Presentation of Acute Lymphoblastic Lymphoma and Colorectal Carcinoma in the Context of Constitutional Mismatch Repair Deficiency Syndrome (CMMRD): a Case Report with Literature Review

  • Muhammad Irfan Basheer Department of Pathology, Shaukat Khanum Memorial Cancer Hospital and Research Centre, Lahore, Pakistan
  • Iftikhar Ali Rana Department of Pathology, Shaukat Khanum Memorial Cancer Hospital and Research Centre, Lahore, Pakistan
  • Umer Nisar Department of Pathology, Shaukat Khanum Memorial Cancer Hospital and Research Centre, Lahore, Pakistan
  • Muhammed Aasim Yusuf Department of Internal Medicine, Shaukat Khanum Memorial Cancer Hospital and Research Centre, Lahore
  • Irfana Ishaq Sindhu Department of Pediatric Oncology, Shaukat Khanum Cancer Hospital and Research Centre, Lahore, Pakistan
  • Asif Loya Department of Pathology, Shaukat Khanum Memorial Cancer Hospital and Research Centre, Lahore, Pakistan
Keywords: Café au lait macules, constitutional mismatch repair deficiency, gastrointestinal tract, mismatch repair proteins

Abstract

Introduction: Constitutional mismatch repair deficiency (CMMRD) is a rare autosomal recessive disease-carrying an increased risk of cancers (pediatric tumors of central nervous system, haemato-lymphoid malignancies along with gastrointestinal (GI) cancer(s), which are usually seen in the second and third decade) leading to syndromic presentation. Causal mutations are detected in DNA mismatch repair (MMR) genes, including MLH1, PMS2, MSH2, and MSH6 that are also known for their established role in Lynch syndrome. We describe a case of CMMRD with an earlier (first decade of life) presentation of mediastinal acute lymphoblastic lymphoma and colorectal malignancy. Case Presentation: A five-year-old boy presented with respiratory complaints, bilateral cervical lymphadenopathy, multiple café au lait macules (CALMs) on the lower back, history of parental consanguinity with the death of three sisters due to brain tumor within 6 months of diagnosis. Computerized tomographic (CT) scan chest revealed a huge mediastinal mass. The patient underwent a trucut-biopsy of the mass. The results were significant for a pre T-cell acute lymphoblastic lymphoma. Suspicion of CMMRD was raised based on a combination of factors described above. A panel of mismatch repair (MMR) proteins was applied on the biopsy tissue that revealed loss of nuclear expression of MLH1 and PMS2 immunostaining in tumor cells with positive external controls. While on maintenance therapy for lymphoma, about a year later, the patient developed sub-acute intestinal obstruction due to a stenosing polypoidal circumferential tumor in the mid-sigmoid colon found on flexible sigmoidoscopy that was followed by endoscopic biopsies and insertion of a fully-covered self-expanding metallic adult biliary stent with a diameter of 10 mm and length of 6 cm leading to immediate relief of obstruction. Biopsies revealed adenocarcinoma with neuroendocrine differentiation. Metastatic tumor deposits were seen in the omentum, anterior abdominal wall, and the left peritoneal wall. Practical Implications: Earlier (first decade) presentation of gastrointestinal malignancy warrants that an earlier screening through radiological scans for any possible tumors and MMR protein expression analysis (loss in tumor plus normal non-tumor cells) are essential in patients having CALMs and family history of pediatric tumors.

Published
2021-12-20
How to Cite
1.
Basheer MI, Rana IA, Sheikh UN, Yusuf MA, Sindhu II, Loya A. Presentation of Acute Lymphoblastic Lymphoma and Colorectal Carcinoma in the Context of Constitutional Mismatch Repair Deficiency Syndrome (CMMRD): a Case Report with Literature Review . J Cancer Allied Spec [Internet]. 2021Dec.20 [cited 2022May24];8(1). Available from: https://journals.sfu.ca/jcas/index.php/jcas/article/view/443