eMedicine Specialties > Orthopedic Surgery > Neoplasms

Malignant Lymphoma

Sharad Mathur, MD, Staff Physician, Department of Pathology, Kansas City VA Medical Center
Timothy A Damron, MD, David G Murray Endowed Professor, Department of Orthopedic Surgery, Professor, Orthopedic Oncology and Adult Reconstruction, Vice Chair, Department of Orthopedics, State University of New York Upstate Medical University at Syracuse

Updated: Jan 8, 2008

Introduction

Primary lymphoma of bone is an uncommon disease and must be separated from skeletal involvement in systemic lymphoma. The former is stage IE (extranodal, see Staging) disease and may present to the orthopedic surgeon prior to biopsy as a solitary bone lesion simulating a bone sarcoma. The latter, by definition, is stage IV disease and is usually not initially seen by the orthopedic surgeon except when a patient is being treated for complications of systemic lymphoma, such as pathologic fracture.

See also the following related articles in eMedicine:
Hodgkin Disease [in the Hematology section]
Hodgkin Disease [in the Pediatrics: General Medicine section]
Lymphoma, B-Cell
Lymphoma, Diffuse Large Cell
Lymphoma, Malignant Anaplastic (Ki 1+)
Lymphoma, Mantle Cell
Lymphoma, Non-Hodgkin
Lymphoma, Bone

See also the following related topics in Medscape:
Resource Center Cancer: Biologic Therapies
CME Improving Outcomes in Patients With Lymphoma
CME Antibody Therapy in Diffuse Large B-Cell Non-Hodgkin's Lymphoma

History of the Procedure

Oberling first suggested the diagnosis of reticulum cell sarcoma in 1928.¹ Parker and Jackson separated it from Ewing sarcoma in 1939.²

Problem

The definition of primary lymphoma of bone continues to be debated. Most authors exclude disseminated or recurrent disease in which the bone is only 1 of many sites of involvement. To be considered primary lymphoma of bone, the following criteria should be met:

• Histologic documentation of lymphoma in the bone
• Solitary bone lesion or multiple skeletal lesions with no prior involvement of lymph nodes or other lymphoid tissue
• No lymph node involvement or involvement of regional lymph nodes only

Soft-tissue extension from the bone lesion is acceptable; the involved soft tissue may be sampled to document malignant lymphoma.

Frequency

Primary lymphoma of bone constitutes 3% of primary bone tumors and 5% of extranodal lymphomas (or approximately 2% of all primary non-Hodgkin lymphomas).³ Secondary involvement of bone marrow is seen in 5-15% of patients with Hodgkin disease and 30-53% of patients with non-Hodgkin lymphoma. Up to 50% of patients with acquired immunodeficiency syndrome (AIDS)–associated Hodgkin disease have secondary bone marrow involvement.⁴

Males are affected more frequently than are females by primary lymphoma of bone, the male-to-female ratio being 1.8:1. All ages are affected, although lymphoma of bone is uncommon in childhood. Most patients are in the fifth to seventh decade of life.

Involved bones are those that normally contain red marrow. Common sites, in order of decreasing frequency, include the following:

• Femur
• Humerus
• Tibia
• Spine
• Pelvis
• Sternum
• Ribs
• Bones of the skull and face

Involvement of the small bones of the hands and feet is rare. The results from some series have suggested that the mandible and maxilla are the most frequently affected sites, but in these studies, documentation of bone as the primary site of disease is not well supported.

Etiology

The etiology of bone lymphoma is unknown. Viral agents and immunosuppression have been implicated in some cases. Primary lymphoma of bone has been documented as a posttransplant lymphoproliferative disorder in patients who have been immunosuppressed. Bone has also been documented as a site for primary lymphoma in patients with acquired immunodeficiency syndrome (AIDS). Rarely, patients with Paget disease of bone may develop malignant lymphoma in the involved bone. However, these associations are not commonly documented, although they are the subject of a few case reports in the literature.

Pathophysiology

Cytogenetic and molecular abnormalities are involved in the pathophysiology of many different lymphomas. These can be documented in the setting of primary bone lymphoma as well.

Some common recurrent abnormalities are as follows:

• t(14;18)(q32;q21) - Overexpression of Bcl-2 protein, seen in 80-90% of follicular B-cell lymphomas and in 20% of diffuse large B-cell lymphomas
• Rearrangements involving band 3q27 - Rearrangement of BCL-6 gene, seen in 35% of diffuse large B-cell lymphomas
• t(8:14)(q24;q32) - Overexpression of Myc protein, seen in 80% of Burkitt lymphomas; variant translocations t(2;8)(p11;q24) or t(8;22)(q24;q11), found in the remaining 20% of cases
• t(2;5)(p23;q35) - Formation of nucleophosmin – anaplastic lymphoma kinase (NPM-ALK) fusion protein, seen in T-cell anaplastic large cell lymphoma
• t(11;14)(q13;q32) - Overexpression of cyclin D1, seen in mantle cell lymphoma (not reported as a primary bone lymphoma)

Presentation

The most common presenting feature of bony lymphoma is bone pain, which occurs in 60-100% of patients. Other presenting characteristics are a palpable swelling or mass, as well as a pathologic fracture. Pediatric patients may present with functional deficits in involved limbs. Systemic symptoms (B symptoms), such as weight loss, fever, and night sweats, are seen in fewer than 10% of patients in true stage IE lymphoma of bone. Regional lymph nodes may be involved in some patients, although as previously mentioned, this occurs more commonly in cases of bone involvement in patients with systemic lymphoma. Hypercalcemia is seen in some pediatric patients and has been associated with a poorer prognosis. As mentioned above, primary lymphoma of bone has rarely been associated with AIDS, immunosuppression, and Paget disease of bone.

