paraneoplastic pemphigus , which was initially described by anhalt et al ( 1 ) , is characterized by non - specific pemphigus accompanying mucosal skin lesions showing erosion and blisters , which occur as a result of the production of autoantibodies against internal tumors .
skin lesions associated with autoantibodies may not only be pemphigus lesions , but also erythema multiforme - like lesions , graft - versus - host disease - like lesions and lichen planus lesions ( 1,2 ) .
these diseases may also cause mortality due to the infiltration of autoantibodies into other organs , thus leading to the term paraneoplastic autoimmune multiorgan syndrome ( pams ) ( 2 ) .
lymphoid hyperplasia is the rapid growth and proliferation of normal cells that resemble lymph tissue , and the majority of lymphoid hyperplasia cells are t lymphocytes ( 2,3 ) .
neoplasms associated with lymphoid hyperplasia include castleman 's disease , non - hodgkin 's lymphoma and thymoma , and these tumors have been frequently associated with pams ( 2 ) .
conversely , sarcoma and malignant melanoma have rarely been associated with pams ( 3 ) .
the most common symptoms of pams are persistent oral lesions that are typically resistant to pharmacological treatment ( 47 ) .
brachytherapy can be attempted when considering the accessibility of the disease lesion , to minimize the side effects to the adjacent organ and to increase the therapeutic radiation dose ( 8) .
the present study is , to the best of our knowledge , the first to report the results of intraluminal brachytherapy application for the treatment of a persistent and pharmacological - resistant oral erosive ulcer in a 42-year - old female patient with giant lymph node hyperplasia ( castleman 's disease ) and erosive skin lesions in the vaginal mucosa and trunk region .
a 42-year - old female patient visited chonbuk national university hospital ( jeonju , republic of korea ) with an 8-month history of erosive skin lesions occurring in the trunk region , oral mucosa and vaginal mucosa .
an abdominal computed tomography ( ct ) scan ( date , 18/6/2008 ) was performed following the detection of elevated ca125 ( 86.4 u / ml ; normal , 037 u / ml ) and ca19 - 9 ( 185.46 u / ml ; normal , < 37 u / ml ) levels in a blood examination .
a retroperitoneal mass identified in the abdominal ct scan was removed ( date , 25/6/2008 ) and the patient was diagnosed with castleman 's disease according to this biopsy ( date , 30/6/2008 ) ( fig .
1 ) . the biopsy was a large ( 126.56.8 cm ) mass with multicentric , hyaline vasular lymph node hyperplasia .
the study was approved by the institutional review board of chonbuk national university hospital and was conducted according to the declaration of helsinki regarding biomedical research involving human subjects .
a detailed explanation of the study was provided to the patient , and written informed consent was obtained from the patient .
biopsies of the skin lesions were performed , and hematoxylin and eosin - stained pathology sections were classified according to their histological features , analyzed under a microscope ( bx50 ; olympus corporation , tokyo , japan ) .
the trunk lesions showed non - caseating granulomous features and positive lichen planus under low magnification , and chronic inflammatory cell infiltration , numerous blood vessels , lymphohistiocytic granuloma infiltrate and multicentric giant cells under high magnification ( fig .
2a ) . in the skin lesions from the vaginal mucosa , epidermal labia majora - acanthosis , separation of the dermoepidermal junction , destruction of the basal layer and deposition of lymphoid cells and neutrophils in the dermis
were observed under low magnification , and dyskeratosis , exocytosis , acantholysis and squamous metaplasia of the epidermis and keratinocytes were observed under high magnification ( fig .
the tongue was ulcerated and lacked the epithelium , and dense lymphoid cell infiltration into the tongue was observed under low magnification .
immunofluorescence ( date , 7/8/2008 ) revealed fibrinogen deposition along the basement membrane ( fig . 2c ) .
for the immunofluorescence assay , the tissue specimen was incubated for 1 h at room temperature using a human igg fluorescence - labeled antibody ( cat .
