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Malignant Lymphoma

Last = Updated: May 13,=20 2002
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Synonyms and related = keywords:=20 osteolymphoma, reticulum cell sarcoma, primary lymphoma of = bone,=20 bone cancer, Paget disease, bone lymphoma, bone=20 pain

  AUTHOR INFORMATION=20 Section 1 of = 11   =20
Author=20 Information Introduction=20 Indications=20 Relevant=20 Anatomy And Contraindications Wo= rkup=20 Treatment=20 Complications=20 Outcome=20 And Prognosis Future=20 And Controversies = Pictures=20 Bibliography
Author: Sharad=20 Mathur, MD, Staff Physician, Department of = Pathology,=20 Kansas City VA Medical Center

Coauthor(s): Timothy=20 Damron, MD, Associate Professor, Department of=20 Orthopedics, Division of Orthopedic Oncology - Joint = Reconstructive=20 Surgery, State University of New York at Syracuse, Upstate = Medical=20 University

Sharad Mathur, MD, is a member of the following medical=20 societies: Academy = of Clinical=20 Laboratory Physicians and Scientists, American Society of Clinical=20 Pathologists, American=20 Society of Cytopathology, American Society of=20 Hematology, College of = American=20 Pathologists, and United States=20 and Canadian Academy of Pathology

Editor(s): Lynn A Crosby, MD, FACS, Chief = of=20 Shoulder Division, Professor, Department of Orthopedic = Surgery,=20 Wright State University School of Medicine; = Francisco=20 Talavera, PharmD, PhD, Senior Pharmacy Editor, = Pharmacy,=20 eMedicine; Sean P Scully, MD, PhD, Senior = Associate=20 Consultant, Department of Orthopedics, Mayo Clinic of = Rochester;=20 Dinesh Patel, MD, Assistant Clinical = Professor of=20 Orthopedic Surgery, Harvard Medical School; Chief of = Arthroscopic=20 Surgery, Department of Orthopedic Surgery, Massachusetts = General=20 Hospital; and Harris Gellman, MD, Clinical=20 Professor of Orthopedic Surgery, University of Arkansas and=20 University of Miami; Consulting Surgeon, Broward Hand Center =

Primary lymphoma of bone is an = uncommon=20 disease and must be separated from skeletal involvement in = systemic=20 lymphoma. The former is stage IE (extranodal, see Staging)=20 disease and may present to the orthopedic surgeon prior to biopsy = as a=20 solitary bone lesion simulating a bone sarcoma. The latter, by = definition,=20 is stage IV disease and usually is not seen initially by the = orthopedic=20 surgeon except for treatment of complications such as pathologic = fracture.

History of the Procedure: Oberling first = suggested the=20 diagnosis of reticulum cell sarcoma in 1928. Parker and Jackson = separated=20 it from Ewing sarcoma in 1939.

Problem: The definition of primary lymphoma of = bone=20 continues to be debated. Most authors exclude disseminated or = recurrent=20 disease in which the bone is only one of many sites of = involvement. To be=20 considered primary lymphoma of bone, the following criteria should = be met:=20

  • Histologic documentation of lymphoma in the bone=20

  • Solitary bone lesion or multiple skeletal lesions with no = prior=20 involvement of lymph nodes or other lymphoid tissue=20

  • No lymph node involvement or involvement of regional lymph = nodes=20 only

Soft tissue extension from the bone lesion is acceptable, and = the=20 involved soft tissue may be sampled to document malignant = lymphoma.

Frequency: Primary lymphoma of bone = constitutes 3% of=20 primary bone tumors and 5% of extranodal lymphomas (or = approximately 2% of=20 all primary non-Hodgkin lymphomas). Secondary involvement of the = bone=20 marrow in lymphoma is seen in 5-15% of patients with Hodgkin = disease and=20 30-53% of patients with non-Hodgkin lymphoma. Up to 50% of = patients with=20 AIDS-associated Hodgkin disease have secondary bone marrow = involvement.=20

Males are affected more frequently than are females = (male-to-female=20 ratio of 1.8:1). All ages are affected, although lymphoma of bone = is=20 uncommon in childhood. Most patients are in the fifth to seventh = decades=20 of life.=20

Involved bones are those that normally contain red marrow. = Common sites=20 in decreasing frequency include the femur, humerus, tibia, spine, = pelvis,=20 sternum, ribs, and bones of the skull and face. Involvement of = small bones=20 of the hands and feet is rare. Some series suggest the mandible = and=20 maxilla as the most frequently affected sites, but in these = series,=20 documentation of bone as the primary site of disease is not well=20 supported.

