[Rare differential diagnosis of an osteolytic lesion of the mandible in a young adult]. / Seltene Differenzialdiagnose bei osteolytischer Läsion des Unterkiefers einer jungen Erwachsenen.

We report a rarely occurring hematologic neoplasm in a young adult. Hematologic neoplasms were first described in 2008 and are now included in both accepted tumor classification systems, i.e., International Consensus Classification and World Health Organization. This hematologic neoplasm shows a characteristic ALK positivity in immunohistochemical examination and correspondingly, ALK fusion genes in the molecular analysis. Pathologists should be aware of this entity, particularly as it is challenging to differentiate from other more frequent neoplasms of the same disease group or mesenchymal neoplasm with ALK aberration.

Mandibular rhabdomyosarcoma with TFCP2 rearrangement and osteogenic differentiation: a case misdiagnosed as fibrous dysplasia or low-grade central osteosarcoma.

Rhabdomyosarcoma with TFCP2-related fusions (TFCP2-RMS) is a rare entity that commonly affects young adults with a predilection for skeletal involvement. We herein report a 40-year-old female patient with TFCP2-RMS who was misdiagnosed as fibrous dysplasia or low-grade central osteosarcoma of the mandible by referring institutions. Histologically, the tumor showed dominant spindle cells and focal epithelioid cells with marked immature woven bone formation. Immunophenotypically, in addition to the characteristic expression of myogenic markers, ALK, and cytokeratins, tumor cells also unusually expressed osteogenic markers, such as MDM2 and SATB2. Through fluorescence in situ hybridization, the tumor cells showed EWSR1::TFCP2 gene fusion and no MDM2 gene amplification. This is a rare case of TFCP2-RMS, which was misdiagnosed as low-grade central osteosarcoma due to its presenting immunophenotype of MDM2 and SATB2, as well as extensive osteoid matrix formation.

Recurrent central odontogenic fibroma in a patient with nevoid basal cell carcinoma syndrome: case report and in vitro analysis.

OBJECTIVE: Central odontogenic fibromas (COF) are rare, benign tumors derived from dental mesenchymal tissue that may occur in the maxilla or mandible. This report describes primary and recurrent COF in the mandible of a patient with nevoid basal cell carcinoma syndrome (NBCCS). STUDY DESIGN: A 36-year-old African American male presented with a COF and its recurrence 17 months later. Tissue pieces were obtained from both occurrences with IRB-approved signed consent. Collected tissue pieces were dissected; one portion was formalin-fixed and paraffin-embedded, and the other was cultured for the isolation of cell populations from the primary (COdF-1) and recurrent (COdF-1a) tumors. Quantification real-time polymerase chain reaction (qRT-PCR), immunohistochemistry, and DNA sequencing were used for gene and protein analysis of the primary tumor and cell populations. RESULTS: Histopathologic analysis of the tumor showed sparse odontogenic epithelial cords in fibrous connective tissue, and qRT-PCR analysis of tumor and cell populations (COdF-1 and COdF-1a) detected VIM, CK14, CD34, CD99 and ALPL mRNA expression. Protein expression was confirmed by immunohistochemistry. CD34 expression in primary tissues was higher than in tumor cells due to tumor vascularization. DNA sequencing indicated the patient had PTCH1 mutations. CONCLUSIONS: Histopathology, mRNA, and protein expression indicate the rare occurrence of COF in a patient with mutated PTCH1 gene and NBCCS.

First presentation of a frameshift mutation in the SETD2 gene of a juvenile psammomatoid ossifying fibroma (JPOF) associated with an aneurysmal bone cyst.

BACKGROUND: The rarity of juvenile psammomatoid ossifying fibroma (JPOF) and lack of cytogenetic studies prompted us to report a novel SETD2 gene mutation in a benign odontogenic tumour. CASE PRESENTATION: A 21-year-old man presented with a hard, expanded mandibular cortex. Computed tomography revealed multilocular radiopacity in the mandible; this was reconstructed via segmental mandibulectomy using a vascularised iliac crest flap. Based on the clinical and histological findings, we diagnosed JPOF associated with an aneurysmal bone cyst. Microscopically, the solid area was characterised by many rounded or angular ossicles in a cellular fibrous stroma. The stromal cells were spindle-like or stellate. Next-generation sequencing detected a frame shift mutation of the SETD2 gene, while the copy number was normal. CONCLUSIONS: Our findings suggest further genetic studies should be performed to assess whether this mutation is related to tumour genesis. .

