The Journal of Bone and Joint Surgery (American) 80:104-10 (1998)
© 1998 The Journal of Bone and Joint Surgery, Inc.
Non-Hodgkin Lymphoma of the Spine. A Report of Three Cases with a Minimum Ten-Year Follow-up*
JOHN J. VAUGHAN, M.D. ,
ROBERT B. WINTER, M.D. ,
JOHN E. LONSTEIN, M.D.,
JOHN R. JOHNSON, M.D. and
JAMES E. DUNNINGTON, M.D.#, MINNEAPOLIS, MINNESOTA
Investigation performed at Minnesota Spine Center, Minneapolis
Primary non-Hodgkin lymphoma of bone is histologically identical to other lymphomas but arises initially as a localized bone lesion. Malignant lymphoma of bone apparently was first described by Wieland in 1901. Oberling and Raileanu, in 1932, characterized these tumors as reticulum cell sarcomas of bone and distinguished them from Ewing sarcomas.
Non-Hodgkin lymphoma of bone is rare. In a study by Freeman et al., it represented less than 5 per cent (sixty-nine) of 1467 extranodal non-Hodgkin lymphomas. Mirra reported that the lesion rarely occurs as a primary bone tumor. Most authors have reported that lymphomas of bone are more common in the appendicular skeleton than in the axial skeleton. Parker and Jackson noted that these tumors have a predilection for the long bones and the over-all prognosis is favorable. However, Craver and Copeland reported on seventeen patients who had lymphosarcoma and found that the spine and the pelvis were involved more frequently.
There have been reports of primary non-Hodgkin lymphomas involving the spine3,5,16,17. Methods of treatment have included irradiation alone, irradiation and chemotherapy, and operative excision of the tumor combined with irradiation or chemotherapy. The optimum treatment of this tumor when it occurs as a primary lesion of the spine is not known.
We report the cases of three patients who had a similar histopathological diagnosis of non-Hodgkin lymphoma of a non-B-cell type involving a vertebral body. All three patients had pain and a neurological deficit at the time of presentation, and all were managed with resection of the tumor, stabilization of the spine, irradiation, and chemotherapy.
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Case Reports
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CASE 1. An eleven-year-old boy noted pain in the back and transient weakness in the lower extremities after he collided with another child. Initially, the pain resolved. Eight months later, however, the pain recurred and tightness developed in the hamstrings. At that time, the patient was diagnosed as having epiphysitis and was managed with salicylates by his pediatrician. The severity of the pain continued to increase. At the time of presentation to our institution, eleven months after the injury, the patient had pain in the thoracic spine, which was worse at night.
Physical examination revealed tenderness over the spinous process of the fourth thoracic vertebra. The patient had full motor strength and sensation in the lower extremities. The deep tendon reflexes in the lower extremities were hyperactive. Plantar reflexes were normal on the right side, and a Babinski response was present on the left side.
Radiographs of the spine showed a compression fracture of the fourth thoracic vertebral body. A technetium bone scan revealed increased uptake in the same area. A computed tomographic scan showed lytic destruction of the vertebral body (Fig. 1-A). There was no evidence of other osseous lesions or disseminated disease.
Excision of the tumor and neural decompression was carried out, and an anterior vertebrectomy of the fourth thoracic vertebra was performed through a thoracotomy. The tumor was grayish-white and non-vascular, and it penetrated through the cortex of the bone into the surrounding soft tissues. A corticocancellous strut graft from the iliac crest was placed from the third to the fifth thoracic vertebra. Three weeks later, the patient had a posterior spinal arthrodesis from the first to the seventh thoracic vertebra with use of a rectangular construct and sublaminar wires. No tumor was seen posteriorly.
Histological examination of the specimen revealed a non-Hodgkin lymphoma with a syncytial growth pattern. The tumor was composed of large, loosely cohesive, pleomorphic cells with abundant pale-to-eosinophilic cytoplasm. The cells contained poorly defined cytoplasmic membranes and pleomorphic vesicular nuclei (Fig. 1-B).
