Microinvasive lobular carcinoma associated with intraductal spread arising in a mammary hamartoma.

A 53 year old woman presented with a lump in the inner lower quadrant of the left breast. Histological examination of the breast tumour confirmed that the lesion was a mammary hamartoma. Carcinoma with foci of microinvasion was observed in the lobules of the hamartoma concomitant with the intraductal spread of lobular carcinoma. Immunohistochemically, the cancer cells were negative for beta-catenin, which generally stained normal breast ducts and ductal carcinomas. This is only the sixth case of breast carcinoma arising in a mammary hamartoma to be reported and, moreover, the fourth case of lobular carcinoma occurring within a hamartoma. Despite the apparent rarity of this case, pathologists should be aware of the possibility of carcinomas arising within mammary hamartomas.

Sentinel lymph node biopsy in patients with papillary thyroid carcinoma.

BACKGROUND: It remains controversial whether modified radical neck dissection (MRND) for patients with papillary thyroid carcinoma improves prognosis. However, it is highly probable that the incidence of local recurrence is reduced by lymph node dissection. Sentinel lymph node (SLN) biopsy (SLNB) for patients with melanoma and breast carcinoma has been validated as an accurate method for assessing lymph node status. The objective of this study was to determine the feasibility of SLNB for the evaluation of cervical lymph node status in patients with papillary thyroid carcinoma. METHODS: After injection of methylene blue around the tumor in 22 patients with papillary thyroid carcinoma, blue-stained lymph nodes were dissected as SLNs. After the SLNB, all patients also underwent subtotal thyroidectomy and MRND. SLNs and other lymph nodes were investigated with regard to their number, distribution, size, lymph node status, and ratio of metastatic area. RESULTS: There was concordance between the SLN findings and the regional lymph node status in 19 of 21 patients (90.5%; 7 patients had both positive SLN and regional lymph node results, and 12 patients had both negative SLN and regional lymph node results). Two patients had negative SLN results but, in the end, had positive nonsentinel lymph nodes (NSLNs). The overall reliability rate of SLNB was 86.3% (19 of 22 patients). The authors experienced no complications with the use of methylene blue for the detection of SLNs. CONCLUSIONS: SLNB using methylene blue is feasible technically and is safe, and the findings correlate with cervical lymph node status. Therefore, SLNB is a good technique for estimating the status of cervical lymph nodes in patients with papillary thyroid carcinoma.

Combined choriocarcinoma and adenocarcinoma of the lung occurring in a man: case report and review of the literature.

BACKGROUND: Human chorionic gonadotropin (hCG)-producing large or giant cell carcinoma of the lung is not uncommon, but primary pulmonary choriocarcinoma is an extremely rare entity. Even rarer are cases occurring in males; to date the authors have found only 12 reported cases in the English literature. METHODS: The clinical record of a 61-year-old man who presented with hemoptysis is described. A review of the literature regarding patients with primary pulmonary choriocarcinoma also is reported. RESULTS: Computed tomography scan of the chest demonstrated an expanding thickness of the bullous wall within areas of emphysematous change in the lower lobe of the right lung. Moreover, a new, round tumor near the thickness appeared and rapidly expanded evenly into the surrounding lung tissue. Exploratory thoracotomy revealed the previous tumor to be adenocarcinoma with a small foci of choriocarcinoma, and the new tumor to be a hemorrhage with choriocarcinoma. Because of the pleural dissemination, the patient was treated with chemotherapy. At last follow-up he was alive and well with a gradually increasing serum hCG-beta level in spite of chemotherapy. CONCLUSIONS: Primary pulmonary choriocarcinoma occurring in men is an extremely rare entity with a fatal prognosis. Of the 12 cases reported to date in the English literature, 3 cases of choriocarcinoma with the coexistence of another type of pulmonary carcinoma were reported. To the authors' knowledge the clinical relation between these two types of carcinoma are unknown because all cases to date have been detected at the time of autopsy. Only in the current study case could the clinical course of the disease be followed and pathologic confirmation achieved, although the pathogenesis of the two types of carcinoma could not be determined.

Vinculin: its possible use as a marker of normal collecting ducts and renal neoplasms with collecting duct system phenotype.

