Malignant Peripheral Nerve Sheet Tumors Research Articles

Neurofibromatosis Type 1-Associated Multiple Malignant Peripheral Nerve Sheet Tumors: A Case Report and Literature Review

Background: Neurofibromatosis type 1 (NF-1) is a genetic disorder characterized by café-au-lait macules, freckling, Lisch nodules, and neurofibromas. NF-1 patients have a special predisposition to tumorigenesis due to genetic mutations, affecting the tumor regulator systems. Malignant Peripheral Nerve Sheet Tumor (MPNST) is a highly aggressive soft tissue tumor that is usually associated with NF-1. Case presentation: A 32-year-old woman was presented complaining of weakness, severe fatigue, weight loss, peripheral paresthesia, progressive generalized myalgia, bone pain, and a mass sensation in her right thigh since three months ago. She was a known case of NF-1 since childhood. After clinical and radiological evaluation, multiple masses were detected in the retroperitoneal cavity adjacent to the left kidney, uterus, and right thigh. Finally, the patient was planned for surgical excision of two masses with subsequent chemotherapy. Both excised masses were confirmed as MPNSTs by histopathological examination. Conclusion: Regarding the predisposition of NF-1 patients to tumorigenesis and the high prevalence of peripheral nerve tumors among these patients, any masses changing their character should raise suspicion for malignancy. One of the serious malignant lesions is MPNST. The primary treatment plan for these malignant lesions is surgical excision with subsequent chemotherapy or radiotherapy based on individual characteristics.

Primary Malignant Peripheral Nerve Sheath Tumor of the Breast: A Rare Case Report

Abstract Introduction/Objective Primary breast sarcomas are uncommon and primary mammary malignant peripheral nerve sheet tumors (MPNST) are exceptionally rare. MPNST’s are malignant variants of peripheral nerve sheath tumors. These neoplasms are often associated neurofibromatosis type I (NF-I) but can also occur sporadically. They tend to occur in the deeper soft tissues, trunk, and extremities. Methods/Case Report A 60-year-old female was referred to our University Hospital for evaluation of an abnormal mammogram. Patient noticed a mass in the left breast 3 months ago and mammogram showed a large solid mass located at the left superior breast. Subsequent biopsy of the left breast lesion showed high grade malignant neoplasm with differential diagnosis of malignant phyllodes tumor, primary sarcoma, and metaplastic carcinoma. The tumor was non-responsive to the initial neoadjuvant therapy. The patient underwent modified radical mastectomy. The excised tumor was well-circumscribed, tan-white, firm, measuring 9.6 x 6.1 x 4.3 cm. The neoplastic cells were positive for CD99, S-100, SOX-10, neuron specific enolase, p53, Vimentin, focally positive for neurofilament, D2-40, p63, and negative for epithelial, melanoma and other sarcoma markers. The tumor was triple negative ER, PR, HER-2, with Ki- 67 at 61%. A diagnosis of primary high grade malignant peripheral nerve sheath tumor of the breast was rendered. The patient does not have a history of NF-1. There was no lympho-vascular or perineural invasion. After the surgery, the patient followed up without complications. Results (if a Case Study enter NA) N/A Conclusion An accurate diagnosis of this rare entity is necessary because it plays a crucial role in the therapeutic options and prognosis. In our case the patient was treated with neo-adjuvant chemotherapy followed by modified radical mastectomy. The purpose of presenting this unique case is to provide awareness of the existence of this entity among pathologists and clinicians for better patient care.

Characteristics, survivals and risk factors of surgical site infections after En Bloc sacrectomy for primary malignant sacral tumors at a single center

