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.     

Aneurysms of the carotid arteries associated with von Recklinghausen's neurofibromatosis.

Aneurysms of both common carotid arteries were seen in a patient with neurofibromatosis. Histologic examination of the involved arteries demonstrated a dense proliferation of spindle cells within the arterial walls accompanied by medial cystic degeneration and disruption of the tunica elastica. These changes were also observed in adjacent, grossly uninvolved segments of the blood vessels. Immunohistochemical analysis of the proliferating cells was positive with antibodies against desmin and muscle-specific actin. The findings demonstrate and confirm the smooth muscle origin of the aberrant proliferated cell population in arteries in a patient with von Recklinghausen's neurofibromatosis.     

Neuropsychological function in adults with von Recklinghausen's neurofibromatosis

The cognitive function of adults with von Recklinghausen's neurofibromatosis (NF-1) was examined. This study sought to replicate in an adult sample the findings of decreased visuospatial and attention abilities reported for many children with NF-1. Specifically, it was anticipated that adults with NF-1 would be classified separately from unaffected controls according to visual and attention-executive function skills. Second, this study examined whether language skills discriminated between adults with NF-1 and unaffected controls. The sample included 20 participants with NF-1 and 25 control participants. All participants were administered a battery of neuropsychological tests (Developmental Test of Visual-Motor Integration (VMI), Judgment of Line Orientation (JLO), Visual Form Discrimination, Booklet Category Test, Figure Cancellation, Peabody Picture Vocabulary Test-Revised (PPVT-R), Sentence Repetition, Controlled Oral Word Association). The results of a discriminant function analysis partially supported the hypothesis: Two of the tests of visual-spatial skill (VMI, JLO) and one of the language tests (PPVT-R) were found to be the best predictors for group membership. The discriminant function accounted for 45% of the variance between the groups and correctly classified 15 of the NF-1 participants and 21 of the control participants. Post hoc exploratory analyses revealed that the VMI was the most important test in discriminating between the groups. It is suggested that patients with NF-1 will tend to have sparing of basic cognitive functions but will have greater impairment on tests that use multiple cognitive skills.     

Leiomyoma of the bladder in a patient with von Recklinghausen's neurofibromatosis

Leiomyomas are an uncommon manifestation of neurofibromatosis type 1 (NF-1) and occur most often in the gastrointestinal tract. Here, they have a proclivity for the proximal small bowel and tend to be multiple. Urinary tract involvement by NF-1 is usually in the form of neurofibromas, and leiomyomas are exceptionally rare. This report describes a case of solitary leiomyoma occurring in a 49 year old woman with NF-1. The patient had symptoms related to a lower urinary tract infection and on examination was found to have a distended bladder. Imaging of the bladder showed a mass involving the posterior wall, neck, and trigone causing bilateral hydronephrosis. The mass was excised with part of the bladder. Microscopic examination revealed typical features of a leiomyoma and there was strong immunoreactivity for desmin and smooth muscle actin. Leiomyoma must be considered in the differential diagnosis of spindle cell neoplasms in patients with NF-1.     

Von Recklinghausen's disease (neurofibromatosis) associated with malignant pheochromocytoma

An autopsy case of von Recklinghausen's disease (vRD) associated with malignant pheochromocytoma is reported. The patient is a 36-year-old Japanese male and diagnosed as vRD both clinically and pathologically. He died from right adrenal tumor with wide spread metastases to lungs and bone marrow. The tumors presented satisfactory histological features in favor of pheochromocytoma and neurosecretory granules were demonstrated in both primary and metastatic lesions ultrastructurally. Statistical study of 182, 673 autopsy cases from Annuals of Japanese Autopsy Cases was also done in order to investigate the relationship between vRD and associating tumors including benign and malignant pheochromocytoma. Cases with vRD showed significantly higher incidences of malignant Schwannoma, neurofibrosarcoma, intracranial glioma, and pheochromocytoma compared to that of non-vRD cases. Other malignancies revealed rather smaller incidences than non-vRD cases. These neurogenic tumors are to be principal life threatening problems in patients with vRD. Rare incidence of malignant pheochromocytoma in vRD is to become from low incidence of pheochromocytoma, though significantly greater than that of non-vRD cases.     

