Histiocyte-rich rhabdomyoblastic tumor: a report of two cases and a review of the differential diagnoses.

Histiocyte-rich rhabdomyoblastic tumor is a recently described skeletal muscle neoplasm of uncertain malignant potential, characterized by slow growth, a fibrous capsule containing peripheral lymphoid aggregates, spindle-to-epithelioid cells with a rhabdomyoblastic immunophenotype, and a dense histiocytic infiltrate. It most commonly arises within the muscles of the lower legs and trunk in young-to-middle-aged men, and initial reports suggest indolent behavior. In this paper, we present two additional cases of histiocyte-rich rhabdomyoblastic tumor with similar clinicopathologic features and discuss the differential diagnosis including its overlap with inflammatory leiomyosarcoma.

Detection of GNAS mutations in intramuscular / cellular myxomas as diagnostic tool in the classification of myxoid soft tissue tumors.

BACKGROUND: Intramuscular / cellular myxomas and low-grade myxofibrosarcomas are two different tumor entities with a significant histological overlap, especially if dealing with small biopsies. Despite the morphological similarities, they differ considerably in their biological behaviour. Intramuscular / cellular myxoma rarely shows signs of recurrence and never metastasizes, in contrast to myxofibrosarcoma that tends to recur more aggressively and to metastasize haematologically. Therefore, it is of great importance to distinguish these lesions - evaluation of GNAS mutation status could be of tremendous help. METHODS: We reviewed 13 cases with intramuscular / cellular myxomas. The 13 cases included 5 men and 8 women, aged from 33 to 71 years (mean age 55.5 years). Immunohistochemistry was performed as well as next generation sequencing. Ten cases were located in the lower extremities and three cases were located in the upper extremities. Two lesions were initially misdiagnosed as a low-grade myxofibrosarcoma. RESULTS: Performing next generation sequencing 12 out of 13 specimens showed a GNAS mutation. CONCLUSIONS: Our findings demonstrate that GNAS mutations are more common in intramuscular / cellular myxomas, than had been reported in literature in the past. Next generation sequencing for determining GNAS mutation status on small biopsies or diagnostically challenging cases facilitates the diagnosis of intramuscular / cellular myxoma and separates this tumor entity from its mimics.

[Clinicopathologic features of atypical spindle cell lipomatous tumor].

Objective: To investigate the clinicopathologic characteristics, immunophenotype, differential and diagnostic features of atypical spindle cell lipomatous tumor (ASLT). Methods: Three cases of ASLT were collected from January 2010 to March 2017 at Zhejiang Provincial People's Hospital. The clinical and imaging features, histomorphology, immunophenotype and prognosis were analyzed. Fluorescence in situ hybridization (FISH) was used to detect MDM2 gene amplification, and relevant literature was reviewed. Results: All three patients were adult males, aged 38, 43 and 54 years, respectively. One tumor originated in the subcutaneous soft tissue in the head and neck, one was located in the left primary bronchus and one in the latissimus dorsi muscle. Grossly, all three tumors were circumscribed and ranged from 4.0 to 5.8 cm in size. Microscopically, all showed a focally infiltrative front. These tumors were composed of variable proportions of spindle-shaped and adipocytic cells in a background of variable fibrous and edematous matrix. Scattered lipoblasts were easily seen. One tumor was composed predominately of spindle tumor cells, one of adipocytic cells, and one of equally mixed cell populations. The spindle tumor cells were generally bland-appearing with focal nuclear enlargement and hyperchromasia noted in one case. Mitosis was not seen in neither the spindle cells nor the adipocytic cells. By immunohistochemistry, diffuse and strong reactivity to CD34 of the spindle cells was noted in all cases, definite loss of Rb expression was noted in one of three cases, and S-100 protein was expressed only in the adipocytic cells. INI-1 was intact and Ki-67 index was 1% to 3%. All other markers including CDK4, MDM2, STAT6, SOX10, CD99, bcl-2, ß-catenin, CD117, GFAP, CK, EMA, SMA and desmin were negative. FISH of MDM2 was done in two cases, and both showed no amplification. The ASLT in the head and neck had two recurrences during 17 months of follow-up, whereas the tumor in the latissimus dorsi was free of disease during 33 months of follow-up. Conclusions: ASLT is a rare subtype of low-grade adipocytic neoplasm and is distinctive from atypical lipomatous tumor/well-differentiated liposarcoma. The histomorpholgy of ASLT has significant heterogeneity and forms a continuous spectrum. ASLT needs to be distinguished from a series of benign and malignant soft tissue tumors.

