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6'1/ .\,.\ ..;0'" DERMATOLOGY VOLUME 31 NUMBER 6 DECEMBER 1994

CONTINUING MEDICAL EDUCATION

Cryosurgery updated
Emanuel G. Kuflik, MD Newark, New Jersey

Cryosurgery is an effective modality for treatment of many benign, premalignant, and ma-
lignantcutaneous lesions. New indications for benign lesions, new data, and recent trendsto-
wards more aggressive treatment of malignant lesions are mentioned. The differences in
managementbetween benign and malignantlesions are addressed. Thisarticlediscusses cry-
obiology, equipment, advantages ofcryosurgery, techniques oftreatment, tissue response, re-
sults, complications, and contraindications. (J AM ACAD DERMATOL 1994;31:925-44.)
Learning objective: At the conclusion of this learning activity participants should be able to
discuss keyaspects of cryosurgery including equipment to be used, advantages anddisadvan-
tages of the procedure, complications and contraindications for its use, and common types
of tissueresponse to cryosurgical techniques.

Cryosurgery uses freezing temperatures to by Dewar to storeoxygen, nitrogen, and hydrogen.

achievespecific effectson tissues. Its popularityhas In 1899,White7 described clinical trials using liquid
increasedduring the past three decades. 1 In a survey air as a sprayor with a swab to treat some benign
undertaken by the American Societyfor Dermato- lesions and early epitheliomas. Several years later,
logic Surgery and reported in 1990,87% of the par- Puseyt usedcarbon dioxide snow that wascollected
ticipants performed cryosurgery? It can be used as in a leather bag and compressed into sticks. These
the treatment of choice, as an alternativemethod,or cryogenic agents were used until the 1940s when
as an adjunct to other methods for diverse benign liquid nitrogen became readily available." The ni-
and malignant cutaneous lesions.l? The word cryo- trogen wasapplied with a cotton swab for the treat-
therapy is often used interchangeablywith cryosur- ment of verrucae and keratoses, but the destructive
gery. 6 However, inthe United States wepreferto use depth of this technique was limitedto a few milli-
the term cryotherapy for nondestructive treatment meters.
of conditions such as acne, alopecia areata, and for In 1961, Cooper, a neurosurgeon, designed an
superficial skin peeling. apparatus using liquid nitrogen in a closed system
that permitted continuous and rapid extraction of
HISTORY
heat from tissues.l? Later in the decade, Zacarian
Freezing was first used by dermatologists around and Adham!' employed solid copper cylinder disks
the turn of the century, after the commerciallique- that were cooled by immersion in liquid nitrogen
faction of air and the development of a vacuumflask before application to the skin and accomplished
greater depthof destruction than cotton-tipped ap-
RTHO The CME articles are made possible through an educational
0'17 plicators. Torrel Z- 14 developed a spray-probe appa-
~ grant from the Dermatological Division, Ortho Pharma- ratus for dermatologic use, and Zacarianl- 16 de-
\..~.J ceutical Corporation.
From the Department of Dermatology, New Jersey Medical School.
vised a hand-held unit. With these advances, deeper
Reprint requests: Emanuel G. Kuflik, MD, ISO E. Kennedy Blvd.,
destruction oftissue couldbeachieved. Thusmalig-
Lakewood, NJ 08701. nant as well as benign lesions becameamenableto
Copyright @ 1994 by the American Academy of Dermatology, Inc. cryosurgical management. Other clinicians then in-
0190-9622/94 $3.00 + 0 16/2/59725 troduced different types of cryosurgical units. 17-19
925
 Journal of the American Academ y of Derma to1ogy
926 Kuflik December 1994

Table I. Cryogens used in cryosurgery studies on the nature of the injury in experimental
Boiling point
frostbite.30, 31Vascular stasis and the ultimate fail-
(oq ure of the microcirculation assure cell destruc-
tion.32,33
Chlorodifluorornethane -41
Dimethyl ether and propane" -24, -42 With repeated freeze-thaw cycles, maximum de-
Carbon dioxide, solid -78 structiveeffectsare produced.H 35 Electron micros-
Nitrous oxide -89 copy studies of normal skin showed damage to all
Liquid nitrogen -196 cell structures after a second freeze-thaw cycle.-"
The effective temperatures may vary.
Effects on tissue
*Trade name is Histofreeze r.
Cryosurgery produces a selective destruction of
tissue and the stroma provides the structural frame-
workfor later repair of the cryogenicwound.'? The
CRYOBIOLOGY
resistanceof collagen fibers and cartilage to damage
Heat transfer by freezingis responsible for favorablehealing. This
The biologic alterations that occur in cryosurgery allows selective destruction of tumors overlyingbone
are caused by reducing the temperature of the skin or cartilage and accountsfor nerve regeneration af-
with consequent freezing. Because the rate of heat ter injury from cold. 38 Melanocytes are more sus-
transfer is a function of the temperature difference ceptibleto damagefrom freezingthan keratinocytes,
between the skin and heat sink, rapid heat flow re- andtheirdestructioncan leadto depigmentation.39-41
sults.The techniques of cryosurgicaltreatment have Repigmentation occurs from the migration of mel-
evolved fromtwomethods of heat transfer.20,21 Boil- anocytes from the margins or from undamaged
ing heat transferoccurswhenliquidnitrogentouches melanocytes in hair follicles. Freezing may also
the skin, asinthedipstickand spraytechniques. Con- lead to development of immune reactivity and the
duction occurs when a cold metal probe is appliedto possibility of beneficial effects on metastatic dis-
the skin. It is slower than boiling heat transfer ease.42,43
because the metal probe acts as additional resis- The excellent results after treatment of benign
tance. The heat transfer coefficient can be improved epidermal lesions depend on the fact that mild
by pressing the cryoprobe firmly against the skin. freezing causesseparationof the epidermisfrom the
dermis. This ablates the lesion with rapid reepithe-
Mechanisms of injury lialization of the wound. In experiments on canine
The mechanisms of injury from the freezing of skin keratinocytes were destroyed at 30° C; at
tissue include direct effects on the cells and the vas- warmer temperatures, evidence of damage was re-
cular stasis that develops in the tissue after thaw- duced.I? Therefore successful treatment of nonma-
ing.22-27 Theeffect of cold on human tissue depends lignant conditions depends on more superficial de-
on several factors: the rate of temperature fall, the struction with a lesser degree of freezing than is re-
rate of rewarming, the solute concentrations, the quired for malignant lesions. In contrast, when a
length of time the cells are exposed to a below- malignancyistreated, goodresultsfrom cryosurgery
freezing temperaturein the 0° to - 50° C range, and occur because cellular components are more sus-
the coldest temperature reached in the target tis- ceptible to coldinjury than are stromal components.
sue.28 Slow cooling produces extracellular ice, but After cryosurgicaltreatment, the structures of basal
this is not as damaging as rapid cooling that cell carcinomas were no longer evident after 3
producesintracellulariceformation.Thereforerapid days.t"
cooling of the target tissue is desirable.F' Added to For many years cryosurgeons used -20 0 C as a
the destructive effects of crystal formation there is target for the coldesttemperature at the base of the
concentration of chemicals in the tissue. With slow malignancy. I I, 45-48 However, new evidence has
thawing, an increased concentration of electrolytes shown that this temperature is not adequate except
and recrystallization occurs that is also damaging to for benign tumors. Present-day techniques require
cells. Thus the rate of rewarming, or thaw, should that the temperature reach -50 0 C when basal cell
proceed slowly. and squamouscellcarcinomasare treated; this is the
Damageis also enhanced by the effect offreezing temperature at which skin is completely fro-
on the circulation. These effects are known from zen.3,34, 49-51
Journal of the American Academy of Dermatology
Volume 31, Number 6 Kuflik 927

