Hemosiderotic Fibrolipomatous Tumor Research Articles

Pleomorphic Hyalinizing Angiectatic Tumor (PHAT): Review of the Literature with Case Presentation.

Pleomorphic hyalinizing angiectatic tumor (PHAT) is a very rare entity of soft tissue considered a “neoplasm of uncertain behaviour of connective or other soft tissue” by the World Health Organization (2020). It develops in subcutaneous tissue of the lower extremities, more frequently in the region of the ankle and foot, and rarely as a deep-seated soft tissue mass in locations such as the perineum, buttock, arms, head and neck, and viscera. Although inconsistent cytogenetic data have been reported on PHAT so far, there are potential morphological and genetic overlaps with hemosiderotic fibrolipomatous tumor (HFLT) and myxoinflammatory fibroblastic sarcoma (MIFS). Here we report a case of PHAT at the level of the upper third of the right thigh in a 48-year-old patient and we also focus on the differential diagnoses of these entities and conduct a literature review of reported cases.

“Pauci-Hemosiderotic” Fibrolipomatous Tumor: A Mimicker of Various Lipomatous Lesions

Hemosiderotic fibrolipomatous tumor is a rare soft tissue tumor that preferentially affects the dorsum of foot, shows recurrent t(1;10) translocation targeting TGFBR3 and OGA (MGEA5) genes, and has a high recurrence potential. Hemosiderin deposits, mature adipocytes, and interspersed spindle cells are the 3 cardinal morphologic features of this tumor. We describe a "pauci-hemosiderotic" example involving the left wrist of a 45-year-old female, posing a diagnostic pitfall. The tumor comprised mature adipose tissue traversed by variably thick fibrous septa containing short fascicles of spindle cells. Prominent small- to medium-sized blood vessels were present, often with perivascular fibrosis or aggregates of foamy histiocytes, sometimes associated with red cell extravasation. Hemosiderin was not conspicuous, but fine deposits could be found focally on careful search and with the aid of Perls stain. The diagnosis was further confirmed by diffuse expression of CD34 and presence of OGA translocation by fluorescence in situ hybridization. Pathologists should be aware that hemosiderin deposition can be scanty and focal in hemosiderotic fibrolipomatous, but the rich vasculature with a "damaged" appearance is a useful diagnostic clue.

The t(1;10)(p22;q24) TGFBR3/MGEA5 Translocation in Pleomorphic Hyalinizing Angiectatic Tumor, Myxoinflammatory Fibroblastic Sarcoma, and Hemosiderotic Fibrolipomatous Tumor.

Pleomorphic hyalinizing angiectatic tumor (PHAT) of soft parts, hemosiderotic fibrolipomatous tumor (HFLT), and myxoinflammatory fibroblastic sarcoma (MIFS) are 3 distinct entities of low-grade spindle cell mesenchymal neoplasm. These tumors have similar clinical presentations and partially overlapping but distinctive pathologic features. A recurrent translocation, t(1;10)(p22;q24), has been detected in a subset of PHAT, HFLT, MIFS, and HFLT/MIFS hybrid cases. Translocation t(1;10)(p22;q24) involves transforming growth factor β-receptor 3 ( TGFBR3) and meningioma-expressed antigen 5 ( MGEA5) genes on chromosomes 1p22 and 10q24, respectively. However, the percentage of translocation in PHAT, HFLT, and MIFS varies significantly among different studies. The relationship among these tumors has been a controversial topic among experts. To discuss the diagnostic and functional significance of translocation t(1;10)(p22;q24) TGFBR3/MGEA5 rearrangement in HFLT, PHAT, and MIFS. PubMed was used for this study. Diagnosis of HFLT, PHAT, and MIFS is challenging because of a lack of unique morphologic, immunophenotypic, molecular, and cytogenetic markers. The recurrent t(1;10)(p22;q24) translocation and/or TGFBR3/MGEA5 rearrangement was reported in 55 patients, with a relatively even distribution among HFLT, PHAT, and MIFS (17 HFLT, 15 MIFS, 13 MIFS/HFLT, and 10 PHAT). This indicates that current morphology-based diagnostic criteria do not identify reliably the subset of soft tissue tumor with t(1;10) translocation. Genetic heterogeneity of these tumors is supported by the recent detection of a mutually exclusive, second recurrent genetic change, t(7;17) TOM1L2-BRAF translocation or BRAF amplification, in a subset of MIFS.

