Case of the Week #27

16 November 2005 – Case of the Week #27

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We thank Dr. Misty Jacobs, Medical University of Ohio, Toledo, Ohio (USA) for contributing this case. We invite you to contribute a Case of the Week by sending an email to NPernick@PathologyOutlines.com with microscopic images (any size, we will shrink if necessary) in JPG or GIF format, a short clinical history, your diagnosis and any other images (gross, immunostains, EM, etc.) that you have and that may be helpful or interesting. We will write the discussion (unless you want to), list you as the contributor, and send you a check for $35 (US) for your time after we send out the case. Please only send cases with a definitive diagnosis.

Case of the Week #27

Clinical History

A 22 year old white female presented with complaints of pelvic pain for two weeks that worsened over the past 24 hours. Her history was positive for a 12 lb weight loss occurring within a month, and also for endometriosis.

Her white blood count was elevated at 103K. Her peripheral blood smear showed: image

Other laboratory tests were as follows:

Test results (reference range)

WBC: 102.7 thous/mm3 (4.0-10.0 thous/mm3)

RBC: 4.09 mill/mm3 (3.5-5.5 mill/mm3)

HGB: 11.8 g/dl (12.0-15.0 g/dl)

HCT: 35.0 % (36.0-48.0 %)

MCV: 85.6 CU MICR (80.0-100.0 CU MICR)

MCH: 28.8 uuG (24.0-32.0 uuG)

MCHC: 33.7 % (32.0-36.0 %)

RDW: 17.4 (11.5-16.9)

Platelets: 398 thou/mm3 (100-400 thou/mm3)

Segs: 51.0 % (50-70%)

Bands 23.0 % (0-4%)

Lymphs: 2.0 % (20-40 %)

Monos: 2.0 % (2-8 %)

Eosin: 1.0 % (0-5%)

Baso: 3.0 % (0-2%)

Leukocyte Alkaline Phosphatase: 27

What is your diagnosis?

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Diagnosis

Chronic Myelogenous Leukemia

Discussion

Chronic myeloid leukemia is the most common chronic myeloproliferative disease, with an annual incidence of 1-2 cases per 100,000 population. It is characterized by an increased proliferation of granulocytes, which retain the capacity to differentiate. It typically affects older adults, usually ages 30-49 years. Presentation in adolescents or young adults is less common, and is often associated with genetic disorders or radiation exposure (Leuk Lymphoma 2004;45:613)

Presentation is typically insidious, with anemia, fatigue and weight loss. Patients often have a dragging sensation due to splenomegaly, which may be massive. Diagnosis is based on clinical features of hepatosplenomegaly (due to extramedullary hematopoiesis) and lymphadenopathy. The bone marrow is up to 100% cellular with increased granulocyte precursors, basophils and eosinophils, but a normal erythroid compartment, and normal or increased megakaryocytes in small clusters. The peripheral blood shows an elevated white blood count, often >100,000, with neutrophils, metamyelocytes and myelocytes, and variable eosinophilia, basophilia and sea-blue histiocytes (image). Half of patients have associated thrombocytosis. Neoplastic granulocytes in >95% of patients have the Philadelphia chromosome, a distinct translocation - t(9;22)(q34;q11) (image). This translocation involves the ABL gene at #9q34 and the BCR gene at #22q11, and produces a 210 kd fusion protein with tyrosine kinase activity. It may be detected by cytogenetics, FISH or PCR. Patients typically also have a low leukocyte alkaline phosphatase score (LAP), in contrast to leukemoid reactions and other chronic myeloproliferative disorders which typically have an increased LAP score. The granulocytes in CML have reduced apoptosis, causing longer lifetimes, but lower levels of enzymes such as alkaline phosphatase. The differential diagnosis of CML includes a leukemoid reaction (high LAP score, no translocation) and other chronic myeloproliferative disorders.

Treatment includes imatinib mesylate (Gleevec/STI571), an oral tyrosine kinase inhibitor, which causes hematologic remission in 90% of patients. Other treatments, more common in the past, were interferon alfa and hydroxyurea. Bone marrow follow up is suggested, because patients may progress to blast crisis even with hematologic response to treatment (Archives 2004;128:980).

Additional references: eMedicine

Nat Pernick, M.D.
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