Indolent Lymphoproliferative T-Cell Disorders Associated With Gastrointestional Disease: Diagnostic Challenges and Outcomes.

Lymphoproliferative diseases arise when the physiological mechanisms that control the proliferation of T and B lymphocytes are disrupted, resulting in an uncontrolled and autonomous increase in immune cells leading to lymphocytosis and lymphadenopathy, and often to the involvement of extranodal sites. The differential diagnosis of malignant T cell tumors involves other neoplasms and non-clonal T cell proliferations. Immunological markers are essential, as a first step, to distinguish between T-cell and non-T-cell disorders. It must be established based on the configuration of the genes of the TCR chain to rule out that the picture is not reactive to other underlying diseases. This clinical review and accompanying case reports highlight the diagnostic challenges associated with indolent lymphoproliferative T-cell disorders, which in many cases may represent the clinical manifestation of a single disease. Particularly we focus on gastrointestinal manifestations that could be expression either of lymphoproliferative disorder either of autoimmune disease either of both. The correct interpretation of the different clinical situations can help in the diagnostic and therapeutic process.

Clonal Hematopoiesis at the Crossroads of Inflammatory Bowel Diseases and Hematological Malignancies: A Biological Link?

Inflammatory bowel diseases (IBDs) are a group of chronic conditions of the gastrointestinal tract in which nationwide studies have revealed a higher risk of hematological malignancies (HMs). Clonal hematopoiesis (CH) is a premalignant condition defined by the presence of an acquired somatic mutation characterized by a variant allele frequency (VAF) of ≥2%, in a gene frequently associated with HMs. A growing body of evidence suggests a correlation between inflammation and CH; its occurrence in the context of IBD has been previously demonstrated. With the aim to assess CH possible co-occurrence in patients with an IBD associated with HMs, we performed a targeted next-generation sequencing analysis in a cohort of thirteen patients who were referred to our center with IBD associated with HMs. Eleven (85%) patients showed one or more mutations in CH-associated genes; DNMT3A was the most frequently mutated gene, followed by ASXL1 and JAK2. These results may suggest that the mechanisms at the basis of the inflammatory environment could potentially select for the growth of hematopoietic clones harboring specific mutations. In this context, CH emergence may be boosted by the proinflammatory IBD environment, thus acting as a biological link between IBD and the HM onset. If these data are confirmed, IBD patients screened and positive for CH should undergo a hematologic follow-up to assess the risk of developing HM. Future study will clarify the relationship between these conditions.