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Immunotherapy of musculoskeletal tumors remains clinically challenging and requires the development of gene-engineered/adoptive exogenous immune cells or the identification of new molecular target(s) that can be therapeutically exploited to improve patient outcome. Recently, endogenous B-cell infiltration into tumor microenvironments appears to be an essential promising prognostic factor controlling tumor progression in musculoskeletal malignancy. Here, we explored the level of T-cell infiltration by analyzing expression profiles of CD3E, CD4, and CD8A in 1366 patients and 23 histological types. The data revealed that CD3E and CD8A expressions were predominantly inhibited in bone tumors when compared with normal bone. CD4 expression was upregulated in limited types of tumors, including chondrosarcoma and giant cell tumor of bone, whereas other tumors demonstrated relatively lower expressions. Similarly, regarding soft tissue sarcoma, the expression of T-cell-related molecules was largely inhibited. Only in patients with rhabdomyosarcoma, CD3E and CD8A expressions were significantly upregulated, showing the nature of immune-active tumor. To visualize the immunological microenvironment of rhabdomyosarcoma, we have developed a novel software aimed at analyzing numerous cell-to-cell and ligand-to-receptor interactions, that is, Environmentome. It has led to the identification of molecular interactions between CD8 + T cell and rhabdomyosarcoma via Galectin3-LAG3 binding, which is a novel immune checkpoint recently identified. In conclusion, musculoskeletal tumors may be defined as immune-quiescent tumors, whereby targeting Galectin-3 and/or immune-infiltrative agents could be crucial in these immunologically noninflamed musculoskeletal tumors, accelerating immunotherapeutic response., (© 2020 Orthopaedic Research Society. Published by Wiley Periodicals LLC.)

We report a case of solitary infantile myofibroma (IM) with partially CD34-positive neoplastic cells on the back of a newborn boy. Ultrasonography showed a multilocular mass with a hypoechoic center surrounded by an isoechoic rim. Histopathological analysis revealed that the lesion was composed of small, round cells that were tightly packed and uniform. The cells had oval nuclei and were pale, CD34-positive, and richly cellular. They had interlacing fascicles of spindle cells with features of myofibroblasts with α-smooth muscle actin positivity. We speculate that neoplastic cells in most IMs differentiate towards myofibroblasts. However, in rare cases, their differentiation is more primitive and they express CD34, with or without α-smooth muscle actin expression.

Background: Pediatric mastocytosis differs from adult mastocytosis in its presentation and clinical course. However, the data regarding the immunophenotypic characterization of mast cells in children are limited. Our objective was to evaluate the immunophenotype of mast cells in pediatric mastocytosis and correlate it with the clinical course., Methods: Biopsy specimens of children with cutaneous mastocytosis were retrieved from the institutions of pathology and were stained for CD25, CD2, and CD30. The percentage of mast cells and the staining intensity were correlated with the clinical data., Results: Twenty-five biopsy specimens were included in the study. Patients' average age was 15.4 at presentation and 37.5 months at biopsy performance. Clinical presentations included maculopapular cutaneous mastocytosis in 79% and mastocytoma in 21% of cases. CD25, CD2, and CD30 were positive in 60%, 44%, and 84% of the biopsy specimens, respectively. The staining score was significantly higher for CD30 as compared to those for CD25 and CD2 (P = 0.02). No correlation was found between the immunophenotype and the clinical form or course of disease., Conclusions: Our results confirm that CD30 is a sensitive marker for pediatric-onset mastocytosis. Nevertheless, its expression does not correlate with clinical subtype or clinical course. The sensitivity of CD25 is higher than that of CD2 in skin lesions., (© 2019 Wiley Periodicals, Inc.)