tumors of the oral mucous membrane -...

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TUMORS OF THE ORAL MUCOUS MEMBRANE CHARLES F. GESCHICKTER, M.D. (From the Siirgical Pathological Loboratory, Department of Swgrry, Johns IIopkins Hospital aiid Univcrdy) Except for epithelial tumors arising from aberrant salivary glands and for growths involving epithelial remnants concerned in the development of the teeth, practically all of the benign and malignant oral-epithelial tumors are derived from the lining cells of the mucous membrane and are epidermoid in character. The benign epithelial growths usually arise in areas of irritation and take the form of a thickening of the mucous membrane, leukoplakia, or of papillonla appearing in such a thickened area, so-called verrucous leuko- plakia. Either form of leukoplakia may be followed by the appearance of ‘~AIiL12 I : Benixn Lesions of the Oral Cuvily lCiwtmLI,u, 1,imow Cysts and adenonias Aberrant salivary atlenomas Ixukoplakia and papillomas IJlcers ~II~SENCIIYMAL TUMORS E’ibronias Ilemangiomas 12ymphangiomas Lipomas Myohlastomas 15 1 40 30 6 37 2 2 1 ~- TOTAL ~ 134 lJpper Lip 3 11 10 - 0 11 1 0 - 36 ‘Tongue 2 85 46 __ 15 15 10 1 1 17.5 Mucous Mein- brane 2 6 65 27 5 27 3 1 - 136 . Total .. . 22 7 20 1 113 26 90 16 4 2 48 1 ulceration and carcinoma. One-fifth of all cases of oral carcinoma will show one or more areas of leukoplakia in the region of the tumor or elsewhere in the mouth. Ulceration without clinical evidence of overgrowth is also a fre- quent starting point for oral cancer. In some instances the ulceration is syphilitic rather than traumatic. BENIGN TUMORS Hemangiomas, lyniphangiomas, fibromas, lipomas, myoblastomas and os- teomas may occur on the tongue and beneath the surface of the mucous mem- branes of the lips, cheeks, or palate. These benign growths are non-epithelial, and, since they are not peculiar to this location, will not be considered here. Benign epithelial tumors include epithelial cysts, occasional papillomas and 586

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Page 1: TUMORS OF THE ORAL MUCOUS MEMBRANE - …cancerres.aacrjournals.org/content/amjcancer/26/3/586.full.pdftumors of the oral mucous membrane ... wart and fissures occurring in an advanced

TUMORS OF T H E ORAL MUCOUS MEMBRANE

CHARLES F. GESCHICKTER, M.D.

( F r o m the Siirgical Pathological Loboratory, Department of Swgrry, Johns IIopkins Hospital aiid U n i v c r d y )

Except for epithelial tumors arising from aberrant salivary glands and for growths involving epithelial remnants concerned in the development of the teeth, practically all of the benign and malignant oral-epithelial tumors are derived from the lining cells of the mucous membrane and are epidermoid in character. The benign epithelial growths usually arise in areas of irritation and take the form of a thickening of the mucous membrane, leukoplakia, or of papillonla appearing in such a thickened area, so-called verrucous leuko- plakia. Either form of leukoplakia may be followed by the appearance of

‘ ~ A I i L 1 2 I : Benixn Lesions of the Oral Cuvily

l C i w t m L I , u , 1,imow Cysts and adenonias Aberrant salivary atlenomas Ixukoplakia and papillomas IJlcers

~ I I ~ S E N C I I Y M A L TUMORS E’ibronias Ilemangiomas 12ymphangiomas Lipomas Myohlastomas

15 1

40 30

6 37

2 2 1 ~-

TOTAL ~ 134

lJpper Lip

3

11 10

-

0 11

1 0 -

36

‘Tongue

2

85 46

__

15 15 10 1 1

17.5

Mucous Mein- brane

2 6

65 27

5 27 3 1 -

136

.

Total

.. .

22 7

20 1 113

26 90 16 4 2

48 1

ulceration and carcinoma. One-fifth of all cases of oral carcinoma will show one or more areas of leukoplakia in the region of the tumor or elsewhere in the mouth. Ulceration without clinical evidence of overgrowth is also a fre- quent starting point for oral cancer. In some instances the ulceration is syphilitic rather than traumatic.

