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\begin{document}

\title{Incidentally detected Castleman disease of the thorax and its surgical
management}



\author[1]{Sudhansoo Khanna}%
\author[1]{Rana  Singh}%
\author[2]{Priyanka Goyal}%
\author[3]{Harsh Mohan}%
\author[3]{Poonam Bhaker}%
\author[4]{Shaleen Rana}%
\author[4]{Sunil Sanga}%
\affil[1]{Department of Cardiovascular and Thoracic Surgery Paras Hospitals Panchkula India}%
\affil[2]{Department of Cardiac Anaesthesia Paras Hospitals Panchkula India}%
\affil[3]{Department of Pathology Dr Gaur Path Lab Paras Hospitals Panchkula India}%
\affil[4]{Department of Radiology Paras Hospitals Panchkula India}%


\vspace{-1em}



  
  \date{May 26, 2024}


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\selectlanguage{english}
\begin{abstract}
Castleman disease (CD) is a rare lymphoproliferative disorder, the
etiology and pathogenesis of which is not clearly established. It
presents more commonly as a localised disease or unicentric CD (UCD),
and less often as generalised disease or multricentric CD (MCD). The
most common site of UCD is in the thorax; however, UCD is rarely
included in the differential diagnosis of an intrathoracic mass due to
its rarity. The lesion is highly vascular and often has dense adhesions
with adjacent organs, making the surgery a difficult task. We report a
case of posterior mediastinal mass located in left paraspinal region
which was detected incidentally in a 53-year old female and was
subsequently resected successfully via left postero-lateral thoracotomy,
and was diagnosed post-operatively on histopathological examination
(HPE) as CD, hyaline vascular variant (HVV). We review the relevant
clinical, pathological and radiological findings of CD, which may act as
clinical pointers for establishing a preoperative diagnosis of CD.
Suspecting CD preoperatively would guide the surgeon for appropriate
surgical planning and may avoid facing such surprise on the operating
table.%
\end{abstract}%



\sloppy


\emph{Title Page}

\textbf{Incidentally detected Castleman disease of the thorax and its
surgical management}

\emph{Sudhansoo Khanna\textsuperscript{1} MCh, Rana Sandip
Singh\textsuperscript{1} MCh, Priyanka Goyal\textsuperscript{2} DM,
Harsh Mohan\textsuperscript{3} MD Poonam Bhaker\textsuperscript{3} MD,}

\emph{Shaleen Rana\textsuperscript{4} DNB, Sunil
Sanga\textsuperscript{4} MD}

\emph{\textsuperscript{1}Department of Cardiovascular and Thoracic
Surgery, Paras Hospitals, Panchkula, India}

\emph{\textsuperscript{2}Department of Cardiac Anaesthesia, Paras
Hospitals, Panchkula, India}

\emph{\textsuperscript{3}Department of Pathology, Dr Gaur Path Lab,
Paras Hospitals, Panchkula, India}

\emph{\textsuperscript{4}Department of Radiology, Paras Hospitals,
Panchkula, India}

\textbf{Short running title} Incidentally detected Intrathoracic
Castleman Disease

\textbf{Corresponding author}

Dr. Sudhansoo Khanna

Attending Consultant

Department of Cardiovascular and Thoracic Surgery

Paras Hospitals,

Sector-22

Panchkula-134109

India

Contact No. : +91-01722559033

Email id: sudhansoo\_84@yahoo.com

\textbf{Funding}

No funds were received for this work

\textbf{Conflicts of interest} -- None

\textbf{IRB approval --} N/A

\textbf{Consent -} Informed written consent was taken from the patient
for the publication.

\textbf{Clinical Trial Registration-} N/A

\textbf{Total word count:} 1977



\textbf{Abstract}

Castleman disease (CD) is a rare lymphoproliferative disorder, the
etiology and pathogenesis of which is not clearly established. It
presents more commonly as a localised disease or unicentric CD (UCD),
and less often as generalised disease or multricentric CD (MCD). The
most common site of UCD is in the thorax; however, UCD is rarely
included in the differential diagnosis of an intrathoracic mass due to
its rarity. The lesion is highly vascular and often has dense adhesions
with adjacent organs, making the surgery a difficult task.

