Hyalinizing Spindle Cell Tumor Research Articles

Sclerosing epithelioid fibrosarcoma of bone with hybrid features: clinicopathologic, radiologic, and molecular analysis of three cases.

Sclerosing epithelioid fibrosarcoma (SEF) occurring as a primary bone tumor is exceptionally uncommon. Even more rare are cases of SEF that show morphologic overlap with low-grade fibromyxoid sarcoma (LGFMS). Such hybrid lesions arising within the bone have only rarely been reported in the literature. Due to their variegated histomorphology and non-specific radiologic features, these tumors maypose diagnostic difficulties. Herein we describe three molecularly confirmed primary bone cases of sclerosing epithelioid fibrosarcoma that demonstrated prominent areas showing the features of LGFMS and with areas resembling so-called hyalinizing spindle cell tumor with giant rosettes (HSCTGR). Two patients were female and one was male aged 26, 47, and 16, respectively. The tumors occurred in the femoral head, clavicle, and temporal bone. Imaging studies demonstrated relatively well-circumscribed radiolucent bone lesions with enhancement on MRI. Cortical breakthrough and soft tissue extension were present in one case. Histologically the tumors all demonstrated hyalinized areas with SEF-like morphology as well as spindled and myxoid areas with LGFMS-like morphology. Two cases demonstrated focal areas with rosette-like architecture as seen in HSCTGR. The tumors were all positive for MUC4 by immunohistochemistry and cytogenetics, fluorescence in-situ hybridization, and next-generation sequencing studies identified EWSR1 gene rearrangements confirming the diagnosis in all three cases.Hybrid SEF is exceedingly rare as a primary bone tumor and can be difficult to distinguish from other low-grade spindled and epithelioid lesions of bone. MUC4 positivity and identification of underlying EWSR1 gene rearrangements help support this diagnosis and exclude other tumor types.

Low-Grade Fibromyxoid Sarcoma: A Rare Case in an Unusual Location

Abstract Introduction Low-grade fibromyxoid sarcoma, also known as Evans tumor, is a low-grade sarcoma that most commonly arises in the deep soft tissue of the proximal extremities or trunk in young adults. It is very rare in the viscera as a primary site with only a few cases reported in the literature. Here we present a case of Evans tumor occurring in an unusual and rarely reported location: the mediastinum. Method A 32-year-old male presented with history of persistent cough, and subsequent imaging revealed a left diaphragmatic tumor measuring around 11 cm with associated chest wall implants. Grossly, the tumor was well circumscribed, arising from the parietal pleura with attachment to both lung and diaphragm and focally involving visceral pleura with no extension into the underlying lung parenchyma. Histologically, the tumor was composed of uniform and bland-appearing spindle cells interspersed among large areas of hyalinized rosettes, so-called giant rosettes. By immunohistochemistry, the tumor was positive for EMA, bcl-2, TLE-1, and MUC-4 and negative for STAT-6, ruling out solitary fibrous tumor. FISH for SYT gene rearrangement was performed and was negative, ruling out synovial sarcoma. Given the overall morphology and the phenotype, the final diagnosis was low-grade fibromyxoid sarcoma with giant collagen rosettes (also known as hyalinizing spindle cell tumor with giant rosettes). Conclusion Mediastinal low-grade fibromyxoid sarcoma is a rare entity that should be considered in the differential diagnosis of visceral soft tissue tumors. Pathologic examination and a thorough immunohistochemical and molecular workup play a vital role in establishing this rare and challenging diagnosis.

Perspectives on Low-grade Sarcomas: The Extraordinary Contributions of Sharon W. Weiss, MD.

Soft-tissue pathology encompasses a wide spectrum of neoplasms that represent some of the most challenging and problematic tumors in surgical pathology. Owing to the intensive work of dedicated pathologists, this once esoteric field has become increasingly well defined. In this review, Dr Sharon Weiss' monumental contributions to low-grade sarcomas, including low-grade fibromyxoid sarcoma/so-called hyalinizing spindle cell tumor, atypical lipomatous tumor/well-differentiated liposarcoma and dedifferentiated liposarcoma, epithelioid hemangioendothelioma, and dermatofibrosarcoma protuberans with fibrosarcomatous transformation will be discussed.

