Primary superficial Ewing sarcoma: A unique entity? A case report including novel findings of ELF3 and TNFRSF14 copy number loss

Primary superficial Ewing sarcoma (psES) cases are exceedingly rare, with fewer than 150 cases reported in the literature. Small case series have suggested differences between psES and Ewing sarcoma (ES) of bone or deep soft tissues: psES appears to have a more indolent course and a higher 5-year overall survival rate. PsES is more common in older adolescent females as opposed to younger males in their peak growth velocity years in bone or deep soft tissue ES. We present a case report of a 17-year-old female with a relatively static nodule on her left thigh for 4 years. Morphologic, immunohistochemical, and molecular evaluations confirmed ES. Patient underwent a gross-total resection and a shortened course of adjuvant chemotherapy without radiation. Cancer gene panel testing found three gene abnormalities (in addition to EWSR1-FLI1 fusion): CCND1 copy number gain, ELF3 copy number loss, and TNFRSF14 copy number loss. To our knowledge, this is the first published case report of psES to include genomic sequencing and the first to report ELF3 and TNFRSF14 abnormalities in ES. Larger series of psES cases with genomic profiling are needed to elucidate a possible genetic etiology for its more indolent clinical course and favorable outcomes.     

Dual‐color,break‐apart fluorescence in situ hybridization probe for distinguishing clear cell sarcoma of soft tissue from malignant melanoma

Background Clear cell sarcoma (CCS) of soft tissue is a rare soft tissue sarcoma with melanocytic differentiation and shares morphologic, immunohistochemical, ultrastructural, and molecular features with malignant melanoma (MM). Because the prognosis of CCS is much different from MM, it is important to distinguish each other by selective method. CCS is well‐recognized as having the t(12;22)(q13;q12) translocation, on the other hand MM is not. Therefore, detecting Ewing sarcoma region 1 (ESWR1) gene rearrangement can serve as a crucial diagnostic determinant. Methods Biopsy was taken from a 52‐year‐old man who reported a 3‐year history of a gradually enlarging nodule on the sole of his left foot. Routine and special stains for melanocytic markers and fluorescence in situ hybridization (FISH) evaluation using dual color break‐apart rearrangement probes specific for ESWR1 was performed for formalin‐fixed tissue. Results Neoplastic cells expressed diffuse but strong positivity for HMB45 and S100 but not for Melan‐A. Dual color, break‐apart interphase FISH revealed EWS(22q12) gene rearrangements in CCS tumor cells. Conclusion Fluorescence in situ hybridization evaluation using ESWR1 gene probe for CCS sharing clinical and histopathological characteristics with MM is a valuable tool to distinguish each other.     

Application of electron microscopic analysis and fluorescent in situ hybridization technique for the successful diagnosis of extraskeletal Ewing's sarcoma

The diagnosis of soft tissue tumors is often challenging. Immunohistochemical investigation, let alone routine histopathological investigation, may not allow definitive diagnosis in some cases. To overcome such difficulties, more advanced techniques need to be adopted. Herein, we report an extremely rare 56‐year‐old Japanese female case of extraskeletal Ewing's sarcoma (ES), successfully diagnosed by electron microscopy (EM) using formalin‐fixed sections and fluorescence in situ hybridization (FISH). The patient had a 2‐year history of a tumor growing on the leg. In routine histopathology, invasive proliferation of tumor cells was observed in the dermis. Tumor cells were round and uniform with large hyperchromatic nuclei, which were positively stained for CD56, VS38c, Ki‐67, MIC2 and vimentin, but not for pan‐keratin AE1 + AE3, cytokeratin 20, chromogranin A, synaptophysin and neuron‐specific enolase. As these findings were not conclusive to make the final diagnosis, EM specimens were prepared from formalin‐fixed sections and subjected to investigation. Cell surface projections and dense core granules were detected, suggestive of either Merkel cell carcinoma or extraskeletal ES. Subsequent FISH analysis identified reciprocal translocation of the ESWR1 gene, enabling the final diagnosis of extraskeletal ES. This study provides useful information enabling the diagnosis of this uncommon soft tissue tumor.     

Ewing's sarcoma with cutaneous metastasis--a rare entity: report of three cases

Ewing's sarcoma (ES) is a small round cell tumor, usually arising from flat bones and diaphyseal region of long bones. It is commonly found in the first two decades of life. It is curable when diagnosed in the localized stage and requires multimodality treatment. ES is a chemosensitive tumor. It metastasizes commonly to lung, pleura and other bones. Less common sites of metastasis are lymph nodes, CNS and liver. Skin metastasis is extremely uncommon. It occurs in up to 9% of all patients with cancer. Growth pattern of cutaneous metastasis is unpredictable and may not reflect that of primary tumor. We hereby report three cases of Ewing's sarcoma that developed skin metastasis.     