[Pseudomyogenic hemangioendothelioma in the upper limb: A case report and literature review]. / Hemangioendotelioma pseudomiogénico en miembro superior: descripción de un caso y revisión de la literatura.

Pseudomyogenic hemangioendothelioma, also called epithelioid sarcoma-like hemangioendothelioma, is a rare, vascular neoplasm usually with indolent behaviour. It was introduced in the latest World Health Organization (WHO) Classification of Tumours of Soft Tissue. We report a case of a 45 year-old patient presenting with a localized, palpable and slightly painful lesion in the left arm. Histologically it consisted of fascicles of spindle and epithelioid cells with ample eosinophilic cytoplasm, without nuclear pleomorphism or significant mitotic activity. Tumour cells showed diffuse expression for cytokeratin AE1/AE3, CD31 and FLI1, intact expression for INI1 and negativity for CD34. We describe the clinical, histological, molecular and immunohistochemical features of pseudomyogenic hemangioendothelioma and review the pertinent literature.

Chemoradiotherapy for Solitary Skeletal Muscle Metastasis from Oesophageal Cancer: Case Report and Brief Literature Review.

BACKGROUND: The incidence of skeletal muscle metastasis from oesophageal cancer is very low, and the treatment strategy has not been established. CASE REPORT: A 77-year-old man underwent oesophagectomy following neoadjuvant chemotherapy for oesophageal squamous cell carcinoma (CT-pT3 N0 M0, CT-pStage II). Fourteen months after surgery, he became aware of a subcutaneous tumour in his left forearm. Computed tomography and fluorodeoxyglucose positron-emission tomography revealed a 65×75 mm intramuscular nodular lesion with a standardized uptake value of 8.5. Further examination by biopsy strongly suggested this was a solitary metastasis from oesophageal cancer. The patient received chemoradiotherapy with two cycles of 5-fluorouracil combined with cisplatin and radiation. Clinical complete response was confirmed by imaging 7 months after chemoradiation and no recurrence has occurred at 20 months since chemoradiation. CONCLUSION: Radiotherapy or chemoradiotherapy can be an alternative locoregional therapy to surgery for solitary skeletal muscle metastasis.

Recurrent SRF-RELA Fusions Define a Novel Subset of Cellular Myofibroma/Myopericytoma: A Potential Diagnostic Pitfall With Sarcomas With Myogenic Differentiation.

Cellular myofibroblastic tumors other than desmoid-type fibromatosis are often diagnostically challenging due to their relative rarity, lack of known genetic abnormalities, and expression of muscle markers which may be confused with sarcomas with myogenic differentiation. In this study we investigate the molecular alterations of a group of cellular myofibroblastic lesions with in the myofibroma and myopericytoma spectrum for better subclassification. Two index cases were studied by paired-end RNA sequencing for potential fusion gene discovery. One chest wall soft tissue tumor in a 3-month-old girl case showed a SRF-C3orf62 fusion, while the other, a forearm lesion in an 8-year-old girl, showed a SRF-RELA fusion. Further screening of 42 cellular examples of myofibroma/myopericytoma by fluorescence in situ hybridization identified additional 8 cases with recurrent SRF gene rearrangements, 6 of them showing identical SRF-RELA fusions. The cohort was composed of 7 females and 3 males, with a wide age range of 3 months to 63 years (mean=17). All tumors showed a densely packed growth of oval to spindle cells with fibrillary eosinophilic cytoplasm, arranged either in intersecting fascicles or with a distinct nested pattern around a rich vascular network. Despite the dense cellularity and variable mitotic activity none of the lesions displayed nuclear pleomorphism or necrosis. All tumors showed coexpression for SMA and desmin, in most cases with a strong and diffuse pattern of staining, while myogenin was consistently negative. No distant metastases were seen in the few cases with follow-up information. A control group of 34 well-characterized myofibroblastic and perivascular tumors, including 10 typical myofibromas and 3 myopericytomas, were also investigated for SRF gene abnormalities by fluorescence in situ hybridization and were negative. In summary, we report a subset of cellular variants of myofibroma and myopericytoma showing a smooth muscle-like immunophenotype and harboring recurrent SRF-RELA gene fusions, which mimic sarcomas with myogenic differentiation.