BENIGN TUMORS

Hemangiomas, lyniphangiomas, fibromas, lipomas, myoblastomas and os- teomas may occur on the tongue and beneath the surface of the mucous mem- branes of the lips, cheeks, or palate. These benign growths are non-epithelial, and, since they are not peculiar to this location, will not be considered here. Benign epithelial tumors include epithelial cysts, occasional papillomas and

586

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F I G . 1. C Y S T S OCCURRIKG I N T H E M U C O U S GL.4NDS O F T I I E LIP AND C H E E K . P A T H . NOS. 35182 AND 31382

FIG. 2. RANULA TREATED BY EXCISION. PATH. NO. 40036

Fic. 3. PHOTOMICROGRAPH OF THE FLATTENED EPITHELIAL LINING OF A Mucous CYST The inflammatory changes shown are a common finding. Rarely squamous-cell cancer may

develop in the lining cells. Path. No. 17030.

587

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588 CHARLES F. GESCHICKTER

epithelial overgrowths appearing in areas of leukoplakia, and aberrant salivary adenomas. Their frequency and distribution in the present series are as shown in Table I.

Epithelial Cysts and Adenomas: Retention cysts of the mucous glands may occur on the inner surfaces of the lip or elsewhere on the oral mucous mem- branes.’ They form rounded, thin-walled masses usually about a centimeter in diameter. The most common sites are the mucous glands of the palate, lower lip, cheek, and Nuhn’s gland on the under surface of the tip of the tongue (Figs. 1-3). Cysts on the under surface of the tongue near the floor of the mouth are known as ranula (frog-like tumors). These cysts do not affect the sublingual glands and may be treated by excision. Rarely epidermoid cysts are observed on the floor of the mouth or the lower surface of the tongue be- tween the two geniohyoglossal muscles. These are congenital tumors pro- duced by embryonic infoldings of the tegument and resemble the epidermoid

FIG. 4 BhNION LYMPIIANGIOMA OCCURRING O N TIIF DORSUM O r TIIL T O V G U I .

Tlic patient died fnllnwiiil: excision. Autopsy showed an enlarged thymus. Path. No. 40800.

cysts found in the skin. Aberrant thyroid tissue and thyroglossal duct cysts may also occur in this location.

Excision of cystic tumors usually suffices for cure, but occasional recur- rences are observed. These lesions must be distinguished grossly from an- giomas, and lymphangiomas (Figs. 4 and 5 ) . Microscopic examination should be made to rule out the presence of aberrant salivary tumors, which show a greater tendency to recur (Fig. 6) .

Aberrant Salivary Adenomas: Aberrant mixed salivary tumors are found most frequently on the hard palate. They are firm, encapsulated grdwths, histologically similar to the more frequent mixed tumors of the parotid gland. The adenomatous tissue shows compressed or dilated acini with abundant in- tercellular substance. If these tumors are not completely excised they may recur and occasionally extend through the palate into the antrum. In our series of 7 cases 5 of the tumors occurred on the hard palate, 1 on the surface of the tonsil, and another, recurrent tumor, apparently originating on the hard

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FIG. 5 . PIIOTOMICROGRAPH O F A SMALL ANCIOMA OCCURRISG BESEATH THE MUCOUS MEMBRANE OF THE LIP. PATH. No. 38990

FIG. 6 . PHOTOMICROGRAPH OF AN ABERRANT SALIVARY TUMOR OCCURRIXC O S THE HARD PALATE

The tumor recurred and invaded the antrum. Path. No. 42550.

589

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590 CHARLES F. GESCHICKTER

palate, invaded the antrum. Li and Yang in 1935 reported 25 cases of aber- rant intra-oral and extra-oral tumors of the mixed salivary type in Chinese patients, and reviewed the literature.

Lcukoplakia: Leukoplakia is the most common precancerous lesion occur- ring in the oral cavity. I t appears in the mouths of smokers and opposite ragged, dirty teeth, in contact with dentures, or where neighboring teeth con- tain fillings of various metals. I t may appear among the tertiary oral lesions

FIG. 7. LEUICOPLAKI.4 OF THE TONGUE Note increased number of cell layers and down-growth of epidermal tissue. Path. No. 37322.

