Neuroendocrine Tumor Arising in a Tailgut Cyst: A Rare Presacral Tumor

Introduction

Tailgut cyst is one of a number of congenital benign cystic hamartomas that can develop in the presacral (retrorectal) space; this is defined as the potential space delimited by the rectum anteriorly, the sacrum posteriorly, the peritoneal reflection superiorly, and the perineal muscles inferiorly.^1-3 Synonymous terms used in the literature to describe tailgut cyst include cyst of postanal intestine, mucous secreting cyst, enterogenous cyst, simple cyst, myoepithelial hamartoma of the rectum, and retrorectal cystic hamartoma. Although the precise embryological origin of tailgut cyst is unknown, it is thought to develop from vestiges of the embryological hindgut, a primitive gut that is temporarily present at the caudal portion of the embryo.

Tailgut cyst has been diagnosed over a wide age range (including infancy) but has been reported most commonly in middle-age females.^1-3 Approximately 50% of cases are asymptomatic and discovered incidentally during routine physical examination or radiological investigation for other complaints. Most of the remaining cases present with anal/rectal discomfort or pain. A tailgut cyst may become secondarily infected or rarely undergo malignant change with adenocarcinoma and neuroendocrine tumor (NET) most commonly described.^4,5

A tailgut cyst needs to be distinguished histologically not only from other congenital malformations that develop in the presacral region but also from benign and malignant neoplasms that occur in this location.^3,6-8 In this report, we document the clinical, radiological, and histopathological features of a case of a tailgut cyst in which a NET developed. We also review previous reports of this lesion and discuss the radiological findings and histological criteria that help distinguish this rare tumor from other presacral lesions.

Case Report

A 25-year-old female presented with coccydynia and urinary frequency after a fall. There was no significant past medical history, and laboratory findings were normal.

A plain radiograph of the pelvis demonstrated a sacrococcygeal malformation with absent coccyx and left S4 and S5 sacral elements (Figure 1). Computed tomography (CT) scan confirmed sacral dysgenesis and showed a lobulated soft tissue lesion interposed between the inferior tip of the remaining sacrum and the levator ani muscle. Magnetic resonance imaging (MRI) studies of the lumbar spine, sacrum, and pelvis showed partial agenesis of the left hemisacrum and coccygeal agenesis with associated rightward deviation of the coccyx and distal sacral segments. In addition, there was a 2.5-cm heterogeneous soft tissue mass centered within the right presacral space (Figure 2). The inferior aspect of the mass was associated with several cystic areas, which extended down to the posterior rectal margin. The lesion was isointense to muscle on T1 and intermediate/low signal on T2, exhibiting mild enhancement with contrast (Figure 2). There was distortion of the adjacent bone of the sacrum but no definite bone marrow involvement was noted.

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Figure 1.

X-ray of the pelvis showing sacrococcygeal malformation with absence of the left sacral elements at S4 and S5 and underdevelopment of the right sacral elements (arrowed). The coccyx is absent.

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Figure 2.

Magnetic resonance imaging of the lesion showing (a) sagittal T1 image demonstrating a mass of intermediate T1 signal (arrowed) adjacent to the tip of the segment. There is a background of sacral dysgenesis; (b) sagittal STIR image demonstrating a mass of intermediate/low T2 signals (arrows) with a tiny cystic component superiorly (arrowed); and (c) axial T1 fat-saturated image following intravenous gadolinium shows only mild enhancement of the mass (arrowed).

A CT-guided core needle biopsy of the lesion was carried out. Histology showed that the tumor was composed of proliferating polygonal cells, which focally had a trabecular arrangement. The tumor cells had abundant eosinophilic, occasionally granular cytoplasm and moderately pleomorphic round or oval nuclei. There was no significant mitotic activity. Immunohistochemistry showed that the tumor cells were strongly positive for chromogranin, synaptophysin, epithelial membrane antigen, and cytokeratin with focal weak staining for CD56. There was no specific staining for S100, CD99, CK7, CK20, podoplanin; and the Ki-67 proliferating fraction was 8%. A differential diagnosis of NET or oncocytic neuroendocrine paraganglioma, possibly associated with a developmental cyst or teratoma, was suggested on the biopsy findings.

