Table 1.
Clinical demographics in study for associated elements in the C19-VAL.
| Design | Study | Country | Participants | Age (Years) |
Medical History | Male N (%) |
Vaccine Type | Vaccine Dose | Last Vaccine to C19-VAL (Days)/Site | Main Finding | Elements |
|---|---|---|---|---|---|---|---|---|---|---|---|
| Single center reprospective study | Yoshikawa T. (2022) [38] | Japan | 433 | 65 ± 11 | No past and current LAD related disease and COVID-19 | 300 (69.28) | NR | 2 (most) | NR/all for ipsilateral axillary | Incidence of C19-VAL is significantly higher in young age and female | Young age and female |
| Shin M. (2021) [45] | Korea | 31 | 45 ± 5 | No history of malignancy, vaccination before 18F-FDG PET/CT | 11 (35) | AstraZeneca | NR | 4–29/bilateral axillary, supraclavicular | Percentage of C19-VAL is significantly higher in female, FDG-avid deltoid muscle can be a helpful sign to presume the reactive LN | Female and reactive change | |
| Park JY. (2022) [20] | Korea | 413 | 48 ± 12 | No history of malignancy, vaccination within 12 weeks, vaccination before ultrasonography | 10 (2.42) | Moderna (19); AstraZeneca (64); Pfizer-BioNTech (330) |
2 (257) | 1–82/axillary | 48.9% cases with C19-VAL. Incidence of C19-VAL is significantly higher in young age, mRNA vaccine and post 1st dose as well as decreased as days from vaccination |
Young age, mRNA vaccine, 1st dose, and days post-vaccination | |
| Nishino M. (2021) [10] | USA | 232 | 40–96 | All with lung cancer, CT scans prior and post vaccination | 88 (37.9) | Moderna (28); Pfizer-BioNTech (204) | 2 | 7–68/axillary, subpectoral | 9% cases with C19-VAL. Incidence of C19-VAL is significantly higher in female and in Moderna |
Female and Moderna | |
| Cocco G. (2021) [18] | Italy | 24 | 25–74 | Without fever and no history of hematological malignancy, autoimmune disease and vaccination before ultrasonography | 10 (41.6) | Moderna (3); AstraZeneca (8); Pfizer-BioNTech (13) | Least 1 | NR/axillary, supraclavicular | All cases with C19-VAL Percentage of C19-VAL is significantly higher post 1 dose vaccination |
1st dose | |
| El-Sayed MS. (2021) [13] | UK | 204 | 68 ± 11 | Without LAD pathologies, vaccination within 12 weeks and before 18F-FDG PET/CT | 98 (48) | AstraZeneca (43); Pfizer-BioNTech (62); unknown (99) | 2 (87) | Up to 70/axillary | 36% cases with C19-VAL. Incidence of C19-VAL is significantly higher in young age, vector vaccine and female |
Young aged, vector vaccine and female | |
| Ah-Thiane L. (2022) [42] | France | 226 | 67–76 | Most prostate cancer, vaccination before ultrasonography, MRI, or 18F-FDG PET/CT |
212 (93.8) | Moderna (11); AstraZeneca (60); Pfizer-BioNTech (152); Janssen (3) | 2 (124) | 14–51/axillary and supraclavicular | 42.5% cases with C19-VAL. Incidence of C19-VAL was significant higher post the 1st vaccination |
1st dose | |
| Maimone S. (2022) [44] | US | 2304 | 30–92 | Vaccination before screening mammography | NR | Moderna (1109); Pfizer-BioNTech (1135); other (41); unknown (18) | 2 (1883) | 0–28 and >28/ipsilateral axillary | 1% cases with C19-VAL. Incidence of C19-VAL was significantly decreased as days from vaccination |
Days post-vaccination | |
| Eifer M. (2022) [43] | Israel | 426 Immunosuppressive treatment (82), hemato-logical malignancy (75) |
