Synonyms: Cutaneous leukemia, extramedullary myeloid tumor
Etiology: Unknown
Associations: Systemic leukemia
Clinical: Erythematous patches, papules, nodules, hemorrhagic and purpuric lesions, blue-green nodules
Histology: Malignant immature hematopoietic precursor cells in dermis, diffusely or in patchy distribution
IHC repertoire: Lymphocyte surface markers and/or markers of specific granules rarely necessary
Staging: Systemic work-up required
Prognosis: Poor, except for CLL
Adverse variables: Histologic subtype of high-grade leukemias
Treatment: No local therapy; systemic chemotherapy
5
Leukemia Cutis
Leukemia cutis is an uncommon cutaneous eruption that may be difficult to diagnose. In the vast majority of patients, there is a known history of leukemia at the time of the skin manifestations. However, leukemia may have its initial manifestation in the skin, in some cases with simultaneous bone marrow involvement, or less com- monly, in the absence of simultaneous marrow involve- ment. (In these cases, the cutaneous eruptions have been called extramedullary myeloid tumors (1)). In one series, approximately 38% of patients had cutaneous fi ndings at the time of bone marrow diagnosis (2). In other series, anywhere from 3% to 7% of patients had cutaneous lesions prior to detection of marrow involvement (3). Patients with all types of leukemia may demonstrate cutaneous lesions. It has been reported in 2% to 3% of patients with acute myelogenous leukemia (4). Cutaneous involvement is less common in patients with acute lymphoblastic leu- kemia (5). Chronic myelogenous leukemia patients have skin manifestations in 6% to 20% of cases (6). The inci- dence ranges from 4% to 20% in patients with chronic lymphocytic leukemia (7).
The clinical manifestations of leukemia cutis are protean. In some cases, the disparate clinical appearances correlate with the subtypes of leukemia involved and the systemic complications caused by these types of leukemia.
For instance, hemorrhagic lesions are commonly found in the subtypes of leukemia that are associated with coagu- lopathies (such as acute promyelocytic leukemia), but are
rarely seen in patients with chronic lymphocytic leuke- mia. Tumor nodules may occur in patients with any subtype of leukemia, but are most commonly seen in those with chronic myelogenous leukemia (Figure 5.1). In other patients, diffuse erythematous papules and nodules correlate with diffuse infiltrates of neoplastic cells throughout the dermis. The etiology for bullae that have been reported in rare patients is less well understood.
Some types of leukemia have more specific findings, such as gingival hyperplasia associated with acute myelomo- nocytic leukemia.
The histologic fi ndings in leukemia cutis are varied. In most cases, there is a diffuse infiltrate of atypical hema- topoietic cells throughout the dermis (Figure 5.2).
In some cases, the neoplastic cells appear in such den- sity as to form dermal tumor nodules. More commonly, however, the cells are dispersed individually throughout the dermis. The cells show little tendency for cohesion and percolate between splayed collagen bundles. In some cases, there is a predilection for aggregates of leukemic cells sur- rounding the peri-eccrine vascular spaces (8).
The cytologic features of the infiltrating cells vary with the type of leukemia. In acute myeloid leukemias, large, immature precursor cells are present (Figure 5.3).
These cells are readily identified with routine sections in most cases. In some cases, a chloroacetate esterase stain or the use of an anti-myeloperoxidase antibody may be helpful in identifying characteristic cytoplasmic granules.
24
5. Leukemia Cutis 25
throughout the dermis. Abundant mitotic activity and individual cell necrosis are commonly seen. These cells are very difficult to classify based upon routine sections or special stains; however, correlation with cytometric studies is helpful, and in most cases, the patient’s prior history makes the diagnosis straightforward. Chronic lymphocytic leukemia (CLL) may also occur in the skin, both in patients with long-standing disease, and as an initial manifestation. In these cases, a de novo diagnosis is difficult to make. The histologic fi ndings include only a monomorphous population of relatively small and unre- markable lymphocytes within the dermis. The key obser- vation is that the usual heterogeneity of cell type is absent, as is the usual variation in lymphocyte size and shape.
