Clinicopathologic and molecular study of superficial CD34-positive fibroblastic tumours mimicking atypical fibrous histiocytoma (dermatofibroma).

AIMS: Superficial CD34-positive fibroblastic tumour (SCD34FT) is an uncommon but distinctive low-grade neoplasm of the skin and subcutis that shows frequent CADM3 expression by immunohistochemistry (IHC). In this study, prompted by an index case resembling 'atypical fibrous histiocytoma (FH)' that was positive for CADM3 IHC, we systematically examined a cohort of tumours previously diagnosed as 'atypical FH' by applying CADM3 and fluorescence in situ hybridization (FISH) for PRDM10 rearrangement, to investigate the overlap between these tumour types. METHODS AND RESULTS: Forty cases of atypical FH were retrieved, including CD34-positive tumours (n = 20) and CD34-negative tumours (n = 20). All tumours were stained for CADM3. All CADM3-positive tumours were evaluated by FISH to assess for PRDM10 rearrangement. Eleven CD34-positive tumours (11/20, 55%) coexpressed CADM3 and were reclassified as SCD34FT. None (0/20) of the CD34-negative atypical FH were CADM3-positive. Reclassified SCD34FT (10/11) arose on the lower extremity, with frequent involvement of the thigh (n = 8). Features suggestive of atypical FH were observed in many reclassified cases including variable cellularity, spindled morphology, infiltrative tumour margins, collagen entrapment, epidermal hyperpigmentation, and acanthosis. Variably prominent multinucleate giant cells, including Touton-like forms, were also present. An informative FISH result was obtained in 10/11 reclassified tumours, with 60% (6/10) demonstrating PRDM10 rearrangement. CONCLUSION: A significant subset of tumours that histologically resemble atypical FH, and are positive for CD34, coexpress CADM3 and harbour PRDM10 rearrangement, supporting their reclassification as SCD34FT. Awareness of this morphologic overlap and the application of CADM3 IHC can aid the distinction between SCD34FT and atypical FH.

Recurrent and metastatic cellular cutaneous fibrous histiocytoma: A case report and literature review.

Cutaneous fibrous histiocytoma (FH) is considered a benign dermal tumor. The cellular variant is rare and poorly documented. Besides presenting a high risk of local recurrence, it has a low but serious metastatic potential. We present a case of metastatic cellular FH and also review the literature on this tumor, given its unusual metastatic development. A 47-year-old male patient presented with a lesion in the anterior surface of the right thigh, which has been present since adolescence but had grown during last year. Anatomopathological evaluation revealed a cellular FH, and the lesion was completely removed. Six months later, tumor recurrence with multiple compartment muscle involvement and pulmonary metastasis were detected. Both lesions were completely resected and after 3 years of follow-up, the patient is asymptomatic and free of the disease. We conclude that FH should be carefully sampled to detect variants with high local recurrence rates or with some metastatic risk such as the cellular one. We recommend wide surgical resection and a close follow-up including chest x-rays or thorax computed tomography (CT) in all cellular FH cases with local recurrence.

Recurrent benign fibrous histiocytoma of the bone benefits from denosumab followed by malignant transformation: a case report.

Benign fibrous histiocytoma of the bone (BFHB) is a rare mesenchymal tumor, representing less than 1% of all benign bone tumors. This controversial entity is characterized by a mixture of fibroblasts arranged in a storiform pattern, varying amounts of osteoclast-type giant cells and foamy macrophages. Curettage or simple resection is usually curative. However, it was reported that up to 11% of the patients suffer from relapse. Here, we report a case of malignant transformation of BFHB after long-lasting disease stabilization under denosumab therapy.

Clinical and pathological analyses of 14 cases of angiomatoid fibrous histiocytoma.

