Pathological findings in the x-linked form of Charcot-Marie-Tooth disease: a morphometric and ultrastructural analysis.

Mutations in the connexin 32 gene (Cx 32) are associated with the x-linked form of Charcot-Marie-Tooth disease (CMTX) and segregate with a CMT 1 phenotype. The gap junction protein Cx 32 is expressed in myelinating Schwann cells and has been localized to regions of non-compacted cytoplasm in paranodes and in Schmidt-Lanterman incisures. Mutant Cx 32 myelin proteins are predicted to impair Schwann cell functions. We have studied the resulting pathology in motor and sensory nerves from the probands of 13 CMTX kindreds with precisely defined genotype. This report provides a detailed descriptive and morphometric analysis of 14 CMTX nerve biopsy samples, taken at various stages in the development of the neuropathy and studied by light and electron microscopic examination. Findings indicated unusually prominent changes in paranodal myelin with resulting widened nodes of Ranvier, but with segmental demyelination being less common. In parallel early axonal cytoskeletal abnormalities were noted, which were followed later by axonal atrophy, degeneration and loss of myelinated nerve fibers, occurring in a length-dependent fashion. Regenerative sprouting was also unusually prominent. Ultrastructural abnormalities included a frequent dilatation of the adaxonal spaces, prominence of the adaxonal Schwann cell cytoplasm and widening of the Schmidt-Lanterman incisures. We conclude that mutations in Cx 32 gap junction protein lead to a compromise of Schwann cell functions and to impaired Schwann cell-axon interactions with subsequent pathology in both myelin and axons.

Combined pleomorphic xanthoastrocytoma-ganglioglioma of the cerebellum.

Combined pleomorphic xanthoastrocytoma-ganglioma is a rare neoplasm, occurring in patients younger than 30 years. The clinical course of these tumors is difficult to predict because of their rarity. We report a case of combined pleomorphic xanthoastrocytoma-ganglioma that, in addition to the patient's age, is unusual in several respects. The lesion was located in the cerebellar vermis of a 60-year-old man and was radiographically solid. Histologically, there was an admixture of markedly pleomorphic astrocytic cells and neoplastic ganglion cells, with permeation of the overlying leptomeninges and surrounding cerebellum. In addition, there was focal capillary endothelial proliferation. There was no necrosis, and mitotic activity was rare at 1 mitotic figure per 40 high-power fields. The patient underwent a near gross total resection and postoperative radiotherapy and remains well through 16 months of follow-up.

Endoneurial vasculitis and tubuloreticular inclusions in peripheral nerve biopsy.

We describe 3 patients in whom nerve biopsy revealed endothelial tubuloreticular inclusions in association with peripheral nerve endoneurial vasculitis. Two of the patients had systemic lupus erythematosus (SLE), while the third was HIV-positive. Review of our biopsy material featuring the much more common finding of epineurial vasculitis failed to disclose any instances in which endothelial tubuloreticular inclusions (TRIs) were present. We conclude that TRIs and endoneurial vasculitis are closely associated. Moreover, if detected on a nerve biopsy specimen, TRIs are very suggestive of SLE or HIV infection. Finally, literature evidence is cited to suggest that an "acid-labile" alpha-interferon may be pathogenically related to the vasculitic process in these patients, perhaps through a process mediated by tumor necrosis factor.

April 1999--44 year old man with a bleeding intracerebral tumor.

A 44 year-old man presented with a three month history of increasing headache and evolving left sided hemiparesis that culminated in an haemorrhage into an intracerebral tumour which was partially resected. Histologic, immunohistochemical, electron microscopic and molecular studies are supportive of a diagnosis of primary embryonal rhabdomyosarcoma. While primary rhabdomyosarcoma of the central nervous system is rare, and 72% of previously reported cases are in the paediatric population, there appears to be subset of these tumours occurring supratentorially in the adult.

June 1999--22 year old female with intraventricular mass.

A 22 year old female presented with a single seizure. CT scan and craniotomy demonstrated an intraventricular papillary tumor with histologic and immunohistochemical features indicative of a choroid plexus carcinoma. Even though the occurrence of this neoplasm is exceptional beyond childhood, pathologists should considered a malignant choroid plexus tumor when postulating the differential diagnosis of intraventricular papillary neoplasms in adults.

Ganglioglioneurocytoma of the posterior fossa.

OBJECTIVE AND IMPORTANCE: Ganglioglioneurocytoma is not yet a well defined clinical and histopathological entity; recent reports outline the histopathological features of this very rare trimorphous tumor, under different names with its basic components of gangliocytoma, neurocytoma and glioma. Four previous reports described this tumor in eleven patients. This is the first case report describing ganglioglioneurocytoma in the posterior fossa. CLINICAL PRESENTATION AND INTERVENTION: A 31-year old male with midline posterior fossa ganglioglioneurocytoma is described, providing the neuroimages and histopathological studies. CONCLUSION: Ganglioglioneurocytoma is a rare mixed neuronal and glial tumor that can also occur in the posterior fossa.

MR imaging of a hemorrhagic and granulomatous cyst of the ligamentum flavum with pathologic correlation.

Cysts of the ligamentum flavum are uncommon causes of neurologic signs and symptoms and usually are seen in persons over 50 years of age. We report a case of an epidural cyst located in the ligamentum flavum, which contributed to spinal stenosis in a 30-year-old man. Radiologic features were similar to those of a synovial cyst, but synovium was not identified histologically. The imaging and pathologic features were unusual, including hemorrhage and a fibrohistiocytic reaction with giant cells.

