Malignant mesothelioma following radiation exposure.

Mesothelioma developed in proximity to the field of therapeutic radiation administered 10-31 years previously in four patients. In three, mesothelioma arose within the site of prior therapeutic radiation for another cancer. Mesothelioma in the fourth patient developed adjacent to the site of cosmetic radiation to a thyroidectomy scar. None of these four patients recalled an asbestos exposure or had evidence of asbestosis on chest roentgenogram. Lung tissue in one patient was negative for ferruginous bodies, a finding considered to indicate no significant asbestos exposure. Five other patients with radiation-associated mesothelioma have been reported previously, suggesting that radiation is an uncommon cause of human mesothelioma. Problems in the diagnosis of radiation-associated mesotheliomas are considered.

Biomarkers for early detection of colon cancer.

There is an increasing demand for biomarkers in colon cancer for risk assessment, early detection, prognosis, and surrogate end points. A number of biomarkers have been identified for early detection of colon cancer, although the risk factors have not been identified extensively. The major advances in understanding colorectal cancer include the identification and the involvement of APC, p53, and Ki-ras in the development and progression of the disease, the identification of the aberrant crypt foci as an early preinvasive lesion, and its relation to the development of cancer. Detecting malignant neoplasms in the early stages offers clinical advantages; therefore, the National Cancer Institute has established an Early Detection Research NETWORK: The emphasis of the network is on translational research and collaboration among scientists.

Delayed hypersensitivity in Graves' disease and exophthalmos: identification of thyroglobulin in normal human orbital muscle.

Patients with Graves' disease and exophthalmos demonstrate delayed hypersensitivity to antigens present in extracts of certain normal human tissue; namely,thyroid gland and retroorbital tissue. The delayed hypersensitivity can be assayed in vitro by quantitating the amount of a lymphokine, migration inhibition factor (MIF), which is produced when T lymphocytes of patients with Graves' disease and exophthalmos are exposed to these antigens. In the present report, a partial purification is described for the retro-orbital tissue antigen which is responsible for the positive leucocyte migration inhibition factor assay (MIF assay) exhibited by a sensitized lymphocytes of these patients. The purified retro-orbital tissue antigen preparation demonstrates a 50- to 150-fold higher specific activity over crude homogenates in its ability to act as an antigen in the MIF assay of exophthalmic patients. Immunodiffusion, ultracentrifugation, and disc electrophoretic data indicate that this purified antigen preparation, obtained from normal human, retro-orbital tissue, contains thyroglobulin or a derivative of thyroglobulin; immunofluorescence studies localize the anti-thyroglobulin reactive material to the plasma membranes of extraocular muscle fibers of normal individuals. On the basis of these data it is concluded that thyroglobulin or a derivative of the thyroglobulin molecule is present in the orbital muscle of normal individuals. Since thyroglobulin purified from normal human thyroid glands and the purified retro-orbital tissue preparation are nearly equivalent as antigens in the MIF assay of exophthalmic patients, we conclude that thyroglobulin or an antigenic component of the thyroglobulin molecule is one of the antigens to which patients with Graves' disease and exophthalmos demonstrate delayed hypersensitivity.

The pathologist as a consultant in cancer patient management: a patterns of care study in pathology.

The Committee on the Pathologist as a Consultant in Cancer Patient Management, a committee of the Cancer Committee of the College of American Pathologists, was formed in response to the demands made on pathologists by other medical specialists to function as consultants. The Committee on the Pathologist as a Consultant in Cancer Patient Management has evolved from the Patterns of Care Steering Committee (1979) which in turn was spawned by the Patterns of Care Study initiated by The American College of Radiology (ACR) in 1973. The objective of the ACR was to improve the quality of care by establishing guidelines for the best current management in radiation oncology through a consensus by peers. Pathology is concerned with establishing a diagnosis, providing a rationale for treatment, estimating prognosis, and evaluating outcome. Consequently, the CAP Patterns of Care Study assumed a different form from that of the ACR, adapting itself to the role of the pathologist as a consultant. Its objective, however, remained the same - to improve the quality of care by providing quality assurance of pathology reports dealing with cancer patients. Three task forces, one for each site, have been established. Each is composed of pathologists and other medical specialists from small and large community hospitals, universities, and private office practice. The primary function of each task force is to develop guidelines for data to be included in routine pathology consultation reports. These guidelines include parameters that document adequate examination of the specimen, and those essential elements which can be used to guide selection of therapy, estimate prognosis, and evaluate outcome, such as the pathologic factors required for staging. Data to help establish these guidelines have been obtained in consultation with medical specialists who are members of the task forces, as well as from the medical literature. This entire process will be discussed. Currently there is great concern about improving the quality of medical care, particularly in a cost effective manner. Assuring the quality of consultation reports is yet another way in which pathology can contribute.

