Diagnosis: Leukemia cutis
A 4-mm punch biopsy was obtained from a representative lesion on the patient’s abdomen. Microscopic evaluation with hematoxylin and eosin staining revealed a normal-appearing epidermis and a hypercellular dermis containing innumerable large atypical cells with large, dark-blue, oval nuclei. The infiltrate appeared to course between collagen bundles, clustering in peri-eccrine and perivascular areas; similar cells were seen in the septa of the subcutis. Immunohistochemical staining revealed these abnormal cells to be positive for myeloperoxidase, lysozyme, CD34, CD43, and CD45. A complete blood count showed leukocytosis with neutropenia, thrombocytopenia, and a moderate normocytic anemia. Comprehensive metabolic panel demonstrated elevated uric acid (UA) and lactate dehydrogenase (LDH). Subsequent bone-marrow biopsy revealed 80% myeloblasts. The patient was diagnosed with acute myelogenous leukemia (AML) and leukemia cutis (LC).
LC is defined by the presence of neoplastic leukocytes infiltrating the dermis and subcutaneous tissue. This condition can occur with acute lymphoblastic leukemia (ALL), chronic myeloid leukemia (CML), and chronic lymphocytic leukemia (CLL) but is most frequently seen in AML and adult T-cell leukemia/lymphoma (ATLL).1 Since ATLL is extremely rare, most patients with LC have AML. Conversely, approximately 10%-15% of patients with AML will have LC, although the incidence rises to close to 50% in certain subtypes of AML (M4 [myelomonocytic] and M5 [monoblastic]).1-4
Although the pathogenesis of LC is unknown, it is thought to be a result of leukemic cells proliferating locally within the skin. The presence of LC is associated with a poor prognosis; it correlates with aggressive disease and an excessive tumor burden.1,5 Ninety percent of patients with LC have demonstrable extramedullary involvement of their leukemia,1 and close to 50% of that subgroup have meningeal involvement.1 Most patients with LC die within one year of diagnosis.1,6 Patients presenting with leukemia may have a normal, elevated, or low leukocyte count; anemia and thrombocytopenia are present to varying degrees, yet none of these predict the development of LC. Only an elevated LDH, and possibly an elevated UA, correlate with the presence of LC.2
Although specific age, gender, racial, and geographic factors are associated with various leukemia subtypes, none correlate with LC.2 LC can present in children and is especially common in congenital leukemia, affecting close to 25%-30% of patients.1 Fortunately, LC in congenital leukemia does not portend a poor prognosis.5
In most instances, LC is only one part of the presenting conglomeration of signs and symptoms of the systemic disease. Patients usually have significant bone marrow involvement. Fatigue and dyspnea will be present, relative to the degree of anemia. Bleeding gums, easy bruising, and cutaneous petechiae result from thrombocytopenia. If neutropenia is severe, patients may also have indications of infection, including fever. When all of these symptoms are present, the diagnosis is straightforward. However, a rare patient may present with aleukemic LC.1 In this setting the tumor can be identified only in the skin. Over time, however, most of these patients develop an overt leukemia or lymphoma.