Vinculin is a cytoskeletal protein associated with membrane actin-filament-attachment sites of cell-cell and cell-matrix adherens-type junctions. In this article, we examine the expression of vinculin to elucidate its role in human renal neoplasms. We reviewed surgically resected specimens and selected available tissue from 79 renal tumors in 78 patients. There were 55 men and 23 women. Their mean age was 61 years and the mean size of the renal tumors was 6.1 cm. All renal tumors were examined by immunohistochemistry using a monoclonal antibody against vinculin. Overall, 17 (21.5%) renal tumor samples reacted with vinculin. The positive ratio in various types of renal tumors was as follows: conventional-type (clear cell), 0/54; papillary-type, 5/12; chromophobe-type, 5/5; sarcomatoid-type, 3/4; collecting duct carcinoma, 3/3; and oncocytoma, 1/1. The positive rate of conventional-type renal cell carcinomas (RCCs) is significantly different from that of other renal tumors (P < .01). Normal kidney, conventional, and papillary-type RCCs exhibited positive signals in Western blot analysis. These results suggest that vinculin may serve as a useful marker of renal neoplasms with collecting duct system phenotype such as chromophobe-type RCC.

Ductal Carcinoma In Situ of the Breast: Is Breast Conserving Treatment Feasible?

Between 1968 and 1993, 43 cases of ductal carcinoma in situ of the breast (DCIS) were treated. We examined the extent of the cancer using multiple sections of surgical specimens and considered whether or not breast conserving treatment (BCT) is feasible for treatment of DCIS. In nine out of 40 patients (23%), extent of the cancer was classified as grade III, defined as extension over a 2.5-cm margin around the tumor. Among those nine cases, 67% (6/9) had extensive microcalcification on mammography. With respect to the correlation between the tumor size and the extent of the cancer, 29%(5/17) of the cases with a small size tumor, ie, 1.0 cm or less, showed grade III or greater. All tumors with a size of 1.1-2.0 cm showed grade II or lower, and 50%(4/8) of cases with a tumor size of 2.1 cm or more showed grade III or greater. Concerning the relationship between the histological subtype and the extent of the cancer, 22%(2/9) of comedo carcinomas and 23%(7/30) of noncomedo carcinomas showed grade III or greater. The histological extent thus showed no difference between comedo carcinoma and noncomedo carcinoma. It follows that, when BCT performed on DCIS consists of lumpectomy alone, BCT is feasible when the tumor size is 1.1-2.0 cm. without extensive microcalcification on mammography. However, BCT for comedo carcinoma should be approached with caution because of its malignant behavior, although there was no difference in histological extent between comedo and noncomedo carcinoma.

High positive rate of pS2 expression in forefront intraductal cancerous area in breast cancer.

Multiple sections of 40 consecutive cases with invasive ductal carcinoma of the breast, all of which bad wide intraductal cancerous extension, were examined by immunohistochemical analysis for evaluation of hormone dependency in several areas of breast cancer tissues. In this study, we examined the expression of pS2 protein in the central invasive area (CIV), central intraductal cancerous area (CDC) and forefront intraductal cancerous area (FDC). pS2 staining was positive in 52.5% (21/40) of CIV and a significant correlation was found between pS2 expression in CIV and the estrogen receptor status (ER). pS2 staining was positive in 77.5% of CDC and 85.0% of FDC, respectively. A majority (68.4%) of the cases that were negative pS2 in CIV were positive for pS2 in FDC. Moreover, the cases with noncomedo intraductal carcinoma in premenopausal status showed a higher positivity of pS2 expression in FDC than the cases with comedo-carcinoma, though the number of cases of comedo-carcinoma was limited. These findings suggest that endocrine therapy may be useful after breast conserving treatment regardless of the ER status of the primary tumor.

[A primary adenosquamous carcinoma of the stomach difficult to differentiate from gastric ulcer].

The case involves a 57-year-old male who complained of an upper abdominal pain when hungry. An adenosquamous carcinoma of the stomach, however, is rare, and to make such an initial preoperative diagnosis endoscopically from a biopsied specimen is extremely unusual. Thus, as can be expected, on first examination, that the patient had a grade II adenosquamous carcinoma of the stomach was not determined. Two months later, however, on second diagnosis, a primary adenosquamous carcinoma of the stomach in the interior part of the angle region was made after an endoscopic study of a biopsied specimen.

