Unusual Soft Tissue Tumor Research Articles

EWSR1::WT1 Fusions in Neoplasms Other Than Conventional Desmoplastic Small Round Cell Tumor: Three Tumors Occurring Outside the Female Genital Tract

Desmoplastic small round cell tumor (DSRCT) is a high-grade, primitive round cell sarcoma classically associated with prominent desmoplastic stroma, coexpression of keratin and desmin, and a characteristic EWSR1::WT1 gene fusion. DSRCT typically arises in the abdominopelvic cavity of young males with diffuse peritoneal spread and poor overall survival. Although originally considered to be pathognomonic for DSRCT, EWSR1::WT1 gene fusions have recently been detected in rare tumors lacking the characteristic morphologic and immunohistochemical features of DSRCT. Here, we report 3 additional cases of neoplasms other than conventional DSCRCT with EWSR1::WT1 gene fusions that occurred outside the female genital tract. Two occurred in the abdominopelvic cavities of a 27-year-old man and a 12-year-old girl, whereas the third arose in the axillary soft tissue of an 85-year-old man. All cases lacked prominent desmoplastic stroma and were instead solid and cystic with peripheral fibrous pseudocapsules and occasional intervening fibrous septa. Necrosis was either absent (1/3) or rare (2/3), and mitotic activity was low (<1 to 3 per 10 hpf). In immunohistochemical studies, there was expression of smooth muscle actin (3/3) and desmin (3/3), rare to focal reactivity for EMA (2/3), and variable expression of CK AE1/AE3 (1/3). Myogenin and MyoD1 were negative, and C-terminus-specific WT1 was positive in both cases tested (2/2). All 3 tumors followed a more indolent clinical course with 2 cases demonstrating no evidence of disease at 20 and 44 months after resection. The patient from case 3 died of other causes at 14 months with no evidence of recurrence. DNA methylation profiling showed that the 3 cases clustered with DSRCT; however, they demonstrated fewer copy number variations with 2 cases having a flat profile (0% copy number variation). Differential methylation analysis with hierarchical clustering further showed variation between the 3 cases and conventional DSRCT. Although further study is needed, our results, in addition to previous reports, suggest that EWSR1::WT1 gene fusions occur in rare and seemingly distinctive tumors other than conventional DSRCT with indolent behavior. Proper classification of these unusual soft tissue tumors with EWSR1::WT1 gene fusions requires direct correlation with tumor morphology and clinical behavior, which is essential to avoid overtreatment with aggressive chemotherapy.

Complementary value of molecular analysis to expert review in refining classification of uncommon soft tissue tumors.

The classification of many soft tissue tumors remains subjective due their rarity, significant overlap in microscopic features and often a non-specific immunohistochemical (IHC) profile. The application of molecular genetic tools, which leverage the underlying molecular pathogenesis of these neoplasms, have considerably improved the diagnostic abilities of pathologists and refined classification based on objective molecular markers. In this study, we describe the results of an international collaboration conducted over a 3-year period, assessing the added diagnostic value of applying molecular genetics to sarcoma expert pathologic review in a selected series of 84 uncommon, mostly unclassifiable mesenchymal tumors, 74 of which originated in soft tissues and 10 in bone. The case mix (71% historical, 29% contemporary) included mostly unusual and challenging soft tissue tumors, which remained unclassified even with the benefit of expert review and routine ancillary methods, including broad IHC panels and a limited number of commercially available fluorescence in situ hybridization (FISH) probes. All cases were further tested by FISH using a wide range of custom bacterial artificial chromosome probes covering most of known fusions in sarcomas, whereas targeted RNA sequencing was performed in 13 cases negative by FISH, for potential discovery of novel fusion genes. Tumor-defining molecular alterations were found in 48/84 tumors (57%). In 27 (32%) cases the tumor diagnosis was refined or revised by the additional molecular work-up, including five cases (6%), in which the updated diagnosis had clinical implications. Sarcoma classification is rapidly evolving due to an increased molecular characterization of these neoplasms, so unsurprisingly 17% of the tumors in this series harbored abnormalities only very recently described as defining novel molecularly defined soft tissue tumor subsets.