Clinicopathological analysis of myxoid proximal‐type epithelioid sarcoma

Proximal‐type epithelioid sarcoma (ES) with a diffuse myxoid stroma is rare. Here, we report the case of a 33‐year‐old man with a perineal mass. Imaging showed the presence of a poorly demarcated 6.9 × 5.3‐cm mass in the subcutaneous perineal region. Macroscopic examination showed that the resected tissues were partially necrotic. Histological examination showed that the tumor comprised numerous large or pleomorphic epithelioid cells with large vesicular nuclei and prominent nucleoli. A clear background of necrosis and inflammatory exudates was also present. Immunohistochemical examination showed that the tumor cells were positive for vimentin and CD34 — both of which were expressed throughout the cytoplasm — but typically did not express nuclear INI1 (SMARCB1). Hematoxylin‐eosin staining (HE staining) showed that the mucin content of the tumor was approximately 80%. The patient was diagnosed with proximal‐type ES with myxoid features. The patient died due to disease progression after 2 months of follow‐up and without undergoing further treatment in our department. To our knowledge, only 2 cases of proximal‐type ES with diffuse myxoid stroma have been reported. Proximal‐type ES is rare, and this is the first case report of proximal ES with myxoid features in the perineal area.     

Primary cutaneous Ewing sarcoma - Case report

Ewing sarcoma is a primitive neuroectodermal tumor rarely occurs in the skin and sobcutaneous tissues. Generally Ewing''s sarcoma is a primary bone tumor, but when present in soft tissues it characterizes an extremely uncommon clinical picture. It usually involves the deep subcutaneous tissue or muscles, and more rarely occurs like a primary skin cancer. Most patients are white, women, and in the second decade of life. The clinical features are a superficial mass, in average measuring 2-3 cm, of soft consistency, freely mobile and sometimes painful. The more affected locations are upper and lower extremities, trunk, head, neck or multiple lesions. The presence of metastases is very rare.     

Epithelioid sarcoma of the right hand

A 35-year-old man presented with swelling, indurations and nodules on the thumb, wrist and fingers of the right hand. History revealed that the findings were slowly progressive and had been present for at least eight years. Histopathologic analysis of a nodule showed a diffuse infiltrate with atypical spindle-shaped cells and expression of cytokeratin, epithelial membrane antigen (EMA) and CD34; the diagnosis of epithelioid sarcoma (ES) was made. Because of diffuse extension of the tumor, forearm amputation was performed along with axillary dissection and local radiotherapy because of axillary lymph node metastases. ES is a rare subtype of soft tissue sarcoma with a harmless appearance and indolent course over years. ES represents a diagnostic challenge, with consequent delay in diagnosis and adequate treatment. The most important measure in the treatment of ES is early surgical excision with adjuvant radiotherapy if local metastases are present.     

Bilateral multifocal upper extremity atypical granular cell tumors presenting as long‐standing right wrist and left hand masses in a 15‐year‐old African‐American female

Granular cell tumor (GrCT) is a benign nerve sheath tumor. Atypical and malignant variants of GrCT are rare but have been well described. We report a case of multifocal symmetric atypical GrCT in the bilateral hand/wrists of a 15‐year‐old African‐American female. The initial clinical impression for both masses was favored to be ganglion cysts. Ultrasound findings of both masses revealed hypoechoic soft tissue lesions with some internal echogenicity favoring complex cysts. On excision, both masses were histologically circumscribed, lobulated and attached to tendon. Large epithelioid cells with abundant granular eosinophilic cytoplasm arranged in syncytial cords and trabeculae percolated through collagen. Many cells had pleomorphism and/or prominent nucleoli. Mitotic figures, spindling, high nuclear‐to‐cytoplasmic ratio and necrosis were absent. Both masses showed diffuse S100 protein but negative desmin and pancytokeratin expression. Ki‐67 index was 1% to 2%. p53 was positive in 5% to 10% of nuclei. Both masses met criteria for atypical (but not malignant) GrCT. Our case shows that atypical GrCT may be not only multifocal but also symmetric. We speculate that migration of defective neural crest stem cells along both upper limb buds during embryogenesis may have allowed these essentially identical tumors to arise in similar locations bilaterally simultaneously.     

