Intravascular Large B-Cell Lymphoma: A Review with a Focus on the Prognostic Value of Skin Involvement

Abstract

Intravascular large B-cell lymphoma (IVLBCL) is an aggressive Non-Hodgkin lymphoma (NHL) characterised by the presence of neoplastic lymphoid cells within small- and medium-sized blood vessels. According to the clinical presentation, the current WHO classification distinguishes the 'classic' (formerly 'Western') from a hemophagocytic syndrome-associated (formerly 'Asian') variant. A third 'cutaneous' variant has been proposed, characterised by a good prognosis and unique clinical features. While laboratory findings can hint at diagnosis, symptoms are rather nonspecific, and deep skin biopsy supported by further measures such as bone marrow aspiration and positron emission tomography-computed tomography scanning is needed to make a definite diagnosis. Treatment is comprised of anthracycline-based chemotherapy supplemented with rituximab and central nervous system prophylaxis. While there are various prognostic models for NHL, only one is specific to IVLBCL, which does not sufficiently represent some patient groups, especially regarding the lack of differentiation within the patient collective with skin involvement. This underlines the necessity for the establishment of further prognostic models in particular for IVLBCL patients with cutaneous manifestations.

Keywords: IVLBCL; R-CHOP; dermato-oncology; intravascular large B-cell lymphoma; prognostic model; skin cancer.

Figure 1

Macroscopic findings in IVLBCL: (A,B) cutaneous lesions before (A) and after (B) two cycles of R-CHOP; (C–F) PET-CT scans of cutaneous and osseous lesions of the legs before (C) and after (D) six cycles of R-CHOP. Adrenal gland lesion before (E) and after (F) six cycles of R-CHOP. PET-CT scanning showed increased uptake of fluorodeoxyglucose (¹⁸F-FDG) in the subcutaneous tissue of both legs, the right tibia, various osseous structures of the right foot (maximal standardised uptake value (SUVmax) = 3.0–21.5), and a nodular lesion in the left adrenal gland (SUVmax = 31).

Figure 2

Microscopic findings in IVLBCL. Haematoxylin and eosin stain of deep skin biopsy at 4-fold (A), 10-fold (B), and 20-fold magnification (C); immunohistological skin biopsy stains for CD20 (D), CD3 (E), and CD79a (F). A skin biopsy taken from the left thigh of a patient with IVLBCL showed normal epidermis with compact cornification. The entire dermis and subcutis showed intravasally located large atypical plasmacytoid lymphocytes. Perivascularly, small chromatin-dense lymphocytes were found. Immunohistochemistry revealed positive staining of intravascular lymphocytes for CD20, CD45, CD79a, Bcl-2, and partially positive staining for CD10 and Bcl-6. Few diffusely dispersed small CD3⁺ lymphocytes were also found.