Etiology: The etiology of bone lymphoma is = unknown.=20 Viral agents and immunosuppression are implicated in some cases. = Primary=20 lymphoma of bone has been documented as a posttransplant=20 lymphoproliferative disorder in patients who were = immunosuppressed. Bone=20 has also been documented as a site for primary lymphoma in = patients with=20 AIDS. Rarely, patients with Paget disease of bone may develop = malignant=20 lymphoma in the involved bone. However, these associations are not = commonly documented and are the subject of a few case reports in = the=20 literature.

Pathophysiology: Cytogenetic and molecular=20 abnormalities are involved in the pathophysiology of many = different=20 lymphomas. These can be documented in the setting of primary bone = lymphoma=20 as well.=20

Some common recurrent abnormalities are as follows:=20

  • t(14;18)(q32;q21) - Overexpression of Bcl-2 protein, seen in = 80-90%=20 of follicular B-cell lymphomas and 20% of diffuse large B-cell = lymphomas=20

  • Rearrangements involving band 3q27 - Rearrangement of = BCL6=20 gene, seen in 35% of diffuse large B-cell lymphomas=20

  • t(8:14)(q24;q32) - Overexpression of Myc protein, seen in = 80% of=20 Burkitt lymphomas; variant translocations t(2;8)(p11;q24) or=20 t(8;22)(q24;q11) in remaining 20% of cases=20

  • t(2;5)(p23;q35) - Formation of nucleophosmin-anaplastic = lymphoma=20 kinase (NPM-ALK) fusion protein, seen in T-cell anaplastic large = cell=20 lymphoma=20

  • t(11;14)(q13;q32) - Overexpression of cyclin D1, seen in = mantle cell=20 lymphoma (not reported as a primary bone lymphoma)

Clinical: The most common presenting feature = of bone=20 lymphoma is bone pain, which occurs in 60-100% of patients. Other=20 presenting features are palpable swelling or mass and pathologic = fracture.=20 Pediatric patients may present with functional deficits in = involved limbs.=20 Systemic symptoms (B-symptoms), such as weight loss, fever, and = night=20 sweats, are seen in fewer than 10% of patients in true stage IE = lymphoma=20 of bone. Regional lymph nodes may be involved in some patients, = although=20 as previously mentioned, this occurs more commonly in cases of = bone=20 involvement in patients with systemic lymphoma. Hypercalcemia is = seen in=20 some pediatric patients and has been associated with a poorer = prognosis.=20 As mentioned above, primary lymphoma of bone has rarely been = associated=20 with AIDS, immunosuppression, and Paget disease of bone.

  INTRODUCTION = Section 2 of = 11   
Author=20 Information Introduction=20 Indications=20 Relevant=20 Anatomy And Contraindications Wo= rkup=20 Treatment=20 Complications=20 Outcome=20 And Prognosis Future=20 And Controversies = Pictures=20 Bibliography

Indications for operative = involvement by=20 orthopedic surgeons in bone lymphoma most commonly fall into 1 of = 3=20 categories: (1) diagnosis, (2) treatment of pathologic or = impending=20 pathologic fractures, and (3) decompression of spinal canal = compromise. At=20 this time, no clear role for surgical debulking procedures or = resection=20 exists for primary bone lymphoma.=20

Indications for diagnostic procedures=20

Diagnostic procedures are indicated most frequently in the = presence of=20 a solitary bone lesion with a differential diagnosis including = lymphoma=20 and metastatic disease, myeloma, and/or primary bone sarcoma. In = most=20 instances, a needle biopsy is adequate to diagnosis lymphoma of = bone, but=20 specific subtyping may necessitate open biopsy when inadequate = tissue is=20 present from the fine needle procedure. Close communication = between the=20 orthopedic surgeon and pathologist is crucial to ensure that the = fresh=20 tissue is processed in such a fashion that all needed information = is=20 obtained. In most instances, this requires following a lymphoma = protocol,=20 which includes obtaining fresh tissue for immunophenotyping, = cytogenetic,=20 and molecular studies (see Diagnosti= c=20 Procedures).=20

