Adenoid cystic carcinoma

Adenoid cystic carcinoma

Adenoid cystic carcinoma Analysis of fifty oral cases Thomas ill. Tarpley, Jr., D.D.X., M.S., ami! Joseph S. Giansanti, M.X.D., Washington, D. C.,...

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Adenoid cystic carcinoma Analysis

of fifty

oral

cases

Thomas ill. Tarpley, Jr., D.D.X., M.S., ami! Joseph S. Giansanti, M.X.D., Washington, D. C., and Lexington, Ky. DEPARTMENT DIVISION

OF ORAL

OF RESEARCH

DEPARTMENT

OF ORAL

PATHOLOGY, GRANTS, PATHOLOGY,

ARMED

NATIONAL

FORCES INSTITUTES

UNIVERSITY

INSTITUTE

OF PATHOLOGY,

OF HEALTH,

OF KENTUCKY

D.M.D.,

AND

COLLEGE

OF DENTISTRY

Fifty cases of oral minor salivary gland adenoid cystic carcinoma (ACC) are analyzed and reported. Oral ACC frequently masquerades as a benign neoplasm, and in the majority of cases there is no pain or ulceration. The most common location is in the palate; a plea is made for incisional biopsy of all oral lesions suspected of salivary gland origin. Survival rates show a progressive decrease with time, and there were no survivors beyond 20 years. In this study, there was a positive correlation between duration of the lesion before diagnosis and the salvage rate, but no correlation was found with the size of the presenting lesion.

A

denoid cystic carcinoma (ACC) is a well-recognized malignant neoplasm which occurs with the greatest frequency in the major and minor salivary glands. It has, however, also been described in the paranasal sinuses, nasopharynx, pharynx, trachea, bronchi, lacrimal gland, skin, breast, and esophagusl, 2 Of all the adenoid cystic carcinomas occurring in the head and neck area, 28 to 42 per cent occur in major salivary glands and 58 to 72 per cent occur in minor glands.3-5 Oral ACC (including lip, tongue, oral tonsil, and all other oral sites) accounts for 34.5 per cent” to 51 per cent5 of all head and neck examples. The percentage of malignant salivary gland tumors occurring in the oral cavity varies from 42.4 per cent’ to 70 per cent.* ACC accounts for 29 per cent9 to 55 per cent? of malignant salivary gland tumors at this site. There is general agreement that the most common oral location is the palate. The floor of the mouth is said by some to be the second most common location,”

The opinions or assertions contained herein are not to be construed as official or as reflecting or the Department of Defense.

484

are the private views of the authors and the views of the Department of the Army

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485

while others state that it is the tongue. 5pI23I3 Our review of the English-language literature produced forty-one cases reported in the floor of the mouth61 “1 14-” as contrasted to eighty-five cases in the tongue,s-5p 7, lo, I2714-201 22-21in fact, the floor of the mouth is the third most common location, since we found forty-seven cases of ACC on the buccal mucosa.3* 7, lo* I2114-lQl21-23 ACC is a problematic lesion. It is frequently asymptomatic. It may be stable on successive examinations. It may not ulcerate. It is locally invasive. A seemingly adequate excision specimen is often found to have malignant cells at its margins. Recurrences or metastases may be long dela.yed.3, 6, *, l*, 25 Evaluation of therapy in the reported series is correspondingly difficult. We wish to report fifty cases of oral ACC with long-term follow-up. These cases were analyzed with regard to the original clinical demonstration, therapy, prognosis, and histopathology in an attempt to determine factors that might affect the ultimate prognosis. MATERIALS AND METHODS The material in this study was obtained from the files of the Armed Forces Institute of Pathology. The fifty-nine cases in the oral cavity were coded as adenoid cystic carcinoma, adenocystic carcinoma, cylindroma, basaloid mixed tumor, cylindromatous adenocarcinoma, adenocystic basal-cell carcinoma, pseudoadenomatous basal-cell carcinoma, adenocystic epithelioma, adenomyoepithelioma, and basal-cell carcinoma with hyaline stroma during the years 1941 to 1967. Follow-up data and case details were obtained. This resulted in a determinate group of fifty cases in which the clinical data, treatment, follow-up, and histopathologic findings were available. In forty-five cases, tissue blocks were on file and additional sections were stained with hematoxylin and eosin, mucicarmine, and the PAS methods. These were evaluated for conventional microscopic criteria as well as for the amount and location of PAS- and mucicarmine-positive material. Tabulations of race, age, anatomic location, presenting signs and symptoms, treatment, outcome, and histopathologic findings follow. CLINICAL FINDINGS Sex Of the fifty patients, there were forty men and ten women. This incidence reflects the biased predominantly male population served by the Armed Forces Institute of Pathology. A review of the English-language literature on oral ACC reveals a total of 342 oral cases in which the sex was known51 s, 15-17*23-25;158 of these patients were males and 184 were females, indicating a slight female predilection. Age at diagnosis (Table I) The age range in our series was from 23 to 84 years and is consistent with other reports in the literature.5, lop12,I’, 25 Th e mean age, 50 years, is about 7 reflects years younger than in most reported serieslO>12317725 and again probably a biased sample. ACC is a rare lesion in children?” Krolls, Trodahl, and Royers27 did not find an example in a patient under the age of 15 in a survey of well over

