Salivary gland tumors

Operative

Oral

SALIVARY HAROLD S. FLEMING,

GLAND

Surgery TUMORS

D.M.D., M.Sc., D.Sc., NEW HAVEN,

CONN.

Introduction T IS the purpose of this report to present salivary gland tumors treated at (formerly New Haven Hospital) from 1922 to 1952. Special reference is given to the so-called mixed tumors. During the period just mentioned, a total of 123 different cases of salivary gland tumors were treated at this hospital. Treatment of salivary gland tumors presents several problems. Since enlargements of the salivary glands are not uncommon, differential diagnosis is at times difficult.

I Grace-New Haven Community Hospital

Investigators have been inclined to emphasize certain clinical aspects of salivary gland tumors that may not be important to the course, treatment, and final disposition of such cases. In most studies such factors as the age and sex of patients, as well as the site and size of tumors, are stressed. This detailed information is necessary perhaps, but its significance is lost if an origin of salivary gland tumors from neural crest remnants is accepted. Embryo-’ logic, histologic, and biologic investigations attest the validity of such a con21,38 cept. 12-15, It is the purpose of this report to present the following aspects in relation to their course and treatment : (a) location and number of tumors, (b) histopathologic diagnoses, (c) separation of tumors, (d) recurrence of tumors, (e) metastases of tumors, and (f) results of treatments.

Historical

Review

From 1750 through 1952 there have been many reports in the literature on salivary gland tumors. In a thesis written in 1841, BBrard5 reports that Kaltschmeid described these tumors as early as 1752. According to Dunet and Creyssel,l’ other early writers on this subject were C. J. and J. B. Seibol, who reported on them in 1793 and 1797, respectively. By the early part of From

the

Yale

University

School

of

Medicine,

683

Department

of

Surgical

Pathology.

684

HAROLD

S. FLEMING

the nineteenth century attempts were made to classify these tumors and differentiate them from other enlargements in the parotid and sublingual areas. BBrard’s5 work was significant because he attempted a separation of salivary gland tumors from cysts, abscesses, carcinomas, and enlarged lymph glands. From the middle to the end of the nineteenth century investigators proposed names for these tumors based on their int,erpretations of the histologic picture. Then, as now, there were differences of opinion concerning the origin and structure of salivary gland tumors and many confusing t,errns were used to describe them. Improvement in microscopes and histologic techniques contributed much to a better understanding of the eomplcs nat,urc of these tnmops. Virchow,35 in 1.863, submitted microscopic drawings with histologic reports on these tumors. Finding them hard to classify, he called them enchondromas and diffuse enchondromas. Tn 1866, after studying their structure, Broca,? in his “Traite des Tumeurs,” supported I,ebert,,18 who formerly had called them adenomas. Later, in 2874. the word mischqes?crulstemeaning “socalled” was introduced and has remained in use to this day.28 With the development of embryology, investigators endeavored to explain the origin and structures of these tumors. Three main theories of origin were proposed by the latter part of the nineteenth century. These were the mesenchymal, the mixed (epithelial and mesenchymal) , and t.he epithelial. The more important supporters of the mesenchymal theory of origin were Virchow,35 Billroth, and Volkman.“fi Virchow3J and Billroth believed that these tumors arose only from connective tissue. Volkman,36 however, influenced many in Germany to support his concept of endothelial origin, which he based on the presence of endothelium found in tumor capsules. Two chief reasons for the weakness of the mesenchymal theory were : first, it wa,sproved that mesenchymal tissue was not the only source of these tumors; and, second, Wood3* and others found Volkrnan’~~~ “peripheral lymph spaces” in tumors to be really tumor alveoli. Belief that salivary gland tumors arose from glandular epithelium had many supporters. Hinsberg16 and others tried to establish proof that the epithelium of these tumors was derived from embryonal glandular anlagen. This concept, supporting the presence of glandular epithelium in the mixed tumors of the salivary glands, had extreme popularity in France by the end of the nineteenth century. Those supporting the epithelial theory claimed that the low columnar cells lining the tumor alveoli degenerated and finally secreted a mucoid and chondromucoid material. This accounted for the cartilage and bone sometimes present in these tumors. It also was noted that the stellate cells in the mucoid matrix had a close resemblance to those found in these tumors. However, this is contrary to pathologic experience. Rawson, Howard, Royster, and HorqS2 in a clinicopathologic study of 160 cases of salivary gland tumors, emphasized the presence of ductlike structures in all mixed tumors, resembling the ducts of normal salivary glands. These ductlike structures filled with a mucoid material were thought by them