The Contribution of Electron Microscopy to the Characterization of Soft Tissue Fibrosarcomas

In recent years, with the application of immunohistochemical and cytogenetic methods, numerous lesions formerly diagnosed as fibrosarcoma were reclassified as other malignant soft tissue tumors, and therefore conventional fibrosarcoma has largely become a diagnosis of exclusion. On the other hand, several new entities belonging to the group of fibrosarcomas have been characterized, including low-grade fibromyxoid sarcoma / hyalinizing spindle cell tumor with giant rosettes, sclerosing epithelioid fibrosarcoma, acral myxoinflammatory fibroblastic sarcoma, and the epithelioid variant of myxofibrosarcoma. Electron microscopy has contributed to the identification of the fibroblastic phenotype in these fibrosarcoma variants and still retains a central role in the differential diagnosis of these soft tissue sarcomas, thus helping to render specific diagnoses and to broaden the spectrum of fibrosarcoma variants.

Low-grade fibromyxoid sarcoma with prominent giant rosettes and heterotopic ossification

Low-grade fibromyxoid sarcoma is a rare soft tissue sarcoma of fibroblastic differentiation characterized by a deceptively benign morphologic appearance with almost consistent MUC4 expression and recurrent chromosomal translocations, t(7;16)(q34;p11) and t(11;16)(p11;p11), resulting in the FUS-CREB3L2 and FUS-CREB3L1 fusion genes, respectively. A subset of the tumors show peculiar histologic features, designated as giant rosettes, and were formerly referred to as hyalinizing spindle cell tumor with giant rosettes. We herein report a case of low-grade fibromyxoid sarcoma showing the presence of numerous giant rosettes, with and without collagenous centers, distributed throughout the lesion and unusual rim-like heterotopic ossification. Such a case might present a diagnostic challenge. The diagnosis of the tumor was confirmed by positive immunoreactivity to MUC4 and the FUS-CREB3L2 fusion detected by molecular testing using formalin-fixed, paraffin-embedded tissue. This case, which has such unusual clinicopathologic features, would help to further expand our knowledge regarding the morphologic diversities of low-grade fibromyxoid sarcoma.

Molecular Particularity in Rare Tumour of Buttock: Case Report and Literature Review

Introduction: Hyalinizing spindle cell tumor with giant rosettes (HSCT) is a very uncommon mesenchymal tumor that has similar morphological and biological features to the low-grade fibromyxoid sarcoma (LGFMS). Case Report: Reported herein is a case of primary tumour of buttock HSCT that had rare FUS-CREB3L1 fusion transcripts, a product of characteristic chromosomal abnormality t (7; 16) (q33; p11) of HSCT and LGFMS. The patient was a 48-year-old man who had a large solitary mass in the buttock. Histologically, it was composed of bland spindle cells with variable cellularity deposited in a densely hyalinized stroma alternating with myxoid areas. Characteristic collagen rosettes were scattered in the cellular areas. Reverse transcription-polymerase chain reaction (RT-PCR) assay using formalin-fixed, paraffin-embedded tissue detected FUS-CREB3L1 fusion transcripts. In our knowledge is the second case may display a variant FUS/CREB3L1 fusion transcript in international literature. Conclusion: LGFMS and HSCT probably have a wider spectrum of morphologic features than previously thought, the awareness of which will help pathologists to avoid diagnostic pitfalls. Demonstration of the t (7; 16) translocation will help to diagnose difficult cases with unusual histologic features.

Low-grade fibromyxoid sarcoma of the perineum with heterotopic ossification: case report and review of the literature

Low-grade fibromyxoid sarcoma was first described more than 20 years ago. Subsequently, it was discovered to carry the recurrent chromosomal translocation t(7;16)(q33;p11) encoding a FUS-CREB3L2 fusion oncoprotein. Molecular tests for this pathognomonic gene fusion can confirm the identity of histologic variants (such as hyalinizing spindle cell tumor with giant rosettes) and suggest that some cases of sclerosing epithelioid fibrosarcoma may represent a high-grade version of this entity. We present a case of an ossifying tumor of the perineum that required an open biopsy and fluorescent in situ hybridization testing for FUS and CREB3L2 for diagnosis as a variant of low-grade fibromyxoid sarcoma. Subsequent excision revealed characteristic areas with collagen rosettes as well as foci of heterotopic ossification. Significant ossification, which is well documented in entities such as synovial sarcoma, ossifying fibromyxoid tumor, and extraskeletal osteosarcoma, has not been reported previously in low-grade fibromyxoid sarcoma. This case demonstrates the value of having a distinctive confirmatory molecular pathology test for diagnosis and expands our knowledge of the histologic variants possible in low-grade fibromyxoid sarcoma.

