Multicentric fibromyxoid peripheral nerve sheath tumor (multicentric schwannoma) in a dromedary camel (Camelus dromedarius): morphopathological, immunohistochemical, and electron microscopic studies.

During postslaughter inspection of a 4-year-old male dromedary camel (Camelus dromedarius), numerous small nodules to large masses up to 4 cm in diameter were found on the serosal surfaces of forestomachs, large intestines, mesentery, liver, and spleen. Grossly, the masses were discrete, round, smooth, and white to gray that bulged from the serosal layer. Cut surfaces of the masses were discrete, round, white, and relatively homogeneous without any necrotic foci. Histopathologically, the masses were encapsulated and composed of a mixture of round and spindle-shaped cells in loose whorls of neoplastic cells with small elongated hyperchromatic wavy nuclei and a small amount of pale eosinophilic, poorly defined cytoplasm. Masson's trichrome staining showed mild amounts of collagen fibers forming an irregular, loose stroma. In immunohistochemistry, immunoreactivity for the Schwann cell marker (S100) was diffusely positive in the neoplastic cells. The immunoreactivity for CK, c-kit, and CD34 were negative. Ultrastructural examination confirmed the tumor was entirely formed of neoplastic Schwann cells. On the basis of the histopathological, immunohistochemical, and ultrastructural findings, the tumors were diagnosed as multicentric fibromyxoid peripheral nerve sheath tumor (multicentric schwannoma). This tumor has not been previously recorded in camel worldwide.

An atypical peripheral nerve sheath tumour with pseudoglandular architecture in a dog.

This case describes a subcutaneous soft tissue tumour in a German Shepherd dog. Histologically, the lesion was characterized by proliferating ovoid cells, loosely arranged in a collagenous to myxoid stroma, and by numerous pseudoglandular structures lined by neoplastic cells. Immunohistochemically, neoplastic cells were labelled with vimentin, glial fibrillary acidic protein and S100 antibodies, but not with cytokeratin, desmin and smooth muscle actin antibodies. Ultrastructurally, neoplastic cells were characterized by numerous mitochondria surrounded by endoplasmic reticulum and contained few secondary lysosomes. This tumour was diagnosed as a subcutaneous peripheral nerve sheath tumour (PNST) with pseudoglandular architecture. This case illustrates the morphological diversity of PNST and provides new insight into the differential diagnosis of cutaneous tumours of similar morphology in the dog.

Hybrid peripheral nerve sheath tumor of the nasal cavity showing schwannomatous, neurofibromatous, and perineuriomatous areas.

Soft tissue hybrid peripheral nerve sheath tumors (PNST), including schwannoma-perineurioma or neurofibroma-perineurioma, have recently been described. However, there are no reports on hybrid PNST arising in the nasopharyngeal area. In this article, we report such a case. A 58-year-old Japanese man presented with nasal obstruction and was found to have bilateral polypoid lesions in the middle meatus of the nose. Subsequently, nasal polypectomy was performed. Histologically, the tumor consisted of three components including schwannoma, neurofibroma, and perineurioma. Immunohistochemically, schwannoma, neurofibroma, and perineurioma components were positive for S-100 protein, CD34, and epithelial membrane antigen, respectively. In conclusion, this is the first case of hybrid PNST reported to occur in the nasopharyngeal area. Pathologists should be aware of the possibility that hybrid PNST may present outside soft tissue.

[Extracranial meningioma: morphological and histogenetical aspects and relations with perineurioma].

The clinicomorphological, immunohistochemical, and ultrastructural characteristics of 11 cases of extracranial meningioma versus 79 soft tissue perineuriomas were studied. There were significant similarities (cell morphology, immunoprofile, ultrastructural features of perineurial differentiation) of both entities. Considering the point of view that arachnoid and perineurial cells are anatomically, embryologically, and functionally related, it is most possible that extracranial meningiomas may be derived from perineurial cells (or their progenitor cell) rather than from displaced arachnoid cells.