Table Jl, Benign conditions amenable to cryosurgery

Acne-vulgaris, cystic Lichen sclerosus et atrophicus ofvulva266
Acne keloidalis Lupus erythematosus/s?
Adenoma sebaceum-l? Lymphangiorna-!'
Alopecia areata Lymphocytoma cutis
Angiokeratomas-I! Molluscum contagiosum
Angiokeratoma of Fordyce Mucocele
Atypical fibroxanthoma Myxoid cyst
Cherry angiornas 260 Or[268
Chondrodermatitis nodularis helicis Porokeratosis plantaris discreta269
Chromoblastomycosis Porokeratosis of Mibelli
Clear cell acanthoma Prurigo nodularis270-272
Condyloma acuminatum Pruritus ani273
Dermatofibroma Psoriasis
Disseminated superficial actinic porokeratosis Rhinoph~a274
Elastosis perforans serpiginosa Rosacea 9
Epidermal nevus Sarcoid275
Erosive adenomatosis of the nipple Sebaceous hyperplasia
Folliculitis keloidalis Seborrheic keratosis
Granuloma annulare261 Solar lentigo
Granuloma faciale 234.262 Syringoma
Granuloma pyogenicum-!' Trichiasis276
Hemangioma Trichoepithelioma277
Herpes labialis263 Varicose veins278
Idiopathic guttate hypornelanosis-s" Venous lakes
Kyrle's disease Verrucae-periungual, plane, vulgaris, filiform,
Leishmaniasis plantar
Lentigines265 Xanthoma-I?
Lentigo simplex

EQUIPMENT
available as hand-held models or as portable table-
To undertake cryosurgery a cryosurgicaldevice, top devices and are self-pressurizing. A thenp.os or
a cryogen, and accessories are needed.52-55 Some a small cup made of rigid polystyrene plastic (Sty-
available cryogenic agents include liquid nitrogen, rofoam)or metal are useful when the dipsticktech-
carbon dioxide, nitrous oxide, and chlorodifluo- nique is used. 64• 65 Additional equipment used in
romethane (Verruca Freeze).56-63 Liquid nitrogenis cryosurgery include spray tips, cryoprobes, spray-
the cryogen of choice for dermatologic surgery be- limiting cones, protectiveitems, and tissue temper-
cause it is the coldest and most versatile; it can also ature monitoring devices.66-69
destroythe large volume of tissuerequired for effec- Although cryosurgery poses a low risk of cross-
tive treatment of malignant lesions (Table I). The contamination, propersterilization ofthe accessories
other cryogens have usefulness for the treatment of shouldbe carried out by dry heat or autoclave." In
inflammatory, benign, or premalignant conditions addition, various plastic disposable attachmentsare
for whichlesserdegrees of freezing willsuffice. Liq- available or can be improvised."
uid nitrogen must be stored in a vacuum-insulated
OBJECTIVES AND GOALS OF TREATMENT
Dewar tank with provision for pressure relief and
withdrawal. These agents are classified as chemical The objective of cryosurgery is to cause selective
hazards and the Occupational Safety and Health necrosis oftissue, the extentofwhich dependson the
Administration regulations are to be followed for type of lesion and the volume of freezing need-
proper storage, labeling, and handling. In addition, ed.23, 24,72-76 Beforetreatment isinitiated, a decision
a material safety data sheet (an MSDS), provided must be made concerning the goal of treatment,
by the manufacturer, is required to be kept on file, namely, improvement, cure) or palliation. If the in-
and hazard labels should be affixed to storage con- tent is improvement or cure of a benign lesion,
tainers and equipment. whetherfor medical or cosmetic purposes, the need
Liquidnitrogen apparatus for derrnatologic useis for destruction of tissue is minimal and a lesser
 Journal of the American Academy of Dermatology
928 Kuflik December 1994

Table III. Premalignant lesions amenable to for tumors located at the inner canthi, free margin
cryosurgery of the ala nasi, and the auditory canal. 84, 85
Actinic cheilitis (leukoplakia) ADVANTAGES
Actinic keratosis
Bowen's disease280 Cryosurgery has advantages that make it strongly
Erythroplasia of Quyrat281 competitive with other techniques- 82:
Keratoacanthoma
Lentigo maligna 1. Suitable for office, nursing home, or outpa-
Squamous cell carcinoma in situ tient facility
2. Low cost
3. General anesthesia not required
amount of freezing is required. The cosmetic and 4. Local anesthesia optional
functional end results are of major importance, and 5. Operative suite not required
cure rate is secondary. If the intent is cure of a ma- 6. Safe and relatively simple procedure
lignant lesion, thorough eradication of the entire tu- 7. No restriction of work or sports
mor must be accomplished and a greater amount of 8. Excellent cosmetic results
freezing is required. In the case of palliative therapy 9. Useful in pregnancy
of inoperable tumors, deep freezing is also required 10. Suitable for patients who are fearful of
even if complete destruction is not achieved. 77, 78 undergoing surgery