Low-grade fibromyxoid sarcoma: a clinicopathologic study of 18 cases, including histopathologic relationship with sclerosing epithelioid fibrosarcoma in a subset of cases

Low-grade fibromyxoid sarcoma (LGFMS) is an uncommon tumor with diverse histopathologic features. It has been found to be histopathologically and genetically related to hyalinizing spindle cell tumor with giant rosettes. Lately, sclerosing epithelioid fibrosarcoma (SEF) has been identified as another rare variant of fibrosarcoma. Very few studies have addressed the aspect of its histopathologic relationship with LGFMS. The present study was conducted to critically analyze the clinicopathologic features of a series of LGFMS cases, including identification of cases with histopathologic similarity with SEF. During a 7-year period, 18 LGFMS cases were diagnosed in 9 male and 9 female patients, had ages ranging from 10 to 69 years (median, 32.5 years), and were most commonly identified in the lower extremities (8 cases, or 44.4%). Most cases (16, 88.8%) showed "classic" features of LGFMS with mild (13 cases, or 72.2%) to moderate atypia (5 cases) and nil mitosis (12 cases, or 66.6 %). Variable features included whorling tumor growth pattern, small rosettes, perivascular hyalinization, and amianthoid-like collagen, along with epithelioid differentiation and nuclear pseudoinclusions within tumor cells. Four cases (22.2%) with large collagenous rosettes were diagnosed as hyalinizing spindle cell tumor with giant rosettes. Distinct SEF-like areas were observed in 6 cases (33.3%). On immunohistochemistry, consistent vimentin positively reinforced fibroblastic lineage of the tumor. Therapeutically, all 4 of 7 cases with available follow-up details, which underwent wide excisions, have been free of disease at 5 to 61 months. Eight excisions with unclear margins included 3 cases free of disease (24, 36, and 52 months) and 1 case with recurrence and metastasis. Two cases of marginal excision had tumor recurrences, including 1 case that recurred after 10 years. Low-grade fibromyxoid sarcoma is an uncommon sarcoma with diverse histopathologic features. Histopathologic relationship exists between LGFMS and SEF in a few cases. An LGFMS is optimally managed with surgical wide excision and follow-up.

Hyalinizing spindle cell tumor with giant rosettes

Low-grade fibromyxoid sarcomas are uncommon deep-seated soft tissue neoplasms that exhibit a deceptively benign appearance microscopically. The finding of a linear or whorled array of spindled cells with few or no mitoses in a characteristic myxoid stroma can pose diagnostic dilemmas. Recurrences are common, and late metastases have been recorded. A closely related tumor, the so-called hyalinizing spindle cell tumor with giant collagen rosettes (HSCTGR), has also been described, with both the neoplasms having a similar cytogenetic abnormality and clinical behavior. Because of the similarities, both lesions are considered to be a single entity within the spectrum of low-grade sarcomas. Two cases of HSCTGR occuring in the lower limb are described in this report.

