Medullary carcinoma of the colon: can the undifferentiated be differentiated?

Abstract

Medullary carcinoma of the colon is a rare variant of colorectal cancer claimed to have a more favorable prognosis than conventional adenocarcinomas. The histopathologic appearance may be difficult to distinguish from poorly differentiated adenocarcinoma. The study aimed to evaluate the diagnostic interobserver agreement and to characterize the immunohistochemical and molecular differences between these two subgroups. Fifteen cases initially classified as medullary carcinoma and 30 cases of poorly differentiated adenocarcinomas were included. Two pathologists reviewed the slides independently without knowledge of the original diagnosis and subgrouped the tumors into the two entities. Agreement was reached in 31 of 45 cases (69 %) with kappa = 0.32. An extensive immunohistochemical panel was performed, and KRAS, NRAS, and BRAF mutational status was assessed. Of the 31 cases with diagnostic agreement, the expression of only MLH-1 along with corresponding expression of PMS-2 differed significantly (p = 0.04). A high rate of BRAF mutations was detected in both subgroups without significant differences. Expression of MLH-1 was superior in dividing the tumors into two separate entities with significant differences in CK20 (p = 0.005) expression and in the rate of BRAF mutations (p = 0.0035). In conclusion, medullary carcinomas of the colon are difficult to discriminate from poorly differentiated adenocarcinoma even with the help of immunohistochemical and molecular analyses. This raises the question whether these morphological subtypes should be maintained or whether an alternative classification of poorly differentiated colorectal adenocarcinomas based on MLH-1 status rather than morphology should be suggested.

Diagnosing colorectal medullary carcinoma: interobserver variability and clinicopathological implications

“…Knox et al [4] used 90% medullary morphology as the cutoff and required the presence of MMR deficiency, and found a 2.8% prevalence. Other studies that required either any amount or undefined amount of medullary morphology [13, 23, 24] or MMR deficiency [13, 16, 23, 25] have reported prevalences ranging from <0.1% [13] to 65.7% [24]. Following the AJCC and CAP recommendation requiring > = 50% of the tumor to lack overt gland formation to diagnose poor differentiation, we regarded 50% as a reasonable cutoff in this study.…”

Original paper Can the histological type of colorectal cancer determine the carcinogenesis pathway?

“…Rare medullary carcinomas in which cells create syncytial cell formations accompanied by diffuse lymphocytic infiltrates around the tumour need to be differentiated from the classic, poorly differentiated adenocarcinomas without MSI-H [21] and characterised by a poorer prognosis. Conversely, cases with mucus lakes in the tumour stroma are often misdiagnosed as classic mucinous adenocarcinoma, while in fact being mucinous carcinoma with MSI features characterised by a better prognosis, indicated by cases in the first group of this study.…”

Colonic Medullary Carcinoma: A Rare Case

“…Micro satellites are repeating sequences in the human genome, and they appear because of a disorder in the mismatch repair system (MMR) that corrects replication mistakes in the DNA (3). MSI is reported to be seen in 10-15% of sporadic colorectal carcinomas, while it is seen in 100% of Lynch syndrome-associated tumors (2,3). The tumors with mutations in MMR genes are proposed to be categorized as low grade without considering histological differentiation (1).…”

“…MC presents like conventional colonic carcinoma and can be confused with poorly differentiated colorectal carcinoma (PDC) due to undifferentiated complexion and high mitotic activity (2,3). MC of the colon is accepted as a subtype of colonic adenocarcinoma with a better clinical course and prognosis than other subtypes (1,4).There are few reports in the literature, but it has been shown that MC is frequently located at the proximal parts of the colon with low incidence of lymphnode metastases.…”

“…MC of the colon is accepted as a subtype of colonic adenocarcinoma with a better clinical course and prognosis than other subtypes (1,4).There are few reports in the literature, but it has been shown that MC is frequently located at the proximal parts of the colon with low incidence of lymphnode metastases. It also has a female tendency according to the literature (2,4,5). It has also been reported that it might have an expansive growth pattern and an association with Lynch syndrome and high microsatellite instability (MSI) (3,6).…”