A morphological study of granulomas induced by subcutaneous injection of leuprorelin acetate

Abstract

Leuprorelin acetate-induced granulomas in subcutaneous injection sites have been occasionally reported, but there have been no detailed morphological examinations. Histopathology of leuprorelin acetate-induced granulomas in six patients was studied, and one of them was evaluated by electron microscopy. Study using haematoxylin and eosin staining revealed that there were many intracytoplasmic vacuoles in the granulomas and degeneration of fat tissue. Ultrastructurally, electron-lucent spherical bodies (microcapsules of leuprorelin acetate products) were observed in the granuloma cells. Needle-shaped crystalloid structures in lipid droplets (degenerated lipid droplets) were observed in the granuloma cells and fat tissue. Degeneration of fat tissues caused by leuprorelin acetate is one of main factors responsible for granuloma formation.

An indurated right arm mass in a patient treated for locally advanced prostate cancer

“…Although very rare cases of foreign body reactions with leuprorelin have been reported, polylactic acid polymers are the main components involved . Moreover, the lipolytic action of LH‐RH in vitro is known and may interfere in the physiopathogenesis of this granulomatous reaction …”

Diagnostic approach to subcutaneous nodules in patients with neuroendocrine tumours treated with depot somatostatin analogs: a cross‐sectional study

“…Histopathological studies of these nodules have revealed subcutaneous injection site granulomas, with a central homogeneous collection . Granulomas have been associated with slow‐release polymers in other medications, such as leuprorelin . Degradable gels can induce a wide set of tissue responses, from localized granulomatous reactions to foreign body nodules and abscesses .…”

Evidence‐based medicine: comparative analysis of luteinizing hormone‐releasing hormone analogues in combination with external beam radiation and surgery in the treatment of carcinoma of the prostate

“…Although, a priori, it might be supposed that intramuscular compounds would be better absorbed than subcutaneous implants, there is no evidence supporting this [43]. A study with subcutaneous leuprorelin acetate [66] shows that the formation of granuloma is caused by both the foreign‐body reaction to the microcapsules and the lipolytic effect described for subcutaneous administration of the LHRHa [67]. Incidence would also be related to the dose administered [66].…”