{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,16]],"date-time":"2026-09-16T02:02:55Z","timestamp":1789524175767,"version":"build-2803163510"},"reference-count":14,"publisher":"Walter de Gruyter GmbH","issue":"1","license":[{"start":{"date-parts":[[2022,1,1]],"date-time":"2022-01-01T00:00:00Z","timestamp":1640995200000},"content-version":"unspecified","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-sa\/4.0"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2022,1,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Introduction<\/jats:title>\n                    <jats:p>Constitutional mismatch repair deficiency (CMMRD) is a rare autosomal recessive disease carrying an increased risk of cancers (paediatric tumours of central nervous system, haematolymphoid malignancies along with gastrointestinal (GI) cancer(s), which are usually seen in the second and third decades), 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.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Case Presentation<\/jats:title>\n                    <jats:p>A 5-year-old boy presented with respiratory complaints, bilateral cervical lymphadenopathy, multiple caf\u00e9-au-lait macules (CALMs) on the lower back and history of parental consanguinity with the death of three sisters due to brain tumour within 6 months of diagnosis. Computerised tomographic 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 MMR proteins was applied on the biopsy tissue that revealed loss of nuclear expression of MLH1 and PMS2 immunostaining in tumour cells with positive external controls. While on maintenance therapy for lymphoma, about a year later, the patient developed subacute intestinal obstruction due to a stenosing polypoidal circumferential tumour 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 tumour deposits were seen in the omentum, anterior abdominal wall and the left peritoneal wall.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Practical Implications<\/jats:title>\n                    <jats:p>Earlier (first decade) presentation of GI malignancy warrants that an earlier screening through radiological scans for any possible tumours and MMR protein expression analysis (loss in tumour plus normal non-tumour cells) are essential in patients having CALMs and family history of paediatric tumours.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.37029\/jcas.v8i1.443","type":"journal-article","created":{"date-parts":[[2022,1,9]],"date-time":"2022-01-09T04:43:40Z","timestamp":1641703420000},"page":"1-5","source":"Crossref","is-referenced-by-count":0,"title":["Presentation of Acute Lymphoblastic Lymphoma and Colorectal Carcinoma in the Context of Constitutional Mismatch Repair Deficiency Syndrome: A Case Report with Literature Review"],"prefix":"10.2478","volume":"8","author":[{"given":"Muhammad Irfan","family":"Basheer","sequence":"first","affiliation":[{"name":"Department of Pathology , Shaukat Khanum Memorial Cancer Hospital and Research Centre , Lahore , Pakistan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Iftikhar Ali","family":"Rana","sequence":"additional","affiliation":[{"name":"Department of Pathology , Shaukat Khanum Memorial Cancer Hospital and Research Centre , Lahore , Pakistan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Umer Nisar","family":"Sheikh","sequence":"additional","affiliation":[{"name":"Department of Pathology , Shaukat Khanum Memorial Cancer Hospital and Research Centre , Lahore , Pakistan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Muhammed Aasim","family":"Yusuf","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine , Shaukat Khanum Memorial Cancer Hospital and Research Centre , Lahore , Pakistan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Irfana Ishaq","family":"Sindhu","sequence":"additional","affiliation":[{"name":"Department of Paediatric Oncology , Shaukat Khanum Memorial Cancer Hospital and Research Centre , Lahore , Pakistan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Asif","family":"Loya","sequence":"additional","affiliation":[{"name":"Department of Pathology , Shaukat Khanum Memorial Cancer Hospital and Research Centre , Lahore , Pakistan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"374","published-online":{"date-parts":[[2022,1,8]]},"reference":[{"key":"2026091601394429593_j_jcas.v8i1.443_ref_001","doi-asserted-by":"crossref","unstructured":"Wimmer K, Kratz CP, Vasen HF, Caron O, Colas C, Entz-Werle N, et al. EU-consortium care for CMMRD (C4CMMRD). Diagnostic criteria for constitutional mismatch repair deficiency syndrome: Suggestions of the European consortium \u2018care for CMMRD\u2019 (C4CMMRD). J Med Genet 2014;51:355-65.","DOI":"10.1136\/jmedgenet-2014-102284"},{"key":"2026091601394429593_j_jcas.v8i1.443_ref_002","unstructured":"Ricciardone MD, Oz\u00e7elik T, Cevher B, Ozdag H, Tuncer M, G\u00fcrgey A, et al. Human MLH1 deficiency predispones to hematological malignancy and neurofibromatosis type 1. Cancer Res 1999;59:290-3."},{"key":"2026091601394429593_j_jcas.v8i1.443_ref_003","unstructured":"Wang Q, Lasset C, Desseigne F, Frappaz D, Bergeron C, Navarro C, et al. Neurofibromatosis and early onset of cancers in hMLH1-deficient children. Cancer Res 1999;59:294-7."},{"key":"2026091601394429593_j_jcas.v8i1.443_ref_004","doi-asserted-by":"crossref","unstructured":"Wang Q, Montmain G, Ruano E, Upadhyaya M, Dudley S, Liskay RM, et al. 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