IntroductionFor prolonged survival, primary malignant sacral tumors (PMST) are treated by En Bloc sacrectomy. Few studies analyzed specifically the surgical site infections (SSI) for this condition and whether they impact on the patients’ survivals. ObjectivesThe objectives were to (1) describe their characteristics; (2) compare the survivals of infected and non-infected patients; (3) identify patients- and surgery-related risk factors. MethodsWe conducted a retrospective single center study on 51 consecutive patients with PMST who underwent an En Bloc sacrectomy. Mean follow-up was 89±68months (range, 13–256months). Histology consisted of 46 chordoma, 3 chondrosarcoma, 1 Ewing tumor, 1 malignant peripheral nerve sheet tumor. Mean age was 57.4±13.7years with 26 (51%) male. Approaches were mainly anterior-and-posterior with, for the anterior approach, 18 laparotomy and 32 laparoscopy. Other surgical characteristics included 39 (76%) sacrectomy above S3; 7 (14%) instrumented cases; 8 (16%) colostomy. A pedicled omental flap with artificial mesh was used for posterior wall reconstruction. Overall and disease-free survivals were compared between infected and non-infected patients using Kaplan–Meier curves and log-rank test. ResultsA total of 29 (57%) patients developed a SSI (7 deep, 22 organ/space) at mean 13.2±7.7days. One patient had also an infected intraperitoneal hematoma at day 150. SSIs were polymicrobial in 26 (90%) cases with Enterococcus sp. (27%) and E. coli (24%) as predominant organisms. Overall and disease-free survivals were not statistically different between infected and non-infected patients. Factors associated with increased likelihood of SSI included age>65years (OR=3.64; 1.06–12.50; p=0.04) and an elevated ASA score (OR=3.28, 1.05–10.80; p=0.046). Neoadjuvant radiotherapy (OR=2.86; 0.97–9.37; p=0.08) demonstrated a trend towards increased risk of SSI. Tumor volume, sacrectomy level, operating time, laparoscopy, colostomy, instrumentation, bowel incontinence were not associated to an increased risk of SSI. ConclusionEn Bloc sacrectomy for PMST led to frequent and early SSI which, however, did not seem to impact survivals. Preoperative frailty was the predominant risk factor found in this series. Further studies are required to identify protective measures. Level of evidenceIII, case-control study.

Neurofibromin Deficiency Causes Epidermal Growth Factor Receptor Upregulation through the Activation of Ras/ERK/SP1 Signaling Pathway in Neurofibromatosis Type 1-Associated Malignant Peripheral Nerve Sheet Tumor.

Neurofibromatosis type 1 (NF1) is an autosomal dominant human genetic disorder. The progression of benign plexiform neurofibromas to malignant peripheral nerve sheet tumors (MPNSTs) is a major cause of mortality in patients with NF1. Although elevated epidermal growth factor receptor (EGFR) expression plays a crucial role in the pathogenesis of MPNST, the cause of EGFR overexpression remains unclear. Here, we assessed EGFR expression levels in MPNST tissues of NF1 patients and NF1 patient-derived MPNST cells. We found that the expression of EGFR was upregulated in MPNST tissues and MPNST cells, while the expression of neurofibromin was significantly decreased. Manipulation of NF1 expression by NF1 siRNA treatment or NF1-GAP-related domain overexpression demonstrated that EGFR expression levels were closely and inversely correlated with neurofibromin levels. Notably, knockdown of the NF1 gene by siRNA treatment augmented the nuclear localization of phosphorylated SP1 (pSP1) and enhanced pSP1 binding to the EGFR gene promoter region. Our results suggest that neurofibromin deficiency in NF1-associated MPNSTs enhances the Ras/ERK/SP1 signaling pathway, which in turn may lead to the upregulation of EGFR expression. This study provides insight into the progression of benign tumors and novel therapeutic approaches for treatment of NF1-associated MPNSTs.

Mesenchymal Tumors Involving the Pancreas: A Clinicopathologic Analysis and Review of the Literature.

Most pancreatic tumors are epithelial, and, among these, more than 90% are of ductal origin. However, a variety of mesenchymal tumors may involve the pancreas and may manifest different clinicopathological characteristics. The literature on mesenchymal tumors in the pancreas is largely limited to individual case reports or analyses of small series, predominantly focusing on radiologic features. Authors' institutional and consultation databases were reviewed to identify the mesenchymal tumors involving the pancreas. Forty cases were identified; twenty-five (63%) tumors were benign/borderline, and the remaining fifteen (37%) were malignant. Of the benign/borderline tumors; 9 were solitary fibrous tumors, 6 gastrointestinal stromal tumors (GISTs), 4 schwannomas, 2 desmoid type fibromatosis, 1 lymphangioma, 1 ganglioneuroma, 1 inflammatory myofibroblastic tumor, and 1 low grade mesenchymal neoplasm. Malignant tumors included 6 cases of leiomyosarcomas, 4 liposarcomas, 2 rhabdomyosarcomas, 1 epithelioid angiosarcoma, 1 malignant peripheral nerve sheet tumor, and 1 undifferentiated pleomorphic sarcoma. Four cases (multicystic schwannoma, desmoid fibromatosis, lymphangioma and inflammatory myofibroblastic tumor) were preoperatively misdiagnosed as a primary epithelial tumor of the pancreas. Mesenchymal tumors rarely involve the pancreas. They are usually benign/borderline neoplasms but may be diagnostically challenging, especially clinically/radiologically, as they may form cystic and/or large lesions in the pancreas. Mesenchymal tumors should be considered in both the clinical/radiological and pathological differential diagnosis of pancreatic lesions.