, waltham , ma , usa ; dilution , 1:200 ) . the patient was diagnosed with pams ( 7/8/2008 ) following analyses of the tissue obtained from the retroperitoneal mass and skin lesions . following the diagnosis ,
retroperitoneal mass resection was performed to alleviate pain caused by the mass and pharmacological treatment was performed for skin and mucosal lesions . pharmacological treatment consisted of a 4-month treatment regime of twice daily methotrexate ( 50 mg ; jw pharmaceutical , seoul , republic of korea ) and thalidomide ( 200 mg ; taytech biogen , seoul ,
republic of korea ) administration , followed by a one - time administration of azaprine ( 100 mg ; korean united pharmaceutical , inc . ,
seoul , republic of korea ) , an immunosuppressive drug , and 10 mg / day prednisolone ( korea pharma , seoul , republic of korea ) for 1 year .
the majority of the skin lesions in the trunk and vaginal mucosa were successfully treated , albeit the erosive lesion in the tongue was non - responsive to systemic pharmacological treatment and caused persistent pain .
, ulsan , republic of korea ) treatment and local injection of tamceton ( 40 mg ; hanall biopharma co. , ltd . ,
seoul , republic of korea ) were administered 20 and 15 times , respectively . however , the tongue lesion was non - responsive to these treatments , and the patient underwent intraluminal brachytherapy .
oral lesions were limited to the anterior half of the tongue , and no ulcerous lesions were observed in the buccal mucosa or gingiva ( fig .
intraluminal brachytherapy was performed ( date , 7/1/2010 ) to treat locally - located lesions , prevent damage to the gingiva and enhance the radiation dose effect .
the device for oral brachytherapy was designed using acrylic resin and consisted of separate molds for the upper and lower jaws .
the mold for the lower jaw consisted of three 6f catheter holes with 1-cm intervals to insert the catheter for brachytherapy ( fig .
the mold for the lower jaw constituted 2-mm lead plates to minimize the radiation exposure to the gingiva and teeth during the therapy , which were located adjacent to the tongue lesion .
a 2-mm lead plate was also inserted into the mold for the upper jaw during each therapy to reduce the radiation exposure to the palate ( fig .
treatment was performed using a lumencath catheter ( 6f 150 cm ; elekta instrument ab stockholm , stockholm , sweden ) for brachytherapy .
radiation treatment consisted of 2 gy per session and two sessions per week , using an iridium-192 high - dose - rate brachytherapy system ( microselectron hdr afterloader ; elekta instrument ab stockholm ) ( fig .
the patient was exposed to a total of 40 gy radiation during 20 therapy sessions .
grade 2 radiation - induced oral mucositis ( 9 ) was observed during the treatment .
chronic side effects were not observed during the follow - up period and the majority of the tongue lesions were successfully treated following brachytherapy ( fig .
no disease progression was observed during the 4-year follow - up period ; the patient 's oral disease lesions completely healed .
pemphigus vulgaris is characterized by acantholysis and intraepidermal blister formation , which are caused by the loss of normal interactions between cells due to the production of autoantibodies against the surface proteins of keratinocytes ( 10 ) . however , anhalt et al ( 1 ) examined a case of pemphigus vulgaris showing non - specific clinical symptoms , including painful erosive mucosal lesions and various skin rashes , that were associated with the production of autoantibodies against a tumor , which they termed paraneoplastic pemphigus .
subsequently , nguyen et al ( 11 ) suggested pams as an alternative and more appropriate name for paraneoplastic pemphigus for various reasons .
first , the heterogeneity of clinical characteristics can be expressed as clear rash without blisters against the cross - section of the cells ; second , autoimmune multiorgan syndrome targeting epidermal cells and internal organs is commonly observed in patients with paraneoplastic pemphigus ; and third , respiratory failure as a result of changes in bronchial epithelial cells is observed , despite not typically being associated with pemphigus .
anhalt et al ( 1 ) suggested that paraneoplastic pemphigus be diagnosed using the results of direct and indirect immunofluorescence analyses , immunoprecipitation assays , an analysis of clinical symptoms , including mucosal lesions with pain , various systemic skin lesions and internal organ tumors , and characteristic histological findings , including necrosis of keratinocytes , disjunction of intraepidermal pickle cells , vacuolization of the basal cell layer and dermatitis in the cell junction area .
however , camisa and helm ( 6 ) reported that pams could not be diagnosed in some cases due to insufficient findings upon examination or a condition that prohibited such examinations .
