Cellular Schwannoma Research Articles

Solitary circumscribed neuroma of the skin (so‐called palisaded, encapsulated neuroma). Clinicopathological analysis of three cases with emphasis on differential diagnosis

AbstractThree cases of solitary circumscribed neuroma (so‐called palisaded, encapsulated neuroma) arising in the dermis have been studied. Two patients were male and one was female, with ages ranging from 27 to 59 years. All lesions arose on the forehead. Histologically, the neoplasms were partly encapsulated and were composed of broad fascicles, nests, and whorl‐like structures of bland appearing spindle cells often separated by artefactual clefts. Immunohistochemically. most of the tumour cells stained positive for S‐100 protein, and a considerable number also for CD 34, but failed to stain for epithelial membrane antigen and melanoma associated antigens. Solitary circumscribed neuroma has to be distinguished from long‐standing dermal melanocytic nevus, mucosal neuromas seen in type lib multiple endocrine neoplasia (MEN) syndrome, classical and cellular schwannoma, neurofibroma. perineurioma, traumatic neuroma, and angioleiomyoma.

Cellular schwannoma of the mandible: A case report with ultrastructural and immunohistochemical observations

Cellular schwannoma of the mandible: A case report with ultrastructural and immunohistochemical observations

Cellular schwannoma: A clinicopathologic, DNA flow cytometric, and proliferation marker study of 70 patients

CancerVolume 77, Issue 3 p. 591-593 CorrespondenceFree Access Cellular schwannoma: A clinicopathologic, DNA flow cytometric, and proliferation marker study of 70 patients Steven I. Hajdu M.D., Corresponding Author Steven I. Hajdu M.D. Department of Laboratories, North Shore University Hospital, Manhasset, New YorkDepartment of Laboratories, North Shore University Hospital, Manhasset, New York===Search for more papers by this author Steven I. Hajdu M.D., Corresponding Author Steven I. Hajdu M.D. Department of Laboratories, North Shore University Hospital, Manhasset, New YorkDepartment of Laboratories, North Shore University Hospital, Manhasset, New York===Search for more papers by this author First published: 1 February 1996 https://doi.org/10.1002/(SICI)1097-0142(19960201)77:3<591::AID-CNCR25>3.0.CO;2-ZCitations: 2AboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinkedInRedditWechat No abstract is available for this article. References 1 Casadei GP, Scheithauer BW, Hirose T, Manfrini M, Van Houton C, Wood MR. Cellular schwannoma: a clinicopathologic, DNA flow cytometric, and proliferation marker study of 70 cases. Cancer 1995; 75: 1109– 19. 2 Hajdu SI. Schwannomas. Mod Pathol 1995; 8: 109– 15. 3 Hajdu SI. Pathology of soft tissue tumors. Philadelphia: Lea & Febiger, 1979. 4 Sordillo PP, Helson H, Hajdu SI, Magill GB, Kosloff C, Golby R, et al. Malignant schwannoma-clinical characteristics, survival and response to therapy. Cancer 1981; 47: 2503– 9. 5 Hajdu SI. Differential diagnosis of soft tissue and bone tumors. Basel: S. Karger AG, 1989. 6 Donohue JH, Collin C, Friedrich C, Godbold J, Hajdu SI, Brennan MF. Low-grade soft tissue sarcomas of the extremities. Analysis of risk factors for metastases. Cancer 1988; 62: 184– 93. 7 Hajdu SI. Peripheral nerve sheath tumors. Histogenesis, classification, and prognosis. Cancer 1993; 72: 2549– 52. 8 Harkin JC, Reed RJ. Tumors of the peripheral nervous system. Washington, D.C.: Armed Forces Institute of Pathology, 1969. 9 Reed RJ, Harkin JC. Tumors of the peripheral nervous system. Supplement. Washington, D.C.: Armed Forces Institute of Pathology, 1983. 10 Ducatman BS, Scheithauer BW, Piepgras DG, Reiman HM, Ilstrup DM. Malignant peripheral nerve sheath tumors: a clinicopathologic study of 120 cases. Cancer 1986; 57: 2006– 21. 11 Russell DS, Rubenstein LJ. Pathology of tumors of the nervous system. 5th edition. London: E. Arnold, 1989. 12 Russell WO, Cohen J, Enzinger F, Hajdu SI, Heise R, Martin RG, et al. A clinical and pathological staging system for soft tissue sarcomas. Cancer 1977; 40: 1562– 70. 13 Hajdu SI, Shiu MH, Brennan MF. The role of the pathologist in the management of soft tissue sarcomas. World J Surg 1988; 12: 326– 31. Citing Literature Volume77, Issue31 February 1996Pages 591-593 ReferencesRelatedInformation

