Epithelioid Malignant Peripheral Nerve Sheath Tumor Research Articles

Epithelioid malignant peripheral nerve sheath tumor: A rare tumor with an unusual presentation in the ankle: A case report and literature review

Malignant peripheral nerve sheath tumor (MPNST) is a rare sarcoma with aggressive clinical zehavior. Epithelioid MPNSTs (EMPNSTs) are distinct and rare variant of MPNST. They are described by the World Health Organization and they account for <5% of these tumors and have unclear clinical behavior. Due to the rarity of the EMPNST and the overlapping features and similarity with other tumors exhibiting epithelioid cytomorphology, EMPNSTs impose a diagnostic challenge. Therefore, it is critical to be aware of this entity and other mimickers to reach the correct diagnosis. Hence, this is a case of a 45-year-old lady who presented with persistent left ankle swelling for 2 years. A biopsy was performed, which confirmed the diagnosis of EMPNST. The aim of reporting this case of this rare tumor with this presentation was to help both pathologists and orthopedic oncology surgeons to understand the behavior of this tumor and help differentiate it from mimickers, and enrich interested readers’ knowledge with the presented literature review.

Cytomorphologic Spectrum of SMARCB1-Deficient Soft Tissue Neoplasms.

The SWI/SNF complex core subunit SMARCB1 is inactivated in a variety of neoplasms that share characteristic "rhabdoid" cytomorphology. The aim of this study was to evaluate SMARCB1-deficient soft tissue neoplasms on cytology to identify diagnostic clues. Eleven SMARCB1-deficient tumors, including six epithelioid sarcomas, three malignant rhabdoid tumors, one epithelioid malignant peripheral nerve sheath tumor (MPNST), and one poorly differentiated chordoma with fine-needle aspiration (FNA), serous effusion, or touch prep (TP) from two institutions, were included. Targeted next-generation sequencing (NGS) was performed in two cases. Evaluation of FNA (n = 4), effusion (n = 4), and TP (n = 3) in nine adult and two pediatric patients demonstrated cellular samples (n = 11), epithelioid cells with rhabdoid morphology (n = 9), eccentrically located nuclei with prominent nucleoli (n = 7), and cytoplasmic bodies (n = 4); two patients were diagnosed on FNA with cell block. Immunohistochemistry (IHC) demonstrated SMARCB1 loss in all cases and keratin and/or EMA expression in all but the epithelioid MPNST; NGS identified SMARCB1 inactivation in both cases. SMARCB1-deficient soft tissue neoplasms comprise a variety of tumors with epithelioid morphology and frequent expression of keratin and/or EMA. Recognition of characteristic rhabdoid morphology on cytology can prompt IHC and/or NGS testing for SMARCB1 deficiency and help establish the diagnosis.

Epithelioid Malignant Peripheral Nerve Sheath Tumor (EMPNST) in Children: About A Case and Review of the Literature

Epithelioid Malignant Peripheral Nerve Sheath Tumor (EMPNST) in Children: About A Case and Review of the Literature

