Primary (Malignant) Lymphoma of Bone

Primary (Malignant) Lymphoma of Bone

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Primary lymphoma of bone (PLB; also referred to as reticulum cell sarcoma, malignant lymphoma of bone, or osteolymphoma) is an uncommon entity that accounts for fewer than 5% of all primary bone tumors. [1] (See the images below.) Orthopedic surgeons typically encounter PLB as a solitary lesion with a variable radiographic appearance. Alternatively, patients with stage IV systemic lymphoma and skeletal involvement may be referred to orthopedic surgeons for the treatment of impending or pathologic fractures. Osseous involvement of disseminated lymphoma is not uncommon.

There have been no randomized therapeutic trials for this rare disease. Most of the literature consists of retrospective reports on various chemotherapy and radiation therapy regimens.

The definition of PLB includes the following criteria:

Soft-tissue extension from the bone is a common feature of PLB.

Commonly involved bones in PLB, in order of decreasing frequency, include the following:

The metadiaphyseal portion of bone is the most common site of disease. Involvement of the small bones of the hands and feet is rare. Some studies suggest that the mandible and maxilla are frequently affected sites, but confirmation that bone is the primary site of disease is not well documented.

The etiology of PLB is unknown. Viral agents and immunosuppression have been implicated in some cases. PLB 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 AIDS. Rarely, patients with Paget disease of bone may develop malignant lymphoma in the involved bone.

Cytogenetic and molecular abnormalities are associated with many different lymphomas. These also can be documented in the setting of primary bone lymphoma.

Some common recurrent abnormalities are as follows:

PLB accounts for fewer than 5% of primary bone tumors and fewer than 5% of extranodal lymphomas (or ~1% of all primary non-Hodgkin lymphomas). [2]

Secondary involvement of bone marrow is seen in 5-15% of patients with Hodgkin disease and 30-53% of patients with non-Hodgkin lymphoma. As many as 50% of patients with AIDS-associated Hodgkin disease have secondary bone marrow involvement. [3, 4]

The median age range for PLB is 36-52 years, but the peak prevalence is between the ages of 50 and 70 years. It is rare in children. Males are affected more frequently than females (male-to-female ratio, 1.51.8:1).

In general, PLB has a better prognosis than most primary bone sarcomas or metastatic lesions do. The Surveillance, Epidemiology, and End Results (SEER) database reported 5- and 10-year survival rates of 58% and 45%, respectively, including patients from 1973-2005. [5] These rates are lower than are reported in most other literature.

A study from Memorial Sloan-Kettering Cancer Center reported a 5-year overall survival rate of 95% with chemoradiation and 78% with single-modality treatment. [6] The patients treated with only chemotherapy, however, tended to have more advanced stage disease. The University of Miami reported a progression-free survival rate of 83% at 4 years. [7] Demircay et al reported a disease-free 5-year survival rate for patients younger than 60 years and older than 60 years of 90% and 62%, respectively. [8]

Positive prognostic factors for outcome include younger age at diagnosis, multimodal treatment, and localized disease; it has been suggested that inclusion of rituximab in the treatment regimen may improve the prognosis. [9] Other factors (eg, type of lymphoma, sex, and lesion size) do not seem to be significant on multivariate analysis.

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

Gao GJ, Yang D, Lin KK, Xiao J, Li X, Liang HY, et al. Clinical analysis of 10 AIDS patients with malignant lymphoma. Cancer Biol Med. 2012 Jun. 9 (2):115-9. [Medline]. [Full Text].

Jawad MU, Schneiderbauer MM, Min ES, Cheung MC, Koniaris LG, Scully SP. Primary lymphoma of bone in adult patients. Cancer. 2010 Feb 15. 116 (4):871-9. [Medline].

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Xu Y, Li J, Ouyang J, Li J, Xu J, Zhang Q, et al. Prognostic relevance of protein expression, clinical factors, and MYD88 mutation in primary bone lymphoma. Oncotarget. 2017 Sep 12. 8 (39):65609-65619. [Medline]. [Full Text].

