Continuing Education Activity

Cryotherapy is a commonly performed dermatologic procedure used to treat a range of benign, premalignant, and selected malignant skin lesions. The technique relies on the controlled application of extreme cold to induce tissue destruction by mechanisms such as intracellular ice crystal formation, vascular stasis, and osmotic injury. Cryotherapy is frequently used for conditions such as actinic keratoses, viral warts, seborrheic keratoses, and selected nonmelanoma skin cancers. Clinical effectiveness depends on appropriate lesion selection, accurate margin identification, and correct execution of freeze–thaw cycles. Expected postprocedural responses include erythema, blistering, and crusting, with healing typically occurring over several weeks. Potential complications include hypopigmentation, scarring, nerve injury, and recurrence, underscoring the importance of technical precision and patient counseling.

This educational activity enhances clinician competence in evaluating skin lesions and applying evidence-based cryotherapy techniques. Participants learn to select appropriate candidates, determine temperature targets, choose open or contact methods, and tailor freeze–thaw cycles based on lesion type and location. The course emphasizes recognizing contraindications, managing adverse effects, and optimizing cosmetic outcomes. Structured guidance on patient education and follow-up supports safe outpatient care. Collaboration within an interprofessional team, including dermatology clinicians, advanced practice clinicians, and nursing staff, strengthens procedural safety, promotes consistent monitoring, and improves treatment outcomes through coordinated care.

Objectives:

• Identify lesion-specific protocols, including optimal technique selection and margin control, to enhance efficacy and safety.
• Determine indications, contraindications, and procedural endpoints to minimize complications and recurrence.
• Evaluate expected healing responses following cryotherapy and identify early signs of recurrence or adverse effects.
• Collaborate within the interprofessional healthcare team to develop unified postprocedural care plans that promote adherence, timely reassessment, and improved patient satisfaction following cryotherapy.

Introduction

Cryosurgery was first described in the 1800s and has since become a mainstay of dermatologic therapy. Cryosurgery is an effective alternative to more invasive techniques and can be delivered quickly and cost-effectively in an outpatient setting. Because this is a noninvasive technique, cryosurgery can produce excellent cosmetic outcomes. Cryosurgery is performed using a cryogen, typically liquid nitrogen, to cool the targeted tissue to subzero temperatures (see Video. Cryotherapy Using Liquid Nitrogen by Cryogun).

This effect induces tissue damage in 2 mechanisms. The first mechanism is the induction of tissue ischemia by damaging blood vessels and capillaries in the target area, leading to ischemic necrosis. The second mechanism damages cells more extensively by forming ice crystals, inducing osmotic cell injury, and disrupting cellular membranes. As tissue cools, ice crystals form between cells, creating an osmotic gradient that rapidly draws water out of the cells. As cooling continues, crystals form within the cell, potentially leading to cellular rupture. The thawing process also damages cells. As the tissue thaws, crystals outside the cells melt, creating a gradient that rapidly draws water back into the cells, which can cause them to swell and burst.[1][2][3] Thus, the ideal process involves rapid freezing followed by slow thawing.

Cryosurgery offers an advantage over excisional techniques in the treatment of malignancies. When a malignant lesion is excised, the host is no longer exposed to the antigens present in the malignant cells. In cryosurgery, however, antigens on dead malignant cells are retained, enabling a host immune response that may lead to systemic targeting of the malignant cells.[4]

The extent of tissue damage increases with each free-thaw cycle. The target temperature for destroying benign cells is −20 °C. Cancerous cells can be more resistant to cell death and require −50 °C to be destroyed. Unfortunately, melanocytes are very susceptible to thermal injury and may die at temperatures below −5 °C.[3]

Zones of spherical freezing advance are known as isotherms. The radius of each isotherm is the same in all directions. For example, a −5 °C isotherm may be 10 mm from the center of freezing at both depths and at the skin surface. The −10 °C isotherm is located 5 mm from the center and represents a temperature of −10 °C at a depth of 5 mm. By knowing the target temperature and understanding isotherms, a cryosurgeon can achieve the desired temperature at a specific depth by measuring the temperature at the periphery of the freezing zone.[5]

Understanding that conduction, the transfer of energy between adjacent bodies, will affect the temperature of a lesion is essential. Air is a poor conductor of heat; therefore, spraying a lesion with liquid nitrogen from a distance is less effective than holding the spray tip close to the lesion. Keratin is also a poor conductor; therefore, in cases of hyperkeratotic lesions, debulking before cryosurgery may be advisable.