We report a case of posterior mediastinal mass located in left
paraspinal region which was detected incidentally in a 53-year old
female and was subsequently resected successfully via left
postero-lateral thoracotomy, and was diagnosed post-operatively on
histopathological examination (HPE) as CD, hyaline vascular variant
(HVV). We review the relevant clinical, pathological and radiological
findings of CD, which may act as clinical pointers for establishing a
preoperative diagnosis of CD. Suspecting CD preoperatively would guide
the surgeon for appropriate surgical planning and may avoid facing such
surprise on the operating table.

\textbf{Keywords:} Castleman disease, lymphoproliferative disorder,
posterior mediastinal mass, incidental diagnosis

\textbf{Text}

\textbf{Introduction}

Castleman disease (CD) is a rare lymphoproliferative disorder of
uncertain etiology, broadly classified as uncentric CD (UCD) and
multicentric CD (MCD). Although thorax is the most common site of UCD,
but overall CD a very rare cause of an intrathoracic mass and is usually
overlooked as a differential diagnosis of an intrathoracic or
mediastinal mass.\textsuperscript{1}

Localised Castleman disease of the thorax is known to be quite
hypervascular and in close proximity to adjacent organs or great vessels
(pulmonary artery or aorta) and often densely adherent to these
surrounding structures.\textsuperscript{2,3} When overlooked, such
tumours may pose surgical challenge (incomplete resection or profuse
bleeding) and may lead to adverse outcome. Hence, identifying Castleman
disease of thorax preoperatively and careful surgical planning may
provide good outcome post-operatively.

We present a case of posterior mediastinal mass detected incidentally in
a 53-year old female that was resected successfully via left
posterior-lateral thoracotomy with a preliminary possibility of
neurogenic tumour/ inflammatory myofibroblastic masss, but was finally
diagnosed on histopathology of surgically resected mass as CD, hyaline
vascular variant (HVV).

\textbf{Case Report}

Informed written consent was taken from the patient for the publication.
A 53-year old female patient presented to us with a provisional
diagnosis of hiatus hernia, which was detected incidentally on a CECT
chest and whole abdomen while she was being evaluated for fibroid
uterus. Outside, CECT chest and abdomen was reported as hiatus hernia
with herniation of omental fat through widened hiatus with heterogeneous
lobulated lesion within herniated omental fat; in addition there was
significant left pleural effusion with passive atelectasis of the left
lung. Patient was asymptomatic from hiatus hernia per se. As the
diagnosis was in question, we re-evaluated the CT images with in-house
radiologist. On re-evaluation, it appeared to be a large well-defined
posterior mediastinal mass approximately 8x8 cm in dimension in left
hemithorax in left paraspinal region, abutting on the descending
thoracic aorta (DTA) with preserved fat planes (?liposarcoma) (Figure
1A, 1B). The mass showed intense enhancement on contrast imaging (Figure
1C). CT- guided biopsy of the mass was reported on histopathology as
possibly inflammatory myofibroblastic tumour. No malignant cells were
detected on diagnostic pleural aspiration.

After evaluating resectability of the mass, patient was taken up for
excision via left posterolateral thoracotomy. Intra-operatively, a large
lobulated mass, approximately 10x10x8 cm in dimension, firm in
consistency occupying the paraspinal aspect of left hemithorax was
detected. It was adherent to DTA with feeder vessels arising from DTA.
The mass was densely adherent to the parieties and to left
hemidiaphragm. On intraoperative assessment, it appeared to be a
malignant tumour. The mass was gently dissected free from DTA after
ligating feeder vessels, necessitating application of partial cross
clamp for short duration to control bleeders from DTA. Mass was
mobilised from left hemidiaphragm and parieties by combination of blunt
and sharp dissection. Approximately 700 ml of straw coloured pleural
fluid was aspirated. Left lung was completely normal and away from the
mass.

Postoperative period was uneventful and patient was discharged in stable
condition on 5th post operative day (POD). The cut section of the
operative specimen showed well-defined tumour surrounded by fatty tissue
on other end (Figure 2). On HPE of the excised mass, it showed
characteristic onion-skin pattern of lymphoid follicles (concentric
layer of lymphocytes surrounding an atrophic germinal centre) and was
diagnosed as CD, hyaline vascular variant (Figure 3A, 3B).

