A 64-year-old Caucasian woman, whose prior medical history was significant for type 2 diabetes mellitus and hypertension, presented to medical attention in mid-2017 with intermittent left upper quadrant abdominal pain and diarrhea of several months duration. Laboratory studies included a normal chemistry panel and an unremarkable complete blood count (CBC) with the exception of a modestly elevated platelet count of 480 x 109 cells/L (normal, 150-400 x 109 cells/L). After 5 weeks of persistent gastrointestinal symptoms, a CT scan of the abdomen identified a hypodense splenic lesion measuring 2.7 cm and no other abnormalities. A diagnosis of sclerosing angiomatoid nodular transformation of the spleen was favored over other potential etiologies.
Five months later, she presented to medical attention complaining of intense abdominal pain, diarrhea, and 20-pound weight loss, which she attributed to increasing pain with eating as well as early satiety. She did not have fevers or night sweats. Her physical exam was notable for the absence of palpable lymphadenopathy or splenomegaly, and her CBC and comprehensive metabolic panel, including serum LDH, were all within normal limits. Her hemoglobin A1C was 6.4% (normal, 4.0%-5.6%). A CT scan of the abdomen showed left-sided colitis, no pathologically enlarged lymph nodes, and an enlarging splenic lesion. An abdominal multi-phase magnetic resonance imaging (MRI) showed the splenic lesion to be 3.5 cm x 4.9 cm in size, multi-lobulated, non-vascular, and with progressive heterogeneous enhancement in the spleen (Figure 1A-C). For her colitis, she received empiric antibiotics consisting of ciprofloxacin and metronidazole, and her abdominal discomfort gradually improved.
Given her changing radiologic findings, medical, surgical, and interventional radiology specialists were consulted to address the concern for splenic infection versus occult malignancy. She was assessed for Toxoplasma gondii and Echinococcosis infection by immunoglobulin titers and for Mycobacterium tuberculosis with blood cultures and Quantiferon-TB Gold release assay. C-reactive protein and erythrocyte sedimentation rate were within normal ranges. Flow cytometry (fluorescence-activated cell sorting [FACS]) analysis from peripheral blood showed no abnormal B-cell, T-cell, or natural killer (NK) cell populations. Our consultants favored laparoscopic splenectomy as both a diagnostic and therapeutic intervention, and prior to surgery, she received vaccinations for Haemophilus influenzae type b, meningococcal meningitis, and Streptococcus pneumoniae. Two months following treatment of her colitis, she underwent an uneventful splenectomy and within a few days after the operation, her persistent left upper quadrant pain had resolved.
Examination of the spleen revealed a nearly 5 cm mass (Figure 1D). Tumor cells were positive for CD20, BCL6, MUM1, and BCL2 by immunohistochemistry and negative for AE1/AE3, CD3, and CD10. The Ki-67 proliferative index was expressed in nearly 100% of B-cell nuclei (Figure 2A to D). The FACS of the splenic tissue showed a monoclonal B-cell population. Fluorescent in situ hybridization (FISH) studies showed abnormal signaling; the MYC probe set showed signal fusions suggesting loss of an MYC locus, and the t (14; 18) probe set showed loss of the BCL2 locus and a gain of the 5-prime IGH locus and no translocations involving MYC, BCL2, and/or BCL6 (double or triple hit NHL). A subsequent posterior iliac crest bone marrow biopsy did not show lymphoma, and a follow-up 18fluorodeoxyglucose positron emission tomography/computerized tomography (18FDG-PET-CT) scan showed no abnormal uptake.
The patient was diagnosed with stage IE DLBCL [Stage IE refers to the Lugano classification of DLBCL (single extra-lymphatic organ/site)] for which we recommended 4 cycles of adjuvant rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) chemo-immunotherapy after hepatitis B and C serology returned non-reactive. She declined treatment recommendations, and 3 years later, she remains without evidence of lymphoma.