Group Title: World Journal of Surgical Oncology 2007, 5:115
Title: Primary presacral neuroendocrine tumor associated with imperforate anus
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Title: Primary presacral neuroendocrine tumor associated with imperforate anus
Series Title: World Journal of Surgical Oncology 2007, 5:115
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Creator: Kim T
Grobmyer SR
Liu C
Hochwald SN
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World Journal of Surgical


B Cntral
nio.. e Central


Case report

Primary presacral neuroendocrine tumor associated with
imperforate anus
Tad Kim', Stephen R Grobmyer', Chen Liu2 and Steven N Hochwald*



Address: 'Division of Surgical Oncology, University of Florida, College of Medicine, Gainesville, FL 32610, USA and 2Departments of Pathology,
Immunology and Laboratory Medicine, University of Florida, College of Medicine, Gainesville, FL 32610, USA
Email: Tad Kim tad.kim@surgery.ufl.edu; Stephen R Grobmyer grobmsr@surgery.ufl.edu; Chen Liu liu@ad.ufl.edu;
Steven N Hochwald* hochwsn@surgery.ufl.edu
* Corresponding author


Published: I I October 2007
World journal ofSurgical Oncology 2007, 5:115 doi:10.1 186/1477-7819-5-115


Received: 27 April 2007
Accepted: I I October 2007


This article is available from: http://www.wjso.com/content/5/l/l 15
2007 Kim et al; licensee BioMed Central Ltd.
This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0),
which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.




Abstract
Background: Presacral masses are unusual growths that have a limited differential diagnosis,
typically not including neuroendocrine tumors (NETs). Classically, NETs are well-differentiated
gastroenteropancreatic tumors of probable benign behavior. These tumors are associated with a
typical morphologic pattern and involve the distal colon, rectum, and genitourinary tract; they are
considered less aggressive, frequently asymptomatic, and rarely cause carcinoid syndrome, even
when metastatic. Neuroendocrine tumors of the presacral region are extremely rare and few have
been described in the literature. They have not been previously reported as being associated with
imperforate anus.
Case presentation: We present an interesting case of a woman with a history of imperforate
anus that was found to have a primary neuroendocrine tumor of the presacral region with no rectal
wall involvement.
Conclusion: We argue that this is a primary gastroenteropancreatic neuroendocrine tumor which
likely originated from cells of hindgut origin that underwent an abnormal migration during
embryonic development.


Background
Neuroendocrine tumors are rare with an incidence rate of
two to five per 100,000, with a higher incidence rate for
African-American men and women. The age distribution
ranges from the second to the ninth decade, with peak
incidence between the ages of 50 and 70. They are the
most common neuroendocrine tumor of the gastrointes-
tinal tract. Around 55% are located in the gastrointestinal


tract and 30% in the bronchopulmonary system. In the
gastrointestinal tract, they tend to arise most commonly
in the small intestine (45%), followed by rectum (20%),
appendix (16%), colon (11%), and stomach (7%) [1].

Neuroendocrine tumors of the presacral region are rare
and usually represent direct extension or metastasis from
primary rectal tumors. Only a handful of primary presac-


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World Journal of Surgical Oncology 2007, 5:115


ral NETs have been reported in the literature and are felt
presumably to derive from hindgut rests, especially given
their histopathologic similarity with primary rectal NETs
[2]. We report a rare case of a primary presacral NET in a
patient with a history of imperforate anus, which is asso-
ciated with abnormalities in hindgut cell migration and
explains the predisposition to develop a classic hindgut-
like gastroenteropancreatic NET in this region.

Case presentation
A 58 year old African-American female reported symp-
toms of abdominal pain and diarrhea. Physical examina-
tion including abdominal, vaginal, cervical and rectal
exam were not contributory. She was found on computer-
ized tomography scan of the abdomen/pelvis to have a
3.2 cm heterogeneous mass anterior to the coccyx, with
central hypodensity and peripheral rim enhancement; the
mass appeared separate from the posterior rectal wall. The
pelvic organs were unremarkable, as no other abnormali-
ties were identified on CT scan. Subsequent CT-guided
biopsy and pathology was consistent with a neuroendo-
crine tumor. Colonoscopy was negative for primary tumor
of the rectum. Transanal endoscopic ultrasound con-
firmed a heterogeneous and hypoechoic mass at 13 cm
from the anal verge, clearly separate from the posterior
rectal wall, with no discernible lymphadenopathy (Figure
1). The posterior vaginal wall was visualized and unre-
markable. Somatostatin receptor scintigraphy scan (SSRS)
revealed uptake in the presacral mass compatible with
neuroendocrine tumor, but no other sites of disease.


Figure I
EUS image of rectal wall and presacral space. Arrow
indicates muscularis propria of the rectum. Tumor is outside
this layer of the bowel wall.