\textbf{Discussion}

Castleman Disease (CD) is a rare non malignant lymphoproliferative
disorder of uncertain etiology, first reported by Benjamin Franklin in
1954.\textsuperscript{1} It is also known as giant lymph node (LN)
hyperplasia or angiofollicular hyperplasia. Although it can present at
any age, its peak incidence is in 3rd and 4th decade.\textsuperscript{4}

It can be classified clinically (on the basis of location) into two
types: Unicentric CD (localised disease) and multricentric CD (diffuse
or systemic disease). Histopathologically, CD is of two types: hyaline
vascular variant (HVV) and plasma cell variant (PCV). UCD is more common
(68-98\%) than MCD. Further, majority of UCD are HVV, whereas majority
of MCD are PCV.\textsuperscript{4,5}

UCD is usually an asymptomatic disease detected incidentally whereas MCD
often presents with constitutional symptoms (fever, night sweats, weight
loss etc). However, occasionally UCD may present with features of mass
effect on adjacent on adjacent organs such as cough, dysphagia, dyspnoea
or pain.\textsuperscript{6}

Although CD can arise at any site where lymph node tissue is present,
but its most common site is in the thorax (70\%). Other sites are
abdomen and pelvis (10-15\%), neck (10-15\%). In the thorax, most common
site of CD is the mediastinum. Other intrathoracic sites of UCD are the
hilum of lung, pleura, and chest wall.\textsuperscript{7}

Identifying Castleman disease preoperatively is difficult. In the
present case, a well-defined posterior mediastinal mass was incidentally
detected on CECT chest in an asymptomatic 53-year old female which on
preoperative biopsy on histopathology was considered as an inflammatory
myofibroblastic tumour. Intra-operatively, the appearance was like that
of a malignant tumour. Preoperative contrast imaging (CT/ MRI) may help
to differentiate CD from other more common posterior mediastinal masses
(neurogenic tumours e.g. schwannoma, neurofibroma, ganglioneuroma). On
imaging, CD presents as a well-defined, homogeneous mass; however, the
characteristic feature of UCD on CECT is \emph{the intense enhancement
during arterial phase} which decreases during portal venous phase. This
intense enhancement is due to hypervascular nature of localised CD
(UCD). Hence, \emph{multiphase} CECT may be performed as the
investigation of choice if UCD is suspected.\textsuperscript{8} Further
CT may reveal relation of mass to adjacent organs and major vessels of
thorax, helping in surgical planning.

Identifying or suspecting UCD preoperatively may be useful for surgical
planning. Localised/Unicentric CD (UCD) is amenable to complete surgical
resection which is curative. However, UCD is known to be hypervascular
and have dense adhesions with adjacent organs or major
vessels\textsuperscript{2} which may pose a surgical challenge. In such
cases, either preoperative embolisation may be done (to reduce
vascularity) \textsuperscript{9} or mass may be excised on
cardiopulmonary bypass (CPB) if dense adhesions with major vessels is
present.\textsuperscript{10} Video-assisted thoracoscopy (VATS) may be
associated with less postoperative pain and less hospital stay; however,
due to dense adhesions and vascular nature of CD, VATS does not appear
to be a lucrative option in CD.\textsuperscript{10}

Prognosis of UCD is good as it behaves as a benign disease and
recurrence is rare; hence complete surgical resection is curative. On
the other hand, MCD can present as an aggressive lymphoproliferative
disease and debulking surgery and/or immunochemotherapy are treatment
options in such cases.\textsuperscript{7}

In conclusion, UCD is a rare cause of intrathoracic mass, the etiology
and pathogenesis of which is unclear. It mimics both benign as well as
malignant lesions in the neck, thorax and abdomen. A high index of
clinical suspicion followed by focused evaluation with multiphase CECT
chest can help to establish its diagnosis preoperatively. Resection of
UCD may be difficult owing to hypervascularity and dense adhesions.
Hence, preoperative presumptive diagnosis of CD may help in proper
preoperative optimisation (embolisation), deciding surgical approach
(open thoracotomy vs VATS vs need for CPB).

