Leukemias

J Cutan Pathol 2008; 35: 180–185. Abstract quote

Background: The histologic diagnosis of myeloid leukemia cutis (LC) can be difficult, requiring confirmatory immunohistochemical stains.

Objective: We reviewed 21 biopsy-proven cases of LC with emphasis on the use of immunohistochemistry in the diagnosis.

Materials and Methods: Clinical and histologic features were reviewed on 21 cases of biopsy proven LC. Immunohistochemical stains for CD4, CD34, CD56, CD68, CD117, CD123, TdT, lysozyme and myeloperoxidase were performed on 12 with available tissue blocks.

Results: Ages ranged from 24 to 88 years (mean = 57), with 12 men: 9 women. Primary hematologic diagnoses included acute myeloid leukemia (n = 14), myelodysplastic syndrome (n = 3), essential thrombocythemia (n = 1) and myeloid leukemia, NOS (n = 3). Monocytic myeloid LC was most common (35%). There was 100% positivity with CD68 and lysozyme. Myeloperoxidase, CD117 and CD34 immunostains were less sensitive in myeloid LC (58%, 33% and 17%, respectively). CD4 was positive in 67%. CD56 was positive in 33%.

Conclusion: Myeloid leukemia with monocytic differentiation more commonly involves the skin than other types of myeloid leukemia. CD68 and lysozyme immunostains, although not lineage specific for monocytes/macrophages, are the most sensitive immunostains in the detection of myeloid LC. Myeloperoxidase immunostains are useful, but immunostains for CD117 and CD34 are insufficiently sensitive. CD4 expression is common, but CD56 expression is not.

Epidemiology
Disease Associations
Pathogenesis
Laboratory/Radiologic/Other Diagnostic Testing
Gross Appearance and Clinical Variants
Histopathological Features and Variants
Special Stains/ Immunohistochemistry/ Electron Microscopy
Differential Diagnosis
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GROSS APPEARANCE/ CLINICAL VARIANTS	CHARACTERIZATION
VARIANTS
LEUKEMIA CUTIS	1-50% of leukemic patients depending upon the type of leukemia Leukemic infiltration of the skin May present as macules, papules, palpable purpura, ulcers, erythroderma, and bullous lesions
Leukemia cutis in a patient with chronic neutrophilic leukemia	J Am Acad Dermatol 2001;44:365-9 Case report of a patient with a 2-week history of a pruritic eruption on the arms, hands, and legs Physical examination revealed red to violaceous plaques on both thighs and knees, in addition to purpuric patches and plaques on the dorsal hands, arms, and legs Leukemia cutis was demonstrated on biopsy specimens of several lesional sites The dermal infiltrate consisted of a mixture of immature and mature neutrophilic elements, rather than a predominantly mature neutrophilic dermatosis-the differential diagnosis included Sweet's syndrome The eruption progressed, despite treatment with topical and systemic corticosteroids Treatment with systemic chemotherapy did affect partial resolution of the eruption, with parallel decreases in bone pain and white blood cell count, but the disease progressed and the patient ultimately died 5 months after her initial skin findings
Cutaneous promyelocytic sarcoma at sites of vascular access and marrow aspiration. A characteristic localization of chloromas in acute promyelocytic leukemia? Sanz MA, Larrea L, Sanz G, Martin G, Sempere A, Gomis F, Martinez J, Regadera A, Saavedra S, Jarque I, Jimenez C, Cervera J, de La Rubia J. Servicio de Hematologia, Hospital Universitario La Fe, Av. Campanar 21, 46009 Valencia, Spain.	Haematologica 2000 Jul;85(7):758-62 Abstract quote Extramedullary disease (EMD) is a rare clinical event in acute promyelocytic leukemia (APL). Although the skin is involved in half of the reported EMD cases, the occurrence of cutaneous promyelocytic sarcoma (PS) has been described very rarely. We report here three cases of PS which have the peculiarity of appearing at sites of punctures for arterial and venous blood and marrow samples (sternal manubrium, antecubital fossa, wrist over the radial artery pulse, catheter insertion scar). At presentation, all patients had hyperleukocytosis and a morphologic diagnosis of microgranular acute promyelocytic leukemia variant confirmed at the genetic level by demonstration of the specific chromosomal translocation t(15;17). A BCR3 type PML/RARa transcript was documented in the two patients for whom diagnostic RT-PCR was available. Patients had morphologic bone marrow remission at the time the PS appeared. A predilection for the development of cutaneous PS at sites of previous vascular damage has been noted, but the pathogenesis remains largely unknown. A potential role for all-trans retinoic acid has been advocated, although one of the three patients in our series had received no ATRA. A review of the literature revealed six similar cases and hyperleukocytosis at diagnosis was a consistent finding in all of them. A careful physical examination of these particular sites in the follow-up of patients at risk, as well as cutaneous biopsy and laboratory examination of suspected lesions are strongly recommended.

PROGNOSIS AND TREATMENT	CHARACTERIZATION
CLASSIFICATION
The immunophenotype of 325 adult acute leukemias: relationship to morphologic and molecular classification and proposal for a minimal screening program highly predictive for lineage discrimination. Thalhammer-Scherrer R, Mitterbauer G, Simonitsch I, Jaeger U, Lechner K, Schneider B, Fonatsch C, Schwarzinger I. Department of Laboratory Medicine, University of Vienna, Austria.	Am J Clin Pathol 2002 Mar;117(3):380-9 Abstract quote Bone marrow cells of 325 adults with acute leukemia were immunophenotyped using a panel of monoclonal antibodies proposed by the European Group for the Immunological Characterization of Leukemias (EGIL). Of these, 97.2% could be assigned clearly to myeloid or lymphoid lineage (254 acute myeloid leukemias [AMLs], 48 B-cell lineage acute lymphoblastic leukemias [ALLs], 14 T-cell lineage ALLs), 1.8% as biphenotypic, and less than 1% as undifferentiated. Immunologic subtyping of ALLs revealed an association between early precursor phenotypes and coexpression of myeloid antigens, particularly CD15/CD65s coexpression and pre-pre-B cell-specific phenotypes and genotypes. The common ALL phenotype was associated with BCR-ABL translocation. Among AMLs, CD2 coexpression was almost exclusively restricted to French-American-British subtypes M3 variant and M4Eo and related molecular aberrations. The most valuable markers to differentiate between myeloperoxidase-negative AML subtypes M0 and ALLs were CD13, CD33, and CD117, typical of M0, and intracytoplasmic CD79a, intracytoplasmic CD3, CD10, and CD2, typical of B cell- or T cell-lineage ALL. Our results confirm excellent practicability of the EGIL proposalfor immunologic classification of acute leukemias. For myeloperoxidase-negative AMLs, we suggest a scoring system based on markers most valuable to distinguish between AML-M0 and ALLs.
TREATMENT	See individual leukemias

Myeloid leukemia cutis: a histologic and immunohistochemical review