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Histiocytic reaction and fibrosis in response to extravasated spermatozoa. About one-third of cases show associated vasitis nodosa or epididymitis nodosa which consist of a benign proliferation of ductular structures. Sperm granuloma may be responsible for at least some cases of post-vasectomy pain syndrome. The first line of therapy for sperm granuloma is conservative - consisting of support, heat or cold (as needed), and non-steroidal anti-inflammatory agents. If the conservative approach fails and the pain is clearly localized to a sperm granuloma, surgical excision can be carried out.