Angiomatoid fibrous histiocytoma (AFH) is a soft tissue tumor of uncertain differentiation. Although its prognosis is good, its diagnosis and differential diagnosis remain a challenge, particularly for tumors with an atypical morphology. We evaluated the clinicopathological characteristics of 14 AFH cases and examined the key factors in its diagnosis or differential diagnosis. The cohort comprised 6 men and 8 women aged 9-65 years (average age: 31.2 years). Most of the tumors (11/14, 79%) were located in soft tissues, whereas 3/14 (21%) were located in the lung (1 case) and brain (2 cases). Tumor cells were spindle-shaped to epithelioid, with a visible fibrous capsule (9/14, 64%), hemorrhagic gap (9/14, 64%), lymphocyte sleeve (7/14, 50%), necrosis (3/14, 21%), and infiltrative boundary (4/14, 29%). The tumors expressed desmin (10/14, 71%) and exhibited low levels of Ki-67. 13 cases (93%) displayed ESWSR1 gene rearrangement. At follow-up, 1 case (7%) experienced local tumor recurrence. AFH is a rare intermediate tumor. Its pathological diagnosis requires a comprehensive analysis of histological, immunophenotypic, and molecular genetic features to avoid misdiagnosis. Our study has further enriched the histological features of AFH, emphasizing the importance of differential diagnosis and providing a reference for clinical practice.

Systemic inflammation caused by an intracranial mesenchymal tumor with a EWSR1::CREM fusion presenting associated with IL-6/STAT3 signaling.

Pediatric neoplastic diseases account for about 10% of cases of fever of unknown origin (FUO), and most neoplastic disease cases are leukemia, lymphoma, and neuroblastoma. Brain tumors are rarely reported as the cause of FUO, although craniopharyngioma, metastatic brain tumor, and Castleman's disease have been reported. We report a case of intracranial mesenchymal tumor (IMT) with a FET:CREB fusion gene, which had inflammatory phenotype without neurological signs. A 10-year-old girl was admitted with a 2-month history of intermittent fever and headache, whereas her past history as well as her family history lacked special events. Sepsis work-up showed no pathological organism, and empirical antibiotic therapy was not effective. Bone marrow examination showed a negative result. Cerebrospinal fluid examination showed elevated protein as well as cell counts, and head magnaetic resonance imaging showed a hypervascular mass lesion with contrast enhancement in the left cerebellar hemisphere. The patient underwent tumor excision, which made the intermittent fever disappear. Pathological examinations resembled those of classic angiomatoid fibrous histiocytoma (AFH), but the morphological features were distinct from the AFH myxoid variant; then we performed break-apart fluorescence in situ hybridization and confirmed the tumor harbored the rare EWSR1::CREM fusion gene (Ewing sarcoma breakpoint region 1 gene (EWSR1) and cAMP response element binding (CREB) family gene). Consequently, we diagnosed the condition as IMT with EWSR1::CREM fusion. Elevated serum concentration of interleukin 6 (IL-6) was normalized after tumor resection, which suggested the fever could be caused by tumor-derived IL-6. This is the first case of IMT with EWSR1::CREM fusion that showed paraneoplastic symptoms associated with the IL-6/signal transducer and activator of transcription 3 (STAT3) signaling pathway. Although brain tumors are rarely diagnosed as a responsible disease for FUO, they should be considered as a cause of unknown fever even in the absence of abnormal neurological findings.

Gene fusions in superficial mesenchymal neoplasms: Emerging entities and useful diagnostic adjuncts.

Cutaneous mesenchymal neoplasms are diagnostically challenging because of their overlapping morphology, and, often, the limited tissue in skin biopsy specimens. Molecular and cytogenetic techniques have identified characteristic gene fusions in many of these tumor types, findings that have expanded our understanding of disease pathogenesis and motivated development of useful ancillary diagnostic tools. Here, we provide an update of new findings in tumor types that can occur in the skin and superficial subcutis, including dermatofibrosarcoma protuberans, benign fibrous histiocytoma, epithelioid fibrous histiocytoma, angiomatoid fibrous histiocytoma, glomus tumor, myopericytoma/myofibroma, non-neural granular cell tumor, CIC-rearranged sarcoma, hybrid schwannoma/perineurioma, and clear cell sarcoma. We also discuss recently described and emerging tumor types that can occur in superficial locations and that harbor gene fusions, including nested glomoid neoplasm with GLI1 alterations, clear cell tumor with melanocytic differentiation and ACTIN::MITF translocation, melanocytic tumor with CRTC1::TRIM11 fusion, EWSR1::SMAD3-rearranged fibroblastic tumor, PLAG1-rearranged fibroblastic tumor, and superficial ALK-rearranged myxoid spindle cell neoplasm. When possible, we discuss how fusion events mediate the pathogenesis of these tumor types, and we also discuss the related diagnostic and therapeutic implications of these events.