INDICATIONS AND CONTRAINDICATIONS TECHNIQUES OF TREATMENT

Cryosurgery is indicated for diverse benign and The choice of which technique to use depends not
premalignant lesions and for selected malignant only on the condition or lesion but also on the per-
ones.n , 73,79-85 The latter include basal cell carci- sonal preference of the operator.
noma, squamous cell carcinoma, basosquamous
carcinoma, and Kaposi's sarcoma. Cryosurgery is Dipstick
not consideredto be a standard treatment for oper- The dipstick technique consists of dipping a cot-
able malignant melanoma. ton-tipped applicator into liquid nitrogen and ap-
The indications are related to patient and lesion plying it on a lesion. This procedure is repeated un-
selection (Tables II and III). Any area of the body til the desired amount of freezing is obtained. It can
can be treated and there are no age limitations. be used to treat nonmalignant lesions such as verru-
Neoplasms amenable to treatment have well-cir- cae, lentigo simplex, lentigines, and actinic kera-
cumscribed borders. Cryosurgery can be used for toses.55, 81
selected recurrent tumors, lesions that are fixed to
cartilage or bone, and palliation. It can be used for Spray
small or large tumors, multiple skin cancers, and The open-spray technique emits a fine spray of a
those located within a plaque of psoriasis or a burn cryogen at the target area and is commonly used by
scar. It can be used for high-risk surgical patients, dermatologists. Lesions that are suitable for this in-
patients with a pacemaker, the elderly, and those clude seborrheic keratosis, cystic acne, actinic kera-
with a coagulopathy. Cryosurgery is useful in pa- tosis, verrucae, actinic cheilitis, lentigo maligna,
tients for whomother methods of treatment are im- keratoacanthoma, and neoplasms.55, 72, 73, 79, 81, 89, 90
practical. It is particularly useful for superficial, irregular, and
There are few contraindications to the use of cry- multiple lesions and for those on a curved surface.
osurgery. Patients with cold urticaria, cold intoler- For large lesions, a paint brush or spiral pattern of
ance, cryofibrinogenemia, and cryoglobulinemia are spray can be used." The spray is emitted from a
best treated by other means.86-88 Tumors with distance of 1 to 2 em from the target site and at a
indistinct borders are not candidates for cryosur- 90-degree angle to it. An intermittent spray of liq-
gery. Deep freezing is generally not recommended uid nitrogen is desirable when malignant lesions are
for lesionsat the corners of the mouth or the vermil- treated to ensure that conversion of the nitrogen to
ion border. Caution should be observed in dark- the gaseous phase is uninterrupted.
skinned patients, for lesions that overlie nerves, and The confined-spray technique is a variation of the
Journal of the American Academy of Dermatology
Volume 31, Number 6 Kuflik 929

open-spray technique that restricts the liquid nitro- tance during cryosurgical procedures are not com-
gen. The spray is directed into a conethat is openat mercially available in the United States becauseno
both ends,and oneend isplaced on the skin. 55, 92 The such device has been approved bythe FoodandDrug
closed-cone technique alsoconfines the spray into a Administration.
cone-shaped accessory that is only open at one Ultrasound has been usedfor noninvasive preop-
end.n , 79 These techniques are suitable for lesions erative imaging of tumors and for diagnosis and
that are rather round. planning.103-\ 07 Withfurtherimprovement inequip-
ment, ultrasonography may come into clinical use
Cryoprobe for cryosurgical management.F"-109
The cryoprobe technique, also known as contact
TREATMENT
therapy, consists of application of a precooled metal
accessory directly against the lesion. 72, 79, 93 It is In general, the salient points of managementin-
usefulfor roundlesions and for thoseonflat surfaces. clude explanation of the procedure and consent;
Venous lakes, hemangioma, dermatofibroma, myx- preparation of the equipment; local anesthesia, if
oid cyst,sebaceous hyperplasia, and granuloma an- desired; biopsy of the lesion; preparation of the pa-
nulare are examples of some conditionsthat can be tient; debulking of the lesion; and actual freez-
managed with this technique. ing.7 4, 79

Carbon dioxide Benign lesions

Solidified carbon dioxide (dry ice) in the form of The factors usedin thetreatmentofbenign lesions
a stick,block, or snowis applied directlyonthe skin. 8 include the freeze time, thaw time, and the lateral
To obtain a light freeze dry ice snow can be mixed spread of freeze. 54,73, 74 Thedurationoffreezing will
with acetoneto treat acne vulgaris, acne cysts, rosa- vary according to the characteristics of the lesion
cea, and flat warts.94, 95 This is known as slush ther- and the technique of treatment. It may range
apy. between 3 and 60 seconds when the open-spray
technique is used.109 With the cryoprobe the freeze
Treatment factors time may be two to three times longer. The thaw
It is necessary to determine the amount and depth time is used by some to monitor treatment and is
of tissue to be frozen.i' : 55, 69, 74 The progress of approximately two to three times longer than the
freezing can be judged by the duration of freezing freeze time. The lateralspreadoffreeze is usedin the
(freezetime), thawing of the lesion(thaw time), and treatment of lesions such as verruca vulgaris, peri-
measurement of the ice-ball beyond the target area ungual warts, dermatofibroma, and myxoid cyst.It
(lateral spread of freeze). Although surfacefreezing should reach approximately 2to 3 mmfortreatment
is visible and can be measured, the depth of freezing to be successful. A single freeze-thaw cycle is gener-
cannot be seen. To supplement clinical estimation, ally sufficient. Because the condition is benign,
the tissuetemperature can be monitored with ther- lesions can be retreated if necessary. 19, 55,74 Large
mocouples mounted in 25- to 30-gaugeneedles that lesionscan be treated in sections; for example, peri-
are insertedinto the skin so that the tip liesbeneath ungual warts, hemangioma, and keloid.
or lateral to the lesion.66-69, 72-76 , 79 Although some
minor error is inherent in the temperature recording Premalignant lesions
system, the available equipment is sufficiently accu- More destruction of tissue is required for treat-
rate for cryosurgical purposes.f?' 68, 96 ment of premalignant lesions. Therefore a longer
Experimentally, the measurement of the electri- freeze time is needed. 55,73, 80, 109 A single freeze-
cal impedanceor resistance in frozen tissuehas been thaw cycleis usuallysufficient. Lentigomalignaand
used to monitor treatment of malignancies.w 97-\ 02 keratoacanthoma are treated similar to a malig-
Freezing of tissue results in decreased electrical nancy with a double freeze-thaw cycle. I10
conductivity, and the abrupt change in the electrical
impedance or resistance is interpreted as sufficient Malignant lesions
freezing to ensure tissue death. This technique In the treatment of malignant lesions the same
requiresinsertionof needleelectrodesin or about the volumeoftissuemustbedestroyed byfreezing insitu
tumor. Devices to measure tissue impedance-resis- that wouldbe excised by conservative local excision
 Journal of the American Academy of Dermatology
930 Kuflik December 1994