Clear Cell Sarcoma of the Premaxillary Soft Tissue: A Case Report

Abstract Casestudy: Clear cell sarcoma of soft tissue (CCSST) is a rare translocation-associated sarcoma which uncommonly presents in the head and neck region. Because the tumor expresses markers of melanocytic differentiation, it can be difficult to distinguish from malignant melanoma and epithelioid malignant peripheral nerve sheath tumor (MPNST), necessitating clinical correlation and ancillary testing specifically fluorescence in situ hybridization (FISH) for EWSR1 rearrangement. Here we report a case of CCSST involving the premaxillary soft tissue. A 61-year-old male without significant past medical history presented with a right premaxillary subcutaneous mass which was slowly enlarging over the course of three years. During surgical resection of the mass, the infraorbital nerve was noted to course into the tumor. Histologic sections revealed a 2.5 cm mass composed of a nodular proliferation of epithelioid tumor cells with pale eosinophilic to vacuolated cytoplasm, large vesicular nuclei with prominent nucleoli, areas of punctate necrosis, and a mitotic rate of 10 mitoses per 10 high power fields. Scattered multinucleated tumor giant cells were also present. No pigment was identified. By immunohistochemistry, the tumor cells were diffusely positive for SOX-10 and S-100 and negative for HMB45, MART1, MITF, inhibin, calretinin, p63 and smooth muscle actin. FISH was positive for EWSR1 rearrangement. Altogether, the morphologic, immunohistochemical and cytogenetic findings supported the diagnosis of CCSST. Because the surgical margins were negative for malignancy, the patient did not require additional surgery but will be receiving adjuvant radiation therapy. Although rare in the head and neck, CCSST should be considered in the differential diagnosis when dealing with an epithelioid soft tissue tumor that expresses any melanocytic markers, and a definitive distinction from malignant melanoma and epithelioid MPNST can be achieved by utilizing FISH for EWSR1 rearrangement.

Epithelioid Malignant Peripheral Nerve Sheath Tumor (Epithelioid-MPNST) Presenting as Bleeding Rectal Polyp: A Case Report with Systematic Literature Review

Case seriesPatient: Male, 65 • Female, 47Final Diagnosis: Epithelioid malignant peripheral nerve sheath tumorSymptoms: Bleeding per rectumMedication: —Clinical Procedure: —Specialty: PathologyObjective:Rare diseaseBackground:Malignant peripheral nerve sheath tumor (MPNST) with pure epithelioid histology MPNST (epithelioid-MPNST) is a distinctly rare variant of MPNST described by World Health Organization. Occurrence of MPNST in the tubular gut is extremely rare with nearly 20 cases reported in the last 40 years.Case Report:In this case report, we described 2 such cases of epithelioid-MPNST occurring in a 65-year male and 47-year-old female, who both presented with bleeding rectal polyps. We also report on our comprehensive systematic literature review.Conclusions:To the best of our knowledge, these are possibly the first two cases of pure epithelioid-MPNST at an unusual site. This needs to be differentiated from lesions more commonly encountered at the related anatomical site, such as malignant melanoma, poorly differentiated carcinoma, lymphoma, or even a gastrointestinal stromal tumor, by appropriate panel of antibodies.

Huge epithelioid malignant peripheral nerve sheath tumor in the left axilla: a case report.

This report describes a patient with a rare huge epithelioid malignant peripheral nerve sheath tumor (MPNST) in the left axilla. A male in his 70s was admitted to our hospital for evaluation of a growing tumor in his left axilla. The tumor was solid and immovable. Examination of a biopsy specimen resulted in a diagnosis of epithelioid MPNST. Two weeks after the biopsy was performed, the tumor grew to 20 cm and became painful, and the patient was unable to feel pressure on his upper arm. Immediately before surgery to remove the tumor, computed tomography suggested the presence of lung metastases. The patient and his family were informed of his disease state, and they elected surgical treatment to ease the symptoms associated with tumor enlargement. Systemic metastases appeared soon after the surgery, and the patient died within 11 weeks. Comparative genomic hybridization (CGH) analysis showed that this tumor was chromosomally unstable, with impairments in gene expression.

Epithelioid malignant peripheral nerve sheath tumor: clinicopathologic analysis of 63 cases.