Table

I. Age at diagnosis Age (years) oto9

No. ofpatients

10to 19

:

20 to 29 30to39 40to49 sot059 60 to 69 70 or more

Table

14 1:

:i

5

Total

_z 50

Location

No. ofpatients

IO

II

Ill.

Per cent of patients 44

22 9

72 fi

;

18

: r 50

i 2

E

Location of lesions from literature Location

I

Palate Hard 117 Hard and soft 37 Soft 18 Not otherwise specified 186 To;;;; Base Not otherwise specified Buccal mucosa Floor of mouth Lip 2z:

8 10

:

Hard palate Hard and soft palate Soft palate Buccal mucosa Maxillary gingiva Mandibular gmgiva Floor of mouth Total

Table

Per cent of patients

No. ofpatients

1

Per cent ofpatients

358

58

103

17

1: 83 :: 29

9 :

i

Not otherwise specified 20 Retromolar area i Tonsil Total 584 *Figures are rounded off; actual total is 99.9.

0.3

0.6 100

9,000 salivary gland tumors. We found reports of only nine cases in which patients were 20 years of age or younge+ B,I2221*28,2’J; this is an incidence of 1.5 per cent of the reported cases of oral ACC surveyed by this report. Race

Forty-three of the patients were Caucasians, six were Negroes, and one was an East Indian. In previous reports, race was specified in twenty-eight cases; twenty-three were Caucasians and five were Negroes.7, I5

Adenoid

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cystic carcinoma

487

Pig. I. Clinical photograph showing a large and ulcerated mass on the right hard palate that had a known duration of 5 years; the patient died of gPnwnlizcd metaatases 9 years later. (AFIP negative No. 71-8999 2.)

location

of lesion

(Table

II)

The palate accounted for ‘72 per cent of the cases; the next most common location was the buccal mucosa, which accounted for 18 per cent. The location of lesions in 584 cases previously reported in the litcrat.ure is shown in Table III; these show the palate, tongue, buccal mucosa, floor of the mouth, and lip as the most common sites 3-7.0, 10,12-25,30,32-341n these, the palate accounts for 58 per cent of the total number. We accept the preferential distribution of the cases in the literature as being more reliable than our own but rannot explain the lack of eases involving the tongue in our series. Clinical

description

Most of the lesions presented as firm masses (Fig. 1) ; a few were described as soft, and one was described as cystic. Seventeen contributors described the shape of the lesion; three stated that it was round, while fourteen (82 per cent) reported that, it was irregular or asymmetrical. Ulceration of the overlying mucosa was seen in 15 per cent of the cases. Pain, tenderness, or soreness was reported in 48 per cent of the cases. TJlceration and pain are reported in the literature, ranging from 11 to 35 per cent and 8 to 30 per cent, respectively.+ 21,an The color of the lesion was stated in forty-one cases. These were brown (three), pink (seven), tan (three), yellow (three), and red (two) ; the remaining 56 per cent were described as gray or white. The size of the lesions in this series varied from 1 to 6 cm., but 67 per cent were under 2 cm. in size. The largest lesion reported previously was 7.5 cm.’ In two series, 65 per cent of the lesions were larger than 2 cm.“’ 2r, The duration of the lesion was noted in fort--eight cases. It varied from 1

480

Tnrpley

md Ginnsnnti

Table

IV. Survival

data*

Duration of follow-up (years)

No. of patients

Less than 5 5 to 10 to 15 to 20 or

Oral Surg. April, 1976

:+

;

9 14 19 more

Alive and well

Dead of tumor

:, 4

9 ,i+ !! 33

i: iG

i 16

*Figures exclude one patiest who died of other causes after tIneludes one patient alive with inoperahle disease.

