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C OPYRIGHT 2011
BY
T HE J OURNAL
OF
B ONE
AND J OINT
S URGERY, I NCORPORATED
Vertebra Plana in an Adolescent
Caused by Multiple Myeloma
A Case Report and Review of the Literature
By Robert M. Greenleaf, MD, Lauren F. Ricciardella, MS, Carmen R. Latona, MD, and Mark J. Sangimino, MD
Investigation performed at Allegheny General Hospital, Pittsburgh, Pennsylvania
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ertebra plana is a radiographic diagnosis that is characterized by flattening of a single, abnormally dense
vertebral body with sparing of the intervertebral disc
space. Vertebra plana in pediatric and adolescent populations is
most commonly caused by Langerhans cell histiocytosis (LCH),
which most often has a benign natural history with nonoperative treatment, although malignant conditions have now been
reported with similar clinical and radiographic presentations.
Fig. 1
Bone scan showing increased isotope uptake at the T10 vertebral body only.
Disclosure: The authors did not receive any outside funding or grants in support of their research for or preparation of this work. Neither they nor a member
of their immediate families received payments or other benefits or a commitment or agreement to provide such benefits from a commercial entity.
J Bone Joint Surg Am. 2011;93:e37(1-7)
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doi:10.2106/JBJS.J.00640
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Fig. 2 Lateral radiograph showing vertebra plana at
T10, with 85% height loss, preservation of adjacent
intervertebral disc spaces and posterior elements,
and a sclerotic-appearing body. Fig. 3-A and 3-B
T2-weighted axial (Fig. 3-A) and sagittal (Fig. 3-B)
magnetic resonance images, made early after
presentation, showing approximately 80% loss of
vertebral height at T10 and preservation of adjacent
disc spaces. Notably, no canal compromise or
posterior element involvement is present. R = right,
p = posterior.
Fig. 2
Fig. 3-A
Fig. 3-B
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Fig. 4 Lateral lumbar radiograph showing a new vertebra plana at
L5 one year after the initial presentation. The prior vertebra plana
at T10 at the top of the image is grossly unchanged on
radiographs.
Fig. 4
Multiple myeloma is a disease of plasma cells produced in
the bone marrow. It is the most common primary bone malignancy and is the second most common blood cancer after
non-Hodgkins lymphoma. Bone pain, especially back pain, is
the most common symptom at the time of presentation.
The inflammatory reaction in the vertebral bodies caused by
the affected plasma cells cause the characteristic ‘‘punched
out’’ lytic lesions on radiographs. To our knowledge, this
is the first report of an adolescent patient who presented
with an uncomplicated vertebra plana caused by multiple
myeloma. The patient and parents were informed that data
concerning this case would be submitted for publication,
and they consented.
Case Report
n otherwise healthy fifteen-year-old boy was referred in
October of 2008 after several months of lower thoracic
back pain and a progressive gait abnormality. He had been seen
at another institution sixteen months earlier because of mild
back pain. A radiograph at that time was negative, but a subsequent bone scan showed increased uptake in the T10 vertebral body (Fig. 1). The patient was managed with a Jewett-type
A
back brace and oral nonsteroidal anti-inflammatory drugs,
with some pain relief. Six months later, radiographs showed an
isolated T10 vertebra plana (Fig. 2). Physical examination revealed only mild tenderness over the T10 area and pain with
extremes of back motion but no neurologic deficits. A complete
blood count with differential and the C-reactive protein level
were within normal limits. Magnetic resonance imaging (MRI)
of the thoracolumbar spine showed an isolated T10 vertebra
plana with 80% loss of vertebral height, maintenance of the
adjacent disc spaces, minimal vertebral retropulsion without
cord compression, minimal edema within the vertebral body,
and no soft-tissue component or posterior element involvement (Figs. 3-A and 3-B). A working diagnosis of vertebra
plana secondary to Langerhans cell histiocytosis was made, and
the patient was managed nonoperatively and was encouraged
to slowly return to activities when asymptomatic. At the time of
the six-month follow-up, the patient had no changes on examination or on radiographs.
More than a year after the initial presentation, the patient
returned to our clinic after three weeks of slowly worsening
lower extremity paresthesias, intermittent subjective coolness
in the foot and ankle bilaterally, an unsteady gait, and wors-
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Fig. 5 Lateral radiograph of the skull, showing lytic lesions
in the parietal and occipital regions. Fig. 6-A and 6-B T2weighted axial magnetic resonance image (Fig. 6-A) and
axial computerized tomography scan (Fig. 6-B) showing
increased retropulsion with cord compression, posterior
element involvement, and a large soft-tissue component
causing circumferential encasement of the thecal sac.
Fig. 5
Fig. 6-A
ening middle and lower back pain. The patient walked with a
mild slapping gait and had difficulty walking in a straight line
without external aids. Physical examination showed grade-5
(of 5) motor strength in all extremities but decreased sensation
to light touch and pinprick in the foot and ankle bilaterally.
