Case Of Malignant Peripheral Nerve Sheath Tumor Research Articles

Malignant Peripheral Nerve Sheath Tumour in a Patient of Type 1 Neurofibromatosis

Malignant peripheral nerve sheath tumours (MPNST) constitute a rare type of soft tissue sarcoma which arises from peripheral nerves or Schwann cells, perineural cells or fibroblasts. MPNST is a rare neoplasm affecting 1 in 1,00,000 population. Here we report a case of a 36 year old male who presented to us with an upper abdominal swelling for last 3 months. At first ,a diagnosis of type 1 neurofibromatosis type 1(NF-1) was made. Contrast enhanced CT scan abdomen and thorax revealed presence of a complex, heterogenous mass in upper abdomen with extension towards left hemithorax. Histopathological examination done from true cut biopsy specimen of the mass was suggestive of malignant peripheral nerve sheath tumour. Positivity of tumour cells on immunohistochemistry to S-100 established the diagnosis of MPNST in type 1 neurofibromatosis. In conclusion, it was a rare case of MPNST in a patient of NF-1. DOI: http://dx.doi.org/10.3329/jom.v13i2.12761 J Medicine 2012; 13 : 219-221

Sox10 and S100 in the Diagnosis of Soft-tissue Neoplasms

Despite a well-characterized lack of specificity, pathologists routinely employ S100 in the diagnosis of neural crest-derived tumors. Recent studies have shown that Sox10 is a reliable marker of neural crest differentiation that is consistently expressed in schwannian and melanocytic tumors. We sought to validate these results in a larger series of soft tissue neoplasms of both neural crest and non-neural crest origin, and to further characterize the sensitivity and specificity of Sox10 for use in clinical diagnosis. We evaluated Sox10 and S100 mRNA levels in 122 cases of peripheral nerve sheath tumors and synovial sarcoma and used immunohistochemistry for Sox10 and S100 protein expression in 1012 tissue specimens. This study includes 174 tissue microarray cases previously reported by Nonaka and colleagues, which include cases of melanoma, dermatofibrosarcoma protuberans, neurofibroma, synovial sarcoma, clear-cell sarcoma, malignant peripheral nerve sheath tumor (MPNST), perineurioma, and schwannoma. Synovial sarcomas expressed significantly higher levels of S100B than Sox10 (P=7.9×10), and no significant Sox10 mRNA expression was identified in synovial sarcoma (n=40), whereas 18/40 cases showed comparatively increased levels of S100 mRNA. The majority of schwannomas (n=26) and neurofibromas (n=28) showed relatively an increased expression of both Sox10 and S100 mRNA. MPNSTs (n=28) showed variable levels of Sox10 and S100 mRNA expression, and these expression levels were highly correlated (Pearson correlation coefficient r=0.79). In contrast, immunohistochemistry performed on a larger and more varied number of cases highlighted significant differences between the 2 proteins. We identified 5 non-neural, nonmelanocytic sarcoma types in which a subset of cases showed S100 protein expression: synovial sarcoma (12/79, 15%), Ewing sarcoma (3/14, 21%), rhabdomyosarcoma (4/17, 24%), chondrosarcoma (3/4, 75%), and extraskeletal myxoid chondrosarcoma (5/11, 45%). For each of these entities, we identified cases with strong and diffuse S100 staining. Of these cases, only 1 case of rhabdomyosarcoma showed focal Sox10 positivity. In 78 cases of MPNST, S100 increased the sensitivity (31/78, 40%) as compared with Sox10 (21/78, 27%), but the majority of these cases were negative for both Sox10 and S100 (44/78, 56%). Sox10 proved superior to S100 in the detection of desmoplastic melanoma (7/9, 78%) and clear-cell sarcoma (4/7, 57%). We also report for the first time Sox10 expression in 26 cases of granular cell tumor, further supporting the neural crest derivation of this tumor. Excluding MPNST, S100 and Sox10 showed similar sensitivity in tumors of neural crest origin (140/148, 95% and 137/148, 93%, respectively). In summary, Sox10 shows an increased specificity for tumors of neural crest origin compared with S100: Sox10 was positive in only 5 of 668 cases (99% specificity) in nonschwannian, nonmelanocytic tumors, whereas S100 was positive in 53 of 668 cases (91% specificity). Sox10 should be used in the place of or along with S100 in soft tissue tumor diagnosis.

