Malignant epithelial tumors of the skin of head and neck

MALIGNANT

EPITHELIAL TUMORS OF THE SKIN OF HEAD AND NECK*

GRANTE. WARD, M.D. AND JAMES W.

HENDRICK,

M.D.

Baltimore, Maryland

I

T is generahy

thought that malignant growths of the skin are best understood of all tumors of the body since they are easiIy accessible for carefu1 examination, diagnosis and treatment. MateriaI for this article was gathered from the Tumor CIinics of the University of Maryland, Johns Hopkins University and private practice. The cases from our private files were taken consecutively from January, 1930, to June 30, 1945, or a period of On account of the large fifteen years. amount of materia1 from the teaching institutions onIy every fourth case was taken. Time did not permit a careful anaIysis of the 1,000 or 1,300 cases in these Iarge institutiona files. It was beIieved that every fourth case wouId give a fairly typical representation of the problems involved and the results obtained. So far as these two groups of cases were concerned the study is more or less a GalIup poll. This gave us a group of 840 patients as a basis for this report. The constant appearance of patients with lingering disease after months or years of various types of treatment has Ied us to a careful study of the reasons for failure of therapy of skin cancer. It would seem that in the early stages too little significance was attached to careful and adequate management. No patient is incIuded without having had a positive biopsy or who had been treated under three years. It is most important in selecting treatment to differentiate between the various histopathologic types. For this purpose we have divided our cases into three genera1 groups, namely, Group I, basal ceII carcinomas, Group II, squamous ceI1 carcinomas or epidermoid carcinomas * From the Tumor Clinics, Department

.June,

I 950

with varying degrees of celIular differentiation and Group III, adenocystic basa1 ceI1 carcinomas. This Iatter group arises from the sweat glands1v13’14 or the coi1 glands. Patients with basal cell carcinomas as a rule give a history of a lesion for a period of TABLE LOCATION

OF 840

I

EPLTHELIAL THE

HEAD

TUMORS AND

OF THE

SKIN

OF

NECK

Eyelid.. Nose............................ Cheeks.......................... Forehead........................ Ears............................. Scalp.. Chin............................ Neck............................

No. of Cases 94 244 217 79 99 34 14 42

years before they become active; they remain local and frequentIy destroy the entire thickness of the skin, an ear, eye or erode through bIood vessels producing excessive hemorrhage. However, these tumors seldom produce regional or distant metastases. On the other hand, squamous cell variety produces local and distant metastases. The third group or adenocystic basal cell carcinoma occasionally produces metastases either Iocally or distantly.g Because of their histoIogy and ceIIuIar differentiation they are more difficult to treat or eradicate than the basal cell lesions. AI1 three types of carcinomas may occur anywhere in the skin of the head and neck but as Figures I and 2 ilIustrate, the areas of predilection are nose, chin, eyeIid and preauricular zones. (Table I.) It has been shown by numerous investigatorsZ*r4 that individuaIs without much pigment in their skins or who have thin, dry skin are frequent candidates for epi-

of Surgery, Johns Hopkins University and University Baltimore, VId.

771

of Maryland

772

Ward,

Hendrick-MaIignant

theIia1 malignancies. Such individuaIs often have multipIe Iesions over a period of years. Such lesions may be either basa1 cell, squamous ceI1 or frequentIy both types may be present at the same time. In many patients areas of thickening of the skin or

Tumors

of Skin

moved. This is more important if they are on areas of the face and neck that are constantIy irritated as by shaving. HertzIer’O stated, “More wart specialists and not boId operators are what is needed to take care of earIy skin maIignancies.”

I

FIGS. I and 2. Locations of 840 malignant epithelial tumors of head and neck irrespective of histologic type. Each dot represents one tumor; the large dots, tumors over 3 cm. in diameter.

if not properly treated, hyperkeratoses, progress and develop into malignancies. Chemical irritants frequentIy act as predisposing factors or as a direct cause of these carcinomas. RecentIy, a man was seen in the offIce who gave a history of having his face repeatedly burned with creosote-arsenic mixture used for preserving railroad ties. In one of these burned areas a rapidly growing squamous ceI1 carcinoma deveIoped that destroyed the ala and the left side of the nose. MaIignancies are prone to deveIop in those who work in open weather and are constantIy subjected to intense sunIight Iike that which is seen in the southwest or northwest. Such individuaIs can protect their skin by using a cream when they are exposed to intense sunIight. It is most important that premaIignant Iesions such as hyperkeratoses, warts, especiaIIy the type of wart that is seen in older patients, and moles should be re-

CLASSIFICATION

Group I. Th is group consists of basal cell epitheliomas (Rodent UIcer; Jacobs’s UIcer; Krompecher’9 cancers). As the name implies these lesions are supposed to develop from basa1 Iayers of the epitheIium and are frequently referred to as rodent uIcers. There are two types of basal cell lesions, one beginning as a ruIe in a dry skin without much pigment. The Iesion appears as a piIing up of siIver scaIes which when removed Ieaves a purplish base. Later as the Iesion progresses and the scaIes are removed, definite bIeeding occurs. (Fig. 6.) As a ruIe in this type of tumor there are groups or cIumps of ceils beneath the dermis which do not have the typica paIisading encountered in the next group. In the second group there is no preIiminary area of hyperkeratosis and without apparent cause or reason a firm noduIe deveIops in the skin that tends to infiltrate rather American