Table V. Survival

times in thirty-one

Time (years) Less than 5 5 to 9 10 to 14 15 to 19 20 or more Total *Measured from date of initial

Per cent survival 66.7 66.1 44.4 28.6 0

7 years.

patients dying of tumor* No. ofpatients

I

II 9 :

I 31

Per cent of total 35.5 29.0 19.4 12.9 3.2 100.0

therapy.

to 144 months; in 62 per cent of the cases there was a duration of 12 months or less. The mean duration was 26 months. The mean duration of lesions in previous reports varied from 6 monthslO to 42.2 months.*l We believe that these wide variations in the means reflect the deceptive nature of these neoplasms, as evidenced by several documented 20-year histories.5, *I In our series, we could not correlate the duration of the lesion with the size. Survival

(Table

IV)

Follow-up data were obtained on every patient. The interval of this follow-up ranged from 3 to 24 years, Of the fifty patients, thirty-one were dead of tumor; two were alive with inoperable disease; one died of other causes; and sixteen were reportedly free of tumor. This gives an over-all crude salvage rate of 32.7 per cent.* The prognosis in this series is worse than those reported by Eneroth, H jertman, and Moberger 25 for lesions of the palate; the salvage rates by these authors are 44 per cent at 10 years and 36 per cent at 20 years. In the only other large series published, that by Spiro and associates,5 the lo-year determinate cure for 105 oral cases was 23 per cent. In the series reported by Leafstedt and colleagues,13 the &year salvage rate for fifteen palatal cases was 66 per cent, while the lo-year salvage rate dropped to 6 per cent. In this same series, a group of fourteen other oral lesions showed a 5-year salvage of 86 per cent, a

*The patient who died of other causes is excluded inoperable lesions are considered to be dead of tumor.

from

the calculations;

the two with

AcZenoid cystic carcinoma

Volume 41 Number 4

Table VI. Duration

of lesion at diagnosis Alive with no evidence of tumor :

Per cent ofpatients ::

No. of patients f:

Duration (months) Less than 6 6to 12 13to36 37 to 60 61 to 120 120or more

489

10 1;

: 8 -! 48

2

Per cent patients alive 41 30.5

i i

ii 37.5 0

No. dead of tumor 18 4

p%En t 18

‘%Een t 40 16.7

Table VII

&cation Hard palate Hard and soft palate Soft palate Buccal mucosa Maxillary gin$va Mandibular gmgiva Floor of mouth *One patient, sidered as dead.

No. of cases* 22

No. alive with no evidence of tumor

::

i 9

:

:

: 1 49

0” 0 ii

; -! 33

dead of other cause, not included;

two patients

ii 44 : 0 with

inoperable

Mean survival (months) 2 14 :i f: tumor

con-

lo-year salvage of 36 per cent, and a 15-year salvage of 21 per cent. In the cases reported by Moran and co-workers,4 83 per cent of a determinate group of twelve patients who were followed an average of 5.6 years were either dead of disease or alive with tumor. Potdar and PaymasteF report a 5-year survival (nineteen patients) of 30 per cent. Conley and Dingman show an increase in the percentage of patients dying of tumor until, at the 20-year follow-up, there were no survivors. The report by Stuteville and Corlep2* shows a 58 per cent 5-year salvage of both primarily and secondarily treated cases and a 67 per cent 5-year salvage of those cases treated primarily. We therefore agree that ACC arising from minor glands has a poorer prognosis than that arising in the major glands. 3, 12,17,19,35,36 Thirty-one of the fatalities occurred in less than 10 years following initial therapy (Table V), with a mean of 8 years. This, combined with a mean duration of 26 months for the lesion before diagnosis, indicated that most cases of ACC will run a course of about 10 years before death ensues. We could find no correlation between the size of the lesion at diagnosis and the prognosis, but the duration of the lesion prior to diagnosis was correlated with the salvage rate (Table VI). In thirty patients the lesion had a known duration of 12 months or less; of these, twelve (40 per cent) were free of disease. In contrast, eighteen patients had lesions with a known duration of 13 months or more; three of these are alive and well (116.7 per cent). These correlations are appropriate to the known insidious and infiltrative nature of ACC.