Whenever soft tissue extension from the bone lesion is apparent = on=20 prebiopsy imaging studies, a biopsy should be taken of the soft = tissue=20 extent in order to avoid further weakening of the bone that could = lead to=20 pathologic fracture. Similarly, in disseminated disease with bone=20 involvement, such as when there is concurrent lymphadenopathy, the = lymph=20 nodes usually are the most accessible and, therefore, most = desirable site=20 for biopsy. In these latter instances, bone biopsy usually can be = avoided=20 if the radiologic features are consistent with the disseminated = disease.=20

Indications for prophylactic stabilization of impending = pathologic=20 fractures=20

Because lymphomas involving bone may result in pathologic = fracture,=20 take appropriate steps to prevent pathologic fracture before it = occurs. In=20 most instances, particularly in patients who are younger and = compliant,=20 protective weightbearing through the time of treatment and until=20 radiologic appearance improves will suffice. However, in selected = patients=20 who are either unable or unwilling to take such measures to avoid = fracture=20 during this often-protracted period, prophylactic stabilization = may be=20 indicated.=20

Essentially, the evaluation for impending pathologic fracture = is the=20 same for bone lymphoma as it is for metastatic bone lesions. The = highest=20 risk lesions are those of a lytic nature involving more than one = half to=20 two thirds the diameter of the involved bone, particularly when = located in=20 the peritrochanteric region, or to a lesser extent, elsewhere in = the lower=20 extremity, and when accompanied by functional weightbearing pain. = Whenever=20 prophylactic stabilization is considered prior to potential = radiotherapy=20 treatment, however, close communication with the radiation = oncologist is=20 important to ensure that the implant will not hamper the planned = treatment=20 course to a great degree.=20

Indications for fixation of pathologic fractures and = excision=20

Once pathologic fracture occurs through bone involved by = lymphoma,=20 operative stabilization is generally indicated, particularly in = the lower=20 extremities, long bones of the upper extremities, and unstable = spine=20 fractures. When internal fixation is needed at the time of = diagnosis or=20 prior to irradiation, close communication with the radiation = oncologists=20 is needed to determine how the internal fixation will affect = radiotherapy=20 treatment options. However, in most cases, if the radiation = employs=20 anteroposterior and posteroanterior fields, the scatter created by = the=20 internal fixation in each direction will cancel out and not create = a great=20 problem.=20

Age, health status, and willingness to comply with protected=20 weightbearing are important considerations in the setting of an = apparent=20 impending pathologic fracture due to bone involvement by lymphoma, = as=20 generally the initially lytic changes on radiograph will fill in = over time=20 following radiotherapy. If the patient is willing and able to use=20 ambulatory aids to limit weightbearing for lower extremity = lesions,=20 avoiding internal fixation is sometimes desirable. In rare cases = with=20 recalcitrant symptomatic local disease, limited extremity = function, or=20 nonunion of pathologic fracture through irradiated bone previously = involved by lymphoma, excision of the involved bone may be = considered.=20

Decompression of spinal canal compromise=20

Occasionally, lymphoma involves the spine. In these cases, = tumor may=20 extend from the bone into the spinal canal. When this soft tissue=20 extension results in progressive neurological deficit, = decompression may=20 be necessary. The need for concomitant fusion is determined in = large part=20 by the extent of instability created by the decompressive = procedure.

  INDICATIONS = Section 3 of = 11   
Author=20 Information Introduction=20 Indications=20 Relevant=20 Anatomy And Contraindications Wo= rkup=20 Treatment=20 Complications=20 Outcome=20 And Prognosis Future=20 And Controversies = Pictures=20 Bibliography
=

Cont= raindications:=20 Operative excision rarely is indicated in the primary = treatment=20 of bone lymphoma. Increasing evidence suggests that the prognosis = for even=20 isolated stage IE bone lymphoma may not be significantly better = than that=20 for disseminated lymphoma with bone involvement, further = underscoring the=20 importance of systemic management for local disease treatment.=20

Because surgical intervention is used only for establishing a = diagnosis=20 (biopsy) and for managing complications, no specific = contraindications to=20 surgery exist.

