A classic presentation of an uncommon leukemia
Authors: Kara N. Maxwell, David L. Porter
Journal: American Journal of Hematology (2012)

A 45-year-old man presented to the Emergency Department with lower back pain, fatigue, weight loss, and shortness of breath. He had an elevated white blood cell count of 36,500 cells/μl with a differential cell count of 35% neutrophils, 1% bands, 22% lymphocytes, 5% monocytes, 1% eosinophils, and 30% “blasts.” The hemoglobin was 4.8 g/dl and platelets were 11,000 cells/μl. His creatinine was 2.9 mg/dl, uric acid 13.0 mg/dl, lactate dehydrogenase 516 units/l, phosphorus 4.9mg/dl, calcium 11.7 mg/dl, and potassium 4.3mg/dl. Review of the blood smear (Image 1A, black arrows) revealed cytologically atypical cells with eccentric irregular nuclei with gray blue cytoplasm. Peripheral blood flow cytometry showed a population of CD13−, CD33−, CD34−, CD64−, CD117−, Human leukocyte antigen (HLA)-DR−, and myeloperoxidase (MPO) (very dim)+ blasts indicative of a poorly differentiated acute leukemia. Bone marrow core biopsy was performed at the right posterior iliac crest; as the marrow was inaspirable, an aspirate was also attempted from the left posterior iliac crest but was again unsuccessful. (A) Peripheral blood smear from the patient at presentation shows cytologically atypical cells with eccentric irregular nuclei with gray blue cytoplasm (black arrows). (B) Examination of H&E-stained bone marrow core biopsy at 5× power shows nearly 100% involvement with multiple myeloma. In the inset, extensive fibrosis is seen in the bone marrow by reticulin staining. (C) Examination of H&E-stained bone marrow core biopsy at 40× power shows cytologically atypical and mitotically active spindle cells with irregular large nuclei and variable amounts of cytoplasm; in addition, normal trilineage hematopoiesis is notably absent. (D) A representative axial T2-weighted section from an MRI with gadolinium of the lumbar spine shows rim enhancing intraosseous lesions (white arrows) and unusual bilateral posterior iliac defects (white arrowheads). The bone marrow evaluation revealed sheets of cytologically atypical and mitotically active spindle cells with irregular large nuclei and variable amounts of cytoplasm, absent trilineage hematopoiesis (Image 1B,C), and marked reticulin fibrosis (Image 1B inset). Immunostains showed that the neoplastic cells were strongly positive for CD138 and weakly positive for cytoplasmic lambda light chain. A second peripheral blood sample revealed a population of cytoplasmic lambda restricted, CD38+, CD138+, CD45(dim)+, CD56− plasma cells. These results confirmed a diagnosis of multiple myeloma in leukemic phase. Flourescent in situ hybridization (FISH) studies showed an atypical Immunoglobulin heavy chain (IGH) rearrangement with an unknown partner (IGH not otherwise specified, NOS). Cytogenetics revealed deletion 6q13–q25, deletion 20q11.2-qter, trisomy 7q, monosomy 7p, monosomy 13, and material of unknown origin replacing 14q32-qter. Given the patient's severe back pain, a Magnetic Resonance Imaging (MRI) scan of the lumbar spine with gadolinium was performed which showed multiple rim enhancing intraosseous lesions involving the lumbar vertebrae, sacrum, and iliac bones bilaterally (Image 1D, white arrows). This study also showed moderate adenopathy in the retroperitoneum, and the findings were felt to be consistent with leukemia versus infection. In addition, unusual bilateral posterior iliac defects were found as shown in the representative axial T2 image (Image 1D, white arrowheads). Soon after presentation, the patient required intubation for progressive pneumonia. His clinical status continued to deteriorate and he died 20 days after presentation despite maximal supportive care. Plasma cell leukemia (PCL) accounts for less than 0.2% of all leukemia cases and has an incidence of 0.2–0.3 cases per million people 1. PCL is considered primary when diagnosed in leukemic phase or can occur in patients previously diagnosed with multiple myeloma, and ∼30% of patients die within 1 month of diagnosis 1, as in this case. PCL is often associated with multiple cytogenetic abnormalities and one study found IGH rearrangements and monosomy 13, as seen in this case, to be the most common abnormalities in PCL, although the effect on prognosis is unclear 2, 3. Patients with PCL can have extramedullary deposits of plasma cells 1, and although bone deposits have not been reported in PCL, MRI findings of multiple myeloma can include peripheral enhancing lesions on T2 images representing tumor nodules as seen in this case 4. This patient's MRI also showed unusual bone defects in the posterior iliac crests which were quickly realized to be the tracks from recent removal of bilateral bone marrow core biopsies. There are no prospective randomized clinical trials to guide treatment of PCL. Current consensus is to treat patients with good performance status with a bortezomib-based regimen such as VDT-PACE (bortezomib, dexamethasone, thalidomide, cisplatin, doxorubicin, cyclophosphamide, and etoposide) 5. Extrapolating from data with multiple myeloma 5, patients under age 65 may be treated with hematopoietic stem cell transplantation. In patients refractory to bortezomib based regimens, there may be a role for high-dose cyclophosphamide salvage therapy 6.