Liver metastases of a neuroendocrine tumor arising from a tailgut cyst treated with interventional locoregional therapies: a case report and review of the literature on recurrent cases

Abstract

A tailgut cyst is a rare, developmental cyst occurring in the presacral space. Although primarily benign, malignant transformation is a possible complication. Herein, we report a case of liver metastases after resection of a neuroendocrine tumor (NET) arising from a tailgut cyst. A 53-year-old woman underwent surgery for a presacral cystic lesion with nodules in the cyst wall. The tumor was diagnosed as a Grade 2 NET arising from a tailgut cyst. Thirty-eight months after surgery, multiple liver metastases were identified. The liver metastases were controlled with transcatheter arterial embolization and ablation therapy. The patient has survived for 51 months after the recurrence. Several NETs derived from tailgut cysts have been previously reported. According to our literature review, the proportion of Grade 2 tumors in NETs derived from tailgut cysts was 38.5%, and four of the 5 cases of Grade 2 NETs (80%) relapsed, while all eight cases of Grade 1 NETs did not relapse. Grade 2 NET may be a high-risk group for recurrence in NETs arising from tailgut cysts. The percentage of Grade 2 NETs in tailgut cysts was higher than that of rectal NETs, but lower than that of midgut NETs. To the best of our knowledge, this is the first case of liver metastases of a neuroendocrine tumor arising from a tailgut cyst that was treated with interventional locoregional therapies, and the first report to describe about the degree of malignancy of neuroendocrine tumors originating from tailgut cysts in terms of the percentage of Grade 2 NETs.

Introduction

Tailgut cysts are rare, congenital, developmental cysts usually present in the presacral space. Complications of tailgut lesions include infection, bleeding, and malignant transformation [1], and accurate diagnosis is difficult. Given the risk of malignancy, resection is considered the primary treatment [2]. The frequency of malignant transformation is reportedly 2–13%. The most common malignant transformation reported in a tailgut cyst is adenocarcinoma. However, other types, including neuroendocrine tumors (NETs) and squamous cell carcinoma, have also been reported [3].

Herein, we report a case of NET with multiple liver metastases that occurred postoperatively, and was controlled by interventional locoregional therapies such as transcatheter arterial embolization (TAE) and ablation therapy. In addition, we reviewed 33 cases of NETs derived from tailgut cysts [1–19] and determined the risk of recurrence and relapse-free survival (RFS) using statistical analyses.

Case report

A 53-year-old woman was referred to our department for the treatment of a cystic lesion in the pelvis. The patient had a history of hypertension and stroke, but no subjective symptoms. No abnormalities were noted in physical and blood examinations, including tumor markers (carcinoembryonic antigen, carbohydrate antigen 19–9, and squamous cell carcinoma antigen). Contrast-enhanced computed tomography revealed a 7.0 × 6.9 cm cystic tumor with enhanced nodular lesions (Fig. 1a). The cystic lesion was located posterior to the rectum with a clear boundary on magnetic resonance imaging (MRI) (Fig. 1b, c). Therefore, we suspected malignancy. For a definitive diagnosis, resection was performed through a transabdominal approach.

Fig. 1.

a Contrast-enhanced computed tomography shows a 7.0 × 6.9 cm cystic tumor in the presacral space and enhanced solid part in the cystic tumor (indicated by arrows). b, c The cystic tumor is in contact with the rectum (indicated by arrowheads), but the border is clear on T2-weighted magnetic resonance image

Macroscopically, the resected specimen was a thin-walled simple cyst measuring 7.8 × 6.5 × 6.0 cm. It contained solid part with necrosis (Fig. 2). Histologically, the cyst lumen was covered with stratified squamous epithelium. The wall contained peripheral nerves, smooth muscles, and mature adipose tissue, consistent with a tailgut cyst (Fig. 3) [20]. The solid part showed atypical columnar tumor cells with oval or round nuclei including coarse-grained chromatin in a cord- or ribbon-like arrangement. Immunohistochemically, the tumor cells were diffusely positive for cytokeratin AE1/AE3, synaptophysin, and CD56, and negative for chromogranin. The Ki-67 index was 5.4% and mitosis occurred in 4–5 cells/2 mm². The solid part was diagnosed as Grade 2 NET (Fig. 3) [21]. The tumor cells infiltrated the cyst wall and lymphovascular invasion was noted. Based on these findings, NET arising from a tailgut cyst was diagnosed.

Fig. 2.

Macroscopic appearance of the resected cystic tumor. On the cut surface, the cyst contains necrotic tissue with hematoma in the solid part, and the cyst wall is stained yellow-to-brown color due to hemosiderin deposition. Tumor cells are observed in a portion of the solid part (indicated by arrowheads)

Fig. 3.

