Aforty-one-year-old woman experienced progressive discomfort of the right
arm, the lower back, and the pelvis during the second trimester of pregnancy.
Ovulation had been pharmacologically induced, but the pregnancy had been
otherwise obstetrically uncomplicated. The symptoms in the right arm acutely
worsened at twenty-eight weeks of gestation when she reached to grab a falling
object. Radiographs demonstrated all three osseous manifestations of multiple
myeloma: focal lytic lesions, osteopenia, and a pathologic fracture of the
surgical neck of the right humerus (Figs.
1-A and
1-B). She was referred to our
orthopaedic oncology service.
Laboratory studies demonstrated severe anemia, with a hemoglobin level of
74 g/L (normal, 120 to 160 g/L); abnormal renal function, with a serum urea
nitrogen level of 33 mg/dL (11.8 mmol/L) (normal, 8 to 25 mg/dL [2.9 to 8.9
mmol/ L]) and a serum creatinine level of 2.8 mg/dL (248 µmol/L) (normal,
0.6 to 1.5 mg/dL [53 to 133 µmol/L]); and hypercalcemia, with a serum
calcium level of 11.6 mg/dL (2.89 mmol/L) (normal, 8.5 to 10.5 mg/dL [2.12 to
2.62 mmol/L]). The serum and urine protein electrophoresis studies both
revealed moderate to large amounts of lambda light chains.
Magnetic resonance imaging of the abdomen and pelvis showed diffuse changes
in the bone marrow of the spine and pelvis that were consistent with
replacement by malignant cells. Vertebral compression fractures were evident
in the upper lumbar region, and two large focal lesions with associated
destruction of the cortex were seen in the left hemipelvis (Figs.
2-A and
2-B). A computed
tomography-guided core biopsy of the right humeral lesion demonstrated sheets
of plasma cells (Fig. 3). A
diagnosis of multiple myeloma was made.
The patient was admitted to the hospital, and a multidisciplinary team
consisting of members of the departments of orthopaedics, obstetrics, and
oncology was established to supervise her care. The fracture of the surgical
neck of the right humerus was stabilized with a brace, and Decadron
(dexamethasone) was given as an induction agent to decrease the tumor mass.
The secondary metabolic abnormalities were treated with the administration of
blood transfusions for anemia; with hydration, diuresis, and the
administration of pamidronate for hypercalcemia; and with the administration
of allopurinol for hyperuricemia. At the recommendation of the orthopaedic
surgeons, the decision was made to deliver the child by cesarean section to
avoid subjecting the diseased lumbosacral spine and pelvis to the stress that
would be associated with a vaginal birth.
At thirty-four weeks of gestation, the patient delivered a 2.27-kg (5-lb,
0-oz) girl by cesarean section. The mother had no operative complications;
however, the child had seizures that were related to difficulties with calcium
regulation. The neonatal urine had no abnormal proteins, and serum protein
electrophoresis revealed negative findings. The baby was discharged from the
hospital at ten days of age and remained healthy and seizure-free at the time
of the most recent follow-up, two years after delivery.
A postpartum skeletal survey of the mother revealed numerous lytic lesions
but no other impending pathologic fractures. The pain in the arm, back, and
pelvis resolved after a course of Decadron (dexamethasone) and monthly
administration of pamidronate. The right humeral lesions healed when
external-beam radiotherapy was added to the treatment regimen. Six months post
partum, the patient began a course of high-dose melphalan chemotherapy with
peripheral autologous stem-cell transplantation, which resulted in complete
remission of disease and normalization of the bone marrow. Fifteen months post
partum, a painful lytic lesion arose in the tibia, potentially heralding the
onset of progressive disease.
In our orthopaedic oncology clinic, we have seen 151 patients (ninety-four
men and fifty-seven women) with multiple myeloma during the past twenty-three
years. The average age at the time of presentation was fifty-eight years
(range, twenty-seven to eighty-five years), and the most common sites of lytic
lesions were the proximal aspect of the femur, the pelvis, and the proximal
part of the humerus. The patient in the current report is the first patient we
have seen with multiple myeloma during pregnancy. The case described here
demonstrates the challenge of balancing the optimal management of the pregnant
cancer patient with the well-being of the fetus.
Ionizing radiation should be used sparingly in a pregnant patient so as to
avoid deleterious effects on the fetus, including prenatal death,
malformations, growth and mental retardation, and the induction of childhood
cancer. These problems are most likely to occur when the exposure to ionizing
radiation takes place during the first trimester and when the cumulative dose
during the pregnancy exceeds 50 mGy (5
rad)13. The
estimated fetal exposure from plain radiographs and computed tomographic scans
of the mother's extremities is far less than this threshold, but when these
same modalities are used to evaluate the lumbosacral
spine14, the fetus
is exposed to approximately 3.6 mGy (0.36 rad) from plain radiographs and 35
mGy (3.5 rads) from computed tomographic scans. Magnetic resonance imaging
does not expose the fetus to ionizing radiation and may be the preferred
method with which to evaluate the spine and pelvis in a pregnant patient with
myeloma. There is a theoretical risk of radiofrequency-induced fetal heating,
which has prompted some radiologists to avoid the use of magnetic resonance
imaging during the first
trimester15.
External-beam radiotherapy often exposes the fetus to >50 mGy (5 rad) and
should be postponed until after delivery, if
possible16.
The effects of chemotherapeutic agents and other drugs on the fetus must
also be considered. Antineoplastic agents, such as melphalan, have caused
fetal death, malformations, growth disturbance, and other long-term sequelae,
particularly when administered during the first
trimester17.
Glucocorticoids, such as Decadron (dexamethasone), have not been associated
with serious adverse fetal effects and are an alternative induction regimen
for a pregnant patient with myeloma. High-dose antineoplastic therapy with
autologous peripheral stem-cell transplantation, a combination recently shown
to yield superior
survival18, must be
deferred until after delivery.
Pharmacologic agents used to treat the secondary metabolic disturbances are
also potentially harmful to the fetus but usually pose less risk than the
underlying abnormalities do. Pamidronate, for example, may be needed
transiently to treat malignant hypercalcemia despite its potentially harmful
effects on the fetus. The monthly administration of pamidronate, given to
alleviate bone pain and reduce the risk of adverse skeletal
events19, is best
postponed until after delivery.
The timing of delivery should favor maternal health while allowing for
fetal maturation; ideally, the pregnancy should be allowed to extend beyond
thirty-four weeks of gestation. The method of delivery depends on obstetric
and nonobstetric factors, including the risk of vaginal delivery in the
presence of axial metastasis. We could not find recommendations in the
orthopaedic, obstetric, or oncologic literature on the management of labor in
the presence of lytic spinal and pelvic lesions. Prompted by the degree of
marrow infiltration, the vertebral compression fractures, and the multiple
sites of pelvic cortical destruction, we recommended delivery by cesarean
section.
Women are becoming pregnant at older ages. Because cancer is the leading
cause of death in women who are forty to fifty-nine years of
age1, orthopaedists
can expect to see an increasing number of pregnant women with osseous lesions.
Skeletal disease should be managed under conditions that minimize fetal
exposure to ionizing radiation and harmful drugs. The dangers of labor and
vaginal delivery may be increased when the patient has lytic lesions of the
lumbosacral spine and the pelvis.