Epithelioid malignant peripheral nerve sheath tumor of the uterine corpus

Epithelioid variant of a malignant peripheral nerve sheath tumor (MPNST) is a rare sarcoma. Rarer still is its occurrence at uncommon sites like the uterine corpus where an index of suspicion for this diagnosis is extremely low. Herein, we report a rare case of a uterine epithelioid MPNST in a young girl who underwent a total abdominal hysterectomy for a uterine tumor that was initially diagnosed as an undifferentiated sarcoma and whose paraffin blocks were submitted to us for review. Biopsy sections showed a malignant tumor, predominantly composed of polygonal cells, including “rhabdoid” forms with conspicuous mitoses. On immunohistochemistry, tumor cells were diffusely positive for vimentin and S-100 and negative for smooth muscle actin, desmin, myogenin cytokeratin, epithelial membrane antigen, melan A, HMB-45, CD10, glial fibrillary acid protein inhibin, synaptophysin, chromogranin, MIC2, FLI-1, and neuron-specific enolase. Diagnosis of an epithelioid MPNST was offered. The case is presented in view of its rarity and also to highlight the value of immunohistochemistry in objectively identifying unusual sarcomas at uncommon sites.     

Cytohistologic correlations of 24 malignant peripheral nerve sheath tumor (MPNST) in 17 patients: the Institut Curie experience

Cytomorphological patterns of malignant peripheral nerve sheath tumor (MPNST) are insufficiently documented in the literature. Cytological and histological specimens in 24 tumors in 17 patients were correlated. The review of the original cytology reports showed that four (16.6%) tumors were correctly diagnosed, eight (33.3%) were diagnosed as sarcoma not otherwise specified, four (16.7%) as fibrosarcoma, three (12.5%) as synovial sarcoma, three (12.5%) as leiomyosarcoma, and one (4.2%) case each as malignant fibrous histiocytoma and rhabdomyosarcoma. At the review tumors were histologically reclassified as well-differentiated MPNST in 11 (45.9%) cases, anaplastic MPNST in 11 (45.9%) cases, and epithelioid MPNST and malignant Triton tumor in one (4.2%) case each. Cytologically, well-differentiated MPNST were composed of polymorphous oval to round cells, small spindle-shaped cells with wavy and comma-like naked nuclei, and a fibrillary, delicate stroma. Anaplastic MPNST, moreover, were composed of anaplastic giant and polymorphous cells. The malignant Triton tumor was composed of oval to round rhabdomyoblastic cells with eccentric nuclei and the epithelioid MPNST of polymorphous and round, epithelial-like cells. The cytological diagnosis of MPNST may be difficult, especially in anaplastic tumors. The correlation between the cytological features and the clinical information--origin of the tumor from a nerve trunk, a preexisting neurofibroma, patients with known history of neurofibromatosis 1--could be indicative of an MPNST diagnosis.     

Purely epithelioid malignant peripheral nerve sheath tumor of the vulva.

Primary malignant peripheral nerve sheath tumors(MPNST) of the vulva are extremely rare and most of them are composed of a spindle cell component. A few cases of MPNST containing partially or purely epithelioid cells have been reported. Purely epithelioid MPNST differ from the ordinary epithelioid MPNST due to the absence of a spindle cell component. We present the first case of purely epithelioid MPNST arising in the vulva reviewing in the world literature without definite evidence of von Recklinghausen''s disease or nerve involvement. The patient was a 63-year-old woman with a palpable vulvar mass, 6 x 4 x 1.5 cm in dimension, was not encapsulated but well-demarcated, ovoid and rubbery and showed pale yellow, homogeneous, fish-flesh appearance with focal cystic changes on cut surface. The histologic features consisted of solely epithelioid cells which were arranged in tight clusters or cords with solid growing pattern and focally scattered rosette-like structures. According to the immunohistochemical results, most of tumor cells were strongly positive for neuron specific enolase, and some of them were weakly positive for S-100 protein and vimentin. We considered that purely epithelioid MPNST would represent a certain degree of differentiation toward nerve or neuronal cells rather than Schwann cells.     