SALIVARY

GLAND

TUMORS

685

to bea productof degenerativechangesof the tumor a.ndnot of the glandular epithelium. Sometimes this mucoid material was acidophilic, but usually it was deeply basophilic. Theories of mixed origin, from both mesenchymal and epithelial tissue, have always been favored and opinions were divided between the branchiogenie and nonbranchiogenic theory of origin. Important consideration was given to the branchiogenic theory about 1908, because mixed tumors often appeared on the face in the region of the first or second embryonic fissures. Lenormant? and his co-workers agreed with CohnheimV hypothesis t,hat the cartilage in tumors of the parotid, sublingual, and submaxillary regions developed from unused cartilaginous remnants of the branchial arches. Since ectoderm, endoderm, and mesoderm are present in branchial anlagen, these tumors could acquire epithelial pearls, glandular epithelium, and fibromyxomatous, or sometimes cartila,ginous, structures. Ahlbom’ states tha.t many were in agreement with this concept. It has not been sustained, however, because it failed to explain the presence of mixed tumors in other locations.13 Those who supported the belief that the tumors arose from embryonal tissues of nonbranchiogenic origin found it necessary to explain the difference between the cartilage in the teratoma and that in the mixed tumor. In the teratoma, the cartilage is organized into masses surrounded by perichonclrium, which is not true of cartilage in a mixed tumor. In his earlier writings, McFarlandzz dealt largely with refuting the branchiogenie theory of Cohnheims and supporting the idea that the source of these tumors was from embryonic cell rests or enclavements. Paus31 and Kux17 agreed with him. Li and Yang21 later suggested that the frequency and location of branchial tumors, adamantinomas, and mixed salivary gland tumors were dependent on the time and place of embryonic rest formation. The idea that embryonic rests were the source of the tumors failed to receive snpport because positive evidence of embryonal inclusions in salivary glands could not be demonstrated as in other structures. Greene12 found that salivary gland tumors will survive transplantation to the anterior eye chambers of laboratory animals, duplicating the histologic picture of the original tumor. Tumors so grown may be purely epithelial, mesenchymal, or both, and proof of the mixed nature of salivary gland tumors thus is confirmed by the continued growth of either or both of the transplanted tumor tissue elements. Salivary gland tumors, meningiomas, and schwannomas a,re the only benign tumors that will survive heterologous intraocular transfer.12 Since the latter two arise from neural crest derivatives, it is felt, with this similarity in biologic reaction on intraocular transfer, that mixed salivary gland tumors may have fragments of the neural crest as their primordia. Methods Data pertaining to the 123 cases of salivary gland tumors treated at the Grace-New Haven Community Hospital during the time mentioned were collected from several sources. The Medical Records Department, the Tumor Registry, and the Department of Surgical Pathology supplied the information.

686

HAROLD

S.

FLEMING

Material so gathered, after being cross-checked for duplication, was then organized into a master chart (which is not presented due to lack of space), and cases were listed in bhe following manner : (1) hospital unit number (except for eleven private cases having no unit number), (2) sex, (3) age, (4) duration, (5) location, (6) symptoms, (7) type and size of growth, (8) pathologic diagnosis and number, (9) treatment(s), (10) recurrence (if any) and tumorfree years, (11) results and final disposition, and (12) cause of death (if deceased). Tumors were listed as benign, except when malignancy was proved histologically by combination of the tumor with any one of the following: a.n epidermoid carcinoma, a squamous cell carcinoma, an undifferentiated carcinoma, or an adenocarcinoma. Such tumors are listed with other malignant tumors in this series.

