Primary Intracranial Angiomatoid Fibrous Histiocytoma: Two Case Reports and Literature Review
TL;DR: Histopathological findings established the diagnosis of intracranial AFH confirmed with fluorescence in situ hybridization and reverse transcriptase polymerase chain reaction testing that demonstrated EWSR1 gene re-arrangement in both cases.
About: This article is published in World Neurosurgery.The article was published on 2020-11-01. It has received 5 citations till now. The article focuses on the topics: Angiomatoid fibrous histiocytoma.
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TL;DR: In this paper, the authors report 11 cases of central nervous system mesenchymal tumors with proven FET:CREB fusion, and they confirm that these fusion transcripts do not represent a single molecular tumor entity, indicating the existence of a distinct epigenetic group that could potentially be partially masked by the low number of cases included.
Abstract: FET:CREB fusions have been described in a variety of tumors from various phenotypes. Recently, these fusion transcripts were reported in intracranial tumors, variably named intracranial mesenchymal myxoid tumors or angiomatoid fibrous histiocytomas. Controversy remains concerning the terminology for these tumors. Here, we report 11 cases of central nervous system mesenchymal tumors with proven FET:CREB fusion. Most DNA methylation profiles were not classifiable using the Heidelberg Brain Tumor or Sarcoma Classifier (v11b4/v12.2). However, by using unsupervised t-SNE and hierarchical clustering analyses, six of the cases constituted a distinct cluster. The remaining four tumors showed no obvious relation to any of the other referenced classes but were close to the clusters of extra-CNS angiomatoid fibrous histiocytomas (n = 1), clear cell sarcomas (n = 1), or solitary fibrous tumors (n = 2). Our findings confirm that intracranial FET:CREB-fused tumors do not represent a single molecular tumor entity, although most samples clustered close to each other, indicating the existence of a distinct epigenetic group that could potentially be partially masked by the low number of cases included. Further analyses are needed to characterize intracranial FET:CREB fused-defined tumors in more detail.
8 citations
TL;DR: A novel histomolecular tumor of the central nervous system, the "intracranial mesenchymal tumor (IMT), FET-CREB fusion-positive" has recently been identified in the literature and will be added to the World Health Organization Classification of Tumors of the Central Nervous System.
Abstract: A novel histomolecular tumor of the central nervous system, the "intracranial mesenchymal tumor (IMT), FET-CREB fusion-positive" has recently been identified in the literature and will be added to the 2021 World Health Organization Classification of Tumors of the Central Nervous System. However, our latest study using DNA-methylation analyses has revealed that intracranial FET-CREB fused tumors do not represent a single molecular tumor entity. Among them, the main subgroup presented classical features of angiomatoid fibrous histiocytoma, having ultrastructural features of arachnoidal cells, for. Another tumor type with clear cell component and histopathological signs of aggressivity clustered in close vicinity with clear cell sarcoma of soft tissue. Herein, we report one case of IMT with a novel SMARCA2-CREM fusion which has until now never been described in soft tissue or the central nervous system. We compare its clinical, histopathological, immunophenotypic, genetic and epigenetic features with those previously described in IMT, FET-CREB fusion-positive. Interestingly, the current case did not cluster with IMT, FET-CREB fusion-positive but rather presented histopathological (clear cell morphology with signs of malignancy), clinical (with a dismal course with several recurrences, metastases and finally the patient's death), genetic (fusion implicating the CREM gene), and epigenetic (DNA-methylation profiling) similarities with our previously reported clear cell sarcoma-like tumor of the central nervous system. Our results added data suggesting that different clinical and histomolecular tumor subtypes or grades seem to be included within the terminology "IMT, FET-CREB fusion-positive", and that further series of cases are needed to better characterize them.
4 citations
TL;DR: The fifth edition of the World Health Organization Classification of Tumors of the Central Nervous System (CNS) now includes mesenchymal tumors that occur uniquely or frequently in the CNS as discussed by the authors .
Abstract: The fifth edition of the World Health Organization Classification of Tumors of the Central Nervous System (CNS) now includes mesenchymal tumors that occur uniquely or frequently in the CNS. Moreover, this version has aligned the terminology of mesenchymal tumors with their soft tissue counterparts. New tumor types have been added, such as the "intracranial mesenchymal tumor, FET-CREB fusion-positive", the "CIC-rearranged sarcoma", and the "Primary intracranial sarcoma, DICER1-mutant". Other entities (such as rhabdomyosarcoma) have remained in the current WHO classification because these tumor types may present specificities in the CNS as compared to their soft tissue counterparts. Based on an extensive literature review, herein, we will discuss these newly recognized entities in terms of clinical observation, radiology, histopathology, genetics and outcome, and consider strategies for an accurate diagnosis. In light of this literature analysis, we will also introduce some potentially novel tumor types.
