Primary bone lymphoma: report of a case with multifocal skeletal involvement
Department of Biomedical Imaging, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia
Primary bone lymphoma is an uncommon tumour accounting for
approximately 4-5% of extra nodal lymphoma and less than 1% of all Non-Hodgkin�s
lymphoma. The radiographic appearance of primary bone lymphoma is variable. As
lesions frequently resemble other disease processes namely chronic
osteomyelitis and metastases, further imaging evaluation and histopathological
examination allow early identification for appropriate treatment. The authors
present a case of anaplastic large cell lymphoma of bone presenting with
multifocal osseus involvement. � 20xx Biomedical Imaging and Intervention
Journal. All rights reserved.
Keywords: Lymphoma, bone, anaplastic large cell lymphoma,
Primary lymphoma of bone (PLB), which is defined as
lymphoma localised to the bone without evidence of lymph nodes or other tissues
at presentation, is one of the rarest primary bone malignancies, accounting for
less than 5% of all primary bone tumours . The vast majority of bone
lymphomas are of the Non-Hodgkin�s type, with Hodgkin�s disease and Burkitt�s
lymphoma accounting for the rest.
The radiographic appearances of PLB are variable and
because the lesions may not be obvious on plain radiography, other modalities
such as radionuclide bone scintigraphy or magnetic resonance imaging (MRI)
should be utilised. Primary bone lymphoma has a better prognosis than many
other malignant tumours, henceforth early identification allows for appropriate
treatment. The authors present a young adult with primary bone lymphoma i.e.,
the anaplastic large cell type with its interesting clinical, radiological and
A 26-year-old male presented with persistent pain and
swelling of the left jaw for the past two months following a left 1st molar
tooth extraction. There was an associated history of prolonged pyrexia
associated with chills and rigors. Patient was treated with a course of
antibiotics as infection of the extraction site was suspected. Several weeks
later, he presented to an oromaxillofacial surgeon as the symptoms progressed.
Physical examination revealed an ill-defined hard swelling arising from the
body of the mandible with an exuberant soft tissue growth anterior to the left
last molar. Full blood count showed hemoglobin of 127 g/L, white blood cell
11.7 x 109 and platelets 397 x 109. The ESR was 48
mm/hour, which was mildly elevated. He was not known to be immunocompromised.
An orthopantomogram (OPG) (Figure 1) and a contrast
enhanced computed tomography (CT) scan of the mandible showed lytic destruction
in the body of the mandible, and anterior and lateral alveolar process
associated with a soft tissue mass (Figure 2). Numerous cervical and submental
lymphadenopathy was noted. Excisional tissue biopsy and, culture and
sensitivity of the soft tissue as well as the mandible showed a heavy growth of
Streptococcus oralis, and Enterococcus within chronic granulation
tissue. The impression at that time was of chronic osteomyelitis of the
mandible. He subsequently developed pain in the occipital region and thoracic
spine. However, plain radiographs of these sites were normal.
In view of the poor response to various courses of
antibiotic treatment and progressive bone pain, radionuclide bone scintigraphy
(99mTC MDP) was performed. This revealed intense radiotracer uptake in multiple
sites in the mandible, manubrium sterni , the upper thoracic and the skull
vault (Figure 3). At this point, a differential diagnoses of multifocal
metastases, Langerhans Histiocytosis and skeletal lymphoma was made. CT scan of
the thorax and abdomen showed no internal organ involvement or abdominal
MRI of the spine showed abnormally high signal changes of
T3 to T5 paravertebral region, erector spinae and trapezius muscle on short
time inversion recovery (STIR) images. Axial post-gadolinium image revealed
heterogenous enhancement of the vertebral body, right pedicle, laminae, and
paravertebral soft tissues at the T4 vertebral level (Figure 4). There was
associated intraspinal extradural infiltration with indentation of the spinal
cord at the T4 vertebral level.
The patient then proceeded to surgery. Intraoperatively,
there was extensive tumour involving the right paraspinal muscles adherent to
the dural sac. Posterior decompression and fixation with instrumentation was
performed. Histopathology showed anaplastic large cell lymphoma. He was started
on a chemotherapy regimen. Follow-up CT scan done in the middle of the
chemotherapy cycle showed regression of the paravertebral lesions as well as
the soft tissue mass at the left mandibular region. He is currently on
follow-up at the Hematology Clinic.
Primary bone lymphoma (PBL) is rare accounting for
approximately 4-5% of extra nodal lymphoma and less than 1% of all
Non-Hodgkin�s lymphoma . The criteria for a diagnosis of PBL initially
suggested by Coley in 1950 with minor modifications are as follows: �Lymphoma
presenting in an osseous site with no evidence of disease elsewhere for at
least six months after diagnosis�. The presence of regional lymph node
involvement does not exclude a diagnosis of PBL, but a histological examination
of the lymph node is necessary. Although the original criteria of Coley implied
the involvement of solitary bone, Ostrowski et al  subclassify
osseous lymphoma into four groups. In their classification, Group 1 consists of
solitary primary bone lymphoma and Group 2 encompasses cases in which more than
one bone is affected but no nodal or visceral disease is present. Group 3
includes cases with distant nodal disease and Group 4 with visceral disease.
