bromochloroacetic-acid and Rhabdomyosarcoma--Embryonal

DICER1-related tumors occur hereditary or sporadically, with high-grade malignancies sharing clinicopathological and (epi)genetic features. We compared 4 pleuropulmonary blastomas (PPBs) and 6 sarcomas by mutation analysis, whole transcriptome sequencing and methylation profiling. 9/10 patients were female. PPB patients were 0-4 years. 3/4 were alive; 2 without disease. One patient died of metastatic disease (median follow-up, 16 months). Sarcoma patients were 16-56 years. Locations included: uterine cervix/corpus (3/1), soft tissue back/shoulder (1) and paravertebral (1). 5/6 patients were alive; 2 developed metastases: intracranial (1) and lung and kidney (1) (median follow-up, 17 months). The deceased patient previously had a PPB and a Sertoli-Leydig cell tumor. Histologically, tumors showed atypical primitive-looking cells with incomplete rhabdomyoblastic differentiation and cartilage (n = 5). Immunohistochemistry demonstrated desmin- (n = 9/10), myogenin- (n = 6/10) and keratin positivity (n = 1/1). Eight cases harbored biallelic DICER1 mutations with confirmed germline mutations in 4 cases. Two cases showed a monoallelic mutation. By RNA expression- and methylation profiling, distinct clustering of our cases was seen demonstrating a close relationship on (epi)genetic level and similarities to embryonal rhabdomyosarcoma. In conclusion, this study shows overlapping morphological, immunohistochemical and (epi)genetic features of PPBs and DICER1-associated high-grade sarcomas, arguing that these neoplasms form a spectrum with a broad clinicopathological range.

Topics: DEAD-box RNA Helicases; Desmin; Female; Humans; Keratins; Male; Mutation; Myogenin; Pulmonary Blastoma; Rhabdomyosarcoma, Embryonal; Ribonuclease III; RNA; Soft Tissue Neoplasms

Topics: Aged; Anaplastic Lymphoma Kinase; Desmin; Diagnosis, Differential; Fatal Outcome; Female; Humans; Immunohistochemistry; Keratins; Muscle, Smooth; MyoD Protein; Myogenin; Neoplasm Metastasis; Rhabdomyosarcoma, Embryonal

Topics: Adult; Diagnosis, Differential; Follow-Up Studies; Humans; Infant; Keratins; Male; Mandibular Neoplasms; Melanoma; Neuroblastoma; Neuroectodermal Tumor, Melanotic; Rhabdomyosarcoma, Embryonal; Synaptophysin

The spindle cell variant of rhabdomyosarcoma (RMS) is uncommon and is most often encountered in the paratesticular region of children in whom it has a good prognosis. Only isolated cases in adulthood have been described. Sixteen cases of spindle cell RMS occurring in adults were retrieved from our files. Eleven patients were male and 5 were female. Patient age ranged from 18 to 79 years (median, 32 years). Tumor size varied from 1.5 to 35 cm (median, 6 cm). The head and neck region, including the oral cavity, parotid gland, nasopharynx, and nasal cavity, was the commonest affected area, accounting for >50% of the cases, followed by retroperitoneum, thigh, leg, subscapular area, hand, vulva, and paratesticular region (1 case each). Follow-up was available in 12 cases, ranging from 1 to 102 months (median, 16.5 months). Treatment modalities included surgery, chemotherapy, and radiation. Two patients died of uncontrolled local disease 13 and 27 months after diagnosis; 4 were alive without disease at 12, 17, 24, and 102 months, including 1 patient with metastasis to 10 of 50 pelvic lymph nodes at presentation; 3 are alive with localized disease at 16, 17, and 19 months; and 1 was followed for 6 months and showed persistent local disease. One patient is alive at 10 months after diagnosis with evidence of metastatic disease to bone, lungs, and breast. All the tumors showed long fascicles of spindle cells with elongated, vesicular nuclei and pale indistinct cytoplasm. Scattered spindled or polygonal rhabdomyoblasts with abundant brightly eosinophilic cytoplasm were present in all cases. In 3 cases, focal areas showed pseudovascular, sclerosing features. There were no round cell or pleomorphic areas. Positive immunohistochemical results were as follows: desmin (15 of 15 cases), myf-4 (12 of 12), fast myosin (7 of 9), myoglobin (2 of 3), HHF-35 (9 of 9), and SMA (11 of 14). One tumor was focally positive for keratins and EMA. All tumors were negative for caldesmon, S-100 protein, and GFAP. Spindle cell RMS is a rare neoplasm in adults and appears to have distinct clinicopathologic features when compared with cases occurring in the pediatric population. Specifically, it appears to be most common in the head and neck region, and although only limited follow-up is available so far, these lesions appear to have a more aggressive clinical course in adults.

Topics: Actins; Adolescent; Adult; Aged; Desmin; Female; Glial Fibrillary Acidic Protein; Humans; Immunohistochemistry; Keratins; Male; Middle Aged; Mucin-1; Myogenic Regulatory Factors; Myoglobin; Myosins; Rhabdomyosarcoma, Embryonal; S100 Proteins; Sarcoma

A human tumor cell line designated RMS-GR was established from an embryonal rhabdomyosarcoma. The monolayer cells were polygonal, round or spindle-shaped. The RMS-GR cell line became stable with a doubling time of 42 h. Tumorigenicity of the cells was confirmed by heterotransplantion into nude mice. Electron microscopic images showed typical cytoplasmic inclusion of aggregated intermediate filaments and myofibril-like thin filaments. The expression of desmin, vimentin, actin and human myoglobin was recognized by cytofluorometric analyses, and a large fraction of CK-MM and small fractions of CK-BB and MCK-1 isoenzymes were found. Chromosomal analysis showed that the modal chromosome number was consistently near triploid with structural abnormalities mostly involving chromosomes 1, 3 and 8, and additional unidentified markers. No alteration of chromosome 2 was observed. The RMS-GR cell line may provide a system to identify genes which are involved in the pathogenic mechanism of rhabdomyosarcomas, and to investigate the modulation of myogenic differentiation.

Topics: Actins; Animals; Cell Division; Chromosome Aberrations; Creatine Kinase; Humans; Isoenzymes; Keratins; Mice; Mice, Nude; Myoglobin; Neoplasm Transplantation; Rhabdomyosarcoma, Embryonal; Transplantation, Heterologous; Tumor Cells, Cultured; Vimentin