The patient had a history of imperforate anus, having
lived with a colostomy up until ten years of age. At that
time she underwent two coloanal pull through procedures
through both an abdominal and transsacral approach
with creation of a neoanus (Figure 2). Prior to our evalu-
ation, her bowel function was described as having fecal
continence with occasional loose stools and irregular
bowel movements. Of note, she did not have any wheez-
ing, flushing, pellagra, or other symptomatology to meet
a constellation typical of the carcinoidd syndrome". Her
abdominal pain resolved prior to any treatment for her
presacral mass and was felt not related to her NET. There-
fore, her NET was considered an incidental finding.

At operation, she underwent transsacral resection of the
NET with partial removal of the sacrum and removal of
the entire coccyx and mass (Figures 3, 4 and 5). The sur-
gery was complicated by the presence of scar tissue from
previous coloanal pull through procedures. A vertical inci-
sion over the sacrum and coccyx was performed. The sub-
cutaneous tissue was divided down to the sacral bone. The
tumor appeared to extend in the presacral plane up to
about the S4-5 level. Thus, the sacral bone was divided at
the S4 level and then the presacral area was entered and
dissection continued in this plane. Notably, the tumor
was slightly adherent to perirectal fat, but not invading or
emanating from the rectal wall. The tumor was dissected
away without difficulty from the posterior rectal wall and
neoanus.

Postoperatively, the patient did well and was discharged
without complications. She had no new symptoms of
incontinence, rectal, or back pain. Her bowel habits and
loose stools remained at her pre-operative baseline. There


Figure 2
Imperforate anus with neoanus.


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Figure 3
Transsacral approach to presacral mass. Intraoperative
picture showing divided sacral bone (long white arrow),
tumor mass (short white arrow) and underlying rectal wall
(black arrow).



was no evidence of recurrence of disease after 10 months
of follow up.

Pathology
The specimen consisted of a tumor mass with surround-
ing fibrous tissue. There was no evidence of lymphatic tis-
sue in the specimen. Permanent sections revealed
cytologically bland and monotonous cells arranged in
cords or ribbons. Nuclei were round to oval, small, and
occasionally featuring nucleoli. Mitotic rate was low, no
necrosis or angioinvasion were noted. Characteristic "salt-
and-pepper" neurosecretory granules were seen. Immuno-
histochemistry showed positivity for synaptophysin, neu-
ron specific enolase, chromogranin and cytokeratin. The
tumor was negative for S-100 (Figure 6). A paraganglioma
was ruled out since the cells did not exhibit a nesting cell
growth pattern. The cells were not large and did not have
abundant cytoplasm. Intracytoplasmic globules were not
present. The cells were positive for cytokeratin, while par-
agangliomas are usually negative. Most characteristically,


Figure 4
Operative field following resection. Operative field fol-
lowing resection of the tumor, showing divided sacral bone
(white arrow) and underlying rectal wall (black arrow).


S-100 staining is positive and highlights the sustentacular
cells between the solid-sheets of a paraganglioma. The
rejected tumor was negative for S-100.

All of these features confirmed this tumor to be a well dif-
ferentiated neuroendocrine tumor according to the WHO
classification.

Discussion
The presacral space is a region bounded by the rectum
anteriorly, sacrum posteriorly, peritoneal reflection supe-
riorly and perineal muscles inferiorly. The differential
diagnosis of lesions arising in this area include solid
tumors such as teratomas, chordomas, paragangliomas
and ependymomas, or cystic lesions, such as tailgut cysts,
duplication cysts, and dermoid cysts, thought to arise
from the embryological tailgut or neurenteric canal. An
association between tailgut cysts and presacral NETs is
described in the literature. Furthermore, NETs of the pre-
sacral space are histopathologically similar to rectal NETs.
The theory is that the presence of remnant hindgut cells


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World Journal of Surgical Oncology 2007, 5:115


Figure 5
Tumor mass. Resected tumor mass.


may be the basis for development of neuroendocrine
tumors in this region.

A review of the literature revealed 15 prior cases of pri-
mary presacral NET [2-14] (Table 1). There may be a
female preponderance with these rare tumors as two-
thirds of the cases have been seen in women. Seven previ-
ously reported cases were associated with tailgut cysts and
two were associated with sacrococcygeal teratomas. Inter-
estingly, we report the first case in the literature of this
tumor arising in a patient who had a history of imperfo-
rate anus.

Incomplete migration and/or fusion of the urorectal sep-
tum with the cloacal membrane lead to persistence of the
cloaca and/or fistulae. Imperforate anus results from per-
sistence of the dorsal cloacal membrane [15,16] and ven-
tral persistence causes absent urethral and vaginal
openings. There appears to be a 'malfunctioning of cells


Figure 6
H&E, synaptophysin, chromogranin and S-100 staining of the rejected tumor. A) H&E stain showing uniform cells
arranged in chords. B) Synaptophysin and C) chromogranin staining were strongly positive. D) S- 100 staining was negative
(positive stain on the photograph represents a nerve which serves as an internal control).




