Merkel cell carcinoma in a male breast: a case report.

Merkel cell carcinoma is a rare skin neoplasm and has not been reported yet in a male breast. We present a case of 74-year-old patient who was referred to the breast clinic with a lump in his right breast, which led first to the core biopsy followed by radical mastectomy and axillary clearance. The clinical characteristics, gross, microscopic and immunohistochemical findings and management of this lesion are discussed. Surgical excision remains the main option for treating this lesion including prophylactic lymphadenectomy and local radiotherapy.

Central liponeurocytoma.

The 2000 World Health Organization has included cerebellar liponeurocytoma in the category of glioneuronal tumors of the central nervous system. Once termed medullocytoma and considered an embryonal tumor, a variant of medulloblastoma, its indolent behavior and morphologic features prompted this nosologic change. Biphasic in appearance, the tumor consists of well-differentiated neurons with the cytology of neurocytes in addition to a population of lipidized cells resembling mature adipose tissue. Such tumors occur in older adults and have a relatively good prognosis. Linking the concept of liponeurocytoma to its occurrence in the cerebellum unnecessarily obscures the existence of similar neoplasms at other sites, such as among classic central neurocytomas of the lateral and third ventricles. Indeed, two such cases have briefly been reported. To these, we add a third example, the first to be ultrastructurally examined. Our case provides evidence that the lipid vacuoles progressively accumulate and coalesce within cells retaining neurocytic features. Thus, these distinctive lesions are the result of tumoral lipidization, rather than true adipose metaplasia.

Menkes disease after copper histidine replacement therapy: case report.

Menkes disease (MD) is an X-linked recessive disorder of copper metabolism, characterized in its untreated state by progressive disorders of multiple systems, especially the central nervous system (CNS) and connective tissue, and death by 3 years of age. Recently, therapy with copper-histidine has modified the severity of MD and permitted survival into adolescence. Clinical response has been greater for the neurological abnormalities than for the connective tissue abnormalities. In this report, we describe the postmortem pathology of one individual who had received copper-histidine therapy and died at age 10; we believe this to be the first such pathological report. The postmortem examination demonstrated significant pathology of mesenchymal tissues, including skeletal abnormalities, vascular degeneration, and bladder diverticula. The CNS, by contrast, showed minimal pathology. The phenotype was more consistent with occipital horn syndrome, a milder allelic disorder of copper metabolism, than with classic MD. The differential sensitivity of CNS and mesenchymal tissues to copper-histidine therapy may result from heterogeneity in the response of different copper-dependent enzymes.

Juvenile xanthogranuloma of peripheral nerve: a report of two cases.

As a rule, juvenile xanthogranuloma (JXG) is a cutaneous lesion most often occurring in infancy. An inflammatory process of unknown etiology, it is self-limited and benign in nature. The spectrum of JXG has expanded to include adult examples, multifocal lesions, and ones arising at extracutaneous locations. Although a variety of extracutaneous sites may be affected, few reported lesions have involved cranial or peripheral nerves. Solitary examples have been reported in trigeminal nerve and spinal nerve root; affected individuals were children or adolescents. An optic nerve lesion has also been described. We describe two additional cases of JXG of nerve. One patient developed multiple dorsal nerve root lesions, as well as skin involvement. The other case featured isolated involvement of the left radial nerve. Both patients were adults with no known underlying systemic disorder. These cases further expand the spectrum of extracutaneous JXG, and underscore its consideration in the differential of nerve "tumors."

Association of infantile neuroaxonal dystrophy and osteopetrosis: a rare autosomal recessive disorder.

The association of neuroaxonal dystrophy and osteopetrosis is reported in 2 siblings born to non-consanguineous parents. The 1st child was diagnosed as having infantile osteopetrosis shortly after delivery. A computed tomography scan of the head revealed agenesis of the corpus callosum. She died at the age of 9 months. Post-mortem examination showed pneumonia and bony sclerosis. Neuropathological examination revealed cerebral atrophy, ventricular dilation, absence of the corpus callosum, and a small hippocampus. Neuroaxonal spheroids were found in hippocampus, basal ganglia, pons, medulla, spinal cord, cranial nerves, cerebellum, and peripheral nerves. Ultrastructural examination revealed membranous cytoplasmic bodies and electron-dense granular deposits within the neuroaxonal spheroids as well as the soma of neurons. The 2nd child was delivered at 36 weeks of gestation because of intrauterine fetal distress. The diagnosis of osteopetrosis and partial agenesis of the corpus callosum was made shortly after delivery. The child died at 1 month without an autopsy. There are rare cases reported previously with the association of neuroaxonal dystrophy and osteopetrosis. We review these cases and compare them with ours.

Increase in enkephalin-like immunoreactivity in hippocampi of adults with generalized epilepsy.

