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Adv Biomed Res 2023,  12:222

Acral Solitary Nodule as a First Clinical Manifestation of Chronic Lymphocytic Leukemia

1 Skin Diseases and Leishmaniasis Research Center, Department of Dermatology, Isfahan University of Medical Sciences, Isfahan, Iran
2 Department of Dermatology, Hamadan University of Medical Sciences, Hamadan, Iran

Date of Submission10-Aug-2022
Date of Acceptance11-Sep-2022
Date of Web Publication31-Aug-2023

Correspondence Address:
Nazila Poostiyan
Skin Diseases and Leishmaniasis Research Center, Department of Dermatology, Isfahan University of Medical Sciences, Isfahan
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/abr.abr_268_22

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Leukemia cutis is a rare cutaneous manifestation of chronic lymphocytic leukemia (CLL) which mostly occurs in the late stages of the disease. We reported an unusual case of a patient with leukemia cutis that developed before the diagnosis of CLL and mimicked cutaneous leishmaniasis (CL). A 52-year-old female presented with an ulcerative nodule on the right forearm. The lesion initially was suspected of being cutaneous leishmaniasis; however, the examination of skin lesion biopsy revealed a dense, diffuse, and monomorphous infiltration of lymphocytes in the dermis. Furthermore, immuno-histochemistry analysis of skin lesion biopsy was indicative of small lymphocytic lymphoma (SLL). The result of laboratory tests showed high white blood cell and lymphocyte counts. The results of bone marrow smear, flow cytometric analysis, and computed tomography of the abdomen and pelvis were suggestive of CLL/SLL (stage I). This case has clinical implications for early diagnosis and management of CLL/SLL.

Keywords: Case report, chronic lymphocytic leukemia, leukemia cutis

How to cite this article:
Mohaghegh F, Poostiyan N, Poostiyan E. Acral Solitary Nodule as a First Clinical Manifestation of Chronic Lymphocytic Leukemia. Adv Biomed Res 2023;12:222

How to cite this URL:
Mohaghegh F, Poostiyan N, Poostiyan E. Acral Solitary Nodule as a First Clinical Manifestation of Chronic Lymphocytic Leukemia. Adv Biomed Res [serial online] 2023 [cited 2023 Sep 28];12:222. Available from:

  Introduction Top

Chronic lymphocytic leukemia (CLL) has been known as the most prevalent leukemia in western countries. The disease mostly affects older adults with a mean age of 72 years, and its risk is twice in men.[1] Cutaneous involvement of leukemia was observed in 4% to 20% of patients, classified into specific and non-specific according to clinical and histopathological criteria. In CLL patients, non-specific lesions are more prevalent and occur most commonly as a result of hematopoiesis disorders, paraneoplastic syndrome, or side effects of medications. They include purpura, petechiae, infections, and drug-related reactions.[2],[3],[4] Skin infiltration with B-lymphocytes is known as a specific cutaneous manifestation of leukemia or leukemia cutis.[5],[6] Leukemia cutis is observed as solitary or multiple lesions that affect the trunk, extremities, and head. Specific cutaneous lesions are frequently observed after or at the same time as the diagnosis of leukemia. However, early presentation of the cutaneous manifestation is very rare and known as aleukemic leukemia cutis.[7] Here, we present a rare case of leukemia cutis which was developed before the hematologic detection of CLL and mimicked cutaneous leishmaniasis (CL).

  Case Report Top

A 52-year-old female, without any significant medical history, presented to our dermatology department (Skin Diseases and Leishmaniasis Research Center) with a 6-month history of an ulcerative cutaneous nodule on the posterior side of the right forearm. According to the patient, the lesion had initially appeared as a single painless and non-itchy papule and gradually progressed to a large crusted ulcerative nodule with an erythematous border [Figure 1]a. The patient had been treated with systemic antibiotics and local wound care for several months before referring to our department, although no improvement had been observed. The physical examination of the patient was unremarkable, and no systemic symptom such as fatigue, weakness, fever, night sweats, and weight loss was detected.
Figure 1: Leukemia cutis as an ulcerative nodule on the right posterior forearm (a) and leukemia cutis remission 4 months after chemotherapy treatment (b)