Indications

Indications for the operative involvement of orthopedic surgeons in bone lymphoma most commonly fall into 1 of following 3 categories:

• Diagnosis
• Treatment of pathologic or impending pathologic fractures
• Decompression of spinal canal compromise

No clear role for surgical debulking procedures or resection currently exists for primary bone lymphoma.

Indications for diagnostic procedures

Diagnostic procedures are indicated most frequently in the presence of a solitary bone lesion with a differential diagnosis that includes lymphoma and metastatic disease, myeloma, and/or primary bone sarcoma. In most instances, a needle biopsy is adequate to diagnose lymphoma of bone, but specific subtyping may necessitate open biopsy when inadequate tissue is present from the fine-needle procedure.⁵ Close communication between the orthopedic surgeon and the pathologist is crucial to ensuring that the fresh tissue is processed in such a fashion that all needed information is obtained. In most instances, this requires following a lymphoma protocol, which includes obtaining fresh tissue for immunophenotyping, as well as for cytogenetic and molecular studies (see Diagnostic Procedures).

Whenever soft-tissue extension from the bone lesion is apparent on prebiopsy imaging studies, a biopsy should be taken of the soft-tissue extent in order to avoid further weakening of the bone (which could lead to pathologic fracture). Similarly, in disseminated disease with bone involvement, as when concurrent lymphadenopathy is present, the lymph nodes are usually the most accessible and, therefore, the most desirable site for biopsy. In these latter instances, bone biopsy can usually be avoided if the radiologic features are consistent with the disseminated disease.

Indications for prophylactic stabilization of impending pathologic fractures

Because lymphomas involving bone may result in pathologic fractures, appropriate steps should be taken to prevent such fractures before they occur. In most patients, particularly those who are younger and compliant, protective weight bearing through the treatment period and until radiologic appearance improves will suffice. However, prophylactic stabilization may be indicated in selected patients who are either unable or unwilling to take such measures to avoid fracture during this often protracted period.

Essentially, the evaluation for impending pathologic fracture is the same for bone lymphoma as it is for metastatic bone lesions. The highest-risk lesions are those of a lytic nature that involve more than one half to two thirds of the involved bone's diameter; this is particularly true of lesions that are located in the peritrochanteric region or, to a lesser extent, elsewhere in the lower extremity, and that are accompanied by pain caused by functional weight-bearing. However, whenever prophylactic stabilization is considered prior to potential radiotherapy treatment, close communication with the radiation oncologist is an important way to ensure that the implant will not hamper the planned treatment course to a great degree.

Indications for fixation of pathologic fractures and excision

Once pathologic fracture occurs through bone involved by lymphoma, operative stabilization is generally indicated, particularly in the lower extremities, in the long bones of the upper extremities, and in unstable spine fractures. When internal fixation is needed at the time of diagnosis or prior to irradiation, close communication with the radiation oncologist is needed to determine how the internal fixation will affect radiotherapy treatment options. In most cases, however, if the radiation employs anteroposterior and posteroanterior fields, the scatter created by the internal fixation in each direction will cancel out and so will not create a great problem.

Age, health status, and willingness to comply with protected weight bearing are important considerations in the setting of what appears to be an impending pathologic fracture resulting from bone involvement by lymphoma. Generally, changes that are initially lytic on radiograph will, following radiotherapy, fill in over time. If patients with lower extremity lesions are willing and able to use ambulatory aids to limit weight bearing, the avoidance of internal fixation is sometimes desirable. In rare cases in which there is recalcitrant symptomatic local disease, limited extremity function, or nonunion of pathologic fracture through irradiated bone previously involved by lymphoma, excision of the involved bone may be considered.

Decompression of spinal canal compromise

Occasionally, lymphoma involves the spine. In these cases, a tumor may extend from the bone into the spinal canal. When this soft-tissue extension results in progressive neurologic deficit, decompression may be necessary. The need for concomitant fusion is determined in large part by the extent of the instability created by the decompressive procedure.

See also the following related topics in eMedicine:
Metastatic Disease to the Spine and Related Structures
Neoplasms, Spinal Cord
Spinal Cord Tumors: Management of Intradural Intramedullary Neoplasms
Spinal Tumors

See also the following related topic in Medscape:
Resource Center Spinal Disorders

Contraindications

Operative excision is rarely indicated in the primary treatment of bone lymphoma. Increasing evidence suggests that the prognosis for even isolated stage IE bone lymphoma may not be significantly better than that for disseminated lymphoma with bone involvement, further underscoring the importance of systemic management for local disease treatment.

Because surgical intervention is only used to establish a diagnosis (biopsy) and for managing complications, no specific contraindications to surgery exist.

