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\begin{document}

\title{Malignant Transformation of Tailgut Cyst to Squamous Cell Carcinoma, a
rare case with poor outcome}



\author[1]{Mahsa Moshtaghian}%
\author[1]{Reza Shahsiah}%
\author[1]{Fatemeh Jafari}%
\author[2]{Mahdi Aghili}%
\affil[1]{Tehran University of Medical Sciences}%
\affil[2]{Tehran University of Medical Sciences School of Medicine}%


\vspace{-1em}



  
  \date{June 17, 2024}


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\selectlanguage{english}
\begin{abstract}
Tailgut cyst, a type of retro-rectal cyst, is a rare condition requiring
evaluation for malignant transformation. We report a case of squamous
cell carcinoma arising in the retro-rectal cyst, in a 51-year-old female
who underwent incomplete resection of the cyst and chemo-radiotherapy,
subsequently became locally recurred and metastatic.%
\end{abstract}%



\sloppy


Title

\textbf{Malignant Transformation of Tailgut Cyst to Squamous Cell
Carcinoma, a rare case with poor outcome}

Running title: \textbf{Malignant transformation of a Tailgut Cyst}

Authors:

\begin{enumerate}
\tightlist
\item
  \textbf{Mahsa Moshtaghian} \textsuperscript{a,b}
\item
  \textbf{Reza Shahsiah} \textsuperscript{c}
\item
  \textbf{Fatemeh Jafari} \textsuperscript{a,b}
\item
  \textbf{Mahdi Aghili} \textsuperscript{a,b}
\end{enumerate}

Affiliations:

\textsuperscript{a} Radiation Oncology Research Center, Cancer Research
Institute, Tehran University of Medical Sciences, Tehran, Iran

\textsuperscript{b} Department of Radiation Oncology, Cancer Institute,
Imam Khomeini Hospital Complex, Tehran University of Medical Sciences,
Tehran, Iran

\textsuperscript{c} Department of pathology, Tehran University of
Medical Sciences, Tehran, Iran

Correspondence to:

Mahsa Moshtaghian, MD (email:\emph{m-moshtaghian@razi.tums.ac.ir}),
(Address: Department of Radiation Oncology, Cancer Institute, Imam
Khomeini Hospital Complex, Qarib Street, Keshavarz Blvd., Tehran, Iran),
(Phone: +982161192585)

Authors declare no conflicts of intrest.

\emph{Figures:} 3

Consent

\textbf{Written informed consent was obtained from the patient's next of
kin to publish this report in accordance with the journal's patient
consent policy.}

\textbf{Malignant Transformation of Tailgut Cyst to Squamous Cell
Carcinoma, a rare case with poor outcome}

\textbf{Introduction}

Tailgut cysts (TGCs), a type of epidermoid cyst developing in the
retro-rectal region, are rare conditions that are often asymptomatic and
require further evaluation for malignant transformation if they become
symptomatic or even incidentally discovered. Symptoms can range from
asymptomatic to local effects on adjacent organs or infectious
processes.

Tailgut cysts may have a malignant transformation and present with
different pathologies that can show different behavior and outcome.
Malignant transformations are often adenocarcinomas and neuroendocrine
forms. Squamous Cell Carcinoma, like what we will report in our case, is
very rare and has been reported in only four patients so far.

\textbf{Case report}

A 51-year-old woman presented with pelvic pain, constipation, and fecal
urgency complaints. She had no past medical history or any familial
history.

In rectal examination she had a palpable rectal mass in distal part with
mild tenderness in touching. The rectal lumen was intact with flat
mucosa on colonoscopy, but posteriorly, the rectum seemed under external
pressure.

The abdominopelvic computed tomography(CT) scan revealed a hypodense
cystic lesion measuring 99*93 mm in the left retro-rectal region without
contrast enhancement, causing a rectal deviation to the right side.
(Figure 1)\selectlanguage{english}
\begin{figure}[H]
\begin{center}
\includegraphics[width=0.70\columnwidth]{figures/image1/image1}

\end{center}
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Figure 1. Contrast computed tomography reveals a hypodense cystic lesion
measuring about 99*93 mm in the left retro-rectal region (arrowhead)
without contrast enhancement, causing a rectal deviation to the right
side.

