Lyme disease and Various Forms of Lymphoma

Topics with information and discussion about published studies related to Lyme disease and other tick-borne diseases.
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Lyme disease and Various Forms of Lymphoma

Postby RitaA » Mon 6 Jun 2011 22:41

I keeping reading about an apparent association between Lyme disease and various forms of lymphoma. Some of these references might already be mentioned here, but this is what I was able to find in a fairly short amount of time. If anyone here (or the author of Relative Risk) has access to the entire 2003 article (for which there isn't even an abstract available), I would appreciate them posting it here or elsewhere:

J Cutan Pathol. 1997 Sep;24(8):457-61.
Infection by Borrelia burgdorferi and cutaneous B-cell lymphoma.
Cerroni L, Zöchling N, Pütz B, Kerl H.
Department of Dermatology, University of Graz, Austria.

In past years, association of primary cutaneous B-cell lymphoma (CBCL) with infection by Borrelia burgdorferi has been reported in a few patients. The evidence for a pathogenetic role was based on clinical grounds or raised titre of antibodies in serum. Both methods, however, do not prove the association between the micro-organism and the CBCL, especially in countries where infection by Borrelia burgdorferi is endemic. Moreover, the exact percentage of Borrelia burgdorferi-positive CBCL is not known. We retrieved from our files 50 cases of CBCL to perform PCR analysis of Borrelia burgdorferi DNA on paraffin-embedded tissue sections. Only patients with primary CBCL were selected. In all cases, monoclonality of the infiltrate was confirmed by immunohistological pattern of immunoglobulin light chains or molecular analysis of JH gene rearrangement, or both. Specific DNA sequences of Borrelia burgdorferi were identified in cutaneous lesions from 9 patients (follicle center lymphoma: 3/20; immunocytoma: 3/4; marginal zone B-cell lymphoma: 2/20; diffuse large B-cell lymphoma: 1/6). Specificity was confirmed by Southern blot hybridisation in all positive cases. We could show that Borrelia burgdorferi DNA is present in skin lesions from a small proportion of patients (18%) with various types of CBCL. Our results may have therapeutic implications. In analogy to Helicobacter pylori-associated MALT-lymphomas, which in some cases can be cured by eradication of Helicobacter pylori infection, a proportion of CBCL may be cured with antibiotic therapy against Borrelia burgdorferi. Although yet speculative, adequate antibiotic treatment for patients with primary CBCL should be considered before more aggressive therapeutic options are applied, particularly in countries where infection by Borrelia burgdorferi is endemic. PCR analysis of Borrelia burgdorferi DNA is a fast test that should be performed in all patients with CBCL to identify those who more likely could benefit from an early antibiotic treatment.

PMID: 9331890

[PubMed - indexed for MEDLINE]

Hautarzt. 1988 Nov;39(11):717-26.
[Cutaneous B cell lymphoma in chronic Borrelia burgdorferi infection. Report of 2 cases and a review of the literature].
[Article in German]
Garbe C, Stein H, Gollnick H, Taud W, Orfanos CE.
Universitäts-Hautklinik und Poliklinik, Klinikum Steglitz der Freien Universität Berlin.
Low-grade malignant B-cell lymphomas of the skin can be distinguished from lymphadenosis benigna cutis (Bäfverstedt) by immunohistological methods developed in the last few years. Its coexistence with Borrelia burgdorferi infection can be shown by clinical and serological findings. In the chronic stage of this infection, lymphocytic cell infiltrations consistent with histological and immunohistological findings of malignant B-cell lymphoma can be found. Predominantly at the extremities, multiple plaque-shaped or nodular lesions are seen, showing a follicular pattern in their periphery. The tumors do not respond to antibiotic therapy. They regress totally after X-ray treatment, but local recurrences are rather common. They show a long persistent course with only slow progression and seem to be of low-grade malignancy independent from the cytological findings. In most cases the tumors remain limited to the skin and to one anatomical site; nevertheless, the development of systemic involvement has been reported. We present two cases of malignant B-cell lymphoma of the skin in patients with chronic B. burgdorferi infection. Both cases showed the typical clinical and histological features of this entity. Similar reports from the literature indicate close relationships with the chronic stage of Borrelia infection, with the simultaneous presence of acrodermatitis chronica atrophicans as an indicator. We conclude that an elevated titer indicating Borrelia infection is an important finding for the diagnosis and prognosis of this particular type of cutaneous B-cell lymphoma.

