Mediastinal tumors of peripheral nervous system origin.

A wide spectrum of benign and malignant tumors of peripheral nervous system origin can arise in the mediastinum. These neoplasms are more frequent in the posterior mediastinum and can develop from peripheral nerves, sympathetic and parasympathetic ganglia, and neural tube embryonic remnants. The clinicopathologic features of mediastinal schwannomas, melanotic schwannomas, neurofibromas, ganglioneuromas, granular cell tumors, malignant tumors of peripheral nerve sheath origin, malignant melanocytic tumors of peripheral nerve sheath origin, neuroblastomas, ganglioneuroblastomas, and pigmented neuroectodermal tumors of infancy are reviewed.     

Intraoral malignant melanotic schwannoma. Ultrastructural evidence for melanogenesis by Schwann's cells

Clinical and light and electron microscopic findings of one case of malignant melanotic schwannoma of the oral cavity are presented. The tumor recurred four times and developed submandibular metastasis. At autopsy, 24 months after manifestation of the initial symptoms, a hematogenous metastatic nodule was present in the liver. Peripheral melanotic schwannomas show a more malignant behavior than intraspinal examples. The Schwann's cell character of the individual tumor cells is demonstrated ultrastructurally by the presence of a prominent basal lamina, desmosomelike junctions between interdigitated elongated cell processes, and melanosomes in all stages of formation. These findings support the concept that neoplastic human Schwann's cells are capable of melanogenesis.     

Cytohistologic correlations in schwannomas (neurilemmomas), including "ancient," cellular, and epithelioid variants

Schwannoma accounts for one of the most common benign mesenchymal neoplasms of soft tissues. Although it is well defined in the cytology literature, particular histologic subtypes such as "ancient," cellular and epithelioid variants could be a source of diagnostic difficulties. We have reviewed cytology aspirates and corresponding histologic sections from 34 schwannomas diagnosed at Institut Curie. Histologically, 24 cases were classic, 5 were "ancient," 4 were cellular, and 1 was epithelioid schwannomas. No example of melanotic schwannoma was recorded. Original cytologic diagnosis was schwannoma in 13 (38.2%) cases, benign soft tissue tumor in 11 (32.4%), pleomorphic adenoma in 2 (6%) cases, angioma in 1 (2.9%) case, nodular fasciitis in 1 (2.9%) case, suspicious in 3 (8.8%) cases, and not satisfactory in 3 (8.8%) cases. There were no major differences between classical, "ancient," cellular, and epithelioid variants on cytology smears. Myxoid stroma, mast cells, and intranuclear inclusions were limited to classical subtype. Similarly, cyto-nuclear atypia was more frequent in classical subtype than in other subtypes. Schwannoma should be differentiated from well-differentiated malignant peripheral nerve sheath tumor, neurofibroma, and pleomorphic adenoma, in the last instance particularly for head and neck lesions.     

A 21-year-old female with a third ventricular tumor

A 21-year-old female presented with a 2-months history of tinnitus, vertigo and nausea. On magnetic resonance imaging of the brain, she demonstrated a small contrast-enhancing mass in the posterior part of the third ventricle. Intraoperatively, the tumor showed a close relationship to the choroid plexus of the third ventricle. Histopathology revealed a benign schwannoma of World Health Organization grade I. To our knowledge, only 9 cases of intraventricular Schwann cell tumors have been published so far. Most of these tumors were benign schwannomas, except for 2 cases of malignant peripheral nerve sheath tumors. The tumor of our patient is the first reported schwannoma of the third ventricle. The origin of intraventricular Schwann cell tumors is unknown. They may arise from autonomic perivascular nerves in the choroid plexus or from ectopic neural crest-derived cells. Histologically, intraventricular schwannoma needs to be distinguished from other spindle cell tumors, in particular pilocytic astrocytoma and fibroblastic meningioma.     

Primary benign schwannoma of the heart.

We report herein a case of a 61-year-old woman who was found to have a mass adjacent to the left atrium. The tumor was resected giving least damage to the left atrium on cardiopulmonary bypass with a subsequent histological diagnosis of a schwannoma. Neurogenic tumors comprise 10% to 34% of mediastinal tumors. Nerve sheath tumors are more common in adults than in children, and these are equally malignant in children and adults. Nerve sheath tumors of the heart are extremely rare. Although there are many malignant cardiac neurilemomas reported, only a few cases of benign schwannomas have been reported. We describe a rare primary benign schwannoma of the left atrium.     