FIG. 8. WART AND FISSURES OCCURRING IN AN ADVANCED CASE OF LPCJKOPLAKIA Microscopically the lesion was negative for cancer. Path. No. 22760.

in syphilis. The thickened white patch, replacing the normal transparent mucosa, corresponds to keratosis on the skin.

Under the microscope the lesion shows an increase in the number of layers of squamous cells with little or no keratin deposit (Fig. 7 ) . Instead, the upper layers of cells are eroded, a phenomenon which may be due to the moisture of the oral surface. The rows of basal cells are usually increased in number and these cells may contain hyperchromatic nuclei with occasional

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TUMORS OF THE ORAL MUCOUS MEMBRANE 591

mitoses. Although the basal cells may show a tendency to extend into the submucous tissue, the basement membrane remains intact. The surrounding connective tissue shows moderate edema.

In leukoplakia of long standing, papillary projections or warts may occur (Fig. 8). In other instances there is ulceration. The margins of the ulcers may show every transition from benign to malignant epithelial activity (Fig. 9) .

FIG. 9. HIGH-POWLR PIIOTOMICROC.HAI~II o r THE BASAI.-PLLL LAYERS o r A BLSIGN PAPILLOMA OCCURRING IN LEUKOPLAKIA, S1rowin.c MARKED EPITHLLIAL PROLIFERATION.

PATH. No. 39738

The treatment of leukoplakia consists in strict oral hygiene. The Wasser- mann test should not be omitted and in those cases in which it is positive antisyphilitic therapy is indicated. ,411 forms of tobacco should be forbidden, and dental irritation should be promptly corrected. Improvement or healing usually follows such treatment. Since the areas are often multiple, removal should be attempted only for persistent patches showing papilloma formation or beginning ulceration. This is best performed with a cautery, with intervals to permit healing between applications. The tissue removed should be ex- amined microscopically to rule out the presence of cancer.

Benign Papillomas: Epithelial papillomas independent of leukoplakia may appear on the oral mucous membranes in elderly patients. They are usually small lesions and are symptomless (Figs. 10 and 11).

On the lips or dorsum of the tongue, papillomas may be heavily kera- tinized and may become secondarily ulcerated. Under the microscope such lesions show increased keratin production and thickening of the epidermal covering, which is thrown into folds. The under surface shows reduplication of the basal-cell layer, increased density of the nuclei, and increase in the

.

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FK:. 10. P H 0 1 0 M I C R O C R A P H O F A SMALL P4PII.T OMA O C C l J R R I N C NEAR TIIE MUCO('UTANLOUS JUNCTION 01.' TIIF: LOWER LIP. PATH. No. 25685

Flti. 11. PIfOlOMICKO(:KAP€I OP A PAP1II.OMA OF TIIE TONGUE. PAlH. NO. 24424

SO2

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FIG 12. A PIIOTOMICROGR9PII S H O W l h G T I I t W 4 R T Y OR PAPILLOMATOIJS S1 AGL 01' L E U K O P L A h l A .

35204 AiVD 21157 B. PIIOTOMI( ROGRAPH SHOWING C4RCINOMA BEGINNING IN S U C H A PAPILLOMA. P A T H . NOS.

593

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5 94 CHARLES F. GESCHICKTER

FlC 1J. A. ~ I I O I O M I C K O ~ : R A I J I € OF BhNlGK ULrLK ON TIIE TONGUE:. B. PIIOTOMICROGRAPTI OF C A N ( IhOMA BPGINVING WIT11 ULCI RATION. PATH. NOS. 39802 A N D 38550

number of mitotic figures. The underlying connective tissue is infiltrated by lymphocytes. The surrounding mucous glands are hypertrophied. In this location malignant change is to be suspected.