Cellular schwannoma: A clinicopathologic, DNA flow cytometric, and proliferation marker study of 70 patients

Cellular schwannoma: A clinicopathologic, DNA flow cytometric, and proliferation marker study of 70 patients

Proliferative potential of sporadic and neurofibromatosis 2-associated schwannomas as studied by MIB-1 (Ki-67) and PCNA labeling.

Neurofibromatosis 2 (NF2), a dominantly inherited disorder, is typically manifested as bilateral vestibular Schwannomas and predisposes to other nervous system tumors. Vestibular Schwannomas also occur sporadically but the onset is usually at an older age. Surgical and histological studies have shown that vestibular Schwannomas of NF2 patients are more invasive than sporadic Schwannomas and that the two groups also have morphological differences. We compared the proliferation activity of 26 vestibular Schwannomas (19 NF2 patients) to that of 27 sporadic cases using the Ki-67 (MIB-1) and PCNA (19A2) monoclonal antibodies. In addition, proliferation was assessed in 20 spinal benign Schwannomas, 4 spinal cellular Schwannomas and 3 spinal malignant peripheral nerve sheath tumors (MPNST). We found a significant difference in the proliferation potential between NF2 and sporadic vestibular Schwannomas (MIB-1-LI: 1.72 +/- 0.93 vs 0.95 +/- 0.57, p = 0.001; and PCNA-LI: 1.40 +/- 0.75 vs 0.81 +/- 0.52, p = 0.001). Age does not explain the detected difference in proliferation, since NF2 vestibular Schwannomas also had higher MIB-1 indices than 34 age-matched sporadic tumors. In spinal tumors, MPNST had higher MIB-1 indices than cellular Schwannomas, and therefore MIB-1 staining may be useful in distinguishing between them. Although the defective NF2 gene is important in the tumorigenesis of both NF2 and sporadic Schwannomas, our results suggest that there are differences in the molecular biology of these tumors.

Immunohistochemical and molecular analysis of p53, MDM2, proliferating cell nuclear antigen and Ki67 in benign and malignant peripheral nerve sheath tumours.

A series of 26 malignant peripheral nerve sheath tumours (MPNST) and 24 benign peripheral nerve sheath tumours (BPNST) were analysed immunocytochemically for p53 expression and the cell proliferation markers proliferating cell nuclear antigen (PCNA) and Ki67 (with MIB1). In 23/26 MPNST, 5%-65% of the tumour cell nuclei were immunoreactive for Ki67 with MIB1 while none of the 24 BPNST had nuclear staining exceeding 5%. Greater than 50% nuclear PCNA staining was detected in 25/26 MPNST compared with 8/24 BPNST; 17/26 MPNST showed 5-100% nuclear staining for p53 (13/26 > 20%), whereas none of the BPNST had nuclear staining exceeding 1%. The Ki67, PCNA and p53 immunostaining results correlated significantly with benign versus malignant (P < 0.001, P < 0.001 and P < 0.005, respectively) as well as mitotic rate (P < 0.001, P < 0.05 and P < 0.05). Ki67 immunostaining results correlated significantly with PCNA and p53, as did p53 and Ki67 and PCNA (P < 0.001 in both). Stepwise (logistic regression forward) multivariate analysis of the variable, benign versus malignant, revealed the strongest correlations with PCNA (P = 0.007) and Ki67 (P = 0.021). Direct confirmation of the presence of p53 protein was obtained by western blot analysis of 3 MPNST and 5 BPNST. Two MPNST, showing 90% and 30% immunoreactivity, were positive for p53, while one MPNST with 5% immunoreactivity and all 5 BPNST were negative. Southern blot analysis performed on the two MPNST with high p53 protein levels revealed no amplification of the MDM2 gene, suggesting that high p53 levels in MPNST are likely to be due to mutation. The results also indicate that PCNA and Ki67 are potentially useful in distinguishing BPNST from MPNST, particularly in problematic cases of cellular schwannoma versus MPNST. The detection of p53 in a large percentage of cells of a plexiform neurofibroma giving rise to MPNST and Ki67 in 5% and 25% of cells of two similar cases suggests that malignant transformation may be detected in some cases by p53 and proliferation markers prior to overt histological evidence of malignancy.