SOX10 as an immunohistochemical marker in cancer diagnostics

SOX10 is a transcription factor that plays an important role in the formation, specification and differentiation of neural crest cells. Recent studies indicate that this protein is expressed in tumors of the nervous system, salivary glands, breast, soft tissues and melanoma cells. Due to its higher sensitivity and specificity in comparison to other available markers, SOX10 protein is mainly used in the diagnosis of malignant peripheral nerve sheet tumor and primary and metastatic melanoma including desmoplastic type. SOX10 has a more readable immunohistochemical staining, which also facilitates histopathological interpretation. Several monoclonal and polyclonal antibodies for diagnostics are currently available. Unification of anti-SOX10 antibodies to increase specificity, eliminate variability and strength of immunohistochemical reactions will support its diagnostic usefulness.

Aspects morphologiques et moléculaires des tumeurs malignes associées à une dérégulation des complexes BAF

BAF complexes are chromatin remodelling complexes made up of 15 subunits which overview transcription regulation. A subset of their subunits are notoriously linked to cancer, with the examples of SMARCB1, SMARCA4, ARID1A/1B and PBRM1. The complexes act as tumor suppressor genes, commonly mutated in a wide array of malignancies with an overrepresentation of sarcomas and tumors of the central nervous system. The recurrent inactivation of their genes points towards their driving role in the tumorigenesis of SMARCB1 in malignant rhabdoid tumors and SMARCA4 in small cell carcinoma of the ovary, hypercalcemic type. These tumors are morphologically similar composed of solid sheets of cells displaying vesicular nuclei dotted with clear chromatin and conspicuous nucleoli. Genomically, they share simple diploid profiles with no other alterations than in the culprit gene. Other mesenchymal tumors, distinct from malignant rhabdoid tumors are associated with BAF alterations, namely epithelioid sarcomas, SMARCA4-deficient thoracic sarcomas. BAF subunits are mostly inactivated through mutations or deletions but also occur through translocations in medullary carcinoma of the kidney and synovial sarcomas. Apart from tumors displaying recurrent alterations of the complexes, some variants or tumor variants display BAF alterations, including epithelioid malignant peripheral nerve sheet tumors and poorly differentiated chordomas. Lastly, some malignancies display low frequency of BAF alterations, in keeping with their passenger role in tumorigenesis with the example of dedifferentiated carcinomas, especially in colon, lung and uterus. BAF complexes alterations correlate with morphological features recognizable by microscopy, paving the way for their routine diagnosis and potential therapeutic prospects.

Establishment and Characterization of Histologically and Molecularly Stable Soft-tissue Sarcoma Xenograft Models for Biological Studies and Preclinical Drug Testing.

Soft-tissue sarcomas (STS) represent a heterogeneous group of rare, malignant tumors of mesenchymal origin. Reliable in vivo sarcoma research models are scarce. We aimed to establish and characterize histologically and molecularly stable patient-derived xenograft (PDX) models from a broad variety of STS subtypes. A total of 188 fresh tumor samples from consenting patients with localized or advanced STS were transplanted subcutaneously in NMRI-nu/nu-immunodeficient mice. Once tumor growth was observed, the material was passaged to a next generation of mice. A patient-derived tumor sample was considered "successfully engrafted" whenever the sample was transplanted to passage 1. A PDX model was considered "established" when observing stable morphologic and molecular features for at least two passages. With every passage, histologic and molecular analyses were performed. Specific genomic alterations and copy-number profile were assessed by FISH and low coverage whole-genome sequencing. The tumor engraftment rate was 32% (61/188) and 188 patient samples generated a total of 32 PDX models, including seven models of myxofibrosarcoma, five dedifferentiated liposarcoma, five leiomyosarcoma, three undifferentiated pleomorphic sarcoma, two malignant peripheral nerve sheet tumor models, and single models of synovial sarcoma and some other (ultra)rare subtypes. Seventeen additional models are in early stages of engraftment (passage 1-2). Histopathologic and molecular features were compared with the original donor tumor and were stable throughout passaging. The platform is used for studies on sarcoma biology and suited for in vivo preclinical drug testing as illustrated by a number of completed and ongoing laboratory studies.

