Fatima is a 70-year-old woman with multiple sclerosis who uses a wheelchair. She requires scheduled catheterization to manage her overflow incontinence. She has had a vulvar rash on and off for several years. It responds well to a topical combination cream containing clotrimazole and betamethasone. However, symptoms relapse within a few weeks of treatment discontinuation. Her caregiver brings her in today because the usual treatments are no longer working. On examination, you note generalized pallor and loss of volume of the labia minora and thinning of the introital skin. The hair-bearing genital area is erythematous and mildly lichenified around the borders, with multiple satellite lesions. A clinical diagnosis of genitourinary syndrome of menopause (GSM), genital candidiasis, and secondary lichen simplex chronicus is made, and a culture and sensitivity swab is obtained. You recommend her to rinse the genital area twice a day with warm water using a perineal bottle, followed by petroleum emollient in the morning and a mid-potency topical corticosteroid (TCS) ointment. You instruct her not to apply any cream to the area. You start her on daily oral antifungal treatment for 2 weeks and offer vaginal estrogen to manage the suspected GSM, which she declines. The swab confirms the Candida species infection. Only a minimum response to treatment is noted at 4 weeks of follow-up. What is the most appropriate next step?

A comprehensive literature search was conducted to identify publications on the topic. The search was performed in PubMed, Google Scholar, and Omni using a combination of Medical Subject Headings and free-text terms, including vulva or vulvar and biopsy or punch biopsy and dermatology or dermatosis or lesion of disease. The search was limited to English-language articles published between 1994 and 2024 on human participants. Articles were included if they addressed indications, technique, diagnostic utility, or clinical application of vulvar punch biopsy (VPB), particularly in primary care or outpatient settings. Review articles, original research, clinical guidelines, and consensus statements were eligible for inclusion. Articles not related to the vulvar biopsy technique or diagnostic evaluation were excluded.

Background. Vulvar concerns are among the most common concerns encountered by primary care providers.1 The presenting symptoms of the most common vulvar dermatoses can be overlapping and nonspecific and may include dyspareunia, pruritus, and pain2 (Table 1).1,3-22 Women and individuals assigned female at birth report a delay in diagnosis due to systemic-based challenges such as a lack of providers’ knowledge and limited specialist access.23 When left untreated, complications, including sexual dysfunction, infertility, and poor self-esteem, can profoundly impact patients’ quality of life.24,25 Some inflammatory dermatoses, such as lichen sclerosus, are associated with an increased risk of malignancy and thus warrant close clinical monitoring or specialist involvement.26 Distinguishing among benign, premalignant, and malignant lesions based solely on clinical features is often challenging. A punch biopsy is a simple, office-based procedure that is listed as a mandatory skin procedure for family medicine graduates.27-29 It can be safely performed on the vulvar skin to assist with diagnostic clarification and identify patients requiring specialist referral for complex conditions, thereby expediting management. Few family physicians, gynecologists, and dermatologists report performing this procedure due to a lack of adequate training, confidence, knowledge, procedural skills, and patient volume, as barriers exist to maintaining their skills in performing this procedure.23,30-32 Family physicians are well equipped to perform a VPB to diagnose and manage many benign inflammatory vulvar conditions safely. They can play a crucial role in reducing delay in diagnosis and expediting referral to the appropriate specialist.

Clinical features and management principles of common vulvar dermatoses

Differential diagnosis. Differential diagnoses for vulvar dermatoses are broad. Table 1 summarizes the most common vulvar dermatoses encountered in primary care, their causes, epidemiology, risk factors, clinical features, and management principles.1,3-22

Indications for a VPB include diagnostic uncertainty; findings on examination concerning for malignancy; chronic, changing, exophytic lesions; or lesions with atypical vascular patterns and treatment failure following an initial diagnosis.33 The algorithm in Figure 1 offers a decision-making process based on clinical examination for a VPB.34 There are no absolute contraindications to VPB.33 Relative contraindications include liver disease, active infection at the biopsy site, and anticoagulation or bleeding diathesis.33

Approach to vulvar punch biopsy in primary care

Potential complications of VPB are rare, reported in less than 1% of patients.35 They may include bleeding, infection, inadequate anesthesia causing pain during and after the procedure, vagal response, scarring, keloid formation (especially in skin of colour), and rare grey pigmentation of the skin called argyria, which occurs when topical silver nitrate or silver-coated wound dressings are used to achieve homeostasis.36 Inadequate specimens for diagnosis are rare, given the distinct pathology of inflammatory and cancerous vulvar conditions.37

A review of medications with special attention to the use of anticoagulants, antiplatelet drugs, nonsteroidal anti-inflammatory drugs, antidepressants, and herbal medications can help reduce the risk of bleeding. Allergies, especially to local anesthetics or antiseptics, must also be reviewed.

Informed consent is recommended after reviewing the indications, contraindications, and potential risks and complications. We recommend having an attendant for the patient during the procedure to ensure the patient’s comfort and to assist in visualizing the vulva skin, especially in patients with a large pannus or excessive adipose tissue.