Identifying the uncommon solitary fibrous tumour in a rare location - A case report.

Introduction and importanceThe authors describe a case work up of an unusual natal cleft soft tissue tumour which eventually was concluded as solitary fibrous tumour. Solitary fibrous tumour is an uncommon fibroblastic tumour which commonly presents in pleural region and very rarely in extrapleural location such as natal cleft. Accurate identification of this tumour, considering the indeterminate nature of the tumour irrespective of the location, avoided misdiagnosis and played a vital role in follow up management of the patient.Case presentation43 year old female patient presented with a painless lump in the natal cleft region for a short duration of 7 months with no other significant medical or surgical or family or psychosocial history. She was not on any regular medications.Clinical discussionDue to unusual location of the tumour broad range of differential diagnosis including benign and malignant entities were discussed based on histological findings and immunophenotyping. Mammary type myofibroblastoma, glomus tumour, clear cell renal cell carcinoma and clear cell sarcoma of soft tissue were few to note. STAT6 immunohistochemical stain played a crucial role in unravelling this case. Due to gradual increase in size of the lump complete surgical excision was performed with no local recurrence of the tumour.ConclusionIt is important to recognise this rare mesenchymal tumour with intermediate malignant potential occurring at uncommon natal cleft region for which complete surgical enucleation is curative.

Clinical presentation and imaging characteristics of clear cell sarcoma-like tumour of the gastrointestinal tract with liver metastasis: a case description.

The clear cell sarcoma-like tumor of the gastrointestinal tract (CCSLTGT) is an unusual malignant soft tissue tumor in the gastrointestinal tract. Although initially identified as a type of clear cell sarcoma (CCS) (1), further studies revealed it to be a new entity that resembles but is different from CCS (2). Only 96 cases have been reported worldwide (3), mostly occurring in the small intestine. Only 13 cases have been reported in the stomach (2-7). However, few studies have been conducted to evaluate the imaging characteristics of CCSLTGT. We report an extremely rare case of CCSLTGT of the stomach with liver metastasis in a middle-aged woman.

An Unusual Soft Tissue Tumor of Uncertain Differentiation: a Case Report.

An Unusual Soft Tissue Tumor of Uncertain Differentiation: a Case Report.

Giant Cell Tumor of Soft Tissue: A Rare Entity.

Giant cell tumor (GCT) of the soft tissue (GCT-ST) is a rare, unusual primary soft tissue tumor that is completely distinct from, and should not be confused with, any giant cell-rich tumor of bone or soft tissue. Currently, GCT-ST is included in the group of so-called fibrohistiocytic tumors of intermediate (borderline) malignancy. The most common symptom is a painless, slow-growing mass in a superficial location. Computed tomography and magnetic resonance imaging show a solid, nonhomogeneous, frequently hemorrhagic mass. Differential diagnosis is broad and should include benign and malignant entities. The treatment and excision margins of GCT-ST are controversial. Incomplete surgical excision is usually followed by local recurrence. Biological behavior is unpredictable. Giant cell tumor of the soft tissue has shown a lower mean local recurrence rate compared to GCT of bone but has a higher metastatic and death rate. Therefore, close clinical follow-up is recommended. [Orthopedics. 2019; 42(4):e364-e369.].