Indications

Cryosurgery has numerous indications for both malignant and benign lesions. Benign lesions that can be treated with cryosurgery include seborrheic keratosis, verruca, skin tags, molluscum contagiosum, solar lentigo, and hypertrophic or keloid scars. Most of these lesions can be treated with a single session of cryosurgery; however, for larger or thicker lesions, treatment may be repeated at 3- or 4-week intervals until resolution occurs. This is especially true for verrucae, which typically require 2 to 6 treatment sessions for resolution.[6][7]

In addition to treating these benign lesions, cryotherapy has potential applications in the management of other benign dermatological conditions. Acne vulgaris, typically treated with topical and oral medications, may also be managed with cryotherapy, particularly in patients for whom medications are contraindicated, such as during pregnancy.[8] The cryoprobe method, first described by Leyden et al in 1974, has demonstrated benefits in the treatment of nodulocystic acne, as the application of liquid nitrogen accelerates lesion healing and reduces pain. Moreover, postinflammatory hyperpigmentation, a common sequela following acne resolution, may also respond to cryotherapy due to its hypopigmenting effects. Given that postinflammatory hyperpigmentation can be as distressing to patients as the acne lesions themselves, further research is warranted to better define the efficacy and safety of cryotherapy in this context.[9] 

Cryotherapy has also demonstrated benefits in alleviating pruritus in patients with chronic dermatological conditions. Results from a study showed that patients with mild to moderate atopic dermatitis who underwent cryotherapy had a lower itch score the day after treatment than those who did not.[10] These findings suggest that cryotherapy may have antipruritic properties and could serve as a useful adjunct in the management of chronic itch symptoms.

Furthermore, cryotherapy has been investigated in the management of hidradenitis suppurativa. In a study, 8 of 10 patients with persistent, painful nodules reported symptom relief following cryotherapy. The authors hypothesized that cryotherapy-induced ulceration and secondary intention healing destroyed the hair follicles and apocrine glands responsible for nodule formation.[11] More recently, a technique known as cryoinsufflation, a form of intralesional cryotherapy, has been applied to treat hidradenitis suppurativa, in which liquid nitrogen is delivered directly into sinus tracts through a needle.[12][13]

Superficial cryotherapy, when used in conjunction with intralesional triamcinolone, can be an effective therapeutic option for the management of keloid scars. Cryotherapy contributes to keloid improvement through several mechanisms: (1) it induces flattening of the lesion via microvascular damage and subsequent tissue ischemia; (2) it promotes tissue edema, facilitating a more uniform distribution of the injected triamcinolone; and (3) it causes direct cellular injury through intracellular ice crystal formation, leading to further tissue destruction.[14]

Premalignant and malignant lesions that can be treated with cryosurgery include actinic keratosis, basal cell carcinoma, and noninvasive squamous cell carcinoma. Typically, low-risk basal cell carcinomas are treated until their temperature reaches −50 °C with a 4- or 5-mm margin. Cryosurgery has been used to treat lentigo maligna melanoma with variable efficacy and recurrence rates. Actinic keratosis is commonly treated with cryosurgery. However, the treatment of malignant lesions with cryotherapy is not a first-line therapy and is typically reserved for patients who are poor candidates for excision. Large lesions that would be significantly disfiguring if excised, or elderly patients who cannot tolerate excision, are examples in which cryosurgery may be indicated.[15][16][17]

Contraindications

Cryosurgery should not be performed on a neoplasm of uncertain behavior. Before cryosurgery is performed, a diagnosis must be made by histologic, clinical, or dermatoscopic methods. Other contraindications for cryosurgery include conditions that may be exacerbated by cold exposure, such as cryoglobulinemia, multiple myeloma, Raynaud disease, cold urticaria, a history of cold-induced injury at the site or limb, and poor circulation at the site or in that limb. Cryosurgery can induce vasoconstriction, so treating a vascularly impaired area with cryosurgery may lead to undesired tissue necrosis. Peripheral arterial disease is a contraindication to cryosurgery. Cryosurgery can induce vasoconstriction, leading to undesired tissue necrosis in a vascularly compromised area, as seen in peripheral arterial disease.

Equipment

Multiple cryogens may be used in clinical practice, including nitrogen gas, carbon dioxide, and other compressed gases; however, liquid nitrogen remains the most widely utilized agent. The boiling point of liquid nitrogen is −196 °C. Liquid nitrogen is typically stored in heavily insulated long-term storage tanks called dewars. Dewars range in size from 4 to 50 L and can store liquid nitrogen for up to 2 months. Devices that generate liquid nitrogen are also available if needed.

