Case of mesenchymal tumor with the PPP6R3‐USP6 fusion,possible nodular fasciitis with malignant transformation

Nodular fasciitis (NF) is a self‐limiting benign disease that is characterized by rapid proliferation of fibroblastic and myofibroblastic cells. The characteristic gene fusion containing the USP6 gene is a genetic hallmark of NF and MYH9‐USP6 is the most frequent fusion, suggesting that NF is not a reactive condition but a neoplastic disease. Malignant transformation of NF has been reported rarely as a single case associated with the PPP6R3‐USP6 fusion. Here we report a case of soft part tumor of which the histological feature was a typical NF but showed aggressive and non‐regressing growth with local invasion. Targeted RNA sequencing and fluorescence in situ hybridization analysis identified PPP6R3‐USP6 with gene amplification. These findings indicate that the present case is the second case of malignant NF, and we suggest potential malignant transformation in certain NF cases.     

Nodular fasciitis of parotid region: a pitfall in the diagnosis of pleomorphic adenomas on fine-needle aspiration cytology

Fine-needle aspiration cytology (FNAC) is routinely employed for the preoperative diagnosis of salivary gland lesions. Although most cases show morphologic features characteristic of specific entities, some lesions can be diagnostically challenging. We report two parotid aspirates, initially diagnosed as pleomorphic adenoma on FNA. The patients, a 33-yr-old white man, and a 24-yr-old white woman, presented with indurated lesions arising in the parotid gland region. The aspirates from both patients were markedly hypercellular. Smears showed a mixture of spindle cells with a well-demarcated cytoplasm showing occasional long cytoplasmic process; and cells with abundant cytoplasm with round to oval eccentric nuclei, giving the impression of plasmacytoid cells of pleomorphic adenoma. The nuclear chromatin was evenly distributed and finely granular with one or two occasional small nucleoli. Intermingled with the tumor cells were scattered neutrophils, eosinophils, and macrophages. Aggregates of spindle cells were also seen embedded in a mucoid background with occasional small tufts of a fibrillar mucoid stroma. These fibrillar tufts were magenta red in the Diff-Quik stain, giving the impression of matrix of pleomorphic adenoma. Both cases were later diagnosed on histologic examination as nodular fasciitis. Nodular fasciitis should be considered in the differential diagnosis of a mass arising in association with the parotid gland.     

Nodular fasciitis in the parotid gland: A case report and review of the literature

Nodular fasciitis (NF) is a benign, reactive lesion with a self‐limiting process. Because NF is rare in the parotid gland and has many cytological similarities to other benign or malignant tumors, cytological misinterpretation is common. The patient, a 30‐year‐old woman, had a painless mass in her right parotid gland. Fine needle aspiration cytology (FNAC) was performed. Spindle cells with basophilic and well‐demarcated cytoplasm were observed in a mucoid‐like background. The mucoid‐like substance was metachromatic and appeared to be the matrix of PA. Histopathologically, spindle‐shaped cells with intervening birefringent mature collagen were arranged in short irregular bundles. Prominent mucoid‐like matrixes as well as few infiltrating neutrophils and lymphocytes were found in the background. Lesional cells were positive for CD10 and β‐catenin in the cytoplasm, but negative for cytokeratin, the S‐100 protein, CD34, and neurofilament. Ultimately, this patient was diagnosed with NF. In FNAC of the parotid gland region, distinguishing NF from other real tumors is important for deciding treatment strategies. Diagn. Cytopathol. 2013;41:829–833. © 2013 Wiley Periodicals, Inc.     

Articular nodular fasciitis of the right shoulder joint: report of an unusual case with focus on immunohistochemical differential diagnosis

The mesenchymal lesion nodular fasciitis (NF) can affect various sites of the body but usually arises in subcutaneous tissue or occasionally skeletal muscle. NF is not commonly known to arise in joints, and articular NF is extremely rare. Herein, we present a case of a 54-year-old woman with articular NF. No sign of recurrence was observed after surgical piecemeal removal with a suspected positive surgical margin. In our case, a differential diagnosis of NF, desmoid-type fibromatosis, and low-grade myofibroblastic sarcoma was considered. Stromal hyalinization, a characteristic of articular NF, made the diagnosis somewhat difficult, although typical NF morphology was present. Immunohistochemical analysis of α-smooth muscle actin, desmin, β-catenin, and protein gene product 9.5 expression along with close morphological examination provided a reliable distinction.     

Pathologic evaluation of the solid variant of aneurysmal bone cysts with USP6 rearrangement with an emphasis on the frequent diagnostic pitfalls

The solid variant of aneurysmal bone cyst (SVABC) is very uncommon and frequently misdiagnosed. We reevaluated and summarized the clinicopathologic features of 17 SVABCs and further discussed the use of this nomenclature to differ SVABCs from extragnathic giant cell reparative granuloma (GCRG) in the setting of the USP6 rearrangement era. The immunohistochemical markers included α‐SMA, SATB2, AE1/AE3, Ki67, S100, CD68 and P63. USP‐6 status was detected by fluorescence in situ hybridization using a break‐apart probe. The 17 patients with SVABCs comprised 10 males and 7 females ranging in age from 4 to 70 years. The involved locations included the long bone (n = 11), hand (n = 4), rib (n = 1) and vertebra (n = 1). The lesions were characterized by proliferated spindle cells with scattered giant cells and hemorrhages with variable positive α‐SMA, SATB2, CD68 and Ki‐67 expression. All patients had USP6 rearrangements without H3F3A glycine 34 mutations. Our study reveals that SVABC shares similar clinical and histologic features with other bone lesions, which may lead to an erroneous diagnosis. The presence of an USP‐6 rearrangement contributes to the diagnosis SVABC; SVABC and most of the previously documented extragnathic GCRGs may be considered within the umbrella of primary aneurysmal bone cysts.     

