Primary neuroendocrine tumors (NETs) in the presacral region are extremely rare, some of which are caused by other primary tumors or metastatic rectal carcinoids. Nevertheless, cases of NETs have been increasing in recent years. This report describes the first primary neuroendocrine tumor in the presacral region that was found at our hospital within the last five years.

The patient was identified as a 36-year-old woman with a presacral mass and pelvic floor pain. A digital rectal examination revealed a presacral mass with unclear margins and obvious tenderness. Magnetic resonance imaging (MRI) demonstrated a 57 mm × 29 mm presacral lump. An ultrasound-guided needle biopsy confirmed a well-differentiated neuroendocrine tumor. No other primary or metastatic tumors were found.

Comprehensive consideration of our case report and literature reported by others suggests that a conclusive diagnosis of NETs should be based on computed tomography/MRI and pathological examinations. The treatment of primary NETs in the presacral region mainly relies on surgical procedures with follow-up.

Neuroendocrine tumors (NETs) are tumors derived from neuroendocrine cells and peptidergic neurons. Research from the Surveillance Epidemiology and End Results in the United States shows that the incidence of NETs has been increasing. A crude rate of occurrence has been estimated to be 5.85/100000 yearly, globally[1]. Although NETs occur mostly in the gastrointestinal tract (about 60%) and the broncho-pulmonary tract (about 30%), any part of the body may act as the primary site[2-4]. The clinical manifestations of NETs mainly depend on the type of hormones produced[5]. NETs are generally classified according to the Ki67 index and the mitotic index based on the 2010 World Health Organization classification of tumors of the digestive system. NETs are divided into three levels: (G1) mitotic index < 2/10 high-power fields and/or Ki67 index ≤ 2%; (G2) mitotic index 2-20/10 high-power fields and/or Ki67 index 3%-20%; and (G3) mitotic index > 20/ 10 high-power fields and/or Ki67 index > 20%. G1 and G2 identify NETs, and G3 identifies neuroendocrine carcinomas. Over 5 years, the survival rates of patients diagnosed with G1, G2, and G3 NET were 95.7%, 73.4%, and 27.7%, respectively. The prognosis for treatment is based on the degree of differentiation, with the higher degree leading to a better prognosis after treatment[6].

This study reports a case of primary well-differentiated NET in the presacral region. This case is an infrequent case of NET without any other primary tumor or metastatic tumor. In addition, we summarize our results regarding the diagnosis and review the literature on presacral NETs for collecting a comprehensive overview of these very rare tumors.

There was no evidence of metastatic disease and no systemic symptoms or signs of carcinoid syndrome (Figure 4). These results confirmed that this was a primary presacral neuroendocrine tumor of level G2. The patient was advised to receive regular follow-up with her physician and MRI.

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Figure 4 Two months after the resection, only the small fistula was not healed.

On March 11, 2018, a small amount of pus was withdrawn during surgery, and the transanal endoscopic ultrasound showed that this was a solid mass. According to the patient's symptoms and signs, an abscess incision was performed with antibiotic therapy and an ultrasound-guided needle biopsy confirmed a well-differentiated neuroendocrine tumor. On April 24, 2018, the patient underwent a sacrococcygeal tumor resection.

One month later, a whole-body emission computed tomography (ECT) scan was performed after the patient was discharged from the hospital. The whole-body ECT scan did not show high expression of somatostatin receptors in the pleural cavity, abdominal cavity, or pelvis.

The number of reported NET cases has increased in past decades because of improvements in diagnostic modalities and surveillance[7,8], but primary NETs in the presacral region are extremely rare. The sacrococcygeal tumors usually remain clinically silent for a long period of time. A physical mass and pelvic pain are often discovered in the context of nerve root compression. For adults, primary tumors arising in this area include chordomas, myxopapillary ependymomas, para-gangliomas, schwannomas, liposarcomas, and chondrosarcomas, etc.[9,10] Some NETs can also result from the metastasis of rectal carcinoids[11].

As shown in this case, a colonoscopy was not performed and a gastrointestinal tract NET was not considered since NETs in the presacral region are very rare, the patient’s previous symptoms aligned with those of an abscess, and the doctor had little experience in this kind of tumor. Along the lines, masses in the presacral region are difficult to pre-diagnose and are reported as NETs by biopsy much later. The current methods for diagnosing NETs include: (1) Somatostatin-receptor nuclear imaging; (2) CT/MRI; and (3) biopsy. NETs are then classified according to the Ki67 index and the mitotic index. At the same time, NET phenotypes can be divided into functional and non-functional tumors based on the absence or presence of hormones and the presence of hormone-related symptoms[5]. While hormone-related markers were not detected in the current case, it was unclear whether the patient suffered from hormone-related symptoms. Consequently, it was also difficult to distinguish whether the tumor was functional or non-function in this case.

Studies have shown that somatostatin-receptor nuclear imaging should be performed as a baseline preoperative test to detect whether a strong SSRT2A immune response is observed in tumor tissues[12]. In this case, the whole-body ECT did not show high expression of somatostatin receptors in the pleural cavity, abdominal cavity, or pelvis.

For treatment, surgery with follow-up is the main form of treatment for NETs in the presacral region. In addition, somatostatin analogs are appropriate initial therapies for most patients with unresectable metastatic NETs for the control of carcinoid syndrome and inhibition of tumor growth. SSAs are typically selected as the first-line systemic therapy[13-15]. In this case, the symptoms of recovery were pain relief and reduced mass size after pus withdrawal. With the mass remaining in the presacral region and a biopsy likely necessary to determine the pathological tendency, there was a risk for exacerbation and the patient needed a sacrococcygeal tumor resection. Nevertheless, the entire body ECT did not show high expression of somatostatin receptors in the pleural cavity, abdominal cavity, or pelvis. Therefore, there was no evidence of metastatic disease and no systemic symptoms or signs of carcinoid syndrome in the end.

Among the 11 cases of primary tumor in the presacral region that we found to be previously reported, the tumors were located mostly within the sacrum[16-26], with one case located at the anorectal junction[18]. Seven of the eleven patients were male. This prompted us to consider the possibility of a relationship between hormones and tumor location (Table 1)[16-26]. Of note, five were associated with a retrorectal cystic hamartoma which was also known as “Tailgut cyst”[16,18,19,24,25]. From those, three originated from a carcinoid tumor, one from a sacrococcoidal carcinoid[22], one from an anterior tibial neuroendocrine tumor[17], and one from a poorly differentiated large cell carcinoma[26].

The main symptoms of the tumor were pain and the presence of a mass, which are also reported in Table 1. Biopsies generally showed positive tumor markers, but not every case had detected SSRT2A. Surgery was the main treatment. If metastasis was observed, adjuvant therapy was needed mainly for SSAs.

The average follow-up time of reported cases was 41.8 mo[16-26]. Most of the patients were alive at the time of the clinical follow-up control. Patients with well-differentiated presacral NETs that only showed a local disease often showed a good prognosis. There was even a patient who had been followed for 28 years after radiotherapy[17]. However, patients with distant metastases need more investigation.

In summary, primary NETs in the presacral region are very rare, and the clinical presentation often involves pain and the presence of a mass. The imaging performance of these tumors is indistinguishable from that of the other tissue masses in this area, making diagnosis difficult. Currently, the most common diagnostic method for NETs is still based on biopsy. If biopsy confirms a well-differentiated NET, a colonoscopy is needed to exclude metastatic disease. In terms of treatment, surgical excision is needed to remove the primary tumor, and follow-ups are necessary to prevent recurrent attacks and metastases.