Hemosiderotic fibrolipomatous tumor: A poorly known entity

Hemosiderotic fibrohistiocytic lipomatous tumor (HFLT) is a rare and supposedly benign fibrolipomatous entity. Clinical and imaging features are not specific. So, histologic, immunohistochemical and molecular analyses are required for diagnosis. The clinic and pathologic aspects of this lesion are diversely reported. Moreover, its reactive or neoplastic origin is still under debate. This lesion should be treated by complete excision. It is mandatory to be aware of its tendency to harbor higher-grade lesions with aggressive outcome. We report a case of HFLT affecting the dorsum of the third right finger in a 52-year-old women, in order to describe histologic patterns of this tumor and to discuss the current literature regarding the etiopathogeny and the cytogenetic features of this rare entity.

Myxoinflammatory Fibroblastic Sarcoma: Review and Update.

Myxoinflammatory fibroblastic sarcoma is a rare soft tissue tumor with most occurring in the distal extremities of adult patients. It has a high rate of local recurrence and a low rate of metastasis. Because it may appear benign on clinical examination, and because the microscopic features are generally underrecognized, it is often inadequately treated and misdiagnosed. In this review, based upon experience and that of the literature, the intent is to highlight salient clinicopathologic features, detail the broad microscopic spectrum including high-grade aggressive variants, review the molecular features, and discuss its relation to hemosiderotic fibrolipomatous tumor.

Hemosiderotic Fibrolipomatous Tumor, Pleomorphic Hyalinizing Angiectatic Tumor, and Myxoinflammatory Fibroblastic Sarcoma: Related or Not?

Hemosiderotic fibrolipomatous tumor is an unusual, distinctive soft tissue neoplasm with locally recurring potential, which most commonly occurs in the ankle and foot. Morphologic evidence strongly suggests that hemosiderotic fibrolipomatous tumor is related to another rare, locally aggressive tumor of the distal extremities, pleomorphic hyalinizing angiectatic tumor, with areas identical to hemosiderotic fibrolipomatous tumor seen at the periphery in most if not all pleomorphic hyalinizing angiectatic tumor. This morphologic evidence is further supported by molecular genetic data, showing recurrent TGFBR3 and/or MGEA5 rearrangements in both hemosiderotic fibrolipomatous tumor and pleomorphic hyalinizing angiectatic tumor. A possible link between hemosiderotic fibrolipomatous tumor and yet another low-grade sarcoma of the distal extremities, myxoinflammatory fibroblastic sarcoma, has also been suggested based on the occurrence of unusual examples of hemosiderotic fibrolipomatous tumor showing progression to myxoid sarcoma, demonstrating some but not all features of myxoinflammatory fibroblastic sarcoma. These "hybrid hemosiderotic fibrolipomatous tumor-myxoinflammatory fibroblastic sarcoma" also commonly show TGFBR3 and/or MGEA5 rearrangements. However, classic myxoinflammatory fibroblastic sarcoma lacks areas resembling hemosiderotic fibrolipomatous tumor, and shows a very low frequency of TGFBR3 and/or MGEA5 rearrangements in prospectively diagnosed cases. This suggests that so-called "hybrid hemosiderotic fibrolipomatous tumor-myxoinflammatory fibroblastic sarcoma" represents a form of malignant progression within hemosiderotic fibrolipomatous tumor, rather than a lesion strictly related to classic myxoinflammatory fibroblastic sarcoma. This article will review the morphologic features, genetic features, and differential diagnosis of these rare neoplasms, and discuss their interrelation, or lack thereof.

