CLINICO-PATHOLOGICAL CONFERENCE
IgD myeloma with systemic amyloidosis with chest discomfort
as an initial symptom
Masahiro Kizaki, Masaki Ieda, Toru Satoh, Norihiro Awaya, Yutaka Hattori, Hiroo Kumagai, Shingo Hori,1Taisuke Mori2 and Harsha Rao3
Departments of Internal Medicine, 1Emergency Medicine and 2Pathology, School of Medicine, Keio University
Tokyo, Japan, 3Department of Medicine, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA(Received for publication on October 8, 2003)

Abstract. A 53-year-old man was admitted to Keio University Hospital because of serious dyspnea
and edema of the lower extremities. Eighteen months previously, the patient had complained of chest
discomfort, and was then admitted for the ﬁrst time to our hospital for evaluation of chest pain. Electrocardiography showed poor R wave progression in leads Vl through V4, and diffuse nonspeciﬁc STsegment and T wave abnormalities with low voltage. However, no deﬁnitive diagnosis could be made at
this initial admission and a calcium-channel blocker was prescribed. Despite this treatment, the patient
was readmitted with worsening dyspnea and lower extremity edema. The diagnosis of heart failure andnephritic syndrome was made at the second admission. In addition, immunoelectrophoresis showed amonoclonal IgD (l) M protein and increased plasma cells in the bone marrow, suggesting a diagnosis
of multiple myeloma. The patient was thus given dexamethasone (20 mg per day for 4 days) intravenously, but his symptoms did not improve. Two weeks later, the patient deteriorated further withcongestive heart failure and renal failure, and subsequently died of cardiac arrest with ventricular ﬁbrillation. On autopsy, IgD (l)-positive plasma cell proliferation was found in the bone marrow, conﬁrming the diagnosis of multiple myeloma. In addition, amyloid deposition was detected in variousorgans including the heart, kidneys, esophagus, duodenum, ileum, colon, tongue, and lungs. In particular, the weight of the heart was 650 g demonstrating a hypertrophic septum and amyloid deposition in
the myocardium and even coronary arteries. In summary, the ﬁnal diagnosis was IgD (l) multiple
myeloma associated with systemic amyloidosis. (Keio J Med 53 (3): 178–191, September 2004)
Key words: multiple myeloma, IgD, amyloidosis, cardiomyopathy, angina

Dr. Kizaki (Moderator): I am going to start the classby introducing Professor Rao. I also have a special
guest from the Division of Nephrology, Dr. Kumagai,
and two hematologists, Dr. Awaya and Dr. Hattori,
from Keio University School of Medicine. They aregoing to give us some comments. Professor Rao is not
at all familiar with today’s case, and has none of thedetails.
The doctor in charge is Dr. Ieda, a cardiologist.
Could you please start today’s case presentation?
Dr. Ieda (Internal Medicine): This case is a 53-yearold male, whose chief complaints were dyspnea andedema of the lower extremities.
Onset and course: The patient was in his usual stateof health until about 18 months prior to the current

admission, when he began feeling exertional chest
discomfort. Seven months later, he was admitted toour hospital. This was his ﬁrst admission. The electrocardiogram (ECG) showed poor R wave progressionin leads V1 through V3 and diffuse nonspeciﬁc STsegment and T wave abnormalities. We performed coronary angiography during this initial admission, anddiscovered minimal atherosclerotic disease. Left ventricular function was normal. Examination of the microscopic specimens from a right ventricular endomyocardial biopsy showed only mild edema. The patient
was released with inconclusive ﬁndings and given a calcium channel blocker, amlodipine, for presumed variant
angina, thus concluding his ﬁrst visit.
Dr. Kizaki: Dr. Ieda has explained the ﬁrst part

This is a record of the 1075th CPC of Keio University Hospital, held on October 8, 2003.
Reprint requests to: Dr. Masahiro Kizaki, Department of Internal Medicine, School of Medicine, Keio University, 35 Shinanomachi, Shinjukuku, Tokyo, 160-8582, Japan178

Keio J Med 2004; 53 (3): 178–191

of this patient’s history. Are there any questions so
far?
Dr. Rao (Pittsburgh University): I have a question.
Please forgive me if this sounds like a criticism, but I
am not sure I would have done a coronary angiogramin a patient who presented in this way, with signs ofheart failure. I would like to know what the indication
was for a coronary angiogram in this patient. That isquestion number one.
The second question is for the cardiologist. If you aregoing to do a coronary angiogram in a patient who
presents with clear clinical signs of right heart failure,
why was just a left heart catheterization done? Why did
you not also do a right heart catheterization?
Dr. Ieda: Before his ﬁrst admission, as an outpatient, we did an exercise stress test using scintigraphy.
From this test, we found that he had diffuse cardiac
ischemia. His complaint was typical angina, so we performed cardio-angiography.
Dr. Rao: May I ask a follow-up question to that? If
you saw generalized ischemia on a nuclear study – thatis what you are saying, aren’t you? – and he was quite
symptomatic, are you sure that he was able to achieve a
degree of stress that would adequately test the myocardium? So, if he had a generalized uptake of theradionuclide, could it have been something else? What
I am trying to point out is this: when you see global
uptake of the radionuclide, it does not necessarily meanthat there is generalized ischemia. I do not want thestudents to infer from your comment that generalized
myocardial uptake of radionuclide always implies generalized ischemia. There is another possibility that I am
alluding to. If you have not really stressed the heart,
you will not be able to identify areas of poor uptake
compared to normal uptake. Under those conditions,generalized nuclide uptake really has little or no significance.
Dr. Ieda: We recognized a broad reversible defect on
scintigraphy. We thought he had angina involving abroad area, such as left main trunk stenosis or threevessel disease, or cardiomyopathy, like hypertrophic
cardiomyopathy (HCM). We thought we had to ruleout cardiomyopathy.
Dr. Rao: The suspicion of a cardiomyopathy is exactly why I said I would not have done an angiogram.
My ﬁrst choice for this patient would be an echocardiogram to determine what pattern of cardiomyopathy is present: is it dilated, restrictive, or hypertrophic
obstructive? Only if the echo shows that he has dilated
cardiomyopathy, would I proceed to a coronary angiogram. On the other hand, if the patient turns out tohave restrictive cardiomyopathy, I would want to do a
double catheterization, i.e., both right and left heart
catheterization. Lastly, if the patient has hypertrophic
cardiomyopathy, then I would do a left heart catheter-

