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\begin{document}

\title{Recurrent Hematuria, Urinary Tract Infections, and Urinary Retention: A
Rare Presentation of Prostate Leiomyosarcoma}



\author[1]{Sowmya Sagireddy}%
\author[2]{Chiya  Abramowitz}%
\author[3]{Sai Sagireddy}%
\author[4]{Marc Pertab}%
\author[4]{Mark Sonnenschine}%
\affil[1]{NYCHHC}%
\affil[2]{NYIT}%
\affil[3]{Baylor University}%
\affil[4]{NYC Health + Hospitals}%


\vspace{-1em}



  
  \date{May 28, 2024}


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\textbf{Authors: Sowmya Sagireddy\textsuperscript{1}, Chiya
Abramowitz\textsuperscript{2}, Sai Sagireddy\textsuperscript{3}, Marc
Sukhoo-Pertab\textsuperscript{1,} Mark
Sonnenschine\textsuperscript{1}}\textsuperscript{1} South Brooklyn
Health, Brooklyn, NY, 11235, USA\textsuperscript{2} New York Institute
of Technology College of Osteopathic Medicine, Old Westbury, NY, 11568,
USA;\textsuperscript{3}Baylor University, Waco, Texas,76706, USA

\section*{}

{\label{section}}

\textbf{Funding/Support:} Not applicable

\section*{Word Count: 1236}

{\label{word-count-1236}}

\textbf{Corresponding Author:}

Sai Sagireddy

1919 S 15\textsuperscript{th} Street

Waco, TX 76706

Phone: 512-661-3696

Email: \emph{Sai\_Sagireddy1@baylor.edu}

\textbf{Abstract:}

Prostatic leiomyosarcoma is quite rare. There is little consensus on the
best treatment for these aggressive tumors. They are most often
characterized by obstructive lower urinary tract symptoms without an
elevated serum prostate-specific antigen level. A high degree of
skepticism may help in detecting them in a timely manner since they lack
specific clinical or imaging features. It can be diagnosed by
immunohistochemical staining as, seen in our patient. Despite the lack
of definitive treatment options, innovative multimodal treatment
strategies may significantly improve the prognosis of patients suffering
from this tumor. This case report describes a leiomyosarcoma of the
prostate with metastasis.

\section*{Introduction:}

{\label{introduction}}

Prostate leiomyosarcoma is reported to be accounted for 0.1\% of all
prostate malignancies. It is a rare, aggressive tumor with fewer than
200 cases reported {[}1{]}; hence, treatment guidelines are not well
established. It was accompanied by non-specific symptoms similar to
those associated with benign prostatic hyperplasia. Our patient reported
having recurrent episodes of hematuria. We present a rare case of
prostate leiomyosarcoma treated with chemotherapy and a literature
review that discusses clinical features, diagnostic methods, and
therapeutic options.



\section*{Case presentation}

{\label{case-presentation}}

A 61-year-old male with no significant past medical history presented to
the emergency department with suprapubic discomfort and urinary
retention. The patient has a twenty-five-pack-year smoking history, a
family history of breast, pancreatic, and lung cancer, and no family
history of prostate cancer. A pelvic/bladder ultrasound revealed an
enlarged prostate gland measuring 8.6 cm x 7.9 cm x 9 cm, which was
heterogenous with a weight of 320 g. PSA was measured to be 1.4 ng/mL.
The patient continued to have frequent visits to the emergency
department for lower urinary tract symptoms, after which he underwent an
elective simple open prostatectomy.~There was a 2.5 cm circumferential
necrotic appearance to the right hemiprostate and asymmetric growth on
the right side. In addition, pathology reported an incidental finding of
leiomyosarcoma.

Immunohistochemical stains showed calponin (+ve), SMA (focal), Desmin
(patchy), smooth muscle myosin heavy chain (+ve), caldesmon (+ve,)
vimentin patchy, CD34 (-ve) and PR (-ve), CK5/6 (-ve). In addition, TSC2
and BRCA 1 genomic alternations were detected. The post-surgical course
was complicated by hematuria, which was resolved with continuous bladder
irrigation.

Computed tomography (CT) of the chest/abdomen and pelvis (CTAP) showed
multiple nodular densities in the left and right lungs. A lobular
contour cyst in the liver measures about 1 cm x 0.59 cm, along with
cysts in the right and left kidneys. In addition, tiny nodes in the
retroperitoneum with prominent vessels are noted. There was a small
amount of intra-abdominal and pelvic ascites noted. The prostate gland,
enlarged with low attenuated lesions in the transitional and central
zones, measures about 4.6 cm x 2.9 cm on the right, and the left
measures about 1.9 cm in the transitional zone. The prostate measures
about 8.1 cm x 8.3 cm x 7.1 cm. NM bone scan revealed heterogeneous
uptake in the right posterior iliac spine, right scapular region, and
right distal region, indicating osseous metastases. The patient was
started on chemotherapy with a doxorubicin regimen every three weeks.

