Vaginal bleeding as a rare presentation of metastatic renal cell carcinoma: Case report and literature review

Abstract

Introduction and importance

Renal cell carcinoma (RCC) is a relatively uncommon malignancy, comprising only 3 % of adult cancers, but it is responsible for 85 % of primary renal tumors. When RCC metastasizes, the most common sites are the lungs, liver, bones, and brain. Although it is rare, RCC can also metastasize to the vagina. About 18–33 % of RCC cases are diagnosed with metastasis at the time of initial diagnosis.

Case presentation

A 48-year-old woman presented with postcoital bleeding and dyspareunia. At the physical examination, a polypoid mass was discovered on the right lateral wall of the upper third of her vagina and CT scan showed a right renal. Biopsies revealed clear cell renal carcinoma with metastasis to the vagina. The patient was diagnosed with stage IV (T3cN2 M1) renal cancer and underwent systemic therapy with Everolimus. However, subsequent imaging showed tumor progression, and the patient opted to halt treatment and was subsequently lost to follow-up.

Clinical discussion

In the past decade, there have been fewer than ten reported cases of RCC metastasizing to the vagina. Diagnosing vaginal clear cell carcinoma is challenging due to overlapping morphology with clear cell renal cell carcinoma, requiring immunohistochemistry. Treatment of vaginal cancers is challenging due to their rarity, and there is a lack of consensus on the optimal approach due to limited prospective studies.

Conclusions

Although the occurrence of RCC metastasis to the vagina is very uncommon, it is important to consider the possibility of metastatic RCC in cases of vaginal bleeding or lesions.

Highlights

• •Vaginal metastases from renal carcinoma are rare.
• •IHC is crucial for establishing the diagnosis.
• •There is no consensus on the management of RCC vaginal metastases.
• •In cases of vaginal bleeding, we should have to keep in mind the possibility of metastasis.

1. Introduction

Clear cell renal carcinoma represents the majority of renal tumors in adults (80 %). Metastatic forms at the time of diagnosis affect 15 to 25 % of patients, with the following preferred sites in order: lungs, lymph nodes, liver, bone, brain, adrenal gland, other kidney, and vagina [1]. Vaginal metastases from renal carcinoma are rare and have been described in only 80 cases in the literature. The vaginal lesion can be the first sign in many cases. About 20 % of patients with renal carcinoma may develop concomitant paraneoplastic manifestations of the disease [2]. The discovery of a vaginal adenocarcinoma should therefore prompt a search for occult renal cell carcinoma to propose appropriate treatment to improve prognosis. We report the case of a 48-year-old patient with clear-cell renal carcinoma revealed by vaginal metastasis. This case report is reported following the SCARE-2020 criteria [19].

2. Case presentation

We hereby present the uncommon case of a multiparous, 48 years-old-woman, with no medical nor surgical history and no family history of neoplastic disease, who presented in our department for postcoital bleeding, accompanied by dyspareunia, without pelvic pain. The patient had no notable gynecologic history. She had been married at 22 years old, had only one sexual partner, and had a history of 3 pregnancies, with 3 vaginal deliveries.

During the clinical examination, a hard, painless, and immobile mass measuring 80 mm was identified on the right flank. Additionally, during the gynecological examination, a polypoid mass measuring 20 × 15 mm in diameter and bleeding upon touch was found on the right lateral wall of the upper third of the vagina, away from the cervix packing was performed to ensure hemostasis. The parameters were non-infiltrated (Fig. 1). A hard, painless, and immobile cervical adenopathy measuring 15 mm in length was also detected.

Fig. 1.

Physical examination of the right vaginal wall mass.

After an abdominal ultrasound, a tumor lesion was detected in the right kidney. To further investigate this lesion, a thoracic-abdominal-pelvic CT scan, and MRI were performed, which revealed a solid tumor measuring 86 mm in diameter located in the lower pole of the right kidney, with a central necrotic area invading the peri-renal fat, adrenal gland, and renal vein. The CT scan also showed hepatic, and osseous, and pelvic lymph node metastases (Fig. 2, Fig. 3). Based on the clinical examination and imaging results, the decision was made to perform biopsies of the vaginal lesion, cervical lymph node, and right renal mass.

Fig. 2.

CT scan image showing the right renal process.

Fig. 3.

MRI image showing the right renal process.

The biopsy of the cervical lymph node revealed a probable tubule-papillary renal tumor process. The renal biopsy confirmed the presence of clear cell renal carcinoma, while the histopathological result of the vaginal biopsy confirmed the presence of metastasis from clear cell renal carcinoma (Fig. 4, Fig. 5, Fig. 6).

Fig. 4.

Image showing cytonuclear atypia of the cells (Hematoxylin-Eosin ×400).

Fig. 5.

Positive staining by anti-PAX 8 antibody of the tumor cells (immunohistochemistry ×400).

Fig. 6.

Absence of staining by anti-P40 antibody (immunohistochemistry ×200).