Epithelioid malignant peripheral nerve sheath tumor (EMPNST) is rare and differs from conventional malignant peripheral nerve sheath tumor by showing diffuse S-100 protein positivity, infrequent association with NF1, and occasional origin in a schwannoma. Loss of INI1 expression is seen in a subset of tumors. The purpose of this study was to further define clinicopathologic features and outcome data in a large series of EMPNST. Sixty-three cases were identified in consultation files. The patient group consisted of 33 men and 30 women; the median age was 44 years (range, 6 to 80 y). One patient was reported to have NF1. One patient had 3 seemingly separate primary EMPNSTs during his 12-year clinical course. The median tumor size was 3.0 cm (range, 0.4 to 20 cm), and tumors were located most frequently on the lower extremity (30/63; 48%) and trunk (16/63; 25%). Most tumors were superficial (5 dermal, 38 subcutaneous); 15 were subfascial, and 5 were visceral. Microscopically, tumors comprised a relatively uniform but clearly atypical population of epithelioid cells. The majority of tumors demonstrated a multilobular growth pattern, with lobules and nests surrounded by myxoid and/or fibrous stroma. Tumor cells were round, polygonal, or ovoid and had round vesicular nuclei and abundant amphophilic to palely eosinophilic cytoplasm. Focal spindled morphology was seen in one third of cases. Most tumors (55/63; 87%) showed marked cytologic atypia with irregular vesicular nuclei and prominent nucleoli. Mitotic rate ranged from 1 to 46/10 HPF (median, 5/10 HPF); atypical mitotic figures were seen in 7 cases. Necrosis was present in 17 tumors. Twelve tumors were associated with a nerve. Nine tumors arose in a schwannoma (6 conventional type, 3 epithelioid) and 1 in a neurofibroma (in the NF1 patient). All tumors expressed S-100 protein, and the majority showed strong and diffuse staining (87%; 55/63). There was no expression of the melanocytic markers Mart-1/Melan-A (0/58), HMB-45 (0/57), and MiTF (0/9). Other immunohistochemical results included variable staining for GFAP (24/40; 60%) and EMA (4/29; 14%), whereas keratin was consistently negative (0/33). INI1 expression was lost in 67% of tumors examined (35/52). Most tumors were treated by surgical resection; 13 also received chemotherapy and/or radiation. Follow-up data were available for 31 cases and ranged in duration from 3 months to 20 years (median, 36 mo). Twenty-two patients have no evidence of disease at the time of follow-up. Nine patients developed local recurrence, 3 of whom were reported to be disease-free at the time of latest follow-up (44 mo, 19 y, and 20 y). Five patients developed distant metastases, and 4 patients died of disease (including 2 with unresectable recurrent tumors). Recurrence, metastasis, and disease-related death were observed independent of anatomic site or depth. In summary, EMPNST is a morphologically distinct variant that most commonly affects adults on the lower extremity or trunk, although a wide age range and site distribution are seen. Most tumors arise in superficial soft tissue, are diffusely S-100 positive, and two thirds show INI1 loss. On the basis of available follow-up information there is a comparatively low risk for recurrence and metastasis, irrespective of tumor depth.

Epithelioid malignant peripheral nerve sheath tumor: a case report and review of literature

Background Epithelioid malignant peripheral nerve sheath tumor (EMPNST) is a rare malignant soft tissue tumor, and is more common in adult male. EMPNST originates from nerve, mainly located in the limbs, head and neck, and spine. It is an aggressive tumor with high tendency for local recurrence, and about half of the cases appear distant metastasis. This paper aims to investigate the clinicopathological features of cervial EMPNST. Methods and Results A 48-year-old male mainly presented weakness of limbs, expecially left lower extremty with ankle swelling. MRI showed space-occupying lesion in segment C3-5, considering recurrence of intraspinal tumor 2 years after operation. Tumor resection, repairing of spinal dura mater and laminectomy were made from inion to C7 level. It was found during the surgery that most part of the tumor was located in front of C3-5 spinal nerve, left intraspinal and outside of dura mater. Because part of the tumor grew through the opening of titanium plate, the tumor could not be totally removed. According to postoperative histomorphological observation, tumor cells arranged in sheets or nests, and were separated by fibrous tissue. Most tumor cells were epithelioid, while small part of tumor cells were fusiform. Frequent mitotic activity was found, and part of the region appeared focal necrosis. Immunohistochemical staining showed that tumor cells were positive for pan cytokeratin (PCK), epithelial membrane antigen (EMA), vimentin (Vim), synaptophysin (Syn), chromogranin A (CgA), and S-100 protein (S-100); and were negative for actin, desmin (Des), progestrone receptor (PR), glial fibrillary acidic protein (GFAP), CD34, CD31 and HMB45; Ki-67 labeling index was above 25% . Reticular fiber staining showed that the epithelioid cell nests were surrounded by reticular fibers. Fluorescence in situ hybridization (FISH) detection showed negative for SS18 gene translocation. Combining with the history, the final pathological diagnosis was cervical EMPNST. Conclusion EMPNST lacks of morphological characteristics, and needs to be differentiated from a variety of benign or malignant tumors exhibiting epithelioid features. It is considered that clinical materials, morphological features and immunophenotype are helpful to avoid confusion with other similar lesions. S-100 is not a specific marker, but is a valuable diagnostic index. PCK and EMA can present strongly positive expression. doi：10.3969/j.issn.1672-6731.2013.11.008

