Ann Dermatol.  2019 Dec;31(6):673-677. 10.5021/ad.2019.31.6.673.

Leukemia Cutis in Chronic Neutrophilic Leukemia Associated with Colony Stimulating Factor 3 Receptor Mutation: Clinical Severity Paralleled with Hematologic Abnormality

Affiliations
  • 1Department of Dermatology, School of Medicine, Daegu Catholic University, Daegu, Korea.
  • 2Department of Dermatology, School of Medicine, Kyungpook National University, Kyungpook National University Hospital, Daegu, Korea. gdpk1217@knu.ac.kr

Abstract

Cutaneous lesions of leukemia cutis (LC) by chronic neutrophilic leukemia (CNL) have been merely reported due to the rare occurrences of CNL. Furthermore cutaneous lesions in relation to clinical severity have been far less studied. A 70-year-old man presented with multiple violaceous papules and excoriations on both lower extremities. The diagnosis was LC based on histologic and laboratory evaluation and the origin was elaborated as CNL with the confirmation of colony stimulating factor 3 receptor (CSF3R) mutation. Interestingly, the patient presented clinical severity in a parallel manner to the hematologic abnormality. To the best of our knowledge, there has been no reported case of CSF3R confirmed LC in CNL featuring explicit skin eruption in relation to laboratory findings.

Keyword

Colony-stimulating factors 3 receptor; Leukemia cutis; Leukemia, neutrophilic, chronic

MeSH Terms

Aged
Colony-Stimulating Factors*
Diagnosis
Humans
Leukemia*
Leukemia, Neutrophilic, Chronic*
Lower Extremity
Skin
Colony-Stimulating Factors

Figure

  • Fig. 1 Serial clinical images. (A) Skin lesion at initial visit featuring multiple red to violaceous papules and plaques with severe oozing and edema on the feet, leukocyte count (63,500/mm3) (B) Aggravation of skin lesion after dosage reduction of hydroxyurea (hydroxycarbamide 0.5 g) leukocyte count (113,000/mm3) (C) Aggravation of skin lesion despite initial dosage of hydroxyurea (hydroxycarbamide 1 g) leukocyte count (98,150/mm3) (D) Improvement of skin lesion after double of initial hydroxyurea dosage (hydroxycarbamide 2 g) with concomitant improvement of leukocytosis, leukocyte count (22,000/mm3).

  • Fig. 2 (A) Peripheral blood smear exhibits dominantly abundant nature of segmented and band form neutrophils with all stages of neutrophil precursors including promyelocytes, myelocyte and metamyelocyte. (B) Bone marrow biopsy reveals hypercellularity of cells and red marrow with dominant number of neutrophilic granulocytes bearing normal maturation. Myelobastic cells are less than 5% on the captured microscopic field. (C) Scanning magnification of the skin biopsy revealed diffuse infiltration of inhomogenous neutrophils with pustular formation (H&E, ×40). (D) Higher magnification reveals variable sizes and shapes of both the nucleus and the cells with characteristics (H&E, ×400). (E) Both immature and mature neutrophilic components are shown with low degree of atypia in size and shapes (H&E, ×400). (F) Positive immunohistochemical staining result to myeloperoxidase stain is observed (MPO, ×200).

  • Fig. 3 Genetic study of the colony stimulating factor 3 receptor through Sanger gene deoxyribonucleic acid (DNA) sequencing chromatogram analysis. (A) Original transcript of the sequenced data (SCLLAB 20170209-310878). (B) Extracted sequence of the abnormality exhibiting pathologic variant at the 1,853th base-sequence, where cytosine was transferred to thymine, leading to subsequent substitution of threonine to isoleucine (red arrow).


Reference

1. Cronin DM, George TI, Sundram UN. An updated approach to the diagnosis of myeloid leukemia cutis. Am J Clin Pathol. 2009; 132:101–110.
Article
2. Li AW, Yin ES, Stahl M, Kim TK, Panse G, Zeidan AM, et al. The skin as a window to the blood: cutaneous manifestations of myeloid malignancies. Blood Rev. 2017; 31:370–388.
Article
3. Elliott MA, Tefferi A. Chronic neutrophilic leukemia 2016: update on diagnosis, molecular genetics, prognosis, and management. Am J Hematol. 2016; 91:341–349.
Article
4. Maxson JE, Tyner JW. Genomics of chronic neutrophilic leukemia. Blood. 2017; 129:715–722.
Article
5. Arber DA, Orazi A, Hasserjian R, Thiele J, Borowitz MJ, Le Beau MM, et al. The 2016 revision to the World Health Organization classification of myeloid neoplasms and acute leukemia. Blood. 2016; 127:2391–2405.
Article
6. Willard RJ, Turiansky GW, Genest GP, Davis BJ, Diehl LF. Leukemia cutis in a patient with chronic neutrophilic leukemia. J Am Acad Dermatol. 2001; 44:2 Suppl. 365–369.
Article
7. Elliott MA, Hanson CA, Dewald GW, Smoley SA, Lasho TL, Tefferi A. WHO-defined chronic neutrophilic leukemia: a long-term analysis of 12 cases and a critical review of the literature. Leukemia. 2005; 19:313–317.
Article
8. Cho-Vega JH, Medeiros LJ, Prieto VG, Vega F. Leukemia cutis. Am J Clin Pathol. 2008; 129:130–142.
Article
9. Patel LM, Maghari A, Schwartz RA, Kapila R, Morgan AJ, Lambert WC. Myeloid leukemia cutis in the setting of myelodysplastic syndrome: a crucial dermatological diagnosis. Int J Dermatol. 2012; 51:383–388.
Article
10. Avivi I, Rosenbaum H, Levy Y, Rowe J. Myelodysplastic syndrome and associated skin lesions: a review of the literature. Leuk Res. 1999; 23:323–330.
Article
11. Kaddu S, Zenahlik P, Beham-Schmid C, Kerl H, Cerroni L. Specific cutaneous infiltrates in patients with myelogenous leukemia: a clinicopathologic study of 26 patients with assessment of diagnostic criteria. J Am Acad Dermatol. 1999; 40(6 Pt 1):966–978.
Article
12. Rochet NM, Chavan RN, Cappel MA, Wada DA, Gibson LE. Sweet syndrome: clinical presentation, associations, and response to treatment in 77 patients. J Am Acad Dermatol. 2013; 69:557–564.
Article
13. Cohen PR, Holder WR, Tucker SB, Kono S, Kurzrock R. Sweet syndrome in patients with solid tumors. Cancer. 1993; 72:2723–2731.
Article
14. Manz MG, Boettcher S. Emergency granulopoiesis. Nat Rev Immunol. 2014; 14:302–314.
Article
15. Maalouf D, Battistella M, Bouaziz JD. Neutrophilic dermatosis: disease mechanism and treatment. Curr Opin Hematol. 2015; 22:23–29.
16. Fleischman AG, Maxson JE, Luty SB, Agarwal A, Royer LR, Abel ML, et al. The CSF3R T618I mutation causes a lethal neutrophilic neoplasia in mice that is responsive to therapeutic JAK inhibition. Blood. 2013; 122:3628–3631.
Article
Full Text Links
  • AD
Actions
Cited
CITED
export Copy
Close
Share
  • Twitter
  • Facebook
Similar articles
Copyright © 2024 by Korean Association of Medical Journal Editors. All rights reserved.     E-mail: koreamed@kamje.or.kr