Fine-needle aspiration cytology of malignant peripheral nerve sheath tumors

The histopathologic features of malignant peripheral nerve sheath tumors (MPNSTs) have been well described. There have been limited studies on the cytologic features of MPNST. In this present study, we have retrospectively reviewed eight histopathology confirmed cases of MPNST over a 5-year period. Detailed cytomorphological analysis of these cases was carried out individually by two observers. On cytology, these cases were diagnosed as benign spindle-cell tumor (two), spindle-cell tumor possibly benign (one), spindle-cell tumor possibly malignant (one), malignant spindle-cell tumor (two), spindle-cell tumor, and neural origin (two). The cardinal cytomorphologic features were loosely cohesive clusters and fascicular arrangement of spindle cells with rounded ends. The kinking of nuclei was not a conspicuous finding. Fibrillary background was noted in two of the cases. Nuclear pleomorphism was ranged from mild to moderate degree. One case exhibited extensive intranuclear pseudoinclusions. Mitotic figures (including atypical forms) were present in almost all the cases. Possibly a constellation of cytologic features such as clusters of short and long fascicles of cells admixed with dissociated spindle cells of round-ended nuclei and prominent nucleoli on myxoid or fibrillary background and frequent mitosis may be helpful in diagnosis of MPNSTs. The cytomorphologic features along with clinical correlation are necessary to increase the diagnostic accuracy of MPNST on aspiration cytology.     

Nestin是恶性周围神经鞘膜肿瘤的一个新的标志物

恶性周围神经鞘膜肿瘤（MPNST）是一种比较常见的软组织恶性肿瘤，最常发生于臀部和大腿。组织学上MPNST很难与其他类型的梭形细胞肿瘤鉴别，免疫组化上S-100蛋白是最常被用于诊断MPNST的标记物，但其特异性差。另外高级别MPNST常不表达S-100蛋白。最近研究发现中间丝蛋白nestin表达于神经外胚层干细胞中，在中枢神经系统，随着神经分化nestin表达明显减少，但在外周神经系统，nestin仍然表达且局限于雪旺氏细胞。[第一段]     

Malignant peripheral nerve sheath tumor with perineurial cell differentiation (malignant perineurioma)

A unique case of malignant peripheral nerve sheath tumor (MPNST) with perineurial cell differentiation occurring in a 63-year-old woman in a subcutis of the forearm is described. The tumor contained cellular and myxoid areas. The neoplastic cells were fusiform with distinct cell borders. They were arranged in storiform pattern and in wavy parallel cell cords in the cellular areas. Focally, a pleomorphism and mitotic activity (including atypical mitoses) similar to those of malignant fibrous histiocytoma were seen. The myxoid parts contained haphazardly oriented cells and scarce lipoblast-like multivacuolated cells mimicking a liposarcoma. In the differential diagnosis, myxoid liposarcoma, dermatofibrosarcoma protuberans, malignant fibrous histiocytoma and low-grade fibromyxoid sarcoma were considered. Immunohistochemically, perineurial differentiation was indicated by the diffuse expression of epithelial membrane antigen and focal reactivity for CD34. The tumor was negative with antibodies to S-100 protein, Leu-7, CD68 (KP1), vimentin and cytokeratin AE1/AE3. Ultrastructure of tumor cells revealed features of MPNST. No recurrence occurred in the patient during 2 years follow up.     

Intraosseous nerve sheath tumors in the jaws

Although the head and neck region is recognized as the most common location for peripheral nerve sheath tumors, central involvement, particularly in the jaw bones, is quite unusual. Neurofibroma is one of the most common nerve sheath tumors occurring in the soft tissue and generally appears in neurofibromatosis 1 (NF1 or von Recklinghausen's disease). Malignant peripheral nerve sheath tumors (MPNSTs) are uncommon sarcomas that almost always arise in the soft tissue. Here, we report four cases of intraosseous peripheral nerve sheath tumors occurring in the jaw bones and compare the clinical, radiologic, and pathologic findings in order to make a 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.     

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.     

