Rare-Site Primary Presacral-Precoccygeal Grade III Neuroendocrine Tumor with Bilobar Hepatic Involvement: A Case Description with Diagnostic and Therapeutic Considerations

Abstract

Primary presacral/precoccygeal neuroendocrine tumors (NETs) are extremely uncommon, however, can present with widespread metastases. We herein report the imaging and therapeutic perspectives in a 45-year-old female patient of presacral-precoccygeal NET who presented with low back pain. Magnetic resonance imaging of the lumbosacral spine showed a soft tissue mass in the presacral region extending into the S1–S2 neural foramen, along with another soft tissue mass in the precoccygeal region. Incidentally, multiple well-defined lobulated hyperintense lesions were detected in both lobes of the liver. ¹⁸F-FDG PET/CT (¹⁸F-fluorodeoxyglucose positron emission tomography/computed tomography) demonstrated tracer accumulation in the primary soft tissue masses in the presacral and precoccygeal regions, while the liver lesions did not show significant tracer uptake. A CT-guided biopsy of the presacral mass confirmed a well-differentiated NET, Grade III, with a Ki-67 index of 20 to 22%. ⁶⁸Ga-DOTATATE PET/CT revealed somatostatin receptor expression in the presacral and precoccygeal masses, as well as in the bilobar liver lesions. Due to the tumor's presentation with widespread metastases, surgery was deemed inappropriate, and peptide receptor radionuclide therapy was planned.

 

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Keywords

neuroendocrine tumors - presacral-precoccygeal grade III NET - ¹⁷⁷Lu-DOTATATE - ⁶⁸Ga-DOTATATE PET/CT - ¹⁸F-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), ⁶⁸Ga-DOTATATE/DOTANOC/DOTATOC PET, ¹⁸F-fluorodeoxyglucose positron emission tomography/computed tomography (¹⁸F-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.

 

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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 ¹⁸F-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 ¹⁸F-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 ¹⁸F-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 ¹⁸F-FDG PET/CT, contrast-enhanced CT, and ⁶⁸Ga-DOTATATE PET/CT images, respectively. ¹⁸F-FDG-concentrating (SUVmax: 4.9) and SSTR-avid (Krenning's score: 4) soft tissue mass in presacral region (red arrow), mildly ¹⁸F-FDG-concentrating (SUVmax: 3.2) and SSTR-avid (Krenning's score: 4) soft tissue mass in precoccygeal region (green arrow), and non-¹⁸F-FDG-concentrating and SSTR avid (Krenning's score: 4) multiple bilobar liver lesions, reference lesion in segment VIII (blue arrow). ¹⁸F-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%. ⁶⁸Ga-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 ¹⁷⁷Lu-DOTATATE therapy.

 

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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, ⁶⁸Ga-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.

 

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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.

 

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Conflict of Interest

None declared.

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Publication History

Article published online:
21 July 2025