Meningioma and Other Meningeal Tumors.

Meningiomas develop from meningothelial cells and approximately account for more than 30 percent of central nervous system (CNS) tumors. They can occur anywhere in the dura, most often intracranially and at dural reflection sites. Half of the cases are usually at parasagittal/falcine and convexity locations; other common sites are sphenoid ridge, suprasellar, posterior fossa, and olfactory groove. The female-to-male ratio is approximately 2 or 3-1, and the median age at diagnosis is 65 years. Meningiomas are generally extremely slow-growing tumors; many are asymptomatic or paucisymptomatic at diagnosis and are discovered incidentally. Clinical manifestations, when present, are influenced by the tumor site and by the time course over which it develops. Meningiomas are divided into three grades. Grade I represents the vast majority of cases; they are considered typical or benign, although their CNS location can still lead to severe morbidity or mortality, resulting in a reported ten-year net survival of over 80%. Atypical (WHO grade II) meningiomas are considered "intermediate grade" malignancies and represent 5-7% of cases. They show a tendency for recurrence and malignant degeneration with a relevant increase in tumor cell migration and surrounding tissue infiltration; ten-year net survival is reported over 60%. The anaplastic subtype (WHO III) represents only 1-3% of cases, and it is characterized by a poor prognosis (ten-year net survival of 15%). The treatment of choice for these tumors stands on complete microsurgical resection in case the subsequent morbidities are assumed minimal. On the other hand, and in case the tumor is located in critical regions such as the skull base, or the patient may have accompanied comorbidities, or it is aimed to avoid intensive treatment, some other approaches, including stereotactic radiosurgery and radiotherapy, were recommended as safe and effective choices to be considered as a primary treatment option or complementary to surgery. Adjuvant radiosurgery/radiotherapy should be considered in the case of atypical and anaplastic histology, especially when a residual tumor is identifiable in postoperative imaging. A "watchful waiting" strategy appears reasonable for extremely old individuals and those with substantial comorbidities or low-performance status, while there is a reduced threshold for therapeutic intervention for relatively healthy younger individuals due to the expectation that tumor progression will inevitably necessitate proactive treatment. To treat and manage meningioma efficiently, the assessments of both neurosurgeons and radiation oncologists are essential. The possibility of other rarer tumors, including hemangiopericytomas, solitary fibrous tumors, lymphomas, metastases, melanocytic tumors, and fibrous histiocytoma, must be considered when a meningeal lesion is diagnosed, especially because the ideal diagnostic and therapeutic approaches might differ significantly in every tumor type.

Angiomatoid fibrous histiocytoma in the spinal canal of T3-T4: a case report and literature review.

Angiomatoid fibrous histiocytoma (AFH) is a rare soft tissue tumour that occurs in the superficial tissue of extremities of children and young adults. A painless mass in the deep dermis and subcutaneous tissue is the main clinical manifestation. AFH also occurs infrequently in the central nervous system and is relatively common in the cranium. However, spinal canal AFH has not been described yet. We report a rare case of AFH in the cervical canal of a 20-year-old male patient. Microsurgical gross total resection of the tumour was performed, and the diagnosis was confirmed by postoperative pathology. To our knowledge, this is the first case of AFH in the spinal canal.

Molecular investigation of ALK-rearranged epithelioid fibrous histiocytomas identifies CLTC as a novel fusion partner and evidence of fusion-independent transcription activation.

