The Journal of Bone & Joint Surgery

The Journal of Bone & Joint Surgery, Volume 88, Issue 12

Scientific Articles | December 01, 2006

Unsuspected Lymphoma Diagnosed with Use of Biopsy During Kyphoplasty

Michael K. Shindle, MD¹; Wakenda Tyler, MD, MPH¹; Folorunsho Edobor-Osula, BA¹; Michael J. Gardner, MD¹; Lisa Shindle, MSN, NP¹; Jose Toro, MD¹; Joseph M. Lane, MD¹

¹ Department of Orthopedic Surgery, Hospital for Special Surgery, 535 East 70th Street, New York, NY 10021. E-mail address for M.K. Shindle: shindlem@hss.edu

View Disclosures and Other Information

In support of their research for or preparation of this manuscript, one or more of the authors received grants or outside funding from Kyphon, Inc. None of the authors received payments or other benefits or a commitment or agreement to provide such benefits from a commercial entity. No commercial entity paid or directed, or agreed to pay or direct, any benefits to any research fund, foundation, educational institution, or other charitable or nonprofit organization with which the authors are affiliated or associated.

Investigation performed at the Department of Orthopedic Surgery, Hospital for Special Surgery, New York, NY

The Journal of Bone and Joint Surgery, Incorporated

J Bone Joint Surg Am, 2006 Dec 01;88(12):2721-2724. doi: 10.2106/JBJS.F.00100

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Abstract

Background: Vertebral augmentation procedures are currently widely performed to treat vertebral compression fractures. In selecting appropriate patients for these procedures, it is important to distinguish the pain caused by a fracture from other causes of back pain. The purpose of this study was to determine the frequency of underlying, previously unrecognized malignant tumors in a consecutive series of patients undergoing kyphoplasty to treat vertebral compression fractures. Our hypothesis was that an unsuspected malignant tumor will exist and that a bone-marrow aspiration from the iliac crest would enhance our ability to detect a malignant tumor.

Methods: A prospective histological evaluation of vertebral body biopsy specimens from presumed osteoporotic vertebral compression fractures and a concurrent bone-marrow aspiration from the iliac crest were performed in order to identify latent hematopoietic dyscrasias. Over a four-year period, vertebral body biopsies from 523 vertebral levels as well as iliac crest bone-marrow aspirations were performed in 238 patients. Both specimens were evaluated histologically, and the prevalence of an underlying occult malignant neoplasm was determined.

Results: All specimens from the vertebral bodies showed signs of bone-remodeling and/or fracture-healing. However, in three patients, both the bone biopsy specimen and the bone-marrow aspirate showed evidence of B-cell lymphoma. The bone-marrow aspirate did not provide any additional information compared with the vertebral body biopsy specimen, and multiple myeloma was not identified in any patient.

Conclusions: Lymphoma is an uncommon cause of a vertebral compression fracture, but on the basis of our experience in this series, we recommend that vertebral body biopsy specimens be obtained in all patients managed with kyphoplasty and vertebroplasty to rule out an unsuspected malignant tumor. However, we do not recommend the routine use of an additional bone-marrow aspiration from the iliac crest during vertebral augmentation procedures because doing so did not appear to enhance our ability to detect a malignant tumor.

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Osteoporosis affects more than twenty-four million Americans, and vertebral compression fractures are the most common skeletal injury resulting from this disease, with an estimated incidence of 700,000 per year in the United States¹. Despite appropriate conservative treatment, over one-third of vertebral compression fractures become chronically painful^2,3. In addition, these compression fractures can lead to progressive deformity and altered spinal biomechanics, which may lead to subsequent fractures. For these reasons, minimally invasive techniques such as vertebroplasty and kyphoplasty have been developed to reduce fracture-related pain and have been shown to be effective in the short term^4-10.

Vertebroplasty involves the percutaneous injection of bone cement into a collapsed vertebral body⁴ and has been performed in the United States since 1993. It has demonstrated substantial immediate pain relief and restoration of the activities of daily living^6,7,11,12. However, vertebroplasty does not expand the collapsed vertebral body and thus does not address spinal deformity. This led to the development of kyphoplasty, which combines vertebroplasty with an inflatable bone tamp¹⁰. With use of a transpedicular or extrapedicular route, a cannula is introduced into the vertebral body followed by insertion of an inflatable bone tamp, which attempts to restore vertebral body height prior to the injection of cement. In the short term, kyphoplasty has also demonstrated good clinical results^13-15. In addition, the balloon tamp creates a preformed low-pressure cavity and thus carries a lower risk of cement extravasation¹⁶. A biopsy specimen obtained during kyphoplasty confers no increased morbidity because a bone tunnel has to be created in order to insert the balloon into the vertebral body. The piece of bone that is removed is the specimen that is sent for pathologic examination. Thus, it does not confer an extra step and does not increase the time or the morbidity of the procedure. Although relatively uncommon, complications of vertebroplasty and kyphoplasty may include cement leakage, cerebrospinal fluid leak, cement embolization, infection, and neurologic injury^17-19.

