Persistent nodules at injection sites (aluminium granuloma) - clinicopathological study of 14 cases with a diverse range of histological reaction patterns

Aims: To assess and document the spectrum of histological appearances of persistent swellings which occur at injection sites following vaccination or allergen desensitization. Methods and results: Fourteen cases were studied. Four overlapping histological reaction patterns were evident. Ten cases showed at least focal fibrosis, fat necrosis and a mixed inflammatory cell infiltrate mainly in the subcutis, giving rise to the features of a non-specific septal and lobular panniculitis. The appearance of three cases, in addition to the non-specific panniculitis pattern, also included prominent lymphoid follicles with germinal centres and a prominent perifollicular infiltrate resembling a lymphoma (pseudolymphoma pattern). A single case mimicked lupus profundus, with a perivascular and periadnexal infiltrate in the dermis and hyaline fat necrosis. Three cases showed a predominantly palisaded histiocytic infiltrate surrounding eosinophilic necrobiosis, in a pattern closely resembling deep granuloma annulare or rheumatoid nodule. The remaining case partly showed this appearance, but in combination with panniculitis, thus demonstrating an overlap of patterns. A common feature in all 14 cases was the focal presence of histiocytes with abundant violaceous granular cytoplasm. These were shown to contain aluminium on energy dispersive X-ray microanalysis. Conclusion: Persistent swellings at injections sites show a variety of overlapping patterns, which mimic other conditions. Identification of characteristic histiocytes with violaceous granular cytoplasm is the key distinctive feature allowing the correct diagnosis to be reached.