Fine‐needle aspiration cytology of epithelioid malignant peripheral nerve sheath tumor: A case report and review of the literature

The epithelioid variant of malignant peripheral nerve sheath tumor (eMPNST) is an extremely rare soft tissue neoplasm comprising less than 5% of all MPNSTs. It is distinguished cytomorphologically from a conventional MPNST by the presence of polymorphous round epithelioid cells arranged in loose clusters with or without spindled tumor cells. These features pose a diagnostic challenge because the differential diagnosis involves a variety of mesenchymal and non‐mesenchymal tumors including epithelioid sarcoma, sclerosing epithelioid fibrosarcoma, malignant rhabdoid tumor, chordoma, metastatic carcinomas, and melanoma. Thus, it may become imperative to perform immunochemical stains on cell blocks of FNA aspirates to arrive at definitive diagnosis. Reports describing the cytologic features of eMPNST are rare. Herein, we report a case of eMPNST with focus on cytomorphologic and cytoimmunochemical features and differential diagnosis. Diagn. Cytopathol. 2016;44:226–231. © 2015 Wiley Periodicals, Inc.     

Fine-needle aspiration of epithelioid malignant peripheral nerve sheath tumor (epithelioid malignant schwannoma)

The epithelioid variant of malignant peripheral nerve sheath tumor (MPNST), also known as malignant epithelioid schwannoma, is a relatively rare and recently characterized clinicopathologic entity. The epithelioid variant of MPNST shares many clinical features with conventional MPNST but is characterized by different histologic and cytologic features. These include a distinctive nesting pattern and an abundance of cytoplasm not seen in histology of conventional nerve sheath tumors. Cytologically, the epitheliod variant shows a propensity to cellular discohesiveness and a plasmacytoid or epitheliod appearance that is in contradistinction to the spindled appearance of the usual MPNST. Herein, we report our experience with fine-needle aspiration (FNA) of two epithelioid malignant schwannomas and discuss the FNA cytologic differential diagnosis. Diagn. Cytopathol. 1997;17:200–204. © 1997 Wiley-Liss, Inc.     

Malignant peripheral nerve sheath tumor with perineurial cell differentiation (malignant perineurioma)

A unique case of malignant peripheral nerve sheath tumor (MPNST) with perineurial cell differentiation occurring in a 63-year-old woman in a subcutis of the forearm is described. The tumor contained cellular and myxoid areas. The neoplastic cells were fusiform with distinct cell borders. They were arranged in storiform pattern and in wavy parallel cell cords in the cellular areas. Focally, a pleomorphism and mitotic activity (including atypical mitoses) similar to those of malignant fibrous histiocytoma were seen. The myxoid parts contained haphazardly oriented cells and scarce lipoblast-like multivacuolated cells mimicking a liposarcoma. In the differential diagnosis, myxoid liposarcoma, dermatofibrosarcoma protuberans, malignant fibrous histiocytoma and low-grade fibromyxoid sarcoma were considered. Immunohistochemically, perineurial differentiation was indicated by the diffuse expression of epithelial membrane antigen and focal reactivity for CD34. The tumor was negative with antibodies to S-100 protein, Leu-7, CD68 (KP1), vimentin and cytokeratin AE1/AE3. Ultrastructure of tumor cells revealed features of MPNST. No recurrence occurred in the patient during 2 years follow up.     