Abstract A29: The NF1 and NF2 pharmacome project, a course in high-throughput screening to identify targets and profile the sensitivity of MPNST cells to candidate drugs

Abstract There are several large-scale efforts to compare the sensitivities of tumor cells to chemotherapeutic drugs and small-molecule pathway probes. However, to date, none of these profiling efforts systematically probed malignant peripheral nerve sheet tumors (MPNST). We initiated a database of drug sensitivities of MPNST as part of a course in high-throughput screening. We first developed a panel of 130 drugs highly relevant to neurofibromatosis (NF1 and NF2) that included a comprehensive set of MEK, RAF, RAS, FTI, PAK, ERK inhibitors, a representative set of drugs against many other cancer pathways including Wnt, Hedgehog, p53, EGF, HDAC, as well as classical cytotoxic agents such as doxorubicin and taxol. Many of the drugs in our panel are in clinical trials themselves, or closely related to drugs in trials for NF1. The drugs were tested against cells in 384-well plates at eight concentrations ranging from .004 μM to 10 μM. Cells were allowed to attach overnight, incubated for 72 hours with drugs, and then analyzed for ATP content using ATPlite. To date, we have profiled nine MPNST cell lines (ST88-14, ST88-3, 90-8, SNF02.2, STS26, T265, S462TY, SNF96.2, SNF94.3) and one NF2 Schwannoma cell line (HEI193). We also tested several cell lines that were tested in other screens so that we can compare our results to the other databases. The IC50 was calculated as a common measure of how effective each drug is using GraphPad Prism software. NF1 cells were distinguished from NF2 cells and STS26 cells (a spontaneous MPNST cell line derived from a patient who did not have NF1) by their strong sensitivity to MEK and Bromodomain inhibitors. Some drugs, including cytotoxic agents, Pak inhibitors, and HDAC inhibitors, were broadly toxic, inhibiting growth regardless of NF1 and NF2 status. None of the drugs in our panel exclusively inhibited HEI193 cells. With this study we initiated a database to archive the drug sensitivities of NF1 and NF2 cells that will be expanded in future versions of our course. Sponsored by Children's Tumor Foundation. Citation Format: Jianman Guo, Michael Grovola, Grace Coggins, Patrick Duggan, Jiale Huang, Claire Song, Gabriela Witek, Danny Lin, Hong Xie, David Schultz, Simon Berritt, Jeffrey Field. The NF1 and NF2 pharmacome project, a course in high-throughput screening to identify targets and profile the sensitivity of MPNST cells to candidate drugs [abstract]. In: Proceedings of the AACR Conference on Advances in Sarcomas: From Basic Science to Clinical Translation; May 16-19, 2017; Philadelphia, PA. Philadelphia (PA): AACR; Clin Cancer Res 2018;24(2_Suppl):Abstract nr A29.

Surgical Approaches to Large Peripheral Nerve Sheets Tumors

Peripheral nerve sheath tumors (PNSTs) are not rare tumors. Its sound management is complete surgical excision. The aim of this study was to describe clinical presentation, accuracy of different investigations and ideal surgical approaches in relation to outcomes. The study is a prospective and included 26 surgically treated large PNSTs in 22 patients operated through different surgical approaches according to the site of the tumors. The fellow up period was 6 - 60 months. The mean age was 41.8 years, 9 were males and 13 were females. The common presentations were pain in 12 lesions, swelling in 8 lesions, neural deficits in 4 lesions and positive Tinel’s test in 2 lesions. These lesions were excised through 6 surgical approaches. Histopathological examination showed 20 benign and 6 malignant lesions. Five cases of malignant peripheral nerve sheet tumors (MPNSTs) had local recurrent, 4 cases had distant metastasis, 4 cases received chemotherapy and radiotherapy, and 4 cases were died in the postoperative fellow up period. It was concluded that surgical approaches to the PNSTs, depends on their locations. Adequate exposure with minimal dissection minimized the neurological deficit and decreased rate of local recurrence.