Workup

Laboratory Studies

• Basic hematology - Obtain a complete blood count (CBC) with differential white blood cell (WBC) count to evaluate peripheral blood for evidence of leukemia, because leukemic deposits may mimic primary lymphoma of bone.
• Routine serum chemistry
  • Serum chemistry studies, including of the patient's calcium level, may reveal hypercalcemia in some individuals.
  • Most patients have elevated lactate dehydrogenase (LDH) levels, although this is directly proportionate to the disease load. In patients with truly isolated stage IE bone disease involving smaller bones, the LDH may be within normal limits.
  • The erythrocyte sedimentation rate also is frequently elevated when there is systemic disease involvement.

Imaging Studies

• Plain radiography and computed tomography (CT) scanning
  • In most cases, these studies depict lytic lesions, which appear as a moth-eaten or permeative pattern of bone destruction.⁶
  • A mixed lytic-sclerotic reaction is evident in approximately 30% of cases, with fewer than 5% of lesions being purely sclerotic. Sclerotic lesions are uncommon in primary non-Hodgkin lymphoma of bone but are seen more frequently in disseminated Hodgkin disease.
  • An associated soft-tissue mass extending from the involved bone is apparent in 50-85% of cases.
  • Periosteal reaction is less common, but it may lead to confusion with other aggressive lesions when present.
  • Lymphomas of bone often are large and may involve the entire bone. Lymphomas may involve the entire end of a bone, including the adjoining metaphysis and epiphysis, down to the subchondral bone, an appearance that may be confused with Paget disease or a benign giant cell tumor of bone.
  • Sequestra are apparent in up to 11% of cases.⁷ These are unusual in malignant bone tumors, with the exception of fibrosarcomas and similar tumors.
  • Differential diagnoses (depending on a lesion's exact radiographic appearance and on the age of the patient) include the following:
    • Metastatic carcinoma
    • Osteosarcoma
    • Ewing sarcoma⁸
    • Malignant fibrous histiocytoma or fibrosarcoma of bone
    • Neuroblastoma and other small round cell tumors
    • Osteomyelitis
    • Langerhans cell histiocytosis
    • Multiple myeloma
    • Leukemic infiltrate
    • Paget disease
    • Giant cell tumor
• Magnetic resonance imaging (MRI)⁹
  • Most lesions appear homogeneous and hypointense on T1-weighted images and enhance with the administration of contrast.¹⁰
  • The appearance on T2-weighted images is inhomogeneous and may be hypointense, isointense, or hyperintense with respect to fat.
  • MRI has high sensitivity in the detection of lesions and in the demonstration of soft-tissue extension. Extension across a joint is rarely seen.
  • Primary lymphoma of bone can be suspected based on MRI if an intact cortex is seen, even in the face of soft-tissue extension, although this finding is by no means specific to lymphoma.
  • In one study, hypointense lesions on T2-weighted images correlated with histologic evidence of intralesional fibrosis. Lesions of osteosarcoma, Ewing sarcoma, multiple myeloma, and neuroblastoma, as well as other small round cell tumors, are always hyperintense on T2-weighted images and typically have destructive cortical penetration if soft-tissue extension is present.
• Technetium-99m (^99m Tc) bone scan
  • Increased uptake usually is noted, particularly at the periphery of the lesions, although a central cold area may be present, representing necrotic tumor.
  • This technique has very good sensitivity, with increased uptake noted in 98% of patients.
• Gallium scan¹¹
  • Increased uptake is noted most commonly throughout the lesions, and the scan is frequently used for initial staging and follow-up.
  • This technique has comparable sensitivity to a^99m Tc scan and can reveal soft-tissue lesions as well.

Other Tests

• Flow cytometry studies
  • This technique uses fresh tissue to document cell-surface markers that identify cell lineage.
  • Identification of the immunophenotype of malignant lymphoma is essential to proper diagnosis, classification, and treatment.
  • Tissue should be submitted to the laboratory fresh or in a tissue culture medium, such as RPMI1640.
• Cytogenetic studies
  • Cytogenetic abnormalities are common in lymphomas and have diagnostic, therapeutic, and prognostic significance.
  • Submit tissue specimens for cytogenetic studies to the laboratory fresh or in tissue culture medium such as RPMI 1640 or Ham's F-10.
  • Bone marrow aspirate and peripheral blood specimens collected with sodium heparin anticoagulant also may be submitted for cytogenetic analysis.
• Molecular pathology studies
  • For molecular studies, fresh tissue should be frozen and kept at -70 º C.
  • Paraffin-embedded tissue from histopathology also is acceptable for some molecular tests.
  • Bone marrow aspirate and peripheral blood specimens collected with ethylenediaminetetra-acetic acid (EDTA) anticoagulant also may be submitted for molecular pathology studies.