The changes of opioid peptide reactivity in seizure activity have been well studied in animals. Increased enkephalin and dynorphin immunoreactivity in the hippocampi of animals are interpreted as the result of seizure induced mossy fibre sprouting. We studied the hippocampi of six patients with a history of long-standing grand mal seizures and six age-matched control patients with no history of epilepsy or neurologic disease, using frozen sections which were immunostained with antibodies against Leu-enkephalin and Met-enkephalin. The staining intensity in the CA3, CA4 and internal molecular layer of the dentate fascia in each case was quantified using optical densitometry image analysis. The CA3 and CA4 of the epileptic hippocampi showed highly significant increase in Leu-enkephalin-like immunoreactivity compared to the controls (P < 0.005) while the inner molecular layer showed only significant increase (P < 0.05). Met-Enkephalin-like immunoreactivity was only significantly increased in CA4 of the epileptic hippocampi (P < 0.05).

Management of hyperkeratotic lesions in the elderly patient.

Many factors contribute in the development of hyperkeratotic lesions in the elderly patient. The internal and external causes render the elderly foot more susceptible to limited ambulation, increased incidence of infection, ulceration, and eventual loss of the limb. Once the lesion is classified and the causes identified, a beneficial treatment plan can evolve. Reduction of the lesion(s), appropriate padding, shielding, splinting, accommodative orthoses, insoles, emollients, and mild keratolytics on regular treatment intervals are helpful in maintaining comfort and allowing function of the elderly foot. If the bony abnormalities or abnormal position of the foot do not respond to conservative measures, then surgical intervention should be considered based on the medical and vascular status of the patient. The evaluation of the elderly patient's presenting footwear, and patient education on the need for proper shoe gear size, shape, and materials cannot be overemphasized. Proper footwear and fitting is essential for the elderly in managing hyperkeratotic lesions. When regular footwear is not beneficial special shoes should be considered to accommodate the foot and treatment plan (e.g., accommodative orthoses, and so forth). The Extra Depth Inlay Thermold, Ambulator, Bunion last and Keystone last are options. If special shoes are too heavy for the elderly patient, there is a wide variety of athletic shoes that are shock absorbent and lightweight. Success in management includes a proper identification of the problem, relief of the symptoms, regular follow-up care, and periodic review of footwear to ascertain the need for repair or modification.

Dense microspheres in the human hippocampus.

Dense microspheres (DMS) are structures found within neuronal processes of the adult human brain. Although best known as a feature of the neocortex, they are also found in the hippocampal formation. We describe a characteristic pattern of DMS distribution in the human hippocampus. The functional significance of this pattern is unknown, but it casts doubt on the proposed relationship of DMS to senile plaques. We also present evidence that DMS are composed of protein, but without a significant component of carbohydrate or neutral glycoprotein.

Delayed changes of chromogranin A immunoreactivity (CgA ir) in human striate cortex during postnatal development.

The changes in chromogranin A expression in the human striate cortex from birth till 67 years were studied by immunohistochemical method in 18 autopsied patients. The first chromogranin A immunoreactivity (CgA ir) was identified at birth in layer IV (especially IVc) mainly as fine nerve terminals. By 6 months, the first perikaryal reactivity was noted in the large pyramidal neurons of layer V. The smaller neurons in layers IV, V and VI showed a progressive increase in CgA ir from 15 months to about 17 years. At approximately 9 years, immunoreactivity began to be noted in supragranular neurons in layers II and III. The final laminar distribution of CgA ir seemed to be attained at about 25 years with relatively little change thereafter. The CgA ir in the striate cortex demonstrates a prolonged period of developmental changes, lasting from birth to about 25 years.

SMI-32 immunoreactivity in human striate cortex during postnatal development.

SMI-32, an antibody which recognizes the non-phosphorylated epitopes on the neurofilament proteins was used to study the morphological changes in the human striate cortex during postnatal development. Striate cortices from 12 autopsied patients with ages ranging from 1 day to 70 years were obtained. Using the avidin-biotin-peroxidase method, the first SMI-32 immunoreactive neurons were identified at sublayers Vb/VIa on the first postnatal day. At 5 months, the next group of neurons to develop immunoreactivity were in IVb. By 15 months, SMI-32 immunoreactive neurons were observed at III, IVa, IVb, V and VI. The changes in SMI-32 immunoreactivity (ir) were stabilized from 3 years and after. The SMI-32 ir in the striate cortex could be a useful morphological correlate for studying developmental diseases affecting the neocortex.

A new syndrome of mental retardation and epilepsy characterized by dense microsphere accumulation.

Dense microspheres (DMS) are enigmatic structures found within dendrites in the normal human cortex; their composition and function are unknown. We describe a case of a 29-year-old male with a history of mental retardation and epilepsy in whom the unique neuropathological finding was a marked excess of DMS, most notably in the neocortex. This is a previously undescribed neuropathological syndrome, and represents the first unequivocal association of DMS with a neurological disorder.

Leigh's disease with clinical manifestations of Cornelia de Lange syndrome.

Leigh's disease was found postmortem in a 5-year-old girl who was diagnosed clinically as Cornelia de Lange syndrome at age 1 year. The child's neurological status began to deteriorate rapidly at age 4.5 years and she died suddenly 6 months later. Postmortem examination of the brain revealed bilateral necrosis of the hypothalamus, subthalamic nuclei, midbrain, pons, and medulla. Previous studies have linked Cornelia de Lange syndrome to hypothalamic lesions. This case demonstrates that Leigh's disease, which also damages the hypothalamus, could present with phenotypic features of Cornelia de Lange syndrome.

