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\begin{document}

\title{Metastatic sigmoid adenocarcinoma to the larynx: a case report and
updated literature review}



\author[1]{Adham  Aljariri}%
\author[1]{Abdulqadir Nashwan}%
\author[1]{Rani  Hammoud }%
\author[1]{Bara  Wazwaz }%
\author[1]{Sameer  Alhyassat}%
\author[1]{Hasan  Haider}%
\affil[1]{Hamad Medical Corporation}%


\vspace{-1em}



  
  \date{May 25, 2024}


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\selectlanguage{english}
\begin{abstract}
Metastatic laryngeal cancers are rare and usually indicate advanced
disease once they are present; we described a case of a 60 years old
male patient with stage IV colorectal cancer (CRC) who presented to our
clinic with dysphonia; further workups showed metastatic CRC.%
\end{abstract}%



\sloppy


\textbf{Metastatic sigmoid adenocarcinoma to the larynx: a case report
and updated literature review}

Adham A. Aljariri MD\textsuperscript{1}, Abdulqadir J. Nashwan
MSc\textsuperscript{2}, Rani Hammoud MD\textsuperscript{1}, Bara Wazwaz
MD\textsuperscript{3}, Samir Al Hyassat MD\textsuperscript{3}, Hassan H.
Ahmad MD\textsuperscript{1}

\emph{Short title: Metastatic sigmoid adenocarcinoma to the larynx}

\textbf{Affiliations}

\begin{enumerate}
\tightlist
\item
  Otolaryngology Department, Ambulatory Care Center (ACC), Hamad Medical
  Corporation (HMC), Doha, Qatar
\item
  Nursing Department, Hazm Mebaireek General Hospital, Hamad Medical
  Corporation, Doha, Qatar
\item
  Pathology Department, Hamad General Hospital (HGH), Hamad Medical
  Corporation (HMC), Doha, Qatar
\end{enumerate}

\textbf{Corresponding author:}

Mr. Abdulqadir J. Nashwan

anashwan@hamad.qa

Tel: (+974) 40240487

Mob: (+974) 66473549

P.O. Box 3050

Hamad Medical Corporation, Doha, Qatar

\textbf{Informed Consent}

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

\textbf{ABSTRACT}

Metastatic laryngeal cancers are rare and usually indicate advanced
disease once they are present; we described a case of a 60 years old
male patient with stage IV colorectal cancer (CRC) who presented to our
clinic with dysphonia; further workups showed metastatic CRC.

\textbf{Key Clinical Message}

Dysphonia is a known speech-related symptom in patients with cancer;
patients must be evaluated promptly and managed accordingly.

\emph{Keywords:} \emph{Colorectal adenocarcinoma; Laryngeal metastasis;
secondary laryngeal tumors; Dysphonia}

\textbf{INTRODUCTION}

Colorectal cancer (CRC) is the world's third most common cancer. (1) The
incidence of CRC is variable among high and low-income countries due to
lifestyle differences and early detection in screening programs of
premalignant lesions or polyps, the presentation of colorectal cancer is
variable depending on the involved location across the colon with more
than 50\% of the patients die from their CRC cancer, metastasis is
usually present in 20\% at the time of diagnosis, most commonly
identified site of metastasis is Liver, Lungs, and brain respectively,
however, no clear information about the exact percentage of each
metastasis as staging system usually stage them as stage IV without
clarifying the involved sites. (2-6) Metastatic laryngeal cancers
represent less than 1\% of all laryngeal malignancies, with Skin
melanoma and Renal cell carcinoma being the most common primary cancers
to metastasize to the larynx as reported by fertile et al. in 1988,
however, a recent review of the English literature showed that
colorectal cancer metastasis to the larynx is the most common and
compromise quarter of 41 cases. (3, 5) Dysphonia is the term used to
describe any impairment or alteration of the voice with hoarseness;
primarily, it is due to vocal muscle irregular oscillation owing to
underlying muscle tension or dysfunction, incomplete closure of glottis
on vocalization, or pressure effect excreted on the vocal folds by mass
or tumor. (4)

\textbf{CASE PRESENTATION}

A 60-year-old Caucasian male patient, known to have Diabetes Mellitus
(DM) type II on oral hypoglycemic agents and obstructive sleep apnea on
continuous positive airway pressure CPAP, the patient was diagnosed with
moderately differentiated sigmoid adenocarcinoma Stage IV (with distant
metastasis to liver and lung at the time of presentation, the patient
was treated with definitive chemotherapy with (FOLFOX/Panitumumab
regimen, he finished 12 cycles then maintenance therapy with 5FU/
Panitumumab), the patient was referred to ENT outpatient clinic due to
hoarseness of voice for 2 weeks duration, and 18 months after his
primary cancer diagnosis, there was no compressive respiratory or
swallowing difficulties.

