Inflammatory Rhabdomyoblastic Tumor: Clinicopathologic and Molecular Analysis of 13 Cases.

Inflammatory rhabdomyoblastic tumors (IRMTs) are newly recognized skeletal muscle tumors with uncertain malignant potential. We investigated 13 IRMTs using clinicopathologic, genetic, and epigenetic methods. The cohort included 7 men and 6 women, aged 23 to 80 years (median, 50 years), of whom 2 had neurofibromatosis type 1. Most tumors occurred in the deep soft tissues of the lower limbs, head/neck, trunk wall, and retroperitoneum/pelvis. Two tumors involved the hypopharyngeal submucosa as polypoid masses. Eight tumors showed conventional histology of predominantly spindled cells with nuclear atypia, low mitotic activity, and massive inflammatory infiltrates. Three tumors showed atypical histology, including uniform epithelioid or plump cells and mitotically active histiocytes. The remaining 2 tumors demonstrated malignant progression to rhabdomyosarcoma; one had additional IRMT histology and the other was a pure sarcoma. All 11 IRMTs without malignant progression exhibited indolent behavior at a median follow-up of 43 months. One of the 2 patients with IRMTs with malignant progression died of lung metastases. All IRMTs were positive for desmin and PAX7, whereas myogenin and MyoD1 were expressed in a subset of cases. Targeted next-generation sequencing identified pathogenic mutations in NF1 (5/8) and TP53 (4/8). All TP53 mutations co-occurred with NF1 mutations. TP53 variant allele frequency was much lower than that of NF1 in 2 cases. These tumors showed geographic (subclonal) strong p53 immunoreactivity, suggesting the secondary emergence of a TP53-mutant clone. DNA methylation-based copy number analysis conducted in 11 tumors revealed characteristic flat patterns with relative gains, including chromosomes 5, 18, 20, 21, and/or 22 in most cases. Widespread loss of heterozygosity with retained biparental copies of these chromosomes was confirmed in 4 tumors analyzed via allele-specific profiling. Based on unsupervised DNA methylation analysis, none of the 11 tumors tested clustered with existing reference entities but formed a coherent group, although its specificity warrants further study.

A delayed diagnostic case with complaints of severe lower back pain and sciatic nerve symptoms caused by osteoid osteoma of the sacrum: A case report.

BACKGROUND: Osteoid sacral osteomas are rare. Patients present with severe lower back pain and, rarely, sciatic nerve symptoms. CASE PRESENTATION: Herein, we report a patient with delayed diagnosis with complaints of severe lower back pain and sciatic nerve symptoms compressed by a sacral osteoid osteoma. En bloc tumor resection was performed using computed tomography (CT)-based navigation. Complete resolution of symptoms was achieved immediately after surgery. CONCLUSION: Even if a patient with an osteoid osteoma has sciatic symptoms, spinal surgeons should recognize a subgroup of patients with unexpected spinal or pelvic tumors compressing the nerve root.

Clinical Outcome of Low-Grade Myofibroblastic Sarcoma in Japan: A Multicenter Study from the Japanese Musculoskeletal Oncology Group.

This retrospective multicenter study aimed to analyze the clinical features and prognosis of 24 patients diagnosed with LGMS between 2002 and 2019 in the Japanese sarcoma network. Twenty-two cases were surgically treated and two cases were treated with radical radiotherapy (RT). The pathological margin was R0 in 14 cases, R1 in 7 cases, and R2 in 1 case. The best overall response in the two patients who underwent radical RT was one complete response and one partial response. Local relapse occurred in 20.8% of patients. Local relapse-free survival (LRFS) was 91.3% at 2 years and 75.4% at 5 years. In univariate analysis, tumors of 5 cm or more were significantly more likely to cause local relapse (p < 0.01). In terms of the treatment of relapsed tumors, surgery was performed in two cases and radical RT was performed in three cases. None of the patients experienced a second local relapse. Disease-specific survival was 100% at 5 years. A wide excision aimed at the microscopically R0 margin is considered the standard treatment for LGMS. However, RT may be a viable option in unresectable cases or in cases where surgery is expected to cause significant functional impairment.

Diagnosis and Treatment of Brown Tumor in the Femur Induced by Parathyroid Carcinoma: A Case Report.

