Low grade malignant peripheral nerve sheath tumor with mesenchymal differentiation: a case report

Malignant peripheral nerve sheath tumor (MPNST) is an uncommon neoplasm. Rarely, MPNST may display focal mesenchymal differentiation and this is more frequently encountered in high than low grade lesions. Here we present an example of a low grade MPNST with osteoid, cartilaginous and probably smooth muscle components occurring in the subtemporal fossa of a 26-year-old male patient with no associated neurofibromatosis type 1. The tumor exhibited diffuse S-100 protein expression, whereas immunostainings for epithelial membrane antigen and smooth muscle actin were positive in a portion of neoplastic cells.     

Actin expression in neural crest cell-derived tumors including schwannomas, malignant peripheral nerve sheath tumors, neurofibromas and melanocytic tumors

Tumors that originate from neural crest-derived cells represent a heterogeneous group of neoplasms including benign and malignant tumors with melanocytic and schwannian differentiation. The immunophenotype of these tumors is well known but little is known about the expression of smooth muscle/myofibroblastic markers in these tumors. A total of 590 neural crest-derived tumors (50 benign schwannomas, five malignant peripheral nerve sheath tumors, 80 neurofibromas, 240 nevocytic nevi, 115 primary melanomas, and 100 melanoma metastases) were studied with respect to α-smooth muscle actin and muscle-specific actin expression. α-Smooth muscle actin and muscle-specific actin-positive tumor cells with a co-expression of S-100 protein were found in one benign schwannoma, one primary cutaneous melanoma, and four melanoma metastases. Four of these cases were examined ultrastructurally, but typical actin filaments with focal densities were not found in any of the four. Other immunohistochemical markers examined including desmin, h-caldesmon and smooth muscle myosin heavy chain were negative in the tumor cells. The present results suggest that neural crest-derived tumors could show expression of α-smooth muscle actin on rare occasion.     

Myofibroblastic tumor of soft tissue displaying desmin-positive and actin-negative immunophenotypes

Myoflbrobiasts have ultrastructural and functional characteristics Intermediate between fibroblasts and smooth muscle cells. Previous studies Indicated that most myoflbroblasts express actin and vlmentin but not desmln Immunophenotypes. Two benign Intramuscular myoflbroblastic tumors which displayed a desmin-positive and actin-negative immunophenotype are reported. The tumors occurred on the back of a 45 year old man who had neurofibromatosls 1 and the thigh of a 37 year old man without neurofibromatosis. Both tumors were encapsulated and composed of short intersecting bundles of spindle cells in a collagenous background. Although the tumors were cellular, nuclear pleomorphism was minimal and mitotic figures were rare. Characteristically, most tumor cells were Immunoreacttve strongly for desmin and vlmentln but gave negative staining for muscle-specific actin, α-smooth muscle actin, α-sarcomeric actin, myosin, S-100 protein, cytokeratins, and CD34. On electron microscopy, the tumor cells were characterized by short spindle-indented nuclei, abundant cytoplasmic intermediate filaments, prominent piasmalemmal pinocytosis and frequent cell coverage by basal lamina. Aggregation of thin myofilaments with focal condensations was identified occasionally. Although the tumors showed distinct morphological and immunohistochemical features enabling delimitation from other soft tissue lesions, they may overlap histologically with myoflbrobiastoma of the breast, lymph node and soft tissue, low grade malignant nerve sheath tumor, lelomyosarcoma, cellular schwannoma, inflammatory flbrosarcoma and nodular fasciitis.     

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.     