Placental-site trophoblastic tumor of the uterus. Clinicopathological and immunohistochemical observations of a case.

The clinicopathological features of a 28-year-old woman with placental-site trophoblastic tumor (PSTT) are described. The patient presented with severe proteinuria and was found to have a cystic uterine tumor. The serum beta-human chorionic gonadotropin (hCG) level was only slightly elevated. The tumor extended to the serosa without gross metastasis, and was resected. The specimen was composed of active intermediate trophoblasts (IT) and degenerative or inactive ITs. The former component had round to oval and vesicular nuclei, and abundant amphophilic or lightly eosinophilic cytoplasm. The latter component had irregular-shaped pyknotic nuclei and deeply eosinophilic cytoplasm. However, the tumor lacked the bilaminar (cyto- and syncytiotrophoblastic) structure that is a characteristic feature of choriocarcinoma. Immunohistochemical evaluation with human placental lactogen (hPL) and hCG antisera revealed that most of the tumor cells contained abundant hPL, whereas only a small number of cells contained hCG. This method seemed to be most helpful for the differential diagnosis of PSTT from other trophoblastic tumors or non-trophoblastic uterine tumors, and also to be useful for determining the prognostic behavior of PSTT.

Effect of poly(ADP-ribose) synthetase inhibitor administration to streptozotocin-induced diabetic rats on insulin and glucagon contents in their pancreas.

This study was conducted in order to clarify whether the poly(ADP-ribose) synthetase inhibitors, nicotinamide and 3-aminobenzamide, have any influence upon the content and physicochemical properties of insulin and glucagon in streptozotocin (STZ)-treated rat pancreas. STZ-treated rats received intraperitoneal injection of 350 mg/kg nicotinamide or 50 mg/kg 3-aminobenzamide 15 min before and 180 min after the administration of STZ and once a day thereafter for 23 weeks. The blood glucose levels and body weight of nicotinamide- and 3-aminobenzamide-treated rats did not differ from those of the control rats at the end of the experiment. The insulin content in poly(ADP-ribose) synthetase inhibitor-treated rat pancreas was restored partially and reached approximately 60% of the control level, while the glucagon content did not differ from that in the normal rats. Treatment with poly(ADP-ribose) synthetase inhibitor resulted in no alteration in the physicochemical properties of extracted insulin and glucagon. Immunohistological examination of the pancreas revealed that insulin- and glucagon-containing cells in the islets in the poly(ADP-ribose) synthetase inhibitor-treated rat appeared to be normalized. These results suggest that poly(ADP-ribose) synthetase inhibitor normalizes the function but not the insulin content of B cells and that it does not act on A cells in STZ-treated rat pancreas. Restoration of the insulin content would be large enough to keep the function of B cells normal.

Inhibition of chemically induced mammary carcinogenesis in rats by long-term exposure to butylated hydroxytoluene (BHT): interrelations among BHT concentration, carcinogen dose, and diet.

