Reactive Axillary Lymphadenopathy to COVID-19 Vaccination on F-18-FDG PET/CT, F-18- Choline PET/CT and Ga-68 DOTATOC PET/CT Scans in Cancer Patients

Giordano A, Gallicchio R, Milella MR, Pellegrino T, Nappi A, Di Cosola M and Storto G

Published on: 2021-06-24

Abstract

Unexpected detection of axillary lymphadenopathy in oncological patients is challenging. It represents a real issue in COVID-19 vaccination era since benign reactions may take place after vaccine inoculation. This secondary effect of vaccination may confound image interpretation in oncological patients undergoing F-18 FDG PET/CT, F-18-Choline PET/CT, and Ga-68 DOTATOC PET/CT. Our early experience for managing COVID-19 vaccine-related lymphadenopathy on PET/CT scans is shown.

Keywords

PET/CT, Axillary Lymphadenopathy, COVID-19, Cancer Patients

Introduction

The incidental and unpredicted finding of axillary lymphadenopathy in oncological patients may represent a critical issue in PET/CT daily practice. This problem is being rise with the COVID-19 mass vaccination. In fact, reactive lymphadenopathy may occur after vaccine inoculation mimicking loco-regional metastases/disease. In this report, we present F-18-FDG PET/CT, F-18- Choline PET/CT and Ga-68 DOTATOC PET/CT incidental findings of unilateral reactive axillary hypermetabolic lymphadenopathy related to recent mRNA COVID-19 vaccination in patients with remitted Hodgkin Lymphoma (HL), bone metastatic prostate cancer and liver metastatic gastro-entero-pancreatic neuroendocrine tumor, respectively. The recognition of benign image findings is of primary importance, to ensure staging and restaging accuracy, to assess properly treatment’s response and to avoid unnecessary biopsy.

Case 1

A 77-years-old woman with history of Hodgkin Lymphoma involving lymph-node regions on both sides of the diaphragm, chemotherapy treated and considered into remission for two years, underwent surveillant F18-FDG PET/CT scan. There was no suspicious radiotracer uptake suggesting tumor recurrence. However, multiple hypermetabolic lymph nodes were visualized at right axillary region, though morphologically benign (Figure 1). According to the method previously used by Thomassen [1], the axillary lymph nodes uptake (SUVmax: Standardized Uptake Value) was defined significant if the ratio >1,5 when compared to the contralateral site (absolute SUVmax: 2.37; SUVmaxRatio: 2.7).  Upon questioning, the patient reported that she had received her second dose of mRNA vaccine against SARS-CoV-2 (Pfizer/BioNTech) three weeks before the F.18-FDG PET/CT scan. Combining vaccine inoculation history, benign features on morphological imaging and ruling out tracer injection at right arm, a diagnosis of reactive lymphadenopathy secondary to COVID-19 vaccination was achieved. Echography confirmed a normal axillar lymph node afterward.

Figure 1: A 77-years-old woman with history of HL. Negative F18-FDG PET-CT scan and right axillar lymph nodes uptake three weeks after vaccine.

Case 2

A 61-years-old man with history of bone metastatic prostate cancer treated by radiotherapy and undergoing chemotherapy, underwent ad interim F-18-Choline PET/CT scan. The examination showed multiple bone metastases and hypermetabolic lymph nodes at left axillary region (Figure 2). Which appeared benign in structure.  Once more, lymph nodes had a SUVmax ratio >1.5 as compared to contralateral nodes (absolute SUVmax: 3.89; SUVmaxRatio: 4.6). The patient had received his second dose of the mRNA vaccine against SARS-CoV-2 (Pfizer/BioNTech) four days before F-18-Choline PET/CT scan. The vaccine inoculation history, the benign lymph nodes characteristics as well as the contralateral arm tracer injection, led to a diagnosis of reactive lymphadenopathy secondary to COVID-19 vaccination. It was confirmed by a negative echography too.

Figure 2: A 61-years-old man with bone metastatic prostate cancer (see right scapula). Positive F18-Choline PET/CT scan and left axillar lymph nodes uptake four days after vaccination.

Case 3

A 60-years-old man with history of liver metastatic gastro-entero-pancreatic cancer (GEP-NET G2), treated by somatostatin analogues, underwent surveillant Ga-68-DOTATOC PET/CT scan. The examination showed significant, focal bowel uptake and multiple liver metastasis. (Figure 3). Furthermore, the scan revealed hypermetabolic lymph nodes at left axillary region, with benign morphological characteristics. Compared to contralateral nodes, lymph nodes had a SUVmax ratio >1.5 (absolute SUVmax: 1.61; SUVmaxRatio: 2.8). The patient had received his second dose of the mRNA vaccine against SARS-CoV-2 (Pfizer/BioNTech) ten days before Ga-68-DOTATOC PET/CT scan. For this last finding a diagnosis of reactive lymphadenopathy secondary to COVID-19 vaccination was made. It was confirmed by negative axillary ultrasound scan being them hypoechoic compared with adjacent muscles and oval in shape. All patients gave their informed consent.

Figure 3: A 60-years-old man with liver metastatic gastroenteropancreatic (GEP-NET) cancer. Positive Ga68-DOTATOC PET/CT scan and left axillar lymph nodes uptake ten days after vaccination.

Discussion

PET/CT findings of unilateral reactive lymphoadenopathy has been reported after multiple vaccinations, including seasonal influenza [2] considering that abnormal lymph node uptake is due to migration and lymphocytes’ proliferation after vaccination [3]. These data are not surprising. In fact, FDG is a well-known non-specific radiotracer for cancer cells since reactive tissues (such as reactive lymph nodes) might accumulate FDG as well. FDG PET/CT is also used to study inflammatory and infectious diseases [4]. Similarly, also F-18- Choline [5] and radiolabeled somatostatin analogues [6-7] uptakes are widely described in reactive tissues. Moreover, there is still a lack of information about the lasting of these post-vaccination findings. Although our findings may appear not astonishing, they deserve caution particularly for cancer patients. The correct interpretation of this secondary effect of vaccine is of primary importance to avoid unnecessary management changes and to rule out undue biopsies [8].  It should be underlined that the above-described incidental findings require the precise evaluation of the co-recorded CT scan lymph nodes characteristics [9] as well as a complete and accurate anamnestic interview (including recent vaccination).  In addition, the warning of the radiotracer site of injection and the subsequent ultrasound appraisal of the suspicious nodes may help to definitely confirm or reject the diagnostic hypothesis.

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