Cellular schwannoma. A clinicopathologic, DNA flow cytometric, and proliferation marker study of 70 patients.

A clinicopathologic study of 70 cases of cellular schwannoma was performed to assess their distribution, response to therapy, and rate of recurrence relative to modern prognostic indicators. Seventy-one cellular schwannomas from 70 patients were retrieved from the files of the Mayo Clinic Tissue Registry. The significance of mitotic index, proliferative marker staining (proliferating cell nuclear antigen and MIB1), immunochemical p53 expression, and DNA ploidy were assessed relative to tumor behavior, particularly recurrence. All parameters were subject to statistical analysis (Student's t test). Cellular schwannomas represented 4.6% of benign peripheral nerve tumors operated on at the Mayo Clinic. In 15% of the cases, an initial diagnosis of malignancy had been made. The median patient age was 47.7 years (range, 15-80 years) and the female-to-male ratio was 1.6:1. The principle tumor locations were the para- and intraspinal regions, including the sacrum (64%), extremities (25%), and intracranial space (8%). All tumors consisted primarily of hypercellular, compact, Antoni A tissue. Mitoses (< or = 4/10 hPF]) were observed in 71% of the cases. Foci of necrosis were noted in 11% of cases. Ultrastructural studies and immunohistochemistry clearly demonstrated features of schwannian differentiation. Surgery was the treatment in all cases. Excision was intralesional to gross total in the majority; total resection with wide margins was undertaken in three tumors, each of which had initially been considered malignant. Follow-up in 47 patients (67%) ranged from 1 to 29 years (mean, 7.7 years) and revealed recurrences in 11 patients (23.4%): no patient experienced metastasis or died of tumor. Although no correlation existed between recurrence and DNA ploidy, percent S-phase determinations, proliferation marker (PCNA, MIB1) staining, or the frequency of p53 immunoreactivity, a statistically significant correlation (P < 0.001) was observed, however, between recurrence and mitotic indices. Proliferation indices, as defined by immunochemical analysis, are not useful predictors of recurrence in cellular schwannoma. In lesions not completely resected, tumor recurrence is significantly correlated with mitotic count. The significant overall frequency of recurrence in this series is attributable to a high proportion of intraspinal and intracranial tumors. Our study confirms the benign nature of cellular schwannoma and underscores the necessity of distinguishing them from malignant peripheral nerve sheath tumors, lesions that often require adjuvant therapy.

Intracerebellar melanotic schwannoma: a case report

Neuro-axial melanotic schwannoma is a rare entity. We report the clinical, CT and pathological features of a solitary, cellular intracerebellar melanocytic schwannoma in a 65-year-old woman. The probable origin of this type of tumour is discussed.