Histopathologic,immunohistochemical and ultrastructural features of a granular cell tumour in an Australian parakeet (Melopsittacus undulatus)

An adult male Australian parakeet (Melopsittacus undulatus) presented a firm nodular lesion in the lateral metacarpal region of the right wing. Microscopically, there were neoplastic cells, round and polyhedral in shape, with abundant, slightly eosinophilic granular cytoplasm; they were strongly periodic-acid Schiff-positive and resistant to diastase digestion. Some groups of neoplastic cells were immunopositive for smooth muscle actin and desmin. There was no immunopositivity for S-100 protein, CD68 and cytokeratin. Ultrastructurally, the neoplastic cells were round and polygonal in shape, and they were characterized by abundant cytoplasm with numerous homogeneous osmophilic bodies covered by an electron-dense membrane (lysosomes). The histopathologic, immunohistochemical and ultrastructural features of the neoplastic tissue are consistent with a granular cell tumour, which has been described in different animal species and anatomic locations; however, this seems to be an infrequent neoplasm in Australian parakeets. The immunopositivity of the neoplastic cells for smooth muscle actin and desmin, as well as slight positivity for muscle with Masson's trichrome, suggest that this is a tumour of myogenic origin.     

Intraosseous epithelioid malignant peripheral nerve sheath tumor of the phalanx. Case report

We report the first case of intraosseous epithelioid malignant peripheral nerve sheath tumor (MPNST) occurring in the phalanx. The patient was a 50-year-old Japanese man with an intramedullary lytic lesion of the proximal phalanx. Microscopically, the tumor was composed of epithelioid cells or polygonal cells, forming large cell nests with central necrosis. Most tumor cells were diffusely and strongly immunopositive for S-100 protein and vimentin, and negative for cytokeratin, epithelial membrane antigen, carcinoembryonic antigen, alpha-smooth muscle actin, and HMB-45. Laminin-positive material was discontinuously demonstrated between the individual tumor cells. Electron microscopy showed prominent external lamina. Our case indicated that laminin is useful for differentiating epithelioid MPNST from metastatic carcinoma and malignant melanoma.     

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.     

Low-grade fibromyxoid sarcoma

A low-grade fibromyxoid sarcoma arising in the thigh of a 16-year-old Japanese girl is described. The patient had a well-circumscribed mass measuring 3.5 cm in its greatest diameter within her left vastus medialis muscle and a 6-month history of pain. Microscopically, the tumour was not encapsulated and filtrated into adjacent skeletal muscle. The tumour was characterized by poor to moderate cellularity, a proliferation of bland-appearing spindle tumour cells, and alternating fibrous and myxoid areas with a whorled pattern of the tumour cells. Neither cellular atypia nor mitotic figures were observed. There was no tumour necrosis. Immunohistochemically, the tumour cells were diffusely and strongly positive for vimentin and desmin. Some cells contained alpha smooth muscle actin. They were uniformly negative for CAM5.2, epithelial membrane antigen, muscle-specific actin (HHF35), factor-VIII-related antigen, S-100 protein, neurofilament, CD34, and CD31. The tumour had a diploid DNA content with S-phase fractions of 6.6% by flow cytometry. The patient was alive with no evidence of disease 11 months after excision.     

Chondromyxoid fibroma: a tumor showing myofibroblastic, myochondroblastic, and chondrocytic differentiation.

Chondromyxoid fibroma (CMF) is a rare primary benign tumor of bone that demonstrates variable histologic features and is often confused with chondrosarcoma. Although the chondroid elements in CMF have been reported to be S-100 protein positive and to have chondrocytic features ultrastructurally, the immunohistochemical and ultrastructural profile of CMF, especially with respect to the peripheral nonchondroid elements, has not been extensively studied. Formalin-fixed, paraffin-embedded tissue from 10 CMFs were stained immunohistochemically with antibodies to vimentin, desmin, muscle actin, smooth muscle actin, S-100 protein, and CD34. Six tumors were also examined ultrastructurally. The chondroid areas showed variable staining for S-100 protein but did not stain for muscle actin or smooth muscle actin. The peripheral areas surrounding the chondroid areas stained diffusely for smooth muscle actin and muscle actin but did not stain for S-100 protein. CD34 highlighted the extensive vascularity that was especially prominent in the peripheral areas; no tumor cells stained for CD34. There was no staining for desmin. Ultrastructural examination showed three different cell types. Some cells showed the classic features of chondrocytes, other cells had the features of myofibroblasts, and the third cell type had the features of both chondrocytes and myofibroblasts ("myochondroblasts"). These findings support the conclusion that CMF is a tumor showing myofibroblastic, myochondroblastic, and chondrocytic differentiation.     