Immunohistochemical staining was strongly positive for UCHL-1, which suggested a non-Hodgkin lymphoma of T-cell origin.
After the operation, the patient received radiation therapy (3500 centigray) and five cycles of chemotherapy consisting of hydroxyurea, cyclophosphamide, vincristine, prednisone, and methotrexate.
Postoperatively, the patient noted substantial relief of pain. He continued to have hyperactive deep tendon reflexes but was otherwise neurologically intact. Fourteen months after the operation, there was radiographic evidence of solid fusion and the brace was removed. The patient returned to full activity, including playing baseball. At the time of the eleven-year follow-up examination, there was no evidence of recurrence of the tumor, the fusion was solid, and the patient was neurologically intact.
CASE 2. A seventeen-year-old boy noted pain in the back after he sustained an injury while skiing. He was managed for four months with exercise and pain medication by the family physician, but the pain worsened. At the time of presentation to us, the patient had difficulty walking because of severe pain.
Physical examination revealed the range of motion of the spine to be restricted and painful. Sitting or standing caused marked discomfort. A tender gibbus deformity of the spine was present. The neurological function of the lower extremities was intact.
Radiographs demonstrated collapse of the second lumbar vertebral body, which produced an appearance of vertebra plana (Fig. 2-A). A bone scan showed increased uptake at the levels of the eighth thoracic and second lumbar vertebrae. A Craig-needle biopsy of the second lumbar vertebral body was performed. Pathological examination of the specimen revealed chronic inflammatory material but no evidence of tumor. A second needle biopsy was performed, and eosinophils were noted to be present in the specimen. A presumptive diagnosis of eosinophilic granuloma was made. The patient received radiation therapy (600 centigray, administered to the lesion), but the pain worsened. He was managed with parenteral administration of large doses of narcotics and oral administration of prednisone. Eight weeks later, the patient had a sudden onset of paraplegia. At the time of the examination, the patient was in severe pain and was unable to void spontaneously secondary to a cauda equina syndrome. A myelogram revealed a complete block of the contrast medium at the level of the second lumbar vertebra (Fig. 2-B).
The patient was managed with an emergency anterior decompressive vertebrectomy and arthrodesis through a thoracolumbar approach. An anterior fixation device (DePuy, Warsaw, Indiana) and a rib-strut graft were used. The tumor was tan, was invading the psoas, and was adherent to the great vessels. One week after the anterior procedure, the patient had a posterior spinal arthrodesis from the twelfth thoracic to the fourth lumbar vertebra with use of a rectangular construct. No tumor was seen posteriorly.
Histological examination of the specimen showed a non-Hodgkin lymphoma that was similar to the one found in the first patient (Case 1) (Fig. 2-C).
Immunohistochemical staining was positive for leukocyte common antigen (CD45) and negative for both kappa and lambda light chains, which supported a diagnosis of non-Hodgkin lymphoma of non-B-cell lymphoid origin.
A staging workup showed no evidence of disseminated disease. Chemotherapy consisted of vincristine, methotrexate, cyclophosphamide, and prednisone. Radiation therapy consisted of 3000 centigray delivered to the eighth thoracic through second lumbar vertebrae.
Postoperatively, the neurological function improved noticeably. At the time of discharge, the patient was able to walk with crutches while wearing an ankle-foot orthosis on the right side. The spine was immobilized in a thoracolumbosacral orthosis.
One year after the operation, radiographs showed a solid fusion and bracing was discontinued. Two years after the operation, the patient was walking without crutches and without a brace on the right lower extremity. At the time of the eight-year examination, the fusion was still solid and the alignment had been maintained (Fig. 2-D). Ten years postoperatively, the patient had no pain in the back and had only mild weakness of dorsiflexion of the ankles. He was employed full-time as an orthotist and was free of disease.
CASE 3. A sixty-three-year-old man had a several-year history of low-back pain. One month before the time of presentation, the pain worsened acutely and the patient lost the ability to walk. The patient was noted to have a compression fracture of the fourth lumbar vertebral body and was managed with a decompressive laminectomy at another institution. A diagnosis of a malignant tumor was made, but the specific nature of the tumor could not be identified on the basis of a pathological examination. The patient was managed with radiation therapy after the procedure.