Journal

of Surgery

Ward,

Hendrick-Mahgnant

Tumors

of Skin

773

FIG. 3. Very early basal cell carcinoma of the right cheek. The patient had a flat seniIe wart for several years. LateIy telangiectasis developed over top of it, and it began to itch and became irritated around the edges. There was no ulceration; treated 4,000 r x-ray with good result.

deepIy. (Fig. 3.) As the growth enlarges telangiectases may deveIop. (Fig. 4.) When this stage is reached, the tumor enIarges rapidIy to produce a buIky mass. In general, this grows sIowIy but occasionaIIy when extending onto the conjunctiva (Fig. 5) of the eye or the mucous membrane of the nose its growth is very rapid. (Fig. 6.) This increased growth on the mucous membrane is Iess resistant to the growth of the tumor ceils because it contains Iess fibrous tissue than the skin and the bIood supply is more abundant. (Fig. 6.) In certain areas as the ternpIe or scaIp if basa1 ceI1 Iesions are Iong neglected, heaIing may be attempted in one area while new Iesions deveIop in others which often produce a compIicated network to confuse the diagnosis. In this study of 840 patients with maIignant skin lesions there were 676 basa1 ceII or 81 per cent. Fourteen patients had two basa1 ceI1 Iesions, six patients had three basal ceII Iesions and fourteen patients had both a basal cel1 and a squamous ceil lesion at the same time. (Fig. 7.) Group II. Squamous ceI1 carcinomas differ from the preceding group in that they deveIop from the prickIe-ceI1 layer. They occur Iess frequentIy there being onIy one hundred six cases in this series or 12.6 per cent, grow more rapidly and tend to metastasize. HistoIogicaIIy, they are made up of June,

1950

FIG. 4. RasaI cc11 carcinoma with squamous cell changes; began in hyperkeratoses one year before. Such hyperkeratoses should be removed as a preventive measure; surgical excision, skin graft.

squamous celIs varying in type from undifferentiated forms to more highIy differentiated ones6 showing few to many epitheIia1 pearIs. They may develop from epitheIia1 papiIIomas, cutaneous horns, warts (Fig. 8) and scars, especiaIIy scars produced by repeated x-ray (Fig. 7) therapy and heat burns or broken down scars from tubercuIosis, syphilis or any chronic irritation. Some have their origin in tiny hyperkeratoses which are often scarceIy visibIe. Those squamous ceI1 carcinomas that have deveIoped from pre-existing Iesions show as early evidence of mischief an area of hyperemia around the previous Iesion. Another sign of maIignant change is the appearance of firm, hard induration. On the other hand, malignancy may occur as a primary protruding mass. These Iesions frequentIy have an area of hyperemia around them which resembIes inffammation. Secondary infection may creep in seemingly accentuating growth. Frequently, cancer nests may be observed at the border of an oId ulcer appearing as gray spots in the red background. Squamous

Ward,

Hendrick-Malignant

Tumors

of Skin

sive destruction of the skin, subcutaneous tissues and bone to form Iarge craters and hideous ulcers. They have a tendency to metastasize. (Figs. IO and I 2.) They perhaps spring from undeveIoped embryonal cells, sweat gIand anlages which faiIed to form gIands or they may form from gIand epidermoid cysts or sweat adenomas, gland. (Fig. 9.) They may exist for some time before the center ulcerates. As a ruIe the surface becomes hyperemic and thin then uIceration begins and scabs form.

SB 5C Basal ceI1 carcinoma of edge of upper eyelid, present six months. If conjunctiva is involved, there is very rapid growth, Removed with electrodesiccation; no recurrence in three years.

FIG.

5.

cel1 carcinomas are not as we11 circumscribed as basa1 ceII Iesions and tend to infiItrate. Sooner or Iater the regional or distant Iymph nodes become invoIved. In this series of cases three patients had two squamous ceII carcinomas at the same time and one had four. The earIy remova of papiIIomas, warts, hyperkeratotic areas and oId uIcers wouId prevent the formation of this type of cancer. UnfortunateIy, these tumors in the earIy stages are painIess; but when mahgnancy deveIops, the patient sometimes notices itching around the border of the previousIy benign or apparentIy innoxious tumor. Any lesion previousIy benign that increases in infiItration or hardness shouId be considered malignant unti1 proven otherwise. (Fig. 9.) Group III. Th is group which is most interesting consists of adenocystic or adenoid epitheIiomas. These tumors often begin in seborrheic areas of the skin and form gIobuIar tumors which after a time undergo proIiferation and become uIcerated. (Figs. 6 and 7.) Hutchinson’ first described them as crateriform uIcers with mahgnant changes. They are more maIignant than basa1 ceII epitheliomas and after a time grow quite rapidIy producing exten-

These tumors Iook more maIicious than the common basa1 ceII carcinoma but do not grow as rapidIy and form metastases as fast as the squamous ceI1 type. The adenocystic carcinomas are an intermediate group between the basa1 ceII and squamous ceI1 neopIasms in cIinica1 behavior and response to treatment. INCIDENCE

MaIes are more frequentIy affected than femaIes. There were 562 maIes and 278 femaIes or 67 per cent maIes. A study of this series of patients substantiates the fact that cancer is more frequentIy seen in AGES

Years ‘4-30

TABLE II OF 840 CASES No. of Cases 44 34 ‘31 176

30-40 40-P jO-f50

60-70

213 178

70-80

80 PIUS

64

the oIder age group (TabIe II) as one-half of these patients were sixty years of age or over and sixty-four patients were over eighty years of age. There were 538 cases that had had no previous treatment other American

Journal

of Surgery

Ward,

Hendrick-Malignant

6~

Tumors

of Skin

775

6~

FIG. 6. Basal

ceI1 carcinoma of ala of nose; began as a small wart-IikepimpIe seventeen years before. Six months before it ulcerated, began to grow rapidty and extended through aIa of nose. Treated with 4,000 r x-ray; slight deformity of ala of nose. No recurrence three years later.