In outbred female Sprague-Dawley rats long-term exposure to dietary butylated hydroxytoluene [3,5-di-tert-butyl-4-hydroxytoluene (BHT); CAS: 128-37-0] 1 week before carcinogen administration to termination resulted in a dose-related inhibition of mammary tumorigenesis and adrenocortical nodulogenesis. In animals fed the cereal-based NIH-07 diet and receiving a low dose (5 mg/rat) of 7,12-dimethylbenz [a] anthracene [(DBMA) CAS: 57-97-6], there was a significant overall inhibitory trend in tumor incidence observed among those receiving 300, 1,000, 3,000, and 6,000 ppm BHT. Maximal inhibition was approximately 50% at the highest concentration of BHT (6,000 ppm). The inhibitory effect of BHT on mammary tumor incidence was less pronounced when BHT was administered to rats initiated with a high carcinogen dose: At 15 mg DMBA/rat maximal inhibition was only 20% at the highest concentration of BHT (6,000 ppm). In contrast, when tumor yield was assessed in terms of latency or tumor multiplicity, the inhibitory effect of BHT was more pronounced in the groups given a high dose of DMBA than in the groups given a low dose. In animals given a low dose of DMBA (5 mg) and fed 6,000 ppm BHT in the casein-based AIN-76A diet, tumor incidence was inhibited by 50% of that of the controls; in contrast, when initiation was with a high dose of DMBA (15 mg), tumor incidence was decreased by only 28% of that of the controls. In animals fed the NIH-07 diet, DMBA-induced adrenocortical nodule formation was also inhibited in a dose-dependent fashion by BHT. At 5 mg DMBA maximal inhibition was 86% of control levels (6,000 ppm BHT); at 15 mg DMBA maximal inhibition was 66% of control levels (6,000 ppm BHT). However, when BHT was incorporated into the AIN-76A diet, its inhibitory effects on adrenocortical nodulogenesis were unexpectedly feeble and unrelated to carcinogen dose: In animals initiated with 5 mg DMBA and administered 6,000 ppm BHT, nodule incidence was decreased by only 25%, whereas in animals initiated with 15 mg DMBA, nodule incidence was decreased by 30% of that of the controls. These results indicate that while chronic exposure to dietary BHT suppressed the development of DMBA-induced mammary tumors and adrenocortical nodules, the degree of suppression depended on the dose of carcinogen administered, the level of BHT in the diet, and the parameter being measured. Diet-dependent differences in BHT action were observed with regard to DMBA-induced adrenocortical nodulogenesis but not with regard to mammary tumorigenesis.

Effects of the hepatocarcinogen nafenopin, a peroxisome proliferator, on the activities of rat liver glutathione-requiring enzymes and catalase in comparison to the action of phenobarbital.

The biochemical effects in the livers of male rats of prolonged administration of the experimental hepatocarcinogen nafenopin, a hypolipidemic agent and peroxisome proliferator, were compared to those of another experimental liver carcinogen, phenobarbital, which acts as a neoplasm promoter. Feeding of nafenopin, 0.03 mmol/kg basal diet for up to 24 weeks increased the numbers of hepatic peroxisomes, increased catalase activity, markedly decreased cytosolic glutathione transferase activities toward two substrates, decreased cytosolic glutathione peroxidase activities toward H2O2 and two organic peroxides, and suppressed the age-related increase in gamma-glutamyl transpeptidase activity. In contrast the livers of rats fed an equimolar concentration of phenobarbital displayed increases in cytosolic glutathione transferase activities and enhancement of gamma-glutamyl transpeptidase activity but no changes in glutathione peroxidase activities. There was also an enhancement of catalase activity without apparent increase in peroxisome number. Enzyme kinetic analyses revealed that the cytosolic glutathione transferase activities toward two halogenonitrobenzene substrates were inhibited in the rats fed nafenopin and displayed elevated Km and decreased Vmax. Kinetic studies of glutathione transferase activities in which nafenopin was mixed with normal rat liver cytosols in the assay system revealed competitive type inhibition toward 1-chloro-2,4-dinitrobenzene and a noncompetitive type of inhibition toward 3,4-dichloronitrobenzene. Likewise activities of glutathione peroxidases toward H2O2 and cumene hydroperoxide were suppressed by in vitro addition. Thus the effects of nafenopin and phenobarbital on liver biochemistry were very different. The inhibition of hepatic biotransformation and scavenger systems by nafenopin is suggested to be relevant to its hepatocarcinogenicity.

Absence of a promoting or sequential syncarcinogenic effect in rat liver by the carcinogenic hypolipidemic drug nafenopin given after N-2-fluorenylacetamide.