The correlation of location in the oral cavity with prognosis is summarized in Table VII. A notable finding in those cases that occurred on the hard palate was that the over-all salvage rate was the same (18.2 per cent) in those that, showed definite antral involvement (eleven cases) and those that did not (eleven cases). This finding is contrary to that reported by Spiro and co-authors.” Metastases

Metastases were documented in 48 per cent of the total number of patients; however, 77 per cent of the patients dying of tumor had metastases. These were to regional lymph nodes only (three casesj , to distant organs only (sixteen), 01 to both (three). The most common sites for distant metastases were the lung (twenty-three cases), liver (seven), brain (five), and bone (four). This incidence of metastases is consistent with most reported series.“. 25.:4i Treatment

The primary mode of therapy was known in forty-nine cases. These fell into three groups: surgery alone, radiation alone, and a combination of surgery and radiation. Five patients were treated by radiation alone, and all are dead of tumor. Thirty-one patients were treated by resection alone, while thirteen patients were treated by a combined approach; the salvage rates for each are 38 per cent and 30 per cent, respectively. We draw no conclusion from these figures; the change in radiation techniques and voltage, the dose, the usual advanced nature of cases treated by radiation therapy, and the recent tendency for surgeons to be more aggressive with ACC are all variables that wc cannot assess. Histopathologic

findings

The histopathologic features of ACC have been well described.14, =, 3’JInstead, we will concentrate on those features that either have not been directly addressed or are controversial. Perineural space invasion was seen in 29 per cent of the cases in this series, while the literature varies from 33 per cent 21 to 85 per cent4 with most figures approximately 50 per cent17, 23g4o (Fig. 2). The over-all salvage rate for those cases exhibiting perineural space invasion is 23 per cent, as compared to 38 per cent of those cases that did not. This apparently supports the contention by others that the prognosis is somewhat worse when this feature is present.2zy 2R,36 The amount of PAS- and mucicarmine-positive material and the presence or absence of significant myxoid areas and stromal hyalinization were not correlated with prognosis. Repeated emphasis in the literature is that the solid variant of [email protected] evolves more rapidly, is more likely to metastasize, and carries a poorer prognosis when compared to the more typical cribriform pattern.l”, w ~3 41,42 However, others disagree and state that there is no difference in the behavior of the two forms 1, 3912,1%23,38,30 In attempting to identify those cases that were solid, we recognized that there

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491

Fig. 8. Photomicrograph illustrating one of many examples of perineural space invasion. Patient died of disease in 5 years. (Hematoxylin and eosin stain. Original magnification, x40.) Pig. 3. Photomierograph showing the solid pattern that is characterized by a component of myoepithelial cells. Patient died of disease in 10 years. (Hematoxylin and eosin stain. Original magnification, x40.)

were two types. The first, and more common, consists of sheets of cells that contain a significant myoepithelial cell component (Fig. 3). This type was always associated with other, more typical, cribriform areas. There were thirteen examples of this type. The second type of solid pattern, of which there were four examples, was one that presented as fairly large islands which usually contained a central area of necrosis (Fig. 4 and ,5). Surrounding these islands were smaller clumps of cells, but these did not usually have the typical cribriform pattern (Fig. 6).

492

Tarpley

Fig.

and Giansanti

4. Photomicrograph

of the solid

Oral April,

pattern

characterized

ceUIs and a central area of necrosis. Patient died of generalized (H ematoxyl lin and eosin stain. Original magnification, x10.) Fig. 5. Higher-power view of specimen Ori lginal malgnification, x64.)

shown in Fig.

Surg. 1976

by a lack of n lyoepi thelial metastases in17n months.

4. (Hematoxylin

and eosin stain.

Each of these groups was then compared with the thirty-three remaining lesions as a control group. The first solid group of thirteen examples did not differ in duration, course, or salvage rate. The second group consisted of only four cases. One of these patients was alive with tumor 8 years after diagnosis; the three others were dead of tumor within 1 year. The duration of the lesions before diagnosis was less than 1 year in all cases. We do not believe that the sizes of these subgroups are large enough to permit any firm conclusions from the data, but it appears likely that the solid type, with necrosis, behaves more aggressively.