  RELEVANT ANATOMY AND = CONTRAINDICATIONS Section 4 of = 11   
Author=20 Information Introduction=20 Indications=20 Relevant=20 Anatomy And Contraindications Wo= rkup=20 Treatment=20 Complications=20 Outcome=20 And Prognosis Future=20 And Controversies = Pictures=20 Bibliography
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Author=20 Information
Introduction
Indications
Relevant=20 Anatomy And Contraindications
Wo= rkup
Treatment
Complications
Outcome=20 And Prognosis
Future=20 And Controversies
= Pictures
Bibliography

Click=20 for related images.

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Lab Studies:

  • Basic hematology: Obtain a CBC with differential WBC count = to=20 evaluate peripheral blood for evidence of leukemia, as leukemic = deposits=20 may mimic primary lymphoma of bone.
  • Routine serum chemistry
    • Serum chemistry studies including calcium level may reveal = hypercalcemia in some patients.
    • Most patients have elevated lactate dehydrogenase (LDH) = levels,=20 although this is directly proportionate to the disease load. = In=20 patients with truly isolated stage IE bone disease involving = smaller=20 bones, the LDH may be within normal limits.
    • Erythrocyte sedimentation rate (ESR) also is frequently = elevated=20 in systemic disease involvement.

Imaging Studies:

  • Plain radiography and CT scanning
    • These studies depict lytic lesions in most cases, with a=20 moth-eaten or permeative pattern of bone = destruction.
    • A mixed lytic-sclerotic reaction is evident in = approximately 30%=20 of cases, and fewer than 5% of lesions are purely sclerotic. = Sclerotic=20 lesions are uncommon in primary non-Hodgkin lymphoma of bone = but are=20 seen relatively more frequently in disseminated Hodgkin=20 disease.
    • An associated soft tissue mass extending from the bone = involved is=20 apparent in 50-85% of cases.
    • Periosteal reaction is less common, but it may lead to = confusion=20 with other aggressive lesions when present.
    • Lymphomas of bone often are large and may involve the = entire bone.=20 Lymphomas may involve the entire end of a bone, including the=20 adjoining metaphysis and epiphysis down to the subchondral = bone, an=20 appearance that may be confused with Paget disease or a benign = giant=20 cell tumor of bone.
    • Sequestra are apparent in up to 11% of cases. These are = unusual in=20 malignant bone tumors other than fibrosarcoma and similar=20 tumors.
    • Differential diagnoses include metastatic carcinoma, = osteosarcoma,=20 Ewing sarcoma, malignant fibrous histiocytoma or fibrosarcoma = of bone,=20 neuroblastoma and other small round cell tumors, = osteomyelitis,=20 Langerhans cell histiocytosis, multiple myeloma, leukemic = infiltrate,=20 Paget disease, and giant cell tumor, depending upon the exact=20 radiographic appearance and the age of the = patient.
  • MRI
    • Most lesions appear homogeneous and hypointense on = T1-weighted=20 images and enhance with the administration of = contrast.
    • The appearance on T2-weighted images is inhomogeneous and = may be=20 hypointense, isointense, or hyperintense with respect to=20 fat.
    • MRI has high sensitivity for detecting lesions and for=20 demonstrating soft tissue extension. Extension across a joint = rarely=20 is seen.
    • Primary lymphoma of bone can be suspected based on MRI if = an=20 intact cortex is seen, even in the face of soft tissue = extension,=20 although this finding is by no means specific to = lymphoma.
    • Hypointense lesions on T2-weighted images correlated with=20 histologic evidence of intralesional fibrosis in one study. = Lesions of=20 osteosarcoma, Ewing sarcoma, multiple myeloma, neuroblastoma, = and=20 other small round cell tumors always are hyperintense on = T2-weighted=20 images and typically have destructive cortical penetration if = soft=20 tissue extension is present.
  • Technetium bone scan
    • Increased uptake usually is noted, particularly at the = periphery=20 of the lesions, although a central cold area may be present,=20 representing necrotic tumor.
    • This technique has very good sensitivity, with increased = uptake=20 noted in 98% of patients.
  • Gallium scan
    • Increased uptake is noted most commonly throughout the = lesions,=20 and the scan frequently is used for both initial staging and=20 follow-up.
    • This technique has comparable sensitivity to a technetium = scan and=20 can reveal soft tissue lesions as well.

