Der aio|ogic surgery

Cryosurgery of cutaneous carcinomas

An 18-year study of 3,022 patients with 4,228 carcinomas
Setrag A. Zacarian, M.D,
Springfield, MA

In the past 18 years, 3,022 patients with a combined total of 4,228 cutaneous
carcinomas were subjected to cryosurgery. Proper selection of patients,
histologic type of the tumor, and its anatomic site are important considerations
to determine the use of cryosurgery as a therapeutic modality. Indications and
contraindications are precisely outlined and the importance of monitoring
neoplasms during freezing is emphasized. A long period of follow-up in this
series is supportive evidence that cryosurgery is a distinct therapeutic tool for
the management of skin cancers and attests to its effectiveness, when properly
administered by the skilled cryosurgeon. (J AM ACAD DERMhTOL9:947-956,
1983.)

Carcinoma of the skin is the most common
malignancy in man. 1 Its early detection and effec-
tive treatment afford a high cure rate. Basal cell
carcinomas, the most common neoplasm of the
head and neck, unlike internal malignancies,
rarely metastasize. Regional lymph gland in-
volvement and systemic spread is in the range of
0.1%. The single most important etiology of skin
cancer is the cumulative exposure to sunlight, in
particular in the white race and those endowed
with blue eyes and sandy complexion. The most
common sites of skin cancers are observed upon
the head and neck and in the order of frequency
constitute basal cell carcinomas, epidermoid (squa-
mous cell) carcinomas, basosquamous cell carci-
nomas, Bowen's disease (carcinoma in situ), and
Hutchinson's melanotic freckle (lentigo maligna).
Melanoma, one of the most malignant of all neo-
plasms, constitutes approximately 1% of cutane-
ous carcinomas and will not be discussed in this
From the Dermatology Service, Baystate Medical Center, Spring-
field, and the Department of Dermatology, Yale Medical School.
Reprint requests to: Dr. Setrag A. Zacarian, 2150 Main St., Suite
105, Springfield, MA 01104.
paper, as cryosurgery has not been used for this
tumor, in this country.
The therapeutic management of cutaneous epi-
theliomas includes: surgical excision, curettage
with electrodesiccation, irradiation, and, for the
more difficult and recurrent carcinomas, Mohs'
chemosurgery. The composite 5-year cure rates of
14,114 carcinomas of the skin, compiled from thir-
teen published reports, as reviewed by Crissey, 2
present the following statistics: Mohs' chemosur-
gery, 99.1%; surgical excision, 95.5%; irradiation
therapy, 94.7%; and curettage with electrodesic-
cation, 92.6%. Cryosurgery for epitheliomas was
first reported at the turn of this century by White '~
and Whitehouse.4 Despite its initial success, it was
abandoned for lack of sophisticated delivery sys-
tem of liquid air and absence of monitoring de-
vices to measure the advancing ice-front within
the frozen tumors. Cryosurgery for malignant
tumors of the skin was reintroduced in the early
1960s by the father of modern cryosurgery, Irving
Cooper) His initial work was subsequently sup-
ported and corroborated by the investigations of
Cahan 6 and Gage. z The first comprehensive text
on the cryogenic effects of subzero temperatures

947
 Journal of the
948 Zacarian American Academyof
Dermatology

Fig. 1. An 88-year-old patient with two carcinomas of the skin. The one on the nose is a
BCC. The one subjected to cryosurgery is a basosquamous cell carcinoma, 23 mm in size,
at the nasolabial fold. The tumor is being monitored during freezing with a thermocouple
needle inserted through a template, allowing the tip of the needle to be positioned 3 mm
below the center of the tumor. The desired temperature to achieve is - 5 0 ~ C. (From
Zacarian SA: Cryosurgery of benign and malignant tumors, in Ablin RJ, editor: Handbook
of cryosurgery. New York, 1980, Marcel Dekker, Inc., chap. 5; reproduced with permis-
sion of editor and publisher.)

