# Tissue‐Equivalents of Lymphoid Clonal Hematopoiesis of Indeterminate Potential (L‐CHIP) and Germline‐Derived Lymphoproliferations: Possible Caveats for Hematopathologists

## TL;DR

This paper explores how certain blood cell mutations may lead to early signs of lymphoma and highlights the importance of identifying these changes in tissue samples.

## Contribution

The paper introduces the concept of L-CHIP tissue-equivalents and germline-derived lymphoproliferations as early indicators of lymphoma.

## Key findings

- L-CHIP populations may expand in peripheral lymphoid tissues and contribute to follicular hyperplasias.
- One patient developed follicular lymphoma after 8 years with the same immunoglobulin rearrangement as an initial biopsy.
- Germline-derived mutations can lead to lymphoproliferations in healthy individuals.

## Abstract

Clonal hematopoiesis of indeterminate potential (CHIP) is a predisposing condition to lymphoma development. CHIP carrying mutations that are recurrently found in lymphomas are designated as L‐CHIP. We presume that bone marrow‐derived L‐CHIP populations are able to expand and manifest in peripheral lymphoid tissues, where they could hence be called L‐CHIP tissue‐equivalents. There, they may proliferate and foster unexplained follicular hyperplasias, and, thus, potentially represent an early precursor of lymphoma. Analogously, we hypothesize that certain germline‐derived mutations lead to lymphoproliferations (germline‐derived lymphoproliferations) in otherwise healthy individuals. We collected seven exceptional cases of symptomatic nodal and extranodal lymphoid hyperplasias, which were all morphologically suspicious and displayed somatic and/or germline‐derived mutations recurrently found in B‐cell lymphomas. One patient developed follicular lymphoma after 8 years carrying the same non‐productive immunoglobulin rearrangement detected in the initial biopsy. L‐CHIP tissue‐equivalents and germline‐derived lymphoproliferations potentially represent first steps in lymphomagenesis and knowledge about their existence might be of diagnostic utility in challenging cases of (atypical) lymphoproliferations. With histology, immunohistochemistry, and molecular testing, such lesions can be identified in situ.