179

ization, with particular attention to the outﬂow tract of
the left ventricle. So, I think it is essential to ﬁrst get an
echocardiogram in order to make the correct decision
regarding heart catheterization.
Dr. Ieda: Before this admission, we did also get an
echocardiogram. I will show you the data.
Dr. Rao: So that was done! Until this moment, no
one said that an echocardiogram had been obtained.
Dr. Kizaki: At this stage, a 53-year-old man was admitted to our hospital because of chest discomfort. The
cardiologist did several examinations: an echocardiogram (ECG), and so on. The tentative diagnosis is angina with inconclusive ﬁndings, and the patient is givena calcium blocker. In this early period, what is the diagnosis of this patient?
Ms. Ono (5th-year student): These ﬁndings are suggestive of cardiomyopathy and variant angina. Infection
is one of the causes of cardiomyopathy; therefore, wewould like to know whether or not he had an infection.
Mr. Oyanagi (5th-year student): I thought the diagnosis was cardiomyopathy.
Dr. Kizaki: At this time, we had relatively few
examinations. We had only ECGs, chest X-rays andechocardiograms.
Dr. Ieda: This ﬁgure shows the ﬁrst ECG and chest
X-ray on the ﬁrst admission (Fig. 1). The left panel
shows the ECG, as you can see. On the right side, you
can see from V1 toV3, the poor R wave progression
and diffuse nonspeciﬁc ST changes. The right panel isthe chest X-ray, showing only mild cardiac hypertrophyand no pulmonary congestion or effusion.
This is the parasternal view of the long axis and thisis a color Doppler image. As you can see, there is mild
mitral valve regurgitation. Here is the left atrium andleft ventricle; here the aorta and right ventricle.
This is the short axis in the parasternal view. As you
can see, this is the left ventricle and here’s the rightheart. There is only mild concentric hypertrophy but
left ventricular wall motion is normal. This provides afour chamber-view from the apex.
Dr. Rao: Do you have an E to A measurement fromthe echo?
Dr. Ieda: Yes, we do.
Dr. Rao: And what was the left ventricle wall thickness?
Dr. Ieda: The left ventricular septum was 1.2 cm, andthe posterior wall was also 1.2 cm.
Dr. Rao: And what about E to A? In other words,
early vs late diastolic wall motion?
Dr. Ieda: E was 113 and A was 56. Dct was 192
msec.
Dr. Kizaki: What did you conclude from these ﬁndings?
Dr. Ieda: From this echocardiogram, we recognized
only mild MR due to thick MV leaﬂets and mild con-

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Kizaki M, et al: Myeloma with systemic amyloidosis

Fig. 1 The ECG and chest radiography at the 1st admission. The ECG showed poor R wave progression in leads V1 through V3, and diffuse
nonspeciﬁc ST-segment and T wave abnormalities. Cardiomegaly was apparent in the chest radiography.

centric LVH. There was no discernible abnormality inthe hemodynamic system.
Dr. Kizaki: The students are suggesting that in thiscase the diagnosis is cardiomyopathy due to some infection. What do you think about that?
Dr. Ieda: It is possible, but he had no fever and thetime course is not typical. I think this presentation differs from those of myocarditis or pericarditis.
Dr. Rao: There are a couple of things here. First, I
am assuming from what you have said, that he does nothave a dilated myocardium.
Dr. Ieda: That’s correct, he did not.
Dr. Rao: Although you have not mentioned it, it
appears from the images that the left ventricular chamber size is not increased. To me, it does not look like acase of dilated cardiomyopathy at all, because the left
ventricular end diastolic volume appears normal. You
did not give me a number, but just looking at it, it does
not seem to be particularly increased.
The second point I want to make is regarding left
ventricle wall motion. It is difﬁcult to tell unless you are
actually at the bedside of the patient while it is being
done, but it does not look at all reduced. Nor does it
look like there is any diastolic dysfunction. There
seemed to be reasonable movement, but that is hard totell from the short view we are being shown. So I haveto ask the cardiologist who was there, because sometimes it can be more subjective and visual: Was there

any diastolic dysfunction from concentric hypertrophy?
Was there any diastolic dysfunction in your opinion, Dr
Satoh?
Dr. Satoh (Internal medicine): I think it is difﬁcult toevaluate diastolic dysfunction. I saw this patient at thattime, and I could not ﬁnd any jugular vein abnormality.
In restrictive hemodynamics, descent of the jugular vein
is exaggerated. The apex beat was felt to be prolonged,
suggesting left ventricular diastolic dysfunction. I think
he had left ventricle hypertrophy, but there was no restrictive left ventricular abnormality. I do not feel thathe showed that restrictive pattern.
Dr. Rao: I want to explain something here to thestudents. Does anyone know why I am asking all thesequestions? No one knows, right?
Let me tell you. What we are trying to decide is,what is the pattern of cardiomyopathy that the patient
had? I am in the same position as you; this case is new
to me; so we all have no idea what is going on in thiscase. The patient came in with heart failure. So our ﬁrst
question is: Does the patient have congestive heart
failure? It certainly looks like we have right heart failure as evidenced by the elevated jugular venous pressure. But there appears to be no clinical evidence to thispoint of left heart failure, because I cannot see any
congestion in the lungs on the chest x-ray. So, I think
we have evidence to suggest that he has a failing rightheart.

Keio J Med 2004; 53 (3): 178–191

When you see that, the next question is: What pattern of cardiomyopathy does the patient have? Is this adilated cardiomyopathy? Is it a restrictive cardiomyopathy? Or is it an obstructive cardiomyopathy?
You have to ﬁnd out before you can investigate what
is causing the cardiomyopathy, because the causes of
the three patterns are very different. It is very important that you do not jump ahead to investigate
the cause before you even know what it is you areinvestigating!
In trying to determine the pattern, you look for somethings on the echo, which is what I have been trying todetermine through all the questions I have been asking.
In a patient with dilated cardiomyopathy, what you
have essentially is a ﬂabby bag of a heart that is notcontracting. So you will see enlarged chambers withfeeble wall motion.
In a patient with restrictive cardiomyopathy, on theother hand, you see increased wall thickness. Thismeans that the myocardium is also very stiff and does
not move appropriately to either contract or relax theventricle. The ﬁrst result of this stiffness is resistance toentry of blood into the ventricle. Initially, this affects
the early, passive phase of ventricular ﬁlling in diastole(called E on the echo). The late phase of ﬁlling, which isdependent on atrial contraction (called A), is initiallyspared, and actually may be exaggerated, so that thenormal E to A ratio is reversed. Later on, when theventricle stiffness is so great that atrial contraction cannot overcome it, the ratio becomes ‘‘normal’’ again.
This is the typical pattern of restrictive cardiomyopathy.
Finally, in obstructive cardiomyopathy you might see
asymmetric septal hypertrophy or a pattern of progressive reduction in ﬂow through the outﬂow tract as systole progresses.
Having said that, though, I must concede that it issometimes very hard to tell in the early stages whatkind of cardiomyopathy a patient has. So, you have torespect the opinion of the cardiologist who has seen thepatient and who does the echocardiogram. And if hesays he did not see wall motion abnormalities, or he did
not see abnormal relaxation, then you must accept it.
So, in this case, where we are told that there were nowall motion abnormalities on echocardiography, a diagnosis of restrictive cardiomyopathy is difﬁcult to sustain. But it does appear from all the clinical evidence
that the patient has a restrictive cardiomyopathy.
Ms. Matsuki (6th-year student): I am just confused,because this patient had chest discomfort; I think wejust jumped to the conclusion that he had a heart disorder. I was wondering whether this patient might haverenal dysfunction that is causing edema and all theseother symptoms. Besides that, he had a history of aheart condition. Would that be a possibility?
Dr. Ieda: On the ﬁrst admission, blood to urine ni-

