Anesth Pain Med 2009; 4: 43～46 ￭증례보고￭

Extraosseous multiple myeloma presenting as repeated

intracranial bleeding and relapsing high fever with respiratory
failure
−A case report−
†
Departments of Neurosurgery, *Anesthesiology and Pain Medicine, Hanyang University College of Medicine, Department of
Anesthesiology and Pain Medicine, The Catholic University of Korea College of Medicine, Seoul, Korea

Hyoung Joon Chun, M.D., Hyeong Joong Yi, M.D., Ji Seon Jeong, M.D.*,
Dong Won Kim, M.D.*, Jae Chul Shim, M.D.*, and Keon Hee Ryu, M.D.†

Multiple myeloma can usually be identified by non-traumatic
vertebral fracture or signs of recurrent infection. Without these
clinical signs, detection is unlikely. We briefly report a case of
extraosseous multiple myeloma presenting as repeated intracranial
bleeding and relapsing high fever. In doing so, we highlight the
importance of subtle changes in laboratory findings. A 67-year-old
man presented with spontaneous acute epidural hematoma, and
hematoma evacuation was performed at the same site 3 times.
A radiologic work-up failed to reveal any osseous lesions and he
made a gradual recovery. In the meantime, he suffered unexplained
o
fever up to 39 C despite normal chest and abdominal radiograms.
Blood chemistry showed mild leukocytosis, high ESR and CRP, and
a slightly elevated globulin. On his 15th hospital day, immuno-
globulin studies confirmed the diagnosis of multiple myeloma. He
was treated in the ICU for difficult breathing and uncontrolled fever.
In spite of intensive critical care, his leukocyte count fell to below
2,000 and he died on postoperative day 28. Apparently normal
laboratory and radiologic findings can hamper swift discovery and
ultimate management of multiple myeloma. When there is une-
xplained repeated intracranial bleeding and accompanying fever, the
possibility of hidden malignancy should be assessed to avoid
delaying or missing treatment. (Anesth Pain Med 2009; 4: 43∼46)
Key Words: Myeloma, intracranial bleeding, laboratory findings,
multiple myeloma.
Multiple myeloma (MM) is a disseminated form of a mono-
clonal proliferation of plasma cell (plasmacytoma) and is
usually confined to the bone marrow.1) But, other related organ
논문접수일：2008년 9월 25일
책임저자：김동원, 서울시 성동구 행당동 17
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우편번호: 133-792
Tel: 02-2290-8680, Fax: 02-2292-0742
E-mail: dongwkim@hanyang.ac.kr
impairment or end-organ damage might occur at the time of
diagnosis or in the course of the disease. Extraosseous MM or
extramedullary MM (EM) is very aggressive and intractable to
the preexisting therapies, particularly when it is present at
diagnosis.2) This EM variant therefore, represents more fulmi-
nating and more systemic spectrum of the same illness ontogeny.
As its name implies, high index of suspicion should be made
to detect and treat EM because it shows quite unusual clinical
and biological behavior.
We herein briefly report a case of an EM presenting as
repeated intracranial bleeding after minor head injury and high
fever with subsequent respiratory failure. In this paper, we
hope to highlight essential, but easily unrecognized clues of
the EM.
CASE REPORT
A 67-year-old man was referred to our department because
of sudden unconsciousness while he was taking magnetic
resonance (MR) imaging of the lumbar spine after minor
collision of the head to the MR apparatus. He had no past
history of significant medical illness. On referral, he was
stuporous, hemiparetic (Grade2/Grade3) and showed mydriatic
pupils. Physical examination showed slight swelling on the left
scalp with small bruise. Computed tomogram (CT) of the head
showed acute subdural bleeds on the left side of the cerebral
hemisphere and, hematoma was urgently evacuated with meti-
culous bleeding control (Fig. 1A). All through the operative
procedure, any culprit evidence of intracranial injury was not
uncovered. He awoke and recovered motor strength soon after
the first craniotomy (Fig. 1B). On the morning of the