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Adenoid cystic carcinoma 493

Fig. 6. Islands of tumor as seen around the typical solid areas with necrosis as illustrated in Fig. 4. Patient was dead of disease in 11 months. (Hematoxylin and eosin stain. Original magnification, x64.) Fig. 7. A focal area of spindle cells that are arranged in a pattern similar to schwannoma. Patient is alive and well 9 years following therapy. (Hematoxylin and eosin stain. Original magnification, x64.)

It appears to us that some of the published photomicrographs in the fourteen cases reported by Koss, Spiro and Hajdu43 as small-cell (oat cell) carcinoma may be this type of solid ACC. One case showed prominent areas of a spindle-cell variant as described by Thackray and Lucas36; this variant bears a remarkable resemblance to schwannoma (Fig. 7). However, a more typical cribriform pattern was present in other areas, and diagnosis was no problem. Two cases exhibited a prominent cystic component (Fig. 8) ; these, also, were surrounded by a more typical cribriform pattern.

494

Tarpley

and Giansanti

Owl surg. April, 19i6

Fig. 8. Prominent cystic component in one of the lesions. Patient died of tumor years. (Hematoxylin and rosin stain. Original magnification, x10.) Fig. !I. Pllotomicrograph with a tumor-free zone subjacent. to the epithelium. Patient of tumor at 10 years. (Hematoxylin and eosin stain. Original magnification, x12.8.)

in 2 died

DISCUSSION AND SUMMARY This report verifies that ACC is a disease primarily of older adults and that it is rare in children. On the basis of reported series, females appear to be affected slightly more frequently than males. The presenting lesion is often asymmetrical and may offer a clinical diagnostic clue to its malignant nature, since benign lesions are usually symmetrical. Ulceration is infrequent but, when seen, should suggest a malignant process. Pain was present in a greater percentage of our patients than in most other published series; while the absence of pain is indicative of nothing, its presence is highly suggestive of malignancy. The duration of ACC before diagnosis is, in most of these cases, less than 1

Volume 41 Number 4

Adenoid cystic carcinoma 495

year. However, longer durations are not uncommon, and durations of 20 years have been reported.5y lo, 21 Lesions with a long duration which also lack ulceration or pain and are firm to palpation may be thought benign. Because of this and the desire to avoid a second surgical procedure, an excisional biopsy is often performed, a practice which we do not recommend. The incidence of malignancy of oral salivary gland tumors is, to us, sufficiently high to justify an incisional biopsy on any lesion suspected of being a salivary gland neoplasm. We strongly recommend that this incisional biopsy include the periphery of the mass and the adjacent normal mucosa. The reason for this is that a small percentage of adenoid cystic carcinomas are microscopically indistinguishable from pleomorphic adenoma ; this has been our experience, as well as the experience of others.ll In these cases, the presence of infiltration is a valuable criterion, and this is usually more evident at the periphery of the lesion than it is in the central portion; in fact, it is not unusual to see a tumor-free zone in this latter area (Fig. 9). For this reason, we urge that incisional biopsy material be taken from the edge and not the center of the lesion. The data presented in this article support the prevalent conception that ACC of minor salivary gland origin is more lethal than the same lesion in the major salivary glands. Unfortunately, there are not enough cases in this study that exhibit a solid pattern with necrosis; however, we believe that they are probably more aggressive as a group than those exhibiting the typical cribriform pattern. We further believe that some of the contradiction in the literature relevant to the behavior of the solid type reflects a failure to distinguish between the solid type with myoepithelial cells and the solid type with necrosis. In this study, the solid myoepithelial type behaved no worse than those having a typical cribriform pattern. The authors wish to express their deep appreciation to the following persons whose efforts made this study possible: Dr. W. R. Sabes, Chairman, Department of Oral Pathology, University of Kentucky; Mrs. Ioln C. Braxton, statistician, Biometrics Branch, AFIP; W. F. Simmons and L. C. Chandler, tissue technicians, University of Kentucky; Jean C. Burgess, who typed the manuscript; and Carol L. Tippery who provided technical assistance. REFERENCES

