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

Tommaso Iannitti¹, Stefania Capone², Antonietta Gatti³, Frederico Capitani⁴, Cetta Francesco^5,6, Beniamino Palmieri^2
1Department 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, Italy

Abstract: 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

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