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\begin{document}

\title{Metastatic Prostate Cancer Presenting as a Posterior Mediastinal Mass: A
Rare Presentation}



\author[1]{Muhammad Haider}%
\author[1]{Arun Mahtani}%
\author[1]{Bachar Botrus}%
\author[1]{Foma kenne}%
\author[2]{Madiha Master}%
\affil[1]{Richmond University Medical Center}%
\affil[2]{Philadelphia College of Osteopathic Medicine}%


\vspace{-1em}



  
  \date{June 13, 2024}


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\selectlanguage{english}
\begin{abstract}
A 68-year-old African American male who presented to the emergency
department with back and abdominal pain. Imaging showed a posterior
mediastinal mass interposed between the carina, the left mainstem
bronchus, and the descending thoracic aorta. Biopsy of the mass favored
a metastatic prostate carcinoma, which is an extremely rare
presentation.%
\end{abstract}%



\sloppy


Metastatic Prostate Cancer Presenting as a Posterior Mediastinal Mass: A
Rare Presentation

Muhammed Haider, MD\textsuperscript{1}, Arun Umesh Mahtani,
MD\textsuperscript{1}, MS\textsuperscript{1}, Bachar Botrus,
MD\textsuperscript{1}, Foma Munoh Kenne, MD\textsuperscript{2}, Madiha
Fatima Master,MA\textsuperscript{3}

Institutional Affiliations:

1) Department of Medicine, Richmond University Medical Center/Mount
Sinai

2) Department of Hematology/Oncology, Richmond University Medical
Center/Mount Sinai

3) Philadelphia College Of Osteopathic Medicine

Disclosures: The authors have nothing to disclose

Funding: No financial support

Competing Interests: The authors declare that they have no competing
interests

Acknowledgments: Not applicable

\textbf{Abstract}

A 68-year-old African American male who presented to the emergency
department with back and abdominal pain. Imaging showed a posterior
mediastinal mass interposed between the carina, the left mainstem
bronchus, and the descending thoracic aorta. Biopsy of the mass favored
a metastatic prostate carcinoma, which is an extremely rare
presentation.

Keywords: Prostate, Prostatic Neoplasms, Mediastinal neoplasms, African
American, Back Pain

\textbf{Background}

According to American cancer society estimates for 2022, there will
about 268,490 new cases of prostate cancer and about 34,500 prostate
cancer related deaths in the United states\textsuperscript{1}. Patients
can have variable symptoms on presentation, including anemia, paralysis
from metastasis to the spinal cord, bone pain, and kidney failure from
ureteral obstruction. Prostate-specific antigen (P.S.A.) and transrectal
ultrasound-guided biopsy remain the best diagnostic tools, although the
use of P.S.A. level for screening remains
controversial.\textsuperscript{3,4} About 12\% of all prostate cancer
has already spread to regional lymph nodes at the time of diagnosis,
with 5\% of cases having distant metastases. The 5-year survival rate is
only 29.8\% in distant metastatic disease.\textsuperscript{1} Skeletal,
lung, and liver metastases are the classic site of tumor spread, with
other sites being quite rare. Our case is unique, as it presented as a
posterior mediastinal metastatic mass.

\textbf{History of Presentation}

A 68-year-old male with a past medical history of hypertension but not
compliant with medication presented to emergency department (E.D.) with
complaints of back and abdominal for the past 2 months. The patient
described the pain as dull, localized to the paraspinal region,
non-radiating, with no aggravating factors, and partially relieved on
taking ibuprofen. He also noticed having unintentional weight loss and
excessive fatigue for the past year. His pain worsened, prompting him to
come to the E.D. He denies having fever, chills, night sweats, chest
pain, nausea, vomiting, diarrhea, constipation, or a history of cancer.

On examination, his vital signs were recorded as; blood pressure (B.P.)
of 223/135 mmHg, a heart rate (H.R.) of 104 beats per minute (B.P.M.), a
respiratory rate of 18 cycles per minute (C.P.M.), and oxygen saturation
of 99\% on room air. On musculoskeletal examination, there was no
paraspinal or spinal swelling inspection, and no paraspinal or spinal
tenderness on palpation. Respiratory and cardiovascular examinations
were normal. His initial working diagnosis was hypertensive urgency, and
he was initially treated with intravenous labetalol 20 mg pushes but was
switched to a nicardipine drip at 5 mg/hr due to poor control.

\textbf{Past Medical and Surgical History}

The patient is hypertensive but is not compliant with antihypertensive
medications. He was on metoprolol 25 mg every 12 hours and nifedipine
extended-release 60 mg every 12 hours. He also has benign prostate
hyperplasia, for which he took doxazosin 1 mg at bedtime. He was
non-compliant to primary care physician visits and had not followed up
in years. No surgeries were reported. He denies smoking cigarettes or
consuming alcohol, but does smoke marijuana.

