\documentclass[10pt]{article}

\usepackage{fullpage}
\usepackage{setspace}
\usepackage{parskip}
\usepackage{titlesec}
\usepackage[section]{placeins}
\usepackage{xcolor}
\usepackage{breakcites}
\usepackage{lineno}
\usepackage{hyphenat}





\PassOptionsToPackage{hyphens}{url}
\usepackage[colorlinks = true,
            linkcolor = blue,
            urlcolor  = blue,
            citecolor = blue,
            anchorcolor = blue]{hyperref}
\usepackage{etoolbox}
\makeatletter
\patchcmd\@combinedblfloats{\box\@outputbox}{\unvbox\@outputbox}{}{%
  \errmessage{\noexpand\@combinedblfloats could not be patched}%
}%
\makeatother


\usepackage{natbib}




\renewenvironment{abstract}
  {{\bfseries\noindent{\abstractname}\par\nobreak}\footnotesize}
  {\bigskip}

\titlespacing{\section}{0pt}{*3}{*1}
\titlespacing{\subsection}{0pt}{*2}{*0.5}
\titlespacing{\subsubsection}{0pt}{*1.5}{0pt}


\usepackage{authblk}


\usepackage{graphicx}
\usepackage[space]{grffile}
\usepackage{latexsym}
\usepackage{textcomp}
\usepackage{longtable}
\usepackage{tabulary}
\usepackage{booktabs,array,multirow}
\usepackage{amsfonts,amsmath,amssymb}
\providecommand\citet{\cite}
\providecommand\citep{\cite}
\providecommand\citealt{\cite}
% You can conditionalize code for latexml or normal latex using this.
\newif\iflatexml\latexmlfalse
\providecommand{\tightlist}{\setlength{\itemsep}{0pt}\setlength{\parskip}{0pt}}%

\AtBeginDocument{\DeclareGraphicsExtensions{.pdf,.PDF,.eps,.EPS,.png,.PNG,.tif,.TIF,.jpg,.JPG,.jpeg,.JPEG}}

\usepackage[utf8]{inputenc}
\usepackage[greek,ngerman,english]{babel}



\usepackage{float}








\begin{document}

\title{Epidermoid cyst of the testis: a report of six cases}



\author[1]{Kimitsugu Usui}%
\author[1]{Ryo Yamashita}%
\author[1]{Yuma Sakura}%
\author[1]{Masafumi Nakamura}%
\author[1]{Hideo Shinsaka}%
\author[1]{Masato Matsuzaki}%
\author[1]{Masashi Niwakawa}%
\affil[1]{Shizuoka Cancer Center}%


\vspace{-1em}



  
  \date{May 27, 2024}


\begingroup
\let\center\flushleft
\let\endcenter\endflushleft
\maketitle
\endgroup





\selectlanguage{english}
\begin{abstract}
Introduction: Testicular epidermoid cysts are rare tumors that occur in
1\% of testicular tumors and are often misdiagnosed as malignant lesions
clinically. We report six cases of epidermoid cysts. Case Presentation:
The chief complaints were scrotal induration in five patients and
pruritus scrotum in one patient, and the patients were aged%
\end{abstract}%



\sloppy


Case report

\textbf{Epidermoid cyst of the testis: A report of six cases}

Kimitsugu Usui, Ryo Yamashita, Yuma Sakura, Masafumi Nakamura, Hideo
Shinsaka, Masato Matsuzaki, Masashi Niwakawa

Division of Urology, Shizuoka Cancer Center, Shizuoka, Japan

\textbf{Correspondence}

Kimitsugu Usui, Department of Urology, Shizuoka Cancer Center, 1007
Shimonagakubo, Nagaizumi-cho, Suntou-gun, Shizuoka 411-8777, Japan.

Email: \emph{usuik@kcch.jp}. Tel: +81-55-989-5222. Fax: +81-55-989-5783

\textbf{Key Clinical Message}

Testicular tumor markers are negative in patients with epidermoid cysts.
Clear margins and sole and small testicular tumors (25 mm or less)
suggest the possibility of epidermoid cyst.

\textbf{Keywords:} epidermoid cyst, testicular tumor, ultrasonography

Written informed consent was obtained from the patient to publish this
report in accordance with the journal's patient consent policy.