We concluded that the patient had stage IV (T4N1M1) according to the EAU Renal Cell Carcinoma TNM classification. Due to the advanced stage, the patient was not a candidate for upfront surgery and received systemic therapy with Everolimus (Afinitor) at a daily dose of 10 mg, as decided by the staff oncology.

One month later, the patient underwent a follow-up imaging scan, which revealed tumor progression according to the RECIST criteria. The results showed the presence of a moderately abundant abdominal effusion, progression of the renal process, and persistence of hepatic, lymph node, and bone metastases. Unfortunately, despite the disease progression, the patient and her family decided not to continue treatment, and the patient was lost to follow-up.

3. Discussion

Primary adenocarcinoma of the vagina represents 9 % of all vaginal neoplasms [3]. Therefore, adenocarcinoma of the vagina should be considered metastatic until proven otherwise [4]. These metastases can originate from the cervix, endometrium, ovary, or colon. However, metastases from the pancreas, stomach, and kidneys are even rarer [5].

Clear cell renal carcinoma is a relatively rare but aggressive form of renal cancer. Metastases can occur in various parts of the body, including lymph nodes, lungs, liver, bones, and in some rare cases, even the vagina. Vaginal metastases of CCRC are uncommon, accounting for less than 1 % of cases of distant metastases [6].

The spread of metastases to the external genital organs in RCC is explained by vascular anatomy. According to this hypothesis, the left gonadal vein directly drains into the renal vein, facilitating the retrograde spread of metastases.

In 2003, Mendese reviewed 85 cases of these tumors. The median age at the time of diagnosis was 57 years. In 65 % of cases, the initial symptoms were characterized by vaginal bleeding. Vaginal metastases of CCRC are typically detected before the diagnosis of the renal tumor, with a predominance of the renal tumor being located on the left side (in 63 % of cases). Vaginal metastases are typically singular and appear on the same side as the primary tumor, mainly located in the lower third of the anterior vaginal wall. The size of the vaginal lesion can vary from 0.5 to 8 cm [5].

Vaginal clear cell carcinoma diagnosis can be challenging due to significant morphological overlap with clear cell renal cell carcinoma. The biopsy is the definitive diagnostic method, but immunohistochemistry is critical due to the overlap in morphology. CA-IX and RCC antigens have the strongest diagnostic value for RCC, as they have no expression in gynecologic clear cell adenocarcinoma [7].

Treatment of vaginal cancers is challenging due to their rarity, and there is a lack of consensus on the optimal approach due to limited prospective studies. Therefore, treatment decisions are often based on retrospective and comparative studies, leading to diverse treatment strategies being implemented.

Table 1 displays the clinical, histological characteristics, and the different therapeutic approaches used in cases reported over the past decade.

Table 1.

The clinical, histological characteristics, and the different therapeutic approaches used in cases reported over the past decade.

Cases	Age	Past medical history.	Menopause	Functional signs	Physical examination	Site of renal cancer	Histology	Immuno-histochimie	Others metastasis	Chronology of metastasis	Need for hemostatic procedure	Treatement	Months
Lin et al. [11]	64	Left nephrectomy (hydronephrosis)	Yes	Vaginal bleeding	Vaginal mass on the right side of the anterior vaginal wall.	RK 18,8 × 19,9 cm Inferior vena cava tumor thrombus	Clear cell carcinoma	Vimentin, CAIX, CK8/18, CD10, AND PAX8: +	None	SM	Gauze tamponade And need to embolization	Sunitinib	12
Moradi et al. [12]	40	No	No	Vaginal bleeding	Mass on the vag- inal wall at approximately 8 o'clock	LK 16 × 12 × 11 cm without renal vein thrombosis	Clear cell carcinoma	No data	None	SM	No data	Radical nephrectomy Sunitinib	3
Yordanov et al. [13]	60	No	Yes	Vaginal bleeding	Soft tumor formation with dimensions 4/6 cm at the entrance of introitus vaginae	LK 6,3 × 5,5 Thrombosis of the left renal vein	Clear cell carcinoma	Vimentin: +	Yes: the lungs	SM	Excision of vaginal masse	No data	No data
Benbrahim et al. [14]	75	No	Yes	Vaginal bleeding	4 × 5 cm mass was found arising from the lower one-third of the vagina	RK 14 × 8 cm Renal vein Thrombosis: -	Clear cell carcinoma	Kl1 and cd10: +	Yes: mediastinal and lombo-aortic lymph nodes	MM		Radical nephrectomy bevacizumab + Interferon External hemostatic radiotherapy	Still alive 6 months later with local controle
Machiele et al. [7]	60	Right nephrectomy: plasma cell neoplasm	Yes	Left abdominal pain Vaginal bleedin	3.5 × 1 cm necrotic mass Left vaginal sidewall, lateral, and posterior to the hymenal ring	LK	Clear cell carcinoma	Vimentin, CK8/18, AE1/3, CD10, AND PAX8: + Ck7, ema, cd117, and mart-1: -	Yes: left hepatic lobe	SM	Vaginal packing monsel-soaked kerlix Artery embolization	No data	No data
Geng et al. [15]	56	Left nephrectomy: severe hydronephrosis	Yes	Intermittent vaginal bleeding	3 cm × 2 cm × 2 cm. Necrotic mass located in the anterior vaginal wall, 3 cm from the vaginal opening	RK 15 × 12 × 10 cm Inferior vena cava tumor thrombus	Clear cell carcinoma	Caix, cd10, vimentin, and CD8/18: +	No	SM	Intravaginal gauze plugging Artery embolization	Sunitinib	9
Pisavadia et al. [16]	79	Copd, type 2 diabetes, hypertension	Yes	Vaginal bleeding	2-3 cm craggy mass, replacing the left bartholin's gland in the lower 1/3rd of vagina and vulva	LK 5.5 cm solid-cystic lesion	Clear cell carcinoma	No data	Yes: liver	SM	No data	Palliative pazopanib	No data
Ouellet et al. [17]	78	No	Yes	Hematochezia Intermittent vaginal bleeding	3 and a 6-mm fragile polypoid lesion, both originating from anterior vaginal wall	LK 8 cm With a renal vein thrombus	Clear cell carcinoma	Ankeratin, cd10, EMA:+ and RCC-		MM	External beam radiotherapy with 20 Gy in 5 fractio	Radical laparo-scopic nephrectomy No systemic treatments	6
Hisano et al. [18]	68	No	Yes	Left flank pain Vaginal bleeding	30 mm long mass in the vagina	LK 7 cm long left renal tumor With a renal vein thrombus	Clear cell carcinoma	Weak expression of pd-l1 cd8: -	Yes: lung	SM	No data	Intitial managment: simultaneous radical nephrectomyhysterectoy, and transperineal vaginectomy Seconde management: sunitinib Nivolumab	7
Benlghazi et al.	48			Vaginal bleeding dyparenia	Polypoid mass measuring 20 × 15 mm	RK 86 mm in diameter with a central necrotic area invading the peri-renal fat, adrenal gland, and renal vein	Clear cell carcinoma	Anti-P40: - Anti-racemase and anti-PAX 8:+	Yes: Bone Liver Pelvic lymph noed	SM	Packing	Everolimus (Afinitor)	3