Physical examination showed unremarkable oral cavity, throat, nose, and
ears; neck examination revealed no palpable lymphadenopathy. Fiberoptic
examination showed paralyzed right vocal cord with left vocal cord
compensation; no masses or lesions were noted along the upper
aerodigestive tract. The computerized tomography (CT) scan with contrast
is shown in (figure I), which confirms the presence of the known distant
lung and liver metastasis.

Open surgical biopsy was taken from the right cricoid cartilage, and
histopathology (Figure II) confirmed the metastatic sigmoid
adenocarcinoma of the right cricoid cartilage. A. Fibrous tissue
infiltrated by adenocarcinoma, B. H\&E x 200. Bone infiltrated by
adenocarcinoma, C. Immunohistochemical stain CDX2, and D.
Immunohistochemical stain with CK20.

The patient was managed from the ENT side by awake tracheostomy and
continued to his course of palliative treatment; 8 months after the
laryngeal metastasis diagnosis, the patient passed away due to cancer
complications.

Neck CT scan with contrast demonstrating destructive right laryngeal
mass destroying the cartilage and causing luminal narrowing with extra
laryngeal extension (Figure I), Chest and abdomen CT with intravenous
contrast showing multiple lung nodules of varying sizes (red arrows),
also multiple lesions on the liver can be noted largest being marked
with the yellow circle.

\textbf{DISCUSSION}

While the local extension of hypopharyngeal and thyroid tumors to the
larynx is common, metastatic laryngeal involvement remains rare; since
fertile et al. in 1987, a 13 laryngeal metastasis was reported in the
English literature from Colo-rectal cancer, and by Zenga et al. in 2016
colorectal was the most common primary site for laryngeal metastasis
followed by renal and prostate cancer 6 cases each, then 5 cases of skin
melanoma, the remaining cases were secondary to lung, bone, breast,
thyroid, liver and female genital tract cancers. (3)

Trans-glottic glottic involvement was the most common compromising about
40\% of the reported cases, followed by supraglottic area, then
subglottic in less than 10\% of the true vocal cords were involved,
about 70\% of the cases were reported in males, with the median age of
59 years, initial presentation in more than 60\% was Dysphonia, the
median time to laryngeal metastasis diagnosis was 3 years. (3)

The treatment modalities for secondary laryngeal metastasis vary
depending on the stage of the disease, the number of the metastatic
focus, and the involvement of other organs; in a case reported by
Therasma et al. in 2008, the laryngeal metastasis was managed with organ
preservation surgery as the patient was in remission from his primary
cancer with no other organ involvement. (7) Another case by Marioni et
al. was managed with total laryngectomy due to extensive laryngeal
involvement, and local control was controlled at the time of laryngeal
diagnosis. (8) Puxeddu et al., Sano et al., and Ta et al. managed their
patients with a tracheostomy to protect the airway from local disease
advancement. (9-11) In other cases, reported the local control of the
disease was achieved by laser excision by Nd-YAG laser and
CO\textsubscript{2} Laser. (5, 12) Summary of laryngeal metastasis
secondary to colorectal cancer is summarized in table 1.