Epithelioid fibrous histiocytoma (EFH) is a rare cutaneous neoplasm, which is characterized by the presence of rearrangements involving the ALK gene. Although EFH was long considered a variant of fibrous histiocytoma, the identification of its unique genetic signature confirmed that it represents a distinct entity. The aim of the present study was to examine a cohort of ALK-immunoreactive EFH cases to further characterize gene fusion partners. Next generation sequencing detected ALK fusions in 11 EFH cases identified in the pathology archives of two different institutions. The most common fusion partner was DCTN1 (N = 4) followed by CLTC (N = 2) and VCL (N = 2), while the remaining cases harbored fusions involving SPECC1L, PPFIBP1, and PRKAR1A. In one case no fusion was detected by NGS and FISH despite suitable sample quality. Notably, IHC demonstrated positive ALK expression and the level of aligned ALK reads was comparable to the fusion-positive cases. To the best of our knowledge, this is the first report of CLTC as a fusion partner in EFH. The two CLTC rearranged cases in our cohort also represent the first two EFH cases in the literature that involve exon 19 of ALK, instead of exon 20. These findings underscore the remarkable plasticity of ALK as an oncogenic driver and further expand the list of its potential fusion partners in EFH. Lastly this is also the first report of ALK-immunoreactive EFH with no underlying fusion suggesting a fusion independent transcription mechanism as seen in other tumors.

Recent advances in the diagnosis, classification and molecular pathogenesis of cutaneous mesenchymal neoplasms.

The diagnosis of cutaneous mesenchymal neoplasms remains challenging, due to a combination of overlapping histological features, the rarity of some diagnoses and often inadequate sampling in superficial biopsies. Here, we describe recent advances in cutaneous mesenchymal neoplasms. We discuss improvements in our understanding of the molecular pathogenesis of non-neural granular cell tumour, epithelioid fibrous histiocytoma, composite and retiform haemangioendothelioma and dermatofibrosarcoma protuberans. We also discuss recently described tumour types, including some discovered via molecular testing: EWSR1::SMAD3-rearranged fibroblastic tumour, clear cell neoplasm with MITF::CREM rearrangement and melanocytoma with CRCT1::TRIM11 rearrangement, and some discovered via traditional histopathology: superficial CD34-positive fibroblastic tumour, plexiform myofibroblastoma and clear cell neoplasm with melanocytic differentiation and ACTIN::MITF translocation.

Undifferentiated high-grade pleomorphic sarcoma of the colon: a rare case report and literature review.

BACKGROUND: Undifferentiated pleomorphic sarcoma (UPS), also known as malignant fibrous histiocytoma (MFH), hardly originates from the colorectum. CASE PRESENTATION: We reported a 65-year-old female presented with UPS in the descending colon. Computed tomography (CT) revealed an irregularly thickened descending colon. On colonoscopy examination, an ulcerative tumour was identified. The patient received radical resection of the left colon and partial enterectomy. The resected tumor was ulcerative, 10 cm × 8 cm × 5 cm in size, and infiltrated the serosa layer. Postsurgical pathology showed that the tumor was high-graded UPS in the colon with large amounts of necrotic tissues. CONCLUSIONS: UPS in the large intestine is a rare malignant tumor with a poor prognosis and unknown pathogenesis. The main treatment for UPS is early complete resection. Postsurgery adjuvant radiotherapy or chemotherapy can be attempted.

Brain parenchymal angiomatoid fibrous histiocytoma and spinal myxoid mesenchymal tumor with FET: CREB fusion, a spectrum of the same tumor type.

Angiomatoid fibrous histiocytomas (AFH) is a rare soft tissue tumor of intermediate malignant potential, and its histology is diverse. It can occur in several organs including intracranial and soft tissues. Here, we report two cases of brain parenchymal classic AFH and spinal extramedullary myxoid mesenchymal tumor with clinicopathological and molecular investigations by next-generation sequencing and a comprehensive review. The current brain parenchymal AFH occurred in a 79-year-old woman, and the spinal myxoid mesenchymal tumor arose in the thoracic spine of a 28-year-old woman; both harbored FET:CREB fusion. The current brain parenchymal AFH has not recurred for 15-months follow-up period, but the spinal myxoid mesenchymal tumor recurred three times and metastasized to T8 spine level for 30-months follow-up period. We reviewed 40 reported cases of central nervous system (CNS) AFHs/myxoid mesenchymal tumors including our two cases to identify clinicopathological features and biological behaviors. They occur with a slight female predominance (M:F = 1:1.7) in children and young adults (median age: 17 years; range: 4-79 years old). Approximately 80% of CNS AFHs were younger than 30 year. Most of them were dura-based and were not just intracranial tumors as they occurred anywhere in the CNS including spinal dura. EWSR1 rearrangement was the most common driver (98%), including FET:CREB (33%), EWSR1:ATF1 (30%), and EWSR1:CREM (27%) fusions, but FUS:CREM fusion (2%) was also present. During the follow-up period (median: 27 months), 43% (17/40) of CNS AFHs recurred between two months and 11 years, and multiple recurrences were also observed. One case showed metastases to the lymph nodes and vertebrae, and among 11 cases that resulted in death, four cases provided available clinical data. Because these tumors are identical to soft tissue AFH or primary pulmonary myxoid sarcoma with an FET:CREB fusion in morphological and immunohistochemical spectra, the authors propose incorporating the two tumor terms into one.

