CASE REPORT
We report the case of a 72-year-old Caucasian woman, with a medical history of hypertension, hypothyroidism and mild obesity, who was admitted to hospital because of progressive dyspnea and appearance of bilateral leg oedemas above the ankles. No weight loss or concomitant fever were reported. Physical examination revealed distant heart sounds. The liver, spleen and peripheral lymph nodes were not palpable. Laboratory data on admission was remarkable for B-type natriuretic peptide level of 1117 pg/ml (normal value: <250 pg/ml). Complete blood count, renal and hepatic function were within normal values and the serum lactate dehydrogenase (LDH) was not elevated. A chest X-ray showed cardiomegaly (figure 1a) and transthoracic echocardiogram revealed pericardial effusion. The patient was admitted to the cardiac care unit, where pericardiocentesis was successfully carried out, yielding 800 mL of serohematic fluid. The pericardial liquid analysis showed features of exudative effusion (glucose <5mg/dl, red blood cells 15871 cell/µL, white blood cells 850 cell/µL with 55% of atypical cells, protein 49.6 g/L, LDH 4034 U/L, ADA 84,2 U/L). Malignant-appearing cells were detected in the cytospin preparation. Microbiological tests were negative including mycobacteria culture and multiplex polymerase chain reaction (PCR) for herpesvirus (VHS1, VHS2, VVZ, CMV and VH6). A whole-body positron emission tomography (PET) scan showed moderately hypermetabolic pericardial and pleural layers and right tonsillar enlargement (figure 1b). Tonsil excisional biopsy showed reactive follicular hyperplasia and a bone marrow biopsy showed no evidence of involvement by lymphoma. Serologic tests were negative for HIV, hepatitis C virus (HCV) and hepatitis B virus (HBV); whereas immunoglobulin G for EBV was positive, indicating a prior infection.
Cytological evaluation demonstrated large atypical cells variable in size and nuclei, ranging from round to more irregular shape with prominent nucleoli and abundant basophilic cytoplasm with vacuoles (figure 2a). Moreover, some mitotic figures were seen (figure 2b). In flow cytometric analysis, these cells were positive for CD45, CD19, CD10, CD20 and CD38 and lacked surface immunoglobulin expression. A formalin-fixed paraffine-embedded cell block was performed for morphology, immunocytochemistry (IHC) and fluorescence in situ hybridization (FISH) evaluation. IHC study showed positivity for CD20 (figure 3a) and PAX5 and negativity for CD3, CD10, CD30, MUM-1, BCL-6, BCL-2 and c-myc. Neither BCL-6, BCL-2 nor C-MYC gene translocation were detected by FISH. Moreover, EBV-encoded RNA (EBER) was negative (figure 3b) and protein latency-associated nuclear antigen 1 (LANA-1) was negative on IHC (figure 3c). High Ki67 expression was observed (>80%). Cytogenetic findings showed a complex karyotype.
All these findings pointed towards a diagnosis of PEL-like or HHV8 and EBV-negative primary EBL according to the ICC.2 The patient was treated with R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine and prednisone) for six cycles achieving complete remission evaluated by PET scan. At the time of this report, the patient remains in complete response for 16 months.