Sporadic Superficial Diffuse Neurofibromas With Repeated Local Recurrence Over Many Years and a Tendency Toward Malignant Change

Sporadic superficial (cutaneous/subcutaneous) neurofibromas are normally small tumors that do not recur after excision or undergo malignant change. In contrast to this, I have encountered 3 cases in which a solitary sporadic superficial diffuse neurofibroma was large, recurred locally on multiple occasions extending over 30 years, and exhibited malignant change at least once. The first patient was a 44-year-old black woman who had a superficial diffuse neurofibroma with a focus of epithelioid malignant peripheral nerve sheath tumor (MPNST) excised from her left upper arm. The tumor recurred locally 14 times over a period of 38½ years; most specimens demonstrated only neurofibroma, but the 11th and 14th recurrences also had areas of epithelioid MPNST (extensive in the latter recurrence). There was no follow-up information after the last recurrence was excised except that the patient died of an unknown cause 3 years later. The second patient was a 39-year-old white woman who had a superficial neurofibroma excised from her scalp. A local recurrence was excised 30 years later and demonstrated a small focus of spindle cell MPNST in addition to neurofibroma. There were 6 further recurrences over the ensuing 14 years, of which the last 3 had components of spindle cell MPNST that extended into the skull bone and skeletal muscle. For these, radiotherapy was performed in addition to excision, and the patient had no evidence of tumor when last seen 1 year after the last recurrence was excised (she died 2 mo later of an unknown and presumably incidental cause). The third patient was a 28-year-old black woman who had a mass excised from her back that she was told was benign. A local recurrence was excised from the same area about 10 years later, again with a benign diagnosis (no details were available about these 2 specimens). Another recurrence was excised 36 years after the original excision; this demonstrated an extensive superficial diffuse neurofibroma with at least 2 small foci of spindle cell MPNST. A further recurrence was excised slightly >1 year later and showed superficial diffuse neurofibroma with some cellular areas but no definite MPNST. The patient was lost to follow-up after this. In addition to their diffuse infiltrative nature, a distinctive finding in the neurofibromas in all 3 cases was the presence of a focal to patchy lymphocytic chronic inflammatory infiltrate. Despite the difference in the character of the MPNST components (epithelioid in the first case, spindle cell in the other 2), the cases had sufficient histologic and clinical similarities to suggest that they represent a distinctive type of superficial neurofibroma.

Clinicopathological features of lymph node metastatic EMPNST: a case report and review of literatures