Malignant Peripheral Nerve Sheath Tumor of the Oral Cavity

Malignant peripheral nerve sheath tumors (MPNSTs) are rare, highly aggressive, soft tissue sarcomas of ectomesenchymal origin that account for 3% to 10% of all sarcomas. They arise de novo or from prexisting benign neurofibromas. The diagnosis of PNST has been described as one of the most difficult nd elusive diagnoses in soft tissue diseases because f its nonspecific clinical and histopathologic presenation. The authors report a rare case of MPNST of he oral cavity and discuss the histopathology, treatent, and prognosis of the condition.

Expression of nestin and Ki-67 in malignant peripheral nerve sheath tumors and its significance

Objective To explore the expression of nestin and Ki-67 in malignant peripheral nerve sheath tumors (MPNST) and its significance in the differential diagnosis. Methods Immunohistochemical technique (SP) was used to detect the expression of nestin and Ki-67 in 42 cases of MPNST and 24 cases of benign peripheral nerve tumor.Results Total expression of nestin was found in 95.2 ％(40/42) of MPNST.Strong expression of nestin was detected more frequent in MPNST compared to benign peripheral nerve tumors [40.5 ％(17/42) versus 4.2 ％(1/24),x2 =8.403,P =0.004].Ki-67 labeling index in MPNST varied from 1％-70 ％.However,greater than 3 ％ labeling index of Ki-67 staining was observed in 64.3 ％(27 / 42) of MPNST while none of the 24 benign tumors had nuclear staining exceeding 3 ％. The higher Ki-67 labeling index showed significant differences between the two groups (x2 =23.518,P =0.000).Conclusion Nestin and Ki-67 are useful markers in distinguishing MPNST from benign tumors. Key words: Malignant peripheral nerve sheath tumor; Nestin; Ki-67; Immunohistochemistry

The cytopathology of malignant peripheral nerve sheath tumor

Among sarcomas, a diagnosis of malignant peripheral nerve sheath tumor (MPNST) is often one of exclusion due to the absence of unequivocally characteristic histopathology, a conclusive immunohistochemical profile, or even a unique chromosomal anomaly. Because of this, the fine-needle aspiration (FNA) cytopathology of MPNST is extremely challenging. In the current study, the authors review their FNA experience with this neoplasm. The authors searched their combined departmental cytology files for all lesions signed out as MPNST or suspicious for MPNST, as well as their own surgical pathology files for any cases of MPNST that had corresponding cytology. FNA was performed using standard techniques. A total of 55 cases of MPNST, all with tissue confirmation, and 1 misdiagnosed example of melanoma were retrieved from 52 patients (M:F ratio of 1.5:1; average age, 46 years), 26 of whom had a history of neurofibromatosis type 1 (NF-1). Aspirates were from primary (27 cases), locally recurrent (14 cases), or metastatic (10 cases) MPNST; 4 primary tumor aspirates were of ex vivo specimens. Sites included the extremities (22 cases), trunk/pelvis (22 cases), head and neck (6 cases), and deep-seated masses (6 cases). FNA diagnoses were MPNST (24 patients); consistent with MPNST (5 patients); sarcoma, not otherwise specified (10 patients); atypical (3 patients); spindle cell neoplasm (6 patients); malignant neoplasm (1 patient); and nondiagnostic (3 patients). A definitive diagnosis of either MPNST or consistent with MPNST was issued in 30%, 93%, and 70%, respectively, of primary, locally recurrent, and metastatic lesions. FNA cytopathology is limited as a diagnostic instrument for the initial diagnosis of MPNST, but is exceedingly accurate and valuable in the recognition of metastatic and locally recurrent MPNST.

