this class of antibiotic agents has an anti - lymphoproliferative effect via down - regulation of the anti - apoptotic proteins bcl-2 and bcl - xl [ 2 , 3 ] ; therefore , macrolides may be clinically applicable in the treatment of malignancy , particularly lymphoid malignancy . there have been several previous reports indicating that malignant lymphoma and plasma cell disorders can be successfully treated with the macrolide clarithromycin ( cam ) alone or in combination with a corticosteroid [ 1 - 4 ] . corticosteroids are key agents for the treatment of lymphoid malignancy due to their ability to induce apoptosis of malignant lymphoid cells . we encountered a case , in which a positive outcome was achieved with the use of cam and prednisolone ( psl ) for the treatment of advanced diffuse large b - cell lymphoma ( dlbcl ) . a 71-year - old woman was admitted to hospital with fever and cervical pain . for the previous year , she had been treated with antituberculars for non - tuberculous mycobacteria ( ntm ) infection of the lung after detection of mycobacterium avium in her sputum . her symptoms reappeared approximately 10 months after completion of antitubercular therapy , and just prior to admission , she had received levofloxacin then amoxicillin for fever based on suspicion of recurrent ntm or another pulmonary infection . however , while chest radiography revealed no new lesions , her symptoms did not improve . on admission lactate dehydrogenase levels were 148 iu / l and serum soluble interleukin-2 receptor ( sil-2r ) levels were increased to 928 u / ml . chest computed tomography ( ct ) revealed axillary lymphadenopathy ( fig . bone scintigram revealed uptake into the vertebrae , sternum , ribs , left scapula , pelvis , and right femur ( fig . magnetic resonance imaging revealed high - intensity areas in the cervical and thoracic vertebrae on t2-weighted imaging . fluorodeoxyglucose ( fdg)-positron emission tomography ( pet ) demonstrated increased spotty uptake of fdg into the vertebrae , sternum , ribs , pelvis , right femur , and bilateral axillary lymph nodes ( fig . moderate serial uptake into the cervical to lumbar - region vertebrae was also evident ( fig . biopsy specimens from the left axillary lymph nodes revealed an absence of follicular structures and diffusely proliferative large lymphoid cells with pleomorphic , irregular nuclei and prominent nucleoli , accompanied by small lymphoid cells ( fig . immunohistochemical staining revealed that the large lymphoid cells were positive for cd20 , bcl-2 , and mib-1 ( fig . biopsy specimens were inadequate for conducting chromosomal analysis or determining genetic rearrangements in the axillary lymph nodes . although neither bone marrow aspiration specimens nor bone marrow biopsy specimens from the ileum revealed large lymphoid cells , the results of bone ct , bone scintigraphy , and fdg - pet indicated multiple lesions of the bone and bone marrow . based on these findings , she was diagnosed with clinical stage iv dlbcl , with low - to - intermediate risk according to the international prognostic index . her cervical pain was thought to be due to invasion of the lymphoma cells into the cervical vertebrae . we therefore began treatment with cam ( 800 mg / day ) and psl ( 20 mg / day ) on the condition that conventional chemotherapy would be started immediately if dlbcl exacerbation was observed . the psl dosage was initially 20 mg / day for 2 weeks and subsequently 15 mg / day for 2 weeks . her sil-2r levels decreased from 928 to 619 u / ml approximately 2 months after beginning cam and psl treatment . at that time complete remission ( cr ) was achieved after 6 months , with improvements in lymphadenopathy and lesions of the bone and bone marrow apparent on both ct ( fig . slightly reduced taste sensation was reported , and was considered a side effect of long - term cam use . as the patient had been treated for ntm until approximately 10 months prior to admission , fever and lymphadenopathy were initially suspected to have been due to recurrent ntm infection . however , chest ct did not demonstrate any exacerbation of infiltration shadows associated with ntm . necrotizing granuloma - containing neutrophils , epithelioid cells , and langhans giant cells , which are suggestive of ntm , were not evident in biopsy specimens from the left axillary lymph nodes . similarly , we could not diagnose reactive lymphoid hyperplasia because no follicular structure was detectable and large lymphoid cells were positive for bcl-2 . several cases have been reported where ntm developed during chemotherapy for cancer , so we initially decided to use cam to treat the lymphoma , rather than conventional chemotherapy . as cam is known to be effective in ntm , this treatment was considered advantageous for both the lymphoma and ntm . we prescribed psl for its anti - inflammatory effects as well as its apoptotic effects on lymphoid cells . serum sil-2r levels are closely related to disease activity in non - hodgkin lymphoma patients . we therefore continued to monitor sil-2r levels to determine disease activity , response to therapy , and risk of relapse . cam has recently been found to have anti - proliferative activities against some lymphomas [ 1 - 3 ] . reported 2 cases of pulmonary mucosa - associated lymphoid tissue lymphoma successfully treated with cam . they speculated that the macrolide induced apoptosis of lymphocytes via the down - regulation of bcl - xl . we have also reported a case of t(14;18)(q32;21)-positive follicular b - cell lymphoma that was successfully treated with cam . as cam is known to induce down - regulation of bcl-2 , and lymphoma cells from our previous case were positive for bcl-2 , we speculated that cam induced apoptosis in the lymphoma cells . chen et al .   reported bcl-2 expression in 68.5% and 50.0% of chinese and western dlbcl cases , respectively . dlbcl is heterogeneous , and bcl-2 expression is variable within the 2 major dlbcl subgroups , being germinal center b - cell - like ( gcb ) or activated b - cell - like ( abc ) dlbcl . iqbal et al .   reported that t(14;18)(q32;q21 ) was frequently observed in the gcb subgroup and was strongly associated with bcl-2 expression . patients with abc dlbcl did not exhibit t(14;18)(q32;21 ) , but demonstrated a markedly higher frequency of amplification for chromosome 18q21 , on which bcl-2 resides . chromosomal analysis was not undertaken in this case , so it was unclear to which subgroup the disease belonged . however , because the lymphoma cells were positive for bcl-2 , cam was likely to have induced apoptosis of the lymphoma cells . nuclear factor ( nf)-b is a transcription factor that up - regulates anti - apoptotic genes , namely bcl-2 , bcl - xl , xiap , and survivin . heckman et al . reported that nf-b activates bcl-2 expression in t(14;18 ) lymphoma cells . reported that nf-b was detected in 25.6% of dlbcl tumors , and nf-b over - expression was found to be a prognostic marker for poor survival in dlbcl . nf-b inhibition has also been shown to down - regulate expression of the down - stream target gene products bcl-2 , bcl - xl , xiap , and survivin , leading to apoptosis of lymphoma cells . as cam has been reported to inhibit nf-b activation of human blood mononuclear cells ( i.e. , lymphocytes and monocytes / macrophages ) , the lymphoma cells in this case may have undergone apoptosis via inhibition of nf-b activation . although the above - mentioned case reports did not discuss the relationships between nf-b and bcl-2/bcl - xl , cam might also have been effective in those cases through its inhibition of nf-b activation . in fact , gc - induced apoptosis has been exploited in the treatment of lymphoid malignancies . the lympholytic effect of gcs is mediated by cytoplasmic steroid receptors that are translocated to the nucleus , where they signal apoptosis . gc - induced apoptosis is attenuated by bcl-2 ; therefore , down - regulation of bcl-2 by macrolide treatment when combined with gc may result in advantageous apoptotic effects . this synergy between cam and psl was effective in the present case of bcl-2-positive dlbcl . although our patient benefited from cam and psl treatment , this combination can not be considered a recommended therapy at present . our case demonstrated that this treatment is an option in patients who refuse chemotherapy or in elderly patients with underlying medical conditions . clinical trials need to be conducted to better determine the efficacy and tolerability of cam and psl in dlbcl before this treatment can be adopted on a wider basis .
we report a case of diffuse large b - cell lymphoma ( dlbcl ) treated successfully with clarithromycin ( cam ) and prednisolone ( psl ) . a 71-year - old woman presented with fever and cervical pain . 
 dlbcl was diagnosed based on histological results from lymph node biopsy . 
 cervical pain was thought to be caused by the invasion of lymphoma cells into the cervical vertebrae . 
 she initially received radiotherapy for the cervical lesion . 
 she did not receive conventional chemotherapy because of the risk of recurrent non - tuberculous mycobacteria infection ; therefore , she was treated with 20 mg / day psl and 800 mg / day cam to induce apoptosis in lymphoma cells . 
 complete remission was achieved after 6 months . 
 the present findings suggest that cam and psl may be effective in some cases of dlbcl .