Prediction of local and metastatic recurrence in solitary fibrous tumor: construction of a risk calculator in a multicenter cohort from the French Sarcoma Group (FSG) database

Solitary fibrous tumors (SFT) are rare unusual ubiquitous soft tissue tumors that are presumed to be of fibroblastic differentiation. At present, the challenge is to establish accurate prognostic factors. A total of 214 consecutive patients with SFT diagnosed in 24 participating cancer centers were entered into the European database (www.conticabase.org) to perform univariate and multivariate analysis for overall survival (OS), local recurrence incidence (LRI) and metastatic recurrence incidence (MRI) by taking competing risks into account. A prognostic model was constructed for LRI and MRI. Internal and external validations of the prognostic models were carried out. An individual risk calculator was carried out to quantify the risk of both local and metastatic recurrence. We restricted our analysis to 162 patients with local disease. Twenty patients (12.3%) were deceased at the time of analysis and the median OS was not reached. The LRI rates at 10 and 20 years were 19.2% and 38.6%, respectively. The MRI rates at 10 and 20 years were 31.4% and 49.8%, respectively. Multivariate analysis retained age and mitotic count tended to significance for predicting OS. The factors influencing LRI were viscera localization, radiotherapy and age. Mitotic count, tumor localization other than limb and age had independent values for MRI. Three prognostic groups for OS were defined based on the number of unfavorable prognostic factors and calculations were carried out to predict the risk of local and metastatic recurrence for individual patients. LRI and MRI rates increased between 10 and 20 years so relapses were delayed, suggesting that long-term monitoring is useful. This study also shows that different prognostic SFT sub-groups could benefit from different therapeutic strategies and that use of a survival calculator could become standard practice in SFTs to individualize treatment based on the clinical situation.

Angiomatoid fibrous histiocytoma: Clinicopathological spectrum of five cases, including EWSR1-CREB1 positive result in a single case.

Angiomatoid fibrous histiocytoma (AFH) is an unusual soft tissue tumor (STT), characterized by recurrences, but rarely metastasis. Later, certain molecular signatures have been identified underlying this tumor, which at times, is either underdiagnosed as a benign vascular tumor, or over diagnosed as a high-grade pleomorphic sarcoma, including a malignant fibrous histiocytoma. Over a 14-year-period, five diagnosed cases of AFH were analyzed. Five tumors occurred in three males and two females, over a wide age-range (median = 21, mean = 30 years); mostly in the extremities (4) (80%). Microscopically, most tumors were circumscribed, comprising large, blood-filed spaces with surrounding histiocytic cells and a "cuff" of lymphoplasmacytic cells. Three tumors revealed solid growth pattern with polygonal to spindle cells, including myxoid matrix in one of these tumors. On molecular analysis, this tumor exhibited EWS-CREB transcript. Immunohistochemically, various tumors were positive for CD68 (n = 2/2), epithelial membrane antigen (n = 3/4), CD99/MIC2 (n = 2/3), and desmin (n = 1/4). All tumors were surgically excised. On follow-up (n = 2), a single patient, who underwent wide-excision was free-of-disease (24 months), while another patient had a recurrence 4 months post tumor excision. This forms as the first documented series on clinicopathological features of AFH, a rare STT, from our country. Significant clinicopathological features include younger age, extremities as commonest site and histopathological appearance of blood-filled spaces with surrounding "cuff" of histiocytic cells and lymphocytes. Tumors with unusual histopathological tumor patterns require molecular confirmation. Surgical resection remains the treatment mainstay.

Infiltrating hybrid mesenchymal tumor of skeletal muscle showing lipomatous, hemangiomatous, leiomyomatous and osseous features – An unusual soft tissue tumor providing insight into the pathogenesis of lipoma variants