7‘4

78

FIG. 7.S quamous

ceI1 carcinoma of right ear of six months’ duration; Iesion treated with 5,000 r x-ray. Regional lymph nodes were invoIved; radica1 neck dissection of the right side done. Patient had basaI ceII carcinoma of left ear at same time; treated with 4,400 r x-ray. No recurrence after three years.

than saIves or ointments. Most of these 538 patients had had their lesions Iess than two years and their lesions were Iess than 2 cm. in diameter in the majority of cases. This is in direct contrast to 302 patients who had Iesions over two years and had had either x-ray therapy, radium, eIectrodesiccation or IocaI surgica1 excision; eighteen of the squamous ceII carcinomas that had been present for over a period of two years and had had various types of treatment had Iymph-node invoIvement and 453 of these cases showed uIceration. In the management of tumors in genera1 it is imperative that the attending surgeon have definite knowledge of what he is treating. Thus after carefu1 evaIuation of the patient and the lesion, a biopsy is done. It seems superffuous to stress this fact so many times but only forty-four patients of June,

1930

the 302 previousIy treated gave a history of having had a biopsy. Adequate biopsy can be done, in most instances, under IocaI anesthesia. The vaIue of accurate diagnosis far outweighs any theoretica danger of dissemination. It shouId aIso be stressed that the pathologist can onIy pass on the materia1 submitted to him. Adequate biopsy should incIude some of the base of the tumor. If the tumor is smaI1, it may be removed with biopsy forceps in its entirety and the bed properIy destroyed with eIectrosurgery or irradiation to prevent recurrence. CarefuI examination shouId incIude a search for Iymph-node invoIvement. TREATMENT

In pIanning treatment the general condition of the patient and the IocaI lesion must be considered. In the present series

Ward,

Hendrick-Malignant

Tumors

of Skin

or more radica1 surgery. cannot be Iaid on the mahgnancies treatment enough.

can

Too much stress axiom that skin

be cured

with

series if such treatment If irradiation

is insufficient,

therapy

the

first

is radical or surgery

there wilI be residual

disease

to continue to grow requiring a second, third or even more treatments in an attempt to effect a cure. It is to be remembered that residua1 tumor ceIIs become increasingly resistant to each succeeding appIication of irradiation or surgery.9 Therefore, it is imperative to destroy or remove every maIignant ceI1 at the first seance or at most the second. Long-standing large lesions previously treated with muItipIe insuffrcient doses of

8~

8c

FIG. 8. Typical squamous cell carcinoma of bridge of nose. The patient had a flat wart for many years. During the previous eight months it became irritated, began to grow and became ulcerated. Treated with small dose of radium then removed with electrosurgery; there is moderate scarring that involves inner canthus of right eye. No recurrence in eight years.

I 78 patients were between seventy and of age and sixty-four were eighty years . _ eighty or oIder. It is obvious that many of these patients cannot undergo extensive surgica1 procedures. The resuIts obtained depend on how early they consuIt the oncologist after the Iesion appears. He shouId have at his command all types of therapy that may be needed for the particular patient at hand. These skin cancers can be adequateIy treated with x-ray, radium, electrosurgery or surgery in the earIy stages or a combination of one or more in the advanced. It is not so much the type of surgery or irradiation which9 gets resuhs but its thoroughness. It has been interesting to trace the deveIopment of treatment in these cIinics over the past twenty-five years and to observe how the results have improved as the tumors were given more intensive therapy

x-ray are diffrcuIt probIems. The tumor certainIy is not responsive to further x-ray or radium therapy. It is better to excise wideIy and either cover the area with a split-thickness graft or with a pedicle graft depending on the Iocation and depth of defect to be fiIIed. When a pedicle graft is planned, it shouId be started some time prior to excision. FrequentIy the base from which the tumor has been removed is markedIy scarred from Iong, inadequate x-ray therapy and has diminished vascuIarity from obIiterating endarteritis. Such changes render it difficult for a split-thickness graft to take and pedicIe grafts are necessary. Cases are commonIy referred with a probabIe diagnosis of an x-ray ulcer or secondary breakdown of the scar which on biopsy show persistence of maIignancy within the scar. These Iesions shouId be wideIy excised and appropriateIy grafted. American

Journal

of Surgery

Ward,

FIG. g. Patient Treated excision

Hendrick-MaIignant

being to give adequate treatment with a wide margin in a11 types of therapy. Lesions and on an area under 2 cm. in diameter other than the eyeIid are controlled in most instances by irradiation. It is our custom to give 4,000 to 4,300 r units distributed over four sittings usuaIIy spaced at twoday intervaIs and in the case of x-ray therapy through a cone providing s cm. to I cm. margin. The broken dose method is thought to be better than one massive dose of 3,000 or 4,000 r. It is to be remembered that tumor ceIIs divide two to four times daily depending on their degree of By dividing the cellular differentiation. tota treatment into severa sessions ceIIs

1950

of Skin

777

9A 9B Adenocystic basa1 cel1 carcinoma, Iater developed squamous changes. cut face with razor five months previously and lesion failed to heal. with radium I,ZOO mg. hr. HeaIed for six months; recurred; surgica1 done. No recurrence in three years.