Hyalinizing Spindle Cell Tumor with Giant Rosettes

Hyalinizing Spindle Cell Tumor with Giant Rosettes

Orbital Hyalinizing Spindle Cell Tumor With Giant Rosettes

To evaluate the clinical and histopathologic characteristics of orbital hyalinizing spindle cell tumor with giant rosettes (HSCTGR). Interventional case series of 2 patients, aged 4 and 9 years referred to the Ocular Oncology Unit. Both patients presented with slowly progressive proptosis with dimness of vision in the second patient. CT was performed for both patients followed by excision of the masses. Histology was performed on tissue sections. CT revealed a localized tumor in the first case and extensive mass extending to the optic canal in the second patient. Histologic analysis revealed features of HSCTGR with characteristic spindle-shaped cells with giant rosettes with hyalinized foci. Tumor cells were positive for vimentin in both cases and focal S100 positivity in first case. However, the second case showed a higher Ki-67 index compared to the first case, suggestive of moderately high proliferative activity. After excision, neither of the tumors demonstrated local recurrence, and both patients were without regional or distant metastases. Mean clinical follow-up was 12 months. HSCTGR involving the orbit has not been previously reported in the literature. We report 2 cases of orbital presentation at a much younger age than has been shown in patients with this type of tumor in other areas of the body. Complete excision of this tumor with close follow-up is the preferred treatment. HSCTGR should be considered in the differential diagnosis of orbital fibrous tumor presenting as painless progressive proptosis.

Hyalinizing spindle cell tumor with giant rosettes arising in the lung: Report of a case with FUS‐CREB3L2 fusion transcripts

Hyalinizing spindle cell tumor with giant rosettes (HSCT) is a very uncommon mesenchymal tumor that has similar morphological and biological features to the low-grade fibromyxoid sarcoma (LGFMS). Lung involvement of HSCT is extremely rare, and only one case has been reported in the English-language literature. Reported herein is a case of primary pulmonary HSCT that had FUS-CREB3L2 fusion transcripts, a product of characteristic chromosomal abnormality t(7;16)(q33;p11) of HSCT and LGFMS. The patient was a 50-year-old woman who had a large solitary mass in the lung. Histologically, it was composed of bland spindle cells with variable cellularity deposited in a densely hyalinized stroma alternating with myxoid areas. Characteristic collagen rosettes were scattered in the cellular areas. Reverse transcription-polymerase chain reaction (RT-PCR) assay using formalin-fixed, paraffin-embedded tissue detected FUS-CREB3L2 fusion transcripts. Despite its bland morphology, it is known as low-grade sarcoma and its recognition in the lung would be helpful for accurate diagnosis and proper management of this rare tumor. RT-PCR for detection of FUS-CREB3L2 fusion transcripts is a useful method for differential diagnosis of primary pulmonary HSCT.

Low-Grade Fibromyxoid Sarcoma: A Brief Review

Low-grade fibromyxoid sarcomas are uncommon deep soft tissue neoplasms first described by Evans in 1987. They exhibit a deceptively benign appearance, with a whorled or linear arrangement of spindle-shaped cells showing few to absent mitoses. A characteristic, but not specific, feature is the presence of areas of myxoid stroma. Recurrences are common, and late metastases have been recorded. A closely related but morphologically distinct tumor, the so-called hyalinizing spindle cell tumor with giant rosettes, has also been described; both neoplasms share the same cytogenetic abnormality, a balanced translocation resulting in a FUS/CREB3L2 fusion gene. Because of similar clinical behavior and the common cytogenetic abnormality, some authors prefer to consider both lesions as a single entity within the spectrum of low-grade sarcomas.

Primary mediastinal hyalinizing spindle cell tumor with giant rosettes

We describe herein a unique case of primary mediastinal hyalinizing spindle cell tumor with giant rosettes that occurred in a 41-year-old man. The clinical and pathologic features together with a brief review of the literature are reported.

Hyalinizing Spindle Cell Tumor with Giant Rosettes: A Case Report

Hyalinizing spindle cell tumor with giant rosettes (HSCTGR) is characterized by both giant rosette-like structures with collagen cores sparsely distributed throughout the tumor and fibromyxoid stroma. It is a rare low-grade sarcoma with indolent behavior, and wide excision with long-term follow-up is the best treatment. Although originally considered a distinct entity, it is now regarded as a variant of low-grade fibromyxoid sarcoma. We present a case of HSCTGR arising in the deep soft tissue of the left knee in a 50-year-old woman and provide a brief review of the literature for comparison.