181

trogen was 9.9 and the creatine level was 0.9, which isnormal.
Dr. Kizaki: I think we should move to the second
stage. The patient developed many more complaints. So
Dr. Ieda, could you explain?
Dr. Ieda: Later, the patient again presented, thistime three months before the ﬁnal admission, withcomplaints of paroxysmal nocturnal dyspnea, constipation and edematous legs. Upon admission, laboratory
tests revealed prominent proteinuria, a low albuminemia and renal insufﬁciency, suggesting nephritic syndrome. Immunoelectrophoresis detected a gammaglobulin peak in serum and urine samples of the IgD(l)type. A bone marrow biopsy specimen showed a monoclonal increase in plasma cells, leading to the diagnosis
of multiple myeloma. A radiograph of the chest, which I
will show you later, was interpreted as showing cardiomegaly with a moderate increase in bilateral pleural
effusions.
A transthoracic echocardiogram revealed increased
echogenicity and symmetric hypertrophy of the myocardium, and wall motion was decreased, suggesting an
inﬁltrative process like amyloidosis. In addition, unsustained VT, atrial ﬁbrillation, hypotension and hypothyroidism were subsequently detected. Several cyclesof furosemide infusions followed by a conversion to oral
therapy partially resolved his dyspnea and lower extremity edema. We consulted with the hematologist andstarted dexamethasone intravenously to treat the multiple myeloma. The patient was discharged after one
month with instructions to follow the oral medication
regimen and to make appropriate lifestyle changes.
Despite this treatment, the patient was readmitted two
weeks later with worsening dyspnea and edema.
Dr. Kizaki: Regarding the second admission, do you
have any questions for Dr. Ieda? During this second
admission, various symptoms were observed – for example, those of the nephrotic syndrome, of multiple
myeloma and of cardiomegaly suggesting amyloidosis.
Mr. Ogura (5th-year student): I think these are typical symptoms of heart failure and nephrotic syndrome,
but it is not clear whether he had symptomatic amyloidosis at this time. I would like to know about the pasthistory of this patient.
Dr. Kizaki: As you can see below, his only previous
illness was hepatitis which was virus antigen positive.
He was a carrier.
Mr. Inokuchi (5th-year student): We have started
considering amyloidosis, so was there any biopsy orcongo red staining to clarify the assumed mitotic activity?
Dr. Ieda: Yes, we did such tests. As you can see
above, we performed an endomyocardial biopsy, andduring the second admission we performed a gastrointestinal biopsy in the duodenum, but no amyloidosis or

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Kizaki M, et al: Myeloma with systemic amyloidosis

Fig. 2 The ECG and chest radiography at the 2nd admission. Low voltage in hind limbs was revealed in the ECG. There is pulmonary congestion and moderate increase in bilateral pleural effusions.

amyloid protein was detected in either specimen (Fig.
2).
Dr. Kizaki: I think the histology was rechecked several times but no amyloidosis was found.
Dr. Rao: Did you do a fat biopsy?
Dr. Ieda: No, we did not.
Dr. Rao: It is my understanding that either thefat pad or gingival biopsy gives you the highest yieldfor conﬁrming the presence of primary amyloid, also
known as AL amyloidosis. The second point to make isthat a symmetrically hypertrophied myocardium does
not imply that the amyloid deposition is diffuse. In
fact, endomyocardial biopsy, more often than not, fails
to pick up the presence of cardiac amyloid. This is because (a) the sample is so small that the yield is very
low in conditions where involvement is not diffuse, and(b) even though we tend to think of amyloid as involving the whole myocardium; it is actually very patchy
involvement. So, it might require several biopsies – farmore than can be safely taken without making a hole in
the heart! – if you really want to ﬁnd amyloid deposition in the myocardium. Of course, that is completely
different in a postmortem study, where you have theadvantage of making serial sections through the heart,and can almost always ﬁnd the amyloid deposition.
But that is why the diagnosis of amyloidosis in thiscase, based on what we have seen so far, must dependon the overall clinical picture. The ﬁrst clue to the diagnosis is a pattern of restrictive heart disease withconcentric ventricular hypertrophy and limitation ofwall motion on echocardiography. In contrast to theﬁrst echo, now we do see diastolic dysfunction with afailure of the myocardium to relax. The most common
cause of this pattern of restrictive cardiomyopathy is
cardiac amyloidosis. The second clue, which is almost
diagnostic, is a classic pattern of nephrotic syndrome
associated with multiple myeloma. There can be noother diagnosis than cardiac amyloidosis in this context,
even if you do not show me a congo red positive biopsy.
In my opinion then, there is no other diagnosis at thispoint. And that brings up a very interesting problem:the calcium-channel blocker was probably the worst
thing to use.
Why is a calcium channel blocker the worst drug you
could have used to treat this patient, if you suspect
cardiac amyloidosis, in retrospect?
Dr. Ieda: For amyloidosis, calcium channel blockers
are contra-indicated.
Dr. Rao: For the sake of the students, again, can you
please explain why a calcium channel blocker is contraindicated?
Dr. Ieda: Calcium antagonists or beta blockers arecontra-indicated in amyloidosis because the toxic side
effect is prominent in cardiac amyloidosis. Even if theKeio J Med 2004; 53 (3): 178–191