Histological appearance. a The cyst wall and tumor component (× 1.25). Tumor cells are intermingled with hemorrhage and necrosis. b Stratified squamous epithelium found in the cyst wall (× 40). c Smooth muscle, nerve bundle, and adipose tissue observed in the cyst wall (× 10) in this lesion. d Hypermagnification of tumor cells showing nuclear atypia and hyperchromatic nuclei with corded and ribbon-like arrangements (× 40). The mitosis is observed in 4–5 cells/2 mm². Granular and coarse chromatin characteristics of neuroendocrine tumor are observed. e Immunohistochemistry, synaptophysin is diffusely positive. f Ki-67 index is 5.4% and mitosis is observed in 4–5 cells/2 mm²: from the above observations, the diagnosis of a grade 2 neuroendocrine tumor was made

Thirty-eight months after surgery, gadolinium-ethoxybenzyl-diethylenetriamine pentaacetic acid (Gd‐EOB‐DTPA)-enhanced MRI showed four liver metastases, ranging from 3 to 9 mm in S3, S4, S6, and S8 (Fig. 4). The patient refused both surgery and systemic chemotherapy. As the metastatic lesions were increasing in size, TAE with bland microspheres of 100–300 μm (Embosphere, Nippon Kayaku, Tokyo, Japan) and microwave ablation (Mimapro, Sheen Man Co. Ltd., Osaka, Japan) were performed. However, recurrences occurred after the initial treatment. Subsequently, five TAEs and three microwave or radiofrequency ablations were performed. The liver metastases disappeared after these interventional locoregional therapies. The patient continues to survive 51 months after the first recurrence.

Fig. 4.

Gadolinium-ethoxybenzyl-diethylenetriamine pentaacetic acid-enhanced hepatocyte-phase magnetic resonance image shows liver metastases ranging from 3 to 9 mm at S3, S4, S6, and S8 (indicated by arrows): a S3 and b S4

Discussion

Tailgut cysts are primarily found as presacral cystic lesions and are difficult to diagnose preoperatively. Surgical resection of the presacral lesion is recommended due to the risk of malignant transformation. The main histological type of malignant transformation in a tailgut cyst is reportedly adenocarcinoma, while other types including NETs and squamous cell carcinomas have also been observed [3]. Based on our literature search on PubMed, 33 cases of NETs derived from tailgut cysts were observed in 30 published reports [1–19]. Previous reports focused on diagnosis and none investigated the prognosis and treatment.

In 34 cases, including our case, the majority of patients were women (68.8%). The median age was 41 (18–73) years for women and 57 (35–77) years for men. Two patients had distant metastases at the initial diagnosis, and eight patients had metastatic recurrence postoperatively. The most frequent distant metastatic organ was the liver (five cases), followed by the brain, bone, and mammary gland (two cases each). Lymph-node recurrence was also observed in three cases. We reviewed 13 cases that underwent curative surgical resection with no missing information on the follow-up time after surgery and NET grade (Table 1). In the literature review, the proportion of grade 2 tumors in NETs derived from tailgut cysts was 38.5% (5/13), and four of the 5 cases of Grade 2 NETs (80%) relapsed, while all eight cases of Grade 1 NETs did not relapse. Grade 2 NET may be a high-risk group for recurrence in NETs arising from tailgut cysts. In several studies, grade 2 tumors have been reported as a risk factor for NET recurrence. However, the proportion of grade 2 tumors varies depending on the primary site of NETs. Grade 2 tumors have been observed in 30–76% [22, 23], 15–60% [24, 25], and 8–9% [26, 27] of pancreatic, midgut, and rectal NETs, respectively. Some studies reported the 5-year RFS rates for pancreatic, midgut, and rectal tumors to be 42–84% [22–24], 61–82% [24–26], and 94–98% [27–29], respectively. These findings suggest a relationship between the proportion of Grade 2 NETs and the degree of NET malignancy at each primary site.

Table 1.

Cases that underwent curative surgical resection with no missing information on the follow-up time after surgery and NET grade

Reference	Years	Age (y)	Sex	Grade of NET	Ki-index (%)	Recurrence	Follow-up time after the surgery (months)
La Rosa et al. [8]	2010	73	F	1	< 2	Absent	5
Niazi et al. [10]	2011	28	F	1	< 2	Absent	12
Spada et al. [9]	2011	63	F	1	< 2	Absent	25
Kim et al. [18]	2014	49	M	2	4	Absent	24
Charalampakis et al. [1]	2014	35	M	1	< 2	Absent	36
Mitsuyama et al. [11]	2015	53	M	2	12.5	Present	10
Acar et al. [12]	2017	39	F	2	2–5	Present	48
Mora-Guzman et al. [13]	2017	56	F	1	< 2	Absent	7
Al Khaldi et al. [3]	2018	53	M	2	5–10	Present	2
Lee et al. [15]	2018	33	F	1	1–2	Absent	7
Singh et al. [17]	2019	63	M	1	< 1	Absent	48
Kodera et al. [16]	2020	68	F	1	< 2	Absent	24
Present case	2021	53	F	2	5.4	Present	38

