Formation and persistence of DNA adducts of 2-amino-3-methylimidazo[4,5-f]quinoline (IQ) in CDF1 mice fed a high omega-3 fatty acid diet.

The potent bacterial mutagen 2-amino-3-methylimidazo[4,5-f]quinoline (IQ) is carcinogenic in the CDF1 mouse, affecting the liver, lungs and forestomach. IQ forms DNA adducts in both target- and non-target organs of the CDF1 mouse. The chemopreventive effects of menhaden oil (MO), a fish oil high in omega-3 fatty acids, are well known. Because DNA adduct formation is considered to be a critical event in the initiation of carcinogenesis, we have assessed the effects of dietary MO on IQ-DNA adduct formation. For the duration of the study, young adult, male CDF1 mice were maintained on either powdered chow diet, AIN-76A diet, or AIN-76A diet modified to contain 19% MO (19% MO diet). After 2 weeks on these diets, all animals received 0.01% (w/w) IQ in the diet for the next 3 weeks. Groups of 4 animals were killed 1, 2, 4, 6, 8 or 12 days thereafter for analysis of IQ-DNA adducts by 32P-postlabeling. IQ-DNA adduct patterns were qualitatively similar in the liver, lungs, stomach, small intestine, cecum, colon, kidneys, heart and spleen. Adduct levels in the liver, lungs, stomach and colon decreased significantly during the 12-day study period, but only to a relatively small extent and only with certain of the diets. On day 1, the 19% MO diet significantly decreased (35.8-90.0%) adduct levels in the stomach, cecum, colon and kidneys, when compared to chow diet or AIN-76A diet. On day 12, adduct levels in the liver, stomach, heart and spleen were decreased (36.5-64.7%) as a result of MO feeding. With the exception of the liver, heart and spleen on day 12, there were no significant differences in organ adduct levels between the chow diet and the AIN-76A diet. It is concluded that feeding 0.01% (w/w) IQ in the diet for 3 weeks results in a relatively slow rate of adduct removal and that this rate is largely independent of the type of diet. Dietary MO inhibits IQ-DNA adduct formation only in certain target- and non-target organs of the CDF1 mouse, a finding similar to our previous results in the F344 rat. MO may affect the initiation phase of IQ tumorigenesis by inhibiting IQ-DNA adduct formation in certain target organs.

An epidemiologic case-control study of central nervous system tumors in children and parental occupational exposures.

A population-based case-control study was conducted with 338 patients less than 15 years of age who were diagnosed with a primary tumor of the central nervous system from January 1968 through December 1977 in 53 contiguous New York counties. The study also included 676 controls who were selected from the birth certificate files of the New York State Department of Health. Parental occupational exposures at the time of each child's birth and at the time of tumor diagnosis were derived from maternal interviews. The current data set failed to show any consistent association between childhood central nervous system tumor risk and paternal occupational exposures to hydrocarbons or to electromagnetic fields, or employment in the aerospace industry or pulp and paper manufacturing. Findings for occupational exposures to ionizing radiation were also inconsistent. A positive association was observed between central nervous system tumor risk and paternal exposures to ionizing radiation based on industrial codes. Odds ratios ranged from 1.71 to 2.15. This association was not observed when paternal occupational titles were used to define exposure (range of odds ratios, 1.01-1.10). Maternal exposures to ionizing radiation were not related to risk regardless of the classification scheme used.

Brain hamartomas and tumors associated with tuberous sclerosis.

Ventricular tumors of tuberous sclerosis are almost always hamartomas or benign tumors occurring predominantly in children or young adults. No clear gross or histological distinctions between the ventricular "candle gutterings" and "tumors" have been identified. The clinical presentation may be acute, with the sudden onset of increased intracranial pressure and possible serious morbidity (visual impairment) or death. When these tumors are surgically removed or decompressed, the prognosis for life seems to be quite good. Malignant change in these lesions is very rare.

Pituitary oncocytoma. Indispensable role of electron microscopy in its identification.

Two surgically resected pituitary adenomas that appeared to be chromophobe or poorly granulated acidophil adenomas by light microscopy were correctly identified as oncocytomas by electron microscopy. The tumor cells ahd markedly hyperplastic, moderately pleomorphic mitochondria in the cytoplasm of virtually all cells. Scattered secretory granules were displaced to the periphery of the cytoplasm but the secretion type of pituitary cell remained obscure. Histochemical and immunocytochemical methods imperfectly characterized these unusual tumors. Even though these neoplasms have been considered rare, they are now being recognized more often after ultrastructural study. Eventually their pathobiologic features may be better understood. One of our patients was 24 years old and is the youngest patient, to our knowledge, in whom a pituitary oncocytoma has been documented.

Focal myositis.