Hemosiderotic fibrolipomatous tumor in axillary localization: case report

Hemosiderotic fibrolipomatous tumor in axillary localization: case report

TGFBR3 and MGEA5 rearrangements are much more common in “hybrid” hemosiderotic fibrolipomatous tumor-myxoinflammatory fibroblastic sarcomas than in classical myxoinflammatory fibroblastic sarcomas: a morphological and fluorescence in situ hybridization study

Myxoinflammatory fibroblastic sarcoma (MIFS) is a rare low-grade sarcoma that most often involves the distal extremities of adults. Some MIFSs have been reported to show TGFBR3 and MGEA5 rearrangements. TGFBR3 and MGEA5 rearrangements have also been reported in hemosiderotic fibrolipomatous tumor (HFLT), in pleomorphic hyalinizing angiectatic tumor (PHAT), and in rare tumors allegedly showing features of both HFLT and MIFS (hybrid HFLT-MIFS). These findings have led to speculation that HFLT, MIFS, PHAT, and hybrid HFLT-MIFS are closely related; however, areas resembling HFLTs are only very rarely encountered in previous series of MIFSs. We studied classic examples of these tumors with the goal of clarifying the relationship between MIFS and HFLT-MIFS. Cases of MIFS (n=31), hybrid HFLT-MIFS (n=8), PHAT (n=2), HFLT (n=1), and undifferentiated pleomorphic sarcoma (n=4) were retrieved from our archives, and the diagnoses were verified by 5 soft tissue pathologists. Using previously validated break-apart fluorescence in situ hybridization probes, we analyzed for TGFBR3 and MGEA5 rearrangements. Only 2 of 31 MIFSs harbored MGEA5 rearrangements; all lacked TGFBR3 rearrangements. Six of 8 hybrid HFLT-MIFSs harbored rearrangements of TGFBR3 and/or MGEA5. Both PHATs were positive for rearrangements of TGFBR3 and/or MGEA5. The HFLT was positive for rearrangements of both TGFBR3 and MGEA5. All undifferentiated pleomorphic sarcomas with focal myxoid change were negative. We conclude that (1) TGFBR3 and/or MGEA5 rearrangements are much more common in hybrid HFLT-MIFSs than in classic MIFSs, (2) HFLTs and MIFSs may be unrelated lesions, and (3) hybrid HFLT-MIFSs most likely represent HFLTs with sarcomatous progression, rather than tumors strictly related to classic MIFSs.

Radiological imaging features and clinicopathological correlation of hemosiderotic fibrolipomatous tumor: experience in a single tertiary cancer center.

To determine the imaging features of hemosiderotic fibrolipomatous tumor (HFLT), which has a propensity towards local recurrence and the potential to transform into myxoinflammatory fibroblastic sarcoma (MIFS). The study included 8 patients with a diagnosis of HFLT and imaging at a tertiary cancer center. Imaging studies included radiographs (n =2), ultrasound (n = 3), and MRI (n = 16). Imaging features were evaluated including location, calcification, sonographic echogenicity, vascular flow, size, border, signal characteristics, contrast enhancement, and blooming on MRI. The HFLT was located in the ankle/foot in 4 out of 8 and was subcutaneous in 8 out of 8, ranging in size from 2 to 18cm. Histology at initial diagnosis was HFLT in 5 out of 8 and HFLT with MIFS in 3 out of 8. None was calcified on radiography. On ultrasound 2 out of 3 were heterogeneously echogenic with ≥10 foci of vascular flow. Two out of 8 patients had MRI only at local recurrence. The tumor border was infiltrative in 4 out of 6 at initial diagnosis and in 2 patients with MRI at recurrence only. Fat and septae were present in 7 out of 8 at initial diagnosis and at recurrence. Signal intensity was iso-/hypointense to muscle on T1-weighted sequences in more than two thirds of the tumor in 4 out of 7 and hyperintense to muscle in at least one third of the tumor on fluid-sensitive sequences in 6 out of 8. Contrast enhancement was heterogeneous in 7 out of 7; blooming in two thirds of the tumor on gradient-echo sequence MRI indicated hemorrhage. The HFLT commonly presents as a mass with an infiltrative border, interspersed fat and septations at initial diagnosis and local recurrence on MRI regardless of histology of HFLT alone or with MIFS. Hemosiderin deposits may be detected as blooming on gradient-echo sequences.

