Malignant Tumors of Salivary Gland Origin:37-Year Review of 184 Cases

Louis ROSENFELD,* M.D., DONALD G. SESSIONS,* * M.D.,BARTON MCSWAIN, M.D., HERSCHEL GRAvEs, JR., M.D.

From the Departments of Surgery and Pathology, Vanderbilt University Schoolof Medicine, Nashville, Tennessee

CARCINOMA of salivary glands is uncom-mon, comprising approximately 25 per centof salivary gland neoplasms. It arises in theparotid, submaxillary and sublingual glands,in minor glands in the lips, oral cavity,pharynx, upper respiratory tract, and inaberrant salivary tissue about the head andneck. In a review of 184 patients, we wereimpressed by the unpredictable course ofsuch lesions, chronicity, multiple recur-rences and stubborn persistence. Stewart,Foote and Becker 19 in 1945 elucidated themuco-epidermoid tumors. In 1946 Quattle-baum, Dockerty and Mayo 15 shed lighton the adenoid cystic adenocarcinomas,commonly known as cylindromas. In 1953Foote and Frazell 7 published their classicalreport on 877 tumors of the major salivaryglands, 223 of which were malignant. Thisreport formed the basis for the ArmedForces Institute of Pathology fascicle onmajor salivary gland tumors.2' In 1954Frazell8 discussed clinical aspects of thedisease. He analyzed 201 determinate caseswith malignant tumors and found that 40.5per cent survived for 5 years. He statedthat this figure may be too optimistic re-garding cure in view of the prolongedcourse of some patients. About 50 per centof the tumors were recurrent when first

Presented before the Southern Surgical As-sociation, Hot Springs, Virginia, December 7-9,1965.

* Address report requests to 11211 21st Ave.,South Nashville, Tenn. 37212.

** Present address: Barnes Hospital, St. Louis,Missouri.

seen. Most reports of malignant salivarygland tumors are clinicopathologic studiespertaining to a specific site of origin, or toa specific histologic type.1-6 9-12, 14, 16-18, 20,22-24

Management of patients with such tu-mors is difficult. We have reviewed theclinical course of 184 patients to secure datawhich will better enable us to comprehendand treat the disease.

Material

Case records of 184 patients who hadmajor or minor salivary gland carcinomasduring the years 1928 to 1965 were securedfrom the files of Vanderbilt University,Nashville General, St Thomas, Mid-StateBaptist and Thayer Veterans' Hospitals. Pa-tients with malignant lymphomas or carci-noma metastatic to salivary glands wereexcluded from this series. Such an extendedstudy period involves a lack of uniformityin management of patients but provides abroad perspective of the natural courseregardless of management. We have currentdata on 183 patients (99.5%o). Microscopicsections have been reviewed in all cases.In 23 patients the disease on admission wastoo far advanced for other than palliativetreatment. Fifteen patients died of inter-current disease.

Clinical EvaluationSex. There were 99 males and 85 fe-

males. This relatively even sex distributionis in contrast to the much higher proportion

726

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MALIGNANT TUMORS OF SALIVARY GLAND ORIGIN 727TABLE 1. Site of Origin

Submaxillary Sublingual Lips, Tongue Misc.Palate Salivary Salivary Oral Cavity (Neck,

Cell Type Parotid Maxilla Gland Gland Pharynx Larynx Cheek) Totals

Adenocarcinoma 39 10 4 1 7 - 1 62

Low-grade muco-epi- 13 2 1 1 2 1 20dermoid carcinoma

High-grade muco-epi- 13 4 3 1 1 22dermoid carcinoma

Adenoid cystic adeno- 6 4 4 3 3 - 20carcinoma

Squamous cell carcinoma 13 - 7 - - - 20

Malignant mixed tumor 7 3 3 1 14

Acinic cell adeno- 3 1 1 5carcinoma

Unclassified carcinoma 18 1 1 - 1 21

Totals 112 23 24 4 14 3 4 184

of males who have squamous cell carcinoma 40 to 80 years, being almost equal in eacharising from surface epithelium of the face, decade. Only two squamous cell carcinomasneck and oral cavity. began under age 41, while about one half

