The malignant peripheral nerve sheath tumor (MPNST) is the malignant counterpart to benign soft tissue tumors such as neurofibromas and schwannomas. This term is preferred to older designations such as malignant schwannomas and neurofibrosarcomas. It is most common in the deep soft tissue, usually in close proximity of a nerve trunk. The most common sites include the sciatic nerve, brachial plexus, and sarcal plexus. The most common symptom is pain which usually prompts a biopsy. Most cases average more than 5 cm in diameter. On sections, it may have a white surface with areas of necrosis or hemorrhage. It is the most common sarcoma arising in the setting of von Recklinghausen's disease.
Epidemiology Disease Associations Pathogenesis Laboratory/Radiologic/Other Diagnostic Testing Gross Appearance and Clinical Variants Histopathological Features and Variants Special Stains/
Differential Diagnosis Prognosis Treatment Commonly Used Terms Internet Links
EPIDEMIOLOGY CHARACTERIZATION SYNONYMS
Malignant schwannomas, neurogenic sarcomas
INCIDENCE 10% of all soft tissue sarcomas seen in consultation with 50% occurring in the setting of neurofibromatosis I AGE RANGE-MEDIAN
Patients with neurofibromatosis develop tumors at an earlier age
Most average 32 years but with a wider age range for neurofibromatosis
SEX (M:F) 80% in neurofibromatosis cases are men
56% of patients with sporadic tumors are men
DISEASE ASSOCIATIONS CHARACTERIZATION von Recklinghausen's disease (Neurofibromatosis)
Neurology. 2005 Jul 26;65(2):205-11. Abstract quote
OBJECTIVE: People with neurofibromatosis type 1 (NF1) have a 10% lifetime risk of developing a malignant peripheral nerve sheath tumor (MPNST). MPNSTs are often metastatic and are a frequent cause of death among people with NF1. Clinical evidence suggests that most MPNSTs in people with NF1 develop from preexisting plexiform neurofibromas. However, it is not known whether an individual's risk of developing an MPNST is associated with the burden of benign neurofibromas. The authors conducted a study to determine whether people with NF1 who have benign neurofibromas of various kinds are at greater risk of developing MPNSTs than patients with NF1 who lack these benign tumors.
METHODS: Clinical information on 476 NF1 probands in the Henri Mondor Database was analyzed by logistic regression to examine associations between MPNSTs and internal plexiform, superficial plexiform, subcutaneous, and cutaneous neurofibromas.
RESULTS: Individuals with subcutaneous neurofibromas were approximately three times more likely to have internal plexiform neurofibromas or MPNSTs than individuals without subcutaneous neurofibromas. Individuals with internal plexiform neurofibromas were 20 times more likely to have MPNSTs than individuals without internal plexiform neurofibromas. When this analysis was done with both subcutaneous and internal plexiform neurofibromas as explanatory variables, only the association of MPNSTs with internal plexiform neurofibromas remained significant.
CONCLUSIONS: The observation that malignant peripheral nerve sheath tumors are strongly associated with internal plexiform neurofibromas suggests that patients with neurofibromatosis type 1 with these benign tumors warrant increased surveillance for malignancy.
Malignant Peripheral Nerve Sheath Tumors Associated With Neurofibromatosis Type 1 A Clinicopathologic and Molecular Study of 17 Patients
Karen Leroy, MD, PhD; Valérie Dumas, MD; Nadine Martin-Garcia, MSc; Marie-Claude Falzone, MSc; Marie-Catherine Voisin, MD; Janine Wechsler, MD; Jean Revuz, MD; Alain Créange, MD; Eric Levy, MD; Laurent Lantieri, MD; Jacques Zeller, MD; Pierre Wolkenstein, MD, PhD
Arch Dermatol. 2001;137:908-913 Abstract quote
Objective To identify potential prognostic factors and criteria for early detection of malignant peripheral nerve sheath tumors associated with neurofibromatosis type 1 (NF1).
Design Retrospective study of malignant peripheral nerve sheath tumors in a cohort of 395 patients with NF1 followed up between October 1, 1988, and January 1, 1999; review of the clinical and histological characteristics of treatment and course; and analysis of p53 mutations and overexpression in tumors.
Setting Teaching hospital referral neurofibromatosis center for adults.
Patients Seventeen patients with NF1 (9 males and 8 females). Mean [plusmn] SD patient age at diagnosis was 32 [plusmn] 14 years.
