Intracellular heavy metal nanoparticle storage: progressive accumulation within lymph nodes with transformation from chronic inflammation to malignancy

Abstract

Tommaso Iannitti1, Stefania Capone2, Antonietta Gatti3, Frederico Capitani4, Cetta Francesco5,6, Beniamino Palmieri21Department of Biological and Biomedical Sciences, Glasgow Caledonian University, Glasgow, UK; 2Department of General Surgery and Surgical Specialties, 3Laboratory of Biomaterials, Department of Specialistic Surgeries, Head and Neck Medical School and Surgical Clinic, University of Modena and Reggio Emilia, Italy; 4Laboratory of Nanodiagnostics, San Vito, Modena, Italy 5Department of Surgery, University of Siena, Siena; 6Institute of Geriatrics, Pio Albergo Trivulzio Hospital, Milan, ItalyAbstract: A 25-year-old man had complained of sudden fever spikes for two years and his blood tests were within the normal range. In 1993, a surgical biopsy of swollen left inguinal lymph nodes was negative for malignancy, but showed reactive lymphadenitis and widespread sinus histiocytosis. A concomitant needle biopsy of the periaortic lymph nodes and a bone marrow aspirate were also negative. In 1994, after an emergency hospital admission because of a sport-related thoracic trauma, a right inguinal lymph node biopsy demonstrated Hodgkin’s lymphoma Stage IVB (scleronodular mixed cell subtype). Although it was improved by chemotherapy, the disease suddenly relapsed, and a further lymph node biopsy was performed in 1998 confirming the same diagnosis. Despite further treatment, the patient died of septic shock in 2004, at the age of 38 years. Retrospective analysis of the various specimens showed intracellular heavy metal nanoparticles within lymph node, bone marrow, and liver samples by field emission gun environmental scanning electron microscopy and energy dispersive spectroscopy. Heavy metals from environmental pollution may accumulate in sites far from the entry route and, in genetically conditioned individuals with tissue specificity, may act as cofactors for chronic inflammation or even malignant transformation. The present anecdotal report highlights the need for further pathologic ultrastructural investigations using serial samples and the possible role of intracellular nanoparticles in human disease.Keywords: Hodgkin’s lymphoma, heavy metals, nanoparticles, nanotoxicity, host–particle interactions, environmental exposure