Isolated Cutaneous Chronic Lymphocytic Leukemia: A Case Report

Abstract

Skin lesions in chronic lymphocytic leukemia (CLL) have been reported in between 4% and 20% of patients with CLL and are a rare entity compared with T-cell leukemia. They can present mainly as leukemic cutis or, frequently, as secondary lesions such like urticaria, itching, pyoderma gangrenosum, cutaneous vasculitis, Sweet’s syndrome, and erythroderma. We report on an adult patient who developed a skin lesion of forearms and hands, leading to the discovery of isolated cutaneous CLL after two biopsies. Isolated CLL cutaneous location is very rare and may be diagnosed late, as in the case of our patient. A better knowledge of the course of the illness and rapid diagnosis of this CLL cutis leukemia will enhance the therapeutic efficacy of the disease.

Introduction

Chronic lymphocytic leukemia (CLL) is defined by the increased developing of mature monoclonal B cells. ¹ The diagnosis is confirmed peripheral blood lymphocyte count greater than 5000 lymphocytes per microliter for a period of time of 3 months and flow cytometry showing the presence of monoclonal B cells expressing CD5, CD20, CD23, CD19, Kappa and Lambda light chains. It is considered an incurable form of indolent non-Hodgkin’s lymphoma (NHL). ² Skin lesions in CLL have been described between 4% and 20% of patients with this disease and are a fairly rare entity compared to T-cell leukemia.^3,4 They may present primarily as leukemic cutis or, more frequently, as secondary lesions like as itching, pyoderma gangrenosum, cutaneous vasculitis, Sweet’s syndrome and erythroderma . Leukemic cutis is a specific skin manifestations in CLL, ⁵ occuring when leukemic cells invade the surface as well as the deep layers of the dermis, ⁶ and it is found in less than 5% of patients with CLL. ⁷ In this article, we report an uncommon diagnosis of isolated cutaneous CLL discovered by inaugural skin lesions.

Observation

In December 2019, a male patient aged of 69 years with no previous medical history, consulted the dermatology unit in front of a recent onset of infiltrated erythematous plaques located in his forearms and hands, occurring over pre-existing scars of a previous cutaneous Leishmaniosis with no associated symptoms. The histological evaluation of the skin lesions showed an erythema elevatumdiutinum with inflammatory dermis infiltration and leukocytoclastic vasculitis. The complete blood count (CBC) showed hemoglobin at 12.6 g/dL, a normal platelet count at 381 000/mm³; leukocytes at 10 600/mm³ with normal lymphocytes count at 3500/mm³. Further physical exam showed no evidence of lymphadenopathy nor hepatoslplenomegaly. The decision was to start treatment with 50 mg of Dapsone per day. The evolution over the 3 following months was marked by a worsening of the skin lesions which became vegetating and ulcerated with occurrence of many secondary infections (Figure 1). A second skin biopsy revealed a pseudo-epitheliomatous hyperplasia of the epidermis along with small lymphocyte proliferation, confirming skin infiltration with CLL. Immunohistochemically, the cells were positive for CD5, CD20, and CD 23 (Figure 2). As consequence of this finding, the patient was referred to the hematology department. The CBC showed the absence of hyperlymphocytosis and the computed tomography (CT) scan revealed absence of deep lymphadenopathy. The treatment with six cycles of rituximab associated with chlorambucil was then started, after the first course of chemotherapy, minimal improvement of the skin lesions was observed. Owing to lack of response by the end of the sixth cycle, salvage therapy with rituximab-bendamustine were introduced, but unfortunately the patient died due febrile neutropenia after the first cycle.

Figure 1.

Vegetating and ulcerated skin lesions in the left forearm and hand.

Figure 2.

(A) Histopathology demonstrating dense mononuclear cell infiltrate (hematoxylin and eosin; 100×). (B) Immunohistochemical (IHC) stains strongly and diffusely positive for CD20; 200×. (C) IHC stain positive for CD5; 200×. (D) IHC stain positive for CD23; 200×.

Discussion

Chronic lymphocytic leukemia is considered to be the most frequent type of leukemia diagnosed in adults (1) with a diagnosis median age of 71 years. ² The positive diagnosis of CLL is confirmed by flow cytometry. It is common to discover CLL when a routine blood test shows an elevated count of lymphocytes, or in some cases, the presence of symptomatic splenomegaly or lymphadenopathy. ⁸ In our case, there was no hyperlymphocytosis, which is why the diagnosis of CLL was not initially considered.

Skin lesions observed in CLL are divided into specific lesions due to leukemic cells of the leukemia cutis type ⁹ and nonspecific lesions assignable to treatment side effects, abnormal hematopoiesis or paraneoplastic lesions. ¹⁰ Histopathological examination is required to differentiate between these two types of skin lesions. Leukemia cutis may be observed before or after CLL-onset, or as an inaugural manifestation, as our case. ⁶ In our case, CLL appears only as an infiltrate of clonal B cells in the skin and can be considered as part of the differential diagnosis, even in the absence of systemic involvement such as lymphocytosis or lymphadenopathy.

Leukemia cutis is considered to be a factor of a poor prognosis. ¹¹ It usually manifests as lumps, bumps, or infiltrated plaques.

Cutaneous leishmaniasis (CL) is an infection caused by carrying a parasite of the Leishmania species.

Cutaneous leishmaniosis is an infection caused by the biting of a female sand fly carrying a parasite of the Leishmania species. This kind of infection is usually found in the middle eastern countries. ¹² Paraneoplastic neutrophilic dermatosis is one of the differential diagnoses especially in this context. The uniqueness of this case is that these lesions are ulcerated and vegetating, and appeared regarding the scars of CL. This may be explained by the cytokine microenvironment and the chronic inflammation generated by the parasite, which attract tumor lymphocytes. ¹³ Some case studies found that biopsies of the lesions of CL demonstrated the presence of B and T lymphocytes expressing light chains of CD3 and CD4 with the coexistence of cells dysplasia and P53 protein, suggesting that these factors induce carcinogenesis. ¹⁴

Treatment options in CLL depends on factors including the presence of clinical symptoms, age, patient’s general health, and red blood cell, white blood cell, and platelet blood counts. Conventional therapy for CLL involves systemic chemotherapy associated with immunotherapy ¹⁵ or newer tyrosine kinase inhibitor such as ibrutinib ¹⁶ and idelalisib. In the case of cutis leukemia with CLL, local treatments can be used such as radiation therapy, electro-chemotherapy using bleomycin, excision intralesional steroids, or electro-chemotherapy with bleomycin. ¹⁷ These local therapeutic options have been reported to provide promising results. Given the extent of our patient’s lesions, he received immunochemotherapy based on rituximab associated to chlorambucil without improvement of the lesions leading us to recommend salvage therapy with rituximab-bendamustine.

Conclusion

Skin manifestations in CLL are rare and difficult to diagnose, they may be revealed by the appearance of infiltrated plaques with necrotic evolution causing confusion with other skin lesions. The positive diagnosis requires confrontation and analysis of clinical, histological as well as immunohistochemical data. Isolated cutaneous lesion as inaugural manifestation of CLL is very rare and must be considered in the presence of any suspicious lesion of the skin and confirmed by biopsy.