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

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


May 04, 2022

Physical Examination and Workup

The patient's initial vital signs are unremarkable. Physical examination findings include trace lower extremity edema as well as a 3/6 systolic murmur. No cervical, supraclavicular, axillary, or inguinal lymphadenopathy or organomegaly is noted. The patient reports that he is in his usual state of health.

Initial laboratory studies are significant for a white blood cell (WBC) count of 16,200/mm3 (reference range, 4500-11,000/mm3) and an absolute lymphocyte count of 9072/mm3 (reference range, 1000-4800/mm3). These laboratory abnormalities are monitored intermittently over the course of the next year without significant change. During this period, the patient remains asymptomatic and in relatively good health otherwise. However, he subsequently begins to develop fatigue in addition to left upper quadrant pain, which prompts further workup.

A peripheral blood smear shows atypical lymphocytes with abundant cytoplasm and hairlike projections. Flow cytometry examination reveals a clonal B-cell population that expresses bright CD11c, bright CD20, and lambda light chain but is negative for CD5, CD10, CD23, and CD25. A bone marrow biopsy is performed, and immunohistochemistry shows that the neoplastic cells are positive for CD20 and PAX5 (Figure 1A and 1B) and negative for CD5, CD10, cyclin D1, BCL-6, and CD123. Immunostaining for annexin-A1 is also negative. Flow cytometric analysis of the bone marrow aspirate detects an abnormal cell population that is larger and more granular than lymphocytes and expresses bright CD11c in addition to CD19, CD20, CD45, CD103, CD123 (dimly in a minor subset), and monotypic lambda light chain (Figure 1D). The abnormal cell population is negative for CD5, CD10, CD23, and CD25.

Figure 1.

Because of his worsening symptoms and lymphocytosis, in addition to marked splenomegaly revealed on imaging, the patient is treated with cladribine. Nine months later, he reports a recurrence of symptoms, and bloodwork shows persistent lymphocytosis. The patient is then treated with cladribine and rituximab and reports an improvement in symptoms. Laboratory values obtained 2 months after treatment show a WBC count of 6200/mm3.

Unfortunately, his disease progresses within several weeks, and bloodwork reveals a WBC count of 52,800/mm3 and an absolute lymphocyte count of 48,570/mm3. A peripheral blood smear shows small- to medium-sized atypical lymphoid cells with cytoplasmic projections (Figure 1C). Flow cytometric analysis of the peripheral blood confirms relapse; however, functional imaging, laboratory studies, and pathologic examination fail to demonstrate transformation into a high-grade cancer. Next-generation sequencing of the patient's B cells unveils a MAP2K1 mutation but is negative for BRAF, IGHV, and downstream MEK/ERK mutations.

In addition to a recurrence of prior symptoms, the patient reports worsening vision along with impairments of right eye adduction and left eye abduction. MRI of the brain shows bilateral variable-sized foci of cerebral hemorrhaging of various ages involving both cerebral hemispheres, the cerebellum, and the brainstem (Figure 2). Cerebrospinal fluid (CSF) collected by lumbar puncture is negative for infectious agents but is positive for atypical hairy lymphoid cells in a background of red blood cells.

Figure 2.


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