Focal myositis, a new distinct clinicopathologic entity, is a benign inflammatory pseudotumor of skeletal muscle. Based on a study of 16 cases, the disease which affects both children and adults typically evolves over a period of several weeks as a localized painful swelling within the soft tissue of an extremity. At surgery the lesion is frequently considered a neoplasm, appearing pale in color and poorly demarcated from the surrounding muscle. Histologically there is lymphocytic infiltration of the perimysial and endomysial spaces, scattered muscle fiber necrosis and regeneration, and interstitial fibrosis. The etiology is unknown, but a history of trauma or family background of a similar disease was specifically excluded. Although polymyositis may be suspected initially because of muscle pain and inflammation, the process remains confined to a single area and signs of systemic disease are not encountered. Follow-up information obtained 2--6 years after surgery indicates no recurrence of the lesion in any of 16 cases.

The ethnic distribution of primary central nervous system tumors: AFIP, 1958 to 1970.

A retrospective ethnic study was made of 16,311 cases of primary central nervous system (CNS) tumors seen at the Armed Forces Institute of Pathology (AFIP), Washington, D.C., from 1958 to 1970. Results showed a considerably higher Caucasian:Negro (C:N) case ratio (13.7:1) than the C:N population ratio (8.4:1), indicating a higher relative frequency of primary CNS tumors in American Caucasians as compared to American Negroes. The glioma was significantly more frequent in Caucasians than in Negroes (p less than 0.005). In contrast, Negroes had an excess of the pituitary adenoma as compared to Caucasians (P less than 0.01). The proportional frequencies of the meningioma and the nerve sheath tumor were also higher in Negroes than in Caucasians. When this pattern of the tumor distribution of American Negroes was compared to that of African Negroes (a composite African series), the preponderance of the pituitary adenoma and the meningioma and the relative paucity of the glioma in the Negro race as compared to Caucasians were again confirmed. The differences in the relative frequency and the tumor distribution between American Negroes and Caucasians and the considerable similarity of the tumor distribution between American and African Negroes emphasize the importance of genetic factors in the development of at least some primary CNS tumors.

A demyelinating disorder associated with cerebrovascular amyloid angiopathy.

Five patients with a demyelinating disorder and associated amyloid angiopathy are presented. The disease affected middle-aged individuals, pursued a fluctuating course, and ended in progressive, fatal deterioration of the central nervous system. Neurologic findings indicated multiple lesions within the neuraxis; profound dementia was prominent in all cases. Pathologically, numerous demyelinated plaques, similar to those in multiple sclerosis, were found in the cerebral white matter, and less consistently in other locations such as optic nerve, brain stem, and spinal cord. Amyloid accumulated massively in and around blood vessels, usually in the immediate vicinity of the plaques. At least one similar case is reported in the literature, but the nosologic status of the condition is uncertain.

Craniopharyngiomas: a clinical and pathological review.

Two hundred and forty-five cases of craniopharyngiomas were obtained from the files of the AFIP and reviewed statistically with reference to their gross and microscopic appearance and clinical data. The majority of the tumors were cystic and microscopically, cysts were formed by squamous epithelial maturation, by degeneration of the stellate cells at the centers of adamantinomatous nests, or by degeneration of the stroma. Transitional forms were seen between adamantinomatous and squamous epithelium and keratohyaline granules and keratin were present in some cases. Because of this overlap, differentiation between craniopharyngiomas and suprasellar epidermoid cysts often is not possible. Significantly increased acturial survival rates were associated with absence of calcification in plain skull films in adults, negative CSF examination, and tumor size under 3.0 cm.

Intradural lipomas of the spinal cord. A clinicopathological correlation.

Nine original cases of intradural spinal cord lipomas have been examined from a clinical and pathological standpoint. These tumors occur more commonly in men in the second to fourth decade and are found most frequently in the thoracic spinal cord. Paraparesis, sensory changes, urinary incontinence, and pain are frequent presenting complaints. Myelography is the diagnostic study of choice. All lipomas in this series were located primarily within the cord; four of these also presented an extramedullary extension. Admixed nerve bundles were present in five cases with associated hypertrophic onion-bulb formation in three. Decompression with biopsy or subtotal resection is the operative procedure of choice.

Haemorrhagic and perivenous encephalitis: a clinical-pathological review of 38 cases.

Clinical and pathological data from eight cases of acute haemorrhagic leucoencephalitis (AHL) confirm the previously documented devastating features of this disease. Data from 30 cases of perivenous encephalitis (PVE) associated with viral diseases reveal pathological changes ranging from lymphocytic cuffing of vessels to severe vasculitis similar to the vasculitis of AHL. Relatively few cases show demyelination as a prominent feature. The pathological changes are unrelated to the type of underlying disease with the exception that the pathology of 'post-rubella' encephalitis tends to be mild. Two cases of rubeola and two of mumps showed viral nodules in the cortex, raising the possibility of direct viral invasion of tissue. Allowing for species differences, these changes are analogous to the pathological features of experimental allergic encephalitis (EAE); with the various pathological changes of PVE paralleling the features of ordinary EAE, while the changes of AHL and the severe cases of PVE strongly resemble hyperacute EAE.