43
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postoperative day 2, he was found unresponsive again with
hemiparesis and dilated pupils. Immediate head CT scan
revealed a subdural hematoma exactly on the same site and
size with the initial one (Fig. 1C). Second craniotomy was
performed very cautiously with special reference to the
bleeding focus. At that time, there was no special point
responsible for bleeding either. While he made a gradual
recovery from craniotomy, two more repeated bouts of
hematoma accumulation happened in postoperative day 3 and
4. And, two more same procedures of the surgical evacuation
were subsequently conducted (Fig. 1D). He awoke and reco-
vered from neurological deficits over the next few days.
Meanwhile, extensive hematologic and radiologic work-up
was done to reveal any causative factors. Radiographic inves-
tigation including X-ray of the chest and skull, abdominal CT,
and cerebral angiogram, failed to disclose any abnormal
Fig. 1. (A) On referral, CT of the head
reveals acute subdural hematoma on
the left side of the hemisphere and
midline shifting. (B) Immediate pos-
tevacuation head CT scan shows
recovery of the midline shift. (C) On
the postoperative day 2, head CT
shows reaccumulated subdural hema-
toma of the same size and site with
the initial bleeds. (D) Head CT
following the last surgical evacuation
shows no evidence of further intra-
cranial hemorrhage.
findings (Fig. 2), whereas hematologic laboratory exhibited
mild leukocytosis (12,100/mm3) and anemia (9.7 g/dl) as well
as thrombocytopenia (51,000/mm3) with high levels of ery-
throcyte sedimentation rate (ESR) and C-reactive protein (CRP)
of 55 and 5.2, respectively. Serum laboratory results showed
lower albumin while high globulin level; vaguely low A/G
ratio of 0.46. From the 7th hospital days, he showed relapsing
high fever up to 39−40oC several times a day, despite normal
chest and abdominal radiograms and negative culture on the
blood, urine and sputum. At 10th hospital day, serologic
studies with immunoglobulin confirmed the diagnosis of MM.
From that time point, he suffered from difficulty in breathing
with paradoxical chest wall motion, and was transferred to the
intensive care unit (ICU) for artificial ventilatory support.
During his ICU stay, febrile attack ceaselessly occurred despite
rigorous antipyretic therapy. Because he became critically
 Hyoung Joon Chun. et al：Extraosseous multiple myeloma 45
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worse, progressively obtunded and totally dependent upon the
ventilator with high body temperature, bone marrow biopsy
and definite therapy against MM could not be provided. His
blood cell count decreased accordingly including leukocyte
3
count of less than 1,000/mm , and self respiratory movement
disappeared soon afterwards. He died from respiratory failure
on the hospital day 18, and his family members denied autopsy.
DISCUSSION
The initial presentation of MM, a hematopoietic malignancy
derived from a single clone of plasma cell, in neurosurgical
perspectives is usually repeated vertebral fracture following
minor trauma. Recurrent episode of unexplained infection is
another clue of the MM. Such clinical manifestations are
attributed to diffuse or multilocular infiltration of the bone
marrow with osteolysis and suppression of the normal hema-
topoesis.1) Radiologic feature is thus, osteolytic lesion called
“punched-out” appearance in most patients. When such culprits
are not present or not distinguished at the time of diagnosis or
during the course of disease, detection and swift management
is highly unlikely.
EM, either form of solitary plasmacytoma or diffuse organ
involvement outside the osseous system, is usually associated
with a more aggressive biologic behavior that is characterized
by increasing anaplasia of plasma cells, elevated serum levels
of lactate dehydrogenase, decreased serum level of paraprotein
and resultant pancytopenia, with consequent fever unrelated to
2)
infection. Clinicopathologic studies identified extraosseous sites
of involvement in 2/3 of patients with MM, with gross disease
Fig. 2. (A) On admission, chest x-ray
shows no parenchymal or skeletal
abnormalities. (B) Skull x-ray also
shows no abnormal osteolytic lesions.
seen in 8−17%. They can arise in any tissue, but lymph
nodes, skin, lung, and central nervous system (CNS) are most
frequently involved.3) Within the confines of CNS, EM com-
monly presented as weakness, changes of mental status, and
cranial nerve palsy with extremely poor prognosis.4) Radiologic
findings of CNS involvement include diffuse leptomeningeal
and skull base enhancement, epidural plasmacytomata, diffuse
calvaria involvement, clivus mass, and swelling of ventricles.5)
Although we did not obtain surgical specimen of the intra-
cranial bleeding, there was not any bit of suspicious invol-
vement in the skull, dura and parenchyma.
Respiratory insufficiency has been described in association
with MM, mainly with parenchymal involvement such as infil-
trative processes, pleural effusion, and localized plasmacytoma.
But, non-parenchymal respiratory failure also happens, and two
mechanisms are recognized; spontaneous flail chest arisen from
multiple osteolytic rib lesions that lead to destabilization of the
bony rib cage, and diaphragmatic paralysis that resulted from
demyelinating polyneuropathy with phrenic nerve involve-
ment.6-8) The cause of respiratory failure in the present case is
deemed diaphragmatic dysfunction without chest wall and lung
parenchymal involvement.
In general, reoperation of acute subdural hematoma is the
result of inappropriate bleeding control, undue brain retraction,
transient hypervolemia during the general anesthesia, systemic
hypertension, osmotic pressure change by mannitol injection
and hemodynamic changes.9) Recurrent collection of subdural
hematoma in the current case could not be explained within
context of the above situations.
In this case, we could not even think of the possibility of
46 Anesth Pain Med Vol. 4, No. 1, 2009
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MM until the fourth craniotomy was held and subtle changes
of laboratory results were encountered. This is primarily because
the patient had no conventional radiologic manifestation for the
MM. The only clue was delicate abnormality in protein com-
position and high inflammatory serum marker at early hospita-
lization. Mild thrombocytopenia without other blood cell defi-
ciency may hamper us from further hemato-oncologic assess-
ment for repeated bleeding. Progressive pancytopenia with
resulting high fever and respiratory insufficiency without radio-
logic evidence of acknowledged malignancy, is not a straight-
forward situation to diagnose MM. And therefore, the possi-
bility of hidden rare malignacy, especially extraosseous MM,
should be strongly considered not to miss or delay ultimate
treatment if there is repeated intracranial hematoma otherwise
unexplained, that is accompanied by relapsing fever and rapidly
progressing respiratory failure.
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