Removal technique. Figure 2 displays the recommended supplies for a VPB.38 A visual demonstration of the procedure, including preparations and indications, is available from https://youtu.be/qdHbepcLRhg. Preparing supplies before placing the patient in the lithotomy position reduces patient discomfort. We recommend elevating the patient’s head to a comfortable height to maintain eye contact and detect patient discomfort or nonverbal withdrawal of consent during the procedure. After washing hands and donning gloves, draw 2 to 3 mL of local anesthetic. Identify the most appropriate representative part of the lesion for biopsy. Avoid ulcerated areas as the epidermal layer is essential for histologic diagnosis. Cleanse the biopsy site with an antiseptic solution. Pull the vulva tissue taut and advance the needle into the subcutaneous tissue. Aspirate gently to ensure that the needle is not inserted into a blood vessel and inject enough anesthetic to form a small wheal under the skin. Wait for a few minutes and test the skin to ensure skin anesthesia is achieved. Pull the vulva tissue taut and place the punch cylindrical blade perpendicular to the skin over the site to be biopsied. When possible, include the entire lesion for complete excision.

Recommended supplies for a vulvar punch biopsy

Gently twist the punch cylinder between your forefinger and thumb clockwise and counterclockwise until the blade reaches the subcutaneous tissue indicated by a loss of resistance against the blade. Remove the punch cylinder and grasp the specimen base using tissue forceps. The specimen can be damaged or crushed when held with forceps to cut the specimen base. Use caution and avoid grasping the centre of the specimen if possible. A 16-gauge needle may be used alternatively to lift the specimen. Cut the specimen base with iris scissors. Place the specimen in the buffered 10% formalin specimen container labelled with the patient’s name. Achieve hemostasis by applying direct pressure to the biopsy site with 20% aluminum chlorohydrate–soaked gauze. If bleeding persists, apply silver nitrate to achieve hemostasis. Although not routinely required for punch biopsies 4 mm and smaller, consider closure with a single simple interrupted absorbable suture if a larger biopsy is needed or if the patient has risk factors that increase the risk of ongoing bleeding, such as taking anticoagulants.

Postprocedure care and follow-up. The patient should avoid strenuous activity for the remainder of the day, as there may be some postprocedural pain. Advise the patient to keep the site clean and dry. If sutured, instruct the patient to avoid showering or bathing for the first 24 hours. Petroleum jelly can be applied; however, antibiotic ointments are not routinely indicated and should be avoided due to the risk of allergic reactions.39 Instruct the patient to avoid engaging in activities that can irritate the vulva, such as cycling and intercourse, until the discomfort is resolved. Sitz baths can help relieve pain, along with the use of over-the-counter analgesics. Counsel the patient to seek care immediately if any signs of post-procedure infection (eg, persistent pain, erythema, swelling, fever) are observed. Arrange for a follow-up appointment to discuss biopsy results and management plan.

Procedure pitfalls. For patients with vulvar pain or needle phobia, 2.5% lidocaine and 2.5% prilocaine cream may be considered. There is evidence that suggests it produces an anesthetic sensation approximately 5 mm deep when applied 30 minutes before the procedure,40 resulting in a lower maximum pain score and a better patient rating of the biopsy experience compared to a 1% lidocaine injection.41 Needle insertion into the vulva tissue can be challenging. Consider bending the needle to 30° to 45°, which alters the syringe’s position and direction relative to the body, for better control and easier insertion and infiltration of the anesthetic into the subcutaneous tissue. To do so, apply gentle pressure while keeping the needle in the needle cap to prevent it from launching into the air and causing injury if it accidentally breaks. Avoid excessive pressure or rotation when performing the biopsy, as this can result in the formation of depressed scars. Abrupt removal of the biopsy cylinder can lead to specimen loss. Consider angling the cylinder 45°, then grasp the specimen base securely using forceps before lifting the cylinder fully.

Patient management. Table 1 summarizes management principles for each diagnosis.1,3-22 General management of all vulvar conditions includes patient education to avoid overcleaning with soap and the application of irritants, especially over-the-counter products.2 Treat co-infections, most commonly Candida species and sometimes bacterial infections, confirmed by culture.2 Comfort measures may include rinsing the genital area twice daily with warm water, followed by the application of petroleum-based emollients. When prescribing topical corticosteroids, ointments are preferred over creams as they are occlusive and contain fewer irritants, such as polyethylene glycol and alcohol, both of which are commonly used in cream vehicles.42

Role of family physicians and other primary care clinicians and when to refer. Family physicians and other primary care clinicians should not biopsy the clitoris, clitoral hood, and urethra.33 If melanoma or squamous cell carcinoma is suspected clinically, an urgent referral to the local tertiary care team should be arranged while awaiting VPB results, as the survival rate does not appear to change based on the type of biopsy performed.43,44

A specialist referral in the care of vulvar lichen planus and psoriasis is recommended, as patients with vulvar lichen planus and genital psoriasis may need immunosuppression if TCS therapy is not effective. An allergist can be consulted for patch testing to confirm the diagnosis of contact allergic dermatitis. Biopsy specimens that suggest the presence of high-grade vulvar dysplasia or cancer should prompt urgent referral to a vulvar gynecologist or gynecologic oncologist for definitive surgical therapy.