Hypermetabolic Lymphadenopathy on PET
CT in Systemic Lupus Erythematosus: A CaseReport
Dana DiRenzo1 and Homa Timlin1*
1Johns Hopkins Division of Rheumatology, Baltimore.
*Corresponding author: Homa Timlin MD MSc, Johns Hopkins Division of Rheumatology, 5501 Hopkins Bayview, Circle/Asthma and Allergy
Building, Suite 1B.1, Baltimore, MD 21224
Received: December 12, 2016; Accepted: January 3, 2017; Published: January 23, 2017
Citation:DiRenzo D, Timlin H (2017) Hypermetabolic Lymphadenopathy on PET CT in Systemic Lupus Erythematosus: A Case Report. J Rheumatol Arthritic Dis 2(1): 1-3.
Background: New onset and active Systemic Lupus
Erythematosus (SLE) may be infrequently associated with diffuse
lymphadenopathy. This is often worrisome for malignancy in which
F18/FDG PET scanning is typically obtained as part of a neoplastic
workup. Results are often difficult to interpret and resemble
lymphoma in many instances. There is sparse literature describing
systematic differences in inflammation versus neoplasm pertaining
to SLE in this context.
Case Series: We have reviewed F18/FDG PET/CT imaging and
histology from three patients with hyper metabolic lymph nodes who
were found to have benign pathology in the setting of active SLE.
Conclusion: FDG PET scanning is an imaging modality that is
infrequently used as a means to non-invasively assess inflammation
in rheumatic diseases. Further studies are needed to determine
metrics for delineating benign inflammation versus neoplasm based
on standard uptake units. However, lymph node biopsy should
remain the gold standard for diagnosis in this particular patient
Keywords: PET scan; Systemic Lupus Erythematosus;
Systemic Lupus Erythematosus (SLE) is an autoimmune
disease that affects multiple organ systems with varied disease
presentations, sometimes dramatic in onset . It may be
associated with lymphadenopathy, especially in instances of
high disease activity . Differentiating malignancies such as
lymphoma versus SLE with lymphadenopathy can be difficult .
Of concern, there is also an increased association of non-Hodgkin’s
lymphoma in patients with SLE which may be associated with
immunosuppressive medications versus high disease activity ,
. In a recent meta-analysis of cancer risk in patients with SLE,
there was a pooled Relative Risk (RR) of 5.40 (95% CI, 3.75-7.77)
for development of non-Hodgkin’s lymphoma .
PET scanning is useful in locating areas of distant metastasis
as part of cancer staging and as a translation of that, may also
useful in localizing areas of inflammation . The ability of
PET scan to qualitatively characterize the degree of systemic
inflammation and organ involvement have been previously
described for SLE . Mechanistically, activated lymphocytes
exhibit higher degrees of glucose metabolism, concentrating in
lymphoid tissues, as seen on PET scan via a radioactively labeled
We have reviewed three cases of new onset SLE with highly
metabolic lymphadenopathy on PET scanning that had benign
findings on biopsy. The PET scans were obtained out of concern
for malignancy in the context of diffuse lymphadenopathy. All
three PET scans posed significant angst to both the physicians
and patients, despite negative biopsy results. To date, there are
very limited studies assessing use of PET scan for characterizing
inflammation and disease activity in patients with SLE and results
may pose diagnostic dilemmas. We argue that lymph node biopsy
in patients with bulky lymphadenopathy should remain the gold
standard for diagnosis.
A 33-year-old female developed progressively worsening
fevers, tachycardia, pleuritic chest pain, and weight loss over
several weeks’ time. Imaging was repeatedly negative for
pulmonary embolism but diffuse lymphadenopathy was noted
on her chest CT scans. This correlated with strikingly enlarged
axillary and cervical lymph nodes on her physical exam, worrisome
for malignancy. She additionally developed arthralgias and was
referred to our rheumatology clinic where she was found to
be leukopenic with positive anti-nuclear antibodies (>1:640,
homogeneous pattern), anti-dsDNA antibodies (1:320), anti-Ro
antibodies, anti-La antibodies, anti-RNP antibodies, anti-Smith
antibodies, low C3 of 60 mg/dL (normal 79-152 mg/dL), and low
C4 of < 2 mg/dL. Her urine protein/creatinine ratio was elevated
to 0.28 (normal 0.00-0.19).
She underwent F18/FDG PET/CT scanning which
demonstrated hyper metabolic cervical, axillary, mediastinal,
retroperitoneal, iliac and inguinal lymph nodes with splenic and
bone marrow involvement also concerning for lymphoma (Figure
1). Her SUVmax was 4.6. However, a fine needle aspiration of a
right axillary lymph node revealed only reactive lymphoid tissue.