Malignant transformation in a hybrid schwannoma/perineurioma: addition to the spectrum of a malignant peripheral nerve sheath tumor

Benign nerve sheath tumors include schwannomas, neurofibromas and perineuriomas. The malignant counterpart of a nerve sheath tumor is designated as a malignant peripheral nerve sheath tumor (MPNST). Lately, benign nerve sheath tumors comprising more than one component have been described, including hybrid schwannomas/perineuriomas. However, malignant transformation in a hybrid schwannoma/perineurioma has not been documented so far. Herein, we present a rare case of a young adult male who presented with a soft tissue mass in his right thigh that was excised elsewhere and submitted to us for histopathological review. One of the tissue sections displayed histopathological features of a hybrid schwannoma/perineurioma, including alternate arrangement of benign schwann and perineurial cells, reinforced with S100-P and epithelial membrane antigen positivity, respectively, along with low MIB1 and negative p53 immunostaining. The other two tissue sections showed a spindly sarcomatous tumor that was immunohistochemically positive for S100-P, CD34, p53 and exhibited high MIB1 (30-40%). Diagnosis of a MPNST arising in a hybrid schwannoma/perineurioma was made. This unusual case forms yet another addition to the spectrum of a MPNST.     

Peripheral nerve sheath tumors of the head and neck

The head and neck region is a common location for benign peripheral nerve sheath tumors (PNST) and a rare site for malignant PNST. The diagnostic distinction between schwannoma (neurilemmoma) and benign neurofibroma remains clinically and prognostically important. Most benign PNST are schwannomas, and these do not have a recognized malignant potential. Malignant PNST arise de novo or from benign neurofibromas. The definitive diagnosis of malignant PNST may be difficult or impossible using only routine light microscopy. Electron microscopy and immunohistochemistry are special techniques that may be helpful. The prognosis in patients with malignant PNST depends heavily on the extent of surgical excision, size of the primary tumor, and presence or absence of von Recklinghausen's neurofibromatosis.     

Immunohistochemical and ultrastructural comparative study of external lamina structure in 31 cases of cellular, classical, and melanotic schwannomas.

Unlike most soft tissue tumors, schwannoma is characterized by the presence of distinct linear, frequently duplicated external lamina (EL). Although electron microscopy remains the gold standard for demonstrating this unique feature and distinguishing its morphologic variants from mimickers, the use of two anti-EL antibodies, laminin and type IV collagen, appears to supersede electron microscopy in terms of current practice. To determine whether immunohistochemical expression correlates with ultrastructural findings, 10 cellular schwannomas, 18 classic schwannomas, and 3 melanotic schwannomas were evaluated ultrastructurally and immunohistochemically using antibodies to type IV collagen and laminin. Immunohistochemically, a moderate to strong intensity in more than 50% of tumor cells was detected using either antibody in most cases of cellular schwannomas (70%), the Antoni A areas of classic schwannomas (78%), and melanotic schwannomas (67%). Ultrastructurally, the presence of diffusely continuous, duplicated EL was observed in 30% of cellular schwannomas and 56% of classic schwannomas, while 50% of cellular schwannomas and 22% of classic schwannomas showed either continuous simple EL or discontinuous but duplicated EL alone. In addition, two cellular schwannomas (20%) and four classic schwannomas (22.2%) had only a simple layer of EL in focal areas. In contrast to the distinct immunostaining surrounding individual cells seen in the former two subtypes, all three melanotic schwannomas displayed a biphasic-staining pattern of the EL (ie, individual cell and nested), which was confirmed at the ultrastructural level. The authors found a significant difference in intensity between the Antoni A and B areas of classic schwannomas using both laminin and type IV collagen. In addition, the intensities of laminin and type IV collagen in the Antoni A areas of classic schwannomas were significantly stronger compared with those of cellular schwannomas. Nevertheless, there was no significant difference either between two antibodies or between cellular and classic variants with regard to the extent of immunoreaction. Only in classic schwannomas did the extent of immunoreaction against both laminin and type IV collagen correlate significantly with the ultrastructural EL distribution pattern (diffusely continuous vs. discontinuous). However, this association was not detected in cases of cellular schwannomas. On the other hand, the intensities of laminin and type IV collagen did not correlate with the ultrastructural thickness of EL, irrespective of the morphologic subtypes. In conclusion, both type collagen IV and laminin are still reliable markers of EL in various types of schwannomas. Schwannomas exhibiting a monolayered EL are as strong in immunoreaction as those displaying reduplicated/thickened EL, indicating that a single layer of EL is thick enough to be identified by both antibodies with sufficient sensitivity. The peculiar biphasic EL pattern seen in melanotic schwannoma remains under-recognized, which may lead to misdiagnosis as malignant melanomas, especially in limited biopsy specimens.     