Malignant peripheral nerve sheath tumor of the uterine cervix expressing both S-100 protein and HMB-45.

A 50-year-old woman presented with a large cervical polypoid mass. Grossly, the mass occupied a substantial proportion of the cervical canal, measuring 6 cm. Histologically, the mass showed a spindle cell malignancy arranged in large fascicles that penetrated deeply into the fibromuscular wall of the cervix. The spindle cells were immunoreactive for both S-100 protein and HMB-45 antigen, but were negative for Melan-A. Electron microscopy showed that cytoplasmic processes of the spindle to oval tumor cells contained microtubules and were lined by basal lamina and abundant intercellular collagen spacing with no melanosomes in any stage. As far as we are aware, this is the ninth reported case of cervical malignant peripheral nerve sheath tumor (MPNST), and the second reported case of MPNST expressing HMB-45 antigen.

Diffusion-weighted imaging of retroperitoneal malignant peripheral nerve sheath tumor in a patient with neurofibromatosis type 1.

We present the diffusion-weighted imaging (DWI) findings for a malignant peripheral nerve sheath tumor arising in a retroperitoneal plexiform neurofibroma in a patient with neurofibromatosis type 1. Signal intensity of the malignant area was high on DWI and low on the apparent diffusion coefficient map and differed from findings for the benign area. DWI enabled clear differentiation between malignant and benign areas of the tumor.

Benign schwannoma with perineurioma-like areas: A clinicopathologic study of 11 cases.

Eleven schwannomas are described. All tumors were well demarcated and surrounded by a true capsule or pseudocapsule and manifested Antoni A and Antoni B areas, Verocay bodies, and hyalinized vessels. In addition to typical schwannoma, there were clear cell areas composed of spindled cells arranged either in parallel sheets or in loops within the myxoid matrix, morphologically identical to retiform (reticular) perineurioma. The Schwann cells in the conventional schwannomatous areas displayed typical ultrastructural features. Those comprising the perineurioma-like areas revealed a primitive morphology. They were slender or polygonal and were devoid of an external lamina, pinocytic vesicles, or junctions. These findings suggest that the perineurioma-like areas consist of primitive or modified Schwann cells, or, alternatively, these perineurioma-like areas represent true, but incomplete perineurial differentiation within otherwise ordinary benign schwannomas. These neoplasms represent a morphologic variant of schwannoma having distinctive perineurial-like areas, a pattern which may elicit diagnostic difficulties.

Description of a neural sheath tumor of the trigeminal nerve: immunohistochemical and electron microscopy study.

CONTEXT: Malignant neural sheath tumors of the trigeminal nerve affecting the nasal cavity and the paranasal sinuses are extremely rare. With conventional optical microscopy, their identification is difficult, and it is necessary to confirm them by means of electron microscopy and immunohistochemical techniques. CASE REPORT: The patient was a 41-year-old woman with a ten-month progressive history of pain followed by painful edema in the left facial region, and with symptoms of bleeding, secretion and nasal obstruction. Studies with imaging methods suggested the presence of an expansive process in the left nasal and paranasal cavities. In the biopsy, the histopathological findings from optical microscopy were suggestive of a tumor of neural origin in the trigeminal nerve. Immunohistochemical and electron microscopy studies confirmed that it was a malignant tumor of the neural sheath of the trigeminal nerve. We describe the clinical, radiological, and histological features of this tumor and review the literature.

[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.

[Perineuriomas and other tumors with perineurial differentiation].

This is a review of the literature on the peripheral nerve sheath tumors with perineural differentiation. The authors provide an overview of the clinicopathological, immunohistochemical, ultrastructural, and genetic features of these neoplasms. Emphasis is laid on various morphological variants of perineurioma (intraneural, retifrm, sclerosing, plexiform, atypical, malignant, etc.) and so-called hybrid tumors (schwannoma-perineurioma, neurofibroma-perineurioma).