Malignant transformation in a hybrid schwannoma/perineurioma: addition to the spectrum of a malignant peripheral nerve sheath tumor

Benign nerve sheath tumors include schwannomas, neurofibromas and perineuriomas. The malignant counterpart of a nerve sheath tumor is designated as a malignant peripheral nerve sheath tumor (MPNST). Lately, benign nerve sheath tumors comprising more than one component have been described, including hybrid schwannomas/perineuriomas. However, malignant transformation in a hybrid schwannoma/perineurioma has not been documented so far. Herein, we present a rare case of a young adult male who presented with a soft tissue mass in his right thigh that was excised elsewhere and submitted to us for histopathological review. One of the tissue sections displayed histopathological features of a hybrid schwannoma/perineurioma, including alternate arrangement of benign schwann and perineurial cells, reinforced with S100-P and epithelial membrane antigen positivity, respectively, along with low MIB1 and negative p53 immunostaining. The other two tissue sections showed a spindly sarcomatous tumor that was immunohistochemically positive for S100-P, CD34, p53 and exhibited high MIB1 (30-40%). Diagnosis of a MPNST arising in a hybrid schwannoma/perineurioma was made. This unusual case forms yet another addition to the spectrum of a MPNST.     

Epithelioid leiomyosarcoma with osteoclast-like giant cells in the rectum

We report a rare case of rectal epithelioid leiomyosarcoma with osteoclast-like giant cells. A 71-year-old Japanese man was admitted to a hospital with melena. Results of a colonoscopy test revealed a polypoid tumor in the rectum, and a biopsy specimen from the lesion showed a sarcoma; the patient underwent rectosigmoidectomy. At gross inspection, the tumor measured 8 x 7 x 4 cm and was polypoid with ulcerations. Necrotic and hemorrhagic foci were scattered. Microscopically, the tumor consisted of 2 cell types: malignant tumor cells with epithelioid features and benign-appearing osteoclast-like giant cells. The tumor cells were polygonal and epithelioid in shape and had eosinophilic or clear cytoplasms, with scattered giant tumor cells. Immunohistochemical examination revealed that the tumor cells were positive for vimentin, muscle actin, alpha-smooth muscle actin, and desmin, whereas the osteoclast-like giant cells were positive for CD68, leukocyte common antigen, and lysozymes. We diagnosed this case as epithelioid leiomyosarcoma with osteoclast-like giant cells. To the best of our knowledge, this is the first case of rectal epithelioid leiomyosarcoma with osteoclast-like giant cells.     

Clinicopathologic features and immunohistochemical spectrum of 11 cases of epithelioid malignant peripheral nerve sheath tumors,including INI1/SMARCB1 results and BRAF V600E analysis

Epithelioid malignant peripheral nerve sheath tumor (MPNST) is a rare, relatively less chemosensitive sarcoma. We report clinicopathologic features of 11 epithelioid MPNSTs, including rare forms, along with INI1 immunostaining and BRAF V600E mutation results. BRAF V600E mutation was tested by Real‐time polymerase chain reaction (PCR) technique. Eleven tumors occurred in six men and five women (M:F ratio = 0.85:1) within an age range of 5–73 years (average = 44), mostly in lower limbs (five), followed by upper limbs (four). Tumor size (n = 6), varied from 3.1 to 15 cm (average = 8.3). Histopathologically, most tumors were multilobular, characterized by epithelioid to round‐shaped, malignant cells, along with spindle cells (three cases), “rhabdoid‐like” cells (seven cases) and pleomorphic giant cells (single case). By immunohistochemistry, tumor cells were positive for S100 protein (11/11) (100%), EMA (3/7) (42.8%), pan CK(2/7) (28.5%), and HMB45 (1/11) (9%), while these were negative for Melan A (0/11) and INI1 (3/11), including a single tumor, displaying HMB45 positivity. BRAF V600E mutation was positive in 1/8 cases, that lacked melanocytic marker expression. All patients (n = 5) were treated by surgical resection. During follow‐up (n = 8, median duration = 23 months), four patients developed tumor recurrences and four developed metastasis, mostly to lymph nodes (3). Finally, four patients were alive with disease, two were alive with no evidence of disease, and two patients died of disease. Epithelioid MPNSTs have a diverse histopathologic spectrum. Loss of INI1 is useful, including in identifying rare forms of epithelioid MPNST, displaying melanocytic differentiation. Most tumors are treated by surgical resection. Loss of INI1 and the presence of BRAF V600E mutation in some cases raises future possibility of exploring targeted therapy in those, rare epithelioid MPNSTs.     

