Malignant peripheral nerve sheath tumors of the buttock and lower extremity. A study of 43 cases

Using strict clinical and pathologic criteria for the inclusion of cases, the authors have reviewed the clinicopathologic features of 43 malignant peripheral nerve sheath tumors of the buttock and extremity seen over a 35-year period. Twenty-three (53%) of the patients had neurofibromatosis (VRN), whereas 20 (47%) did not. Fifty-one percent of the patients were women. The mean age at presentation was 36 years for patients with VRN and 44 years for patients without VRN. A nerve of origin was identified for 72% of the cases and an associated neurofibroma for 44% (65% with VRN and 20% without VRN). The mean greatest dimension of the tumors was 12.3 cm, and this did not differ significantly between the two groups. The predominant histologic pattern in 86% of the tumors was that of tightly packed spindle cells in an interlacing and woven pattern; heterologous sarcomatous elements were noticed in 12% of the cases. Surgical resection was the main modality of treatment for all patients; 65% also received adjuvant therapy. Follow-up evaluation was done in every case. An unexpected finding was the absence of a significant difference in survival rates between patients with and without VRN. Overall, 63% of the patients died of tumor: 65% of the patients with VRN and 60% of the patients without VRN. Large tumor size and high mitotic rate (greater than 20 per 10 high-power fields) portended a poor prognosis, as did the need for resection by amputation. Adjuvant radiation therapy and chemotherapy did not affect survival rates.     

Malignant peripheral nerve sheath tumors in childhood

Summary Malignant peripheral nerve sheath tumor (MPNST) is an uncommon sarcoma in the pediatric population; however, its presence should be considered in a child with an enlarging or painful soft-tissue mass. Diagnosis of this neoplasm depends on either the demonstration of its origin within a peripheral nerve or the association with a contiguous neurofibroma. We have identified 16 cases of MPNST involving children 16 years of age or less, which represent 12.8% of the total cases seen at the Mayo Clinic. Most of the lesions arose in children with von Recklinghausen's disease and were associated with a contiguous neurofibromatous component. The mean survival of patients who were known to have died of tumor was only 1.8 years. This sarcoma requires prompt aggressive therapy utilizing wide surgical excision. Because of the association of MPNST with von Recklinghausen's neurofibromatosis, a careful workup and family history should be obtained for the potential prognostic value and for the purpose of genetic counseling.     

Malignant peripheral nerve sheath tumors of the head and neck: A clinicopathological study

Twenty-seven cases of malignant peripheral nerve sheath tumors involving the head and neck region over a period of 7 years were reviewed. They were graded from 1–3 based on necrosis, mitosis, cellularity, and pleomor-phism. Mean age of occurrence was 42 years, with a range of 12–70 years. Male preponderance was noted (M:F = 3.5:1). The most common site of involvement was the neck (44.6%). The main presenting symptom was an enlarging mass. The nerve of origin could be identified in 33% of patients. Treatment consisted of wide excision. The 5-year observed survival was 33%. Fifty-two percent of patients developed local recurrence of disease. Fifteen percent of patients died due to advanced local disease within 18 months of treatment. Distant metastasis was seen in 18.5% of patients. Lymph node metastasis was not seen. At the end of 5 years 15% of patients remained disease free. Large tumor size (>5 cm) adversely affected the prognosis (P = < 0.1). No significant correlation was noted between the grade of tumor and survival. © Wiley-Liss, Inc.     

Malignant peripheral nerve sheath tumors associated with neurofibromatosis type 1

We report 4 cases of malignant peripheral nerve sheath tumors (MPNST) with neurofibromatosis type 1 (NF1). Mean age was 29.5. Two of them had a family history. Three of them were male. All of them had enlarging mass and pain in the background of neurofibromas. Locations were popliteal, thigh and forearm. The masses were greater than 5 cm in diameter in each case. In two cases the mass was showing continuity with a nerve. One patient had a nonossifying fibroma as well as a MPNST. Wide excision and radiotherapy were applied to three of the patients. One of them did not take any therapy after surgical resection. Two of the patients died of lung metastases after a mean period of 12.5 months. In a majority of NF1 patients MPNST emerges from a preexisting neurofibroma. The patients with NF1 are at greatest risk for developing sarcomas, so they should be followed closely.     