Ossifying fibromyxoid tumor may express CD56 and CD99: a case report

Ossifying fibromyxoid tumor (OFMT) is an uncommon soft tissue neoplasm characterized by a combination of myxoid and/or fibrous stroma with areas of ossification. Although most authors postulate a neuroectodermal origin for this peculiar tumor, there is no agreement in the literature regarding its histogenesis. In this article, we present the immunohistochemical findings of a case of a 39-year-old white male with an OFMT of the soft tissue in the mandibular region. The tumor was positive to S-100 protein, glial fibrillary acidic protein, CD99, CD56 and negative to smooth muscle actin, cytokeratins AE1/AE3, epithelial membrane antigen, and CD68. To the best of our knowledge, this is the first case reported to be positive to CD56 and CD99. Immunoreactivity to these two antibodies, together with reactivity for S-100 protein and glial fibrillary acidic protein, suggests that OFMT is of a neuroectodermal origin. In our opinion, in the absence of reactivity to at least one neuroectodermal marker one should seriously question a diagnosis of OFMT.     

Perivascular epithelioid cell tumor of the uterus: immunohistochemical, ultrastructural and molecular study

A case of perivascular epithelioid cell tumor of the uterus is reported, occurring in a 32-year-old woman. The tumor (8.0 cm in dimension) showed exophytic growth from the outer half of the myometrium. Histopathologically, the tumor was composed of thick blood vessels and perivascular epithelioid cells. The neoplastic cells were strongly immunoreactive for HMB45 antigen, CD117 (c-kit), vimentin and the progesterone receptor, but completely negative for S-100 protein, smooth muscle actin, desmin, CD34, the estrogen receptor and p16. The Ki-67 labeling index was low (1.25%). Ultrastructurally, the neoplastic cells had numerous premelanosomes with some glycogen deposits. Single-stranded DNA conformational polymorphism of p53 and methylation-specific polymerase chain reaction of p16 revealed negative results. Definite melanosomes on electron microscopic analysis and coexpression of HMB45 antigen and stem cell factor receptor (CD117) may provide the clue to understanding perivascular epithelioid cell tumor because angiomyolipoma also coexpresses HMB45 antigen and CD117.     

Aschoff bodies of rheumatic carditis are granulomatous lesions of histiocytic origin

The histogenesis of the Aschoff body of rheumatic carditis is controversial. Proliferative Aschoff bodies in heart sections from 6 patients with acute rheumatic heart disease were tested by avidin-biotin peroxidase labeling methods for the presence of desmin, muscle-specific actin, S-100, neurofilament, leukocyte common antigen, receptor for Ulex europeus I lectin, Factor VIII-related antigen, vimentin, alpha 1-antichymotrypsin, and myeloid/histiocyte antigen. Lack of Aschoff body labeling for desmin and muscle-specific actin, S-100 and neurofilament, and Ulex europeus I and Factor VIII-related antigen is not consistent with histogenesis from smooth or striated cardiac muscle, nerve or nerve sheath, and lymphatic or vascular endothelium, respectively. Strong labeling of Aschoff body cells for vimentin is evidence for a mesenchymal origin, and labeling for myeloid/histiocyte antigen is consistent with a histiocytic origin. Furthermore, weak, variable labeling of Aschoff body cells for leukocyte common antigen suggests that at least some Aschoff body cells were originally derived from blood-borne monocytes. Both multinucleated Aschoff cells and "owl's eye," Anitschkow cells label identically, suggesting a common origin. Alpha 1-Antichymotrypsin, a widely utilized marker of histiocytes, was unexpectedly negative. Perhaps histiocytes that form Aschoff bodies do not express this lysosomal enzyme. Aschoff bodies appear to be a unique and distinctive form of granuloma.     

