Malignant lymphoma presenting as fulminant hepatic failure

A patient with fulminant hepatic failure who had a T8 malignant 
lymphona is described. A review of the literature yields 11 other cases with hematologic 
malignancies with similar presentation. To the authors’ knowledge this is 
the first case in which cell marker analysis was performed. Pitfalls in morpholog1c 
diagnosis are discussed.

L !VER INVOLVFMENT DURING TIi i course of both Hodgkin's and non-Hodgkm 's lymphoma is not unusual ( I) and Jaundice may develop (2.3)However, fulminant hepatic failure ts rarrly a presenttng feature of malignant lym phomas and , when tt occurs, the clime:, I picture may strongly suggest virus.alcohol or drug mduced hepatttis ( 4 ).A case whose presentation with malignant lvm• phoma was dominated by fulmmant and fatal hepatic failure is described A rl'view of the literature yields 11 other cases with a similar presentation (6-11 ).

CASE PRESENTATION
A 66-ycar-old caucas1an wom:in was hospttal1zeJ having presented \\'tth lethargy.anorexia anJ vomiu ng of several Jays duratton Thl• patient also noted decreasing energy and a 2.5 kg weight los:.over a period of one year since h,ning a tooth abscess complicated by scp-NIZAI !Kera/ ticemia There were no other ,ymptoms The pauen t did not consume alwh0l and there wa~ no history of b lood transfusions; hypercens1on was treated with a diuretic Physical examination revealed feve r ( 38.8°C) and an erythemarous pharynx with no exudate.T h e remainder ot th e ex,1mination \l'as normal.including the abdominal examination.
Investigations revea led hemoglobin 145 g/L, white blood cell count 6600/mm 1 and hyponatrcmia (sodium 127 mEq/L).Despite supportive, steroid a nd ampicillin treatmen t. on day 6 the patient's abdomen became distended ,md tender with righ t upper q uadrant pain and peripheral edema .T h is was accompanied by hypcrbilirubinemia, hypoproteinemia and thrombocytopenia On transfer ro the authors' hospital on the next day, blood pressure was 110/80 mm Hg, respiratory rate 24/min.pulse 100 heats/ mm and temperature 38.7°C.The patient was lethargic and orien ted to person only.T h ere was dehydration , jaundice, an asarca, palmar erythema.astcr-ix1s and oral petechiac.The abdomen was obese hut also distended and soft.and there was shifti ng dullness.

BON E MARROW
The first bone marrow aspirate showed some atypical lymphoid cells hut this was not diagnosttc and a second spl'Cimen was requested.Thl' second bone mnrrow aspirate showed replacement of normal marrow with lymphoid cells with nuclei of vnrying size and shnpc with nucleoli and mitoses.Some similnr small abnormal lymphrnd cells were present in the peripheral blood and these increased in number terminally Eryth rophagocy-tos1s was seen in benign h 1stiocytes.
Cell ..,urfoce marker analysis was perfo rmed on the cclb obtained from the second bone marrow aspirate, using a method from Ortho Diagnostic Systems lnc(Rarirnn, New Jersey).Mouse monoclonal an tibodies OKT3.OKT4.OKT8 and OK I al from Ortho Diagnostic Systems, anc.lNK H I from Coulter and B from Mcloy were used .

