\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[T2A]{fontenc}
\usepackage[polish,ngerman,english]{babel}



\usepackage{float}








\begin{document}

\title{``An unusual case of diffuse cystic lung disease: A teenager with lung
metastasis''}



\author[1]{Sevim Guler}%
\author[2]{Hull NC}%
\author[3]{Manuel Arteta}%
\author[3]{Nadir Demirel}%
\affil[1]{Istanbul University-}%
\affil[2]{Mayo Clinic Minnesota Department of Radiology}%
\affil[3]{Mayo Clinic Minnesota}%


\vspace{-1em}



  
  \date{May 24, 2024}


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





\selectlanguage{english}
\begin{abstract}
We are presenting a teenage girl with a recent history of virilism who
presented with tension pneumothorax. Subsequent contrast-enhanced chest
CT revealed multiple bilateral irregular thin-walled cysts of varying
sizes with numerous solid noncalcified pulmonary nodules and pulmonary
artery pseudoaneurysms. Lung biopsy revealed trophoblastic neoplasm with
metastasis to both lungs. We discussed the differential diagnosis of
diffuse cystic lung diseases. While diffuse cystic lung diseases in
children are rarely due to malignancy, we emphasize that clinicians be
aware of the possibility of metastatic lung diseases and their
radiologic features when encountering diffuse cystic lung diseases.%
\end{abstract}%



\sloppy


TITLE: ``An unusual case of diffuse cystic lung disease: A teenager with
lung metastasis''

Sevim Guler, MD

Istanbul University-Cerrahpasa School of Medicine, Istanbul, Turkey

Nathan C. Hull, MD

Division of Pediatric Radiology, Department of Radiology

Mayo Clinic, Rochester, Minnesota

Manuel Arteta, MD

Division of Pediatric Pulmonology, Department of Pediatrics and
Adolescent

Medicine, Mayo Clinic, Rochester, Minnesota

Nadir Demirel, MD

Division of Pediatric Pulmonology, Department of Pediatrics and
Adolescent

Medicine, Mayo Clinic, Rochester, Minnesota

Corresponding Author:

Sevim Guler, MD

Istanbul University-Cerrahpasa School of Medicine, Istanbul, Turkey

\selectlanguage{polish}İ\selectlanguage{english}stanbul \selectlanguage{ngerman}Üniversitesi-Cerrahpa\selectlanguage{polish}ş\selectlanguage{english}a, Cerrahpa\selectlanguage{polish}ş\selectlanguage{english}a T\selectlanguage{polish}ı\selectlanguage{english}p Fak\selectlanguage{ngerman}ültesi Yerle\selectlanguage{polish}ş\selectlanguage{english}kesi
Kocamustafapa\selectlanguage{polish}ş\selectlanguage{english}a Caddesi No:53 Cerrahpa\selectlanguage{polish}ş\selectlanguage{english}a 34098 Fatih/\selectlanguage{polish}İ\selectlanguage{english}stanbul

Tel. No.: +90 (212) 414 30 00

Fax No.: +90 (212) 632 00 25

sevimguler2212@gmail.com

Keywords: Cystic lung lesions, diffuse lung disease, lung cysts,
metastatic lung disease

Financial Disclosure: The authors have indicated they have no financial
relationships relevant to this article to disclose.

Funding: No external funding.

Short title: ``Metastatic lung disease with multiple cystic lesions''

To the Editor,

A 13-year-old girl with a history of virilism for six months presented
with acute onset chest pain and shortness of breath to the emergency
room. Chest-X ray showed a large left tension pneumothorax (Figure 1),
and an emergent chest tube was placed. Subsequent contrast-enhanced
chest CT (Figure 2) revealed multiple bilateral irregular thin-walled
cysts of varying sizes with numerous solid noncalcified pulmonary
nodules and pulmonary artery pseudoaneurysms (PAPAs). Abdominal CT
identified a heterogeneously enhancing solid-appearing mass-like
structure in the right adnexal region. Further imaging workup with
transabdominal pelvic ultrasound and contrast-enhance pelvic MRI showed
an enlarged right ovary with an area of central heterogeneity but
without a discrete mass or lesion (Figure 3).

On clinical examination, signs of virilism were noted. A
multidisciplinary investigation revealed a normal hepatic function
panel, elevated beta HCG (194 IU/L), elevated total testosterone (413
ng/dL), elevated serum free testosterone level (7.09 ng/dL), elevated
androstenedione level (556 ng/dL), normal LH, FSH, normal estradiol and
antimullerian hormone levels. Ovarian venous sampling revealed
bilaterally increased beta HCG (181 mIU/mL) and testosterone levels
(\textgreater{}7000 ng/dL).

CA-19-9 (42U/mL) and CA-125 (46 U/mL) were also elevated; AFP was
normal.

A fluorodeoxyglucose-positron emission tomography (FDG-PET) showed no
occult malignancy or increased radiotracer uptake in the lungs or the
adnexa. Lung biopsy revealed trophoblastic neoplasm with metastasis to
both lungs. She underwent laparoscopic right salpingo-oophorectomy, coil
embolization of the largest pulmonary pseudoaneurysms (Figure 4)
bilaterally, and chemotherapy was initiated.