Chondroid Syringoma of the Hypothenar Region.

To the Editor, Chondroid syringoma (CS) is a benign adnexal tumor of eccrine/apocrine sweat glands. CS constitutes of 0.01–0.1% of primary skin tumors (1). CS is usually seen in elderly males as a painless, slowly growing, well demarcated subcutaneous/intradermal nodular lesion originating from the skin of the region of the head and neck, especially the cheek, nose and lip (2). Rare localization areas are the axillary region, abdomen, trunk, genitalia and extremities (1,2). There are a few case reports defining the cytological characteristics of CS in the English language literature (2–5). A 30 year-old female patient was admitted because of a slowly growing painless swelling in the right hypothenar region for 5 years (Figure 1). The swelling was in a character of well demarcated subcutaneous nodular lesion. Aspiration smears had moderate cellularity with mild nuclear pleomorphism. Single or small groups of tumor cells with slightly eccentric nuclei on chondromyxoid matrix were noticed (Figure 2). The cytological findings reminded benign mixed tumor of salivary glands. We reported the case as a benign tumoral lesion with chondroid matrix. The excised lesion was a well demarcated and partially capsulated nodular lesion with bright, solid gray-white colored cut-section. The lesion had dimensions of 2.5×2×1.5 cm. Microscopy showed an intradermal/subcutaneous tumoral lesion consisting of small clusters or short chords of benign epithelial or myoepithelial cells in chondromyxoid matrix. There were no findings of necrosis, atypical mitoses, meaningful nuclear pleomorphism and vascular invasion. We diagnosed CS on the basis of the histopathological findings. No recurrence was observed 3 years after the excision. Informed consent was obtained from the patient. FIG. 1. A subcutaneous nodular lesion with overlying intact skin on right hypothenar region FIG. 2. a, b. Groups of the cells with monomorphic and mildly eccentric nuclei, amphophilic staining cytoplasm in chondromyxoid stroma on aspiration smears (MGG, ×20) (a), tumor cell cords and groups intermingled with myxoid stroma (HE, ×15) (b) ... Despite CS usually being benign tumors, malignant forms have been also reported (1,2). Malignant forms usually localize on the trunk and extremities and are mostly seen in young women. They are rapidly growing masses and their diameters are larger than 3 cm. Erosion/ulceration of the overlying skin is frequent. Mortality rates are high due to metastasis to the lung in malignant forms. Histological evidences of malignancy and satellite nodules favor the diagnosis of malignant CS (1,2). Chondroid syringoma should be differentiated from other subcutaneous tumoral lesions. Some of these lesions are dermoid cysts, sebaceous cysts, peripheral nerve sheet tumors (PNST), lipoma, hemangioma, dermatofibroma and pilomatrixoma, myxoid liposarcoma, extraskeletal myxoid chondrosarcoma, myxofibrosarcoma and malignant PNST (1,2). The diagnosis is usually made by histopathological examination. However, there are only a few reports describing the cytological characteristics of CS (2–5). The presence of uniform plasmacytoid cells and myoepithelial cells in the chondromyxoid matrix favor the cytological diagnosis of CS (2). These findings may also be seen on aspiration smears obtained from mesenchymal tumors, especially chondroid tissue tumors. Cytological discrimination between malignant CS and sarcomas is very difficult. The age of our case and localization of the mass were not usual for benign CS. However, there were no histological/cytological and clinical evidences of malignancy. Some cases may be overlooked in routine practice. Hence, if aspiration smears from a subcutaneous nodular lesion show plasmacytoid cells in a chondromyxoid matrix, CS should be considered in the spectrum of differential diagnosis.