Site of Origin. 112 (60%) of the 184 of the low-grade muco-epidermoid carci-tumors originated in the parotid gland. nomas began in patients under age 51.24 arose in the submaxillary salivary gland Otherwise, the age incidence is ratherwhile only four arose in the sublingual evenly distributed as to cell type.salivary gland. The palate and maxilla were Cell Type. Neoplasms (184) have beenthe sites of origin of 23. Table 1 shows the classified, as nearly as possible, to coincideanatomic distribution of the lesions in rela- with the groups as presented in the A.F.I.P.tion to cell types. fascicle on tumors of major salivary glandsAge. Age by decades, at onset of symp-toms and according to cell type, is shown in uTable 3). Carcinomas arising in salivaryTable 2. There are five patients under 10 tissue range in aggressiveness from rela-years of age at the onset of their disease, tively indolent to highly malignant.and these five are divided among three The surgical procedure is planned accord-cell types. The greatest frequency is from ing to the pathologists' interpretation of

TABLE 2. Age at Onset of Symptoms

Cell Type 0-9 10-19 20-29 30-39 40-49 50-59 60-69 70-79 80-89 90+

Acinic cell adenocarcinoma 1 2 1 - 1Low-grade muco-epidermoid carcinoma 2 - 4 2 5 2 4 1 - -

Malignant mixed tumor 5 1 4 1 1 2 -Adenoid cystic adenocarcinoma - 4 4 1 4 5 2 -

Adenocarcinoma 1 4 11 9 14 11 10 1High-grade muco-epidermoid carcinoma 1 3 2 7 5 2 2 -Unclassified carcinoma 2 1 2 1 4 5 5 1Squamous cell carcinoma 1 1 3 3 6 4 2

Totals 5 2 21 24 31 33 36 27 3 1

728 ROSENFELD, SESSIONS, McSWAIN AND GRAVES

TABLE 3. Cell Type of Salivary Gland Carcinoma

PerCell Type No. Cent

Acinic cell adenocarcinoma 5 3Low-grade muco-epidermoid carcinoma 20 11Malignant mixed tumor 14 7Adenoid cystic adenocarcinoma 20 11Adenocarcinoma 62 34High-grade muco-epidermoid carcinoma 22 12Unclassified carcinoma 21 11Squamous cell carcinoma 20 11

Total 184 100

the neoplasm. Salivary gland tumors do notfall into neatly, well defined classifications,with each neoplasm having a preferredtreatment and a predictable future. Twenty-six of 184 lesions were originally diagnosedmicroscopically as benign. Microscopic sec-tions from one portion of a tumor may sug-gest a low degree of maligancy while asection from a different portion may revealgreater invasive characteristics. Obviously,therefore, small biopsies may not showthe nature of the lesion. The diagnosis oftenwill be made from frozen sections, which,despite excellent cryostat technic, are in-ferior to permanent sections.McFarland in 194213 demonstrated the

inability of a group of 25 pathologists to

TABLE 4. Data on 7 Patients Who Survized Morethan 21 Years after Recognition of

Pulmonary Metastases

Years Duration ofNo. Since Disease to

Cell Type Cases Noted* Date (Years)

Adenocarcinoma 512 L 23 122 4 1, 621

Low-grade muco-epi- 1 21 L 61dermoid carcinoma

Adenoid cystic adeno- 3 L 14carcinoma 2 51 D 161

Malignant mixed 1 21 D 141tumor

Unclassified car- 1 4 L 1512cinoma

* 12 patients lived over 1 year after pulmonarymetastases noted.

Annals of SurgeryMay 1966

TABLE 5. Local Recurrence (Curative Attempts-Minus Operative Deaths)

Per Cent

Acinic cell adenocarcinoma 0Low-grade muco-epidermoid carcinoma 26Malignant mixed tumor 50Adenoid cystic adenocarcinoma 53Adenocarcinoma 33High-grade muco-epidermoid carcinoma 58Unclassified carcinoma 50Squamous cell carcinoma 53

Total 40

prognosticate the likelihood of recurrence

in 50 cases of so-called benign mixed tu-mors. Predictions were correct in 52 per

cent and in error in 48 per cent. There was

some disagreement among the 25 patholo-gists on the interpretation of every slide.WVe gave microscopic slides from 76 tumorsto pathologists and asked for opinionsregarding prognosis. Their interpretationswere correct in 66 per cent and incorrectin 34 per cent. This further emphasizes thatpredicting the future clinical courses ofpatients with salivary gland carcinoma isdifficult.