67 ± 12 | Vaccination before PET/CT and without malignancy involving axillary LN | 219 (51) | Pfizer-BioNTech | 2 (103) | 5–18/axillary | Incidence of C19-VAL is significantly higher in young age, 2nd vaccination and increased in days post last vaccination, but lower in immunosuppressive treatment and hematologic malignancy | Young age, 2nd vaccination, days post-vaccination, immunosuppressive, and hematologic malignancy | |
| Cohen D. (2021) [88] | Germany | 137 Recent anti-CD20 (34), no recent anti-CD20 (68) |
>16 | Hematologic malignancy without MHL | 75 (54.7) | NR | Either of 1 or 2 | 6–27/ipsilateral axillary or supraclavicular | Incidence of C19-VAL in recent anti-CD20 vs. no recent anti-CD20 (8.8 vs. 41.1%, significant) | B cell germinal center response | |
| Case series | Fernández-Prada M. (2021) [19] | Spain | 20 | 20–60 | Autoimmune disease (4), thyroid cancer (2) | 0 | Pfizer-BioNTech (19) Moderna (1) | 2 (14) | 0–4/supraclavicular | 12 of 20 patients reported high injection site, biopsy of LN from two type vaccines revealed reactive change | High injected site and reactive change |
| García-Molina F. (2021) [36] | Spain | 6 | 27–62 | NR | NR | Pfizer-BioNTech | 1 | 5/axillary or supraclavicular | Cytological for FNA and biopsy: nonspecific chronic adenitis, resolution of ALAD and SLAD after anti-inflammation drug | Inflammation | |
| Özütemiz C. (2021) [48] | USA | 2 | 62 | Current metastatic breast cancer (1), two cancer history | 1 (50%) | Moderna (1) Pfizer-BioNTech (1) |
3 | 1–2/ipsilateral axillary | Due to imaging and vaccine history, reactive LN | Reactive change | |
| Heaven CL. (2022) [47] | New Zealand | 5 | 41–76 | High suspicion of cancer | 2 (40%) | Pfizer-BioNTech | 2 | 7–34/bilateral cervical | Biopsy: reactive follicular hyperplasia with no evidence of atypia or malignancy | Reactive change | |
| Hagen C. (2021) [49] | Switzerland | 5 | 41–66 | Lung cancer (2), neuroendocrine tumor (1) | 2 (40%) | Pfizer-BioNTech (2) Moderna (3) |
1 (3) | 3–33/bilateral axillary, supraclavicular | FNA: reactive follicular hyperplasia | Reactive change | |
| Brown AH. (2021) [46] | UK | 2 | 48, 67 | Breast cancer for right (1) and for left (1) | 0 | NR | NR | 14, 21/ipsilateral axillary, subpectoral | FNA: reactive change without malignancy | Reactive change | |
| Case report | Goldman S. (2021) [86] | Belgium | 1 | 66 | Hypercholesterolemia, type 2 diabetes, recent cervical lymphadenopathies | 1 | Pfizer-BioNTech | 2 | 150/ipsilateral supraclavicular, cervical, left axillary and abdomen | FNA of CLN: atypical T cell infiltrate with high endothelial venules proliferation; NGS: positive AITL, the number and distribution of LAD increased after 3rd vaccination | AITL |
| Wolfson S. (2022) [50] | USA | 2 | 50, 60 | No (1), simultaneously left ductal carcinoma | 0 | Moderna | 1 | 10, 63/ipsilateral axillary | FNA: begin reactive LN for no medical history, biopsy: metastatic adenocarcinoma for left ductal carcinoma patients | Reactive change | |
| Mizutani M. (2022) [85] | Japan | 2 | 67, 80 | NR | 1 | Pfizer-BioNTech | 2 | 14, 1/left axillary | Persistent ALAD from 1st dose vaccination and gradually enlarged post 2nd dose, finally diagnosed as DLBC by IHC of biopsy | DLBCL | |
| Sekizawa A. (2022) [84] | Japan | 1 | 80 | Hypertension, angina pectoris, mitral valve regurgitation, ovarian tumor | 0 | Pfizer-BioNTech | 2 | 21/ipsilateral temporal cervical, submandibular, and jugular | Persistent ipsilateral temporal after 1st dose vaccination, and sudden enlarged post 2nd dose, finally diagnosed as MZL | MZL | |
