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Primary lymphoma of the bone mimicking metastatic carcinoma:  Importance of a systematic approach

Joo Young Song*, Louis DePalma

The George Washington University, Department of Pathology
Washington , District of Columbia

Address for Correspondence:
Joo Young Song
2300 Eye Street, NW
, Ross Hall 502, Washington, DC 20037 .


Patients with metastatic carcinoma commonly have multiple lytic bone lesions.  We present a patient with multiple bone lytic lesions who by clinical, radiologic and morphologic evidence appeared to have metastatic carcinoma.  MRI revealed lesions in the right ilium, right sacroiliac joint, right proximal femur, left ilium and left side of the sacrum.  Both CT and MRI did not disclose any soft tissue mass or lymphadenopathy.  A biopsy of the left posterior iliac crest showed a high grade undifferentiated neoplasm with a marked desmoplastic response.  Only after exclusion of non-hematopoietic neoplasms by an extended immunohistochemical panel was the diagnosis of primary bone lymphoma (PBL, centroblastic variant) made.  This report illustrates the necessity of radiologic and morphologic correlation in establishing the correct diagnosis.  PBL can infrequently involve multiple bones of the pelvis in the absence of a soft tissue mass or regional lymphadenopathy with an associated carcinoma-like desmoplastic response.

J.Orthopaedics 2009;6(2)e7


lymphoma; bone; metastatic; carcinoma



PBL is an infrequent bone lesion, representing only 5% of all bone neoplasms.1  Patients typically complain of localized pain and/or a palpable mass.  PBL is defined as a lymphoma involving a single skeletal site with or without involvement of regional lymph nodes.2  Less commonly, PBL involves multiple bones with an associated soft tissue mass.  Long bones are most frequently involved, primarily at the diametaphysis.  Thus clinical and radiologic criteria may be used to suggest PBL in the differential diagnosis.  The presence of multiple lytic bone lesions, especially in flat bones such as the pelvis, in the absence of an associated soft tissue mass and with no regional lymphadenopathy is more frequently associated with metastatic carcinoma.3  We report a patient with the later presentation who after careful pathologic and radiologic correlation was diagnosed with a PBL.  This report demonstrates the importance of clinicopathologic evaluation as well as a systematic immunohistochemical approach to the diagnosis of PBL.  Furthermore, PBL may be associated with a striking carcinoma-like desmoplastic reaction.

Case Report:

A 53 year old woman complained of generalized abdominal pain as well as back pain.  Physical exam did not reveal any specific findings.  A CT scan disclosed a lytic lesion involving the left portion of the sacrum adjacent to the inferior portion of the left sacroiliac joint.  An MRI revealed lytic lesions in the right ilium, the right sacroiliac joint, right proximal femur, left ilium and left side of the sacrum near the left sacroiliac joint (Figure 1).  No soft tissue mass or lymphadenopathy was seen.  The radiologic impression was that of metastatic disease. 

Figure 1: MRI of the pelvis and femoral heads showing multiple lesions in the right inferior pelvis, right proximal femoral head, left ilium and left sacrum.

A bone biopsy of the left posterior iliac crest was performed.  Approximately 20-30% of the bone biopsy showed a high grade malignancy with associated fibrous tissue and bone sclerosis (Figure 2).

Figure 2: Infiltrative malignant cell population with fibrosis and bone sclerosis, suggestive of metastatic carcinoma (hematoxylin-eosin, original magnification X10).

The cells revealed large nuclei with vesicular chromatin and non-prominent nucleoli infiltrating in a non-cohesive pattern (Figure 3, 4).

Figure 3: Large, malignant non-cohesive cells with associated fibrosis (hematoxylin-eosin, original magnification X20).

Figure 4: Malignant cells with large nuclei and vesicular chromatin pattern (hematoxylin-eosin, original magnification X40).

In addition there were areas of osteoclastic and osteoblastic activity with prominent woven bone formation and sclerosis.  Immunohistochemistry showed the atypical population was positive for CD45, CD20, and CD79a (Figure 5).  They were focally positive for BCL-6 and CD10.  These cells were negative for CK7, CK20, Cam5.2, Mak6, CK AE1/AE3, EMA, TTF-1, MART-1, HMB-45, EMA, CD3 and CD138.  Based on the immunohistochemical findings, the diagnosis of large B cell lymphoma, centroblastic variant was made. Of note, the bone marrow aspirate did not reveal any malignant cells.

Figure 5: The malignant cells reveal CD20 positive immunostaining (original magnification X40).