Main Outcome Measures (1) Clinical symptoms, (2) comparison of p53 mutations and overexpression in benign vs malignant tumors; and (3) median survival.
Results Twelve patients had high-grade tumors. All tumors except 1 developed on preexisting nodular or plexiform neurofibromas. Pain and enlarging mass were the first and predominant signs. None of the benign tumors displayed significant p53 staining or p53 mutations. Six of 12 malignant tumors significantly overexpressed p53, and 4 of 6 harbored p53 missense mutations. Median survival was 18 months overall, 53 months in peripheral locations, and 21 months in axial locations.
Conclusions Malignant peripheral nerve sheath tumors are highly aggressive in NF1. They mostly arise from plexiform or nodular neurofibromas. Investigations and deep biopsy of painful and enlarging nodular or plexiform neurofibromas should be considered in patients with NF1. Late appearance of p53 mutations and overexpression precludes their use as predictive markers of malignant transformation.
PATHOGENESIS CHARACTERIZATION GENERAL For malignant tumors, very few if any of these tumors exhibit deletions in the neurofibromatosis locus on chromosome 17 t(X;18) Mod Pathol 2000;13:1253-1263
Until recently, this translocation was thought to be specific for synovial sarcoma, this paper describes 15/20 (75%) of cases positive for this translocation
Malignant Peripheral Nerve Sheath Tumors are t(X;18)-Negative Sarcomas. Molecular Analysis of 25 Cases Occurring in Neurofibromatosis Type 1 Patients, Using Two Different RT-PCR-Based Methods of Detection.
Coindre JM, Hostein I, Benhattar J, Lussan C, Rivel J, Guillou L.
Bergonie Institute and the University of Bordeaux 2, Bordeaux, France.
Mod Pathol 2002 Jun;15(6):589-92 Abstract quote
To verify the absence of the synovial sarcoma translocation t(X;18) (SYT-SSX) in malignant peripheral nerve sheath tumors, 34 tumor samples from 25 neurofibromatosis type 1 patients were examined in two independent laboratories (Bordeaux, France, and Lausanne, Switzerland) using reverse transcriptase polymerase chain reaction (RT-PCR)-based techniques.
RNA was extracted from paraffin blocks using standard methods, reverse transcribed, and conventional (in one laboratory) versus real-time (in the other laboratory) PCR performed. Twenty-seven tumor samples from 19 patients were negative for the t(X;18) in both laboratories; six additional tumors that were t(X;18)-negative in one laboratory gave noninterpretable results in the other, due to lack of internal positive controls; one case was noninterpretable in both places.
In conclusion, malignant peripheral nerve sheath tumors in neurofibromatosis type 1 patients do not bear the synovial sarcoma t(X;18) (SYT-SSX). Laboratories that use PCR-based techniques for diagnostic purposes would benefit from quality assurance programs.
- Aberrant expression of CHFR in malignant peripheral nerve sheath tumors.
Kobayashi C, Oda Y, Takahira T, Izumi T, Kawaguchi K, Yamamoto H, Tamiya S, Yamada T, Iwamoto Y, Tsuneyoshi M.
 1Department of Anatomic Pathology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan  2Department of Orthopaedic Surgery, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.
Mod Pathol. 2006 Apr;19(4):524-32. Abstract quote
Mitotic checkpoint maintains genomic integrity before mitosis. Numerous observations have suggested that mitotic abnormalities produce chromosomal instability and aneuploidy.
In MPNST, complex karyotypes showing numerical and structural aberrations have been described. 'Checkpoint with forkhead-associated domain and ring finger' (CHFR) was recently identified as defining a new early mitotic checkpoint. We examined the expression of CHFR in 96 cases of MPNST by immunohistochemical and molecular methods.
We found reduced (score, </=3) expression of CHFR in 63 out of 96 (66%) cases of MPNST, and such alteration was significantly correlated with a high mitotic count, a high Ki-67-labeling index, and a poor prognosis. In addition, MPNST with normal karyotype showed a strong (score, =5) expression of CHFR. Our results support the assertion that CHFR functions as an inhibitor of tumor proliferation.
- Malignant peripheral nerve sheath tumors (MPNST) in neurofibromatosis type 1 (NF1): diagnostic findings on magnetic resonance images and mutation analysis of the NF1 gene.