level of the medication is at the normal treatment target, side effects could possibly occur, so we do not use
it.
Dr. Rao: And that toxicity occurs because calcium
channel blockers bind irreversibly to amyloid ﬁbers. So
once they are bound, the calcium channels are permanently blocked, and myocardial contractility will become profoundly impaired. That is why you must not
use a calcium channel blocker if you suspect amyloidosis.
Dr. Kizaki: Dr. Rao, now back to the diagnosis of
this second admission. I will ask Mr. Ogura. What do
you think of the diagnosis of nephrotic syndrome in thispatient? What is the cause of the nephrotic syndrome?
Is the diagnosis of nephrotic syndrome correct?
Mr. Ogura: Yes, it is.
Dr. Kizaki: If it is correct, then what is the cause of
the nephrotic syndrome in this patient?
Mr. Ogura: Amyloidosis is one of the most attractive
candidates.
Dr. Kizaki: How about other causes?
Mr. Ogura: Other causes are globular nephritis, diabetes mellitus or hepatitis B, and so on.
Dr. Kizaki: Dr. Kumagai, could you comment on the
diagnosis of nephrotic syndrome at that time?
Dr. Kumagai (Internal medicine): The most probable genesis of the nephrotic syndrome of this patientwas, as he said, amyloidosis, and/or what is shown below. Nephrotic syndrome is a very typical manifestationof amyloidosis in this patient because the position ofamyloid growth in the monitor destroys protein selectivity, which prevents a protein molecule from moving
out of the capillary into the urinary space. So, nephrotic
syndrome is a very difﬁcult syndrome. It is a typical signof amyloidosis.
Dr. Kizaki: In the ﬁrst admission, we could not detectthe deposition of amyloid. We could not diagnose thispatient as having amyloidosis, or conﬁrm its absence,
during this period. Then, in the second period, hedeveloped nephrotic syndrome, so the nephrologists
suggested that it may have been due to amyloidosis. But
even in these terms, we cannot prove there is amyloid,
right? We performed biopsies, but no amyloidosis wasfound. However, from the clinical symptoms, amyloidosis is the most likely diagnosis at this time.
He was also diagnosed with multiple myeloma. Dr.
Awaya, as a hematologist, what do you think? There isa diagnosis of nephrotic syndrome, multiple myeloma
and amyloidosis. What do you think?
Dr. Awaya (Internal Medicine): Obviously the patient had proteinuria and I assume this is a combinationof nephrotic syndrome and paraprotein. Although
we did not see the electrophoresis pattern, it seems thepatient had paraprotein in his urine. I am not sure
about the description of the increase in plasma cells, but183

if it was compatible with plasmacytoma, based on thesetwo pieces of evidence, I think it is reasonable to makea diagnosis of multiple myeloma. Thus, the underlying
disease of this patient was multiple myeloma and hedeveloped the amyloidosis due to the multiple myeloma. The nephrotic syndrome was also secondary to
the amyloidosis. I think it is reasonable to combine thethree issues.
Dr. Rao: May I just ask what criteria you used todeﬁne an increase in plasma cells? Was it at least ten
percent?
Dr. Awaya: Yes. It seems that an aspiration was
performed.
Dr. Rao: So, was it a core biopsy or was it an aspiration?
Dr. Kizaki: Both, in the bone marrow. Also, I canshow you the results of protein analysis. Dr. Awaya, I
have a question. During the ﬁrst admission, there was
no evidence of multiple myeloma. Then, the patient wasdiagnosed with multiple myeloma one year later. Whatdo you think about the time elapsed until the diagnosis
of multiple myeloma? It was only one year.
Dr. Awaya: Do you mean that you would like an
explanation of why we did not make the diagnosis ofamyloidosis at the initial presentation?
Dr. Kizaki: Yes.
Dr. Awaya: Probably the answer to that question isthis. Now we know he was diagnosed with IgD myeloma. And with IgD myeloma, as you know, it is hard to
make the diagnosis because the M peak level is relatively low, compared to IgG or IgA. So, I speculate thatthe patient might have had multiple myeloma at theinitial presentation.
Dr. Kizaki: I think the key point for the diagnosis
was the results of the bone marrow biopsy. As shownby immunoelectrophoresis, Bence-Jones protein wasseen in the urine only on the second admission. Only
the IgD(l)M protein was detected in serum. The diagnosis of multiple myeloma may have been deﬁnitive at
this time.
Dr. Rao: There is little further to say! The patient
had a multiple myeloma: there were Bence-Jones proteins in his urine, which are nothing other than thelambda light chains we have identiﬁed, he had a single
immunoglobulin spike on plasma immunoelectrophoresis, and he had an increase in plasma cells in the bonemarrow. And that makes the diagnosis certain. And it
also means that cardiac amyloidosis was a result of amultiple myeloma.
Dr. Kizaki: We do not have much experience withIgD myeloma. How about you?
Dr. Rao: I have none. So, I will wait for the hematologist to tell us.
Dr. Kizaki: Ms. Ono, what are the characteristics of
IgD myeloma? What are the clinical manifestations?

184

Ms. Ono: Extra nodal plasmacytoma and amyloidosis
are more frequently seen than in other types of myeloma.
Dr. Kizaki: Dr. Hattori, what do you think of the
choice of dexamethasone at this point?
Dr. Hattori (Internal Medicine): I think it was agood choice. Firstly, because dexamethasone has lessnephro and cardiac toxicity, secondly because there is
no bone marrow suppression, and thirdly because dexamethasone works very quickly compared with melphalan and prednisone.
Dr. Kizaki: But at this time, the patient’s diagnosis
was amyloidosis. Was there any evidence of the effectiveness of dexamethasone on amyloidosis?
Dr. Hattori: No. Basically, there is no effective therapy against established amyloidosis. One paper shows
melphalan plus prednisolone to be an effective treatment for prevention of progression of amyloidosis. So,
dexamethasone is good for the treatment of multiple
myeloma, but I do not know how effective it is foramyloidosis.
Dr. Kizaki: Ms. Okishio, do you think the choice of
dexamethasone was good for this patient or not? If not,do you have any comments on the treatment?
Ms. Okishio (5th-year student): I think the dexamethasone was chosen for the patient’s quality of life
because other therapies may have considerable toxicity.
So, I think the choice was good.
I have a question. In this case, maybe thalidomide
was available. The toxicity of thalidomide is mild and it
can improve the patient’s quality of life.
Dr. Kizaki: This is a very old case, so thalidomide
was not available at that time.
Dr. Hattori: I looked for papers describing the efﬁcacy of thalidomide for amyloidosis, but found only
one. Sixteen patients were enrolled in this study, 14 hadrenal involvement, and 4 had cardiac involvement.
Thalidomide was effective for reducing Bence-Jones
proteins. However, there was no comment on the improvement of amyloidosis. More importantly, the article also emphasized an unexpectedly high frequency ofsevere toxicity. Grade 3 or 4 toxicity was observed in
50% of the patients, which also reinforces the idea thateven if thalidomide had been available, it should havebeen used with special caution in this patient.
Dr. Kizaki: Professor Rao, what do you think of the
choice of dexamethasone, and what do you think ofthalidomide?
Dr. Rao: First of all, there is no evidence to showthat any treatment makes a difference in amyloidosis:
not a single study shows that anything works. As fortreating his multiple myeloma, that is equally futile,
because his heart is going to give out long before anything else. Once this degree of cardiac failure develops,
the prognosis is extremely bad for most patients withcardiac amyloid. So, if he had presented with multiple