Diagnostic Procedures

• Tissue must be obtained from the involved bone or associated soft-tissue mass in order to document malignant lymphoma, as a means of diagnosing primary lymphoma of bone. The possibility of a nonlymphoid primary bone tumor cannot be excluded until the biopsy has been evaluated. It is important that the biopsy be carried out in a manner that allows for excision of the biopsy tract with a subsequent en bloc resection, if necessary. Therefore, such biopsies are best performed by surgeons trained in oncologic resection. The following diagnostic procedures can be employed:
  • Fine-needle aspiration
  • Core-needle biopsy
  • Open biopsy
• Obtaining sufficient tissue for ancillary studies in order to avoid repeat procedures is imperative. Consultation with the pathologist and/or laboratory personnel before performing a diagnostic procedure is essential if lymphoma is being considered as a differential diagnosis of a bone lesion. This communication should continue at the time of biopsy. Frozen section confirmation of tissue viability and adequacy should be requested. In many centers, it is possible to submit fresh tissue to the pathologist, who then distributes it to various sections for ancillary studies as deemed appropriate. The pathologist may also perform intraoperative studies to determine the adequacy of the specimen. If these guidelines are not followed, at least 50% of patients will require additional diagnostic procedures before treatment is initiated. The proper diagnosis, classification, and management of malignant lymphomas involve the following:
  • Histopathology
  • Immunohistochemistry
  • Immunophenotyping (flow cytometry) studies
  • Cytogenetic studies
  • Molecular pathology studies

Histologic Findings

Malignant lymphomas are classified based on the Revised European American Lymphoma (REAL) classification or on the proposed World Health Organization (WHO) classification. These systems are similar, being based on immunophenotype and morphology.

In adults, diffuse large B-cell lymphoma is the most common subtype of malignant lymphoma to appear as primary lymphoma of bone, accounting for 60-90% of such cases. These cases show a diffuse population of large lymphoid cells, sometimes with convoluted nuclear contours. Admixed fibrosis is present with a background population of small, reactive lymphocytes.

Other types of lymphoma that are seen in primary bone lesions include follicular lymphoma, Burkitt lymphoma, precursor B-lymphoblastic lymphoma, and B-cell small lymphocytic lymphoma. T-cell lymphomas are distinctly uncommon. Cases of anaplastic large cell lymphoma, peripheral T-cell lymphoma, and adult T-cell lymphoma have been reported, with adult T-cell lymphoma having been associated with human T-cell lymphotrophic virus type I (HTLV-I) infection.¹²

Histologic differential diagnoses include Ewing sarcoma, neuroblastoma and other types of small round cell tumors, granulocytic sarcoma, and Langerhans cell histiocytosis.

Staging

• Most primary lymphomas of bone are considered stage IE or IIE in the Ann Arbor staging system. This system is suboptimal for staging primary bone lymphoma and is applied inconsistently in the published literature. The following modification of the Ann Arbor system has been proposed:
  • Stage I - One bony lesion with or without soft-tissue extension
  • Stage II - Two bony lesions on the same side of the diaphragm or 1 bony lesion with regional lymph node involvement
  • Stage III - Involvement on both sides of the diaphragm
  • Stage IV - Involvement of the central or peripheral nervous system or of bone marrow on staging biopsy
• In addition to employing images of the primary lesion (in the form of plain radiographs, CT scans, or MRI scans) and physical examination, staging studies use^99m Tc bone scans, bilateral iliac crest bone marrow biopsy, and CT scans of the chest, abdomen, and pelvis. In children, examination of cerebrospinal fluid also is recommended to exclude central nervous system involvement.

Treatment

Medical Therapy

Medical treatment is the mainstay therapy for primary lymphoma of bone. Chemotherapy and radiation therapy are used in conjunction in most cases.

The usual chemotherapy utilizes CHOP (cyclophosphamide, Adriamycin, vincristine, prednisone) or another, similar regimen for several cycles.^13,14 This may be combined with radiation therapy to the affected bone in a 40-60 Gy dose, fractionated over several weeks. Some studies indicate that the results of combined modality therapy (chemotherapy and radiation therapy) are better than those from radiation therapy alone, while other studies have not documented any statistically significant difference.^{13,15,16,17,18} Because of the relative rarity of this disease, standard treatment protocols have not been developed and followed, and the data in the literature are retrospective.

In children, aggressive chemotherapy alone appears to be as effective as combined modality therapy. Because radiation therapy in children is associated with an increased incidence of adverse, growth-related consequences, it should be avoided in this population.

Therapeutic agents, such as rituximab (an anti-CD20 antibody), have been employed against B-cell lymphomas.¹⁹ Refractory cases have been treated with allogeneic bone marrow transplantation.

See also the following related topics in Medscape:
Resource Center Biologic Therapies in Cancer
CME Antibody Therapy in Diffuse Large B-Cell Non-Hodgkin's Lymphoma
CME Biologic Therapies in Oncology: Volume 4

Surgical Therapy

No standard role for surgical therapy exists in the primary management of bone lymphomas, beyond its use as a means of obtaining tissue for diagnosis and of treating complications, such as pathologic fracture. Before the advent of radiation and chemotherapy, some patients were treated with amputation, but with current medical treatment, amputation is generally not necessary.

Complications

Complications of treatment include the following:

• Fracture
• Fracture nonunion
• Wound infection
• Osteonecrosis
• Secondary arthritis following collapse of osteonecrotic bone
• Neuropathy
• Toxicity of chemotherapy
• Thrombophlebitis

Fractures are most common in weight-bearing bones and have been associated with the primary disease, with radiation therapy, and with avascular necrosis following chemotherapy.

