bromochloroacetic-acid and Solitary-Fibrous-Tumors

Solitary fibrous tumor is a rare mesenchymal neoplasm, characterized by peculiar histological features composed by the proliferation of spindle cells in "patternless pattern". Although it has been known to sometimes be accompanied by epithelioid cells, the presence of a well-formed epithelial structure is far more rare. We describe herein the case of a 60-year-old female with the radiological finding of a single nodular lesion in the anterior mediastinum. Histopathological examination of the surgically resected specimen led to the diagnosis of solitary fibrous tumor of the thymus with a spectrum of well-formed epithelial components: i) glandular structure, reminiscent of breast or eccrine gland, ii) neural tube-like structure, and iii) clusters of endocrine-like cells. Immunohistochemical analysis revealed that the spindle cells expressed CD34, vimentin, bcl-2 and Stat-6, but not keratin (cytokeratin-AE1/AE3) or epithelial membrane antigen. In contrast, the epithelial components lost expression of most of these marker proteins, including Stat-6, but continued to express vimentin and strongly expressed keratin. Since no relevant past literature was found, the current case could be interpreted as a unique and previously undescribed variant of solitary fibrous tumor comprising conventional spindle cells with a spectrum of well-formed epithelial components. Pathogenesis that may have given rise to these variegated mixtures of spindle cells and epithelial components in a single tumor is also discussed.

Topics: Antigens, CD34; Biomarkers, Tumor; Epithelial Cells; Female; Humans; Immunohistochemistry; Keratins; Middle Aged; Proto-Oncogene Proteins c-bcl-2; Solitary Fibrous Tumors; Spindle Apparatus; STAT6 Transcription Factor; Thymus Neoplasms; Vimentin

The archetypal solitary fibrous tumor (SFT) features fibroblastic cells with varying cellularity without any particular architectural arrangement in a collagenous matrix, with staghorn vessels, CD34 and STAT6 expression, and NAB2::STAT6. To date, this fusion is thought to be specific for SFT. With more routine use of fusion gene panels, the histologic diversity of NAB2::STAT6-positive tumors is increasingly appreciated. Here we present four head and neck tumors harboring NAB2::STAT6 but exhibiting remarkably unusual morphologic features for SFT. All cases were pulled from the authors' consultation files. Immunohistochemistry was performed, along with targeted RNA sequencing in all cases, plus DNA next-generation sequencing on two. The cases arose in the nasal cavity (n = 2), retromolar trigone (n = 1) and parapharynx (n = 1), in patients ranging from 39 to 54 (mean, 44). Both nasal cases were biphasic, with a variably cellular collagenized stroma that resembled SFT but also interspersed malignant epithelial and neuroepithelial nests. One of the nasal cases also exhibited overt rhabdomyoblastic differentiation within both components. The two non-nasal cases were comprised of plump, epithelioid cells that were diffusely positive for pan-cytokeratin. One of these cases had prominent cystic change lined by overtly squamous epithelium. STAT6 immunostaining was positive in all cases, although the epithelial/neuroepithelial nests in the sinonasal cases were negative. All cases were confirmed to harbor NAB2::STAT6 by RNA sequencing. The two sinonasal cases were also found to harbor oncogenic mutations. The presented cases highlight a much broader histologic diversity than previously known for neoplasms with NAB2::STAT6. The biphasic nasal cases closely resemble teratocarcinosarcoma, while the epithelioid, cytokeratin-positive cases could be conceptualized as "adamantinoma-like," to borrow terminology already in use for Ewing sarcomas with complex epithelial differentiation. To identify similar cases, pathologists should have a low threshold for using STAT6 immunohistochemistry on any difficult-to-characterize head and neck tumor.

