Oncology Case Challenge: A Retired Man With Left Upper Quadrant Pain, Leukocytosis

Kevin Zablonski; Jerry Wong, MD, PhD; Francisco J. Hernandez-Ilizaliturri, MD

Disclosures

May 04, 2022

Discussion

Hairy cell leukemia (HCL) is a rare lymphoproliferative B-cell disorder. In the United States, the incidence is approximately 1000 cases per year, and HCL accounts for roughly 2% of all leukemia diagnoses.[1] About 10% of cases involve a variant form of the disorder (HCL-v),[2] which often progresses more rapidly and requires multiple lines of therapy.[3,4] In rare cases, HCL can involve the CNS, which corresponds with worse outcomes.[5]

HCL is typically treated with single-agent cladribine therapy, with high overall response rates that translate into a prolonged remission.[6] Nevertheless, HCL is an incurable disease, and an estimated 25%-40% of patients with HCL develop relapsed or refractory disease within 5-10 years of treatment.[7,8,9] The management of relapsed or refractory HCL considers prior lines of therapy, comorbid conditions, age, and more recently, the variable expression of cell surface proteins (such as CD20, CD22, and CD25) and the presence of DNA mutations (such as those encoding BRAF V600E) in B cells that can distinguish HCL-v from HCL.[10,11,12]

In this case, the differential diagnosis was initially narrowed to HCL or HCL-v owing to the presence of hairy cells in the peripheral blood, a bone marrow biopsy showing evidence of neoplastic cells, and an evaluation of the CD surface molecule expression. B-cell–associated markers (CD19, CD20, and CD22), as well as CD11c and CD103, are expressed in both HCL and HCL-v.[10] However, the expression of CD25 and CD123 varies. HCL-v B cells lack CD25 and exhibit reduced expression (40%) or no expression (60%) of CD123, whereas B cells in HCL are typically positive for both.[12] Because flow cytometry in this case revealed expression of CD11c, CD20, CD22, CD103, as well as diminished expression of CD123 and absence of CD25, HCL-v was suspected. This suspicion was further supported by the absence of both annexin-A1 and the BRAF V600E mutation, which are present in 74% and 76%-100% of HCL cases, respectively.[12,13]

Other cancers, such as acute lymphoblastic leukemia (ALL), chronic lymphocytic leukemia (CCL), and chronic myelomonocytic leukemia (CMML) can be ruled out on the basis of the patient's pathologic workup. Unlike the large, granular cell population noted on bone marrow aspirate in this case, the cell population in ALL is characterized by small size and the absence of granules.[14] Moreover, patients with ALL are positive for CD34 in about 70% of cases and are often positive for CD13 and/or CD33.[15] CLL exhibits positive expression of CD5, CD10 (in some cases), and CD23, in addition to typical B-cell markers, excluding it as a possible diagnosis.[16] Part of the diagnostic criteria of CMML includes over 3 months of peripheral blood monocytosis (≥ 1 × 109/L), with monocytes accounting for 10% or more of the WBC count, which was not observed in this case.[17]

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