Alan L. Morrison

Rosai-Dorfman disease isolated to the central nervous system: a report of 11 cases.

Sinus histocytosis with massive lymphadenopathy, also known as Rosai-Dorfman Disease (RDD), is an idiopathic histiocytic proliferation affecting lymph nodes. Although extranodal involvement has been reported in diverse sites, central nervous system (CNS) manifestation, particularly in the absence of nodal disease is uncommon. We report 11 cases of RDD primary to the CNS without evidence of other sites of involvement. The cases included 7 males and 4 females ranging in age from 22 to 63 years (mean: 41 y). The patients presented with headaches, seizures, numbness, or paraplegia. Eight cases involved the cranial cavity and three cases, the spinal canal. Lesions were most often extra-axial and dura based. Only one presented in the CNS parenchyma. Histologically, the lesions consisted of variable numbers of pale-staining histocytes with emperipolesis often overshadowed by extensive lymphoplasmacytic infiltrates and fibrosis in the background. Special stains for organisms were negative. By immunohistochemical analysis, the characteristic histiocytes were positive for S100 protein and CD68 and negative for CD1a. Treatment consisted of surgical biopsy or excision. Follow-up, available for 10 cases with intervals ranging from 5 days to 42 months (mean: 15 mo), disclosed one patient dying of operative complications 5 days after biopsy and nine patients with no evidence of disease progression RDD should be considered in the differential diagnosis of inflammatory lesions of the CNS. Our study suggests that this entity may have been misdiagnosed in the past as plasma cell granuloma or inflammatory pseudotumor.

Foamy cells with oligodendroglial phenotype in childhood ataxia with diffuse central nervous system hypomyelination syndrome

Abstract Childhood ataxia with diffuse central nervous system hypomyelination syndrome (CACH) is a recently described leukodystrophy of unknown etiology. To characterize the neuropathological features and gain insight as to the pathogenesis of this disorder, we studied cerebral tissue from six patients with the CACH syndrome. Evaluation of toluidine blue-stained, semithin sections of white matter from CACH patients disclosed unusual cells with “foamy” cytoplasm, small round nuclei and fine chromatin. Electron microscopy (EM) revealed cells in the white matter with abundant cytoplasm containing many mitochondria and loosely clustered, membranous structures, but lacking the lysosomal structures seen in macrophages. Further analysis of tissue sections with antibodies and special stains demonstrated that the abnormal cells with abundant cytoplasm labeled with oligodendroglial markers, but did not react with macrophage or astrocytic markers. Double immunolabeling with macrophage and oligodendroglial markers clearly distinguished macrophages from the “foamy” oligodendroglial cells (FODCs). Proteolipid protein (PLP) mRNA in situ hybridization demonstrated PLP mRNA transcripts in a high proportion of oligodendrocytes in CACH patients compared to control patients, and PLP mRNA transcript signal in cells, morphologically consistent with FODCs. Normal and pathological brain control tissues did not contain FODCs. These neuropathological findings will be useful pathological identifiers of CACH, and may provide clues to the pathogenesis of this disorder.

Chordoid glioma of the third ventricle: a report of two new cases, with further evidence supporting an ependymal differentiation, and review of the literature.