Friedrich RE, Kluwe L, Funsterer C, Mautner VF.
Maxillofacial Surgery Clinic, Eppendorf University Hospital, University of Hamburg, Germany.
Anticancer Res. 2005 May-Jun;25(3A):1699-702. Abstract quote
Plexiform neurofibroma (PNF) is a typical feature of neurofibromatosis 1 (NF1). About 10% of patients with NF1 develop malignant peripheral nerve sheath tumors (MPNST), usually arising from PNF, and this is the major cause of poor prognosis. A better prognosis can be achieved if the tumors are diagnosed at an early stage. Our objective was to establish magnetic resonance imaging (MRI) criteria for MPNST, and to test their usefulness in detecting early malignant changes in PNF and to correlate the findings with the mutations of the NF1 gene.
PATIENTS AND METHODS: NF1 outpatients were diagnosed according to the NIH criteria. All patients underwent a complete dermatological, ophthalmological and neurological examination and ultrasound of the abdomen between 1997 and 2002. The study was approved by the Institutional Review Board and all patients gave informed consent to analyze clinical records and tumor material for scientific purposes. MRI was performed with devices at 1.5 Tesla field strength (Siemens Magnetom Symphony) or in some patients at 1.0 Tesla field strength (Siemens Impact Expert). T1- and T2-weighted sequences including STIR-sequences were acquired. Ultra-rapid image sequences with HASTE technique were performed for trunk imaging. In patients with no contraindication for the application of contrast media, Gadolinum-DTPA Magnevist was administered intravenously.
RESULTS: MRI was performed on 50 patients with NF1 and nerve sheath tumors, of whom 7 had atypical pain, tumor growth or neurological deficits indicative of malignancy; the other 43 were asymptomatic. On MRI, all 7 symptomatic patients had inhomogeneous lesions, due to necrosis and hemorrhage and patchy contrast enhancement. In one patient, the multiplicity of confluent tumors with inhomogeneous areas in addition to central lesions did not allow the exclusion of malignancy. Only 3 of the 43 asymptomatic patients had comparable changes; the other 40 patients had tumors of relatively homogeneous structure on T1- and T2-weighted images before and after contrast enhancement. All 3 asymptomatic patients with inhomogeneous lesions were shown to have MPNST. Analysis of mutations of the NF1 gene of the 10 MPNST patients revealed a variety of mutations. Concerning the correlation of genetic findings and MPNST in NF1, the sample size of this study group was too small to define genotype-phenotype relations. In this cohort, all types of mutations were found.
CONCLUSION: This study provides evidence for certain radiographic findings on MRI in PNF of NF1 patients that have to be considered as signs of malignancy, in particular indicating an MPNST. These findings are especially valuable in the long term follow-up control of patients with large tumors (plexiform neurofibromas).
HISTOLOGICAL TYPES CHARACTERIZATION GENERAL
Spindled cells with characteristic wavy nuclei resembling Schwann cells
Arranged in sweeping fascicles alternating with myxoid areas
Nuclear palisading uncommon, present in 10% of cases
Hyaline bands and nodules resembling giant rosettes may be present
Heterotopic islands of cartilage and bone
Mitotic figures present
Subcutaneous malignant epithelioid schwannoma with cartilaginous differentiation
Tetsuji Yamamoto1, Rieko Minami2 and Chiho Ohbayashi2 1
Department of Orthopaedic Surgery, Kobe University School of Medicine, Kobe, Japan, 2 Department of Pathology, Kobe University School of Medicine, Kobe, Japan
Journal of Cutaneous Pathology 2001;28 (9), 486-491Abstract quote
Background: Malignant epithelioid schwannoma is a rare tumor. The aim of this study is to describe a case of subcutaneous malignant epithelioid schwannoma with cartilaginous differentiation.
Methods: Histological, immunohistochemical, and ultrastructural examinations were performed on a tumor that arose on the back of a 37-year-old woman.
Results: Histologically, the tumor predominantly consisted of small, round or polygonal cells arranged in cords or nests. Immunohistochemical study revealed that the tumors cells were positive for vimentin, S-100 protein, glial fibrillary acidic protein and neuron specific enolase. The cells were negative for HMB-45, keratin, epithelial membrane antigen, and CAM5.2. Electron microscopic study showed closely associated cells with undifferentiated features. The cells were devoid of external laminae and cellular junctions.