\textbf{Family History}

No family history of cancer reported

\textbf{Investigations}

His initial lab results showed a white blood cell (WBC) count of 3.9
K/uL, hemoglobin of 12.5 gm/dL, a platelet count of 187 K/uL, blood urea
nitrogen (BUN) of 19 mg/dL, and creatinine (Cr) of 1.6 mg/dL. Other
investigations showed an iron level of 57 ug/dl, total iron binding
capacity (TIBC) of 227mcg/L, ferritin of 469.4 ng/dL, a lactate
dehydrogenase of 286 U/L, an E.S.R. of 31mm/hr, a high sensitivity
troponin of 30.8 ng/L, plasma total free metanephrine of 75 pg/mL,
plasma normetanephrine of 236 pg/mL, and total plasma metanephrine of
311 pg/mL.

An electrocardiogram (EKG) was done, which showed normal sinus rhythm.

A chest x-ray (C.X.R.) was also done, which showed a 1.3 cm nodule noted
projecting over the fifth rib anterolaterally and in the right, mid lung
field peripherally, widening of the mediastinum, and sclerotic 1 cm
density in the right, and 1.1 cm density in the left humerus shaft
{[}figure1{]}.

Following this result, he underwent a computed tomography angiogram
(C.T.A.) of the chest, abdomen, and pelvis (C.A.P.) to rule out aortic
dissection. It showed a large enhancing soft tissue mass in the
posterior mediastinum measuring 5.0 x 4.3 cm {[}figure 2 and 3{]}. The
thoracic aorta was unremarkable. There was no pericardial or pleural
effusion. The lungs were clear. There was no thoracic lymphadenopathy,
and extensive retroperitoneal abdominal lymphadenopathy was noted.
Additionally, mild left-sided hydronephrosis and hydroureter were seen
due to lymphadenopathy.

A renal sonogram revealed minimal left kidney hydronephrosis,a pre-void
bladder volume of 135.3 ccs, and prostatomegaly measuring 5.0 x 5.0 x
5.8 cm and weighing 75.6 gms. The right kidney was unremarkable on the
renal sonogram {[}figure 4{]}.

Given the findings of the C.T.A., interventional radiology (I.R.) was
consulted to biopsy the mass. The biopsy was technically challenging due
to the overlying rib, the adjacent descending thoracic aorta, and
intercostal vessels in the single available window. The needle was
successfully positioned in the posterior border of the mass. No bleeding
was incurred.

The biopsy results favored metastatic prostate carcinoma with positive
immunostaining of NKX3.1 and positive immunohistochemistry of PD-L1 CPS
{[}Figures 5 and 6{]}.

\textbf{Management}

His symptoms improved with conservative medical management, and he was
discharged with instructions to follow up with a hematologist-oncologist
on an outpatient basis for further treatment of his mediastinal lesion.

\textbf{Discussion}

Prostate cancer is the third leading cause of cancer death in
men.\textsuperscript{4} It is the most common non-cutaneous cancer in
men in the United States.\textsuperscript{5} It typically affects males
above the age of 50. However, younger age groups have been identified
since using P.S.A. as a screening tool.\textsuperscript{6} The five-year
survival rate of localized and regional prostate cancer is more than
99\%, whereas metastatic prostate cancer is only
30\%\textsuperscript{1}. At presentation, about 78\% of the lesions are
localized, and only 6\% of cases present with
metastasis.\textsuperscript{1} Spread to other body parts usually occurs
through lymphatic, hematogenous, or direct extension. Bone and lymph
nodes are common sites among those with metastatic lesions, with
pulmonary, hepatic, retroperitoneal, or abdominal metastasis very
uncommon.\textsuperscript{6} Mediastinal metastasis is exceedingly rare
and can present with mediastinal adenopathy in 0.6\% of the
cases.\textsuperscript{7} Only one other case of prostate cancer is
reported presenting with a mediastinal mass.\textsuperscript{8} In the
United States, significant racial differences exist in the management of
prostate cancer.\textsuperscript{9}

Management initially begins with screening, either by measuring P.S.A.
once a patient reaches above the age of 50 or performing a digital
rectal examination to check for a palpable
abnormality.\textsuperscript{6} Confirmatory tests involve performing an
ultrasound-guided transrectal prostate biopsy in a grid-like pattern and
staging it based on Gleason's scoring.\textsuperscript{10} Even though
it is the standard of care, it can miss up to 28\% of lesions and
undergrade up to 17\%.\textsuperscript{11} Hence, newer diagnostic
tests, biomarkers, and imaging modalities have been developed to improve
diagnosis and risk stratification accuracy.\textsuperscript{10} One such
biomarker that is specific to primary prostatic adenocarcinoma is
NKX3.1.\textsuperscript{12,13}, coded for by a gene located on
chromosome 8p, which aids prostate development and acts as a tumor
suppressor gene. Loss of this marker correlates with microenvironment
inflammation, usually found in the early stages of prostate
cancer.\textsuperscript{14}

