Available online 1 June 2023

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Benign lymphadenopathy is common in the pediatric population and may be clinically striking. As in adults, lymph node evaluation in pediatric patients requires careful morphologic and immunohistochemical assessment and clinical contextualization of the findings. It is important for the pathologist to be familiar with benign and reactive conditions that may mimic malignancy. This review presents non-neoplastic or indolent processes or patterns of lymphoid hyperplasia that may be confused with or raise the differential of lymphoma, with a focus on those more commonly encountered in the pediatric/adolescent population.

Section snippetsFollicular hyperplasia

Follicular hyperplasia is a commonly encountered pattern of lymphoid hyperplasia characterized by retained nodal architecture and numerous secondary follicles (Figure 1). Reassuring features include adequate separation of follicles (not confluent), intact mantle zones, germinal center polarization, and a mixture of centrocytes and centroblasts within the germinal centers2. Germinal center polarization results in a light zone comprised mostly of centrocytes and a dark zone with increased

Infectious mononucleosis

Acute EBV infection (infectious mononucleosis) causes characteristic changes in lymph nodes and the lymphoid tissue of Waldeyer's ring17. There is typically follicular hyperplasia with paracortical expansion caused by variable numbers of small and medium-sized lymphocytes, immunoblasts, occasional Reed-Sternberg-like cells, and plasma cells (Figure 3). The immunoblasts may be scattered, form large aggregates, or comprise a diffuse infiltrate. Immunoblasts are moderate to large in size with

Progressive transformation of germinal centers (PTGC)

The term progressive transformation of germinal centers refers to macronodules (up to 2x the size of a normal secondary follicle) comprised of IgD-positive mantle zone cells infiltrating and replacing the germinal centers of secondary follicles. It is common to identify a few (1-2 per section) nodules of PTGC within a lymph node showing follicular hyperplasia (Figure 4). In our practices, we restrict the use of the term “progressive transformation of germinal centers” in the diagnostic line to

Indolent lymphoblasts in lymph node

Indolent T-lymphoblastic proliferations (iT-LBP) are extra-thymic non-clonal, non-neoplastic expansions of T-lymphoblasts, distinguished from ectopic thymus by the lack of epithelial elements. iT-LBP presents as sheets or clusters of TdT and CD3 positive cells without morphologic atypia, found primarily in interfollicular regions with preservation of the general follicular lymphoid architecture (Figure 5)27. The cells are small to medium-sized with blastic chromatin and indistinct nucleoli. The

Histiocytic necrotizing lymphadenitis (Kikuchi-Fujimoto lymphadenitis)

Histiocytic necrotizing lymphadenitis is a generally self-limited process of unknown etiology that can have a striking clinical presentation. It most commonly presents with unilateral cervical lymphadenopathy and fever in a young adult age group. Within the pediatric population, most cases are in adolescents with only rare patients younger than 10 years of age reported31. Three histologic subtypes of histiocytic necrotizing lymphadenitis have been described, representing different stages of the

Summary

The diagnostic approach to a lymph node biopsy in pediatric patients requires careful morphologic and immunohistochemical assessment and clinical contextualization of the findings. Several benign and reactive conditions may mimic malignancy and it is important for the pathologist to be familiar with these conditions. Ancillary testing such as flow cytometry, cytogenetic/FISH, and or gene rearrangement studies may aid in the exclusion of malignant entities in some cases.

Declaration of Competing Interest

The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

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