2. A rare primary lung MPNST exhibiting peculiar ‘small cell’ features diagnosed through fna with tissue correlation

Background We report a case of primary intraparenchymal lung malignant peripheral nerve sheath tumour (MPNST) originally diagnosed through fine needle aspiration biopsy (FNAB) incidentally presenting with a peculiar feature in an adult female without NF-1. Aim To present, document and describe the cytomorphological features and tissue correlation of a case of primary lung MPNST with ‘small cell’ features. Case history The patient was an adult female with hemoptysis. CT scan revealed a left lower lobe mass. CT-guided FNAB was performed and MPNST was considered. One month later, she was eventually admitted for dyspnoea. She was subsequently scheduled for thoracotomy with frozen section. Wedge biopsy was done and submitted for histopathological examination. Results FNA cytology showed loose clusters atypical epithelioid cells and spindle cells as singles. The cellblock revealed interlacing fascicles of spindle cells with plump hyperchromatic nuclei and tapered cytoplasm. Some fragments showed epithelioid cells with rosette-like formation. Epithelioid and spindle cells were negative for cytokeratin, desmin and SMA. NSE was positive in >50% of the tumour cells. Frozen section diagnosis favoured small cell carcinoma. The mass appeared hypercellular in the preserved areas and was composed of epithelioid to spindle-shaped cells. Extensive areas of necrosis were noted. Mitotic count was high at 8–12 per 10 HPF. The lesional cells showed positivity against vimentin and weak focal positivity against S-100, while synatophysin, SMA, desmin and TTF-I all showed negative reactions. Conclusion We have documented and described a case of primary MPNST of the lung in an adult female without NF-1 with peculiar ‘small cell’ features. With careful attention to the cytomorpholo-gical details of MPNST, it could be confidently considered through FNA with the aid of immunohistochemistry.

Malignant Peripheral Nerve Sheath Tumors: Differentiation Patterns and Immunohistochemical Features - A Mini-Review and Our New Findings

Malignant peripheral nerve sheath tumors (MPNST) represent a group of highly heterogeneous human malignancies often with multiple histological origins, divergent differentiation patterns, and diverse immunohistochemical presentations. The differential diagnosis of MPNST from other spindle cell neoplasms poses great challenges for pathologists. This report provides a mini-review of these unique features associated with MPNST and also presents the first cases of MPNST with six differentiation patterns.

Malignant peripheral nerve sheath tumors: clinicopathological aspects, expression of p53 and survival

Malignant peripheral nerve sheath tumors (MPNSTs) arerare and highly aggressive neoplasms, representing only 5%of soft tissue sarcomas (1,2). Approximately half of MPNSTcases occur in association with neurofibromatosis type 1(NF1) (3). MPNSTs may appear de novo or develop from themalignant transformation of a benign neural neoplasm,generally a plexiform neurofibroma (1). Solitary (unasso-ciated with NF1) and localized (or discrete; multiple in NF1)neurofibromas do not have malignant transformationpotential (1,3). NF1 loss of heterozygosity (LOH) has beendemonstrated in NF1-associated and sporadic MPNSTs.Although NF1 LOH is believed to be sufficient for neu-rofibroma development, MPNST pathogenesis has beensuggested to be a multistage process that includes othermolecular alterations (4,5). TP53 mutations have been foundin a subgroup of MPNSTs, indicating that a p53-mediatedpathway is involved in their development (5,6).Some clinicopathological features (e.g., the presence ofNF1,high histologicalgrade,necrosis,andrhabdomyoblasticdifferentiation) have been indicated to be important factorsforlower survival in MPNST cases in some studies butnotinothers (2,7–10). The clinical significance of p53 expression inMPNSTs is also a controversial issue. We aimed to study p53expression in MPNSTs and investigate its impact, as well astheimpactsoftheclinicopathologicalfeaturesofMPNSTs,onthe survival rates. We also compared p53 expression inMPNSTswith theirclinicopathological features and with p53expression in neurofibromas.