Results and Discussion The locations of these tumors compare favorably with reports of Ackerman and Regato,l Ahlbom,*s 3 Cheyne, Tiecke, and Horne,s McFarland,22-27 Rawson, Howard, Royster, and Horn,32 and Stout.33 The investigation disclosed the following result : parotid gland, eighty-four ; submaxillary gland, fifteen ; hard palate, five ; soft palate, two ; sublingual gland, two ; lip, three ; tongue, two ; antrum and maxilla, four ; buccal mucosa, three ; ear, one ; and nose and orbit, two. According to the histopathologic diagnoses, eighteen of these tumors are listed as malignant and 105 as mixed. The percentage of mixed tumors found in this study (85 per cent) is higher than Rawson, Howard, Royster, and Horn? report covering a similar period. Thoma34 says that mixed tumors have higher incidence than is shown in reports, for lack of proper diagnosis, and this may account for the frequent unfavorable results. In this report, several mixed tumors were clinically considered malignant because of their destructiveness and continued recurrences, but the slides were always read as mixed tumors. The sites of the mixed tumors (105) were as follows : parotid gland (less one recurrent tumor diagnosed as a cyst), seventy-two; submaxillary gland, fifteen ; hard palate, three ; soft palate, two ; sublingual gland, one ; lip, three ; tongue, two ; antrum and maxilla, two ; buccal mucosa, three ; ear, one ; and nose and orbit, one. The sites of the malignant tumors (eighteen) were as follows. Parotid Gland-twelve. (One anaplastic carcinoma, three adenocarcinomas, two sarcomas, one carcinoma and mixed tumor, one adenocarcinoma and mixed tumor, one squamous cell carcinoma and mixed tumor, and three epidermoid carcinomas.) Maxilla and Antrum-two. (One mixed tumor and carcinoma, cinoma.)

and on.e undifferentiated

car-

SALIVARY

GLAND

687

TUMORS

Sublingual Gland-one. (Epidermoid carcinoma.) Hard Palate-two. (One adenocarcinoma, Tonsil-one. (Aberrant

squamous

and one epidermoid

carcinoma.)

cell carcinoma.)

Since most salivary gland tumors are benign, they are radioresistant and surgical excision is the accepted method of treatment. Such radiologists as Ahlbomzj 8 and Ledermanlg believe that radiotherapy is always indicated, either as the sole method of treatment or with surgery. It is claimed by them that McFarlandz6 had a high incidence of recurrence because of his reluctance to accept radiotherapy. In this report the recurrence of surgically treated tumors averages almost the same a.s those of McFarland. The favored way of treating these tumors in the present series was by surgery. X-ray therapy was given after surgery in twenty-six cases. In some of these instances the physical condition of the patients or the location of the tumor contraindicated further surgery. In other instances further surgery In three cases x-ray therapy was the only treatment followed x-ray therapy. given. The treatment given was as follows : eighty-seven cases, surgery; twentysix cases, x-ray and surgery ; three cases, x-ray alone ; and seven cases, no treatment. Bailey4 states that careless seeding of the operative site with tumor cells having a great potentiality for growth is the chief reason for recurrence. Difficulty in removing entire parotid gland tumors also may contribute to this high frequency. Table I shows that there were thirty-six recurrent tumors, twenty-six Twenty-six tumors were benign and ten were being in the parotid gland area. malignant. Ten cases had tumor-free survival beriods of four or more years after the last operation. Four cases had a two-year tumor-free period before recurrence. In the remaining instances the tumor recurred in less than two years or was not eliminated. The frequency of recurrence led New,29 New and Childrey,30 and Dixon and BensonlO to state that all parotid gland t.umors are invariably malignant. These investigators based their opinions on cases that were difficult to handle because they never could be completely removed surgically and, with continued recurrences, became very destructive. They concluded that, because of the unpredictable behavior of salivary gland tumors in the parotid areas, they could be handled better clinically if all were McFarlandZ3 atconsidered malignant, regardless of the histologic picture. tempted to relate the duration and size of the tumor to recurrence as well as the age at onset. Recurrence in this series does not confirm this, but it does bring out the importance of adequate original treatment. Out of twenty biopsied tumors in this study, only three had satisfactory tumor-free survival