Background Mesenchymal malignancies prefer hematogenous spread, while epithelial malignancies tend to prefer lymphatic spread. However, mesenchymal malignancies occasionally generate lymphatic metastases. Objective To investigate the clinicopathological features of the epithelioid malignant peripheral nerve sheath tumor (EMPNST). Methods The clinical data, histopathological, histochemical and immunohistochemical features in one case of EMPNST with lymph node metastases were retrospectively analyzed, and the related literatures were reviewed. Results A 42 ⁃ year ⁃ old woman presented right upper arm and shoulder numbness with a right axillary nodule measuring 4 cm × 4 cm × 3 cm for 2 months. Type⁃B ultrasonic examination showed substantive lesions in right axillary which appeared to be a neurofibroma. CT scan showed soft tissue masses in right axillary with multiple enlarged lymph nodes were considered to be malignant lesions. MR image showed nodules in right armpit muscles were considered to be malignant tumor. The multiple nodules were identified in right axillary and the largest one was about 5 cm × 3 cm × 3 cm intraoperatively. The section of specimen was hard, gray⁃red and sallow in color with focal necrosis. The nodules were partly circumvoluted with blood vessel and without distinct border. The surrounding nerves were not obviously compressed. Microscopically, the structure of lymph node was damaged. The tumor invaded the surrounding fibrous connective tissue and adipose tissue with focal hemorrhage and necrosis. Tumor cells arranged in sheets, nests, and were separated by thin fibrous and blood vessels tissue. Most tumor cells were epithelioid. They were large in size with abundant cytoplasm. Cell border was indistinct, and the cytoplasm consisted of fine granules. Nuclei were invariably intensely hyperchromatic with coarse chromatin, and were vacuolated with prominent nucleoli in the center of the nuclei. Tumor cells showed frequent mitotic activity. Multinucleated giant cells and interstitial mucous degeneration were presented. Immunohistochemical staining showed that tumor cells were positive for S⁃100 protein, strong nuclear reactivity for Sox⁃10, and were positive for vimentin and Col⁃Ⅳ, and were negative for CK, CEA, EMA, Melan⁃A, CD56, CD3 and CD20. P53 positive revealed by 40% nuclear of tumor cells. Ki⁃67 labeling index was above 90%. Histochemical staining showed that the tumor cells were surrounded by reticular fibers. The patient had a medical history which recorded a tumor at the right wrist was removed in other hospital 8 years ago, and the wrist tumor recurred 5 years ago. The pathological diagnosis of the recurred wrist tumor was EMPNST with focal hemorrhage and necrosis. According to the history and the final pathological diagnosis, axillary tumor was diagnosed as lymph node metastasis of EMPNST in right axillary. Conclusion The metastasis of MPNST is mostly through the blood channel. This is the first case of the lymph node metastasis of EMPNST. In clinical work, it should be differentiated from other tumors with similar histopathology. DOI：10.3969/j.issn.1672⁃6731.2012.02.017

Advanced Epithelioid Malignant Peripheral Nerve Sheath Tumor Showing Complete Response to Combined Surgery and Chemotherapy: A Case Report

Malignant peripheral nerve sheath tumor (MPNST) is a rare high-grade soft tissue sarcoma. The epithelioid variant accounts for 5% or less of MPNSTs; the clinical behavior of this variant is unclear. Reports of approximately 40 cases are available in the English literature; however, most reports addressed clinicopathological features rather than therapeutic procedures or clinical courses. We describe a case of a 62-year-old male with an epithelioid MPNST of the left foot. Multiple lung metastases developed after radical surgery on the primary lesion. The response to adjuvant chemotherapy including doxorubicin and ifosfamide was favorable, and thoracoscopic resection was subsequently performed on the remaining three metastases. No evidence of recurrence or metastasis was observed at the 12-month followup after the first operation. Further followup and chemotherapy may be required.

Multicentric Malignant Peripheral Nerve Sheath Tumors of Small Intestine and Thigh: Report of a Case

Primary malignant peripheral nerve sheath tumor (MPNST) of the small bowel is an extremely rare disease. We report a multicentric MPNSTs of the left thigh and jejunum in a 59-year-old male, who visited our hospital twice in seven months because of a subcutaneous lump on the posterior aspect of the left thigh and life-threatening melena respectively. Laparotomy was performed for the small bowel tumor and a segment of the jejunum containing the tumor near its midportion was resected with end-to-end jejunojejunostomy. Histologically, the tumor which had been excised seven months previously was diagnosed as classical MPNST occurring in the left thigh, and that resected this time, as epithelioid MPNST occurring in the jejunum. Distant metastasis to multiple organs occurred one month after resection of the jejunal MPNST, and the patient died three months later. This is the first case of an MPNST arising in the small intestine reported in Taiwan.