The term chordoid glioma of the third ventricle was first used to describe a rare and slowly growing neoplasm of uncertain histogenesis, with chordoid appearance, occurring preferentially in middle-aged women. Herein we report two additional examples of this novel entity together with a literature review based on the 25 cases previously published. Our review fully confirms the strikingly stereotyped clinical, neuroradiologic, and pathologic features of this unique tumor. The female/male ratio was 1.7:1, and the age range was 24–70 years (mean 44.9 years). In all 27 cases imaging findings were similar showing a well-defined mass (mean 2.8 cm in largest dimension), ovoid in shape, hyperdense on CT scans, with uniform and intense contrast enhancement, arising in the hypothalamic/suprasellar/third ventricular region. Histologically, the main consistent characteristics were cords and clusters of epithelioid cells within an abundant mucinous and often vacuolated background. Mitoses were sparse or absent and anaplastic features, endothelial proliferation, and necrosis were not identified. Lymphoplasmacytic infiltrates with Russell bodies were frequent throughout the tumor and its interface with adjacent brain parenchyma. Most of the tumor cells revealed a strong and diffuse expression of vimentin and glial fibrillary acidic protein. Additionally, the vast majority of tumors showed focal coexpression of cytokeratins, CD34, S-100 protein, and epithelial membrane antigen; the MIB-1 labeling indices were uniformly low. Surprisingly for a glioma assigned WHO grade II, the 19 patients with an available but short follow-up (mean 22.5 months; range 6–68 months) experienced a rather poor outcome (three recurrences and seven deaths), probably reflecting the anatomic site of the neoplasm that precludes a complete surgical excision rather than its histologic composition. Ultrastructural examination of 10 cases demonstrated findings in line with a glial derivation and a putative ependymal origin such as cytoplasmic intermediate filaments, microvilli, intermediate junctions or desmosomes, and focal basal lamina formation. In our case no. 1, and for the first time in this tumor, we observed sparse and abnormal cilia in an aberrant juxtanuclear location, a further argument for considering chordoid glioma as a subtype of ependymoma. However, a better understanding of the biologic behavior and histogenesis of this distinctive clinicopathologic entity needs to be investigated with a larger series. Nevertheless, taking into account its strikingly consistent anatomic localization, its unique histopathologic and immunohistochemical profile, in conjunction with the most recent and convincing ultrastructural arguments, we suggest that chordoid glioma of the third ventricle could be better classified as chordoid ependymoma of the lamina terminalis area.

Cytokeratin 7 and 20 expression in choroid plexus tumors : utility in differentiating these neoplasms from metastatic carcinomas

Tumors derived from choroid plexus epithelium are uncommon and may exhibit a wide variety of histologic patterns. They often are difficult to distinguish from metastatic carcinomas. Previous studies that addressed this issue yielded conflicting results. Recent reports have demonstrated that evaluation of coordinate expression of cytokeratin (CK) 7 and CK20 aids in distinguishing primary from metastatic lesions in a number of anatomic sites and that tumors that commonly are metastatic to the brain retain their CK7/CK20 immunophenotype in this location. We examined 35 choroid plexus tumors with a panel of antibodies to determine their CK7/CK20 immunophenotype. Tumors from 35 patients (7 male, 28 female; mean age, 25 years), including 31 choroid plexus papillomas and 4 atypical papillomas, were evaluated. All tumors were intraventricular or within the cerebellopontine angle and composed predominantly of orderly columnar epithelial cells resting on distinct fibrovascular cores. Atypical papillomas contained combinations of focal loss of architectural pattern, increased mitotic activity, necrosis, and brain parenchymal invasion. No lesion was unequivocally malignant. Twenty-six tumors (74%), including all atypical papillomas, were CK7 positive and CK20 negative. Two tumors stained with both markers, one stained with CK20 only, and six stained with neither marker. Other findings included expression of glial fibrillary acidic protein in 24 tumors, S-100 protein in 19 tumors, transthyretin in 31 tumors, Ber EP4 in 1 tumor, CAM5.2 in 33 tumors, epithelial membrane antigen in 4 tumors, and pancytokeratin in 27 tumors. Our results indicate that the majority of choroid plexus tumors have a CK7-positive/CK20-negative immunophenotype. This finding may be useful in differentiating these lesions from metastatic carcinomas that have differing CK7/CK20 profiles.

Mycobacterial spindle cell pseudotumor of the brain: A case report and review of the literature

Spindle cell pseudotumors found in the skin, lymph nodes, bone marrow, spleen, lungs, and retroperitoneum have been reported recently in immunosuppressed patients, including those with acquired immunodeficiency syndrome. The authors report a similar lesion limited to the brain in a 38-year-old human immunodeficiency virus-negative man receiving steroid therapy for treatment of sarcoidosis. Histopathologically the lesions were composed of spindle and epithelioid histiocytes, small foci of necrosis, and numerous acid-fast bacilli. The acid-fast bacilli were determined by culture and polymerase chain reaction to be Mycobacterium avium intracellulare. Because of the uncommon histologic appearance of this lesion and the potential for treatment if recognized, mycobacterial spindle cell pseudotumors should be included in the differential diagnosis of spindle cell lesions in the brain in immunosuppressed patients.