Intestinal perineuriomas: clinicopathologic definition of a new anatomic subset in a series of 10 cases.

Benign peripheral nerve sheath tumors are uncommon in the gastrointestinal tract, and perineuriomas have not previously been reported to occur at this anatomic location. In this study, we analyzed the clinicopathologic and immunohistochemical features of 10 perineuriomas arising in the intestine. Eight patients were female and 2 male (median age, 51 years; range, 35-72 years). Eight of the lesions were intramucosal perineuriomas presenting as small sessile polyps detected during colonoscopy; 6 of these 8 patients were asymptomatic and undergoing colorectal cancer screening. The remaining 2 cases were submucosal masses, one each located in the colon and jejunum. Of the mucosal polyps, six were located in the rectosigmoid or sigmoid colon and one each was detected in the descending colon and transverse colon. The polyps ranged from 0.2 to 0.6 cm (median, 0.4 cm) in greatest dimension. The colonic and jejunal masses measured 3 cm and 4.5 cm, respectively. Histologically, the intramucosal perineuriomas were composed of uniform bland spindle cells having ovoid to elongated nuclei and pale indistinct cytoplasm, with no cytologic atypia, pleomorphism, or mitotic activity. The lesions had a fine collagenous stroma, demonstrated irregular borders with the adjacent lamina propria, and entrapped colonic crypts. Five cases exhibited hyperplastic changes in the adjacent or entrapped epithelium. The colonic submucosal tumor was microscopically well circumscribed, whereas the jejunal perineurioma showed focal infiltration through the muscularis propria into the subserosa. The stroma was collagenous in the colonic tumor and predominantly myxoid in the jejunal tumor. The spindle cells in the submucosal perineuriomas demonstrated tapered nuclei and elongated bipolar cytoplasmic processes. All tumors except one were positive for epithelial membrane antigen (EMA); 4 of 10 expressed claudin-1 and 2 of 10 expressed CD34. All tumors were negative for S-100 protein, glial fibrillary acidic protein, neurofilament protein, smooth muscle actin, desmin, caldesmon, KIT, and pan-keratin. Electron microscopy was performed on the tumor lacking EMA expression, revealing typical features of perineurioma, namely, spindle cells with long bipolar cytoplasmic processes and prominent pinocytotic vesicles, surrounded by discontinuous basal lamina. Clinical follow-up was available for 4 patients (median, 34 months; range, 8-53 months). No tumor recurred. In summary, perineuriomas may arise in the intestine, most often as intramucosal lesions detected as colorectal polyps with distinctive histologic features including entrapment of colonic crypts. Distinguishing perineuriomas from other spindle cell neoplasms of the gastrointestinal tract can be facilitated by immunostaining for EMA and claudin-1.

Perineurial malignant peripheral nerve sheath tumor (MPNST): a clinicopathologic, immunohistochemical, and ultrastructural study of seven cases.