Histological and immunohistochemical observations of dedifferentiated leiomyosarcoma of the uterus.

A case of dedifferentiated leiomyosarcoma of the uterus was examined using immunohistochemistry. The tumor arose in the myometrium, and was a whitish large nodule with hemorrhage and necrosis. Histologically it was a well differentiated leiomyosarcoma with foci showing epithelioid pattern, and in part resembling malignant fibrous histiocytoma (MFH) and giant cell tumor (GCT). Additionally, small round neoplastic cells arranged in an alveolar manner, simulating alveolar rhabdomyosarcoma, were seen in some areas. Neoplastic cells in well differentiated areas expressed desmin, muscle-specific actin and LeuM1, whereas those in epithelioid and poorly differentiated areas lacked these antigens. Instead, tumor cells in epithelioid and small round cell areas were positive for keratin. Interestingly, most tumor cells in well differentiated, epithelioid and small round cell areas were also positive for MB1. However, tumor cells in GCT- and MFH-like areas reacted with none of the antibodies used. Ultrastructurally, some tumor cells possessed various amounts of microfilaments with or without dense patches, whereas others lacked them. These findings suggest that the divergent antigen expression was attributable to different levels of differentiation, and that poorly differentiated components had lost their native features.     

骨原发性上皮样血管肉瘤2例报道并文献复习

目的提高对骨原发性上皮样血管肉瘤(epithelioid angiosarcoma,EA)的认识,避免误诊。方法对2例原发于骨的EA进行临床病理、组织学及免疫组化分析,并进行文献复习。结果 2例均为男性,为骨组织内的多灶性、溶骨性病变,组织学上肿瘤主要由实性片状排列的上皮样细胞组成,瘤细胞核大,空泡状,含有明显核仁,可见细胞内空泡和血管腔样结构形成。免疫组化标记显示瘤细胞表达CD31、FⅧRAg、CK、vimentin。分别进行单纯化疗和手术治疗。1例失访,1例2个月后死亡。结论骨原发性EA是一种具有上皮样特征的高度恶性血管源性肿瘤,必须与转移癌等鉴别,CD31、CK等血管标记物对鉴别诊断具有重要的意义。     

Histological and Immunohistochemical Observations of Dedifferentiated Leiomyosarcoma of the Uterus

A case of dedifferentiated leiomyosarcoma of the uterus was examined using immunohistochemistry. The tumor arose in the myometrium, and was a whitish large nodule with hemorrhage and necrosis. Histologically it was a well differentiated leiomyosarcoma with foci showing epithelioid pattern, and in part resembling malignant fibrous histiocytoma (MFH) and giant cell tumor (GCT). Additionally, small round neoplastic cells arranged in an alveolar manner, simulating alveolar rhabdomyosarcoma, were seen in some areas. Neoplastic cells in well differentiated areas expressed desmin, muscle-specific actin and Leu Ml, whereas those in epithelioid and poorly differentiated areas lacked these antigens. Instead, tumor cells in epithelioid and small round cell areas were positive for keratin. Interestingly, most tumor cells in well differentiated, epithelioid and small round cell areas were also positive for MB1. However, tumor cells in GCT-and MFH-like areas reacted with none of the antibodies used. Ultrastructurally, some tumor cells possessed various amounts of microfilaments with or without dense patches, whereas others lacked them. These findings suggest that the divergent antigen expression was attributable to different levels of differentiation, and that poorly differentiated components had lost their native features. Acta Pathol Jpn 41: 466–472, 1991.     