Conclusion: Malignant epithelioid schwannoma should be pathologically differentiated from other epithelioid tumors with cartilaginous elements.
EPITHELIOID Epithelioid variant
Am J Surg Pathol 1986;10:478
Am J Surg Pathol 1991;15:1136
GLANDULAR Glandular malignant schwannoma (MPNST with with glands) Cancer 1991;67:1076
Most occur in Neurofibromatosis
Few scattered glands with well-differentiated ciliated cuboidal or columnar cells
May have heterotopic elements
Malignant peripheral nerve sheath tumor with perineurial differentiation: 'malignant perineurioma'.
Rosenberg AS, Langee CL, Stevens GL, Morgan MB.
Department of Pathology, University of South Florida College of Medicine, USA Department of Dermatology, University of South Florida College of Medicine, USA James Haley V. A. Hospital, Tampa, Florida, USA.
J Cutan Pathol 2002 Jul;29(6):362-7 Abstract quote
BACKGROUND: Although benign tumors derived from the nerve sheath perineurial cell have been described from a variety of anatomic sites and are known to be a component of a number of benign neoplasms, malignant nerve sheath tumors of perineurial origin are exceedingly uncommon.
METHODS: We report an unusual case of a 70-year-old male who presented with a rapidly growing mass of the left arm, subsequently shown to be a malignant nerve sheath tumor with perineurial differentiation. A brief microscopic differential diagnosis and review of the literature are discussed.
RESULTS: Histologic sections show a partially circumscribed tumor of atypical spindle cells arranged in sweeping fascicles embedded in a myxoid matrix with focal whorling. Nuclear pleomorphism was evident among scattered typical and atypical mitotic figures (mean mitotic index of 7/10 high-power fields). The immunophenotypic profile consisted of only vimentin and epithelial membrane antigen (EMA) positivity, while antibodies to S-100, CD34, smooth muscle actin, and pankeratins were negative. Ultrastructural features included spindle cells with long cytoplasmic processes invested by interrupted basal lamina and pinocytotic vesicles, consistent with perineurial differentiation.
CONCLUSIONS: While the histogenic source of the benign perineurioma, the perineurial cell has only rarely been described in conjunction with malignant tumors. All cases to date have shown EMA-positive and S-100-negative atypical spindled cells arranged in fascicles embedded in a myxoid matrix. In addition to immunohistochemistry, ultrastructural examination may be necessary to support the diagnosis. The diagnostic differential includes melanoma, spindle cell squamous cell carcinoma, atypical fibroxanthoma, leiomyosarcoma, and conventional malignant peripheral nerve sheath tumor, most commonly of Schwannian differentiation. Recognizing perineurial differentiation is important since few cases have been reported to date and the biological potential of these neoplasms is not known.
RHABDOID Cutaneous epithelioid malignant nerve sheath tumor with rhabdoid features J Cutan Pathol 2000;27:529-534 SUPERFICIAL
Am J Clin Pathol. 2005 Nov;124(5):685-92. Abstract quote
We reviewed the clinicopathologic features of 5 cases of malignant peripheral nerve sheath tumor (MPNST) manifesting in superficial locations associated with cutaneous neurofibromas (4 cases) or superficial peripheral nerve (1 case).
Four cases had spindle cell morphologic features and were at least focally positive for S-100 protein, whereas the associated benign neural elements had more extensive S-100 immunoreactivity. The single epithelioid case was diffusely and strongly positive for S-100 protein. Melanoma markers, epithelial membrane antigen, glial fibrillary acidic protein, neurofilament, pancytokeratin (AE1/AE3), CD34, smooth muscle actin, and desmin were negative in all cases. There were no local recurrences, but 3 patients died of metastatic disease within 2 to 30 months (median, 21 months). MPNSTs can occur in a superficial location and may have an aggressive clinical course.
Immunohistochemical markers are helpful in excluding other lesions in the differential diagnosis. However, identification of a benign precursor or origin from a nerve may be the most definitive way to properly classify these rare lesions.
TRITON TUMOR Triton Tumor (MPNST with rhabdomyoblastic differentiation) 2/3 of cases occur in Neurofibromatosis
Most occur in head and neck and trunk
- Clinicomorphologic features of a series of 10 cases of malignant triton tumors diagnosed over 10 years at a tertiary cancer hospital in Mumbai, India.