Non-neoplastic glandular structures in a benign peripheral nerve sheath tumor

It is a recognized fact that glandular structures sometimes occur in peripheral nerve sheath tumors (PNST). Reports indicate that epithelial potential could be expressed in malignant PNST, while the glands in most benign PNST could be trapped skin adnexa. We present a case of spindle cell tumor with glandular structures. The patient was a 55-year-old man who had a subcutaneous tumor excised. The spindle cell tumor had histological characteristics of neurofibroma. The glandular structures had a pattern of immunohistochemical staining that was similar to that of the secretory coils and excretory ducts of normal eccrine glands. Therefore, the glands were thought to be naturally existing eccrine glands. The glands were completely enclosed within the tumor and not connected to one another; a cluster formation was not observed. The upper portion of tumor included some glands of skin adnexa. The spindle cell tumor may have originated from the nerves distributed around the skin adnexa, and grown to the subcutaneous tissue. The glands may have been left behind rather than have been trapped in the tumor.     

Dramatic response to entrectinib in a patient with malignant peripheral nerve sheath tumor harboring novel SNRNP70-NTRK3 fusion gene

Neurotropic tropomyosin receptor kinase (NTRK) gene rearrangements have been reported in limited cases of sarcomas; however, to date, there has been only one report of such rearrangements in malignant peripheral nerve sheath tumors (MPNSTs). Herein, we describe a 51-year-old male patient with a buttock tumor arising from the sciatic nerve, which was diagnosed as MPNST with positive S-100 staining, negative SOX10 staining, and loss of trimethylation at lysine 27 of histone H3 (H3K27me3) confirmed by immunohistochemistry. Soon after the resection of the primary tumor, the patient was found to have pulmonary and lymph node metastases. Chemotherapy with eribulin and trabectedin showed limited effects. However, the patient responded rapidly to pazopanib, but severe side effects caused discontinuation of the treatment. RNA panel testing revealed a novel fusion gene between Small Nuclear Ribonucleoprotein U1 Subunit 70 (SNRNP70) gene and NTRK3 gene. Furthermore, loss of NF1, SUZ12, and CDKN2A genes was confirmed by DNA panel testing, which is compatible with a histological diagnosis of MPNST. SNRNP70 possesses a coiled-coiled domain and seems to induce constitutive activation of NTRK3 through dimerization. In fact, immunohistochemistry revealed diffuse staining of pan-TRK within tumor cells. Treatment with entrectinib, which is an NTRK inhibitor, showed a quick and durable response for 10 months. Although NTRK rearrangements are very rare in MPNST, this case highlights the importance of genetic testing in MPNST, especially using an RNA panel for the detection of rare fusion genes.     

肺原发性恶性外周神经鞘瘤的临床病理分析

目的 探讨肺脏原发性恶性外周神经鞘瘤(MPNST)的临床病理学特征及诊断、鉴别诊断要点。方法 对2例肺MPNST进行临床病理学分析及免疫组织化学与超微结构研究。结果 2例光镜下均显示MPNST的形态特点，免疫组织化学显示S-100蛋白、MBP、Vim、NSE肿瘤细胞呈阳性表达，电镜观察1例可见特征性Luse小体。结论 肺原发性MPNST极为罕见，临床诊断较困难。根据其光镜病理形态特征，S-100蛋白、MBP免疫组织化学检测和(或)电镜检查可确诊。结合文献，该肿瘤早期无明显临床症状，一般发现时已属晚期，预后差。病理学上应与肺脏平滑肌肉瘤、纤维肉瘤、单相型滑膜肉瘤、肉瘤样癌鉴别。     

恶性外周神经鞘膜瘤中MMP-2和TIMP-2的表达

目的 探讨恶性外周神经鞘膜瘤(malignant peripheral nerve sheath tumors,MPNST)中基质金属蛋白酶-2(matrix metalloproteinase-2,MMP-2)及其相应的组织金属蛋白酶抑制剂-2(tissue inhibitor of metalloproteinase-2,TIMP-2)蛋白表达与病理分级、转移及预后的关系。方法 采用免疫组化S-P法检测MPNST中MMP-2及TIMP-2表达,并行回顾性随访。结果 58例MPNST中MMP-2阳性表达51例,阳性表达率是87．9％,TIMP-2阳性表达36例,阳性表达率是62．1％。MMP-2蛋白表达与病理学分级、远处转移率呈正相关,与术后生存率呈负相关;而TIMP-2则相反。结论 MMP-2、TIMP-2与MPNST病理学分级、远处转移及术后生存期有关,可作为判断肿瘤恶性程度及预后的有用的参考指标。     

