Leukemia Cutis Workup

A complete blood count is performed to assess the degree of anemia, thrombocytopenia, and neutropenia or leukocytosis. If these measurements are low, supportive treatments may be given or precautionary measures may be initiated. A peripheral blood smear to look for circulating leukemic cells and to assess for disseminated intravascular coagulation should be performed.

Chemistry profile is necessary to assess baseline levels for BUN and creatinine prior to initiation of chemotherapy and to monitor these levels during chemotherapy as a reflection of renal function. Most patients with leukemia have an elevated lactic dehydrogenase (LDH) level and an elevated uric acid level. Elevation of LDH is often a poor prognostic sign.

Liver function tests and BUN and creatinine determinations are necessary prior to the initiation of therapy because many chemotherapeutic agents may adversely affect either renal function or hepatic function. Additionally, some agents, such as methotrexate, may be contraindicated in individuals with hepatic dysfunction.

Some leukemias may have other electrolyte abnormalities, including hypokalemia, hypocalcemia, and/or hypomagnesemia. In adult T-cell leukemia/lymphoma (ATLL), hypercalcemia occurs in approximately one third of all patients.

Appropriate cultures should be obtained in patients with fever or signs of infection.

Imaging studies should be obtained based on the patient's symptoms to determine the extent of extramedullary involvement of leukemia or potential sites of infection. Some imaging studies may be needed to assess the baseline status prior to chemotherapy administration; for example, echocardiography may be performed prior to the initiation of chemotherapy.

In all the leukemias, chest radiography may show evidence of an infection, such as pneumonia. In some cases of T-cell acute lymphocytic leukemia (ALL), mediastinal lymphadenopathy may be present.

Typical hepatomegaly and splenomegaly may be imaged by using a liver/spleen scan. Most often, these findings are so obvious in cases of chronic lymphocytic leukemia (CLL), hairy cell leukemia, and ATLL that imaging is unnecessary because the organs are easily palpable. In milder cases, liver or spleen scan or ultrasonography may reveal more subtle organomegaly.

Computed tomography of the chest, the abdomen, or the pelvis is generally not required for staging purposes. However, be careful not to miss lesions, such as obstructive uropathy or airway obstruction, that are caused by lymph node compression on organs or internal structures.

Cytogenetic studies and flow cytometry on peripheral blood may be performed. In cases of ATLL, studies to assess monoclonal integration of the HTLV-I genome into genomic DNA are helpful.

Skin biopsy

Skin biopsy with appropriate immunohistochemical staining is the key to diagnosing aleukemic leukemia cutis or identifying leukemia cutis, a sign of extramedullary extension of the leukemia, and a poor prognosis. This diagnosis will likely impact the most appropriate course of treatment.

Bone marrow aspiration and biopsy are the definitive diagnostic tests for the diagnosis of systemic leukemia. Bone marrow aspirates should be stained with either Wright stain or Giemsa stain for morphologic analysis. In addition, slides should be stained with immunocytochemical stains to determine the cell lineage and the degree of maturation. Bone marrow samples should be sent for cytogenetic and flow cytometric studies.

Immunophenotyping

Immunophenotyping of infiltrates with specific markers is a valuable adjunct in confirming the diagnosis of leukemia cutis and in differentiating specific from nonspecific cutaneous infiltrates. Specific markers include the following: CD3 (T cells), CD45RO (mature T cells), CD45/LCA (leukocyte common antigen) (lymphocytes, monocytes), CD43 (T cells, monocytes, and granulocytes), CD20 (B cells), CD30 (activated T cells), CD68 (monocytes), and lysozyme (granulocytes, monocytes) (see Table 2 below).

Table 2. Recommended Immunohistochemical Stains For Leukemia Cutis (Open Table in a new window)

Chloroacetate esterase stains CML and most subtypes of AML but not AML-M4. However, lysozyme should stain all forms of AML and CML.

AML-M4 types express CD43 and CD68 as well. CD43, CD45, and CD15 are positive in almost all types of AML-M5 and AML-M4.

B-cell CLL cells express B-cell markers, including dimCD20. In T-cell CLL, CD45RO and CD3 are either negative or only weakly positive. ATLL cells stain with CD3, CD4, and CD25. CD8 is most often negative.

Hairy cell leukemia cells, which are of the B-cell lineage, stain strongly with tartrate-resistant acid phosphatase. Hairy cells have a mature B-cell phenotype and express immunoglobulin light chains and B-cell antigens, such as CD19, CD20, and CD22, but not CD21. Monoclonal Bly-7 has a high sensitivity and specificity for hairy cell leukemia. CD22 stains hairy cell leukemia more prominently than normal B cells.

The histologic findings in leukemia cutis vary depending on the subtype of leukemia. Typically, little epidermal involvement with an underlying grenz zone is present. A dermal infiltrate of leukemic cells, which is often perivascular and periadnexal, is present. Collagen bundles may be prominently separated by leukemic cells. The leukemic cells may also infiltrate along the fibrous septae of the subcutaneous fat. The cells may be seen in the lumina of the blood vessels as well as infiltrating the walls, producing a leukemic vasculitis.

Cells in AML are large with an oval, vesicular nucleus and basophilic cytoplasm. Note the images below.

In CML, a variety of cells at varying degrees of maturation are present. Eosinophils may be present. Note the image below.

ALL shows medium-to-large blast cells, with a high nuclear-to-cytoplasmic ratio.

CLL shows small, more uniform, mature lymphocytes. These have dense nuclear chromatin. T-cell CLL may show epidermotropism, as do other T-cell leukemias.

Monocytic leukemia may be confused with large cell lymphoma because of the large nucleus with fine chromatin and prominent nucleoli. The nuclei are often indented or kidney shaped and slightly basophilic in appearance. Monocytic leukemia often involves the entire dermis and the superficial panniculus.

ATLL cells show an indented to lobulated nucleus, which has led to the term flower cells to describe the morphology. ATLL unlike many of the other leukemic infiltrates often shows epidermotropism. Pautrier microabscesses, as can be seen in mycosis fungoides, may be present.

Hairy cell leukemia, like many other forms of leukemia cutis, infiltrates the dermis and the subcutaneous fat. It too shows prominent periadnexal and perivascular infiltration. The infiltrate consists of monomorphous mononuclear cells. A grenz zone is typically present. Note the images below.

Staging is extensively discussed in other articles about each of the subtypes of leukemia elsewhere in the eMedicine Journal.