1. Foote, F. W., Jr., and Frazell, E. L.: Tumors of the Major Salivary Glands. In Atlas of Tumor Pathology, Washington, D. C., 1954, Armed Forces Institute of Pathology, Sect. 4, Fast. 11, p. 103. Adenocystic Carcinoma (Cylindromatous 2. Nelms, D. C., and Luna, M. A.: Primary Carcinoma) of the Esophagus, Cancer 29: 440-443, 1972. in the Head and Neck 3. Conley, J., and Dingman, D. L.: Adenoid Cystic Carcinoma (Cylindroma) , Arch. Otolaryngol. 100: 81-90, 1974. 4. Moran, J. J., Becker, 5. M., Brady, L. W., and Rambo, V. B. : Adenoid Cystic Carcinoma; a Clinmopathologic Study, Cancer 6: 1235-1250, 1961. 5. Spiro, R. H:, Koss, L. G. Hajdu, S. I., and Strong, E. W.: Tumors of Minor Salivary Origin; a Cbnicopathologic Study of 492 Cases, Am. J. Surg. 128: 512-520, 1974. 6. Smith, L. C., Lane, N., and Rankow, R. M.: Cylindroma (Adenoid Cystic Carcinoma) ; a Report of Fifty-eight Cases, Am. J. Surg. 110: 519-526, 1965. 7. Frable, W. J., and Elzay, R. P.: Tumors of Minor Salivary Glands; a Report of 73 Cases, Cancer 25: 932-941, 1970.

1

Y

April,

1976

8. Spiro, K. H:, KOSS, 1~. G., Hajdu, S. I., and Strong, E. W.: Tumors of Minor Salivary Origin; a Clmicopathologic Study of 492 Cases, Cancer 31: 117-129, 1973. '). . Vellios, F., and Shafer, W. G.: Tumors of the Intraoral Accessory Salivary Glands, Surg. Gvnccol. Ol&ct. 108: 450-456. 1959. 10. Epker, B. N., and Henny, ‘F. A.: Clinical, Histopathologic, and Surgical Aspects of Intraoral Minor Salivarv Gland Tumors: Review of 90 Cases. J. Oral Burg. 27: 792-804. 1969. 11. Thackray, A. C., and Lucas, R. 13.: The Histology of Cylindroma of Mucous Gland Origin, Br. 5. Cancer 14: 612-620. 1960. 12. Chaudhy, A. P., Vickers, R. A., and Gorlin, R. J.: Intraoral Minor Salivary Gland Tumors; an Analysis of 1,414 Cases, ORAL SURG.14: 1194.1226, 1961. 13. Leafstedt, S. W., Gaeta? J. F., Sako, K., Marchetta, F. C., and Shedd, D. P.: Adenoid Cystic Carcinoma of Malor and Minor Salivarv Glands, Am. J. Sure. 122: 756-762, 1971. 14. Eby, L. S., Johnson, D: S., and Baker, H. iv.: Adenoid Cystic Carcinoma of the Head and Neck, Cancer 29: 1160-1168, 1972. Glands, 15. Fine, G., Marshall, R. B., and Horn, R. C.: Tumors of the Minor Salivary Cancer 13: 653-669, 1960. 16. Hendrick, J. W., Nichols, R. D., Horn, R. C., Bloor, R. A., and Stine, P. H.: Treatment of Tumors of Minor Salivary Glands, South. Med. J. 63: 809.815, 1970. Gland Tumors of the 17. Luna, M. A., Stimson, P. G., and Bardwil, J. M.: Minor Salivary Oral Cavitv: a Review of Sixtv-eieht Cases. ORAL Sum. 25: 71-86. 1968. 18. McDonald; J. R., and Havens: F.-Z.: A Study of Malignant Tumors of Glandular Nature Found in the Nose, Throat, and Mouth, Surg. Clin. North Am. 28: 1087-1106, 1948. 19. Ranger, D., Thackray, A. C., and Lucas, R. B.: Mucous Gland Tumors, Br. J. Cancer 10: l-16, 1956. 20. Russell, H. : Adenomatous Tumours of the Anterior Foregut Region Showing thr Cylindroma Pattern, Br. J. Surg. 43: 248-254, 1955. 21. Atuteville, 0. H., and Corley, R. D.: Surgical Management of Tumors of Intraoral Minor Salivary Glands; Report of Eighty Cases, Cancer 20: 1578-1586, 1967. 22. Potdar, G. G., and Paymaster, J. C.: Tumors of Minor Salivary Glands, ORAL RIJRG.28: ”

310-319, 1969.