Anaplastic large cell lymphoma (ALCL) represents
approximately 2% of all Non-Hodgkin�s lymphomas according to the recent
Non-Hodgkin�s Lymphoma Classification Project . ALCL commonly involves nodal
as well as a wide variety of extranodal sites, although primary or secondary
involvement of bone is rare . Anaplastic large cell lymphoma (ALCL),
previously known as Ki-1 lymphoma, is a heterogeneous group of Non-Hodgkin�s
lymphomas of T-cell, B-cell, and null-cell phenotypes. Subsequently, it was
recognised that T-cell and null-cell ALCL occur more often in younger patients
and generally have a better prognosis than histologically similar B-cell
PBL occurs in patients from 1 year 6 months to 86 years
(median range 36-56 years) with a peak prevalence among patients in the 6th and
7th decade of life. The femur (29%) is the most common site of predilection
followed by (in descending order of frequency): pelvis (19%), humerus (13%),
skull (11%) and tibia (10%) . Vertebral involvement is not unusual. In the
long bones, lymphoma is usually metaphyseal or diaphyseal in location, rarely
involving the epiphysis. When primary bone lymphoma disseminates, its spread to
other bony sites is recognised .
The clinical presentation reflects the nature of the
disease process, usually manifesting as insidious and intermittent bone pain
that may persist for months. Other signs include local swelling, palpable mass
and systemic symptoms such as pyrexia and loss of weight, all the
manifestations that this patient had. But these symptoms are also associated
with that of chronic osteomyelitis. Plain radiographic appearance is variable
and non-specific. Lymphoma of bone almost invariably arises in the medullary
portion of the bone presenting as predominantly destructive and osteolytic bony
lesions. The lytic pattern may be permeative characterised by numerous small,
elongated rare fractions that are parallel to the long axis of the bone and
relatively uniform in size or �moth-eaten� � a pattern of many medium to large
areas of radiolucency, which are poorly marginated. Occasionally, the disease
may manifest with focal lytic areas with well-defined margins.
The lytic destructive pattern is the most common
radiographic appearance of PBL and it was reported in approximately 70% of 237
cases reviewed by Mulligan et al . Cortical breakthrough, pathological
fracture and soft tissue masses represent a more aggressive pattern of
involvement and poor prognosis. Periosteal reactions and presence of sequestra
are recognised associated imaging findings. Other plain radiographic findings
such as blastic-sclerotic pattern and near absence of detectable abnormalities
have been described. Cases such as these are best further evaluated by MRI and
bone scintigraphy, which clearly demonstrate patterns of abnormal marrow
The appearances of primary bone lymphoma on radionuclide
bone imaging are usually non specific, depicting lesions of abnormality as
areas of increased tracer uptake. This pattern may also be seen with other
marrow infiltrating tumours such as leukemia, multiple myeloma, metastatic
disease as well as multifocal osteomyelitis. In view of this patient�s young
age and the combination of scintigraphic abnormality in the mandible, skull and
sternum, metastatic disease was thought unlikely and a differential diagnosis
of skeletal lymphoma was suggested.
MRI typically shows a focus of marrow replacement and the
extent of surrounding soft tissue mass. Generally, lesions demonstrate low
signal intensity on T1-weighted imaging within the marrow with bright signal
intensity on T2-weighted imaging . However presence of fibrosis may show low
signal intensity on both sequences . STIR also delineate the abnormality in
the bone marrow. Gadolinium contrast enhanced images will demonstrate areas of
enhancement within the lesion. MRI is also particularly useful in evaluation of
spine involvement and any spinal cord compression.
This particular case demonstrated the clinicians� as well
as the radiologists� initial diagnostic difficulty. This may be attributed to
inadequate tissue sampling especially if it was not done under imaging
guidance. One solution to overcome this difficulty is to perform an open bone
biopsy, which this patient had during posterior spinal decompression surgery.
Adequate biopsy sample for histopathology, immunotyping and immunohistochemistry
study of the lymphoma cells is critical in the definitive diagnosis of ALCL.
Primary lymphoma of bone usually responds well to a
combination of radiation therapy and chemotherapy regimens with an overall
response rate of 94% in some series and a 5-year survival rate, better than
that achieved with most other primary osseous malignancy . ALCL is a
high-grade lymphoma and it usually needs prompt treatment with chemotherapy.
The current treatment approach for primary systemic ALCL is identical to that
for other types of diffuse aggressive Non-Hodgkin�s Lymphomas. A combination of
cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) is the
standard first-line treatment. If CD20 antigens are positive, rituximab should
be added. Radiation therapy to bulky sites of disease may be necessary after
completion of chemotherapy. From the clinical and radiological point of view,
lymphoma of bone should be considered in the differential diagnosis of a young
adult presenting with multifocal osseous involvement.
Figure 1 Orthopantomogram shows lytic destruction of the left side involving the left first molar bed (arrow) and the root of the 2nd premolar.
Figure 2 CT scan at level of body of the mandible (left: bone WW: 2344, WC: 440 and right: soft tissue window WW: 250, WC: 50) showing lytic destruction (arrow in left figure) with associated soft tissue swelling. Enlarged bilateral anterior cervical nodes noted.
Figure 3 Radionuclide bone scintigraphy using MDP 99m-Technicium showing intense radiotracer uptake in the left side of mandible, manubrium sterni, upper thoracic vertebra and the skull vault (arrows).
Figure 4 a) Sagittal MRI (STIR, TR 3586.0 TE 60.0) showed abnormally increased signal intensity in the T4 vertebral body and the subcutaneous tissues of the thoracic paravertebral region; b) Axial Post gadolinium image revealed heterogenous enhancement of the vertebral body, right pedicle, laminae, and paravertebral soft tissues at the T4 vertebral level.
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|Received 15 April 2007; received in revised form 5 November 2007, accepted 27 November 2007
Correspondence: Department of Biomedical Imaging, Faculty of Medicine, University of Malaya, 50603 Kuala Lumpur, Malaysia. Tel.: +603-79492069; Fax: +603-79581973; E-mail: firstname.lastname@example.org (Kartini Rahmat).
Please cite as: Rahmat K, Wastie ML, Abdullah BJJ,
Primary bone lymphoma: report of a case with multifocal skeletal involvement, Biomed Imaging Interv J 2007; 3(4):e52
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