| Sasa S. (2022) [87] | Japan | 1 | 80 | Right breast | 0 | Pfizer-BioNTech | 2 | 90/ipsilateral axillary | Multilobulated cystic mass and branches on ultrasonography, finally diagnosed as lymphangioma and resected | Lymphangioma | |
| Saito K. (2022) [41] | Japan | 1 | 66 | Current malaise and oral bleeding and purpura | 0 | Pfizer-BioNTech | 1 | 2/systematic | Low platelet count, markedly increased megakaryocytes in bone marrow, and present of serum anti-glycoprotein IIb/IIIa, finally diagnosed ITP | ITP | |
| Hoffmann C. (2022) [90] | Germany | 1 | 20 | Fever, centigrade, loss of appetite, malaise, weakness, and exertional dyspnea post vaccination | 1 | Pfizer-BioNTech | 2 | 18/supraclavicular, axillary | iMDC post vaccination | iMDC | |
| Girardin FR. (2022) [89] | Switzerland | 1 | 40 | Recent EBV infection | 0 | Moderna | 2 | 1/bilateral axillary and supraclavicular | EBV positive parafollicular immunoblastic cells in LN, induce repeated and extend C19-VAL through enhancing the vaccine immunity | EBV | |
| Cha HG. (2022) [66] | Korea | 1 | 66 | Injection site tenderness and fatigue post 1st dose, acute idiopathic thrombocytopenic purpura | 0 | AstraZeneca | 2 | 3/ipsilateral supraclavicular | Persistent LAD up to 8 weeks, further revealed multiple FDG avid-LNs not limited in supraclavicular, LN biopsy of SLN: chronic granulomatous inflammation, PCR positive for TB | TB | |
| Ganga K. (2021) [24] | USA | 1 | 58 | Hypertension | 1 | Moderna | NR | 2/left neck | FNA for LN of left neck: negative for malignancy and positive for inflammatory cells, improvement and resolution of neck swelling and dysphagia by antibiotic treatment | Inflammation | |
| Cheong KM. (2022) [80] | Taiwan | 1 | 32 | NR | 0 | AstraZeneca | 1 | 2/lower neck | Neck lymphadenitis diagnosed on ultrasonography | Inflammation | |
| Andresciani F. (2022) [79] | Italy | 1 | 62 | Prostate cancer | 1 | Pfizer-BioNTech | 2 | 21/ipsilateral axillary, paratracheal, paraaortic, subcarinal, and bilateral hilar | Choline intensity decreased in LN, finally diagnosed as inflammatory LN, not oncological disease | Inflammation | |
| Tsumura Y. (2022) [83] | Japan | 1 | 31 | Metastatic Ewing sarcoma |
0 | Pfizer-BioNTech | NR | 21/ipsilateral axillary | An inflammatory lesion rather than metastatic lymph node swelling | Inflammation | |
| Tan HM. (2021) [39] | Singapore | 2 | 18, 34 | Current fever | 1 | Pfizer-BioNTech | 1–2 | 17–35/left axillary, supraclavicular, subpectoral | Fever, transient leukopenia, LAD, negative for infection, necrotizing lymphadenitis in LN biopsy, finally diagnosed KD | KD | |
| Caocci G. (2022) [40] | Italy | 1 | 38 | Recent fever for ten day, chills, and fatigue, C19-VAL post 1st dose | 0 | Pfizer-BioNTech | 2 | 31/left axillary | Fever, negative for infection, leukopenia, LAD, and biopsy of LN: histiocytic necrotizing lymphadenitis (numerous CD68+ histiocytes and CD3+ T cells, few CD20+ B cells), finally diagnosed KD | KD | |
| Kashiwada T. (2022) [82] | Japan | 1 | 27 | Recent repeated fever, C19-VAL post 1st dose | 0 | Pfizer-BioNTech | 2 | 68/ipsilateral axillary | Fever, negative for infection, leukopenia, LAD, and necrotizing lymphadenitis in LN biopsy, finally diagnosed KD | KD | |
| Guan YY. (2022) [81] | China | 1 | 36 | Current fever and fatigue | Sinopharm | 1 | 28/left cervical, neck | Fever, LAD and necrotizing lymphadenitis (numerous CD68+ histiocytes and CD3+ T cells, few CD20+ B cells) in LN, finally diagnosed KD | KD | ||