Parotid

Parotid Subm axillarp

27

28 32

z”:

Parotid Parotid Parotid Parotid Parotid Parotid Parotid

Excision Excision

Biopsy and excision Excision Excision and x-ray Excision Excision Excision Excision Several biopsies, excision, and x-ray Several biopsies

Parotid

ORIGlNAL TREATMENT

Excision Excision Excision Excision Excision Excision

(

I OF

TABLE

2

Excision Excision

1 Not given

Excision

3

2

Excision Excision Excision Excision Excision Excision ex-

x-ray

and

x-ray

1

I

TUMORS

excision

and

and

-

TREATMENTOF RECURRENTTUMOR

-___-___

RECURRENT

i 3, 4, 9 7 3, 8 3%

/

\

I.

Aspiration cision Excision X-ray and Excision Excision Excision Excision All types

4

1, 1, 1

13 7% 2, 1, :

PRIMARYTUMOR TO RECURRENCE / (YEARS)

MOVAL

\ TIMEFROMRE-

_.___.~~_

Parotid Submaxillary Submaxillary Parotid Parotid Parotid

1

ORIGIPiAI, SITEOF TUMOR

13 16 18 19 22

2

CASE NlJMBER

I

.-__

__-

Adenoearcinoma and mixed Mixed tumor Mixed tumor

Mixed tumor Sarcoma Carcinoma Mixed tumor Mixed tumor Mixed tumor Mixed tumor

------

TYPE OF TUMOR

--

tumor

Mixed tumor Mixed tumor Mixed tumor Carcinoma Mixed tumor Carcinoma and adenocarcinoma Mixed tumor

HISTOLOGIC RECURRENT

---

j

I

No No

recurrence recurrence

Metastases

for for

to neck

Possible extension Local extension No recurrence for No recurrence for No recurrence for No recurrence for Metastases to neck

nodes

years years years years nodes

4 years 12 years

5 6 6 4

nodules

for 7 vears to both &illary for 7y2 years to lymph nodes to lymph nodes to cervical nodes recurrent

No recurrence Metastases No recurrence Metastases Metastases Metastases Bmall

-__

RESULT OF TREATMENT RECURRENT TUMOR

___~~-

nodes

OF

Excision

Excision

Biopsy Excision Excision Excision

Submaxillary

Antrum

Antrum

Parotid Parotid Parotid Parotid

88

90

92

2 106 108

Parotid

121

Site Total number Malignant Mixed tumors Tumor-free survival *our years or more

Antrum Tonsil (aberrant)

116 119

26

4 mo. eliminated 12 5

eliminated

eliminated

RECAPITUL;MIT;;i~F

1:

6

RECURRENT

2

;

Subma~llary

TUMORS

eliminated

Not

Not

Not

Not

1

Excision

x-ray

x-ray

given

Not given 2 Not eliminated

3 4 Not 2

3 1

divot eliminated Not eliminated

and

and

and

Excision Excision

Excision

Excision Excision Excision

Parotid Parotid Parotid

69 70 77

Et

Parotid Tongue Parotid Ear

48 50

Excision Biopsy, x-ray, excision Excision Excision Excision Excision

Parotid Parotid

40 45 and

x-ray

(TOTAL

36)

Excision

Excision Excision and

and and x-ray

x-ray x-ray

2

4’

6

and

ex-

Other

Several radical cisions Radical excision x-ray Excision None Excision Several excisions

Excision Excision and x-ray Not given Mastoidectomy and x-ray Excision Excision and biopsy Many radical excisions Excision

Bxcision Excision

tumor tumor

cyst Mixed Mixed

tumor tumor tumor tumor

tumor

carci-

sites

Mixed tumor epidermoid cinoma

cinoma

and car-

Mixed tumor Mixed tumor and squamous cell car-

Mixed Mixed Mixed Mixed

Mixed

Epidermoid noma Carcinoma

tumor tumor tumor tumor

Mixed Mixed Mixed Mixed

Mixed tumor Adenocarcinoma for for

for

extension

to face

and

Extension

to side

of face

Local extension Local extension Recurrence after 2 years Local extension to side of face, death No recurrence for 2 years No recurrence for 2 years