Infiltrating angiolipoma and osteolipoma of the hand are rare. A 40-year-old man presented with slowly enlarging swelling of his right hand for two and half years without functional deficit but it became painful with slight limitation of movement for the past few months. Plain radiograph showed a large soft tissue swelling with specks of calcifications. Ultrasonography and magnetic resonance imaging revealed an infiltrative mass in the right palm deep to the flexor tendons. As biopsy suggested infiltrative angiolipoma of skeletal muscle, debulking of the tumor was performed. The tumor showed coexistence of all four mesenchymal elements, fat, blood vessel, smooth muscle and bone in various combinations in the form of angiolipomatous, osteolipomatous, ossified intramuscular hemangiomatous, myolipomatous and angiomyolipomatous patterns throughout the entire tumor. Small meningothelial-like whorls of spindle cells were focally seen, some showed intramembranous ossification forming small woven bony spicules in their centers. There were no atypical cells or lipoblasts. Staining for CDK4, MDM2, p16, HMB45 and Melan A was negative. The diagnosis was “infiltrating hybrid mesenchymal tumor of skeletal muscle showing lipomatous, hemangiomatous, leiomyomatous and osseous features”. The fairly even admixture of the various components supports the neoplastic participation of each individual element. Hybrid mesenchymal tumor most probably originates from multipotent neoplastic cells showing multidirectional differentiation.

Unusual soft tissue tumors

In this session, the detailed clinicopathological and genetic findings, and the differential diagnosis of the following five unusual soft tissue tumors will be demonstrated. 1) Inflammatory myofibroblastic tumor occurs in abdominal soft tissue, GI tract, and lung of children and young adult. The prediction of biological behavior is difficult. Cytogenetic study demonstrates ALK rearrangement in more than half cases. 2) Pseudomyogenic hemangioendothelioma is rarely metastasizing endothelial neoplasm. It was initially named as epithelioid sarcoma-like hemangioendothelioma and mimicking myoid tumor or epithelioid sarcoma. FLI1 and ERG are useful markers for this tumor. 3) Myoepithelioma predominantly involve lower or upper limb of young to middle aged adult. This intermediate tumor have broad spectrum of biological behavior, according to cytological atypia. 45% of the tumor shows EWSR1 rearrangement. 4) Malignant rhabdoid tumor is very aggressive tumor and it arises in the deep axial location, such as neck and paravertebral region of infants and children. Tumor cells show the loss of SMARCB1/INI1 protein expression and its gene alterations. 5) PEComa predominantly affects retroperitoneum, uterus and GI tract of female. Definitive criteria of malignant PEComa has not been established yet. The tumor with malignant histology shows aggressive biological behavior.

Neurothekeomas of the thoracic and lumbar area in an adult man: A case report

Neurothekeomas are unusual benign soft tissue tumors of the peripheral nervous system, which commonly occur on the head, neck and upper extremities of young females in the second and third decades of life. This is the first case report of neurothekeoma developing simultaneously in the thoracic and lumbar area in a 51-year-old male. The two tumors were completely excised along the capsule under local anaesthesia and the incisions were closed in layers following adequate hemostasis. Histopathologically, the examination of the microscopic slides from the thoracic and lumbar masses revealed the presence of spindle and similar epithelioid cells arranged in fascicles, often in a geographical pattern, in a background of myxoid stroma. The immunohistochemical analysis demonstrated that the tumor cells were positive for vimentin, CD57 and actin and negative for S-100 protein, HMB-45 and CD34. The tumors were diagnosed as neurothekeomas. The patient remains alive and well on follow-up at 7 years, without evidence of recurrence.

Mediastinal hibernoma presenting with hoarseness

Hibernoma is an unusual benign soft tissue tumor derived from a specialized form of brown fat. A case of a 52-year-old female who was admitted with a slowly worsening hoarseness is presented. Further investigation revealed a left upper mediastinal mass next to the aortic arch. Upon surgical exploration a soft encapsulated mass was identified. Pathology was consistent with hibernoma. Despite their benign behavior, some variants of hibernoma can be confused histologically with liposarcoma. Therefore, long-term follow-up is advisable.

Abdominal wall desmoid tumors associated with pregnancy: current concepts

The desmoid tumors (DTs) are unusual soft-tissue tumors that have a propensity for aggressive local growth and may develop during, or soon after pregnancy. Pregnancy-associated DTs are uncommon and optimal management of this tumor has yet to be defined. Currently, controversy centers on the timing of surgical resection and is influenced by the potential for tumor growth and the effects of a gravid uterus. A review of current literature in which DTs were managed either during pregnancy or in the postpartum period, was carried out. Surgical resection of these tumors has been performed successfully both during and soon after delivery, and the role of postpartum radiotherapy, chemotherapy and other medical intervention remains controversial. Management of DTs diagnosed during pregnancy is complex and treatment must be individualized.