Case of the month: February 1999--54 year old man with severe muscle weakness.

A 54 year old man developed rhabdomyolysis one year after beginning treatment with a combination of lovastatin (an HMGCoA reductase inhibitor) and niacin. Muscle biopsy showed a severe necrotizing myopathy affecting both fibre types. Recovery occured gradually with cessation of medication. The spectrum of cholesterol lowering agent myopathy may include delayed cases of unusual severity.

November 1998--70 year old woman with SLE, paraproteinemia and polyneuropathy.

A 70 year old woman developed a sensory-motor polyneuropathy 12 years after almost continuous treatment with hydrochloroquine for SLE. Sural nerve biopsy disclosed abundant lipid inclusions in schwann cells and vessels against a background of axonal degeneration. After cessation of therapy the patient improved moderately. This case underscores the usefulness of nerve biopsy in the study of management of patients with peripheral neuropathy associated with systemic illnesses.

Vasculitic polyradiculopathy in systemic lupus erythematosus.

A 22 year old woman with recently diagnosed systemic lupus erythematosus presented with subacute progressive areflexic paraparesis, electrophysiologically identified as a pure axonal polyradiculopathy. Sural nerve biopsy disclosed necrotising vasculitis. A striking radiological feature was marked enhancement of the cauda equina with gadolinium.

Cytology of pituitary thyrotroph hyperplasia in protracted primary hypothyroidism.

Pituitary thyrotroph hyperplasia, a rare cause of pituitary enlargement, is usually associated with protracted primary hypothyroidism. We present here a case of pituitary thyrotroph hyperplasia in a 51 year old woman who was thought to have a pituitary macroadenoma with suprasellar extension. The cytologic investigation of the intraoperative touch preparation identified hyperplastic thyrotrophs, provided the correct diagnosis and helped to limit further aggressive surgical removal of the lesion, which is known to regress after adequate thyroid hormone replacement therapy. This is the first study to describe the cytologic features of pituitary thyrotroph hyperplasia confirmed subsequently by histology, immunocytochemistry and transmission electron microscopy.

The effect of bipolar electrocautery on peripheral nerves.

Although bipolar cautery was designed to minimize trauma to the central nervous system, little is known about the effects of bipolar cautery on peripheral nerve tissue. This experiment was designed to study the effect of direct bipolar cautery on a peripheral nerve and the muscles innervated by that nerve. Lewis rats (n = 200) were assigned to five different groups: control, sham, and three cautery groups (duration of either 0.5, 1.0, or 1.5 seconds). The hind limb tibial nerves were isolated in the sham group and isolated and cauterized in the cautery groups. Assessments performed at 2 hours, 2 weeks, 4 weeks, and 8 weeks postoperatively included isometric contractile function studies of both a fast- and a slow-twitch muscle, muscle weights, and nerve histology/morphometry. Significant muscle weight loss and reduced muscle function were found in the cautery groups at 2, 4, and 8 weeks (p < 0.05). Histologically, the nerves of the cautery groups showed nerve damage consistent with Sunderland's type 4 nerve injury when examined at 2 weeks and showed nerve regeneration at 4 and 8 weeks. Both the fast-twitch muscle and the shorter duration cautery were associated with faster recovery relative to the slow-twitch muscles and longer duration cautery, respectively. Bipolar cautery, as administered to rat tibial nerves in this experiment, is associated with a significant injury to the nerve and loss of function of the muscles innervated by the nerve.

Isolated intracranial involvement in Rosai-Dorfman disease: a report of two cases and review of the literature.

Rosai-Dorfman disease is an idiopathic histiocytic disorder of lymph nodes and extranodal sites. Central nervous system manifestations of this disease are rare, and to our knowledge only 16 cases of intracranial involvement have been reported previously. Intracranial Rosai-Dorfman disease clinically and radiologically resembles meningioma, and histologic examination is essential for a definitive diagnosis. We report two cases of isolated, intracranial, dural-based Rosai-Dorfman disease, review the literature, and discuss the differential diagnoses of this lesion.

Malignant transformation of ganglioneuroma into spinal neuroblastoma in an adult. Case report.

Ganglioneuroma is generally considered to be a benign tumor and potentially surgically curable. The authors present a case of a 21-year-old woman who underwent resection of a retroperitoneal ganglioneuroma and developed spinal neuroblastoma 11 years later. She has survived 10 more years with only recent development of metastases. To the authors' knowledge, this is the first report of malignant transformation of a ganglioneuroma into a neuroblastoma. Also, such long-term survival in an adult with spinal neuroblastoma has not been reported previously. This case raises the possibility of a dedifferentiating potential for ganglion cells in a ganglioneuroma or the presence of a long-term, quiescent form of neuroblastoma.

Granulocytic sarcoma of the spine in nonleukemic patients: report of three cases.

OBJECTIVE AND IMPORTANCE: Granulocytic sarcomas involving the spine in patients without myelogenous leukemia are rare. We report three cases and review the literature. CLINICAL PRESENTATION: Three patients presented with spinal epidural tumors, which caused spinal cord compression in one and cauda equina compression in two. INTERVENTION: All patients underwent surgery, and biopsies revealed histological features of granulocytic sarcomas. Bone marrow aspirates and biopsies showed no evidence of acute leukemia at initial presentation, for all three patients. CONCLUSION: Granulocytic sarcomas in nonleukemic patients are rare, and when they affect the spine they are frequently misdiagnosed. Appropriate therapy for these tumors requires early identification.