Diffuse cystic lung diseases (DCLDs) are a heterogeneous group of
pulmonary disorders characterized by multiple air-filled spaces, or
cysts, within the lung parenchyma. Cysts are thin-walled (2 mm wall
thickness), spherical, air-filled lucencies interfaced with normal lung
tissue \textsuperscript{1}. In adults, DCLD can occur with
lymphangioleiomyomatosis (LAM), Langerhans cell histiocytosis,
lymphocytic interstitial pneumonia, Birt-Hogg-Dub\selectlanguage{ngerman}é syndrome, primary and
metastatic cancers, and amyloidosis \textsuperscript{2}. DCLD in
children is frequently associated with lung development and growth
abnormalities. The most frequent cause of DCLD is bronchopulmonary
dysplasia, and lesions are usually bilateral. Congenital pulmonary
airway malformation can also present as DCLD, but more frequently, it is
focal \textsuperscript{3}. Other rare congenital causes of DCLD include
congenital lobar emphysema, congenital bulla, congenital bronchiectasis,
and bronchial atresia \textsuperscript{3}. Blunt trauma to the chest can
also lead to cysts known as post-traumatic pseudocysts or pneumatoceles.
Infections such as Pneumocystis jirovecii or Staphylococcus aureus may
cause DCLD with pneumatoceles \textsuperscript{4}. Recurrent respiratory
papillomatosis can rarely present with DCLD. Other rare causes of DCLD
in children include Birt-Hogg-Dubé syndrome and LAM. Birt-Hogg- Dubé
syndrome is a rare, autosomal-dominant disorder characterized by the
development of hair follicle tumors, renal neoplasms, and pulmonary
cysts. LAM is caused by lung infiltration with smooth muscle cells that
arise from an unknown source, spread via blood and lymphatics, and
contain growth-activating mutations in tuberous sclerosis
genes\textsuperscript{2, 3}.

Individuals with pulmonary cysts are generally asymptomatic or have mild
nonspecific symptoms (mild cough, dyspnea) and are discovered
incidentally on chest imaging. A small part of patients may present with
pneumothorax \textsuperscript{2}. In children, DCLD rarely develops due
to a malignant process, typically secondary to metastases from
peripheral sarcomas and mesenchymal tumors \textsuperscript{4}.
Pleuropulmonary blastoma is the most common primary pediatric lung
neoplasm; it typically presents in children under six years of age and
can manifest as a multilocular cystic neoplasm \textsuperscript{4}.

PAPAs may be congenital or acquired, with infections being the most
common cause of the acquired form; pyogenic bacteria, such as
Staphylococcus aureus and Streptococcus pyogenes, are commonly
implicated. Massive hemoptysis is a fatal complication of ruptured
PAPAs\textsuperscript{5}.

In summary, DCLD is rare in children and has multiple etiologies. We
present a case of DCLD caused by metastatic lung disease and, to the
best of our knowledge, the first case of a lung metastatic trophoblastic
tumor in a child. Even though it is rare, clinicians should be aware of
the possibility of metastatic lung diseases as the cause of DCLD.

\textbf{References}

1. Obaidat B, Yazdani D, Wikenheiser-Brokamp KA, Gupta N. Diffuse Cystic
Lung

Diseases. Respir Care. 2020 Jan;65(1):111-126.

2. Raoof S, Bondalapati P, Vydyula R, Ryu JH, Gupta N, Raoof S, Galvin
J, Rosen

MJ, Lynch D, Travis W, Mehta S, Lazzaro R, Naidich D. Cystic Lung
Diseases:

Algorithmic Approach. Chest. 2016 Oct;150(4):945-965.

3. Gupta N, Vassallo R, Wikenheiser-Brokamp KA, McCormack FX. Diffuse
Cystic Lung Disease. Part II. Am J Respir Crit Care Med. 2015 Jul
1;192(1):17-29.

4. Gupta N, Vassallo R, Wikenheiser-Brokamp KA, McCormack FX. Diffuse
Cystic Lung Disease. Part I. Am J Respir Crit Care Med. 2015 Jun
15;191(12):1354-66.

5. Koneru H, Biswas Roy S, Islam M, et al. Pulmonary Artery
Pseudoaneurysm: A Rare Cause of Fatal Massive Hemoptysis. Case Rep
Pulmonol 2018; 2018:8251967.\selectlanguage{english}
\begin{figure}[H]
\begin{center}
\includegraphics[width=0.70\columnwidth]{figures/Figure-1/Figure-1}

\end{center}
\end{figure}\selectlanguage{english}
\begin{figure}[H]
\begin{center}
\includegraphics[width=0.70\columnwidth]{figures/Figure-2/Figure-2}

\end{center}
\end{figure}\selectlanguage{english}
\begin{figure}[H]
\begin{center}
\includegraphics[width=0.70\columnwidth]{figures/Figure-3/Figure-3}

\end{center}
\end{figure}\selectlanguage{english}
\begin{figure}[H]
\begin{center}
\includegraphics[width=0.70\columnwidth]{figures/Figure-4/Figure-4}

\end{center}
\end{figure}

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