Epithelial papillomas are also found in the region of the uvula and on the niucous membranes of the cheeks. Many of these small reduplicated folds of epitheliuni are secondary to underlying granulomas or fibromas resulting

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TUMORS OF T H E ORAL MUCOUS MEMBRANE 595

FIG. 14. PAPILLARY OR NODULAR CARCINOMA OF THE TOKGUE The microscopic picture shows a low-grade keratinizing squamous-cell cancer. Path. No. 26601.

from injury and are not true epithelial tumors. Such papillary fibromas or granulomas are not uncommon along the edge of the tongue. At the base of the tongue epithelial proliferation occurs as a result of hypertrophy of the papillae, Often the papillary area is entirely within normal limits but, be-

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596 CHARLES F. CESCHICKTER

cause of unrelated symptoms, will be examined by one unfamiliar with these normal structures and will be treated unnecessarily. Occasionally, however, there is actual thickening and down-growth of the epidermis over one or several of these structures. Unlike leukoplakia, papillomas do not regress

FIG. 15A. SMALL ULCEROUS CARCINOMA 01: TIJE TONGUE Thc patient is living seven years after cxcision of the tumor and resection of the cervical notlcs.

Path. No. 42120.

under simple hygienic measures. microscopic examination.

They should be excised and subjected to

CANCER OF THE ORAL Mucous MEMBRANE

Keratosis and ulceration, referred to as “ smoker’s burn,” are the conimon precancerous lesions of the lip. On the tongue, the floor or roof of the mouth, and on the buccal mucous membrane, the keratosis is more diffuse or multiple and takes the form of leukoplakia with or without papilloma formation. U1- ceration appears in an area of irritation, usually in contact with the teeth or dentures. Cancer may begin in an area of keratosis without ulceration or in ulceration without marked keratosis (Figs. 12 and 1 3 ) . In some instances no preceding lesion is demonstrable and the carcinoma appears beneath a crevice in an atrophic epidermis, the eroded surface being only a few millimeters in diameter. In one case in our series, the patient complained of enlarged cervical nodes, which were removed and showed metastatic carcinoma. After microscopic demon- stration of squamous-cell cancer, further investigations revealed a small crev- ice on the lower lip which had been present over a year. On excision, this area showed squamous-cell carcinonia.

Grossly cancer in papilloma is described as papillary or nodular and cancer beginning with ulceration is referred to as ulcerous or fissured. Cade

In rare instances the mucosa may heal or remain intact.

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TUMORS OF THE ORAL MUCOUS MEMBRANE 597

recognizes four varieties, papillary, nodular, ulcerous, and fissured, these rep- resenting the order of the degree of malignancy, the last named being ex- tremely malignant, Grade IV in Broders’ classifications. While this classifica- tion can be verified for large groups of cases, there are many exceptions and

FIG. 15B. LOW-POWER A S D HIGH-POWER PIIOTOMICROGRAPEIS OF THE SMALL ULCEROPS CARC~NOMA SIIOWN IN FIG. 15A, A HIGHLY MALIGNANT OR ANAPIASTIC FORM OF SQUAMOUS-CELL CANCER

in general carcinoma of the oral mucous membranes is characterized sooner or later by ulceration, with a hard raised nodular or papillary edge (Figs. 14 and 15A and B).

While the pathologic types of buccal cancer and the relationship to pre- ceding benign lesions are usually cited as strong evidence in favor of chronic irritation as the causative factor, the leading clinical features of cancer in this location do not fall in line with such a conception. The frequency of

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598 CHARLES F. GESCHICKTER

oral cancer is inversely proportional to the area of exposed mucous membrane. Thus, generally speaking, cancer of the lip is more frequent than cancer of the tongue, and cancer of the tongue more frequent than cancer of the mucous membranes of the cheek, palate, and floor of the mouth. Although the surface area of the lip is less than that of the tongue, and that of the tongue less than that of the remainder of the intraoral cavity (Table 11). Moreover, the

Tanr.rr I I : hfalipznnt Tunaors .f the Oral Cavity

Lip

Rlales . . . . . . . . . 445 Females. . . . . . . 47

Imwer. . . . . . . . 467 IJpper. . . . . . . . 10

~ _ _ _ _ _ _ ~

Age peak. . . . .40-~ 60

Cures. . . . . . . . .52';/0

I m v e r . . . . . . . . 15 llpper . . . . . . . . 29

Tongue

Males.. . . . . . . . 282 Females . . . . . . . 29

Mid-bortler.. . . 118 Rase . . . . . . . . . . 56 Under surface. 60 l i p . . . . . . . . . . . 38

Age peak. . . . . 50-60

Cures. . . . . . . . 16:;;

-

,.