Discussion :

Metastatic neoplasms are the most frequent of all malignancies of bone.3  In most cases the diagnosis is readily made since the lesions are numerous and the presence of the primary malignancy is known or evident.  The great majority of bone metastases originate in breast, lung, prostate, thyroid or kidney.4  Approximately 70% of bone metastases affect the axial skeleton (skull, ribs, spine, sacrum). The remaining metastatic lesions involve large bones of the limbs alone or in combination with the axial skeleton.

Radiologically, the lesions are usually osteolytic, but may be osteoblastic or both.5, 7 Periosteal bone proliferation and exuberant new bone formation can less commonly occur.  In the absence of a known primary, histological evaluation combined with a selective immunohistochemical panel can narrow or confirm the nature of the neoplasm. Associated histologic findings such as a marked desmoplastic response may be also be helpful in identifying the presence of carcinoma.6

In contrast to metastatic bone neoplasms, PBL is infrequent.  Although PBL usually affects the diaphysis or metaphysis of a long bone, it can more rarely involve multiple bones, thus simulating metastases.7  The absence of an associated soft tissue mass or lymphadenopathy does not exclude the presence of PBL.  The diagnosis of PBL clearly requires histologic as well as immunohistochemical analysis.  Usually the H and E stained tissue suggests a lymphoma as opposed to a carcinoma, even in those cases where the clinical and radiological findings are more suggestive of bone metastases.

Our patient revealed considerable clinical and radiological overlap with bone metastases. PBL was not clinically suspected due to the multifocal lytic lesions of the pelvis and the right proximal femur. Furthermore, the absence of a soft tissue mass, lymphadenopathy or “B” symptoms did not raise the possibility of PBL to the clinicians or radiologists.  The presence of a high grade malignant cell infiltrate associated with marked fibrosis and new bone formation continued to suggest the diagnosis of bone metastasis even after reviewing the H and E slides of the biopsy.  In fact, carcinoma frequently evokes a desmoplastic response with new and sclerotic bone formation.  PBL usually infiltrates in an interstitial pattern with at most associated increased reticulin fibers surrounding individual or clusters of malignant cells.2

The establishment of the correct diagnosis in this unusual presentation of PBL required an extensive immunohistochemical panel as well as correlation of the clinical and radiological findings.  Only with an understanding of the less common pattern of bone involvement by PBL as well as excluding carcinoma or other non-hematopoietic neoplasms due to the marked associated fibrosis was the diagnosis made.  Furthermore, subtyping of the non-Hodgkin lymphoma is critical to appropriate management.8,9  This PBL was of the centroblastic variant, germinal-center like (BCL-6+, CD10+). In conclusion, a systematic approach to the pathologic evaluation of bone lesions is of fundamental importance.  PBL has quite different therapeutic and prognostic significance than the other more frequently present neoplasms in the differential diagnosis. Thus, missing the diagnosis of an atypical PBL presentation can have serious consequences.

Reference :

  1. Hicks DG, Gokan T, O’Keefe RJ et al.  Primary Lymphoma of the Bone.  Cancer 1995;75:973-980.

  2. Unni KK, Hogendoorn PCW.  Malignant Lymphoma, In : Fletcher CDM, Unni KK, Mertens F, eds.  WHO Classification of Tumours: Pathology and Genetics of Tumours of Soft Tissue and Bone, Lyon, France: IARC Press; 2002:306-308.

  3. Simon MA, Bartucci EJ.  The search for the primary tumor of patients with skeletal metastases of unknown origin.  Cancer 1986;58:1088-1095.

  4. Berrettoni BA, Carter JR.  Mechanisms of cancer metastasis to bone.  J Bone Joint Surg 1986;68:308-312.

  5. Mulligan ME, McRae GA, Murphey MD.  Imaging features of primary lymphoma of bone.  Am J Rad 1999;173:1691-1697.

  6. Krishnan C, George TI, Arber DA. Bone marrow metastases: a survey of nonhematologic metastases with immunohistochemical study of metastatic carcinomas. Appl Immunohistochem Mol Morphol 2007; 15: 1-7.

  7. Huebner-Chan D, Fernandes B, Yang G, Lim M.  An immunophenotypic and molecular study of primary large B-cell lymphoma of bone.  Modern Pathology 2001; 14: 1000-1007.

  8. De Leval L, Braaten KM, Ancukiewicz M et al.  Diffuse large B-cell lymphoma of bone: An analysis of differentiation-associated antigens with clinical correlation.  Am J Surg Pathol 2003: 27:1269-1277.

  9. Pettit CK, Zukerberg LR, Gray MH et al.  Primary lymphoma of bone.  A B-cell neoplasm with a high frequency of multilobated cells.  Am J Surg Path 1990;14:329-334.

This is a peer reviewed paper 

Please cite as: Joo Young Song: Primary lymphoma of the bone mimicking metastatic carcinoma:  Importance of a systematic approach.

J.Orthopaedics 2009;6(2)e7





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