Cellular ‘neurothekeoma’: an epithelioid variant of pilar eiomyoma? Morphological and immunohistochemical analysis of a series

Cellular neurothekeoma is a recently recognized benign cutaneous neoplasm, which is currently regarded as being of nerve sheath origin and is thought to represent a variant of conventional neurothekeoma (dermal nerve sheath myxoma). Nine new cases presenting predominantly in adolescents or young adults are described. Morphologically they were characterized by short fascicles or small nests of palely eosinophilic epithelioid or spindle-shaped cells which ramified in an ill-defined manner between dermal collagen bundles. Myxoid matrix was absent or sparse. Scattered normal mitoses and multinucleate giant cells were often present. Immunohistochemically all nine cases were strongly NK1/C3 positive, seven were weakly NSE positive and three were smooth muscle actin positive. Staining for S-100 protein, PGP 9.5, epithelial membrane antigen and desmin was negative in all cases. In view of its distinctive architecture and immunophenotype, both of which are totally different from conventional neurothekeoma, it is proposed that cellular 'neurothekeoma' is a separate discrete entity which may represent an epithelioid variant of pilar leiomyoma.     

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.     

Malignant peripheral nerve sheath tumor with rhabdomyoblastic differentiation and glandular component

An exceptional case of malignant peripheral nerve sheath tumor with striated muscle differentiation and glandular component is reported, in a 52-year old man. This tumor measured 8 cm in diameter, and was localized in the chest wall, infiltrating the skeletal muscle. The mesenchymal portion of the tumor was composed mostly of spindle cells arranged in interlacing fascicles. Between these fascicles, there were large cells with abundant eosinophilic cytoplasm and clear elongated nucleus. Immunohistochemical study demonstrated cytokeratin, EMA and CEA expression in the glandular component and S100 protein expression in the major portion of the mesenchymal component. The large cells identified as rhabdomyoblasts, expressed desmin, myoglobin, alpha-SR actin and alpha-SM actin. The tumor recurred 5 years after its resection. Histological and immunohistochemical features were identical. We think that positivity of neoplastic striated muscle cells with alpha-SM actin reflects an early differentiation phase of these cells.     

Gastric fibromyxoma, a distinct entity of pure fibroblastic tumor--an ultrastructural study

A rare case of fibromyxoma arising in the stomach of a 78-year-old male is presented. A well-defined, encapsulated tumor measuring 27x17x8 cm showed a lobular growth in the submucosa and muscularis propria, with no association with the propria mucosa. Histologically, the tumor was characterized by a diffuse, widely spaced proliferation of small spindle, stellate and round cells with dendritic outlines with fibromyxoid stroma. Neither cellular atypia nor mitotic figures were observed. Immunohistochemically, the tumor was positive for vimentin and CD34 but negative for CD117, alpha-smooth muscle actin, muscle actin, desmin and S-100 protein. Ultrastructurally, the tumor cells had irregularly shaped nuclei and cytoplasm containing moderate amounts of mitochondria, rough endoplasmic reticulum, subplasmalemmal densities, and short interdigitating processes. These findings indicated the fibroblastic nature of the tumor. The patient was well without recurrence 20 months after surgery. It is important to recognize that gastric fibromyxoma is a distinct entity and to include it in the differential diagnosis of gastric mesenchymal tumors, as the tumors show a different clinical behavior and as limited surgery with local excision is possible.     

