James M. Henry

Primary malignant lymphomas of the central nervous system

Eighty‐three cases of primary malignant lymphomas of the central nervous system (CNS) from the files of the AFIP were studied according to various clinical and pathologic parameters. The histologic patterns observed are analogous to those seen in the spectrum of malignant lymphomas arising in the reticuloendothelial system of other organs. The authors favor the diagnosis of primary malignant lymphoma of the CNS rather than that of “reticulum cell sarcoma” or “microgliomatosis” used in the past. Lesions are frequently multifocal, and surgery, other than for diagnostic biopsy, is not usually beneficial. The clinical course can be significantly prolonged by radiation therapy.

Human Herpesvirus 6 and Multiple Sclerosis: Systemic Active Infections in Patients with Early Disease

By means of immunohistochemical staining, cells actively infected with human herpesvirus 6 (HHV-6) were found in central nervous system tissues from 8 (73%) of 11 patients with definite multiple sclerosis (MS). Interestingly, 17 (90%) of 19 tissue sections showing active demyelination were positive for HHV-6-infected cells compared with only 3 (13%) of 23 tissue sections free of active disease (P<.0001). Central nervous system tissues from 2 of 28 normal persons and patients with other inflammatory demyelinative diseases were positive for HHV-6-infected cells (P<.0001), and the 2 positive cases were diagnosed as having HHV-6 leukoencephalitis. By use of a rapid culture assay, blood samples from 22 (54%) of 41 patients with definite MS were found to contain active HHV-6 infections, compared with 0 of 61 normal controls (P<.0001). No significant difference was found between HHV-6 viremia-positive and HHV-6 viremia-negative MS patients with respect to type of disease (relapsing/remitting or progressive). In contrast, patients with active HHV-6 viremia were significantly younger and had shorter durations of disease than did HHV-6 viremia-negative patients.

cerebral pilocytic astrocytoma

Cerebral pilocytic astrocytoma is a known intracranial tumor, but its biological characteristics are less well documented. The authors report 30 patients with cerebral pilocytic astrocytoma who were accessioned by the Armed Forces Institute of Pathology between 1970 and 1980. Histological appearance of the tumor was correlated with clinical characteristics. Mean age of onset was 22.15 years, mean preoperative duration of symptoms was 3.77 years, and mean postoperative survival was 5.91 years, with 20 of 23 (87%) known to ultimately survive surgery. These cases of cerebral pilocytic astrocytoma exhibited histologic characteristics consistent with that of a low‐grade tumor. Although several of these tumors were of guarded prognosis due to location, degree of infiltration or cyst recurrence, they generally demonstrated a natural course of a relatively low‐grade neoplasm.

Spinal metastases. A rare mode of presentation of brain tumors

An analysis of more than 18,000 primary central nervous system (CNS) tumors revealed only 18 cases (0.01%) in which dropped spinal metastases had caused the presenting symptoms. This group included 11 males and 7 females in whom there was no history of surgical intervention or irradiation. Primitive neuroectodermal tumors (PNET, medulloblastoma), comprised the largest group (11 patients) followed by high‐grade astrocytomas (anaplastic astrocytoma and glioblastoma) (5 patients). One case each of germinoma and ependymoma were also identified. The clinicopathologic data of these cases, and a brief review of the literature are presented.

Immune reconstitution inflammatory syndrome of the brain: case illustrations of a challenging entity.

Immune reconstitution inflammatory syndrome represents a spectrum of clinicopathologic entities encountered in human immunodeficiency virus-infected patients who have received highly active anti-retroviral therapy. The diagnosis is often challenging, treatment options are limited, and the prognosis is variable. To increase awareness and define the clinicopathologic features, we present our experience with 6 probable cases involving the brain, including 1 autopsy. Clinicopathologic review was supplemented by immunohistochemical analysis. There were 5 men and 1 woman, ranging in age from 34 to 47 (mean, 41; SD, 5.39) years. All patients experienced neurologic deterioration (focal deficits in 5/6) after highly active anti-retroviral therapy. All specimens showed a predominance of CD8+ lymphocytic inflammation. Concurrent CNS infections included human immunodeficiency virus encephalitis, progressive multifocal leukoencephalopathy, cryptococcal meningitis, and syphilis. One patient died, 1 was lost to follow-up, 2 improved, and 2 showed no substantial clinical changes. Subtle and overlapping features may preclude a definitive diagnosis. To capture all suspected cases, it is important to consider the possibility of this entity. In this study, the degree of CD8+ inflammation was more pronounced in the single fatal example, and mast cells were not identified in the infiltrates. Although nonspecific, imaging findings may offer clues to early diagnosis.