Malignant schwannoma of the liver in a patient without neurofibromatosis: a case report and review of the literature

Primary schwannomas of the liver are extremely rare. We report a case of malignant schwannoma of the liver occurring in a 49-year-old man, who did not have neurofibromatosis, and review the literature. The clinical and histologic findings of benign and malignant schwannomas of the liver are compared.     

Fine-needle aspiration cytologic diagnosis of metastatic melanotic schwannoma: familial case of a mother and daughter with Carney's complex and literature review

Carney's complex is an autosomal dominant, multisystem tumorous disorder that includes myxomas, spotty skin pigmentation, endocrine tumors, and peripheral nerve tumors. Psammomatous melanotic schwannomas have recently been included as a part of this complex. Here, we describe the first known familial case of a mother and daughter, both presenting with malignant, already metastatic, pigmented schwannomas initially diagnosed as metastatic melanoma by CT guided fine-needle aspiration.Patients with highly pigmented, extra-cutaneous lesions that are clinically and pathologically suspicious for metastatic malignant melanoma, without known primary tumor, should be evaluated for possible Carney's complex. Additional screening of family members should be recommended to exclude the presence of potentially malignant neoplasms, such as psammomatous melanotic schwannomas.     

Peripheral nerve sheath tumours--a short series with some uncommon variants

Peripheral nerve sheath tumours are rarely malignant (0.001%), such malignant peripheral nerve sheath tumours (MPNST) are more common in upper extremities than in head and neck. Chondroid differentiation in benign peripheral nerve sheath tumours and melanotic schwannoma are very uncommon. In a retrospective analysis of 25 peripheral nerve sheath tumours over a period of two years, we reported two MPNST one of which was in a parapharyngeal location while the other MPNST showed melanotic differentiation. Similar melanotic differentiation was also seen in another benign melanotic schwannoma. Chondroid differentiation in a schwannoma was also observed which is usually documented in MPNST.     

Intraosseous schwannoma: histologic features, ultrastructure, and review of the literature

Intraosseous schwannoma, a rare benign neoplasm, has a characteristic radiographic appearance. The histologic features, although similar to those of soft tissue schwannomas, may be obscure when the lesions are highly cellular and the Antoni Types A and B patterns are subtle. Four additional cases of intraosseous schwannoma are presented, with ultrastructural studies from two tumors, one of which was highly cellular and presented a diagnostic problem. The ultrastructural features of intraosseous schwannomas have not been documented previously; however, the findings are essentially the same as those observed in soft tissue schwannomas. The radiographic, histologic, and ultrastructural findings in the cases reported are discussed in relation to published data for intraosseous and soft tissue schwannomas. The authors propose that the comparatively high frequency of mandibular involvement by intraosseous schwannoma may be related to the fact that schwannomas, in general, arise most frequently in the head and neck regions. Furthermore, since schwannomas arise mainly in association with sensory nerves, probably the dearth of such fibers within bone accounts for the rarity of intraosseous schwannoma.     

Vascular alterations in schwannoma

Schwannomas or neurilemmoma are benign peripheral nerve sheath tumors, which most frequently occur at the cerebellopontine angle. This morphologic study examines vascular alterations in these tumors, comparing them to other benign spindle cell neoplasms of the nervous system, while correlating these findings with evidence of vascular permeability. Thirty-four nervous system spindle cell neoplasms, sixteen schwannomas, nine fibroblastic/transitional meningiomas and nine peripheral neurofibromas were stained with H&E, Prussian-blue stain, and immunoreacted for factor VIII-related antigen and interstitial albumin. Schwannomas had focal clusters of vascular proliferation including groups of small thin-walled vessels, as well as larger vessels with extensive hyalinization. Neurofibromas and meningiomas almost uniformly had modest numbers of well-defined, thin walled individual vessels. Free hemosiderin and hemosiderin-laden macrophages were frequently identified in schwannomas. Prussian-blue stain for iron revealed focal or fairly widespread positivity in almost all schwannomas, only one meningioma and none of the neurofibromas. Immunoreaction for albumin demonstrated leakage of vascular proteins into the interstitium confirming tumor vessel permeability in schwannomas. Neither neurofibromas nor meningiomas displayed any detectable interstitial albumin. The above findings confirm a degree of reactive proliferation of vessels in schwannoma along with functional deficits in their vascular integrity with permeability to protein and blood. The presence of hyalinized vessels, hemosiderin, both free and within macrophages, and more readily evident Prussian blue staining, may provide an additional diagnostic clue in discriminating between histologically similar spindle cell lesions. The study however raises the possibility that these changes likely precede or facilitate the degenerative ‘ancient change’ seen in some schwannoma.     