upon the skin and malignant tumors was written
b y me. 8
METHODOLOGY AND CLINICAL
APPLICATION
Biopsy examination of all suspicious cutaneous
neoplasms must first be done. The establishment
of the histology will guide the clinician as to his
choice of therapeutic modality. This decision is
not only made upon the skill of the therapist but is
also determined by whether the tumor is a primary
growth or a recurrent one, and equally important is
its histology, the anatomic site, the age of the
patient, and the dimensions of the epithelioma.
The criteria for freezing will be discussed in detail
further in this paper.
If cryosurgery is selected, a safe margin of 3 to
5 m m is outlined with a skin pencil marker, be-
yond the visible margins of the tumor, for once the
ice-front extends laterally, the tumor and adjacent
normal skin turn white and delineation is ob-
scured. Local anesthesia is not required unless one
were to monitor the epithelioma during freezing,
either by insertion of thermocouples or primary
electrode needles (Fig. 1). The flow of liquid ni-
trogen ( - 196.5 ~ C) is directed upon the center of
the tumor target. The spray is very fine and deliv-
ered by way of a 20- or 21-gauge needle. An in-
termittent spray of the refrigerant is desirable, for
a continuous spray will produce a rapid lateral ex-
tension of the ice-front at the expense of in-depth
penetration of the coolant. A continuous spray will
also cause droplets of liquid nitrogen to flow
downward from the tumor surface onto the pa-
tient, and this is disconcerting. Some cryosur-
geons use a closed probe or a disc with circulating
liquid nitrogen within the probe, firmly pressed
upon the neoplasm. I use a closed probe for the
most part for oral lesions.
Adequate freezing of the tumor is determined
by clinical judgment and palpation and also by the
size of the epithelioma. For tumors overlying bony
prominences on the scalp, forehead, temples,
zygoma of the face, and upper aspect of the nose,
freezing is continued until the ice-front has ex-
tended down to the periosteum and the overlying
skin is immobile. For tumors overlying cartilage,
the ear, and the nares of the nose, freezing is carried
out until the opposing side is cooled; and on the
ear, I will very often freeze through the cartilage
Volume 9
Number 6
December, 1983
until a tiny visible speck of frozen white tissue is
noted on the opposing side. It is extremely un-
common for a skin cancer to extend down to the
periosteum and even rarer to have neoplastic in-
vasion of the perichondrium. Chondronecrosis
from freezing, to my knowledge, has not been
reported, and subsequent permanent perforation of
the cartilage from cryosurgery has occurred only
when the neoplasm itself has involved the carti-
lage. Infrequently, loss of cartilage has been ob-
served at the helix and ala nasi.
Monitoring of the frozen tumor and its advanc-
ing ice-front is mandatory for the novice, who is
unskilled in cryosurgery, and even in the hands of
a competent clinician for epitheliomas in critical
sites, such as the medial canthus of the eyelid,
ala nasi, nasolabial fold, anterior to the tragus of
the ear, and the postauricular sulcus. One or two
thermocouple needles can be employed and pre-
cise depth of insertion within and below the tumor
is determined by the use of a template (Fig. 1). A
desired temperature for effective cryonecrosis for
malignant tumors is in the range of - 5 0 ~ C. 9,1~
Once the epithelioma is frozen adequately, it is
allowed to thaw and a second freeze is instituted.
This is referred to as a double freeze-thaw cycle.
The second freeze-thaw cycle will be achieved in
less time than the first, because the microvessels
are still under partial vasoconstriction from the
initial freezing and will afford less resistance to
the advancing ice-front, with the second freeze, n
It is interesting to note that the duration of the
thaw time is twice as long as the freezing period.
For an example, if an average epithelioma is fro-
zen adequately in a period of llA minutes, it will
take 3 minutes for complete thawing, following
which a second freeze is instituted. With the use of
plastic cones to deliver the liquid nitrogen, the
thaw period is four times as long as the freeze
time. The use of cones concentrates the refrigerant
to the tumor target, with minimal marginal spread
of the ice-front, and allows for a deeper in-depth
freeze within and below the tumor. A clinical
guide of measuring the lateral spread of freeze
beyond the plastic cone to estimate the depth of
freeze within and below the tumor has been postu-
lated. 12 This observation is validated when one
uses truncated or otoscopic cones. In my own
Cryosurgery of cutaneous carcinomas 949
Fig. 2. The Freeze Depth Indicator. This device moni,
tors the electrical current flow within the epithelioma
during cryosurgery. On the extreme lower right are five
primary electrode needles whose distal end is plugged
into five respective channel indicators to measure im-
pedance or resistance. On the extreme left is the distal
or indifferent electrode cuff which is attached to the
patient's wrist. (From Zacarian SA: J Dermatol Surg
Oncol 6:627-632, 1980; copyright 1980, The Journal
of Dermatologic Surgery and Ontology, Inc.)