The patient continued to have recurrent hospitalizations for urinary
retention, suprapubic pain, worsening hematuria, and urinary tract
infections. He was treated with antibiotics and multiple blood
transfusions. Further course was complicated by left-sided
hydronephrosis, requiring left-sided nephrostomy tube placement.

The patient is currently being managed with an outpatient chemotherapy
regimen.

\textbf{Discussion}

This case study highlights the distinct challenges clinicians face when
diagnosing and managing prostatic leiomyosarcomas and determining the
etiology of concurrent urologic symptoms over the course of its
management. Prostate leiomyosarcomas are extremely rare, as they compose
0.1\% of primary prostate tumors; sarcomas account for 1\% of
malignancies, with 5\% of sarcomas arising from the genitourinary tract
{[}2{]}. In each of the rare cases, the condition may present with a
plethora of non-specific genitourinary symptoms such as recurrent
hematuria, urinary frequency or urgency, recurrent urinary tract
infections (UTIs), urinary retention, or generalized suprapubic pain.
The FNCLCC grading system and histopathological examination are
typically used for the definitive diagnosis. The tumor histology is
notable for marked necrosis, hypercellularity, nuclear pleomorphism
without degenerative features, positive histochemical stains such as
smooth muscle actin, Desmin, vimentin, calponin, and CD34, and is
commonly differentiated from other prostatic stromal lesions known as
STUMP {[}3{]}. In contrast to more common tumors of the prostate, normal
or slightly elevated PSA values can be noted in prostate
leiomyosarcomas, as the tumor has a nonepithelial origin. Although no
standard recommendations are established to treat prostate
leiomyosarcoma, a wide variety of treatments may be used and can include
surgery, if operable, as well as chemotherapy and radiotherapy. However,
the long-term survival rate and overall prognosis remains poor {[}4{]}.

The described case features an unusual presentation of a rare prostate
malignancy associated with multiple postoperative hospitalizations for
recurrent hematuria, urinary retention, suprapubic pain, and urinary
tract infections (UTIs). Although urinary frequency and urgency are
commonly reported symptoms in patients with prostate leiomyosarcomas,
recurrent hematuria and urinary retention have only been reported in a
handful of isolated cases. In this case of a 61-year-old male with a
strong smoking history and a normal PSA level, hematuria may be a rare
obvious symptom that can delay its diagnosis {[}5{]}. This patient's
unique symptoms of recurrent hematuria and acute urinary retention may
be associated with either the malignancy or due to a multitude of other
factors.

The urinary retention and recurrent UTIs may have occurred secondary to
a significantly enlarged prostate and underlying BPH. In contrast, the
recurrent hematuria that began shortly after the prostatectomy may be
attributed to a documented adverse event from either the operation
{[}6{]}, post-operational radiotherapy {[}7{]}, or doxorubicin
treatments {[}8{]}. Despite the multifactorial etiology of the recurrent
hematuria, the hematuria was most likely caused directly by the
leiomyosarcoma. This is because recurrent hematuria has been linked to
prostate leiomyosarcomas due to hypervascularity {[}9, 10{]}. The
involvement of the anterior transitional zone and right distal ureter in
this patient's tumor, rather than the commonly affected peripheral zone
in other prostate malignancies, may have also contributed to the
resulting hematuria. In addition, dysuria and stranguria, or symptoms of
bladder outlet obstruction, have been noted to occur with prostate
sarcomas {[}2, 4{]}.

As prostate leiomyosarcomas with recurrent episodes of hematuria are
rare, it is of note that this case may have an etiological genetic
component. While the patient denied any family history of prostate
cancer or bleeding disorders, the patient's sister and maternal
grandmother had breast cancer in their early 60s and 80s, respectively.
In addition, his mother was diagnosed with pancreatic cancer at 75. This
may be due to a germline mutation through his maternal lineage, as
prostate cancers such as leiomyosarcomas have been associated with a
family history of breast and pancreatic cancers diagnosed at a younger
age {[}11{]}.

Prostate leiomyosarcomas can have several systemic manifestations and
may be difficult to diagnose in certain situations. Aside from the
clinical symptoms due to the primary prostatic growth, the metastatic
and extra-prostatic manifestations of the sarcoma, such as the ascites
and osteoblastic pulmonary lesions, can be debilitating and have a
significant impact on the quality-of-life of the affected patient. For
this reason, its complex pathology requires clinicians to be aware of
the masquerading effects of other genitourinary conditions and
postoperative adverse events on potential neoplastic symptoms and the
multifactorial etiology of non-specific symptoms such as hematuria and
urinary retention.

The constellation of typical constitutional symptoms and physical exam
findings, including recurrent hematuria, urinary retention, suprapubic
pain, and UTIs, is non-specific and may be due to either infectious,
iatrogenic, or neoplastic conditions. For this reason, determining the
etiology of these symptoms is paramount in establishing a timely
diagnosis and preventing significant delays in disease management and
treatment. In addition, diagnostic tests such as a timely abdominal CT
scan can detect malignant ascites that may significantly affect the
patient's prognosis and management. Although prostate leiomyosarcomas
are not often seen in clinical practice, it is crucial to be aware of
its presentation as an accurate diagnosis may improve the patient's
quality and life expectancy.

