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\begin{document}

\title{Ectopic Production of Beta-hCG in Anal Cancer: A Case Report}



\author[1]{Sierra Silverwood}%
\author[2]{Peter Kohler}%
\author[2]{Yelena Kier}%
\affil[1]{Michigan State University College of Human Medicine}%
\affil[2]{Munson Medical Center}%


\vspace{-1em}



  
  \date{May 28, 2024}


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\begin{abstract}
\textbf{Objective:} This case report describes the second reported case
of ectopic production of beta-hCG in anal cancer \textbf{Case:}
53-year-old female presented with a new anal lesion. Biopsy showed a
poorly differentiated squamous cell cancer (SCC) with undifferentiated
sarcomatoid features, stage IIIA (cT2cN1cM0). Before starting concurrent
chemotherapy and radiation, the patient had%
\end{abstract}%



\sloppy


\textbf{Ectopic Production of Beta-hCG in Anal Cancer: A Case Report}

Sierra Silverwood\textsuperscript{1}, Peter Kohler,
MD\textsuperscript{2}, and Yelena Kier, DO\textsuperscript{2}

\textsuperscript{1} Michigan State University College of Human Medicine,
Traverse City, MI, USA

\textsuperscript{2} Cowell Cancer Center, Munson Healthcare Foundation,
Traverse City, MI, USA

Corresponding Author: Sierra Silverwod, silverwo@msu.edu

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

\textbf{Abstract}

\textbf{Objective:} This case report describes the second reported case
of ectopic production of beta-hCG in anal cancer

\textbf{Case:} 53-year-old female presented with a new anal lesion.
Biopsy showed a poorly differentiated squamous cell cancer (SCC) with
undifferentiated sarcomatoid features, stage IIIA (cT2cN1cM0). Before
starting concurrent chemotherapy and radiation, the patient had a
positive urine pregnancy test. The beta-human chorionic gonadotropin
(beta-hCG) production was attributed to the tumor, and upon completion
of treatment, beta-hcg normalized. Six weeks from treatment completion,
recurrence was noted along with (+) beta-hCG urine testing.

\textbf{Conclusion:} This case aims to highlight beta-hCG as an ectopic
hormone that can indicate the presence of squamous cell anal cancer and
discuss the potential implication it may have on management.

Keywords: Anal Cancer, Ectopic Hormones, Multidisciplinary Care,
Diagnostic Techniques

\emph{Introduction}

Beta-human chorionic gonadotropin (beta-hCG) is produced by the villous
syncytiotrophoblast that forms during pregnancy. It has numerous
functions but primarily promotes progesterone production and maintenance
of the corpus luteum.1 While the syncytiotrophoblast is the
physiological origin of beta-hCG, it can be produced ectopically.
Elevated beta-hCG levels are found in association with several tumors:
seminomatous and nonseminomatous testicular tumors, ovarian germ cell
tumors, and non-testicular teratomas.2 Data from one study by Burcynska
et al. (2013) examining beta-hCG in a mouse model suggest it may result
in a diminished response to radiotherapy and expedited metastasis.
Several other studies have also found ectopic production correlated with
poorer prognosis.3,4 This hormone, however, has rarely been associated
with anal cancer.

In the one documented account of beta-hCG production in anal cancer by
Pokharel et al., a 43-year-old female presented with p-16 positive
squamous cell anal cancer.5 During the patient's pre-treatment
screening, beta-hCG was positive. Treatment was held until it was
determined that the tumor was producing the hormone. With treatment, the
levels of beta-hCG eventually dropped to zero. It was postulated that
this ectopic hormone production was likely due to the association
between the development of precancerous anal and cervical lesions
through human papillomavirus (HPV). The study concluded that beta-hCG
expression might be the first sign of a primary malignancy.

An elevated beta-hCG has not been explored as a prognostic factor in
anal cancer. Currently, the most important factors for prognosis in anal
cancer are T and N stages, while grade and histology have no clear
role.6 This represents the second case report of a female patient who
presented with squamous cell carcinoma of the anus with ectopic
production of beta-hCG.

\emph{Case Presentation}

In 2017, a 53-year-old female presented with a calcified mass in the
left upper lobe of the lung, diagnosed as a carcinoid tumor. She
underwent a video-assisted thoracoscopic surgery (VATS) upper lobectomy
in 2018 with a final pathological staging of pT2aN0, stage II. Four
years later, she was diagnosed with stage 1B HPV-negative squamous cell
carcinoma of the left labia majora and underwent a left radical
hemivulvectomy and sentinel lymph node biopsy.

The patient presented with a new anal lesion in June 2022. Biopsy
revealed a poorly differentiated squamous cell cancer undifferentiated
with sarcomatoid features (Images 1 and 2). This lesion was staged as
IIIA (cT2, cN0 vs. cN1, cM0) SCC of the anus (Images 1 and 2).
Pre-treatment testing demonstrated a positive urine pregnancy test and
serum beta-HCG of 87.5 mlU/mL. The patient was postmenopausal by history
and had a prior uterine ablation. The ultrasound did not identify
intrauterine pregnancy. Given these results, the patient was treated
with standard chemo-radiation.

The immunohistochemistry from the biopsy was positive for beta-hCG
(Image 3). Beta-hCG was monitored via weekly urine pregnancy tests. The
patient completed chemotherapy and radiation treatment in late August.
Urine beta-hCG was negative. Six weeks after completing treatment,
testing of urine beta-hCG was found, once again, to be elevated. A
positron emission tomography (PET) scan in October 2022 revealed a
persistent hypermetabolic mass with a maximum standardized uptake value
(SUVmax) of 17.6 (not felt to be substantially changed from the previous
scan). There was no evidence of metastatic disease. Given the persistent
disease, robotic-assisted abdominoperineal resection with a colostomy
was performed post-treatment. Imaging seven months later demonstrated
disease recurrence and progression. Subsequently, the patient started
palliative pembrolizumab.