Surgical management of primary undifferentiated pleomorphic sarcoma of the rectum: a case report and review of the literature.

BACKGROUND: Undifferentiated pleomorphic sarcoma (UPS) is a malignant soft tissue tumor that has been reclassified from malignant fibrous histiocytoma with the development of the pathological diagnosis. It principally occurs in the extremities but rarely occurs in the rectum. We herein report a rare case of UPS arising in the rectum. CASE PRESENTATION: A 85-year-old woman was referred to our hospital with a complaint of anal pain, which had persisted for several months. Computed tomography (CT) showed a 53 × 58 × 75 mm mass on the left side of the rectum. Colonoscopy revealed a submucosal elevation in the rectum without any exposure of the tumor to the surface. Contrast-enhanced CT and magnetic resonance imaging revealed an 80-mm mass that originated in the rectal muscular propria, and we suspected a gastrointestinal stromal tumor. No lymph node metastasis or distant metastasis was observed. We performed a laparoscopic Hartmann's operation. Intraoperatively, severe adhesion around the tumor caused tumor injury and right ureteral dissection. Thus, laparoscopic right ureteral anastomosis and ureteral stenting were additionally performed. The operation time was 6 h and 3 min, and the estimated blood loss was small. The patient was discharged without complications 25 days after surgery. A pathological examination showed that the tumor was composed of highly heterogeneous cells with no specific differentiation traits, leading to a diagnosis of UPS. Contrast-enhanced CT performed 2 months after surgery showed bilateral pelvic lymph node enlargement, which indicated recurrence. Considering the patient's age, we performed radiotherapy (50 Gy/25 Fr targeting the pelvic region). At present, 16 months have passed since the completion of radiotherapy. Contrast-enhanced CT shows that the recurrent lymph nodes have disappeared, and no new distant metastasis has been observed. CONCLUSIONS: We reported a case of UPS arising in the rectum. The surgical procedure and indication of preoperative therapy should be carefully selected because complete removal of the tumor is desirable in UPS.

A case of pseudomyogenic hemangioendothelioma misdiagnosed as low-grade malignant fibrous histiocytoma and review of literature. / è¯¯è¯Šä¸ºä½Žåº¦æ¶æ€§çº¤ç»´ç»„ç»‡ç»†èƒžç˜¤çš„å‡è‚Œæºæ€§è¡€ç®¡å† çš®ç˜¤1ä¾‹å¹¶æ–‡çŒ®å¤ä¹ .

Pseudomyogenic hemangioendothelioma (PHE) is a rare angiogenic tumor. Histologically, the morphological characteristics of neoplastic vessels and endothelial differentiation are not obvious, and it is easy to be confused with epithelioid sarcoma, epithelioid hemangioendothelioma and myogenic tumor. PHE usually occurs in arms and legs in young people and has a significant male predominance. The tumor has a predilection for the distal extremities and its typical manifestation is multiple center invasion of a single limb, which can involve all layers of skin and subcutaneous tissues,and is often accompanied by abvious pain. Histologically, PHE is characterized by infiltrative growth of tumor. Most tumor lesions are composed of sheets and loose fascicles of plump spindle or epithelioid cells within a background of variably prominent inflammatory infiltration, which was commonly composed of neutrophils. Some cells may resemble rhabdomyoblasts, and nuclear atypia and mitosis were rare. The tumor cells generally expressed positive cytokeratin (CK), ETS-related gene (ERG), Friend leukemia virus integration 1 (FLI1) and integrase interactor 1(INI1). In some cases, the tumor cells expressed CD31. A case of a young woman was reported in this paper, who presented with a subcutaneous mass with severe pain and was chronologically misdiagnosed with herpes zoster, low-grade malignant fibrous histiocytoma and epithelioid hemangioendothelioma. In this study, the clinical and pathological features, differential diagnosis and the latest progress in therapy of PHE were analyzed based on relevant literature.