lesion can be transformed into a shallow one by

means of curettage and debulking.P: 116-118
An additional factor, advocated by Torre et
a1.,51, 53-55 is the halo thaw time, which is the mea-
surement of the duration of the surface thawing of
the area beyond the target site. It is a post hoc mea-
surement to signify that freezing is supposedly ade-
quate to form an ice ball and not merely light dust-
ing of the liquid nitrogen. This is usually in the range
of 60 seconds. When the depth dose estimation is
achieved, that is, as the treatment factors coincide,
freezing is halted. The frozen site is then permitted
to thaw spontaneously. Kuflik and Gage79., 119 and
Zacarian72 recommend a repetition of the freeze-
thaw cycle for all malignancies.
A larger tumor can be successfully eradicated by
Fig. 1. Exudation at treated siteand periorbital edema
48 hours after cryosurgery of basal cell carcinomaon the dividing it and treating the individual sections on the
left cheek. same day or on subsequent visits,?9, 120 Wound
healing is not hindered by overlapping of the freez-
ing. For multiple tumors the depth of freezing for
if that had been the chosen procedure. Through re- each should be related to its particular characteris-
search and experience a system has been devised for tics and to whether it is a primary or recurrent
estimation of the depth dose.>': 53, 55, 72, 74, 76, 79 This lesion.79, 121-124 Selected recurrent lesions are ame-
consists of monitoring treatment by use of the clin- nable to cryosurgical destruction, but treatment
ical features and measurement of the tissue temper- should be aggressive.
ature below the lesion. An interrelation exists be-
tween the freeze time, lateral spread of freeze, and Tissue response
tissue temperature, and the adequacy of treatment After freezing, the tissue responds in a predictable
is based on these.50, 79, Ill, 112 The freeze time is ap- manner that leads to healing of the wound by
proximately 45 seconds for a I em lesion when the secondary intention .24, 72,125 The reactions that en-
open-spray technique is used, two to three times sue after freezing include erythema, vesiculation,
longer when the cryoprobe technique is used, and edema, exudation, and sloughingl/" (Fig. 1). Post-
about half the time of the open-spray method when operative care varies according to the lesion, loca-
the closed-cone technique is used. The thaw time is tion, and depth offreeze. Most benign lesions require
generally two to three times longer than the freeze little or no aftercare, but malignant lesions require
time, but often a longer period is allowed. The lat- frequent washing of the wound with soap and water
eral spread of freeze should reach at least 3 to 5 mm during the exudative stage. A dry gauze dressing is
but can be greater.llJ-113 all that is required. The wound begins to dry between
The temperature reached below the base 5 and 14 days after freezing and an eschar develops.
of the tumor should be between -50 0 and -60 0 It is allowed to dry and fall off spontaneously. Benign
C,3,5, 49-51,72 When measured with a thermocouple and premalignant lesions usually heal between 2 and
the temperature reading is only at the site of the 4 weeks." Malignant lesions on the face, eyelids,
needle placement so more than one thermocouple is nose, ears, and neck generally heal between 4 and 6
needed for larger lesions. II 0,114, 115 In the treatment weeks. Large tumors and those on the trunk and ex-
of a shallow skin cancer, that is, one that does not tremities take longer to heal, sometimes up to 14
extend more than 3 mm below the skin surface, weeks. The cosmetic results after cryosurgery, in'
monitoring clinical features is of paramount impor- some locations, are often equal or superior to those
tance. Therefore instead of use of a thermocouple, achieved by other modalities. Edema, particularly
knowledge of the biologic behavior of the disease can periorbital, can be minimized or ameliorated with
be substituted for tissue temperature." A thicker open wet compresses, steroid cream.P? or a short
Journalof the American Academy of Dermatology
Volume 31, Number 6 Kuflik 931

Table IV. Overall cure rates of 3540 skin cancers Table V. Five-year cure rate of skin cancers
0971-1989) (I 980-1984): Basal cell carcinoma
Recurrences Cure rate S-Year
Location (No.) ( %) Lesions Recurrences cure rate
Location (No.) (No.) ( %)
Face/neck 495 24 95.3
Lip 32 I 96.8 Face 178 2 98.8
Nose 385 9 97.6 Neck 19 0 100.0
Ears 233 10 95.7 Lip II 0 100.0
Scalp 80 0 100.0 Nose 165 I 99.3
Eyelids 95 3 96.8 Ears 63 I 98.4
Trunk 1985 9 99.5 Scalp 2 0 100.0
Vulva 2 0 100.0 Eyelids 18 1 94.4
Extremities 233 0 100.0 Trunkj 172 1
- 99.4
Total 3540 56 98.4 extremities
Total 628 6 99.0