experimental studies and clinical application, I use
closed plastic cones attached to my cryosurgical
unit, wherein lateral spread of freeze is not sig-
nificant. 13 When using a cone-technic freezing
procedure, either after the first or second freeze,
lift the cone from the tumor site and lightly spray
the liquid nitrogen circumferentially around the
edge of the surface of the tumor. This will give a
feathering effect, and upon healing of the tumor
site the white depigmented area will blend with the
adjacent nonfrozen skin surface.
A more accurate monitoring device for measur-
ing effective cryonecrosis in malignant tumors
was introduced by LePivert et al. 14 He measured
the electrical current flow within the tumor during
freezing by inserting a series of electrode needles
and observing the impedance that develops be-
tween parallel-placed electrode needles. It has
been observed that electrical flow within cells and
tissue decreases as the freezing temperatures are
lowered. When all of the available water within a
cell is converted to ice and all of its electrolytes
are crystallized, the cell is no longer viable and
will no longer allow the conduction of electricity.
This phase is referred to as the eutectic state where
there is compIete impedance or resistance to elec-

950 Zacarian
Fig. 3. A BCC over 22 mm at the outer canthus of the
eyelid. (From Zacarian SA: J Dermatol Surg Oncol
6:627-632, 1980; copyright 1980, The Journal of Der-
matologic Surgery and Oncology, Inc.)
Fig. 4. After local anesthesia at the tumor site, three
primary electrode needles are inserted, one at the center
and the others at opposing margins. The electrode nee-
dles are calibrated in millimeters, allowing selection of
specific depth of penetration. Average depth of inser-
tion is 3 to 5 mm from the tumor surface. (From Zaca-
rian SA: J Dermatol Surg Oncol 6:627-632, 1980;
copyright 1980, The Journal of Dermatologic Surgery
and Oncology, Inc.)
trical current flow. This state is reached in close
correlation to a temperature range of - 5 0 ~ C, if
one were to monitor the tumor with a thermo-
couple needle. One must appreciate that cryone-
crosis is achieved not only by the formation of ice
crystals within cells and the interspaces between
them but also b y thrombosis and complete occlu-
sion of the microvessels within the skin and the
frozen tumor. ~ The latter produces ischemic ne-
crosis of the frozen site, and malignant cells which
might well survive subzero temperatures no longer
Journal of the
American Academy of
Dermatology
Fig. 5. Each area of the tumor inserted by a primary
electrode needle is subjected to cryosurgery. Freezing
is continued until the eutectic state is reached by the
tissue immediately surrounding the tips of the needles.
(From Zacarian SA: J Derrnatol Surg Oncol 6:627-632,
1980; copyright 1980, The Journal of Dermatologic
Surgery and Oncology. Inc.)
remain viable. The electrical flow technic of
LePivert was modified by Savic and me. 1, Instead
of using primary electrodes alone and monitoring
the impedance between them, we utilized a sec-
ondary as an indifferent electrode, distant from the
primary electrode needles. The indifferent elec-
trode is placed around the wrist of the patient. This
electrical device incorporating a small voltage bat-
tery, with selective channels for the insertion of
the distal end of the primary electrode needles
along with the indifferent electrode, is referred to
as the Freeze Depth Indicator (Fig. 2). Other in-
vestigators 17"18'* have also modified LePivert's
work.
This electrical monitoring device offers a num-
ber of advantages over temperature monitoring.
Thermocouple needles are not absolutely accurate
and present an error of conduction of approxi-
mately 15%. l~ Where one or perhaps two ther-
mocouple needles can be inserted in the tumor to
monitor temperature gradients which develop
within the tumor, one can utilize as many as five
primary electrode needles within the tumor at dif-
ferent sites.