therefore , authors of that study proposed novel criteria for the diagnosis of pams based on distinguishing between major and minor findings ( 6 ) .
the major findings included various types of skin rashes , associated internal tumors and characteristic immunoprecipitation results , whereas the minor findings included the confirmed disjunction of pickle cells via histological analysis , precipitation of immunoreactants between the basal cell layer and cells upon direct immunofluorescence and positive findings in indirect immunofluorescence analyses using epithelial cells from rat urinary bladders ( 6 ) . using this method ,
pams may be diagnosed if all the three major findings are identified or if any two of the major findings and any two of the minor findings are observed ( 6 ) . in the present study ,
the patient was diagnosed with pams since she showed two of the major findings and two of the minor findings identified previously ( 1,4,10 ) .
this may be because many cases of pams are misdiagnosed as other diseases , including erythema multiforme , stevens - johnson syndrome , toxic epidermal necrolysis , lichen planus , pemphigus and graft - versus - host disease , due to its diversity of clinical manifestations and histopathological findings ( 11 ) . at present
, pams is considered an autoimmune disease and thus is treated with palliative treatments , including removal of the symptom - causing mass or administration of immunosuppressive drugs or adrenal cortical hormones ( 37 ) . however , a clear method for its treatment has yet to be established ( 38 ) .
painful oral erosive ulcers and various forms of skin rashes are typical skin lesions associated with pams ( 2 ) . in particular
stomatitis is observed in the earliest stage of the disease and shows the strongest resistance to treatment , such that it is often the most persistent of the associated symptoms .
it typically occurs on the lateral side of the tongue and extends towards the lip versmilion , thus causing pain .
notably , pams has been shown to have more severe symptoms and a wider range of clinical manifestations , as compared with normal pemphigus ( 10,11 ) . in the present case ,
the first symptom experienced by the patient was an erosive lesion in the oral mucosa and tongue , which was associated with severe pain .
other symptoms experienced by the patient , including skin lesions of the trunk and vaginal mucosa , were improved following surgical resection of the mass from the retroperitoneum , which was associated with the patient 's castleman 's disease , as well as treatment with an adrenal cortical hormone , methotrexate , thalidomide and an immunosuppressive drug , azaprine . however , the oral lesion was unresponsive to the pharmacological treatment and surgical resection , and was the cause of persistent severe pain .
previous studies have reported that autoimmune disorders may be sensitive to radiation ( 12,13 ) .
therefore , radiation therapy was considered for the present case . in the present study ,
the patient underwent brachytherapy to minimize radiation exposure to the surrounding organs . as a result of brachytherapy ,
the lesions in the tongue were controlled without causing serious acute or chronic side effects .
in addition , neither worsening nor progression of the lesion was observed during the 4-year follow - up period . in conclusion , the present study has demonstrated that brachytherapy is a promising therapeutic strategy for the persistent and drug - resistant oral lesions that are often observed in patients with pams .
however , regular observation of the patient may be required due to the slow response of pams to treatment and the high rate of relapse of this disease .
 paraneoplastic autoimmune multiorgan syndrome ( pams ) , also known as paraneoplasic pemphigus , involves the skin , internal organs and mucosa . 
 pams - associated mortality may occur as a result of autoantibody formation against internal tumors and their infiltration into organs other than the skin lesions that characterize pams . 
 the most common symptoms of pams include pain associated with continuous oral ulceration and resistance to pharmacological treatment . 
 the present study reports the case of a 42-year - old female patient who was admitted with an 8-month history of erosive skin lesions within the trunk region , oral mucosa and vaginal mucosa . 
 the patient was diagnosed with pams based on computed tomography scans and histological analyses of the lesions . 
 the lymphoid hyperplasia in the retroperitoneum and lesions in the vaginal mucosa and trunk area were improved following pharmacological treatment and resection of the lymph node showing hyperplasia . 
 however , the oral lesion was treated with intraluminal brachytherapy due to its resistance to long - term pharmacological treatment . 
 the majority of the lesions were improved following treatment , in the absence of any severe side effects . 
 in addition , neither worsening nor progression of the oral lesion was observed during the 4-year follow - up period . 
Introduction
Case report
Discussion