Medullary Colorectal Carcinoma Revisited: A Clinical and Pathological Study of 102 Cases

Knox, Robert D.; Luey, Nathan; Sioson, Loretta; Kedziora, Andrew; Clarkson, Adele; Watson, Nicole; Toon, Christopher W.; Cussigh, Carmen; Pincott, Stuart; Pillinger, Stephen H.; Salama, Yasser; Evans, Jeff; Percy, J.; Schnitzler, Margaret; Engel, Alexander; Gill, Anthony J.

doi:10.1245/s10434-014-4355-5

Cited by 53 publications

(66 citation statements)

References 20 publications

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“…For example, lymphocytic infiltration of the colon cancer is associated with an improvement in the OS and RFS in many studies irrespective of the presence of DNA mismatch repair defects [32–34]. Our data showed higher 5-year RFS in the lymphocytic infiltration group (72% vs. 43%).…”

Section: Discussionsupporting

confidence: 48%

Factors associated with short recurrence-free survival in completely resected colon cancer

Alnimer

Ghamrawi

Aburahma

et al. 2017

Journal of Community Hospital Internal Medicine Perspectives

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Background: Several factors could affect disease recurrence in surgically resected colon cancer. While the role of certain factors such as cancer stage and grade is well established, the role of other factors (e.g., histological subtypes) is yet to be determined. Objective:Therefore, we conducted a study to evaluate the impact of several factors in recurrence-free survival (RFS) in patients who were disease free following surgical resection of the colon cancer. Design/Methods: Data were collected for patients with Stage I–III colon cancer who underwent complete surgical resection of the tumor between January 2010 and December 2015 in our institution. A total of 90 subjects met the inclusion criteria and were included in the study. The following factors were collected at the time of surgical resection of the colonic tumor: patient’s age, gender, colon cancer stage, grade and histological subtype, body mass index, hemoglobin A1c, and smoking history. Results: A total of 28 patients (31%) developed recurrence and had a mean follow-up time of 19.8 months (range: 2–54.4 months). Median RFS was 54.4 months with a 5-year RFS of 49%. Advanced colonic cancer stage and mucinous histological subtype were associated with shorter RFS with an HR of 2.37, 95% CI = 1.38–4.06, and 95% CI = 1.02–5.90, respectively. Current smokers or those who quit less than 15 years earlier tended to have worse RFS with an HR of 2.47, 95% CI = 0.98–6.27. Conclusion: Advanced colon cancer stage and mucinous histological subtype are independent risk factors for cancer recurrence and shorter RFS in completely resected colonic tumor.

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Section: Discussionsupporting

confidence: 48%

Factors associated with short recurrence-free survival in completely resected colon cancer

Alnimer

Ghamrawi

Aburahma

et al. 2017

Journal of Community Hospital Internal Medicine Perspectives

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“…Medullary carcinoma tipically present a lesser rate of nodal metastasis and a minor tendency toward extramural and invasion, when compared to poorly differentiated adenocarcinoma, 4,7 while the linfovascular invasion con be relatively high (62.9 vs 36.5%). 7 In comparison with undifferentiated and poorly-differentiated adenocarcinomas of the large intestine, MC has a better prognosis 3 and it improves further in case of MSI - H. 8 …”

