DEFINITION AND PATHOGENESIS
- (formerly reticulum cell sarcomalymphosarcoma, or follicular lymphoma)
Ann Arbor Staging System
- Stage I: primary lesion only (node, bone, other)
- Stage II: nodes involved in more than two anatomic regions on the same side of the diaphragm
- Stage III: nodes involved on both sides of the diaphragm
- Stage IV: bony mets
- Non-Hodgkin's lymphomas are classified under the general headings:
- Low grade
- Intermediate grade
- High grade
- Primary NHL of bone may represent tumors of post-germinal center B-cells (bone marrow is the normal site of homing of plasma cells which are terminally-differentiated, immunoglobulin-secreting post-germinal center B-cells (NHL may represent tumors of post-germinal center B-cells)
- About 4-5X as common as Hodgkin's disease of bone
- 3-7% of all primary osseous malignancies
- ± diffuse or dull, aching bone pain, fatigue
- ± fever, ? wt, night sweats
- Accounts for approximately 4-5% of all primary bone tumors (most non-Hodgkin's, usually diffuse histiocytic lymphoma)
- May present with pathologic fracture and soft tissue mass
- Compression fx/vertebral plana in axial locations
- Sxs may be present for up to several years
- Neurologic deficits in spinal lesions
- Secondary involvement of bone is about 25% in children
- (most frequent areas are spine, pelvis, skull)
- M:F = 1.5-1.8:1 (also whites:blacks)
- Wide age range (2-88 yrs, mean 42-51 reported)
- ???? alk?
- Joint effusion may occur from local extension from bone
- Epidural extension may occur in spinal locations and cause neurologic sxs
- direct lymphomatous involvement of peripheral nerves
- reported rare association with Guillain-Barre syndrome
- Has been reported arising in chronic osteomyelitis
- Most common sites: distal femur, proximal tibia, proximal femur, proximal humerus, mid-shaft femur
- Femur (29%), pelvis (19%), humerus (13%), tibia (10%)
- Osteolytic lesions (70%) with permeative bone destruction to mixed lytic/blastic (28%) or blastic (2%) lesions
- Cortical destruction often associated with adjacent muscle and soft tissue involvement
- Sequestra (also seen in EG, osteomyelitis, fibrosarcoma, MFH, desmoplastic fibroma) may be seen (16%)
- Periosteal reactions are often (47%) present (esp long bones)
- Soft tissue mass (48%) is best visualized with MRI
- Isointense to hypointense signal (compared to muscle) on T1-weighted MRI, 2/3 with heterogeneity on T2-weighted images
- Pathologic fx may be the presenting finding (~20%)
- Compression fx in spinal lesions (vertebra plana)
- Bone scan may reveal "silent" bony lesions, usually (98%) shows uptake
- Failure to show uptake may hinder the dx
- Isointense to hyperintense to muscle on T1-weighted images
- Hyperintense to fat on T2-weighted images
- More sensitive than gallium scan (which has low spatial resolution and lack of specificity)
- PET fused with CT increases sensitivity because of physiological uptake in the abdomen
- Sensitivity reported 85-95% and 8-59% of pts will have a change of stage using PET
- Uptake varies with grade of disease
- 18F-FDG is not tumor specific (eg, inflammatory cells, hyperplastic bone marrow, infection)
- Should not be performed until 2-3 months following XRT; 1 month following chemotx
- Sensitivity (79-84%) and specificity (90-92%) for detection of residual disease (accuracy of 85%)
- Used during and at the end of therapy to provide a more accurate response classification than assessment by CT
- Can identify refractory disease early
- Grossly soft, less likely to show pus-like necrosis
- Larger round cells, moderate cytoplasm, clear borders, hyperchromatic nuclei (pleomorphic)
- ~92% are diffuse large B cell lymphomas
- Special stains:
- + PAS, ??diastase
- ± reticulin
- + common leukocyte antigen
- B or T cell positivity
- + CD19, CD20 immunoperoxidase (B cell marker)
- Kappa light chain markers
- + UCHL-1 for T-cell origin
DIFFERENTIAL CLINICOPATHOLOGIC DIAGNOSIS
- Metastatic or secondary lymphoma
- Ewing sarcoma
- Metastatic neuroblastoma
- Metastatic embryonal rhabdomyosarcoma
- Eosinophilic granuloma (ddx in vertebra plana)
- Hodgkin's disease
DISEASE COURSE AND TREATMENT
International Harmonization Project criteria for response assessment in lymphoma
- Complete response (CR): complete disappearance of all detectable disease with (a) FDG-avid prior to tx; mass of any size permitted if PET negative, or (b) varibly FDG-avid or PET negative; regression to normal size LNs on CT; spleen/liver not palpable, nodules disappear; normal bone marrow bx on repeat bx, immunochemistry negative
- [Complete response unconfirmed (Cru): as in CR but with residual mass >1.5cm that has regressed by >75% has been removed because of the advent of PET]
- Partial response (PR): at least 50% reduction in the sum of the product of the greatest diameters of the 6 largest nodes with no increase in the size of the other nodes and no new sites of disease; Hepatic and splenic nodules should also decrease by at least 50%; bone marrow irrelevant if + previously; (a) FDG-avid or PET + prior to tx: one or more PET + at previously involved site; (b) variably FDG-avid or PET negative: regression on CT
- Stable disease (SD): response is less than PR but not progressive; (a) FDG-avid or PET positive prior to tx: PET positive at prior sites of disease and no new sites on CT or PET; (b) variably FDG-avid or PET negative: no change in size of previous CT lesions
- Progressive disease (PD) or Relapsed disease (RD): appearance of new lesion(s) >1.5cm in any axis, >50% increase in sum product of the diameters in >1 node, or >50% increase in longest diameter of a previously identified node >1cm in short axis; lesions PET + if FDG-avid lymphoma or PET + prior to tx; >50% increase from nadir in the sum product of the diameters of any previous lesions; new or recurrent bone marrow involvement
- Lymph node bx (if enlarged nodes present) at the time of bone bx is indicated to establish dx and proper stage
- Isolated bony lesion: neoadjuvant chemotherapy (± XRT), ± wide resection, reconstruction and adjuvant chemotx
- Large cleaved cell lymphomas with a better prognosis than large noncleaved cell lymphomas
- Pathologic fractures: may do best with resection (± XRT) since XRT alone will lead to delay in fx healing
- An indicator of poor prognosis for freedom from relapse
- Surgery indicated for bx, prophylactic fixation of impending fxs, fixation of fxs
- > 60 yrs of age at time of diagnosis is an indicator of poor prognosis for survival
- CNS involvement has worse outcome
- Diffuse bony lesions: XRT ± IM fixation devices using fixation criteria as in metastatic disease
- 5-yr DFS 30-50%, 10-yr survival 48%
- Intercurrent disease with no LR must be monitored
- 5-yr overall survival in pelvic locations 38%
- An indicator of poor prognosis for freedom from relapse
- Development of multiple myeloma with primary T-cell lymphoma of bone has been reported
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