Outcome and Prognosis

Compared with other malignant tumors of bone, primary lymphoma of bone has a good overall prognosis.²⁰ With effective chemotherapy and radiation therapy, most series site an overall 5-year survival of 60% or higher.¹⁵ In the pediatric population, aggressive chemotherapy has led to 5-year survival rates of greater than 90%. One study found no statistically significant difference in survival between patients with primary lymphoma of bone (stage IE) and persons who had nodal lymphoma with bone metastasis (stage IV). This may reflect the overall improvement in survival statistics for non-Hodgkin lymphoma.

Most patients who relapse do so early. Local recurrence and distant spread are observed. Radiation therapy helps to decrease the incidence of local recurrence. Therefore, series appearing in the literature have portrayed a relatively higher incidence of distant spread.

Adverse prognostic factors are as follows:

• Higher stage at diagnosis (lymph node and/or soft-tissue involvement)
• Advanced age (>60 y)
• Poor performance index

One study noted higher local recurrence rates in lesions of the jaw, and another study found lower survival rates in patients with lesions involving the pelvic bones. In children, hypercalcemia is associated with a poorer prognosis. No prognostic significance has been attached to the sex of the patient, the histologic type of lymphoma, the size of the primary lesion, and the treatment modality employed.

Future and Controversies

The relative rarity of primary lymphoma of bone has resulted in the absence of therapeutic trials and of standardized definitions of the disease. Most studies in the literature are retrospective, and the number of patients reported on is usually too small for subgroup analysis. Prospective studies are needed to clarify the impact that specific histologic subtypes and therapeutic modalities have on outcome.

Multimedia

Media file 1: An elderly woman presents with complaints of left shoulder pain of several months duration. A plain radiograph of the left shoulder (glenoid view) reveals a destructive lytic process eroding the cortical margins of the acromial process.

Media file 2: Total skeleton technetium-99m (^99mTc) nuclear medicine scan shows increased uptake in the left acromion, the site of bony involvement by lymphoma in this patient (same patient as in Image 1). The initial differential diagnosis suggested metastatic disease to bone in addition to multiple myeloma and lymphoma, in that order.

Media file 3: Coronal, T1-weighted magnetic resonance imaging (MRI) scan of the left shoulder (same patient as in Images 1-2) reveals the replacement of the left acromion by a low-signal process extending into the surrounding soft tissue.

Media file 4: Coronal, T2-weighted magnetic resonance imaging (MRI) scan of the left shoulder (same patient as in images 1-3) reveals a high-signal process involving the left acromion and extending to the surrounding soft tissue. The MRI scan's features are suggestive only of a very high cellularity fluid-containing process, but they are nonspecific. Biopsy is required for a specific diagnosis.

Media file 5: Sections of the biopsy (same patient as in Images 1-4) show a diffuse infiltrate of atypical large lymphoid cells with vesicular nuclei, small nucleoli, and moderate cytoplasm. Small reactive lymphocytes are in the background.

Media file 6: An immunohistochemical stain using an antibody directed against CD20 (B-cell marker) shows strong positivity in the large lymphoid cells. This is an example of a diffuse large B-cell lymphoma. Same patient as in Images 1-5.

Media file 7: A woman who is in the early part of her fifth decade presents with progressive left thigh pain and a limp. An anteroposterior radiograph of her left proximal femur reveals a lytic destructive process involving the subtrochanteric region, with medical cortical erosion, soft-tissue extension, and an associated lesser trochanteric avulsion fracture. The proximal femur is the most common site for primary bone lymphoma.

Media file 8: Total skeleton technetium-99m (^99mTc) nuclear medicine scan reveals an isolated increased uptake in the left proximal femur at the site of this patient's bone lymphoma. Same patient as in Image 7.

Media file 9: Diffuse infiltrate of large lymphoid cells is present, with cleared cytoplasm and hyperchromatic nuclei. Admixed small, reactive lymphocytes also are noted. Same patient as in Images 7-8.

Media file 10: Immunohistochemical stain using an antibody against CD20 is positive in the large cells; this is a diffuse large B-cell lymphoma. Same patient as in Images 7-9.

Media file 11: Clinical photo of a left shoulder shows a prominence in the midportion of the left clavicle. This 45-year-old man was suffering from local pain and tenderness but had no history of prior trauma.

Media file 12: Technetium-99m (^99mTc) total skeleton nuclear medicine scan shows increased uptake in the midportion of the left clavicle, an area corresponding to the clinical site of bone enlargement. Same patient as in Image 11.

Media file 13: Anteroposterior radiograph of the left clavicle reveals a mixed lytic and sclerotic destructive process within the midportion of the bone, with indistinct, permeative borders. Same patient as in Images 11-12.

Media file 14: Another example of a diffuse large cell lymphoma. In addition to the large lymphoid cells with moderate cytoplasm, a few cells with lobate nuclei also are seen. Such cells are often observed in large cell lymphoma of the bone. Same patient as in Images 11-13.

