A 76-year-old woman was referred to oncology with new palpable left
axillary lymph node. Her past medical history was significant for marginal zone
lymphoma that was diagnosed in 1999 (received chemotherapy), hypertension and
type 2 diabetes. Her ECOG performance status was 2 and physical exam was
significant for 1.5 cm left axillary lymph node. Her labs showed white blood
cell count of 5.9, hemoglobin of 13.4, platelets of 232, Bun/Cr 22/0.9 and LDH
Her initial staging PET/CT showed 1.2 cm × 0.6 cm left cervical
lymph node with maximum standard uptake value (SUV) of 2.1, 1.1 cm × 2 cm
left axillary lymph node with a maximum SUV of 4.1, hypermetabolic activity in
the spleen with a maximum SUV of 4.1, abdominal lymphadenopathy around the
superior mesenteric artery measured 3.2 cm × 6.7 cm × 9 cm with a
SUV ranging from 4.5 to 10.4, a second nodal mass in the lower region measured
1.6 cm × 2.7 cm × 5.4 cm with a maximum SUV of 6.3 and 8 mm left
external iliac node, which was not significantly hypermetabolic. She underwent
a core biopsy of the abdominal nodal mass (tissue was obtained from the area
with maximum SUV), and pathology showed benign lymphoid tissue and flow
cytometry was limited due to the presence of few monoclonal B cells. She
subsequently underwent a core biopsy of left axillary lymph node, which was
A repeat PET/CT was done four months later that showed interval increase
in size of the left cervical lymph node to 1.8 cm × 1.2 cm with a maximum
SUV of 4.6, left axillary lymph node 1.1 cm × 2 cm (unchanged) with an
increased maximum SUV of 5.0, abdominal lymphadenopathy around the superior
mesenteric artery measured 3.2 cm × 6.7 cm × 9 cm, unchanged in
size but with interval increase in SUV from 4.5-10.4 to 19.5, increased second
nodal mass to 4.7 cm × 4.6 cm × 10 cm with an increased SUV to
16.2, left external iliac lymph node 8 mm (unchanged), new left inguinal lymph
node 1.4 cm with a SUV of 4.2 and resolution of hypermetabolic activity in the
spleen. The patient underwent laparoscopic guided biopsy of abdominal nodal
mass and pathology showed a diffuse infiltrate of small lymphoid cells in
fibrous and adipose tissue. Immunohistochemical studies showed neoplastic
B-cells CD20+, CD23partial+, BCL6+, BCL2+, CD5 negative, CD43 negative, cyclin
D1 negative and CD 10 equivocal. The proliferation marker Ki67 was low
(<10%). Flow cytometry showed a population of Monoclonal B-cells of
approximately 20% being CD10+dim, CD19+dim, CD20+, CD22+, CD5-, Kappa+ and
Lambda-. The overall findings favored low-grade follicular lymphoma. Bone
marrow showed no evidence of lymphoma.
She has low grade follicular lymphoma by histology with no B symptoms,
no cytopenias and normal LDH. Given the performance status and increase in SUV
in the lymph nodes within just a few months, her treatment options include
enrollment into a clinical trial or R-CVP while waiting for treatment records
1: PET/CT examination demonstrates hypermetabolic activity (yellow circle)
associated with a hypermetabolic left axillary lymph node in a patient with
follicular cell lymphoma. The top set of images taken from 4/22/08 and the
bottom set of images taken from 8/5/08 demonstrate an interval increase in the
SUV from 4.2 to 5.0.
Upper left image is axial CT scan, upper right image is
corresponding PET image, lower left image is fusion image containing PET images
displayed on a color scale and CT images displayed on a gray scale. Lower right
image is maximum intensity project image of whole body PET study.
2: Initial PET/CT examination demonstrates hypermetabolic activity (yellow
circle) associated with enlarged retroperitoneal lymph nodes. There has been
interval increase in the hypermetabolic activity from an SUV of 1.96 in 4/22/08
(top) when compared to an SUV of 8.09 in 8/5/08 (bottom). Display convention is
the same as Figure 1.
3: PET images from 4/22/08 demonstrate increased metabolic activity
throughout the entire bone marrow involving the axial and appendicular
skeleton, suspicious for bone marrow involvement. Bone marrow biopsy was
consistent with follicular lymphoma.
Source: M. Ghsani
The initial evaluation of the patient with non-Hodgkins lymphoma
is to establish the precise histologic subtype, staging and prognostic score.
NHLs can be further divided into indolent (follicular, small cell lymphocytic
lymphoma, marginal zone lymphoma, lymphoplasmacytic, mycosis fungoides),
aggressive types (diffuse large B-cell, mantle cell, peripheral T-cell,
anaplastic large cell lymphoma), and highly aggressive (Burkitt-type,
lymphoblastic). NHL is staged as per the Ann Arbor staging system.