Natural History. A review of the rec-

ords confirmed our impression that many

of these neoplasms might be called "chroniccancers." While some of the more aggres-sive lesions force the patient to seek med-ical help within a few months of onset, itis not unusual for a patient to carry un-

treated a less aggressive lesion for 5, 10and even 15 years.

TABLE 6. Cervical Node Metastases in Relation to CellType (Proved Microscopically)

PerNo. Cent

Acinic cell adenocarcinoma 0 0Low-grade muco-epidermoid carcinoma 2 10Malignant mixed tumor 3 21Adenoid cystic adenocarcinoma 1 5Adenocarcinoma 13 21High-grade muco-epidermoid carcinoma 10 45Unclassified 6 29Squamous cell carcinoma 8 40

MALIGNANT TUMORS OF SALIVARY GLAND ORIGIN

80

70

SC3C49U)

60

40

tn

2C

|-_-___

-_

lye 15- Z-3 3-4 4-5 5-10 1-20 21-25 26-30 30#

TIME (Years)

FIG. 1. Duration of symptoms beforedefinitive treatment.

Data on the year symptoms began in181 patients are presented in Figure 1.Fifty-eight per cent knew their tumors were

present for more than one year, and in26 per cent the lesions were evident formore than 5 years. Seventeen patients hadneoplasms for more than 15 years and threefor longer than 30 years. In Figure 2 theduration of disease in 81 patients who died,including seven operative deaths, is plotted.Thirty-five patients had their disease forover 5 years, and 12 for over 15 years. Only13 died within one year of onset. Thecourse of many of the tumors is a slow butsteady progression. Therapeutic success de-pends, among other factors, on the stage ofdisease at which operation is performed.Pulmonary Metastases. Extended sur-

vival is also evident in many patients whohad pulmonary metastases. Twenty-ninepatients had x-ray, operative, or autopsyevidence of extension to the lungs. Twelvesurvived for over one year, and seven forover 21/2 years after metastases were firstnoted. Table 4 summarizes this data.Figures 3-5 illustrate x-ray films of three ofthe patients.

Local Recurrences. Twenty-two per centof the 184 patients underwent one to fiveoperations before admission to our hos-

pitals. Forty per cent of patients in our

hospitals required additional operations for

c10 11 | | I I 1 l l l l 11|1

Iyr. I-Z 2-3 3-4 4-5 5-10 10-15 15-20 20-25 25-30 30-

TIME (Years)

FIG. 2. Total duration of disease in 81 patients whohave died as a result of their neoplasm.

local recurrences. Of 161 patients in whomcurative operations were attempted, seven

died postoperatively. There were, therefore,154 patients susceptible to recurrences, and64 (40%) had local recurrent disease.Local excision or enucleation of the tumorwas performed in 86 (53% ) of the 161curative attempts. Table 5 illustrates thefrequency of local recurrence in relationto cell type.

Cervical Metastases. With palpablelymph nodes in the neck, radical neck dis-section is indicated. Decision as to advis-ability of prophylactic neck dissection ismore difficult. Of 62 patients who under-went neck dissection, metastatic carcinomawas present in 43 (70%) and absent in 19(30%). Five-year survival of those withcancer in nodes was 33.3 per cent, whereas62.5 per cent of those in whom no cervi-cal nodes were involved survived 5 years.

Table 6 shows that high-grade muco-epi-dermoid and squamous cell carcinomas are

most likely to spread to cervical nodes.None of five patients with acinic adeno-carcinoma, and only one of 20 with ade-noid cystic adenocarcinoma, had cervicalnode metastases. These data suggest thatwith aggressive unclassified carcinoma,high-grade muco-epidermoid, and squa-

mous cell carcinoma, neck dissection in theabsence of palpable cervical lymph nodesis justified.

Survival. These malignant neoplasms, inmost instances, existed for many years.

