Immunohistochemical and genetic analysis of osteoclastic giant cell tumor of the pancreas.

Clinical, histopathologic, immunohistochemical, and genetic analyses of 2 osteoclastic giant cell tumors of the pancreas are presented. The neoplasms were composed of osteoclastic giant cells and pleomorphic cells (PCs). The tissue-specific markers gave evidence of mesenchymal nature of the osteoclastic giant cells, as well as other components of the tumor, and lacked any signs of epithelial differentiation in both patients. The nonepithelial nature of both components in the osteoclastic giant cell tumors presented may be associated with a better prognosis, which corresponds to the previous reports of similar neoplasms. A positive immunoreactivity to neuron-specific enolase was recorded in patient 2. The presence of CD68 in osteoclastic giant cells proved their histiocytic nature. Both components of the tumors showed a negative immunoreactivity to desmin and only a scattered reactivity to smooth muscle cell actin, typical markers of myofibroblastic differentiation. Mutation analysis of the tumor revealed the wild state of both p53 and K-ras oncogenes in both patients. A positive immunoreactivity for p53 in PCs of both osteoclastic giant cell tumors was recorded, whereas osteoclastic giant cells did not express this protein. The expression of p21 was recorded in osteoclastic giant cells in patient 1. The absence of Ki-67 in the osteoclastic giant cells and its expression in PCs gave evidence of a different proliferation rate of both cell populations. Different tissue-specific markers, a different proliferation rate, and a different state of oncogene activation in the osteoclastic giant cell tumors contribute to the idea that the tumor derives from a pluripotent cell that may differentiate into an array of phenotypes.

Critical illness polyneuromyopathy: the electrophysiological components of a complex entity.

OBJECTIVE: To evaluate the spectrum and time profile of electrophysiological parameters in the detection of neuromuscular involvement in critically ill patients and establish their correlation with biopsy findings. DESIGN: Prospective clinical and neurophysiological study. SETTING: One general and one neurological intensive care unit in a university hospital. PATIENTS: Forty-six critically ill patients with failure of at least two organ systems were enrolled and completed the 1-month follow up. INTERVENTIONS: Detailed clinical and electrophysiological evaluation including direct muscle stimulation was performed in all cases on entry and at the end of the follow-up. Muscle biopsy was performed in 11, and sural nerve biopsy in 5, cases. MEASUREMENTS AND RESULTS: Electrophysiological signs of new or progressing neuromuscular involvement at the end of the first month were detected in 26 patients (56%) and could be classified into three groups: "pure motor syndrome" (12 cases), combined motor syndrome and sensory polyneuropathy (13 cases) and isolated sensory polyneuropathy (1 case). Direct muscle stimulation showed decreased muscle membrane excitability in 11 of these abnormal cases. Muscle biopsy disclosed various myopathic abnormalities in all 11 cases examined with motor syndrome, in 7 of them in association with denervation/re-innervation changes. CONCLUSIONS: Electrophysiological and histological examinations showed significant overlapping of several pathogenic components of neuromuscular involvement in critically ill patients, namely decreased muscle excitability, myopathy, axonal motor neuropathy and sensory neuropathy. The characterisation of the electrophysiological components of a complex polyneuromyopathy is preferred to the strict categorisation of abnormalities into critical illness myopathy and polyneuropathy.