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Review
. 2024 Sep;103(9):3369-3383.
doi: 10.1007/s00277-024-05854-1. Epub 2024 Jul 25.

Extramedullary and extranodal manifestations in chronic lymphocytic leukemia - an update

Tadeusz Robak  1   2 , Anna Puła  3   4 , Marcin Braun  5 , Ewa Robak  6
Affiliations
Review

Extramedullary and extranodal manifestations in chronic lymphocytic leukemia - an update

Tadeusz Robak et al. Ann Hematol. 2024 Sep.

Abstract

Chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) is a common leukemia characterized by clonal expansion of mature CD5+/CD23 + B cells in the blood, bone marrow (BM) and lymphoid tissues. CLL can undergo extramedullary and extranodal infiltration, with one study noting an incidence of only 0.3 per 100,000 people, and in 17.6% of CLL patients in another report. The most common extranodal sites of leukemic involvement are the skin and central nervous system; however, other organs, including liver, lungs, kidney, gastrointestinal tract, bone, prostate and heart, are occasionally involved. The prognostic significance of extra-medullary CLL is still under debate, but the prognosis in such patients seems to be better in the era of novel targeted drugs. Following a diagnosis of extranodal CLL, survival appears to depend on the site of infiltration. This review presents an overview of CLL in patients with extramedullary and extranodal leukemic lesions, focusing on its epidemiology, pathogenesis, prognosis, clinical characteristics and treatment results.

Keywords: Chronic lymphocytic leukemia; Extramedullary; Extranodal; Infiltrations; Small lymphocytic lymphoma.

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Conflict of interest statement

The authors declare no competing interests.

The authors declare that they have no conflicts of interest.

Figures

Fig. 1
Fig. 1
Skin changes in a 75 year old patient with CLL; they are present in the form of symmetrical nodular infiltrates and numerous, scattered red-blue papules and nodules with a hemorrhagic reaction on the torso (A and B). Biopsy of the skin torso infiltration in hematoxylin and eosin staining (C) showed strong positivity in immunohistochemistry (magnification 100x) for CD23 (D), negativity for CD3 (E), and strong positivity for CD5 (F) and CD20 (G)
Fig. 2
Fig. 2
A PET/CT (A) and a CT scan of a CLL/SLL heart infiltration. Infiltration of CLL/SLL in intracardiac biopsy (digitalized, Philips IntelliSite scanner) of the masses in right ventricular epicardium with cytomorphology of small B-cells (C) immunophenotype showed negativity for CD3 (D) and strong positivity for CD23 (E) and CD5 (F)
Fig. 3
Fig. 3
Richter transformation in the stomach visible in a CT (A) and a PET/CT scan (B). A biopsy (magnification 100x) showing infiltration by diffuse large B-cell lymphoma in hematoxylin and eosin staining (C), weak positive in immunohistochemistry for CD5 (D), while negative for BCL6 (E), CD10 (F) and CD23 (G), and showing high proliferation index Ki-67 of about 85% (H)
Fig. 4
Fig. 4
Infiltration of CLL/SLL in kidney biopsy (magnification 100x) with cytomorphology of small B-cells (A). Immunohistochemistry showed strong positivity for CD20 (B), CD5 (C), and CD23 (D); and negativity for CD3 (E). The proliferation index Ki-67 was low - of about 10-15%
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