Malignant peripheral nerve sheath tumours associated with von Recklinghausen's neurofibromatosis.

AIMS: A retrospective study was conducted of patients with von Recklinghausen's neurofibromatosis who developed malignant peripheral nerve sheath tumours to determine their clinical characteristics, treatment outcome and prognostic factors. METHODS: During the period 1987-1995, 29 patients with von Recklinghausen's neurofibromatosis (VRN) were seen at the Royal Marsden Hospital, of whom 23 had malignant peripheral nerve sheath tumours (MPNSTs). RESULTS: The median age of the patients with MPNSTs was 30 years and the sex distribution was equal. The commonest site was the lower extremity, with a tendency for tumours to occur in the proximal parts. A nerve of origin was identified in 59% of the tumours and heterologous differentiation was present in 26%. Multiple primary MPNSTs occurred in four patients (17%) and other malignant tumours developed in three (13%). The overall 5-year survival was 35% with a median survival of 36 months. The incidence of local recurrence was 38% and 75% of them occurred within 2 years. CONCLUSIONS: MPNSTs which develop in association with VRN occur in a younger age group, tend to be of a higher histological grade and are associated with a very poor prognosis. Tumour size > or = 10 cm (P=0.003) and high tumour grade (P=0.003) were adverse independent prognostic factors for overall survival.     

Malignant peripheral nerve sheath tumor of proximal third tibia

A 16-year-old man had aswelling over the anterior aspect of the proximal third of the tibia for 1 year, which was peanut size initially and progressively increased to its present size of 10 cm × 8 cm. He underwent fine needle aspiration cytology (FNAC) twice during this period and reported aspindle cell sarcoma. Malignant peripheral nerve sheath tumor (MPNST) is a malignancy of the connective tissue surrounding the nerves. Previously, MPNST was also known as neurofibrosarcoma, malignant schwannoma, andneurogenic sarcoma. We are reporting this case for its rarity and peculiar mode of presentation. FNAC/core biopsy can be used as an effective tool to achievethe correct pathological diagnosis.     

Cytogenetic findings in malignant peripheral nerve sheath tumors

Clonal chromosome aberrations were detected in 8 short-term cultured malignant peripheral nerve sheath tumors (MPNST). Seven had a near-triploid chromosome number and I was in the hyperhaploid-hypodiploid range. No recurrent structural rearrangements were found; the bands most frequently involved (3 tumors) were 7p11, 12p13 and 14q11. The most common numerical changes were loss of a sex chromosome (all tumors) and loss of at least 1 copy of chromosomes 8, 16 and 22 (4 tumors). Pooling our data with those on the 20 previously published MPNST with abnormal karyotypes, we found that the chromosome number has often been in the triploid range (12 tumors), with stem line variation between 34 and 270. All chromosome arms, except 22p and the Y chromosome, were involved in recombinations. The most frequently rearranged bands were 7p22 (6 tumors) and 1p21, 7p11 and 14q11 (5 tumors each). Most numerical and unbalanced structural aberrations have led to loss of genetic material, in particular from Xq26-qter (13 tumors); 11q22-qter and 13p (12 tumors); 9p22-pter, 11p13-pter, 17p and 17q11-21 (11 tumors); 1p22-32 and 1p34-pter (10 tumors) and 6q25-qter and chromosome 16 (9 tumors). © 1995 Wiley-Liss, Inc.     

