Mark Cohen

Ubiquitin immunostaining and inclusion body myositis: Study of 30 patients with inclusion body myositis

Distinction of inclusion body myositis (IBM) from other forms of inflammatory myopathy is significant from prognostic and therapeutic standpoints. This study retrospectively examines ubiquitin expression by paraffin immunohistochemistry in muscle biopsy material from 30 patients with IBM. Patients included 19 men and 11 women (ages 29 to 80 years; mean, 64 years). All biopsies were characterized by endomysial chronic inflammation, muscle fiber degeneration and regeneration, rimmed vacuoles, and angular atrophic esterase-positive muscle fibers. Ragged red fibers were identified in biopsies of five patients and a partial cytochrome C-oxidase deficiency by enzyme histochemistry in biopsies of 10 patients. Evidence of intranuclear or cytoplasmic tubulofilamentous structures confirming a diagnosis of IBM was observed in all 30 cases. Paracrystalline mitochondrial inclusions were noted in five patients. Discrete myocyte intranuclear ubiquitin-positive inclusions were noted in 14 patients (47%). Discrete intracytoplasmic ubiquitin-positive inclusions were noted in 24 (80%) patients. Positive staining of rimmed vacuoles by ubiquitin was observed in 25 (83%) patients. Diffuse staining of scattered muscle fibers was observed in 21 (70%) patients. In a control group including patients with polymyositis (n = 3), dermatomyositis (n = 3), necrotizing vasculitis (n = 1), and granulomatous myositis (n = 1), discrete intranuclear or cytoplasmic ubiquitin-positive inclusions were not observed. Rimmed vacuoles were not seen either by light microscopy or ubiquitin immunostaining in any of the eight cases. Occasional myofibers from all eight cases showed diffuse, positive muscle fiber staining. Although not present in all cases, evidence of ubiquitin-positive myocytic intranuclear or cytoplasmic inclusions or positive-staining rimmed vacuoles in the setting of an inflammatory myopathy may be suggestive of a diagnosis of inclusion body myositis. Use of ubiquitin immunohistochemistry may be useful in cases in which frozen tissue or tissue processed for electron microscopy is not available, and IBM is suspected. Light or electron microscopic evidence of mitochondrial abnormalities were noted in a significant subset of patients (13 of 30; 43%) of patients with IBM.

Comparative Immunohistochemical Study of Insulin-like Growth Factor II and Insulin-like Growth Factor ReceptorType 1 in Pediatric Brain Tumors

Insulin-like growth factor (IGF)-II is an important growth factor in development of the central nervous system. The purpose of this study was to evaluate expression of IGF-II and IGF receptor type 1 (IGFR1) in various pediatric brain tumors. Immunohistochemistry for IGF-II and IGFR1 was performed on 15 choroid plexus papillomas (CPPs) including 1 atypical CPP, 2 choroid plexus carcinomas (CPCs), 5 anaplastic ependymomas, 7 nonanaplastic ependymomas (simply referred to as “ependymoma”), 5 medulloblastomas, 1 cerebral neuroblastoma, and 1 atypical teratoid/rhabdoid tumor (ATRT) along with 10 non-neoplastic choroid plexus and 3 non-neoplastic ependymal linings. All non-neoplastic choroid plexus, CPPs, CPCs, anaplastic ependymomas, ATRT, 71% of ependymomas, and 67% of non-neoplastic ependymal linings showed cytoplasmic positivity for IGF-II, whereas all medulloblastomas and the cerebral neuroblastoma were negative for IGF-II. In addition to cytoplasmic positivity for IGFR1, membranous positivity was observed in 73% of CPPs, both CPCs, the ATRT, 22% of non-neoplastic choroid plexus, 80% of anaplastic ependymomas, and 29% of ependymomas, but not in any medulloblastoma, cerebral neuroblastoma, or non-neoplastic ependymal lining. IGF-II and IGFR1 may play roles in the pathogeneses of CPP, CPC, anaplastic ependymoma, ependymoma, and ATRT. Immunohistochemical testing for IGF-II and IGFR1 may be useful in differentiating ATRT, CPC, and anaplastic ependymoma from medulloblastoma and cerebral neuroblastoma.

Plasma cell granulomas of the brain: pediatric case presentation and review of the literature

Plasma cell granulomas (inflammatory pseudotumors) are benign inflammatory masses that have been observed in virtually every organ system but are most often described in the lung. Rare cases have been reported in which the brain and spinal cord are affected. We present the case of a 5-year-old girl with personality and behavioral changes, discovered to be harboring an intracerebral plasma cell granuloma. The literature on plasma cell granuloma of the central nervous system is discussed with emphasis on the clinical, radiological, and pathological features of these lesions.

Isolated dropped head due to adult-onset nemaline myopathy treated by posterior fusion

Neck extensor muscle weakness causing dropped head is most commonly associated with myasthenia gravis, ALS, and paraspinous myopathy.1–3 Less often, myotonic dystrophy, facioscapulohumeral muscular dystrophy, hypothyroidism, chronic inflammatory demyelinating polyneuropathy, polymyositis/dermatomyositis, and inclusion body myositis are associated with dropped head.1 We describe a patient with isolated dropped head and no limb weakness due to adult-onset nemaline myopathy that improved with a posterior cervical spinal fusion.nnA 72-year-old man presented with a 10-year history of a progressive head drop. He denied limb weakness, diplopia, or imbalance. There was no family history of neuromuscular disorders. His physical examination revealed isolated neck extensor weakness with normal limb muscle strength (figure, A). Deep tendon reflexes and sensation were normal. Creatine kinase, thyroid-stimulating hormone, and acetylcholine receptor antibodies were normal or negative. Cervical spine MRI demonstrated multilevel degenerative changes. Sensory and motor …

Immunohistochemical expression of cathepsin D in meningiomas.

We retrospectively studied the expression of cathepsin D by immunohistochemical analysis in 86 meningiomas (World Health Organization [WHO] grade I, n = 44; WHO grade II, n = 21; WHO grade III, n = 21) and correlated the results with tumor grade and outcome. Staining was scored semiquantitatively based on distribution among neoplastic cells as follows: 0, no staining; 1+, 5% or less of the cells; 2+, 6% to 20%; 3+, 21% to 50%; and 4+, more than 50% of the cells. Cathepsin D expression was observed as follows: 0, 10 cases (12%); 1+, 25 cases (29%); 2+, 15 cases (17%); 3+, 12 cases (14%); and 4+, 24 cases (28%). A higher degree of cathepsin D immunostaining was associated with low tumor grade (P = .0014), low mitotic count (P < .0001), low apoptotic count (P < .0001), and the development of recurrence (P = .035). There was no correlation with outcome or MIB-1 proliferation index. Cathepsin D expression by immunohistochemical analysis was identified in the majority (88% [76/86]) of meningiomas studied. A greater degree of immunoreactivity was observed in the WHO grade I group.

Ascending cord necrosis. Complication of intrathecal chemotherapy with radiologic-pathologic correlation.

Eight days later, the child was readmitted with ascending paralysis, some loss of sensation in the upper extremities, and fecal and urinary incontinence. Despite continued high-dose steroid therapy, he experienced a progressive ascending motor and sensory loss. Repeat MRI examinations (T1and T2-weighted) and gadolinium-enhanced images demonstrated decreased signal within a markedly widened cervical cord to the level