PMID: 3072322

[PubMed - indexed for MEDLINE]

Am J Surg Pathol. 2003 May;27(5):702-3.
Borrelia-associated primary cutaneous MALT lymphoma in a nonendemic region.
de la Fouchardiere A, Vandenesch F, Berger F.

PMID: 12717258

[PubMed - indexed for MEDLINE] ... lltext.pdf

Infectious Agents in Mucosa-Associated Lymphoid Tissue–Type Lymphomas: Pathogenic Role and Therapeutic Perspectives

Mucosa-associated lymphoid tissue (MALT) lymphoma probably constitutes the best in vivo model showing how complex interplay between B lymphocytes and the surrounding microenvironment may lead to a neoplastic disorder. After the seminal discovery of the pathogenic association between Helicobacter pylori and gastric MALT lymphomas, evidence suggests the possible involvement of other infectious agents in the development of MALT lymphomas arising at different body sites. Although several other bacteria (Borrelia burgdorferi, Campylobacter jejuni, and Chlamydia psittaci) and viruses (Hepatitis C virus) seem to play a role in lymphomas presenting at different locations, a possible common pathogenic mechanism is emerging. Several lines of evidence suggest that different infectious agents might provide a chronic antigenic stimulation that elicits host immune responses able to promote clonal B-cell expansion. This model is also substantiated by the increasing number of patients with MALT lymphomas who exhibit objective clinical responses after antimicrobial therapy. A multidisciplinary approach is critical to better understand the complex etiopathogenesis of MALT lymphomas with the final goal to dissect the clinicopathologic heterogeneity of these disorders and design more tailored preventive and therapeutic approaches.

Clinical Lymphoma & Myeloma, Vol. 6, No. 4, 289-300, 2005 ... 2997a.html

Molecular Diagnostics
British Journal of Cancer (2006) 94, 879–883. doi:10.1038/sj.bjc.6602997
Published online 21 February 2006

Mycosis fungoides: is it a Borrelia burgdorferi-associated disease?

Mycosis fungoides (MF) is the most frequently found cutaneous T-cell lymphoma with an unknown aetiology. Several aetiopathogenetic mechanisms have been postulated, including persistent viral or bacterial infections. We looked for evidence of Borrelia burgdorferi (Bb), the aetiologic agent of Lyme disease (LD), in a case study of MF patients from Northeastern Italy, an area with endemic LD. Polymerase chain reaction for the flagellin gene of Bb was used to study formalin-fixed paraffin-embedded lesional skin biopsies from 83 patients with MF and 83 sex- and age-matched healthy controls with homolocalised cutaneous nevi. Borrelia burgdorferi-specific sequence was detected in 15 out of 83 skin samples of patients with MF (18.1%), but in none out of 83 matched healthy controls (P<0.0001). The Bb positivity rates detected in this study support a possible role for Bb in the aetiopathogenesis of MF in a population endemic for LD.

Here's the 2008 article "Borrelia infection and risk of non-Hodgkin lymphoma" previously posted by Yvonne:


Edited to add:

Volume 74, Issue 3, Pages 156-162 (June 2010)

Primary cutaneous marginal zone lymphoma

Stéphane Dallea, Luc Thomasa, Brigitte Balmea, Charles Dumontetb, Catherine Thieblemontc
Accepted 16 September 2009. published online 12 October 2009.