Lesions over cartiIage of the nose or ear require more intensive irradiation during the first course of treatment than lesions over more vascular areas of the cheek or scaIp. Healing is exceIIent following such proper therapy but healing is proIonged and often associated with breakdown of the cartiIage if the irradiation is repeated over a long time. Basal Cell Carcinoma. The early basal cell lesions are eradicated by x-ray, radium, eIectrosurgery or surgery, the only probIem

June,

Tumors

that are not caught in the first or second sitting will be destroyed in the third and fourth. There is usually a marked erythema or blistering persisting from a few days to three or four weeks. We beIieve that this mode of treatment is perhaps better than the use of radium as the x-rays are distributed over the entire tumor more unithe Iesion can be adeformIy. However, quateIy treated if so desired with radium; usuaIIy eight to ten t.e.d.‘s are necessary. If smaI1 the Iesion can be compIeteIy eradicated with electrodesiccation, care being exercised to get we11 around and beIow it, or it can be surgicaIIy excised. Larger Iesions are either over 235 or 3 cm. in diameter treated with x-ray or surgical excision followed by skin grafting if indicated. X-ray to such large carcinomas sometimes Ieaves ugIy scars which need subsequent correction. The hne decision between x-ray and surgica1 excision and plastic repair depends upon experience and upon the Iocation of the tumor and the cosmetic result desired. We have found smaI1 basal cell Iesions on the eyeIids are best removed with electrodesiccation Ieaving a minimum of scarring and without injury to the eye or loss

77 8

Ward,

Hendrick-MaIignant

Tumors

of Skin

with a wide margin preferabIy I cm. and carried to a total of about j,ooo to 6,000 r distributed in four to five doses at two- to three-day intervals. These Iesions can also be treated with a radium plaque made to conform to the surface. Twelve to fourteen t.e.d.‘s are necessary to efFect a cure. The patient must be carefully examined for lymph-node involvement12 which if present reduces the prognosis. Sinc.e metastases do not respond readily to radiation therapy even though the parent tumor may be sensitive, wide surgical excision is preferable providing the patient’s general condition permits. An exception to this rule is the occasional single metastatic node which at times is controIIed indefinitely by the implantation of radon seeds or radium element needles (ten t.e.d.‘s are required). Small squamous cell cancers may be treated with electrocoagulation provided a wide margin is given on all sides and the

IOB

IOC

FIG. 10. BasaI cell carcinoma of lower eyelid, one year’s duration. Hyperkeratosis three years previousIy; rolIed up edges with ulceration in center. Treated with h,ooo r x-ray; no recurrence in five years.

of function of the eyelid and with minima1 loss of ciIia. They can also be treated with x-ray or radium by placing a shield over the eye in the conjunctiva1 sac. (Figs. IO and II.) Squamous Cell Carcinoma. Squamous cell Iesions are apt to i&Itrate, uIcerate and produce regional and distant metastases depending on the degree of ceIIuIar differentiation and the age of the patient. (Fig. I I.) It is an established fact that the younger the patient the more rapid his growth. The depth of infihration must be taken into consideration’l in planning treatment. Lesions under 2 cm. in diameter and with moderate infihration wiI1 respond we11 to proper x-ray therapy. (Fig. 12.) The irradiation is given through a cone

base thoroughly destroyed at the same time. Surgery is aIso an adequate method of treatment of these Iimited Iesions. (Fig. 13.) It has the advantage of being a simple procedure yieIding tissue for biopsy and heaIing in a short time. The scar in most instances is satisfactory. A skin graft is done foIIowing the surgica1 remova of Iarger tumors. It is important to remember that radica1 rather than conservative therapy for carcinoma of the skin is the treatment of choice. (Fig. 14.) The Adenocystic Basal Cell Carcinoma. response of this form of carcinoma to irradiation Iies between the more sensitive basal ceI1 and more resistant squamous cell carcinoma being more nearIy responsive to the latter. This characteristic is probably due American

Journal

of Surgery

Ward,

Hendrick-MaIignant

FIG. I I. Basal ceII carcinoma of upper eyeIid, present ten months; was thought to be Herpes for several months. Treated with 3,600 r x-ray with protection to eye; no recurrence in four years; IittIe scarring of eyeIid.

to the greater degree of differentiation of the ceIIs than in basa1 cell carcinoma. If x-ray is used, our experience necessitates that from 4,300 to 3,500 r’s are necessary given in broken doses at two- to three-day intervaIs. A careful examination for metastases is essential. If eIectrosurgery or surgica1 excision is used, a wide margin should be given around and beneath the tumor. There is a tendency for this tumor to recur and occasionally to metastasize. ANALYSIS