Hyalinizing Spindle Cell Tumor with Giant Rosettes and Low-grade Fibromyxoid Sarcoma: An Immunohistochemical and Ultrastructural Comparative Investigation

Hyalinizing spindle cell tumor with giant rosettes (HSCTGR) and low-grade fibromyxoid sarcoma (LGFMS) are 2 variants of fibrosarcoma, which share several clinicopathologic features. This study compares the light microscopic, immunohistochemical, and ultrastructural features of 2 examples of HSCTGR and 3 of LGFMS to determine the degree of overlap of these 2 tumors. HSCTGR were composed of bland spindle cells within hyalinized to myxoid stroma. Scattered throughout the lesions were characteristic rosette-like structures, formed by a central collagenous core surrounded by spindled neoplastic cells. LGFMS consisted of a mixture of fibrous and myxoid areas, composed of fibroblast-like cells arranged in a swirling, whorled growth pattern. Immunohistochemical analysis showed diffuse positivity for vimentin in all cases, while few scattered tumor cells stained for CD57, CD34, factor XIIIA, and actin. The extracellular matrix showed intense positivity for type IV collagen, laminin, and fibronectin, with the exception of myxoid areas of LGFMS and the central core of the giant rosettes in HSCTGR. Ultrastructurally, both tumor types were composed of cells with the features of fibroblasts, embedded in a collagenous stroma with irregular deposits of amorphous basal lamina-like substance. In conclusion, HSCTGR and LGFMS share similar immunophenotypic and ultrastructural features, and together with other fibrosing fibrosarcomas, like sclerosing epithelioid fibrosarcoma, may constitute a subset of fibrosarcomas formed by fibroblasts capable of producing large amounts of basal lamina-like material.

Hyalinizing Spindle Cell Tumor with Giant Rosettes and Low-grade Fibromyxoid Sarcoma: An Immunohistochemical and Ultrastructural Comparative Investigation

Hyalinizing spindle cell tumor with giant rosettes (HSCTGR) and low-grade fibromyxoid sarcoma (LGFMS) are 2 variants of fibrosarcoma, which share several clinicopathologic features. This study compares the light microscopic, immunohistochemical, and ultrastructural features of 2 examples of HSCTGR and 3 of LGFMS to determine the degree of overlap of these 2 tumors. HSCTGR were composed of bland spindle cells within hyalinized to myxoid stroma. Scattered throughout the lesions were characteristic rosette-like structures, formed by a central collagenous core surrounded by spindled neoplastic cells. LGFMS consisted of a mixture of fibrous and myxoid areas, composed of fibroblast-like cells arranged in a swirling, whorled growth pattern. Immunohistochemical analysis showed diffuse positivity for vimentin in all cases, while few scattered tumor cells stained for CD57, CD34, factor XIIIA, and actin. The extracellular matrix showed intense positivity for type IV collagen, laminin, and fibronectin, with the exception of myxoid areas of LGFMS and the central core of the giant rosettes in HSCTGR. Ultrastructurally, both tumor types were composed of cells with the features of fibroblasts, embedded in a collagenous stroma with irregular deposits of amorphous basal lamina-like substance. In conclusion, HSCTGR and LGFMS share similar immunophenotypic and ultrastructural features, and together with other fibrosing fibrosarcomas, like sclerosing epithelioid fibrosarcoma, may constitute a subset of fibrosarcomas formed by fibroblasts capable of producing large amounts of basal lamina-like material.

Connective tissue tumors.

Connective tissue consists of collagen, elastic fibers and ground substances produced by fibrocytes. These cells are usually spindle-shaped with slender nuclei and bipolar cytoplasmic extensions. Apart from labeling for vimentin and variable reactivity for factor XIIIa and CD34, fibrocytes are immunonegative. Electron microscopy reveals prominent endoplasmic reticulum, but is otherwise indistinct. Lesions with fibrocytic differentiation can be divided into five categories: scars, keloids, dermatofibromas, nodular fasciitis, and superficial fibromatoses are inflammatory lesions. Thereby, dermatofibromas and their subcutaneous/deep soft tissue counterpart nodular fasciitis can present with a wide variety of clinicopathologic variants which may be misinterpreted as malignancies. Prurigo nodularis, chondrodermatitis nodularis helicis, acanthoma fissuratum, and knuckle pads are hyperplasias; fibroma molle, fibrous papules, connective tissue nevi, and elastofibroma are hamartomas; and fibroma of tendon sheath, pleomorphic fibroma, and giant cell tumor of tendon sheath are benign neoplasms. Deep fibromatoses, dermatofibrosarcoma protuberans, giant cell fibroblastoma, giant cell angiofibroma, hyalinizing spindle cell tumor with giant rosettes, solitary fibrous tumor, myxofibrosarcoma, low-grade fibromyxoid sarcoma, acral myxoinflammatory fibroblastic sarcoma, and classical fibrosarcoma, are malignant neoplasms, that is fibrosarcomas of variable malignant potential. Lesions dominated by myocytes/ myofibroblasts, e.g. cutaneous myofibroma/infantile myofibromatosis, or by macrophages, e.g. xanthogranulomas, are not part of this chapter.