Plexiform Malignant Peripheral Nerve Sheath Tumor of Infancy and Childhood

We present nine cases of an atypical cellular peripheral nerve sheath tumor, designated plexiform malignant peripheral nerve sheath tumor (MPNST) of infancy and childhood, occurring in five boys and four girls aged 50 days to 13 years (median, 1.5 years). The tumors were located in the lower extremities (five cases), upper extremities (three cases), and the orbital region (one case), and they ranged from 1.5 to 8 cm in size (median, 3 cm). Two lesions were congenital, and another was associated with a history of von Recklinghausen's disease. Follow-up, available in six cases, ranged from 6 months to 15 years (median, 51 months); four patients had local recurrences within 8 to 31 months after excision of the initial lesion, and one with an orbital tumor died of locally invasive disease within 6 months. Histologically, the initial lesions were characterized by a predominantly superficial location within the dermis and subcutis, with occasional extension into deeper soft tissues, had infiltrative or sharply demarcated margins, and resembled entangled or intertwined hypercellular nerve trunks, resulting in a plexiform appearance at low magnification. The nuclei were oval to serpentine with a vesicular chromatin pattern and small basophilic nucleoli; mitoses were seen in all cases and averaged from 1 to 18/10 high-power fields (hpf) (median, 4/10 hpf). Neither necrosis nor vascular invasion was seen. Features diagnostic of plexiform or cellular schwannoma, such as nuclear pleomorphism, Antoni B areas, thick-walled hyalinized blood vessels, and secondary degenerative features were lacking. Other than a prominent plexiform architecture, the lesions were indistinguishable from MPNST occurring in other sites in infants and children. Although none metastasized, the histologic similarity of plexiform MPNST to other childhood MPNST, its relatively high propensity for local recurrences, and its potential to behave in a locally aggressive manner indicate that it is best regarded as low-grade malignant. Overall, the behavior of plexiform MPNST is better than other MPNST in children, probably because of its relatively small size, peripheral and superficial location in most instances, absence of necrosis or vascular invasion, occurrence in young patients, and infrequent association with von Recklinghausen's disease rather than a function of its prominent plexiform architecture. Distinction of plexiform MPNST from cellular and plexiform schwannoma, plexiform neurofibroma, and hamartomatous lesions of childhood is important. Complete excision should be ensured to prevent local recurrences and potential metastases.

Spinal malignant nerve-sheath tumor or cellular schwannoma? A striking difference in prognosis.

Cellular schwannoma, a recently delineated entity, has a histological appearance mimicking that of malignant neoplasms. The aim of this study was to determine the outcome for patients treated for a spinal cellular schwannoma or malignant nerve-sheath tumor. A histological re-examination was conducted of 283 spinal tumors, considered to originate from a nerve root, that were treated in the Department of Neurosurgery between 1953 and 1985. After re-examination, 50 of these were determined to be other tumors or non-neoplastic lesions. The review yielded eight cellular schwannomas and six malignant nerve-sheath tumors out of 233 of nerve-sheath origin. Immunohistochemical staining with a commercially available polyclonal antibody against S-100 protein was positive in all cases of cellular schwannoma, but negative for the malignant tumors. Clinical outcome was favorable for patients with cellular schwannomas, but uniformly poor for those with the malignant tumors.

Degenerative ("ancient") changes in benign cutaneous schwannoma. A light microscopic, histochemical and immunohistochemical study.

We studied the degenerative "ancient" changes in 19 cases of benign cutaneous schwannoma (BCS). Using conventional and immunohistochemical stains, we found (a) degenerative changes in 15 of 19 BCS; (b) prominent vascular abnormalities in 11 of 15 BCS; and (c) cytologic atypia in 15 of 19 BCS, without mitotic figures. We concluded that (1) degenerative, i.e., "ancient" changes are common in BCS and are qualitatively similar to those described in cellular schwannoma; (2) vascular abnormalities may be related to these degenerative changes; (3) cytologic atypia is commonly associated with "ancient" changes in BCS, but BCS is less cellular and has few if any mitotic figures as opposed to cellular schwannomas; and (4) the changes in "ancient" schwannoma do not indicate a "cellular" schwannoma.