She underwent surgical cystectomy drainage and incomplete resection of
the cyst. Histopathologic examination showed a cyst wall containing
smooth muscle bundles lined by squamous or columnar epithelium. The
stroma was infiltrated by nests of neoplastic cells with vesicular
nuclei and abundant eosinophilic cytoplasm with foci of keratin-like
material (Figure 2). In immunohistochemical staining, CK7, HMWCK, and
P63 were positive, but CK20 was negative. These findings were compatible
with squamous cell carcinoma arising on tailgut cyst.\selectlanguage{english}
\begin{figure}[H]
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\includegraphics[width=0.70\columnwidth]{figures/image2/image2}

\end{center}
\end{figure}

Figure 2. A: Cyst wall containing smooth muscle bundles and lined by
squamous and columnar epithelium (H\&E, x100). B: The stroma is
infiltrated by nests of neoplastic cells with vesicular nuclei and
abundant eosinophilic cytoplasm with foci of keratin-like material.

A Post-operative CT scan reveals no gross tumor residue. According to
the multidisciplinary team's recommendation, the patient was decided to
undergo radiation therapy similar to the anal canal radiation fields; 36
Gy in 20 fractions to the pelvic and inguinal lymph nodes and then up to
54 Gy to the surgical bed, concurrently with Capecitabine.

Three months after the treatment was completed, she complained of
continued pelvic pain. On the pelvic MRI, there was a 23*20*28 mm
multi-loculated cystic, solid lesion in the pre-coccygeal space in the
midline posterior cavity suspicious of residual disease or recurrence.
These results were confirmed by FDG-PET/CT scan; high SUV (17) presacral
mass indicating malignancy and also a small soft tissue lesion in the
anterior pelvic wall (SUV=6.3) suspicious for metastatic disease.
(Figure 3)\selectlanguage{english}
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\includegraphics[width=0.70\columnwidth]{figures/image3/image3}

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Figure 3. FDG-PET/CT scan A: There is an FDG avid (SUVmax = 17.0) soft
tissue mass in the pre-coccygeal region (arrows) measuring 3.8 x 3.0 cm.
B: There is an FDG avid (SUVmax = 6.3) soft tissue lesion in anterior
pelvic wall (blue arrow) measuring 1.3 x 1.2 cm reveals metastatic
lesion.

She underwent CT guided biopsy from the per-sacral mass, and it revealed
poorly differentiated carcinoma.

Due to the multiple recurrent lesions and the presence of metastasis,
she was referred for chemotherapy. There was no treatment response
despite the numerous chemotherapy courses, and the disease progressed.
Her pelvic pain was difficult to control by the nerve block and
palliative measures. Finally, one year after the diagnosis, she,
unfortunately, passed away due to the progression of metastatic
abdominopelvic lesions.

\textbf{Discussion}

Tailgut cysts (TGCs), also known as retro-rectal cystic hamartoma (RCH)
or epidermoid cysts in presacral and retro-rectal space, are cystic
lesions that occur due to developmental abnormalities in the embryonic
pathways and they are the remnants of the embryonic hindgut. (1) Tailgut
cysts are very rare, have an incidence rate of 1 of 40,000--63,000
patients, and are more common in middle-aged women. (2,3)

Histologically, TGCs are multilocular cysts with squamous, mucinous,
simple, pseudostratified ciliated, or transitional lining cells or may
contain bundles of smooth muscle in the cyst's wall. Meningeal tissue,
thyroid tissue, and glomus bodies have also been reported (4).