Kizaki M, et al: Myeloma with systemic amyloidosis

myeloma without the cardiac amyloid, I would havepursued aggressive chemotherapy with melphalanprednisolone. But at this point in the patient’s course,
the prognosis is really grim. In terms of survival, he has
weeks, or maybe months at the most to live. So, itwould really make no sense, as already mentioned by
one of the students, to ruin what little quality of life hemight have left to him by using toxic alkylating agents.
And because he has CHF, a steroid without a signiﬁcantmineralocorticoid effect, like dexamethasone, is a good
idea.
Dr. Kizaki: I think this discussion is very difﬁcultfor everyone. Could someone summarize the diagnosis of the second admission to the students? Ms.
Ogawa? What was the diagnosis at the second admission? Amyloidosis or multiple myeloma? Nephrotic
syndrome? Heart failure? Please summarize what happened in the second admission.
Ms. Ogawa (5th-year student): The major diagnosis
is multiple myeloma, accompanied by amyloidosis. The
nephrotic syndrome is also attributable to the amyloidosis.
Dr. Kizaki: If so, what do you think of the ﬁrst admission? You say this is multiple myeloma, associatedwith amyloidosis which possibly induced the nephrotic
syndrome. But in the ﬁrst admission, only angina was
detected. Do you think multiple myeloma was alreadypresent at that time?
Ms. Ogawa: Yes, I believe it was.
Dr. Kizaki: We are going to discuss this later, after
the pathologists make some comments. Now, we will
look at the patient’s last admission.
Dr. Rao: I think this patient had multiple myeloma
from the time when the symptoms began. At that time,maybe, the only clue may have been the presence ofsome light chains in the urine. But that would be missed
unless an immunoelectrophoretic analysis of the urine
was performed. And that is certainly not warranted forevery patient with CHF who walks in the door. Without
that, though, you will not pick up light chains in theurine. And those light chains would be deposited continually in the tissues and the patient will eventually
end up with amyloidosis. So, in my opinion, the patient
had multiple myeloma at his ﬁrst presentation.
Dr. Kizaki: All right. This is the basic summary ofthis case.
Ms. Matsuki: If the patient, in fact, had multiple
myeloma from the beginning, and if we want to conﬁrm
this retrospectively, for instance as you mentioned, if
the patient only had Bence-Jones protein at the time hepresented with angina, do we see a difference in the
total protein level at the time as an increase in total
protein, which might suggest that he had multiple myeloma at that time?
Dr. Rao: The answer to your question is ‘no’. Bence-Keio J Med 2004; 53 (3): 178–191

Jones proteins are not measured in total plasma proteins. These are only light chains. And, as previously
mentioned, in IgD myeloma there is usually a verysmall increase in IgD. For reasons that are not clear,
IgD appears to be a much more toxic form of myeloma.
Dr. Kizaki: Actually, at the ﬁrst admission, the total
protein level was normal.
Dr. Kumagai (Internal Medicine): Dr. Ieda, is there
a possibility that the deposition of amyloid moleculeson the coronary arteries is a genesis of angina or the ST
depression seen on EKG?
Dr. Ieda: Yes, it is possible. About 10 or 20 percent,a small fraction, of amyloidosis patients have vessel
amyloid deposition, and our patient had typical angina
pectoris, so this might be the case. But he also had cardiac hypertrophy due to amyloidosis, so both ﬁndings
were present.
Dr. Kumagai: Did you ﬁnd any amyloid deposition in
the cardiac septum? I recognized some, looking at yourﬁrst echocardiogram. I also think amyloid deposition
existed.
Dr. Rao: I do not think I saw any evidence of cardiac
amyloid in that ﬁrst echo. Clearly in the second echo,
you give a very striking description of a classic patternof the granular appearance of cardiac amyloid.
Dr. Kizaki: In this discussion, from the beginning thispatient had multiple myeloma and amyloidosis.
Dr. Ieda: This is the second admission echocardiogram. As you can see, this is a parasternal view, longaxis. This is the left ventricle. The left ventricle echodensity was a little bit higher than on the ﬁrst admission
and contractility was signiﬁcantly decreased comparedto the ﬁrst admission. You can see here a small amountof pericardial effusion.
This is a short axis view. This is the left ventricle andit is not clearly seen in this video. You can see the pericardial fusion here and the thickness appears to be
increased signiﬁcantly. The echo density was very high,higher than on the ﬁrst echocardiogram. Decreased
contractility is apparent. The calculated IVS diameter is
1.4, that of the posterior wall 1.4, and of the ejection
fraction 50%. We did not check E to A here, but the
IVC value was determined to be 2.1 cm and respiratorychange markedly decreased. This is the four-chamber
view.
Dr. Rao: Now you can see it very clearly. If you
look in the region of the interventricular septum, you
can see the bright spots going through it. That is what iscalled a speckled granular pattern. The words that are
sometimes used to describe it are ‘‘like stars in thenight.’’
Dr. Kizaki: So shall we move to the last admission?
And Dr. Ieda, could you explain the clinical course?
Dr. Ieda: The patient was thought to have worsening
congestive heart failure. Here, this is the third admis-