\textbf{Introduction}

Testicular epidermoid cysts are rare tumors that occur in approximately
1\% of testicular tumors and are often found in young men 10--39 years
of age.\textsuperscript{1--4} They are benign tumors that are often
misdiagnosed as malignant lesions in clinical practice. Although a
preoperative diagnosis can avoid unnecessary orchiectomy, it is often
difficult to achieve. Therefore, high inguinal orchiectomy is performed
in \textgreater{}80\% of the reported cases.\textsuperscript{1}Notifying
the possibility of a benign tumor (1\%) to patients is crucial before
surgery. We summarized specific preoperative findings differentiating
epidermoid cysts from malignant lesions. Herein, we report six rare
cases of epidermoid cysts in the testes.

\textbf{Case presentation}

We encountered six patients with epidermoid cysts at our hospital
between April 2010 and March 2022 (Table 1). The median age (range) was
20 (9--30) years. The tumors occurred in the right testes in two
patients and the left in the other four patients. The chief complaints
were scrotal induration in five patients and pruritus in the scrotum in
one patient. The patients had no family or medical history of testicular
cancer. Their blood counts, biochemical test results, and levels of
testicular tumor markers (lactate dehydrogenase, alpha-fetoprotein,
human chorionic gonadotropin, and human chorionic gonadotropin-\selectlanguage{greek}β\selectlanguage{english}) were
within the normal ranges. Ultrasonography (US) was performed in all
patients (Figure 1). The median tumor size (range) was 17.5 (12--22) mm.
Well-defined, clear rims were observed in five patients. Since we did
not rule out malignant testicular tumors, we performed high inguinal
orchiectomy in all patients. All tumors were macroscopically
well-defined, white-toned masses (Figure 2). Microscopically, they were
cysts with thin fibrous capsules. The inner surface of each cyst was
covered with stratified squamous epithelium, and the inside was filled
with keratinized substances (Figure 3). There were no skin appendages or
other tissue components inside the cyst. All patients were diagnosed
with testicular epidermoid cysts.

\textbf{Discussion}

Testicular epidermoid cysts, first reported by Dockerty et al. in 1942,
are benign tumors that account for 1\% of all testicular
tumors.\textsuperscript{1} They commonly affect patients 10--39 years of
age, which was almost similar to the susceptible age of having germ cell
tumors (between 20 and 39 years). Epidermoid cysts are classified as
prepubertal teratoma, but we have to realize that they frequently occur
in adulthood.\textsuperscript{2,5} Price et al. reported that 87\% of
all testicular epidermoid cysts were small tumors of \textless{}30 mm in
size.\textsuperscript{2} According to the 2016 WHO classification,
epidermoid cysts are classified as prepubertal teratomas unrelated to
germ cell neoplasia in situ (GCNIS). Postpubertal teratomas are
considered malignant because they are derived from GCNIS. Contrarily,
prepubertal teratomas arise from normal primordial embryos which makes
them, including epidermoid cysts, benign lesions.\textsuperscript{6}

More than 70\% of pediatric testicular tumors are benign; therefore,
testicular-sparing surgery is often performed.\textsuperscript{7} The
prerequisites for the tumor to be considered benign prior to
testicular-sparing surgery are particular US findings (cystic lesions
with clear borders and calcified contents) and AFP negativity. In
addition, it is necessary to confirm that there are no malignant
findings on intraoperative frozen section examination
(FSE).\textsuperscript{8,9} We encountered one pediatric patient, but
because the boundary was relatively ill-defined on US findings (Figure
1C), high inguinal orchiectomy was performed, considering the risk of
malignant dissemination after tumor enucleation alone.

Testicular epidermoid cysts are recognized as benign tumors, and there
have been no reports of their metastasis. A report of 69 cases of
testicular epidermoid cysts worldwide showed no metastases or death from
this disease during the 1-month to 24-year observation
periods.\textsuperscript{1} In the present report, no recurrence was
observed during the observation period of 2 weeks to 3 years.

Testicular tumor markers were negative in patients with epidermoid
cysts. Previous studies have also indicated that 80\% of small tumors
(less than 20--25 mm, regardless of age) are benign, and small-sized
tumors are a predictor of benign tumors.\textsuperscript{10--12} In this
study, all patients were negative for tumor markers, and their tumors
were within 25 mm in size.

US is highly useful for making preoperative diagnoses. Typically, the
outer edge has a hyperechoic partition, called an echogenic rim. A
low-echo level concentric ring (represented as an onion ring or a bull's
eye) is seen inside when the alternating layers of compressed keratin
and exfoliated squamous epithelial cells are regular. However, when the
layers are randomly arranged with a slightly alternating pattern, the
lesion looks like a heterogeneous mass and can present varied findings.
Reflecting the internal keratinization, it is avascular in Doppler
US.\textsuperscript{13,14} In five of our six patients, hyperechoic
septa were confirmed on the outer edges and well-defined tumors were
visualized.