30 Jun 2021
TL;DR: The clinical case of a 68-year-old man who presented with AFH on the right arm is reported, and the disease relapsed a few years after surgical excision.
Abstract: Angiomatoid fibrous histiocytoma is a rare neoplasm with an intermediate malignant potential, that mostly occurs in the subcutis and features varying proportions of epithelioid, ovoid and spindle cells in a nodular and syncytial growth pattern, with hemorrhagic pseudovascular spaces. Here, we report the clinical case of a 68-year-old man who presented with AFH on the right arm; the disease relapsed a few years after surgical excision. We also conduct a brief review of the literature, focusing on the biological and genetic characteristics and the differential diagnosis from other more or less similar entities.
TL;DR: The first jugular foramen angiomatoid fibrous histiocytoma case and the first treatment with preoperative endovascular embolization are described, which may decrease the need for adjuvant radiation in rare skull base tumors in young patients.
Abstract: Objective We describe the first jugular foramen angiomatoid fibrous histiocytoma (AFH) case and the first treatment with preoperative endovascular embolization. AFH is a rare intracranial neoplasm, primarily found in pediatric patient extremities. With an increase in AFH awareness and a well-described genetic profile, intracranial prevalence has also subsequently increased. Study Design We compare this case to previously reported cases using PubMed/Medline literature search, which was performed using the algorithm [“intracranial” AND “angiomatoid fibrous histiocytoma”] through December 2020 (23 manuscripts with 46 unique cases). Patient An 8-year-old female presented with failure to thrive and right-sided hearing loss. Work-up revealed an absence of right-sided serviceable hearing and a large jugular foramen mass. Angiogram revealed primary arterial supply from the posterior branch of the ascending pharyngeal artery, which was preoperatively embolized. Intervention Gross total resection was performed via a translabyrinthine approach. Conclusion The case presented is unique; the first reported AFH at the jugular foramen and the first reported case utilizing preoperative embolization. Preoperative embolization is a relatively safe technique that can improve the surgeon's ability to perform a maximally safe resection, which may decrease the need for adjuvant radiation in rare skull base tumors in young patients.
References
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TL;DR: Most likely it is a tumor of fibroblast‐ and histiocyte‐like cells, akin to malignant fibrous histiocytoma, but different in its age incidence, microscopic appearance, and behavior.
Abstract: This article describes 41 examples of an unusual fibrohistiocytic sarcoma which occurred primarily in the extremities of young individuals between the ages of 5 and 25 years (median 13 years). It manifested as a nodular subcutaneous growth that seldom caused tenderness or pain, and clinically was often mistaken for a hematoma or a hemangioma. Grossly, the tumor presented as a circumscribed, multinodular or multicystic, hemorrhagic mass that ranged in size from 0.7 to 10 cm (median 2.5 cm). On microscopic examination, it consisted principally of 1) solid arrays or nests of fibroblast- and histiocyte-like cells, not infrequently containing varying amounts of intracellular hemosiderin or lipid, 2) focal areas of hemorrhage or hemorrhagic cyst-like spaces, sometimes occupying the major portion of the tumor, and 3) aggregates of chronic inflammatory cells, chiefly lymphocytes and plasmacytes, a feature that caused confusion with a lymph node metastasis in several cases. Follow-up information, available in 24 patients, revealed a variable clinical course. Twenty-one patients were alive, 11 with recurrence (including one with 9 recurrences in a 21-year period) one with recurrence and metastasis and one with metastasis. Three patients had died of metastasis 1, 3, and 13 years respectively, after the initial surgical therapy. The exact histogenesis is still obscure. Most likely it is a tumor of fibroblast- and histiocyte-like cells, akin to malignant fibrous histiocytoma, but different in its age incidence, microscopic appearance, and behavior.
342 citations
TL;DR: The resemblance of these lesions to lymph nodes, clinically and morphologically, the finding of similar desmin positive cells in the adjacent lymphoid infiltrate, and the fact that 66% cases were found in sites of normal lymphoid tissue raise the possibility that some ofThese lesions may arise from or be related to myoid cells of lymphoid tissues.
219 citations
TL;DR: It is concluded that angiomatoid malignant fibrous histiocytoma is intrinsically a low-grade tumor, and assessment of various histologic parameters or grading provides little or no additional prognostic information.