23. Smout, M. S., and French, A. J.: Prognosis of Pseudoadrnomatous Basal-Cell Carcinoma, Arch. Pathol. 72: 107-112, 1961. of Major and Minor Salivary Gland 24. Wawro, N. W., and McAdams, G.: Cylindromata Origin, Arch. Surg. 68: 252-261, 1954. 25. Eneroth. C.-M.. Hiertman, L., and Mobewer. G.: Adenoid Cvstic, Carcinoma of the Palate, Acta Otblaryngol.“66: 248266, 1968. - ’ 26. Calich, R.: Salivary Gland Neoplasms in Childhood, Arch. Otolaryngol. 89: 878-882, 1969. 27. Krolls. S. 0.. Trodahl. 5. N.. and Bovers. R. C.: Salivarv Y Gland Lesions in Children: a Survey of 430 Cases, dancer j0: 459-489,1972. 28. Danziger, H. : Adenoid Cystic Carcinoma of the Submaxillarv Gland in an R-Month-Old Infanr, Can. Med. Assoc. J. 91: 759-761, 1964. 8. L., and Stout, A. P.: Tumors of the Major Salivary Glands in Children, 29. Kauffman, Cancer 16: 1317-1331. 1963. 30. Bergman, F. : Tumors of the Minor Salivary Glands; a Report of 46 Cases, Cancer 23: 538-543, 1969. Glands: a Reoort of 23 Cases. Am. J. 31. Edwards. E. G.: Tumors of the Minor Salivarv I Clin. Patbol. 34: 455-463, 1960. 32. Reynolds, C. T., McAuley, R. L., and Rogers, W. P., Jr.: Experience With Tumors of Minor Salivary Glands, Am. J. Surg. 111: 168-174, 1966. of Malignant Tumors of Minor Salivary Glands, Arch. 33. Shumrick, D. A.: Treatment Otolaryngol. 88: 100-105, 1968. Natural History and Results of Treatment of Mucous Gland 34. Snelling, M. I).: Histology, Tumors, Am. J. Roentgenol. 90: 1032-1041, 1963. 35. Smith, J. F.: Tumors of the Minor Salivary Glands, ORAL SURG.15: 594-602, 1926. 36. Thackray, A. C., and Lucas, R. B.: Tumors of the Major Salivary Glands. In Atlas of Tumor Pathology, Washington, D. C. 1974, Armed Forces Institute of Pathology, second series, fast. 10,pp. 91-99. .37. Eneroth, C.-M. : Incidence and Prognosis of Salivary Gland Tumours at Different Sites; a Study of Parotid, Submandibular and Palatal Tumours in 2,632 Patients, Acta Otolaryngol. 263: 174-178, 1970 (Supp.). of the Head and Neck. Arch. 38. Adams. G. L.. and Duvall. A. J.: Adenocarcinoma Otolaryngol. 9i: 261-270, 1971. L. : Adenoid Cystic Carcinoma of the Submandibular Gland, 39. Eneroth, D.-M., and Hjertman, Laryngoscope 76: 1639-1661, 1966. 40. Bardwil, J. M., Reynolds, C. T., Ibanex, M. L., and Luna, M. A.: Report of One Hundred Tumors of the Minor Salivary Glands, Am. J. Surg. 112: 493.497,1966.

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of Salivary Glands, a report of 80 41. Berdal, P., Besche, A. de, and Mylius, E.: Cylindroma Cases, Acta Otolaryngol. 263: 170-173, 1973 (Supp.). 42. Stewart, J.: Carcinoma of Salivary Glands Showing the Cylindroma Pattern, Br. J. Surg. 49: 241-245, 1961. 43. Koas, L. G., Spiro, R. H., and Hajdu, S.: Small Cell (Oat Cell) Carcinoma of Minor Salivary Gland Origin, Cancer 36: 737-741, 1972. Reprint requests to: Dr. Thomas M. Tarpley, Jr., Executive Secretary Oral Biology and Medicine Study Section Division of Research Grants National Institutes of Health Room 4A03, Westwood Building Bethesda, Md. 20015