Because the concern for lymphoma was so high, she underwent a
complete excisional right axillary lymph node biopsy which was
consistent with benign dermatopathic lymphadenopathy.
A 38-year-old female with known history of systemic lupus
erythematosus and overlap pauci-immune glomerulonephritis
was admitted to a large tertiary care center in the setting
of pancytopenia, diffuse lymphadenopathy, and 20-pound
weight loss over several weeks. Her lupus was diagnosed 12
years previous to this presentation and was characterized
by malar rash, photosensitivity, arthritis, pancytopenia,
hypocomplementemia (nadir C3 52 mg/dL, normal 79-152 mg/
dL; C4 mg/dL, normal 12-42 mg/dL), anti-nuclear antibodies
(1:160), anti-dsDNA antibodies (1:640), and anti-RNP antibodies.
She was also noted to be short of breath with progressively
worsening cough. She had CT imaging of her chest, abdomen, and
pelvis which revealed periportal, peripancreatic, retroperitoneal,
axillary, and supraclavicular lymphadenopathy. A F18/FDG
PET/CT scan was obtained and revealed diffuse, highly metabolic
lymphadenopathy. One hyperintense subcarinal lymph node
measured 13.2 SUVmax. However, a supraclavicular excisional
lymph node biopsy was performed which showed histiocytic
lymphoproliferation with coagulative necrosis consistent with
A 25-year-old female developed axillary and cervical
lymphadenopathy, recurrent pleurisy, and severe arthritis over
several months’ time. She was referred to our rheumatology clinic
where her immunologic studies were notable for anti-nuclear
Figure 1:A) F18/FDG PET Scan from Case 1 demonstrating diffuse hyper
metabolic cervical, axillary, mediastinal, retroperitoneal, iliac, and
inguinal lymph nodes with splenic and bone marrow involvement.
B) Histology of right axillary lymph node demonstrating reactive
lymphoid tissue without evidence of malignancy.
antibodies (>1:640), anti-Smith antibodies, anti-dsDNA (1:20),
and anti-SSA and anti-SSB antibodies. She had low complements
with a C3 of 58 mg/dL (normal 79-152 mg/dL), and low C4 of 3
mg/dL (normal 12-42 mg/dL). She was subsequently diagnosed
with SLE. Because of persistent axillary lymphadenopathy over
serial examinations, there was concern for a neoplastic process
and further imaging was obtained. A F18/FDG PET CT showed
hyper metabolic activity isolated to her axillary lymph nodes.
The reported SUVmax was 4.1. She underwent a fine needle
aspiration of a right axillary node which revealed reactive
lymphoid tissue with follicular and paracortical hyperplasia.
Each of these cases represents development of bulky
lymphadenopathy in the context of SLE that generated concern
for lymphoma. All three of these cases displayed hyper metabolic
lymph nodes on PET scanning, but without congruent features
or intensities. While PET scanning may theoretically be used
as a non-invasive modality for diagnosing inflammation versus
malignancy, it lacks the precision for defining these very different
entities. We argue that biopsy should remain the gold standard
for assessing lymphadenopathy in lupus patients, a population at
higher risk for lymphoma.
PET scanning may be used to differentiate malignancy versus
inflammation in other entities, but current literature is limited
to case reports in terms of SLE. In a retrospective analysis of
32 patients with Sjogren’s Syndrome, 4 patients developed
lymphoma and their imaging was notable for relatively higher
standard uptake unit (SUV) max compared to those with solely
reactive lymphadenopathy (5.4 vs 3.2 SUVmax, p=0.05). A study
analyzing 48 patients with Fever of Unknown Origin (FUO) noted
the mean SUV reached 10.4 (range 7.2–15.3) in tumors, 3.8 (range
3.2–5.6) in inflammation respectively . However, we noted
that in Case 2, biopsied to be benign lupus lymphadenitis, the
SUVmax was 13.2. Importantly, PET scanner and reconstruction
methods are factors that intimately affect SUV measurements
and stringent quality control measures are necessary when
comparing studies .
Another high risk feature noted on PET scan concerning for
lymphoma is bone marrow infiltration. In a meta-analysis of
patients with newly diagnosed diffuse large B-cell lymphoma,
positive FDG PET/CT findings of bone marrow involvement
negated the need for a bone marrow biopsy for the detection of
bone marrow involvement in these patients .
There is an additional need for larger scale, high powered
studies to better define measurements to easily delineate
inflammation versus malignancy on PET scanning. While this
would idealistically serve to avoid invasive surgical procedures,
the gold standard for diagnosis in these high risk patients should
remain lymph node biopsy. These cases serve to demonstrate the
high burden of inflammation in developing SLE that is variable in nature.
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