Genetic and molecular reappraisal of spindle cell adamantinoma of bone reveals a small subset of misclassified intraosseous synovial sarcoma

Abstract

Adamantinoma represents a distinct group of bone tumors showing both mesenchymal and epithelial differentiation most commonly involving the tibial diaphysis. Most adamantinomas contain a fibro-osseous component and an epithelial component consisting of squamous or basaloid cells. Adamantinomas are considered malignant neoplasms requiring en bloc excision that frequently recur locally and can rarely metastasize. Rare adamantinomas show an epithelial component consisting predominantly of monomorphic spindle cells, which, combined with an epithelial immunophenotype, can mimic monophasic synovial sarcoma. Synovial sarcoma is very rare in bone. It is considered a high-grade sarcoma that typically necessitates chemotherapy. However, the relationship between spindle cell adamantinoma and intraosseous synovial sarcoma has not been investigated. The current study was prompted by identification of a presumed spindle cell adamantinoma of the tibia with diffuse keratin expression that harbored a SS18 gene region rearrangement. FISH of eight additional bone tumors initially classified as spindle cell adamantinoma based on clinicoradiopathologic findings revealed one additional case with SS18 rearrangement. Histologically, both intraosseous synovial sarcoma and spindle cell adamantinoma demonstrated uniform fusiform nuclei with scant cytoplasm, short fascicles and low mitotic activity. The adamantinomas, but not the synovial sarcomas, were more likely to show overt epithelial differentiation in the form of pseudoglands or squamous nests. Immunohistochemistry of all cases, irrespective of SS18 status, showed diffuse keratin positivity in the spindle cell component, and less consistent EMA positivity. Clinical follow-up was available in both intraosseous synovial sarcomas, one of which recurred and the other metastasized. Two of the six spindle cell adamantinomas with follow-up metastasized. The above findings highlight the morphologic and immunophenotypic overlap between spindle cell adamantinoma and intraosseous synovial sarcoma of the tibia. Investigation of SS18 status to exclude synovial sarcoma is suggested prior to rendering a diagnosis of spindle cell adamantinoma.

Primary intraosseous hybrid epithelioid schwannoma/perineurioma in the proximal tibia: a case report of benign hybrid neoplasm with local hypercellularity

“…Primary intraosseous SS is rare, and only a few cases have been reported [29–33]. These tumours displayed similar histopathology to their soft tissue counterparts [32]. The variable cellularity and the hypercellular areas in our case show some resemblance of monophasic SS.…”

Primary Intraosseous Synovial Sarcoma with Molecular Confirmation: Expanding and Clarifying the Spectrum of This Rare Neoplasm

“…Adding to this controversy, synovial sarcoma has been documented as arising in a variety of anatomic sites, including but not limited to the lung and pleura [25][26][27][28][29], heart and pericardium [30,31], kidney [12, 32-37], prostate [38], and gastrointestinal tract [39][40][41][42][43]. Regarding connective tissues, synovial sarcoma may have its origins within intramuscular [44], para-articular [23], intraneural [45][46][47], or intraosseous tissues [2][3][4][5][6][7][8][9][10][11]. For the above reasons, some have proposed renaming synovial sarcoma as "carcinosarcoma of connective tissue," reflecting the concept of true epithelial differentiation in association with a spindle cell sarcoma and the absence of true synovial differentiation [48,49].…”

“…Interestingly, the majority (10/13 cases, 76.9%) of molecularly confirmed primary intraosseous synovial sarcomas are histologically monophasic (see Table 1). Regarding the potential for a biphasic histologic appearance, it has recently been documented that primary bone synovial sarcoma, especially given the fact that it commonly involves the tibia, may be misdiagnosed as adamantinoma [5]. The possibility of misdiagnoses of other potentially biphasic-appearing malignancies that arise in (or may involve) jaw bones, such as ameloblastoma, including "malignant" ameloblastoma/ameloblastic carcinoma, in younger patients, or sarcomatoid carcinoma, in older patients, should certainly be considered in the differential diagnoses of "synovial sarcoma" from the craniofacial region and may account for discrepancies in the literature.…”

“…The appendicular skeleton, especially the long bones of the lower extremities, is far more commonly involved than the axial skeleton. Specific primary sites of involvement have included the tibia (5 cases) [2][3][4][5], ulna (2) [6,7], radius (1) [8], fibula (1) [9], femur (1) [10], and thoracic spine (1) [11]. An additional 26 reported cases, lacking molecular or cytogenetic confirmation of the diagnosis, are also identifiable within the English-language literature Table 2), some of which may not represent "true" synovial sarcomas [12][13][14][15][16][17][18][19][20][21][22].…”

Genetic characteristics and molecular diagnostics of bone tumors

“…Solitary Fibrous Tumor [151][152][153] Intrachromosomal inversion of 12q13 region NAB2-STAT6 Synovial Sarcoma [154][155][156][157] t(X;18)(p11;q11) t(X;20)(p11;q13)…”