185sion. The left panel is the ECG and the right panel isthe chest X-ray. As you can see, premature ventricular
contraction can be seen here and the poor R progression was not changed much, but the voltage of the precordial leads, and you can see it in the limb leads, wassigniﬁcantly lower than at the ﬁrst admission. As you
can see in the right panel, this is, as you know, the heartand here are the lungs. Clearly, the heart was enlarged
and you can see that pulmonary effusion and pulmonary congestion have appeared at this time.
The patient was thought to have worsening congestive heart failure due to cardiac amyloidosis. He underwent Swan-Ganz catheter placement. The meanright atrial pressure was 9 mmHg, the right ventricle
pressure was 43/11 mmHg, that in the pulmonary artery
43/22 mmHg and mean pulmonary capillary wedge
pressure 36 mmHg with a cardiac index of 1.6. Wethought he had very severe congestive heart failure.
First of all, we administered low dose dopamine, furosemide and a PDE III inhibitor intravenously. The nextday, sudden-onset spontaneous ventricular ﬁbrillation
occurred but was converted back to a sinus rhythm withDC shock treatment.
Although initial basic blood chemistry results wereunremarkable, the serum CRP rose to 20 and bilateralpulmonary edema increased. So, we started ten-day
treatment with antibiotics and immunoglobulin infusion, which reduced the inﬂammation as the heart
failure subsided. By the 20th hospital day, however,his blood pressure dropped as low as 70/40 mmHg
and multiple syncopal episodes were recorded. The
patient’s renal failure and constipation also worsened.
Cardiac function continued to deteriorate. The cardiac
index was 0.7 and the pulmonary capillary wedge pressure was now 20 mmHg. On the 23rd hospital day, hisrhythm again deteriorated into ventricular ﬁbrillation,but on this occasion he could not be resuscitated (Fig.
3).
Dr. Kizaki: At the third admission, congestive heart
failure worsened and very serious arrhythmia occurred.
In addition, further renal failure was noted. Then, I
think the attending doctor attempted multiple resuscitations but to no avail and the patient died. We should
discuss the last part, which is the cause of death. Mr.
Ogura, what was the cause of death in this patient?
Mr. Ogura: The immediate cause of death wasthought to be acute deterioration of his heart failure.
Dr. Kizaki: We should sum up the clinical diagnosisof this patient. We have discussed several points since
the beginning of this session. I will ask Mr. Oyanagi tosummarize the diagnosis of this patient. After a great
deal of discussion, the diagnosis was multiple myeloma.
Mr. Oyanagi: In this case, who typiﬁed the clinicalcourse of amyloidosis associated with multiple myeloma, common manifestations of multiple myeloma,

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Kizaki M, et al: Myeloma with systemic amyloidosis

Fig. 3 The ECG and chest radiography at the 3rd admission. There is sinus tachycardia and PVCs in the ECG. There is severe bilateral pleural
effusion in the chest radiography.

such as myeloma kidney and bone lesions, could not
be identiﬁed. The major symptom, which was cardiac,
resulted mainly from amyloidosis. But neither ventricular myocardial biopsy nor gastrointestinal biopsy
revealed any apparent amyloid deposition. The cause ofdeath might thus have been a bacterial infection, or
possibly congestive heart failure, but we still as a groupdo not have a deﬁnitive conclusion.
Dr. Rao: At this time, after being on a high dose of
dexamethasone for so many days, was he administeredstress dose steroids while he was sick? Could he havegone into hypotensive shock because he did not get
steroids after his adrenals were suppressed for months
with high dose dexamethasone?
Dr. Ieda: No, in the third admission, we did not use
dexamethasone.
Dr. Rao: The reason that it is important is because
he was getting dexamethasone as an out-patient.
Dr. Ieda: No, we did not prescribe it.
Dr. Rao: But you said he was given dexamethasone.
Dr. Ieda: In the second admission.
Dr. Rao: You said he was told to follow the oral
medication regimen. After the second admission, thepatient was discharged after one month with instructions to follow the oral medication regimen, which was
dexamethasone. I am assuming that means that he wason dexamethasone when he came in for his admission
the third time.
So, assuming that he was taking it until he got admitted, and it was no longer given, it is possible that thispatient collapsed because of an adrenal crisis precipitated by the fact that he was not given ‘‘stress dose’’steroids after admission. His own adrenals were suppressed from high dose steroids as an outpatient, andunless he was given steroids in hospital, he would collapse and die.

Dr. Kizaki: I think the patient was given only one
course of dexamethasone for four days at the second
admission. After that, no dexamethasone.
Dr. Ieda: That is correct. We could not continue
dexamethasone.
Dr. Rao: So what ‘‘oral medication regimen’’ was thepatient given when he was discharged with the diagnosis of multiple myeloma after the second admission?
Dr. Kizaki: It says in the ﬁrst page: ‘‘a regimen oforal medication, and to make appropriate lifestylechange.’’Dr. Ieda: This was not dexamethasone. It was another medication.
Dr. Kizaki: Do you have any opinions on the diagnosis? The students say it was multiple myeloma, that
is, amyloidosis associated with multiple myeloma, andthen worsened heart and kidney failure.
Dr. Ieda: We thought so but the biopsy did not show
a clear view of amyloid deposition, making a diagnosisof amyloidosis difﬁcult in this case.
Dr. Kizaki: From the clinical symptoms, you can diagnose amyloidosis.
Ms. Matsuki: Since his CRP rose to 20, did you nottake blood or any types of culture?
Dr. Ieda: You mean during the third admission?
Dr. Kizaki: Is your concern about sepsis?
Ms. Matsuki: Yes.
Dr. Kizaki: I believe several blood cultures were
performed.
Ms. Matsuki: Since they were not mentioned, I presume they were all negative.
Dr. Kizaki: The results were consistently negative.
The blood cultures were repeated but they were negative. Do you have any other opinions or questions?
Dr. Rao: Were any treatments given for the patient’s
hyperthyroidism?