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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].

Lucas DR, Bentley G, Dan ME, Tabaczka P, Poulik JM, Mott MP. Ewing sarcoma vs lymphoblastic lymphoma. A comparative immunohistochemical study. Am J Clin Pathol. 2001 Jan. 115 (1):11-7. [Medline].

Ozdemirli M, Fanburg-Smith JC, Hartmann DP, Azumi N, Miettinen M. Differentiating lymphoblastic lymphoma and Ewing’s sarcoma: lymphocyte markers and gene rearrangement. Mod Pathol. 2001 Nov. 14 (11):1175-82. [Medline].

Liu Y. The role of 18F-FDG PET/CT in staging and restaging primary bone lymphoma. Nucl Med Commun. 2017 Apr. 38 (4):319-324. [Medline].

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Bruno Ventre M, Ferreri AJ, Gospodarowicz M, Govi S, Messina C, Porter D, et al. Clinical features, management, and prognosis of an international series of 161 patients with limited-stage diffuse large B-cell lymphoma of the bone (the IELSG-14 study). Oncologist. 2014 Mar. 19 (3):291-8. [Medline]. [Full Text].

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Susnerwala SS, Dinshaw KA, Pande SC, Shrivastava SK, Gonsalves MA, Advani SH, et al. Primary lymphoma of bone: experience of 39 cases at the Tata Memorial Hospital, India. J Surg Oncol. 1990 Aug. 44 (4):229-33. [Medline].

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Vincent Y Ng, MD Fellow, Musculoskeletal Tumor Surgery, University of Washington Medical Center

Vincent Y Ng, MD is a member of the following medical societies: American Academy of Orthopaedic Surgeons, American Medical Association, Mid-America Orthopaedic Association, Ohio State Medical Association, American Association of Hip and Knee Surgeons, International Congress for Joint Reconstruction

Disclosure: Nothing to disclose.

Ernest Upshur “Chappie” Conrad, III, MD Associate Professor, Department of Orthopedics, University of Washington School of Medicine; Chair/Co-Director, Department of Orthopedics, Seattle Children’s Hospital; Director, Sarcoma Service, Department of Orthopedics, Professor of Orthopedics and Sports Medicine, University of Washington Medical Center; Chairman, Pediatric Orthopedic Tumor Clinic; Children’s Hospital and Medical Center

Ernest Upshur “Chappie” Conrad, III, MD is a member of the following medical societies: American Academy of Orthopaedic Surgeons, American Association for the Advancement of Science, American Association of Tissue Banks, American College of Surgeons, American Medical Association, American Orthopaedic Association, Connective Tissue Oncology Society, SWOG, Western Orthopaedic Association, Children’s Oncology Group, American Society of Clinical Oncology, Musculoskeletal Tumor Society, Pediatric Orthopaedic Society of North America, International Society of Limb Salvage, Tuberous Sclerosis Alliance, The Paget Foundation, Washington State Orthopaedic Association

Disclosure: Nothing to disclose.

Francisco Talavera, PharmD, PhD Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Received salary from Medscape for employment. for: Medscape.

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, Leonard M Miller School of Medicine; Clinical Professor of Surgery, Nova Southeastern 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, Arkansas Medical Society, Florida Medical Association, Florida Orthopaedic Society

Disclosure: Nothing to disclose.

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: Lippincott, Williams, and Wilkins Royalty Editing/writing textbook; Genentech Grant/research funds Clinical research; Orthovita Grant/research funds Clinical research; National Institutes of Health Grant/research funds Clinical research; UpToDate Royalty Update Preparation Author; Wright Medical, Inc. Grant/research funds Clinical research

Sharad Mathur, MD Chief, Pathology and Laboratory Medicine Service, Kansas City Veterans Affairs Medical Center

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

Disclosure: Nothing to disclose.

Primary (Malignant) Lymphoma of Bone

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