\emph{Discussion}

The production of ectopic beta-hCG outside the usual placental location
is concerning in several cancer types.2 Previous research suggests that
ectopic beta-hCG production may indicate a poor prognosis in breast
cancer.1,2 However, the occurrence of ectopic beta-hCG production in the
context of anal cancer is rare, with only two reported cases to date.5

Currently, the diagnostic process for hormone-producing anal cancer can
be challenging due to the rarity of the condition and the need for
specialized testing.5 Further research into new or improved diagnostic
techniques, such as biomarker testing or imaging methods, may help to
identify these tumors more accurately and efficiently. This research
could lead to earlier diagnosis and treatment, potentially improving the
prognosis for patients with hormone-producing anal cancer.

Additionally, research into hormone therapies targeting
hormone-producing cells may offer these patients an effective treatment
option.13 Studies have shown that targeted therapies, such as aromatase
inhibitors, have effectively treated hormone-producing breast and
ovarian cancers.14,15 Similar approaches may be effective in the
treatment of hormone-producing anal cancer. Therefore, it is essential
to explore these treatment options to improve outcomes for patients with
this condition.

In conclusion, hormone-producing anal cancer is a rare tumor that can be
challenging to diagnose and may resist standard chemotherapy and
radiation therapies. Therefore, coordinated multidisciplinary care is
essential to optimize patient care and outcomes. The case presented
highlights the importance of considering the potential for hormone
production in anal cancer and the need for specialized testing and
management.

\emph{Disclosures}

No conflicts of interest.

No funding was received.

\textbf{References}

1. Cole LA. Biological functions of hCG and hCG-related
molecules.\emph{Reproductive Biology and Endocrinology}. 2010;8.
doi:10.1186/1477-7827-8-102 2. Beta-Human Chorionic Gonadotropin,
Quantitative, Serum - Mayo Clinic Laboratories \textbar{} Neurology
Catalog. Accessed January 1, 2023.
https://neurology.testcatalog.org/show/BHCG 3. Iles RK. Ectopic hCG\selectlanguage{greek}β
\selectlanguage{english}expression by epithelial cancer: Malignant behaviour, metastasis and
inhibition of tumor cell apoptosis. \emph{Mol Cell Endocrinol}.
2007;260-262. doi:10.1016/j.mce.2006.02.019 4. Inoue N, Watanabe H,
Takehara H, Hamazaki M, Kagami S. Refractory pediatric
nonrhabdomyosarcoma soft tissue sarcoma associated with ectopic
production of beta hCG and hypercalcemia induced by PTHrP.\emph{Pediatr
Blood Cancer}. 2011;57(7). doi:10.1002/pbc.23271 5. Pokharel K, Gilbar
PJ, Mansfield SK, Nair LM, So A. Elevated beta human chorionic
gonadotropin in a non-pregnant female diagnosed with anal squamous cell
carcinoma. \emph{Journal of Oncology Pharmacy Practice}. 2020;26(5).
doi:10.1177/1078155219893428 6. Das P, Crane CH, Eng C, Ajani JA.
Prognostic factors for squamous cell cancer of the anal canal.
\emph{Gastrointest Cancer Res}. 2008;2(1). 7. Key Statistics for Anal
Cancer. Accessed January 1, 2023.
https://www.cancer.org/cancer/anal-cancer/about/what-is-key-statistics.html
8. Yao JN, Zhang XX, Zhou HN, et al. Human papillomavirus related anal
squamous cell carcinoma survival: A systematic review and
meta-analysis.\emph{Transl Cancer Res}. 2017;6(3).
doi:10.21037/tcr.2017.06.13 9. Types of anal cancer \textbar{} Cancer
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https://www.cancerresearchuk.org/about-cancer/anal-cancer/stages-types/types
10. Anal Cancer Screening for People at High Risk \textbar{} OncoLink.
Accessed January 1, 2023.
https://www.oncolink.org/risk-and-prevention/prevention-screening/anal-cancer-screening
11. Anal Cancer Survival Rates. Accessed January 1, 2023.
https://www.cancer.org/cancer/anal-cancer/detection-diagnosis-staging/survival-rates.html
12. Sch\selectlanguage{ngerman}üler-Toprak S, Treeck O, Ortmann O. Human chorionic gonadotropin
and breast cancer. \emph{Int J Mol Sci}. 2017;18(7).
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al. Differential impact of endocrine therapy and chemotherapy on quality
of life of breast cancer survivors: a prospective patient-reported
outcomes analysis.\emph{Annals of Oncology}. 2019;30(11).
doi:10.1093/annonc/mdz298 14. Chumsri S, Howes T, Bao T, Sabnis G,
Brodie A. Aromatase, aromatase inhibitors, and breast cancer.
\emph{Journal of Steroid Biochemistry and Molecular Biology}.
2011;125(1-2). doi:10.1016/j.jsbmb.2011.02.001 15. Simpkins F,
Garcia-Soto A, Slingerland J. New insights on the role of hormonal
therapy in ovarian cancer. In: \emph{Steroids}. Vol 78. ; 2013.
doi:10.1016/j.steroids.2013.01.008 16. Taberna M, Gil Moncayo F,
Jané-Salas E, et al. The Multidisciplinary Team (MDT) Approach and
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doi:10.3389/fonc.2020.00085

\textbf{Hosted file}

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