In each lower extremity, he had 41 ankle reflexes, a positive
Babinski sign, and decreased great toe proprioception. Radiographs showed continued T10 flattening with a new 50% loss
of height of the L5 vertebral body (Fig. 4). A skeletal survey
showed vertebra plana of T10 and L5 with radiolucencies in the
Fig. 6-B
left second and right tenth ribs and in the right parietal skull
region (Fig. 5). A repeat MRI showed increased vertebral retropulsion with cord compression, posterior element involvement at T10, and a large soft-tissue component at T10 causing
circumferential encasement of the thecal sac. There were interval T2 signal changes within the vertebral bodies of T3, L1,
L4, and L5, with mild retropulsion and an associated soft-tissue
mass (Fig. 6-A). Additional findings on computerized tomography (CT) with contrast included a soft-tissue component on
the left second rib lesion and expansile radiolucencies in the left
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Fig. 7
Biopsy section from L5, showing osseous trabeculae with marrow spaces filled with clusters of plasma cells in
sheets (hematoxylin and eosin, ·200). The cells have a uniform appearance, eccentric nuclei with a perinuclear
pale zone, and occasional mitoses.
ninth rib, left glenoid, bilateral iliac wings, and right posterior
acetabulum (Fig. 6-B). Computerized tomography with contrast of the chest, abdomen, and pelvis demonstrated negative
findings, with no organomegaly or lymphadenopathy.
Given the multiple lesions and clinical findings, the patient was referred to a pediatric oncologist and was admitted to
the hospital. Serum studies included a complete blood count,
including a white blood-cell count (5.2 · 109/L), hemoglobin
(14.5 mmol/L), hematocrit (44.9%), platelets (323 · 109/L),
and absolute neutrophil count (3000 cells/mL; normal, 1500 to
8000 cells/mL). Electrolytes, renal function, liver function, albumin, prealbumin, and serum uric acid were all within normal
limits. The sedimentation rate and the lactate dehydrogenase
were mildly elevated at 43 mm/hr and 280 IU/L, respectively.
Computerized tomography-guided biopsy was performed at
L5, with hematoxylin and eosin staining showing a preponderance of plasma cells (Fig. 7). Langerin, CD1, and S100 were
negative. CD79a and CD138 showed variable positive staining.
There was no staining for kappa and diffuse staining for
lambda. Heavy chain stains showed IgA restriction in the
plasma cells, with no staining for IgG, IgM, or IgD. Subsequent
blood work showed elevated serum IgA (1440 mg/dL; normal,
<435 mg/dL). Serum and urine immunoelectrophoresis identified a monoclonal IgA protein. Serum protein electrophoresis
(SPEP) showed an increase in alpha-II globulin as well as
gamma globulin and a monoclonal protein detected at a concentration 1.33 g/dL. The biopsy was negative for the 13q14.2
deletion, for loss of the ATM tumor suppressor gene, and for
the CCND1 and IgH rearrangements. Radiation therapy to the
T10 and L5 vertebrae and intravenous dexamethasone were
started during the initial admission, with substantial neurologic improvement by two days. A combination of Revlimid
(lenalidomide) and steroids was initiated, with enoxaparin
followed by aspirin for prophylaxis against deep-vein thrombosis. The patient continued to receive zoledronic acid every
month along with calcium and vitamin-D supplementation. In
April 2010, the patient underwent an uneventful stem cell
transplantation. The back pain had remained minimal, and the
neurologic symptoms had not recurred since the initiation of
treatment. At the time of the latest follow-up, the patient had
not had any major illnesses or adverse reactions to treatment
but did complain of fatigue.
Discussion
ertebra plana was first described by Jacques Calvé in 1925
in a report on two pediatric patients with a single compressed vertebral body1. Calvé believed that the radiographic
finding represented vertebral body osteochondritis, which he
described as ‘‘what Keohler’s disease is to the foot.’’ The work by
Calvé and Buchman defined the classic radiographic findings as
(1) involvement of only one vertebra, (2) lack of adjacent intervertebral disc involvement, (3) widened intervertebral disc
space, and (4) greater opacity of the involved, collapsed vertebral
body1,2. Compere et al.3 and Lichtenstein4 reviewed multiple
case reports and proposed that the cause of vertebra plana was
eosinophilic granuloma. Eosinophilic granuloma along with
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Hand-Schüller-Christian disease and Letterer-Siwe disease are
three variations of Langerhans cell histiocytosis (LCH), which
is the term that is most commonly used today. There is an
annual incidence of 5.4 cases per million children per year5.
Eosinophilic granuloma is the most common and benign form,
is isolated to bone, and is typically monostotic but may occur in
multiple locations, including the spine, skull, and ilium5,6. The
peak incidence occurs between five and ten years of age6. Radiographic findings include lytic vertebral lesions with poorly
defined margins, sparing of posterior elements, preservation of
the adjacent disc space, and a predilection for the thoracic spine5.
Surgical interventions, including curettage, grafting, decompression, and stabilization, have been advocated in the past7.
Recent long-term follow-up studies have shown good results
following nonoperative treatment in children, so surgery should
be reserved for adults with neural compromise or substantial
deformity or instability8,9.
