Sex: F
Vaccine: COVID19
Symptoms: Haemoglobin, Haptoglobin, Immunohistochemistry, Next-generation sequencing, Pathology test
Clinical narrative: Angioimmunoblastic T Cell Lymphoma; This is a literature report for the following literature source(s).  A 60-year-old female patient with a medical history of distant, resected melanoma in situ received her first dose of Pfizer/BioNTech (BNT162b2) mRNA vaccine in August 2021. On the same day, she noticed palpable right axillary lymph node (LN) enlargement. She received the second dose of the same vaccine as per the vaccine schedule 4 weeks later. Thereafter, she noticed multiple other LN enlargements in her neck and groin area as well. She visited her primarycare physician for an annual visit around 6 months from her first vaccine dose. Because of persistent LN enlargement and nonspecific B symptoms, the physician recommended an excisional biopsy of the enlarged posterior cervical and left inguinal LNs. The LN pathology revealed benign follicular hyperplasia with positive cells for Epstein-Barr virus (EBV), with no evidence of malignancy. However, due to persistent LN enlargement and B-symptoms, an oncology referral was sent. Oncology evaluation and workup revealed diffuse lymphadenopathy noted on contrast-enhanced computed tomography (CT) chest, abdomen, and pelvis. Her initial laboratory work-up was normal including hemoglobin, white blood cell count, and platelet counts, except LDH 525 U/L. Around 2 weeks later from her oncology appointment, she presented to the emergency department (ED) with acute onset intractable nausea and vomiting associated with generalized weakness and fatigue. In the ED, vitals were stable, but lab work-up revealed her hemoglobin 6.1 g/dL, hematocrit 13%, platelet count 356000/uL, LDH 737 U/L, total bilirubin 6.0 mg/dL, indirect bilirubin 5.3 mg/dL, and undetectable haptoglobin. The initial peripheral smear showed significant agglutination rendering nonanalysis of reticulocyte count and direct Coombs testing. The patient was accordingly diagnosed with acute hemolytic anemia (AIHA) and admitted for prednisone 80 mg per day, rituximab, and blood transfusion as needed. After discussion with inpatient oncology services, she underwent an excisional biopsy of the right axillary LN, which was her primary LN which had enlarged following the initial vaccination. Pathology showed effaced nodal architecture by atypical lymphoid infiltration composed of a mixture of small lymphocytes with nuclei that showed condensed chromatin and medium-sized cells with round to irregular nuclei and clear cytoplasm. In the background, there was prominent vascular proliferation and numerous inflammatory cells. Immunohistochemistry on the right axillary LN specimen showed infiltrates that marked as a neoplastic population with CD3 (dim)-positive T cells that co-expressed CD4, CD2, CD5, TCR beta F1, dim to diminished expression of CD7, and high Ki-67 proliferation index. They also expressed the TFH cell marker CD10, some of which associated with focally expanded CD21-positive follicular dendritic cell meshwork. Fluorescence in situ hybridization (FISH) was positive for Epstein-Barr virus-encoded RNA (EBER). The above description was consistent with the diagnosis of angioimmunoblastic T-cell lymphoma. Next-generation sequencing showed TET-2, IDH-2, and RHOA-G17V mutations. Following the diagnosis of angioimmunoblastic T-cell lymphoma, a positron emission tomography/computed tomography (PET/CT) scan was performed and showed hypermetabolic lymphadenopathy in the involved LNs. There was no evidence of disease in the bone marrow. Following stabilization of her AIHA with steroids and rituximab, the patient was discharged from the hospital. After shared decision-making, she received 6 cycles of CHOEP regiment with cyclophosphamide 750 mg/m2, doxorubicin 50 mg/m2, vincristine 1.4 mg/m2 on day 1, etoposide 100 mg/m2 iv over 60 minutes daily on days 1 to 3 and prednisone at 100 mg daily PO days 1 to 5 total (CHOEP) as per the National Comprehensive Cancer Network guidelines. Repeat interim PET/CT following cycle 3 showed excellent response with no hypermetabolic lymphadenopathy. She eventually underwent autologous stem cell transplant and has been in complete remission since then. Although the initial biopsy showed benign follicular hyperplasia, but the persistent lymphadenopathy, presence of B symptoms, detection of EBV, and development of AIHA suggested underlying hematological malignancy and prompted to proceed with another excisional biopsy of the right axilla. It is unclear, however, whether (angioimmunoblastic lymphoma) AITL appeared de novo or was simply unmasked after vaccination with underlying mutations TET-2, IDH, RHOA G17V. This case shows a plausible association of mRNA vaccine and lymphomatous processes, especially AITL.; Sender's Comments: The event angioimmunoblastic T-cell lymphoma is conservatively assessed as related to the suspect drug BNT162B2 based on close temporal association but consider also possible contributory effects from medical history of the patient and/or concomitant medications. The impact of this report on the benefit/risk profile of the Pfizer product is evaluated as part of Pfizer procedures for safety evaluation, including the review and analysis of aggregate data for adverse events. Any safety concern identified as part of this review, as well as any appropriate action in response, will be promptly notified to Regulatory Authorities, Ethics Committees, and Investigators, as appropriate.,Linked Report(s) : US-PFIZER INC-PV202400066458 Same article/drug/event/patient and different dose;