The cancer family syndrome. Rare cutaneous phenotypic linkage of Torre's syndrome.

Sebaceous neoplasia have been observed in members of four families exhibiting the cancer family syndrome (CFS). This disorder is characterized by adenocarcinomas, particularly involving the (proximal) colon, endometrium, and ovary; an excess of multiple primary cancer; early age of cancer onset; and autosomal dominant pattern of inheritance. Multiple adenomatous polyps are lacking in this disorder. In four patients from three of these cancer-prone kindreds, cutaneous lesions were accompanied by multiple visceral adenocarcinomas, fulfilling the criteria for Torre's syndrome, a disease that heretofore has not shown notable familial clustering characteristic of the CFS. Therefore, the coexistence of rare sebaceous neoplasia and visceral cancer in CFS supports the notion that some cases of Torre's syndrome may in fact represent the more full phenotypic expression of the gene responsible for the CFS.

Cutaneous carbohydrate studies. IV. The skin glucose content of fasting diabetics with and without infection.

Enzymatic analyses of the skin and blood glucose content of fasting diabetic patients without signs of any infection show that: 1. The fasting skin glucose level reflects the blood glucose level which in turn depends upon diabetic control. 2. The ratio of skin to blood glucose is slightly higher in diabetics taking insulin (71%)than in diabetics controlled with tolbutamide or diet alone (69%) and both are statistically higher than in normal persons (55%) (P < 0.01). Comparison of diabetics with cutaneous infection and diabetics without cutaneous infection show that: 1. The presence of cutaneous infection in diabetics does not consistently correlate with higher ratios of skin to blood glucose as measured by the technics used in this study. 2. In certain instances the skin glucose may equal the blood glucose concentration (i.e. skin: mg/100 gm (w.w.)/blood: mg/100 cc (vol.).

Dermatitis herpetiformis and herpes gestationis. Analysis of γA and γM serum proteins by immunoelectrophoresis.

Serums from patients with dermatitis herpetiformis, herpes gestationis and pemphigus vulgaris were examined and compared with serums from normal individuals. Consistent deviations from normal were found, in that the γA globulin fraction was increased. The γM globulins appeared normal in dermatitis herpetiformis and herpes gestationis but decreased in pemphigus vulgaris. The γA and γM globulin changes in dermatitis herpetiformis and in herpes gestationis were similar.

Familial pancreatic cancer: a review.

The cause of pancreatic cancer remains elusive. The most consistently identified epidemiological risk factor is cigarette smoking. Genetic factors are known to play a significant role in perhaps 5% of the total pancreatic cancer burden. Recent discoveries in molecular biology, particularly germline mutations in inherited conditions which feature pancreatic cancer as an integral part of the tumor spectrum such as in adenomatosis polyposis and hereditary nonpolyposis colorectal cancer, provide powerful incentive to search for other "cancer genes" in this heterogeneous disease. Early detection of this dreadful disease is crucial because its mortality rate approximates its incidence; the ability to identify high-risk patients on the basis of genetic analysis would significantly enhance the potential for early diagnosis. This review addresses the genetic epidemiology of pancreatic cancer and updates our views on screening, surgery, chemotherapy, and genetic counseling, all of which must be used to gain value from genetic predictability of risk status.

Tinea Pedis caused by Trichophyton violaceum.

This, to authors' knowledge, is the first report in the United States of Tinea pedis caused by Trichophyton violaceum in a recent Southeast Asian immigrant. Because of the recent entry into this country of refugees from an area of the world where T. violaceum is endemic, this anthropophilic dermatophyte may become a significant cause of dermatophytosis in the United States.

Cancer genetics in the new era of molecular biology.

The role of primary genetic factors in the etiology of cancer has become of intense interest to the research and clinical community. This interest has been heightened by recent discoveries that germ-line mutations such as BRCA1 and BRCA2 in hereditary breast cancer are responsible for an increasing percentage of common solid tumors. A potpourri of proto-oncogenes and tumor-suppressor genes has been identified in hereditary as well as certain common sporadic and rare cancer types, and new cancer genes will likely be discovered every month to account for the 5 to 10% of the cases of cancer that can be attributed to primary genetic factors. Molecular mechanisms in the pathogenesis of hereditary cancer can result in more-targeted cancer-control measures. At least four mutator genes (MHS2, MLH1, PMS1 and PMS2) appear to account for 70-80% of hereditary nonpolypoid colorectal cancer (HNPCC). When one of these germ-line mutations is present in an HNPCC family, the physician is then able to determine the patient's lifetime cancer destiny with an accuracy of about 90% (limited only by the penetrance of the gene). This will enable highly targeted surveillance to be initiated early, such as colonoscopy beginning at ages 20 to 25 or prophylactic subtotal colectomy. Also, in multiple endocrine neoplasia syndromes (MEN 2A and 2B), the identification of the culprit RET proto-oncogene now enables a secure diagnosis and permits testing of children who might benefit from prophylactic total thyroidectomy. Central to translation of these momentous molecular genetic discoveries into patient care is the necessity of determining who requires DNA testing. The cancer family history is the linchpin in making this decision.