TGFBR3 and MGEA5 Rearrangements in Pleomorphic Hyalinizing Angiectatic Tumors and the Spectrum of Related Neoplasms

Pleomorphic hyalinizing angiectatic tumor (PHAT) is a rare, locally aggressive tumor of the distal extremities with a proclivity for local recurrence. PHATs contain characteristic ectatic, thin-walled vessels, lined by fibrin, and are surrounded by groups of variably pleomorphic spindled to epithelioid neoplastic cells. The putative precursor lesion of PHAT, originally termed "early PHAT" shares many clinicopathologic features with hemosiderotic fibrolipomatous tumor (HFLT). HFLT, myxoinflammatory fibroblastic sarcoma (MIFS), and tumors showing hybrid features of HFLT and MIFS often show TGFBR3 and MGEA5 gene rearrangements. To date, only a small number of PHATs has been tested for either rearrangement; all have been negative. We hypothesized that PHATs contain TGFBR3 and/or MGEA5 rearrangements. Cases of PHAT (all containing areas of HFLT) (N=10), HFLT (N=7), MIFS (N=6), hybrid HFLT/MIFS (N=3), and PHAT-like undifferentiated pleomorphic sarcomas (N=7) were retrieved from our institutional and consultation archives and analyzed for TGFBR3 and MGEA5 rearrangements using a break-apart probe strategy for FISH. Six of 10 PHATs harbored TGFBR3 and/or MGEA5 gene rearrangements: 4 cases had both TGFBR3 and MGEA5 rearrangements, and 2 cases contained MGEA5 rearrangements. Two of 7 HFLTs were positive: 1 case had a TGFBR3 rearrangement, and 1 case had an MGEA5 rearrangement. One of 6 MIFSs had an MGEA5 rearrangement. All 3 hybrid HFLT/MIFS cases were positive: 2 cases had both TGFBR3 and MGEA5 rearrangements, and 1 case had a TGFBR3 rearrangement. All PHAT-like undifferentiated pleomorphic sarcomas were negative. We report, for the first time, the presence of TGFBR3 and/or MGEA5 rearrangements in tumors showing mixed features of HFLT and PHAT. The presence of such rearrangements strongly suggests that HFLT is related to both PHAT and MIFS and that the latter 2 tumors may represent morphologic variants of a single, genetically defined entity in which only MIFS has acquired the capacity to metastasize.

Pleomorphic hyalinizing angiectatic tumor of soft parts: Case Report with unusual ganglion-like cells and review of the literature

Pleomorphic hyalinizing angiectatic tumor (PHAT) is a recently described, non-metastasizing tumor of uncertain lineage. This tumor distributes equally between the genders and has a predilection for the subcutaneous soft tissue, particularly in lower extremity, other locations are rare. Based on the recent literature, PHAT is suspected to encompass the morphological spectrum with other tumors such as myxoinflammatory fibroblastic sarcoma (MIFS) and hemosiderotic fibrolipomatous tumor (HFLT), although cytogenetic data remain inconsistent. We report a case of PHAT that arose in the upper arm with unusual morphology which showed ganglion-like cells similar to Reed-Sternberg-like cells found in MIFS. The tumor had strong immunohistochemical expression of CD34, CD99, and was negative for S-100. The ganglion-like cells were positive for both CD34 and CD68 but negative for CD30. The translocation between chromosome 1 and 10, a frequent finding of MIFS and HFLT, was not identified by FISH excluding the possibility of hybrid PHAT and MIFS. We conclude FISH can be a potential useful tool to separate PHAT with atypical morphology from hybrid tumor in doubted cases. Due to the rarity of PHAT and lack of consistent pathogenetic signatures, more cases and further studies will be needed to elucidate the pathogenesis and nature of this tumor.