The patient in Fig. 3 presents a nodular ulcer-
ative basal cell carcinoma over 2 cm in size at the
*Tot-re D: Paper delivered at the 2nd Annual Meeting of The Ameri-
can College of Cryosurgery, Buffalo, NY, June 15, 1979.
Volume 9
Number 6
December, 1983
Fig. 6. The complete electrical circuitry during cryo-
surgery. The electrical current is generated from the
impedance meter (above left). The current flows through
the primary electrode needles and then passes through
the body of the patient to the indifferent or secondary
electrode attached to the right wrist of the patient.
When the electrical current flow ceases, by virtue of
complete cryonecrosis of tissue surrounding the tips of
the primary electrode needle, the circuit breaks and the
impedance meter signals an audiovisual warning. (From
Zacarian SA: J Dermatol Surg Oncol 6:627-632, 1980;
copyright 1980, The Journal of Dermatologic Surgery
and Oncology, Inc.)
outer right canthus. Once the tumor site is locally
anesthetized, three primary electrode needles are
inserted within the tumor and at its margins (Fig.
4). The distal ends of the primary electrode nee-
dles are inserted to corresponding selective chan-
nels in the Freeze Depth Indicator. The electrode
needles are extremely thin, 25-gauge, and are cal-
ibrated in millimeters, which enables the clinician
to predetermine depth of tumor penetration. The
depth of insertion may vary from 3 to 5 mrn from
the surface of the epithelioma. Liquid nitrogen
spray is directed in the area of each primary elec-
trode separately. When the specific site is ade-
quately frozen and electrical current flow ceases,
impedance or resistance is established and the
Freeze Depth Indicator will exhibit a red light at
its respective selector channel along with an au-
ditory sound, signaling the end of freezing. The
clinician will then freeze another electrode site and
so on until all monitored sites have been ade-
quately frozen (Fig. 5).
The complete electrical monitoring circuit is
demonstrated in Fig. 6, during the freezing proce-
dure. The electrical flow is initiated by a small-
Cryosurgery of cutaneous carcinomas 951
Fig. 7. After the initial freeze, the two marginal primary
electrode needles are repositioned and a second freeze
is instituted. (From Zacarian SA: J Dermatol Surg
Oncol 6:627-632, 1980; copyright 1980, The Journal
of Dermatologic Surgery and Oncology, Inc.)
Fig. 8. Four weeks following cryosurgery, granulation
tissue is still present, as expected. (From Zacarian SA:
J Dermatol Surg Oncol 6:627-632, 1980; copyright
1980, The Journal of Dermatologic Surgery and On-
cology, Inc.)
voltage battery within the device. This current
passes through each primary electrode needle,
through the tumor at that site, through the body of
the patient, and on to the indifferent or secondary
electrode attached to the patient's wrist. From
there, the current is carried to the impedance meter
at the selected channel, completing electrical flow.
When the tissue immediately surrounding the tip
of the electrode needle is completely frozen, to its
eutectic point, as mentioned earlier, the electrical
flow ceases, and, with the absence of conduction
of electric current to the secondary electrode at the
wrist, the circuit is broken and the audiovisual
signal is set off by the impedance meter. The

952 Zacarian
Fig. 9. Eight weeks following cryosurgery, hyper-
trophic scar is present. This is self-limited and will
spontaneously involute. (From Zacarian SA: J Der-
matol Surg Oncol 6:627-632, 1980; copyright 1980,
The Journal of Dermatologic Surgery and Oncology,
Inc.)
clinician then selects a second and then a third
channel to initiate his electrical monitoring at each
respective site within the tumor. As many as five
primary electrode needles can be monitored sepa-
rately for larger epithelioma.
After the initial freeze, the primary electrode
needles are repositioned (Fig. 7), and a second
freeze is initiated. A double freeze-thaw cycle is
advocated for malignant tumors unless they are
very superficial. Graham 1'~ presented a paper in
Tokyo at the International Meeting in 1982, stat-
ing that she had treated over 600 basal cell carci-
nomas, including many superficial carcinomas,
with a single freeze-thaw cycle with 95% cure
rate. Superficial basal cell carcinomas may well
respond to a single freezing procedure, but I
would feel more comfortable with a double
freeze-thaw cycle with the nodular and ulcerative
carcinomas. With a single freeze, certainly the
cosmetic end results will be much more accept-
able. Cryonecrosis is enhanced not only by rapid
freezing and slow thawing but also by the second
freeze. 2~ This entire cryosurgical procedure was
accomplished within 15 minutes, in my office.