Microarray Comparative Genomic Hybridization Detection of Copy Number Changes in Desmoplastic Melanoma and Malignant Peripheral Nerve Sheath Tumor

Desmoplastic melanoma (DM) and malignant peripheral nerve sheath tumor (MPNST) can appear morphologically and immunophenotypically similar. We attempted to determine whether microarray comparative genomic hybridization could detect copy number differences between them to aid in the diagnosis. S-100 immunohistochemistry was performed on 5 cases of DM and 9 cases of MPNST using formalin-fixed paraffin-embedded specimens. Genomic DNA was extracted from microdissected cells. Whole genome amplification was performed on 5 of 5 DMs and 6 of 9 MPNST cases. A multiplex polymerase chain reaction assay was used to determine the quality of the DNA samples, which were run on the Spectral Chip 2600 bacterial artificial chromosome array platform. DM showed gains involving chromosomes 1p, 2p, 9q, 13q, 14q, and 20q and losses involving chromosomes 5p, 11p, 12q, 15q, and 18q. Several cancer-associated genes were involved, including gain of BCL2L1, ARTN, AMPK, NRAS, and CCNA1 and loss of IGF2, CDKN1C, PAX6, WT1, TRAF6, MAPK8IP1, and IMP3. MPNST had gains involving chromosomes 1p, 2q, and 19p and loss of chromosome 21q. Gains of MUM1, APC2, MAP2K2, JMJD2B, SP110, PTMA, GPI, and CDKN2D were detected. DM and MPNST have chromosomal alterations detected by array comparative genomic hybridization that might be useful in distinguishing these 2 tumors, although further studies with a larger sample size will be needed to test this.

Report of a Case of Malignant Peripheral Nerve Sheath Tumor of the Neck with an Early Local Recurrence

Malignant peripheral nerve sheath tumor (MPNST), which originates in Schwann cells, is uncommon in the head and neck. These highly aggressive sarcomas are characterized by local recurrence and distant metastasis. Many are associated with neurofibromatosis type 1; the survival rate in such cases is poorer than the rate associated with tumors that arise de novo. Hypercellularity and pleomorphism are cardinal microscopic features. Immunohistochemical staining is widely used to determine S-100 positivity and a Ki-67 score, either of which may establish the prognosis. We present a case of MPNST of the neck that arose in a 17-year-old girl, who was also found to have a parapharyngeal neurofibroma. The cervical mass was excised (intraoperative complications precluded removal of the parapharyngeal mass) and radiotherapy was administered, but the patient experienced a recurrence within 2 months. Another surgery was performed, and this time both tumors were removed. At 1 year of follow-up, the patient was without disease, but in postoperative year 2, she died from complications of a cervical recurrence and mediastinal metastasis.

Recurring Intracranial Malignant Peripheral Nerve Sheath Tumor: Case Report and Systematic Review of the Literature

To report the clinical presentation and management of an intracranial frontoparietal malignant peripheral nerve sheath tumor (MPNST) and its recurrence in a 6-year-old girl, along with a systematic review of the literature. A previously healthy 6-year-old girl presented with severe signs of increased intracranial pressure. Magnetic resonance imaging (MRI) revealed a large heterogeneously enhancing mass at the right frontoparietal convexity. The tumor was completely removed, the histological diagnosis was MPNST, and the patient underwent adjuvant radio- and chemotherapy. Fifteen months later, MRI revealed a small local recurrence. After upfront chemotherapy, the recurrence was removed in a radical, ie, true oncological, neuronavigationally guided, en bloc resection, including approximately 1 cm surrounding gray and white matter and overlying dura mater. Neuropathological examination revealed tumor-free margins. The patient again received adjuvant chemotherapy. Four years after diagnosis and 20 months after cessation of adjuvant therapy, there are no signs of tumor recurrence. The literature search resulted in 17 cases of intracranial MPNSTs not associated with cranial nerves. Despite macroscopically complete resection in many cases and adjuvant radio- and chemotherapy, overall survival was poor, with only 5 patients still alive upon publication (including the current patient). Intracranial MPNSTs not associated with cranial nerves are extremely rare and highly malignant tumors with poor overall survival, probably because of infiltrating growth into surrounding brain tissue. We therefore advocate consideration of nonconventional true oncological en bloc resection when approaching this rare tumor or its recurrence.

