A Rare Case of A Low-Grade Inflammatory Leiomyosarcoma/Histiocyte-Rich Rhabdomyoblastic Tumor in the Neck of An Adolescent Male.

Inflammatory leiomyosarcoma (LMS) is a newly included rare tumor entity in the group of smooth muscle tumors in the recent WHO classification. Recent studies have shown skeletal muscle expression within this tumor and its proximity with histiocyte-rich rhabdomyoblastic tumor (HRRT). A 17-year-old male presented with a soft tissue lump over the back of his neck of one-year duration. Radiologically, a lesion measuring 5.9 cm in the largest dimension was seen, extending from the skull base up to the C2 vertebral level, abutting the occipital bone. The initial biopsy was reported as a fibrohistiocytic tumor at the referring laboratory. A microscopic review of the sections from the initial biopsy and subsequent resection revealed a well-circumscribed, cellular tumor composed of plump spindle and polygonal-shaped tumor cells with relatively bland nuclei, moderate to abundant eosinophilic cytoplasm and numerous interspersed histiocytes, including foam cells and lymphocytes. Immunohistochemically, the tumor cells were positive for desmin, MYOD1 and SMA, focally positive for myogenin, while negative for h-caldesmon, SOX10 and S100P. A diagnosis of inflammatory leiomyosarcoma/HRRT was offered. Subsequently, the tumor was tested for MYOD1 (L122R) mutation and was found to be negative. The patient underwent adjuvant radiation therapy and is free-of-disease at 12 months post-treatment. This case constitutes an extremely rare case of an inflammatory LMS/HRRT, identified in the neck region. This tumor should be differentiated from its close mimics, such as a spindle cell/sclerosing rhabdomyosarcoma, as the latter is treated more aggressively, including with chemotherapy, given its relatively poor prognosis.

Cytomorphology of spindle cell/sclerosing rhabdomyosarcoma, including MYOD1 (LI22R) mutation result.

Spindle cell/sclerosing rhabdomyosarcoma (RMS), characterized by MYOD1 (L122R) mutation in a subset of cases is a newly described subtype of RMS. Presently, there is no documentation of cytomorphological features, especially of sclerosing RMS. Case 1: A 24-year-old male presented with pain and swelling in his wrist for a one-year duration. MRI revealed a well-defined soft tissue lesion measuring 5.3 cm, encasing the lower end of the ulna. Fine-needle aspiration cytology (FNAC) smears revealed clusters of tumor cells with round to oval to spindle-shaped nuclei, scant to moderate amount of cytoplasm with the wisps of the metachromatic stroma. Histopathological examination revealed a malignant tumor comprising cells with polygonal to spindle-shaped nuclei, arranged in a sclerotic stroma. Immunohistochemically, the tumor cells were positive for desmin, myogenin, and MYOD1. A diagnosis of sclerosing RMS was offered. Furthermore, the tumor revealed MYOD1 (L122R) mutation. Case 2: A 43-year-old male presented with a 4-month history of "nasal stuffiness" and pressure. Imaging revealed a poorly defined infiltrative lesion in his nasal cavity. FNAC smears revealed loose and tightly cohesive clusters of malignant cells with oval to spindle-shaped nuclei, a moderate amount of ill-defined bluish to finely vacuolated cytoplasm, and focal streak artifact with interspersed stromal fragments. Histopathological examination revealed a malignant tumor composed of oval to spindle-shaped nuclei, embedded in a variably hyalinized stroma. Immunohistochemically, the tumor cells were positive for desmin, and myogenin. Diagnosis of spindle cell/sclerosing RMS was offered. The present study constitutes one of the first documentation of cytomorphological features of two rare cases of spindle cell/sclerosing RMS. The differential diagnoses and treatment-related implications are presented.

Genomic characterization of tobacco/nut chewing HPV-negative early stage tongue tumors identify MMP10 asa candidate to predict metastases.

OBJECTIVES: Nodal metastases status among early stage tongue squamous cell cancer patients plays a decisive role in the choice of treatment, wherein about 70% patients can be spared from surgery with an accurate prediction of negative pathological lymph node status. This underscores an unmet need for prognostic biomarkers to stratify the patients who are likely to develop metastases. MATERIALS AND METHODS: We performed high throughput sequencing of fifty four samples derived from HPV negative early stage tongue cancer patients habitual of chewing betel nuts, areca nuts, lime or tobacco using whole exome (n=47) and transcriptome (n=17) sequencing that were analyzed using in-house computational tools. Additionally, gene expression meta-analyses were carried out for 253 tongue cancer samples. The candidate genes were validated using qPCR and immuno-histochemical analysis in an extended set of 50 early primary tongue cancer samples. RESULTS AND CONCLUSION: Somatic analysis revealed a classical tobacco mutational signature C:G>A:T transversion in 53% patients that were mutated in TP53, NOTCH1, CDKN2A, HRAS, USP6, PIK3CA, CASP8, FAT1, APC, and JAK1. Similarly, significant gains at genomic locus 11q13.3 (CCND1, FGF19, ORAOV1, FADD), 5p15.33 (SHANK2, MMP16, TERT), and 8q24.3 (BOP1); and, losses at 5q22.2 (APC), 6q25.3 (GTF2H2) and 5q13.2 (SMN1) were observed in these samples. Furthermore, an integrated gene-expression analysis of 253 tongue tumors suggested an upregulation of metastases-related pathways and over-expression of MMP10 in 48% tumors that may be crucial to predict nodal metastases in early tongue cancer patients. In overall, we present the first descriptive portrait of somatic alterations underlying the genome of tobacco/nut chewing HPV-negative early tongue cancer, and identify MMP10 asa potential prognostic biomarker to stratify those likely to develop metastases.