Local

Metastases

kidney

2 years 4 years

2 years

Patient lost Local extension Continued extension-locally vasive Local extension

No recurrence No recurrence Not given Local invasion

No recurrence Local extension

in-

5 E

2

L3

z -! 0 r k-

T c

690

HA4ROLD

S. FLEMING

periods. One of these tumors had a tumor-free period of thirteen and one-half years after biopsy and excision, but in this case the biopsy was performed two days prior to surgery. The palate was the site of the tumors in the other two cases, where there were tumor-free survival periods of six and seven years. In parotid gland tumors where surgery was performed a month or more after the tumor was biopsied, bhere was always recurrence in four years or less. TABLE CASE NTTMRER 3 11

TYPE OF TTJRZOR Mixed tumor, recurrent hnaplastic carcinoma, rwurrent Mixed tumor Adenocarcinoms and carcinoma,

16

recurrent Sarcoma

18

Clarcinoma,

19

Mixed

27

hfixed tumor carcinoma Mixed tumor

6 9

24 32 44 45 50 54 58 79 81

Total

SITE

I

I

Submaxillary Parotid Parotid Parotid

tumor,

Parotid

recurrent and recurrcnt~

Parotid Parotid

recurrent recurrent

hIixed

rwurrent,

tumor,

adeno-

cell

Submaxillary Submaxillary Parotid Tongue Hard palate Hard palate Parotid Parotid

(:arotid sheath nodes Regional lymph Regional lymph Neck nodes Carotid sheath Neck nodes Neck nodes Cervical nodes Neck nodes

recur-

t’:troti(l i\ntrum

(‘ervical nodes and F’aw and kidney

I’arotitl Parotid Parotid Parotid Parotid Paroticl Antrum

General Muscles and carotid sheath (:rrvical lymph nodes Neck nodes To throat To face F’aw and kidney To fwr and right lung

recurwrit

Parotid these

tumors.

we

lIntI

the

Histologically Malignant

living

XETASTATIC SITE Lymph nodes, cervical I;vmDh nodes. cervical N&c nodes Neck nodes Neck nodes and carotid sheath Supraclavicular nodes and thyroid iinterior cervical triangle and palm Neck nodes

Parotid

recurrent

Mixed tumor, Mixed tumor -kdenocarcinoma, Mixed tumor,

following

tumors

: 15

and

neck

nodes nodes and

nodes

spine

facts:

Hist.oZogicaZZl/ Mixea9

dead

27 metastatic

METASTASES --. --

Parotid

Mixed tumor Rarcoma Mixed tumor am1 squamous carcinoma Adenocarcinoma x7 Irndifferentiated carcinomu 90 rence 91 Mixed tumor 93 Mixed tumor Flpidermoitl cawinoma 94 Rpidermoid carcinoma 95 99 Rpidermoid carcinoma 100 htlenocarainoma 102 Mixed tumor and carcinoma 106 Mixed tumor In summing ug the metastases of Patients Patients

II.

(3

both

malignant

anti

mixcc1)

Tumor _1 i

12

This emphasized the fact that biopsy of a mixed tumor must be followed as soon as possible by excision, for long intervals between biopsy and excision may allow tumor elements to develop at new sites. In this series, twenty-seven tumors metastasized to other sites (Table II). Most of the metastases were in regional lymph nodes. Very few were found at distant sites. It was previously observed that fifteen of the eighteen tumors classified as malignant metastasized.

SALIVARY

Fig. subsequently magnification. Fig. picture as Fig. Fig. tion, x450:

GLAND

TUMORS

691

l.-Photomicrograph of a salivary gland tumor removed in 1932 from a patient who had thirty-seven additional operations without eradication of the tumor. (Original X 650 : reduced V,. 1 2.-Photomicrograph of the tumor in 1952 presenting essentially the same histologic it did originally. (Original magnification, X450 ; reduced vs.) 3.-Mixed tumor of palate. (Original magnification, x450 ; reduced 1h.) 4.-Epidermoid carcinoma in another section of same tumor. (Original magniflcareduced $$,.I