Department of Pathology, Tata Memorial Hospital, Mumbai 400012, India.
- Ann Diagn Pathol. 2008 Apr;12(2):90-7. Abstract quote
A rhabdomyoblastic differentiation in a malignant peripheral nerve sheath tumor is unusual and is termed as a malignant triton tumor. A series of 10 such cases with their clinicomorphological features, diagnosed over a 10-year period, is presented. The average age of occurrence was 30 years, with the maximum number of cases in the second decade and with male outnumbering female patients. More cases were seen in the setting of neurofibromatosis.
On histology, 80% of the cases were of high grade. Distinct rhabdomyoblastic cells were identified in the areas of malignant peripheral nerve sheath tumor.
Immunohistochemistry confirmed the neurogenic differentiation with varying S-100 expression and the rhabdomyoblastic differentiation with desmin and myoglobin positivity in all cases. Surgery with adequate margins constituted the treatment mainstay with adjuvant chemotherapy and/or radiotherapy in individual cases. On follow-up with 7 cases, 3 showed local recurrences, including one that, in addition to another 2 cases, showed lung metastasis. One patient died of the disease. This case along with another high-grade case displayed a diffuse Ki-67 and p53 positivity.
Malignant triton tumor is an uncommon tumor associated with an aggressive behavior. Surgery with clear margins is the treatment mainstay. Adjuvant radiotherapy is effective.
Schwannoma with rhabdomyoblastic differentiation: a unique variant of malignant triton tumor.
Kurtkaya-Yapicier O, Scheithauer BW, Woodruff JM, Wenger DD, Cooley AM, Dominique D.
Am J Surg Pathol. 2003 Jun;27(6):848-53. Abstract quote
A 54-year-old woman presented with intractable perianal, bilateral buttock, and radiating thigh/calf pain. An MRI scan showed an intradural, contrast-enhancing, ovoid mass in the cauda equina region at L1-L2.
At laminectomy, the ovoid mass arose from a nerve root and, intact, was gross totally resected. Histologically, the dominant pattern was that of schwannoma. One year thereafter, the symptoms recurred. An MRI scan demonstrated an irregular, heterogeneously enhancing tumor recurrence. A repeat laminectomy disclosed a large fleshy tumor involving multiple nerve roots. The lesion was subtotally resected and showed pluridirectional differentiation toward embryonal rhabdomyosarcoma, primitive neuroectodermal tumor, and rare malignant epithelial cells. Review of the original tumor disclosed only foci of embryonal rhabdomyosarcoma and primitive neuroectodermal tumor.
Based upon available data regarding divergent differentiation in peripheral nerve sheath tumors, this is a unique, previously undescribed tumor demonstrating rhabdomyosarcomatous, primitive neuroectodermal tumor and scant epithelial differentiation in a schwannoma.
In essence, it is a variant of malignant Triton tumor because of its origin in a tumor consisting of well-differentiated Schwann cells. It supports the contention that the Schwann cell is the source of a variety of heterologous elements in nerve sheath tumors.
CHARACTERIZATION IMMUNOPEROXIDASE Tumor cells positive for S100 CD34
Immunohistochemical Demonstration of EMA/Glut1-Positive Perineurial Cells and CD34-Positive Fibroblastic Cells in Peripheral Nerve Sheath Tumors.
Hirose T, Tani T, Shimada T, Ishizawa K, Shimada S, Sano T.
Department of Pathology (TH, TT, TS, KI, SS), Saitama Medical School, Saitama.
Mod Pathol 2003 Apr;16(4):293-8 Abstract quote
To clarify the cellular composition of various peripheral nerve tumorous lesions (traumatic neuroma, 5 cases; schwannoma, 10 cases; neurofibroma, 14 cases; perineurioma, 3 cases; conventional malignant peripheral nerve sheath tumor (MPNST), 7 cases; perineurial MPNST, 4 cases), expression of several markers specific to nerve sheath cells, including glucose transporter protein 1 (Glut1) and CD34, were immunohistochemically investigated with highly sensitive detection methods.
In normal nerves and neuromas, perineuriums were positive for Glut1 as well as for epithelial membrane antigen (EMA), and there were some CD34-positive fibroblast-like cells in the endoneurium. Schwannomas consisted principally of S-100 protein-positive Schwann cells, whereas a few CD34-positive fibroblastic cells were present in Antoni B areas. Neurofibromas and conventional MPNST exhibited a mixed proliferation of S-100 protein-, EMA/Glut1-, and CD34-positive cells, indicating a heterogeneous composition of the constituents.