| Xu GY. (2021) [51] |
USA | 1 | 72 | Mantle cell lymphoma | 1 | Pfizer-BioNTech | NR | 2/ipsilateral axillary | With FDG-avid deltoid muscle, reactive LN, recurrent lymphoma | Reactive change | |
| Özütemiz C.(2021) [8] | USA | 2 | 38, 46 | Breast cancer (1) | 0 | Pfizer-BioNTech | 2 (1) | 8–15/ipsilateral axillary, supraclavicular | Biopsy: reactive follicular hyperplasia in lymph node without any evident of breast cancer and malignancy | Reactive change | |
| Nawwar AA. (2021) [52] | UK | 1 | 75 | Prostate cancer | 1 | AstraZeneca | 1 | 3/ipsilateral axillary | With 18F-Choline-avid left deltoid muscle, reactive active LN | Reactive change | |
| Mitchell OR. (2021) [53] | UK | 2 | 47, 55 | NR | 0 | NR | NR | 3/ipsilateral supraclavicular | Reactive LN by clinical and ultrasonographic examination |
Reactive change | |
| Ulaner GA. (2021) [54] | Canada | 1 | 68 | Current right melanoma | 1 | Moderna | 1 | 21/ipsilateral axillary | Unlike metastasis of right melanoma, reactive to vaccination | Reactive change | |
| Wong FC. (2022) [55] | USA | 1 | 74 | Prostate cancer | 1 | Moderna | 2 | 6/ipsilateral axillary | Unlike metastasis of prostate cancer and findings for C19-VAL, considering to reactive to vaccination | Reactive change | |
| Garreffa E. (2021) [56] | UK | 1 | 38 | NR | 0 | Pfizer-BioNTech | 1 | 7/ipsilateral clavicle | Reactive LN by ultrasonographic examination | Reactive change | |
| Prieto PA. (2021) [57] | USA | 1 | 48 | Melanoma | 0 | Moderna | 1 | 5/ipsilateral axillary, neck | Biopsy: consistent with reactive LN and negative of melanoma | Reactive change | |
| Roca B. (2021) [58] | Spain | 1 | 29 | NR | 0 | Pfizer-BioNTech | 1 | 7/ipsilateral supraclavicular | C19-VAL disappeared over the next few weeks | Reactive change | |
| Tan JHN. (2021) [59] | Singapore | 1 | 34 | No malignancy history | 0 | Pfizer-BioNTech | 1 | 1/ipsilateral supraclavicular | FNA: reactive follicular hyperplasia | Reactive change | |
| Gable AD. (2021) [60] | USA | 1 | 24 | Current ED, never smoker, no medical or surgical history, no ED related disease | 1 | NR | 2 | 4/ipsilateral axillary | ED due to typical bronchial carcinoid and LAD significant reduced later | Reactive change | |
| Suleman A. (2021) [61] | Canada | 1 | 38 | Current left Hodgkin lymphoma | 0 | Pfizer-BioNTech | 1 | 7/ipsilateral axillary | Reduced later | Reactive change | |
| Tintle S. (2021) [62] | USA | 1 | 23 | Asthma, eczema, and hypothyroidism, simultaneously fever and acute kidney injury |
0 | Moderna | 2 | 7/left axillary and abdomen | Biopsy of ALN: reactive lymphadenitis |
Reactive change | |
| Weeks JK. (2021) [63] | USA | 1 | 50 | Current sigmoid adenocarcinoma | 0 | Moderna | 2 | 30/bilateral axillary | Improvement of C19-VAL | Reactive change | |
| Mori M. (2022) [64] | Japan | 1 | 30 | NR | 0 | Pfizer-BioNTech | 1 | 9/axillary | Resolution later | Reactive change | |
| Tzankov A. (2021) [65] | Switzerland | 1 | 30 | Current right papillary thyroid cancer | 1 | Moderna | 1 | 21/left axillary | Biopsy: extrafollicular proliferation of B-blasts and resolution later | Reactive change | |
| Chan HP. (2022) [66] | Taiwan | 1 | 71 | Thyroid cancer, right renal cell carcinoma | 1 | Moderna | 1 | 6/ipsilateral axillary | Due to imaging and vaccine history, reactive to vaccination | Reactive change | |
| Adin ME. (2022) [67] | USA | 1 | 41 | Simultaneously right breast cancer | 0 | Moderna | 2 | 16/ipsilateral axillary, | Due to imaging and vaccine history, reactive to vaccination | Reactive change | |
