COVID-19-vaccine-associated hypermetabolic lymphadenopathy; The initial case was missing the following minimum criteria: ICH-Unspecified product. Upon receipt of follow-up information on (29Nov2022), this case now contains all required information to be considered valid.  This is a literature report.  A 61-year-old female presented with an enlarging right-sided supraclavicular lymph node in 2017. Past medical history was notable for hypertension. Social history was notable for a 45-pack-year smoking history. Family history was noncontributory. She has no prior history of an autoimmune condition. A needle biopsy of the lymph node confirmed poorly differentiated carcinoma with PD-L1 expression of 20%. Immunohistochemistry stained weakly for progesterone receptor (estrogen receptor and HER-2 receptors were negative) raising initial concerns for breast cancer. However, no breast masses or axillary/intramammary lymph nodes had been detected on mammogram or computed tomography (CT) scans. An esophagogastroduodenoscopy revealed no malignancy. Initial positron emission tomography-computed tomography (PET-CT) scan was notable for fluorodeoxyglucose (FDG) avid lymph nodes in the mediastinum, bilateral pulmonary hilum, right infrahyoid jugular chain and a 3 cm tumor in the right upper lung, consistent with Stage IVA (T2N3M1a) lung carcinoma. She initiated chemotherapy with carboplatin and paclitaxel but developed disease progression following three treatment cycles. At the time of progression, PET-CT revealed multiple intensely FDG avid bilateral pulmonary nodules and lymphadenopathy involving bilateral hilar, mediastinal, and supraclavicular regions encroaching upon the lower neck. She initiated second-line treatment with nivolumab (checkpoint inhibitor) 240 mg intravenous infusion every 2 weeks, achieving a partial response to therapy. Following 12 treatment cycles, there was a notable reduction in size of right upper lobe pulmonary nodule (1 cm) and decrease in FDG avidity of the confluent multi-station mediastinal, right hilar lymphadenopathy and bilateral supraclavicular lymph nodes. She continued immunotherapy for a total of 4 years with stable disease and without significant adverse events, except for grade 1 arthralgias affecting hands and feet. She tolerated immunotherapy well and had an excellent performance status (ECOG 0). During these 4 years, she underwent routine tumor surveillance with full physical exams, routine labs and imaging every 3-4 months, which revealed no changes in mediastinal and right hilar lymphadenopathy. At the recommendation of her oncologist and following CDC guidelines, the patient went on to receive the Pfizer-BioNTech COVID-19 vaccination two-shot series in the right deltoid muscle in March 2021 and had experienced no symptoms except for left-sided retroauricular lymphadenopathy. A CT chest performed 3 months prior to her COVID-19 vaccine revealed interval decrease in the right lower lobe nodular opacity, unchanged 10 mm nodular opacity in the left lower lobe, and unchanged mediastinal and right hilar lymphadenopathy, with the largest right paratracheal lymph node measuring 1.5 cm. Two weeks following her vaccination, she developed a palpable lymph node behind her left ear. Follow-up PET-CT scan revealed new left supraclavicular hypermetabolic lymph node [8 mm with maximum standardized uptake value (SUVmax) 14.8], a new left-sided retroauricular lymph node with intense FDG activity (1.8 cm with SUVmax 20) and decrease in size and FDG activity of cervical lymph nodes. The FDG avid lymph nodes raised concern for potential treatment failure. At the time of her follow-up appointment with her medical oncologist, she noticed a significant reduction in the size of her left retroauricular lymph node. Physical exam was notable for palpable and non-tender left supraclavicular lymph node and left-sided retroauricular lymph node. Labs revealed a normal complete blood count (CBC, white blood cell count 7300 per microliter, hemoglobin 14.2 g/dL, platelet count 218,000 per microliter), normal renal and liver panels, and normal thyroid function tests. Although subjectively the adenopathy was improving, she underwent an ultrasound-guided core needle biopsy of the left preauricular lymph node, which confirmed tumor recurrence with poorly differentiated carcinoma. Immunohistochemistry (IHC) revealed that malignant cells were diffusely and strongly positive for cytokeratin 7, but weakly positive for GATA3 and negative for CK20, TTF-1, Napsin A, CDX2, PAX8, uroplakin, mammoglobin, estrogen receptor (ER), progesterone receptor (PR), GCDFP15, and p63 (Fig. 2). CancerTypeID molecular profiling determined with 90% probability that tumor of origin was lung. Following discussions regarding her diagnosis, prognosis, and systemic treatment options, patient agreed to pursue chemotherapy to delay and/or prevent tumor growth and spread. She initiated second-line chemotherapy with docetaxel 75 mg/m2 intravenous infusion every 3 weeks and tolerated treatment well, except for grade 1 fatigue. Following three treatment cycles, she had achieved a partial treatment response and her CT scans revealed interval decrease in size of multiple supraclavicular, mediastinal, and R hilar lymphadenopathy. She transitioned to a phase 2 study of oradoxel, an oral dosage form of docetaxel with a novel P-glycoprotein inhibitor. She continued to respond well to treatment after three cycles. While clinical context remains a key determinant in the evaluation and management of patients with lung cancer, evolving information regarding COVID-19 vaccination has shaped the approach and level of caution. While the patient appeared to have a durable response to immunotherapy, new adenopathy after prolonged immunotherapy maintenance needed to be evaluated by histological exam to distinguish vaccine- associated hypermetabolic lymphadenopathy from local tumor recurrence. COVID-19 vaccination can contribute to regional lymphadenopathy, making it difficult to discern reactive lymphadenopathy from malignancy. The patient developed unilateral adenopathy, which is typical for vaccine associated lymphadenopathy, but the distribution of lymphadenopathy forewarned lung cancer progression and prompted a diagnostic biopsy. COVID-19-vaccine-associated hypermetabolic lymphadenopathy may last up to 10 weeks.   No follow-up attempts are possible; information about lot/batch number cannot be obtained. No further information is expected.; Sender's Comments: Based on the current available limited information in the case provided, the causal association between the events and the use of suspect product BNT162B2 cannot be fully excluded. 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.