The catalyzed signal amplification (CSA) system demonstrated more numerous EMA-positive perineurial cells in neurofibromas than did the ENVISION+ method. Perineurial cell tumors (benign and malignant) were composed of EMA/Glut1-positive and S-100 protein-negative tumor cells.
The present study confirmed the characteristic cellular composition to each nerve sheath tumor immunohistochemically and showed the usefulness of the nerve sheath cell markers. Glut1 as well as EMA are specific to perineurial cells, and CD34 seems to be immunoreactive to endoneurial fibroblasts.
Tyrosinase expression in malignant melanoma, desmoplastic melanoma, and peripheral nerve tumors.
Boyle JL, Haupt HM, Stern JB, Multhaupt HA.
Department of Pathology, Pennsylvania Hospital, Philadelphia, PA 19107, USA.
Arch Pathol Lab Med 2002 Jul;126(7):816-22 Abstract quote
CONTEXT: Pathologists may encounter problems in the differential diagnosis of malignant melanoma, spindle and epithelioid neoplasms of peripheral nerves, and fibrohistiocytic tumors. Tyrosinase has been demonstrated to be a sensitive marker for melanoma.
OBJECTIVE: To determine the specificity of tyrosinase expression in the differential diagnosis of melanoma, desmoplastic melanoma, and peripheral nerve sheath tumors.
DESIGN: Immunoreactivity for tyrosinase, HMB-45 (anti-gp100 protein), S100 protein, CD34, and vimentin was studied in 70 tumors, including 15 melanomas (5 desmoplastic, 4 amelanotic, 6 melanotic), 13 malignant peripheral nerve sheath tumors; 10 schwannomas (1 pigmented), 12 neurofibromas (4 pigmented), and 20 fibrohistiocytic tumors (10 dermatofibrosarcoma protuberans and 10 dermatofibromas). Microwave-based antigen retrieval was performed in 10mM citrate buffer, pH 6.0, for 20 minutes at 121 degrees C.
RESULTS: All melanomas demonstrated positive immunostaining for tyrosinase, HMB-45, and S100 protein. Immunoreactivity for HMB-45 was generally stronger than that for tyrosinase in amelanotic lesions and significantly stronger in 1 of the desmoplastic lesions. The 4 pigmented neurofibromas were focally positive for tyrosinase, but did not stain for HMB-45. The pigmented schwannoma was focally positive for both tyrosinase and HMB-45. The malignant peripheral nerve sheath tumors, dermatofibrosarcoma protuberans, and dermatofibromas were nonreactive for tyrosinase and HMB-45.
CONCLUSIONS: Our results support the sensitivity of tyrosinase expression and demonstrate the relative specificity of tyrosinase as a marker for melanocytic lesions, including desmoplastic melanoma, although pigmented peripheral nerve tumors may demonstrate focal positive staining. Immunoreactivity for tyrosinase and HMB-45 may have been enhanced by the microwave-based antigen-retrieval technique used in this study.
DIFFERENTIAL DIAGNOSIS KEY DIFFERENTIATING FEATURES EPITHELIOID NERVE SHEATH TUMORS
Am J Surg Pathol. 2005 Oct;29(10):1310-5. Abstract quote
Mucosal nerve sheath tumors have been well described in the gastrointestinal tract and other mucosal sites. In a series of mucosal biopsies, we have encountered a distinct subset of mucosal peripheral nerve sheath tumors characterized by small epithelioid cells and a benign clinical course. Such epithelioid nerve sheath tumors have been observed as a component of a larger study of colorectal "schwannomas," but herein we describe them in detail.
- A series of 7 of these lesions detected on mucosal biopsies (6 colonic, 1 bladder) was received by a single large institution in consultation material. The histologic and clinicopathologic features of the cases were reviewed. The mean age at presentation was 58.6 years with a slight female predominance (4 females, 3 males). Five of the colonic lesions were from the left colon and one from the right colon. The bladder biopsy was from the bladder neck. All of the colonic lesions were discovered as small (0.2-1.0 cm) polyps during the time of colonoscopy (3 at the time of routine screening, 2 for the workup of occult blood in the stool). The bladder neck mass was seen on bladder ultrasound after the patient presented with vaginal bleeding. None of the patients had a known history of neurofibromatosis.
