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Multiple Colorectal Neoplasms in X-Linked Agammaglobulinemia

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X-linked agammaglobulinemia (XLA) is a primary immunodeficiency disorder caused by germline mutation of the Bruton tyrosine kinase (BTK) gene. It is characterized by disturbed B-cell development, decreased immunoglobulin levels, and increased patient susceptibility to infection. An increased risk of cancer has been suggested, but most reports were described before the identification of BTK gene mutation as the cause of XLA. Here we describe 2 patients with genetically ascertained XLA and multiple colorectal neoplasms, supporting an increased risk of colorectal cancer in XLA and highlighting the potential importance of colorectal surveillance in these patients.

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Case 1

A 45-year-old man with XLA underwent colonoscopy for an assumed increased CRC risk associated with XLA. He was treated with intravenous immunoglobulins and had experienced recurrent lower respiratory tract infections. At 37 years of age he experienced persistent malabsorption and weight loss caused by villous atrophy of the small intestine, for which he received overnight tube feeding.

His family history revealed a brother dying at age 32 from urosepsis. His mother died at 60 years of age as a

Literature Review of Gastrointestinal Cancer in X-Linked Agammaglobulinemia

Literature reports suggest that XLA patients are at increased risk of gastrointestinal cancer. A review of literature revealed 8 colorectal carcinomas,5, 7, 8, 10, 14 four gastric cancers,7, 11, 12, 13 and 1 carcinoid tumor16 in XLA patients (Table 1). The reported age of cancer ranged between 10–36 years.

Two studies reported a high relative risk for gastrointestinal malignancies in XLA.7, 8 Van der Meer et al8 found 3 patients with CRC in a cohort of 52 individuals with XLA and estimated a

Discussion

An increased risk for colorectal,5, 7, 8 gastric,7, 11, 12, 13 and lymphoreticular cancer5 in XLA has been suggested. However, literature reports about cancer incidence in XLA are conflicting, raising uncertainty about the cancer risk and localization. For example, malignancies were not found in 2 XLA patient cohorts,6, 17 although in one study the mean age was 14 years.6 Importantly, BTK mutation analysis is the only definitive test to establish the diagnosis of XLA, and most reports of

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