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\begin{document}

\title{A RARE CASE OF PRIMARY VAGINAL MALIGNANT MELANOMA-CASE REPORT}



\author[1]{Shreya Singh Beniwal}%
\author[2]{Rahul  Chikatimalla}%
\author[3]{Srikanth  Dogiparthi }%
\author[4]{Yukti Tomar}%
\author[5]{Kiranmai  Kanaparthi }%
\author[6]{Vikaskumar  Patel }%
\author[7]{Roshan Bhandari}%
\affil[1]{Lady Hardinge Medical College}%
\affil[2]{Kamineni Institute of Medical Sciences}%
\affil[3]{St. Martinus University Faculty of Medicine}%
\affil[4]{School of Medical Science and Research}%
\affil[5]{Malla Reddy Medical College for Women}%
\affil[6]{GMERS Medical College and Hospital Dharpur}%
\affil[7]{Tribhuvan University Institute of Medicine}%


\vspace{-1em}



  
  \date{May 27, 2024}


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\textbf{A RARE CASE OF PRIMARY VAGINAL MALIGNANT MELANOMA-CASE REPORT}

Shreya Singh Beniwal\textsuperscript{1}, Rahul
Chikatimalla\textsuperscript{2}, Srikanth Dogiparthi\textsuperscript{3},
Yukti Tomar\textsuperscript{4}, Kiranmai Kanaparthi\textsuperscript{5},
Vikaskumar Jitendrakumar Patel\textsuperscript{6}, Roshan
Bhandari\textsuperscript{7}

\textsuperscript{1}Lady Hardinge Medical College, Connaught Place, New
Delhi-110001, India

\textsuperscript{2}Kamineni Institute of Medical Sciences, Narketpally,
Telangana, India

\textsuperscript{3}St.Martinus University Faculty of Medicine, 122-124
Sta.Rosaweg, Willemstad, Cura\selectlanguage{ngerman}çao

\textsuperscript{4}School of Medical Science and Research, Greater
Noida, Uttar Pradesh, India

\textsuperscript{5}Malla Reddy Medical College for Women, Suraram,
Hyderabad, Telangana, India

\textsuperscript{6}GMERS Medical College, Dharpur, Patan, Gujarat, India

\textsuperscript{7}Maharajgunj Medical Campus, Institute of Medicine,
Tribhuvan University, Kathmandu-44600, Nepal

\textbf{Correspondence:}

Roshan Bhandari

Maharajgunj~Medical Campus

Institute of Medicine, Tribhuvan University

Maharajgunj, Kathmandu-44600, Nepal

Email:~bhandariroshan369@gmail.com

Phone: +977-9844930583

\textbf{Consent Statement:}

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

\textbf{Conflict of Interest Statement:} None

\textbf{Acknowledgements:} None

\textbf{Source of Funding Statement:} None

\textbf{Key Clinical Message:}

Rare, aggressive primary vaginal melanoma presents late with bleeding
and palpable masses. Histology and immunohistochemistry confirm the
diagnosis. Nivolumab and Ipilimumab offer hope in advanced stages. Early
diagnosis is critical for better outcomes.





\section*{ABSTRACT}

{\label{abstract}}

Only a few examples of vaginal melanoma have been documented in the
literature, making it an unusual change. Patients frequently present
with vaginal bleeding, discharge, or a lump that may be felt.
Post-menopausal Caucasian women between the ages of 60 and 80 are most
commonly affected. The prognosis for vaginal melanomas is worse because
the diagnosis is made when the condition is further advanced. This case
involves a 54-year-old woman who visited the clinic complaining of
foetid tranvaginal haemorrhage. The diagnosis of aggressive melanoma
with AJCC stage IV was made based on the biopsy results. The patient
declined drastic surgery due to her advanced age and the severity of her
cancer, so postoperative radiation and conservative surgery were used
instead. Nivolumab and ipilimumab immunotherapy was subsequently used.