Most malignant peripheral nerve sheath tumors (MPNST) are schwannian in nature. The pathologic features of MPNST with perineurial cell differentiation remain to be characterized. To determine the clinicopathologic, immunohistochemical, and ultrastructural characteristics of perineurial MPNST, 121 MPNST from the Mayo Clinic Tissue Registry were examined. Of these 23 spindle cell tumors with long processes disposed in whorls or storiform patterns, features typical of perineurioma, were studied. On the basis of immunohistochemistry (epithelial membrane antigen+/S-100-), 5 perineurial MPNST were identified among 23 tumors selected. These and two previously characterized perineurial MPNST are the subject of this study. None of seven tumors was associated with NF-1. Patients included five males and two females ranging in age from 11 to 83 years (mean, 45.7 years). The tumors measured 1.5 to 30 cm (mean, 9.1 cm) and arose in the extremities (two), trunk (two), face (one), mediastinum (one), and retroperitoneum (one). Only one tumor was nerve associated (phrenic nerve). All tumors were surgically removed. No encapsulation or neurofibroma components were noted. Necrosis was seen in three lesions. Four tumors were classified as high-grade malignant and three as low grade. Mitotic indices varied from 1 to 85/10 high-power fields (median, 16). Immunoreactivities included epithelial membrane antigen (100%), vimentin (100%), Leu-7 (57%), and CD34 (14%). Stains for S-100 protein, muscle markers, and cytokeratin were nonreactive. Ultrastructurally, perineurial-like cells were noted in three tumors and cells intermediate between perineurial and Schwann cells in one. Four tumors recurred and two metastasized; no deaths of disease were noted at follow-ups of 28 to 98 months (mean, 66.9). In conclusion, 4% of MPNST show perineurial cell differentiation. An NF-1 association has yet to be described. Nerve involvement is infrequent. Their immunophenotype (epithelial membrane antigen+/S-100-) frequently indicates ultrastructural perineurial differentiation. The prognosis of perineural MPNST appears to be more favorable than that of conventional MPNST.

A case of von Recklinghausen's disease with bilateral pheochromocytoma-malignant peripheral nerve sheath tumors of the adrenal and gastrointestinal autonomic nerve tumors.

A 48-year-old man with neurofibromatosis type 1 presented with chest pain, paroxysmal hypertension, tachycardia, and progressive respiratory insufficiency. Clinical investigation displayed calcified tumors in the anterior mediastinum and pararenal region. Histological examination at autopsy revealed composite tumors consisting of pheochromocytoma and malignant peripheral nerve sheath tumor (MPNST) at two sites: the left adrenal gland and the region surrounding the inferior vena cava, probably corresponding to the right adrenal gland. The MPNST component showed a varied histological appearance, including hyalinized bands with polygonal cells, a cartilaginous and myxoid stroma, a hemangiopericytomatous architecture, and a fibrosarcomatous structure, which suggested osteosarcoma, chondrosarcoma, angiosarcoma, and fibrosarcoma, respectively. In addition, based on the ultrastructural findings, the gastrointestinal tract was involved with mesenchymal tumors showing neurogenic differentiation. These lesions suggest the divergent cellular differentiation of neural crest-derived cells to mesenchymal elements as well as neuroectodermal neoplasms.

Malignant peripheral nerve sheath tumor of the pleura with epithelial and rhabdomyoblastic differentiation: report of a case clinically simulating mesothelioma.

A primary malignant peripheral nerve sheath tumor (MPNST) of the pleura that clinically mimicked a malignant mesothelioma in a 57-year-old man is described. Histologically, the tumor had features similar to those described in cases of the so-called epithelioid MPNST. A unique finding in this case was the demonstration of keratin expression in the epithelioid component of the tumor, as well as the presence of rhabdomyoblasts. This is the first example of an MPNST with heterologous elements arising in the pleura. Immunohistochemical and ultrastructural studies were important in differentiating this tumor from other malignancies with sarcomatoid and epithelioid features involving the pleura.

A new human malignant peripheral nerve sheath tumour-cell line, HS-sch-2, harbouring p53 point mutation.

Only a few human malignant peripheral nerve sheath tumour (MPNST)-cell lines have been reported, and their characteristics have not been fully established. In this study, we established a new human cell line, HS-Sch-2, from an MPNST of the ordinary type which arose in a 54-year-old woman without von Recklinghausen's disease. This cell line was characterized by chromosome analysis, immunohistochemistry, ultrastructural examination, and direct sequencing of the p53 gene. The HS-Sch-2 cells have grown for more than 48 months in vitro, and exhibited hypotriploid karyotypes with complex chromosome abnormalities lacking a specific pattern. Histological features of the heterotranplanted nude mouse tumours were essentially the same as those of the original MPNST, with positive reactions for S-100 protein and neuron-specific enolase but not for epithelial membrane antigen, fibronectin or CD34. Ultrastructural examination in vivo revealed intricate interdigitation of long cytoplasmic processes and basal lamina-like structures. In addition, direct sequencing of the p53 gene detected a point mutation from CGT to CAT at codon 273 in exon 8. This HS-Sch-2 cell line, which exhibits distinctive morphological characteristics of MPNST and a p53 point mutation, will be useful for biological and pathological investigations of MPNST.