Recently characterized soft tissue tumors that bring biologic insight

Previously unrecognized but clinicopathologically (and often molecularly) distinct types of soft tissue tumor continue to be characterized, allowing wider recognition, more consistent application of diagnostic criteria, more reliable prediction of tumor behavior and enhancement of existing classification schemes. Examples of such ‘entities' that have become much better understood over the past decade or so include deep ‘benign' fibrous histiocytoma, hemosiderotic fibrolipomatous tumor, PEComa, spindle cell liposarcoma, myoepithelial tumors of soft tissue and spindle cell/sclerosing rhabdomyosarcoma. These tumor types, as well as the insights which they have engendered, are briefly reviewed here.

SNP array and FISH findings in two pleomorphic hyalinizing angiectatic tumors

Pleomorphic hyalinizing angiectatic tumor (PHAT) is a rare soft tissue tumor of intermediate malignancy and uncertain cellular origin and lineage of differentiation. Although PHAT is still poorly characterized at the genetic level, there is a potential genetic overlap with two other soft tissue tumors: myxoinflammatory fibroblastic sarcoma (MIFS) and hemosiderotic fibrolipomatous tumor (HFLT); MIFS and HFLT share a characteristic t(1;10)(p22;q24) with breakpoints in the TGFBR3 locus on chromosome 1 and near the MGEA5 locus on chromosome 10. Recently, a PHAT with a similar t(1;10) was reported, suggesting a genetic link between MIFS/HFLT and PHAT. To ascertain whether PHAT is also associated with this translocation, two cases were subjected to single nucleotide polymorphism (SNP) array and fluorescence in situ hybridization analyses. Neither PHAT showed a t(1;10) or other types of rearrangement of the TGFBR3 or MGEA5 loci. Both tumors showed imbalances in the SNP array analysis, but none was shared. Thus, the results indicate that PHAT is genetically distinguishable from MIFS and HFLT, but further studies are needed to identify the salient genetic pathways involved in PHAT development.

Consistent t(1;10) with rearrangements of TGFBR3 and MGEA5 in both myxoinflammatory fibroblastic sarcoma and hemosiderotic fibrolipomatous tumor

Despite their shared predilection for superficial soft tissue of distal extremities and frequent local recurrences, myxoinflammatory fibroblastic sarcoma (MIFS) and hemosiderotic fibrolipomatous tumor (HFLT) have distinct morphologic appearances. Recent studies have identified an identical t(1;10)(p22;q24) in five cases of MIFS and two of HFLT, as well as common amplifications on 3p11-12. To investigate further their potential relationship and to determine the incidence of t(1;10) in a larger cohort, we subjected seven MIFS, 14 HFLT, and three cases with mixed morphology, to molecular and cytogenetic analysis. Fluorescence in situ hybridization (FISH) analysis for rearrangements of TGFBR3 on 1p22 and of MGEA5 on 10q24 was performed in all cases, whereas the status of VGLL3 gene amplification on 3p12.1 was investigated in 12 cases. Conventional karyotyping was performed in one HFLT and two cases with mixed MIFS/HFLT histology. Overall 83% of cases showed rearrangements in both TGFBR3 and MGEA5. All three cases with mixed features of MIFS and HFLT were positive. Cytogenetic analysis performed in three cases confirmed an unbalanced der(10)t(1;10)(p22;q24). VGLL3 gene amplification was noted in 10/12 cases of both histologies. The high incidence of t(1;10) in MIFS and HFLT reinforces a shared pathogenetic relationship. Furthermore, the co-existence of both components either synchronously or metachronously in a primary or subsequent recurrence, suggest either different morphologic variants or different levels of tumor progression of a single biologic entity. FISH analysis for TGFBR3 and MGEA5 rearrangements can be applied as a reliable diagnostic molecular test when confronted with limited material or a challenging diagnosis.