Analysis of 338 Cases in Which There Was No Previous Treatment Other Than Salves and Ointments before Coming to Our Clinics. This statistical study is based on the number of patients whose diagnosis is proven by biopsy. Such examinations were made by the Department of PathoIogy University of MaryIand, the Johns Hopkins University and by our own examinations of tissue removed from our offIce patients. The period covered is from 1930 to JuIy, I 945. No case is reported which has not been folIowed-up for a period of three to eighteen years. One hundred thirty-four patients were not foIIowed as they disappeared after the initiaI treatment or were June,

19~0

Tumors

of Skin

779

FIG. 12. Squamous ceI1 carcinoma floor both nares; patient stated he had repeated fever blisters that would not hea during the previous three months. This demonstrates the importance of adequate biopsy of any lesion that persists for any period of time; treated with 4,400 r x-ray at the base of each naris.

followed for onIy a few months. The resuits of their therapy are unknown. (TabIes III to VI.) There were 404 cases in this group of 538 that have been foIIowed up to date. Therapy in these was as outIined before. In genera1 these patients came in an earIy stage of their disease; most of the Iesions were under 2 cm. in diameter and had been present for Iess than two years. There were 321 cases of basa1 ceI1 carcinomas of which 290 were treated with x-ray therapy; 280 or 96.5 per cent of the patients have remained free of disease for from three to eighteen years. Recurrences deveIoped in I o or 3.5 per cent; the patients remain free of disease after being treated with surgical measures. There were thirtyone cases of basa1 celI carcinoma that were treated with eIectrosurgica1 or wide scaIpe1 excision. The reason for surgica1 therapy in these thirty-one cases was the Iocation of the tumor or that it was rather extensive and better cosmetic resuIts couId be obtained. There were no recurrences in this group of thirty-one cases. There were fifty-two patients with squamous ceII carcinoma that were adequateIy foIIowed since therapy. Twenty-six were treated with x-ray therapy; nine or 38.5 per cent recurred; twenty-six cases were aIso treated by eIectrosurgica1 or surgica1

Ward,

780

Hendrick-MaIignant

Tumors

FIG. 14. Squamous cel1 carcinoma right ala of nose treated elsewhere with 2,000 r x-ray. Surgically excised, later pIastic reconstruction; no recurrence in three years.

FIG. 13. Squamous cell carcinoma of right forehead, developed from hyperkeratosis; numerous other keratoses on face. Wide surgica1 excision, skin graft; no recurrences in five years.

There were thirty-one patients with adenocystic basa1 cell carcinoma fourteen of whom were treated with x-ray therapy and four developed recurrence. The recurrence was in the region of the parent tumor. There were seventeen patients with that adenocystic basa1 cell carcinomas were treated with electrosurgical or surgical excision, with one recurrence. There were no metastases in this group. These recurrences were treated with surgical measures with wide excision and grafted when necessary and have al1 remained free of disease.

excision and one recurred. (Fig. I 5.) These ten recurrences were satisfactorily removed by surgery. One without Iocal recurrence died of metastases after extensive block dissection. Perhaps it is better to treat squamous cell carcinomas over r>$ or 2 cm. in diameter by surgical measures, i.e., wide surgica1 or electrosurgica1 excision as outhned under treatment. Four patients developed metastases to the regional Iymph nodes requiring radica1 block dissection of the neck. TABLE RESULTS

OF

538

c~sns IN

of Skin

III

THERE

WHICH I

WAS No

Basal Ceil 423

PREVIOUS

THERAPY

Squamous Cell 72

Adenocystic

Total

43

538

I_ Indeterminate group, were unabIe to follow-up.. Total number studied.

TABLE

Total number studied. Number that had x-ray therapy. ,I Number treated with etectrosurgery or wide surgical excision and plastic procedures when necessary.

12

52

3’

I

‘34 404

/ Squamous Cell ~Adenocystic ~ 1~~ i

32r 290

52 26

3’

26

Basal Cell

Squamous Cell

TABLE

.

20

__~~.

IV Basal Cell

Number that had x-ray therapy. Primary lesions healed.

_~~~i_

I-

3’

~ I

Totnl _

i

14

4”4 330

17

74

v

290

280-96.5

yO

26 16-61,5O/u

14

1o-7 I

330 2 @/o

~ American

Total

Adenocystic

30692%

~ Journal

of Surgery

Ward,

Hendrick-MaIignant

Tumors

of Skin

781

anaIysis of these patients. Many of them came from a distance. Most of them had a lesion over 3 cm. in diameter and stated that their disease had been present for a period of from two to fifteen years. They gave a history of having had the foIlowing treatment, nameIy, x-ray in 102 patients, radium in eighty-four patients and Iocal surgical excision in I 64 patients. An endeavor was made in many instances when x-ray, radium or both had been used to find out from their physicians how much of each method and over how Iong a period of time it had been given. No information of value was obtained as a ruIe. Many of the patients stated that the Iesion recurred within a short time to a few months after treatment and a Iarge number stated that the Iesion persisted throughout the treatment. When information was obtained reIative to the amounts of x-ray or radium given, it was reveaIed that only IOO to I5*

I5C IEB FIG. I 5. Squamous ccl1 carcinoma of scalp. Began as a papillomatous wart five years before; became ulcerated, grew rapidly and became infected; palpable no&s in posterior triangle of neck. Treated with 4,000 r x-ray; Lion heaIed completeIy. No recurrence in three years.