There is no fear of disturbing the rate of a pace-
maker, should a patient have one. Unlike the use
of an electrodesiccation procedure for epitheli-
omas, this electrical device can be used with
safety.
Four weeks following cryosurgery, the patient
Journal of the
American Acadealyof
Dermatology
Fig. 10. Three months following cryosurgery there is no
clinical evidence of the previous carcinoma. The su-
perior cosmetic end result is unequaled by any other
modality. This patient has been followed for over 4
years without a recurrence. (From Zacarian SA: J Der-
matol Surg Oncol 6:627-632, 1980; copyright 1980,
The Journal of Dermatologic Surgery and Oncology,
Inc.)
presents the expected granulation tissue at the fro-
zen site (Fig. 8) and a hypertrophic scar in Fig. 9,
8 weeks following freezing. Hypertrophic scars
can develop following cryosurgery but will spon-
taneously involute; to enhance their resolution, a
single intralesional injection of 10 mg of triam-
cinolone will hasten their disappearance. Keloid
formation following cryosurgery has not been
seen, even in those who have a diathesis for
keloids.
Three months following cryosurgery (Fig. 10),
there is no clinical evidence of the earlier basal
cell carcinoma. This patient has been followed for
over 4 years without a recurrence. The cosmetic
end result from cryosurgery of epitheliomas is one
of the salient attributes of this modality.
INDICATIONS AND CONTRAINDICATIONS IN
CRYOSURGERY
As with any therapeutic modality for the eradi-
cation of cutaneous carcinomas, cryosurgery has
its own guidelines. I consider the following as
indications for cryosurgery for epitheliomas: (1)
nodular and or ulcerated carcinomas; (2) tumors
with well-defined borders with palpation or by in-
strument delineation as with a curet; (3) most
rumors overlying bone or cartilage; (4) selective
epitheliomas of the eyelid, in particular the medial
Volume 9
Number 6
December, 1983
canthus, where, unlike surgical excision or irradi-
ation, the lacrimal apparatus is spared from de-
struction. Tumors in the medial canthus are the
most difficult neoplasms facing a dermatologist
and should be undertaken only by the experienced
cryosurgeon; (5) tumors situated at the tip of the
nose--cryosurgery produces less deformity than
surgical extirpation; (6) recurrent tumors from
previous radiotherapy; (7) lentigo maligna; (8) pa-
tients of advanced age or who are poor surgical
risks; (9) patients with anesthesia idiosyncrasies;
(10) patients with far-advanced tumors as a pal-
liative measure; (11) physicians skilled in cryo-
surgery.
I should like to divide contraindications for
cryosurgery of carcinoma of the skin into absolute
and relative contraindications. In the category of
absolute contraindications, I should like to include
the following: (1) patients with abnormal cold
tolerance, cryoglobulinemia, cryofibrinogenemia,
Raynaud's disease, autoimmune disease, and
platelet deficiency disorders and (2) patients with
morphea or sclerosing type of basal cell carci-
nomas. I have abandoned cryosurgery for scleros-
ing type of basal cell carcinoma because the recur-
rence rate from freezing is too high. The reason
for this is that its borders are ill-defined; nests of
cancer cells migrate a considerable distance along
the collagen fibers, far from the site of origin.