Media file 15: Plain radiographs in this 12-year-old patient with severely progressive right shoulder pain were interpreted as being normal. At most, they showed the existence of localized osteopenia in the right proximal humerus, but they did not demonstrate the presence of a discrete lesion within the bone. Based on the initial evaluation and plain radiographs, the patient was thought to have referred pain from the cervical region or brachial plexus.

Media file 16: Coronal, T1-weighted magnetic resonance imaging (MRI) scan of the upper thorax and bilateral shoulders (same patient as in Image 15) reveals a marrow replacement low-signal process involving the entire right proximal humerus. The corresponding T2-weighted MRI scan showed a high-signal process in this area. This MRI scan was produced after plain radiographs were interpreted as normal and an MRI scan of the cervical spine and brachial plexus revealed the unsuspected findings in the humerus.

Media file 17: Histologic sections reveal a highly cellular neoplasm composed of cells with a high nucleus-to-cytoplasm ratio, scant cytoplasm, and fine nuclear chromatin. The cells showed immunohistochemical evidence of B-cell lineage and expressed terminal deoxynucleotidyl transferase (TdT), consistent with a precursor B-lymphoblastic lymphoma. Same patient as in Images 15-16.

References

1. Oberling C. Les reticulosarcomes et les reticuloendotheliosarcomes de la moelle osseuse (sarcomes d'Ewing). Bull Assoc Fr Etude Cancer (Paris). 1928;17:259-296.

2. Parker F, Jackson H. Primary reticulum cell sarcoma of bone. Surg Gynecol Obstet. 1939;68:45-53.

3. Baar J, Burkes RL, Gospodarowicz M. Primary non-Hodgkin''s lymphoma of bone. Semin Oncol. Jun 1999;26(3):270-5. [Medline].

4. Aboulafia AJ, Khan F, Pankowsky D. AIDS-associated secondary lymphoma of bone: a case report with review of the literature. Am J Orthop. Feb 1998;27(2):128-34. [Medline].

5. Fend F, Kremer M. Diagnosis and classification of malignant lymphoma and related entities in the bone marrow trephine biopsy. Pathobiology. 2007;74(2):133-43. [Medline].

6. Mulligan ME, McRae GA, Murphey MD. Imaging features of primary lymphoma of bone. AJR Am J Roentgenol. Dec 1999;173(6):1691-7. [Medline]. [Full Text].

7. Mulligan ME, Kransdorf MJ. Sequestra in primary lymphoma of bone: prevalence and radiologic features. AJR Am J Roentgenol. Jun 1993;160(6):1245-8. [Medline]. [Full Text].

8. Malloy PC, Fishman EK, Magid D. Lymphoma of bone, muscle, and skin: CT findings. AJR Am J Roentgenol. Oct 1992;159(4):805-9. [Medline]. [Full Text].

9. Hermann G, Klein MJ, Abdelwahab IF. MRI appearance of primary non-Hodgkin''s lymphoma of bone. Skeletal Radiol. Nov 1997;26(11):629-32. [Medline].

10. Haussler MD, Fenstermacher MJ, Johnston DA. MRI of primary lymphoma of bone: cortical disorder as a criterion for differential diagnosis. J Magn Reson Imaging. Jan 1999;9(1):93-100. [Medline].

11. Bar-Shalom R, Israel O, Epelbaum R. Gallium-67 scintigraphy in lymphoma with bone involvement. J Nucl Med. Mar 1995;36(3):446-50. [Medline]. [Full Text].

12. Chan JK, Ng CS, Hui PK. Anaplastic large cell Ki-1 lymphoma of bone. Cancer. Nov 15 1991;68(10):2186-91. [Medline].

13. Ferreri AJ, Reni M, Ceresoli GL. Therapeutic management with Adriamycin-containing chemotherapy and radiotherapy of monostotic and polyostotic primary non-Hodgkin''s lymphoma of bone in adults. Cancer Invest. 1998;16(8):554-61. [Medline].

14. Susnerwala SS, Dinshaw KA, Pande SC. Primary lymphoma of bone: experience of 39 cases at the Tata Memorial Hospital, India. J Surg Oncol. Aug 1990;44(4):229-33. [Medline].

15. Christie DR, Barton MB, Bryant G, et al. Osteolymphoma (primary bone lymphoma): an Australian review of 70 cases. Australasian Radiation Oncology Lymphoma Group (AROLG). Aust N Z J Med. Apr 1999;29(2):214-9. [Medline].

16. Baar J, Burkes RL, Bell R, et al. Primary non-Hodgkin's lymphoma of bone. A clinicopathologic study. Cancer. Feb 15 1994;73(4):1194-9. [Medline].

17. Dubey P, Ha CS, Besa PC. Localized primary malignant lymphoma of bone. Int J Radiat Oncol Biol Phys. Mar 15 1997;37(5):1087-93. [Medline].

18. Rathmell AJ, Gospodarowicz MK, Sutcliffe SB. Localised lymphoma of bone: prognostic factors and treatment recommendations. The Princess Margaret Hospital Lymphoma Group. Br J Cancer. Sep 1992;66(3):603-6. [Medline].