AUTOPSY R ESULTS
The liver was cholestatic and weighed 1700 g.There was no biliary ohstructinn and there was mild splcnomegaly (250 g).The cystic duct, pa ncreatic and one para-aortic lymph nodes were enlarged (2.5crneach).l).The patients, seven males and four females, ranged in age from 24 co 79 years.Death occurred within 48 h to TABLE 1 Lymphoma presenting os fulm1nant hver failure Fi~urc 2) L11•er ,/wH"mg an expanded Jwrwl rrc1c1 in the c:enrrc u•u/i a 1/Jcctnan of h•m/1lw1d .:ell,a/;o 111Ji/tnmng m1mo1d., r x 'i lOJ three months.[n l1111l' cases the liver fa ilure was clinically attributed to acute infccum1:-or drug induced hcpmitis; only two ca,l's were attn bu red to neoplasm• disease The diseases were Hodgkrn's disease ( five cases).non-Hc)dgkin's lymphoma (two cases) and malignant histiocycosis (three cases).One was designated only as pnmitivc lymphorcticulnr malignancy hut \vrts suspected to he malignant histiocytosis.At autopsy, a ll except one patient showed tumour involvement of the liver In most cases, rnl'olvement of the spleen and lymph node was nOLl'd .In the exception, the hi led uet was ohscructeJ hy 111volved porm hcpau~ nodes The present case rest•mblcJ 5ome of the ,1hovc cases morphologically.lt 1,, 111tercsting to nme rh::n Colby and La-Brccque (6) dcscrihc a polyrnorphou~ int"iltrate with bizarre hyperlobatcd nuclei and some crythmphagocytm,1s, par11cularly in view of the eryrhrophagocytosis the :iuthors observed in benign h1s-tit1Cytc~ Tt1 thl' authors' knowledge.the present case is the first such case in which the \'.:ell surface markers were considered.
Other coses of malignant lyphomo presenting as fulminont hepatic failure  The cells were mature T lymphocytes which expressed the T3 antigen and were of rhe T S cytoroxic-su ppressor subset.
Histologically, the authors designated this as malignant lymphoma.large cell immunoblastic and polymorphous in the working formulation ( 12).This subtype of high grade immunoblastic lymphoma was included in the formulation to encompass th e wide spect rum of T cell lymphoma reported in Japan and referred to as adult T cell lymphomaleukemia ( 13).These neoplasms are endemic in southwestern Japan and are associated with a type C retrovirus.
HTLV-1.The patients have lyrnphade-nopathy with no mcdiastinal mass.They may have h epatosplenomegaly, skin involvement and osteolytic bone lesions with hypercalcemia.The median survival is less than one year.H istologically. the large majority of cases (80°{>) are of medium sized cell rype and pleomorphic type.In the latter, there are prominent giant cells, sometimes resembling Reed -Sternberg cells.Nuclear polymo rphism is a striking feature of all subtypes.All Japanese cases are of the T4 he lperinducer subset.However.adult T cell lymphoma-leukemia has been described in o ther racial groups ( 14,15)  Whik the pre~ent case lacb many of the clinical featu res of the Japanese T cell lymphoma-le ukemia and is of the T8 p hen otype.antibody testing for HTLV-1 was pe rformed.Frozen scrum was obtain ed post mortem to determine whether there were antibodies to HTLV-1 ; the test was negative.
In summ ary, lymphomas presenting acutely as fulminant hepatic failure are extremely rare.The authors believe this is the first such case in which cell surface markers were done and this shows a peripheral T cell lymphoma o f TS phenotype.This adds some further information to the spectrum of the T cell malignancies.
Figure I) Lymph nod,• 1hmm1.~/wlymor/1ho111 hm/i/101rl m/ilrr@• 1rirh <1 Re,•,/ Srrrn/,rr)! /1k,, cd/ ( ctn<Hd; IX~ k\)/ Histology showed Jiff use non-Hodgkin's lymphoma involvi ng thnr::icic and abdominal lymph node,, spll'en and hone marrow, liver, myocard ium, lungs, kidney a n d cervix.The infi ltrate wa, pleornorphic, consisting ofbiwrre atypical lymphocytes Thl' nucleus varied in size and ,hape.Some nuclei were hyperchromatic and hypl•rlohated.while others were vesicular with prominenL nucleoli.Some cells resembled RL•ed-Sternberg ce lls ( Figure I) There were widespread infiltrates in ptwtal trncts and adjacent sinusoids with cholcstasis (Figure 2) T he remaining hep,1tocytes appeared norm:,I.Cw1cl1J<1 alhica111 cp1glottitis :ind esnphagitb \\'ere also noted DISCUSSION Fulminant hep:ltlc failure is defined as a clinical syndrome of sudden onse t resulting from severe impairment oflivcr function ( 'i) There shou Id he no preexisting liver diseast.'The mt)st common cause b massive hepatic necrosis due lO acute vira l hepmitis A, hepmitis B or non-A, non-B hepatitis In this case.the syndrome should occur within eight weeks ofonsct of symptoms.Alcohol ::ind drugs such as halmh ane.monoamine oxidasc inhibitors, i:onia:iJ and acetaminophen have also been reported to gl\ c rise to fulminant hepatic failure.Less commonly, fatty liver of pregnancy and surgical shock a rc responsible.Lymphoma 1s dis••Tictly an uncommon ca use.A review of the literature yielded 11 other patients with lymphoprolifcrative and malignant histiocytic disorders who presented in a similar fashion w ith fulminant hepatic failure (6-11) (Table