Section: Discussionmentioning

confidence: 92%

Microsatellite Instability in Medullary Carcinoma of the Colon

et al. 2016

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Medullary carcinoma (MC) of the large intestine is a relatively new histological type of adenocarcinoma characterized by poor glandular differentiation and an intraepithelial lymphocytic infiltrate. MC can be associated to a defective mechanism for DNA mismatch repair, caused by the so-called microsatellite instability (MSI). We present the case of a 44 years old Caucasian woman, who referred to the Emergency Room with symptoms mimicking an acute appendicitis. Computed tomography and colonoscopy demonstrated an ulcerated and stenotic lesion of the caecum without signs of metastasis and peritoneal carcinosis. Patient underwent a laparoscopic right colectomy. The final pathologic findings provided the diagnosis of medullary carcinoma with MSI. Patient then underwent adjuvant chemotherapy according to the FOLFOX-4 protocol (association of 5-Fluorouracil, Leucovorin, and Oxaliplatin) for twelve cycles. At two-years follow-up, patient is disease free. MC in association with MSI is a non-frequent tumor of the colon characterized by a better prognosis compared to other types of poorly differentiated adenocarcinoma. In the observed case, 24 months after the surgical operation, the patient is in good health and there is no evidence of metastasis or relapse.

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“…At least 90% of the tumor had to contain a solid and syncytial growth pattern (sheets, nests, or trabeculae) consisting of mediumsized cells with vesicular nuclei and prominent nucleoli with a pushing or expansile pattern of growth. 19 Poorly differentiated (high grade) carcinomas were defined as having 0-49% gland formation and well-differentiated carcinomas (low grade) were defined as having 50-100% gland formation according to the WHO. 20 …”

Section: Patients and Samplesmentioning

confidence: 99%

Medullary carcinoma of the colon: a distinct morphology reveals a distinctive immunoregulatory microenvironment

Friedman

Brodsky

et al. 2016

Modern Pathology

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Medullary carcinoma of the colon is a unique histologic subtype of microsatellite unstable colorectal carcinoma but little is known regarding its tumor-immunoregulatory microenvironment. The aims of this study were to characterize the immune environment of medullary carcinoma and compare it with other microsatellite unstable and microsatellite stable colorectal carcinomas. An initial gene expression microarray analysis of six cases of medullary carcinoma was used to detect potentially differentially expressed genes. We extended this analysis utilizing genomic data from the Cancer Genome Atlas to compare eight cases of medullary carcinoma with other microsatellite unstable and stable carcinomas. Finally, we evaluated expression of key immune pathway proteins and lymphocyte subsets via immunohistochemistry of a large group of medullary carcinomas (n = 105) and compared these findings with three other groups: poorly differentiated, microsatellite unstable well-differentiated and microsatellite stable well-differentiated carcinomas. Microarray and the Cancer Genome Atlas data analysis identified significant upregulation of several immunoregulatory genes induced by IFNγ including IDO-1, WARS (tRNA(trp)), GBP1, GBP4, GBP5, PDCD1 (PD-1), and CD274 (PD-L1) in medullary carcinoma compared with other microsatellite unstable and microsatellite stable tumors. By immunohistochemistry, IDO-1 was expressed in 64% of medullary carcinomas compared with 19% (9/47) of poorly differentiated carcinomas, 14% (3/22) of microsatellite unstable, and 7% (2/30) of the microsatellite stable well-differentiated carcinomas (Po 0.0001). tRNA(trp) was overexpressed in 81% (84/104) of medullary carcinomas, 19% (9/47) of poorly differentiated, 32% (7/22) of microsatellite unstable, and 3% (1/30) of microsatellite stable well-differentiated carcinomas (Po 0.0001). Medullary carcinoma had higher mean CD8+ and PD-L1+ tumor-infiltrating lymphocytes compared with all other groups (P o0.0001). This study demonstrates overexpression of several immunoregulatory genes in microsatellite unstable colorectal carcinomas and that expression of these genes and proteins is more prevalent in the medullary carcinoma subtype, which may be of use both diagnostically and therapeutically.

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Medullary Colorectal Carcinoma Revisited: A Clinical and Pathological Study of 102 Cases

Cited by 53 publications

References 20 publications

Factors associated with short recurrence-free survival in completely resected colon cancer

Factors associated with short recurrence-free survival in completely resected colon cancer

Microsatellite Instability in Medullary Carcinoma of the Colon

Medullary carcinoma of the colon: a distinct morphology reveals a distinctive immunoregulatory microenvironment

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