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 neuroectodermal tumor with melanocytic and rhabdomyoblastic differentiation

Malignant melanoma can metastasize widely and vary significantly in its histological appearance; it rarely presents as a deep-seated mass without an obvious primary site elsewhere. Malignant peripheral nerve sheath tumor (MPNST) is a high-grade sarcoma characterized by conventional and epithelioid subtypes. MPNST can demonstrate heterologous differentiation, usually in the form of osteosarcomatous, chondrosarcomatous, or rhabdomyosarcomatous differentiation. MPNST does not harbor true melanocytic differentiation, although epithelioid MPNST typically is diffusely S-100 protein positive and superficially can resemble malignant melanoma. An unusual intra-abdominal mass was recently encountered with features of both melanoma and conventional or epithelioid MPNST containing a fascicular spindle cell component, an epithelioid component with melanocytic differentiation, as well as a rhabdomyosarcomatous component. The terminology “malignant neuroectodermal tumor with melanocytic and rhabdomyoblastic differentiation” is proposed to describe this neoplasm, reflecting the unusual concomittant lines of differentiation as well as offering a possible rationale for nosologically challenging aspects of this neoplasm.

Epithelioid malignant peripheral nerve sheath tumor. Report of a case with inflammatory infiltration

The epithelioid malignant peripheral nerve sheath tumor (EMPNST) is a rare sarcoma originating from the supportive non-neuronal components of peripheral nerves. Our patient was a 75-year-old Japanese man who presented with complaints about pain and a mass in the left thigh. Characteristic histopathological features were large epithelioid-like cells closely resembling a malignant melanoma or another type of soft tissue tumor. Notable infiltration of neutrophils in the tumor was seen. Immunohistochemically, the tumor cells proved positive for S-100, NSE, GFAP, MBP, chromogranin A and synaptophysin, and negative for CEA, keratin, HMB-45, G-CSF, and GM-CSF. Tumor-related inflammatory infiltration may be caused by an autonomous production of some cytokines. However, these tumor cells were negative for G-CSF and GM-CSF so that the mechanism triggering inflammatory infiltration is unclear. Electron microscopy revealed the presence of an extracellular basal lamina, intermediate cell junctions, and numerous dense-cored granules in the cytoplasm. These findings suggested a schwannian derivation, consistent with the diagnosis of EMPNST. There have been reports on S-100 positivity and HMB-45 negativity of this tumor type, but to the best of our knowledge, this is the first description of an EMPNST positive for MBP, chromogranin A, and synaptophisin. Where unequivocal features are lacking, these markers might be useful for differential diagnosis.

Immunohistochemical Diagnosis of a Rare Case of Epithelioid Malignant Peripheral Nerve Sheath Tumor with Multiple Metastases

The epithelioid variant of malignant peripheral nerve sheath tumor (MPNST) is a rare tumor with poor prognosis that sometimes involves the head and neck. The diagnosis is based principally on the histological examination, and it is generally very difficult to reach the correct diagnosis. An 84-year-old Japanese woman presented with a tumor mass of 2 week's duration in the right medial canthal region. Although the tumor was excised surgically, metastases occurred three times on her face and head, and the patient died of distant systemic multiple metastases. In the histopathological analysis, the tumor showed a composite pattern comprising spindle or polygonal cells arranged in irregular bands, and a population of larger epithelioid cells in solid sheets and nests. In the immunohistochemical analysis, the tumor cells were positive for S-100 protein, vimentin, and nerve growth factor receptor (NGFR), and negative for cytokeratin and HMB 45 (melanoma-associated antigen). These findings confirmed the diagnosis of MPNST. Epithelioid MPNST has complex histopathological findings and histopathological features similar to other epithelioid tumors, especially malignant melanoma. Immunohistochemical examination using NGFR and HMB-45 is important in the differential diagnosis.

