Introduction: Inflammatory myofibroblastic tumor (IMT), a locally aggressive neoplasm capable of metastasis, may show an IgG4-rich lymphoplasmacytic infiltrate. Prior reports suggest that storiform-fibrosis and obliterative phlebitis aid in the distinction of IMT from IgG4-related diseases. Herein, we highlight the morphologic overlap between the two diseases, and emphasize the importance of a multiplex fusion assay in the distinction of IgG4-RD from IMT. Methods: We identified 7 IMTs with morphologic and immunohistochemical features of IgG4-RD; 3 patients were originally diagnosed with IgG4-RD. Demographic, clinical and morphologic data was recorded. We also re-evaluated 56 patients with IgG4-RD. We performed immunohistochemistry for IgG4, IgG, ALK and ROS1. In situ hybridization for IgG4 and IgG was performed in selected cases. A multiplex next-generation sequencing (NGS) based RNA assay for gene fusions was performed to detect all known IMT-related gene fusions. Results: All 7 IMTs showed a dense lymphoplasmacytic infiltrate and storiform-type fibrosis, with obliterative phlebitis noted in 3 cases. The neoplastic stromal cells constituted <5% of overall cellularity and stromal atypia was either absent or focal and mild. Elevated numbers of IgG4 positive cells and increased IgG4 to IgG ratio was identified in all cases. Four cases showed ALK related abnormalities; while two patients showed ROS1 and NTRK3 fusions. One tumor was negative for known IMT-related gene fusions. All 56 IgG4-RD cases were negative for ALK and ROS1 on immunohistochemistry; 6 cases were negative on the fusion assay. Conclusion: Highly-inflamed IMTs are indistinguishable from IgG4-RD both histologically and on immunohistochemistry for IgG4. We advocate scrutinizing patients with presumptive single organ IgG4-RD for IMT and the diagnostic algorithm should include ALK and ROS1 immunohistochemistry and, in selected cases, a NGS-based fusion assay that covers known IMTassociated gene fusions.

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Myeloid sarcoma (MS) is a malignant extramedullary tumour, which consists of immature cells of myeloid origin. It may occur de novo, concurrently or precede the diagnosis of acute myeloid leukemia (AML), myelodysplastic syndrome (MDS) or chronic myeloid leukemia (CML). MS can also be a manifestation of the relapse of the disease. The more frequent sites of involvement are the skin, orbit, bone, periosteum, lymph nodes, gastrointestinal tract, soft tissue, central nervous system and testis. Because of its different localization and symptoms, and the lack of diagnostics algorithm, myeloid sarcoma is a real diagnostic challenge, in particular in patients without initial bone marrow involvement. The correct diagnosis of MS is important for adequate therapy, which is often delayed because of a high misdiagnosis rate. In the paper, the role of immunohistochemistry, cytogenetic and molecular genetic analyses is emphasized as well as the breadth of unclear aspects of this disorder in children.

The clinical and pathologic features of 8 primary myoepitheliomas of bone were analyzed. There were 5 female and 3 male patients who ranged in age from 16 to 49 (mean, 33.5) years. Three tumors arose in the ilium, 2 in the tibia, and 1 each in the maxilla, sacrum, and L1 vertebral body. Microscopically, the tumors had a solid, lobulated, reticular, or storiform growth pattern and were predominantly composed of spindle-shaped cells arranged in intersecting fascicles with eosinophilic cytoplasm. The round to polygonal epithelioid cells were arranged randomly or formed small clusters and contained variable amounts of eosinophilic or clear cytoplasm. Immunohistochemically, all the tumors were positive for vimentin and S100 protein, and 7 were positive for epithelial membrane antigen. No tumors were positive for keratin (AE1.3/CAM5.2). Smooth muscle actin was positive in 3 tumors and negative in 4, whereas desmin was negative in all 7 tumors tested. Nuclear staining for p63 was negative in 3 tested tumors. Staining for GFAP and CD34 was performed on 4 and 5 tumors, respectively, and all showed no expression. Fluorescence in situ hybridization for EWSR1 rearrangement was performed in 7 tumors. Five tumors (71%) showed the presence of EWSR1 gene rearrangement, and 2 were negative. Cytogenetic studies conducted on 1 tumor showed 46,XY,t(1;22)(q21;q12) associated with EWSR1-PBX1 fusion. Surgical procedures included curettage in 3 patients, resection in 3 patients, and 2 patients only had an open biopsy. Follow-up information was available for 4 patients; all remain free of disease with no recurrence. Although experience with primary myoepithelioma of bone is limited, histologically, banal tumors appear to behave in a benign manner, and conservative surgery appears to be sufficient treatment. Immunohistochemical and molecular analyses are helpful in their accurate identification.

These recommendations, concerning the diagnostics and treatment of differentiated thyroid cancer (DTC) in children and adolescents, are the first such Polish guidelines created by the group of delegates of National Societies that declare their willingness to participate in their preparation. The signal that gathered specialists involved in the medical care of children with thyroid carcinoma was the publication of the guidelines of the

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The distinction of atypical lipomatous tumor/well-differentiated liposarcoma (ALT/WDL) from its benign counterpart, lipoma, may represent a challenge. MDM2 DNA amplification is used as the gold standard as MDM2 immunohistochemistry lacks specificity and sensitivity. Herein, we investigate the diagnostic utility of MDM2 RNA in situ hybridization (RNA-ISH) and compare the test with MDM2 immunohistochemistry and MDM2 DNA fluorescence in situ hybridization (FISH) in benign and malignant lipomatous neoplasms. We evaluated 109 neoplasms including 27 lipomas, 25 spindle cell lipomas, 32 ALTs/WDLs, and 25 dedifferentiated liposarcomas (DDL). The validation cohort included 14 lipoma-like neoplasms that lacked unequivocal features of ALT/WDL and in which MDM2 immunohistochemistry was either equivocal, negative or falsely positive. Immunohistochemistry, automated RNA-ISH and DNA-FISH for MDM2 were performed. Tumors with diffuse nuclear staining or >50 dots per cell on RNA-ISH were considered positive. All lipomas and lipoma variants were negative for RNA-ISH while all ALTs/WDLs and DDLs were positive. Eighty percent (24/30) and 92% (22/24) of ALTs/WDLs and DDLs were positive for MDM2 immunohistochemistry. Lipomas and its variants were negative for MDM2 amplification; 92% and 100% of ALTs/WDLs and DDLs showed MDM2 DNA amplification. The mean percentage of ALT/WDL tumor cells showing MDM2 RNA-ISH positivity was 73% compared with 24% on MDM2 immunohistochemistry. RNA-ISH correctly classified all 10 ALTs/WDLs and all 4 lipomas in the validation cohort. The performance of MDM2 RNA-ISH and MDM2 DNA-FISH are equivalent. MDM2 RNA-ISH can be of diagnostic value in histologically challenging lipomatous neoplasms. The automated MDM2 RNA-ISH assay should allow for more widespread use of MDM2 testing and for a more sensitive and specific diagnosis of ALT/WDL.