Upfront rational therapy in BRAF V600E mutated pediatric ameloblastoma promotes ad integrum mandibular regeneration.

Ameloblastoma is a neoplasm arising in the craniofacial skeleton. Proliferating odontogenic epithelial cells comprise this benign, yet locally invasive tumor, often causing severe disfiguration. High recurrence rate entails ablative surgical resection, which is the current standard of care, resulting in subsequent critical size osteocutaneous defects. The high incidence of BRAF mutations in ameloblastoma, most notably the BRAF V600E mutation, enabled the use of BRAF inhibiting agent in a neoadjuvant setting. In this investigator-initiated, open-label study, three consecutive pediatric patients, with confirmed BRAF V600E ameloblastoma deemed marginally resectable, were treated with BRAF inhibiting agents, prior to undergoing surgery. The use of upfront BRAF inhibitor treatment resulted in substantial tumor regression, allowing for non-mutilating complete surgical removal, ad integrum bone regeneration and organ preservation. All patients showed a marked radiologic and clinical response to medical treatment, enabling successful conservative surgery. Microscopically, all patients showed evidence of minimal residual tumor with extensive tumor necrosis, fibrosis and generation of new bone. At a median follow-up of 31 months, all patients remained free of disease. Face preservation therapy was achieved in pediatric patients presenting with BRAF V600E mutated ameloblastoma. Our study demonstrates the translational potential of targeted therapy as a neoadjuvant agent. Patient-specific organ preservation therapy should be considered as the new standard of care in ameloblastoma, mainly for children and adolescents.

Comparison of Immunohistochemistry and DNA Sequencing for BRAF V600E Mutation Detection in Mandibular Ameloblastomas.

This study aimed to investigate the presence of BRAF V600E mutation in mandibular ameloblastoma by comparing the results of molecular detection and immunohistochemical analysis. A 128 cases of mandibular ameloblastoma and 30 cases of dentigerous cyst (control group) were selected for analysis. Detection of BRAF V600E mutation was performed with immunohistochemistry (IHC) and polymerase chain reaction techniques. Clinico-pathologic data were collected in order to investigate possible associations with the mutation. Of the 128 cases submitted to IHC, 81.2% (108 cases) showed positivity for anti-BRAF V600E antibody, whereas 24 were negative (18.8%). Molecular analysis of the BRAF V600E mutation by polymerase chain reaction was possible in 116 cases due to DNA quality. Of these cases, 96 were positive (82.8%) and 20 negative (17.2%). All cases of dentigerous cyst were negative for BRAF V600E mutation in both techniques. Considering the sequencing as a gold standard method, the receiver operating characteristics curve analysis showed sensitivity of 0.99 and specificity of 1 (area under the curve=0.995, standard error=0.006; P<0.001; 95% confidence interval=0.983 to 1). We also tested the agreement between the techniques by using the Cohen's κ coefficient, with κ being 0.97 (P<0.001). IHC is a reliable test for identifying the BRAF V600E mutation in ameloblastomas, presenting advantages such as being more frequently used in surgical pathology laboratories and requiring fewer critical steps for paraffin-embedded tissue compared with molecular biology techniques.

FET(EWSR1)-TFCP2 Rhabdomyosarcoma: An Additional Example of this Aggressive Variant with Predilection for the Gnathic Bones.

An example of a mandibular rhabdomyosarcoma in a 15-year-old male is described featuring EWSR1-TFCP2 fusion with homolateral lymph node metastasis and apparent metastasis to the thoracic vertebra T7. This type of rhabdomyosarcoma has preference for the craniofacial skeleton. Histologically, the tumor was composed of spindle and epithelioid cells characterized by nuclear pleomorphism, cytologic atypia and brisk mitotic activity. Immunohistochemically, it featured diffuse positive nuclear staining MYOD1, only focal staining for myogenin and patchy cytoplasmic staining for desmin. Tumor cells were positive for keratins and nuclear staining for SATB2 was also observed. Interestingly, tumor cells were diffusely positive for calponin. Currently, the patient is under chemotherapy treatment.

Osteosarcoma of the Mandible in a Patient with Florid Cemento-Osseous Dysplasia and Li-Fraumeni Syndrome: A Rare Coincidence.

