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Review
. 2025 Apr;117(2):101-110.
doi: 10.32074/1591-951X-1207.

Head and neck hematolymphoid proliferations: what is new?

Silvia Varricchio  1 , Rosaria Cappiello  1 , Francesca Magnoli  2 , Daniela Russo  1 , Giovanna Motta  3 , Clara Bertuzzi  3 , Elena Sabattini  3 , Gennaro Ilardi  1 , Mariarosaria Cervasio  1 , Claudia Giordano  4 , Alessandro Severino  4 , Marco Picardi  4 , Massimo Mascolo  1
Affiliations
Review

Head and neck hematolymphoid proliferations: what is new?

Silvia Varricchio et al. Pathologica. 2025 Apr.

Abstract

In 2024, the World Health Organization published its 5th edition of tumor classification, which comprises several updates and modifications in the "blue book" focused on head and neck tumors. These changes feature a systematized and expanded discussion on haematolymphoid proliferations using a multi-parameter approach that comprises clinical features, morphology, immunophenotype, and genetic data, with the latter becoming an essential characteristic for classification. Moreover, for the first time, the World Health Organization has included non-neoplastic diseases, such as reactive lymphoid proliferations, alongside several recognized independent disorders, including Epstein-Barr Virus positive mucocutaneous ulcers and IgG4-related diseases. Also, various neoplastic diseases, such as paediatric-type follicular lymphoma and large B-cell lymphoma with IRF4 rearrangement, are recognized as independent entities. Finally, the focus has expanded to include different types of histiocytic neoplasms. This review examines and illustrates the main changes and updates on hematolymphoid proliferation and neoplasia in the Head and Neck chapter of the 5th Edition of the Head and Neck WHO classification.

Keywords: World Health Organization; head and neck; hematolymphoid proliferations and non-neoplastic conditions.

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Conflict of interest statement

The authors report no conflict of interest.

Figures

Figure 1.
Figure 1.
EBV mucocutaneous ulcer: (A) Hematoxylin and eosin staining, 40x magnification. (B) Hematoxylin and eosin staining, 200x magnification. (C) Hematoxylin and eosin staining, 600x magnification. (D) Immunostaining for CD20, 200x magnification. (E) Immunostaining for CD30, 200x magnification. (F) Immunostaining for PAX5, 200x magnification. (G) Immunostaining for EBV, 200x magnification. (H) Immunostaining for CD3, 200x magnification.
Figure 2.
Figure 2.
IgG4-related disease. (A) Hematoxylin and eosin staining, 200x magnification. (B) Trichrome Masson staining, 20x magnification. (C) Immunostaining for IgG, 200x magnification. (D) Immunostaining for IgG4, 200x magnification. (E) Immunostaining for kappa, 200x magnification. (F) Immunostaining for lambda, 200x magnification.
Figure 3.
Figure 3.
Pediatric follicular lymphoma (PFL): (A) Hematoxylin and eosin staining, 20x magnification. (B) Immunostaining for CD20, 100x magnification. (C) Immunostaining for BCL2, 100x magnification. (D) Immunostaining for BCL6, 100x magnification. (E) Immunostaining for CD10, 100x magnification. (F) Immunostaining for CD3. (G) Immunostaining for CD23, 100x magnification. (H) Immunostaining for MIB/Ki67, 100x magnification.
Figure 4.
Figure 4.
Rearranged IRF BCL: (A) Giemsa staining, 100x magnification. (B) Immunostaining for BCL2, 200x magnification. (C) Immunostaining for BCL6, 200x magnification. (D) Immunostaining for CD10, 100x magnification. (E) Immunostaining for c-MYC, 100x magnification. (F) Immunostaining for Ki-67, 100x magnification (G) Immunostaining for MUM1, 100x magnification.
Figure 5.
Figure 5.
Nasal type T-cell lymphoma TCL: (A) Hematoxylin and eosin staining, 20x magnification. (B) Immunostaining for CD3, 100x magnification. (C) Immunostaining for CD8, 100x magnification. (D) Immunostaining for CD5, 100x magnification. (E) Immunostaining for CD56, 200x magnification. (F) Immunostaining for MIB/Ki67, 100x magnification. (G) Immunostaining for TIA, 200x magnification. (H) Immunostaining for EBV, 100x magnification.
See this image and copyright information in PMC

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