Cellular Schwannomas of the Intracranial and Intraspinal Compartment: Morphological and Immunological Characteristics Compared with Classical Benign Schwannomas

The concept of cellular schwannoma as an unusual benign tumor is well established for peripheral nerves but has never been tested in neurosurgical series. In order to test the validity of this concept in cranial nerves and spinal roots we performed an analysis of the clinical and morphological characteristics of 12 cellular and 166 classical benign schwannomas. Immunohistochemical detection of antigen expression in Schwann cells including proliferating cell nuclear antigen (PCNA) was also performed. This study shows that cellular schwannomas in neurosurgical series manifest at a lower age than the classical benign variant and occur mainly in the spinal roots. Mitotic activity and sinusoidal vessels appear more frequently in cellular schwannomas and constitute with high cellularity, the most valuable criteria separating both entities. The postoperative course in both types of tumors was free of metastases or sarcomatous changes. Immunoexpression of S-100 protein, vimentin, epithelial membrane antigen and glial fibrillary acidic protein is not statistically different between the two variants. In contrast, PCNA is more highly expressed in cellular schwannomas. These These results confirm the concept that cellular schwannomas are a clinico-pathological variant of benign schwannomas and provide significant support for the introduction of this entity in neurosurgical oncology.

Cellular schwannoma of the vagina

Schwannomas of the female genital tract are rare, and an example in the vagina has not previously been reported. The case of a 37-year-old woman with a cellular schwannoma of the vagina is described and is accompanied by a review of schwannomas in the female genital tract.

Malignant peripheral nerve sheath tumor of the orbit

Malignant peripheral nerve sheath (MPNS) tumor is a rare neoplasm of the orbit. The authors report a 78-year-old woman with an anaplastic MPNS tumor of the orbit that arose from a pre-existing encapsulated tumor composed of cells having a low mitotic index and displaying ultrastructural features of Schwann cells. The encapsulated tumor was unusual for a schwannoma because of its greater cellularity, absence of Antoni B tissue, and rarity of nuclear palisading. This combination of morphologic findings has two possible interpretations: (1) the anaplastic portion of the tumor arose from a variant of benign schwannoma known as a cellular schwannoma, or (2) the entire tumor was an MPNS tumor with variable differerentiation and extensive growth within markedly thickened perineurium.

Newly Recognized Neural Neoplasms Relevant to the Dermatopathologist

Several forms of neural neoplasia have recently been described and are still not well known. Entities such as nerve sheath myxoma, cellular schwannoma, plexiform schwannoma, and palisaded encapsulated neuroma have special clinicopathologic relevance and should be diagnosed correctly by the dermatopathologist. Familiarity with these new entities and with their differential diagnosis contributes to better patient management.

Clonal chromosome abnormalities and in vitro growth characteristics of classical and cellular schwannomas

Cytogenetic analysis was performed on 12 schwannomas, 10 classical and two of the cellular type. Electron microscopic examination of cultured cells from two classical and two cellular schwannomas revealed features compatible with a Schwann cell differentiation. Immunohistochemical analysis of the cultures demonstrated immunoreactivity for S-100 protein in 6 of 6 cases and for vimentin in 2 of 2 cases of classical schwannoma, thus further supporting the authenticity of the cultured cells. Cultured cells from one cellular schwannoma also exhibited immunoreactivity for glial fibrillary acid protein (GFAP). Cytogenetic analysis of the 12 tumors revealed clonal abnormalities in 10 of the cases. In the majority of tumors, cells with a normal karyotype coexisted with different abnormal clones and sporadic deviations. Numerical changes predominated and were found in all tumors, while structural rearrangements were detected in eight tumors. The most common abnormality was clonal or sporadic loss of chromosome 22, which was found in all cases. Other clonal abnormalities included loss of one sex chromosome found in five cases, −15 found in three cases, and −12, +5, +7, +20 found in two cases each. These results provide further evidence in support of a role for loss of chromosome 22 in the pathogenesis of schwannomas. Our findings also indicate that there exist several different evolutionary pathways for schwannomas, and that some of these are shared by several other types of benign and malignant tumors of the nervous system.