Vertebral augmentation procedures are now widely performed to treat vertebral compression fractures. However, in selecting appropriate patients for these procedures, it is important to distinguish the pain caused by fracture from the other numerous causes of back pain. The differential diagnosis includes not only osteoporosis but also various causes of metabolic bone disease, malignant tumors, and infection. Even in patients with normal results on laboratory studies, a vertebral body biopsy can identify patients with unrecognized malignant tumors such as multiple myeloma²⁰. In this prospective study, we sought to determine the prevalence of underlying metabolic derangements that may have contributed to a fracture. Our hypothesis was that an unsuspected malignant tumor will exist and that a bone-marrow aspiration from the iliac crest would enhance our ability to detect a malignant tumor.

Materials and Methods

Materials and Methods | Results | Discussion | References

After approval by our institutional review board, a prospective histological evaluation of biopsy specimens from presumed osteoporotic vertebral compression fractures and concurrent bone-marrow aspirations obtained from the iliac crest was performed to identify latent hematopoietic dyscrasias. Inclusion criteria were the presence of an osteoporotic vertebral compression fracture, with persistent pain with a grade of =4 on a scale of 10 (with 10 indicating maximum pain) and/or 40% collapse, and preoperative, intraoperative, and postoperative imaging studies. Initial management included short-term bed rest, physical therapy with extension exercises, and narcotics. All patients had a magnetic resonance imaging scan to evaluate for evidence of edema in the fractured vertebral body on T2-weighted images. Patients who had a hemoglobin level of <10 g/dL, or an erythrocyte sedimentation rate of >30 mm/hr had a workup for multiple myeloma, including serum protein electrophoresis and urine protein electrophoresis. As the study progressed, serum calcium and 25-hydroxyvitamin-D studies were obtained for all patients. A 25-hydroxyvitamin-D level of <30 ng/mL was considered abnormal, but we did not evaluate undecalcified, tetracycline-labeled biopsy specimens because the specimens were obtained from vertebral fracture sites where expected increased osteoid would complicate the interpretation of osteomalacia. A vertebral compression fracture known to be associated with a malignant lesion (including multiple myeloma) was an exclusion criterion, and only the patients with osteoporotic and traumatic compression fractures were included in this study.

Each procedure was performed with the patient in the prone position and through the unipedicular approach with use of biplane fluoroscopy with two C-arms statically placed in the posteroanterior and lateral positions. The biopsy was performed after identification of the lateral wall of the pedicle. A Jamshidi needle (an 11-gauge bone-access needle) was first tapped in place, and then it was exchanged for a guidewire and then for a working cannula. With use of the working cannula, a cement administrator was advanced across the vertebral body until it reached the anterior cortex on the lateral view and passed the midline on the posteroanterior view coring a 1 by 2-mm bone specimen. Syringe suction was applied to retain the biopsy specimen, and the cement administrator was then removed. The osseous contents inside the cement administrator were extracted with a cement pusher and were tagged accordingly. A bone-marrow aspiration was then done at the end of the procedure. The prominence of the posterior iliac crest was palpated, and a Jamshidi needle was placed perpendicular to this prominence. Twenty milliliters of bone marrow was obtained in every patient. The biopsy specimens were fixed in 70% ethanol. Histological examination with use of hematoxylin and eosin staining was performed.

From August 2001 to September 2005, 293 patients presented with vertebral compression fractures. Thirty-four patients were excluded because of the presence of multiple myeloma or metastatic disease, four patients were lost to follow-up, and seventeen were excluded because consent had not been obtained. Overall, 238 patients underwent a kyphoplasty procedure with an average of 2.2 levels per patient for a total of 523 biopsy specimens.