A case of a sporadic malignant peripheral nerve sheath tumor of the urinary bladder with concomitant in situ urothelial carcinoma treated by transuretheral resection

Malignant peripheral nerve sheath tumor (MPNST) of the urinary bladder is a very rare clinical entity. The association of such a tumor with urothelial carcinoma is even more unusual. Differential diagnosis between coexisting two distinct primary tumors and carcinosarcoma of the urinary bladder is very important as both the treatment and prognosis vary widely. Herein, we report a case of an MPNST with a concomitant in situ urothelial carcinoma in a 53-year-old man. To our knowledge, this is the first documented case of MPNST of the bladder that is treated by transuretheral resection which is in contrast with the previous reports that used cystectomy.

Intraoral presentation of multiple malignant peripheral nerve sheath tumors associated with neurofibromatosis-1

Neurofibromatosis-1 (NF-1) is a relatively common autosomal dominant disease characterized by multiple cutaneous fibromatoses and café au lait spots. It is associated with the mutation of NF-1 gene, a tumor suppressor gene located on chromosome 17q11.2. Hence, it can be considered as a familial cancer predisposition syndrome in which the affected individuals are at increased risk of developing malignancies. Intraoral neurofibromas associated with NF-1 are quite common, but the occurrence of malignant peripheral nerve sheath tumor (MPNST) in the oral cavity is very rare. Oral MPNST can occur either de novo or by malignant transformation of neurofibromas or very rarely can represent a metastatic lesion. Here, we present a case of MPNST involving the maxillary region, in a patient with NF-1. Since MPNST often creates a diagnostic dilemma, histopathologic criteria for the diagnosis of MPNST are also discussed.

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.

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.

Cutaneous malignant peripheral nerve sheath tumors

Cutaneous malignant peripheral nerve sheath tumors (MPNSTs) are rare entities compared with their deep soft tissue counterparts. We describe two cases of cutaneous MPNSTs. The first case, occurring in a 27-year-old woman with neurofibromatosis I, presented with recent growth of a pre-existing nodule on her back. A biopsy showed a densely cellular area within a conventional neurofibroma composed of atypical, hyperchromatic epithelioid and spindled cells with frequent mitotic figures (MFs). The second case presented in an 88-year-old man with no stigmata of neurofibromatosis as a rapidly growing subcutaneous tumor of the right calf. A biopsy showed a diffuse neurofibroma that abruptly transitioned to a densely cellular proliferation of hyperchromatic atypical spindled cells arranged in short fascicles with frequent MFs. The diagnosis of MPNST was rendered in both cases. MPNSTs of the dermis and subcutis are rare sarcomas. They can occur as sporadic tumors or in the setting of neurofibromatosis. They are often associated with pre-existing neurofibromas. Increase in size of pre-existing neurofibromas is an indication for biopsy. Recognition of the cellular atypia, increased cellularity and mitotic activity is key to the diagnosis.

Malignant Peripheral Nerve Sheath Tumor of the Breast in a Patient without Neurofibromatosis: A Case Report

Malignant peripheral nerve sheath tumors (MPNSTs) are malignant variants of peripheral nerve sheath tumors that develop at major or minor peripheral nerve branches or at the sheaths of peripheral nerve fibers. These tumors are derived from Schwann cells or pluripotent cells of a neural crest origin. Malignant tumors of the peripheral nerve sheath are most commonly seen in deeper soft tissues, and usually in the proximity of a nerve trunk. MPNSTs of the breast are very uncommon and they have rarely been reported on. We report here on a case of MPNST of the breast in a 59-year- old female who presented with a painless breast lump for two months. The excisional biopsy revealed a malignant peripheral nerve sheath tumor based on the microscopic findings and immunohistochemical staining. We performed wide excision of breast tissue around the biopsy site and there- after the patient underwent radiation therapy. The patient remains well without signs of recurrence 1 year following surgery.