Graham 19 reported cure rates of 94% with cryo-
surgery of sclerosing basal cell carcinomas under
2.0 cm in size. In a recent study of 496 recunent
basal cell carcinomas, Levine and Balin "1 found
sclerosing cell type constituted 27.4%. With im-
proved monitoring devices, freezing sclerosing
basal cell carcinomas more vigorously, and ex-
tending the freeze at least 5 mm beyond the visible
margins of the tumor, a higher and more accept-
able cure rate from cryosurgery may be possible,
Under relative contraindications, I would in-
clude the following: (1) neoplasia of the scalp; (2)
ala nasi and nasolabial fold; (3) epitheliomas an-
terior to the tragus of the ear and postauricular
sulcus; (4) tumors situated on the free margin of
the eyelids; (5) neoplasia near the vermilion bor-
der of the upper lip; (6) tumors of the lower legs;
(7) nodular ulcerative neoplasia over 3 cm in size;
(8) carcinomas fixed to the underlying bone or
Cryosurgery of cutaneous carcinomas 953
cartilage; (9) tumors situated on the lateral mar-
gins of the fingers and at the ulnar fossa of the
elbow; (10) recurrent carcinomas after surgical
excision. The recurrence rate of epitheliomas sit-
uated at anatomic sites, such as the ala nasi, naso-
labial fold, anterior tragus, and the postauricular
area, is over 10% when they are subjected to
cryosurgery. This represents twice the recurrence
rate of epitheliomas at other sites when freezing
technic is employed. The reason for this may be
due to anatomic embryologic fusion planes at
these sites, wherein tumor cells migrate along
these planes. Even surgical excision and irradia-
tion carries a high recurrence rate for neoplasms at
these locations. Freezing tumors near the vermil-
ion border of the upper lip will often produce a
permanent uplifting or tenting of the mucosa.
Freezing tumors on the free margin of the eyelids
can result in total loss of eyelashes at the frozen
site, but, more seriously, notching of the lid is a
sequela which can result. ~2 Nodular or ulcerated
carcinomas, beyond 3 cm, are not amenable to
cryosurgery (except those that are superficial and
multicentric, even those that are 4 to 7 cm in
width). These tumors I will freeze in quadrants
and achieve a high cure rate with less hypertrophic
scars than encountered by surgical excision.
I hasten to point out that relative contraindica-
tions do not exclude the use of cryosurgery in the
hands of a skilled cryosurgeon, and, where indi-
cated, the tumors are monitored during the freez-
ing procedures. We are practicing in a period of
time in which many of our patients are in their late
sixties, seventies, and beyond and often present
considerable operative risks, in particular where
major reconstructive surgery is contemplated. Re-
spectful of the guidelines I have outlined, under
relative contraindications I will not hesitate to use
cryosurgery in the best interest of the patient, tak-
ing into account age, operative risks, and other
mitigating circumstances.
COMPLICATIONS FROM CRYOSURGERY
The immediate sequela following cryosurgery is
edema, especially when freezing tumors in the
periorbital area, temple, and forehead, This sub-
sides in a few days, A short period of exudation at
the tumor site is followed with an eschar which

954 Zacarian
Table I, 3,022 patients with a combined total
of 4,228 carcinomas of the skin subjected to
cryosurgery (1964-1982)
Histology of the neoplasms Number
Basal cell carcinomas
3,869
Epidermoid carcinomas
203
Basosquamous cell carcinomas
78
Bowen's disease (carcinoma in
52
situ)
Hutchinson's melanotic freckle 26
(lentigo maligna)
4,228
30% of all carcinomas were under 1.0 cm
60% of all carcinomas were 1.0-2.0 cm
10% of all carcinomas were over 2.0 cm
Table II. The follow-up cure rate of 4,228
carcinomas of the skin in 3,022 patients
subjected to cryosurgery (1964-1982)
Of the total number of patients (3,022) C u r e rate
110 recurrences (3.6%)* 96.4%
Of the total 4,228 combined carcinomas C u r e rate
110 recurrences (2.6%)* 97.4%
Of the 110 recurrences 36 or 33% were recurrent carci-
nomas
When recurrences were noted:
43.3% appeared during the first year
24.3% appeared during the second year
19.0% appeared during the third year
86.6% of all carcinomas manifested recurrence
within the first 3 years, if they were to recur
"155 patients have died or were lost in follow-up (error of correc-
tion, 0.3%).
eventually sloughs off within 4 weeks. No special
care is required of the treated site other than daily
cleansing and the application of a nonadhesive
dressing. Tumors subjected to freezing on the
chest and back take longer to heal, and those on
the lower legs m a y take as long as 8 to 10 weeks
and may occasionally become secondarily in-
fected.