Hyalinizing Spindle Cell Tumor with Giant Rosettes of the Broad Ligament

Background. Hyalinizing spindle cell tumor with giant rosettes (HSTGR) is a rare, recently described tumor that most commonly occurs in the peripheral deep soft tissues.Case. A 53-year-old woman was operated on because of a mass in the broad ligament which was first noted 17 years previously. The tumor showed typical features of HSTGR. Two years after surgery, the patient is alive with no evidence of disease.Conclusions. To our knowledge, the present case is the first description of HSTGR occurring in the broad ligament. Despite its bland morphology, HSTGR is a low-grade sarcoma, most probably a variant of low-grade fibromyxoid sarcoma. A wide resection of the tumor and prolonged follow-up are needed because patients may develop late metastases.

Low-grade fibromyxoid sarcoma and hyalinizing spindle cell tumor with giant rosettes: a clinicopathologic study of 73 cases supporting their identity and assessing the impact of high-grade areas.

Low-grade fibromyxoid sarcoma (LGFMS) is a rare sarcoma characterized by bland histologic features and a paradoxically aggressive clinical course. The hyalinizing spindle cell tumor with giant rosettes (HSCT) is a closely related tumor characterized by the presence of giant collagen rosettes. Only a single example of a metastasizing HSCT has been reported. A small subset of both LGFMS and HSCT display areas of increased cellularity and atypia which qualify as intermediate- to high-grade sarcoma; the significance of these features has not been definitively assessed. We present the clinicopathologic features of 77 cases of LGFMS and HSCT to determine the degree of overlap of these two lesions, their biologic behavior, and the significance of the occasional presence of intermediate- to high-grade sarcoma within both. The patients (33 female, 40 male) ranged from 3 to 78 years of age (median, 34 yrs). Fourteen cases occurred in patients less than 18 years of age. The tumors measured from 1 to 23 cm (median, 4.5 cm) and occurred predominantly in the trunk and lower extremities in both the deep (66 cases) and superficial (7 cases) soft tissues. In 15 cases, the tumor was present > 1 year before diagnosis. All tumors showed predominantly the typical hypocellularity and bland cytologic features of typical LGFMS; however, areas of hypercellularity and nuclear enlargement and hyperchromatism were identified in 12 of 73 (16%) and 7 of 73 (10%), respectively. Necrosis and mitotic activity >5/50 high-powered fields (HPF) were present in 6 of 73 (8%) and 5 of 73 (7%), respectively. Epithelioid areas were present in 33 of 73 (45%) and rosettes in 22 of 73 (30%). Follow up (54 cases; range, 2-192 mos; median, 24 mos; mean, 38 mos) showed 5 recurrences, 3 metastases, and 1 death. The diagnosis of LGFMS or HSCT was made prospectively in 51 patients; none had metastatic disease. Two of the metastatic tumors were LGFMS and one was a HSCT. LGFMS may occur more often in the pediatric population and show a much wider histologic spectrum than previously thought. A significant number of LGFMS possess inconspicuous collagen rosettes characteristic of HSCT, indicating that these two tumors are ends of a common spectrum rather than distinct entities. HSCT, like LGFMS, are low-grade sarcomas with metastatic potential. The presence of focal areas of intermediate- to high-grade sarcoma does not portend a worse outcome in the short term. The better prognosis reflected in this study compared with previous ones might reflect the fact that all were initially diagnosed as sarcomas and treated with aggressive surgery. The fact that the only three patients to develop metastatic disease were patients whose LGFMS or HSCT was identified retrospectively supports this concept.