The clinical manifestations of TGC can range from asymptomatic to
atypical clinical symptoms because of compressive effects of mass,
including constipation, rectal filling, dyschezia, infertility, dysuria,
and abdominal pain. The infectious process like repeated urinary tract
infection, abscess, and fistula formation may also occur with symptoms
including high fever, pain, and frequent micturition. (5--11)

Differential diagnoses that should be considered for retro-rectal masses
include anal gland cyst, duplication cyst, endometriotic cyst, sacral
meningocele, or pilonidal sinus. (4)

Although FNA or other cytological biopsies have been recommended in some
older articles, tissue sampling has not been recommended in more recent
data due to the risk of the tumor spreading into the abdominal cavity,
and the role of imaging in preoperative diagnosis has become more
prominent. (12) Tissue biopsy might be considered only for patients with
high surgical risks who are not a candidate for surgery. We may have to
find out about the pathology through the biopsy in this setting. (9)

CT and MRI are required to diagnose and characterize differential
diagnosis and treatment strategies. (10,11) Malignant and benign lesions
show different characteristics on MRI examination, especially on
T2-weighted images (12). Sarkar et al. believed that radiological
examination could contribute to diagnosing cystic lesions in the
presacral space; however, the definitive diagnosis can only be achieved
by surgical exploration and histological examination (13).

Malignant transformation in TGCs can occur but are rare, and the clear
pathogenesis remains unknown. The most frequent histological types
include adenocarcinoma and neuroendocrine tumors. Others include
carcinoid tumors, squamous cell carcinoma, endometrioid carcinoma,
adenosquamous carcinoma, transitional cell carcinoma, and sarcoma were
rarely reported (5,9,14). Squamous cell carcinoma was previously
reported in just four reports (15--17), and our case was the fifth.

Generally, the reported incidence rate of malignant tumors arising from
epidermoid cysts is 0.011 \% --2.2 \% (6,7). However, a higher rate of
malignant transformation has been reported in some reviews of TGCs. Feng
Liang et al. have mentioned in a review article that about 30 \% of
reported cases of TGCs in the literature were malignant. (8) It could be
probably due to the higher chance of developing symptoms in these
malignant cases. Therefore they are more likely to be diagnosed.
Similarly, K. Nicoll et al. have also reported that the overall rate of
neoplastic transformation was 26.6\% and noted the low metastatic rate
in these malignancies. (18) We have found only 2 cases of metastasis in
the literature review which were SCC and NET. (15,19)

The treatment of choice for all TGCs is complete surgical excision.
Additional chemotherapy or radiation therapy treatments are given if
malignancy is detected based on the pathology report. The minimally
invasive transanal or transrectal approach is indicated for small
low-lying, non-infected cases because of the risk of pelvic infection in
these surgical approaches (20). A transabdominal surgery approach is
preferred in patients with suspected malignancy because of better access
and visualization for a complete oncological surgery(20).

In the case of pre-rectal cysts, of which Tailgut cysts can be one, the
possibility of malignant transformation should be considered, and in
this case, surgical resection and complete evacuation of the cyst with a
suitable margins may be the best measure for potential diagnosis and
treatment of these lesions. In our case, complete oncological surgery
was not performed, leading to early disease progression and metastasis
despite chemo-radiation therapy. This case highlights the critical role
of extensive surgery, and if it is not expected to be possible,
neoadjuvant treatments may facilitate this goal. If surgery is done
first, it would be logical to consider adjuvant therapies. Eventually,
there is no conclusive guideline or standard policy on adjuvant
treatment indications in malignant tailgut cysts. Further research is
needed, so treating such patients in a multidisciplinary team is
reasonable.

\textbf{References}

1. Prasad AR, Amin MB, Randolph TL, Lee CS, Ma CK. Retrorectal cystic
hamartoma: Report of 5 cases with malignancy arising in 2. Arch Pathol
Lab Med. 2000;

2. Baek SK, Hwang GS, Vinci A, Jafari MD, Jafari F, Moghadamyeghaneh Z,
et al. Retrorectal Tumors: A Comprehensive Literature Review. World J
Surg. 2016;

3. Mullaney TG, Lightner AL, Johnston M, Kelley SR, Larson DW, Dozois
EJ. A systematic review of minimally invasive surgery for retrorectal
tumors. Techniques in Coloproctology. 2018.