Role of electron microscopy in the evaluation of soft tissue neoplasms, with emphasis on spindle cell and pleomorphic tumors.

The current significant role of transmission electron microscopy in the evaluation of soft tissue tumors when correlated with conventional histological and immunohistochemical studies is discussed for the following entities: myxofibrosarcoma, storiform-pleomorphic fibrosarcoma (malignant fibrous histiocytoma), and myofibrosarcoma; dermatofibrosarcoma protuberans; hemangiopericytoma; monophasic synovial sarcoma; extrarenal rhabdoid tumor; soft tissue perineurioma; and gastrointestinal stromal tumors, notably the so-called autonomic nerve variant.

Differential diagnosis of non-epithelial tumors of the pancreas: malignant non-epithelial pancreatic tumor with focal pigmentation.

Non-epithelial tumors only rarely affect the pancreas. In this report, we describe a malignant non-epithelial tumor with combined characteristics of malignant peripheral nerve sheath tumor (MPNST) and malignant melanoma. To more closely define the differential diagnosis of MPNST with focal pigmentation versus metastatic melanoma resembling MPNST, the tumor was investigated using histomorphology, immunohistochemistry, electron microscopy, and comparative genomic hybridization. As a result, from these analyses and from clinical findings, the diagnosis of a pancreatic MPNST with focal pigmentation was favored. However, the diagnosis of a malignant melanoma or a composite tumor could not be definitely ruled out, due to the considerable morphological and genotypical overlap between both entities, which can be explained by the close histogenetic relationship between both tumor entities.

Intra-osseous soft tissue perineurioma of the inferior alveolar nerve.

This report describes an intra-osseous perineurioma affecting the inferior alveolar nerve, the second at this site, of a 53-year-old man. It produced a well defined, partially corticated, round radiolucency associated with resorption of the root apices of 36 and 37. Histology showed a circumscribed, partially encapsulated cellular tumour composed of bland spindle cells with undulating nuclei and indistinct cell membranes arranged in interlacing fascicles. The tumour was strongly positive for epithelial membrane antigen, collagen IV and laminin, with only scattered S100-positive cells and lack of CD34 expression. Electron microscopy showed elongated cells with continuous external laminae of basement membrane-like material, subplasmalemmal densities, desmosome-like junctions, and variable numbers of micropinocytotic vesicles. The lesion was surgically excised and in 9 months there has been no recurrence.

Comparative ultrastructural and immunohistochemical study of perineurioma and neurofibroma of the oral mucosa.

In the course of assessing the cellular composition of intraoral neurofibroma (NF), we encountered a unique gingival tumor of putative perineurial (PN) origin. The lesion showed the ordinary light microscopic NF pattern, but the ultrastructural features of well-differentiated PN cells as well as an epithelial membrane antigen (EMA)-positive, S-100 protein-negative immunoprofile confirmed the diagnosis of soft tissue perineurioma (STP). In our small series of NF, there were three ultrastructural subtypes: Type I (common Schwann cell type), Type II (NF with a high content of PN cells) and Type III (predominantly fibroblastic NF), although inhomogeneous and overlapping assembly of cellular elements. A significant number of tumor cells in Type II showed the substantial reactivity for EMA, whereas many CD34-positive cells were noted in Type III. The present results confirm previous findings that PN lineage is an important constituent in the formation of NF and reinforce the value of electron microscopy in the diagnosis of peripheral nerve sheath tumors.