Received Date: June 25, 2012; Accepted Date: August 09, 2012; Published Date: August 11, 2012
Citation: Orejudos MP, Hutton RL, Hilton JO (2012) Extraskeletal Myxoid Chondrosarcoma: A Case Report with Cytologic Features, Histopathology, and Variant Translocation. J Cytol Histol 3:146. doi:10.4172/2157-7099.1000146
Copyright: © 2012 Orejudos MP, et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
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Extraskeletal Myxoid Chondrosarcoma (ESMC) is a rare soft tissue sarcoma, of which its histopathologic and cytogenetic features have been thoroughly examined; however, limited reports on the description of the cytologic findings are present within the literature. We report a case of ESMC with typical cytomorphologic and histopathologic features, and cytogenetic confirmation with expression of a variant translocation. A 75 year-old male presented with a large slow-growing right arm mass discovered on imaging studies upon initial work-up. Cytologic imprint preparations of image-guided needle core biopsies demonstrated groups of a monotonous population of round to oval cells, some with grooves, embedded within a myxoid-appearing stroma. Chromosome analysis performed on incisional biopsy tissue displayed the t (9:17) instead of the more common t (9:22) translocation, and resection of the mass provided additional histologic and immunophenotypic confirmation of the diagnosis. Although ESMC has distinctive cytologic features, these are not entirely specific, and ancillary cytogenetic studies can aid in confirmation of diagnosis resulting in the best-possible (and perhaps in the near-future, more individualized) treatment of these myxoid tumors.
Extraskeletal myxoid chondrosarcoma; Variant translocation; T translocation; Myxoid tumors
Extraskeletal Myxoid Chondrosarcoma (ESMC) is a rare soft tissue sarcoma, first described by Stout and Verner , and later coined as a distinct clinicopathologic entity by Enzinger and Shiraki  in 1972 within a 34 case study. Patients with ESMC tend to be middleaged adults (>35 years) with a median age in the fifth decade and a slight male predominance (approximately 2:1), although rare cases have been described in children . The predominant sites are the proximal extremities and trunk. ESMC is considered a low-grade soft tissue tumor, which is usually slow-growing and well-circumscribed. However, recurrences and metastasis can occur several years after primary diagnosis. Few case reports describing the cytomorphologic features of Extraskeletal Myxoid Chondrosarcoma have been reported in the literature [4-9]. We present a case with diagnostic findings on cytology with histologic and molecular confirmation.
The patient is a 75 year old male who initially presented with a right arm mass, proximal to the elbow joint. The patient reported that this mass was tender to the touch and slowly growing over several months. Imaging studies demonstrated a large heterogenous soft tissue density mass centered within the brachialis muscle, which extended from the level of the distal humoral diaphysis to the myotendinous junction. Contiguous non-contrast axial CT images showed the mass was predominantly hypo-attenuating in comparison to the adjacent skeletal muscle with no evidence for osseous invasion or invasion of the overlying neurovascular bundle. MRI with pre and post-contrast imaging demonstrated the lesion was iso to mildly T1 hyper-intense to the adjacent skeletal muscle and on T2-weighted imaging, the lesion was hyper-intense (Figure 1). Following gadolinium administration, there was enhancement of the solid component of the mass more proximally.
Image-guided needle core biopsies of the mass were obtained and touch imprint preparations performed at the procedure demonstrated a relatively uniform population of round to oval cells with fine dark chromatin and inconspicuous nucleoli (Figures 2 and 3), and some with nuclear grooves to include “coffee bean” appearing nuclei (Figure 4). The tumor cells are arranged in clusters and occasional cords and embedded within a brightly metachromatic myxoid stroma (Diff Quick stain) which is fibrillar in quality, reminiscent of pleomorphic adenoma of the salivary gland (Figure 5). On the Papanicolau stain, the myxoid stroma exhibited a pale blue-green and more transparent appearance (Figure 6).
Histopathology and Immunohistochemistry
The patient later underwent resection of the tumor which measured 7.0 cm in greatest dimension and exhibited a gelatinous and nodular cut surface. Histologic examination revealed a multi-lobular tumor composed of uniform oval to elongated cells arranged in loose sheets and anastamosing cords, imparting a reticular appearance (Figures 7 and 8). The tumor cells were present in a background of abundant myxoid/mucoid material (Figure 8). The individual cells showed eosinophilic cytoplasm and vesicular nuclei with mild-to-moderate pleomorphism. Rare mitoses were identified, averaging 2 per 10 HPF. Immunohistochemical staining displayed a positive reaction for vimentin only. The CD31, CD99, Desmin, Myogenin, Smooth Muscle Actin (SMA), S-100, EMA, Lu-5 (pan-cytokeratin), Synaptophysin, and CD45 immunostains were all negative.