Studies have also shown that NKX3.1 interacts with M.Y.C., and a
reduction in the former results in proliferative effects of M.Y.C.,
leading to cancer progression and relapse.\textsuperscript{15} It can
also distinguish between high-grade prostate cancer and high-grade
bladder cancer.\textsuperscript{16} It can be used to identify
metastasis and has shown a sensitivity and specificity of 98.6 and
98.7\% respectively in a cohort of metastatic
tumors.\textsuperscript{17} Studies have also shown that it is more
specific than P.S.A. when identifying prostate
cancer.\textsuperscript{18} Based on our discussion, our case also has
similar pertinent findings. Our patient was an African American male
aged 68 years with a late diagnosis due to patient non-compliance; a
biopsy of his metastatic mass was positive for NKX3.1. Even though a
digital rectal exam or a prostate-specific antigen due to the absence of
genitourinary symptoms and a different presentation, a diagnosis was
confirmed based on immunohistochemistry. Since his primary symptoms
improved his condition was further managed on an outpatient basis with
the hematology-oncology team.

Author Contributions:

1, Muhammad Haider - Department of Medicine, Richmond University Medical
Center/Mount Sinai

Prepared, reviewed and edited the manuscript

2, Arun Umesh Mahtani- Department of Medicine, Richmond University
Medical Center/Mount Sinai

Reviewed and edited the manuscript/figures

3, Bachar Botrus - Department of Medicine, Richmond University Medical
Center/Mount Sinai

Reviewed and edited the manuscript/figures

4, Foma Munoh Kenne - Department of Hematology/Oncology, Richmond
University Medical Center/Mount Sinai

Reviewed and edited the manuscript

5, Madiha Fatima Master - Philadelphia College Of Osteopathic Medicine

Reviewed and edited the manuscript

\textbf{References}

1. Cancer of the Prostate. Accessed July 17th 2022.
https://seer.cancer.gov/statfacts/html/prost.html

2. Harvey CJ, Pilcher J, Richenberg J, Patel U, Frauscher F.
Applications of transrectal ultrasound in prostate cancer. \emph{Br J
Radiol} . Nov 2012;85 Spec No 1(Spec Iss 1):S3-17.
doi:10.1259/bjr/56357549

3. Sadeghi-Nejad H, Simmons M, Dakwar G, Dogra V. Controversies in
transrectal ultrasonography and prostate biopsy. \emph{Ultrasound Q} .
Sep 2006;22(3):169-75. doi:10.1097/01.ruq.0000226875.35184.15

4. Miller KD, Siegel RL, Lin CC, et al. Cancer treatment and
survivorship statistics, 2016. \emph{C.A. Cancer J Clin} . Jul
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5. Alshaikh S, Harb Z. Prostate cancer presenting as huge Mediastinal
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6. Fitzmaurice C, Allen C, Barber R.M., et al. Global, regional, and
national cancer incidence, mortality, years of life lost, years lived
with disability, and disability-adjusted life-years for 32 cancer
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disease study. \emph{JAMA oncology} . 2017;3(4):524-548.

7. Baer J, McGowan P, Pandya S. Prostate cancer metastasis presenting as
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8. Teah KM, Bong CP, Mudin K, Soe MZ, Thevarajah S, Yeap BT. Case
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9. Smith ZL, Eggener SE, Murphy AB. African-American Prostate Cancer
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10. Litwin MS, Tan H-J. The diagnosis and treatment of prostate cancer:
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11. Bjurlin MA, Carter HB, Schellhammer P, et al. Optimization of
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12. Griffin J, Chen Y, Catto JW, El-Khamisy S. Gene of the month: NKX3.
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13. Gurel B, Ali TZ, Montgomery EA, et al. NKX3.1 as a marker of
prostatic origin in metastatic tumors. \emph{Am J Surg Pathol} . Aug
2010;34(8):1097-105. doi:10.1097/PAS.0b013e3181e6cbf3

14. Song H, Zhang B, Watson MA, Humphrey PA, Lim H, Milbrandt J. Loss of
Nkx3. 1 leads to the activation of discrete downstream target genes
during prostate tumorigenesis. \emph{Oncogene} . 2009;28(37):3307-3319.

15. Abeshouse A, Ahn J, Akbani R, et al. The molecular taxonomy of
primary prostate cancer. \emph{Cell} . 2015;163(4):1011-1025.

16. Oh WJ, Chung AM, Kim JS, et al. Differential immunohistochemical
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18. Pitra T, Pivovarcikova K, Alaghehbandan R, et al. Utility of Nkx3. 1
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Consent Statement:

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

Conflict Of Interest:

There are no conflicts of interest to declare

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