Wallach's Interpretation of Diagnostic Tests: Pathways to Arriving at a Clinical Diagnosis (340 page)

   The most common mutation associated with the myeloproliferative variant of the
HES
is that presenting with the fusion tyrosine kinase FIPIL1/ PDGFRA (F/P).

   F/P is cytogenetically cryptic and requires FISH analysis for detection. Patients with these genetic markers respond to tyrosine kinase inhibitors such as imatinib mesylate and are considered and classified as separate entities.

   
CEL
: Certain clonal abnormalities may be demonstrated, most frequently involving chromosomes 5, 7, 8 (the 8p11 syndrome), 10, 15, or 17. The best defined entity in CEL is t(5;12)(q33;p13) involving PDGFRB. In the absence of clonal abnormalities, the diagnosis is more difficult, and the hypereosinophilic syndrome may be considered.

   Interleukin 5: overproduction in some patients.

   Elevated troponin levels suggest cardiac involvement by HES.

Suggested Readings

Klion AD. How I treat hypereosinophilic syndrome.
Blood.
2009;114:3736–3741.

Oliver JW, Deol I, Morgan DL, et al. Chronic eosinophilic leukemia and hypereosinophilic syndromes.
Cancer Genet Cytogenet.
1998;107:111–117.

Tefferi A. Blood eosinophilia: a new paradigm in disease classification, diagnosis, and treatment.
Mayo Clin Proc.
2005;80:75–83.

CHRONIC LYMPHOCYTIC LEUKEMIA (CLL)/SMALL LYMPHOCYTIC LYMPHOMA (SLL)

   Definition

CLL/SLL is an indolent clonal proliferation of mature B lymphocytes, leading to an accumulation of these cells in the peripheral blood, bone marrow, spleen, and lymph nodes. B-cell CLL is considered identical (one disease at different stages) with the mature B-cell neoplasm small lymphocytic lymphoma (SLL), an indolent non-Hodgkin lymphoma. SLL by itself refers to the nonleukemic cases. This section will present CLL/SLL as one entity.

   Who Should Be Suspected?

Individuals who present with persistent (at least 3 months) absolute lymphocytosis of ≥5,000/μL, frequently with lymphadenopathy and splenomegaly. The patient may be asymptomatic or present with symptoms related to anemia, neutropenia, or immune deficiency, but rarely bleeding.

In the absence of extramedullary tissue involvement, there must be ≥5,000/μL monoclonal lymphocytes with CLL phenotype in the peripheral blood for the diagnosis of CLL. CLL/SLL is more common in patients >55 years of age, but it may be encountered in young individuals.

   Diagnosis

The simplest way to diagnose CLL is by flow cytometry, where the presence of a clone of mature B lymphocytes with characteristic immunophenotype confirms the diagnosis (see below for details).

   Laboratory Findings

   CBC

   Anemia, when present, is normochromic, normocytic and connotes advanced disease. In some cases, it is autoimmune, with a positive direct Coombs test. If the etiology of anemia is autoimmune, the anemia by itself does not categorize the disease as being in an advanced stage. Autoimmune hemolytic anemia may also develop as a complication of purine analog therapy.