Initially, the pain decreased and the patient was able to walk again. Three months later, however, the pain returned and the patient was unable to stand. He also complained of pain and numbness in the medial aspect of both feet.
Physical examination revealed that the strength of the right extensor hallucis longus was grade 4 (of 5). All other motor groups had grade-5 strength. The patient had decreased sensation in the right fourth lumbar dermatome. Deep tendon reflexes were hypoactive but symmetrical. The incisions had healed well.
Radiographs showed collapse and flattening of the fourth lumbar vertebral body. Myelography revealed stenosis resulting from the posterior bulging of the tumor (Fig. 3-A).
The patient then had a posterior procedure that involved bilateral decompression of the fourth lumbar nerve roots and internal fixation with use of a rectangular construct, sublaminar wires, and methylmethacrylate. No gross tumor was evident, and the specimens were negative for tumor cells.
Initially, the patient had good relief of pain. Two months later, however, he had severe pain in the back and in the left leg and was unable to get out of bed.
The patient then had an anterior retroperitoneal decompressive vertebrectomy followed by stabilization with methylmethacrylate. Tumor was found to have invaded through the bone into the surrounding soft tissues and was adherent to the great vessels.
Histological examination of the specimen revealed a non-Hodgkin lymphoma that was similar to the ones found in the other two patients (Cases 1 and 2) (Fig. 3-B).
Immunohistochemical staining showed positive reactivity for leukocyte common antigen (CD45), UCHL-1, and alpha1-antitrypsin. The L-26 (CD20) immunostaining pattern was negative. These findings were consistent with the diagnosis of non-Hodgkin lymphoma of the T-lymphoid T-cell type.
Postoperatively, the patient remained neurologically intact. The pain in the back and the leg had resolved. He was managed with a thoracolumbosacral orthosis. He received chemotherapy consisting of cyclophosphamide, Adriamycin (doxorubicin), Oncovin (vincristine), and prednisone. This was followed by radiation therapy consisting of 3000 centigray administered to the area of the fourth lumbar vertebra. Bracing was discontinued ten months after the operative procedure.
Ten years after the most recent operation, radiographs indicated spinal stability (Fig. 3-C). At the time of the most recent follow-up (eleven years postoperatively), the patient was free of disease and was able to walk two miles (3.2 kilometers) per day. He had back pain that occasionally necessitated the use of aspirin, but he was neurologically intact.
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Discussion
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In all three of the patients in the present series, the earliest presenting symptom of non-Hodgkin lymphoma of the spine was pain in the back in the area of the lesion. The duration of the pain ranged from four months to several years. This was consistent with the finding of Huvos that patients frequently have a long history of pain before the diagnosis is made.
All three patients eventually demonstrated some degree of neurological abnormality. The first patient (Case 1) had a Babinski response on the left side preoperatively. Frank paraplegia developed preoperatively in the second patient (Case 2). The third patient (Case 3) had bilateral radiculopathy of the fourth lumbar nerve roots.
The patients in the present study were eleven, seventeen, and sixty-three years old at the time of presentation. Many authors2,4,18,19have noted a similarly wide distribution of ages in association with non-Hodgkin lymphoma. Huvos reported that the mean age at onset was in the fifth decade (range, the second to the seventh decade).
All three patients were male. The predominance of male patients has been noted by other authors7,14.
The appearance of primary non-Hodgkin lymphoma of the spine on radiographs has been described as a poorly defined lytic lesion that gradually expands and breaks through the cortex. The aggressive-appearing lytic lesion may have calcific mottling and may be accompanied by sclerotic reactive bone1. A compression fracture was associated with the tumor in all three of the patients in the present study. Myelographic studies demonstrated posterior bulging of the tumor into the spinal canal. These fractures gave the appearance of vertebra plana, which often is associated with eosinophilic granuloma. One patient (Case 2) was diagnosed mistakenly as having an eosinophilic granuloma.