Cytogenetic and molecular genetic analysis
Paraffin embedded tissue from the surgical biopsy specimen was submitted for Fluorescence In-Situ Hybridization (FISH) and the tumor was found to be negative for ESWR1, FUS, and CHOP rearrangements. However, chromosome analysis revealed a t (9:17) (q22; q11) variant translocation.
Extraskeletal Myxoid Chondrosarcoma is an uncommon tumor which arises predominantly in the soft tissues of the extremities with the most common location in the deep thigh. Other sites include the hand, retroperitoneum, head and neck, with rare cases arising in the retroperitoneum or the thoracic cavity. The cytologic features and immunohistochemistry, although far from specific and not entirely characteristic, can be helpful in distinguishing this entity from other neoplasms with myxoid features. More recently, ESMC has been found to demonstrate a consistent translocation, t (9; 22) (q22; q12), involving the Ewing Sarcoma (EWS) gene, resulting in a gene fusion product, and providing a more specific marker for this tumor.
Diagnostic cytomorphologic criteria for ESMC have been described in the literature among few case reports and small case series [4-9]. Common features include 1) a background myxoid matrix with embedded tumor cells, 2) anastamosing cords and lacelike arrangements or clusters of uniform round to spindle-shaped cells with bland appearing nuclei and inconspicuous nucleoli, and 3) grooved or cleaved nuclei suggesting chondroblast-like derivation; all of which were identified in our case. Other cell types have been reported to occur but only in rare cases, including epithelioid cells with vesicular nuclei, prominent nucleoli, and abundant cytoplasm; rhabdoid cells with hyaline cytoplasmic globules, or anaplastic cells (ranging from small blue cells to spindle cells to pleomorphic cells). However, other myxoid tumors of soft tissue should also be considered in the differential diagnosis based on cytology to include myxoid liposarcoma, myxofibrosarcoma, malignant fibrous histiocytoma, myxoid peripheral nerve sheath tumor, chordoma/parachordoma, and myxoma.
Our case demonstrated the typical ESMC histologic findings to support the initial cytologic impressions. The tumor was composed of multiple myxoid lobules, some separated by fibrous septa. The tumor cells demonstrated cord and strand-like arrangements forming netlike and linear interconnected patterns. The cells were round to stellate with hyperchromatic, uniform, round to oval nuclei and scant to moderately abundant eosinophilic cytoplasm. Mitotic activity was low and no significant pleomorphism was noted.
However, ESMC has no distinct diagnostic immunohistochemical profile and vimentin is generally expressed, as in our current case, with S-100 protein and EMA positivity reported in 20-50% and 30% of reported cases, respectively. There have been few reported cases of EMSC showing variable immunoreactivity with synaptophysin, chromogranin, and NSE, suggesting possible neuroendocrine differentiation .
Ancillary cytogenetic and molecular studies can be extremely useful in establishing a definitive diagnosis for ESMC. ESMC is marked by a reciprocal translocation: t (9:22) (q22; q12), generating a EWS/NR4A3 gene fusion, in approximately 75% of cases [11-13]. A variant (9:17) (q22; q11) translocation resulting in the fusion of NR4A3 gene at 9q22 with TAF15 gene at 17q11 has also been identified in ESMC [14,15]. Our case demonstrated negative FISH results with the EWSR1 and FUS probes, which correspond to rearrangements involving chromosomes 22 and 16, respectively. The negative EWSR1 FISH results corroborated the lack of the most common ESMC translocation in our case. This finding also aided in ruling out additional entities, such as Ewing’s Sarcoma/PNET, which admittedly don’t often demonstrate myxoid features microscopically, but can show small cell-type morphology with rearrangements involving chromosome 22. Additionally, the negative FUS by FISH also assisted in ruling out myxoid liposarcoma (often involving rearrangements on chromosome 16), which can demonstrate myxoid features both cytologically and on histopathology, similar to those seen with ESMC. Finally, chromosome analysis performed on our case confirmed the presence of the variant t (9:17) translocation in support of the classic ESMC microscopic findings observed.
ESMC is a rare tumor which should be considered in the differential diagnosis when encountering a myxoid soft tissue neoplasm, especially given the large number of distinct entities which share the common feature of a myxoid background. Therefore, a multi-modal approach to include histopathologic correlation and the utilization of ancillary cytogenetic and molecular testing may be necessary in establishing a more definitive diagnosis, which may ultimately lead to a more targeted and specific treatment for patients.