1

Mucous Menihranc

Males . . . . . . . . . 20X 1;emales. . . . . . . 37

Cheek . . . . . . . . 132 Gum . . . . . . . . . . 60 Palate.. . . . . . . 29 Floor. . . . . . . . . 15

___ ____

Age peak. . . . .60-70

Cures . . . . . . . . 172,

theory of chronic irritation does not account for the fact that squamous-cell cancer is approximately fifty times more common on the lower than on the upper lip, and that on the lower lip cancer is more common a t the muco- cutaneous junction than on the surfaces in contact with the teeth or objects held between the lips, as pipes and cigarettes. In the present series the ratio of males to females is approximately ten to one, which is not in keeping with the relative frequency of irritation in the two sexes, unless tobacco is con- sidered the sole etiologic factor (Fig. 16A and B) .

In regard to age, cancer of the lip occurs more frequently under the age of fifty than either cancer of the tongue or of the intra-oral mucous membrane. Two patients in this series were less than twenty. Cancer of the tongue is most frequent between the ages of fifty and sixty, whereas the highest inci- dence of cancer of the mucous membranes is between sixty and seventy. If chronic irritation were a leading factor, it would seem inconsistent for cancer to appear most frequently in the locality where it occurs earliest (on the lip) and less frequently where it appears latest (mucous membrane).

On the lip, where the lesion is readily visible, the duration of symptoms is longest. Two-thirds of the patients in this series gave a history averaging five years in duration. In 10 per cent of the cases excluded from this average, symptoms had been present from ten to thirty years. The patients had noticed a crack, ulceration with crusting, or a pimple with scaling or weeping. Pain was rare. In the remainder of the cases the tumor grew rapidly and had been present, on an average, less than five months at the time of examination.

The duration of symptoms in oral cancer varies with location.

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TUMORS OF THE ORAL MUCOUS MEMBRANE 599

For lesions on the tongue the duration of symptoms averages less than for cancer elsewhere on the oral mucous membranes. Ninety per cent of our patients gave a history in terms of weeks or months, the average being under six months. In only 10 per cent of the cases did the history extend between two and three years, and only rarely did the onset date back niore than five years. Here the white patch, nodule, ulceration or fissure is readily felt and constitutes an annoyance in eating and talking. Here also pain, bleeding, and

F I G . 16.4. CARCINOMA OF THE LIP AKD TONGUE IN CHARACTERISTIC LOCATIONS

FIG. 16B. CARCINOMA O F TIIE C H E E K AND GVM I S CHARACTERISTIC LOCATIONS

fixation of the tongue, most often noted at meals, are common features. In this series slightly under 10 per cent of the patients gave a history of syphilis, although more than this number had received anti-luetic treatment for leuko- plakia.

In cancer of the mucous membranes of the gum, cheek, palate, and floor of the mouth, the duration of symptoms in 75 per cent of the cases was in terms of months, averaging between six months and a year. The remaining 2 5 per cent (57 cases) had an average duration of five years. Thirty-one of these lesions were on the cheek and twenty on the lower gum. In these locations the lesions were between the teeth and the buccal or labial fold and escaped contact with the tongue in talking and eating.

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600 CHARLES F. GESCHICKTER

i\lTTUOR'S Sl iKIl iS Cases followed

I'ercentage of cures

I'ercentage of cures b,. locat ion

The treatment in the present series of cases was surgery, most often performed with the cautery. Irradiation was combined with such treatment in some instances, but the dosage could not be considered adequate from the modern standpoint. Prior to 1917 it was a rule to perform dissection of the cervical nodes in all cases. In extensive cancer of the tongue and floor of the mouth, block dissection was performed, with removal of the lymph nodes, the floor of the mouth, the tongue, the anterior mandible, and the tonsils (Fig. 17).

Although the duration of symptoms in cancer of the tongue was briefer than for cancer in other localities, the five-year cures in this group were lowest, averaging slightly over 15 per cent in the 223 cases followed. In cancer of the lower lip, in which the duration of symptoms was longest, the cures were highest, 49 per cent of 395 cases. In 213 cases of cancer on the other mucous membranes, adequately followed, there were 17 per cent of five-year cures (Table 111).

