Skin Manifestations of Intravascular Lymphoma Mimic Inflammatory Diseases of the Skin

J. Röglin; A. Böer

Disclosures

The British Journal of Dermatology. 2007;157(1):16-25. 

In This Article

Discussion

Our review of the literature revealed that 40% of patients with IVL present with lesions in the skin, thus demonstrating a need for dermatologists to be aware of the typical clinical appearance of such lesions. Many of the articles reviewed by us were case reports: only a few studies included more than one patient. Interestingly, many of the articles could not be retrieved from a simple Medline search but were found only by analysing scrupulously the references quoted by other authors, thus demonstrating the deficiencies of the search engines of the Medline database. Unfortunately, in one of the largest studies, undertaken by Ferreri et al., in which 10 patients were said to have lesions in the skin, clinical findings of skin lesions are given only in the form of a brief summary of all of the 10 patients, no patient being presented individually. Therefore, assessment of these patients in regard to the clinical appearance is not possible in retrospect.[92]

Many of the reports studied by us did not include photographs of clinical lesions but only photomicrographs or electron microscopic images. In numerous patients the authors described only a few lesions in the skin but did not document a full-body examination. Often descriptions of clinical lesions are not detailed and data about site, signs and symptoms such as pain or tenderness are incomplete.

Early reports from the 1960s up to the early 1980s did not include results of sophisticated ancillary laboratory techniques. Exact classification of patients into lymphoma of B-cell or T-cell differentiation was only possible after the advent of immunohistochemistry and as but one example, the differentiation of cells in the original report by Pfleger and Tappeiner[1] and of many patients published thereafter is unclear.

Our analysis of descriptions of clinical lesions as well as of photographs presented in the articles revealed that the presentation in the skin of IVL shares many features with inflammatory diseases of the skin. Lesions may be red, painful, accompanied by oedema, and waxing and waning. Often the clinical findings are misinterpreted when the patient first consults a dermatologist. Common misdiagnoses are listed in Table 4 and include 'thrombophlebitis', 'thrombophlebitis migrans', 'erythema nodosum', 'vasculitis' and 'livedo racemosa'.[51,56,61] Associated findings such as fever, malaise, and elevation of lactate dehydrogenase and erythrocyte sedimentation rate may also mislead a dermatologist to suspect an inflammatory condition rather than a lymphoma. Whereas most patients with IVL present with cytopenias, mainly anaemia and thrombocytopenia, identifiable involvement of the bone marrow is rare, especially early in the course of the disease.

The fact that skin lesions of IVL mimic inflammatory diseases of the skin can be explained by clinicopathological correlation. Occlusion of vessels by blasts of T- or B-cell differentiation activates the coagulation cascade and thrombi develop within the lumina of vessels. The clinical signs may be indistinguishable from those of thrombophlebitis. If superficial vessels are involved in the process the clinical pattern may be that of livedo racemosa; if vessels in the deep dermis or the septa of the subcutaneous fat are involved, clinical lesions mimic those of erythema nodosum or nodular vasculitis. If many vessels are involved in the process, patchy erythema along with haemorrhage may call to mind the clinical diagnosis of erysipelas. That lesions are waxing and waning can be explained by thrombi being recanalized or bypassed by neovascularization. Reorganization of thrombi is usually accompanied by local increase of the tissue temperature which may simulate an authentic inflammatory or even infectious condition of the dermis or subcutis. Telangiectases are clinical evidence of recanalization and of recurrences of lesions at the very same site. They are an important clue to the diagnosis of IVL, but they are not present invariably and, moreover, they may be misinterpreted as varicosities.

Patients who are diagnosed with IVL early in the course when lesions are still restricted to the skin have a much more favourable prognosis. In contrast, patients in whom the disease is diagnosed only when several organs are already involved have a poor prognosis despite treatment with polychemotherapy. Not uncommonly, the disease goes entirely undiagnosed and the correct diagnosis is only made on post mortem examination.[24,51,53,56,61,69,77] Our comparison of lesions in patients with IVL restricted to the skin with skin lesions that appeared together with involvement of other organs by IVL did not reveal any significant differences, indicating that the clinical course of an individual patient cannot be predicted from the morphology of skin lesions. It is essential, therefore, that patients with lesions of IVL in the skin are examined fully. Ultrasound of lymph nodes, blood cell count, bone marrow biopsy, abdominal ultrasound and chest X-ray are recommended. Neurological examination and renal function tests should also be performed because the brain and the kidney are other sites commonly involved in IVL. Skin manifestations of IVL-TCL seem not to differ from those encountered in IVL-BCL, the only exceptions being that IVL-TCL may also, at times, involve the face and the anogenital region and that patients with IVL-TCL seem to be younger than patients with IVL-BCL, and have a slightly worse prognosis.

It is a matter of controversy whether patients with IVL restricted to the skin should be treated aggressively. Experience with such patients is limited and no controlled studies exist so far. Usually patients receive polychemotherapy for large B-cell or T-cell lymphoma, and the composition of such treatment regimens changes whenever guidelines for treatment of lymphomas are revised. When blasts of IVL-BCL are strongly CD20 positive, treatment with antibodies to CD20 is a new option for treatment. Clinical follow-up is mandatory in order to detect early progression of the disease with involvement of other organs in the disease process.

In conclusion, lesions of IVL in the skin may mimic inflammatory conditions such as thrombophlebitis, thrombophlebitis migrans, erythema nodosum or chronic erysipelas because lesions may present as red, painful patches and plaques, accompanied by oedema, situated on the leg or the thigh, and may be waxing and waning. Whenever a patient is diagnosed with 'recurrent thrombophlebitis', 'recurrent erythema nodosum' of unknown cause or with an erysipelas unresponsive to antibiotic treatment, the possibility of an IVL should be considered. A deep excisional biopsy specimen is requisite to confirm the diagnosis.

Unfortunately, neither the differentiation of the lymphoma nor the clinical course of an individual patient can be predicted from the morphology of skin lesions seen clinically. Every patient with IVL in the skin needs a complete staging for involvement of other organs in the process. However, if staging does not reveal any involvement of other organs at the time of diagnosis of skin lesions, the prognosis is favourable based on the data provided in articles reviewed by us.


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