A whole-body 18F-fluorodeoxyglucose (FDG) positron emission tomography (PET)/CT was performed 6 weeks later. This showed a mildly FDG avid (maximum standardized uptake value [SUV max] = 4.7), 2.5 cm soft tissue nodule abutting the inferior tip of the sacrum (Figure 3). No other disease or malignancy was recognized. The decision of the multidisciplinary team was to continue to follow-up the lesion using MRI and to intervene surgically if the lesion continued to enlarge or if symptoms worsened. Over the next 8 months, 2 MRIs showed that the lesion had increased in size to 2.7 cm and then 3 cm. The patient complained of worsening pain over this period.

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Figure 3.

Axial image for FDG-CT shows a right-sided presacral mass with mild FDG uptake, with a SUV max of 4.7.

Surgical resection was performed using a posterior approach. Partial agenesis was identified in the left sacrum (S4 and S5) with posterior element defect. There was no evidence of bony infiltration, and the tumor was easily mobilized from bone. Two nerve roots, which were adherent to the tumor, were identified and preserved without macroscopic capsular breach. The distal extent of the tumor was difficult to define as there was continuity with thickened surrounding soft tissue for several centimeters; it was noted that the lesion was larger than imaging studies had indicated. Total excision of the tumor was achieved.

Grossly, the excised lesion measured 6.7 × 2 × 1.8 cm, was lobulated, and had both solid and cystic elements. Histologically, the cystic component consisted of multiple cysts lined either by columnar epithelial cells, some of which had clear cytoplasm, or by keratinizing squamous epithelial cells (Figure 4a). Surrounding these cysts, there was mature adipose tissue and focal prominent smooth muscle fascicles within which there were small nerve bundles. The solid component consisted of a proliferation of polygonal/cuboidal cells with granular eosinophilic cytoplasm and round vesicular nuclei (Figures 4b, 4c, and 5a). There was mild nuclear pleomorphism, and there was focal typical mitotic activity (up to 2 per 10 high-power fields; Figure 5b). The cells were arranged mainly in ribbons with occasional small gland-like or rosette-like structures (Figure 5a). There were focal areas of tumor necrosis (Figure 5c), and there was a scattered chronic inflammatory cell infiltrate in the fibrous stroma. There was evidence of perineural invasion (Figure 5d) but no lymphovascular invasion was noted. As in the biopsy, immunohistochemistry showed strong positive staining of tumor cells for cytokeratin, chromogranin, and synaptophysin; the Ki-67 proliferating index was noted to be 20%, and there was no expression of estrogen or progesterone receptor. The tumor was diagnosed as a tailgut cyst in which a Grade 2 NET had developed.

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Figure 4.

Histology of the cystic component of the lesion showing (a) cyst lined by columnar epithelium (arrowed) with underlying discontinuous smooth muscle fascicles (*); (b) cyst lined by columnar epithelium with underlying smooth muscle fascicles, fat, and neuroendocrine tumor (NET; arrowed); and (c) cyst lined by stratified squamous epithelium (arrowed) with NET (*).

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Figure 5.

Histology of solid component of the presacral tumor showing: (a) lobules of neuroendocrine tumor (NET) containing clumps and ribbons of tumor cells; (b) tumor cells with variable plump, occasionally granular cytoplasm and vesicular nuclei. There is typical mitotic activity (arrowed) (c) viable (arrowed) and necrotic (*) areas of NET and (d) perineural invasion (arrowed) by NET.