Malignant transformation of neurofibromatosis-1 into low-grade malignant peripheral nerve sheath tumor: a case report

Malignant Peripheral Nerve Sheath Tumor (MPNST) is a malignant mesenchymal tumor. The majority of MPNSTs are found in patients with neurofibromatosis type 1 (NF-1) who have a high-grade sarcoma. At the moment, there are just a few instances of low-grade MPNST caused by NF-1. We present a case of malignant transformation of NF-1 into low-grade MPNST in a patient with a long history of the disease. Multiple protruding masses with ulceration on the right shoulder and chest wall were discovered during physical examination. Complete tumor excision was done, followed by hematoxylin-eosin and immunohistochemical staining. A portion of the tumor had higher cellularity, hyperchromatic cell nuclei, and mitoses were seen in only five out of ten high-power fields. S-100 and vimentin were positive, whereas cytokeratin, desmin, SMA, and CD34 were negative. Ki-67 (MIB1) labeling index hot-spotting was around 25%. This was thought to be NF-1 malignant transformation into low-grade MPNST. Overall, knowing the clinical and pathologic characteristics of the disease, plus growing knowledge or experience with the condition, may improve preoperative diagnostic accuracy and extending survival time.     

Peripheral nerve sheath tumors: an update and review of diagnostic challenges

Peripheral nerve sheath tumors (PNSTs) are one of the more common soft tissue neoplasms encountered in the daily surgical pathology practice, most of which have classic histologic features. There are, however, some common diagnostic challenges encountered by surgical pathologists and neuropathologists, as well as controversies regarding classification and grading of PNSTs. As molecular studies advance and novel targeted therapies are developed, it has become imperative that we become familiar with the diagnostic criteria for these common neoplasms and their potential mimics.     

恶性外周神经鞘瘤52例临床病理分析

目的观察恶性外周神经鞘瘤的临床病理学特征、诊断及鉴别诊断。方法回顾性分析52例恶性外周神经鞘瘤的临床病理学及免疫表型特征并复习相关文献。结果 52例患者中,男女发病率为1∶1,年龄4~71岁,头颈部18例(35%),四肢12例(23%),躯干9例(17%),深部组织8例(15%),椎管内4例(8%),生殖道1例(2%)。镜下肿瘤组织呈束状或漩涡状排列,瘤细胞短纺锤形、卵圆形、梭形,核分裂象易见。免疫表型:瘤细胞局灶表达S-100蛋白,Ki-67增殖指数10%~70%。结论恶性外周神经鞘瘤罕见,侵袭性高,预后差,其组织形态复杂多样,需与滑膜肉瘤、纤维肉瘤、血管外皮瘤、富于细胞性神经鞘瘤、纤维型脑膜瘤以及平滑肌肉瘤等鉴别。     

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.     

Liposarcomatous differentiation in malignant peripheral nerve sheath tumor: A case report

A 63-year-old man was admitted at the emergency department in an acute confusional state, and a computerized tomography scan (CT) revealed hydrocephalus. Despite the rapid introduction of a ventriculo-peritoneal shunt, the patient died soon thereafter. At the post-mortem examination, a large solid mass was found to be firmly attached to a nerve root at the L1–L2 level. Microscopically, the tumor showed the classical features of a malignant peripheral nerve sheath tumor (MPNST) with rhabdomyoblastic differentiation. In addition, there were randomly distributed lobules of well-differentiated adipose tissue with unequivocal atypical nuclei. The diagnosis of MPNST with rhabdomyoblastic and lipoblastic differentiation was made. We are not aware of previously reported lipoblastic differentiation in MPNST. Herein, we present details of the case.