We reviewed cases of liver metastases of NETs originating from tailgut cysts. Details of six cases, including our case, with information on treatments are presented in Table 2. We observed three cases with chemotherapy (5-fluorouracil (5-FU), streptozocin (STZ), carboplatin and etoposide, and everolimus), one case with somatostatin analog therapy, and three cases with peptide receptor radionuclide therapy (PRRT). Furthermore, surgical resection of liver metastases was performed in one case, and TAE was only performed in our case. All chemotherapy regimens were refractory, except a regimen combining 5-FU and STZ, which showed tumor control for approximately 12 months. The tumor control rates for somatostatin analog therapy and PRRT were as high as 75–100%. In one case with PRRT, the effect on the tumor was complete response. Thus, PRRT appears to be the most promising treatment in cases with somatostatin receptor-positive lesions. In our case, we performed the combination treatment with TAE and ablation, because the recurrent lesions were localized to the liver. Additionally, at the time the recurrence was identified, PRRT was not provided to our patient, because it was not approved by the Japanese insurance system. Currently, the treatment with PRRT is approved by the Japanese insurance system.

Table 2.

Neuroendocrine tumor arising from tailgut cyst with distant metastases

References	Years	Age (y)	Sex	Size of cyst (mm)	Grade of NET	Ki-index (%)	Preoperative distant metastases	Postoperative metastases
Song et al. [5]	2004	42	F	20	NA	NA	–	Liver, brain
Wöhlke et al. [19]	2011	55	F	70	2	20	Liver	Presacral lymph node, bone
Spada et al. [9]	2011	41	F	NA	2	18	Liver	Left adnexa, bone
Al Khaldi et al. [3]	2018	53	M	76	2	5–10	–	Inguinal lymph node, lung, liver
Erdrich et al. [14]	2018	77	M	63	2	8.6	Liver	–
Present case	2022	53	F	78	2	5.4		Liver

References	Duration from surgery to recurrence (months)	Treatment for metastases	Follow-up time from the first treatment (months)
Song et al. [5]	12	CT (5-FU)b	15
Wöhlke et al.	–	PRRTa,b	30
Spada et al. [9]	–	CT (carboplatin and etoposide)b, PRRTa, adrenalectomya, SSAa, PPRTa	78
Al Khaldi et al. [3]	2	CT (5-FU and streptzocin)a,b, CT (everolimus), PRRTc	46
Erdrich et al. [14]	–	NA	NA
Present case	38	TAEa,b, Ablationa	75

CT chemotherapy, NA not available, NET neuroendocrine tumor, PRRT peptide receptor radionuclide therapy, SSA somatostatin analog, TAE transcatheter arterial embolization, 5-FU 5- fluorouracil, M male, F female

^aTreatment that was effective in controlling tumors

^bInitial treatment for distant metastases

^cTumor control efficacy was unknown

Multimodality treatment, including surgery, is recommended for the treatment of NETs of gastrointestinal origin [30]. Several randomized controlled trials evaluated cytotoxic and somatostatin analog therapy for unresectable recurrent NETs. These demonstrated that everolimus and somatostatin analog were associated with improved progression-free survival [31, 32]. TAE and thermal ablation have been reported to be useful for topical treatment, as an alternative for surgery, particularly for liver metastases of NETs. [33]. The overall survival after treatment for liver metastases of NETs has been reported to be 35–60 months [34]. In the present case, the patient has survived 51 months since the initial treatment with TAE. Therefore, interventional locoregional therapies such as TAE and ablation therapy may also be useful in the treatment of liver metastases of NETs arising from tailgut cysts as well as from other primary sites.

In conclusion, we presented the first case of postoperative liver metastases of NET arising from a tailgut cyst that was treated with interventional locoregional therapies. TAE and ablation for liver metastases of NETs derived from tailgut cysts could also be effective for NETs derived from other organs. Grade 2 NETs arising from tailgut cysts may be at a high risk of recurrence and should be proactively followed up. Additionally, we suggest that the malignancy of NETs arising from the tailgut cysts is better than that of rectal NETs and is compatible to that of midgut and pancreatic NETs in terms of the percentage of Grade 2 NETs.

Abbreviations

NET

Neuroendocrine tumors

TAE

Transcatheter arterial embolization

RFS

Relapse-free survival

MRI

Magnetic resonance imaging

Gd‐EOB‐DTPA

Gadolinium-ethoxybenzyl-diethylenetriamine pentaacetic acid

5-FU

5-Fluorouracil

STZ

Streptozocin

PRRT

Peptide receptor radionuclide therapy

Author contributions

Conception and design: KF, FK, and HK. Analysis and interpretation of the data: KF, FK, HK, SO, YI, TT, TT, TS, SH, TU, CO, HN, TT, and MS. Drafting of the manuscript: KF, FK, and YI. Final approval of the manuscript: KF, FK, HK, SO, YI, TT, TT, TS, SH, TU, CO, HN, TT, and MS.

Data Availability

The data that support the findings of the study are available on request from the corresponding author. The data are not publicly available due to privacy reasons.

Declarations

Conflict of interest

The authors declare that they have no conflict of interest.

Research involving human participants and/or animals

As this article is a case report, we did not need the ethics approval of our institutional review board per our institutional policy. This article does not contain any study with animals performed by any of the authors. All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

Informed consent

Written informed consent was obtained from the patient for the publication of this case report and any accompanying images.