Other Tests:

  • Flow cytometry studies
    • This technique uses fresh tissue to document cell surface = markers=20 that identify cell lineage.
    • Identification of the immunophenotype of malignant = lymphoma is=20 essential for proper diagnosis, classification, and=20 treatment.
    • Submit tissue to the laboratory fresh or in a tissue = culture=20 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=20 fresh or in tissue culture medium such as RPMI1640 or Ham's=20 F-10.
    • Bone marrow aspirate and peripheral blood specimens = collected with=20 sodium heparin anticoagulant also may be submitted for = cytogenetic=20 analysis.
  • Molecular pathology studies
    • For molecular studies, fresh tissue should be frozen and = kept at=20 -70 degrees Celsius.
    • Paraffin-embedded tissue from histopathology also is = acceptable=20 for some molecular tests.
    • Bone marrow aspirate and peripheral blood specimens = collected with=20 ethylenediaminetetraacetic acid (EDTA) anticoagulant also may = be=20 submitted for molecular pathology studies.

Diagnostic Procedures:

Histologic Findings:=20 Malignant lymphomas are classified based on the Revised = European=20 American Lymphoma (REAL) classification or on the proposed World = Health=20 Organization (WHO) classification, both of which are similar and = are based=20 on immunophenotype and morphology.=20

In adults, the most common subtype seen as primary lymphoma of = bone is=20 diffuse large B-cell lymphoma, which accounts for 60-90% of cases. = These=20 cases show a diffuse population of large lymphoid cells, sometimes = with=20 convoluted nuclear contours. Admixed fibrosis is present with a = background=20 population of reactive small lymphocytes.=20

Other types of lymphoma seen in primary bone lesions include = follicular=20 lymphoma, Burkitt lymphoma, precursor B-lymphoblastic lymphoma, = and B-cell=20 small lymphocytic lymphoma. T-cell lymphomas are distinctly = uncommon.=20 Cases of anaplastic large cell lymphoma, peripheral T-cell = lymphoma, and=20 adult T-cell lymphoma have been reported, the latter associated = with human=20 T-cell lymphotrophic virus type I (HTLV-I) infection.=20

Histologic differential diagnoses include Ewing sarcoma, = neuroblastoma=20 and other small round cell tumors, granulocytic sarcoma, and = Langerhans=20 cell histiocytosis.

Staging:

  WORKUP = Section 5 of = 11   
Author=20 Information Introduction=20 Indications=20 Relevant=20 Anatomy And Contraindications Wo= rkup=20 Treatment=20 Complications=20 Outcome=20 And Prognosis Future=20 And Controversies = Pictures=20 Bibliography

Medical therapy: = The=20 mainstay therapy for primary lymphoma of bone is medical. = Chemotherapy and=20 radiation therapy are used in conjunction in most cases.=20

The usual chemotherapy is CHOP (cyclophosphamide, Adriamycin,=20 vincristine, prednisone) or other similar regimens for several = cycles.=20 This may be combined with radiation therapy to the affected bone = in the=20 dose of 40-60 Gy fractionated over several weeks. Some studies = indicate=20 that results of combined modality therapy (chemotherapy and = radiation=20 therapy) are better than those from radiation therapy alone, while = other=20 studies have not documented any statistically significant = difference. Due=20 to the relative rarity of this disease, standard treatment = protocols have=20 not been developed and followed, and the data in the literature = are=20 retrospective.=20

In children, aggressive chemotherapy alone appears to be as = effective=20 as combined modality therapy. Because radiation therapy in = children is=20 associated with an increased incidence of growth-related adverse=20 consequences, it should be avoided in this population.=20

Therapeutic agents such as anti-CD20 antibody (rituximab) have = been=20 used for B-cell lymphomas. Refractory cases have been treated with = allogeneic bone marrow transplantation.

Surgical therapy: No standard role for = surgical=20 therapy exists in the primary management of bone lymphomas beyond=20 obtaining tissue for diagnosis and treatment of complications such = as=20 pathologic fracture. Before the advent of radiation and = chemotherapy, some=20 patients were treated with amputations, but amputations generally = are not=20 necessary with the medical treatment available today.

