Original article
Unusual cutaneous manifestations of B-cell chronic lymphocytic leukemia

https://doi.org/10.1016/j.jaad.2008.12.047Get rights and content

Background

B-cell chronic lymphocytic leukemia (B-CLL) is a low-grade lymphoproliferative disorder with characteristic histomorphologic features and an identifiable immunophenotype. The skin can be involved in the context of known disease, but cutaneous signs are rarely the presenting findings.

Objective

Evaluation of unusual clinical cutaneous presentations of B-CLL.

Methods

We conducted a retrospective case series analysis of 3 patients with unusual cutaneous clinicopathologic presentations of B-cell chronic lymphocytic leukemia, including erythematous plaques, angiomatosis/telangiectasia, and erosive skin changes, respectively, without a previous clinical history of chronic lymphocytic lymphoma. Main outcome measures were clinical cutaneous presentations and histopathologic results in the diagnosis of underlying disease.

Results

In the 3 cases, lesion locations were the lower cheek, lower extremity, and penis (groin region). Histomorphologic testing showed mild to dense perivascular and periadnexal lymphoid aggregates throughout the dermis and extending into the panniculus, consistent with B-CLL. The diagnosis was confirmed with immunohistochemical studies that showed coexpression of CD5 and CD20 in the neoplastic lymphocytic infiltrate.

Limitations

None.

Conclusion

Cutaneous manifestations are an uncommon presentation of subclinical B-CLL. Cutaneous changes were the presenting features of underlying lymphoma in all 3 cases, highlighting the importance of maintaining a high index of suspicion for a lymphoproliferative process in cases with unusual or atypical clinicopathologic features. Additional investigations into the behavior of B-CLL in the skin may elucidate further the evolution of cutaneous lesions in this disease.

Introduction

B-cell chronic lymphocytic leukemia (B-CLL) is a low-grade, B-cell lymphoproliferative monoclonal disorder characterized by progressive accumulation of functionally immunoincompetent lymphocytes that affect immune function and normal hematopoiesis. B-CLL is the most common form of leukemia found in adults in Western countries and has a male predilection. The medical literature detailing cutaneous manifestations in patients with B-CLL is limited and, in most cases, represents nonspecific manifestations related to an impaired immune system. Examples of these phenomena include cutaneous neoplasms, such as squamous cell carcinomas, and infections.

Specific cutaneous infiltrates of B-CLL occurring at sites of infection with herpes simplex and herpes zoster viruses, and Borrelia burgdorferi have been well documented.1, 2 In such cases, the purported pathologic mechanism is recruitment of normal and neoplastic B lymphocytes from peripheral blood to the lesional skin as part of the physiologic response to antigenic stimulation.2 This hypothesis is supported by the favorable prognosis in patients with specific cutaneous infiltrates of B-CLL.2 This outcome is in contrast to the poor prognosis typically associated with leukemia cutis.

The histopathologic features found in skin infiltrates in most of the cases described by Cerroni, Zenahlik, and Kerl1 were characterized as a variably dense perivascular and periadnexal infiltrate of small, hyperchromatic lymphocytes throughout the entire dermis and extending into the subcutaneous fat. However, other reports have described dense, diffuse dermal infiltrates of small, hyperchromatic lymphocytes.1, 2 The histologic features of specific skin infiltrates in B-CLL have varied with respect to the density and pattern of the neoplastic B lymphocytes and have highlighted the frequent presence of admixed reactive T lymphocytes.

Some histopathologic features help distinguish between reactive inflammatory dermatoses and neoplastic lymphoid processes, such as dense, bottom-heavy lymphoid infiltrates, marked cytologic atypia, and crush artifact in the latter. However, in rare cases the diagnosis of a neoplastic lymphoid process may be missed and requires clinical and pathologic correlation with adjunctive immunohistochemical stains.

B-CLL may involve the skin either in isolation or as incidental findings seen in biopsy specimens from other skin lesions, including such nonrelated skin tumors as basal cell carcinomas or squamous cell carcinomas, and other benign inflammatory dermatoses. Rarely, B-CLL presents with cutaneous involvement as an unexpected incidental finding, and this finding creates a clinical and histopathologic diagnostic pitfall.

We present 3 patients with unusual cutaneous manifestations of subclinical B-CLL, in which the cutaneous lesions represented the first sign of disease and prompted further work-up and confirmation of the underlying disease process.

Section snippets

Materials and methods

Three cases were retrieved prospectively from the dermatology and dermatopathology files at Mayo Clinic, Rochester, Minnesota. Clinical data and follow-up information were obtained from the clinical records. Histologic examination was performed on tissues fixed in neutral, buffered formalin and subsequently embedded in paraffin. All tissue sections were stained with hematoxylin and eosin, and 1 to 10 histologic sections were analyzed in each case.

Representative paraffin-embedded tissue blocks

Results

The patients were two men and one woman whose ages ranged from 60 to 83 years (mean age, 71.5 years). The patients presented with clinical cutaneous changes (Table I) and supportive histopathologic findings (Table II) that led to a diagnosis of unsuspected underlying B-CLL.

Discussion

B-CLL is the most common type of leukemia in adults in the Western world. It is predominantly a disease of persons older than 50 years and has a male predilection.4 The etiology of the clonal proliferation of B lymphocytes is unknown. Most patients are asymptomatic at diagnosis, and the most common presenting symptoms and signs include fatigue, fever, easy bruising, and generalized lymphadenopathy.5

The incidence of chronic lymphocytic leukemia (CLL) has increased during the past decade.6

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    Funding sources: None.

    Conflicts of interest: None declared.

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