Neoadjuvant Imatinib Therapy for Dermatofibrosarcoma Protuberans

Dermatofibrosarcoma protuberans (DFSP) is an unusual soft-tissue tumor with a propensity for subclinical extension and local recurrence. Surgical excision, even with tissue-sparing techniques, may cause significant deformity or disability because of the infiltrative nature of DFSP. In this study, we evaluate retrospective data obtained from 4 patients with locally advanced or recurrent DFSP who received neoadjuvant imatinib mesylate therapy before undergoing Mohs micrographic surgery. Patients treated with neoadjuvant imatinib therapy had an average tumor size reduction of 36.9%. This clinical response was paralleled by histopathologic changes, including decreased cellularity in 100% of the total area as well as significant hyalinization. Imatinib therapy for DFSP before Mohs micrographic surgery was associated with 100% local control at a maximum follow-up of 4 years. Neoadjuvant imatinib therapy is a well-tolerated, novel approach to DFSP that reduces tumor burden and facilitates resection. Larger prospective studies are needed to confirm and expand on these results.

Angiomatoid fibrous histiocytoma with cystic structures of sweat duct origin

Angiomatoid fibrous histiocytoma is an unusual soft tissue tumor, mostly arising in the subcutaneous fibro-adipose tissue of children and young adults and measuring a few centimeters in greatest dimension. Reported herein is a unique case of angiomatoid fibrous histiocytoma containing epithelium-lined cystic structures. This large tumor (12 cm) was located in the subcutaneous tissue of the left leg of a 28-year-old woman. The cystic structures were variably sized and were lined by a double cell layer with areas of squamous metaplasia. Their overall histological features suggested a sweat duct origin. Immunohistochemical stains confirmed such origin, demonstrating an inner epithelial and an outer myoepithelial (smooth muscle actin and cytokeratin 17 positive) cell layer. The present case is illustrative of a mechanism of sweat duct dilatation that may occur during the growth of neoplasms involving the dermis and subcutis, resulting in formation of tumors with unusual histological features.

Giant Cell Fibroblastoma of the Vulva at the Site of a Previous Fibroepithelial Stromal Polyp

Giant cell fibroblastoma (GCF) is an unusual soft tissue tumor, occurring predominantly in infants and children, and rarely in adults. Giant cell fibroblastoma develops de novo in the dermis or subcutis with a predilection for the extremities, the abdominal and chest walls, umbilical and inguinal regions. A GCF arose at the same site (labium majus of vulva) as a previous cellular fibroepithelial stromal polyp in a 28-year-old woman. We report a case of GCF of the vulva, an unreported site.

Intramuscular Myxomas: A Clinicopathologic Study with Emphasis on Surgical Management

Intramuscular myxomas (IMs) are rare myxoid tumors named for their abundance of noncollagenous mucinous stroma. IMs are benign tumors characterized by a paucity of cells, diminished vascularity, and minimal mitotic figures. The objectives of this study were to examine clinicopathologic features of IM and to discuss clinical management of these unusual soft tissue tumors. A 10-year retrospective study at Orlando Regional Medical Center was conducted from May 1993 to May 2003. A case report of a 48-year-old male with a right gluteal mass is presented. Four cases with histologically confirmed diagnosis of intramuscular myxoma were reported. Three patients presented with lesions of the lower extremity and one with an extrafascial IM of the eighth rib. One of the lower extremity cases was shown to be cellular myxoma, a recently characterized subtype of IM. All cases were treated with at least marginal excision of the mass. There have been no known recurrences. Our findings are consistent with described characteristics for IM with respect to anatomic location and gross and microscopic appearance. As it may be unreliable to differentiate IM from malignant myxoid tumors preoperatively, we favor excision with wide margins in the surgical management of these tumors.