La concordance du diagnostic histopathologique des sarcomes osseux et des tissus mous entre deux centres anticancéreux de l’Europe de l’Est et de l’Ouest : une expérience de collaboration

This study aims to assess the degree of concordance of histological diagnosis of bone and soft tissue sarcomas between a Comprehensive Cancer Center (CCC) of Eastern Europe -not specialized in this area of pathology- and an important CCC of Western Europe, which is one of the coordinators of a clinical reference network in sarcoma pathology. The goal is to have an overview of the sarcomatous pathology in a region of Eastern Europe and to discover diagnostic discrepancies between the two centers, while determining their cause. The initial diagnosis was compared with the revised diagnosis on 110 specimens from 88 patients with bone or soft tissue sarcomas from East-European CCC, in a one-year period of time. Complete diagnostic agreement was observed in 55 cases (62.5%), a partial agreement in 23 cases (26.1%) and a major disagreement in 10 cases (11.4%). Major discrepancies of the histological type was observed in only 3 cases (3.4%): one case of discordance benign/malignant and 2 cases of discordance mesenchymal/non mesenchymal. Minor histological discrepancies -not affecting the management of the patient- were observed in 18 cases (20.4%). A major discordance in grading -potentially changing the management of the patient- was noted in 7 cases (7.9%), and a minor discrepancy in 5 cases (5.7%). Some histological types were clearly overdiagnosed, like "adult fibrosarcomas" and "malignant peripheral nerve sheet tumors" (MPNST), mostly converted after the audit into "undifferentiated spindle cell sarcomas" or other types of sarcomas. Some "unclassified" sarcomas and "undifferentiated pleomorphic sarcomas" could be re-classified with the aid of an extensive panel of antibodies. Overall, immunohistochemistry was responsible, but not in exclusivity, for half of the minor discrepancies, and for 2 out of 3 cases of major histological discrepancies. Otherwise, the main cause of discrepancies was the difficulties in the interpretation of the morphology. Molecular biology was decisive in one case. Most grading discrepancies resulted from the appreciation of the mitotic index. The profile of the sarcomatous pathology in the northwest region of Romania does not appear to differ significantly from other parts of Europe or the world, but a prospective epidemiological study would be necessary to confirm this assessment. The expansion of immunohistochemical antibody panel, the over-specialization of pathologists and, in the future, the establishment of a national network of referral centers in sarcoma pathology, are required for a high level of histological diagnosis in Eastern Europe. A periodic external audit, continuing this trans-European collaboration between the two centers, would be beneficial for monitoring progress.

The more you look, the more you find: challenging results on FDG-PET CT in a patient with neurofibromatosis type I

BackgroundFDG-PET/CT is part of the standard diagnostic management of a patients with a large variety of common and less common malignant tumors, based on the increased glucose metabolism within tumors.Case presentationA hybrid fluorodeoxyglucose positron emission tomography and computed tomography (FDG-PET/CT) was performed in a neurofibromatosis patient to rule out relapse of malignant peripheral nerve sheet tumor. The scan revealed non-malignant neurofibromas, a testis seminoma and hypermetabolic syphilitic granulomata.ConclusionThis case stresses the need to rule out infectious diseases when atypical hypermetabolic lesions are present.

Resection of Plexiform Neurofibromas in Children With Neurofibromatosis Type 1

Large plexiform neurofibromas can cause significant morbidity, functional impairment, and may be even life threatening. They most commonly arise in association with major nerve trunks and follow the distribution of the involved peripheral nerves, and can be subject to transformation into malignant peripheral nerve sheet tumors. They produce large infiltrative masses, which can involve major portions of the trunk or extremities. The main goal of this project is to analyze our surgical experience with plexiform neurofibromas excision and to describe our surgical technique that may help the surgeon to reduce intraoperative bleeding and facilitate tumor excision. A retrospective chart and radiograph review was carried out for all cases of children with neurofibromatosis type 1 followed at our institution. Patients with plexiform neurofibromas of the trunk or extremities and who underwent surgical resection of the tumor were reviewed. Eleven female and 3 male patients with neurofibromatosis type 1 with 20 surgically treated lesions were evaluated. The mean age of the patients at time of surgery was 13.4 years (range, 2.9 to 19.1 y). The average follow-up was 65.5 months (range, 24 to 145 mo). Five lesions (25%) were surgically treated before the age of 10 years and 15 lesions (75%) were treated after the age of 10 years. Further debulking was required in 7 lesions and a below knee amputation was performed in 1 case. The main goal of surgical resection of large lesions is to partially restore the normal appearance and function of the affected part and to ameliorate pain, when possible. One of the major complications of this particular surgery is the potential for significant blood loss. This complication seems to be particularly frequent in large plexiform neurofibromas located in those parts of the skeleton where the application of a tourniquet is not possible. Applying large retention sutures during dissection helps in minimizing bleeding and reduces the risk of complications. Level IV, retrospective study. See the guidelines online for a complete description of level of evidence.