Brown tumors are rare destructive bone lesions caused by hyperparathyroidism. As their clinical symptoms, radiographic findings, and laboratory results closely mimic those of metastatic tumors or multiple myeloma, the diagnosis may often be mistaken. We report a case of a 61-year-old woman with brown tumors in both femurs due to parathyroid carcinoma. The patient presented with multiple osteolytic lesions that caused pain in the right thigh. Whole-body computed tomography (CT), including the neck, suspected a parathyroid tumor, and a biopsy of the bone lesion revealed no malignancy. Following parathyroidectomy, she was diagnosed with a brown tumor with hyperparathyroidism due to a very rare parathyroid carcinoma. Although the right femoral lesion was indicated as an impending fracture, conservative treatment was performed because of the instability of her general condition after parathyroidectomy and her wishes. Bone remodeling of the right femur progressed, and the patient was ambulatory; however, 9 months postoperatively, the patient fell, developed a pathological fracture, and underwent internal fixation. When multiple osteolytic bone lesions are present, CT imaging of the neck should be performed to determine the possibility of a brown tumor due to parathyroid disease. Bone lesions of brown tumors are known to be naturally cured after treatment for hyperparathyroidism. However, when the lesion of a brown tumor in the femur is an impending fracture, prophylactic internal fixation is recommended aggressively if the patient's general condition permits.

A case of dermatofibrosarcoma protuberans with neurofibromatous change.

A 31-year-old man with posterior neck mass visited a hospital. The mass recurred four times on the same location during the past 6 years. Needle biopsy diagnosis was suspicious for benign stromal tumor. Tumor excision was performed 3 months after the biopsy. The tumor size was 8.3 × 4.5 cm and was located at subcutaneous tissue. Histologically, main tumor cells showed comma-shaped nuclei, which are same as neurofibroma. Immunohistochemically, tumor cells were positive for vimentin, CD34, but were negative for S-100. Fluorescence in situ hybridization analysis disclosed a split signal of PDGFB gene. Reverse transcriptase-polymerase chain reaction clarified COL1A1 exon 47/PDGFB exon 2 chimeric gene. Final diagnosis was dermatofibrosarcoma protuberans (DFSP) with neurofibromatous change. DFSP with neurofibromatous change is rare and could be misdiagnosed as benign tumor, especially in a biopsy specimen. Molecular diagnosis is a promising aid in a challenging case and in biopsy specimens.

Distinction between benign and malignant soft tissue tumors based on an ultrasonographic evaluation of vascularity and elasticity.

The initial diagnostic distinction between benign and malignant soft tissue tumors is critical for decisions regarding the appropriate course of treatment. The current study aimed to evaluate the vascularity and elasticity of soft tissue tumors by superb microvascular imaging and shear wave elastography using ultrasonography (US), to determine their usefulness in distinguishing malignant soft tissue tumors, and to further establish the diagnostic accuracy and usefulness of a scoring system (SS) based on these evaluations. The present study used 167 lesions of soft tissue tumors examined by US prior to biopsy, surgery and pathological tissue diagnosis. The vascularity index (VI) and the maximal shear velocity (MSV), as indices of vascularity and elasticity respectively, were evaluated using US. The tumor size and depth were also evaluated via magnetic resonance imaging (MRI). Based on the odds ratio of these parameters determined by multivariate logistic regression analysis, an original SS was established to identify the malignancy of soft tissue tumors. VI and MSV exhibited significantly high values for malignant tumors. Tumor size was also significantly larger for malignant than benign tumors. The areas under the curves (AUCs) of the receiver operating characteristic analysis for VI, MSV and tumor size were 0.75, 0.84 and 0.69, respectively, indicating that these methods were effective for the diagnosis of malignancy. An original SS consisting of VI, MSV and tumor size, excluding tumor depth, was established, and revealed an AUC value of 0.90, with 93.6% sensitivity and 79.2% specificity for malignancy distinction. US evaluation of vascularity and elasticity was an effective technique to distinguish malignant soft tissue tumors, and the current SS based on US evaluations including tumor size via MRI demonstrated a high diagnostic accuracy for malignant soft tissue tumors.

Uptake of fluorescent D- and L-glucose analogues, 2-NBDG and 2-NBDLG, into human osteosarcoma U2OS cells in a phloretin-inhibitable manner.

Mammalian cells take in D-glucose as an essential fuel as well as a carbon source. In contrast, L-glucose, the mirror image isomer of D-glucose, has been considered merely as a non-transportable/non-metabolizable control for D-glucose. We have shown that 2-[N-(7-Nitrobenz-2-oxa-1,3-diazol-4-yl)amino]-2-deoxy-D-glucose (2-NBDG), a D-glucose analogue combining a fluorophore NBD at the C-2 position, is useful as a tracer for monitoring D-glucose uptake through glucose transporters (GLUTs) into mammalian cells. To more precisely evaluate the stereoselectivity of 2-NBDG uptake, we developed an L-glucose analogue 2-NBDLG, the mirror-image isomer of 2-NBDG. Interestingly, 2-NBDLG was taken up into mouse insulinoma MIN6 cells showing nuclear heterogeneity, a cytological feature of malignancy, while remaining MIN6 cells only exhibited a trace amount of 2-NBDLG uptake. The 2-NBDLG uptake into MIN6 cells was abolished by phloretin, but persisted under blockade of major mammalian glucose transporters. Unfortunately, however, no such uptake could be detected in other tumor cell lines. Here we demonstrate that human osteosarcoma U2OS cells take in 2-NBDLG in a phloretin-inhibitable manner. The uptake of 2-NBDG, and not that of 2-NBDLG, into U2OS cells was significantly inhibited by cytochalasin B, a potent GLUT inhibitor. Phloretin, but neither phlorizin, an inhibitor of sodium-glucose cotransporter (SGLT), nor a large amount of D/L-glucose, blocked the 2-NBDLG uptake. These results suggest that a phloretin-inhibitable, non-GLUT/non-SGLT, possibly non-transporter-mediated yet unidentified mechanism participates in the uptake of the fluorescent L-glucose analogue in two very different tumor cells, the mouse insulinoma and the human osteosarcoma cells.