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World Journal of Surgical Oncology 2007, 5:115


Table I: Previous case reports describing the presence of a presacral carcinoid


Case number


Author(reference)


[3]
[4]
[5]
[6]
[7]
[2]
[2]
[2]
[8]
[9]
[10]
[I I]
[12]
[13]
[14]
This report


ingressing from an end-stage primitive streak' that leads to
defective development of the dorsal cloaca [17]. Our pos-
tulate is that incomplete or impaired migration of hindgut
cells led to both our patient's imperforate anus, and the
predisposition to develop a primary neuroendocrine
tumor from persistent hindgut rests in the presacral
region. In fact, there was no evidence suggesting that the
tumor emanated from the rectal wall. Colonoscopy failed
to show a primary rectal tumor. EUS and CT images
clearly demonstrate the tumor location outside the rectal
wall. At surgery, the tumor was found to not involve the
rectal wall. A somatostatin receptor scintography scan
ruled out the chance that this tumor was metastatic from
elsewhere as primary uptake was found in the presacral
mass with no uptake in other sites. While carcinoid
tumors can arise from other pelvic organs, besides the rec-
tum, there was no evidence of primary tumors in the
vagina, cervix or ovaries.

Our patient presented initially with abdominal pain and
diarrhea, and was found to have an incidental presacral
mass on CT scan. It was determined that her presenting
symptoms were not related to the presence of this tumor
but to a brief episode of nonspecific colitis. The neuroen-
docrine tumor was diagnosed after an appropriate diag-
nostic work-up following the most current guidelines
[18,19]. Classically, gastroenteropancreatic neuroendo-
crine tumors are indolent and do not manifest symptoms
unless they are either secretary tumors or are locally
advanced to cause obstructive symptoms or have metasta-
sized. The carcinoid syndrome, characterized by such
symptoms as flushing, diarrhea, and wheezing, usually
results from liver metastasis and subsequent release of
vasoactive compounds such as serotonin [18]. The soma-
tostatin receptor scintigraphy scan demonstrated no
metastasis, nor did our patient exhibit a constellation of


Age/sex

61/Male
35/Female
18/Female
61/Male
NA/Female
19/Female
19/Female
21/Female
42/Female
69/Female
52/Male
68/Male
41/Female
NA/NA
37/Male
58/Female


Associated anomaly

Sacrococcygeal teratoma
Presacral teratoma
Tailgut cyst
None
None
Tailgut cyst
None
None
None
Tailgut cyst
Tailgut cyst
Tailgut cyst
Tailgut cyst
Tailgut cyst
Sacrococcygeal teratomas
Imperforate anus


symptoms to suggest an actual carcinoid syndrome. Fur-
thermore, she did not present with obstructive-type symp-
toms secondary to the mass. The histopathologic findings
were of a well-delineated mass composed of highly differ-
entiated neuroendocrine cells, displaying no angioinva-
sion and with a low mitotic index. The tumor cells were
positive for chromogranin, synaptophysin, cytokeratin
and negative for S-100. A paraganglioma was ruled out
based on these findings and the lack of the typical histo-
logic appearance. Our patient's clinical picture and above
histopathologic findings are all consistent with the stand-
ard World Health Organization (WHO) classification of a
well-differentiated gastroenteropancreatic neuroendo-
crine tumor of probable benign behavior [18,20,21].

In conclusion, we report the first case of primary presacral
neuroendocrine tumor, of likely gastroenteropancreatic
and, more specifically, originating from abnormal migra-
tion of hindgut cells in a patient with imperforate anus.
There was no tumor involvement of the rectal wall on
preop EUS or CT imaging or during surgical resection. The
presence of previous surgery in the pelvis to create a neoa-
nus resulted in increased complexity when determining
the treatment options for this patient. However, as dem-
onstrated by this case for tumors below the S3 level,
despite previous surgery in the low pelvis, a transsacral
approach for resection should be feasible, with careful
preservation of the rectal wall [8].

Competing interests
The authors) declare that they have no competing inter-
ests.

Authors' contributions
TK- Participated in the design of the study and helped to
draft the manuscript. SRG- Conceived of the study and


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World Journal of Surgical Oncology 2007, 5:115


participated in its design and coordination and help to management of gastroenteropancreatic neuroendocrine
draft the manuscript. SNH- conceived of the study, partic- tumous (including bronchopulmonary and thymic neo-
plasms). Part II-specific NE tumour types. Acta Oncol 2004,
ipated in its design and coordination and helped to draft 43:626-636.
the manuscript, performed the revisions. All authors read 21. Rindi G, Capella C, Solcia E: Introduction to a revised clinico-
pathological classification of neuroendocrine tumors of the
and approved the final version of the manuscript. gastroenteropancreatic tract. Q] Nucl Med 2000, 44:13-21.


Acknowledgements
Written informed consent was obtained from the patient for publication of
this case report.

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