Permanent loss of pigment at the tumor site fol-
lowing freezing is unavoidable. The darker the
complexion of the patient the more noticeable is
the hypopigmentation; and yet, I have seen
cryosurgery of keloids in several black patients
wherein the pigment has completely returned. Hy-
J0umal of the
American Academy of
Dermatology
Table III. Follow-up of 4,228 carcinomas of
the head and neck subjected to cryosurgery
(1964-1982)
Percent Follow-up
15% Under 3 yr
91.60
25% 3-5 yr
4.80
40% 5-10 yr
1.80
20% l0 yr and over
1.20
0.60
perpigmentation is infrequently seen, and when
100.0 noted it spontaneously disappears within a few
months. Atrophic scars are seen on the mid
forehead more often than other sites, but this
complication is more often observed when the
tumor itself has invaded deep underlying fascia.
Atrophy following cryosurgery is not common.
Hypertrophic scars following freezing have
been discussed and are transient. Neuropathy fol-
lowing cryosurgery has been reported. It is seldom
seen, however, and in all cases which have been
carefully followed, there has been full return of
both motor and sensory functions.
STATISTICAL DATA AND CONCLUSIONS
In the past 18 years I have carefully compiled
the number of patients with cancers of the skin.
Approximately 80% of the carcinomas were on the
head and neck; the other 20% were situated on the
trunk and extremities. The histologic classification
of the epitheliomas has been recorded. In Table I,
one observes the number of patients, the combined
carcinomas, and morphologic classification of
tumor types. Epitheliomas for the most part were
under 2 cm in size. In this age of education, pa-
tients are conscious of recognizing an indolent
sore and seek medical advice.
The cure rate of carcinomas of the skin sub-
jected to cryosurgery varies between 96% and
97% (Table II). It is interesting to note that most
recurrences, if observed, occur within the first 3
years. I have made it a rule to follow patients
annually for 5 years and longer. Patients who pre-
sented epitheliomas in critical sites, such as
eyelids, ala nasi, nasolabial fold, and the face an-
terior to the tragus and postauricular areas, will be
followed every 6 months. In my own series, one
patient in every five has returned within 5 years
Volume 9
Number 6
December, 1983
with a new epithelioma. Table III outlines the pe-
riod o f f o l l o w - u p in the past 18 years. Almost two
thirds of the patients h a v e been followed between
5 and 10 years.
There are cancer therapists who question the
value of c r y o s u r g e r y for epitheliomas of the skin.
Some surgeons are skeptical and invariably argue
that c r y o s u r g e r y does not lend itself to submission
of the s p e c i m e n to the pathologist for examination
and evaluation of adequate ablation. Some clini-
cians will also argue about how a cryosurgeon can
determine the depth and extent of the epithelioma
subjected to freezing and the proper placement of
monitoring devices.
Careful histologic studies o f extirpated cutane-
ous c a r c i n o m a s have shown that over 90% of
epitheliomas reside within the first 2 m m of the
skin. This observation is f r o m m y own unpub-
lished work on examining over two hundred ran-
dom biopsy specimens of carcinomas of the skin.
When t h e r m o c o u p l e needles or primary electrode
needles are inserted at 3 or 4 m m below the sur-
face of the t u m o r , cryosurgery is effective and
cryonecrosis is accomplished.
The clinician w h o looks with dismay upon
cryosurgery as curative for epitheliomas has for 80
years accepted radiation therapy as effective. Yet
the radiotherapist does not submit a specimen to
the pathologist for examination after irradiation of
the given neoplasia, nor does he k n o w exactly the
extent of depth of the tumor. The radiotherapist
and the c r y o s u r g e o n use similar skills and judg-
ment in following their respective modalities.
There is no one best method for the eradica-
tion of cutaneous carcinomas. Each of the exist-
ing modalities has its strengths and its weak-
n e s s e s - - c r y o s u r g e r y is no exception. It is a new
field, and as such it will remain a controversial
modality for years to come. It will require more
time, greater n u m b e r of cases, and, along with all
existing therapeutic r e g i m e n s , proper selection
and individualization o f each patient and each epi-
thelioma. T h e simplicity of cryosurgery, its supe-
rior cosmetic end result in the hands of the skilled
cryosurgeon, as well as economic considerations
are features e v e r y cancer therapist will do well to
consider. I a m reminded of a quotation from the
English essayist, William Hazlitt, who in 1830
C13,osurgery of cutaneous carcinomas 955
remarked: " W h e n a thing ceases to be a subject of
controversy, it ceases to be a subject of i n t e r e s t . "
I thank the National Institute of Health for their initial
support for the basic work in cryogenics I undertook
with Dr. David Stone and The Zacarian Cancer Re-
search Foundation. I also acknowledge Drs. Arthur M.