course of systemic corticosteroids. Kuflik and ation,88, 142 tendon rupture,143 alopecia.Iv' ectropi-
Webb l28 prefer an intramuscular injection of be- on,145 hypopigmentation.l'f scarring/" and tissue
tamethosone phosphate, 1 ml 30 minutes before defect. The reason for failure to cure may be attrib-
treatment, and followed by oral prednisone, 20 ttig] uted to inadequate depth of freeze, insufficient
day, for 3 days. treatment, and the difficulty, in some cases, of
defining the extent of a neoplasm.l"?
Complications
MALIGNANT LESIONS AMENABLE TO
It is important to distinguish between expected
CRYOSURGERY
sequelae and untoward results or complications.l->
The incidence of complications after cryosurgery is Basal cell and squamous cell carcinomas
low. Untoward reactions may be unforeseen or During the past decade there has been an in-
inexplicable, or may arise from poor patient or lesion creased use of colder temperature, greater use of
selection.P? They may also result from improper debulking techniques, and a trend toward more ag-
treatment, equipment malfunction, or inexperience gressive treatment. Kufiik and Gage 119 reported a
of the operator. series of 3540 new skin cancers, the majority of
Complications may be classified as temporary or which were basal cell carcinomas, treated with the
perrnanent.Uv 125, 130-132 The frequent temporary open-spray technique, and found an overall cure rate
ones include edema'{' or pain during and immedi- of 98.4% (Table IV). They also reported a 5-year
ately after treatment. Infrequent or rare complica- cure rate of 99% for 684 new tumors (Table V). Za-
tions include delayed bleeding, headache, infection, carian 148 reported a cure rate of 97.3% in the treat-
syncope, febrile reaction, cold urticaria, nitrogen gas ment of 4228 carcinomas. He recently reported the
insufflation, milia, pyogenic granuloma.Pv 135 hy- treatment of 5400 skin cancers with similar re-
pertrophic scarring.t" hyperpigmentation, and neu- sultS. 149
ropathy or paresthesia. 136-1 38 Sonnex et al. 139 found Graham 109 had an overall cure rate of 98.2% for
full recovery .of transmissions along nerves after 3593 new basal cell and squamous cell carcinomas,
freezing. Millns et a1.140 reported complete resolu- using mostly the open-spray technique. Holt l50
tion of sensory deficit in two patients at 6 weeks and reported a cure rate of 97% in 279 skin cancers us-
3 months, respectively. In a report of paresthesia of ing the spray technique. Ascensao and Goncalves'P
the fingertips in two dermatology residents, caused reported a cure rate of 94.2% in 52 patients after 5
by handling the frozen nozzle of a cryosurgical unit, years. However, the cure rate for recurrent tumors
normal sensitivity returned in 5 to 6 weeks after is lower (88.4%) .151 Although a recurrence usually
avoidance of further contact.l''! develops during the first 2 years after cryosurgery, it
Permanent complications include retraction of can appear at any time. Torre50 cited a recurrence
tissue (lips, eyebrows, ala nasi), neuropathy, ulcer- after 12 years.
 Journ al of the American Academy of Dermatology
932 Kufiik Decemb er 1994

well-circumscribed tumors on the nose154-1 57 and

cars158-160 because cartilage is resistant to freezing
injury and the architecture of the organ is preserved.
Freezing tumors on the face is beneficial because
a minimum amount of tissue is sacrificed. Nodu-
loulcerative tumors on the scalp require aggressive
treatment but heal well with a flat scar.
Zacarian 161 introduced the use of cryosurgery for
eyelid cancers. Fraunfelder et al. 162had a recurrence
rate of 4.2% in the treatment of 310 eyelid basal cell
carcinomas. In a later report Fraunfelder et a1. 163
had a cure rate of 93% in recurrent lesions of the
eyelids. Kuflik164-167 reported a cure rate between
94% and 97% and excellent cosmetic results (Fig. 2).
Biro and Price l68 had a cure rate of 97% for 135
basal cell carcinomas. Tumors in the vicinity of the
lacrimal duct system are good candidates for cryo-
surgery because the likelihood of damage is mini-
mal. 169
Cryosurgery is particularly useful for treatment
oflarge lesions on the trunk and extremities153, 170, 171
(Figs. 3 and 4). Other areas of usefulness include the
neck, lips, hands, penis, and vulva. 3

Kaposi's sarcoma
Cryosurgery is ideal for patients with macular or
maculopapular lesions of Kaposi's sarcoma, but
eradication of large plaques is difficult. Tappero et
al.172, \73 prefer to use a hand-held spray device with
two freeze-thaw cycles per treatment, repeated at
3-week intervals, with a mean of three treatments
Fie. 2. A Nodular basal cell carcinoma on marzin a ,f per lesion. For best results, they recommend thaw
lower eyelid in n-year~old man. B, Complete healing 5
months after treatment. Note loss of cilia. times of 10 to 20 seconds per freeze-thaw cycle for
macular lesions and 30 to 60 seconds for papular le-
sions. adam also employs the spray technique with
a thaw time of 30 to 45 seconds. * Lesions are treated
Mclntosh et a1. 152 compared recurrence rates af- again if they are persistent or if the disease is
ter excision, radiotherapy, or cryosurgery. The low- progressive. He stated that the response rate is 70%
est (2%) occurred with radiotherapy, and excision with cryosurgery alone. Freezing can be combined
with primary closure had the highest recurrence rate with intralesional vinblastine therapy. Side effects
(9%). These authors also reported that cryosurgery include mild pain, blistering, and hypopigmentation.
was quickest to perform, provided the best cosmetic
NONMALIGNANT mSEASES AMENABLE TO
results, and was cost-effective.
CRYOSURGERY
Zacarian 72 and Kuflik and Gage! advocate the
use of a double freeze-thaw cycle that is often pre- Acne
ceded by curettage. Graham 109 and Torre'" have Acne vulgaris can be improved with carbon diox-
used single and double freeze-thaw cycles alone or in ide slush or liquid nitrogen spray,8, 89, 174-178 Papu-
a combination with shave excision or curettage. lopustular acne lesions are lightly frozen for several
Cryosurgery is ideal for the patient with multiple
tumors that are either scattered or confined to one "'Presented at the Fifty-second Annual Meeting of the American
anatomic area. 121, 123,124,153 It is effective for Academy of Dermatology, Washington, D.C., Dec. 4-9, 1993.
Journal of the American Academy of Dermatology
Volume 31, Number 6 Kuflik: 933