Cryosurgical devices are 300 to 500 mL units that can temporarily hold liquid nitrogen and typically include various attachments for the desired treatment technique. Several treatment approaches are discussed below; however, the equipment necessary for those treatments is described here. In open-spray techniques, cryosurgical units feature a spray gun with interchangeable tip sizes, enabling precise control based on the size of the treatment area.

Cones that resemble an otoscope tip and plates with various-sized cutouts can provide more targeted delivery of liquid nitrogen. Various probe sizes can be attached to cryosurgical units for direct-contact treatment. Additionally, forceps or needle drivers may be cooled in liquid nitrogen for 20 to 30 seconds, then used to grasp and treat pedunculated lesions. In addition, forceps or needle drivers can be dipped into the cryosurgical units, frozen for approximately 20 to 30 seconds, and then used to grasp pedunculated lesions. 

When treating malignant lesions, it is advisable to use a device to measure tissue temperature. For probes, a thermometer may be built into the device, allowing the physician to estimate the temperature at the probe tip. Infrared thermometers may also be used in conjunction with spray devices to estimate tissue temperatures at various isotherms.

Preparation

Minimal skin preparation is required for cryosurgery. Antiseptics are not typically indicated in most cryosurgeries. However, for the treatment of malignant lesions, especially with a contact probe, topical antiseptics should be applied, as there is a risk of bleeding. Additionally, the probe may need to be cooled beforehand to prevent tissue damage upon contact with the skin.

For hyperkeratotic lesions, curettage should be performed to facilitate effective, precise application of liquid nitrogen. For small lesions, injection of local anesthetic may be more painful than the cryosurgery itself and is therefore not indicated. In general, cryosurgery for small lesions is well tolerated. For larger treatment areas, topical anesthetics can be applied several hours before the procedure to help reduce pain associated with freezing. Notably, anesthetics may be less effective in reducing pain experienced during the thawing phase.

Technique or Treatment

Cryosurgical techniques vary based on the lesion being treated. Benign lesions can typically be treated with a single freeze-thaw cycle with a target temperature of −25 °C for keratinocytic tumors and −5 °C for pigmented lesions. In contrast, malignant lesions are typically treated with 2 cycles and a target temperature of −50 °C. An exception to benign lesions receiving 1 freeze-thaw cycle is verrucae, which, due to their relative resistance to treatment, may be treated with 2 freeze-thaw cycles at the surgeon’s discretion.[18]

Thawing is complete when the entire lesion returns to its original color and frost is no longer visible. Allowing the lesion to thaw completely results in the greatest tissue destruction, as thawing itself causes damage. As a general rule for benign lesions, it is preferable to err on the side of caution and undertreat, as any persistent lesion can be treated at a subsequent visit. This approach can help prevent unnecessary complications, such as hypopigmentation.

Benign lesions should be frozen until the white halo extends 1 to 2 mm beyond the lesion's border to ensure complete removal. The duration of freezing for solar lentigines is typically around 3 to 4 seconds, as melanocytes are more sensitive to cold injury, whereas benign lesions are typically frozen for 5 to 10 seconds. The margins for solar lentigines should be just beyond the border of the lesion to prevent persistent pigment at the margins of the lesion.

Although cryosurgery is the first-line treatment for actinic keratosis, it is not a first-line therapy for malignant lesions. Treatment of actinic keratosis or malignant lesions is typically performed with 2 freeze-thaw cycles, with the margin size depending on the malignancy. Actinic keratosis is typically frozen for approximately 10 to 15 seconds with a 2-mm margin. The target temperature for malignant lesions is −50 °C for each of the 2 freeze-thaw cycles. Typically, it takes approximately 40 to 90 seconds to achieve these temperatures. In general, nonmelanoma skin cancers should have a margin of at least 5 mm. There have been reports of melanoma in situ being treated with cryosurgery with a 10-mm margin.[19]

Recurrences are difficult to identify, and reported recurrence rates range from 6% to 34%. In contrast to benign lesions, cryosurgery of malignant lesions should err on the side of overtreatment and be more aggressive because margin control is not possible with this technique. Since there is no excised tissue to be examined following this procedure, there is no definitive way to ensure that margins have been cleared, which may lead to the possibility of recurrence. For this reason, caution should be used with this approach, and regular follow-up is recommended to monitor for recurrence.[5][20]

Several techniques are available for administering liquid nitrogen. The most commonly used method is the open technique, in which liquid nitrogen is sprayed directly onto the target lesion. Intermittent release of liquid nitrogen provides a more controlled, precise application than continuous spraying. The semi-open technique is best for papular lesions. In this technique, a cone or plate is used to cover or direct liquid nitrogen to the target area, allowing for a more precise treatment field.

