ABSTRACT. We describe a pediatric patient with histiocytic sarcoma involving the T6 and L4 vertebral bodies and the lungs. His tumor progressed during chemotherapy designed for Langerhans' cell histiocytosis and sarcoma. High-dose radiation, on the other hand, was effective. Pediatrics 2005;116:e322-e325. URL: www. pediatrics.org/cgi/doi/10.1542/peds.2005-0026; sarcoma, histiocytes, Langerhans' cell histiocytosis, histiocytic sarcoma.ABBREVIATIONS. LCH, Langerhans' cell histiocytosis; CT, computed tomography; 2CdA, 2-chlorodeoxyadenosine.H istiocytic and dendritic neoplasms are rare, especially in children. These tumors arise from antigen-processing phagocytes (histiocytes) and antigen-presenting dendritic cells. The cell types are derived from hematopoietic or mesenchymal stem cells. 1 Currently, the World Health Organization includes the following 6 entities under this designation: Langerhans' cell histiocytosis (LCH), Langerhans' cell sarcoma, follicular dendritic cell sarcoma, interdigitating dendritic cell sarcoma, dendritic cell sarcoma not otherwise specified, and histiocytic sarcoma. 2 The latter malignancy is a proliferation of histiocytes (tissue macrophages), which are characterized by positive expression of the macrophage-associated antigen CD68, negative expression of the T-cell-associated antigen CD1a, negative expression of the dendritic cell-associated antigens CD21/CD35, and lack of Birbeck granules on electron microscopy. 3 The rarity of histiocytic sarcoma continues to make its management challenging, and we are unaware of any recommended therapy for young children. We describe a child with histiocytic sarcoma to highlight his poor response to LCH-and sarcoma-based chemotherapy. By contrast, high-dose radiation proved to be effective. CASE REPORTThis previously healthy 3-year-old boy experienced intermittent low back pain radiating to the right inguinal region for ϳ2 months. His symptoms initially responded to ibuprofen. The pain intensity increased over a 2-week period, and he refused to walk. Review of systems was significant for pain with urination. With the exception of being unable to stand, his physical examination was unremarkable. The laboratory tests showed normal blood counts and normal liver and renal function. An MRI showed collapse of the T6 and L4 vertebral bodies and a soft tissue mass in the anterior epidural space at the level of L4 (Fig 1 A and B). The chest and abdominal computed tomography (CT) scans were normal. Bone marrow aspiration revealed no malignant infiltration. A technetium bone scan showed increased uptake limited to the T6 and L4 regions. CT-scan-guided needle biopsy of the L4 mass revealed infiltrative proliferation of the bone and soft tissue by sheets and clusters of large ovoid cells with abundant eosinophilic cytoplasm (Fig 2A). The nuclei were round/oval, eccentric, and pleomorphic with occasional grooving. Distinct, small nucleoli were present. Multinucleated giant cells were also present ( Fig 2B). Immunohistochemistry showed expression of CD68 (macroph...

Parachordoma, or myoepithelioma, is a very rare tumor histologically resembling chordoma but occurring in the nonaxial soft tissues. It typically has an indolent nature, with occasional late recurrence and even rare metastases. Review of existing literature reveals a male predilection, with the tumor typically occurring in the fourth decade of life in the lower extremity. It typically is managed with wide resection. We report the case of a 60-year-old woman with a right distal upper arm parachordoma treated with wide resection of the tumor.

