Objective: To investigate the clinicopathological features, immunophenotypes and molecular genetics of EWSR1-SMAD3 positive fibroblastic tumor (ESFT) with an emphasis on differential diagnosis. Methods: The clinicopathological data, immunohistochemical profiles and molecular profiles of 3 ESFT cases diagnosed at the Department of Pathology, Fudan University Shanghai Cancer Center from 2018 to 2021were analyzed. The related literature was also reviewed. Results: There were two males and one female. The patients were 24, 12 and 36 years old, respectively. All three tumors occurred in the subcutis of the foot with the disease duration of 6 months to 2 years. The tumors were presented with a slowly growing mass or nodule, accompanied with pain in 1 patient. The tumors ranged in size from 0.1 to 1.6 cm (mean, 1.0 cm). Microscopically, the tumors were located in the subcutaneous tissue with a nodular or plexiform growth pattern. They were composed of cellular fascicles of bland spindle cells with elongated nuclei and fine chromatin. One of the tumors infiltrated into adjacent adipose tissue. There was no nuclear atypia or mitotic activities. All three tumors showed prominent stromal hyalinization with zonal pattern present in one case. Focal punctate calcification was noted in two cases. The immunohistochemical studies showed that tumor cells were diffusely positive for ERG and negative for CD31 and CD34, with Ki-67 index less than 2%. Fluorescence in situ hybridization on the two tested cases identified EWSR1 gene rearrangement. The next generation sequencing analysis demonstrated EWSR1-SMAD3 fusion in all three cases. During the follow up, one patient developed local recurrence 24 months after the surgery. Conclusions: ESFT is a benign fibroblastic neoplasm and has a predilection for the foot, characterized by ERG immunoreactivity and EWSR1-SMAD3 fusion. Local recurrence might occur when incompletely excised. Familiarity with its clinicopathological features is helpful in distinguishing it from other spindle cell neoplasms that tend to occur at acral sites.
Adult ; Child ; Female ; Humans ; Male ; Biomarkers, Tumor/analysis* ; China ; In Situ Hybridization, Fluorescence ; Neoplasms, Fibrous Tissue/pathology* ; RNA-Binding Protein EWS/genetics* ; Smad3 Protein/genetics* ; Soft Tissue Neoplasms/surgery*

Humans ; Sarcoma, Small Cell/pathology* ; Transcription Factors ; Gastrointestinal Tract/pathology* ; Oncogene Proteins, Fusion/genetics* ; Biomarkers, Tumor ; Soft Tissue Neoplasms

Humans ; Sarcoma, Small Cell/pathology* ; Sarcoma/pathology* ; Oncogene Proteins, Fusion ; Biomarkers, Tumor ; Soft Tissue Neoplasms/genetics*

Bone Neoplasms/genetics* ; Consensus ; Humans ; Molecular Diagnostic Techniques ; Pathology, Molecular ; Soft Tissue Neoplasms/pathology*

Objective: To investigate the clinicopathological features and differential diagnoses of paratesticular liposarcoma. Methods: The cases were collected from 2012-2020, from the archives of the Department of Pathology, Peking University Third Hospital, with diagnosis confirmed by histology, immunostaining and FISH tests. Results: Totally 19 patients were enrolled (including 11 in-hospital patients and 8 consultant cases). The patients aged 37-84 years (mean 57 years). The preoperative clinical diagnoses were spermatic cord/inguinal masses (nine patients), scrotal masses (seven patients), and inguinal hernia (three patients). Six lesions recurred after local resection, including one case extending from pelvic liposarcoma. Histologically, there were 10 cases of well-differentiated liposarcoma (WDLPS) and nine cases of dedifferentiated liposarcoma (DDLPS). WDLPSs mostly showed the combined features of lipoma-like, inflammatory and sclerosing subtypes (six patients); the other four WDLPSs had pure lipoma-like subtype features. DDLPSs were low-grade (three patients) or high-grade (six patients), with the morphology resembling myxofibrosarcoma, inflammatory myofibroblastoma, spindle cell sarcoma, pleomorphic undifferentiated sarcoma and pleomorphic liposarcoma. Intense inflammatory cells infiltration was commonly observed in five WDLPSs and two DDLPSs. Ossification was observed in three tumors. Immunohistochemically, the tumors were positive for MDM2 (8/10) and CDK4 (10/10), which were expressed in lipo-differentiating cells, spindle cells in WDLPS, and in dediffferentiated components. S-100 was only expressed by lipocytes (10/10). CD34 expression was positive and diffuse in the stromal cells of WDLPSs and focal or diffuse in dedifferentiated areas (10/10). FISH tests with an MDM2 gene probe were positive (12/12). Conclusions: Paratesticular liposarcoma may be overlooked by both clinicians and pathologists. WDLPS and DDLPS predominate, showing various histologic divergences. The presence of amplification of the 12q14-q15 region (containing the MDM2 and CDK4 genes) is helpful for making the correct diagnosis.
Adult ; Genital Neoplasms, Male/surgery* ; Humans ; In Situ Hybridization, Fluorescence ; Liposarcoma/surgery* ; Male ; Proto-Oncogene Proteins c-mdm2/genetics* ; Soft Tissue Neoplasms