The classification of non-Hodgkin lymphomas has been revised over time. Before 1956, non-Hodgkin lymphomas were classified as lymphosarcomas, reticulum cell sarcomas, or follicular lymphomas18. Rappaport described a classification system that was based on the cytomorphology and the growth pattern. In that system, most reticulum cell sarcomas were classified as histiocytic lymphomas. In 1974, Lukes and Collins proposed a classification system that was based on the immunophenotypic markers of tumor cells. That system required the use of specific immunohistochemical stains in order to classify the tumor cells. Most lesions were classified as tumors of B-cell or T-cell origin. Histiocytic lymphomas were thought to be tumors of B-cell origin. In 1982, a panel of experts proposed the Working Formulation for Clinical Usage11. That system combined elements of the systems described by Rappaport and by Lukes and Collins. The term large-cell lymphoma now is often applied to tumors that were described as histiocytic lymphomas by Rappaport.
The histomorphological characteristics of the tumor in all three of our patients were similar. The tumors had a diffuse syncytial growth pattern and were composed of neoplastic, large lymphoid cells. The nuclei were folded and demonstrated a peripheral condensation of chromatin and prominent eosinophilic nucleoli.
These pathological findings indicate that all three tumors were high-grade, pleomorphic, large-cell, diffuse non-Hodgkin lymphomas of a non-B-cell type. In two patients (Cases 1 and 3), the tumor was determined to be of T-cell origin on the basis of immunohistochemical staining that was positive for UCHL-1. The tumor in the third patient (Case 2) was a non-B-cell lymphoma, but further characterization was not possible because the immunohistochemical stain for UCHL-1 was not available at the time of diagnosis. Therefore, the tumor may have been of T-cell origin or of true histiocytic origin.
The optimum treatment for non-Hodgkin lymphoma of the spine is not known. Irradiation has been a mainstay of treatment of malignant lymphomas of bone. Aprin recommended irradiation alone for the treatment of a solitary malignant lymphoma of the spine. Loeffler et al. recommended a combination of irradiation and chemotherapy for the treatment of non-Hodgkin lymphoma of bone.
Those reports of non-operative management did not address the issue of neural compression and spinal instability caused by non-Hodgkin lymphomas of the spine. Delamarter et al. reported the cases of two patients who had excision of the tumor in combination with irradiation and chemotherapy for the treatment of histiocytic lymphoma of the spine. There was no mention of stabilization of the spine in that report. Shehata et al. described the case of a patient in whom a small-cell lymphocytic lymphoma of the spine was treated with local resection, stabilization of the spine with use of a rib-strut graft and methylmethacrylate, and radiochemotherapy. The patient had a stable spine eleven years after the operation.
In instances of non-Hodgkin lymphoma of the spine, we believe that, in addition to destroying the tumor with irradiation and chemotherapy, it is necessary to decompress the neural elements and to reconstruct the spine. All three of the patients in the present series had neurological abnormalities as well as severe destruction and collapse of a vertebral body at the time of presentation. All were managed with decompression and reconstruction, and all had a pain-free, stable spine and either no or only slight neurological abnormalities at the most recent follow-up examination.
The five-year rate of disease-free survival for patients managed for primary skeletal lymphoma has been reported by various authors to be 30 per cent (twenty-one of sixty-nine patients)6, 44 per cent (forty-three of ninety-eight patients)2, and eight of sixteen patients19. All three of our patients were disease-free at a minimum of ten years after the treatment of a non-Hodgkin lymphoma of the spine; these findings appear to compare favorably with the five-year results that have been reported by other authors after the treatment of primary skeletal lymphomas2,6,19.
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FIG1-A: Figs. 1-A and 1-B: Case 1, an eleven-year-old boy who had a non-Hodgkin lymphoma that involved the fourth lumbar vertebral body.
Fig. 1-A: Computed tomographic scan showing lytic destruction of the fourth thoracic vertebral body.
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FIG1-B: Fig. 1-B Photomicrograph of the tumor, showing large, loosely cohesive lymphoid cells with pleomorphic vesicular nuclei and single prominent nucleoli (trichrome stain, oil; x 1000).