Histologically, the lesions showed an infiltrative growth pattern and were composed of spindled to predominantly epithelioid cells arranged in nests and whorls. The epicenters of the lesions were located in the lamina propria and extended to the superficial submucosa. The proliferating cells had uniform round to oval nuclei with frequent intranuclear pseudoinclusions and eosinophilic fibrillary cytoplasm. No mitoses were seen. All lesions expressed diffuse S-100 protein, and 3 of 5 lesions stained showed CD34 labeling in supporting cells. All were negative for CD117. All 5 lesions tested were negative for calretenin, while SM31 showed no intralesional neuraxons. One lesion was stained for epithelial membrane antigen and was negative. One lesion was associated with superficial mucosal erosion, and 1 had an inflammatory infiltrate predominantly composed of eosinophils. On follow-up of 5 patients, none has had any symptoms or recurrence of disease.
Mucosal epithelioid nerve sheath tumors are a rare entity characterized by prominent epithelioid round to oval cells with an infiltrative growth pattern. These lesions are often discovered incidentally and have a benign clinical course.
NEUROFIBROMAS Cellular neurofibromas and neurilemoma in Neurofibromatosis
In neurofibromas, presence of mitotic figures distinguishes MPNST from this-if only a small focus is malignant in an otherwise typical neurofibroma, the term "neurofibroma with focal malignant change" has been used with a conservative excision recommended
For neurilemomas, mitotic figures still may be accepted in benign tumors
Congenital and childhood plexiform (multinodular) cellular schwannoma: a troublesome mimic of malignant peripheral nerve sheath tumor.
Woodruff JM, Scheithauer BW, Kurtkaya-Yapicier O, Raffel C, Amr SS, LaQuaglia MP, Antonescu CR.
Am J Surg Pathol. 2003 Oct;27(10):1321-9. Abstract quote
SUMMARY: We present six cases of a plexiform nerve sheath tumor of childhood that previously had been designated a form of malignant peripheral nerve sheath tumor (MPNST), and we provide evidence that such tumors are in fact benign plexiform cellular schwannomas. At presentation, the four girls and two boys ranged in age from 2 to 15 months with tumors of the leg (four), deep groin and upper thigh (one), and pelvis (one). Of the six lesions, five were congenital and none was associated with type 1 neurofibromatosis. Tumor sizes ranged from 2.0 to 9 cm, with three larger than 5 cm. Three tumors were well circumscribed, two were purely infiltrative, and one had a mixed circumscribed and infiltrative growth pattern. Peripheral nerve involvement was evident in two cases. Grossly, the tumors were multinodular or plexiform in configuration and, on sectioning, lobulated and homogeneously tan without necrosis.
Characteristic histologic features included hypercellularity, composition of cells spindle in shape with elongate hyperchromatic nuclei, and indistinct cellular outlines. Their nuclei varied minimally in size and shape but were at least three times the size of typical neurofibroma nuclei. Mitoses were seen in every tumor and in the areas of greatest proliferative activity ranged from 4 to 31/10 high power fields. MIB-1 staining of at least 30% of the cells was noted in three cases. In five cases in which p53 immunoreactions were performed, no nuclear staining was evident. That the tumors are schwannomas was evident from their uniform strong staining for S-100 protein and an ultrastructure in all five cases showing only differentiated neoplastic Schwann cells. Architecturally, the tumors differed from conventional schwannoma and nonplexiform cellular schwannomas by their lack of both well-formed capsules and degenerative changes. Follow-up was available in all cases and ranged from 2 to 13.6 years. All tumors recurred locally and were treated by local resections. With the exception of one child lost to follow-up at 25 months, all the children are alive and free of disease.
Our data combined with cases previously reported by Meis-Kindblom and Enzinger show a childhood peripheral nerve tumor unassociated with type 1 neurofibromatosis, occurring most commonly in infants, often presenting as a congenital tumor and, though prone to local recurrence, having no metastatic potential.
The behavior is that of a benign tumor, although its often rapid growth, hypercellularity and increased mitotic activity, sometimes locally aggressive behavior, and difficulties encountered in obtaining tumor-free margins are unsettling to pathologist and clinician alike. These features may lead to a misdiagnosis of malignancy, which could result in harmful overtreatment.