A Clinicopathological Study of 15 Patients With Neuroglial Heterotopias and Encephaloceles of the Middle Ear and Mastoid Region

Objectives/Hypothesis Heterotopic masses of neuroglial tissue involving non‐midline structures, specifically, the middle ear region, are exceptional. The pathogenesis of these lesions and, in particular, their relation to encephaloceles, is uncertain.

Air bag-associated injury to a child in the front passenger seat.

We report the case of a 3.5-year-old front seat passenger who suffered significant head and neck injuries as a result of air bag deployment in a collision of <30 mph. These lesions included multiple abrasions of the lower half of the face, nose, forehead, and right ear, torn frenula, conjunctival petechiae, comminuted fractures of the left and right lateral frontal regions and right parietal bone, diastatic fracture of the coronal suture, subgaleal and subarachnoid hemorrhages, cortical contusions, subluxation of the atlantooccipital joint, and fracture of the C4 vertebral body. These lesions are consistent with trauma secondary to the deploying air bag and the head striking the interior of the car. The findings in this case further support the Centers for Disease Control and Prevention (CDC) guidelines of keeping children properly restrained, preferably in the back seat, or as far as possible from air bags.

Acceleration-deceleration injuries to the brain in blunt force trauma

Blunt force trauma to the stationary head is generally associated with cortical-subcortical injuries located at the site of impact (i.e., coup contusions). We present 2 cases of cerebral contusion injury secondary to falling tree limbs hitting the head, illustrating an exception to this observation. In each case, the most prominent lesions were white matter hemorrhagic contusions similar to those associated with acceleration-deceleration types of injuries characterizing falls or motor vehicle accidents (i.e., contrecoup contusions). The proposed pathogenesis for these observed lesions is a forceful impact resulting in the acceleration of the head and brain of a magnitude comparable with that in a motor vehicle accident or a fall.

Ear bleeding: A sign not to be underestimated in cases of strangulation.

Otorrhagia is commonly associated with cranial trauma and diving accidents. In some forensic manuals, bleeding in the ears is anecdotally associated with strangulation. We report 2 cases of criminal strangulation with hemotympanum and otorrhagia, emphasizing the importance of this sign with strangulation. We present the proposed pathophysiology of the injuries and the value of otoscopic evaluation to complete the external examination in forensic cases suspicious for strangulation.

Dysembryoplastic neuroepithelial tumor: An immunohistochemical study with myelin oligodendrocyte glycoprotein

CONTEXT The dysembryoplastic neuroepithelial tumor (DNT) is an uncommon lesion characterized by a heterogeneous population of neurons, astrocytes, and oligodendroglia-like cells (OLCs). The basic nature of the DNT and its constituent cells, particularly the OLCs, remains unresolved; some authors favor a neuronal origin, and others propose a glial or mixed origin for these cells. DESIGN We examined 11 DNTs with antibodies to myelin oligodendrocyte glycoprotein, a marker of mature oligodendrocytes. RESULTS All DNTs studied (7 from males, 4 from females; age range of patients, 2-37 years) were composed of varying proportions of neurons, astrocytes, and OLCs. Membrane or cytoplasmic immunoreactivity for myelin oligodendrocyte glycoprotein was found in many OLCs in 9 of 11 cases. The number of myelin oligodendrocyte glycoprotein-positive OLCs was variable: >75% of the OLCs were positive in 5 cases, 25% to 75% of the OLCs were positive in 2 cases, and <25% of the OLCs were positive in 2 cases. CONCLUSION These findings suggest that many of the OLCs represent mature oligodendrocytes and support the notion that DNTs are heterogenous lesions composed of multiple, mature cell types.