Cemento-osseous dysplasia (COD) is the most common benign fibro-osseous lesion of the jaws and generally considered non-neoplastic and self-limited. Here, we present a 30-year old female who noticed a bilateral swelling of her posterior mandible with irregular periapical mineralization and incomplete root resorption on panoramic radiographs. A biopsy revealed florid COD and no further treatment was initiated. 9 years later, she presented with a progressive expansion of her left posterior mandible after being treated for bilateral breast cancer 4 and 8 years before. CT scans showed expansile and densely mineralized lesions in all four quadrants with the left posterior mandible showing a focal penetration of the buccal cortical bone. Biopsies revealed an osteoblastic high-grade osteosarcoma in the left and a COD in the right mandible, notably with cellular atypia in the spindle cell component. The patient underwent segmental resection of the left mandible with clear margins and adjuvant chemotherapy. Subsequent genetic testing identified a heterozygous germline TP53 mutation (p.V173G) which confirmed the clinically suspected Li-Fraumeni syndrome (LFS). 3 years after the resection, the patient is free of disease and the other foci of COD remained stable in size on follow-up imaging analyses. Our case illustrates LFS-related osteosarcoma developing within florid COD. Given the rarity of this coincidence, a causative relation between the two lesions seems unlikely but in patients with tumor predisposition syndromes it might be advisable to closely monitor even benign lesions like COD.

Whole-Genome and Segmental Homozygosity Confirm Errors in Meiosis as Etiology of Struma Ovarii.

Strumae ovarii are neoplasms composed of normal-appearing thyroid tissue that occur within the ovary and rarely spread to extraovarian sites. A unique case of struma ovarii with widespread dissemination detected 48 years after removal of a pelvic dermoid provided the opportunity to reexamine the molecular nature of this form of neoplasm. One tumor, from the heart, consisting of benign thyroid tissue was found to have whole-genome homozygosity. Another tumor from the right mandible composed of malignant-appearing thyroid tissue showed whole-genome homozygosity and a deletion of 7p, presumably the second hit that transformed it into a cancerous tumor. Specimens from 2 other cases of extraovarian struma confined to the abdomen and 8 of 9 cases of intraovarian struma showed genome-wide segmental homozygosity. These findings confirm errors in meiosis as the origin of struma ovarii. The histological and molecular findings further demonstrate that even when outside the ovary, strumae ovarii can behave nonaggressively until they receive a second hit, thereafter behaving like cancer.

Biallelic PTCH1 Inactivation Is a Dominant Genomic Change in Sporadic Keratocystic Odontogenic Tumors.

Keratocystic odontogenic tumors (KCOTs) are locally aggressive odontogenic neoplasms with recurrence rates of up to 60%. Approximately 5% of KCOTs are associated with nevoid basal cell carcinoma (Gorlin) syndrome and 90% of these show genomic inactivation of the PTCH1 gene encoding Patched 1. Sporadic KCOTs reportedly have PTCH1 mutations in 30% of cases, but previous genomic analyses have been limited by low tumor DNA yield. The aim of this study was to identify recurrent genomic aberrations in sporadic KCOTs using a next-generation sequencing panel with complete exonic coverage of sonic hedgehog (SHH) pathway members PTCH1, SMO, SUFU, GLI1, and GLI2. Included were 44 sporadic KCOTs from 23 female and 21 male patients with a median age of 50 years (range, 10 to 82 y) and located in the mandible (N=33) or maxilla (N=11). Sequencing identified PTCH1 inactivating mutations in 41/44 (93%) cases, with biallelic inactivation in 35 (80%) cases; 9q copy neutral loss of heterozygosity targeting the PTCH1 locus was identified in 15 (34%) cases. No genomic aberrations were identified in other sequenced SHH pathway members. In summary, we demonstrate PTCH1 inactivating mutations in 93% of sporadic KCOTs, indicating that SHH pathway alterations are a near-universal event in these benign but locally aggressive neoplasms. The high frequency of complete PTCH1 loss of function may provide a rational target for SHH pathway inhibitors to be explored in future studies.

Sclerosing Epithelioid Fibrosarcoma of the Bone With Rare EWSR1-CREB3L3 Translocation Driving Upregulation of the PI3K/mTOR Signaling Pathway.