| Kang ES. (2022) [68] | South Korea | 1 | 59 | Simultaneously SCC of the right mandibular gingiva |
1 | Moderna | 2 | 10/ipsilateral axillary, bilateral cervical | FNA: only small lymphoid cells, reactive to vaccination | Reactive change | |
| Yu Q. (2022) [69] |
China | 1 | 34 | Allergic disease, tuberculosis, past malignant tumors, recent infection, trauma | 0 | Sinovac | 2 | 120/ipsilateral axillary | FNA: reactive hyperplasia and resolution later, reactive to vaccination | Reactive change | |
| Ashoor A. (2021) [70] | Italy | 3 | 61–72 | No (2), simultaneously breast cancer (1) | 0 | AstraZeneca | 1 (1), 2 (2) | 1–27/ipsilateral axillary | Imaging is normal and biopsy: benign reactive changes, reactive to vaccination | Reactive change | |
| Lee SM. (2022) [71] |
South Korea | 1 | 21 | NR | 1 | Pfizer-BioNTech | 2 | 2/ipsilateral axillary | Radial neuropathy associated with ipsilateral ALAD, FNA: reactive hyperplasia |
Reactive change | |
| Kado S. (2022) [72] |
Japan | 1 | 31 | NR | 0 | Pfizer-BioNTech | 1 | 8/ipsilateral clavicle, scapular | FNA: follicular hyperplasia and resolution later, reactive to vaccination | Reactive change | |
| Aalberg JJ. (2021) [73] | USA | 1 | 73 | Metastatic renal cell carcinoma to lung and bone | Moderna | 2 | 2/ipsilateral axillary | With FDG avid-ipsilateral deltoid muscle and FNA: polymorphous lymphoid population with no evidence of metastasis | Reactive change | ||
| Cardoso F. (2021) [74] | Portugal | 1 | 48 | Usual contraceptive medication, Mercilon® | 0 | Pfizer-BioNTech | 2 | 1/right cervical | Due to persistent LAD after first dose, FNA: reactive follicular hyperplasia | Reactive change | |
| Lam DL. (2022) [75] | USA | 1 | 39 | Simultaneously right breast cancer | 0 | Pfizer-BioNTech | 2 | 1/ipsilateral axillary | C19-VAL resolution later, FNA for sentinel LN: negative metastasis and consistent with reactive to vaccination | Reactive change | |
| Musaddaq B. (2021) [76] | UK | 1 | 57 | Left breast cancer, simultaneously right breast cancer | 0 | Astra Zeneca | 1 | 3/ipsilateral axillary | IHC: reactive LN with follicular hyperplasia and without metastasis cancer | Reactive change | |
| Dirven I. (2022) [77] | Belgium | 1 | 60 | MEN 1 syndrome and simultaneously right lung nodule | 0 | Pfizer-BioNTech | 1 | 13/ipsilateral axillary | FNA: LN with a benign reactive pattern without metastatic disease | Reactive change | |
| Pudis M. (2021) [78] | Spain | 1 | 30 | Neuroendocrine tumor | 0 | Pfizer-BioNTech | 2 | 40/bilateral axillary, unilateral supraclavicular and cervical | No infection, Biopsy: benign reactive LN with CD10+ B cell population, immune system activation to vaccination | Reactive change |
NR: not reported; LN: lymph node fine needle aspiration; IHC: immunohistochemistry; ALAD: axillary lymphadenopathy; SLAD: supraclavivular lymphadenopathy; LAD: lymphadenopathy; MEN: multiple endocrine neoplasia; MHL: malignant axillary and supraclavicular hypermetabolic lymphadenopathy; ED: episode of hemoptysis; SCC: squamous cell carcinoma; AITL: angioImmunoblastic T cell Lymphoma ; NGS: next generation sequencing; iMDC: idiopathic multicentric castleman Disease; DLBL: large B-cell lymphoma; MZL: marginal zone B-cell lymphoma; HLH: hemophagocytic lymphohistiocytosis; KD: Kikuchi-Fujimoto disease; ITP: immune thrombocytopenia; TB: mycobaterium tuberculosis; EBV: Epstein–Barr virus.