SM: synchronous metastasis.

MM: metachronous metastasis.

RK: right kidney.

LK: left kidney.

+: positive.

-: negative.

Given the frequency of vaginal bleeding, hemostasis is crucial in the initial management. Several techniques are available depending on the severity of bleeding, ranging from standard surgical techniques such as suture ligation, electrocautery, and packing to uterine artery embolization [7].

The management of vaginal metastases from renal cancer depends on several factors, including the number and size of the metastases, their location, and the patient's overall health [8].

Depending on the location and size of the vaginal lesion, surgical resection may be recommended, followed by radiation therapy if necessary.

In certain cases, surgical treatment of the primary tumor may be indicated, especially if the tumor is localized or there is a single metastasis.

Immunotherapy, such as nivolumab and pembrolizumab, as well as targeted therapy, such as sunitinib and pazopanib, are treatment options for metastatic renal cancer. However, their effectiveness in treating vaginal metastases from renal cancer has not been well studied [9].

For patients with vaginal metastases, the prognosis of these patients essentially depends on the presence or absence of other metastatic sites. Cases of metachronous metastases have a longer survival than those with synchronous metastases. Finally, the median survival is 19 months (1 to 96 months) [10].

4. Conclusion

Primary vaginal cancer is rare, with metastasis being more common and presenting with bleeding. Diagnosis relies on biopsy and immunochemistry. Metastasis of RCC to the vagina is uncommon but can be devastating if not promptly treated. In cases of vaginal bleeding, we should have to keep in mind the possibility of metastatic renal cell carcinoma.

Abbreviations

CT scan

computed tomography scan

MRI

magnetic resonance imaging

RCC

renal clair carcinoma

IHC

immunohistochemistry

RECIST

response evaluation criteria in solid tumors

EAU

The European Association of Urology

SCARE criteria

The work has been reported in line with the SCARE criteria.

Consent

Written informed consent was obtained from the patient for publication of this case report and any accompanying images. A copy of the written consent is available for review by the Editor-in-Chief of this journal.

Ethical approval

Ethical clearance was not required for this case report as it involved only a single patient and did not involve any experimental or invasive procedures. The patient provided written informed consent for their personal and medical information to be used in this report

Funding

None.

Author contribution

Abdelhamid Benlghazi, Moad Belouad, Rachid Aitbouhou, and Hallak Mohammed were responsible for the patient's diagnosis and clinical management. Abdelhamid Benlghazi and Mohammed Hallak wrote the manuscript. Rachid Ait Bouhou contributed to the analysis, supervision, writing, reviewing, and editing of the manuscript for intellectual content. All authors have read and approved the final manuscript.

Guarantor

Benlghazi Abdelhamid.

Research registration number

Our article is a single case report and does not involve a research study with a specific research question or hypothesis. As such, research registration may not be necessary.

Declaration of competing interest

The authors declare no conflict of interest.