Sclerosing epithelioid fibrosarcoma (SEF) is an uncommon neoplasm that rarely presents in bone. It is characterized by epithelioid cells arranged in nests and single-file cords within a sclerotic stromal background which may mimic neoplastic bone. SEF harbors an EWSR1 translocation, which may complicate its distinction from Ewing sarcoma in cases with histomorphologic overlap. We present a diagnostically challenging case of SEF in the mandible of a 16-year-old girl. Our experience highlights the lack of specificity of traditional morphology and EWSR1 break-apart fluorescent in situ hybridization. Open-ended RNA-based fusion gene testing coupled with MUC4 immunohistochemistry aided the eventual diagnosis in this case. Herein, we report the third case of SEF with EWSR1-CREB3L3 translocation and show that this fusion leads to aberrant upregulation of the phosphoinositide 3-kinase/mammalian target of rapamycin signaling pathway in heterologous cell models.

Mutational Signatures in Mandibular Ameloblastoma Correlate with Smoking.

Ameloblastoma is a rare tumor of odontogenic epithelium, the low incidence rate of which precludes statistical determination of its molecular characterizations. Despite recent genomic and transcriptomic profiling, the etiology of ameloblastomas remains poorly understood. Risk factors of ameloblastoma development are also largely unknown. Whole exome sequencing was performed on 11 mandibular ameloblastoma samples. We identified 2 convergent mutational signatures in ameloblastoma: 1) a signature found in multiple types of lung cancers with probable etiology of tobacco carcinogens (COSMIC signature 4) and 2) a signature present in gingivobuccal oral squamous cell carcinoma and correlated with tobacco-chewing habits (COSMIC signature 29). These mutational signatures highlight tobacco usage or related mutagens as one possible risk factor of ameloblastoma, since the association of BRAF mutations and smoking was demonstrated in multiple studies. In addition to BRAF hotspot mutations (V600E), we observed clear inter- and intratumor heterogeneities. Interestingly, prior to BRAF mutation, important genes regulating odontogenesis mutated (e.g., corepressor BCOR), possibly playing important roles in tumorigenesis. Furthermore, recurrent mutations in the CDC73 gene, the germline mutations of which predispose patients to the development of jaw tumors, were found in 2 patients, which may lead to recurrence if not targeted by therapeutic drugs. Our unbiased profiling of coding regions of ameloblastoma genomes provides insights to the possible etiology of mandibular ameloblastoma and highlights potential disease risk factors for screening and prevention, especially for Asian patients. Because of the limited sample size and incomplete habitual, dietary, and occupational data, a causal link between tobacco usage and ameloblastoma still requires further investigations.

RBM10 truncation in astroblastoma in a patient with history of mandibular ameloblastoma: A case report.

Astroblastoma is a rare glial neoplasm composed of cells that have broad processes oriented perpendicular to central vessels and often demonstrate vascular sclerosis. The WHO 2016 classification does not specify a grading system for astroblastoma, and categorizes them as well-differentiated or malignant. These broad classification rubrics, however, do not accurately predict clinical outcome. Genetic profiling of astroblastoma has therefore been of particular interest in the recent years. These efforts, although in small number, have revealed heterogeneous molecular findings that may explain astroblastoma's unpredictable clinical outcome. Here, we report a case of recurrent astroblastoma in a 23-year-old female with a unique molecular characteristic. Our patient's tumor harbored an RNA-binding motif 10 (RBM10) truncation. RBM10 codes for a widely expressed RNA binding protein, and its mutation has been described in a variety of solid cancers. RBM10 is thought to be involved in stabilization of pro-apoptotic proteins in breast cancer, and its reduced protein expression is associated with advanced stages of lung adenocarcinoma. To our knowledge, this is the first report of astroblastoma harboring RBM10 truncation. Interestingly, our patient also has a history of mandibular ameloblastoma, but the link between these two rare tumors is unclear.

BRAF V600E expression in ameloblastomas-A 36-patient cohort from Helsinki University Hospital.