  TREATMENT = Section 6 of = 11   
Author=20 Information Introduction=20 Indications=20 Relevant=20 Anatomy And Contraindications Wo= rkup=20 Treatment=20 Complications=20 Outcome=20 And Prognosis Future=20 And Controversies = Pictures=20 Bibliography

Complications of treatment = include the=20 following:=20

Fractures are most common in weightbearing bones and have been=20 associated with the primary disease, with radiation therapy, and = with=20 avascular necrosis following chemotherapy.

  COMPLICATIONS = Section 7 of = 11   
Author=20 Information Introduction=20 Indications=20 Relevant=20 Anatomy And Contraindications Wo= rkup=20 Treatment=20 Complications=20 Outcome=20 And Prognosis Future=20 And Controversies = Pictures=20 Bibliography

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

Most patients that relapse do so early. Local recurrence and = distant=20 spread both are observed. Radiation therapy helps to decrease the=20 incidence of local recurrence. Therefore, recent series in the = literature=20 portray a relatively higher incidence of distant spread.=20

Adverse prognostic factors are as follows:=20

One study noted higher local recurrence rates in lesions of the = jaw,=20 and another study found lower survival rates in patients with = lesions=20 involving the pelvic bones. In children, hypercalcemia is = associated with=20 a poorer prognosis. No prognostic significance has been attached = to sex of=20 patient, histologic type of lymphoma, size of primary lesion, and=20 treatment modality.

  OUTCOME AND = PROGNOSIS=20 Section 8 of = 11   
Author=20 Information Introduction=20 Indications=20 Relevant=20 Anatomy And Contraindications Wo= rkup=20 Treatment=20 Complications=20 Outcome=20 And Prognosis Future=20 And Controversies = Pictures=20 Bibliography

The relative rarity = of=20 primary lymphoma of bone has resulted in the absence of = standardized=20 definitions for the disease and therapeutic trials. Studies in the = literature mostly are retrospective, and the numbers of patients = usually=20 are too small for subgroup analysis. Prospective studies are = needed to=20 clarify the impact of histologic subtype and therapeutic = modalities on=20 outcome.

  FUTURE AND = CONTROVERSIES=20 Section 9 of = 11    =
Author=20 Information Introduction=20 Indications=20 Relevant=20 Anatomy And Contraindications Wo= rkup=20 Treatment=20 Complications=20 Outcome=20 And Prognosis Future=20 And Controversies = Pictures=20 Bibliography