Hybrid Myxoinflammatory Fibroblastic Sarcoma/Hemosiderotic Fibrolipomatous Tumor: Report of a Case Providing Further Evidence for a Pathogenetic Link

Myxoinflammatory fibroblastic sarcoma and hemosiderotic fibrolipomatous tumor are rare, slow-growing soft tissue tumors of the distal extremities with recurrent potential. Recent cytogenetic studies have shown a t(1;10)(p22;q24) or der(10)t(1;10) in combination with aberrations of chromosome 3 in a limited number of cases of both entities. Here we report a case of a 42-year-old female with a soft tissue tumor of the ankle showing hybrid morphologic features of myxoinflammatory fibroblastic sarcoma and hemosiderotic fibrolipomatous tumor, a der(10)t(1;10), and abnormalities of chromosome 3. This hybrid lesion provides further evidence for a close relationship between these 2 tumor types.

Case Report: Hemosiderotic Fibrohistiocytic Lipomatous Lesion

A hemosiderotic fibrohistiocytic lipomatous lesion, also called hemosiderotic fibrolipomatous tumor, is a rare and recently described fibrolipomatous entity. Initially considered the result of a reactive inflammatory process from trauma or vascular disease, newer evidence suggests it may be neoplastic in origin. We report the case of a 56-year-old woman with a painful mass in the dorsal aspect of the foot diagnosed as a hemosiderotic fibrohistiocytic lipomatous lesion. We reviewed all 31 published cases of hemosiderotic fibrohistiocytic lipomatous lesions looking for common clinical, imaging, and histologic patterns. Hemosiderotic fibrohistiocytic lipomatous lesions occur predominantly in the fifth and sixth decades of life (average age, 49.5 years; range, 0.67-74 years). Females predominate 22 to 9. Thirteen of 28 patients had histories of trauma or vasculopathy. Twenty-six of 31 lesions were in the foot. The MRI signal of a hemosiderotic fibrohistiocytic lipomatous lesion follows fat in all sequences. Stranding or septations also frequently are seen. Histologically, the lesions are composed of three main elements in varying proportions: mature adipocytes, spindle cells, and hemosiderin pigment. Ten of 27 resected lesions recurred. Resection types are not reported in many cases. Four of 15 lesions recurred after marginal/intralesional excision, whereas none of three lesions treated by wide excision recurred. The high recurrence rate may be related to the difficulty in determining intraoperatively that a resection is complete, secondary to the lack of anatomic boundaries such as a pseudocapsule. Any attempt at wide resection must weigh the morbidity of this surgery against that of a recurrence after a resection which seemed complete intraoperatively. There have been no reports of metastasis.

Cytogenetic analysis of a hemosiderotic fibrolipomatous tumor

Hemosiderotic fibrolipomatous tumor is an extremely rare, nonencapsulated, fatty lesion with a consistent histologic appearance that was originally considered reactive in nature. To our knowledge, there are no previous reports on the cytogenetics of this lesion. Reported here is a case of hemosiderotic fibrolipomatous tumor arising within the subcutaneous tissue of the right foot, dorsal aspect, of an otherwise healthy 35-year-old woman. Subsequent cytogenetic analysis revealed a clonal reciprocal translocation between chromosomes 1 and 10, with a further rearrangement involving this derivative chromosome 1 and chromosome 3. This, in addition to its characteristic morphology and immunophenotype, supports the neoplastic nature of this tumor and may aid in its diagnosis.