Retroperitoneal Cellular Schwannoma: Report of a Case Diagnosed by the Presence of S-100 Protein.

A case of cellular schwannoma originating from the retroperitoneum is reported. The histological features of the tumor resembled those of a smooth muscle tumor. However, the tumor cells were positive for S-100 protein, which is almost exclusively identified within nerve sheath tumor cells. This finding confirmed the diagnosis of cellular schwannoma. This type of tumor is generally considered to be benign but is sometimes mistaken for a malignant tumor. These findings indicate that it is important to prove whether or not S-100 protein is present in the cells of a tumor of unknown origin especially arising in the mediastinum or retroperitoneum.

Cellular schwannoma. A clinicopathologic study of 57 patients and 58 tumors

The cellular schwannoma is a variety of schwannoma with a predominantly cellular growth but no Verocay bodies. Because doubt has been raised about the original assessment of this tumor as benign, the clinical and pathologic characteristics of 58 cellular schwannomas from 57 patients were reviewed. The patients were most often middle aged (63% were female), and their tumors most commonly were painless masses with a predilection for the paravertebral region of the retroperitoneum, pelvis, and mediastinum. Most tumors were solitary and encapsulated, and an associated nerve was identified for 43% of the cases. Electron microscopic and immunohistochemistry studies confirmed the tumor's Schwann cell nature. Worrisome features such as bone erosion, hypercellularity, foci of necrosis (four tumors), hyperchromasia, nuclear pleomorphism, and the presence of mitotic figures led to a malignant diagnosis for 28% of the cases. Treatment in all but one case was surgical excision. Two patients also received radiation therapy and chemotherapy. Follow-up of from 1 year to 24 years, 7 months (median of 6 years and mean of 7 years) for 61% (35 cases) of the cases reveals three patients with a local recurrence but no cases in which the tumor metastasized or the patient died of the tumor. Awareness of this tumor type is important so that the surgeon will avoid unnecessary sacrifice of functionally important nerves attached to these tumors and so that needless adjuvant radiation and chemotherapy will not be instituted.

Cellular schwannoma

A series of 29 cellular schwannomas is described in terms of their clinical presentation and course, light and electron-microscopic appearance, immunohistochemical properties and cytogenetics. The study indicates that cellular schwannoma can be defined as a subtype of classical schwannoma, characterized by spindle cells forming a compact fascicular, sometimes fibrosarcoma-like growth pattern, a low mitotic activity, a generally moderate nuclear and cellular polymorphism and a high degree of Schwann cell differentiation as seen by electron microscopy and immunohistochemistry. The tumour is characteristically located close to the vertebral column, in the mediastinum or retroperitoneum and has a benign course. Occasionally bone destruction and neurological symptoms develop. The clinical appearance together with the high cellularity, fascicular pattern and mitotic activity had led to the erroneous diagnosis of a soft tissue sarcoma in a few cases, and cellular schwannoma may thus be considered to be a pseudosarcoma. Immunohistochemically, cellular schwannomas appear to deviate from classical schwannomas and malignant peripheral nerve sheath tumours by their expression of glial fibrillary acidic protein. The chromosome analysis revealed a normal diploid stemline karyotype, with a variety of abnormal clones, including one with monosomy 22.

Primary Omental Tumor with Ultrastructural Features of Cellular Schwannoma and Absence of S-100 Antigen Reactivity

We report a primary well-delimited, large mesenchymal omental neoplasm which appeared in a 58 year old man without neurofibromatous traces. The histological and ultrastructural features were consistent with a Schwann cell origin. However, repeated immunohistochemical reactions failed to demonstrate protein S-100 antigen reactivity in the neoplastic cells, the latter only expressing vimentin. The differential diagnosis with hemangiopericytoma is proposed.