Multiple melanotic schwannoma

Melanotic schwannoma is a rare pigmented neural tumor most commonly occurring in the paraspinal region. In a small minority of instances, melanotic schwannoma may have multiple nodules. Here, a 52-year-old woman is presented with multiple melanotic schwannomas of paraspinal region.     

Schwannoma in head and neck: preoperative imaging study and intracapsular enucleation for functional nerve preservation

Purpose

In treating schwannoma patients, it is critical to determine the origin of the tumor to preserve nerve function. We evaluated the validity of preoperative imaging studies in distinguishing the neurological origin of the schwannomas of the head and neck, and the efficacy of intracapsular enucleation in preserving nerve function.

Materials and Methods

In 7 cases of schwannomas in the head and neck region, we predicted whether the tumor originated from the vagus nerve or the cervical sympathetic chain through imaging studies including computed tomography (CT) and magnetic resonance imaging (MRI). All patients were performed intracapsular enucleation, and the function of the vagus nerve and the sympathetic nerve was evaluated preoperatively and postoperatively.

Results

Preoperative imaging studies showed 6 cases where the tumor was located between the carotid artery and the internal jugular vein, and 1 case where the tumor was located posteriorly, displacing the carotid artery and the internal jugular vein anteriorly. At the time of operation, we confirmed schwannoma originating from the vagus nerve on the first 6 cases, and schwannoma originating from the sympathetic nervous system on the last case. All patients went through successful intracapsular enucleation, and of the seven schwannoma cases, 6 patients maintained normal postoperative neurological function (85.7%).

Conclusion

Preoperative imaging studies offer valuable information regarding the location and origination of the tumor, and intracapsular enucleation helped us to preserve the nerve function.     

Malignant schwannoma associated with von Recklinghausen's neurofibromatosis

Summary A series of 46 malignant schwannomas occurring in soft parts of patients having von Recklinghausen's neurofibromatosis was analyzed. The diagnosis of malignant schwannoma was based upon the occurrence of malignant spindled cells closely resembling Schwann cells in the neoplasm and the close association or origin of the malignant schwannoma in a neurofibroma (27 tumors), or a large peripheral nerve (31 tumors). Additional histologic features useful in making the diagnosis of malignant schwannoma included the arrangement of the spindled tumor cells in a whorled pattern about thin-walled, gaping blood vessels, perivascular cellular proliferation and the presence of prominent myxoid stroma containing abundant hyaluronidase-sensitive acid mucopolysaccharides. Nuclear palisading was present in only one case. Eight tumors containing both neoplastic Schwann cells and rhabdomyoblasts and five containing both neoplastic Schwann cells and rhabdomyoblasts (malignant Triton tumors) and five containing foci of malignant cartilage cells were included in the series. The neoplasms occurred principally in adults (median age, 34 years) and were most common in the lower extremity (18 cases) and retroperitoneum (11 cases). A mass with or without pain was the most common presenting symptom (28 cases). The median size of excised tumors was 11 cm. The malignant schwannomas were highly malignant neoplasms, causing the death of 39 patients within five years and two patients within 6–10 years after diagnosis. Only four patients were alive and free of tumor 5–15 years after diagnosis.Dedicated to Professor E. Uehlinger on the occasion of his 80th birthdayThe opinions and assertions contained herein are the private views of the authors and are not to be construed as official or as reflecting the views of the Department of the Army or the Department of Defense.     

Characterization of human soft tissue sarcomas in nude mice. Evidence for histogenic properties of malignant fibrous histiocytomas.