Topics: Adamantinoma; Ameloblastoma; Biomarkers, Tumor; Head and Neck Neoplasms; Humans; Keratins; Repressor Proteins; Solitary Fibrous Tumors; STAT6 Transcription Factor

We report the case of a dedifferentiated solitary fibrous tumor with heterologous rhabdomyosarcomatous differentiation in a 74-year-old male presenting with a rapidly growing, large soft tissue tumoral mass in the gluteal muscles of the right hip. Dedifferentiation in solitary fibrous tumor had not been recognized until very recently and is an extremely rare phenomenon in this tumor type. In the present case, the diagnosis of dedifferentiated solitary fibrous tumor was difficult because of the absence of areas of conventional solitary fibrous tumor with a predominantly poorly differentiated, anaplastic tumor component in the incision biopsy composed of heterogeneous areas with small blue round cell (Ewing sarcoma-like), rhabdoid, epithelioid, and pleomorphic morphology. Moreover, the "unforeseen" strong patchy to multifocal positivity for cytokeratin AE1/AE3 and desmin made the diagnosis of a dedifferentiated solitary fibrous tumor even more challenging in this case. The morphology (presence of branching thin-walled, hemangiopericytoma-like blood vessels) and the immunohistochemical profile (including STAT6 and GRIA2 positivity) were very useful to differentiate this very challenging case of a cytokeratin-positive dedifferentiated solitary fibrous tumor with heterologous rhabdomyosarcomatous differentiation from a broad list of differential diagnoses.

Topics: Aged; Biopsy; Buttocks; Cell Dedifferentiation; Humans; Immunohistochemistry; Keratins; Male; Receptors, AMPA; Rhabdomyosarcoma; Solitary Fibrous Tumors; STAT6 Transcription Factor

Topics: Abdominal Neoplasms; Adult; Aged; Aged, 80 and over; Antigens, CD34; Female; Humans; Keratins; Middle Aged; Solitary Fibrous Tumor, Pleural; Solitary Fibrous Tumors; STAT6 Transcription Factor

Topics: Abdominal Neoplasms; Female; Humans; Keratins; Solitary Fibrous Tumor, Pleural; Solitary Fibrous Tumors

Calretinin is an intracellular calcium-binding EF-hand protein of the calmodulin superfamily. It plays a role in diverse cellular functions, including message targeting and intracellular calcium signaling. It is expressed in the mesothelium, mast cells, some neural cells, and fat cells, among others. Because of its relative specificity for mesothelial neoplasms, calretinin is widely used as one of the primary immunohistochemical markers for malignant mesothelioma and in differentiating it from adenocarcinoma. On the basis of our sporadic observation on calretinin immunoreactivity in desmoid fibromatosis, we systematically evaluated calretinin, keratin cocktail (AE1/AE3), and WT1 immunoreactivity in 268 fibroblastic/myofibroblastic neoplasms. Calretinin was observed in 75% (44/58) of desmoid fibromatosis, 50% (21/42) of proliferative fasciitis, 23% (8/35) of nodular fasciitis, 33% (13/40) of benign fibrous histiocytoma, 35% (22/62) of malignant fibrous histiocytoma, and 13% (4/31) of solitary fibrous tumors but not in normal connective tissue fibroblasts at various sites. Keratin AE1/AE3 immunoreactivity was also commonly (6/13) present in the large ganglion-like cells of proliferative fasciitis and sometimes in nodular fasciitis (3/35), solitary fibrous tumor (3/27), and malignant fibrous histiocytoma (9/62). Nuclear immunoreactivity for WT1 or keratin 5 positivity was not detected in myofibroblastic tumors. On the basis of these observations, it can be concluded that calretinin and focal keratin immunoreactivity is fairly common in benign and malignant fibroblastic and myofibroblastic lesions. Calretinin-positive and keratin-positive spindle cells in desmoid and nodular fasciitis or calretinin-positive ganglion-like cells in proliferative fasciitis should not be confused with elements of epithelioid or sarcomatoid mesothelioma. These diagnostic pitfalls can be avoided with careful observation of morphology, quantitative differences in keratin expression, and use of additional immunohistochemical markers such keratin 5 and WT1 to verify true epithelial and mesothelial differentiation typical of mesothelioma.

Topics: Calbindin 2; Cell Nucleus; Diagnosis, Differential; Diagnostic Errors; Fasciitis; Fibromatosis, Aggressive; Histiocytoma, Benign Fibrous; Histiocytoma, Malignant Fibrous; Humans; Keratins; Myofibroma; S100 Calcium Binding Protein G; Solitary Fibrous Tumors; Tissue Array Analysis; WT1 Proteins

Topics: Epithelioid Cells; Humans; Keratins; Male; Middle Aged; Pleural Neoplasms; Solitary Fibrous Tumors