Malignant peripheral nerve sheath tumor: analysis of treatment outcome

Purpose: To analyze the results of therapy for malignant peripheral nerve sheath tumor (MPNST) and to identify prognostic factors of survival, and of local and distant control of disease.Methods and Materials: From 1975 through 1993, 134 MPNSTs were diagnosed and treated at our institution. Tumor sites included extremities in 36 (27%) cases and non-extremities in 98 (73%). Median follow-up for survivors was 53 months (range: 7–280). There were 14 tumors of histologic grade I disease (10%), 43 of grade II disease (32%), 43 of grade III disease (32%), and 32 of grade IV (24%). Seventy-three patients (54%) underwent radiation therapy (RT) as part of their initial treatment of the primary tumor, including 14 (10%) who had brachytherapy and 16 (12%) who had intraoperative electron irradiation (IOERT) as part of their radiation course.Results: The 5- and 10-year survival rates were 52% and 34%, respectively. Local and distant failure rates at 5 years were both 49%. On univariate analysis, prognostic factors significantly related to survival (log-rank: p < 0.05) included tumor size, location of disease, history of neurofibromatosis type 1 (NF-1), history of prior irradiation, surgical margin status, use of IOERT or brachytherapy, disease stage, histologic grade and tumor subtype, as well as mitotic rate and the presence or absence of necrosis. On multivariate analysis, only history of prior irradiation (p = 0.023), and surgical margin status (p = 0.0044) remained significant. For local control of disease, univariate analysis showed location of disease, surgical margin status, history of NF-1, history of prior irradiation, mitotic rate, radiation dose ≥ 60 Gy, and use of IOERT or brachytherapy to be significant prognostic factors. On multivariate analysis, only surgical margin status (p = 0.0024), RT dose (p = 0.021), and use of IOERT or brachytherapy (p = 0.016) remained significant. For distant control of disease, significant prognostic factors on univariate analysis included tumor size, stage, tumor grade, mitotic rate, presence or absence of necrosis, and histologic subtype. On multivariate analysis, tumor size (p = 0.0065), grade (p = 0.036), and histologic subtype (p = 0.001) remained significant. Patients with perineurial MPNSTs had a much lower rate of distant metastasis and a better overall survival as compared with other histologic subtypes.Conclusion: Management of patients with MPNST involves a multi-modality approach. The goal of surgery is complete resection with negative margins. Adjuvant irradiation to doses ≥ 60 Gy and the inclusion of IOERT or brachytherapy are associated with improved local control of disease.     

Diagnosis of peripheral nerve sheath tumors around the pelvis

OBJECTIVE: To distinguish between benign and malignant peripheral nerve sheath tumors around the pelvis. METHODS: A retrospective study of 30 patients with benign and malignant peripheral nerve sheath tumors located around the pelvis was performed. Clinical, imaging and histological features of 19 benign and 11 malignant peripheral nerve sheath tumors around the pelvis were reviewed retrospectively. RESULTS: Nearly all patients exhibited pain at presentation in cases involving both benign and malignant tumors. Although tumor size, duration of symptoms and presence of sensory disturbance possessed little value in differential diagnosis, severe motor weakness was observed exclusively in patients presenting with malignant tumors. On CT or MRI, central enhancement was apparent in 11 of the 19 benign tumors; in contrast, central enhancement was evident in one of the 11 malignant tumors. Fine needle aspiration cytology was performed in 11 tumors; correct diagnosis was achieved in four tumors. Core needle biopsy was performed in five tumors, all of which were correctly diagnosed with no neurological deficits. Immunohistochemically, all benign tumors were diffusely positive for S-100 protein, whereas malignant tumors were negative or focally positive for S-100 protein. Ki-67 index was less than 4% in all benign tumors; additionally, this index was 7-36% in malignant tumors. CONCLUSION: Central enhancement pattern on imaging studies strongly suggests a benign tumor; in contrast, severe motor weakness suggests malignant lesions. Core needle biopsy was reliable with respect to preoperative diagnosis.     

Genetics of neurofibromatosis 1-associated peripheral nerve sheath tumors

Neurofibromatosis 1, an inherited disorder that affects 1/3500 individuals worldwide, predisposes to the development of benign and malignant peripheral nerve sheath tumors. The disorder results from inactivation of one of the NFI genes. The second NFI gene is typically inactivated in Schwann cells during tumor formation. This article reviews the different types of genetic alterations in NFI in both constitutional and tumor tissues and genetic alterations of other genes that may affect tumorigenesis. These studies have provided insight into the genetic basis of both the variable expression of the disorder and of benign and malignant peripheral nerve sheath tumorigenesis.     