  PICTURES = Section 10 of=20 11   
Author=20 Information Introduction=20 Indications=20 Relevant=20 Anatomy And Contraindications Wo= rkup=20 Treatment=20 Complications=20 Outcome=20 And Prognosis Future=20 And Controversies = Pictures=20 Bibliography
Caption: = Picture 1.=20 Malignant lymphoma. An elderly woman presents with = complaints of=20 left shoulder pain of several months duration. Plain = radiograph of=20 the left shoulder (glenoid view) reveals a destructive lytic = process=20 eroding the cortical margins of the acromial process. Same = patient=20 as in Images 2-6.
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Picture = Type:=20 X-RAY
Caption: = Picture 2.=20 Malignant lymphoma. Total skeleton technetium Tc 99m nuclear = medicine scan shows increased uptake in the left acromion, = the site=20 of bone involvement by lymphoma in this patient. Initial=20 differential diagnosis suggested metastatic disease to bone = in=20 addition to multiple myeloma and lymphoma, in that order. = Same=20 patient as in Image 1 and Images 3-6.
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Picture = Type:=20 X-RAY
Caption: = Picture 3.=20 Malignant lymphoma. Coronal T1-weighted MRI of the left = shoulder=20 reveals replacement of the left acromion by a low-signal = process=20 extending into the surrounding soft tissue. Same patient as = in=20 Images 1-2 and Images 4-6.
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Picture = Type:=20 MRI
Caption: = Picture 4.=20 Malignant lymphoma. Coronal T2-weighted MRI of the left = shoulder=20 reveals a high signal process involving the left acromion = and=20 extending to the surrounding soft tissue. The MRI features = are=20 suggestive only of a very high cellularity fluid-containing = process=20 but are nonspecific, and biopsy is required for a specific=20 diagnosis. Same patient as in Images 1-3 and Images = 5-6.
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Picture = Type:=20 MRI
Caption: = Picture 5.=20 Malignant lymphoma. Sections of the biopsy show a diffuse = infiltrate=20 of atypical large lymphoid cells with vesicular nuclei, = small=20 nucleoli, and moderate cytoplasm. Small reactive lymphocytes = are in=20 the background. Same patient as in Images 1-4 and Image = 6.
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Picture = Type:=20 Photo
Caption: = Picture 6.=20 Malignant lymphoma. An immunohistochemical stain using an = antibody=20 directed against CD20 (B-cell marker) shows strong = positivity in the=20 large lymphoid cells. This is an example of a diffuse large = B-cell=20 lymphoma. Same patient as in Images 1-5.
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Picture = Type:=20 Photo
Caption: = Picture 7.=20 Malignant lymphoma. This woman, early in her fifth decade of = life,=20 presents with progressive left thigh pain and a limp.=20 Anteroposterior left proximal femur radiograph reveals a = lytic=20 destructive process involving the subtrochanteric region = with=20 medical cortical erosion, soft tissue extension, and an = associated=20 lesser trochanteric avulsion fracture. The proximal femur is = the=20 most common site for primary bone lymphoma. Same patient as = in=20 Images 8-10.
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Picture = Type:=20 X-RAY
Caption: = Picture 8.=20 Malignant lymphoma. Total skeleton technetium Tc 99m nuclear = medicine scan reveals isolated increased uptake in the left = proximal=20 femur at the site of this patient=92s bone lymphoma. Same = patient as=20 in Image 7 and Images 9-10.
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Picture = Type:=20 X-RAY
Caption: = Picture 9.=20 Malignant lymphoma. Diffuse infiltrate of large lymphoid = cells is=20 present, with cleared cytoplasm and hyperchromatic nuclei. = Admixed=20 small reactive lymphocytes are also noted. Same patient as = in Images=20 7-8 and Image 10.
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Picture = Type:=20 Photo
Caption: = Picture 10.=20 Malignant lymphoma. The immunohistochemical stain using an = antibody=20 against CD20 is positive in the large cells; this is a = diffuse large=20 B-cell lymphoma. Same patient as in Images 7-9.
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Picture = Type:=20 Photo
Caption: = Picture 11.=20 Malignant lymphoma. Clinical photo of left shoulder shows a=20 prominence in the mid portion of the left clavicle in this=20 45-year-old man with local pain and tenderness. He had no = history of=20 prior trauma. Same patient as in Images 12-14.
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Picture = Type:=20 Photo
Caption: = Picture 12.=20 Malignant lymphoma. Technetium Tc 99m total skeleton nuclear = medicine scan shows increased uptake in the mid portion of = the left=20 clavicle corresponding to the clinical site of bone = enlargement.=20 Same patient as in Image 11 and Images 13-14.
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Picture = Type:=20 X-RAY
Caption: = Picture 13.=20 Malignant lymphoma. Anteroposterior radiograph of left = clavicle=20 reveals a mixed lytic and sclerotic destructive process = within the=20 mid portion of the bone with indistinct, permeative borders. = Same=20 patient as in Images 11-12 and Image 14.
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Picture = Type:=20 X-RAY
Caption: = Picture 14.=20 Malignant lymphoma. Another example of a diffuse large cell=20 lymphoma. In addition to the large lymphoid cells with = moderate=20 cytoplasm, a few cells with lobated nuclei are also seen. = Such cells=20 are often seen in large cell lymphoma of the bone. Same = patient as=20 in Images 11-13.
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Picture = Type:=20 Photo
Caption: = Picture 15.=20 Malignant lymphoma. Plain radiographs in this 12-year-old = patient=20 with severely progressive right shoulder pain were = interpreted as=20 being normal. At most, they show localized osteopenia in the = right=20 proximal humerus but no discrete lesion within the bone. The = patient=20 was thought to have referred pain from the cervical region = or=20 brachial plexus based upon initial evaluation and plain = radiographs.=20 Same patient as in Images 16-17.
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Picture = Type:=20 X-RAY
Caption: = Picture 16.=20 Malignant lymphoma. T1-weighted coronal MRI of upper thorax = and=20 bilateral shoulders reveals a marrow replacement low signal = process=20 involving the entire right proximal humerus. The = corresponding=20 T2-weighted MRI showed a high signal process in this area. = This MRI=20 was done after plain radiographs were interpreted as normal = and an=20 MRI of the cervical spine and brachial plexus revealed the=20 unsuspected findings in the humerus. Same patient as in = Image 15 and=20 Image 17.
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Picture = Type:=20 MRI
Caption: = Picture 17.=20 Malignant lymphoma. Histologic sections reveal a highly = cellular=20 neoplasm composed of cells with high nuclear to cytoplasmic = ratio,=20 scant cytoplasm, and fine nuclear chromatin. The cells = showed=20 immunohistochemical evidence of B-cell lineage, and = expressed=20 terminal deoxynucleotidyl transferase (TdT), consistent with = a=20 precursor B-lymphoblastic lymphoma. Same patient as in = Images=20 15-16.
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Picture = Type:=20 Photo

