Aberrant Partial Chromosomal Instability With Chemotherapeutically Resistant Metachronous Colorectal Cancer Following a Synchronous Primary Colorectal Cancer: A Case Report.

Jerry Lorren Dominic,Abilash Muralidharan,Pragatheeshwar Thirunavukarasu,Asma Ahmed,Shah Huzaifa Feroz

doi:10.7759/cureus.11308

Abstract

The diagnosis of synchronous colorectal cancer (CRC) is crucial as the management, including the extent of surgical resection, depends on it. There have been numerous studies on the clinicopathological features of synchronous CRC; however, only a few studies have discussed synchronous cancer treatment. The guidelines to best manage the synchronous and metachronous CRC are limited, especially the most appropriate surgical treatment and chemotherapy based on mutational analysis of mismatch repair genes and the carcinoma sequence model. We present a rare case of a metachronous CRC with intact nuclear expression of microsatellite instability markers following a synchronous CRC, and it failed to show any significant response to surgical resection and chemoradiotherapy.A 53-year-old female presented in June 2016 with bleeding per rectum for one month, weight loss, and a recent history of altered bowel habits. The per rectal examination revealed a circumferential growth. Colonoscopy and biopsy yielded multiple polyps throughout the colon and invasive adenocarcinoma in the upper and lower one-third of the rectum. The above features were highly suggestive of synchronous CRC. Serologic studies revealed elevated carcinoembryonic antigen (CEA). Excisional biopsy of mesenteric and retroperitoneal lymph nodes during proctocolectomy and end ileostomy was negative for metastasis, including the other metastatic workup preoperatively-eight months post-resection and adjuvant chemotherapy patient developed metachronous CRC. Mutational analysis showed positivity only for adenomatous polyposis coli (APC) while negative for KRAS, NRAS, and BRAF. Immunohistochemistry (IHC) markers for mismatch repair (MMR) proteins showed intact protein expression. The patient was given multiple chemotherapy cycles throughout her course, including oral capecitabine, XELOX (capecitabine + oxaliplatin), cetuximab-capecitabine, cetuximab-irinotecan, and FOLFIRI (5‐fluorouracil [5‐FU] + irinotecan + folinic acid)-bevacizumab, as is the standard chemotherapy regimen for these tumors.The diagnosis of metachronous CRC with intensive follow up is crucial. IHC markers for MMR proteins showed intact protein expression ruling out the possibility of microsatellite instability and Lynch Syndrome. The only presence of APC mutation indicates a partial chromosomal instability. During the course, the patient had either stable size of the masses or developed new metastatic growth despite intensive chemotherapeutic regimes. Unfortunately, there are no precise guidelines based on aberrant mutational analysis regarding synchronous and metachronous CRCs management.

Highlights

Synchronous colorectal carcinoma is a rare type of colorectal malignancy, defined by the presence of more than one primary colorectal carcinoma at the time of initial presentation [1]
The guidelines to best manage the synchronous colorectal cancer (CRC) are limited, primarily the most appropriate surgical treatment and chemotherapy based on mutational analysis results of mismatch repair genes and the adenoma-carcinoma sequence model
Classifying patients at high risk for developing metachronous colorectal cancer is crucial as it may contribute to more accurate patient information, customized follow-up plans, and adequate management

Summary

Introduction

Synchronous colorectal carcinoma (synchronous CRC) is a rare type of colorectal malignancy, defined by the presence of more than one primary colorectal carcinoma at the time of initial presentation [1]. In light of the familial polyposis nature and early colorectal cancer, the patient received adjuvant chemotherapy from July 2016 to September 2016 with oral capecitabine (two cycles of 21 days). After completion of the five cycles of chemotherapy, a repeat PET-CT was obtained in June 2017 to evaluate his response to treatment It yielded a resolution of hepatic metastasis in the left lobe; the peritoneal and mesenteric deposits remained stable and non-FDG avid. January 2020: Stable size (Figure 5c) and activity September 2020: Multiple metastatic lesions in various segments of the liver Considering she was non-responsive to chemotherapy, the surgical team, as per the National Comprehensive Cancer Network (NCCN) guidelines version 4.2020, planned to perform a needle core biopsy from the metastatic lesion in the left lobe of the liver for immunohistochemistry testing, to detect microsatellite instability or mismatch repair, to guide chemotherapeutic regime.

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Disclosures