Case 162 - Discussion

Uploaded: 2008-01-04, Updated: 2008-01-05

 

Medullary Adenocarcinoma of the Colon

The Key Features

  • Large ulcerative mass in the proximal colon;

  • Poorly differentiated, in nests, cords, trabecula and sheets; infrequent glandular differentiation;

  • Crohn's-like lymphoid reaction;

  • Most cases MSI-H

CLINICAL FEATURES

  • Age: elder, mean age of 71 years; slightly female predominance;

  • Marked predilection for the proximal colon with most  cases located proximally to the splenic flexure.

GROSS FINDINGS

  • Always show an expanding pattern of growth with an ulcerated mucosal component, but the tumor are principally in the submucosa
    and often invade through the entire bowel wall;

  • Larger than classic poorly differentiated colonic adenocarcinoma, 70% medullary adenocarcinoma over 7 cm.

MICROSCOPIC FINDINGS

  • Tumor cells are usually arranged in nests, cords, trabecula and sheets with extensive infiltration into the intestinal wall;

  • Glandular differentiation is absent or minimal;

  • Perineural and angiolymphatic invasion are common;

  • Crohn's-like lymphoid reaction with intense peri-tumor and intra-tumor lymphoid infiltrate;

  • Tumor cells

    • Small to medium size cells with a variable amount of eosinophilic or amphophilic cytoplasm;

    • High N/C ratios, round to oval nuclear contours, vesicular chromatin, and prominent nucleoli;

    • Mitotic figures are prominent, as were apoptotic bodies.

IMMUNOHISTOCHEMISTRY AND SPECIAL STAINS

  • A minority of cases are positive for chromogranin A and synaptophysin.

CYTOGENETIC STUDIES

  • Most of cases show MSI-H status;

  • MSI (also termed DNA replication errors, RER, or ubiquitous somatic mutation): abnormality results in extensive instability in repeated nucleotide sequences called microsatellites that is termed microsatellite instability. MSI is caused by inactivation of one of a group of genes responsible for nucleotide mismatch repair, including hMSH2, hMLH1, PMS1, PMS2, hMSH6/GTBP, and hMSH3. Hereditary nonpolyposis colorectal cancer syndrome (HNPCC) is usually the result of a germline mutation in hMSH2 or hMLH1.

TREATMENT AND PROGNOSIS

  • Better clinical outcome compared with classic poorly differentiated colonic adenocarcinoma.

REFERENCES

  • Journal of Clinical Oncology, Vol 17, Issue 8 (August), 1999: 2429.

  • American Journal of Pathology, Vol 150, 1815-1825.

  • Am J Clin Pathol 2005;123:56-65.

  • Histopathological identification of colon cancer with microsatellite instability. Am J Pathol. 2001 Feb;158(2):527-35.