'1'AHLlt I I I : lilve-ycnr Ciirc.c i i j Cuizrcr [g the Orul L'imity - ~- - ~~- - ~ - ________ ._

'Tongue

395 223 213

5L$4j 1.5(;;> 17';b

Upper.. 85% Tip . . . . . . . . . . . . 2074, I.ower g u m . , . . . . 25',';, Imver. . 49% Mid-border.. . . . . 11% Floor of mouth . . 20'j;,

Under surface. . . 11 Cheek. . . . . . . . . . 10% IJase. . . . . . . . . . . 5% Palate . . . . . . . . . . lo':;,

Anterior dorsum. 21% IJnder surface. . . 160/, Rase. . . . . . . . . . . 8'%,

1<EGAtTl>'S SERIRS li (436 cases treated by ra- tlium; 16% cures)

Lower gum. . , , . , 16');) Floor of mouth . . 16c/;1 Cheek. . , . . , . . , . 19',>;> rwate . . . . . . . . . . 4"' /ll

* Regaud, C. Id.: J. de niecl. et chir. p a t . 103: 15, 1932

The prognosis of carcinoma of the oral mucosa is determined by the extent of the disease. Hard, palpable cervical lymph nodes are presumptive clinical evidence of metastases and restrict the curability of the lesion, the disease being hopeless if the nodes are numerous, large, and fixed to the surrounding tissue. Regaud estimates, however, that only 60 per cent of the palpable lymph nodes in cancer of the lip and only 86 per cent in cancer of the tongue are actually invaded by tumor. The size of the lesion, the location, and the microscopic grade of malignancy are important prognostic factors, since they indicate the rapidity and extent of probable invasion.

In this series the diameter of the tumor rarely exceeded 2 cm. in patients with lingual cancer living five years or more after treatment. Cures, how- ever, were effected with larger lesions, but these were on the anterior dorsal or ventral surface of the tongue. In the cured cases palpable nodes were not present or were present only in the submaxillary region a t the time of treatment; microscopically, the carcinoma was well differentiated with few

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TUMORS OF THE ORAL MUCOUS MEMBRANE 60 1

exceptions. In these exceptions the lesion was a small ulcer not exceeding a centimeter in diameter on the anterior third of the tongue and without node involvement, although dissections of the neck were performed.

On the lower gum in the molar region or on the cheek just opposite the molars, the primary tumor in the cured cases was usually under 2 cm. in diameter and rarely exceeded 1 cm. The malignant ulcer was usually present in an area of leukoplakia. The lesion was excised with a cautery after split- ting the cheek. The area of excision on the gum was cauterized down to bone; on the cheek the wound was re-cauterized. In approximately one-half

FIG. 17. TISSUE REMOVLD I N A BLOCK DISSLCTION O F CANCLR O F TIIE TONCUE ALOXG WITIT A POR- TION o p THE LOWER JAW, LYMPII NODES AND FLOOR OF THE MOUTH. PATH. NO. 18662

of the cured cases no nodes were palpable and neck dissection was not per- formed, or if it was performed the nodes were microscopically negative. Posi- tive nodes were found only in the submental or submaxillary regions. In only three cases in which a five-year cure was obtained were nodes at the bifurcation of the carotid involved by cancer. Microscopically the lesions were well differentiated forms of squamous-cell cancer.

In 80 per cent of the cured cases of carcinoma of the lip the lesion was less than 2 cm. in diameter and there was no enlargement of the cervical lymph nodes. In the remaining 20 per cent of the five-year cures the lesion on the lip either exceeded 2 cm. in diameter or the cervical nodes were microscopically proved to contain metastases. Prior to 1917, dissections of the neck were the routine whether or not the cervical lymph nodes were palpable. After that date the operation was limited to V-excision of the primary tumor if the lesion was

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FIG. 18. 1,OW-POWER AND HIGH-POWER ~'lIOTOMICROGRAPHS O F GRADE 111 CARCINOMA OF TIIE LIP

The gross specimen, inset in the lower Iefthand corner, shows a typical V-excision performed Ilissection of the nodes of the neck was performed

Path. No. 38932. for a small indurated crack on the lower lip. because of the high degree of malignancy.

602

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TUMORS O F THE ORAL MUCOUS MEMBRANE 603

under 2 cm. in diameter and no nodes were palpable in the neck. This routine was varied in the few cases which on microscopic examination proved highly malignant (Figs. 18 and 19). The percentage of five-year cures was appar- ently not diminished by thus restricting the operation.

