Linkage of an American pedigree with palmoplantar keratoderma and malignancy (palmoplantar ectodermal dysplasia type III) to 17q24. Literature survey and proposed updated classification of the keratodermas.

OBJECTIVES: To determine linkage in a pedigree with palmoplantar keratoderma (PPK) associated with squamous cell carcinoma of the esophagus. DESIGN: A large American pedigree was studied and the clinical phenotype was described. Linkage analysis was performed using genomic DNA from key individuals. SETTING: A community-based family study. PATIENTS: The family pedigree was expanded from a single index case. MAIN OUTCOME MEASURES: To demonstrate linkage and the relative risk of squamous cell carcinoma of the esophagus in this pedigree. RESULTS: Focal PPK was inherited as an autosomal dominant with variable expression, but signs were not limited to the palmoplantar epidermis. The generalized nature of this pattern of PPK was highlighted by the perifollicular papules and oral hyperkeratosis. Affected individuals (125 individuals) in 7 generations were identified, with 17 affected individuals having associated cancer. Seven of the 8 squamous cell carcinomas of the esophagus occurred in smokers. Other tumors were seen in nonsmokers, but these were not significantly increased. The combined male-female expected incidence of squamous cell carcinoma of the mouth and esophagus was 0.21; observed, 8 (relative risk of 38; P < .001). Linkage to the tylosis and esophageal cancer gene locus on 17q24 was demonstrated with a maximum 2-point lod score of 8.20 at zero recombination fraction for the DNA marker D17S1603. CONCLUSION: The distinctive clinical phenotype in this family suggests a new classification for PPKs, in particular a reappraisal of the phenotype as a focal PPK. A very similar phenotype is found in patients with keratin K16 gene mutations.

Carcinoma of the esophagus and tylosis. A lethal genetic combination.

Hyperkeratosis of the palms and soles (tylosis) is an uncommon genetic disorder. A small number of English families, however, have been described in which it is associated with carcinoma of the esophagus. The current report is of the first American family described with this condition. Members of those families affected with tylosis have at least a 90% risk of esophageal carcinoma by age 65 years. The paired conditions have an autosomal dominant mode of transmission and probably are controlled at a single genetic locus. The actual pathologic state might be mediated through an increase in epidermal growth factor receptors in the abnormal tissues.

Muscular pseudotumor of the breast following doxorubicin and radiation therapy for oat cell carcinoma of the lung.

Two male patients developed muscular pseudotumor of the breast following combined treatment of radiation and chemotherapy with cyclophosphamide, doxorubicin, methotrexate and procarbazine for oat cell carcinoma of the lung. The pathologic findings of the biopsy specimens revealed muscle and capillary changes similar to previously reported myocardiotoxicity from doxorubicin and radiation therapy. Discussed is a possible additive or synergistic toxic effect of doxorubicin and radiation therapy in the development of muscular pseudotumor of the breast.

Breast cancer in brothers: case reports and a review of 30 cases of male breast cancer.

Two brothers with breast cancer are presented. One died 8 years after diagnosis and the other is presently living at 1 year with metastatic disease. The courses of 28 other previously unreported male patients with carcinoma of the breast are reviewed, and the possibility of male breast carcinoma being metastatic disease from the prostate is discussed. Useful etiologic information might be obtained from following the offspring of male breast cancer patients to see if they are at increased risk of developing the disease.