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  BIBLIOGRAPHY = Section 11 of=20 11   =
Author=20 Information Introduction=20 Indications=20 Relevant=20 Anatomy And Contraindications Wo= rkup=20 Treatment=20 Complications=20 Outcome=20 And Prognosis Future=20 And Controversies = Pictures=20 Bibliography
NOTE: =
Medicine is a = constantly=20 changing science and not all therapies are clearly = established. New=20 research changes drug and treatment therapies daily. The = authors,=20 editors, and publisher of this journal have used their best = efforts=20 to provide information that is up-to-date and accurate and = is=20 generally accepted within medical standards at the time of=20 publication. However, as medical science is constantly = changing and=20 human error is always possible, the authors, editors, = and=20 publisher or any other party involved with the publication = of this=20 article do not warrant the information in this article is = accurate=20 or complete, nor are they responsible for omissions or = errors in the=20 article or for the results of using this information. The = reader=20 should confirm the information in this article from other = sources=20 prior to use. In particular, all drug doses, indications, = and=20 contraindications should be confirmed in the package = insert. FULL = DISCLAIMER=20

= Malignant=20 Lymphoma excerpt

=A9 Copyright 2004, eMedicine.com, = Inc.

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ORTHOPEDIC SURGERY=0A= - Medical Reference
 
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Table of = Contents
Alphabetical Index = of Topics

Biomechanics
Elbow
Foot And Ankle
Hand And Upper = Extremity
Hip
Knee



Neoplasms
Pediatrics
Shoulder
Spine
Systemic Diseases
Trauma
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Dennis P Grogan, MD
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Carlos J Lavernia, MD
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Jessica B Johnson
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Kelly Nikkila
Tammy Pomernackas
Nancy J Taubenheim, = DPT
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Amer Suleman, MD
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Jonathan Black, PhD
Robert D Bronstein, = MD
Howard A Chansky, MD
Michael S Clarke, MD
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Timothy Damron, MD
James K DeOrio, MD
John S Early, = MD
Dennis P Grogan, MD
William J Hozack, MD
William L Jaffe, = MD
James F Kellam, MD
Mininder S Kocher, MD, MPH
Jegan = Krishnan, MBBS, FRACS, PhD
Cato T Laurencin, MD, PhD
Mark D = Lazarus, MD
M Mike Malek, MD, FACS
Phillip J Marone, MD
Charles = T Mehlman, DO, MPH
Peter M Murray, MD
N Ake Nystrom, MD, PhD
A = Lee Osterman, MD
Albert W Pearsall IV, MD
Steven Rabin, = MD
Daniel Riew, MD
Lee H Riley III, MD
Miguel A Schmitz, = MD
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Heidi M Stephens, MD, MBA
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Paul E Di Cesare, MD, FACS
Robert H = Fitzgerald, Jr, MD
Thomas R Hunt III, MD
Shepard R Hurwitz, = MD
Pekka A Mooar, MD
Robert J Nowinski, DO
N Ake Nystrom, MD, = PhD
Sean P Scully, MD, PhD
William O Shaffer, MD
George H = Thompson, MD
John W Uribe, MD
Jerome D Wiedel, MD
Michael = Yaszemski, MD, PhD


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