No Evidence of Association between Borrelia burgdorferi and Primary Cutaneous B-Cell Lymphomas in Marche Region, in Italy.
Authors: Goteri Gaia , Capretti Roberta , Rupoli Serena , Ranaldi Renzo , Menso Stefano , Pulini Stefano , Tassetti Angela , Morichetti Doriana , Scortechini Anna Rita , Mulattieri Simonetta , Stronati Andrea , Nicolini Massimiliano , Cicilioni Elio Grilli , Serresi Stefano , Offidani Anna Maria , Leoni Pietro 
Published: April 2020

Abstract
Extranodal marginal zone B-cell lymphomas are considered at the present time as “infection-associated” tumors, because their occurrence has been observed in the background of a chronic antigenic stimulation started by some recognised pathogenic microbial agents, which do not cause the lymphoid transformation by a direct infection of the lymphocytes, but by maintaining the cells with a prolonged antigenic stimulation in a continuous proliferative status and thus increasing the probabilities of a neoplastic transformation. Among them, the Helicobacter pilori is known to be active in the stomach, the Campylobacter jejuni in the ileum, the Chlamydia psittaci in the eye, the Hepatitis C virus in the spleen, whereas in the skin Borrelia burgdorferi, the agent of Lyme’s disease, which can present as erithema migrans as well as a lymphocytoma cutis, has been indicated as a potential agent involved in the pathogenesis of B-cell lymphomas. In some instances, the eradication of the Borrelia has been associated with skin lymphoma regression in cases with documented infection. In Italy there is a great variability of incidence of the disease, which is trasmitted by arthropode-bites and few cases have been observed also in our region, the Marche; this region has approximately one and half million of inhabitants. The aim of our study was to analyse by molecular techniques the presence in tissue of Borrelia burgdorferi DNA in 72 cases of primary cutaneous B-cell lymphomas, diagnosed at the Institute of Anatomic Pathology of Polytechnic Marche Region in Ancona from 1990 and 2004. In all the cases the clinical history was retrieved from clinical charts. On the basis of the pathological findings together with a complete phenotypical and clonality analysis, each case was reclassified according to the recent WHO/EORTC scheme, as follows: 16 cases of marginal-zone lymphomas, 33 cases of follicle-center lymphomas, 23 cases of diffuse large B-cell lymphomas, subdivided in “leg-type” (7), and “other” (16). DNA was extracted by paraffin-embedded tissue and amplified as previously reported, together with DNA extracted from colonies of Borrelia burgdorferi as positive control. None of the 72 cases resulted positive. The efficacy of the PCR method was documented by the expected bands obtained with control samples. Based on our results, the role of Borrelia burgdorferi in the pathogenesis of B-cell lymphomas seems to be unlikely in our geographical area, in agreement with a very low incidence of the Lyme’s disease. Therefore, also the specific antibiotic therapy do not seem to have a rationale in lymphoma treatment. Our negative results should represent a basis for searching a different combination of immunological, infectious and genetic factors to explain the occurrence of primary B-cell lymphomas, particularly the marginal types, in our region.