Results

Materials and Methods | Results | Discussion | References

The average age of the patients was seventy-three years (range, thirty-seven to ninety-three years). There were forty-six men (19.3%) and 192 women (80.7%). The preoperative magnetic resonance imaging scans did not show any evidence of lymphoma. In the 238 patients, 523 biopsy levels included T5 (seven specimens), T6 (ten), T7 (twenty-three), T8 (thirty-six), T9 (thirty-seven), T10 (forty), T11 (fifty-six), T12 (eighty-four), L1 (eighty-four), L2 (fifty-four), L3 (forty), L4 (forty-one), and L5 (eleven). Seventy-six patients had a one-level vertebral body biopsy; seventy-seven, a two-level biopsy; forty-eight, a three-level biopsy; thirty-six, a four-level biopsy; and one, a five-level biopsy. All vertebral body specimens showed signs of bone-remodeling and/or fracture-healing; woven bone and cartilaginous tissue, representing callus formation, were often found. The iliac crest bone-marrow aspiration typically demonstrated normal hematopoietic cells in various stages of maturation. No patient was identified as having an unsuspected multiple myeloma. However, the vertebral body biopsy specimen and iliac crest aspirate obtained from three patients (1.3%) showed hypercellularity with collections of lymphocytes (Fig. 1). When this occurred, additional immunohistochemical studies were performed and they included testing for the following cell markers: cytokeratin AE-1/AE-3, CD45, CD3, CD5, CD10, CD20, CD21, CD23, BCL-1, BCL-2, BCL-6, kappa and lambda chain determinants, and IgD. DNA studies were also obtained in order to assess the presence of immunoglobulin heavy-chain gene rearrangements. After these studies, all three patients were diagnosed as having low-grade B-cell lymphomas and were referred to specialists in hematology-oncology. Because of the early diagnosis of lymphoma, two patients in this study required only observation and were treated with bisphosphonates. However, one patient also had anemia as a manifestation of the lymphoma that was unresponsive to darbepoetin and was treated with a bisphosphonate and an immune modulator. All three of these patients had had multiple-level procedures performed, and all biopsy specimens were adequate to make the diagnosis of lymphoma. In all three patients, the bone-marrow aspiration also confirmed the diagnosis but did not provide any additional information.

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Fig. 1: Low-power photomicrograph with hematoxylin and eosin staining, showing hypercellularity due to interstitial infiltration of small lymphocytes with regular contours, which is consistent with the diagnosis of lymphoma.

Discussion

Materials and Methods | Results | Discussion | References

Vertebral augmentation procedures are now widely performed to treat low-energy vertebral compression fractures. However, it is important to distinguish the pain caused by a fracture from other causes of back pain. Patients requiring a percutaneous cement augmentation procedure are usually very fragile with multiple medical conditions. Thus, the differential diagnosis should include not only osteoporosis but also osteomalacia, endocrinopathy, malignant tumor, and infection. Three patients in this series were diagnosed as having an unsuspected malignant tumor and were referred to an oncologist for further evaluation and treatment.

Most of the procedures that involved more than three levels were performed earlier in the study, and currently we do not treat more than three levels during one operation to minimize the risk of cement leakage and excessive monomer release, which can result in catastrophic pulmonary collapse and death.

While lymphoma has been an uncommon cause of vertebral compression fractures, three (1.3%) of 238 patients in this prospective study were diagnosed as having unsuspected lymphoma. Approximately 60,000 patients are diagnosed as having lymphoma each year in the United States, and about 25,000 patients die each year from lymphoma²¹. In addition, it is the fifth most common malignant disorder and the third most common cause of death from cancer in the United States²¹. All three patients who were found to have newly diagnosed lymphoma from this study had a non-Hodgkin low-grade, B-cell type of lymphoma.

Although lymphadenopathy is classically described as the most common presenting symptom for patients with non-Hodgkin lymphoma, most patients are asymptomatic. This explains why >80% of patients present with stage-III or IV disseminated disease²². Anywhere between 10% and 70% of patients have bone-marrow involvement at the time of presentation²². Treatment may vary from aggressive multiagent chemotherapy to observation and bisphosphonate administration. Treatment is more difficult and less successful with later presentation. Because of the early diagnosis of lymphoma, two patients in this study were treated only with bisphosphonates but the third was anemic and was also treated with an immune modulator.

Togawa et al. recently performed a histological evaluation of 178 biopsy specimens obtained from 142 patients during 246 kyphoplasty procedures for presumed osteoporotic vertebral compression fractures²⁰. The biopsy specimens obtained from thirty patients (21%) were suggestive of osteomalacia, and one patient was diagnosed as having an unsuspected plasma cell dyscrasia. In addition, plasma cell dyscrasia was confirmed histologically in three patients. On the basis of these findings, the authors recommended that a vertebral body biopsy should be performed during each first-time vertebral augmentation procedure²⁰.

We agree with the recommendation of Togawa et al. that vertebral body biopsies should be performed in patients undergoing vertebral augmentation procedures for fractures. However, during multiple-level procedures, we recommend a biopsy of only one vertebral body because in our three patients every vertebral body had evidence of lymphoma. We do not recommend the routine use of a bone-marrow aspiration during vertebral augmentation procedures because, in this study, it did not enhance our ability to detect a malignant disorder compared with the use of a direct biopsy of the fractured vertebrae. ?

References

Materials and Methods | Results | Discussion | References

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Topics

biopsy ; cancer ; fracture ; lymphoma ; pain ; bone marrow ; kyphoplasty ; spinal compression fractures ; vertebral body

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Michael K. Shindle, Wakenda Tyler, Folorunsho Edobor-Osula, Michael J. Gardner, Lisa Shindle, Jose Toro, Joseph M. Lane; Unsuspected Lymphoma Diagnosed with Use of Biopsy During Kyphoplasty. The Journal of Bone & Joint Surgery. 2006 Dec;88(12):2721-2724.

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