The patient is a 47-year-old man with fairly well-controlled HIV/AIDS,
hepatitis B without cirrhosis and former polysubstance user, with pulmonary
dysfunction secondary to idiopathic fibrosis. He was diagnosed with stage IV
Hodgkins disease involving the liver and bone marrow. His baseline
diffusion capacity for carbon monoxide was decreased, precluding therapy with
bleomycin. As such, he received CEPP regimen that consisted of cyclophosphamide
600 mg/m2 IV on day 1 and 8; etoposide 70 mg/m2 IV on
days 1 to 3; procarbazine (Matulane, Sigma Tau) 60 mg/m2 orally on
days 1 to 10; and prednisone 60 mg/m2 orally on days 1 to 10.
The treatment was interrupted because of patient noncompliance and
infectious complications. He eventually received five cycles, but
unfortunately, he refused further treatment and never achieved a complete
He relocated to New York and established care in our institution shortly
after. His PET/CT at that time showed diffuse lymphadenopathy with significant
hypermetabolic uptake in the appendix, without clinically evident appendicitis,
bone, liver and splenules. Of note, the patient had a history of remote
splenectomy caused by trauma. The bone marrow biopsy confirmed classic
Hodgkins disease with lymphohistiocytic infiltrate CD30, PAX5-positive
and CD20, CD45-negative.
He received two cycles of ICE salvage therapy that consisted of
carboplatin (area under the curve of 6) on day 1; ifosfamide 1,500
mg/m2 on days 1 to 3; mesna 300 mg/m2 on days 1 to 3; and
etoposide 100 mg/m2 with growth factor support. The restaging CT of
chest, abdomen and pelvis demonstrated excellent response, so he received an
additional two cycles.
After four cycles of ICE therapy, his PET/CT showed a complete
remission. Prominent bone marrow activity was felt to be benign and attributed
to etoposide administration. He was referred to the transplant center for the
evaluation of autologous stem cell transplant. Unfortunately, he refused to
undergo the stem cell collection. His HIV was not controlled adequately,
although he was taking an antiretroviral regimen.
Although the patient is post-splenectomy, there is a rounded
soft tissue mass (red circle) in the left upper quadrant that likely
regenerated splenic tissue. At the time of this scan in December, there is
normal mild FDG activity within this tissue as expected in a normal spleen.
Images courtesy of L Makarian; N
Gupta; M Ghesani
This subsequent scan in September after multiple rounds of
chemotherapy demonstrates a new subtle small hypodense lesion in the splenule
(red circle). The corresponding functional PET image demonstrates a focus of
abnormal FDG uptake with a standard uptake value of 3, which is above the
background splenic activity. This is highly suspicious for recurrent disease.
About 4 months later, he started to complain of abdominal pain, and the
abdomen and pelvis CT showed an interval development of a 2.5-cm right
paravertebral soft tissue at T9-T10 level that was suspicious for recurrent
lymphoma. He also had minimally increased small and borderline lymph nodes in
the abdomen and pelvis.
His axillary lymph nodes were stable, and small bilateral inguinal lymph
nodes became slightly larger. PET/CT was recommended for suspected recurrence,
although bilateral axillary and inguinal lymph nodes were felt to be
indeterminate, as they often are with HIV-associated lymphadenopathy. PET/CT
not only showed increasing metabolic activity in the nodes but also a new
hypodense lesion in the accessory spleen with associated subtle but suspicious
hypermetabolic activity. The latter finding strongly supported the possibility
of recurrent lymphoma.
This initial PET/CT in December demonstrates foci of mildly
increased FDG activity within the bone marrow of the pelvic bones suspicious
for disease involvement.
This PET/CT in May demonstrates intense uptake throughout the
marrow containing spaces of the pelvis, markedly increased from the initial
scan. Notice on the whole body MIP image, there has been interval development
of intense uptake throughout the ribs, spine, and pelvis compared to the prior
exam (Figure 3). This is consistent with the effect of etoposide, although
evaluation for focal lesions cannot be made on this background.
He also had new foci of hypermetabolic activity associated with the
cervical and portacaval lymph nodes. There was 3.1-cm × 1.1-cm right
paravertebral soft tissue mass at the level of T9 and T10, with suggestion of
metabolic activity associated with this soft tissue. He had an interval
progression of skeletal involvement. Interestingly, there was a significant
decrease in prominent diffuse bone marrow activity, as etoposide was no longer
being given. The biopsy of the paravertebral mass is currently planned.
Finally, this PET/CT in September demonstrates decrease in the
diffuse marrow uptake throughout the spine, ribs, and pelvis that was seen on
the May exam; however there has been interval development of multiple focal
regions of abnormal intense uptake (red circles along the left sacrum and left
iliac wing). The decrease in diffuse marrow activity is consistent with
resolving etoposide effect, while the development of focal abnormal uptake is
highly suspicious for recurrent disease.
PET/CT is recommended and is widely used for staging and after
completion of the therapy to assess the response in the Hodgkins
lymphomas. Additionally, the importance of interim PET/CT in the midst of
therapy to predict response was reported by Dann and colleagues. He studied it
after two cycles of BEACOPP therapy in 47 patients with standard and high-risk
disease. Almost 30% of patients relapsed if the interim PET/CT was positive,
and only 2.3% patients relapsed if interim PET/CT was negative. Several current
trials in Hodgkins disease include interim PET/CT in the algorithm, and
if positive, they escalate the therapy after two cycles of doxorubicin,
bleomycin, vinblastine and dacarbazine (ABVD).
The role of PET/CT in post-therapy surveillance, however, remains
controversial. In fact, the National Comprehensive Cancer Network guidelines do
not recommend it for routine use. Moreover, in patients with HIV, the finding
could be harder to interpret. The fluorine-18 fluorodeoxyglucose detects active
lymphoid tissue associated with any condition, including HIV infection.
Goshen retrospectively studied the role of PET/CT and correlated it with
concurrent clinical, immunologic and viral load data. PET/CT accurately
correlated with the extent of lymphoma in 12 of 16 patients. In the cases in
which PET and CT findings were discrepant, increased viral loads and CD4 levels
implied benign HIV-related lymphadenopathy.
In our patient, presence of a new hypodense hypermetabolic lesion in the
splenule makes it very suspicious for recurrence. This is further supported by
evidence of worsening of skeletal involvement.
Liana Makarian, MD, is an oncology Fellow at St Lukes-Roosevelt
Neil Gupta, MD, is a resident in radiology at St
Lukes-Roosevelt Hospital Center.
Munir Ghesani, MD, is an attending radiologist at St.
Lukes-Roosevelt Hospital Center and associate clinical professor of
radiology at Columbia University College of Physicians and Surgeons.
For more information:
- Dann EJ. Blood. 2007;109:905-909.
- Goshen E. Clin Nucl Med. 2008;33:610-614.