November 2003

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Diagnosis: Leukemia Cutis

Pathology: Leukemia cutis is characterized by a dense infiltrate of leukemic cells in the upper and deep dermis, sometimes extending to the subcutis (see Figure 3). There is often a grenz zone, but this may be obliterated by the leukemic infiltrate. The leukemic cells spread between the collagen bundles (see Figure 4) and may involve the vasculature or cutaneous appendages. In AML, the infiltrate is usually made of large myeloblasts with round or oval nuclei, along with smaller cells with clefted nuclei, and mitoses are common (See Figure 5).

Course:
The patient's AML had been diagnosed approximately 8 months prior to her presentation with leukemia cutis. She underwent chemotherapy, achieved remission, then relapsed 6 months later when she presented with a cranial nerve palsy and was found to have leukemic involvement of her CNS. She was treated with intrathecal chemotherapy, radiation, and once again achieved remission. She then underwent total body irradiation and allogeneic bone marrow transplantation. A bone marrow biopsy done approximately two weeks prior to her presentation with leukemia cutis showed no evidence of acute leukemia. The cutaneous relapse is being treated with chemotherapy.

Discussion:
Cutaneous manifestations of leukemia are described as specific (infiltrates of leukemic cells, or leukemia cutis) or nonspecific (inflammatory, paraneoplastic, or secondary to marrow failure).

Leukemia cutis is a specific sign of systemic leukemia and is the result of dissemination of leukemic cells to the skin. The most common lesions are multiple flesh-colored, pink, red, or red-brown papules, nodules, or infiltrated plaques. They are typically firm or rubbery in consistency, and can become purpuric if the patient is thrombocytopenic. Unusual presentations include those resembling figurate erythemas, guttate psoriasis, stasis dermatitis, and ulcers, among others. There are also reports of leukemia cutis localizing to sites of herpetic lesions, trauma, intravenous catheters, and recent surgeries.

The incidence of leukemia cutis varies according to the type of leukemia. It is most common in the acute myelomonocytic and monocytic leukemias, occurring in 10-50% of cases. Of note, gingival hypertrophy is especially common in these groups. It occurs in up to 13% of cases of acute myelogenous leukemias, 8-20% of cases of chronic lymphocytic leukemia (CLL), and less than 5-10% of cases of acute lymphoid leukemia, hairy cell leukemia, or chronic granulocytic leukemia. Although leukemia cutis is less common in CLL, because CLL is the most common chronic leukemia, it accounts for the largest group of patients with leukemia cutis. In general, the incidence of skin involvement is much higher in T-cell lymphoproliferative disorders than in their B-cell counterparts.

Leukemia cutis may follow, precede, or occur concomitantly with the diagnosis of systemic leukemia. The majority of leukemia cutis occurs at presentation with systemic leukemia (23-44%) or in the setting of an established leukemia (44-77%). Rarely, leukemia cutis can predate the development of detectable leukemia in the peripheral blood and/or bone marrow, and this is termed aleukemic leukemia cutis. Leukemia cutis has also been reported in patients with myelodysplastic syndrome undergoing leukemic transformation.

Because there is a strong correlation between leukemia cutis and the presence or development of leukemia in other extramedullary sites, leukemia cutis has generally been associated with a worsened prognosis. There is no specific treatment for leukemia cutis other than that directed at the underlying systemic leukemia.

Nonspecific cutaneous signs of leukemia are much more common than leukemia cutis, occurring in up to 30-40% of patients with leukemia. The most common nonspecific signs are hemorrhagic, including petechiae, purpura, and ecchymoses. Other signs related to marrow failure include those associated with infections, such as those associated with varicella-zoster virus, herpes simplex virus, or cutaneous mycoses. The list of reactive or paraneoplastic lesions is long and includes generalized pruritus, Sweet's syndrome, pyoderma gangrenosum, exfoliative dermatitis, urticaria, erythema multiforme, erythema nodosum, ichthyosis, and vasculitis. There is also an increased incidence of drug eruptions in patients with leukemia.

References:
1. Agis H et al. A comparative study on demographic, hematological, and cytogenetic findings and prognosis in acute myeloid leukemia with and without leukemia cutis. Ann Hematol 81: 90-95, 2002.
2. Bolognia J, Rapini R, Jorrizzo J,eds. Dermatology. Mosby, 2003.
3. Ratnam, KV et al. Leukemia cutis. Derm Clinics 12(2): 419-431, 1994.
4. Weedon, D. Skin Pathology. Churchill Livingstone, 1997. pp. 917-919.
5. Su, WPD. Clinical, histopathologic, and immunohistochemical correlations in leukemia cutis. Seminars in Dermatol 13(3): 223-230, 1994.

My thanks to Dr. Jerri Hoskyn for assisting in the preparation of this case.