Epithelioid sarcoma with angiomatoid features: report of an unusual case arising in an elderly patient within a burn scar

Epithelioid sarcoma (ES) is a rare, aggressive soft tissue tumor with a characteristic predilection for adolescents and young adults, and a tendency to occur on distal extremities. We report a case of ES arising in an 80-year-old woman within a burn scar that histopathologically showed unusual 'angiomatoid' features. The patient presented initially with a solitary nodule on her right wrist arising at the site of a burn scar. Histopathologically, the tumor was composed of a proliferation of relatively bland, epithelioid and spindle cells focally arranged in a nodular pattern around areas of 'geographic' necrosis. In addition, there were prominent foci of hemorrhage and blood-filled spaces as well as tumor cells with intracytoplasmic vacuoles, features suggestive of an angiomatous process. Immunohistochemistry showed positivity of tumor cells for cytokeratins and epithelial membrane antigen (EMA) whereas all vascular markers tested were negative. The overall histopathologic features were consistent with a diagnosis of ES. Follow up showed multiple recurrences arising proximally along the right upper extremity. Our case underlines the clinical and histopathological heterogeneity of ES, emphasizing the unusual occurrence of ES with 'angiomatoid' features in the elderly. In this uncommon setting, this tumor should be especially distinguished from epithelioid hemangioendothelioma and epithelioid angiosarcoma. The significance of development of ES on a healed burn scar is uncertain, but may suggest a possible causal relationship.     

Lymphangiectatic Kaposi's sarcoma in a patient with AIDS

Kaposi''s sarcoma is a malignant disease that originates in the lymphatic endothelium. It has a broad spectrum of clinical manifestations. Its four distinct clinical forms are: classic, endemic, iatrogenic and epidemic Kaposi''s sarcoma. In non-HIV-associated Kaposi''s sarcoma, the disease is typically limited to the lower extremities, but in immunodeficient patients, it is a multifocal systemic disease. The clinical course of the disease differs among patients, ranging from a single or a few indolent lesions to an aggressive diffuse disease. Advanced Kaposi''s sarcoma lesions, typically those on the lower extremities, are often associated with lymphedema. In this paper, we report a case of a patient with a rare form of AIDS-associated Kaposi sarcoma called lymphangiectatic Kaposis''s sarcoma.     

Epithelioid sarcoma: a puzzling soft tissue neoplasm in a child

Epithelioid sarcoma (ES) is a rare soft tissue neoplasm that usually occurs on the upper extremity of adolescents and young adults. It rarely occurs during childhood. ES is a slowly growing tumor with a high propensity for recurrences and metastases. This neoplasm is likely to be confused with a variety of benign and malignant conditions. Recognition of ES is important. The treatment consists of wide excision. Misdiagnosis can lead to inappropriate treatment and local recurrences or metastases. We report the case of a 5-year-old girl with an ES on the right forefinger.     

Epidermotropic metastatic epithelioid sarcoma: a potential diagnostic pitfall

Epithelioid sarcoma (ES) represents an aggressive soft tissue tumor with varied morphologic and histopathologic presentations that typically elicits a broad differential diagnosis, including granuloma annulare, necrobiotic granuloma, fibrous histiocytoma, synovial sarcoma, amelanotic melanoma and poorly differentiated primary cutaneous and metastatic adenocarcinoma. ES is characterized microscopically by a nodular arrangement of abundant, deeply eosinophilic, polygonal tumor cells with frequent central necrosis and hemorrhage, rare mitotic figures and minimal pleomorphism. At the periphery, tumor cells are spindle shaped and may exhibit frequent local infiltration along tendons, fascial planes and neurovascular bundles. Immunohistochemistry typically reveals expression of both epithelial and mesenchymal antigens, such as cytokeratin and vimentin, respectively. The absence of a connection between tumor cells and the overlying epidermis, with or without an in situ carcinoma component, typically rules out a primary cutaneous squamous cell carcinoma. We report a case of stage IV proximal‐type ES that mimicked molluscum contagiosum clinically and was histopathologically reminiscent of invasive squamous cell carcinoma because of attachment and colonization of the overlying epidermis. The case represents an unusual pathologic presentation of ES and highlights potential pitfalls in establishing the diagnosis.     

Tumor‐to‐bone distance of invasive subungual melanoma: An analysis of 30 cases

Subungual melanoma (SUM) is rare and represents approximately 2–3% and 20% of all cutaneous melanomas in Caucasians and Asians, respectively. Amputation has usually been performed for invasive SUM; however, not all invasive SUMs invade or attach to the distal phalanx. To investigate the possibility of non‐amputative surgery for patients with invasive SUM, the distances between the deepest base of the melanoma cells and the bony surface in the surgical specimens of invasive SUM were measured. Thirty surgical specimens of invasive SUM were retrospectively reviewed. The contents of the specimens were as follows: 14 first toes, 10 thumbs, three second fingers, two third fingers, and one fifth finger. Four specimens showed bone invasion, and the tumor was attached to the bone in four specimens. The tumor‐to‐bone distance exceeded 0.9 mm in all the specimens with thicknesses <4 mm. In the non‐ulcerated SUMs (nine specimens), only one SUM specimen showed bone attachment. There was a higher likelihood of bone attachment or invasion when tumor thickness (TT) exceeded 4 mm (Pearson chi‐square test, P = 0.009; Fisher exact test, P = 0.004; student t test, 0.033). Univariate and multivariate analysis also revealed that thick TT had a statistically significant affect (odds ratio 1.807 and 1.865, 95% CI 1.11–3.01 and 1.11–3.13, P = 0.023 and 0.018). Non‐amputative surgery may be possible for SUM tumors that are of intermediate‐thickness. However, there has been little evidence demonstrating survival with non‐amputative surgery for invasive SUM. A large, randomized, prospective clinical study is required to address this issue.     