Hereditary malignant melanoma: a unifying etiologic hypothesis.

The recent increase in incidence of malignant melanoma in many of the "sun belts" of the world has focused intense interest on its etiology. Although sunlight is an important factor, only a fraction of those individuals exposed to significantly large amounts of sunlight develop malignant melanoma. Genetic susceptibility undoubtedly plays an important etiologic role. We have put forth a multifaceted hypothesis, which we believe provides unification for the genetic-environmental interaction in the etiology of malignant melanoma. Genetic heterogeneity in the familial atypical multiple mole melanoma (FAMMM) syndrome and other single gene disorders that predispose to malignant melanoma are particularly stressed. The possibility of polygenic or multifactorial factors in the etiology of malignant melanoma remains to be elucidated.

A review of hereditary malignant melanoma including biomarkers in familial atypical multiple mole melanoma syndrome.

This review provides a comprehensive coverage of hereditary malignant melanoma with emphasis upon its heterogeneity as well as newly developed biomarker investigations. The recently described familial atypical multiple mole melanoma (FAMMM) syndrome is featured. Particular attention has been given to findings of increased hyperdiploidy observed as an in vitro phenomenon in cultured skin fibroblasts from high-risk and FAMMM-affected subjects. The FAMMM genotype is complex in that it predisposes a patient not only to melanoma (cutaneous and intraocular malignant melanoma) but also to other histologic varieties of cancer, including cancer of the lung, pancreas, and breast. Attention is given to cancer surveillance and management programs for patients at increased risk for the several forms of hereditary malignant melanoma. This approach capitalizes advantageously upon employment of a knowledge of genetics and hereditary cancer syndrome identification, with particular attention to tumor associations.

Chromosome instability and the FAMMM syndrome.

Our study involved two extended familial atypical multiple mole melanoma (FAMMM) kindreds wherein a sufficient number of informative, high genetic risk, and affected patients enabled collection of pertinent tissue samples (normal skin/fibroblasts and atypical nevi/melanocytes) for cytogenetic analysis, and peripheral blood lymphocytes for DNA usage for linkage studies. We observed marked chromosome instability, as evidence by increased frequencies of cells with chromosomal rearrangements (translocations, deletions, and inversions) in cell cultures from atypical nevi and normal skin. There was no evidence of linkage of the FAMMM disease locus to any of the markers for the short arm of chromosome 1p in these two families. Well-characterized FAMMM kindreds provide an opportunity for biomarker investigations for elucidating heterogeneity and, ultimately, improving cancer control.

Pancreatic cancer and the familial atypical multiple mole melanoma (FAMMM) syndrome.

The role of host factors in the etiology of pancreatic cancer has received a paucity of systematic investigation. Anecdotal reports and one population-based study have supported the concept that familial clustering of this disease exists. We have studied a kindred with a cancer-associated genodermatosis known as familial atypical multiple mole melanoma (FAMMM) syndrome (hereditary dysplastic nervus syndrome). Three key relatives have manifested pancreatic carcinoma. Since FAMMM may account for as much as 10% of the total malignant melanoma burden, its association with pancreatic cancer harbors important public health implications. Given the fact that the etiology of pancreatic cancer remains enigmatic, it is important to investigate all possible clues to its causality, including the potential role of host factors.

Abnormalities of T-cell subsets in Behçet's syndrome.

T cells and T-cell subsets were determined in the peripheral blood of 12 patients with Behçet's syndrome and 30 normal healthy control subjects. When compared with the control group, the mean percentage of T cells for the group with Behçet's syndrome was significantly decreased (73% v 61%). The mean percentage of T mu (helper) cells for the group with Behçet's syndrome (26%) was also significantly decreased from the mean value of the control group (42%). There was a concomitant significant increase of T gamma (suppressor) cells of the group with Behçet's syndrome (19%) over the mean value of the control group (10%). These results clearly indicated that there were alterations of T cells and T-cell subsets in this disease.