\textbf{Conclusion:}

Detecting prostate leiomyosarcoma can be difficult due to the
variability in clinical presentations, as well as the lack of clear
clinical signs of malignancy. Leiomyosarcoma of the prostate is a rare
neoplasm, often presents in the metastatic stage with normal PSA levels
and usually takes an aggressive course. Therefore, a multidisciplinary
approach is essential for the appropriate management of this cancer.

\textbf{Authorship:}

Sowmya Sagireddy searched the literature, wrote, and revised the
manuscript. Chiya Abramowitz wrote discussion and searched the
literature. Sai Sagireddy and Marc Sukhoo-Pertab revised and edited the
manuscript. Mark Sonnenschine approved the final version and is the
article's guarantors. All authors certify that they contributed
sufficiently to the intellectual content and data analysis. Each author
has reviewed the final version of the manuscript and approves it for
publication.

\textbf{Acknowledgments:}

Not applicable

\textbf{Conflicts of Interest:}

Not applicable

\textbf{Availability of data and materials:} All data generated during
this study are available from the corresponding author upon request

\textbf{Ethics approval:}

This study protocol was reviewed and the need for approval was waived by
the ethics committee at South Brooklyn Health.

\textbf{Consent for publication:}

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

\textbf{References}

\begin{enumerate}
\tightlist
\item
  Zazzara M, Divenuto L, Scarcia M, Cardo G, Maselli FP, Ludovico GM.
  Leiomyosarcoma of prostate: Case report and literature
  review.~\emph{Urol Case Rep} . 2017;17:4-6. Published 2017 Dec 5.
  doi:10.1016/j.eucr.2017.11.024
\item
  Mondaini N, Palli D, Saieva C, et al. Clinical characteristics and
  overall survival in genitourinary sarcomas treated with curative
  intent: a multicenter study.~\emph{Eur Urol} . 2005;47(4):468-473.
  doi:10.1016/j.eururo.2004.09.013
\item
  Zazzara M, Divenuto L, Scarcia M, Cardo G, Maselli FP, Ludovico GM.
  Leiomyosarcoma of prostate: Case report and literature review. Urol
  Case Rep. 2017 Dec 5;17:4-6. doi: 10.1016/j.eucr.2017.11.024. PMID:
  29276684; PMCID: PMC5735258.
\item
  Chen HJ, Xu M, Zhang L, Zhang YK, Wang GM.~\emph{Zhonghua Nan Ke Xue}
  . 2005;11(9):683-685.
\item
  Loghmari A, Ben Othmane M, Belkacem O, Bouassida K, Hmida W, Jaidane
  M. Recurrent hematuria: A rare presentation of leiomyosarcoma of the
  prostate.~\emph{Ann Med Surg (Lond)} . 2022;77:103634. Published 2022
  Apr 16. doi:10.1016/j.amsu.2022.103634
\item
  Nargund VH, Noble JG, Cranston D, Fellows GJ. Haematuria: a long-term
  problem after prostatectomy.~\emph{Urol Int} . 2001;66(1):1-3.
  doi:10.1159/000056552
\item
  Turchan WT, Cutright D, Wu T, et al. Hematuria following
  Post-Prostatectomy Radiotherapy: Incidence Increases with Long-Term
  Followup.~\emph{J Urol} . 2022;207(6):1236-1245.
  doi:10.1097/JU.0000000000002443
\item
  Afsar T, Razak S, Almajwal A, Al-Disi D. Doxorubicin-induced
  alterations in kidney functioning, oxidative stress, DNA damage, and
  renal tissue morphology; Improvement by~\emph{Acacia hydaspica}
  ~tannin-rich ethyl acetate fraction. Saudi J Biol Sci. 2020
  Sep;27(9):2251-2260. doi: 10.1016/j.sjbs.2020.07.011. Epub 2020 Jul
  10. PMID: 32884406; PMCID: PMC7451730.
\item
  Singh JP, Chakraborty D, Bera MK, Pal D. Leiomyosarcoma of prostate: a
  rare, aggressive tumor.~\emph{J Cancer Res Ther} . 2013;9(4):743-745.
  doi:10.4103/0973-1482.126482
\item
  Wang MQ, Zhang JL, Yuan K, et al. Large inoperable leiomyosarcoma of
  the prostate: treated by transcatheter arterial chemoembolization with
  drug-eluting microspheres.~\emph{Ther Adv Med Oncol} .
  2020;12:1758835920917573. Published 2020 May 18.
  doi:10.1177/1758835920917573
\item
  Brand\selectlanguage{ngerman}ão A, Paulo P, Teixeira MR. Hereditary Predisposition to Prostate
  Cancer: From Genetics to Clinical Implications.~\emph{Int J Mol Sci} .
  2020;21(14):5036. Published 2020 Jul 16. doi:10.3390/ijms21145036
\end{enumerate}

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