Gordon R. Hennigar

Adenosquamous carcinoma of the nasal, oral and laryngeal cavities. A clinicopathologic survey of ten cases

Ten cases of an unusual form of carcinoma involving the submucosal glands and ducts of the nasal and oral cavities and the larynx were collected and reviewed. The histopathologic features were defined and four distinct component parts were classified: ductal carcinoma in situ, adenocarcinoma, squamous cell carcinoma, and a mixed carcinoma. This tumor was found to be extremely aggressive and highly malignant, with 80% of the cases showing histopathologically proven metastases. The histopathologic features and the clinical behavior of this tumor were sufficiently distinctive to warrant the designation adenosquamous carcinoma. The mode of therapy was evaluated and the treatment of choice appears to be radical surgery. However, the limited number of cases indicates that further collection and subsequent analyses of additional cases must be performed before any definitive conclusions can be drawn.

Malignant mixed tumors of salivary gland origin

One hundred and thirty‐four salivary gland tumors originally diagnosed as malignant mixed tumor at the Armed Forces Institute of Pathology and the Medical College of South Carolina were analyzed. These were reclassified and only 25 were found to possess specific histopathologic criteria necessary for the diagnosis of malignant mixed tumor. Where possible, the clinical behavior, therapy, and prognosis were correlated with the histopathology. The malignant mixed tumor was found primarily in the parotid gland and was observed more frequently in men. The median age of patients with this tumor was 38 years (60% occurred prior to age 40). Pain and fixation of the tumor could not be correlated with malignancy. Sixty‐four percent of these tumors presented as primary malignant mixed tumors. Histologically proven metastases were observed in 71% of the cases, with lung, lymph node, central nervous system, and bone the most frequent sites. Certain histopathologic features of the malignant mixed tumor can be correlated with eventual metastases. Although the pathogenesis of the malignant mixed tumor remains undetermined, the results of this study indicate that this neoplasm is malignant from the onset and does not develop from malignant transformation of a preexisting “benign” mixed tumor.

Prolonged ingestion of commercial DDT and PCB; effects on progesterone levels and reproduction in the mature female rat

A report linking human polycystic ovary with increased exposure to environmental DDT (Heinrichset al. 1971) prompted the present study comparing effects of PCB and DDT or their combination on reproduction in female rats under more realistic conditions with respect to level (75 and 150 ppm), route of administration (dietary contaminant), and period of exposure (8 and 36 weeks). Evaluation of estrous cycle length, mating frequency, number and size of litters; as well as plasma levels of DDT, PCB, progesterone (P), and 17α=hydroxyprogesterone (17α=OH-P), permitted comparison of short and long term reproductive changes from ingestion of two levels of DDT and/or PCB.PCB reduced plasma progesterone (p<.01) while plasma 17α OH-P was unchanged by PCB or DDT. High DDT and PCB abolished reproduction. Histologically, distinct ovarian stromal changes accompanied 150 ppm of PCB, while increased numbers of more prominent follicular cysts were evident with 150 ppm of DDT. Although DDT and PCB generally reduced or abolished litter production, no treatment tested significantly altered litter size. Long term chronic ingestion of more realistic levels of technical DDT (85%p,p′, 15%o,p′-DDT) in these studies did not lead to polycystic ovaries in adult rats comparable to those reported following i.v. administration of pureo,p′-DDT to immature rats. Plasma DDT levels above 800 ppb are clearly detrimental to reproduction, while levels below 500 ppb had little effect. Finally, we present the first evidence reported to our knowledge demonstrating that prolonged ingestion of PCB (150 ppm) markedly reduces reproduction (p<.05) accompanied by significantly reduced progesterone in plasma (p<.01) as well as by histologically characteristic ovarian stromal changes not seen with DDT alone.

Acute, subchronic, and chronic toxicity of chlordecone

Oral LD50 values were 132 mg/kg for male rats, 126 mg/kg for female rats, 71 mg/kg for male rabbits, and approximately 250 mg/kg for dogs. The percutaneous LD50 for male rabbits was 410 mg/kg. Deaths were preceded by the development of severe tremors. Gross autopsy findings were essentially negative. Rats were fed chlordecone in concentrations of 1, 5, 10, 25, and 80 ppm for up to 2 years. All rats on 50 and 80 ppm died during the first 6 months. Depressed growth occurred at concentrations at low as 10 ppm for females and 25 ppm for males. Food consumption tended to increase as the dietary concentration of chlordecone became greater. This effect was associated with a measured increase in the metabolic rate. Concentrations of 5 ppm and higher accelerated and intensified the rate of development of proteinuria. Increased liver-to-body weight ratios were consistently observed. Elevated ratios for other organs measured (kidney, heart, spleen, and testes) were found at certain periods, but at higher chlordecone concentrations than required for liver. Principal histopathologic findings in rats were degenerative changes in liver cells (fatty changes, hyperplasia), kidney lesions (primarily glomerulosclerosis), and testicular atrophy. Hematocrit and hemoglobin values were reduced in rats receiving concentrations of 25 ppm and above. There was no evidence of a clotting defect, although some rats receiving 50 and 80 ppm showed a bleeding tendency. Beagle dogs fed chlordecone at concentrations of 1,5, and 25 ppm for periods up to 127 weeks exhibited few gross or histopathologic signs of toxicity.

