Keywords neuroendocrine tumors - presacral-precoccygeal grade III NET -
177 Lu-DOTATATE -
68 Ga-DOTATATE PET/CT -
18 F-FDG PET/CT - bilobar liver metastasis - peptide receptor radionuclide therapy (PRRT)
- PET/CT
Introduction
Neuroendocrine neoplasms (NENs) constitute a diverse category of tumors that arise
from the neuroendocrine cell system.[1 ] These tumors are characterized by an endocrine phenotype, which can be confirmed
through immunohistochemical staining for synaptophysin and chromogranin A.[2 ] The gastrointestinal system and lungs are the most frequently affected sites.[1 ] Primary presacral space tumors are very uncommon, among which presacral NEN is exceptionally
rare.[3 ] Imaging tests for neuroendocrine tumors (NETs) include magnetic resonance imaging
(MRI), 68 Ga-DOTATATE/DOTANOC/DOTATOC PET, 18 F-fluorodeoxyglucose positron emission tomography/computed tomography (18 F-FDG PET/CT),[4 ] while treatment includes surgery, somatostatin analogue (SSA) therapy, peptide receptor
radionuclide therapy (PRRT), and chemotherapy.[4 ]
We present a 45-year-old female diagnosed with a primary presacral NET through a pathological
biopsy, with multiple bilobar liver metastases. Due to its rarity, only a few studies
have been reported on the imaging and pathological characteristics of presacral NETs.
This report aims to provide a thorough description of a rare case of a NET of the
presacral region.
Case Report
A 45-year-old female presented with initial complaints of low back pain of 2 years'
duration, with temporary relief from oral anti-inflammatory medication. Upon recurrence
of symptoms, an MRI of the lumbosacral spine was performed, which showed altered marrow
signal intensity involving the S2 vertebra on the left side, with adjacent soft tissue
extending into the S1–S2 neural foramen and encasing the nerve root. Another ill-defined
lobulated soft tissue mass was observed in the precoccygeal region in the midline,
extending to the right side, along with incidentally detected multiple well-defined
lobulated hyperintense lesions involving both lobes of the liver, the largest seen
in the right lobe measuring 8.5 × 5.5 cm.
Subsequently, the patient underwent 18 F-FDG PET/CECT, which showed an ill-defined FDG-concentrating heterogeneously enhancing
soft tissue mass in the presacral region (SUVmax: 4.9), extending into the S1–S2 neural
foramina, measuring approximately 3 × 2 × 3.5 cm (AP [anteroposterior] × TR [transverse] × CC
[craniocaudal]). Another mildly 18 F-FDG-concentrating (SUVmax: 3.2) lobulated midline soft tissue mass, extending to
the right side, was seen in the precoccygeal region, measuring approximately 4.3 × 2.7 × 2.8 cm
(AP × TR × CC). Moderate hepatomegaly with multiple discrete and confluent hypoenhancing
lesions was observed in both lobes of the liver without any significant 18 F-FDG concentration, the largest lesion seen in segment VIII measuring approximately
8.7 × 8.3 × 9 cm (AP × TR × CC)([Fig. 1 ]).
Fig. 1
(A –C) Images showing 18 F-FDG PET/CT, contrast-enhanced CT, and 68 Ga-DOTATATE PET/CT images, respectively. 18 F-FDG-concentrating (SUVmax: 4.9) and SSTR-avid (Krenning's score: 4) soft tissue
mass in presacral region (red arrow), mildly 18 F-FDG-concentrating (SUVmax: 3.2) and SSTR-avid (Krenning's score: 4) soft tissue
mass in precoccygeal region (green arrow), and non-18 F-FDG-concentrating and SSTR avid (Krenning's score: 4) multiple bilobar liver lesions,
reference lesion in segment VIII (blue arrow). 18 F-FDG PET/CT, 18F-Fluorodeoxyglucose Positron Emission Tomography/Computed Tomography;
SSTR, somatostatin receptor.
The patient underwent a CT-guided biopsy of the presacral mass, which was diagnosed
as a well-differentiated NET, Grade III, positive for synaptophysin, chromogranin
A, and INSM1, and negative for pan-CK, S100, SOX10, p63, and SMA Beta-Catenin, with
a Ki-67 index of 20 to 22%. 68 Ga-DOTATATE-PET/CT showed somatostatin receptor (SSTR) expression in the aforementioned
presacral mass (SUVmax: 20.6), precoccygeal mass (SUVmax:16.09), and heterogeneous
SSTR expression in bilobar liver lesions, with the reference lesion in liver segment
VIII (SUVmax: 21.5; [Fig. 1 ]).