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FIG2-A: Figs. 2-A through 2-D: Case 2, a seventeen-year-old boy who had a non-Hodgkin lymphoma that involved the second lumbar vertebral body.
Fig. 2-A: Radiograph made at the time of the initial examination, demonstrating collapse of the second lumbar vertebral body.
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FIG2-B: Fig. 2-B: Emergency myelogram made eight weeks later, showing a complete block of the contrast medium at the second lumbar level.
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FIG2-C: Fig. 2-C Photomicrograph of the tumor, showing large, loosely cohesive lymphoid cells. The lymphoma cells are quite large compared with the endothelial cells that line the vessel at center (trichrome stain, oil; x 1000).
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FIG2-D: Fig. 2-D Radiograph made eight years postoperatively, demonstrating that the fusion was solid both anteriorly and posteriorly and that alignment had been fully maintained.
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FIG3-A: Figs. 3-A, 3-B, and 3-C: Case 3, a sixty-three-year-old man who had a non-Hodgkin lymphoma that involved the fourth lumbar vertebral body.
Fig. 3-A: Myelogram showing a complete block of the contrast medium due to posterior bulging of the tumor.
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FIG3-B: Fig. 3-B Photomicrograph of the tumor, showing large, loosely cohesive lymphoid cells and a diffuse syncytial growth pattern. The lymphoma cells are quite large and have pleomorphic nuclei, single prominent eosinophilic nucleoli, and peripheral condensation of nuclear chromatin (trichrome stain, oil; x 1000).
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FIG3-C: Fig. 3-C Radiograph made at the time of the ten-year follow-up evaluation, demonstrating a stable spine and no evidence of recurrence of the tumor. The spine had been stabilized with methylmethacrylate anteriorly and with a rectangular construct with sublaminar wires and autologous bone graft posteriorly.
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*No benefits in any form have been received or will be received from a commercial party related directly or indirectly to the subject of this article. No funds were received in support of this study.
Kentucky Spine Institute, 135 East Maxwell Street, Suite 208, Lexington, Kentucky 40508.
Minnesota Spine Center, 606 24th Avenue South, Minneapolis, Minnesota 55455.
Spine Institute for Special Surgery, 210 East Gray Street, Louisville, Kentucky 40202.
#Pathology Associates, 135 East Maxwell Street, Suite 401, Lexington, Kentucky 40508.
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References
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- Braunstein, E. M., White, S. J. Non-Hodgkin's lymphoma of bone. Radiology, 135: 59-63. 1980;[Abstract/Free Full Text]
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- Delamarter, R. B., Sachs, B. L., Thompson, G. H., Bohlman, H. M., Maldey, J. T., Carter, J. R. Primary neoplasms of the thoracic and lumbar spine. An analysis of 29 consecutive cases. Clin. Orthop., 256: 87-100. 1990;
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- Lukes, R. J., Collins, R. D. A functional approach to the classification of malignant lymphoma. Recent Results Cancer Res., 46: 18-30. 1974;
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- Rappaport, H.: Tumors of the hematopoietic system. In Atlas of Tumor Pathology. Sect. 3, fasc. 8. Washington, D.C., Armed Forces Institute of Pathology, 1966.
- Reimer, R. B., Chabner, B. A., Young, R. C., Reddick, R., Johnson, R. E. Lymphoma presenting in bone: results of histopathology, staging, and therapy. Ann. Intern. Med., 87: 50-55. 1977;[Abstract/Free Full Text]
- Shehata, W. M., Meyer, R. L., Panke, T. L., Tew, J. M., Rath, R. K., Sammarco, G. J. Primary lymphocytic lymphoma of the dorsal spine apparently cured by radiochemotherapy. Spine, 11: 1035-1036. 1986;[Medline]
- Sweet, D. L., Mass, D. P., Simon, M. A., Shapiro, C. M. Histiocytic lymphoma (reticulum-cell sarcoma) of bone. J. Bone and Joint Surg., 63-A: 79-84. Jan. 1981;[Abstract/Free Full Text]
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