castleman 's disease is a rare b - cell non - clonal lymphoproliferative disorder first described over 50 years ago characterized by its variegated presentation .
it can practically affect any region within the body , the most common being the chest in about 70% , the abdomen in about 15% and the remaining occurring within the neck .
this condition may resemble other entities causing lymphadenopathy including lymphomas , infectious or inflammatory causes .
the predominant histopathological variants include the more common hyaline vascular type , the plasma cell type which is usually associated with poems syndrome , castleman 's disease seen with hhv-8 infection usually found in hiv and immunosuppressed patients and an unspecified form of multicentric castleman 's disease .
castleman 's disease is clinically classified into a unicentric variety , which is usually asymptomatic , or a multicentric variety , which can be associated with systemic inflammatory state manifesting with constitutional symptoms such as fever , night sweats and weight loss , depending on the number of lymph nodes involved [ 1 , 2 ] . in certain cases
, this systemic inflammatory state can be complicated by secondary amyloidosis characterized by deposition of serum amyloid a protein within the extracellular tissue .
castleman 's disease has not demonstrated any sex predilection , with unicentric variety peaking in incidence within the second to fourth decades of life , while multicentric variety occurs in older populations .
secondary ( aa ) amyloidosis has been reported with both unicentric   and multicentric variants   of castleman 's disease .
the prognosis of castleman 's disease is related to the extent of systemic involvement either directly from the disease itself or from co - existing systemic amyloidosis .
untreated systemic amyloidosis also often has an unrelenting clinical course , leading to multiorgan failure and death .
the degree of regression of amyloidosis itself is often contingent upon the variant of castleman 's disease , with surgical excision of the primary tumor in a unicentric variant being potentially curative [ 1 , 2 ] .
we report a rare association of unicentric castleman 's disease with secondary ( aa ) amyloidosis .
a 51-year - old african - american man who had been born and raised in the united states first presented to the medical clinic with complaints of generalized weakness , fatigue , unintended weight loss , anorexia and progressively worsening abdominal distension of 3 months duration .
physical examination at the time was significant for a firm , indurated right - sided submandibular mass , hepatomegaly and mild epigastric tenderness .
an initial set of laboratory studies showed abnormal liver enzymes ( alanine transaminase of 61 iu / l , aspartate transaminase of 83
iu / l , markedly elevated alkaline phosphatase of 1,003 iu / l and gamma - glutamyl transferase of 1,879 iu / l with normal bilirubin levels ) .
additional work - up done for evaluation of abnormal liver enzymes including viral hepatitis panels ( hepatitis a , b and c ) , anti - nuclear antibody , anti - smooth muscle antibody , anti - liver kidney microsomal antibodies and anti - mitochondrial antibody were negative .
the patient underwent biopsy of the submandibular mass that revealed features of castleman 's disease ( fig .
1 ) . a subsequent liver biopsy revealed perisinusoidal deposition of eosinophilic , amorphous material within the extracellular matrix with hepatocyte atrophy , consistent with hepatic amyloidosis ( fig .
bone marrow biopsy revealed diffuse extracellular eosinophilic , amorphous material consistent with amyloidosis with increased kappa light chain - restricted plasma cell count ( 6% of hematopoietic bone marrow cells ) ( fig .
the patient underwent a colonoscopy that revealed no gross mucosal lesions ; biopsies were unremarkable . a definitive diagnosis of secondary ( aa ) reactive amyloidosis with hepatic involvement
ascitic fluid analysis revealed an elevated serum - ascites albumin gradient of 1.7 and very low protein of 0.9 g / dl .
he was treated with intravenous antibiotics . a computed tomography scan of the abdomen done at the time revealed dilated loops of small bowel consistent with small bowel obstruction , which resolved with conservative management .
he was not considered for chemotherapy in view of active infection and was not a liver transplant candidate because of his poor physical condition .
the patient was discharged to be readmitted only 2 weeks later with recurrent ascites from decompensated liver disease .