The classic radiographic findings of vertebra plana are
strongly suggestive of eosinophilic granuloma. Other, less common causes include trauma10, Gaucher disease11, osteomyelitis12,13,
coccidiodomycosis14, tuberculosis15, myofibromatosis16, aneurysmal
bone cyst17,18, osteosarcoma19,20, leukemia21, lymphoma22,23, Ewing
sarcoma24-29, and giant-cell tumor30. To our knowledge, there
have been no reported cases of multiple myeloma presenting as
isolated vertebra plana.
Multiple myeloma is the most common primary bone
malignancy and is the second most common blood cancer after
non-Hodgkin lymphoma. It is an adult disease, with a median
age of seventy years at the time of diagnosis, and rarely presents
before the age of forty years. Plasma cells are a type of B cell that
normally produces immunoglobulins in the bone marrow. In
multiple myeloma, myeloma plasma cells proliferate uncontrollably and overproduce the cell’s respective immunoglobulin;
these serum monoclonal immunoglobulins are known as the M
protein. The presenting symptoms of multiple myeloma, in
order of prevalence, are bone pain (especially back pain), fatigue,
pathologic fractures, weight loss, and paresthesias. One-third of
patients are asymptomatic when diagnosed31-33, and osseous lesions often show decreased uptake on nuclear bone scans34.
The definitive diagnosis of multiple myeloma requires
advanced testing. Electrophoresis identifies excess protein from
monoclonal antibodies (the M protein) in the blood and detects the light-chain component of these antibodies in urine
(Bence-Jones proteinuria). Biopsy of bone marrow aspirate
allows histological confirmation, with characteristic sheets of
plasma cells with eccentric nuclei and perinuclear clear zones
(Fig. 7). The specific monoclonal immunoglobulin may be
characterized, and several additional biochemical and genetic
markers are being used or investigated to offer prognosis and
predictions regarding response to therapy31,32.
Treatment strategies should be individualized; some
milder variations of the disease require no treatment, whereas
older or sicker patients may not be able to tolerate aggressive
chemotherapy regimens. Multiple myeloma is very sensitive to
radiation therapy, and, in patients with spinal cord compression,
radiation can rapidly reduce both pain and neurologic symptoms.
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Autologous stem cell transplantation is the gold standard for
patients who can tolerate the associated chemotherapy.
There is controversy about whether biopsy is necessary to
determine the exact cause of the vertebra plana. Biopsy of the
vertebral body is an invasive procedure that risks damage to the
vertebral growth plates, which are typically spared by eosinophilic granuloma. Growth plate injury, at least in theory, may
hinder reexpansion of the vertebral body in these young patients35. However, we found no reported cases of iatrogenic
growth plate injury during biopsy. O’Donnell et al. suggested
performing open biopsy in suspected cases of eosinophilic
granuloma vertebra plana except when a strict set of criteria for
observation was met: an age of less than twenty years; no radiating pain or neural compression; no constitutional symptoms
or abnormal laboratory findings; and monostotic, symmetric
vertebral body collapse with sparing of the posterior elements36.
However, their review and recommendations predated the
widespread use of MRI, which would likely play a role now in the
selection of biopsy candidates. More recently, some authors have
suggested reserving biopsy for atypical cases in patients with
either an associated soft-tissue mass on MRI, involvement of
the disc space, or the presence of neurologic symptoms7,18,37-39.
When biopsy is warranted, there is still no consensus
regarding the use of an open or percutaneous technique. Older
reports in the literature cited a low diagnostic yield with percutaneous needle biopsy19,23,36,40,41. However, CT-guided needle
biopsy is being increasingly advocated in light of more recent
reports showing lower morbidity and higher yields than previously reported. Yasko et al.42 reported 90% accuracy in a
cohort of thirty-nine patients, whereas Elsheikh et al.43 found
100% accuracy in three cases.
In conclusion, our adolescent patient with vertebra plana
and back pain did not have any atypical clinical or radiographic
findings for nearly two years after the onset of symptoms. Our
strategy of frequent follow-up with serial imaging is consistent
with most contemporary treatment algorithms. Multiple myeloma is exceedingly rare in patients this young, and little is
known about its natural history, prognosis, and optimal treatment. The initial workup for vertebra plana should include MRI
and a skeletal survey to evaluate for systemic disease or atypical
findings as described above. We recommend a strong consideration of CT-guided needle biopsy if there is any suggestion of
malignant disease or if the diagnosis is doubtful. If the results of
the needle biopsy are inconclusive, open biopsy may be done. n
Robert M. Greenleaf, MD
Lauren F. Ricciardella, MS
Carmen R. Latona, MD
Mark J. Sangimino, MD
Allegheny General Hospital, 1307 Federal Street,
2nd floor, Pittsburgh, PA 15212.
E-mail address for R.M. Greenleaf: bob.greenleaf1@gmail.com.
E-mail address for L.F. Ricciardella: goldnwlf@gmail.com.
E-mail address for C.R. Latona: clatona@wpahs.org.
E-mail address for M.J. Sangimino: msang@zoominternet.net
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