LC has a widely variable clinical presentation; it may indicate a new diagnosis of leukemia or a relapse.1,6,7 Lesional color ranges from flesh-colored, erythematous, reddish-brown, to violaceous.1,5 Typical lesions are asymptomatic, firm, and nontender papules, nodules, and plaques.1,3,5,6 However, ulceration and bullae formation can occur, as can cutaneous hemorrhage and palpable purpura.1,3,6 Although most patients have numerous lesions widely distributed over the head, neck, and trunk, some have fewer lesions or localized disease.1,5 LC characteristically develops in old scars and active areas of cutaneous inflammation or trauma.1 Another abnormal presentation is the development of a single or multiple green-blue nodules. These tumors are called chloromas due to the unique color, caused by myeloperoxidase within the blastic cells, and typically herald the development or relapse of AML.5,8 Although rare, chloromas may also be found in bone or other soft tissue.8 These widely assorted presentations underscore the importance of procuring a biopsy with appropriate immunohistochemical staining not only for diagnosis but for staging and prognosis as well. Medullary involvement is confirmed by bone marrow aspiration and biopsy.9
The differential diagnosis of LC is myriad and depends on lesional morphology and degree of bone marrow destruction. Nonspecific pink-to-erythematous papules of LC must be differentiated from solid-tumor metastatic disease, lymphocytoma cutis, pseudolymphocytoma cutis, lupus, sarcoidosis, erythema nodosum, various drug eruptions, and Jessner’s lymphocytic infiltration of the skin. Hemorrhagic or purpuric lesions of LC must be distinguished from other hemorrhagic processes, including vasculitis or simple hemorrhage from thrombocytopenia. Cutaneous ulcers could represent other malignancies, including cutaneous T-cell lymphoma, vasculitis, or other destructive entities. Sweet’s syndrome, a neutrophilic dermatosis most commonly associated with AML, must also be considered. If the patient presents with skin lesions, neutropenia, and fever, the possibility of a disseminated infection must not be overlooked; wide-spectrum antimicrobial therapy should be initiated until the diagnosis is clear. Neutropenic patients are at risk for disseminated bacterial and fungal infections that may be rapidly fatal if not treated.
Treating the underlying leukemia is the only effective treatment for LC. Various chemotherapeutic regimens are available and determined by the type of leukemia, but these are beyond the scope of this article.1,9 Local or whole-body radiation treatment may be necessary if the lesions persist after systemic chemotherapy.1,9 However, even with appropriate aggressive therapy, the prognosis remains grave.
The patient described in this case was admitted to the hematology/oncology service for induction chemotherapy. Although he initially responded to this therapy, the patient immediately relapsed and underwent a stem-cell transplantation. Several months after transplantation, his tumor and skin lesions returned. He failed subsequent therapy and died.
Ms. Corley is a fourth-year medical student at Virginia Commonwealth University School of Medicine in Richmond. Dr. Nunley is professor of dermatology at Medical College of Virginia Hospitals, also in Richmond. Neither author has any relationship to disclose relating to the content of this article.
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- Cho-Vega JH, Medeiros LJ, Prieto VG, Vega F. Leukemia cutis. Am J Clin Pathol. 2008;129:130-142.
- Agis H, Weltermann A, Fonatsch C, et al. A comparative study on demographic, hematological, and cytogenetic findings and prognosis in acute myeloid leukemia with and without leukemia cutis. Ann Hematol. 2002;81:90-95.
- Ali R, Ozan U, Ozkalemkas F, et al. Leukemia cutis in T-cell acute lymphoblastic leukaemia. Cytopathology. 2006;17:153-161. 2006.
- Hussein MR, Al bshabshe AA, Dalati T. Leukemia cutis: case report and review of the literature. Appl Immunohistochem Mol Morphol. 2010;18:190-191.
- Sambasivan A, Keely K, Mandel K, Johnston DL. Leukemia cutis: an unusual rash in a child. CMAJ. 2010;182:171-173.
- Paydas S, Zorludemir S. Leukaemia cutis and leukaemic vasculitis. Br J Dermatol. 2000;143:773-779. 2000.
- Stern M, Halter J, Buser A, et al. Leukemia cutis preceding systemic relapse of acute myeloid leukemia. Int J Hematol. 2008;87:108-109.
- Lev N, Atar E, Halperin M, et al. Chloroma of the hip as a presenting sign of acute myeloid leukemia. J Chinese Clin Med. 2008;3:156-158.
- Rashid BA, Houshmand EB, Heffernan MP. Hematologic diseases. In: Wolff K, Goldsmith LA, Katz, SI, et al, eds. Fitzpatrick’s Dermatology in General Medicine. New York, N.Y.: McGraw-Hill; 2008:1384-1385.
All electronic documents accessed September 15, 2010.