Twenty-two human sarcomas were grafted subcutaneously into nude mice. Twelve tumors grew successfully. Nine of these 12 tumors had an aneuploid DNA content, whereas only 1 of 10 nonsuccessful tumors was aneuploid. The 12 sarcomas included two leiomyosarcomas, two malignant schwannomas, one synovial sarcoma, and seven malignant fibrous histiocytomas (MFHs). With light and electron microscopic and immunolabeling studies the original and xenografted tumors (the latter for at least two generations) were histopathologically compared. The xenografted leiomyosarcomas showed ultrastructurally a more pronounced leiomyodifferentiation, and one of the malignant schwannomas a more pronounced schwannian differentiation. The second malignant schwannoma and the synovial sarcoma, however, remained unchanged. Five storiform pleomorphic MFHs expressed features that were not observed in the original tumors. Tumor cells of three of these xenografted sarcomas showed leiomyogenic differentiation (filamentous densities, pinocytotic vescicles, and desmin immunoreactivity), whereas cells of the two others demonstrated schwannian differentiation (long cytoplasmic processes, basal lamina). A xenografted myxoid MFH and a pleomorphic MFH gave rise to pleomorphic sarcomas composed of undifferentiated cells. It appeared that under transplantation conditions tumor cells of storiform pleomorphic MFH can differentiate into various directions.     

Spinal melanotic schwannoma: a tumour with poor prognosis

AIM: To clarify the prognosis of melanotic schwannoma. This is a rare tumour which is generally considered as a benign lesion, reported in many cases with a short follow-up only. METHODS AND RESULTS: Five cases of spinal melanotic schwannoma were retrospectively studied. The tumours were examined using standard histological, immunohistochemical and ultrastructural methods. No features of malignancy (high mitotic count, atypia or necrosis) were found in the primary tumours. The follow-up period ranged from 3 to 7 years. Malignant clinical behaviour was clear-cut in four cases: three patients died from metastases to various sites and one presented several discrete spinal tumours of the same type seven years after the first operation. Only one patient presented no recurrence and was free of disease 6 years after initial diagnosis. The review of 57 cases of the literature (including our cases), showed that 15% of the cases had recurrences and 26.3% were complicated by metastasis. Only 53% of the cases followed for more than 5 years, were free of disease vs. 67.5% of the cases with shorter follow-up. Twenty additional cases had no follow-up. CONCLUSION: Appropriate long-term follow-up is required for all melanotic schwannomas, as it may recur or metastasize after more than 5 years, even in the absence of overt malignant histological features.     

Fine-needle aspiration cytology of "ancient" schwannoma.

The term "ancient" schwannoma was proposed for a group of neural tumors showing degenerative changes and marked nuclear atypia. Prior to the realization that the observed atypia was a regressive phenomenon, many of these lesions were erroneously diagnosed as sarcomas. Fine-needle aspiration (FNA) cytologic material from five patients is included in this study. Tissue examined histologically included four resected tumors and 18 gauge core biopsies of one tumor. Aspirates of ancient schwannoma showed many of the same features as FNA of regular schwannoma: aggregates of spindled cells with indistinct cytoplasm and elongate nuclei with blunt point ends. The feature unique to these lesions was nuclear pleomorphism, which was identified in all aspirates. Nuclear inclusions were identified in all but one case. Cystic degeneration, xanthomatous changes, and perivascular sclerosis were identified in excised lesions. Ancient schwannomas show most of the FNA features of benign schwannomas but can demonstrate marked nuclear atypia. The FNA features of ancient schwannoma are important to note because of the potential to confuse this lesion with a more serious one such as sarcoma on FNA.     

Melanocytic schwannoma. Light-and electron microscopic findings on the morphology, diagnosis, and differential diagnosis

A melanocytic schwannoma was extirpated from the posterior mediastinum of a ten-year old girl The tumor consisted of cells which were spindle-shaped to polygonal in shape. Spindle-shaped cells were arranged in short, somewhat curved fascicles. In some areas a strand-like arrangement of cells gave rise to an epithelioid appearance. Typical features of benign schwannomas such as nuclear palisading and myxoid texture were absent. The essential histologic hallmarks were melanin deposition and the presence of small psammoma body-like, calcified spherules. Electron microscopic examination confirmed the schwannian differentiation of the tumor cells. These features included interlocking cellular processes, along with a tendency to display the wrap-around phenomenon and a sometimes multi-layered lamina externa. Intracytoplasmic melanin synthesis was evidenced by demonstration of melanosomes in different phases of maturation. The differential diagnosis is discussed with particular emphasis on the need to distinguish this tumor from malignant melanoma. Melanocytic schwannomas should be regarded as potentially malignant. The tendency and degree of invasiveness, mitotic frequency and the ability of tumor cells to form lamina externa have the greatest prognostic value.