multicentric reticulohistiocytosis ( mrh ) is a rare multisystem syndrome characterized by polyarthritis and papulonodular skin lesions with typical dermal infiltration of histiocytes and multinucleated giant cells .
the disease may involve the skin , tendon sheath , synovium , bone , liver , salivary gland , kidney , lymph node , heart and lung . in mrh ,
an association with hyperlipidemia ( 3058% ) , a positive skin tuberculin test ( 1250% ) , systemic vasculitis and autoimmune disease has been described . of utmost clinical importance
such an association has been documented in up to 28% of all reported cases in the world literature , the most common being bronchial , breast , stomach , and cervical carcinomas . here ,
we report , for the first time , a case of mrh presenting with liver carcinoma , thus highlighting the association of mrh with malignant disease .
a 61-year - old man presented with a 4-month history of a nonpruritic rash , which started on his forearm and face after sun exposure and subsequently spread to the ear , scalp and upper chest , after which asymptomatic skin lesions appeared on the lateral margin of his finger .
the patient denied any history of photosensitivity but complained of low - grade fever and painful swelling of the joints in his wrist , knee and ankle , accompanied by restricted activity for 1 month .
he had a sensation of a foreign body in his pharynx with difficulty in swallowing for about 1 month .
the patient also had a history of hepatitis b , which was diagnosed in the 1970 's , and severe knee joint pain with bony spurs , which were confirmed by x - ray , for at least 2 years .
treatment with hydroxychloroquine and thalidomide for solar dermatitis in other hospitals showed no therapeutic effect .
physical examination showed a confluent erythematous eruption affecting his scalp , face , neck and the extensor aspect of his forearm , which was characterized by ruby - red , translucent and grouped papules ( fig .
red nodules could also be found on the dorsum of the nose , lateral area of the fingers and tongue tip ( fig .
an extensive laboratory evaluation , including white cell count , urinalysis , stool studies , renal function , electrolytes , cholesterol and triglycerides , erythrocyte sedimentation rate , antistreptolysin o level , rheumatoid factor and antinuclear antibody were normal .
u / l ) , alt 125 u / l ( < 50 u / l ) , alp 159
u / l ) , ggt 100 u / l ( 345 u / l ) , total bilirubin 30 mol / l ( 3.420.4 mol / l ) , tba 21 mol / l ( < 6.8 mol / l ) and total protein , albumin and globulin were normal .
hepatitis index studies showed hbsag(+ ) , hbsab < 0.2 iu / l ( > 10
iu / l ) , hbeab(+ ) , hbsab < hbeag( ) , hbeab(+ ) , hbcab(+ ) , hbcigm( ) , havigm( ) and hcv( ) .
the afp level was significantly elevated ( 6,820 g / l , normal range < 10
type - b ultrasonic examination revealed a solid tumor ( 91  69 mm ) on the right lobe of the liver , which was suspected to be a small hepatocellular carcinoma .
five - fu , oxaliplatin and thp were used as anticancer drugs . the afp level after the interventional treatment was 1,027.5 g / l , and the tumor mass decreased to 67  66 mm .
the cutaneous symptoms improved significantly within 1 month ( several large nodules disappeared immediately ; later , the erythematous rash and grouped papules resolved and the patient 's arthralgia and swelling of joints gradually improved ) .
skin biopsy on the right forearm showed infiltration of the dermis with polymorphic histiocytes and giant cells with 
the histiocytic marker cd68 was positive , as were leukocyte common antigen , hla - dr , lysozyme and vimentin ( fig .
langerhans cell markers ( s-100 and cd1a ) were negative and the histological appearances were consistent with mrh .
mrh , often referred to as lipoid dermato - arthritis , was first reported in 1937 by weber and freudenthal .
mrh is so rare that fewer than 300 cases have been reported in the literature . in 1969 ,
barrow and holubar   first raised the question of whether there was an association between mrh and malignancy .
snow and muller   reported a malignancy rate of 25% in 133 cases of mrh reported in the literature until 1994 .
eleven [ 6 , 7 , 8 , 9 , 10 , 11 , 12 , 13 , 14 , 15 ] of the 66 cases we reviewed ( english - language literature from 1995 until now ) had cancer and were evaluated for the following parameters : age , sex , type of neoplasm at presentation , duration preceding or following the diagnosis of cancer that mrh developed and treatment response of both the tumor and mrh .
the results are presented in table 1 ( including the present case ) . for most of these cases ( including the present case ) , the onset of malignancy and mrh occurred within approximately 3 years , and in some cases , the onset of mrh also occurred in close proximity to the time of recurrence of a previously diagnosed malignancy [ 13 , 15 ] .
this is the first case report of mrh with liver carcinoma . although the etiology of mrh is unknown , the possibility that mrh reflects a constellation of symptoms seen within paraneoplastic syndrome
is supported by the frequency of associated neoplasm ( 18% based on our review ) , the remission of the lesions after tumor treatment ( 6 of 12 cases [ 6 , 7 , 8 , 10 , 11 , 12 ] ) and the onset of mrh just prior to the relapse of the neoplasm ( case no . 8   of table 1 ) .
 we report a unique case of multicentric reticulohistiocytosis ( mrh ) associated with liver carcinoma . a 61-year - old man presented with a 4-month history of nonpruritic , generalized , ruby - red papules and nodules , accompanied by fever , joint swelling and difficulty in swallowing . 
 skin histology showed polymorphic histiocyte infiltration with typical  
 ground glass cytoplasm . 
 further immunohistochemical studies characterized the lesions as positive for leukocyte common antigen , hla - dr and cd68 . 
 the patient had a history of hepatitis b , and systemic examination , including carcinoma index and type - b ultrasonic examination , revealed high levels of afp and a solid tumor , which was considered malignant , localized on the right lobe of the liver . 
 treatment of the liver carcinoma resulted in a significant improvement of the skin symptoms . 
 this is the first case study to report an association between mrh and liver carcinoma . 
 a review of the english - language literature reveals the close linkage between mrh and malignancy . 
 all patients with mrh should be evaluated and monitored carefully to determine the underlying neoplasm . 