Gene Rearrangement ; Humans ; RNA-Binding Protein EWS ; genetics ; Soft Tissue Neoplasms ; genetics

Antineoplastic Agents ; therapeutic use ; Benzamides ; therapeutic use ; Biopsy, Large-Core Needle ; Drug Delivery Systems ; Humans ; Imatinib Mesylate ; In Situ Hybridization, Fluorescence ; Piperazines ; therapeutic use ; Protein Kinase Inhibitors ; therapeutic use ; Protein-Tyrosine Kinases ; antagonists & inhibitors ; Pyrimidines ; therapeutic use ; Soft Tissue Neoplasms ; classification ; diagnosis ; genetics ; pathology ; therapy

OBJECTIVETo study the clinicopathologic features, immunophenotype, molecular genetics and differential diagnosis of solid variant of angiomatoid fibrous histocytoma.

METHODSThe clinicopathologic features of 3 cases of solid variant of angiomatoid fibrous histocytoma were analyzed and the literature was reviewed.

RESULTSThere were a total of 2 males and 1 female. The age of patients ranged from 9 to 12 years. The patients presented with a painless mass located in left forearm, left knee or back. The lesions were treated by complete surgical resection. On gross examination, the tumors varied from 1.6 cm to 4.5 cm in greatest dimension. They were well-circumscribed and had pale yellow to grayish-red solid cut surface. Histologically, the tumor was composed of histocytoid cells arranged in sheet-like pattern. A fibrous pseudocapsule surrounded by lymphocytes and plasma cells was identified. Immunohistochemical study showed that the tumor cells in all cases were positive for vimentin and CD68. They were negative for S100 protein, cytokeratin, CD34, CD31, smooth muscle actin, CD35, CD21 and CD30. Two cases also expressed CD99 and one of them was positive for desmin and epithelial membrane antigen. Fluorescence in-situ hybridization was positive for EWSR1 gene.

CONCLUSIONSSolid type represents a variant of angiomatoid fibrous histocytoma and is considered as tumor of borderline malignant potential. Definitive diagnosis requires thorough histologic examination and clinical correlation. Immunohistochemistry and EWSR1 gene study are helpful in further delineation and differential diagnosis. Complete resection or wide local excision with post-operative follow up is the main modality of treatment.

Antigens, CD ; metabolism ; Antigens, Differentiation, Myelomonocytic ; metabolism ; Back ; Calmodulin-Binding Proteins ; genetics ; Child ; Dendritic Cell Sarcoma, Follicular ; metabolism ; pathology ; Diagnosis, Differential ; Female ; Forearm ; Histiocytoma, Malignant Fibrous ; genetics ; metabolism ; pathology ; surgery ; Humans ; Knee ; Male ; Neoplasms, Muscle Tissue ; pathology ; Neurilemmoma ; metabolism ; pathology ; RNA-Binding Protein EWS ; RNA-Binding Proteins ; genetics ; Soft Tissue Neoplasms ; genetics ; metabolism ; pathology ; surgery ; Vimentin ; metabolism

Diagnosis, Differential ; Fetus ; Fibroma ; metabolism ; pathology ; Fibrosarcoma ; congenital ; genetics ; metabolism ; secondary ; Hemangiopericytoma ; metabolism ; pathology ; Humans ; Kidney Neoplasms ; pathology ; secondary ; Liver Neoplasms ; pathology ; secondary ; Lung Neoplasms ; pathology ; secondary ; Male ; Nerve Sheath Neoplasms ; metabolism ; pathology ; Rhabdomyosarcoma, Embryonal ; metabolism ; pathology ; Soft Tissue Neoplasms ; congenital ; genetics ; metabolism ; pathology ; Vimentin ; metabolism

Adolescent ; Biopsy, Fine-Needle ; Chromosomes, Human, Pair 18 ; Female ; Humans ; In Situ Hybridization, Fluorescence ; Oncogene Proteins, Fusion ; genetics ; Proto-Oncogene Proteins c-bcl-2 ; metabolism ; Sarcoma, Synovial ; genetics ; metabolism ; pathology ; Soft Tissue Neoplasms ; genetics ; metabolism ; pathology ; Translocation, Genetic ; Vimentin ; metabolism