Primary cutaneous marginal zone B-cell lymphoma (PCMZL) is included in the group of extranodal marginal zone B-cell lymphoma involving mucosal sites. Many evidences suggest that chronic antigen stimulation is a key-player in its pathogenesis. While Helicobacter pylori seems not to be implicated in PCMZL, Borrelia Burgdorferi's role is still matter of debate since the results are discordant between European and North American/Asian countries. However Borrelia subspecies are different between the studied areas and this difference could be a confounding factor. Then ubiquitous candidate antigen is still missing. Beyond these discrepancies the treatment of diffuse PCMZL has been recently improved. If local therapies (surgery, radiation) are the gold standard for localized disease, rituximab can also be considered as an alternative for disseminated or plurifocal PCMZL.

Here's a website that deals with various types of lymphoma, and there does seem to be some kind of association between Lyme disease and at least some types of lymphoma:

Infections strongly associated with MZL include:

H. pylori,

C. jejuni,

B. burgdorferi,

C. psittaci, and

Hepatitis C Virus (HCV)

Source: Infection-associated lymphomas derived from marginal zone B cells: a model of antigen-driven lymphoproliferation. Blood. 2006 Apr 15;107(8):3034-44. Epub 2006 Jan 5. Review. PMID: 16397126 | Related articles
Last edited by RitaA on Fri 26 Dec 2014 21:02, edited 1 time in total.

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Joined: Thu 1 Jul 2010 8:33

Re: Lyme disease and Various Forms of Lymphoma

Postby RitaA » Tue 7 Jun 2011 2:51

I wonder if different borrelia strains and/or genetics or even environmental factors might account for some of the first study findings:

Mod Pathol. 2008 Dec;21(12):1517-26. Epub 2008 Sep 26.

Primary cutaneous marginal zone B-cell lymphoma: a molecular and clinicopathological study of cases from Asia, Germany, and the United States.

Takino H, Li C, Hu S, Kuo TT, Geissinger E, Muller-Hermelink HK, Kim B, Swerdlow SH, Inagaki H.
Department of Pathology, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan.
Primary cutaneous marginal zone B-cell lymphoma is considered the cutaneous counterpart of extranodal marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue. Although its molecular pathogenesis is currently unknown, an etiological link with Borrelia burgdorferi infection has been identified in European, but not in American or Asian cases. To better understand the pathogenesis and the geographical differences of cutaneous marginal zone B-cell lymphoma, 60 cases from the East Asia, Germany, and the United States at their initial presentation were subjected to the following analyses; (1) clinicopathological comparison between the geographical regions, (2) detection of B. burgdorferi DNA, (3) detection of the API2-MALT1 fusion transcript, a gene alteration specific to mucosa-associated lymphoid tissue lymphoma, and (4) inactivation of tumor suppressor genes (death-associated protein kinase (DAPK), p16(INK4a), p14(ARF), MGMT, TIMP3, CDH1, and RARB) by hypermethylation of the CpG islands. Cases from the three geographical regions showed similar clinicopathological features. However, moderate/marked tissue eosinophilia was found in 9/25 Asian cases, but only 1/23 German cases (P=0.011) and 0/12 American cases (P=0.015). All 60 cases were negative for either Borrelia DNA or API2-MALT1 fusion. Tumors from the three regions were highly methylated for DAPK (38-50% of the cases, mean 43%) and p16(INK4a) (42-70%, mean 49%), and the positivities were significantly higher than those of nonneoplastic skin (8%, P=0.0010 and 14%, P=0.0032, respectively). Methylation of these genes had no significant association with progressive features of the tumor. Primary cutaneous marginal zone B-cell lymphomas from the three geographical regions have common clinicopathological features, however, moderate/marked tissue eosinophilia is a feature found almost exclusively in Asian cases. Borrelia infection and API2-MALT1 fusion are not significant in this tumor. Methylation of DAPK and p16(INK4a) genes is a frequent event in this lymphoma at its initial presentation, but may not be associated with tumor progression.