Discussion

Tumors arising within the presacral space are rare and include developmental cysts, neural tumors, chordoma, and other skeletal tumors, vascular tumors, teratomas, and other neoplasms.^3,6-8 Moreover, 25% to 50% of presacral masses in adults have been reported to be malignant or to have areas of malignant change within them.^3,7,8 In our case, we noted malignant change to a NET in a tailgut cyst.

Radiologically, this case was challenging as it was difficult to characterize precisely the nature of the lesion in the presacral space. On MRI and CT, the lesion was noted to have cystic and solid elements. It was located in the midline, raising the possibility of chordoma or a lesion associated with a developmental cyst. However, it was not possible to characterize the cystic component of the lesion as a tailgut cyst by imaging alone as radiological findings of this lesion overlap with those of other retrorectal cysts including rectal duplication, epidermal cysts, and cystic teratomas.^3,9 Other cystic lesions considered in the radiological differential diagnosis were infection with abscess formation and cystic change within a primary or secondary tumor.^3,6 With such a wide differential, it was essential to establish the nature of the lesion to permit effective medical/surgical management. Excision biopsy of a lesion of uncertain nature in this surgically challenging anatomical location was not considered sensible as it ran the risk of spread of a possibly infective lesion or incomplete excision of a neoplastic lesion. For this reason, a CT-guided biopsy was undertaken. Biopsy histology showed that the lesion was neuroendocrine in nature; however, there was insufficient tissue to permit distinction histologically between NET and paraganglioma or to determine with confidence tumor grade and likely behavior. PET/CT was useful in this regard as it showed that the lesion had a relatively low SUV and that there were no other lesions elsewhere in the body. Aggressive primary and metastatic lesions are usually FDG avid and have a high SUV; in contrast, benign cystic lesions and low-grade tumors have a low SUV. On MRI, the solid component of the tumor was intermediate/low signal on T2. This contrasts with findings in primary NETs, including primary sacrococcygeal NETs, which usually show high intensity on T2-weighted MRI images.^10-13 MRI was employed to monitor progress of the lesion, and it documented continued growth over several months. Both MRI and CT were useful in surgical planning showing the anatomical relation of the lesion to surrounding vessels, nerves, and other structures, in particular the sacral bone which the lesion abutted but did not infiltrate.

Histologically, the cystic component of the lesion showed features in keeping with a tailgut cyst.^1-3 This lesion is usually multicystic and, in contrast to other congenital presacral cysts, lined by a wide range of epithelial cell types including stratified squamous, transitional, simple columnar, or pseudostratified columnar with a predominance of intestinal type epithelium noted.^1,3 The cyst wall commonly contains patchy but well-formed smooth muscle fascicles, which are not arranged in any organized pattern. In contrast, a duplication cyst has a well-formed smooth muscle wall with 2 layers of muscle bundles around a unilocular cyst, which is commonly lined by the epithelium containing villi, crypt, and glands, simulating the normal mucosa of the gut. ⁶ A cystic teratoma or dermoid cyst is also usually unilocular and lined by stratified squamous epithelium with associated adnexal structure. Hjermstad and Helwig specified that histological criteria for the diagnosis of a tailgut cyst are the following: (a) the epithelial lining of the luminal surfaces of the cysts must contain transitional and/or glandular-type (columnar) epithelium, with or without a stratified squamous component; (b) the underlying stroma must be composed of fibrous tissue containing scattered, discontinuous bundles of smooth muscle fibers, that is, without a well-defined muscular layer. ¹ All these features were seen in our case.

Malignant change has been reported to occur in a minority of tailgut cysts with carcinoma, NET, and sarcoma, described in descending order of frequency.^4,5 In our case, malignant transformation was to a NET (or carcinoid tumor). This tumor arises from cells of the diffuse neuroendocrine system, which include enterochromaffin cells in the intestine. These cells are found in the glandular epithelium of tailgut cysts and would appear to represent the cell of origin for NET development. NET tumor cells, as in our case, characteristically express cytokeratin, chromogranin, and synaptophysin.

