Approximately 1% to 3% of all gastric cancers are associated with families exhibiting an autosomal dominant pattern of susceptibility. E-cadherin (CDH1) truncating mutations have been shown to be present in approximately 30% of families with hereditary diffuse gastric cancer (HDGC) and are associated with a significantly increased risk of gastric cancer and lobular breast cancer.

Individuals from a large kindred with HDGC who were identified to have a CDH1 mutation prospectively underwent comprehensive screening with stool occult blood testing, standard upper gastrointestinal endoscopy with random gastric biopsies, high-magnification endoscopy with random gastric biopsies, endoscopic ultrasonography, CT, and PET scans to evaluate the stomach for occult cancer. Subsequently, they each underwent total gastrectomy with D-2 node dissection and Roux-en-Y esophagojejunostomy. The stomach and resected lymph nodes were evaluated pathologically.

Six patients were identified as CDH1 carriers from a single family. There were 2 men and 4 women. The mean age was 54 years (range, 51-57 years). No patient had any signs or symptoms of gastric cancer. Exhaustive preoperative stomach evaluation was normal in each case, and the stomach and adjacent lymph nodes appeared normal at surgery. However, each patient (6 of 6, 100%) was found to have multiple foci of T1 invasive diffuse gastric adenocarcinoma (pure signet-ring cell type). No patient had lymph node or distant metastases. Each was staged as T1N0M0. Each patient recovered uneventfully without morbidity or mortality.

CDH1 mutations in individuals from families with HDGC are associated with gastric cancer in a highly penetrant fashion. CDH1 mutations are an indication for total gastrectomy in these patients. This mutation will identify patients with cancer before other detectable symptoms or signs of the disease.

Malpractice actions against surgical pathologists are still relatively uncommon, but they have increased in frequency over time and are associated with sizable indemnity figures. This discussion categorizes areas of liability in surgical pathology into three groups: those that represent health system flaws (problems with specimen identification, or transportation, or both; lack of clinical information or erroneous information; sampling effects and defects; and poorly reproducible or poorly defined diagnostic or prognostic criteria), others that exist at the interface between the system and individuals (allowing clinicians to bypass pathologic review of referred specimens; acceding to clinical demands for inadvisable procedures; and working in a disruptive environment), and truly individual errors by pathologists (lapses in reasoning; deficiencies concerning continuity in the laboratory; invalid assumptions regarding recipients of surgical pathology reports; over-reliance on the results of "special" tests; and problems with peer consultation). Finally, two important topic areas are discussed that commonly enter into lawsuits filed against surgical pathologists; namely, "delay in diagnosis" of malignant neoplasms and "failure to provide adequate prognostic information." Based on a review of the pertinent literature, we conclude that the clinical courses of most common malignancies are not affected in a significant manner by delays in diagnosis. Moreover, the practice of using "personalized external validity" for supposedly prognostic tests is examined, with the resulting opinion that prognostication of tumor behavior in individual patients is not reliable using anything but anatomic staging systems.