Spindle cell variant of epithelioid cell histiocytoma (spindle cell histiocytoma) with ALK gene fusions: Cases series and review of the literature.

BACKGROUND: Epithelioid fibrous histiocytoma (EFH) is an uncommon dermal neoplasm expressing anaplastic lymphoma kinase (ALK) protein. Rarely a histopathological variant of this entity exhibits exclusively spindle cells. We report three cases of EFH that do not completely fulfill phenotypic criteria featuring spindle cell morphology and expressing ALK protein. We also analyze the fusion partner genes rearranged with ALK in these cases. METHODS: ALK expression and rearrangement status were evaluated by immunohistochemistry (IHC), fluorescence in situ hybridization (FISH), and next generation sequencing based gene fusion analysis. RESULTS: Three cases, all from females between 25 and 55 years old, have been biopsied from back, left arm, and thumb. All three cases showed tumor with exclusively spindle cell morphology without any epithelioid cells. The tumor cells exhibited strong ALK expression by IHC and FISH study confirmed ALK gene rearrangement in all three cases. DCTN1-ALK fusion was identified in two cases. CONCLUSION: EFH is not always purely epithelioid and its spindled cell variant, spindle cell histiocytoma, should be included in the differential diagnosis of superficial dermal spindled cell neoplasms. ALK immunostain is a useful diagnostic marker for this entity and further studies may be useful to investigate whether DCTN1-ALK fusion mutations are specific to EFH with spindled cell features.

Cholesterotic fibrous histiocytoma: Case report and literature review.

Cholesterotic fibrous histiocytoma is a particularly rare variant of dermatofibroma that is distinguished histopathologically by the presence of prominent cholesterol deposits within the lesion. We report the case of a 54-year-old male with poorly controlled hyperlipidemia who presented with a firm violaceous papule on the right shin, diagnosed as a cholesterotic fibrous histiocytoma. We also review and summarize the existing literature on this uncommon entity.

Expression of connexin 43 by atypical fibroxanthoma.

INTRODUCTION: Connexins are transmembrane channel proteins that interconnect adjacent cells and allow the exchange of signaling molecules between cells and the extracellular milieu. They have been investigated in many tumors to obtain information about tumor nature, behavior, and prognosis. METHODS: Herein, we present a study on the immunohistochemical expression of connexin (Cx) 43 in 16 cases of atypical fibroxanthoma (AFX). For the immunohistochemical staining, a tissue array was obtained from the paraffin-embedded blocks. RESULTS: The expression was membranous and cytoplasmic in all cases. Thirteen cases (81.25%) showed strong staining. In the other three cases (18.75%), the staining was medium. None of the cases showed nuclear staining. Fifteen out of 16 cases showed a diffuse pattern, and only one case showed a focal pattern. CONCLUSIONS: Our results suggest that Cx43 may play an important role in the natural behavior of AFX.

Intracranial myxoid angiomatoid fibrous histiocytoma with "classic" histology and EWSR1:CREM fusion providing insight for reconciliation with intracranial myxoid mesenchymal tumors.