PMID: 18820662
[PubMed - indexed for MEDLINE]

J Intern Med. 2009 Apr;265(4):421-38.

Infectious agents and lymphoma development: molecular and clinical aspects.

Ferreri AJ, Ernberg I, Copie-Bergman C.
Unit of Lymphoid Malignancies, Medical Oncology Unit, Department of Oncology, San Raffaele Scientific Institute, Milan, Italy.
This review is focused on the role of infectious agents in the development of some lymphoma entities. Associations involving bacterial infections mostly regard marginal zone B-cell lymphomas of mucosa-associated lymphoid tissue (MALT)-type. Some paradigmatic examples of these associations include the Helicobacter pylori-related gastric MALT lymphoma and the more recently reported links between Chlamydophila psittaci and ocular adnexal MALT lymphomas and Borrelia burgdorferi and cutaneous MALT lymphomas. The well-documented association between Epstein-Barr virus infection and related lymphoproliferative disorders are analysed as an example of lymphotropic virus with tumourigenic activity. Molecular, biological and clinical features as well as therapeutic implications of these associations are analysed and future perspectives in this field are discussed.

PMID: 19298458
[PubMed - indexed for MEDLINE]

Hautarzt. 2010 Feb;61(2):145-7.

[Cutaneous marginal zone lymphoma (SALT) and infection with Borrelia burgdorferi].

[Article in German]
Fühler M, Ottmann KW, Tronnier M.
Klinik für Dermatologie, Venerologie und Allergologie, Klinikum Hildesheim GmbH, Weinberg 1, 31134 Hildesheim.
A relationship between Borrelia burgdorferi and the development of cutaneous B-cell lymphoma (CBCL) has been long discussed. B. burgdorferi DNA has been detected in patients with CBCL and a response of CBCL to antibiotics has been observed. In our patient with a Borrelia infection, a marginal zone lymphoma (SALT) regressed after ceftriaxone therapy. This further case of a combined appearance of CBCL and B. burgdorferi underlines a possible relationship as an example of an infectious trigger in tumorigenesis.

PMID: 19399378
[PubMed - indexed for MEDLINE]

I read elsewhere that autoimmune issues may be triggered by various infectious agents -- and particularly in genetically vulnerable people. Autoimmunity also appears to increase the risk of lymphoma. I'm not the only one to have noticed this association: ... .full.html

Malignant Lymphomas in Autoimmunity and Inflammation: A Review of Risks, Risk Factors, and Lymphoma Characteristics

Karin Ekström Smedby1, Eva Baecklund3 and Johan Askling2
1Department of Medical Epidemiology and Biostatistics, Karolinska Institutet; 2Clinical Epidemiology Unit and Rheumatology Unit, Department of Medicine, Karolinska Hospital, Stockholm, Sweden; and 3Department of Rheumatology, Akademiska Hospital, Uppsala, Sweden

Over recent decades, the worldwide incidence of malignant lymphomas has increased dramatically (1). In the United States, non-Hodgkin lymphoma (NHL) is now the fifth most commonly diagnosed malignancy (2). The causes of most new cases of lymphoma are poorly understood, as reflected by the relatively few risk factors that have been established (1). Over the years, several studies have linked certain autoimmune and chronic inflammatory conditions, including rheumatoid arthritis (RA), Sjögren's syndrome, systemic lupus erythematosus (SLE), celiac disease, dermatitis herpetiformis, and chronic thyroiditis to an increased occurrence of lymphoma (3). However, the magnitude of the average lymphoma risk increase in each disorder varies considerably among studies (4). About the exposure, it is unclear whether the increased risk pertains equally to all individuals or varies among groups of patients with different phenotypic or treatment-related disease characteristics, which in turn remain to be defined. About the outcome, it is unclear to what extent the increased lymphoma occurrence is mediated through specific subtypes and whether the relevant subtypes vary among different inflammatory conditions. Another important question is whether elevated lymphoma risk accompanies states of chronic inflammation in general or whether it is specifically linked only to some disorders.

