a 27-year - old hispanic man was admitted to the queens hospital center because of cough , weakness , night sweats , and weight loss . the patient was well until 1 month before admission when he started having weakness , coughing , and sweats .
on return to the united states he saw a physician for the above symptoms and was prescribed azithromycin for 5 days .
however , the symptoms progressively worsened over weeks and at presentation also included drenching night sweats and dizziness .
his coworkers noted him to be paler . on interview , he was noted to have lost 25 pounds over 4 to 6 weeks .
he had fatigue , and felt early satiety due to pressure in the left upper quadrant of abdomen .
he denied any travel to the countryside , significant outdoor activities , hiking or spelunking .
he also denied any bright red blood per rectum , melena , myalgia , arthralgia , hematuria or dark colored urine .
he was a non - smoker , drank socially , and did not take any illicit or recreational drugs .
his father was recently diagnosed with multiple myeloma and his mother had diabetes mellitus . on physical examination , the patient was alert and oriented .
the blood pressure was 119/76 mmhg , the temperature 100.0f , the pulse 119/min with regular rhythm , the respiratory rate 16/min with oxygen saturation 100% on ambient air .
the patient had pale conjunctiva , icteric sclera , non - tender left supraclavicular and cervical lymphadenopathy , hepatomegaly with palpable liver edge 23 cm below right costal margin and splenomegaly . on hospital day
( hd ) 1 , his complete blood count showed white blood cell count 3,100/mcl , hemoglobin 6.6 g / dl , hematocrit 20% and platelets 76,000/mcl .
liver function tests ( lfts ) were abnormal with alkaline phosphatase of 611 u / l , aspartate aminotransferase ( ast ) of 42 u / l , gamma glutamyl transpeptidase ( ggt ) of 68 u / l , lactate dehydrogenase ( ldh ) of 581 u / l , total bilirubin of 2.67 mg / dl and conjugated bilirubin of 1.25 mg / dl .
anemia workup revealed a reticulocyte count of 1,231/l with reticulocytes 5.53% ( 0.5%1.5% ) , iron 60 g / dl ( 60160 g / dl ) , total iron binding capacity ( tibc ) of 213 g / dl ( 250460 g / dl ) , ferritin of 3,128 ng / ml ( 15200 ng / ml ) , vitamin b12 level of 1,387 pg / ml ( 200900 pg / ml ) and serum folate 11.25 ng / ml ( 2.520 ng / ml ) .
initial review of a peripheral blood smear showed thrombocytopenia with occasional large platelets , poikilocytosis , polychromasia , decreased white blood cells without toxic granulation and no schistocytes .
tests for hemolysis , including direct anti - globulin test and haptoglobin level , were negative on hd 2 . a computed tomography ( ct ) scan of chest , abdomen , and pelvis done on hd 1 revealed enlarged lymph nodes in the mediastinum , retroperitoneum and splenomegaly and hepatomegaly .
a lymph node biopsy was requested , given pancytopenia and concurrent lymphadenopathy and performed on hd 6 .
the bone marrow biopsy showed a markedly hypercellular marrow ( 90%100% ) with erythroid hyperplasia , left shifted granulocytic series , and increased megakaryocytes with atypical and dysplastic forms , suggesting a myelodysplastic or myeloproliferative disorder .
the bone marrow aspirate smears showed occasional abnormal mononuclear cells , likely vacuolated lymphoid precursors and mature myeloid and erythroid lines with no evidence of blasts .
the findings were later interpreted as an unusual reaction to hodgkin s lymphoma ( hl ) .
cytogenetic analysis of a bone marrow specimen revealed tetraploidy , aneuploidy , and multiple abnormalities including xxy , add(2)(p25 ) , add(5)(p15)2 , add(6)(q27 ) , add(10)(q23 ) , add(13)(p11 ) , add(14 ) , del(10)(q22,q23 ) , + 5 , + 8 and + 9 .
the liver enzymes including total and direct bilirubin worsened while awaiting results from the biopsies .
a magnetic resonance cholangiopancreatography did not show any intra or extra hepatic biliary obstruction or any clear involvement of the liver by lymphoma , but it identified multiple hypodensities in the spleen .
a hepatobiliary iminodiacetic acid scan showed marked hepatomegaly with smooth contour , but no evidence of focal defects .
drug - induced hepatitis was considered as the patient had been on fluconazole and acetaminophen during the course of his hospital stay .
lfts showed a predominantly obstructive pattern initially and the serum acetaminophen level at presentation was less than 10 g / ml .
prednisone was started on hd 14 in an attempt to stop further decline in lfts . despite steroids , his total bilirubin on hd 20
had increased up to 9.22 mg / dl with conjugated bilirubin of 5.76 mg / dl .
a left cervical lymph node biopsy revealed mixed cellularity classical hl with multiple reed sternberg and hodgkin cells with immunohistochemical expression of pax5 , cd30 and cd15 , background cd3 positive t cells and cd 20-positive residual follicles .
due to elevated lfts , major dose reductions or omission of most chemotherapeutic agents would be needed .
gemcitabine was considered because of its ability to be used even with hepatic impairment and its effectiveness as a salvage regimen .
after first dose of gemcitabine with methylprednisone , total bilirubin , conjugated bilirubin and alkaline phosphatase levels decreased .