Due to unfamiliarity with secondary laryngeal cancers, there is no
census of the treatment guidelines; treatment options depend on the
stage at the time of diagnosis, solitary laryngeal involvement, or the
presence of other metastatic focus; however, it is thought that
laryngeal cancer is still under-reported, as one post-mortem study
reported by Prescher et al. showed laryngeal involvement in 6 autopsies
out of 6 patients with prostate cancer and Horny and Kaiserling found 10
out of 14 patient with hematopoietic malignancy found to have laryngeal
metastasis. (13, 14) Incidental laryngeal metastasis without symptoms is
also evident, as reported by Xia et al. when a PET CT (positron emission
tomography-computed scan) was done for an elevated AFP (Alfa
fetoprotein) showed increased uptake in the larynx. (15)

\textbf{CONCLUSION}

Any laryngeal lesion in patients with malignancy or high-risk factors
for malignancy should be worked out promptly to avoid any delay in
diagnosis and management; even though secondary laryngeal malignancy is
rare, micro-metastasis and subclinical disease is evident; however,
laryngeal cancer metastasis indicates advance disease and poor
prognosis, but intervention aims to avoid any respiratory distress or
direct mortality from airway obstruction.

\textbf{Declarations}

\textbf{Ethics approval and consent to participate}

The article describes a case report. Therefore, no additional permission
from our Ethics Committee was required.

\textbf{Availability of data and material}

All data generated or analyzed during this study are included in this
published article.

\textbf{Competing interests}

The authors declare that they have no competing interests.

\textbf{Funding}

This study was not funded.

\textbf{Authors' contributions}

AAA, AJN, RH, BW, SH, HHA: Data Collection, Literature Search,
Manuscript Preparation

All authors read and approved the final manuscript

\textbf{Acknowledgments}

Open Access funding provided by the Qatar National Library.

\textbf{REFERENCES}

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P. Preoperative neutrophil-to-lymphocyte Ratio, Platelet-to-Lymphocyte
Ratio, and CEA as the Potential Prognostic Biomarkers for Colorectal
Cancer. Canadian Journal of Gastroenterology and Hepatology. 2022;2022.

2. Ma Y, Hu M, Zhou L, Ling S, Li Y, Kong B, et al. Dietary fiber intake
and risks of proximal and distal colon cancers: A meta-analysis.
Medicine. 2018;97(36).

3. Zenga J, Mehrad M, Bradley JP. Metastatic cancer to the larynx: a
case report and update. Journal of Voice. 2016;30(6):774. e9-. e12.

4. Reiter R, Hoffmann TK, Pickhard A, Brosch S. Heiserkeit-Ursachen und
Therapie. Dtsch Arztebl Int. 2015;112(19):329-37.

5. Heyes R, Balakumar R, Ramdoo K, Tatla T. Subglottic Metastatic Rectal
Adenocarcinoma: A Specialist Multidisciplinary Airway Team Approach for
Optimized Voice and Airway Outcome. Case Reports in Otolaryngology.
2017;2017.

6. Engstrand J. Liver metastases from colorectal cancer. 2017.

7. Terashima S, Watanabe S, Shoji M. Long-term survival after resection
of metastases in the lungs and larynx originating from sigmoid colon
cancer: report of a case. Fukushima journal of medical science.
2014;60(1):82-5.

8. Marioni G, De Filippis C, Ottaviano G, Lorusso M, Staffieri C,
Bernini G, et al. Laryngeal metastasis from sigmoid colon adenocarcinoma
followed by peristomal recurrence. Acta oto-laryngologica.
2006;126(6):661-3.

9. Puxeddu R, Pelagatti C, Ambu R. Colon adenocarcinoma metastatic to
the larynx. European archives of oto-rhino-laryngology.
1997;254(7):353-5.

10. Sano D, Matsuda H, Yoshida T, Kimura Y, Tanigaki Y, Mikami Y, et al.
A case of metastatic colon adenocarcinoma in the larynx. Acta
oto-laryngologica. 2005;125(2):220-2.

11. Ta JQ, Kim JY. Rectal adenocarcinoma metastatic to the larynx. Ear,
Nose \& Throat Journal. 2011;90(4):E28-E31.

12. Nicolai P, Puxeddu R, Cappiello J, Peretti G, Battocchio S,
Facchetti F, et al. Metastatic neoplasms to the larynx: report of three
cases. The Laryngoscope. 1996;106(7):851-5.

13. Prescher A, Schick B, St\selectlanguage{ngerman}ütz A, Brors D. Laryngeal prostatic cancer
metastases: an underestimated route of metastases? The Laryngoscope.
2002;112(8):1467-73.

14. Horny H-P, Kaiserling E. Involvement of the larynx by hemopoietic
neoplasms: an investigation of autopsy cases and review of the
literature. Pathology-Research and Practice. 1995;191(2):130-8.