Nonautoimmune Inflammatory Conditions

Several infectious agents have been specifically linked to certain subtypes of lymphoma. These agents include the viruses HIV, EBV, human T-cell lymphotrophic virus-1, human herpes virus-8 (1), and hepatitis C virus (124) and the bacteria Helicobacter pylori (125), Borrelia burgdorferi (126), and most recently also Chlamydia psittaci (127) and Campylobacter jejunei (128). Most of these agents are believed to exert their lymphomagenic mechanisms primarily or partially through chronic immune stimulation (124, 126, 128-130). Infection-related systemic activation of the immune response, as observed in tuberculosis, malaria, herpes zoster, pneumonia, or pyelonephritis, was suggested as a risk factor for lymphoma in some studies (21, 60, 131, 132). Excess lymphoma risk in association with frequent use of antibiotics may reflect similar mechanisms (39). Chronic bronchitis is another inflammatory state that was associated with NHL risk in one study (133). However, asthma, similarly characterized by airway inflammation and hyperreactivity, seems to be inversely associated with NHL risk along with other allergic disorders (134). Thus, although a biological association is plausible, available data are yet insufficient to establish or exclude a general link between nonautoimmune inflammation and lymphoma risk.

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Re: Lyme disease and Various Forms of Lymphoma

Postby RitaA » Fri 8 Jul 2011 6:11

Cas Lek Cesk. 2011;150(3):161-8.

[Lymphoproliferative disease in patients with autoimmune and inflammatory diseases: significance of antigenic stimulation and inflammatory processes].

[Article in Czech]
Tvarůzková Z, Pavlová S, Doubek M, Mayer J, Pospísilová S.
SourceMasarykova univerzita v Brne, Lékarska fakulta, Interní hematoonkologická klinika FN Brno, Centrum molekulárni biologie a genové terapie.


Evidence has been growing that the pathogenesis of lymphoproliferative disease involves immune processes deregulation. It is believed that antigens or immunological elements can trigger transformation of normal lymphocyte polyclonal population into monoclonal neoplastic disorder--lymphoproliferative disease. Extensive studies point to the link between malignant lymphoma development and autoimmune or inflammatory diseases--namely rheumatoid arthritis, Sjörgen's syndrome, coeliac disease, systemic lupus erythematosus or thyroiditis. Increased risk of lymphoproliferative disease development was also proved for some infections. These infections involve both viral (e.g. Epstein-Barr virus, HIV or hepatitis C virus) and bacterial agents (e.g. Helicobacter pylori, Borrelia burgdorferi). Besides various lymphomas, the links to autoimmune/inflammatory diseases have also been described in chronic lymphocytic leukaemia. Regarding clinical medicine, it is necessary to distinguish patients with autoimmune, inflammatory and infectious diseases who are at the increased risk of tumour development. New approaches must be found to lower this risk. Also, the relationship between autoimmune/inflammatory disease therapy and lymphoma development should be clarified. Although lymphomas associated with autoimmune and inflammatory diseases represent only a small proportion of all lymphomas, any new findings regarding these diseases can cast light on lymphoma pathogenesis as a whole.

PMID: 21560455 [PubMed - indexed for MEDLINE]

Posts: 1637
Joined: Mon 3 Dec 2007 2:53

Re: Lyme disease and Various Forms of Lymphoma

Postby rlstanley » Mon 14 Nov 2011 2:43 ... 8.abstract

Prevalence of Borrelia Burgdorferi Infection in a Series of 98 Primary Cutaneous Lymphomas

Oncologist. 2011 Nov 9.