Mixed Tumors, Myoepitheliomas, and Oncocytomas of the Soft Tissues Are Likely Members of the Same Family: A Clinicopathologic and Ultrastructural Study

Four diagnostically unusual soft tissue tumors are presented. All lesions were of consistent size and long duration. Histologically, one lesion was analogous to mixed tumors of the usual sites (i.e., salivary glands), one lesion was totally spindled, and the two other lesions both had oncocytic appearances ( epithelioid and spindle biphasic pattern in a case, purely epithelioid in the other). Immunohistochemically, the mixed tumor was positive for vimentin, cytokeratins, S-100 protein, and focally for EMA. The purely spindled tumor exhibited immunoreactivity for vimentin, actins, S-100 protein, EMA (focally), and GFAP. The oncocytic biphasic tumor was positive for mitochondrial antigen, vimentin, and actins. The purely epithelioid oncocytic neoplasm was immunoreactive only for mitochondrial antigen and vimentin. Ultrastructurally, in the epithelial-like portion of the first (mixed) tumor, peripheral arrays of contractile filaments were detected along with well-developed desmosomes. In the second (spindled) case, peripheral contractile filaments and attenuated desmosomes were also seen. In the third case, a huge number of mitochondria, some desmosomes, and actin-type microfilaments were found. In the fourth case, desmosomes and punctate subplasmalemmal densities, in addition to numerous mitochondria, were documented. In all cases an external basal lamina were present, which was discontinuous in the first three cases and almost continuous in the fourth. These tumors were respectively designated as mixed tumor, myoepithelioma of the classic type, myoepithelioma of oncocytic type with biphasic cell architecture, and true oncocytoma. So far, all tumors have followed benign clinical courses (median follow up: 12 months). Comparisons with similar tumors of other sites are drawn, and suggestions for considering all of them as members of the same myoepithelial-derived tumor family are given.

An unusual soft tissue tumour and peripheral eosinophilia.

An unusual soft tissue tumour and peripheral eosinophilia.

Unusual Soft Tissue Tumor with Features of Angiomatoid Malignant Fibrous Histiocytoma Composed of Bimodal CD34 and Factor XIIIa Positive Dendritic Cell Subsets: CD34 and Factor XIIIa in Angiomatoid MfH

CD34 and factor XIIIa (FXIIIa) antibodies delineate subsets of embryonic dendritic stromal stem cells that persist in adult mesenchyme. CD34 stains interstitial and adventitial dendritic cells that may function as multipotential precursor cells. FXIIIa+ dendrophages are tissue histiocytes active in tissue repair. Angiomatoid malignant fibrous histiocytoma (AMFH) is an enigmatic fibrohistiocytic tumor with limited vascular features. We examined an unusual soft tissue tumor from the nasolabial subcutis of a 57 year old man that showed histologic features of AMFH. Most of the tumor cells expressed CD34. 10-30% of the tumor cells were FXIIIa+ dendrophages. Sinusoidal areas were largely composed of FXIIIa+ cells that also expressed HLA-DR and CD68 suggesting macrophage differentiation. CD31 and Factor VIII antigen highlighted capillaries and single cells among the CD34+ tumor cells. The vessels had actin+ myopericytes and there were single actin+ tumor cells. Electron microscopy showed primitive dendritic cells and fewer histiocyte-like cells. The Ki 67 index was 15% including both FXIIIa+ and CD34+ cells. The patient is disease free three years after wide excision. We conclude that this AMFH-like neoplasm is a fibrohistiocytic tumor in which CD34+ fibroblast-like precursors and FXIIIa+ tissue dendrophages combine to build both sinusoidal tissue with endothelial and macrophage elements as well as capillary vascular tissue that is invested with myopericytes. Study of additional AMFH lesions from this standpoint is desirable.