19. Cooney-Qualter E, Krailo M, Angiolillo A, et al. A phase I study of 90yttrium-ibritumomab-tiuxetan in children and adolescents with relapsed/refractory CD20-positive non-Hodgkin's lymphoma: a Children's Oncology Group study. Clin Cancer Res. Sep 15 2007;13(18 Pt 2):5652s-5660s. [Medline].

20. de Camargo OP, dos Santos Machado TM, Croci AT, et al. Primary bone lymphoma in 24 patients treated between 1955 and 1999. Clin Orthop Relat Res. Apr 2002;(397):271-80. [Medline].

21. Altamirano J, Esparza JR, de la Garza Salazar J, et al. Staging, Response to Therapy, and Restaging of Lymphomas with (18)F-FDG PET. Arch Med Res. Jan 2008;39(1):69-77. [Medline].

22. Coppes MJ, Patte C, Couanet D. Childhood malignant lymphoma of bone. Med Pediatr Oncol. 1991;19(1):22-7. [Medline].

23. Desai S, Jambhekar NA, Soman CS. Primary lymphoma of bone: a clinicopathologic study of 25 cases reported over 10 years. J Surg Oncol. Apr 1991;46(4):265-9. [Medline].

24. Edeiken-Monroe B, Edeiken J, Kim EE. Radiologic concepts of lymphoma of bone. Radiol Clin North Am. Jul 1990;28(4):841-64. [Medline].

25. Fairbanks RK, Bonner JA, Inwards CY. Treatment of stage IE primary lymphoma of bone. Int J Radiat Oncol Biol Phys. Jan 15 1994;28(2):363-72. [Medline].

26. Fidias P, Spiro I, Sobczak ML. Long-term results of combined modality therapy in primary bone lymphomas. Int J Radiat Oncol Biol Phys. Dec 1 1999;45(5):1213-8. [Medline].

27. Hermann G, Abdelwahab IF, Capozzi J. Primary non-Hodgkin lymphoma of bone: unusual manifestation of lymphoproliferative disease following liver transplantation. Skeletal Radiol. Mar 1999;28(3):175-7. [Medline].

28. Heyning FH, Hogendoorn PC, Kramer MH. Primary non-Hodgkin''s lymphoma of bone: a clinicopathological investigation of 60 cases. Leukemia. Dec 1999;13(12):2094-8. [Medline].

29. Iravani S, Singleton TP, Ross CW. Precursor B lymphoblastic lymphoma presenting as lytic bone lesions. Am J Clin Pathol. Dec 1999;112(6):836-43. [Medline].

30. Ishizawa M, Okabe H, Matsumoto K. Anaplastic large cell Ki-1 lymphoma with bone involvement: report of two cases. Virchows Arch. 1995;427(1):105-10. [Medline].

31. Jones D, Kraus MD, Dorfman DM. Lymphoma presenting as a solitary bone lesion. Am J Clin Pathol. Feb 1999;111(2):171-8. [Medline].

32. Karnad AB, Martin AW, Koh HK. Nonsecretory multiple myeloma in a 26-year-old man with acquired immunodeficiency syndrome, presenting with multiple extramedullary plasmacytomas and osteolytic bone disease. Am J Hematol. Dec 1989;32(4):305-10. [Medline].

33. Kroft SH, McKenna RW. Bone marrow manifestations of Hodgkin's and non-Hodgkin's lymphomas and lymphoma-like disorders. In: Knowles DM, ed. Neoplastic Hematopathology. 2^nd ed. Philadelphia, Pa: Lippincott Williams & Wilkins; 2001:1447-1504.

34. Lewis SJ, Bell RS, Fernandes BJ. Malignant lymphoma of bone. Can J Surg. Feb 1994;37(1):43-9. [Medline].

35. Limb D, Dreghorn C, Murphy JK. Primary lymphoma of bone. Int Orthop. Jun 1994;18(3):180-3. [Medline].

36. Melamed JW, Martinez S, Hoffman CJ. Imaging of primary multifocal osseous lymphoma. Skeletal Radiol. Jan 1997;26(1):35-41. [Medline].

37. Moon TY, Kim EE, Kim YC. Comparison of nuclear bone and gallium scans in the therapeutic evaluation of bone lymphoma. Clin Nucl Med. Aug 1995;20(8):721-4. [Medline].

38. Ostrowski ML, Unni KK, Banks PM. Malignant lymphoma of bone. Cancer. Dec 15 1986;58(12):2646-55. [Medline].

39. Ozdemirli M, Fanburg-Smith JC, Hartmann DP. Precursor B-lymphoblastic lymphoma presenting as a solitary bone tumor and mimicking Ewing''s sarcoma: a report of four cases and review of the literature. Am J Surg Pathol. Jul 1998;22(7):795-804. [Medline].

40. Pettit CK, Zukerberg LR, Gray MH. Primary lymphoma of bone. A B-cell neoplasm with a high frequency of multilobated cells. Am J Surg Pathol. Apr 1990;14(4):329-34. [Medline].

41. Shannon JA, Bell DR, Levi JA. Bone presentation of non-Hodgkin's lymphoma: experience at the Royal North Shore Hospital, Sydney; highlighting primary bone lymphoma. Aust N Z J Med. Dec 1994;24(6):701-4. [Medline].