Teriparatide may accelerate the growth of a pre-existing malignant tumor in an elderly patient with osteoporosis: A case report.

The present report describes a case in which teriparatide, which is widely used to treat osteoporosis, may have accelerated the growth of an undiagnosed pre-existing bone tumor of the femur. A 76-year-old woman visited hospital with pain in the right thigh after falling from a ladder. A non-pathological femoral shaft fracture was diagnosed by plain radiography. There were no findings of pathological fracture on the examination. In addition, the patient underwent intramedullary femoral nail fixation and started teriparatide treatment for osteoporosis. The teriparatide was discontinued after 2 months due to nausea. A total of 6 months after surgery, the woman visited Hirosaki University Hospital with abnormal swelling of the right thigh. Following a diagnosis of high-grade malignant mesenchymal bone tumor by needle biopsy, the patient underwent right hip disarticulation. Pathological examination provided a definitive diagnosis of osteoblastic osteosarcoma. The present case is a reminder that teriparatide may accelerate the growth of a pre-existing malignant tumor and that fractures, particularly in elderly patients, should be screened for pathological fracture prior to administering teriparatide.

Diagnosis and conservative treatment of a rare case of femoral intraosseous arteriovenous malformation in a patient with polyostotic fibrous dysplasia: A case report.

Pure intraosseous arteriovenous malformation (AVM) in a limb bone is extremely rare. Furthermore, there is currently insufficient information on the diagnostic and therapeutic strategies for pure intraosseous AVMs. We herein report a case of pure intraosseous AVM of the proximal femur occurring in a patient with polyostotic fibrous dysplasia. The patient was a 39-year-old woman who presented with pain in the right thigh. Plain radiographs and computed tomography scans revealed a medullary lytic lesion with expansion and thinning of the bone cortex in the right proximal femur, mimicking a primary bone tumor. Magnetic resonance imaging (MRI) examination revealed intramedullary signal voids and feeding arteries arising from the deep femoral artery. A non-surgical approach using embolization and denosumab achieved satisfactory results, which included complete obliteration of the AVM, increased cortical thickness of the right proximal femur, and attenuation of the high-turnover bone metabolism 1 year later. Careful review of MRI images is crucial for distinguishing between bone tumors and intraosseous AVM, which exhibit signal voids and feeding arteries, in order to avoid unnecessary interventions such as bone biopsy or surgery.

Potential of exogenous cartilage proteoglycan as a new material for cartilage regeneration.

BACKGROUND: Although proteoglycan (PG) is one of the major components of cartilage matrices, its biological function is not fully elucidated. METHODS: The objectives of this study were to investigate the proliferation and differentiation of chondrocytes embedded in atelocollagen gel with exogenous cartilage PG (PG-atelocollagen gel) in vitro, and also to evaluate the repair of cartilage defects by PG-atelocollagen gel in vivo. In the in vitro study, rabbit chondrocytes were cultured in the PG-atelocollagen gel. Cell proliferation and mRNA expression levels were measured, and gels were histologically evaluated. In the in vivo study, cultured PG-atelocollagen gel containing chondrocytes were transplanted into full-thickness articular cartilage defects in rabbit knees, and evaluated macroscopically and histologically. RESULTS: For the in vitro study, chondrocyte proliferation in 5.0 mg/ml PG-atelocollagen gel was enhanced, and the gene expression of Col2a1 and Aggrecan were decreased. In contrast, chondrocyte proliferation in 0.1 and 1.0 mg/ml PG-atelocollagen gel was not enhanced. The gene expression of Aggrecan in 0.1 and 1.0 mg/ml PG-atelocollagen gel was increased. For the in vivo study, the histological average total score of the 0.1 mg/ml PG-atelocollagen gel was significantly better than that of the group without PG. CONCLUSIONS: Although the appropriate concentration of PG has not been defined, this study suggests the efficacy of PG for cartilage repair.