\textbf{Author contributions}

Dr. Sudhansoo Khanna - Data analysis, Drafting article.

Dr. Rana Sandip Singh - Critical revision of article.

Dr. Priyanka Goyal- Data Collection

Dr. Harsh Mohan -- Critical revision of article.

Dr. Poonam Bhaker - Data collection.

Dr. Shaleen Rana - Data collection.

Dr. Sunil Sanga -- Critical Revision of the article.

\textbf{References}

Castleman B, Towne VW. Case records of the Massachusetts General
Hospital: Case No: 40231. N Eng J Med 1954;250:1001-5.

Iyoda A, Yusa T, Hiroshima K, Fujisawa T, Ohwada H. Castleman's disease
in the posterior mediastinum: report a case. Surg Today 2000;30: 473-6.

Seirafi PA, Ferguson E, Edwards FH. Thoracoscopic resection of Castleman
disease: case report and review. Chest 2003;123:280-2.

Dispenzieri A, Armitage JO, Loe MJ, Geyer SM, Allred J, Camoriano JK, et
al. The clinical spectrum of Castleman's disease. Am J Hematol
2012;87(11): 997--1002.

Casper C. The aetiology and management of Castleman disease at 50 years:
translating pathophysiology to patient care. Br J Haematol
2005;129(1):3--17.

Ye B, Gao SG, Li W, Yang LH, Zahoor SH, Ma K, et al. A retrospective
study of unicentric and multicentric Castleman's disease: a report of 52
patients. Med Oncol 2010;27(4):1171--1178.

Moloney F, Twomey M, Hinchon J, Maher M. Castleman diasease: an
unexpected cause of a solitary pleural mass. Case Rep Radiol
2013;2013:130515. Doi:10.1155/2013/130515.

McAdams HP, Rosado-de-Christenson M, Fishback NF, Templeton PA.
Castleman disease of the thorax: radiologic features with clinical and
histopathologic correlation. Radiology 1998;209(1):221--228.

Robert JH, Sgourdos G, Kritikos N, Didier D, Terraz S. Preoperative
embolization of hypervascular Castleman's disease of the mediastinum.
Cardiovasc Intervent Radiol 2008;31:186-8.

Lim KE, Tsai KT, Yue CT, Hsu YY. Surgical treatment of Castleman Disease
using cardiopulmonary bypass. Acta Cardiologica Sinica 2014;30(2):169.

\textbf{Figure legends}

\emph{Figure 1A:} Non contrast CT (NCCT) chest (axial view) showing a
well-defined hypodense soft tissue density mass (black arrows) in the
posterior mediastinum with eccentric specs of calcification, with
proliferation of adjacent fat (white star). Note the presence of a large
feeder vessel from DTA and left pleural effusion (blue star).

\emph{Figure 1B:} NCCT chest (coronal reformatted view) shows a well
defined, mass located above left hemidiaphragm. Rest of the findings are
same.

\emph{Figure 1C} : CECT chest (axial view) showing avidly enhancing well
defined mass (green star) with central non-enhancing areas suggestive of
central necrosis (black star). Also note a large feeder vessel from DTA.

\emph{Figure 2} : Cut section of the operative specimen shows
well-defined tumour surrounded by fatty tissue on other end.

\emph{Figure 3A} : Photomicrograph shows lymphoid follicles (F) with
atrophic germinal centres and central hyalinisation (yellow arrow head).
Interfollicular stroma shows vascular and fibroblastic proliferation
along with numerous lymphocytes and plasma cells.

\emph{Figure 3B} : Photomicrograph (Inset image) shows lymphoid follicle
having concentric layering of lymphocytes in an onion-skin
pattern~(yellow arrow) encircling an atrophic germinal centre (yellow
arrow head). This so called targetoid onion-skin appearance and is
highly suggestive of CD.\selectlanguage{english}
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\includegraphics[width=0.70\columnwidth]{figures/Figure-1A/Figure-1A}

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\includegraphics[width=0.70\columnwidth]{figures/FIGURE-2-final/FIGURE-2-final}

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\includegraphics[width=0.70\columnwidth]{figures/FIGURE-3B/FIGURE-3B}

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