Scientific Papers

Colonic medullary carcinoma: an exceedingly rare type of colorectal malignancy: a case report and review of the literature | Journal of Medical Case Reports

Medullary carcinoma (MC), a relatively recently identified, extremely rare type of adenocarcinoma (with incidence reported to range from approximately 0.3% to 3%) [2, 6, 7] is characterized by a poorly differentiated carcinoma with a syncytial growth pattern, and with areas that resemble endocrine tumors but lack neuroendocrine marker expression and show a dense lymphoid host response and extensive lymphovascular invasion. So-called dirty necrosis, suggestive of microsatellite instability is also seen, with all tumors showing mismatch repair protein abnormalities. Therefore, these are best classified as a subtype of microsatellite instable carcinoma and may be sporadic or syndromic (Muir–Torre syndrome). Recently, these tumors have been shown to overexpress immunoregulatory genes [8] that, along with dense lymphoid host response, may possibly account for better overall survival when compared with ‘usual’ poorly differentiated adenocarcinoma. Colarossi et al. [9] highlighted immunohistochemical loss of expression of ARID1A along with a higher incidence of BRAF (V600E) mutation. Like other MSI tumors, the mutational burden of these tumors is low. This coupled with overexpression of immunoregulatory genes seems to confer a better prognosis in medullary carcinoma compared with usual-type poorly differentiated adenocarcinoma and may provide unique therapeutic targets. Therefore, correct identification and workup is essential. Especially given that the diagnosis of MC is challenging and can be confused with the diagnosis of other histological subtypes of colon MC, which necessitate a comprehensive pathological examination, in addition to immunohistochemical staining, to confirm the diagnosis of medullary adenocarcinoma of the colon [8, 10].

Table 1 summarizes the key findings in recently published cases of medullary colon cancer based on a review of recent literature on the subject. Around ten cases were found in which the MMR status, the immunohistochemical analysis of the disease, the staging, and the location of the tumor were discussed.

Table 1 The reported cases in the literature

Our patient was a young gentleman diagnosed with cecal adenocarcinoma and regional lymph node involvement. He had an aggressive disease that led to an obstruction that necessitated an urgent surgical resection. Unlike our patient, most cases of colon MC are in older patients, typically over 60 years old (as presented in Table 1), and predominantly in females [3]. Moreover, almost all patients who were diagnosed with colon MC presented with abdominal pain or bleeding per rectum (Table 1) rather than an obstruction.

The histopathological study of the mass showed invasive MC with features resembling neuroendocrine tumors and with only focal areas with dense lymphoid infiltrate. Like most reported cases, there was prominent lymphovascular invasion and a lack of neuroendocrine biomarkers, along with loss of MMR by immunostaining, indicating microsatellite instability. Unlike most reported cases, the tumor cells expressed CDX2 and instead of MLH1 loss, highlighted retained MLH1 and loss of both MSH2 and MSH6. BRAF was not mutated (Table 1). Hence, this case showed that MC can present with different morphological and immunohistochemical patterns and that there are variations in the ‘usual’ molecular signature. Therefore, this expands the diagnostic spectrum of MC and highlights the diagnostic challenges in the absence of an established clinical, molecular, and histopathological pattern for this type of cancer. Reporting rare cases such as colon MC helps clinicians and pathologists with the diagnosis and management of such rare conditions, and can aid in identifying the characteristic of the subtypes of colon cancer and improve our understanding of such rare entities.

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