Intestinal-type adenocarcinoma of the gallbladder. A clinicopathologic study of seven cases.

Seven examples of a distinctive morphological variant of well-differentiated adenocarcinoma of the gallbladder with intestinal features are reported. Four tumors were composed predominantly of goblet cells and absorptive columnar cells, two of which had, in addition, a few Paneth cells and neuroendocrine cells. Three neoplasms closely resembled colonic carcinoma, and one of these also contained neuroendocrine cells. Serotonin-immunoreactive cells were demonstrated in three of the seven intestinal-type adenocarcinomas, two of which also had cells that stained for somatostatin pancreatic polypeptide and cholecystokinin. Four adenocarcinomas were associated with cholelithiasis, and three with intestinal metaplasia of the uninvolved mucosa. Despite the well-differentiated character of all neoplasms and the deceptively benign microscopic appearance of two of them, three patients died with extension to the liver and metastasis. Of the two survivors, one had carcinoma in situ and the other had a carcinoma that extended only to the muscle layer of the gallbladder. The various cell phenotypes found in these gallbladder adenocarcinomas can be explained on the basis of intestinal differentiation.

Carcinoma in situ of the gallbladder. A clinicopathologic study of 18 cases.

Eighteen cases of carcinoma in situ of the gallbladder collected over a 7-year period at the General Hospital of Mexico City are reported. All patients were females whose ages ranged from 26 to 83 years with a mean of 55. Their symptoms and signs were related to the presence of stones. Grossly, the in situ carcinomas could not be differentiated from chronic cholecystitis. In only one case was the diagnosis suspected on macroscopic examination. Thirteen lesions were located either in the fundus or body of the gallbladder. Histologically there were two types of in situ carcinoma--papillary (two cases) and nonpapillary (16 cases). Hyperplasia of the antral-type glands was associated with 12 cases and cholecystitis follicularis with four. The atypical changes began on the surface epithelium and extended into the epithelial invaginations and later into the antral-type glands. Four carcinomas in situ exhibited limited invasion into the underlying lamina propria or inner part of the muscle layer. In the 15 cases that were examined, immunoperoxidase stains revealed cytoplasmic staining for carcinoembryonic antigen (CEA). All patients we were able to follow (those who had only carcinoma in situ) are symptom-free after cholecystectomy. One of the four patients with microinvasion died 7 years after cholecystectomy with clinical evidence of liver metastasis.

Mucinous cystadenocarcinoma of the pancreas. Morphologic and immunocytochemical observations.

Twenty mucinous cystadenocarcinomas of the pancreas, most of which occurred in the tail of the pancreas in middle-aged women, were examined histologically and by immunohistochemical stains. Thirteen tumors displayed a marked histological heterogeneity and expressed intestinal differentiation as shown by the colonic appearance of the glands both at the light- and electron-microscopic levels. Other intestinal features included varying numbers of goblet cells, argyrophil and argentaffin cells, and even Paneth cells. By immunohistochemistry, endocrine cells were present in 13 of the 20 tumors (65%) and were more numerous in the poorly differentiated than in the well-differentiated epithelial component of the tumors. Serotonin-containing cells were the most common endocrine cells, followed by somatostatin-containing cells and cells that showed immunoreactivity for pancreatic polypeptide and gastrin. However, none of the patients had clinical manifestations of carcinoid, somatostatinoma, or the Zollinger-Ellison syndrome. The findings support the hypothesis that mucinous cystadenocarcinomas of the pancreas arise from an "endodermal stem cell" that differentiates into cells with intestinal phenotypes.