The closed/contact technique uses a probe cooled with liquid nitrogen, which is applied directly to the skin. Probes may freeze to the skin during the procedure, and forced removal of the probe can rip tissue off the treatment area and lead to bleeding. To prevent this, the probe should be frozen prior to touching the skin. If the probe becomes frozen to the skin, it should be gently warmed, or warm water may be applied to release it. Another form of the closed/contact technique involves using liquid nitrogen to cool the tips of forceps or needle drivers, which are then used to grasp pedunculated lesions.

Complications

Patients should be counseled about the expected outcomes following cryosurgery before the procedure. Cryosurgery induces controlled tissue injury that heals by secondary intention, which may take longer than healing after excision, particularly on the lower extremities. Healing time correlates with the depth of freezing; therefore, lesions treated more aggressively require longer recovery periods. Brief pain is common and typically lasts less than one minute. Treated areas usually progress through erythema, edema, and vesiculation over several days. Depending on treatment depth, serous exudate may persist for up to 2 weeks. Mummification or eschar formation often follows the exudative phase and may be gently debrided as appropriate.

Complications of cryosurgery include dyspigmentation, alopecia, pseudoepitheliomatous hyperplasia, depressed scarring, and tissue distortion such as nail dystrophy or cartilage notching. Dyspigmentation is the most common adverse effect, with hypopigmentation most frequently observed due to melanocytes' high sensitivity to cold injury. Individuals with darker skin types may instead develop postinflammatory hyperpigmentation. Alopecia may occur when cryotherapy is performed on the scalp or other hair-bearing areas, as cold-induced damage to hair follicle bulge cells can result in permanent hair loss.

Pseudoepitheliomatous hyperplasia is a benign reactive process that typically resolves spontaneously without intervention. Deep or aggressive freezing may lead to depressed scars, which often improve gradually over time. Injury to underlying structures, including the nail matrix or auricular and nasal cartilage, may result in permanent distortion or notching.

Clinical Significance

Cryosurgery is a common dermatologic procedure used to treat a variety of benign and malignant conditions. Importantly, for any clinician performing cryosurgery, it is essential to understand the mechanism of action and the proper application of cryosurgical techniques for treating these conditions. Clinicians should use their knowledge of cryosurgery's uses and contraindications to select appropriate candidates for this treatment. Patients should be counseled regarding expected outcomes and potential complications associated with cryosurgery.

Enhancing Healthcare Team Outcomes

Cryosurgery is a minimally invasive dermatologic procedure that uses a cryogen, most commonly liquid nitrogen, to destroy tissue by rapid freezing and slow thawing. First described in the 1800s, it has become a mainstay of outpatient therapy because it is efficient, cost-effective, and capable of producing excellent cosmetic outcomes. Tissue injury occurs through vascular ischemia and direct cellular damage from intracellular and extracellular ice crystal formation. Benign lesions such as seborrheic keratoses, verrucae, molluscum contagiosum, and keloids may be treated with one or more freeze–thaw cycles, whereas premalignant and selected malignant lesions, including actinic keratoses and low-risk basal cell carcinoma, require lower target temperatures and wider margins. Cryosurgery is not first-line therapy for most malignancies and requires careful patient selection, understanding of isotherms, and awareness of contraindications such as vascular compromise or cold-sensitive disorders.

High-quality outcomes depend on coordinated interprofessional care. Physicians and general practitioners must confirm diagnosis before treatment, select appropriate candidates, determine target temperatures and margins, and counsel patients about expected healing by secondary intention and risks such as dyspigmentation or scarring. Advanced practitioners often perform procedures in outpatient settings and should demonstrate technical proficiency, recognize complications, and arrange timely follow-up to monitor for recurrence. Nurses play a central role in patient education, equipment preparation, pain management, wound care instruction, and reinforcement of adherence across multiple sessions. Pharmacists contribute by advising on analgesics, topical anesthetics, and corticosteroids used adjunctively, while ensuring safe medication use in patients with comorbidities. Effective communication among team members regarding lesion type, freeze parameters, contraindications, and follow-up plans enhances patient safety, supports shared decision-making, and optimizes cosmetic and oncologic outcomes.

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Disclosure: Phuong Daniels declares no relevant financial relationships with ineligible companies.

Disclosure: Alexandra Taylor declares no relevant financial relationships with ineligible companies.

Disclosure: Alexa Lum declares no relevant financial relationships with ineligible companies.

Disclosure: Joseph Prohaska declares no relevant financial relationships with ineligible companies.

Disclosure: Nishad Sathe declares no relevant financial relationships with ineligible companies.