\textbf{KEYWORDS:} Foetid Transvaginal Haemorrhage, Immunotherapy,
Postmenopausal Women, Vaginal Melanoma,

\textbf{INTRODUCTION}

It is believed that melanocytic cells found in the skin and mucosal
membranes are where malignant melanoma cells develop. Primary malignant
melanoma of the vagina is a rare tumour that has a short survival period
and a significant risk of recurrence. even though the first mention of
it was in 1887 {[}1{]}. Few than 250--300 cases have been documented in
the literature, or just 0.46 cases per million women annually {[}2{]}.
Malignant melanoma makes up 3-5\% of all vulvar malignancies and 10\% of
all female genital tract melanomas and for 0.3--0.8\% of all malignant
melanomas {[}2{]}. Primary malignant melanoma of the vagina typically
affects postmenopausal women aged 60 to 80 (average age is 68){]}
{[}3,4{]}. Vaginal discharge, vaginal bleeding, the development of
widespread, irregular, occasionally mottled macular hyperpigmentation,
or a palpable mass, are the most typical symptoms of this tumour.
Despite treatment, 5-year survival rates for melanoma of the vagina have
been reported to be less than 30\% due to the disease's markedly greater
aggressiveness compared to its cutaneous counterparts {[}6{]}. The case
of vaginal melanoma is described in the current article, along with a
review of the available treatments.

\section*{CASE PRESENTATION}

{\label{case-presentation}}

A 54-year-old female patient who visited the oncology unit with myalgia,
arthralgia, and fatigue, as well as a palpable mass and pain in the
genital area with foetid transvaginal bleeding that had progressed over
two weeks, reported the following medical history: history of
gynaecology and obstetrics, menarche at 11 years of age, the start of an
active sexual life at 20 years of age, two sexual A prolapse of the
vaginal vault with an ulcerated tumour measuring roughly 10 centimetres,
extending from the proximal third to the distal third, hyperpigmented,
friable, and with transvaginal haemorrhage, was discovered during the
gynaecological examination . When the lesion was biopsied, it revealed
abnormalities in the epithelial cells that were suggestive of melanoma
{[}Figure 1{]}, melanoma with lymphovascular invasion, with vertical
growth and superficial dissemination, with mucosal ulceration present,
with four mitoses per mm\textsuperscript{2}, and surgical limit of
excision of the vulva in focal contact with the limit. CKAE1/AE3 (+/++),
vimentin (+/+++), CD45 (-) and chromogranin (-), PS-100 ++/+++ (40\%),
and HMB45 ++/+++ (40\%), were all focally positive according to the
immunohistochemistry report. A thoracoabdominal tomography revealed lung
metastases, a tumour mass in the uterine topography, and multifocal
liver disease with metastasis. With acceptable tolerance, treatment
began with a conservative surgical resection, followed by post-operative
radiation and biological therapy using nivolumab and ipilimumab.\selectlanguage{english}
\begin{figure}[H]
\begin{center}
\includegraphics[width=0.70\columnwidth]{figures/image1/image1}

\end{center}
\end{figure}

10X image showing epithelioid neoplasm with rhabdoid characteristics,
with significant nuclear pleomorphism.

40X image showing the characteristics of the cytoplasm, hyperchromasia
and nuclear pleomorphism.

\section*{Figure 1. Vaginal melanoma: histopathological
pictures.}

{\label{figure-1.-vaginal-melanoma-histopathological-pictures.}}

\textbf{DISCUSSION}

Melanoma is a highly metastatic, highly aggressive tumour of melanocytes
that most frequently develops in the skin but can also occur in the eyes
and mucous membranes to a much lower level. One percent of all melanomas
are mucosal, and 18 percent of them develop in the vulvovaginal areas.
Even more infrequently, between the ages of 60 and 80, just 0.46
instances per million women are diagnosed with vaginal melanoma each
year {[}2{]}. As in our instance, vaginal melanomas are typically
located in the lower portion of the anterior vaginal wall. There are no
clear identifiable causes of vaginal melanomas, and the literature does
not show any appreciable variations among racial or ethnic groups
{[}1{]}. The cellular microenvironment and interactions between any of
these have been implicated in proposed mechanisms of its pathogenesis
and etiological variables, however these hypotheses are at best {[}6{]}.

Our patient's clinical symptoms included myalgias, arthralgias,
weariness, a palpable mass in the genital area, pain, and 2 weeks' worth
of foetid transvaginal haemorrhage. According to the bibliography,
genital bleeding (80\%) and a palpable mass (15\%), genital secretions
(25\%), and local pain (10\%) are among the symptoms of vaginal melanoma
{[}1,3{]}. Vulvar and vaginal melanomas have beginnings that are
typically missed by routine examination, with the anatomical location of
the lesion being the primary factor in the late diagnosis and poor
prognosis of these lesions. {[}4{]}, Any discoloured growth in the
vagina with complaints of vaginal bleeding should be believed to be
melanoma since the growth is typically blue-black or blackish with
plaques or ulceration {[}3{]}.