OBJECTIVES: We aimed to investigate BRAF V600E percentage immunohistochemically in ameloblastomas of a single institute cohort. We were interested if age, location, histological properties, or tumor recurrence depend on the BRAF status. SUBJECTS, MATERIALS AND METHODS: We had 36 formalin-fixed, paraffin-embedded ameloblastoma tissue samples of patients treated at the Helsinki University Hospital between the years 1983-2016. Tissue sections underwent immunohistochemistry by Ventana BenchMark XT immunostainer using Ms Anti-Braf V600E (VE1) MAB. We used R 3.4.2 and RStudio 1.1.383 to conduct statistical analysis for BRAF positivity and earlier onset as well as tumor location. We used chi-squared tests and 2-by-2 table functions to determine connections between BRAF positivity and recurrence, growth pattern, and type. RESULTS: BRAF-positive tumors occurred in younger patients compared to BRAF-negative tumors (p = 0.015) and they located mostly to the mandible (p < 0.001). Growth patterns were limited to two in BRAF-negative tumors when BRAF-positive tumors presented with one to four growth patterns (p = 0.02). None of the maxillary tumors showed BRAF positivity and of these, 72.2% recurred. CONCLUSIONS: An immunohistochemical BRAF marker could be a beneficial tool to predict the outcome of patients with this aggressive, easily recurring tumor.

Heterozygosity for CMT Type 4 Predicts a Severe Vincristine-induced Polyneuropathy Phenotype: A Case Report and Review of Literature.

Vincristine (VCR) is a common chemotherapeutic agent used in the treatment of multiple types of pediatric tumors. VCR's adverse effects are well documented and commonly involve peripheral neuropathy via axonal degeneration. Neuropathic severity is dose-dependent, with sensory deficits occurring with as little as 4 mg cumulative dose. Severe peripheral neuropathy is generally rare, but its effects become additive when given to patients with undiagnosed hereditary peripheral neuropathy such as Charcot-Marie-Tooth. We report a case of an effect of VCR administration given to a patient who developed grade 4 neuropathy and was found to be a carrier of Charcot-Marie-Tooth disease type 4.

Immunohistochemical analysis of BRAF V600E mutation in ameloblastomas.

OBJECTIVE: This study aimed to investigate the presence of BRAF V600E mutation in mandible ameloblastomas by correlating clinical and imaging data on the cases studied. METHODS: Eighty-four cases diagnosed as mandibular ameloblastoma were selected for analysis. The specimens were submitted to immunohistochemistry for detection of BRAF V600E mutated protein. Clinical-pathological data such as age, gender, tumour size, mandibular location, radiographic aspects, histological type and sub-type, and tumour status were collected. The clinical-pathological parameters were categorised and analysed according to BRAF V600E detection. RESULTS: Of the 84 patients, 78.6% (66 cases) demonstrated positivity for anti-BRAF V600E antibody, whereas 18 were negative (21.4%). The correlation between BRAF expression and variables showed statistical significances for mandibular location (P = 0.0353) and tumour size (P = 0.008), whereas no statistical significance was observed for gender, age, radiographic aspect, histological pattern, histological sub-type and tumour status. Multivariate logistic regression revealed a significant risk for BRAF positivity in tumours with posterior mandibular location (OR = 7.23, P = 0.0451) and size > 4 cm (OR = 7.29, P = 0.0150). CONCLUSION: BRAF V600E mutation is common in mandibular ameloblastomas, especially in cases of tumours larger than 4 cm and in the posterior region of the mandible. In addition, this mutation can occur regardless of histological type of the tumour, age, gender, radiographic aspect and tumour status. CLINICAL SIGNIFICANCE: The association between clinical-pathologic features and BRAF V600E mutation in ameloblastomas may provide directions for the treatment of this neoplasia. The use of BRAF inhibitors for targeted therapy could lead to an establishment of an alternative compared to the resective surgery.

Clinicopathologic study on a rare variant of ameloblastoma with basal cell features.

OBJECTIVES: To investigate the clinical features, pathologic manifestations, and biologic behaviors of a variant of ameloblastoma with basal cell features (AM-BC). MATERIALS AND METHODS: Following retrospective review of the clinical and pathological data of six cases of AM-BC, we described their histological and immunohistochemical (IHC) features and discussed the biologic behaviors, prognoses, pathogenesis, and clinical relevance of AM-BC. Direct sequencing of polymerase chain reaction products was also performed in all cases. RESULTS: The six cases of AM-BC involved four women and two men, aged 22-82 years. Four lesions occurred in the maxilla and two in the mandible. Histologically, the basal cells tended to be arranged as unequally sized follicles, strands, or cords of odontogenic epithelium in the connective tissue stroma. Little or no stellate reticulum was present in the central portion of the nest. Expression of CKs was consistent with other histological variants of ameloblastoma (AM), but AM-BC had significantly higher p53 and Ki-67 (p < 0.05) labeling indices than other histological variants of AM. Two patients had BRAF gene mutations. CONCLUSION: Ameloblastoma with basal cell features is a very rare variant of AM. Our study showed the differences and relationships that exist between AM-BC and other variants of AM, which could enhance understanding of AM-BC.