Neurogenic sarcomas in patients with neurofibromatosis (von Recklinghausen's disease)

Summary Thirteen soft tissue neurogenic sarcomas from twelve patients with neurofibromatosis (Von Recklinghausen's disease) were ultrastructurally examined. Electron microscopic studies revealed a wide spectrum of morphological manifestations varying from schwannian to fibroblastic, histiocytic, fibrohistiocytic and relatively undifferentiated cellular proliferations. A similar variation on light microscopic appearances has been previously reported in these neurogenic sarcomas. Neurogenic sarcomas occurring in patients with neurofibromatosis (Von Recklinghausen's disease), represent a heterogenous group of neoplasms with various patterns of differentiation identified ultrastructurally. The morphologic expressions of these neurogenic neoplasms can be conceptualized as a disorderly growth of the various peripheral nerve cellular components, or, as has been previously suggested, as a result of the multipotential nature and metaplastic ability of Schwann cells. S-100 protein immunohistochemistry was only positive in those neoplasms ultrastructurally proven to represent schwannian cellular proliferations.This study serves to document the range of fine structure that may be found in neurogenic sarcomas, to correlate the ultrastructural findings with the light microscopic appearance of these tumors, to determine the specificity of the electron microscopic findings, and immunohistochemistry for S-100 protein and assess their possible value in differential diagnosis.     

Study on the ultrastructure and acetylcholinesterase activity in von Recklinghausen's neurofibromatosis.

The cutaneous nodules obtained from seven patients with von Recklinghausen's neurofibromatosis were investigated by electron microscopy, and ultrastructural localization of acetylcholinesterase activity was demonstrated in the nerve fibers of this tumor for the first time using Karnovsky's thiocholine method. The enzymatic activity was mainly found in unmyelinated fibers, exactly associated with their axonal membranes, the interspace between the apposing axonal and Schwann cell membrane, and some different mesaxons, which indicated their cholinergic nature. Almost all myelinated fibers and some unmyelinated fibers did not possess the activity. The relationship between axon and Schwann cell was quite similar to that of normal peripheral nervous system, but two striking alterations of the nerves existed: One is the dissociation of unmyelinated fibers, and the other is the degenerative changes of the axon and the myelin sheath. As the evidence of schwannian proliferation, onion bulb formations and collagen pockets were observed. Some signs of fibroblastic proliferation were also found. From the present study and the review of the literature, the probable histogenesis of this disease was discussed.     

Duodenal carcinoid (somatostatinoma) combined with von Recklinghausen's disease. A case report and review of the literature

We report the immunohistochemical and ultrastructural features of a case of duodenal carcinoid (somatostatinoma) combined with cutaneous-type von Recklinghausen's disease in a 65-year-old woman. The duodenal tumor located at the 2nd portion was composed of tumor cells arranged in a trabecular, glandular or nest-like pattern, occasionally associated with eosinophilic globules in the glandular structures. The tumor cells mostly showed strong immunoreactivity with anti-somatostatin antibody. Electron microscopy revealed that every tumor cell contained intracytoplasmic granules with electron-dense cores, 100-300 nm in size, in varying numbers, and intracytoplasmic lumina were rarely detected. The present case including identical cases reported so far suggest that the disease entity is likely to be a combination of duodenal somatostatinoma and von Recklinghausen's disease and/or phaeochromocytoma. This is the tenth case of duodenal carcinoid associated with von Recklinghausen's disease and/or phaeochromocytoma in the world literature and the third case reported as duodenal somatostatinoma.     

Gliosis of the brain in Recklinghausen's neurofibromatosis

An autopsy case of Recklinghausen's disease is described with a large neck neurofibroma, skin melanosis, skull bones and teeth changes, elephantiasis of the head soft tissues, megalocephaly. Histologically an isomorphic-cell brain gliosis as a rare manifestation of neurofibromatosis is found.     

Granulomatous gastritis. Apropos of 2 cases

We report two cases of granulomatous gastritis, one unexplained, one in the setting of Crohn's disease. Granulomatous gastritis is an uncommon entity. An etiopathogenetic diagnosis can be reached only by combining the morphological examination with clinical and laboratory investigations. Isolated granulomatous gastritis is a diagnosis of exclusion, distinct from Crohn's disease, sarcoidosis, infections, foreign bodies, malignancy or vasculitis.     

