Keywords Fluorodeoxyglucose-positron emission tomography/computed tomography - mantle cell
lymphoma - recurrent lymphoma - treatment response
Introduction
Mantle cell lymphoma (MCL) is a type of non-Hodgkin's lymphoma which accounts for
approximately 6% of all lymphomas and is considered aggressive and incurable.[1 ],[2 ] The 5-year survival ranges from <15% to 60%.[3 ] It commonly occurs in the lymph nodes, bone marrow, or spleen. The gastrointestinal
tract and Waldeyer ring are other important sites of extranodal involvement.[4 ] Although considered incurable, a variety of life-prolonging treatments is available
or being studied. The most common kind of treatment is immunochemotherapy, e.g., variations
of R-CHOP, R-bendamustine, R-BAC, and R-DHAP. BTK inhibitors such as ibrutinib are
rather new substances that are used for the treatment of patients with relapsed or
refractory MCL.[5 ] Additional research is being conducted, especially exploring the use of radioimmunotherapy
and targeted therapy.
Fluorodeoxyglucose (FDG)-positron emission tomography/computed tomography (PET/CT)
is commonly used to diagnose and manage lymphoma patients. The unique value of FDG-PET/CT
lies within its ability to differentiate between residual metabolically active tumor
and inactive scar tissue or necrosis, which makes it a superior tool in the assessment
of treatment response.[6 ] Interim FDG-PET/CT scans performed after two to three cycles of chemotherapy can
be used as an independent predictor of overall and progression-free survival of patients
with high-grade non-Hodgkin's lymphoma.[7 ]
This report presents a unique case of MCL with the appearance of FDG-avid, biopsy-proven
recurrence in unusual locations despite complete metabolic resolution of previous
sites of disease.
Case Report
A 77-year-old woman with a known history of MCL in remission since her last chemotherapy
(chlorambucil and rituximab) in 2016 was referred for investigation of possible recurrence.
Physical examination revealed palpable splenomegaly, and blood tests showed an elevated
white blood cell count at 199.8 × 109/L.
Bone marrow biopsy demonstrated molecular cytogenetic evidence of a relapse of the
MCL.
The FDG-PET/CT scan revealed moderately increased FDG uptake greater than the liver
in the enlarged spleen. The spleen measured 19.6 cm in the vertical dimension. There
were several FDG-avid lymph nodes above and below the diaphragm; measuring up to 2
cm. Diffuse heterogeneous increased bone marrow activity was consistent with lymphomatous
involvement. The findings were in keeping with FDG-PET-positive recurrence of MCL,
with nodal, splenic, and bone marrow involvement.
The patient received one cycle of R-CHOP followed by ibrutinib and venetoclax, but
this was complicated by severe neutropenia; therefore, G-CSF was administered, and
rituximab, bendamustine, and cytarabine (R-BAC) treatment were commenced.
After completing one cycle of R-BAC followed by two cycles of R-Bendamustine, the
patient presented for restaging FDG-PET/CT. This showed complete metabolic response
in previously documented FDG-avid nodal lesions and normalization of splenic uptake
associated with significant decrease in size. Diffuse homogenous FDG uptake in the
bone marrow was due to posttreatment reactive changes. However, new foci of metabolic
activity corresponding to underlying subcutaneous rounded soft-tissue densities had
developed in the right anterolateral chest wall, left lateral chest wall adjacent
to the 9th rib, and anterior mid-abdominal wall at the level of L1/L2 [Figure 1 ] and [Figure 2 ].
Figure 1 Pretreatment positron emission tomography scan demonstrating primary sites of disease
(arrows) on anterior maximum intensity projection (MIP) image (a). Posttreatment positron
emission tomography scan anterior (b) and oblique (c) MIP images showing complete
metabolic resolution in the sites of primary disease but new fluorodeoxyglucose-avid
lesions (arrowheads)
Figure 2 Axial images of the new subcutaneous lesion in the right anterolateral chest wall
(row a), left lateral chest wall (row b), and anterior midabdominal wall (row c) demonstrated
on computed tomography, positron emission tomography, and fused positron emission
tomography/computed tomography
Based on the FDG-PET/CT findings consistent with a complete metabolic response of
previously documented multifocal nodal disease, the new FDG-avid subcutaneous lesions
were thought to potentially be inflammatory in etiology, but an ultrasound was suggested
for further evaluation.
Targeted ultrasound assessment of the palpable bilateral chest wall lesions demonstrated
abnormal lobulated subcutaneous nodules of mixed echogenicity and increased internal
vascularity [Figure 3 ].
Figure 3 Ultrasound images of the subcutaneous left lateral chest wall lesion (a). Ultrasound
images with color Doppler of a newly developed palpable subcutaneous lesion in the
right upper chest wall demonstrating the internal vascularity present in all lesions
(b)
Given the atypical ultrasound features in the setting of a complete metabolic response
of the nodal disease and spleen, a core biopsy of the right chest wall lesion was
performed under ultrasound guidance. The histopathology showed features in keeping
with pleomorphic MCL [Figure 4 ].
Figure 4 Pleomorphic mantle cell lymphoma demonstrated in the histopathology (hematoxylin
and eosin stain) of a pretherapy bone marrow sample (a) and tissue obtained with ultrasound-guided
core biopsy of the new posttreatment subcutaneous lesion in the left chest wall (b)
Discussion
The usefulness of FDG-PET/CT in patients with MCL has been questioned in the past,
due to the disease's incurable nature and often low FDG avidity. Current literature
suggests that FDG-PET/CT is still a valuable tool in the management of patients with
MCL.[8 ]
In the presented case, despite the FDG-PET/CT findings being in keeping with a complete
metabolic response of the patient's primary disease, new FDG-avid subcutaneous lesions
were detected in multiple sites, initially thought to be inflammatory based on the
complete metabolic response in all primary sites of disease, but this was biopsy proven
to be recurrent disease. Shortly after the scan was performed, the patient's recurrent
MCL progressed clinically, with multiple new palpable subcutaneous lesions.
MCL is known to be an aggressive type of lymphoma with a continuously high risk of
recurrence. Therefore, suspicion should be directed toward any new FDG-avid lesions,
despite being in unusual sites for recurrence, and should be closely followed up.
A complete metabolic response of the sites of primary disease does not necessarily
lead to the conclusion of new lesions having a different underlying pathology in this
type of lymphoma.
According to the Lugano classification, a complete metabolic response is defined as
a score of 1 or 2, debatably 3, on the five-point scale based on the Deauville criteria
without the occurrence of any new lesions.[9 ],[10 ] The appearance of new FDG-avid foci is considered progressive disease as long as
the lesions are more likely to be lymphoma than another etiology.[10 ] It is important to be mindful that commonly benign, infectious, or inflammatory
processes are the cause of cutaneous or subcutaneous foci of FDG avidity. Most benign
tumors demonstrate no or low FDG avidity, yet there are some that have higher FDG
uptake. In addition, there is a variety of PET-positive infectious and inflammatory
processes, particularly in relation to chemotherapy. The correlation with morphologic
features on the CT can be helpful. However, it is most important to consider the biology
of the lymphomatous disease being assessed when interpreting new FDG-avid lesions,
and further investigation, such as a biopsy, might be required in some cases.[11 ]