Intraosseous intraneural perineurioma derived from the inferior alveolar nerve with an abnormality of chromosome 22 and expression of the BCR-ABL fusion gene: report of a case and review of recent literature.

BACKGROUND: Perineurioma (PN) is a peripheral nerve disease that primarily develops in the limbs and trunk and very rarely occurs in the oral cavity. PN is classified into two types: intraneural perineurioma (INPN) and soft tissue perineurioma (extraneural perineurioma, ENPN). In this article, we report a patient with mandibular body INPN derived from the perineurium of the inferior alveolar nerve. CASE PRESENTATION: The patient was a 43-year-old male. He consulted our department for a detailed examination of the right mandibular body. A biopsy was performed at another hospital and he was diagnosed with a schwannoma. At his first visit, hypesthesia extending from the right lower lip to the mental region was recognized and enlargement of the right mandibular canal was confirmed with X-ray CT and MRI. Considering the possibility of future tumor growth, we extirpated the tumor under general anesthesia. Cystic tumor was seen continuously in the inferior alveolar nerve. Immunohistologically, the tumor cells were positive for Glut-1, weakly positive for EMA, and weakly positive for Claudin-1, and the histopathological diagnosis was INPN. In addition, absence of the BCR region of chromosome 22 and expression of the BCR-ABL fusion gene were observed by fluorescent in situ hybridization (FISH), and a chromosome 22 abnormality was confirmed. These findings indicated that the disease was a neoplastic lesion. CONCLUSION: Expression of the BCR-ABL fusion gene in INPN that develops in the oral cavity is thought to be very rare, and to the best of our knowledge, ours is the first case to be reported in the literature. About three postoperative years have passed, but findings suggestive of recurrence have not been observed.

Unilateral Creeping Destruction of Deformed Mandibular Ramus and Angle Associated with Extensive Facial Plexiform Neurofibroma in Neurofibromatosis Type 1: A Case Report with Analysis of the Literature for Diagnosing Osteolytic Events of the Mandible in Tumor-suppressor Gene Syndrome.

Neurofibromatosis type (NF1) is an autosomal dominant inherited tumor-suppressor gene syndrome of significant phenotypic variability with probable complete penetrance of the disease. Skeletal malformations of the skull belong to the phenotype of NF1. In the skull, defects of the calvaria and the sphenoid bone are diagnostically groundbreaking findings in NF1. Malformations of the facial skull are usually diagnosed in patients with NF1 in a topographical context with a plexiform neurofibroma (PNF). This report describes the rare occurrence of slowly advancing, unilateral destruction of proportions of the mandible in NF1, with the affected bone segment completely surrounded by a PNF. A malignant process was ruled out as a cause of partial organ loss. Various hypotheses on the pathogenesis of the rare finding are presented.

Spindle cell rhabdomyosarcoma of bone with FUS-TFCP2 fusion: confirmation of a very recently described rhabdomyosarcoma subtype.

AIMS: Rhabdomyosarcomas of bone are extremely rare, with fewer than 10 reported cases. A very rare subtype of spindle cell/sclerosing rhabdomyosarcoma harbouring a FUS-TFCP2 fusion and involving both soft tissue and bone locations has been reported very recently. We report only the fourth case of this unusual, clinically aggressive rhabdomyosarcoma. MATERIAL AND RESULTS: A previously well 72-year-old male presented with a destructive lesion of the mandible. Morphological and immunohistochemical study of a needle biopsy and the subsequent resection showed a spindle cell rhabdomyosarcoma. RNA-seq, RT-PCR and FISH confirmed the presence of the FUS-TFCP2 fusion. CONCLUSIONS: Spindle cell rhabdomyosarcomas carrying the FUS-TFCP2 fusion are very rare rhabdomyosarcoma variants with osseous predilection. The classification and differential diagnosis of this unusual molecular variant of spindle cell/sclerosing rhabdomyosarcoma are discussed.