The hypolipidemic agent nafenopin, (NF), has been reported to be carcinogenic to rat liver. To determine whether nafenopin exerts a promoting or syncarcinogenic effect in rat liver, its effect on liver carcinogenesis induced by N-2-fluorenylacetamide (FAA) was studied. In two separate experiments, male F344 rats were fed 0.02% FAA for either 10 or 8 weeks to induce preneoplastic liver lesions. Following a recovery period of 1 week, rats were given 0.01 or 0.02% NF in the diet for 23 weeks in one experiment and 0.05 or 0.1% for 24 weeks in the other. The final incidence of neoplasms, and their numbers, size distribution, and degrees of differentiation were not significantly different in groups given NF after FAA compared to those maintained on a basal diet after FAA. In the group treated with the highest dose level of NF following FAA, however, there was a decrease in the number of grossly visible small neoplasms. In contrast, the liver neoplasm promoter phenobarbital increased the multiplicity, although not the incidence, of liver neoplasms when given after FAA. Thus, four different dose levels of NF showed no promoting or syncarcinogenic effect on FAA-induced hepatocarcinogenesis.

Morphologic and cytochemical properties of mouse liver neoplasms induced by diethylnitrosamine and promoted by 4,4'-dichlorodiphenyltrichloroethane, chlordane, or heptachlor.

The relationships between the gross appearance, histologic types, and cytochemical characteristics of hepatocellular neoplasms were studied in B6C3F1 mice given the liver carcinogen diethylnitrosamine either alone or followed by the organochlorine pesticides, 4,4'-dichlorodiphenyltrichloroethane, chlordane, or heptachlor as promoting agents. Hepatocellular neoplasms were categorized according to their cytoplasmic staining properties with hematoxylin and eosin. Acidophilic neoplasms more often displayed increased activity of alkaline phosphatase than did basophilic neoplasms. The activities of glucose-6-phosphatase and adenosine triphosphatase were decreased in both acidophilic and basophilic neoplasms. There was no difference in the activities of these enzymes or gamma-glutamyltranspeptidase between adenomas and carcinomas, although most neoplasms did not display gamma-glutamyltranspeptidase. Chlordane or heptachlor exposure increased the alkaline phosphatase activity in neoplastic cells, but not that of other enzymes. The majority of neoplasms displayed a deficiency of iron accumulation. The macroscopic appearance of neoplasms was closely related to their cytoplasmic staining properties and cytochemical characteristics.

Effect of dietary Laminaria angustata (brown seaweed) on azoxymethane-induced intestinal carcinogenesis in male F344 rats.

The effect of dietary Laminaria angustata (brown seaweed) on azoxymethane (AOM)-induced intestinal carcinogenesis was studied in male F344 rats. Five-week old rats were fed semipurified diets containing 0 and 10% seaweed. When the rats were 7 weeks old, all except the vehicle-treated groups received weekly subcutaneous injections of AOM in normal saline for two weeks (20 mg/kg body wt/week). All animals were fed the experimental diets until the termination of the experiment, which was 28 weeks after the last AOM injection. The incidence (percent of animals with tumors) and multiplicity (tumors/animal) of small intestinal tumors did not differ significantly between the control and seaweed groups. The incidence and multiplicity of colon adenomas along with the size of colon tumors were increased in rats fed the seaweed diet compared with those fed the control diet. Dietary seaweed had no major effect on the concentration of fecal bile acids; however, the concentration of fecal cholesterol and total neutral sterols was decreased in the seaweed group. These results suggest that dietary seaweed increases the risk for colon tumors.

Effects of the hepatocarcinogenic peroxisome-proliferating hypolipidemic agents clofibrate and nafenopin on the rat liver cell membrane enzymes gamma-glutamyltranspeptidase and alkaline phosphatase and on the early stages of liver carcinogenesis.

The effects of the hepatocarcinogenic peroxisome proliferating hypolipidemic agents clofibrate (CF) and nafenopin (NF) on rat liver carcinogenesis initiated by N-2-fluorenylacetamide (FAA) were studied and compared with that of the neoplasm promoter phenobarbital (PB). Male F344 rats were fed 0.02% FAA for 8 weeks to induce hepatocellular altered foci, and were then given no chemical or equimolar amounts (0.03 mmol/kg diet) of the chemicals for 24 weeks in the diet. In groups of animals killed sequentially, 0.07% PB had a marked enhancing effect on FAA-induced foci, while 0.073% CF produced only slight enhancement and 0.093% NF produced none. At the end of the experiment, only PB increased the incidence and multiplicity of liver neoplasms. NF suppressed histochemical gamma-glutamyltranspeptidase activity in the abnormal hepatocytes of foci as well as in periportal hepatocytes. In homogenates of livers from rats fed NF, gamma-glutamyl-transpeptidase activity was reduced, and this occurred to a lesser degree with CF, whereas PB enhanced activity. NF also induced alkaline phosphatase activity in hepatocytes throughout the lobule, but not in altered hepatocytes, thereby making foci demonstrable in sections reacted for alkaline phosphatase. These findings thus reveal significant cell membrane effects of NF and CF and suggest that their involvement in hepatocarcinogenesis is more complex than a promoting action.

