Dr. Johnson treated us to a interesting case where a patient who had a known diagnosis of myelodysplastic syndrome presented with leukemia cutis.
What are Myelodysplastic Syndromes?
The myelodysplastic syndromes (MDS) are clonal disorders of the hematopoietic stem cells characterized by dysplastic and ineffective blood cell production. They results in reduced production of red blood cells, platelets, and mature granulocytes, although patients can also have functional defects.
These occur predominantly in patients older than age 60. Bone marrow biopsy will reveal a hypercellular marrow with dyserythropoiesis.
Keys to diagnosis:
Look for cytopenias in 2 out of the 3 cell lines!
Up to 50% of patients may present only with anemia and an elevated MCV in the setting of normal Vitamin B12 & folate levels
Deletions involving chromosomes 3, 5, 7, 8 & 17 are supportive of MDS as a diagnosis
There is a variable risk of transformation to acute leukemia: this is a feared complication because it is uniformly resistant to treatment and associated with short survival. Most patients either progress to this or die of complications related to bone marrow failure.
Because of this natural history, the revised International Prognostic Scoring System (IPSS-R) for Myelodysplastic Syndromes is used to determine management.
Low-risk MDS is managed with symptomatic transfusions and observation. High-risk and very high risk patients should be offered bone marrow transplantation if young or treatment with azacytidine and decitabine if not a candidate for BMT.
What is AML?
Acute myeloid leukemia (AML) is a malignant clonal proliferation of immature myeloid cells.
AML can appear:
De novo
After exposure to radiation, benzene, or chemotherapy
As a transformation from CML, MDS, or PV
Age is the greatest risk factor. The mean age at presentation is 67 years.
Clinically, AML can present with the following:
-Symptoms of anemia/neutropenia/thrombocytopenia
-Pallor, petechiae, ecchymosis
-Gingival Hypertrophy
-Leukemia cutis
Clues to the diagnosis of AML:
The diagnosis is suggested by an elevated leukocyte count, anemia, thrombocytopenia, and blasts on the peripheral smear.
AML is the leukemia most likely to involve significant thrombocytopenia!
Patients often present with bruising, bleeding, petechiae and/or infection.
If the patient has lymphadenopathy or hepatosplenomegaly, it is very unlikely to be AML!
Auer rods are pathogonomic for AML. These can be seen on the peripheral blood smear.
Diagnosis requires 20% or more myeloblasts in either the peripheral blood or the marrow. Cytogenetic studies should be done, because these can classify patients based on their risk for relapse and other prognostic factors.
APL
Acute promyelocytic leukemia (APL) is a special case: this is defined by the presence of the t(15;17) translocation resulting in disruption of a retinoic acid receptor. Patients generally present acutely ill, with significant bleeding or even in DIC. ATRA is the backbone of therapy for acute promyelocytic leukemia. These patients are at risk for developing differentiation syndrome, which characteristically presents with fever, pulmonary infiltrates, hypoxemia, and potentially hyperleukocytosis. Treat with dexamethasone.
What do I do if I think my patient has leukemia?
It is CRITICAL to involve hematology/oncology as soon as possible if you suspect an acute leukemia because your goal is to start induction chemotherapy within 24 hours for some types of leukemia.
To do this, you need to first confirm if the patient actually has leukemia. You should exclude leukemoid reaction, atypical monocytosis, and chronic leukemias. This generalyl involves a peripheral blood smear and flow cytometry.
If leukemia is confirmed, is it AML versus ALL?
If AML, you want to then exclude APL. Start treatment (induction) with cytarabine and an anthracycline if non-APL AML. Start treatment with ATRA if APL.
If ALL, you have a little more time...
References
Up-to-Date
Dr. Ehab Atallah didactic sessions on leukemia service
Bakst RL, Tallman MS, Douer D, Yahalom J. How I treat extramedullary acute myeloid leukemia. Blood 2011; 118:3785.
Kaleem Z, Crawford E, Pathan MH, et al. Flow cytometric analysis of acute leukemias. Diagnostic utility and critical analysis of data. Arch Pathol Lab Med 2003; 127:42.
Ratnam KV, Khor CJ, Su WP. Leukemia cutis. Dermatol Clin 1994; 12:419.
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