It is of interest to compare the results of treatment obtained surgically in the present series of cases with the results obtained in a series of similar tumors treated by radium. Regaud (Table 111) reports 16 per cent five-year cures in 436 cases of carcinoma of the tongue and other oral mucous mem- branes, exclusive of the lip. In the present series there were 15 per cent five-year cures in 223 cases of cancer of the tongue and 1 7 per cent in 213

F I G . 19. PHOTOMICROGRAPH S H O W I N G INVASION O F THE LYMPH NODES BY CANCER I N THE CASE SHOWS IN FIG. 18

Following the V-excision of the tumor in the lip in January 1927, the nodes in the neck were treated by deep x-ray therapy. The neck dissection was not performed until November 1927. Only one lymph node showed metastases on microscopic examination. In March 1928 recurrent nodes low in the neck were excised and radium treatments given, but the patient died in July 1928.

cases of intraoral carcinoma elsewhere. The percentage of cures and the number of cases followed in the two series are practically identical. For carcinoma of the lip Kelly reports 81.8 per cent five-year cures for small lesions without palpable cervical nodes and 2 5 per cent for 12 larger lesions also without palpable nodes. In the present series there were 85 per cent five-year cures in lesions under 2 cm. in diameter without palpable nodes and 10 per cent five-year cures where the lymph nodes were involved.

These figures show that when the tumor is radiosensitive and when treat- ment, whether by surgery or by irradiation, is adequate, the cures are de- pendent upon the extent of the disease as compared to the extent of the field sterilized by treatment. Where the area involved by tumor is accessible alike to surgery and irradiation, there is little or no choice between the two methods from the standpoint of cures effected. From the practical stand-

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604 CHARLES I?. OESCHICKTER

point, carcinoma in the posterior part of the oral cavity is more accessible to radium therapy, and this produces less mutilation and a lower treatment mortality. I t is generally agreed (Duffy) that surgery is preferable to irradia- tion in treating the cervical nodes. In many cases, however, a judicious combination of surgery and irradiation gives the best results.

Embryogancsis of Oral Carcinoma: The lower lip, the lower gums, and the buccal area of the tongue, as distinguished from the pharyngeal area, are derived from the mandibular arch (Fig. 20). In the fifth week of embryonic life the right and left lingual buds arise from this arch and bury the median bud (tuhr~rculum impar). The pharyngeal portion of the tongue arises from

MANPIBULAR ARCH---)

FIG. 20. SKETCH OF TIIE MANDII~ULAR ARCH IN RELATION TO THE OTHER VISCERAL ARCIIES O F T I I E

The buccal portion of the tongue, the lower PHARYNX O F T I I E HUMAN EMBRYO AT TlIE FIFTH \vEEK (AFTER HIS)

Roman numerals indicate the liranchial arches. lip, :ind the gums are derived from the first nr mandibular arch.

the hyoid arch. Until the seventh week the two portions of the tongue are separate, the buccal portion being fused with the alveolar and labial ridges of the mandibular arch. The buccal portion is then separated from the alveolar ridge, which in turn is separated from the labial ridge by an upgrowth of mesoderm. The epithelium covering these derivatives of the mandibular arch is in part ectoderm derived from the primitive stomodeum and in part entoderm from the primitive pharynx.

Approximately 90 per cent of cancers of the oral mucous membrane affect the epithelium covering derivatives of the mandibular arch-the lower lip, the lower gum, the buccal portion of the tongue, and portions of the cheek in the region of the lower molars. It is interesting that this is the only one of the branchial arches lined by both entoderm and ectoderm. Carcinoma of the oral cavity appears to be most frequent at the junction of the skin and niucous membrane of the lip and the junction of ectoderm and entoderm of the mucous membrane within the oral cavity. These embryologic factors and

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FIG. 2 1. LOW-POWER AND HIMI-POWER PHOTOMICROGRAPEIS OF A RECURRENT BAS~L-CELL CARCI- NOM4 COMPLICATED BY OSTEOCENIC SARCOMA ARISIRG I N AN ABERRANT MIXED TUMOR

IN THE Mucous MEMRRANE OF TIIE CIIEEE; The patient was a woman of forty-two years who had noticed a lesion the size of a pea for

The lesion recurred after two years and Four years after the first operation Dr. Bloodgood performed ex-

B (high-power) shows

nine >ears. x-ray treatments were given. cision with the cautery. carcinoma invading fibrous tissue. Path. No 37850

Excision and radium treatments were given.