Pseudolipoblastic perineurioma: an unusual morphological variant of perineurioma that may simulate liposarcoma.

Perineuriomas are rare peripheral nerve sheath tumors arising from or differentiating along the lines of normal perineurial cells. They can be divided into intraneural and soft tissue types, with the latter category including a significant number of morphological variants. Herein, we further expand their morphological spectrum to include "pseudolipoblastic" perineuriomas. These lesions occurred in the tongue of a 30-year-old man and in the triceps of a 67-year-old woman and were characterized by bland, epithelioid cells with striking intracytoplasmic vacuolization. The architecture varied, with some areas showing a striking "net-like" or "microreticular" pattern and smaller areas having a more typical spindled and whorled appearance. Clinical follow-up (5months and 52months, respectively) showed no evidence of local recurrence or metastasis. Multiple perineurial markers, including epithelial membrane antigen, claudin-1, GLUT-1, and collagen IV, were diffusely positive. Both cases were submitted in consultation out of concern that they represented high-grade liposarcomas. To the best of our knowledge, this unusual morphological variant of perineurioma has not been reported. These tumors appear to be entirely benign and should be cured with simple excision. Pseudolipoblastic perineuriomas should be distinguished from round cell and epithelioid pleomorphic liposarcomas, as well as from other tumors that may show prominent intracytoplasmic vacuolization.

Two cases of histiocytic sarcoma with BCL2 translocations and occult or subsequent follicular lymphoma.

Histiocytic sarcoma is rare and difficult to distinguish from histologic mimics such as myeloid sarcoma due to its relatively nonspecific immunoprofile. A subset of histiocytic sarcomas are clonally related to synchronous or metachronous follicular lymphomas. Interestingly, the histiocytic tumor component has been shown to harbor BCL2 gene translocations that are identical to those found in the lymphoma. We present one case of histiocytic sarcoma and initially occult follicular lymphoma in which detection of a BCL2 gene translocation helped support the diagnosis. We also provide follow-up regarding a previously published case of histiocytic sarcoma with IGH/BCL2 fusion gene in which the patient subsequently developed follicular lymphoma and, later, diffuse large B-cell lymphoma. Our findings suggest that BCL2 gene translocations are a recurrent feature of a distinct subset of histiocytic sarcomas that are associated with follicular lymphoma; the follicular lymphoma component may be clinically occult at the time of diagnosis. Testing for an IGH/BCL2 translocation should be considered in the diagnostic workup of difficult-to-characterize neoplasms with histiocytic/monocytic morphology and immunoprofile.

Epithelioid Schwannomas: An Analysis of 58 Cases Including Atypical Variants.

The histologic features and outcome of 58 cases of epithelioid schwannoma were studied to determine the significance of atypical histologic features. Cases were retrieved from personal consultation files from 1999 to 2013. Patients (31 male and 26 female patients) ranged in age from 14 to 80 years (median, 38 y). Two patients had schwannomatosis 1. Tumors developed in the dermis/subcutis (n=56) or muscle (n=2) of the upper extremity (34.5%), lower extremity (34.5%), thorax/abdomen/back (18%), and less common anatomic locations including the scalp, neck, lip, and breast. They ranged in size from 0.25 to 4.5 cm (median, 2.0 cm). Typically circumscribed and surrounded by a perineurium, they comprised single or small groups of epithelioid schwann cells with a moderate amphophilic cytoplasm and occasional nuclear pseudoinclusions. Stroma varied from myxoid to hyalinized, often with thick-walled vessels (55 cases). Mitotic rate ranged from 0 to 9 mitoses/10 high-power field (HPF) (2.37 mm) in the most active areas (mean, 2 to 3 mitoses/10 HPFs). Thirteen cases (22%) were "atypical," defined by a high mitotic rate (≥3 mitoses per 10 HPFs) and nuclear size variation (≥3:1). All (56/56) expressed S100 protein; type IV collagen invested groups or individual cells (16/17). Melanoma markers were negative, except for melan A (1 case). Follow-up in 39 patients (median, 78 mo; range, 6 to 174 mo) indicated that 31 (79%) were alive without disease (including 9/13 atypical cases; median, 78 mo), 7 (18%) were alive with unknown status, and 1 patient had died of unrelated causes. One tumor recurred, but none metastasized. Epithelioid schwannomas, even those with atypical features, are benign and do not constitute a histologic continuum with epithelioid malignant peripheral nerve sheath tumors, which typically occur in deep soft tissues and have more anaplastic features.