692

HAROLD

8. FLEMING

In addition to recurrence and metastasis, several other unfavorable results were found to follow treatment. In parotid gland tumors, these were Facial paralysis can result from treatment or it facial paralysis and fistulas. may arise from invasion of the branches of the facial nerve by the tumor. Fistalas, when present, will sometimes disappear without surgical intervention, but occasionally, as in a case in this study, they may persist for years. Excessive lacrimation and loss of hearing are infrequent complications. Unfavorable results of treatment were as follows : eighteen cases of facial paralysis, one case of excessive lacrimation, one case of loss of hearing, and two cases of parotid fistulas.

Fig. ‘kc )

5.-Adenocystic

mixed

tumor

Fig. 6.-Metastatic cylindroma magnifkation, X225 ; reduced l/5.1

The predicted. tumor-free represent tive with generally Figs.

of the parotid. from

left

parotid

(Original to

left

magnification, lower

lobe

X225 ; reduced of lung.

(Original

prognosis of these cases is difficult, for their behavior can never be After adequate and sufficient treatment, followed by ten or fifteen years, there is often recurrence. Cases 24, 65, 70, 77, 92, and 108 repeatedly recurrent tumors that have become increasingly destruceach recurrence. Here, the best treatment that can be offered is palliative. 1 to 6 show microscopic sections from this series that are of interest.

One hundred twenty-three cases Grace-New Haven Community Hospital and the findings are as follows.

of salivary gland tumors treated at from 1922 to 1952 have been reviewed,

SALIVARY

GLAND

TUMORS

693

1. The parotid gland was the most frequent tumor site. 2. Malignant and recurrent tumors were found most often in the parotid gland. 3. All biopsied tumors recurred, with three exceptions. 4. The tumor-free survival period of surgically treated recurrent tumors was low. 5. Treatment was generally by surgery. X-ray therapy sometimes was used after surgery, but it was seldom used alone. 6. A small group of patients with histologic benign tumors presented a problem from t,he point of therapy because of repeated recurrence. 7. Standardization of histologic criteria would simplify and contribute much in comparative studies of these tumors.

References 1. Ackerman, 2. 3. 4. 5. 6. 7. 8.

L. V., and de1 Regato, J. A.: Cancer-Diagnosis, Treatment and Prognosis, St. Louis, 1947, The C. V. Mosby Company, pp. 618-644. Mischtumoren vom Typ der Schleimund Speicheldriisengeschwiilste und Ahlbom, H.: ihre Behandlung, Acta. Radiol. 16: 174-184, 1935. Ahlbom, H.: Mucousand Salivary-Gland Tumours, Acta. Radiol., Supp. 23, pp. l-452, 1935. Bailey, H.: The Treatment of Tumors of the Parotid Gland With Special Reference to Total Parotidectomy, Brit. .J. Surg. 28: 337-346, 1941. BBrard, A.: Des Operations que Reclament les Tumeurs Developees dans la Region Parotidienne, Paris, 1841, These du. Cone. d. Mea. Operat. Von Billroth, T.: Beobachtungen ijber Geswulste der Speicheldrussen, Arch. f. Path. Anat. und Physiol. 17: 357-375, 1855. Traite des Tumeurs, I: 240, Paris, P. Asselin, 1866. Broca, P. L.: Cheyne, V. D., Tiecke, R. W., and Horne, E. V.: A Review of So-Called Mixed Tumors of the Salivary Glands, Including an Analysis of Fifty Additional Cases, ORAL

SURG., ORAL MED., AND ORAL PATH. 12: 359,1948.