Analysis of 302 Cases in Which There In contrast to the Was Previous Therapy. 538 patients who had no previous treat-

ment there were 302 that had received therapy before they consuIted our cIinics. It is rather difFicuIt to make a carefu1 June,

1930

1,000 r had been administered over a period of a few weeks or months or extended in a few instances over a period of ten to fifteen years. Such smaI1, ineficient appIications repeated indefiniteIy onIy serve to make the cancer toIerant to irradiation.

Ward,

782

Hendrick-Malignant

Tumors

TABLE

of Skin

VI

I BasaI CeII

Number treated with eIectrosurgery or wide surgica1 excision and pIastic procedures when necessary. Primary Iesions healed. Recurrence folIowing surgery.. Total number of recurrences. Number that developed metastases to regional lymph nodes folIowing initial therapy. Successful treatment of recurrences by surgical measures..................................... Deaths from disease..

I Squamous

Cell

3I jr-100%

26

i

25-95 76 r-4%

o IO-3.5%

I r-21@/,

o

5-3.6~0

IO-100%

302

CASES

17 1694% ~-6% 5-16%

74 72-97 % 2-3 % 266.4% 5-9.6%

0

I o-go c/c

o

5-1000/,

I-4 %

25-&o/,

0 /

I

TABLE 0F

TotaI

~

I

RESULTS

Adenocystic

VII

IN WHICH

THERE

WAS

PREVIOUS

THERAPY

I BasaI CeII

Squamous

Cell

Adenocystic

48

232

TotaI

/

22

302 ~.._.~

Indeterminate group; disappeared during therapy; resuits of therapy unknown; 18 died of other causes.. Total number studied. .

1 I

TABLE

28

64 238

VIII BasaI Cell

Total number studied. Irradiation therapy; dosage varying greatly; a period of months to years.. ControI of lesion by irradiation..

6 16

20

38 '94

( Squamous CeII Adenocystic 28

~ 194

Total

16

238

given over 117 6656.4% TABLE

2

123 67-53~

'-50%

IX BasaI CeII

-___

4 o-0 C/‘

Squamous

CeII

Adenocystic

___-

EIectrosurgicaI excision; skin grafts when advisabIe. ControI lesion by electrosurgical measures. Wide surgical excision; skin grafts when advisabIe. Control of Iesion by surgica1 measures.

64 48-74.4~~ 56 46-82 yO TABLE

18

13--720/a 8 5~62%

8 6-75 %

TotaI

l-90 67-74 % 71 57-80%

k85”;

x

1 Basal CeII 1Squamous Cell ) Adenocystrc. ~ Total number studied............................. ControI Iesions by irradiation or multipIe surgical procedures........................................ Patients having a continuation of the disease after multipIe procedures.. . . .. . ... Deaths from recurrences or from operative procedures.

Total

194

28

16

238

I 60-82 yO

18-64 %

13-81%

rgr-80%

28 6

2 II

American

Journal

31 r8-7.5%

of Surgery

Ward,

Hendrick-Malignant

Tumors

of Skin

783

In this group x-ray, radium, radon seeds, electrosurgery and wide surgica1 excision fohowed by pIastic procedures were necessary. These modaIities were used either singly or combined. Patients thought to be responsive to irradiation were so treated. Frequently, the dosage amounted to two or three times that which would have been necessary to eradicate the same type of lesion if it had been seen early. Sixty-four patients in this group were lost sight of; they either disappeared during treatment or failed to return for foIIow-up examina-

1613

16~

FIG. 16. BasaI ceII carcinoma of nose and upper lip. Began as a papillomatous wart on nose three years before and started to grow, producing a large, uIcerating, fungating lesion. Treated with 10,000 r x-ray; Iarge defect right naris. These defects are amendabIe to pIastic procedures.

When the patients were Hurst seen, eighteen had regiona lymph-node invoIvement, six had extension into the maxiIIa or mandibIe and six others had injury to an eye which necessitated enucIeation. Eight patients had radio-osteonecrosis of the maxiha or mandible, eieven had rather extensive invoIvement and destruction of the nose and two had aImost the entire nose destroyed. Seven patients had marked defect of the ear and four had lost aImost the entire ear. Extensive sloughs developed in five patients that were severe enough to erode a large vessel necessitating ligation of the external carotid artery. June,

1930

tion. Consequently, the results of their therapy are unknown. Eighteen died of other diseases leaving a total of 238 which forms the basis for this study. (Tables VII to x.) Of 194 patients with basal cell carcinoma I I 7 were treated with irradiation. (Fig. I 6.) The Iesion was controlled only in sixty-six or 56.4 per cent of the cases. Electrosurgical excision was used in sixty-four and the lesion controhed in forty-eight, 74.4 per cent. Wide surgical excision was performed in fifty-six patients with favorable resuhs in forty-six or 82 per cent. One hundred sixty, 82 per cent, of these previously