Effects of prolonged exposure to dietary DDT and PCB on rat liver morphology

Livers from mature female rats exposed for up to 36 weeks to dietary levels of Aroclor® 1242 (75 or 150 ppm) and/or commercial grade DDT (75 or 150 ppm) were compared to those from animals receiving basal diets. In earlier studies, reproductive effects of the test substances were assessed. Moreover, the markedly abnormal gross appearance of the livers led to examination of the hepatic effects of PCB and DDT in more detail, at both the light microscope (LM) and electron microscope (EM) levels.Light microscopy revealed focal liver cell necrosis in rats fed PCB, DDT, and PCB-DDT combinations. Higher levels of PCB (150 ppm) increased the severity of necrosis. Feeding both DDT and PCB produced similar effects at 75 ppm, and caused atypical centrolobular regeneration, occasionally forming nodules resembling small tumors. The experimentally induced injury was associated with the marked accumulation of iron-containing pigment in hepatocytes and Kupffer cells.Electron micrographs demonstrated the presence of whorl structures (myelin figures) within liver cell cytoplasm, and for the first time clearly illustrated the endocytotic expulsion of these membranous whorls from hepatocytes into the bile canaliculi and sinusoids. Other ultrastructural changes were similar to those previously reported in rat livers injured by several hepatotoxic substances. Mitochondria enclosed by or projecting into large non-lipid vacuoles were present in several experimental groups.The electron micrographs provide the most convincing evidence to date to support the hypothesis that myelin figures may be the vehicle whereby the cell rids itself of specific hepatotoxic substances.

Acute and subchronic toxicity of mirex in the rat, dog, and rabbit.

Abstract The acute and subchronic (13 weeks) toxicity of orally administered mirex was studied in mongrel dogs, beagle dogs, and rats. Percutaneous toxicity was evaluated in rabbits. The acute oral LD50 in male mongrel dogs was found to be > 1000 mg/kg. Beagles of both sexes fed 4 and 20 ppm of mirex for 13 weeks exhibited no toxic effects. Two animals receiving 100 ppm died during the test period. Also observed at this dosage level were a reduced rate of weight gain, abnormal blood chemistry values, increased liver/body weight ratios, and decreased spleen/body weight ratios. No histopathologic changes were attributed to mirex. Male and female rats received diets containing 0, 5, 20, 80, 320, and 1280 ppm. No significant adverse effects were observed at levels of 5, 20, and 80 ppm. The following were observed at 320 and 1280 ppm; depressed growth, decreased hemoglobin concentrations, elevated white cell counts, enlarged livers showing histopathological changes, and deaths in the 1280-ppm groups. Rabbits exposed percutaneously to 3.33 or 6.67 g of mirex bait/kg, 6–7 hr each day, 5 days a week, for 9 weeks, exhibited no evidence of mirex intoxication.

A toxicologic evaluation of 5-ethoxy-3-trichloromethyl-1,2,4-thiadiazole (ETMT)☆☆☆

Abstract The following studies were conducted on 3-ethoxy-3-trichloromethyl-1,2,4-thiadiazole (ETMT, Terrazole), a soil fungicide: acute oral toxicity in rats, rabbits, and dogs; acute and subchronic percutaneous toxicity in rabbits; subchronic feeding to rats and dogs; 2-year feeding to rats and dogs; and a three-generation reproduction study in rats. CD rats, albino rabbits, and mongrel and beagle dogs were employed. The acute oral toxicity values (LD50 ± SD) were: rats, 1077 ± 78 mg/kg; rabbits, 779 ± 532 mg/kg; dogs > 5000 mg/kg (premedicated with morphine). The test material was added to the diet of rats at levels of 0, 78, 156, 312, 625, and 1250 ppm (subchronic study) and 0, 10, 80, and 640 ppm (chronic study and reproductive study); and to the diet of dogs at levels of 0, 100, 400, and 1600 ppm (subchronic study); and 0, 10, 100, and 1000 ppm (chronic study). Three-month feeding in rats resulted only in growth inhibition at 1250 ppm and elevated liver to body weight ratios at 625 and 1250 ppm. Dogs fed 3 months showed a decrease in spleen-to-body weight ratios at all feeding levels and a higher liver-to-body weight ratio at 1600 ppm. No consistent adverse dose-related effects were apparent in the 2-year rat feeding study. The following findings were noted only in dogs that received the 1000-ppm diet: a lesser body weight gain, increases in SAP, SGOT, serum cholinesterase, BSP retention, liver weights; cholestatic hepatosis with secondary bile nephrosis. No adverse effects were apparent at 10 or 100 ppm. In the three-generation reproduction study, no adverse effects were apparent on fertility, gestation, viability, lactation, number of stillborn, and mean number of pups born and weaned per litter. Adverse effects occurred only on the 640-ppm diet and these consisted of lower weaning weights of offspring and depressed body weight gains of parent rats.

Angiomatoid neuroblastoma with cytoplasmic glycogen a case report and histogenetic considerations

A case of angiomatoid neuroblastoma with intracytoplasmic glycogen demonstrable by both light and electron microscopy is presented. A review of the histogenesis of the adrenal medulla indicates that glycogen‐containing tumors of the adrenal medulla originate from a more primitive cell than their non‐glycogen‐containing counterparts.

Analgesic-enhanced glycogen accumulation in renal collecting tubules of rabbits.

Abstract Rabbits were exposed to varying levels of a combination of the analgesics aspirin, phenacetin, and caffeine (APC) for periods of 6 hr to 1 month. Morphological and histochemical alterations in the renal medulla were observed. APC induced a marked, diffuse increase in glycogen content of collecting tubular cells in the papilla. With lower doses over a longer period of time, APC produced no increase in glycogen content, compared with the control animals.