Maurilio Ponzonia,c, Andrés J. M. Ferrerib,c, Silvia Mappab,c, Elisa Pasinid, Silvia Govib,c, Fabio Facchettie, Daniele Fanonig, Alessandra Tuccif, Arianna Vinoa, Claudio Doglionia,c, Emilio Bertig and Riccardo Dolcettid

Correspondence: Maurilio Ponzoni, M.D., Unit of Lymphoid Malignancies, Pathology Unit, San Raffaele Scientific Institute, Via Olgettina 60, 20132 Milan, Italy. Telephone: 0039-02-26432544; Fax: 0039-02-26432409; e-mail:

Received April 1, 2011.
Accepted August 16, 2011.

Disclosures: Maurilio Ponzoni: None; Andrés J. M. Ferreri: None; Silvia Mappa: None; Elisa Pasini: None; Silvia Govi: None; Fabio Facchetti: None; Daniele Fanoni: None; Alessandra Tucci: None; Arianna Vino: None; Claudio Doglioni: None; Emilio Berti: None; Riccardo Dolcetti: None.


Borrelia burgdorferi has been variably associated with different forms of primary cutaneous lymphoma. Differences in prevalence rates among reported studies could be a result of geographic variability or heterogeneity in the molecular approaches that have been employed.

In the present study, we investigated the prevalence of Borrelia burgdorferi sensu lato DNA in diagnostic tissue samples from fresh cutaneous biopsies of 98 primary cutaneous lymphomas and 19 normal skin controls. Three different polymerase chain reaction (PCR) protocols targeting the hbb, flagellin, and Osp-A genes were used. Direct sequencing of both sense and antisense strands of purified PCR products confirmed the specificity of the amplified fragments. Sequence specificity was assessed using the Basic Local Alignment Search Tool, and MultAlin software was used to investigate the heterogeneity of target gene sequences across the different samples.

Borrelia DNA was not detected in 19 controls, 23 cases of follicular lymphoma, 31 cases of extranodal marginal zone lymphoma, or 30 cases of mycosis fungoides. A single case of 14 diffuse large B-cell lymphoma cases was positive for B. burgdorferi.

This study does not support a pathogenic role of B. burgdorferi in primary cutaneous B- and T-cell lymphomas from areas nonendemic for this microorganism and the consequent rationale for the adoption of antibiotic therapy in these patients.


The prevalence of Borrelia infection in tumor tissue is extremely rare in patients with cutaneous lymphoma diagnosed in areas nonendemic for this microorganism and/or Lyme disease. In these areas, Borrelia probably has no pathogenetic role in cutaneous lymphomas; accordingly, the search for it is expensive and has no clinical relevance,rendering antibiotic therapy useless.

Conversely, in areas endemic for Borrelia infection, the use of antibiotics like ceftriaxone would constitute a rational choice to induce objective clinical responses in patients with these malignancies.

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Re: Lyme disease and Various Forms of Lymphoma

Postby RitaA » Sun 14 Apr 2013 0:34

My thanks to Camp Other for tweeting this:

J Cutan Pathol. 2013 May;40(5):477-84. doi: 10.1111/cup.12102. Epub 2013 Mar 8.

Primary cutaneous marginal zone lymphoma associated with juxta-articular fibrotic nodules in a teenager.

Ghatalia P, Porter J, Wroblewski D, Carlson JA.


Department of Pediatric Hematology/Oncology, Albany Medical College, Albany, NY, 12208, USA.