Dermatofibrosarcoma Protuberans of the Vulva: A Clinicopathologic and Immunohistochemical Study of 13 Cases

Dermatofibrosarcoma protuberans (DFSP) is a low-grade sarcoma seldom seen in the vulva with only 29 cases reported. We present the clinicopathologic and immunohistochemical features of 13 such cases seen in our institution over a period of 29 years (1978 to 2007). Patient age ranged from 23 to 76 years (mean, 46 y). Twelve patients had a vulvar mass. One patient presented with a pigmented skin lesion. Tumor size ranged from 1.2 to 15 cm (median, 4 cm). Microscopically, all the cases showed typical features of DFSP. In 1 case, myxoid changes were also noted; 3 cases showed fibrosarcomatous transformation. Of interest, in 7 of our 13 cases, a variety of diagnoses, such as cellular dermatofibroma, cellular leiomyoma, neurofibroma, low-grade leiomyosarcoma, fibrosarcoma, low-grade malignant schwannoma, desmoplastic melanoma, cellular neurofibroma, and low-grade malignant peripheral nerve sheet tumor were initially considered. All 11 cases tested for CD34 were positive, whereas 7/9 cases, 8/9 cases, and 9/9 cases were positive for PDGFR-alpha, PDGFR-beta, and c-abl, respectively. All patients were initially treated with excisional biopsy, wide local excision, or radical vulvectomy. Local recurrences occurred in 7 cases. One patient also developed distant metastases. All recurrences were treated surgically; 1 patient also received chemotherapy and radiotherapy and another received imatinib (Gleevec). Follow-up data ranging from 2 to 444 months was available for all patients. Nine patients had no evidence of disease, 2 patients were alive with disease, 1 patient had died of disease, and 1 patient had died of other causes. DFSP affects women of a wide age range and has a propensity to recur locally. The frequent expression of PDGFR-alpha, PDGFR-beta, and c-abl in these cases agrees with the findings of other investigators and supports the use of imatinib (Gleevec) in cases that are recurrent or not amenable to surgery.

Loss of Y Chromosome in the Malignant Peripheral Nerve Sheet Tumor of a Patient with Neurofibromatosis Type 1

Neurofibromatosis type 1 (NF1) is one of the most commonly inherited autosomal dominant disorders. In order to determine whether genomic alterations and/or chromosomal aberrations involved in the malignant progression of NF1 were present in a Korean patient with NF1, molecular and cytogenetic analyses were performed on the pathologically normal, benign, and malignant tissues and primary cells cultured from those tissues of the patient. The comparative genomic hybridization (CGH) array revealed a Y chromosome loss in the malignant peripheral nerve sheet tumor (MPNST) tissue. G-banding analysis of 50 metaphase cells showed normal chromosomal patterns in the histopathologically normal and benign cultured cells, but a mosaic Y chromosome loss in the malignant cells. The final karyotype for the malignant cells from MPNST tissue was 45,X,-Y[28]/46,XY[22]. The data suggest that the somatic Y chromosome loss may be involved in the transformation of benign tumors to MPNSTs.

Sarcomas Often Express Constitutive Nitric Oxide Synthases (NOS) But Infrequently Inducible NOS