In our study, the primary presacral mass, as well as the precoccygeal mass and multiple
bilobar liver lesions, showed increased SSTR expression (Krenning's score: 4, uptake
greater than spleen) and a NET-PET score of 2 (SSTR > FDG), which was helpful in deciding
on treatment with 177 Lu-DOTATATE therapy.
Discussion
NENs arising from the neuroendocrine cell system are most commonly seen in the gastrointestinal
system and lungs.[1 ] The presacral space, which contains embryological vestiges comprising various tissues,
is situated between the rectum anteriorly, the sacrum posteriorly, and the endopelvic
fascia laterally.[5 ] Presacral space tumors are very uncommon, among which presacral NEN is very rare
and has been reported in only a limited number of studies.[6 ] A key factor in differentiating NEN from other primary tumors or metastases is immunohistochemistry.[1 ]
Presacral NENs are often well-differentiated tumors with local involvement, although
there have also been examples of distant metastasis, according to the data available
so far. The immunohistochemistry profile closely resembles that of rectal NEN, which
aligns with the theory that they share an origin from the embryonal hindgut.[7 ] In our study, a CT-guided biopsy revealed the diagnosis to be Grade III NET, with
a Ki-67 index of 20 to 22%. Clinically, the majority of patients present with locoregional
symptoms, such as discomfort in the lower abdomen, pelvis, sacral region, or perineum.
In our case, the presenting complaint was also low back pain.
NETs can be identified by scintigraphy or, particularly, by SSTR PET/CT, as SSTR expression
is a hallmark of NETs. Since their sensitivity is higher than that of other imaging
modalities, SSTR-PET/CT scans are useful for staging disease, planning treatment,
and ruling out other potential primary sites.[8 ] In our case, 68 Ga-DOTATATE PET/CT showed SSTR-avid soft tissue masses in the presacral and precoccygeal
regions, as well as multiple bilobar liver lesions. Although the presacral and precoccygeal
masses showed FDG concentration, the liver lesions revealed no significant FDG concentration.
FDG avid primary disease with non-FDG avid liver metastasis can be explained by the
phenomenon of inter-lesional heterogeneity. It arises due to genetic and epigenetic
variations or differences in the tumor microenvironment. Tumor heterogeneity is commonly
seen in NETs, which can be due to a progressive increase in their Ki-67 index and
changes in interlesional distribution of Ki-67.[9 ] This phenomenon is explained in numerous studies and case reports, which can be
used to predict tumor progression, prognosis, and response to targeted therapies.[9 ]
[10 ]
[11 ]
,
For well-differentiated presacral NETs that are localized or have a low burden of
metastases, surgical excision is the recommended course of treatment.[6 ] However, most patients present at an advanced stage of disease. SSAs, PRRT, everolimus,
and tyrosine kinase inhibitors are the treatment options available for metastatic
NENs.[12 ] SSAs such as octreotide or lanreotide have been shown to be effective treatments
in a few studies.[6 ]
[13 ]
[14 ] A few reported cases of presacral NET have been treated with PRRT, all of which
have shown encouraging long-term stabilization and remission.[13 ]
[14 ] In a multi-center cohort, 79% of cases showed clinical benefit (43% responses and
36% disease stabilization) with PRRT, making it the most effective treatment in that
study.[6 ]
Presacral NENs have shown low sensitivity to cytotoxic drugs, and chemotherapy has
often not been effective in treating these tumors, according to some studies.[6 ] In our case, the aggressive histology and multiple liver metastases deemed surgery-inappropriate.
Given a Krenning's score of 4 in most of the lesions and a NET-PET score of 2, PRRT
therapy was considered the best option for the patient. These findings highlight the
importance of using complementary imaging modalities for accurate staging and treatment
planning in NETs.
Conclusion
In summary, this report presents a rare and intriguing example of a primary presacral-precoccygeal
Grade III NET with bilobar liver metastases,characterized with dual-tracer PET/CT
and managed with PRRT. Through this case report, we emphasize the need to consider
NENs as a differential diagnosis in retroperitoneal tumors. The discordant FDG and
SSTR uptake patterns and use of Krenning and NET-PET scoring added value in guiding
optimal management strategies.