784

Ward,

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treated basa1 ceII carcinomas were controlled satisfactoriIy by one or more of these types of therapy singly or in combination. There were twenty-eight squamous cell carcinomas, four treated with irradiation, none of which were adequately controhed. EIectrosurgicaI methods were used in eighteen cases with satisfactory contro1 of thirteen or 72 per cent. Wide surgical excision in eight cases satisfactorily controlled Iive or 62 per cent. That is, there was satisfactory contro1 of eighteen, 64 per cent, of the twenty-eight cases of squamous ceI1 cancer. There were sixteen patients with adenocystic basal cell carcinoma, two of whom were treated with irradiation and one favorably responded, 50 per cent. Eight were treated with eIectrosurgica1 measures with favorable results in six or 75 per cent. Seven had surgical excision, six or 65 per cent of which were favorably controlled. Thirteen of the sixteen, 81 per cent, adenocystic basal Iesions were controlled with these various modaIities. Of the total 238 studied (302 minus sixtyfour of indeterminate group) 191 or 80 per cent of the patients were satisfactorily controIIed by these various methods of therapy. There were eighteen deaths resuIting from metastases or following operative procedures, a mortality of 7.5 per cent. There were thirty-one patients that could not be satisfactorily classified as cured or having their disease eradicated. Some of these patients are stil1 in the process of being treated; their disease had been in progress for a period of over three years. Death and continuation of the disease (eighteen plus twenty-nine) give a total failure of fortynine or 19.8 per cent or control of the cancer in 80.2 per cent of these advanced cases. Many of these patients are in the old age group which precludes extensive eIectrosurgical or surgical procedures. It became necessary then in these aged patients to try to control a tumor by irradiation which had acquired resistance to such therapy by previousIy prolonged inadequate doses.

Tumors

of Skin COMMENTS

During the past twenty-five years we have used various methods of treatment for skin cancer. At frequent intervaIs the resuIts were evaIuated and changes were made in therapy as deemed advisabIe. It has been found that increasing doses of x-ray and radium were necessary to effect a cure. FormerIy, it was thought that 800 or 1,000 r units of x-ray were efficacious but it was soon found that there were recurrences or persistence of growth foIIowing this amount of treatment. GraduaIly the amount of x-ray or radium has been increased to the amount discussed in this paper. The question is often presented by the patient or his referring physician of the danger of an x-ray burn or slough, of danger to the cartiIage of the nose or ear or a probabIe osteonecrosis of the underlying bone. The patient is informed that it is more important to eradicate the disease than to be perturbed about the breakdown of tissue from treatment. Also, it is emphasized that heavy doses given properry and within two or three weeks’ time wiI1 destroy the disease without permanent damage to the underlying cartiIage. A number of patients enter the clinics each year compIaining that they have an x-ray or radium uIcer Iingering long after treatment. In many instances a biopsy demonstrated persistence of the malignancy indicative of insufficient x-ray or radium therapy. It is frequently expIained to the patient that death rarely occurs from x-ray or radium burns of the skin from treatment of skin cancers but all too frequentIy death occurs from uncontroIIed mahgnancy. Also, biopsy must be used as a guide in folIowing the effects of treatment, especialIy when healing is delayed or the irradiation scar breaks down. Delayed heaIing and/or subsequent scar breakdown are due to one or both of two pathologic processes. These processes are obliterating endarteritis and sclerosis from the irradiation and persistence of the cancer. Biopsy wiII make American

Journal

of Surgery

Ward,

Hendrick-MaIignant

the proper diagnosis. Far too often irradiation is continued to an unheaIed area or is given to a broken down scab months or years after treatment on the clinical assumption that cancer remains. Such continued therapy serves only to aggravate the condition. If biopsy reveals no growth, excision and grafting if indicated are the proper procedures. If biopsy reveaIs persistent or recurrent growth, wider excision and plastic repair shouId be done. In other words it is not good therapy to reradiate secondary breakdowns in irradiation scars or to reradiate skin lesions that have faiIed to heal after the first or second series of treatments at most. The main purpose of this study is the comparison of two groups of patients. The lirst group came without any previous surgery or irradiation therapy. Many of them had had innocuous salves but such treatment was not counted as being efficacious upon the growth. All skin cancers have smal1 beginnings. If they can be eradicated during the earIy stages, it is obvious that good results will be obtained. The results in our first group bear out this contention. On the other hand, the fact that we have been able to review 238 cases that have come after previous irradiation therapy or surgery indicates their previous treatment did not contro1 the disease. In all of these cases this fact was proven by biopsy. The residua1 tumor ceIIs had developed resistance to irradiation therapy, a condition which requires more treatment for the destruction than would have been required in the early stages of the disease. AIso, much infection and pain were present. The onIy way to contro1 these symptoms was by eIectrosurgica1 or surgical excision with a wide margin and the proper pIastic procedures. Not onIy is our percentage of three-year resuhs poorer in this group than in the primary group but there was at the time of admission and there wiI1 be more permanent disfigurement, dysfunction and proIonged disability than in the group havJune,

1950

Tumors

of Skin

785

ing had no previous treatment. The economic difficulties are evident. In these previously treated patients much Ionger courses of therapy and often proIonged hospitalization were required. It is obvious that many of the primary cases were early which is an important factor in yielding good resuIts; this is one of the points of emphasis of this article. In the previousIy treated group there were I 17 basal cell carcinomas treated by irradiation therapy; only sixty-six or 56.4 per cent were controhed in contrast to 96.5 per cent in the primary cases. Of the fifty-one uncontroIIed some were subsequentIy controIled by eIectrosurgica1 or surgica1 removal. This retreating by another method accounts for some overIapping of numbers. In other words some of these cases which were not controIIed by irradiation were controlled by other methods of therapy. It is evident then that in these extensive cases which have been previously irradiated more heroic methods are needed than had been used previousIy. If the patient’s general condition permits, all of these shouId have radical electrosurgical removal and suitable plastic repair. From Table III it would appear that somewhat better results were obtained with a wide surgical excision and plastic repair than with electrosurgical excision. This fact is explained on the premise that one is apt to Ieave too narrow a margin when removing a tumor with the electrosurgical current. The average surgeon using a scaIpe1 will give a wider margin than with electrosurgery. If as wide a margin is given with eIectrosurgery as with scalpel surgery, there wouId be better resuhs with the former. Also, those treated with electrosurgery were more extensive than those operated upon with the scaIpe1 and many couId not have been adequateIy removed with the scalpel, i.e., involvement of ear and scaIp, erosion of nose, maxiIIa, orbit, etc. EIectrosurgery leaves behind a wound sterilized by heat with less likelihood of seeding with cancer ceIIs.