For histological diagnosis, Price et al. reported four diagnostic
criteria: first, the cyst wall exists in the parenchyma of the testis;
second, the inside contains layers of keratinized and non-structural
substances; third, the cyst wall surrounds the stratified squamous
epithelium; and fourth, an epidermoid cyst is defined as having no
teratoma-like tissues or skin appendages consisting of fibrous
connective tissues.\textsuperscript{2}

Recently, testicular-sparing surgery has begun to be recognized to avoid
the overtreatment of benign lesions and preserve sexual functions.
According to the European Association of Urology clinical guidelines
(2022), high inguinal orchiectomy without intraoperative FSE should not
be performed in patients with suspected benign testicular
tumors.\textsuperscript{15} Fankhauser et al. reported the accuracy of
intraoperative FSE for testicular tumors.\textsuperscript{16} Axel et
al. performed testicular-sparing surgeries in 18 patients with
testicular epidermoid cysts. All patients were accurately diagnosed as
having epidermoid cysts by FSE.\textsuperscript{4}

\textbf{Conclusion}

In this study, we reported six cases of rare testicular epidermoid
cysts. When encountering patients with negative tumor markers, clear
margins, negative Doppler flow, and sole small testicular tumors ([?]25
mm), we should always consider the possibility of benign epidermoid
cysts to avoid overtreatment.

\textbf{Author Contributions}

Kimitsugu Usui: Conceptualization; data curation; writing -- original
draft. Ryo Yamashita: Conceptualization; data curation; project
administration; writing -- review and editing. Yuma Sakura:
Conceptualization; data curation; project administration; writing --
original draft. Masafumi Nakamura: Data curation; writing -- review and
editing. Hideo Shinsaka: Data curation; writing -- review and editing.
Masato Matsuzaki: Data curation; writing -- review and editing. Masashi
Niwakawa: Project administration; supervision; writing -- review and
editing.

\textbf{Acknowledgments}

We thank Dr. Takashi Sugino of the Department of Pathology for reviewing
the tissue slides.

\textbf{Funding information}

The authors did not receive support from any organization for the
submitted work.

\textbf{Conflict of interest statement}

The authors declare no conflict of interest.

\textbf{Data availability statement}

The authors confirm that the data supporting the findings of this study
are available within the article.

\textbf{Ethics statement}

The protocol for this research project has been approved by a suitably
constituted Ethics Committee of the institution, and it conforms to the
provisions of the Declaration of Helsinki. Institutional review board of
Shizuoka Cancer Center, Approval No. 3625.

\textbf{Consent}

The study information was displayed on the hospital website homepage to
provide a means for patients to opt out.