Malignant fibrous histiocytoma of jaws. A clinicopathologic study of 11 cases

Malignant fibrous histiocytoma (MFH) of the jaws is a highly malignant tumor that recurs, metastasizes, and usually causes death despite aggressive surgical therapy. This clinicopathologic review looks at five patients with MFH of the maxilla and six with MFH of the mandible. Five male and six female patients ranged in age from 12 to 75 years (mean, 35.4 years). All patients had large lytic areas of bone destruction, often with soft tissue extension. Two cases were postirradiation sarcomas, one of the maxilla and the other of the mandible. All patients underwent surgery and eight patients received chemotherapy when disease recurred locally or metastasized. Seven patients had local recurrences 3 to 13 months following surgery, and six patients had distant metastases. Of the 11 patients, 7 died of their disease, 1 died of unknown causes, and another with extensive local disease was lost to follow-up after 1.7 years. Two patients with recurrent disease are alive at 18 and 27 months postoperatively.     

Malignant peripheral nerve tumors: a clinicopathological and electron microscopic study

Sixteen cases of malignant peripheral nerve tumors that wererecorded in the files of the Department of Orthopedics, NationalCancer Center Hospital, Tokyo, between 1972-July 1983 were studiedclinicopathologically. The patients' ages ranged from 24–51years, and both sexes were affected equally. Histologically,in 13 cases of nerve sheath tumors the tumors were spindle-celltype, two of these patients had manifestation of multiple neurofibromatosis(von Recklinghausen's disease). One malignant epithelioid schwannomawas found to arise from the tibial nerve. Other two cases wereof primitive neuro-ectodermal tumors (primary malignant peripheralneuroblastoma) which showed rosette formation. The common primarysymptoms in all patients were a noticeable mass which increasedin size over a variable period of time, with or without associatedpain and tenderness. Ultrastructural findings of spindle-celltype (in 7 tumors examined) and epithelioid type (1 tumor) showedevidence of Schwann cell differentiation of the tumors in allcases. Immunohistochemically, by the PAP method (Sternberger), stainingfor S-100 protein was positive in 3 of 14 tumors. Ultrastructuralfindings in two S-100 protein-positive cases showed evidenceof Schwann cell differentiation better than the S-100 protein-negativecases, such as pronounced interdigitation of cytoplasmic processes,presence of fibrous long-spacing collagen and well-developedbasal lamina. Local recurrence occurred in nine patients, and metastasis wasfound in five. The total 5-year survival rate was 58.5%. Tumorsassociated with multiple neurofibromatosis and primary peripheralneuroblastmas had the worst prognosis. Complete removal of thetumor by means of wide excision as primary treatment seemedto be the most important factor in decreasing the morbidityand mortality rates.     

枕骨恶性外周神经鞘膜瘤1例报道

恶性外周神经鞘膜瘤（malignant peripheral nerve sheath tumors,MPNST）又称为恶性神经鞘瘤、恶性施万细胞瘤（ma-lignant schwannoma）、神经纤维肉瘤（neurofibrosarcoma）或神经源性肉瘤（neurogenic sarcoma）,是一种较少见的来源于神经软组的织恶性肿瘤。恶性外周神经鞘瘤50％发生在躯干,30％发生在四肢,头颈部大约占20％,颅部发生率较低,多起源于三叉神经或听神经［1］。本文报告我科近期收治的1例发生在枕骨的恶性外周神经鞘膜瘤,现报道如下。     

Malignant histiocytosis and related tumors. A clinicopathologic study of 42 cases using cytological, histochemical and ultrastructural parameters

Light and electron microscopical, immunohistochemical and clinical characteristics in 42 cases of malignant neoplasms, arising from true histiocytes, are described. These were separated in a lymphoma-like subtype, called true histiocytic lymphoma (29 patients) and a disseminated variant, called malignant histiocytosis (9 patients). In addition 4 related histiocytic tumors are discussed, including 2 tumors arising from interdigitating cells. Sinus pattern and cytologic features, especially 'window' nuclei, are emphasized as diagnostic criteria. Erythrophagocytosis was not a constant finding. Electron microscopic features, presence of acid phosphatase, acid alpha-naphthylacetate esterase, lysozyme, alpha 1-antitrypsin, alpha 1-antichymotrypsin, Ia-antigen and absence of B- and T-cell markers, were important in establishing the histiocytic nature or excluding a non-histiocytic tumor. A distinct male predominance existed (male:female = 2.5:1) with a higher relapse free period in females (p = 0.032). A high number of mitotic figures appeared to be a favourable sign, p = 0.020 and 0.019, for remission rate and relapse free period respectively. The degree of cell differentiation and the immunohistochemical pattern did not show a correlation with remission and relapse free period. Extranodal involvement and the presence of short profiles of endoplasmic reticulum were prognostically unfavourable signs. True histiocytic lymphomas showed a higher remission rate (p = 0.041) and relapse-free period (p = 0.017) than malignant histiocytosis.     