Nitric oxide (NO) has a dual action in tumors, with both pro-tumor and anti-tumor activities. NO is produced by nitric oxide synthases (NOS). There are three enzyme isoforms: two of them are constitutively produced (neuronal or brain NOS and endothelial NOS), and one is an inducible form (iNOS). NOS expression has been shown in several epithelial tumors, but there is no report addressing NOS expression in sarcomas. The authors evaluated the expression of NOS in 97 cases of various sarcomas spotted in duplicate in a tissue array paraffin block. Eighty-four of the 97 tumor specimens (86.6%) expressed nNOS, and most of them showed a strong expression of the isoenzyme. Only chondrosarcomas and liposarcomas had significant numbers of negative cases, and all pleomorphic sarcomas, alveolar soft part sarcomas, angiosarcomas, gastrointestinal stromal tumors, and synovial sarcomas showed some degree of positivity. Forty-three cases (44.4%) showed eNOS immunostaining, but only 15.5% showed a strong signal, with emphasis on angiosarcomas, chondrosarcomas, alveolar soft part sarcomas, and synovial sarcoma. Strong expression of iNOS was observed in only 9 cases (9.3%), with weak expression in another 26 cases (26.8%). Strong expression of iNOS was found in malignant peripheral nerve sheet tumors, liposarcomas, pleomorphic sarcomas, fibrosarcomas, chondrosarcomas, and synovial sarcomas. Apparently alveolar soft part sarcomas are unusual in their capacity of expression of NOS isoforms, and in a very peculiar pattern. In conclusion, sarcomas in general commonly express constitutive NOS, and only a few types of sarcomas can express iNOS, the isoenzymes capable of releasing large amounts of NO. More comprehensive studies should be performed to better understand the clinical importance of NOS expression and NO production in sarcomas.

Localized unresectable non‐rhabdo soft tissue sarcomas of the extremities in pediatric age

Treatment of initially unresectable nonrhabdo soft tissue sarcomas (NRSTS) in pediatric age is debated, due to their different chemosensitivity. The authors objective was to evaluate clinical features and treatment results observed in a series of Italian patients over a 24-year period. Fifty-two patients age 8-18 years (median 8 years) were observed (1979-2002). Primary sites were on the lower limbs in 41 and on the upper limbs in 11 cases. Clinical TNM and surgical Intergroup Rhabdomyosarcoma Staging systems were adopted. Therapeutic guidelines recommended an initial biopsy plus neoadjuvant chemotherapy. Aggressive delayed surgery of residual disease, including compartmental resections, was recommended. Radiotherapy was suggested only for patients age > 3 years when surgery was incomplete or not feasible. The evaluation was performed dividing the patients into two categories according to their chemosensitivity. Chemosensitive (CTs) sarcomas, 21: synovial sarcoma, 11; extraosseous Ewing sarcomas, 5; primitive peripheral neuroectodermic tumors, 5. Nonchemosensitive (CTns) sarcomas, 31: fibrosarcoma, 11; malignant peripheral nerve sheet tumors, 10; liposarcoma, 2; hemangiopericitoma adult type, 2; epithelioid sarcoma, 2; and alveolar soft part sarcoma, leiomyosarcoma, clear cell sarcoma, and sarcoma NOS, each 1. Nineteen of 21 patients with CTs-NRSTS were alive without disease: the 5-year overall survival (OS) and progression-free survival (PFS) were 94.4% and 79.3%, respectively; 23 of 31 patients with CTns-NRSTS were alive without disease: 5-year OS and PFS were 75.3% and 68.3%, respectively. Response to neoadjuvant chemotherapy was complete or partial in 10 of 20 evaluable CTs and in 8 of 26 evaluable CTns tumors. The achievement of complete delayed resection was particularly important for CTns-NRSTS. Tumor size < 5 cm, distal site, and tumor grading for CTns sarcomas were often linked to a favorable outcome; no conclusive results were detected concerning age of the patients or T status of the tumor. Multidisciplinary treatment without mutilating procedures allowed the cure of most patients with CTs and CTns-NRSTS. Relapses were cured in several cases of CTs tumors, whereas almost all patients with relapsed CTns tumors died due to the high rate of metastatic spread.

Colonic Infiltration By A Metastatic Malignant Peripheral Nerve Sheet Tumor Arising In The Lower Limb

A 74-year-old man presented a mass located in the left leg near the knee which was characterized as a malignant peripheral nerve sheet tumor (MPNST). Multiple lung lesions and a 5-cm mass in the caecum were detected by Computed Tomography. This appearance was equivocal. By colonoscopy and related biopsies colonic infiltration by sarcoma cells was detected. In this case, a primitive MPNST and bowel metastasis were diagnosed. Given the relative rare tumor it is difficult to estimate the incidence of bowel metastasis, but secondary bowel involvement in MPNST must be taken into consideration in presence of suggestive radiographic images and/or clinical symptoms (bleeding and anemia).