\textbf{Registry and the Registration No. of the study/trial~}

Number J2022-150

\textbf{Shizuoka Cancer Center Clinical Research Ethics Review
Committee}

\textbf{References}

\begin{enumerate}
\tightlist
\item
  Shah KH, Maxted WC, Chun B. Epidermoid cysts of the testis: a report
  of three cases and an analysis of 141 cases from the world literature.
  \emph{Cancer} . 1981;47(3):577-582.
\item
  Price EB Jr. Epidermoid cysts of the testis: a clinical and pathologic
  analysis of 69 cases from the testicular tumor registry. \emph{J Urol}
  . 1969;102(6):708-713.
\item
  Dieckmann KP, Loy V. Epidermoid cyst of the testis: a review of
  clinical and histogenetic considerations. \emph{Br J Urol} .
  1994;73(4):436-441.
\item
  Heidenreich A, Engelmann UH, Vietsch HV, Derschum W. Organ preserving
  surgery in testicular epidermoid cysts. \emph{J Urol} .
  1995;153(4):1147-1150.
\item
  Dockerty MB, Priestly JT. Dermoid cysts of the testis. \emph{J Urol} .
  1942;48(4):392-400.
\item
  Moch H, Cubilla AL, Humphrey PA, Reuter VE, Ulbright TM. The 2016 WHO
  classification of tumours of the urinary system and male genital
  organs-part A: renal, penile, and testicular tumours. \emph{Eur Urol}
  . 2016;70(1):93-105.
\item
  Pohl HG, Shukla AR, Metcalf PD, et al. Prepubertal testis tumors:
  actual prevalence rate of histological types. \emph{J Urol} .
  2004;172(6 Pt 1):2370-2372.
\item
  Hisamatsu E, Takagi S, Nakagawa Y, et al. Prepubertal testicular
  tumors: A 20-year experience with 40 cases. \emph{Int J Urol} .
  2010;17(11):956-959.
\item
  Ross JH, Rybicki L, Kay R. Clinical behavior and a contemporary
  management algorithm for prepubertal testis tumors: a summary of the
  Prepubertal Testis Tumor Registry. \emph{J Urol} . 2002;168(4 Pt
  2):1675-1678; discussion 1678-1679.
\item
  Paffenholz P, Held L, Loosen SH, Pfister D, Heidenreich A. Testis
  sparing surgery for benign testicular masses: diagnostics and
  therapeutic approaches. \emph{J Urol} . 2018;200(2):353-360.
\item
  Gentile G, Rizzo M, Bianchi L, et al. Testis sparing surgery of small
  testicular masses: retrospective analysis of a multicenter
  cohort.\emph{J Urol} . 2020;203(4):760-766.
\item
  Carmignani L, Gadda F, Gazzano G et al. High incidence of benign
  testicular neoplasms diagnosed by ultrasound. \emph{J Urol} .
  2003;170(5):1783-1786.
\item
  Maizlin ZV, Belenky A, Baniel J, Gottlieb P, Sandbank J, Strauss S.
  Epidermoid cyst and teratoma of the testis: sonographic and histologic
  similarities. \emph{J Ultrasound Med} . 2005;24(10):1403-1409; quiz
  1410-1411.
\item
  Cho JH, Chang JC, Park BH, Lee JG, Son CH. Sonographic and MR imaging
  findings of testicular epidermoid cysts. \emph{Am J Roentgenol} .
  2002;178(3):743-748.
\item
  Heidenreich A, Paffenholz P, Nestler T, Pfister D. European
  Association of Urology Guidelines on testis cancer: important take
  home messages. \emph{Eur Urol Focus} . 2019;5(5):742-744.
\item
  Fankhauser CD, Roth L, Kranzb\selectlanguage{ngerman}ühler B, et al. The role of frozen
  section examination during inguinal exploration in men with
  inconclusive testicular tumors: A systematic review and
  meta-analysis.\emph{Eur Urol Focus} . 2021;7(6):1400-1402.
\end{enumerate}

\textbf{Figure legends}

\textbf{Figure 1} Ultrasonography of the testicular tumor. Well-defined,
clear rims are observed in all cases except C.

\textbf{Figure 2} Macroscopic appearance of epidermoid cyst of the
testis. A round white nodule with a keratinized material inside is seen.

\textbf{Figure 3} Microscopic appearance of an epidermoid cyst of the
testis. The cystic mass is filled with keratinized material. The wall is
composed of dense fibrous tissues lined by stratified squamous
keratinized epithelium.

\textbf{Table 1} Characteristics of the six patients with testicular
epidermal cysts\selectlanguage{english}
\begin{longtable}[]{@{}lllllll@{}}
\toprule
& Age (years) & Side & Chief complaint & Tumor size (mm) & Tumor marker
levels & Figure\tabularnewline
\midrule
\endhead
Case 1 & 27 & Left & Scrotal induration & 22 & Normal & A\tabularnewline
Case 2 & 19 & Left & Scrotal induration & 18 & Normal & B\tabularnewline
Case 3 & 9 & Right & Scrotal induration & 17 & Normal & C\tabularnewline
Case 4 & 21 & Left & Scrotal induration & 15 & Normal & D\tabularnewline
Case 5 & 30 & Left & Pruritus scrotum & 20 & Normal & E\tabularnewline
Case 6 & 18 & Right & Scrotal induration & 12 & Normal &
F\tabularnewline
\bottomrule
\end{longtable}

\textbf{Hosted file}

\verb`Fig_1.docx`  available at \url{https://authorea.com/users/630802/articles/650427-epidermoid-cyst-of-the-testis-a-report-of-six-cases}

\textbf{Hosted file}

\verb`Fig_2.docx`  available at \url{https://authorea.com/users/630802/articles/650427-epidermoid-cyst-of-the-testis-a-report-of-six-cases}

\textbf{Hosted file}

\verb`Fig_3.docx`  available at \url{https://authorea.com/users/630802/articles/650427-epidermoid-cyst-of-the-testis-a-report-of-six-cases}

\selectlanguage{english}
\FloatBarrier
\end{document}