A (low-power) shows typical basal-cell cancer

605

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606 CHARLES F. GESCHICKTER

the sex differences in endocrine physiology must be considered along with chronic irritation in the etiology of oral cancer.

FIG. 22. PlIOTOMICROC,RAPlIS SHOWING OSTEOCENIC SARCOMA 'PROM THE TUMOR SHOWN 1N

FIG. 21 A AND B A shows malignant fibroblasts and B cartilage and osteoid material.

BASAL-CELL CARCINOMA

In the present series it was twice as frequent on the upper lip, the ratio being 29 to 15 cases. On the upper lip all but three of these lesions occurred on the cutaneous

Basal-cell cancer occurs on both the upper and lower lip.

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TUMORS OF THE ORAL MUCOUS MEMBRANE 607

surface above the mucous membrane, often extending to the alae of the nose. On the lower lip, also, the cutaneous surface rather than the mucous mem- brane was affected, the mucous membrane being secondarily involved in two cases. The age distribution and duration of symptoms were approximately the same as for squamous-cell cancer, but the curability is far greater; none of these lesions metastasized.

Basal-cell carcinoma is rare on the intraoral mucosa, but is more frequent on the cheek and palate than on the lips, tongue, or gum. In the present series one case occurred on the tongue, one on the lower gum in the molar region, three on the cheek, and four on the palate. The ages ranged from forty-two to seventy-eight years, with one exception. This patient was a girl of seventeen with a tumor on the palate which had been present two years and which terminated fatally after two operations. The lesion involved the antrum and it was difficult to say whether it was secondary or primary on the palate. Two other patients died of local recurrence and two have re- mained well following excision with the cautery. One of the cases which involved the cheek is of special interest, since the basal-cell carcinoma was secondary to a benign aberrant salivary tumor and the recurrent tumor was complicated by osteogenic sarcoma (Figs. 2 1 and 2 2 ) .

The patient was a white woman aged forty-two who had for nine years had a lesion, the size of a pea, on the mucous membrane of the cheek. I t was treated by excision and radium applications. It recurred two years later, and deep x-ray therapy was given. Four years after the first operation Dr. Bloodgood partially excised the recurrent tumor, splitting the cheek and cauterizing the region of excision. The patient at the time of this operation was unable to open her mouth more than 2 cm. There was swelling over the region of the right antrum. At the junction of the cheek and palate was an ulcerated area extending to the bone. The ulcerated area had a raised edge and on palpation suggested carcinoma. There were no palpable lymph nodes.

At the ulcerated margin of the mucous membrane the tumor was growing in definite acinar forma- tion (Fig. 21A). In the muscle and fibrous tissue the carcinoma cells had a far more malignant appearance (Fig. 21B). The deeper portions of the tumor showed malignant spindle cells, cartilage, osteoid tissue and osteoblasts, a structure characteristic of osteogenic sarcoma (Fig. 22).

This occurrence of both osteogenic sarcoma and basal-cell carcinoma in an aberrant salivary tumor supports the contention that the cartilage and osteoid substance are independent components of so-called benign mixed tumors and are not degenerative secretory products of the epithelial cells.

Microscopic study of the tissue removed showed adenocystic basal-cell cancer.

BIBLIOGRAPHY

BLOODGOOD, J. C.: Internat. J. Orth., Oral Surg. 18: 491, 1932. CADE, s.: Lancet 1: 8, 1929. DUFFY, J.: Am. J. Roentgenol. 29: 241, 1933. KELLY, E.: J. A. M. A. 100: 388, 1933. Lr, P. L., AND YANG, CHI-SHIH: Am. J. Cancer 25 : 259, 1935. LUND, C. C., AND HOLTON, H. M.: New England J. Med. 208: 775, 1933. MEKIE, D. E. C.: Am. J. Cancer 16: 971, 1932. REGAUD, C.: J. de mkd. et chir. prat. 103: IS, 1932.