Establishment and characterization of a novel human malignant peripheral nerve sheath tumor cell line,FMS-1, that overexpresses epidermal growth factor receptor and cyclooxygenase-2

Malignant peripheral nerve sheath tumor (MPNST) is a rare soft tissue sarcoma. We established a new human MPNST cell line (designated FMS-1) from MPNST of the right brachial plexus of a 69-year-old woman with NF1. The cell line has been maintained for >24 months with >100 passages. FMS-1 cells showed a fibrosarcoma-like or epithelioid pattern in the heterotransplanted tumor, compared with a fascicular growth pattern of short-spindle tumor cells in the primary tumor. Immunophenotypically, FMS-1 cells showed almost the same characteristics as the primary tumor. Cytogenetic and molecular analyses revealed a deletion in exons 5-8 of the p53 gene. Epidermal growth factor receptor (EGFR) and cyclooxygenase (COX)-2 were expressed in FMS-1 cells. To improve the highly aggressive course and poor prognosis and establish new therapeutic methods, molecular genetic and biological characterizations of MPNST are required. Thus, FMS-1 cells might be useful for investigating biological behaviors and developing new molecular-targeting antitumor drugs for MPNST expressing EGFR or COX-2.     

Ultrastructural and Immunohistochemical Study of Epithelioid Hemangioendothelioma of Bone: Coexpression of Epithelial and Endothelial Markers

Four cases of epithelioid hemangioendothelioma of bone—a borderline malignant tumor of vascular origin —were studied ultrastructurally and immuno histochemically. The epithelioid tumor cells were positive for vimentin, polyclonal and monoclonal cytokeratins, and the endothelial markers factor Vlll-related antigen (FVIII:RAg) and Ulex europaeus agglutinin I. The coexpression of polyclonal cyto keratin and FVIII:RAg was demonstrated by means of step sections in the same tumor cells. The endothelial origin of epithelioid tumor cells was supported ultrastructurally by identification of Weibel-Palade bodies.     

Superficial malignant peripheral nerve sheath tumor: a rare and challenging diagnosis

We reviewed the clinicopathologic features of 5 cases of malignant peripheral nerve sheath tumor (MPNST) manifesting in superficial locations associated with cutaneous neurofibromas (4 cases) or superficial peripheral nerve (1 case). Four cases had spindle cell morphologic features and were at least focally positive for S-100 protein, whereas the associated benign neural elements had more extensive S-100 immunoreactivity. The single epithelioid case was diffusely and strongly positive for S-100 protein. Melanoma markers, epithelial membrane antigen, glial fibrillary acidic protein, neurofilament, pancytokeratin (AE1/AE3), CD34, smooth muscle actin, and desmin were negative in all cases. There were no local recurrences, but 3 patients died of metastatic disease within 2 to 30 months (median, 21 months). MPNSTs can occur in a superficial location and may have an aggressive clinical course. Immunohistochemical markers are helpful in excluding other lesions in the differential diagnosis. However, identification of a benign precursor or origin from a nerve may be the most definitive way to properly classify these rare lesions.     

Malignant peripheral nerve sheath tumor. An immunohistochemical study of 62 cases

Malignant peripheral nerve sheath tumor (MPNST) commonly presents a diagnostic challenge and may resemble a variety of other soft tissue neoplasms microscopically. The authors have examined 62 examples of MPNST immunohistochemically, using antibodies to S-100 protein, myelin basic protein (MBP), and Leu-7, all of which are potential neural markers. Sixty-eight percent of all cases expressed at least one of these three determinants, representing a higher rate of immunoreactivity than that seen for single nervous system antigens in previous studies. Conjoint reactivity for S-100/Leu-7, S-100/MBP, and MBP/Leu-7 was seen in 34%, 34%, and 24% of cases, respectively. This coexpression of antigens is important, because none of them in isolation is immunospecific for nerve sheath tumors. In addition, stains for epithelial membrane antigen were reactive in two epithelioid tumors in this series, and eight spindle-cell neoplasms demonstrated desmin positivity. Analyses for cytokeratin, carcinoembryonic antigen, and Factor VIII-related antigen were negative in all cases. These results indicate an overlap between the immunocytochemical attributes of malignant peripheral nerve sheath tumors and other soft tissue sarcomas and emphasize the desirability of assessing multiple neural markers in such cases.     