Rhenium-186 liposomes as convection-enhanced nanoparticle brachytherapy for treatment of glioblastoma

Although external beam radiation is an essential component to the current standard treatment of primary brain tumors, its application is limited by toxicity at doses more than 80 Gy. Recent studies have suggested that brachytherapy with liposomally encapsulated radionuclides may be of benefit, and we have reported methods to markedly increase the specific activity of rhenium-186 ((186)Re)-liposomes. To better characterize the potential delivery, toxicity, and efficacy of the highly specific activity of (186)Re-liposomes, we evaluated their intracranial application by convection-enhanced delivery in an orthotopic U87 glioma rat model. After establishing an optimal volume of 25 µL, we observed focal activity confined to the site of injection over a 96-hour period. Doses of up to 1850 Gy were administered without overt clinical or microscopic evidence of toxicity. Animals treated with (186)Re-liposomes had a median survival of 126 days (95% confidence interval [CI], 78.4-173 days), compared with 49 days (95% CI, 44-53 days) for controls. Log-rank analysis between these 2 groups was highly significant (P = .0013) and was even higher when 100 Gy was used as a cutoff (P < .0001). Noninvasive luciferase imaging as a surrogate for tumor volume showed a statistically significant separation in bioluminescence by 11 days after 100 Gy or less treatment between the experimental group and the control animals (χ(2)[1, N= 19] = 4.8; P = .029). MRI also supported this difference in tumor size. Duplication of tumor volume differences and survival benefit was possible in a more invasive U251 orthotopic model, with clear separation in bioluminescence at 6 days after treatment (χ(2)[1, N= 9] = 4.7; P = .029); median survival in treated animals was not reached at 120 days because lack of mortality, and log-rank analysis of survival was highly significant (P = .0057). Analysis of tumors by histology revealed minimal areas of necrosis and gliosis. These results support the potential efficacy of the highly specific activity of brachytherapy by (186)Re-liposomes convection-enhanced delivery in glioma.

Oral contraceptives and stroke in young women: A clinicopathologic correlation

Pathologic studies of women with fatal cerebrovascular disease who have received oral contraceptives are infrequently found in the literature. Three cases of this type are reported here. The pathologic findings included an intrinsic vascular lesion in the form of intimal hyperplasia with and without associated thrombosis, found in arteries supplying the brain. Similar vascular lesions have been reported previously in other sites of the vascular system in association with exogenous or endogenous steroids. They have also been found in other species under the influence of steroids. This hyperplasia of vessel intima may be found in association with other clinicopathologic entities, but stigmata of other diseases were not found in these three patients.

Pseudomyogenic hemangioendothelioma (epithelioid sarcoma-like hemangioendothelioma, fibroma-like variant of epithelioid sarcoma) of the thoracic spine.

PurposePseudomyogenic hemangioendothelioma is a soft tissue tumor found in young adults, predominantly males. The tumor has been reported in various locations in the body, including the head, neck, chest wall, abdominal wall, genital region, and extremities. Until now, there has been no indication of occurrence in the spine.MethodsA 25-year-old male presented with spinal cord compression, due to an extradural tumor involving the third and fourth thoracic vertebrae with extension into the right pleural cavity.ResultsHistopathologic examination revealed a pseudomyogenic hemangioendothelioma, also described as epithelioid sarcoma-like hemangioendothelioma, or fibroma-like variant of epithelioid sarcoma.ConclusionWe describe the first occurrence of pseudomyogenic hemangioendothelioma in the thoracic spine. According to previous reports based on other locations, the tumor has an indolent clinical course with a small risk of metastasis, therefore complete macroscopic excision is the treatment of choice. Local recurrence may occur even with complete surgical resection, requiring close follow-up; adjuvant therapy is warranted.

Calcifying pseudoneoplasm of the atlantoaxial joint in a Child: Case report

Calcifying pseudoneoplasm of the spine is a rare nonneoplastic lesion of unknown origin described in adolescents and adults. Its clinical manifestations include axial pain, myelopathy, or radiculopathy. Surgery is the preferred method of treatment. The authors report the occurrence of calcifying pseudoneoplasm at the C1-2 cervical segment in a 22-month-old child who became completely asymptomatic 2 months after open biopsy. A review of the literature is presented, emphasizing the uniqueness of the presented case in comparison with the previously published cases. The 22-month-old healthy girl presented with sudden onset of neck pain. Due to persistence of the symptoms 2 weeks after onset, imaging studies were performed that revealed an inhomogeneous calcified mass extending from the transverse ligament to the C1-2 interlaminar space and facet joint on the left side. Open biopsy of the mass at the C1-2 lamina was performed. The histological features were consistent with calcifying pseudoneoplasm. The childs neck pain progressively improved and she remained asymptomatic at the 1-year follow-up. The postoperative MRI at 8 months did not reveal any progression of the lesion. Contrary to reported cases, calcifying pseudoneoplasm of the spine may occur as early as 2 years of age and should be included in the differential diagnosis of calcified lesions in this age group. Complete resection is not a prerequisite to clinical improvement when there is no compromise of neural structures; conservative management is appropriate.

Astrocytoma arising in meningeal fibrosarcoma

SummaryThe authors describe a rare case of mixed glioma-sarcoma arising in primary meningeal fibrosarcoma as described by Rubinstein, in contrast to the more familiar mechanism of sarcoma arising from hyperplastic blood vessels in primary glioblastoma as described by Feigin. The two interpretations are by no means mutually exclusive, as both have been documented with a higher proportion of such mixed glioma-sarcomas being of the Feigin type. There exist, therefore, dual pathways in the histogenesis of mixed glioma-sarcoma, both of which are sufficiently well documented as to justify resurrection of the historical term “gliosarcoma”, in accordance with the rigid criteria stipulated for diagnosis of this truly biphasic CNS tumor.