Chu [4] Case 8 11 F C6-C7 0.4 Monophasic H,IM,M Chu [4] Case 9 13 F Ulnar 4.5 Monophasic H,IMM,M Boccon-Gibod References Brecht IB, Ferrari A, Int-VennC, Schuck A, Mattke AC, Casanova M, Bisogno G, Carli M, Koscielniak E, Treuner J : Grossly-resected synovial sarcoma treated by the German and Italian pediatric soft tissue sarcoma cooperative groups : discussion on the robe of adjuvant therapies. Pediatr Blood Cancer 2006, 46 : 11-7. Ceccheto G, Alaggio R, Dall'Igna P, Bisogno G, Ferrari A, Gigante C, Casanova M, Sotti G, Zanetti I, Carli M : Localized unresectable non-rhabdo soft tissue sarcomas of the extremities in pediatric age. Results from the Italian studies. Cancer 2005 ; 104 : 2006-12. Chesser TJS, Geraghty JM, Clarke AM : Intraneural synovial sarcoma of the median nerve. J Hand Surg 1999 ; 3 : 373-5. Chu PG, Benhattar J, Weiss LM, Meagher-Villemure K : Intraneural synovial sarcoma : two cases. 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