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729

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ROSENFELD, SESSIONS, McSWAIN AND GRAVES Annals of SurgeryMay 1966

TABLE 7. Five-Year Survival in Relation to Cell Type

Potential Five-yearSurvivors Survivors Determinate Cases

Per Cent ofDeterminate Cases

Acinic cell adenocarcinoma 2 1 1 100Low-grade muco-epidermoid carcinoma 14 13 (1 c disease) 13 100Malignant mixed tumor 9 7 8 87Adenoid cystic adenocarcinoma 14 12 (2 c disease) 14 86Adenocarcinoma 43 22 41 54High-grade muco-epidermoid carcinoma 18 7 18 39Unclassified carcinoma 18 5 (1 c disease) 16 31Squamous cell carcinoma 14 3 13 21

Totals 132 70 (4 c disease) 124 55

TABLE 8. Ten-Year Survival in Relation to Cell Type

Potential Ten-year Per Cent ofSurvivors Survivors Determinate Cases Determinate Cases

Acinic cell adenocarcinoma 2 1 1 100Low-grade muco-epidermoid carcinoma 4 4 4 100Malignant mixed tumor 6 4 6 66.6Adenoid cystic adenocarcinoma 7 4 (1 c disease) 7 57Adenocarcinoma 29 12 27 44High-grade muco-epidermoid carcinoma 10 1 9 11Unclassified carcinoma 15 3 (1 c disease) 13 23Squamous cell carcinoma 6 2 6 33

Totals 79 31 (2 c disease) 73 42

TABLE 9. Fifteen-Year Survival in Relation to Cell Type

Potential 15-year Per Cent ofSurvivors Survivors Determinate Cases Determinate Cases

Acinic cell adenocarcinoma 1 1 1 100Low-grade muco-epidermoid carcinoma 3 2 2 100Malignant mixed tumor 4 1 4 25Adenoid cystic adenocarcinoma 4 1 (c disease) 4 25Adenocarcinoma 17 2 14 14High-grade muco-epidermoid carcinoma 5 0 5 0Unclassified carcinoma 13 1 12 8Squamous cell carcinoma 2 0 2 0

Totals 49 8 (1 c disease) 44 18

Prolonged follow up is mandatory to de-termine ultimate results of therapy. Tables7-9 demonstrate 5, 10 and 15-year sur-

vivals of all patients except one whose dateof death could not be determined, and 15patients who died of other diseases. Thesedata show the relationship of time ofsurvival to cell type. This relationship isfurther emphasized in Table 10 which

shows the type of neoplasm in 81 patientswho died. The aggressive tumors composedof adenocarcinomas, high-grade muco-epi-dermoids, unclassified and squamous cellcarcinomas have a poor prognosis. In con-

trast, acinic cell, low-grade muco-epider-moid and adenoid cystic adenocarcinoma,and malignant mixed tumors, are less ag-

gressive. With less aggressive neoplasms,

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Volume 163Number 5

MALIGNANT TUMORS OF SALIVARY GLAND ORIGIN

7

FIG. 3. Patient L. D. Adenoid cystic adenocarcinoma of hard palate. Chest x-rays left:March 1963. Right: September 1965. Living with disease 14 years.

wu_kI....... M...NR

;' FIG. 4. Patient M. E. Unclassified malignant salivary gland carcinoma arising in left upperlateral neck. Chest x-rays left: November 1961 prior to excision of the solitary metastasis tothe lingula. Right: October 1965 living with disease 13% years.

recurrence may be late in developing. Eventhough such lesions are frequently first seenat a late stage of disease and poorly treatedas compared with present standards it isremarkable that 55 per cent of patientssurvived for 5 years, 42 per cent for 10years, and 18 per cent for 15 years. Table11 compares survival of patients treatedbefore 1951 with those treated from 1951to 1961. There is an appreciable improve-ment in results in the past 10 years.

DiscussionPrognosis in any patient with malignant

disease depends essentially on three fac-tors: 1) cell type, 2) stage of the diseasewhen first seen and 3) adequacy of treat-ment.The cell type of salivary gland carcinoma

is of extreme importance. The stage atwhich patients with this disease are treatedcan only be improved by education andbetter understanding of potential dangers.