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The skin lesion was initially suspected of being cutaneous leishmaniasis (CL) because of its endemism in our country. However, the microscopic examination of the Giemsa-stained smears of skin lesion was negative. Therefore, the patient underwent an incisional biopsy of the skin lesion. The histopathological examination of the biopsy specimen showed a dense, diffuse, and monomorphous infiltration of lymphocytes in the dermis, which rejected the diagnosis of CL. The infiltrate was composed of small lymphocytes with rounded hyper-chromatic nuclei without any atypical features, indicating a lymphoproliferative disorder [Figure 2]. The result of immuno-histochemistry analysis of skin lesion biopsy was positive for CD5, CD20, and BCL2 but negative for CD3, BCL6, cyclin-D1, and C10, suggesting a small lymphocytic lymphoma (SLL) [Figure 3]. Laboratory tests showed an elevated white blood cell (35.4 × 103/μL, normal range: 4–11 × 103/μ) and lymphocyte count (28320 lymphocytes/mcl, normal range: 800–500 lymphocytes/mcl), although the level of red blood cells (4.14 million/mm3, normal range: 4–5.4 million/mm3) and platelets (150 *1000/μL, normal range: 450 *1000/μL) were within the normal range. Microscopic examination of peripheral blood smears revealed the presence of numerous small lymphocytes with round nuclei, clumped chromatin and scant cytoplasm, few smudge cells, and 15% of prolymphocytes. Therefore, the patient was referred to an oncologist for a definitive diagnosis of the disease and treatment. Microscopic assessment of bone marrow biopsy indicated the proliferation of mature lymphocytes in interstitial and diffuse patterns. Flow cytometric analysis of bone marrow aspirate revealed mature lymphocytes expressing CD5+CD19, CD5, CD19, and CD23. The computed tomography (CT) scanning of the abdomen and pelvis was normal and excluded the involvement of the internal organs. Finally, the lesion was diagnosed as leukemia cutis (involving stage I of SLL/CLL). The patient underwent four cycles of systemic chemotherapy using rituximab, followed by one cycle of therapy with chlorambucil (2 mg/day). She tolerated the chemotherapy regimen very well. After 4 months of the treatment initiation, the lesion resolved completely [Figure 1]b and counts were in the normal range. Upon her last follow-up, which was 9 months after chemotherapy treatment, the patient was in complete remission and no sign of lesion recurrence was observed.
Figure 2: Histopthology of the skin lesion showing diffuse infiltrates of small cells with rounded hyper-chromatic nuclei and scant cytoplasm (H&E stain, a: ×40, b: ×100)

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Figure 3: The immuno-histochemical examination showed that the tumor cells were strongly positive for CD5 (a), CD20 (b), and Bcl-2 (c) but negative for CD3 (d), Bcl-6 (e), and CD10 (f) (×100)

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  Discussion Top

Specific cutaneous manifestation of leukemia or leukemia cutis is defined as the infiltration of neoplastic leukocytes or their precursors into the skin and observed in less than 5% of patients with CLL.[3],[7] Leukemia cutis has various clinical presentations, including nodules, papules, plaques, ulcerations, and exfoliative erythroderma.[8] In more than 90% of patients with leukemia, specific cutaneous lesions appear after the diagnosis of systemic disease.[1] Diverse clinical presentations of leukemia cutis or its appearance before systemic involvement can make its distinction from other skin lesions difficult. Leukemia cutis in the present case developed before the diagnosis of systemic leukemia and was initially considered to be CL. CL is a clinical presentation of leishmaniasis that is caused by the transmission of an intra-cellular parasite to humans by the bite of sandflies in exposed areas of the body (face, legs, and forearms). Initially, the lesion appears as an erythematous papule that transforms into a crusted ulcerative nodule within 1 to 3 months.[9] Furthermore, CL has been known to be one of the most frequent endemic diseases in Iran.[10] The skin lesion in the current case was regarded as CL because of its clinical presentation and the endemism of the disease in our region. However, the microscopic examination of the lesion smear and biopsy rejected the diagnosis of CL.

Our case is among a small number of previous patients with leukemia cutis as the first presentation of CLL.[11],[12],[13],[14] In a series reported by Welther et al., leukemia cutis was the first sign of the disease in two of six cases of CLL.[12] Another series demonstrated clinical and histopathologic features of 42 CLL patients with leukemia cutis; 16.7% of patients presented leukemia cutis before the systemic diagnosis of CLL.[14] The appearance of specific cutaneous lesions in patients with leukemia in the absence of systemic symptoms leads to a delay in the diagnosis of lesion and underlying disease. Therefore, a combination of clinical and laboratory data is required to distinguish these lesions from other infectious and inflammatory lesions. The diagnosis of leukemia cutis is performed according to the clinical appearance of the lesion, evaluating the pattern of lymphocyte infiltration in skin biopsy and immuno-histochemistry features of tumor cells. Three major architectural patterns have been detected for leukemia cutis in CLL patients comprising peri-vascular and peri-adnexal, nodular and diffuse (such as the current case), and band-like.[14] The histopathological examination of the biopsy specimen showed a dense, diffuse, and monomorphous infiltration of lymphocytes in the dermis with clumped chromatin and scant cytoplasm. Immuno-histochemistry analysis of skin lesion biopsy was positive for CD5, CD20, and BCL2 but negative for CD3, BCL6, cyclin-D1, and C10, suggesting anSLL. The differential diagnosis of leukemia was performed through microscopic examination of bone marrow biopsy, flow cytometry analysis of bone marrow aspirates, and CT of the abdomen and pelvis, suggesting stage I of SLL/CLL.