Mucinous tumors of the ovary. A clinicopathologic study of 70 cases

Seventy cases of mucinous ovarian tumor were reviewed. All patients were followed for a minimum of 5 years. Clinicopathologically, three groups were defined: (1) mucinous cystadenoma, which demonstrated no nuclear stratification and no stromal invasion (15 cases); (2) mucinous tumor of uncertain malignant potential, which was characterized by nuclear stratification of two to three layers and no stromal invasion (21 cases); and (3) mucinous carcinoma, which showed stromal invasion and/or nuclear stratification in excess of three layers (34 cases; 15 with invasion, 19 without). All patients with mucinous cystadenomas remained tumor-free after initial surgery. Two patients with mucinous tumors of uncertain malignant potential died of tumor at 55 and 72 months, respectively, whereas 18 with mucinous carcinomas died after intervals ranging from 2 to 71 months. All mucinous tumors of uncertain malignant potential were Stage I at presentation. Twenty-one mucinous carcinomas were Stage I (six tumor deaths), one was Stage II (tumor death), ten were Stage III (nine tumor deaths), one was Stage IV (tumor death), and one was of uncertain stage (tumor death). Patients with mucinous carcinomas having stromal invasion demonstrated poorer survival (10 of 15 dead) than those with mucinous carcinomas lacking this finding (8 of 19 dead); however, stromal invasion was related to higher stage (5 with invasion Stage I; 16 without invasion Stage I).     

Malignant peripheral nerve sheath tumors: Prognostic impact of rhabdomyoblastic differentiation (malignant triton tumors), neurofibromatosis 1 status and location

Purpose

The purpose of this study was to assess the impact of rhabdomyoblastic differentiation [malignant triton tumors (MTT)], neurofibromatosis 1 (NF1) status and location on the outcome of malignant peripheral nerve sheath tumors.

Methods

In this IRB-approved, HIPAA-compliant retrospective study medical records of 84 patients with pathologically confirmed MPNST from 1999 to 2011 were retrospectively reviewed. Patient and tumor characteristics including size, location, NF1 status, absence or presence of rhabdomyoblastic differentiation (MPNST versus MTT, respectively), recurrence and metastatic patterns and outcomes were evaluated.

Results

Of 84 patients, 62 were MPNST and 22 were MTT. MTT occurred in older patients than MPNST (50 years versus 40.7 years, p = 0.04) and were larger (12.3 cm versus 8.1 cm, p = 0.01). While there was no difference between the location, rate of recurrent or metastasis disease, and metastatic pattern between MTT and MPNST groups, MTT had shorter metastasis-free interval (median, 1 month versus 9 months, p = 0.02) and shorter survival (median, 10 months versus 43 months, p < 0.0001). NF1 status, while associated with earlier diagnosis (mean age, 35.1 years versus 46.5 years, p = 0.008), had no impact on rate of MTT or on prognosis. Patients with primary in the torso had shorter survival than those with extremity primary (median, 15 months versus 47 months, p = 0.0004). Multivariate analysis using the Cox proportional hazard regression model yielded age (p = 0.029), size (p = 0.0001), presence of rhabdomyoblastic differentiation (MTT) (p = 0.001), and location in the torso (p = 0.01) as independent predictors of survival.

Conclusions

Among patients with malignant peripheral nerve sheath tumors, rhabdomyoblastic differentiation (MTT) and location in the torso are associated with poor prognosis. NF1 status has no impact on the prognosis.