An immunohistochemical study of the mesenchymal and epithelial components of pulmonary chondromatous hamartomas

Twenty-five cases of solitary pulmonary chondromatous hamartomas (PCH) were examined by immunohistochemistry to evaluate the mesenchymal and epithelial components. PCH composed of predominantly mature cartilage were designated as C type, those predominantly composed of fibromyxoid tissue as FM type, and those predominantly composed of adipose tissue as A type. FM type PCH revealed various amounts of cartilage in various developmental stages, adipose tissue and fibromyxoid tissue, compared with a uniform pattern of cartilage tissue in C type. The cells of transitional form between spindle cells, stellate cells and chondrocytes were present in FM type. Epithelial components in PCH were bronchial, bronchiolar and cuboidal cells, mostly at the periphery of PCH. S-100 protein consistently stained chondrocytes, stellate and spindle cells in the fibromyxoid tissue of solitary PCH. Fibroblast growth factor was immunolocalized to chondrocytes, spindle and stellate cells in the fibromyxoid tissue. The collagen type was associated with differentiation from primitive mesenchymal cells to chondrocytes (i. e. type I and III collagen appeared in fibromyxoid matrix and type II collagen in the cartilaginous matrix). Fibronectin coordinately appeared with type I and III collagens. The proliferating cell nuclear antigen labeling index of epithelial cells was comparable to those of neoplastic mesenchymal cells, but it was not significantly different between C type and FM type PCH. The primitive mesenchymal cells in the bronchial walls of the control premature neonates were also observed. This immunohistochemical study showed that the progenitor mesenchymal cells in the bronchial and bronchiolar walls may differentiate along chondrocytes, lipocytes, and smooth muscle cells in PCH and that epithelial proliferation is reactive and closely associated with neoplastic proliferation of the mesenchymal component.     

Alveolar soft part sarcoma: immunological evidence of rhabdomyoblastic differentiation

Two cases of alveolar soft part sarcoma have been studied immunocytochemically using antisera against epithelial membrane antigen, lysozyme, keratins, S-100 protein, desmin, vimentin, fetal myosin, slow myosin, alpha-skeletal muscle actin, alpha-smooth muscle actin and myoglobin. The neoplastic cells were negative with all antisera employed with the exception of the alpha-skeletal muscle actin antiserum which stained the cytoplasm of numerous neoplastic elements, including the crystalloid rods, typical cytoplasmic inclusions of these tumours. It is suggested that the presence of this protein indicates rhabdomyoblastic differentiation of these tumours.     

Ossifying fibromyxoid tumor: Report of a case with cytomorphologic description

Ossifying fibromyxoid tumor (OFMT) is a rare soft tissue neoplasm with uncertain histogenesis. Most cases behave in a clinically benign fashion; however, a small percentage of tumors may locally recur or metastasize. Herein we present a case of a 56‐year‐old man who presented with an enlarging left groin mass, left inner thigh numbness, burning paresthesia and discomfort in his left groin. The mass sampled by fine‐ needle aspiration and needle core biopsy. Cytology showed bland‐appearing epithelioid cells with round nuclei and fine chromatin, with fragments of fibromyxoid stroma in the background. Immunohistochemical stains performed on the core biopsy showed that the lesional cells were focally positive for S100 protein and negative for desmin, smooth muscle actin, CD34 and cytokeratin AE1/AE3. A benign neoplasm was favored with ossifying fibromyxoid tumor as the main entity in the differential diagnosis. A subsequent resection showed a well‐circumscribed 5 cm mass with firm consistency and focal areas of calcifications. Histologically, the tumor had a nodular growth pattern with relatively bland spindle cells containing round to oval nuclei suspended in a variably collagenous to myxoid stroma. Significant ossification and bone formation was also noted. There was no significant atypia, necrosis or increased mitoses. Ossifying fibromyxoid tumors have distinct cytologic features and should be considered in the differential diagnosis of soft tissue tumors with prominent ossification. Diagn. Cytopathol. 2015;43:646–649. © 2015 Wiley Periodicals, Inc.