Multiple small intestinal stromal tumors with skeinoid fibers in association with neurofibromatosis 1 (von Recklinghausen's disease)

A case of multiple small Intestinal stromal tumors (SIST) with skeinoid fibers of the jejunum arising in a 50 year old male with neurofibromatosis 1 (NF-1) is reported. Seven small tumors of the jejunal wall were incidentally found and excised during an operation for abdominal and retroperitoneal neuroflbromas. Histologlcally, the tumors were composed of uniform spindle-shaped cells with fascicular pattern, almost indistinguishable from the histology in leiomyoma. Periodic acid Schiff stain-positive hyaline globules were observed among the tumor cells. Ultrastructurally, these globules were stromal tangles of curvilinear, fluffy fibrils, consistent with skeinoid fibers. The electron-dense granules, possibly neurosecretory granules, were found In the cytoplasm of the tumor cells. Immunohistochemically, the tumor cells were positive for vimentin, neuron specific enolase and CD34, but negative for muscle markers and S100 protein. The association of NF-1 and multiple SIST with skeinoid fibers may have clinical implications. The multiple occurrence of SIST with skeinoid fibers seems to be often cited as one of the gastrointestinal manifestations of NF-1. The possible site of origin of SIST with skeinoid fibers in NF-1 may be the enteric autonomlc nerve plexus in the small intestinal wall.     

Pathogenicity of Fusobacterium. Apropos of 2 cases

Two cases of severe septico-pyohaemia due to Fusobacterium necrophorum are reported. Clinical data from human cases and experimental results from infections of laboratory animal with Fusobacterium necrophorum suggest: the important role of individual factors which enhance anaerobic growth (i.e. decrease of tissular redox potential); the involvement of thrombophlebitis with septic thrombi increasing the frequency of metastases; the early and long-lasting bacterial localisation in tissues, particularly in the liver where the proliferation of Fusobacterium necrophorum in Küpffer cells impairs macrophage function.     

Neurofibromin and NF1 gene analysis in composite pheochromocytoma and tumors associated with von Recklinghausen's disease.

Composite tumor of pheochromocytoma and neuroblastoma, or ganglioneuroma, or ganglioneuroblastoma (composite pheochromocytoma), also known as mixed neuroendocrine and neural tumor, are sometimes combined with neurofibromatosis type 1 (NF1). To better understand the relationship between NF1 and composite pheochromocytoma, an immunohistochemical study using anti-neuro-fibromin that is an NF1 gene product and DNA sequence of NF1 Exon 31 were carried out in five cases of composite pheochromocytoma and in various tumors from five patients with NF1. Neurofibromin was not expressed in Schwann cells and sustentacular cells of composite pheochromocytomas and was very weakly or negatively expressed in neurofibroma of NF1 patients. However, it was strongly expressed in ganglionic cells and pheochromocytoma cells of the composite pheochromocytomas and also in mucosal ganglioneuromas, a gangliocytic paraganglioma, and in pheochromocytomas from the patients with NF1. Although there was no mutation in NF1 Exon 31, it could not be ruled out that there were mutations in other sites of the NF1 gene. Neurofibromin insufficiency may induce abnormal proliferation of Schwann cells in composite pheochromocytomas as well as in neurofibromatosis.     

Ancylostomiasis in the mines. Apropos of 2 cases

The etiological importance of Ancylostomidae in miners' anaemia has been discovered in 1880 by Perroncito during the boring of the Saint-Gothard tunnel in a dreadful epidemic. Thereafter in France, the illness disappeared between 1930 and 1940 because of the preventive dispositions realized. Two present cases of contamination in the coal mines of Lorraine due to N. americanus drive us to remember the interest of systematic faecal examinations of the miners at the engagement and every five years.     

Malignant "triton" tumor with metastatic hemangiopericytoma in a patient associated with von Recklinghausen's disease

An autopsy case of malignant schwannoma in a 31-year-old female associated with von Recklinghausen's disease with unusual elements is reported. The patient who was diagnosed as von Recklinghausen's disease from a biopsy specimen of a subcutaneous tumor in her shoulder and multiple café au lait spots in her chest and back, complained of gradual increase in pain in her lower abdomen. A large mass measuring about 18 cm in diameter was located in her left retroperitoneum. Malignant schwannoma associated with von Recklinghausen's disease was indicated by the cellularity of the tumor, intersecting bundles of spindle cells, alternating cellular and less cellular myxoid areas in the peripheral portion of the tumor, whereas a large part of the tumor had a hemangiopericytoma-like arrangement with gaping blood vessels. In addition, however, foci of rhabdomyosarcomatous differentiation and of angiosarcomatous components were found in some areas of this tumor. Moreover, intravascular schwannian growth, which was presumably related to von Recklinghausen's disease, was observed in the heart and thyroid. This tumor should be classified as a malignant triton tumor because of the presence of rhabdomyoblasts.