4. Elliot Weisenberg MD. Pathology Outlines - Tailgut cyst
{[}Internet{]}. 2020 {[}cited 2021 Dec 31{]}. Available from:
https://www.pathologyoutlines.com/topic/anustailgutcyst.html

5. Moulopoulos LA, Karvouni E, Kehagias D, Dimopoulos MA, Gouliamos A,
Vlahos L. MR imaging of complex tailgut cysts. Clin Radiol. 1999;

6. Morgan MB, Stevens GL, Somach S, Tannenbaum M. Carcinoma arising in
epidermoid cyst: a case series and aetiological investigation of human
papillomavirus. Br J Dermatol. 2008;

7. Bauer BS, Lewis VL. Carcinoma arising in sebaceous and epidermoid
cysts. Ann Plast Surg. 1980;

8. Liang F, Li J, Yu K, Zhang K, Liu T, Li J. Tailgut cysts with
malignant transformation: Features, diagnosis, and treatment. Med Sci
Monit. 2020;

9. Chhabra S, Wise S, Maloney-Patel N, Rezac C, Poplin E. Adenocarcinoma
associated with tail gut cyst. J Gastrointest Oncol. 2013;

10. Manco G, Giliberti G, Rolando G, Gelsomino F, Zunarelli E, Rossi A.
Malignant transformation of a tailgut cyst. Annali italiani di
chirurgia. 2017.

11. Song DE, Park JK, Hur B, Ro JY. Carcinoid Tumor Arising in a Tailgut
Cyst of the Anorectal Junction with Distant Metastasis: A Case Report
and Review of the Literature. Archives of Pathology and Laboratory
Medicine. 2004.

12. Sheikh AA, Rotimi O, Jacob D, Hyland R, Sagar PM. Transitional cell
carcinoma arising in a tailgut cyst. J Surg Case Reports. 2015;

13. Sarkar K, Kabiraj P, Deoghuria D, Bardhan J. A case of symptomatic
tailgut duplication cyst(retro-rectal cystic hamartoma) in an adult
male. BJR\textbar{}case reports. 2017;

14. Vinciguerra GLR, Mercantini P, La Torre M, Pilozzi E, Ziparo V,
Vecchione A. Transitional cell carcinoma of the retrorectal space arisen
in tailgut cyst: A case report and review of the literature.
International Journal of Surgical Pathology. 2014.

15. Tay SK, Azhar R. Metastatic squamous cell carcinoma arising from a
retrorectal cystic hamartoma (tailgut cyst). Hum Pathol Case Reports.
2020;

16. Ohsawa M, Kagawa T, Ochiai R, Kobayashi N, Hato S, Nozaki I, et al.
Rare squamous cell carcinoma arising from a presacral epidermoid cyst: A
case report. Int J Surg Case Rep. 2020;

17. Gaud U, Goyal T, Shukla M, Kumar V, Pandey M. Synchronous occurrence
of adenocarcinoma of the rectum with squamous cell carcinoma of a
retrorectal cyst: Report of a case and review of the literature. BMJ
Case Rep. 2009;

18. Nicoll K, Bartrop C, Walsh S, Foster R, Duncan G, Payne C, et al.
Malignant transformation of tailgut cysts is significantly higher than
previously reported: systematic review of cases in the literature.
Colorectal Disease. 2019.

19. W\selectlanguage{ngerman}öhlke M, Sauer J, Dommisch K, Görling S, Valdix A, Hinze R. Primary
metastatic well-differentiated neuroendocrine tumor arising in a tailgut
cyst. Pathologe. 2011;

20. Haydar M, Griepentrog K. Tailgut cyst: A case report and literature
review. Int J Surg Case Rep. 2015;\selectlanguage{english}
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