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.

Expanding the spectrum of malignant change in schwannomas: epithelioid malignant change, epithelioid malignant peripheral nerve sheath tumor, and epithelioid angiosarcoma: a study of 17 cases.

Schwannomas (neurilemmomas) rarely undergo malignant change, most often in the form of either malignant peripheral nerve sheath tumor (MPNST) or angiosarcoma. We characterize the clinical features and the histopathologic spectrum of 17 schwannomas with evidence of malignant change. The study group comprised 7 males and 10 females with an age range of 16 to 76 years, (median, 40 yrs). None of the patients had neurofibromatosis. Lesions ranged in size from 0.6 to 10.5 cm (median, 4.0 cm) and arose mainly in the limbs/limb girdles (7 cases) or head and neck region (7 cases). All tumors contained areas of conventional benign schwannoma. Four cases of pure epithelioid malignant peripheral nerve sheath tumor (EMPNST) were identified, three of which showed immunopositivity for S-100 protein. Four angiosarcomas were identified, predominantly epithelioid-type. Ten schwannomas had an appearance that we have designated epithelioid malignant change (EMC) and, in one of these, EMC coexisted with EMPNST. Large epithelioid cells with abundant eosinophilic cytoplasm, vesicular chromatin, and prominent nucleoli (morphologically similar to cells of EMPNST) were distributed throughout the schwannoma--singly, in clusters, and in one case a microscopic nodule of such cells was also present. These large epithelioid cells were strongly positive for S-100 protein. Although follow-up data so far are limited, 1 of 5 patients with EMC in whom meaningful follow up was available developed repeated local recurrence (median follow up, 21 mos), one patient each with EMPNST and angiosarcoma died of local and metastatic disease. Pure EMPNST is rare; however, we confirm the tendency of MPNST to show epithelioid cytomorphology when arising in a benign schwannoma. We also confirm the distinctive (albeit infrequent) tendency of angiosarcoma to arise in schwannomas. We describe EMC in schwannomas and suggest that this represents a putative precursor lesion of EMPNST. At this time, we do not have an explanation for the tendency of schwannomas to show epithelioid cytomorphology when they undergo malignant change.

Cytologic Features of Malignant Peripheral Nerve Sheath Tumor

To study the cytomorphologic features of malignant peripheral nerve sheath tumor (MPNST), including the epithelioid cell variant, and to establish differential diagnostic features with benign neurogenic tumors and other sarcomas. Cytologic smears from primary, recurrent and metastatic tumors in 10 patients with MPNST were reviewed. Three patients had neurofibromatosis 1 (NF1), and in two others the tumor arose from a preexisting neurofibroma. Immunocytochemical evaluation of S-100 protein was performed in four cases. A complete pathologic study was available in all cases. To assess the validity of morphologic recognition, a blinded study, including eight cases of spindle MPNST among smears from histologically proven schwannomas, synovial sarcomas, leiomyosarcomas, malignant fibrous histiocytomas and liposarcomas, was performed. Neurogenic differentiation was recognizable in four cases (differentiated), while the other four (anaplastic) were indistinguishable from other pleomorphic sarcomas. The presence of elongated, slender, often wavy nuclei and less commonly a delicate, fibrillary metachromatic stroma were features suggestive of nerve sheath differentiation. Other cytologic, as well as clinical, features permitted their identification as malignant. Two cases of epithelioid MPNST disclosed large, polygonal to plasmocytoid tumor cells without specific cytologic features. S-100 immunoexpression was positive in two of the four cytologic samples tested. Although no morphologic findings are specific to MPNST, the above-mentioned cytologic features may suggest, in differentiated cases, its neurogenic differentiation. On the basis of morphologic features alone, the diagnosis of anaplastic and epithelioid MPNST is not possible, and immunocytochemical and ultrastructural studies are necessary. A specific cytodiagnosis is possible in recurrences, metastases and cases of NF1 or a preexisting neurofibroma.