a 43-year - old man with a past medical history of wolff - parkinson - white syndrome presented with a 2-month history of an asymptomatic parieto - occipital skin lesion ( a 1.5-cm red - yellow nodule ) . occasionally , engulfed lymphocytes were noted in the cytoplasm of the histiocytes . immunological staining showed that the invading histiocytes were positive for cd68 and s-100 protein and were negative for cd1a and cd20 . these findings were consistent with the characteristics of rosai - dorfman disease ( rdd ) . the tests for hepatitis b surface antigen and antibodies to hepatitis c virus were negative . neither antibodies to human t - cell leukemia virus 1 or human immunodeficiency virus nor epstein - barr virus rna were observed . thoracic and abdominal ct showed a normal lung field with no mediastinal lymphadenopathy , no hepatosplenomegaly and no large lymphadenopathy . the patient was eventually diagnosed with sinus histiocytosis with massive lymphadenopathy involving the skin . because he also described a 1-year history of pain in his right inferior maxillary area , a positron emission tomography ( pet ) scan was performed , which showed fluorodeoxyglucose uptake in the right inferior maxillary area ( suv 8.7 ) . histological examination of the mucosal biopsy specimen showed large histiocytic cells with small round - to - oval nuclei , which were strongly positive for s-100 and cd68 , without emperipolesis . the patient remained asymptomatic with no signs of recurrence at the 3-month follow - up . sinus histiocytosis with massive lymphadenopathy ( shml ) is a rare disorder that is characterized by non - malignant proliferation of distinctive histiocytic / phagocytic cells within lymph node sinuses and the lymphatic system in extranodal sites . although shml is relatively rare , purely cutaneous rdd is even less common , accounting for approximately 3% of shml cases in one large study . shml skin lesions may be diverse and can be found in virtually any location , including the face , ears , trunk , extremities or genitalia [ 1 , 3 ] . several authors have suggested that cutaneous rdd is a distinct clinical entity because of its unique epidemiology and the lack of systemic involvement even with long - term follow - up [ 3 , 4 , 5 ] . extranodal disease is documented in 3040% of patients , and in some patients it presents without associated lymphadenopathy , which may develop later in the course of disease . extranodal involvement of at least one site is not uncommon , and it is rarely the initial and only manifestation of the disease . the most commonly affected extranodal sites include the skin and soft tissue , the upper respiratory tract and bone followed by the genitourinary tract , the lower respiratory tract , the oral cavity , the gastrointestinal tract , the orbit   and the testes . in cutaneous rdd , extranodal disease may also develop at other sites , e.g. the eye , most commonly leading to uveitis [ 8 , 9 ] . clinical laboratory findings include hematologic abnormalities , such as normocytic or microcytic anemia [ 1 , 11 ] and polyclonal hypergammaglobulinemia ( 90% ) . rarely , patients exhibit rheumatoid factor , antinuclear antibodies and a reversal of the cd4/cd8 ratio among peripheral lymphocytes . immunological abnormalities are found in a significant number of patients and often lead to a clinically unfavorable disease course . consistent serologic findings are lacking , although antibodies to pathogens , including ebv and human herpesvirus ( hhv-6 ) , have been reported . a small subset of patients also has concurrent neoplasia , including non - hodgkin lymphoma , other histiocytic proliferations , myeloma , melanoma and carcinoma . in the case presented herein , there was no relation to ebv , hiv or hhv-6 infection , or to any other neoplasia . the hallmark of the shml histiocyte is the presence of a variable number of intact lymphocytes within the cytoplasm of the cell , which is a phenomenon referred to as lymphophagocytosis or emperipolesis . the histological differential diagnosis includes langerhans cell histiocytosis , histiocytic sarcoma , storage disorders such as gaucher 's disease , classical hodgkin 's lymphoma , metastatic melanoma and carcinoma , as well as infections caused by histoplasma and mycobacteria that involve the lymph nodes . the most useful immunohistological markers for shml histiocytes are the s-100 protein and the pan - macrophage antigens ( cd86 , cd14 , cd15 and cd64 ) . whereas langerhans cells positively stain for the s-100 protein and cd1a , the clinical course of shml is characterized by spontaneous resolution in most cases , especially in those presenting with localized lymph node involvement . sometimes , there are episodes of exacerbation alternating with periods of remission that continue for many years . persistence of lymphadenopathy or progression to widespread dissemination may occur , particularly in shml that involves the kidneys , the lower respiratory tract or the liver with associated immunological dysfunction . the reported mortality rate is 7% , with many patients who have a fatal outcome having concomitant immune dysfunction . the pathogenesis of this disease is poorly understood , although some researchers have suggested that either infection or immunodeficiency might play a role . the disease is self - limiting in most cases . in a recent review of treatment strategies for shml , 50% of patients ( 40/80 ) did not require any treatment . only 2 of a total of 12 patients achieved complete and durable remission after treatment with methotrexate . high - dose interferon- was given to 1 patient , which resulted in long - term remission . in a recent report , the use of the purine analogue 2-chlorodeoxyadenosine was found to be of clinical utility in these cases . cutaneous lesions have been reported to respond to radiotherapy , cryotherapy , excision [ 4 , 5 ] , topical and oral corticosteroids , and high - dose thalidomide . the diagnosis of rdd should be considered in any atypical chronic inflammatory lesion with a histiocytic component involving multiple organ systems , especially the skin . in our case , the inflammatory lesion was localized to the maxillary area . immunohistochemical stains for the s-100 protein should be performed in these cases . to our knowledge , this is the first case reported with such characteristics .
sinus histiocytosis with massive lymphadenopathy ( shml ) or rosai - dorfman disease ( rdd ) was first described as a distinct clinicopathological entity by rosai and dorfman in 1969 . 
 shml is commonly characterized by painless cervical lymphadenopathy , and its clinical course is generally benign and self - limiting . 
 this disorder commonly involves the lymph nodes but may secondarily involve the skin 
 . however , purely cutaneous disease without lymphadenopathy or internal organ involvement rarely occurs . in the absence of the massive lymphadenopathy 
 that is characteristic of rdd , the diagnosis of purely cutaneous rdd may be complicated by the rare , nonspecific clinical appearance of skin lesions and the broad histopathological differential diagnosis of this disorder . 
 a high level of suspicion of this disease on the part of the clinician or pathologist is often required . 
 we present a case of cutaneous rdd associated with involvement of periodontal tissue .