Promotion of mouse liver neoplasms by the organochlorine pesticides chlordane and heptachlor in comparison to dichlorodiphenyltrichloroethane.

The organochlorine pesticides chlordane and heptachlor were demonstrated to be liver neoplasm promoters in mice. Male B6C3F1 mice exposed to diethylnitrosamine (DEN) for 14 weeks followed by 25 weeks on control diet developed a 40% incidence of liver neoplasms whereas those given chlordane or heptachlor afterwards had approximately an 80% incidence of liver neoplasms, as did mice given DDT, a positive reference compound. Mice exposed to DEN also developed neoplasms of the forestomach and lung, but the incidences of these were not increased by chlordane, heptachlor or any other exposure. None of the chemicals given alone for the last 25 weeks of the study increased the incidence of liver neoplasms and none given before DEN produced a syncarcinogenic effect.

Induction of respiratory tract tumors in Syrian golden hamsters by a single dose of 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) and the effect of smoke inhalation.

Four groups of 10 male and 10 female Syrian golden hamsters were given single s.c. injections of either 0.3 ml of trioctanoin or of 0.3 ml of trioctanoin containing either 1.0 mg, 3.3 mg, or 10.0 mg of the tobacco specific carcinogen, 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK). These hamsters were then exposed to cigarette smoke for the next 72 weeks. Four control groups received the same injections of NNK or trioctanoin but were treated by sham smoking. All groups treated with NNK had tumors of either the lung, nasal mucosa, and/or trachea. These tumors were not observed in hamsters injected with trioctanoin. These results demonstrate that even a single dose of NNK can induce respiratory tract tumors in Syrian golden hamsters. Smoke inhalation did not result in an increase in respiratory tract tumor incidence in most of the NNK treated groups.

Specific red cell adherence test in benign and malignant lesions of the prostate.

The specific red cell adherence test (SRCA) for blood group antigens has been shown to have some bearing on the invasive potential of bladder tumours. Hitherto there have been few data published from patients with prostatic disease. The results of SRCA testing in 69 such patients are presented. Each of the 30 cases of adenocarcinoma was antigen negative. However, as 18 of 39 patients with only benign hyperplasia were also antigen negative, the test clearly does not reflect extant tumour and is probably not an indicator of subsequent growth of prostatic cancer. Antigen expression was also negative in sections showing prostatitis. As the test was invariably negative in patients with adenocarcinoma, whether or not metastases were present and whatever the degree of differentiation of the primary tumour, it lacks the power to discriminate invasive potential.

Bladder carcinogenesis in mice induced by N-butyl-N-(4-hydroxybutyl) nitrosamine and N-ethyl-N-(4-hydroxybutyl)-nitrosamine with reference to the effect of cyclophosphamide.

The carcinogenicities of N-butyl-N-(4-hydroxybutyl) nitrosamine (BBN) and N-ethyl-N-(4-hydroxybutyl) nitrosamine (EHBN) on the urinary bladder were compared in male BALB/c mice. The effect of cyclophosphamide (CPA) on the carcinogenicities was also investigated. The carcinogenic activity on the bladder mucosa of EHBN was similar to that of BBN, and there was no difference in the growth patterns, histological types or invasive characters of carcinomas induced by BBN and EHBN. Benign or malignant tumors of vascular origin developed in the urinary bladders of 15 mice treated with these carcinogens. The incidence of vascular tumors induced by EHBN was significantly higher than that of tumors induced by BBN. Intraperitoneal injections of CPA seemed to have no effect in the incidence of bladder carcinomas induced by these carcinogens, or on the development of vascular tumors in the bladder wall induced by EHBN.