Primary cutaneous marginal zone lymphoma (PCMZL) has rarely been reported in teenagers and is occasionally associated with Borrelia burgdorferi infection. Juxta-articular fibrotic nodules represent a unique, localized fibrosing response to spirochete infections, namely Borreliosis. Herein, we report a 15-year-old healthy boy who presented with a 4-year history of progressive acquisition of asymptomatic, erythematous nodules, ≤3 cm, beginning with his right forearm (3), then right arm (1) and lastly his right inner thigh (1). Biopsy showed PCMZL in three of five samples, and inflamed, fibrotic nodules, near the elbow in two. The bottom heavy lymphomatous nodules consisted of mostly small CD20+ CD43+ lymphocytes, some with plasmacytoid features. Mature plasma cells were lambda light chain restricted by in situ hybridization. The juxta-articular fibrotic nodules were located in the deep dermis and subcutis, had peripheral plasma cell-rich infiltrates, and showed nodular sclerosis (morphea profunda-like) in one, and lamellar and angiocentric sclerosis in the other reminiscent of quiescent lesions of chronic localized fibrosing leukocytoclastic vasculitis. Immunohistochemistry for B. burgdorferi revealed rare positive organisms; however, polymerase chain reaction (PCR) and serology were negative for B. burgdorferi as were serologic and/or PCR assays for Bartonella henselae, Ba. quintana, Ehrlichia chaffeensis, Treponema pallidum, Helicobacter pylori and Babesia microti. No evidence of extracutaneous disease was found by the review of systems and imaging studies. A 4-week trial of doxycycline therapy failed, whereas intralesional (IL) corticosteroid therapy induced rapid regression of his nodules. After two local recurrences, also treated with IL corticosteroids, he is well, without cutaneous disease, 20 months later. A literature review of 19 pediatric cases PCMZL reveals a similar natural history as adult PCMZL. Despite negative serology and PCR for B. burgdorferi, the occurrence of ipsilateral juxta-articular fibrotic nodules, positive B. burgdorferi immunohistochemistry and rapid response to IL corticosteroids implicate the presence of a replicative or non-replicative infectious (spirochetal) antigen in the initiation and promotion of this teenager's PCMZL.

© 2013 John Wiley & Sons A/S. Published by Blackwell Publishing Ltd.

PMID: 23578183 [PubMed - in process]

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Re: Lyme disease and Various Forms of Lymphoma

Postby RitaA » Wed 19 Mar 2014 21:49

Looks like I missed this 2000 article from Scotland: ... ia.12.aspx

American Journal of Surgical Pathology:
September 2000 - Volume 24 - Issue 9 - pp 1279-1285
Original Articles

Primary Cutaneous B-Cell Lymphoma and Borrelia burgdorferi Infection in Patients From the Highlands of Scotland

Goodlad, John R. M.D.; Davidson, Marilyn M. F.R.C.Path.; Hollowood, Kevin M.D.; Ling, Claire M.Sc.; MacKenzie, Carol M.N.C.; Christie, Irene M.N.C.; Batstone, Paul J. B.Sc.; Ho-Yen, Darrel O. M.D.


Although a link beteen primary cutaneous B-cell lymphoma (PCBCL) and Borrelia burgdorferi infection has long been suspected, previous studies have not demonstrated a significant association. The authors looked for evidence of B. burgdorferi in 20 cases of PCBCL from the Scottish Highlands, an area with endemic Lyme disease, and compared their findings with those in 40 control patients (20 undergoing wide reexcision at sites of malignant melanoma and 20 biopsies of inflammatory dermatoses). All studies were performed on formalin-fixed, paraffin-embedded tissues. The cases of PCBCL were classified according to criteria described by the European Organization for Research and Treatment of Cancer Cutaneous Lymphoma Project Group using a combination of morphology, immunohistochemistry, and seminested polymerase chain reaction (PCR) for immunoglobulin heavy chain gene rearrangement. A nested PCR was performed on deoxyribonucleic acid (DNA) extracts from the lymphoma and control cases using primers to a unique conserved region of the B. burgdorferi flagellin gene. B. burgdorferi-specific DNA was detected in seven of 20 lymphoma cases (five of 12 marginal zone lymphomas, one of five primary cutaneous follicle center cell lymphomas, one of three diffuse, large B-cell lymphomas of the leg) and in one melanoma reexcision patient of 40 control subjects. The relationship between B. burgdorferi and PCBCL was significant when compared with the control groups separately (p <0.05) or in combination (p <0.01). These results provide strong evidence to support the concept of B. burgdorferi-driven lymphomagenesis in the skin.

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