Intravascular large b-cell lymphoma C83.8

Extremely rare B-cell lymphoma; usually systemic with proliferation of multicentric, intravascular tumor cell infiltrates leading to occlusion of small and medium-sized vessels of different organs. Systemic intravascular lymphomas affect the integument in about 40%. Isolated integumentary involvement of intravascular lymphomas is very rare. Characteristic for the skin involvement of all intravascular lymphomas is the histological pattern with strictly intravascular tumor cell volumes that do not infiltrate the surrounding tissue.

There is a rare, purely cutaneous form of progression, which is listed as a separate entity in the current WHO classification under the name " intravascular large B-cell lymphoma".

The clinical picture is limited to the skin, variegated and clinically not very suggestive. Mostly formation of solitary, asymptomatic (occasionally also painful), blurred, reticular or homogeneous, extensive erythema. However, disseminated, indurated, small or large plaques have also been described, as have subcutaneous, sometimes panniculitic nodules. Rarer are localized papular foci interspersed with petechiae or telangiectasias. The skin manifestations of the purely cutaneous or the systemic form of intravascular lymphoma do not differ essentially.

General: Fever, B-symptomatics, variable systemic involvement (especially lymph nodes, CNS with neurological deficits) may occur.

Intravascular pleomorphic B-cell lymphocytes with round or oval chromatin dense nuclei. Blood vessels in the dermis, sometimes also in the subcutis (see case report), are dilated and increasingly filled with highly pleomorphic, hyperchromatic cells. The cells may be embedded in fibrinous thrombi. Immunohistologically, these cells characterize as B lymphocytes(CD19, CD20, pos.; high proliferation rate). Evidence of a clonal lymphocyte population. They do not express antigens characteristic of endothelial cells. Note: Loss of lymphocyte function antigens prevents extravasation of lymphoma cells!

Clinical differential diagnoses:

• Cutaneous B-cell lymphomas of various entities.
• Angioendotheliomatosis, reactive (benign)
• Intravascular cutaneous T-cell lymphoma.

The very rare purely cutaneous variant of intravascular lymphoma ("lymphoma, cutaneous B-cell lymphoma, intravascular, large cell") is listed as an entity in the current WHO classification.

In this compilation, intravascular lymphoma is considered a clinically and prognostically heterogeneous group of lymphomas with a variable cutaneous pattern of involvement characterized by a uniform histologic pattern. Case reports exist of T-cell - or NK-cell-associated intravascularlymphoma (lymphoma, cutaneous T-cell lymphoma, intravascular).

Originally, intravascular lymphoma (IVL) was misinterpreted as a tumor of endothelial cells. This resulted in the older term "malignant angioendothelioma" or "angioendotheliomatosis proliferans systematisata" (see below Angioendothelioma). The primary systemic angioendotheliomatosis proliferans systematisata was contrasted in the older literature with the benign or reactive angioendotheliomatosis " angioendotheliomatosis, reactive (benign)". This disease corresponds with that of the purely cutaneous form of intravascular lymphoma.

In a 64-year-old female patient, indolent skin-coloured swellings suddenly appeared in the area of both legs; evidence of 2 painless, approximately 3 cm large lumps on the right thigh. Clear B-symptoms with weight loss of about 15 kg in the last 6 months. Diagnostics: Laboratory: Completely inconspicuous. Examination of bone marrow, MRI skull, PET-CT, chest and upper abdomen sonography, duplex sonography: Insufficiency of the venae saphenae magnae, grade III n. Hach; mainly for thrombosis of the lateral branches of the vena saphena magnae rechs. Histology (Nodules: Intravascular pleomorphic B-cell lymphocytes with roundish chromatin dense nuclei). In addition partial thrombotic occlusion of the venules and microthrombi in the capillaries. Immunohistologically positive for CD20 and CD79. Ki 67: Intravascular lymphocytes with extremely high proliferation rate (about 70 to 80%.) Detection of a B-cell clone. Therapy and course: Initiation of a therapy according to the R-CHOP protocol (rituximab, cyclophosphamide, hydroxy-doxorubicin, vincristine, prednisolone). In addition, the patient received enoxaparin 2x80 mg/day; accompanying consistent compression therapy. A total of 6 cycles; RE staging after 6 months: no evidence of lymphoma; rapid improvement of clinical symptoms.

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2. Crane GM et al (2014) Primary effusion lymphoma presenting as a cutaneous intravascular lymphoma. J Cutan Pathol 41: 928-935.
3. Han K et al (2003) Regression of cutaneous intravascular lymphoma with rituximab. Cutis 72: 137-140
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