Intravenous pulse methylprednisolone for the treatment of a child with Sjögren's nephropathy.

Six years after the onset of polyarthritis and after several episodes of recurrent parotitis, our patients developed the abrupt onset of renal insufficiency. Kidney histopathology showed interstitial and peritubular lymphocytic infiltration typical of Sjögren's nephropathy. Treatment with high dose intravenous methylprednisolone resulted in rapid and sustained normalization of kidney function. The favorable response of our patient to intravenous pulse corticosteroids suggests that this therapy is effective for the treatment of Sjögren's nephropathy.

Chromogranin A-like immunoreactivity in the human brain: distribution in bulbar medulla and cerebral cortex.

Chromogranin A is a glycoprotein stored in secretory granules of a variety of neuroendocrine cells. Among other functions, chromogranin A is a calcium-binding protein, and a precursor of modulatory peptides. Although known to be expressed in mammalian CNS neurons, it was previously believed that antibodies directed against human chromogranin A did not label neurons. A method is reported for the immunohistochemical demonstration of chromogranin A-like immunoreactivity in adult human post-mortem brain, utilizing the previously characterized monoclonal antibody LK2H10. Chromogranin A-like immunoreactivity of human brain could be absorbed with heat-stable protein extract from adrenal medulla, but not from liver, and a similar preparation of human cerebral cortex eliminated the labeling of adrenal medulla by LK2H10. However, unlike adrenal medullary chromogranin A-like immunoreactivity, cerebral chromogranin A-like immunoreactivity was destroyed by embedding the tissue in paraffin or treating frozen sections with methanol during the endogenous peroxidase blocking step, suggesting differences in post-translational processing of these two forms of chromogranin A. In both cerebral regions studied, bulbar medulla and parietal cortex, chromogranin A-like immunoreactivity was widespread in neuronal perikarya, dendrites, and axonic terminals, but restricted to certain neuronal populations. Among other findings it is reported that the main olivary neurons are immunoreactive for chromogranin A; this implies a new co-localization of chromogranin A, with corticotropin-releasing factor. The cerebral neocortex showed a laminar pattern of staining of perikarya in layers III-VI, and of the neuropil in the supragranular layers. In conjunction with the evidence of neuromodulatory action in the periphery, these results raise the possibility of a major neurotransmitter role for chromogranin A in the human brain.

Megalencephaly in the epileptic chicken: a morphometric study of the adult brain.

The epileptic chicken is a genetic model of generalized epilepsy in which epilepsy is combined with megalencephaly. We have performed a morphometric study of the brains of adult epileptic hens, using heterozygous carrier hens as controls. There is no obvious disorder of cell form or of architectural arrangement in the megalencephalic brains. We have found that the enlargement of the epileptic brain is not uniform: it is most marked in the telencephalon, and is present to a lesser degree in the cerebellum, but neither the optic tectum nor the diencephalic nucleus rotundus shows a significant increase in size. The enlarged regions are characterized by a decrease in the packing density of neurons. There is an increase in the total neuron population in some of the enlarged areas (archistriatum), despite the lower density per unit volume, but in other enlarged areas (hippocampus) there is no difference in total neuron numbers. The glial cells, by contrast, show no significant alteration in packing density. These findings suggest that the megalencephaly of the epileptic chicken is due to an increase in neuron size, with a contribution from increased numbers of neurons and glial cells. The epileptic chicken may provide a valuable model for further dynamic studies of aberrant neuronal development, and of structural-functional relationships in epilepsy.

A systematic approach to examining the patient with nail disease.

The majority of patients who present to the clinician for podiatric care do so because of complaints involving the nail and its surrounding structures. All too often the clinician's examination of the nail is incomplete and in many instances completely overlooked. The authors present a systematic approach to the examination of the patient who presents with nail pathology.

Serous cystadenocarcinoma of the pancreas: a new entity?

Microcystic cystadenoma of the pancreas is a well-recognized although rare pathological entity. All previously reported examples of this tumor have been uniformly benign in behavior. In this case report, we present a primary tumor of the pancreas that was histologically indistinguishable from microcystic adenoma, but which behaved in a malignant fashion. Metastases were found in the stomach and liver. We believe that this case represents a new entity, which we have termed "serous cystadenocarcinoma of the pancreas."

Absence of gliosis in the brains of epileptic fowl.

Chickens homozygous for the epi gene (epileptics) suffer from spontaneous seizures throughout their life, whereas heterozygous (carriers) are phenotypically normal. Seizures can also be evoked in epileptics by photic stimulation. In addition, epileptic chickens' brains are 25% heavier than those of carriers. We have investigated whether hyperplasia or hypertrophy of astrocytes or increased numbers of astrocytic processes are involved in the development of seizures and the megalencephaly in this model by quantitative comparison of sections immunocytochemically stained for glial fibrillary acidic protein (GFAP). No statistically significant differences between epileptics and controls were found in any of seven areas selected for comparison. In this model gliosis is not involved in the development of epilepsy, nor does it result from repeated seizures.