Twenty-two previous cases of NET developing in a tailgut cyst have been reported (Table 1).^2,12-29 Including our case, 15 have arisen in females. Liang et al found strong estrogen receptors immunoreactivity in squamous and columnar epithelial cells lining cysts as well as in NET cells and on this basis suggested that NET development in a tailgut cyst may be hormone-associated. ²¹ In our case, there was no expression of estrogen or progesterone receptors. In none of the previously reported cases were clinical features of carcinoid syndrome noted. Moreira et al observed that the finding of a malignant transformation in 2 cases of tailgut cyst is associated with a mutation in the tumor inhibitory gene p53. ³⁰ They suggested that the dysplasia-carcinoma sequence in a tailgut cyst was similar to that seen in colonic carcinomas.

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Table 1.

Previous 22 Cases of NET Developing in a Tailgut Cyst.

Reference	Age	Sex	Sacral/Coccyx Invasion	Surgical Resection	Follow-up Term	Preoperative Metastasis	Recurrence	Postoperative Metastasis	Grade	Ki-67
Mora-Guzmán et al 24	56	Female	−	+	7 months	—	−	—	1	<2%
Mitsuyama et al 12	53	Male	+	+	28 months	—	−	Lymph node	2	12.5%
Kim et al 19	49	Male	−	+	24 months	—	−	—	2	4.0%
Charalampakis et al 15	35	Male	−	+	36 months	—	−	—	1	Low grade
Abukar et al 14	61	Male	−	+	NA	—	NA	—	1	Low grade
Damato et al 16	24	Female	+	+	3 months	—	−	—	NA	NA
Spada et al 29	63	Female	−	+	25 months	—	−	—	1	<2%
	41	Female	−	+	79 months	Liver	+	Left adnexa, multiple bone	2	18.0%
Niazi et al 26	28	Female	+	+	12 months	—	−	—	1	Low grade
La Rosa et al 20	73	Female	−	+	5 months	—	−	—	1	<2%
Liang et al 21	51	Female	−	+	NA	—	−	NA	1	<1%
Mathieu et al 23	49	Female	−	+	24 months	—	−	—	NA	NA
Luong et al 22	37	Male	+	−	NA	Liver, lung, nodal, bone	NA	NA	1	2.9%
Song et al 28	41	Female	−	+	13 months	—	−	Liver, brain	NA	NA
Jacob et al 18	42	Female	+	+	NA	—	NA	NA	NA	NA
Mourra et al 25	68	Male	+	+	12 months	—	NA	NA	NA	NA
Prasad et al 2	69	Female	−	+	24 months	—	−	—	NA	NA
Oyama et al 27	52	Male	+	+	6 months	NA	NA	NA	NA	NA
Horenstein et al 17	19	Female	−	+	48 months	—	−	—	NA	NA
	19	Female	+	+	36 months	—	−	—	NA	NA
	21	Female	−	+	13 months	—	+	Breast	NA	NA
Schnee et al 13	61	Male	+	+	24 months	—	−	—	NA	NA

Abbreviations: NET, neuroendocrine tumor; NA, not available.

Surgical resection of NET arising in a tailgut cyst was carried out in all but one of the previously reported 22 cases. Of these, 2 cases recurred and 4 developed distant metastasis.^12,17,18,29 Histological grading of NETs in terms of tumor cell proliferation, differentiation, and necrosis is used in prognostic assessment of NET. ³¹ With regard to presacral NETs, in those cases where the histological grade of the NET was noted, 8 were found to be Grade 1 and 4 were Grade 2.^12,16,20,29 None of the Grade 1 tumors recurred or developed metastasis postoperatively, but this was seen in half of the Grade 2 cases. Therefore, higher histological grade (as in our case) is a significant factor in terms of prognosis. Regular follow-up by CT or MRI is recommended in these cases.