Case Presentation: A 64-year-old male with a medical history of psoriatic arthritis on etanercept, coronary artery disease, adrenal insufficiency and alcohol use disorder who presented to the hospital with complaints of weakness, fatigue, night sweat, and transient slurring of speech. Physical examination was normal. Laboratory investigation showed Hemoglobin of 10, Platelets 150, WBC 6, CRP 300, Ferritin 1280, total iron 45, TIBC 266, Retic count 2.6% and SPEP negative for M proteins. The peripheral smear was unremarkable, and bone marrow showed normal trilinear hematopoiesis with no diagnostic immunophenotypic abnormalities. MRI brain was equivocal; neurology recommended a transition to Plavix from Aspirin. CT chest/abdomen/pelvis was negative for malignancy. Anemia was then attributed a multifactorial causality. The patient improved and was discharged only to be re-admitted with transient aphasia. Repeat imaging was negative; mild thrombocytopenia was noted at this time. Symptoms improved and he was discharged home to continue further outpatient workup and evaluation with his specialists. However, he developed sudden onset dyspnea three days after discharge and was readmitted for the third time in two months. Thrombocytopenia and anemia were noted to have worsened, with decreased haptoglobin and up-trending LDH; peripheral smear showed no schistocytes. A tentative diagnosis of atypical hemolytic uremic syndrome was made. The panel showed equivocal results with normal ADAM 13 activity; SMAC and Soluble-ILR 2 genetic testing were sent out to rule out hemophagocytic syndrome. The patient was started on Eculizumab with minimal improvement after three doses. CTA showed no pulmonary embolus, PFTs showed reduced DLCO, lung biopsy showed intravascular large B cell lymphoma, double and triple hit negative. R-CHOP was initiated along with rasburicase. The patient later developed neutropenia which was treated with Neulasta. MRI showed no intracranial disease and CSF studies showed negative cytology and flow cytometry for lymphoma. A plan was made for 6 cycles of R-CHOP with concomitant 4-8 cycles of immunotherapy followed by high-dose methotrexate for 2-4 cycles. Treatment with Intrathecal methotrexate was declined by the patient, and he received a total of 5 cycles of chemotherapy with marked improvement. He subsequently developed seizures approximately 8 months after diagnosis. CT head showed a lobulated mass with possible intracranial hemorrhage; MRI showed vasogenic edema, the patient succumbed to his illness due to complications.
Discussion: IVLBCL is a rare but extremely lethal variant of extranodal lymphoma (DLBCL). This combination of rarity and obscure clinical presentation makes it a diagnostic conundrum. Clinical features are highly variable, the most consistent being fever and night sweats. Pertinent labs usually show elevated ferritin, LDH, and hemophagocytosis; anemia and thrombocytopenia also occur. IVLBCL almost exclusively occurs within small and medium-sized vessels, making routine bone marrow biopsies negative, especially in the early phase of the disease; Two varieties based on organ involvement have been described. Regardless of subtype, IVLBCL is considered Lugano stage IV and carries a poor prognosis.
Conclusions: The challenging nature of these cases takes an inordinate amount of the hospitalists time and resources. High index of suspicion and systematic approach is needed to improve outcomes of such rare conditions.