Ganglioneuroblastoma in Yemenite chameleon (Chamaeleo calyptratus): the first recorded case of a tumor of neuroectodermal histogenesis in reptiles

Nerve tissue tumors are rarely encountered in reptiles and mainly represented by some documented cases of malignant peripheral nerve sheath tumor (MPNST). The paper is the first to describe a tumor mimicking MPNST by some ultrastructural features of tumor cells; however, significantly differing in the combination of immunohistochemical characteristics. Based on the data of electronic microscopy, immunohistochemistry, cytology, and histology, the tumor was classified as ganglioneuroblastoma. Since this nosological entity, unlike MPNST, cannot be assigned to a group of sarcomatoid tumors, the described pathology should be regarded as the first registered case of neuroectodermal histogenesis of tumors in reptiles.     

A case of fibroblastic low-grade malignant peripheral nerve sheath tumor--a true neurofibrosarcoma

The authors report a case of low-grade retroperitoneal malignant peripheral nerve sheath tumor (MPNST) showing Schwannian and fibroblastic differentiation in individual tumor cells. The tumor was detected in a 29-year-old male and posed diagnostic difficulty because of the unusual morphologic and immunophenotypic features. Morphologic examination of the H&E sections revealed a rather circumscribed, highly vascular, moderately cellular spindle cell tumor. The neoplastic cells were arranged in vague, short fascicles, distributed haphazardly amid hemangiopericytoma-like vascular channels, and showed occasional whorls. Myxoid stroma and keloid-like collagen bundles were frequently seen. There were satellite nodules outside the main tumor mass and low mitotic activity but no necrosis. The tumor cells stained strongly and diffusely for both S-100 protein and CD34. Electron microscopy revealed cells with processes and focal lamina, and prominent rough endoplasmic reticulum. Although the capacity of MPNST to exhibit divergent differentiation is well known, fibroblastic differentiation is generally poorly and inconsistently documented. The present case represents an unambiguous demonstration of the co-expression within individual tumor cells of Schwannian and fibroblastic differentiation in a low-grade MPNST. The literature on this subject is reviewed.     

Readers' Forum Smooth-Muscle-Type Myofilaments and Actin in Reactive and Neoplastic Nonmuscle Cells

The authors report a case of low-grade retroperitoneal malignant peripheral nerve sheath tumor (MPNST) showing Schwannian and fibroblastic differentiation in individual tumor cells. The tumor was detected in a 29-year-old male and posed diagnostic difficulty because of the unusual morphologic and immunophenotypic features. Morphologic examination of the H&;E sections revealed a rather circumscribed, highly vascular, moderately cellular spindle cell tumor. The neoplastic cells were arranged in vague, short fascicles, distributed haphazardly amid hemangiopericytoma-like vascular channels, and showed occasional whorls. Myxoid stroma and keloid-like collagen bundles were frequently seen. There were satellite nodules outside the main tumor mass and low mitotic activity but no necrosis. The tumor cells stained strongly and diffusely for both S-100 protein and CD34. Electron microscopy revealed cells with processes and focal lamina, and prominent rough endoplasmic reticulum. Although the capacity of MPNST to exhibit divergent differentiation is well known, fibroblastic differentiation is generally poorly and inconsistently documented. The present case represents an unambiguous demonstration of the co-expression within individual tumor cells of Schwannian and fibroblastic differentiation in a low-grade MPNST. The literature on this subject is reviewed.