Keio J Med 2004; 53 (3): 178–191

Dr. Ieda: Hyperthyroidism was managed startingfrom the second admission. Thyradin S was prescribed.
Are you familiar with this?
Dr. Rao: But hyperthyroidism will not give you lightchains in the urine. It will not give you an immunoglobulin spike. And if you are treating hypothyroidismwith thyroid hormone therapy, the patient is not goingto die. This patient was dying of multiple myeloma andcardiac amyloidosis.
Dr. Kizaki: Are there any other opinions on theclinical diagnosis of this patient? Is the multiple myeloma diagnosis right? Dr. Awaya, what do you think?
The students say the diagnosis of multiple myeloma wasassociated with the amyloidosis. What do you think
about their diagnosis? Is it right?
Dr. Awaya: As I said before, I think the diagnosis ofmultiple myeloma was deﬁnite. We were not able toobtain evidence by biopsy, which could prove the existence of amyloidosis. From the clinical perspective,
however, the patient had macroglossia, nephrotic syndrome and so forth. So, the clinical course was highlysuggestive of amyloidosis. I think it is reasonable to
make a diagnosis of amyloidosis in this case.
Dr. Kizaki: What do you think about the causeof death? The students think it was heart failure due
to amyloidosis, perhaps with some infection, hyperthyroidism or an adrenal crisis.
Dr. Awaya: I think an adrenal crisis is very unlikely
in this case because we treated him with a very shortcourse of dexamethasone. A typical clinical course of
cardiac amyloidosis, like Dr. Rao said, is very rapid andprogressive, so I think the cause of death in this case is
obviously cardiac amyloidosis.
Dr. Rao: That was my impression right from thestart, so I am in no position to change it now; multiple
myeloma with cardiac amyloidosis. The only reason
that it was not seen on biopsy was because the wrong
tissue was biopsied. It should have been the gums or thefat.
Dr. Kizaki: Dr. Mori, could you explain the autopsy
ﬁndings?
Dr. Mori (Pathology): I will now show you the bonemarrow biopsy ﬁndings. First, I would like to show thehistology of the bone marrow biopsies. As you can see,the bone marrow shows hypercellularity, with a typicalplasmacytoid cell proliferation at high magniﬁcations.
These cells stained positively for anti-EMA and VS38C.
Based on these ﬁndings, we made a diagnosis of multiple myeloma.
This slide shows biopsy specimens from the duodenum and myocardium. Although amyloidosis was clinically suspected, we could not demonstrate amyloid deposition in these tissues. You can see some congo red
staining in this section, but we could not see green
birefringence under polarized light microscopy. Thus,

187

amyloidosis was concluded to be negative. In addition,
we did not examine gingival or fat tissue.
I will now show you the autopsy ﬁndings. These are
the gross ﬁndings of the vertebrae. As you can see,bone lysis was present in this area.
This slide shows the bone marrow in the area ofbone lysis. You can see hypercellular bone marrow at
low magniﬁcations and at high magniﬁcation particular
plasmacytoid cells, indicating multiple myeloma.
These are the immunohistochemical ﬁndings fromthe plasmacytoid cells. There is positive staining forboth anti-VS38C antibody and anti l; k chain, but the kchain was negative. This is kappa chain; this is lambda
chain (Fig. 4).
Figure 5 shows the patient’s heart. The horizontal
section of the heart shows a hypertrophic septum with apacked, waxy appearance. The weight of the heart was
650 g.
The myocardium had amyloid deposition. You can
see amorphous, eosinophilic material in the myocardium. The congo red staining is positive here. Under
the polarized light microscope, there is green birefringence.
Dr. Rao: Could you just point out to the students thespotty nature of involvement? So, if you take a biopsyof the heart, it will not be positive for amyloid.
Dr. Mori: This epicardial region has a small numberof amyloid deposits. Almost all the amyloid depositions
were in this other area.
This slide shows microscopic ﬁndings of the kidney.
As you can see, amyloid deposition is apparent in theperivascular area and interstitial areas. Glomerularbasement membranes also show deposition.
Here is a hyalinized cast in the tuberous area, but inthis case there were only a few amyloid deposits, so I
think the kidneys could not be deﬁned as harboring
amyloid.
Amyloid deposition was also found in other organs.
This slide shows amyloid in the esophagus. This area
demonstrates green birefringence.
The lungs also had amyloid deposits.
This patient had a persistent infection with hepatitis
B virus. The liver weighed 1,600 g and showed a nodular appearance. These are microscopic and macroscopicﬁndings.
The patient’s pathologically marked congestion was
conﬁrmed and with elastica van Gieson staining. Periportal ﬁbrosis was also observed. This shows periportalﬁbrosis and congestion.
At high magniﬁcation, lymphoid cell inﬁltration wasseen in the portal area and piecemeal neo-necrosis was
identiﬁed. Thus, I made a diagnosis of chronic active
hepatitis.
This is the ﬁnal pathological diagnosis for this patient(Fig. 6). The main disease was multiple myeloma. The

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Kizaki M, et al: Myeloma with systemic amyloidosis

Fig. 4 Autopsy ﬁndings of the bone marrow. Shown are atypical plasmacytoid cells proliferation H-E (A) and Vs38c (B). Immunohistochemical staining of l chain protein (C) and k chain protein (D).

autopsy ﬁndings were myeloma cell inﬁltration and invasion, particularly proliferation of a typical plasmacytoid cells.
Invaded areas included the vertebrae and costae.
Deposition of amyloid light chains, i.e. lambda chains,
was seen in the visceral organs; the heart, kidney, duodenum, stomach, ileum, colon, tongue and lungs. Systemic congestion and edema were seen in many organs
including the liver, spleen and kidneys, and the lower
extremities. There was pleural effusion, ascites, andpericardial effusion. Chronic active hepatitis was present, and additionally, there were no septic ﬁndings.
I prepared one more ﬁgure illustrating amyloidosis(Fig. 7). Amyloidosis is deﬁned as a disease of abnormal deposition of insoluble amyloid microﬁbers which
are characterized under electron microscopy as 10 to 15
nm microﬁbers. This is a microscopic ﬁnding. With H-E

staining, amyloid ﬁbers stain as eosinophilic amorphousmaterials and are positively stained with congo red.
Under a polarizing microscope, amyloid shows green
birefringence, as you can see here. Biochemically, they
are formed from protein comprised of many materials
and amyloid ﬁbers are classiﬁed into several groups
according to the amyloid light chain, the AL, which isderived from plasma cells. AA (amyloid associated) is
not associated with immunoglobulin proteins, which are
made by the liver. b2 microglobulin is a normal serum
protein that complicates the course of patients on longterm hemodialysis. Amyloidosis is grouped into generalized and localized forms. As you can see from thisﬁgure, this case ﬁts into the category in which the major
ﬁber protein is AL and lambda chains.
Dr. Kizaki: Thank you, Dr. Mori. I think it is quitepossible that the pathological diagnosis is compatible

Keio J Med 2004; 53 (3): 178–191

189

Fig. 5 Autopsy ﬁndings of the heart. H-E (A) and congo-red (B) staining shows myocardium deposition of amyloid and apple green birefringence is observe under polarized light microscopy (C). Horizontal section of the heart: Hypertrophic and packed appearance was observed(D). The heart weight was 650 g.

