From Focal Sensory Deficit to Systemic Diagnosis: Unmasking Large B-Cell Intravascular Lymphoma

A 55-year-old woman presents to the Emergency Room with a 3-month history of right hemibody hypoesthesia and increasing difficulty performing activities of daily living. No fever was reported. Blood tests showed: lactate dehydrogenase (LDH) 310 U/L, C-reactive protein (CRP) 66.4 mg/L, hemoglobin 10.6 g/dL, mean corpuscular volume (MCV) 95 fL, white blood cell count (WBC) 11,93 x10³/µL (neutrophils 9,04, lymphocytes 1,43, monocytes 1,300 x10³/µL), platelets 188 x10³/µL. Coagulation tests and peripheral blood smear were normal. Brain MRI revealed multiple bilateral hyperintense T2/FLAIR lesions with patchy leptomeningeal enhancement (images 1a and 1b). Lumbar puncture was normal, with no atypical cells or microbiological isolates. Bone marrow aspiration and biopsy (BMA and BMB) revealed no pathological findings, and flow cytometry (FC) showed no evidence of atypical cells. Autoimmunity testing, protein electrophoresis, peripheral blood FC, abdominal ultrasound, and additional microbiological studies were all unremarkable. A diagnosis of acute disseminated encephalomyelitis (ADE) was made, and the condition resolved spontaneously over time.

Two months later, the patient returned to the Emergency Department with sudden-onset headache and decreased visual acuity. MRI showed an acute/subacute infarct in the territory of the right posterior cerebral artery (images 1c and 1d). PET-CT demonstrated splenomegaly with diffuse hypermetabolism in the spleen and bone marrow, suggestive of a reactive process. Laboratory results were as follows: CRP 8.3 mg/L, LDH 230 U/L, uric acid 5.3 mg/dL, ferritin 1,211 ng/mL, hemoglobin 12 g/dL, WBC 4,92 x 10³/µL, platelets 220 x10³/µL, and reticulocyte count: 45,8 x10⁹/L (1.23%). High-dose corticosteroids (methylprednisolone 1 g/day for 3 days) were initiated, leading to clinical improvement. A new BMA and BMB revealed 2–4% large, blast-like cells of medium to large size with basophilic cytoplasm and reticulated chromatin nuclei, some with prominent nucleoli (image 2). Flow cytometry identified a small population (0.21% of total nucleated cells) of B-lineage cells with increased size and complexity (FSC and SSC), displaying a mature immunophenotype and monoclonal origin with surface kappa light chain expression (image 3). BMB confirmed these cells were CD20+ and PAX5+, negative for CD30 and EBER, and not associated with vascular involvement.

Due to suspicion of intravascular lymphoma, skin biopsies were performed at three separate healthy skin sites¹. All of them showed infiltration of small and medium-sized vessels by atypical B-lymphoid cells (CD20+, PAX5+, BCL2+, BCL6+, MUM1+; negative for CD3, CD5, CD10, CD30, ALK, EMA, VSKH, and EBER) (image 4), leading to a final diagnosis of intravascular large B-cell lymphoma. Treatment was initiated with 6 cycles of R-CHOP (rituximab, cyclophspamide, hydroxydaunorubicin, vincristine and prednisone) plus 2 cycles of high-dose R-MTX (rituximab and methrotrexate) every 2 weeks after the third cycle, along with CNS prophylaxis with intrathecal MTX^2,3.