Fig. 3. A, Superficial basalcellcarcinoma (II em) outlined for cryosurgeryon the back of
76-year-old man. B, Cryosurgery to entire tumor with open-spray technique. Note lateral
spread of freeze. C, Completed healing 6 months after treatment, with mild hypertrophic
scarring at center.

seconds to hasten resolution. Acne cysts require a optimal results, an average of 80% improvement,
longer freeze time, approximately 5 to 10 seconds, can be achieved with cryosurgery for early lesions.
and periodic treatment. Cryotherapy is particularly
useful for reducing the cysts in mutilating nodulo- Actinic keratosis
cystic acne when treatment with I3-cis-retinoic acid Freezing is an excellent modality for actinic
therapy is not feasible or desired because of its ter- keratoses. 55, 73, 74,180 Lubritz and Smolewski'U had
atogenic effects (Fig. 5). a cure rate of 98.8% in the treatment of 70 patients
Acne keloids respond to a combination of freez- with 1002 lesions. The open-spray technique, with a
ing and intralesional steroid injection.V Layton et freeze time of 5 to 10 seconds, is effective, or the
al. 179 conducted a double-blind study comparing dipstick technique may be used 109 (Fig. 6). Usually,
treatment with intralesional triamcinolone and cry- one treatment is sufficient and various spray patterns
osurgery in II patients with multiple acne keloids. are effective." In this manner, multiple lesions in
The open-spray technique with two IS-second any area can be treated. Chiarello'< reported suc-
freeze-thaw cycles was used. Their data suggest that cessful removal of many actinic keratoses, along
 Journal of the American Academy of Dermatology
934 Kufiik December 1994

Fig. 4. A, Nodular squamous cell carcinoma (2 em) on Fig. 5. A, Severe cystic acne on face of 21-year-ok~
Jack of hand in 70-Year-old man. B, Excellent results 16 woman. B Dramatic resolution of GYsts 12 weeks after
llJUlllll1S a u.cr lIcU1I11ClIl. urwcclUY rlyuru 1II11u!>clI1ipray tnerapy wuuout oral mea-
ication.

with seborrheic keratoses and lentigines, during Alopecia areata

full-face spraying of sun-damaged skin with liquid Treatment of alopecia areata is often not wholly
nitrogen. satisfactory, but cryotherapy has given some prom-
ising results. Lei et al. 184 used the cotton swab tech-
Actinic cheilitis
nique for alopecia areata in a large group of children
Cryosurgery is effective in the treatment of actinic and adults. Liquid nitrogen was lightly applied twice
cheilitis, or leukoplakia, with either the closed-probe until the alopecic area became just slightly frozen
or the open-spray techniques.A?" Lubritz and (about 2 to 3 seconds). They found that new hair
Smolewski 183 found a cure rate of 96.2% in the growth occurred in more than 60% of the involved
treatment of 53 lesions of the lower lip in 37 patients. area in 70 of 72 patients. However, the study was not
The open-spray technique was used, and the thaw double-blind or controlled. Huang et al. 18S treated
time ranged between 60 and 90 seconds. The freeze 123 patients with the spray method, causing pain
time with nitrogen spray can range between 10 and and bullae, and found a cure rate of 71.5%.
15 seconds for an area up to 2 em. Millns et aL conducted an open study of 100 pa-
Journal of the American Academy of Dermatology
Volume 31, Number 6 Kujlik 935

tients older than 5 years of age with alopecia areata

of at least 2 months' duration. * They utilized the
open-spray or open-cone technique, with a freeze
time of 5 to 10 seconds and a double freeze-thaw
cycle. An average of four sessions was needed to
achieve excellentresults. Overall, a moderate to ex-
cellent responsewasfound in 70%. The authors were
uncertain of the mechanism of action of cryotherapy
but question whether there is an immunomodulator
effect, placebo effect, or simply enhanced circula-
tion.
Clear cell acanthoma
This uncommonbenign epidermal tumor tends to
occur as an asymptomatic solitary lesion on the ex-
tremities and demonstrates no tendency towards Fig. 6. Cryosurgery to multiple actinic keratoses on
spontaneous regression.P" Two reports have been scalp of 81-year-old man.
published of successfuleradication of a single lesion
by means of the open-spray technique with a freeze
time of 60 seconds and a lateral spread of freeze of
2 to 5 mm.187, 188 One lesion cleared after 3 weeks rom halo of normal tissue. Hill et al. 195 reported good
with a singletreatment; the other required a second results after using the cryoprobe technique in the
treatment. Cryosurgery has also been employed in treatment of 154 lesions. Spiller and Spiller 196 used
the treatment of multiple clear cell acanthomas.189 the open-spray technique and a single or double
freeze-thaw cycle in 45 lesions. Lanigan and Robin-
Chromoblastomycosis son'?? used the open-spray technique and a single
Chromoblastomycosis is a chronic fungal infec- freeze-thaw cycle.The results were good or excellent
tion of the skin and subcutaneous tissuesthat is un- in more than 90% of cases. Torre 198 reported im-
responsive to most treatment. Ramlrez'P'' first used provement in 101 of 109 dermatofibromas treated
cryosurgeryto treat one patient, and others reported with the cryoprobe technique.
cure with liquid nitrogen in seven additional pa-
tients.191-193 Elastosis perforans serpiginosa
Pimentel et aL194 treated 11 cases caused by Several reports oftreatment of elastosis perforans
Fonseca pedrosoi with cryosurgery. They achieved serpiginosawith cryosurgerydemonstrate that freez-
cure, or disappearance oflesions, in five patients with ing is a usefulmodality. Frigiderm (Freon 114) and
localized disease and in three with generalized dis- solidified carbon dioxidehave been effectivein some
ease. The open-spray technique was used and the cases.199. 200 Liquid nitrogen spray was used in one
freeze time variedfrom 30 secondsto 4 minutes.One case of penicillamine-induced elastosis perforans
freeze-thaw cyclewas sufficient to cure localized le- serpiginosa with a freeze time of 8 seconds and a
sions, and recurrences that developed in patients thaw time of 20 seconds.P' Two treatments, given
with generalized lesions were treated again. The au- 7 days apart, resulted in disappearance of the lesions
thors believed that destruction of fungi was second- without scar f ormation, In another caseof idiopathic
ary to tissue necrosis. disease, nitrogen was applied with the dipstick tech-
nique for about 10 seconds on five occasions in 4
Dermatofibroma months and again 3 months later. This resulted in
Cryotherapy is effective for eradication of der- disappearance of the lesions with minimal scar-
matofibromas, but more than one treatment may be ring. 202
necessary. The nodules are frozen includinga 2 to 3
Epidermal nevus
*Presented at the Fifty-second Annual Meeting of the American Recently severalauthors have described the use of
Academy of Dermatology, Washington, D.C., Dec. 4-9, 1993. cryosurgeryto treat linear verrucous epidermal nevi.
 Journal of the American Academy of Dermatology
936 Kujiik December 1994