Clonality can be ascertained in most cases, if the diagnosis is entertained based upon routine sectioning. Some inves- tigators have noted a tendency for the neoplastic lympho- cytes in CLL to comprise the immune response underlying primary keratinocytic neoplasms or infectious processes (9,10). This may be the first clue to the diagnosis in some patients.
The prognosis for patients with cutaneous involvement by leukemia is generally poor. It suggests widely dissemi- nated disease in most cases. However, for patients with CLL, there is no evidence that the presence of neoplastic lymphocytes within the dermis serves as any type of adverse marker and long-term survival has been seen in these patients.
There is no specific treatment for the cutaneous leuke- mia other than palliation and symptomatic relief. Aggres- FIGURE5.1. Widely scattered viola-
ceous nodules of leukemia cutis.
FIGURE5.2. Low power photomicrograph of dense dermal infil- trate in leukemia cutis. Note the Grenz zone typical of this condition.
Similarly, the chronic myeloid leukemias feature imma- ture myeloid forms coursing throughout the dermis.
In these types of leukemia, abundant mitoses and indi- vidual cell necrosis are common features. This subtype of leukemia is usually straightforward to recognize in the skin.
The lymphoid leukemias are more difficult to recognize as involving the skin. In acute lymphoblastic leukemia (ALL), large and atypical immature cells are present
26 Deadly Dermatologic Diseases
sive and appropriate treatment of the bone marrow–derived process is the appropriate regimen. Even in patients with no evidence of leukemia on bone marrow biopsy, close clinical follow-up is essential and treatment is indicated in some patients.
References
1. Traweek ST, Arber DA, Rappaport H, Brynes RK.
Extramedullary myeloid cell tumors: An immunohisto- chemical and morphologic study of 28 cases. Am J Surg Pathol 1993; 17: 1011–1019.
2. Su WPD, Buechner SA, Li C-Y. Clinicopathologic correlations in leukemia cutis. J Am Acad Dermatol 1984; 11: 121–128.
3. Stawiski MA. Skin manifestations of leukemias and lymphomas. Cutis 1978; 21: 814–818.
4. Baer MR, Barcos M, Farrell H, Raza A, Preisler HD. Acute myelogenous leukemia with leukemia cutis: Eighteen cases seen between 1969 and 1986. Cancer 1989; 2192–2200.
5. Forjaz de Lacerda J, do Carmo A, Guerra L, Soares de Almeida L, Fernandes A, Forjaz de Lacera JM. Leukemia
FIGURE5.3. High power detail of neoplastic infiltrate. Note the large atypical cells with vesicular nuclei and surrounding myeloid precur- sors with eosinophilic cytoplasm.
cutis in acute lymphoblastic leukemia. J Am Acad Dermatol 1994; 30: 1041–1043.
6. Long JC, Mihm MC. Multiple granulocytic tumors of the skin: Report of six cases of myelogenous leukemia with initial manifestations in the skin. Cancer 1977; 39:
2004–2016.
7. Kaiserling E, Horny H-P, Geerts M-L, Schmid U. Skin involvement in myelogenous leukemia: Morphologic and immunophenotypic heterogeneity of skin infiltrates. Mod Pathol 1994; 7: 771–779.
8. Longacre TA, Smoller BR. Leukemia cutis: Analysis of 50 biopsy-proven cases with an emphasis on occurrence in myelodysplastic syndrome. Am J Clin Pathol 1993; 100:
276–284.
9. Cerroni L, Zenahlik P, Kerl H. Specific cutaneous infiltrates of B-cell chronic lymphocytic leukemia arising at the site of herpes zoster and herpes simplex scars. Cancer 1995; 76:
26–31.
10. Smoller BR, Warnke RA. Cutaneous infiltrate of chronic lymphocytic leukemia and relationship to primary cutaneous epithelial neoplasms. J Cutan Pathol 1998; 25:
160–164.
