EBER in situ hybridization in subcutaneous aluminum granulomas/lymphoid hyperplasia: A diagnostic clue to differentiate injection‐associated lymphoid hyperplasia from other forms of pseudolymphomas and cutaneous lymphomas

Abstract

Background Subcutaneous vaccination or desensitization may induce persistent nodules at the injection sites. Without the knowledge of prior injection, histopathological work‐up may be challenging. Objective Aim of this study was to contribute to the histopathological work‐up of unclear subcutaneous nodules, especially their differentiation from cutaneous lymphoma. Methods We retrospectively reviewed clinical data and histopathological slides of four patients with subcutaneous nodules, which were suspected to suffer from cutaneous T‐ or B‐cell lymphoma. Sections of these cases and 12 negative controls were stained with hematoxylin and eosin and a standardized immunohistochemical panel of B‐ and T‐cell markers including EBER in situ hybridization as well as electron microscopy. Results In all cases, large histiocytes with granular cytoplasm compatible with intracellular aluminum hydroxide were present. EBER in situ hybridization revealed positive staining of these granular histiocytes while staining was absent in negative controls. Limitations Post hoc completion of medical history revealed that vaccination or specific immunotherapy had been applied before at the biopsy site in only three out of four patients; one patient was lost to follow‐up. Conclusion EBER in situ hybridization is an adjunctive tool to differentiate aluminum‐induced granuloma/lymphoid hyperplasia from other forms of pseudolymphoma and cutaneous B‐ or T‐cell lymphomas.

Post-Transplant Lymphoproliferative Disorder, Monomorphic Type, in a Kidney Transplant Patient After Administration of Anti-Influenza Vaccine

“…5 Interestingly, EBER positivity has been described in the cytoplasmic granules of histiocytes in these responses to aluminum in the vaccine. 6 These local pseudolymphomatous responses at the injection site have also been described with other types of vaccines, including vaccines against early summer meningoencephalitis, tetanus, hepatitis A and B, 7,8 and the anti-COVID vaccine. 9,10 Pseudolymphomatous responses have also been described after injections of allergens.…”

Hemostatic aluminum fails to stain by the EBER‐ISH method

“…We write in reference to a recent report in which the authors described positive staining of aluminum‐laden histiocytes with Epstein–Barr‐encoding region in situ hybridization (EBER‐ISH) in four patients 1 …”

“…patients. 1 Aluminum compounds have utility as hemostatic agents and may be components of vaccines. Their granular appearance is important for the dermatopathologist to recognize because of resemblance to pathologic processes such as organisms in parasitized histiocytes.…”