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ROSENFELD, SESSIONS, McSWAIN AND GRAVES Annals of SurgeryAMay 1966

FIG. 5. Patient A. H. Adenocarcinoma, of parotid Chest xrays left December 1961.

Right: May 1965. Living with disease 61/2 years.

TABLE 10. Patients Dead of Disease in Relationto Cell Type

No. PerPatients Dead Cent

Acinic cell adenocarcinoma 5 0 0

Low-grade muco-epidermoid 20 2 10carcinoma

Malignant mixed tumor 14 3 21.4

Adenoid cystic adeno- 20 6 30carcinoma

Adenocarcinoma 62 30 48

High-grade muco-epidermoid 22 13 59carcinoma

Unclassified carcinoma 21 14 66.6

Squamous cell carcinoma 20 13 65

Totals 184 81 44

Adequate surgical extirpation, avoidinglocal excisions or enucleations, should im-prove results. The obvious parotid carci-noma with skin involvement, facial nerveparalysis or cervical node metastases re-quires wide local exenteration and radicalneck dissection. Smaller encapsulated, mo-

TABLE 11. Comparison of Survival of Patients Before1951 with those Treated from 1951 to 1961

5 Years 10 Years 15 Years

1928 to 1951 45% 34% 18%1951 to 1961 60% 45% -

bile and seemingly innocuous parotid tu-mors are most often mistreated. The proper

surgical approach to all apparently benignparotid neoplasms is lateral lobectomy,identifying the facial nerve as it comes outof the stylomastoid foramen before its firstbifurcation, preserving, if possible, its rami-fications and removing the lobe with thetumor intact. The specimen is submitted tothe pathologist for frozen section. Gross ap-

pearance will provide information as to in-filtration. One or more upper cervical nodesobtained early in the operation are alsosubmitted to the pathologist. Metastaticdisease in a lymph node is easily identi-fiable. Should frozen section of the primarytumor show acinic cell or a low-grademuco-epidermoid carcinoma, total paroti-dectomy with preservation of the facialnerve is carried out. If an aggressive neo-

plasm is found, radical neck dissection withexenteration of the parotid area is war-

ranted. We do not do aspiration or in-

cisional biopsies. Malignant mixed tumors

and adenoid cystic adenocarcinomas shouldbe treated more radically than has beencustomary. We employ total parotidectomy,preserving, if possible, the facial nerve

fibers to the eyelids.Submaxillary and sublingual gland le-

sions are suitable for ipsilateral radical neck

732

Volume 163 MALIGNANT TUMORS OF SALIVARY GLAND ORIGIN 733Number 5

dissection. Occasionally the floor of themouth and at times a portion of the man-dible must be sacrificed. Lesions arising inthe palate require resection of the maxilla.Cervical node metastases may be evidentin patients with minor as well as majorsalivary gland carcinoma.

Patients are asked to return for post-operative examinations as long as theylive. Cervical node metastases have de-veloped after 9 years free of disease. Threepatients had solitary pulmonary metastasesremoved and all subsequently had multiplepulmonary metastases. One is living for 4years and another for more than 5 yearssince thoracotomy. Irradiation alone has notbeen used as a curative procedure but asadjuvant treatment during the immediatepostoperative period in patients with squa-mous cell and high-grade muco-epidermoidcarcinomas. Irradiation therapy may alsoalleviate pain in patients with incurabledisease.

Summary and Conclusions

Hospital records of 184 patients with pri-mary salivary gland carcinoma have beenreviewed for a 37-year period and the clini-cal manifestations and results of treatmentpresented.The data suggest that prognosis and

choice of surgical treatment are dependentupon accurate identification of the cell typeof salivary gland carcinomas.

Survival for 5 to 10 years or longer isnot unusual, creating a false sense of se-curity regarding local excision or enuclea-tion of malignant tumors of salivary glands.

Prognosis can be improved by an under-standing that a seemingly innocuous, pain-less nodule in a salivary gland may beserious.The neoplasms comprise eight cell types,

four of which are aggressive and have apoor prognosis and four of which are lessaggressive though difficult to eradicate.