with our clinical diagnosis. The students here were excellent. I think your diagnosis is right. But we should
ask some questions of the pathologist. Do you have any
questions for Dr. Mori?
Dr. Kumagai: Did you ﬁnd amyloid deposition in thecoronary arteries and thyroid gland?
Dr. Mori: We found coronary arterial deposition ofamyloid.
Dr. Kumagai: How about the thyroid gland?
Dr. Mori: The thyroid probably did not have prominent deposition.
Dr. Kumagai: Thank you so much.
Dr. Kizaki: That means the reason for the patient’s
ﬁrst admission, the angina, was ultimately the amyloidosis. How about other questions?
Dr. Satoh: Some reports have stated that if you perform an electron microscopic study of the cardiac biopsy specimen, you can obtain a diagnosis of amyloi-

dosis. We suspected amyloidosis at the ﬁrst admission.
We then asked pathologists to perform congo red
staining. If we had asked you to do an electron microscopic study, could we have obtained the correct diagnosis?
Dr. Mori: Yes, I think so.
Dr. Rao: I am sorry. I have to disagree with you.
Cardiac amyloid is a patchy disease, and that is why you
do not see it on endomyocardial biopsy. My recommendation, if I would have thought of amyloidosis in
this patient and if the endomyocardial biopsy cameback negative, would have been to do a gingival biopsy
or a fat pad biopsy. In fact, I would go for three fat pad
biopsies, or even four, one from each quadrant of theabdomen. Alternatively, I might ask the oral surgeon to
do a gingival biopsy. If all of those specimens were
negative, only then would I say there is no amyloidosis.
Can I just add one more point? The new classiﬁca-

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Kizaki M, et al: Myeloma with systemic amyloidosis

Pathological diagnosis
1.

Multiple myelomai ) Diagnostic biopsy of the bone marrow:
Plasmacytoid cell infiltration, marked, compatible with multiple myeloma(Keio Univ. Hosp. P202-01) VS38c (+), EMA (+), AL ( λ ), Bence-Jones protein (+)
ii ) Myeloma cell proliferation and invasion: vertebrae, costaeiii) Post status of steroid therapyiv) Amyloidosis:
Deposition of amyloid light chain (AL) in the visceral organs including
heart (650g), kidneys (220, 200g), esophagus, stomach, duodenum, ileum,colon, tongue and lungs.

2.

Systemic congestion and edema:
Liver (1600g), spleen (100g), and lower extremities

3.

Pleural effusion (1300, 1200ml), ascite ( small amount) and pericardial effusion(45ml)

4.

Chronic active hepatitis
HBV-Ag(+), Inuyama classification (A2, F1)

5.

Atherosclerosis of the aorta, moderate
Fig. 6

Pathological diagnosis of the autopsy.

Amyloidosis
Amyloidosis isclassified
by amyloid proteinsand distribution of
their deposition.

Heart
Amyloid micro fibrils
10-15nm (diameter) fibrils

H-E

Fig. 7

Congo red/ Green birefringence

Summary of amyloidosis.

Keio J Med 2004; 53 (3): 178–191

tion of amyloidosis is basically split into three – AL
amyloid, AA amyloid and other. AL amyloid is the onethat is composed of amyloid light chains. On the other
hand, AA amyloid is due to the deposition of ﬁbrils of aprotein called serum amyloid protein A. This is anacute phase reactant, but we have no idea why it gets
deposited in situations associated with chronic inﬂammation. The last form is familial amyloid. In one variant, the amyloid protein consists of transthyretin, which
is an abnormal thyroid binding protein, but there is no
thyroid disorder.
Dr. Kizaki: At ﬁrst admission, Dr. Ieda, the doctor in
charge, suspected amyloidosis and he performed cardiac biopsies but he could not detect amyloid. So, yourrecommendation would be to perform another biopsy
just using fat or some other tissue specimens?
Dr. Rao: That is where we rely on the pathologist totell us that they could not ﬁnd it in the endomyocardial
biopsy, and that the only way to make the diagnosis isfrom a fat pad or from the gingival tissue.
Dr. Kizaki: Any questions for Dr. Mori, the pathologist? Or, any comments on the diagnoses of this patient? No further comments or opinions?
Dr. Awaya: I think this case can be summarized in
two points. First, it is very difﬁcult to make a diagnosisof IgD myeloma. Secondly, as Dr. Rao stressed, when
you elect to make a diagnosis of amyloidosis, you needto choose the proper tissue, which is basically fat.
Dr. Rao: In defense of whoever was taking care ofthis patient, making the diagnosis would have changed
nothing at all. You would not have been able to do athing to prevent this patient from dying.
Dr. Hori (Emergency Medicine): My question is notregarding the cause of his death but I am thinking about
his clinical course during the second admission. Clinicians probably were able to predict his clinical outcome
would be grave. As such, what kind of diagnosis was
made? Did the doctor in charge announce it to the patient himself? My second question is, in the UnitedStates, Dr. Rao, if your patient has a similar clinicalentity with a grave clinical cause such as cardiac amyloid, how do you deal with such a patient, regarding thepresentation of the diagnosis to them?
Dr. Ieda: In the second admission, we thought hehad cardiac amyloidosis and myeloma, so his prognosis
was very bad. Previously, I told his family his survival

191

would be about six months. After consulting with hisfamily, we presented this information as fully to thepatient as we had to his family. Perhaps he died suddenly.
Dr. Kizaki: Dr. Rao, suppose you have the same patient in the United States, what would you do?
Dr. Rao: Basically, I would break the news to thepatient very kindly, very gently. The students should
recognize that this is one of the most delicate of all
functions that you will ever perform as a physician. You
must be very, very understanding, very gentle, and very
compassionate. Look at it this way: you are signing thepatient’s death warrant. You have given the patient a
sentence of death. There is no more serious task you
will ever perform in your lives than telling a patient, ‘‘I
can do nothing for you and you are going to die.’’ You
do not take that responsibility lightly. Just think about
it, there is not a thing you can do and the patient knowsthat he is going to die. You need to be very sensitive tothat situation.
And you need to involve the family. In most situations, you cannot tell the family without telling thepatient, unless there is a reason the patient cannot
comprehend or cannot understand the signiﬁcance – forexample, if there is some CNS involvement, or if you
think the patient will not understand the signiﬁcance ofwhat you are telling them. That is a different story. But
as a general rule, the patient is the ﬁrst to know. You
have to tell the patient, and then have a family conference.
If there is a silver lining to this dark cloud, it is thatmost patients who are this sick know they are going todie. They are not stupid. This patient probably knew.
But it was just a question of someone conﬁrming it forhim. So, when you do that, you have to be understanding. I know that the students are still very young andinexperienced, but rest assured that when you do it
often enough you will really get a sense of how to do it.
Only by doing it will you learn. No one can tell you how
to do it. If you are a kind person and you really care foryour patients, you will ﬁnd your own way to tell them.
Dr. Kizaki: Thank you. That is a very difﬁcult problem; how we should treat dying patients. Any questions
or comments? If not, then this CPC is over. Thank youvery much to the participating doctors and thank youvery much, Dr. Rao.