Dendritic fibromyxolipoma in the latissimus dorsi: a case report and review of the literature.

Dendritic fibromyxolipoma is an uncommon benign soft tissue tumor. Here, we report a case in a 53-year-old man presenting a painless mass located deep in the latissimus dorsi of the right back. Microscopically, the tumor was mainly consisted of small spindle and stellate cells, abundant myxoid stroma, collagen bundles and mature adipose tissue. Immunohistochemical study showed the spindle and stellate cells were positive for CD34, Bcl-2 and Vimentim, but not for Keratin, EMA, SMA and Desmin. To date, one year after operation, the patient is well without evidence of recurrence or metastasis. The implication of this report is to provide insights into further understanding of this rare tumor with review of the literature.

Gastrointestinal stromal tumor solitary distant recurrence in the left brachialis muscle.

Gastrointestinal stromal tumors (GISTs) are mesenchymal tumors of the gastrointestinal tract that are most commonly found in the stomach. Although GISTs can spread to the liver and peritoneum, metastasis to the skeletal muscle is very rare and only four cases have previously been reported. These cases involved concurrent skeletal metastases of primary GISTs or liver metastases. Here, we report the first case of a distant recurrence in the brachialis muscle after complete remission of an extra-luminal gastric GIST following a wedge resection of the stomach, omental excision, and adjuvant imatinib therapy for one year. Ten months after therapy completion, the patient presented with swelling and tenderness in the left arm. Magnetic resonance imaging revealed a large mass in the brachialis muscle, which showed positivity for c-kit and CD34 upon pathologic examination. This is the first reported case of a solitary distant recurrence of a GIST in the muscle after complete remission had been achieved.

A novel CIC-FOXO4 gene fusion in undifferentiated small round cell sarcoma: a genetically distinct variant of Ewing-like sarcoma.

Differential diagnosis of small round cell sarcomas (SRCSs) grouped under the Ewing sarcoma family of tumors (ESFT) can be a challenging situation for pathologists. Recent studies have revealed that some groups of Ewing-like sarcoma show typical ESFT morphology but lack any EWSR1-ETS gene fusions. Here we identified a novel gene fusion, CIC-FOXO4, in a case of Ewing-like sarcoma with a t(X;19)(q13;q13.3) translocation. The patient was a 63-year-old man who had an asymptomatic, 30-mm, well-demarcated, intramuscular mass in his right posterior neck, and imaging findings suggested a diagnosis of high-grade sarcoma. He was treated with complete resection and subsequent radiotherapy and chemotherapy. He was alive without local recurrence or distant metastasis 6 months after the operation. Histologic examination revealed SRCS with abundant desmoplastic fibrous stroma suggesting a desmoplastic small round cell tumor. Immunohistochemical analysis showed weak to moderate and partial staining for MIC2 (CD99) and WT1, respectively. High-throughput transcriptome sequencing revealed a gene fusion, and the genomic rearrangement between the CIC and FOXO4 genes was identified by fluorescence in situ hybridization. Aside from the desmoplastic stroma, the CIC-FOXO4 fusion sarcoma showed morphologic and immunohistochemical similarity to ESFT and Ewing-like sarcomas, including the recently described CIC-DUX4 fusion sarcoma. Although clinicopathologic analysis with additional cases is necessary, we conclude that CIC-FOXO4 fusion sarcoma is a new type of Ewing-like sarcoma that has a specific genetic signature. These findings have important implications for the differential diagnosis of SRCS.

Pseudomyogenic hemangioendothelioma: report of an additional case with aggressive clinical course.