Oat cell carcinoma of the gallbladder.

Among 448 malignant epithelial tumors of the gallbladder, 19 were classified as oat cell carcinomas. Seventeen cases occurred in elderly women. Eighteen of the patients had cholelithiasis. The neoplasms were highly lethal, metastasizing early and causing death shortly after diagnosis. All 19 patients died as a direct result of the tumors, with liver, regional lymph node, and/or lung metastases. Combination chemotherapy produced objective responses in two patients, the longest survivors of the series (11 and 13 months). The salient morphologic features of oat cell carcinomas of the gallbladder include large size at the time of diagnosis, extensive necrosis, and propensity for submucosal growth. Histologically, these tumors are composed of variable proportions of two cell types, round and fusiform, arranged in solid sheets, cords, or festoons. In areas of necrosis, the deposition of DNA in vessel walls is seen occasionally. Four tumors contained neoplastic glands similar to those present in well-differentiated adenocarcinomas of the gallbladder. These tumors were considered to be a combined form of oat cell carcinoma. With the use of immunoperoxidase stains, focal carcinoembryonic antigen reactivity was demonstrated in three of 11 tumors. Electron microscopic examination revealed neurosecretory granules. Morphologically, these tumors resembled the oat cell carcinomas that occur at other sites.

Intestinal metaplasia of the gallbladder: a morphologic and immunocytochemical study.

The morphologic spectrum of intestinal metaplasia was studied in 49 gallbladders that had been excised because of cholelithiasis. Based on the absence or presence of endocrine cells, the cases of intestinal metaplasia were arbitrarily divided into two groups. The gallbladders from the first group (26 cases) contained isolated or small clusters of mature goblet cells, while those from the second group (23 cases), in addition to the goblet cells, contained argyrophil and argentaffin cells and, less frequently, Paneth cells and gland-like structures similar to colonic crypts. Pseudopyloric glands and superficial gastric-type epithelium were present in both groups. Argyrophil cells outnumbered argentaffin cells by a ratio of 4 to 1. By immunocytochemical methods serotonin-containing cells were found to be the most common endocrine cells. Other endocrine cells showed immunoreactivity for somatostatin, cholecystokinin, gastrin, and pancreatic polypeptide. The presence of gut endocrine cells and Paneth cells in the pseudopyloric glands suggests that these glands are also an integral component of intestinal metaplasia of the gallbladder. The findings support the hypothesis that cholelithiasis induces the appearance of a stem endodermal cell that, in turn, may differentiate into cells with mature intestinal or gastric phenotypes.

Conditional survival among patients with carcinoma of the lung.

OBJECTIVE: One- and 5-year probabilities of survival or death change once a patient has already survived > or = 1 year after diagnosis. The current paper reports these probabilities for lung cancer patients according to histologic subtype, stage, and age at diagnosis. METHODS: Cumulative observed survival rates were calculated and compared among 95,283 patients with histologically confirmed lung cancer (diagnosed from 1983 to 1992 and followed through 1995) by the life-table method using population-based tumor registries participating in the Surveillance, Epidemiology, and End Results (SEER) Program of the National Cancer Institute. On the basis of the cumulative survival estimates, we derived the probability of death in the next year, conditioned on having already survived to the start of the year (annual hazards), and the probability of survival conditioned on having already survived > or = 1 year (conditional survival). These rates were reported according to histologic subtype, stage, and age groups. RESULTS: At the time of diagnosis, annual hazard rates differ greatly among histologic subtypes. However, by 5 years after diagnosis, the rates become similar. Bronchioloalveolar carcinoma displays the lowest annual hazards and small-cell carcinoma displays the highest annual hazards. Stage-age subcategories within histologic subtypes continue to show large differences in annual hazard rates. Five-year conditional survival probabilities are also reported, providing survival information that is consistent to that obtained from the annual hazards. CONCLUSIONS: One- and 5-year prognosis for lung cancer patients is influenced by years already survived and histology, stage, and age at diagnosis. Annual hazards and conditional survival provides useful and more relevant information than conventional survival estimates for patients and their physicians. These statistics can be directly obtained from cumulative survival estimates and should be more widely reported.