Original articleUnusual cutaneous manifestations of B-cell chronic lymphocytic leukemia
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.