42. Stephens GC, Lennington WJ, Schwartz HS. Primary lymphoma and Paget's disease of the femur. Am J Clin Pathol. Jun 1994;101(6):783-6. [Medline].

43. Stiglbauer R, Augustin I, Kramer J. MRI in the diagnosis of primary lymphoma of bone: correlation with histopathology. J Comput Assist Tomogr. Mar-Apr 1992;16(2):248-53. [Medline].

44. Stroszczynski C, Oellinger J, Hosten N. Staging and monitoring of malignant lymphoma of the bone: comparison of 67Ga scintigraphy and MRI. J Nucl Med. Mar 1999;40(3):387-93. [Medline]. [Full Text].

45. Suryanarayan K, Shuster JJ, Donaldson SS. Treatment of localized primary non-Hodgkin''s lymphoma of bone in children: a Pediatric Oncology Group study. J Clin Oncol. Feb 1999;17(2):456-9. [Medline].

46. Suzukawa K, Kojima H, Mori N. Anaplastic large-cell lymphoma of null-cell type with multiple bone involvement. Ann Hematol. Dec 1998;77(6):287-90. [Medline].

47. Takemoto S, Matsuoka M, Sakata K. Primary adult T cell leukemia of bone: two patients with primary bone lesion showing monoclonal integration of HTLV-I proviral DNA. Leukemia. Feb 1996;10(2):333-7. [Medline].

48. Unni KK. Dahlin's Bone Tumors: General Aspects and Data on 11,087 cases. 5^th ed. Philadelphia, Pa: Lippincott-Raven; 1996:237-248.

49. Wang JC, Kim DS, Goldberg M. Anaplastic large cell Ki-1 lymphoma: primary bone presentation in an elderly man. Acta Haematol. 1996;96(1):45-9. [Medline].

50. White LM, Schweitzer ME, Khalili K. MR imaging of primary lymphoma of bone: variability of T2-weighted signal intensity. AJR Am J Roentgenol. May 1998;170(5):1243-7. [Medline]. [Full Text].

51. Wollner N, Lane JM, Marcove RC. Primary skeletal non-Hodgkin's lymphoma in the pediatric age group. Med Pediatr Oncol. 1992;20(6):506-13. [Medline].

Keywords

osteolymphoma, reticulum cell sarcoma, primary lymphoma of bone, bone cancer, Paget disease, bone lymphoma, bone pain

Contributor Information and Disclosures

Author

Sharad Mathur, MD, Staff Physician, Department of Pathology, Kansas City VA Medical Center
Sharad Mathur, MD is a member of the following medical societies: Academy of Clinical Laboratory Physicians and Scientists, American Society of Clinical Pathologists, American Society of Cytopathology, American Society of Hematology, College of American Pathologists, and United States and Canadian Academy of Pathology
Disclosure: Nothing to disclose.

Coauthor(s)

Timothy A Damron, MD, David G Murray Endowed Professor, Department of Orthopedic Surgery, Professor, Orthopedic Oncology and Adult Reconstruction, Vice Chair, Department of Orthopedics, State University of New York Upstate Medical University at Syracuse
Timothy A Damron, MD is a member of the following medical societies: American Academy of Orthopaedic Surgeons, American College of Surgeons, American Medical Association, Children's Oncology Group, Connective Tissue Oncology Society, Musculoskeletal Tumor Society, Orthopaedic Research Society, and Society for Experimental Biology and Medicine
Disclosure: Nothing to disclose.

Medical Editor

Lynn A Crosby, MD, FACS, Chief of Shoulder Division, Professor, Department of Orthopedic Surgery, Wright State University School of Medicine
Lynn A Crosby, MD, FACS is a member of the following medical societies: Alpha Omega Alpha, American Academy of Orthopaedic Surgeons, American College of Sports Medicine, American College of Surgeons, American Fracture Association, American Medical Association, American Medical Tennis Association, American Orthopaedic Association, American Orthopaedic Foot and Ankle Society, Arthroscopy Association of North America, Mid-America Orthopaedic Association, and Orthopaedic Research Society
Disclosure: Nothing to disclose.

Pharmacy Editor

Francisco Talavera, PharmD, PhD, Senior Pharmacy Editor, eMedicine
Disclosure: Nothing to disclose.

CME Editor

Dinesh Patel, MD, FACS, Associate Clinical Professor of Orthopedic Surgery, Harvard Medical School; Chief of Arthroscopic Surgery, Department of Orthopedic Surgery, Massachusetts General Hospital
Dinesh Patel, MD, FACS is a member of the following medical societies: American Academy of Orthopaedic Surgeons, American Association of Physicians of Indian Origin, American College of International Physicians, and American College of Surgeons
Disclosure: Nothing to disclose.

Chief Editor

Harris Gellman, MD, Consulting Surgeon, Broward Hand Center, Voluntary Clinical Professor of Orthopedic Surgery and Plastic Surgery, Departments of Orthopedic Surgery and Surgery, University of Miami School of Medicine
Harris Gellman, MD is a member of the following medical societies: American Academy of Medical Acupuncture, American Academy of Orthopaedic Surgeons, American Orthopaedic Association, American Society for Surgery of the Hand, and Arkansas Medical Society
Disclosure: Nothing to disclose.

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