Distal‐type epitheloid sarcoma mimicking a wart in a child: A diagnosis not to be missed

Epithelioid sarcoma is a rare soft‐tissue tumor that occurs mainly in children and young adults. It typically presents as a subcutaneous or deep dermal mass in distal extremities. Due to its benign‐appearing clinical presentation, infrequent occurrence, and histologic similarities with other pathologies, the diagnosis of epithelioid sarcoma in its early stages can be extremely difficult and can be easily confused with benign lesions such as warts or foreign body granuloma. In this paper, we report the case of a 12‐year‐old boy with a distal‐type epithelioid sarcoma of the hand and wish to emphasize the difficulties of diagnosing this potentially lethal tumor both clinically and histologically.     

Primary cutaneous Ewing sarcoma in a young boy

We report a 10-year-old boy with the challenging presentation of a left toe nodule that failed empiric treatments and was biopsied. Immunohistochemistry and florescence in situ hybridization enabled the diagnosis of Ewing sarcoma (ES). This case emphasizes the importance of including ES on the clinical differential to minimize diagnostic delays.     

Mesenchymal stem cell therapy for immune‐modulation: the donor,the recipient,and the drugs in‐between

Adoptive transfer of cultured bone marrow stromal cells (mesenchymal stem cells also known as MSCs) is a promising new way to aid tissue regeneration and treat a wide variety of diseases where regulation of inflammatory responses is derailed. Although significant advances have been made in the field, pinpointing important mechanistic details about how MSCs function in vitro and in vivo, there are still many unanswered questions that need to be addressed before welcoming MSCs in the therapeutic arsenal of immune mediated diseases. In this viewpoint, we highlight and discuss a few factors that we believe are critical in terms of therapeutic success employing cultured MSCs. Selecting the right donor population, choosing the best culture conditions and picking the patient population that is most likely to give a favourable therapeutic response is just as important as considering interactions between MSCs and the combination of drugs in the recipient's body. Given the complexity of MSC–host interactions, it is also imperative to develop screening tools that account for as many variables as possible and predict precisely the in vivo response rates before MSCs enter the body. To achieve this, a multidisciplinary approach is required with comprehensive knowledge of basic MSC biology, immunology, pharmacology and good clinical practice.     

Primary giant cell tumor of soft tissue of the groin – a case of 46 years duration

Background: Soft tissue giant cell tumor (GCT-ST) of low malignant potential is an uncommon neoplasm, considered the soft tissue counterpart of giant cell tumor of bone. GCT-ST mainly affects young to middle-age adults and presents as a painless growing mass mainly located in the lower extremities and trunk. Histologically, this tumor is characterized by a mixture of uniformly scattered osteoclast-like multinucleated giant cells intimately admixed with short fascicles of spindled cells. Complete excision with negative surgical margins is associated with a benign clinical course in most cases.
Methods: The authors report the clinicopathological and immunohistochemical features of an unusual GCT-ST of 46 years duration previously histologically misdiagnosed as Kaposi's sarcoma.
Results: Histologically, the tumor was characterized by a multinodular growth pattern with osteoclast-like multinucleated giant cells admixed with spindle cells partially arranged in a storiform pattern, fibrosis and foci of haemorrhage and mature bone. Immunohistochemistry revealed CD68 reactivity of the multinucleated giant cells.
Conclusion: GCT-ST is a rare neoplasm characterized by benign clinical course if excised adequately, as shown by our case of exceptionally long duration. Emphasis is placed on the importance of differential diagnosis with other giant cell-rich soft tissue neoplasms because clinical behaviour, prognosis and treatment significantly differ.     

Sarcomas—a clinicopathological guide with particular reference to cutaneous manifestation III. Angiosarcoma, malignant haemangiopericytoma, fibrosarcoma and synovial sarcoma

In Part 1 of this review (Fletcher & McKce, 1984), the malignant fibrohistiocytic tumours and the epithelioid sarcoma of Enzinger were discussed. In Part II (Fletcher and McKee, 1985), malignant nerve sheath tumours and sarcomas arising from smooth and striated muscle were dealt with. In this third part, the malignant vascular tumours (excluding Kaposi's sarcoma which is currently receiving extensive coverage in the world literature) are reviewed along with fibrosarcoma and synovial sarcoma, which present less commonly to the dermatologist.