Most patients have advanced disease when they are first diagnosed
{[}1{]}. Vaginal melanomas are diagnosed using a combination of
histological analysis and visual inspection. When the protein S-100,
Melan A, and HMB-45 markers are positive, the diagnosis is confirmed by
pathological investigation using IHC of the biopsy sample {[}1{]}.
Histologically, there are three main forms of vaginal melanomas:
epithelioid (which accounts for 55\% of cases), spindled, and mixed
{[}2{]}. The big, spherical cells of the epithelioid type have a lot of
eosinophilic cytoplasm. They have peppered moth nuclei, which are
vesicular nuclei with coarse, uneven chromatin and peripheral
condensation. The most typical locations for this cell type in melanomas
are nodular and superficial spreading. The pigment is distributed
erratically, there is dermal fibrosis, and the inflammatory infiltrate
is varied (brisk, non-brisk, or nonexistent) in the stromal compartment
{[}4{]}. In order to identify the tumor's Breslow depth, the quantity of
mitoses, the kind of ulceration, the presence of microsatellites, and
the look of the tumour margins, a thorough pathological investigation
should also be carried out {[}1{]}, as described in the case of our
patient.

Prognostic variables and treatment regimens for vaginal melanoma are not
well characterised because there are not enough patients to conduct
randomised clinical studies.

The American Joint Committee on Cancer's tumour, node, and metastases
and the International Federation of Obstetrics and Gynaecology systems
are currently used to stage primary vaginal melanoma, but the evidence
from various studies suggests that the AJCC stage, tumour size, and
lymph node status are the main prognostic factors. Poorer outcomes were
linked to AJCC stage III, tumour size 3 cm, and lymph node involvement.
In general, MM has a 10-to-20\% 5-year overall survival rate compared to
93\% for CM.

Additionally, the vaginal melanoma 5-year survival rate is less than
15\% {[}5{]}. In appropriate circumstances, surgery is the go-to
treatment because it's linked to a higher overall survival rate. Quality
of life and patient preferences are crucial in determining the extent of
surgery, as is the case with our patient, who refused extensive surgery.
However, the radicality of the surgery had no discernible impact on
outcomes. Routine groyne or pelvic lymphadenectomy is not advised for
individuals without signs of clinical or radiological involvement due to
the low rate of regional lymph node metastases; instead, prognosis is
the key consideration {[}5{]}. In the absence of lymph node metastases,
local excision of recurrence results in a 50\% 5-year disease-free
survival rate {[}1{]}. If surgical resection is not possible, lymphatic
invasion, regional extension, or as a palliative measure, radiotherapy
may be utilised as a neoadjuvant treatment {[}4{]}. Immune checkpoint
inhibitors or targeted therapy are the preferred first-line treatments
for metastatic or incurable vaginal melanoma in the context of driver
mutations. Nivolumab and ipilimumab combination therapy or anti-PD1
monotherapy with pembrolizumab or nivolumab are the recommended starting
regimens for advanced stages (stage III-IV), respectively. This was the
treatment of choice for our patient {[}2,4{]}. Agents including
dacarbazine, iterleukin-2, and interferon alpha-2b have showed promise
in extending survival {[}2{]}.

According to evidence, cytotoxic therapy mostly employs dacarbazine,
temozolomide, cisplatin, and paclitaxel as neoadjuvant or palliative
care {[}2,4{]}. It is worthwhile to investigate topical imiquimod as an
adjuvant treatment further {[}6{]}. Adjuvant chemotherapy (dacarbazine)
or the combination of targeted therapy (ipilimumab) and radiotherapy
have also been mentioned in the literature, with promising outcomes, in
addition to surgical excision.

\section*{CONCLUSION}

{\label{conclusion}}

The least common gynaecological neoplasia, primary vaginal melanoma has
an aggressive evolution and a bad prognosis since it has a marked
tendency to produce metastases. For these reasons, it is typically
detected at an advanced stage. It is advised to perform a biopsy and an
immunohistochemistry study of any lesions suspected of being cancerous
when a hyperpigmented tumour is found during a gynaecological
examination as this is suggestive of vaginal melanoma. Being so unusual,
there are no standardised recommendations for the therapy. The current
main therapy strategy appears to be surgery followed by postoperative
radiation. In the instance of our patient, no tumour regression or
metastasis was seen despite cautious surgical resection, postoperative
radiotherapy, and 5 rounds of immunotherapy, however the patient was
still alive after 2 years after diagnosis. It takes a multidisciplinary
effort involving gynaecologists, pathologists, dermatologists, and
surgeons to have a standardised diagnostic and therapeutic approach to
this pathology as early diagnosis is currently the only way to modify
the prognosis of this neoplasm.



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{\label{references}}

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