15. Xia Y, Qi C, Zhang S, Huang Z, Chen Y. Elevated 18F-NaF uptake in
cricoid cartilage in a patient with laryngeal carcinoma: a case report
and literature review. Medicine. 2017;96(49).

16. Cavicchi O, Farneti G, Occhiuzzi L, Sorrenti G. Laryngeal metastasis
from colonic adenocarcinoma. The Journal of Laryngology \& Otology.
1990;104(9):730-2.

17. Hilger AW, Prichard AJ, Jones T. Adenocarcinoma of the larynx--a
distant metastasis from a rectal primary. The Journal of Laryngology \&
Otology. 1998;112(2):199-201.

18. Ramanathan Y, Rajagopalan R, Rahman NA. Laryngeal metastasis from a
rectal carcinoma. Ear, Nose \& Throat Journal. 2007;86(11):685-6.

\textbf{Figure legends}

Figure 1 - Neck, Chest, and Abdomen CT with contrast showing (A.
Right-sided laryngeal mass involving and destroying the laryngeal
cartilages with luminal narrowing and extra laryngeal extension, B.
widely scattered variable-sized (4-10 mm) pulmonary metastatic nodules,
C. Demonstration of multiple extensive hepatic metastatic involvement)

Figure 2 -- Findings of A. H\&E x 40., B. H\&E x 200. C. CDX2, and D.
CK20.

\textbf{Table 1 -- summery of cases of colon cancer from 1987 -2022}\selectlanguage{english}
\begin{longtable}[]{@{}llllllll@{}}
\toprule
& Author & Age/Sex & Country & Initial presentation & Involved site &
Management & Other involved sites\tabularnewline
\midrule
\endhead
1990 & Cavicchi et al (16) & 59/Female & Italy & Dysphonia & Subglottic
& Mass excision & Mediastinal Lymph nodes\tabularnewline
1996 & Nicolai et al (12) & 69/Male & Italy & Dysphonia & Glottic &
Radiation then total laryngectomy & Lung, Pleura, Brain, Adrenal
gland\tabularnewline
& & 53/Female & & Dyspnea & Subglottic & Local resection with Laser
(Nd-YAG) & Lung, Lymph nodes\tabularnewline
& & 58/Female & & Dyspnea & Subglottic & Local resection with Laser
(Nd-YAG) & Lung, Liver\tabularnewline
1997 & Puxeddu et al (9) & 65/Male & Italy & Dysphonia + respiratory
distress & Glottic & Tracheostomy + Local palliative irradiation &
Liver, Lung\tabularnewline
1998 & Hilger et al (17) & 73/Female & United Kingdom & Biphasic stridor
& Glottic & Tracheostomy followed by extended laryngectomy & Cervical
Lymph nodes\tabularnewline
2005 & Sano et al (10) & 81/Female & Japan & Dysphonia and Dyspnea &
Subglottic & Tracheostomy & Lung, Sacrum, Liver\tabularnewline
2006 & Marioni et al (8) & 78/Female & Italy & Neck swelling & Glottic &
Total laryngectomy and thyroidectomy & Lung, Thyroid\tabularnewline
2007 & Ramanathan et al (18) & 51/Male & Malaysia & Dysphonia & Glottic
& Palliative & Liver, Pelvis\tabularnewline
2011 & Ta et al (11) & 60/Male & USA & Dyspnea & Subglottic &
Tracheostomy + Debulking & Lung\tabularnewline
2014 & Therasma et al (7) & 54/Male & Japan & Dysphonia & Subglottic &
Partial laryngectomy & None\tabularnewline
2016 & Zenga et al (3) & 52/Male & USA & Incidental by PET CT & Glottic
& Tracheostomy + Palliative Chemoradiation & Brain, Lung,
Sacrum\tabularnewline
2017 & Heyes et al (5) & 56/Female & UK & Shortness of breath &
Subglottic & Local excision with CO2 Laser & Lung, Liver\tabularnewline
2022 & Present case & 60/Male & Qatar & Dysphonia & Glottic &
Tracheostomy & Lung, Liver\tabularnewline
\bottomrule
\end{longtable}\selectlanguage{english}
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