his clinical condition rapidly deteriorated with superimposed severe metabolic acidosis resulting from acute renal dysfunction .
castleman 's disease often presents in sixth to seventh decades of life   with more than half of affected patients being male .
patients with multicentric castleman 's disease universally present with peripheral lymphadenopathy as seen in our patient . only a few cases of secondary ( aa )
amyloidosis complicating castleman 's disease [ 7 , 8 , 9 ] have been reported in the literature .
extensive hepatic involvement from primary systemic amyloidosis is seen in almost two - thirds of the patients [ 10 , 11 ] , but to a lesser degree in secondary ( aa ) amyloidosis [ 12 , 13 ] .
hepatic amyloidosis is often asymptomatic , the most common presentations being hepatomegaly in more than two - thirds of those affected and elevated alkaline phosphatase .
hepatic amyloidosis is characterized by parenchymal replacement by amyloid leading to pressure atrophy of the hepatocytes .
ascites , as seen in our patient , is a rare finding and is often a function of decreased cardiac contractility from amyloid infiltration or hypoalbuminemia from nephrotic syndrome .
our patient had a normal cardiac ejection fraction of 71% on echocardiogram , but was profoundly hypoalbuminemic from heavy proteinuria .
he was observed to have cholestatic liver function tests with jaundice , which is exceedingly rare and often portends poor outcome [ 15 , 16 ] .
he also likely had collateral gastrointestinal amyloidosis with symptoms like unintended weight loss and was found to have intestinal pseudo - obstruction as well , which likely resulted from enteric neuropathy from amyloid deposition .
it has been noted in a small - size study that use of ursodeoxycholic acid could be of benefit in hepatic amyloidosis , with improvement in serum alkaline phosphatase and gamma - glutamyl transferase levels .
the role of liver transplantation was studied extensively in familial variants of amyloidosis [ 19 , 20 , 21 ] , to a lesser degree in primary ( al ) amyloidosis , but not in secondary reactive amyloidosis
. however , the crux of treatment of secondary ( aa ) reactive amyloidosis lies at treating the underlying precipitating inflammatory condition .
there has been a steady increase in survival in patients with reactive amyloidosis secondary to advances in treatment strategies for underlying inflammatory disorders .
excision of unicentric castleman 's tumor often leads to regression of aa amyloidosis by suppressing cytokine production .
however , our patient did not show an optimal clinical response even after excisional biopsy of the submandibular castleman 's tumor . to our knowledge , this case is one amongst only few that presented systemic amyloidosis complicating castleman 's disease .
this case is unique in that extensive , diffuse amyloid deposits were observed in the liver with cholestatic jaundice .
it is also the first reported case where secondary amyloidosis failed to regress even after removal of the primary trigger , the focal castleman 's tumor .
the authors do not have a direct financial relation with the commercial identities mentioned in the paper that might lead to a conflict of interest .
 we report this case of secondary amyloidosis associated with castleman 's disease . a 51-year - old man presented with systemic symptoms of generalized weakness , fatigue , unintended weight loss , anorexia and progressively worsening abdominal distension . on examination 
 he was found to have an indurated right - sided submandibular mass and tense ascites . 
 he was found to have multiorgan dysfunction with deranged liver function tests and renal failure . 
 ascitic fluid analysis revealed evidence of spontaneous bacterial peritonitis . 
 biopsy of the submandibular mass revealed angiofollicular lymph node hyperplasia consistent with a diagnosis of castleman 's disease . 
 a subsequent liver biopsy showed extensive deposition of amyloid protein . 
 bone marrow biopsy also showed the presence of amyloid and increased kappa light chain - restricted plasma cells . 
 the patient was not considered a candidate for chemotherapy or solid organ transplantation in view of active sepsis and poor physical condition . 
 secondary systemic amyloidosis complicating castleman 's disease is very rare . 
 untreated secondary systemic amyloidosis often has a rapidly fatal course , such as seen in our patient . 