Pusey! first reported treatment of nevi in 1907. Fox The contact method was used and a single freeze-
and Lapins 203treated numerous lesions of epidermal thaw cycle was given per session. Meltzer220 re-
nevi in a child with several different modalities but ported satisfactory results in 32 patients using a cry-
concluded that cryosurgery was most beneficial. oprobe and a double freeze-thaw cycle.
They first anesthetized the area and then froze it Freezing has been performed before or after
with liquid nitrogen spray, using a double freeze- intralesional injection of corticosteroids. Ceilly and
thaw cycle with approximately t to 2 minutes of Babin-?' found it advantageous to freeze the lesion
thaw time. The treated sites healed within 6 weeks first. Others have combined this with shave exci-
without apparent scarring, and no recurrences were sion.222 Torre'" prefers to remove part of the lesion
noted in 2 years. The authors believed that results surgically before freezing the base. Other authors
were best when treatment was limited to an area of have had poor results with cryosurgery, but this may
2 to 3 em to minimize morbidity and chance of be due to inadequate freeze times or insufficient
scarring. Dupre et al. 204 reported favorable results treatment sessions.P!
in one patient using solidified carbon dioxide, but
others found a lack of response to the same meth- Keratoacanthoma
od.2oS Kennedy-i" reported satisfactory short-term Keratoacanthoma is an epidermal neoplasm that
results with cryotherapy bu t did not elaborate on may be regarded as a premalignant lesion.224 Cry-
details. osurgery is useful for solitary or multiple kerato-
acanthomas, and treatment is similar to that of a
Hemangioma
malignancy. Holt225 reported the treatment of eight
Cryosurgery is effective for selected hemangio- lesions using the open-spray technique with a dou-
mas in children and adults.207.210 Castro-Ron?'! ble freeze-thaw cycle and a freeze time of 30
recommends it for those lesions that are growing seconds. One patient with a large keratoacanthoma
rapidly, interfere with organ function, bleed, or are on the tip ofthe nose did not respond to cryosurgery
located where surgical removal is difficult. He uses and was later treated with radiotherapy.
the cryoprobe technique for hemangiomas or other
vascular birthmarks, employing a flat or rounded- Leishmaniasis
end probe. The lesion is compressed during freezing Cryosurgery is a simple and effective modality for
and a single freeze-thaw cycle is carried out. Treat- acute cutaneous leishmaniasis.226,227 Success was
ment may need to be repeated at 6-week intervals, achieved with various methods including liquid
depending on the response and size of the lesion. For nitrogen (dipstick, cryoprobe, open-spray, and spray-
deep hemangiomas, he uses an intralesional cryo- cone techniques) and a carbon dioxide probe.228-23I
probe. The reports relate to patients from Europe, South
America, and the Middle East. Freezing leads to'
Keloids rapid destruction of Leishmania organisms and le-
Cryosurgery has been used alone , in combination sions heal within 3 to 8 weeks.P? Sufficient freezing
with surgery, or with intralesional steroid injections to cause a bullous reaction appears necessary. The
to treat keloids and hypertrophic scars,?3. 89, 21 2-216 treated sites heal with no or minimal scarring.228
More than one treatment is usually needed, and ei- There are no adverse effects, but mild hypopigrnen-
ther the spray or cryoprobe technique is effective. tation is possible.
Generally the freeze time ranges from IOta 30 sec- Leibovici and Aram 230 used a cotton-tipped ap-
onds, and a single or double freeze-thaw cycle is plicator on 40 lesions and found a cure rate of 100%.
carried out. Large keJoids require a longer freeze Bassiouny et al. 228 treated 30 patients and all were
time.217 Younger lesions seem to respond better to cured. Faber229 treated three patients with the
cryotherapy than older ones. open-spray technique using a single freeze-thaw cy-
Rusciani et al. 218 treated 65 lesions in 40 patients cle and freezing to -25° C. One patient was treated
with the open-spray technique and performed two or with a spray-cone and a freeze time of 30 seconds.
three freeze-thaw cycles. They achieved complete All healed without complications. Light freezing
flattening in 48 scars (73 %), and no recurrences with a cryoprobe for 10 seconds was combined with
were seen in up to 42 months of observation. intralesional stibogluconate injection in 23 lesions
Zouboulis et al.219 treated 93 patients and found and was found to be superior to either modality used
good to excellent responses in 57 patients (61. 3%). separately.Pt
Journal of the American Academy of Dermatology
Volume 31, Number 6 Kufiik 937

Fig. 7. A, Venous lake on lower lip of 67-year-old man. Fig. 8. A, Large periungual wart on thumb of 26-year-
B, No evidence of lesion 3 months after treatment. old woman. B, Excellent results 4 months after treatment.