Abstract: Described by Enzinger in 1979, angiomatoid malignant fibrous histiocytoma is a distinctive tumor of adolescence and early adult life characterized by sheets of relatively bland rounded or spindled cells separated by areas of cystic hemorrhage and surrounded by a prominent inflammatory infiltrate and often a fibrous pseudocapsule. On the basis of the original 41 cases, the tumor has been considered a low-grade malignancy. We are reporting the clinicopathologic findings and follow-up information of 108 new cases of angiomatoid malignant fibrous histiocytoma to determine the long-term behavior of this tumor and whether various histologic features (atypia, mitoses, infiltrative borders, and inflammatory infiltrate) are useful in predicting outcome. Follow-up information was obtained in 94 (87%) cases. Local recurrences developed in 11 patients (12%), all of whom were cured by re-excision. The initial excision in all patients developing local recurrence appeared to be incomplete. Local recurrence was statistically associated with irregular tumor border and head and neck location. Five patients developed metastases. Four had only local metastases, which responded to surgery, whereas the fifth patient developed presumed pulmonary and cerebral metastases and died. The development of both local and distant metastases was correlated with invasion into the deep fascia or muscle but not to various histologic parameters such as mitotic rate and pleomorphism. We conclude that angiomatoid malignant fibrous histiocytoma is intrinsically a low-grade tumor, and assessment of various histologic parameters or grading provides little or no additional prognostic information. Because death from disease occurred in only one patient (1%) in our series, it seems reasonable to reclassify angiomatoid malignant fibrous histiocytoma with fibrohistiocytic tumors of intermediate malignancy rather than with the conventional malignant fibrous histocytoma, the majority of which are high-grade sarcomas.
215 citations
TL;DR: A distinct group of myxoid mesenchymal neoplasms occurring in children or young adults with a predilection for intracranial locations is reported, suggesting a novel entity.
Abstract: Recurrent gene fusions involving EWSR1 with members of the cAMP response element binding protein (CREB) family (ATF1 and CREB1) have been reported in a diverse group of tumors including angiomatoid fibrous histiocytoma (AFH), soft tissue and gastrointestinal clear cell sarcoma, primary pulmonary myxoid sarcoma, and hyalinizing clear cell carcinoma of salivary gland. We have recently encountered a group of 5 myxoid mesenchymal tumors positive for EWSR1 fusions with one of the CREB family member (ATF1, CREB1, and CREM), with histologic features distinct from any of the previously described pathologic entities. Tumors occurred in children or young adults (12 to 23 y; mean, 18 y), with equal sex distribution. All except 1 were intracranial (intra-axial, 2; meningeal, 2), whereas 1 was perirectal. Histologically, the tumors were well circumscribed, often lobulated, composed of uniform ovoid to round cells, and arranged in cord-like or reticular structures in a myxoid background. All except 1 displayed unique sunburst amianthoid fibers. Immunohistochemically, tumors were positive for epithelial membrane antigen (5/5; 4 focal, 1 diffuse) and desmin (3/5). A novel EWSR1-CREM fusion was identified by RNA sequencing in the perirectal tumor, which was further confirmed by fluorescence in situ hybridization (FISH) and reverse transcription-polymerase chain reaction (RT-PCR). A second case with similar EWSR1-CREM fusion was identified by RT-PCR and FISH in a meningeal tumor. The remaining cases studied by FISH showed the presence of EWSR1-CREB1 fusion in 2 cases and EWSR1-ATF1 in 1. In conclusion, we report a distinct group of myxoid mesenchymal neoplasms occurring in children or young adults with a predilection for intracranial locations. Although the immunoprofile [epithelial membrane antigen (EMA), desmin] and the fusion type raise the possibility of a myxoid AFH, none of the typical histologic findings of AFH were present, suggesting a novel entity.
99 citations
TL;DR: The first pathologically confirmed case of an AFH presenting as an intracerebral primary in a previously healthy 25-year-old man is reported, and genetic analyses revealed a t(12;22)(q13;q12) and a unique underlying clear cell sarcomalike type 1 EWS/ATF-1 gene fusion.
Abstract: Angiomatoid fibrous histiocytoma (AFH) is generally considered a soft tissue sarcoma of low malignant potential that occurs in children/young adults and most frequently affects the extremities. AFH infrequently recurs and rarely metastasizes. AFH has a characteristic histomorphology, and immunohistochemical reactivities for desmin and CD68 have led to myofibroblastic and fibrohistiocytic histogenetic hypotheses, respectively. Although only a limited number of AFH cases have been molecularly characterized, many have demonstrated evidence of an underlying translocation event. Reverse transcription-polymerase chain reaction and fluorescence in situ hybridization studies suggest that chromosomal rearrangement in AFH most frequently involve the EWS, CREB, ATF-1, and FUS genes. We report the first pathologically confirmed case of an AFH presenting as an intracerebral primary in a previously healthy 25-year-old man. Genetic analyses revealed a t(12;22)(q13;q12) and a unique underlying clear cell sarcomalike type 1 EWS/ATF-1 gene fusion.
85 citations