thirteen days after the administration of gemcitabine , lfts were still abnormal but improved sufficiently that dose reduced adriamycin , bleomycin , vinblastine , and dac - arbazine ( abvd ) could be administered .
a follow - up bone marrow biopsy was done after completing six cycles of abvd , which showed 70% cellularity with trilineage hematopoiesis , all three cell lines proceeding to maturity and no cytogenetic evidence of an abnormal clone . a repeat ct scan of the chest , abdomen , and pelvis showed decrease in the size of mediastinal , left supraclavicular , abdominal , and pelvic lymph nodes .
a follow - up whole body positron emission tomography / ct scan showed no evidence of fluorodeoxy ( fdg ) avid tumor and decreased splenomegaly .
hl originates from clonotypic b cells.1 the standard regimens used in the usa at the time the patient presented were abvd , stanford v regimen and , less commonly , dose escalated beacopp ( bleomycin , etoposide , adriamycin , cyclophosphamide , vincristine , procarbazine , prednisone ) .
older regimens such as mopp ( mechlorethamine , vincristine , procarbazine , prednisone ) are less effective than abvd.2,3 there is a paucity of data and published case reports for treatment of patients with hl and severely impaired liver function as this patient presented .
case reports have been published using chemotherapy agents for patients with hl presenting with high bilirubin levels.46 many of the active agents used in treatment for hl require extensive dose reduction for severe liver impairment ( table 3 ) .
liver involvement is uncommon at presentation in patients with hl , and is exceptionally rare in the absence of splenic involvement.7,8 the hepatic involvement could range from hepatic infiltration by lymphoma to biliary obstruction by lymph node masses or infiltration of the common bile duct.911 the lfts in our case revealed a cholestatic picture with high alkaline phosphatase and conjugated hyperbilirubinemia . vanishing bile duct syndrome as a cause of jaundice has also been reported to be associated with hl.4,12,13 in one case report , bilirubin level normalized after two cycles of mopp , one cycle of reduced dose p(v)ag ( prednisone , vinblastine was excluded due to potential neurotoxicity , doxorubicin and gemcitabine ) followed by six cycles of full dose p(v ) ag from 5.4 to 0.15 mg / dl.4 however , the treatment course in that case was complicated with prolonged fever , pancytopenia , severe peripheral polyneuropathy and toxic interstitial pneumonitis , requiring intensive care after receiving two cycles of mopp . a case report of successful use of dhap ( full - dose dexamethasone , high - dose cytarabine , and cisplatin ) in a patient with stage iv nodular sclerosis classical hl with severe hepatic dysfunction resulted in significant improvement in the hepatic function after the administration of dhap regimen as evidenced by the normalization of serum bilirubin from 6.5 mg / dl to 1.2 mg / dl.5 gemcitabine has been shown to be effective as a salvage regimen in patients with refractory hl with a response rate of 39% with mild drug related toxicities.14 currently , three gemcitabine based regimens , gvd ( gemcitabine , vinorelbine and pegylated liposomal doxorubicin),15 gdp ( gemcitabine , dexamethasone and cisplatin),16 and gcd(r ) ( gemcitabine , carboplatin , dexamethasone , rituximab)17 have been evaluated for use in relapsed and/or refractory hl .
a retrospective study has shown that gemcitabine combined with vinorelbine or cisplatinum and steroid is an effective treatment option with a manageable toxicity profile in patients with post - transplant progression of hl and in patients eligible for allogeneic or second autologous stem cell transplantation as a pre - transplant option.18 manufacturer drug package insert and phase i pharmacokinetic trials of gemcitabine in patients with hepatic or renal dysfunction have demonstrated that dose adjustments are not necessary for elevated transaminases nor elevated bilirubin and creatinine levels.19,20 finally , chromosomal abnormalities in hl have not been well studied to characterize a coherent cytogenetic picture.21 recent studies have designated some common chromosomal aberrations including gains of short arm of chromosome 2 involving rel oncogene locus1,22 and chromosomal breakpoints involving immunoglobulin loci.23 frequent occurrence of abnormalities involving 1p , 1q and 6q chromosomal arms was shown in a case series.21 the cytogenetic studies in our case were not typical for hl except 6q involvement and the clinical significance of these chromosomal findings and its disappearance in complete remission still remains to be elucidated . in summary , we present an unusual case of hl with severe hepatic impairment , splenomegaly and multiple chromosomal abnormalities , which was treated successfully with gemcitabine and steroids to initially improve lfts , such that six cycles of abvd could be given .
 hodgkin s lymphoma ( hl ) originates from clonal b cells and is the most common malignancy in the second decade of life . 
 liver involvement is uncommon at presentation in patients with hl and there is a paucity of data for treatment of patients with severely impaired liver function . 
 we present an unusual case of hl with severe hepatic impairment , splenomegaly and multiple chromosomal abnormalities that was treated initially with gemcitabine and steroids . 
 once liver function tests improved , six cycles of adriamycin , bleomycin , vinblastine , and dacarbazine were administered . 
 the patient remains in remission at 3.5 years of follow - up . 
Case report
Initial diagnostic results
Patient outcome and initial hospital course
Lymph node biopsy
Definitive treatment and follow-up
Discussion