Nodular fasciitis: a novel model of transient neoplasia induced by MYH9-USP6 gene fusion

Nodular fasciitis (NF) is a relatively common mass-forming and self-limited subcutaneous pseudosarcomatous myofibroblastic proliferation of unknown pathogenesis. Due to its rapid growth and high mitotic activity, NF is often misdiagnosed as a sarcoma. While studying the USP6 biology in aneurysmal bone cyst and other mesenchymal tumors, we identified high expression levels of USP6 mRNA in two examples of NF. This finding led us to further examine the mechanisms underlying USP6 overexpression in these lesions. Upon subsequent investigation, genomic rearrangements of the USP6 locus were found in 92% (44 of 48) of NF. Rapid amplification of 5'-cDNA ends identified MYH9 as the translocation partner. RT-PCR and direct sequencing revealed the fusion of the MYH9 promoter region to the entire coding region of USP6. Control tumors and tissues were negative for this fusion. Xenografts of cells overexpressing USP6 in nude mice exhibited clinical and histological features similar to human NF. The identification of a sensitive and specific abnormality in NF holds the potential to be used diagnostically. Considering the self-limited nature of the lesion, NF may represent a model of 'transient neoplasia', as it is, to our knowledge, the first example of a self-limited human disease characterized by a recurrent somatic gene fusion event.     

IL-6 receptor blockage inhibits the onset of autoimmune kidney disease in NZB/W F1 mice

In the present study, we examined the preventive effect of anti-mouse IL-6 receptor (IL-6R) antibody, MR16-1, on the development of autoimmune kidney disease in female NZB/W F₁ (BWF₁) mice. Immunological tolerance to MR16-1 or isotype-matched control antibody, KH-5, was induced by the simultaneous administration of anti-CD4 MoAb in mice. Thereafter, mice were intraperitoneally given 0.5 mg of MR16-1, 0.5 mg of KH-5 or saline once a week from 13 to 64 weeks of age. MR16-1 treatment dramatically suppressed proteinuria and prolonged the survival time of BWF₁ mice. Only one out of 10 mice died with high levels of proteinuria throughout the experiment. MR16-1 almost completely suppressed the production of IgG forms of anti-DNA and anti-TNP antibodies, but not the IgM forms of these antibodies. In particular, all IgG subclasses (IgG1, IgG2a, IgG2b and IgG3) of anti-DNA antibody production were significantly suppressed. Moreover, serum IgG1, IgG2a and IgG3 levels in MR16-1-treated mice were lower than those in saline- and KH-5-treated mice, whereas serum IgM and IgA levels were not influenced. In conclusion, MR16-1 potently suppressed the development of autoimmune disease in BWF₁ mice, and this was attributed to its effect of specific suppression of IgG class antibody production.     

The diversity of soft tissue tumours with EWSR1 gene rearrangements: a review

Many soft tissue sarcomas have chromosomal translocations with resultant formation of new fusion genes. Among the genes that can be rearranged, the EWSR1 gene has been identified as a partner in a wide variety of clinically and pathologically diverse sarcomas as well as some non‐mesenchymal tumours. The former include Ewing sarcoma and similar (Ewing‐like) small round cell sarcomas, desmoplastic small round cell tumour, myxoid liposarcoma, extraskeletal myxoid chondrosarcoma, angiomatoid fibrous histiocytoma, clear cell sarcoma of soft tissue and clear cell sarcoma‐like tumours of the gastrointestinal tract, primary pulmonary myxoid sarcoma, extrasalivary myoepithelial tumours and sporadic examples of low‐grade fibromyxoid sarcoma, sclerosing epithelioid fibrosarcoma and mesothelioma. EWSR1 is a ‘promiscuous’ gene that can fuse with many different partner genes, but sometimes this results in phenotypically identical tumours. EWSR1 can, conversely, partner with the same genes in morphologically and behaviourally different neoplasms. This paper reviews the diversity of the several soft tissue tumour types that are associated with rearrangement of the EWSR1 gene.     

The value of microscopic‐observation drug susceptibility assay in the diagnosis of tuberculosis and detection of multidrug resistance

Inexpensive, rapid, and reliable tests for detecting the presence and drug susceptibility of Mycobacterium tuberculosis complex (MTBC) are urgently needed to control the transmission of tuberculosis. In this study, we aimed to assess the accuracy and speed of the microscopic‐observation drug susceptibility (MODS) assay in the identification of MTBC and detection of multidrug resistance. Sputum samples from patients suspected to have tuberculosis were simultaneously tested with MODS and conventional culture [Löwenstein‐Jensen (LJ) culture, BACTEC MGIT? 960 (MGIT) system], and drug susceptibility testing (MGIT system) methods. A total of 331 sputum samples were analyzed. Sensitivity and specificity of MODS assay for detection of MTBC strains were 96% and 98.8%, respectively. MODS assay detected multidrug resistant MTBC isolates with 92.3% sensitivity and 96.6% specificity. Median time to culture positivity was similar for MGIT (8 days) and MODS culture (8 days), but was significantly longer with LJ culture (20 days) (p < 0.0001 for both comparisons). Median time to availability of the susceptibility results was significantly (p < 0.0001) shorter with MODS assay (8 days) than MGIT system (20 days). In conclusion, MODS is an inexpensive and rapid test with good performance characteristics for direct diagnosis of tuberculosis and detection of multidrug resistance.