786

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CONCLUSIONS I. Malignant epithelia1 lesions of the skin of the face, neck and scalp are frequently encountered. 2. Benign lesions such as hyperkeratoses, papillomas, seniIe warts and moles should be removed before malignant transformation develops. 3. An adequate biopsy should be taken of every suspicious Iesion. 4. It is advantageous to differentiate between the three types of mahgnant lesions; by so doing proper pIans of therapy are instituted. 5. X-ray, radium, electrosurgery or surgical excision are efficacious in the management of early skin cancer if given in adequate amount and a good margin around the tumor is included. 6. Careful follow-up examinations are necessary to determine the effectiveness of treatment and to watch for recurrences so that further treatment may be instituted when necessary. 7. This study. has shown that a high percentage of skm cancer is curable in the early stages if properly treated. This conclusion is substantiated by comparing two Iarge series. In the first series primarily treated by us the resuIts were excellent; whereas, in the second series which had become resistant by previous insufficient treatment the resuIts were poorer even when radical measures were used. REFERENCES W. B. PatholocricaI HistoIoav. P. 373. PhiIadeIphia, 1914. W. B. Saunders Company.2. MARKENSTEIN. H. Exoerimentehe Unterschuchueer uber Strahlenemfinhlichket be1 Exeroderma figmentosum. Arch. f. Dermat. u. Sypb., 147: 4gg508, 1924. I. MALLORY,

Tumors

of Skin

3. BONNEY, B. Skin matignancy. Lancet, I I: 138g,396, ,908. 4. BRODERS, A. C. Grading epitheiial tumors. Ann. Surg., 73: 41-51, 1921. 5. Idem. Tumors skin. .T. A. M. A., 72: 856-862,1g1g. 6. KROMPECHER, H. Zeitler’s Beitrage. 28: 1-14, IgoO. 7. HUTCHINSON, L. P. PathoIogy of adenoid tumors of the skin. Brit. J. Surg., g: 529-534, 1922. 8. EWING, JAMES. NeopIastic Diseases. 3rd ed., p. 862. Philadelphia, 1929. W. B. Saunders Company. 9. CUTLER, M., BUSCHKE, F. and CANTRIL, S. Cancer. P. 66. PhiIadeIphia, 1938. W. B. Saunders Co. IO. HERTZLER, ARTHUR. Surgical PathoIogy of the Skin. P. 71. PhiIadeIphia, 1931. J. B. Lippincott Company. BLAIR, V. P., MOORE, S. and BYARS, L. T. Cancer II. Face and Mouth. P. 24. St. Louis, hfo., 1941. C. V. Mosby Co. 12. POTTER, W. A. and WHITE, J. P. PathoIogy skin malignancy. Ann. Surg., 46: 649656, 1907. 13. WARD, G. E. and HENDRICK, J. W. Treatment of Tumors of the Head and Neck. Baltimore, Md., 1949. WiIIiams and Wilkins. 14. BOWEN, J. T. Precancerous Dermatoses, J. Cut. DiS., 30: 241-255, 1912. ‘5. ELLER. J. J. and ANDERSON. N. P. BasaI cell epitheIiomas with excessive pigment formation; their relation to meIanomas. Arch. Dermat. cz Swb., 27: 277-291, 1933. 16. I IORN, R. C., JR. MaIignant papillary cystadenoma of sweat glands with metastases to the regional lymph nodes. Surgery, 16: 348-355, 1944, 17, IIUEPER, W. C. Occupational Tumors and Allied Diseases. SpringfieId, III., 1942. Charles C. Thomas. 18. HYDE, J. N. On the inAuence of light in the production of cancer of the skin. Am. J. M. SC., 131: 1-22, 1906. con‘90 MOHS, F. E. Chemosurgery, microscopically troIIed method of cancer excision. Arch. Surg., 42: 279-295, 1941. 20. MONTGOMERY,H. Early recognition and treatment of skin cancer. S. Clin. North Americu, 17: 124g1264, 1937. dermatosis and 21. MONTGOMERY, H. Precancerous epithelioma in situ. Arch. Dernat. @ Sypb., 39: 387-408, 1939. 22. STOUT, A. P. Gross pathoIogy of cutaneous cancer. Arch. Dermat. @ Sypb., 53: 597-598, 1946. 23. WARREN. SHIELDS. GATES, 0. and BC~ERFIELD, P. W.‘The value of histoIogic differentiation of basal cell carcinomas, New England J. Med., z I 5 : 1060-1064, 1936. 24. WARREN, S. and WARVI, W. N. Tumors of sebaceous gIands. Am. J. Patb., rg: 44x-459, 1943.

American

Journal

of Surgery