PROGNOSIS AND TREATMENT CHARACTERIZATION Prognostic Factors Size and location of tumor
Adequacy of margins
Age of patient
Malignant peripheral nerve sheath tumor: a comparison of grade, immunophenotype, and cell cycle/growth activation marker expression in sporadic and neurofibromatosis 1-related lesions.
Zhou H, Coffin CM, Perkins SL, Tripp SR, Liew M, Viskochil DH.
Am J Surg Pathol. 2003 Oct;27(10):1337-45. Abstract quote
SUMMARY: This study investigates differences in expression of the cell cycle/growth activation markers p53, p16, and p27, and their relationship with nerve sheath cell and proliferation markers among plexiform neurofibromas (PNF), NF1-related and non-NF1 MPNSTs of different histologic grades and between benign-appearing and malignant areas in the MPNSTs associated with PNFs.
Formalin-fixed, paraffin-embedded archival tissue from PNFs and MPNSTs were immunostained using the avidin-biotin-complex method with antibodies to S-100 protein (S-100), Leu7 (CD57), CD34, p16, p27, p53, Mib-1, and topoisomerase II-alpha (TopoIIalpha), with appropriate controls. All PNFs and most low-grade MPNSTs displayed diffuse or focal reactivity for S-100, Leu7, CD34, p16, and p27 and negative reactivity for p53, Mib-1, and TopoIIalpha. Most high-grade MPNSTs displayed decreased or negative reactivity to S-100, Leu7, CD34, p16, and p27 but increased reactivity to p53 (59%), Mib-1 (72%), and TopoIIalpha (72%). In addition, combined nuclear and cytoplasmic (nucleocytoplasmic) p27 staining, which was not seen in the PNF or low-grade MPNST, was observed in 33% of high-grade MPNSTs. These findings suggest that p53, p16, and p27 may be involved in tumor progression in the PNF-MPNST sequence. However, alterations in p53, p16, and p27 do not distinguish between low-grade MPNST and PNF, including PNF adjacent to high-grade MPNST. Although p53, p16, and p27 are unlikely to be reliable markers for early detection of tumor progression in MPNST, p53 reactivity was more frequent in NF1-associated high-grade MPNST and appeared to be a marker for high tumor grade.
Combining immunohistochemical stains with histologic grading with careful examination of mitotic activity may provide insight into the progression of peripheral nerve sheath tumors.
Survival 5YRS of 43.7% Recurrence 40% with local recurrence Metastasis
Lung, bone, pleura, and retroperitoneum
Regional lymph nodes rare
Tumor tends to spread along nerve sheath and may enter the subarachnoid space
Treatment Please see above
Macpherson and Pincus. Clinical Diagnosis and Management by Laboratory Methods. Twentyfirst Edition. WB Saunders. 2006.
Rosai J. Ackerman's Surgical Pathology. Ninth Edition. Mosby 2004.
Sternberg S. Diagnostic Surgical Pathology. Fourth Edition. Lipincott Williams and Wilkins 2004.
Robbins Pathologic Basis of Disease. Seventh Edition. WB Saunders 2005.
DeMay RM. The Art and Science of Cytopathology. Volume 1 and 2. ASCP Press. 1996.
Weedon D. Weedon's Skin Pathology Second Edition. Churchill Livingstone. 2002
Fitzpatrick's Dermatology in General Medicine. 6th Edition. McGraw-Hill. 2003.
Weiss SW and Goldblum JR. Enzinger and Weiss's Soft Tissue Tumors. Fifth Edition. Mosby Elesevier 2008
Soft Tissue Sarcomas
Basic Principles of Disease
Learn the basic disease classifications of cancers, infections, and inflammation
Commonly Used Terms
This is a glossary of terms often found in a pathology report.
Learn how a pathologist makes a diagnosis using a microscope
Surgical Pathology Report
Examine an actual biopsy report to understand what each section means
Understand the tools the pathologist utilizes to aid in the diagnosis
How Accurate is My Report?
Pathologists actively oversee every area of the laboratory to ensure your report is accurate
Recent teaching cases and lectures presented in conferences
Last Updated March 21, 2008
Send mail to The Doctor's Doctor with questions or comments about this web site.
Read the Medical Disclaimer.
Copyright © The Doctor's Doctor