The treatment of underlying leukemia using chemotherapy is the main treatment goal in patients with leukemia cutis. We treated the current patient with four cycles of rituximab following one course of chlorambucil. Rituximab alone or in combination with other chemotherapeutic agents has been known as an effective treatment option in the treatment of CLL patients.[15] Previous studies have shown the promising effects of chemotherapy with rituximab plus chlorambucil in the treatment of patients with CLL.[16],[17] Our patient tolerated the chemotherapy regimen very well and remained in complete remission for 9 months after treatment. We reported this case to notify dermatologists of the appearance of leukemia cutis as the first presentation of leukemia in CLL patients for early diagnosis and management of the disease.


A signed written consent was obtained from the patient for publication of the current case report.

Ethical approval

All authors declare that current manuscript has not been published totally or partly elsewhere.

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Conflicts of interest

There are no conflicts of interest.

  References Top

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Cho-Vega JH, Medeiros LJ, Prieto VG, Vega F. Leukemia cutis. Am J Clin Pathol 2008;129:130-42.  Back to cited text no. 2
Robak E, Robak T. Skin lesions in chronic lymphocytic leukemia. Leuk Lymphoma 2007;48:855-65.  Back to cited text no. 3
Szukalski Ł, Sysakiewicz-Buda M, Mêciñska-Jundziłł K, Białecka A, Czyż J, Czajkowski R. Cutaneous manifestation of chronic lymphocytic leukemia: A case report and a literature review. Adv Dermatol Allergol 2019;36:778.  Back to cited text no. 4
Ratnam KV, Khor CJ, Su WD. Leukemia cutis. DermatolClin 1994;12:419-31.  Back to cited text no. 5
Bonvalet D, Foldes C, Civatte J. Cutaneous manifestations in chronic lymphocytic leukemia. J Dermatol Surg 1984;10:278-82.  Back to cited text no. 6
Wagner G, Fenchel K, Back W, Schulz A, Sachse MM. Leukemia cutis–epidemiology, clinical presentation, and differential diagnoses. J Dtsch Dermatol Ges 2012;10:27-36.  Back to cited text no. 7
Agnew KL, Ruchlemer R, Catovsky D, Matutes E, Bunker CB. Cutaneous findings in chronic lymphocytic leukaemia. Br J Dermatol 2004;150:1129-35.  Back to cited text no. 8
Iddawela D, Vithana SM, Atapattu D, Wijekoon L. Clinical and epidemiological characteristics of cutaneous leishmaniasis in Sri Lanka. BMC Infect Dis2018;18:108.  Back to cited text no. 9
Norouzinezhad F, Ghaffari F, Norouzinejad A, Kaveh F, Gouya MM. Cutaneous leishmaniasis in Iran: Results from an epidemiological study in urban and rural provinces. Asian Pac J TropBiomed2016;6:614-9.  Back to cited text no. 10
Mittal A, Gogia A, Mallick S, Gupta R. Leukemia cutis: A rare initial presentation of chronic lymphocytic leukemia. Indian J Hematol Blood Transfus 2019;35:367-8.  Back to cited text no. 11
Walther BS, Gibbons G, Chan EF, Ziselman E, Rothfleisch JE, Willard RJ, et al. Leukemia cutis (involving chronic lymphocytic leukemia) within excisional specimens: A series of 6 cases. Am J Dermatopathol2009;31:162-5.  Back to cited text no. 12
Cerroni L, Zenahlik P, Höfler G, Kaddu S, Smolle J, Kerl H. Specific cutaneous infiltrates of B-cell chronic lymphocytic leukemia: A clinicopathologic and prognostic study of 42 patients. Am J Surg Pathol1996;20:1000-10.  Back to cited text no. 13
Buechner SA, Li CY, Su WD, Hunter JA, Holubar K. Leukemia cutis A histopathologic study of 42 cases. Am J Dermatopathol1985;7:109-20.  Back to cited text no. 14
Jaglowski SM, Byrd JC. Rituximab in chronic lymphocytic leukemia. SeminHematol 2010;47:156-69.  Back to cited text no. 15
Hillmen P, Gribben JG, Follows GA, Milligan D, Sayala HA, Moreton P, et al. Rituximab plus chlorambucil as first-line treatment for chronic lymphocytic leukemia: Final analysis of an open-label phase II study. J Clin Oncol2014;32:1236-41.  Back to cited text no. 16
Laurenti L, Innocenti I, Autore F, Ciolli S, Mauro FR, Mannina D, et al. Chlorambucil plus rituximab as front-line therapy for elderly and/or unfit chronic lymphocytic leukemia patients: Correlation with biologically-based risk stratification. Haematologica 2017;102:e352.  Back to cited text no. 17


  [Figure 1], [Figure 2], [Figure 3]


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