The natural course of most of these tu-mors is characterized by long duration, re-peated local recurrences and frequent me-tastases to regional lymph nodes and to thelungs.Wide surgical extirpation, the extent a

function of tumor type, is the treatment ofchoice.

References

1. Abrams, A. M., Cornyn, J., Scofield, H. H.and Hanson, L. S.: Acinic Cell Adenocarci-noma of the Major Salivary Glands. Cancer,18:1145, 1965.

2. Bhaskar, S. N. and Bernier, J. L.: Muco-Epi-dermoid Tumors of Major and Minor SalivaryGlands. Cancer, 15:801, 1962.

3. Byars, L. T. and Ackerman, L. V.: Letter tothe Editor. J.A.M.A., 152:354, 1953.

4. Chaudhry, A. P., Vickers, R. A. and Gorlin,R. J.: Intraoral Minor Salivary Gland Tu-mors. Oral Surg., 14:1194, 1961.

5. Clifford, R. H., Kelly, A. P., Jr. and Brush, B.:Primary Cancer of the Salivary Glands. Plast.Reconstr. Surg., 19:478, 1957.

6. Fine, G., Marshall, R. B. and Hom, R. C., Jr.:Tumors of the Minor Salivary Glands. Can-cer, 13:653, 1960.

7. Foote, F. W., Jr. and Frazell, E. L.: Tumorsof Major Salivary Glands. Cancer, 6:1065,1953.

8. Frazell, E. L.: Clinical Aspects of Tumors ofMajor Salivary Glands. Cancer, 7:637, 1954.

9. Gaisford, J. C. and Hanna, D. C.: SalivaryGland Tumors and Miscellaneous AssociatedProblems. Plast. Reconstr. Surg., 19:458,1957.

10. Grage, T. B. and Lober, P. H.: Malignant Tu-mors of the Major Saiivary Glands. Surgery,52:284, 1962.

11. Gray, J. M., Hendrix, R. C. and French,A. J.: Muco-Epidermoid Tumors of SalivaryGlands. Cancer, 16:183, 1963.

12. Hendrick, J. W.: The Treatment of Tumors ofMinor Salivary Glands. Surg. Gynec. Obstet.,118:101, 1964.

13. McFarland, J.: Histopathologic Prognosis ofSalivary Gland Mixed Tumors. Amer. J. Med.Sci., 203:502, 1942.

14. Moran, John J., Becker, Stanley M. and Brady,L. W.: Adenoid Cystic Carcinoma. A Clini-copathologic Study. Cancer, 14:1235, 1961.

15. Quattlebaum, F. W., Dockerty, M. B. andMayo, C. W.: Adenocarcinoma CylindromaType of Parotid Gland: Clinical and Patho-logic Study of 21 Cases. Surg. Gynec. Ob-stet., 82:342, 1946.

16. Rawson, A. J., Royster, H. P. and Horn, R. C.,Jr.: Tumors of Salivary Glands; Clinico-pathological Study of 160 Cases. Cancer, 3:445, 1950.

17. Simons, J. N., Beahrs, 0. H. and Woolner,L. B.: Tumors of the Submaxillary Gland.Amer. J. Surg., 108:485, 1964.

734 ROSENFELD, SESSIONS, MIcSWAIN AND GRAVES Annals of SurgeryMlay 1966

18. Slaughter, D. P., Southwick, H. WV. and Wal-ter, L.: Fate of Recurrent or Persistent Paro-tid Tumors. Surg. Gynec. Obstet., 96:535,1953.

19. Stewart, F. W., Foote, F. XV. and Becker,W. F.: Muco-Epidermoid Tumors of SalivaryGlands. Ann. Surg., 122:820, 1945.

20. Thomas, W. H. and Copp, E. D.: DistantMetastases From Mixed Tuimors of the Sali-vary Glands. Amer. J. Surg., 109:724, 1965.

21. Tumors of the Major Salivary Glands: SectionIV, Fascicle II, Atlas of Tumor Pathology.

Washington, D. C., The Armed Forces In-stitute of Pathology, 1954.

22. Vandenberg, H. J., Jr., Kambouris, A. andPryzybylski, T.: Salivary Tumi1ors. Clinico-pathologic Review of 190 Patients. Amer. J.Surg., 108:480, 1964.