Since the introduction of computed tomography, technological advances
in imaging have largely replaced staging laparotomy and nodes greater than 1 cm
in short axis are generally considered positive for malignancy. Traditionally,
67Gallium-citrate (Ga) has been widely used as a functional imaging tool to
evaluate viable tumors in patients with history of treated lymphoma and is
proven to be useful in differentiating benign tissue vs. residual disease while
demonstrating 90% sensitivity and 93% specificity.
Widespread use of PET and PET/CT using radio labeled glucose analog
fluorine-18-deoxyglucose (18F FDG) as a tumor marker has replaced
gallium scanning in this application.
PET is highly sensitive in detecting nodal and extranodal involvement
of common types of lymphoma (eg, diffuse large B-cell NHL, follicular NHL,
mantle cell NHL, HL). Routinely used 18FFDG avidity has a
sensitivity that exceeds 80% and a specificity of about 90%, which is superior
to CT. PET scan upstages disease in 15% to 20% of patients. However, the impact
of therapy is less than 8% and not routinely recommended for initial staging
due to the very little change in management. PET scan is generally used in
conjunction with a diagnostic CT as a PET/CT examination, which is generally
performed at the time of initial diagnosis as a staging exam as well as a
baseline examination prior to initiation of therapy. During therapy and
particularly upon completion of therapy, PET/CT is useful in distinguishing
viable tumor from necrosis or fibrosis. In general, PET/CT has a consistently
high negative predictive value averaging about 85% across studies including
patients with HL and/or diffuse large B-cell NHL. There are data in recent
literature demonstrating usefulness of PET/CT in aggressive lymphoma in
assessing response to therapy three weeks after completion of chemotherapy and
preferably six to eight weeks after chemotherapy or chemoimmunotherapy and
eight to 12 weeks after radiation or chemoradiatiotherapy. The role of PET/CT
for response assessment of aggressive NHL subtypes other than DLBCL and of
indolent and mantle-cell lymphomas, is less clear.
Usefulness of PET/CT in assessment of transformation in indolent
lymphomas has not been clearly defined despite its higher incidence and
prevalence. In assessment of this application, studies have suggested that a
maximum SUV of more than 10 is highly associated with aggressive behavior but a
latter study showed that the intensity of the radionuclide uptake is
independent of histological grading. Given the risk of histological
transformation of follicular lymphoma to aggressive lymphoma in order of 17% to
22% at five years and 28% to 31% at 10 years, further studies are warranted in
defining 18FFDG avidity for differentiating various grades of
follicular lymphoma and histological transformation. The above case illustrates
limitation of PET/CT in this application, with rapidly increasing size and
18FFDG avidity in one particular nodal site while the histology is
still of low grade follicular lymphoma. However, there still remains the
possibility that histologic transformation is not uniform throughout the
suspicious lymph node and cytologic sampling from a given site within the lymph
node may not necessarily represent the highest tumor grade in that lymph node.
Therefore, this patient should be followed closely for assessment of interval
progression in the future.
Munir Ghesani, MD, is Associate Clinical Professor of Radiology at
Columbia University College of Physicians and Surgeons and Attending
Radiologist at St. Lukes-Roosevelt Hospital Center.
Vamsee Torri, MD, is a Chief Fellow in Hematology/Oncology at St.
Lukes-Roosevelt Hospital Center.
Robert Chen, MD, is a Resident in Radiology, Beth Israel Medical
For more information:
- Kwee TC, Kwee RM, Nievelstein RA . Imaging in staging of malignant
lymphoma: a systematic review. Blood. 2008;111:504-516.
- Seam P, Juweid ME, Cheson BD. The role FDG-PET scans in patients
with lymphoma. Blood. 2007;110:3507-3516.
- Juweid ME, Strooants S, Hoekstra OS, et al. Use of positron
emission tomography for response assessment of lymphoma: consensus of the
imaging subcommittee of international harmonizing project in lymphoma. J
Clin Oncol. 2007;25:571-578.
- NCCN Non-Hodgkins Lymphoma guidelines version 3.2008.
- Schoder H, Noy A, Gonen M et al. Intensity of 18fluorodeoxyglucose
uptake in positron emission tomography distinguishes between indolent and
aggressive non-Hodgkins lymphoma. J Clin Oncol.
- Wohrer S, Jaeger U, Kletter K, et al. 18F-fluorodeoxy-glucose
positron emission tomography (18F-FDG-PET) visualizes follicular
lymphoma irrespective of grading. Ann Oncol. 2006;17:780-784.