9. Cohnheim, J. F.: Vorlesungen iiber allgemelne Pathologie, 2 V., ch. 16, Berlin, 1882, A. H. Hirschwald. C. F., and Benson, R. E.: Surgical Management of Large Tumors of the Neck, 10. Dixon, Am. J. Surg. 69: 384-390, 1945. 11. Dun&, C., and Creyssel, J.: Cancer des glandes salivaires, Paris, 1933, Gaston Doin & Cie. 12. Greene, H. S. N.: Unpublished Papers on Mixed Tumors of Salivary Glands, Department of Pathology, Yale School of Medicine. 13. Halpert, B.: Salivary Gland Tumors in Rare Sites, Yale J. Biol. & Med. 5: 5, 1933. 14. Halpert, B.: Anlage Tumors About the Mouth, ORAL SURG., ORAL MED., AND ORAL PATH. 5: 9, 993-999, 1952. W. F., Dawson, E. K., and Innes, J. R. M.: 15. Harvey, Debatable Tumors-Mixed Tumors of Salivary Glands, London, 1940, Oliver & Boyd, Ltd. 16. Hinsberg, K. : Beitrlge zur Entwicklungsgeschicte und Natur der Mundspiecheldrijsengeschwulste, Deutsche Ztschr. f. Chir. 51: 281-355, 1899. E.: Zur Histogenese der sogenannten Mischgeschwiilste der Speicheldriisen, Vir17. Kux, chows Arch. f. path. Anat. 180: 175, 1931. Physiol. Path. (J. B. BailliBre, Paris), 2: 254, 1845. 18. Lebert, H.: Mucous and Salivary Gland Tumours; a Report of 57 Cases, Brit. J. 19. Lederman, M.: Radiol. 14: 329-368, 375, 1941. 20. Lenormant, H., Rubens! D., and Cottar<‘, 114.: Les Tumeurs Mixtes de la Joue & des Levres, Rev. de Chir. 38: l-38, 19cr. C. S.: An Inquiry Into the Origin of the Mixed Tumors of Sali21. Li, P. I., and Yang, vary Glands With Reference to their Embryonic Interrelationships, Am. J. Cancer 25: 259-272, 1935. Mixed Tumors of the Salivary Glands and Neck, Am. J. M. SC. 172: J.: 22. McFarland, 804, 1926. J.: Three Hundred Mixed Tumors of the Salivary Glands, Surg., Gpnec. $ 23. McFarland, Obst. 63: 457, 1936. Tumors of the Parotid Region, Surg., Gynec. & Obst. 57: 104-114, 1933. J.: 24. McFarland,

694

2: 27. 28. 29. 30. 31. 32. 33. it: 36. 37. 38.

lIAROlD

S. Fl,EMING

of the Salivary Glands, Am. ,J. M. SC. 174: 362-378, 1927. McFarland, J. : Adenomas The Histonatholoaical Prognosis of Salivary Gland Mixed Tumors. McFarland. J.: Am. J: M. SC. 203: 502-519, 1942. The Mysterious Mixed Tumors of the Salivary Glands, Surg., Gynec. McFarland, J.: & Obst. 76: 23-34, 1943. Ueber gemitsche Geschwulste der Parotis, Inaugural Dissertation, GitMinssen, H.: tengen, 1874, G. Hofer. Mixed Tumors of the Throat, Mouth and Face, Tr. Sect. Laryng., Otol. New, 0. B.: 65 Rhin., A. M. A. 33: 1930. Tumors of Tonsil and Pharynx, Arch. Otolaryng. 14: New, G. B., and Childrey, ..I. H.: 699-730, 1931. Paus, N.: Mischgeschwulsts der Gesichts, Beitr. z. path. Anat. 70: 96-120, 1922. Rawson, A. J., Howard, J. M., Royster, H. P., and Horn, R. C.. Jr.: Tumors of the Salivary Glands, Cancer 3: 445-458, 1950. Stout, A. P.: Tumor Seminar, Texas State J. Med. 41: 564, 1946. Thoma, K.: Oral Pathology, ed. 2, St. Louis, 1944, The C. V. Mosby Company. Virchow, R. L. Ii’.: Die Krankhaften Geschwulste, Berlin, 1863, A. Hirschwald. Volkman, R. : reber endotheliale Geschwulste, Deutsche. Ztschr. f. Chir. 41: l-180, 1895. Ward, G. E.: Tumors of the .Jaws, ORAL SURG., ORAL MED., AND ORAL PATH. 5: 675704,

1952. Wood, F. C.:

Mixed

Tumors

of

Salivary

Glands,

Ann.

Surg.

39:

57-97,

207-239,

1904.