23. Vellios, F. and Davidson, ID.: Natuiral Historyof Tumors Peculiar to Salivary Glands. Amer.J. Clin. Path., 25:147, 1955.

24. Wawro, N. W. and MIcAdams, George: Cylin-dromata of Major and Mlinor Salivary Glands.Arclh. Surg., 68:252, 1954.

DISCUSSION

DR. HARWELL WILSON (Memphis): I thinkthere is a tremendous amount of very worthwhilematerial in this presentation, which you will beable to see when you have an opportunity to studythis manuscript, as I was privileged to do yester-day. I rise to emphasize two points which Dr.Rosenfeld brought out, and to cite certain figuresfrom our institution-the Cancer Clinic of theUniversity of Tennessee at MIemphis-which I be-lieve tend to substantiate some of the points thathave been brought out by Dr. Rosenfeld.

First, I think that it is certainly worthy ofemphasis-and we should also remember-that thecharacteristic microscopic appearance of these tu-mors varies tremendously in different areas of thetumor. Therefore, a small frozen section or apermanent section from only one area may ac-tually mean very little. The tumor may appearbenign in one area, and it may appear very malig-nant in another.

A second thing which is obvious to all of us,I think, who are fair-minded, and particularly tothose of us who during our training were privilegedto spend a certain period of time in a surgicalpathology laboratory, is to recall again the limita-tions of the method. This has nothing to do withthe competency of the pathologist, but essentiallyis a limitation of the pathologic method, as wasshown in 1942 by MacFarland, that the pathologistis unable to predict accurately the outcoimie in per-haps half of the cases, and by Dr. Rosenfeld'sstudy revealing that competent pathologists canpredict the outcome in approximately two-thirds ofthe cases.

Dr. Ralph Braund, who is the Director of ourCancer Clinic, and Dr. J. D. Piggot, also of ourfaculty, have been interested in studying this prob-lem, and I asked them to allow me to quote thefigures which they have recently summarized. It'sinteresting that as of December 31, 1964, therehave been 203 parotid tumors. Of this number,140 were benign and 63 malignant. There havebeen 63 submaxillary tumors. However, 39 ofthese were malignant, and 24 were benign. Ac-cessory salivary gland tumors-that is, intraoraltumors-total 52, 20 of which were benign and 32

mlalignant. It's rather interesting to note that of theparotid tumors 22 had had from one to fourprevious operative procedures. Facial nerve in-jury was present in 25%o of the malignant patients.The over-all survival rate in the malignant lesionswas 63%, of those followed by Drs. Braund andPiggot for 5 years.

DR. BARTON MICSWAIN (Nashville): I had tolook at the slides on all these 184 patients (rang-ing from one to 12 slides on each patient). Therewere about a thousand sections, and I learned acouple of things from that.

One thing that might be thought is: in viewof the fact that the outlook was so bad in thesesquamous cell carcinomiias, perhaps they were notprimiary salivary gland squamous cell carcinomas,but metastases from some undiscovered primarysite. However, as we went over the sectionsthe final time, we threw out a good many of themwhich had been found to be secondary from aprimary site. I think it is highly unlikely, in viewof that careful scanning and the number of yearsthat these were followed, that they were anythingexcept primary squamous cell carcinoimias of thesalivary gland.

The other point, although it has been oftenquoted from 'MacFarland, that it is impossible topredict whether or not a benign mixed tumor willrecur on the basis of the microscopic appearance,in a microscopic study of these malignant salivarygland tumors one can prognosticate pretty well onthe basis of the microscopic findings.

All other things being equal, (in those rela-tively low grade ones-that is, the acinic cell car-cinomas, the adenoid cystic adenocarcinomas, thelow grade muco-epidermoid carcinomas, and themalignant mixed tumors) the outlook is much betterthan in the other group of unqualified adenocar-cinomas, the high grade muco-epidermoid car-cinomas, the squamous cell carcinomnas, and thosewhich fall into none of these other seven cate-gories.

The final point is not entirely relevant to thispaper, but it is made with the intention of makingsome people indignant enough to strengthen theirefforts along this line: as you have noticed, we