Medullary carcinoma of the large intestine: a population based analysis

Abstract

Medullary carcinoma (MC) of the colorectum is a relatively new histological type of adenocarcinoma characterized by poor glandular differentiation and intraepithelial lymphocytic infiltrate. To date, there has been no epidemiological study of this rare tumor type, which has now been incorporated as a separate entity in the World Health Organization (WHO) classification of colorectal cancers. We used the population-based registries of the Surveillance, Epidemiology and End Results (SEER) database to identify all cases of colorectal MC between 1973 and 2006 and compared them to poorly and undifferentiated colonic adenocarcinomas (PDA and UDA, respectively). We observed that MCs were rare tumors, constituting approximately 5-8 cases for every 10,000 colon cancers diagnosed, with a mean annual incidence of 3.47 (+/-0.75) per 10 million population. Mean age at diagnosis was 69.3 (+/-12.5) years, with incidence increasing with age. MCs were twice as common in females, who presented at a later age, with a lower stage and a trend towards favorable prognosis. MCs were extremely rare among African-Americans. MCs were most common in the proximal colon (74%), where they present at a later age than the sigmoid colon. There were no cases reliably identified in the rectum or appendix. Serum carcinoembryonic antigen levels (CEA) were elevated prior to first course of treatment in 40% of the patients. MCs were more commonly poorly differentiated (72%), with 22% being undifferentiated. MCs commonly presented with Stage II disease, with 10% presenting with metastases. Only one patient presented with N2b disease (>7 positive nodes). Early outcome analyses showed that MCs have 1- and 2-year relative survival rates of 92.7 and 73.8% respectively. Although MCs showed a trend towards better early overall survival, undifferentiated MCs present more commonly with Stage III, with comparatively worse early outcomes.

Figure 1

Histological appearance with hematoxylin and eosin stains of (A) medullary carcinoma (original magnification ×25) and (B) poorly differentiated adenocarcinoma (original magnification ×40). Reproduced with permission from Hum Pathol (Elsevier) (13).

Figure 2

Incidence of medullary carcinoma by age.

Figure 3

Temporal trends in incidence rates. The exponential increase in incidence since 2000 may be an artifact due to increasing awareness of medullary carcinoma as a separate histological entity.

Figure 4

Kaplan-Meier curves for early outcomes by overall survival. *Not statistically significant despite better early outcomes, probably due to sample size limitations; generalized Wilcoxon, p=0.103; Mantel-Cox (log-rank), p=0.204; Tarone-Ware, p=0.126. **Generalized Wilcoxon, p=0.046; Mantel- Cox (log-rank), p=0.09; Tarone-Ware, p=0.05. The numbers at the bottom denote the number of patients at risk at each given time point in all groups compared. MC, medullary carcinoma; PDA, poorly differentiated adenocarcinoma; UDA, undifferentiated adenocarcinoma.

Figure 5

Kaplan-Meier curves for early outcomes by overall survival of medullary carcinomas by histological grade. *Not statistically significant despite better early outcomes probably due to sample size limitations; generalized Wilcoxon, p=0.546; Mantel-Cox (log-rank), p=0.365; Tarone- Ware, p=0.458. The numbers at the bottom denote the number of patients at risk at each given time-point in all groups compared. PD-MC, poorly differentiated medullary carcinoma; UD-MC, undifferentiated medullary carcinoma.

Figure 6

Kaplan-Meier curves for early outcomes by overall survival. *Not statistically significant despite better early outcomes probably due to sample size limitations; generalized Wilcoxon, p=0.105; Mantel-Cox (log-rank), p=0.098; Tarone-Ware, p=0.097. **Generalized Wilcoxon, p=0.058; Mantel- Cox (log-rank), p=0.049; Tarone-Ware, p=0.049. The numbers at the bottom denote the number of patients at risk at each given time-point in all groups compared. PD-MC, poorly differentiated medullary carcinoma; PDA, poorly differentiated adenocarcinoma; UDA, undifferentiated adenocarcinoma.