Sher and Stanley F. Glazer in my office who have
referred a number of patients with skin cancers treated
with cryosurgery in the past 8 years.
REFERENCES
1. Urbach F: Geographic distribution of skin cancer. J Surg
Oncol 3:219-234, 1971.
2. Crissey JT: Curettage and eleetrodesiccation as a method
of treatment for epitheliomas of the skin. J Surg Oncol
3:287-290, 1971.
3. White AC: Liquid air in medicine and surgery. Med Rec
56:t09-114, 1899.
4. Whitehouse HH: Liquid air in dermatology: Its indica-
tions and limitations. JAMA 49:371-377, 1907.
5. Cooper IS: Cryogenic surgery; new method of destruc-
tion or extirpation of benign or malignant tumors. N Engl
J Med 268:743-749, 1963.
6. Cahan WG: Cryosurgery of malignant and benign
tumors. Fed Proc 24:(suppl 15):$241-248, 1965.
7. Gage AA, Emmings FC: Treatment of human tumors by
freezing. Cryobiology 2:24-27, 1965.
8. Zacarian SA: Cryosurgery of skin cancer and cryo-
genic techniques in dermatology. Springfield, IL, 1969,
Charles C Thomas, Publisher, chap. 3, pp. 11-21.
9. Gage AA: What temperature range is lethal for cells? J
Dermatol Surg Oncol 5:459-460, i979.
l 0. Zacarian SA: How accurate is temperature monitoring in
cryosurgery and is there an alternative? J Dermatol Surg
OncoI 6:8,627-632, 1980.
11. Zacarian SA, Stone D, Ctater M: Effects of cryogenic
temperatures on microcirculation on the Golden Syrian
Hamster Cheek Pouch. Cryobiology 7:27-39, 1970.
12. Tone D: Cryosurgieal treatment of epitheliomas using
the cone-spray technique. J Dermatol Surg Oncol
3:432-436, 1977.
13. Zaearian SA: Is lateral spread of freeze a valid guide to
depth of freeze? J Dermatol Surg Oneol 4:561-563,
1978.
14. LePivert PJ, Binder P, Ougier T: Measurement of in-
tratissular bioelectrical low frequency impedance: A new
method to predict preoperatively the destructive effect of
cryosurgery. Cryobiology 14:245-250, 1977,
15. Zacarian SA: Cryosurgical advances in dermatology and
tumors of the head and neck. Springfield, IL, 1977,
Charles C Thomas, Publisher, chap. 1, pp. 3-37.
16. Savic M, Zacarian SA: A new impedance based method
for controlled cryosurgery of malignant tumors. J Der-
matol Surg Oncol 3:592-593, 1977.
17. Gage AA: Correlation of electrical impedance and tem-
perature in tissue during freezing. Cryobiology 16:56-
62, 1979.
18. Torte D: Cryosurgical equipment. Paper given at 2rid
Annual Meeting of The American College of Cryosur-
gery, Buffalo, June 15-16, 1979.
 Journal of the
956 Zacarian American Academy of
Dermatology

19. Graham GF: Statistical data, presented at the XVI Inter-
national Congress of Dermatology, Tokyo, May 27,
1982.
20. Stone D, Zaearian SA, DiPeri C: Comparative studies of
mammalian normal and cancer cells subjected to cryo-
genic temperatures in-vitro. J Cryosurg 2:43-52, 1969.
21. Levine HL, Balin PL: Basal cell carcinomas of the head
and neck: Identification of the high risk patient. Laryn-
goscope 90:955-961, 1980.
22. Fraunfelder FT, Zacarian SA, Limmer BL: Cryosurgery
for malignancies of the eyelid. Ophthalmology 87:461-
465, 1980.

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