Myxoid liposarcoma with or without a round cell component is the most common subtype of liposarcoma. The diagnosis of myxoid liposarcoma could be challenging with histology, as a variety of soft tissue tumors with myxoid change might mimic myxoid liposarcoma, especially on small biopsy tissues. Chromosomal translocations of t(12,16) (q13;p11) and t(12;22) (q13;q12), rendering gene fusions of DDIT3 (previously CHOP) with FUS and EWSR1, have been found to be characteristic of myxoid liposarcoma, and were identifiable in more than 95% cases. These genetic alterations, therefore, are ideal as molecular markers to facilitate the diagnosis of this type of tumor. DDIT3 (12q13) dual-color break-apart rearrangement probe for fluorescence in situ hybridization has been commercially available. However, its consistency with DDIT3-associated gene fusion and its clinical use, including sensitivity and specificity, have not been adequately evaluated. In this study, we assessed the locus specificity of the probe on metaphase, and then tested it on 8 cases of myxoid liposarcoma, 12 cases of other sarcomas, and 18 cases of tumors with myxoid differentiation. All 8 myxoid liposarcomas showed DDIT3 gene break-apart, whereas all 12 other sarcomas were negative. All the cases with DDIT3 break-apart also showed FUS-DDIT3 fusion by reverse transcription-polymerase chain reaction, with 100% consistency. In addition, the FISH assay has been clinically applied on 18 myxoid tumors with promising outcome. In conclusion, FISH with DDIT3 break-apart probe is a highly sensitive and specific assay for detection of DDIT3-associated gene fusions, and therefore is a valuable adjunct in diagnosis or differential diagnosis of myxoid liposarcoma.

Expression of the transducin-like enhancer of split 1 (TLE1) by immunohistochemistry (IHC) has been widely used as a biomarker for the diagnosis of synovial sarcoma. Although TLE1 expression can be identified in more than 90% of synovial sarcomas, positive staining has been reported in up to one third of nonsynovial sarcomas, including peripheral nerve sheath tumors and neoplasms of fibrous and adipose tissues. The low specificity of this test in soft tissue tumors raises concern on its clinical application as a diagnostic biomarker. As synovial sarcoma is frequent among the differential diagnosis of unclassified high-grade sarcomas, and considering that the specificity of TLE1 antibody in this tumor group remains unclear, we evaluated TLE1 expression by IHC in 42 unclassified high-grade sarcomas. SS18 (SYT) gene break-apart analyses by fluorescence in situ hybridization were simultaneously performed as a gold standard biomarker for synovial sarcoma. Five cases that were positive for the SS18 break-apart by fluorescence in situ hybridization were also positive for TLE1 by IHC, whereas the remaining 37 cases negative for SS18 break-apart were all negative for TLE1. The results showed no evidence of nonspecific TLE1 expression in the nonsynovial high-grade sarcomas. We concluded that TLE1 is a highly specific biomarker for synovial sarcoma in the setting of differential diagnosis of unclassified high-grade sarcomas.

The characteristic immunoprofile for the diagnosis of synovial sarcoma, a neoplasm of unclear tissue origin, is expression of transducer-like enhancer of split 1 (TLE-1), CD99, partial expression of cytokeratin, and epithelial membrane antigen by immunohistochemistry (IHC). Diagnostic dilemma or misdiagnosis can occur due to overlap in IHC and morphology with carcinomas, and particularly poorly differentiated and metastatic tumors. The frequency of TLE-1 and CD99 expression in carcinomas by IHC has not been previously assessed. We evaluated TLE-1 and CD99 expression in various carcinomas and evaluated the expression of the SS18 (SYT) gene rearrangement (a characteristic biomarker for synovial sarcoma) in tumors with TLE-1 and/or CD99 expression. Immunostains of TLE-1 and CD99 were performed in 100 various carcinomas. Seven of the 98 cases (7%) of carcinomas showed TLE-1 expression, including 1 each of prostate adenocarcinoma (ADCA), esophageal ADCA, basal cell carcinoma, adrenocortical carcinoma, endometrial ADCA, ovarian serous carcinoma, and small cell carcinoma. Twenty-one of the 100 cases (21%) of carcinomas demonstrated CD99 expression, including 6 prostate ADCA, 3 esophageal ADCA, 5 squamous cell carcinomas, 2 hepatocellular carcinomas, 1 each for endometrial ADCA, renal cell carcinoma, urothelial cell carcinoma, neuroendocrine carcinoma, and mucoepidermoid carcinoma. An esophageal ADCA was positive for both TLE-1 and CD99. None of the carcinomas with positive TLE-1 (n=7) or CD99 (n=21) by IHC showed SS18 gene rearrangement by fluorescent in situ hybridization. TLE-1 and CD99 expression were identified in 7% and 21% of carcinomas, respectively. This is a potential pitfall in the IHC interpretation for diagnosis of synovial sarcoma. SS18 gene rearrangement by fluorescent in situ hybridization is helpful for the diagnostically challenging cases, either for confirmation or exclusion of synovial sarcoma.