: Pseudomyogenic hemangioendothelioma is a recently described vascular tumor that occurs predominantly in the distal extremities of young adults. Because of multifocal presentation, epithelioid morphology, and strong cytokeratin expression, the tumor was frequently misdiagnosed as epithelioid sarcoma. However, substantial immunohistochemical studies revealed an endothelial nature. It has been currently considered a tumor of intermediate malignancy with frequent local recurrence but low risk of distant metastasis. In this report, we describe a case of pseudomyogenic hemangioendothelioma occurring in a 22-year-old man who presented with multifocal disease in the lower extremity and developed bilateral pulmonary metastases within a short period.

Sclerosing rhabdomyosarcoma presenting in the masseter muscle: a case report.

Sclerosing rhabdomyosarcoma (SRMS) is exceedingly rare, and may cause a great diagnostic confusion. Histologically, it is characterized by abundant extracellular hyalinized matrix mimicking primitive chondroid or osteoid tissue. So, it may be easily misdiagnosed as chondrosarcoma, osteosarcoma, angiosarcoma and so on. Herein, we report a case of SRMS occurring in the masseter muscle in a 40-year-old male. The tumor showed a diverse histological pattern. The tumor cells were arranged into nests, cords, pseudovascular, adenoid, microalveoli and even single-file arrays. Immunostaining showed that the tumor was positive for the Vimentin, Desmin and MyoD1, and was negative for CK, P63, NSE, CD45, CD30, S-100, CD99, Myoglobin, CD68, CD34, CD31, and α-SMA. Based on the morphological finding and immunostaining, it was diagnosed as a SRMS. In addition, focally, our case also displayed a cribriform pattern resembling adenoid cystic carcinoma. This may represent a new histological feature which can broaden the histological spectrum of this tumor and also may lead to diagnostic confusion. VIRTUAL SLIDES: The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/1615846455818924.

Cavernous hemangioma arising from the diaphragm.

A 51-year-old man was referred to our hospital with an abnormal nodule in the right lung field. Computed tomography revealed a homogeneous nodule adjacent to the diaphragm, which appeared to be an extrapulmonary lesion. No hilar or mediastinal lymph node swelling was detected, and positron-emission tomography showed no significant uptake. At surgery, 2 red papillary tumors were found, originating from the right diaphragm, and tumor extirpation was performed. The pathological diagnosis was cavernous hemangioma.

Skeletal muscle metastases from lung cancer.

Lung cancers are diagnosed at a metastatic stage in 40% to 50% of cases. Skeletal muscle metastases are rare and usually discovered at autopsy. We report 3 cases of skeletal muscle metastasis. Muscular metastasis revealed the cancer in one patient. The metastases were asymptomatic in all patients. The diagnosis was confirmed histologically in one case and by radiography in the other 2. The evolution was characterized by tumor progression and death after 1-7 months.

Hibernoma with metabolic impact?

A hibernoma is a benign tumour of brown adipose tissue (BAT). BAT is also present in physiological depots, previously considered residual. However, in 2009 functional BAT in adults was reported. Metabolically active BAT is suggested to significantly influence the energy balance and increasing BAT activity could possibly treat obesity. This strongly increased the interest in BAT in man and currently more research is conducted. We describe the case of an intramuscular hibernoma and illustrate the pathophysiology of the observed hibernoma in relation to recent insights on physiological BAT. Immunofluorescence staining of the hibernoma showed the presence of uncoupling-protein-1, a protein specific for active BAT. This suggests that this hibernoma contains BAT that could possibly contribute to the human energy balance.

Intramuscular, extraskeletal mesenchymal chondrosarcoma.

Extraskeletal mesenchymal chondrosarcoma (EMC) is a rare and a malignant chondrogenic neoplasm. As a particularity of this neoplasm, about one-third of the cases develop outside the bone, with intramuscular site being a very rare location for development of EMC. The diagnosis of mesenchymal chondrosarcoma can be very challenging, especially in cases without conspicuous cartilaginous differentiation. In such cases its distinction from other small cell mesenchymal neoplasms cannot be safely established. This, however, is of major clinical interest as it implicates different treatment protocols as well as a different prognosis. We hereby present a case of EMC at a unusual location in a 23-year-old female with the purpose to highlight its morphologic features and to discuss its differential diagnosis.