Vulvar Basal Cell Carcinoma in Postmenopausal Women: Two Case Reports

Abstract

Basal cell carcinoma (BCC) is a major non-melanoma skin cancer, and its incidence is increasing worldwide. Although the main etiology is sun exposure, BCC may develop in sun-protected areas such as the vulva. The sonic hedgehog signaling pathway mutation may explain the mechanism underlying the occurrence of vulvar BCC. Owing to the rarity of metastases, wide local excision is an appropriate treatment option. Here, we report the cases two postmenopausal women with vulvar BCC who were surgically treated.

INTRODUCTION

Basal cell carcinoma (BCC) is major non-melanoma skin cancer, and its incidence is increasing worldwide [1]. The paramount environmental factor of BCC is sun exposure [2]. Risk factors related to the development of BCC include light skin color, tanning-bed use, ionizing radiation, and immunosuppression [2]. Although BCC has traditionally occurred in sun-exposed areas such as the head and neck, it may arise in sun-protected areas, including the breasts and genitalia [3,4]. Herein, we present two cases of vulvar BCC in postmenopausal women.

CASE REPORT

Case 1

An 81-year-old Asian female patient had blisters with itching and slight pain around her labia majora for several months. It continued to recur and resolve itself. Suddenly, it spread to the surroundings, and she visited a private hospital. A biopsy of the suspicious lesion from the left labia majora was performed, and BCC was diagnosed. The patient was then referred to a tertiary hospital. Pelvic examination revealed no visible lesions after the biopsy. She denied a history of radiotherapy or a family history of skin cancer. The patient underwent preoperative magnetic resonance imaging (MRI) and positron emission tomography/computed tomography (PET/CT) to differentiate locoregional disease from distant metastasis (Fig. 1). There were no abnormal findings, except for a small mass lesion without hypermetabolism in the right vulva. The patient underwent wide local excision in both vulvar areas. Pathological examination revealed BCC with a clear resection margin in the left labia majora and hyperkeratosis with mild chronic inflammation in the right labia majora. The BCC lesion of the left vulva was 4 mm in diameter, 0.5 mm in depth, and 7 mm in the resection margin. Histologically, the tumor in the left vulva showed a proliferation of atypical basal epithelial cells with peripheral palisading (Fig. 2). She had no postoperative complications like cellulitis or wound dehiscence. She had no evidence of local recurrence or distant metastasis at 1 year of regular follow-up.

Fig. 1. A small mass lesion of the right vulvar (yellow arrow) was identified in MRI. The patient had no evidence of locoregional and distant metastasis in preoperative (A) axial view of pelvic MRI and (B) coronal view of positron emission tomography/computed tomography. MRI: magnetic resonance imaging.

Fig. 2. The tumor in the left vulva showed proliferation of atypical basal epithelial cells with peripheral palisading (yellow arrows) (hematoxylineosin stain, 100× magnification).

Case 2

A 79-year-old Asian woman had a history of perineal warts for 2 years. Recently, she developed a similar vulvar lesion and presented to a private hospital. A prompt skin biopsy was performed, and BCC was diagnosed. The patient was referred to a tertiary hospital for further evaluation. The patient denied vulvar pain or itching. She had no evidence of local or distant metastasis on pelvic MRI or PET/CT (Fig. 3). She underwent wide-local excision of the left vulvar area. The excised tumor was 1.7 mm in diameter and 0.8 mm in depth. The free margin was 4 mm. Microscopically, invasive tumor nests of atypical basaloid cells were accompanied by the decomposition of melanin pigments and chronic inflammatory cells (Fig. 4A). Basal cell carcinoma showed positive for p63 immunohistochemical stain (Fig. 4B). She had no immediate postoperative complications. The patient remained in good condition without recurrence for 8 months after surgery.

Fig. 3. The preoperative imaging studies revealed a non-locally advanced or metastatic basal cell carcinoma. (A) Axial view of pelvic magnetic resonance imaging. (B) Coronal view of positron emission tomography/computed tomography.

Fig. 4. Microscopic features of the basal cell carcinoma. (A) Invasive tumor nests of atypical basaloid cells (yellow arrow) were accompanied by the decomposition of melanin pigments and chronic inflammatory cells (white arrow) (hematoxylin-eosin stain, 80× magnification) (B) Basal cell carcinoma showed positive for p63 immunohistochemical stain (80× magnification).

DISCUSSION

BCC originates from the basal layer of the epidermis. Physical risk factors associated with BCC are fair skin, blond hair, and light eye color, which increase susceptibility to ultraviolet (UV) radiation damage [2]. Although the frequency of BCC correlates with lighter skin color, UV radiation is a pivotal predisposing factor, regardless of race [5]. The incidence of BCC in Asians has also increased globally [6].

Vulvar BCC is a rare clinical entity, accounting for less than 1% of all BCC and 2–4% of all vulvar cancers [4,7]. Considering the main role of UV exposure in BCC, the mechanism underlying vulvar BCC development remains unknown. Trauma, chronic infection, and previous radiotherapy are considered risk factors for BCC in sun-protected areas, like sun-exposed areas [8]. Inappropriate activation of the sonic hedgehog (HH) signaling pathway plays an important role in the development of BCC [2]. Genetic mutations could help understand the mechanisms of BCC arising in sunprotected areas.

The appropriate diagnosis of vulvar BCC is challenging because of its rarity as well as asymptomatic or nonspecific clinical features such as vulvar lump, pruritus, pain, and bleeding [9]. It is an indolent tumor that rarely metastasizes and commonly occurs in the elderly [9]. Vulvar BCC is classified as a high-risk group for recurrence regardless of size [10]. Therefore, it is important to promptly perform a biopsy for histological confirmation when a suspicious skin lesion is found despite a previous benign lesion. It should be considered that vulvar dermatoses deteriorate the patient’s quality of life [11].

The mainstay of treatment for vulvar BCC is surgical excision. If Mohs micrographic surgery is feasible, it is the preferred method over wide local excision because it is possible to intraoperatively confirm margin involvement [12]. Although ambiguous margin safety due to clinical diversity remains in the high-risk group, wide local excision is adequate as primary therapy in most cases [10]. Systemic therapy is recommended in cases of positive margins after excision, locally advanced BCC, or metastatic BCC [10,13]. One of the systemic therapies is vismodegib, a selective inhibitor of the HH signaling pathway [13]. Watson et al. reported a case of treatment with vismodegib in patients with pulmonary metastases of vulvar BCC [14].

The prognosis of BCC is related to the potential recurrent risk after primary therapy [15]. The recurrent risk depends on the lesion's location and histopathologic features [10,15]. Poor prognostic features are associated with the following lists: (1) high-risk locations like the head, neck, hands, and anogenitalia, (2) aggressive histology such as morpheaform or infiltrate type, or (3) recurrent tumor [10,15]. At least 30% of patients may develop recurrent BCC within 5 years [16]. Therefore, follow up including history and physical examination every 6 to 12 months up to 5 years, followed annually for the rest of the life is necessary [10].

CONCLUSION

Vulvar BCC is an uncommon malignant condition that is rare in the Asian population. As the symptoms are atypical, meticulous physical examination and prompt skin biopsy are important to avoid the delayed diagnosis, especially in the elderly. Although the disease has a favorable prognosis, regular follow-up over a long period is critical because of its locally aggressive nature and high risk of recurrence.