Immunohistochemical study of GLUT‐1 in oral peripheral nerve sheath tumors

To investigate the immunoexpression and diagnostic applicability of human erythrocyte-type glucose transporter protein (GLUT-1) in oral peripheral nerve sheath tumors. Specimens diagnosed as oral peripheral nerve sheath tumors archived in the Oral Pathology Service of Universidade Federal de Minas Gerais from 1966 to 2006 were evaluated. Thirty-four lesions were included: 15 traumatic neuromas, 11 neurofibromas, four neurilemmomas, and four malignant peripheral nerve sheath tumors (MPNST). One case of neurofibroma was associated with neurofibromatosis type I. Immunohistochemistry for S-100 and GLUT-1 was performed. S-100 was immunopositive in all lesions. Benign lesions were immunopositive for GLUT-1 except in two (18.2%) cases of neurofibromas. In the traumatic neuroma, the perineuriums were immunopositive for GLUT-1. In the neurofibroma, the immunoreactivity was heterogeneous. Immunopositivity was observed at levels of 54.5% in the periphery of the lesion, 9.1% in the center, and 18.2% in both. The neurilemmoma demonstrated immunopositivity in the capsule. One case (25%) of MPNST presented GLUT-1 positive stain in occasional cells distributed homogeneously in all the tumor area. GLUT-1 is a useful marker for perineurial cells and should be included in the oral peripheral nerve sheath tumors immunophenotyping thus aiding in the correct diagnosis of these lesions.

Differential expression of angiogenic factors in peripheral nerve sheath tumors

It is difficult to differentiate some malignant peripheral nerve sheath tumors (MPNST) from benign peripheral nerve sheath tumors (BPNST) histologically, and to predict the clinical outcome of patients with MPNST. In this study, the expression of VEGF and MVD were evaluated immunohistochemically in 22 cases of MPNST, 14 of neurofibroma and 19 of schwannoma and correlation of the staining grade of VEGF or MVD and the various clinical factors were analyzed, and statistically evaluated. Levels of VEGF mRNA expression were also determined with real-time RT-PCR. Statistically higher positive staining for VEGF was observed in MPNST compared to neurofibroma (P=0.004) and schwannoma (P<0.001). Even low grade MPNST showed higher VEGF positive staining than neurofibroma. Moreover, high VEGF expression statistically correlated with the poor prognosis of the patients with MPNST (P=0.015). Although MVD in MPNST was significantly higher than that in neurofibroma (P=0.038) and schwannoma (P<0.001), MVD could not predict the prognosis of the patients with MPNST. Although VEGF mRNA expression tended to be higher in MPNST compared to neurofibroma, the difference was not significant. Levels of VEGF protein expression serve as a novel diagnostic and prognostic tools for peripheral nerve sheath tumors.

Expression and significance of EGFR in malignant peripheral nerve sheath tumor

10588 Background: Malignant peripheral nerve sheath tumor (MPNST) is a rare aggressive sarcoma. Epidermal growth factor receptor (EGFR) has been implicated in the pathogenesis of several cancers and is also a target for treatment. There is little information regarding its role in MPNST. The aim of our study was to investigate the expression and prognostic influence of EGFR in MPNST. Methods: Formalin-fixed, paraffin-embedded sections from cases of primary and metastastatic MPNST were immunostained with antibodies to EGFR. This total EGFR expression (membranous and cytoplasmic) was analyzed by morphometry, scoring both % positivity and the intensity. An EGFR composite score (range 0–300) was calculated by multiplying the intensity of labeling (total EGFR overexpression score 0–3) by the grade (percentage of positive cells). A composite score of above 10 was considered as an EGFR overexpression. Finally, EGFR expression was correlated with clinicopathologic features, and clinical outcome. Results: We have i...