eMedicine Specialties > Orthopedic Surgery > Neoplasms

Malignant Lymphoma: Workup

Author: Sharad Mathur, MD, Staff Physician, Department of Pathology, Kansas City VA Medical Center
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
Contributor Information and Disclosures

Updated: Jan 8, 2008

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:
  • 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 a99m 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 use99m 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.

More on Malignant Lymphoma

Overview: Malignant Lymphoma
Workup: Malignant Lymphoma
Treatment: Malignant Lymphoma
Follow-up: Malignant Lymphoma
Multimedia: Malignant Lymphoma
References
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Further Reading

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Keywords

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

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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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