Angiomatoid fibrous histiocytoma (AFH) is an uncommon soft tissue neoplasm that can exhibit diverse morphological features, including myxoid change. Rarely, the tumor occurs intracranially and poses considerable diagnostic challenges to neuropathologists. This is compounded by a recently coined entity, referred to as intracranial myxoid mesenchymal tumor (IMMT). These tumors show significant overlaps with intracranial myxoid AFH from clinicopathological and molecular genetic viewpoints. We described an unusual intracranial tumor in a 30-year-old man. The tumor exhibited "classic" histological features of myxoid AFH and EWSR1:CREM fusion, a relatively novel variant of EWSR1:CREB family fusion, first identified in IMMT. We also performed a comprehensive literature review comparing the clinicopathological features of intracranial AFHs and IMMTs. Peritumoral lymphoplasmacytic cuffing appears to be the only morphological finding that is consistently absent in reported cases of IMMT while being present in most intracranial AFHs. Otherwise, both tumors showed considerable overlaps in clinical, histological, and immunohistochemical features and have a common molecular genetic signature of EWSR1:CREB family fusion, including EWSR1:CREM fusion. Our case appeared to be the first described EWSR1:CREM-fused intracranial tumor to show prominent peritumoral lymphoplasmacytic cuffing and myxoid change in addition to most of the other "classic" morphologic features of AFH. As such, while the current literature appears to be lacking when it comes to defining intracranial myxoid AFH and IMMT as separate nosological entities, they likely represent a morphological spectrum of a common entity characterized by EWSR1 rearrangement, akin to solitary fibrous tumors and hemangiopericytomas with the signal transducer and activator of transcription 6 gene (STAT6) rearrangement.

A case of intracranial myxoid mesenchymal tumor with EWSR1:CREM fusion in an adult female: Extensive immunohistochemical evaluation.

Intracranial myxoid mesenchymal tumor (IMMT) is a recently described, extremely rare group of neoplasms characterized by fusions between the female-expressed transcript (FET) family genes and the cAMP response element-binding protein (CREB) family genes. Controversy persists regarding whether the tumor is a myxoid variant of angiomatoid fibrous histiocytoma or a completely distinct clinicopathological entity. Here, we report a case of IMMT arising in the posterior fossa in a 65-year-old woman with a history of breast cancer. We performed total removal of the tumor, which histologically demonstrated features characteristic of IMMT but also bore a partial resemblance to conventional angiomatoid fibrous histiocytoma. Immunohistochemically, tumor cells were diffusely positive for desmin, vimentin, cluster of differentiation (CD) 99 (CD99), glucose transporter-1, and cytokeratin (CK) 8/18 (CK8/18), and focally positive for CK7, epithelial membrane antigen, mucin 4, anaplastic lymphoma kinase, calponin, and CD68. Molecular genetic analysis revealed a fusion between the Ewing sarcoma breakpoint region 1 (EWSR1) gene (EWSR1) and the cAMP-responsive element modulator (CREM) gene (CREM) called EWSR1:CREM fusion, which confirmed the diagnosis. The overlap of the pathological features of IMMTs and angiomatoid fibrous histiocytomas may support the recent theory that these tumors are two manifestations of a single entity. Moreover, our study indicated the broad spectrum of immunohistochemical phenotypes of these tumors, which should be noted during diagnosis. Further studies are needed to elucidate the histopathological concept, long-term prognosis, optimal treatment strategy, and factors associated with the prognosis and therapeutic options of this condition.

Mast Cell Tumors and Histiocytomas in Domestic Goats and Diagnostic Utility of CD117/c-Kit and Iba1 Immunohistochemistry.

Cutaneous round cell tumors in goats present a diagnostic challenge. In this article, we provide a description of caprine cutaneous mast cell tumors (MCT) and histiocytomas, and report on the validation of anti-human antibodies to CD117/KIT and Iba1 by immunohistochemistry on a range of caprine tissues. Cells immunolabeled for CD117/KIT included resident mast cells in normal lung and skin, interstitial cells of Cajal (intestine), and neuronal cell bodies (brain). Cells immunolabeled for Iba1 included resident macrophages in many tissues including normal lung, dendritic cells (hemolymphatic tissues), Kupffer cells, and microglia. Of 5 cutaneous MCT, only one had metachromasia of cytoplasmic granules; however, neoplastic cells of all 5 MCT had positive immunolabeling for CD117/KIT. The CD117/KIT immunolabeling pattern was predominately focal paranuclear in 3 cases, and cytoplasmic or membranous in 1 case each. Two histiocytomas were identified and had strong positive immunolabeling for Iba1 but not CD117/KIT. All 7 cutaneous round cell tumors described herein occurred in goats less than 4 years of age; the 2 cutaneous histiocytomas were in goats less than 14 months of age. Neither of the cutaneous histiocytomas recurred within 24 months of surgical removal.