Lentigo maligna manner the abnormal melanocytes in the epidermis,

Although excision is the usual treatment of len- hair follicles, and adnexa are destroyed. 238 With the
tigo maligna, the lesion's size or location may open-spray technique, Zacarian-I? described two
preclude this. Cryosurgery is an effective alternative recurrences in 20 patients with an average follow-up
that yields excellent cosmetic and curative results. of 42.6 months. Bohler-Sornmeregger et al.240 de-
The cryosurgical technique requires that the entire scribed three recurrences after treatment of 20 pa-
pigmented lesion, including atypical cells that may tients.
extend into clinically normal skin, be destroyed.
Reports of cryosurgical treatment indicate a Lymphocytoma cutis
recurrence rate of about 10%.232-236 In a recent re- The prototype lesion of pseudolymphoma is lym-
port, Kuflik and Gage23? found a recurrence rate of phocytoma cutis, which is a benign lesion charac-
6.6% in 30 patients using the open-spray technique terized by one to several nonscaling, usually viola-
with an average follow-up of 3 years. Aggressive ceous nodules or plaques.P" Kuflik and Schwartze'?
treatment was recommended including double treated five cases successfully with liquid nitrogen
freeze-thaw cycle, tissue temperature of -40 0 to using the open-spray technique. One treatment with
-50 0 C and a 1 em lateral spread of freeze. In this a single freeze-thaw cycle and a freeze time of 15 to
 Journal of the American Academy of Dermatology
938 Kufiik December 1994

20 seconds was carried out; one case required treating many verrucas. 249 Verruca vulgaris can be
anothertreatment. All healed withoutscarring in 3 treated with the dipstick or open-spray tech-
to 6 weeks. niques." 55, 14 The freeze time using the former
ranges between 20and 60seconds, depending onthe
Myxoid cyst size andthickness oftbe wart. To achieve success it
Although myxoid cysts are easily diagnosable, is imperative to form a bulla, caused by separation
management can be difficult and disappointing. atthederrnoepidermaljunction, that extends slightly
Cryosurgery is easily performed and thecurerate is beyond the lesion. One treatment usually suffices
high.243-246 and healing occurs within 3 weeks. Kuflik:246,250 re-
Bardach243reported cure in 12 of 14 patients us- ported a cure rate of 97.4% in 80periunguallesions
ing a single freeze-thaw cycle and the spray tech- using the dipstick technique (Fig. 8). Large lesions
nique. Bohler-Sommeregger and Kutschera- that encircle thenailare treatable, and the cosmetic
Hienert245 also used the spray technique in the results are excellent.
treatment of 18 cysts and recommended a double Flat warts can be eradicated by freezing lightly
freeze-thaw cycle. In a series of 57 myxoid cysts in forseveral seconds with carbon dioxide slush, a cot-
51 patients, Kuflik246 obtained a cure rateof76.7%. ton-tipped applicator, or with the open-spray tech-
The open-spray or cryoprobe technique was com- nique. Production of vesicles is to be avoided, and
bined withderoofing of the lesions. A single freeze- repeated treatments are generally needed. Digitate
thawcycle was used, the lateralspread offreeze was warts usually require one freeze-thaw cycle using
2 rom, and the freeze time was 20 to 40 seconds. either a cotton-tipped applicator or a cryoprobe. Al-
Myxoid cysts healwithin 3 to 5 weeks with resto- though cryosurgery may be effective for someplan-
ration of normal appearance. The open-spray or tar warts, it is not preferred by all cryosur-
cryoprobe techniques are effective. 55 Lesions can be geons.25i.252
treatedagain after a recurrence, generally within 12 Condylomata acuminata also respond well to
months, without sacrificing good cosmetic results. cryosurgery.253-256 O'Connor257 reported treatment
of many patients with both liquid nitrogen and
Psoriasis nitrous oxide. Damstraand vanVloten 258treated 59
Freezing mayimprove smallpsoriatic plaques. Its patients with small penile and extravaginal condy-
effect is probably related to destruction ofthe elon- lomas using the open-spray technique and found a
gatedpapillae in psoriasis. 241 Scoggins248 treated 12 cure rate of 92% after 3 months.
patients with individual plaques of psoriasis and re- I thank Willi Webb, LPN, for her assistance in the
portedthat resolution occurred in about halfthe le- preparation of this manuscript.
sions. Cryotherapy was performed with a spray or
cotton applicator. The factors that promoted opti-
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Answers to CME examination* Identification No. 894-111

November 1994issue of the JOURNAL OF THE AMERICAN ACADEMY OF DERMATOLOGY

Questions 1-33, Koff AB, Rosen T . JAM ACAD DERMATOL 1994;31:693-708.
1. e (p 693, c 2, pa 2) 17. a (p 694, C 2, pa 2)
2. a (p 693, C 2, pa 2) 18. b (p 694, C 2, pa 3)
3. b (p 694, c 1, pa 2) 19. b (p 694, c 2, pa 3)
4. d (p 694, C 1, pa 2) 20. a (p 698, c 2, pa 3)
5. d (p 694, C 1, pa 2; p 704, C 2, pa 2) 21. b (p 698, C 2, pa 3)
6. d (p 694, C 2, pa 2) 22. b (p 704, c 1, pa 1)
7. c (p 694, C 2, pa 3) 23. a (p 704, C 1, pa 1)
8. d (p 694, C 2, pa 3) 24. b (p 704, e 1, pa 1)
9. d (p 697, C 2, pa 1; p 698, C 1, pa 2; p 698, c 2, 25. a (p 704 , C l , pa 2)
pa 2) 26. C (p 704, C I, pa 2)
10. a (p 698, C 1, pa 2) 27. a (p 704, e I, pa 2)
11. a (p702,c l,pa2) 28. a (p 704, C 1, pa 3)
12. C (p 702, C 1, pa 4; p 702, e 2, pa 1) 29. a (p 704, C 1, pa 3)
13. e (p 698, C 2, pa 3; P 699, C 1, pa 3) 30. b (p 704, C 1, pa 4)
14. a (p 703, c 2, pa 2) 31. C (p 704, C 2, pa 1)
15. e (p 703, e 2, pa 3) 32. c (p 704, c I, pa 5; p 704, C 2, pa 1)
]6. a (p 694, C 2, pa 2) 33. d (p 704, C 1, pa 5; p 704, C 2, pa 1)
.p: page; c: column; pa: paragraph.
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