- Email: [email protected]
Acinic cell tumors of minor salivary gland origin
oral pat hology Editor:
CHARLES E. TOMICH, D.D.S., M.S.D. Academy of Oral Pathology
American
Indiana University School of Dentistry I 121 West Michigan Street Indianapolis, Indiana 46202
Acinic cell tumors of minor salivary gland origin Albert M. Abrams, D.D.S., Los Angeles, CalijY DEPARTMENT SOUTHERN
OF PATHOLOGY,
MS.,
and Raymond
SCHOOL
OF DENTISTRY,
J. Melrose,
D.D.S.,
UNIVERSITY
OF
CALIFORNIA
Acinic cell tumors of minor salivary glands are most uncommon. Search of the English language literature revealed twenty previously reported cases. Nine additional cases are newly described. Most patients presented with asymptomatic swellings, but pain and tenderness were experienced by some. Sites of involvement were variable, with the palate, tongue, and floor of the mouth being the most commonly afflicted. One new case occurred centrally within the mandible. There was no sex predominance. A spectrum of histomorphologic characteristics included solid, microcystic, papillary cystic, and follicular patterns composed of acinic, intercalated duct, vacuolated, and nonspecific glandular cells. Follow-up data on ten cases from the literature and the nine new cases revealed that one patient died of tumor, one was alive with distant metastases, and one had been successfully treated for local recurrence. The patient representing the single fatality was treated by irradiation only. Surgical excision with a border of normal tissue seems to be effective treatment. The use of “carcinoma” as an appropriate designation for this neoplasm is questioned.
A cinic cell tumors (ACT) representa well-established, albeit uncommonentity in the classification of neoplasmsof salivary gland origin. Most of what is known about this tumor has been derived from studiesof those occurring in major glands, and characteristics have been well documentedduring the past 25 years.‘, 12**j* 2sAlthough data vary, acinic cell tumors compriseabout 2.5 percent of parotid tumors4*13*3oand 17to 19percent of parotid gland malignant neoplasms.4 Women are afflicted more often than men; occurrence in children is consideredto be rare.2 This investigation was supported in part by the California Tumor Tissue Registry, Los Angeles County/USC Medical Center, and by Grant IR25CAl9270-02 awarded by the National Cancer Institute, Department of Health, Education and Welfare.
220
0030-4220178102460220.$01.40/O
0
1978 The C. V. Mosby
Co.
Volume 46 Number 2
Acinic cell tumors of minor salivary gland origin
221
Because histopathologic features are often markedly similar to normal serous cells, some investigators believe that tumors are derived from acinar cells.“* I5321*3oHowever, the presence of intercalated duct-type cells and the considerable variety of histomorphologic patterns suggest tumor origin from the more pluripotential duct cells, as do the serous cells in normal gland development.‘, 6 In spite of a fairly broad spectrum of microscopic features, attempts at correlating histomorphologic characteristics with clinical features, anticipated behavior, and prognosis have been unsuccessful .*, 12*3o Attempts to identify and separate a benign variety from those possessing malignant potential so far have failed, even with the use of microspectrophotometric DNA analysis. I3 Compared to many other salivary gland malignancies, patients with ACT have a relatively good prognosis (over 80 percent) on the basis of .5-year follow-up’5; however, long-term studies indicate a more ominous outlook, as recorded by the finding of Eneroth, Jakobsson, and Blanck12 of 56 percent survival at the end of 20 years. Not only are prognostic predictions risky, but sites of metastasis to include lung, bone, and brain in addition to lymph nodes suggest a potential for occasional hematogenous spread. I, I,3 Local recurrences tend to be multiple,15 a fact which may reflect more on variegated treatment than on tumor biology.’ Current custom seems to advocate the term “acinic cell tumor,” rather than the more menacing “acinic cell carcinoma,” as the most appropriate designation for a neoplasm which, in a vast majority of instances, behaves in a benign fashion.4, “3 3o But the unpredictable nature of the disease convinces others that “carcinoma” is a more meaningful label. “* 27 Recent experiences stimulated a search of the English-language literature in quest of information on ACT of minor salivary gland derivation. Twenty previously reported examples were discovered (Table I). Details of case characteristics were generally sparse and of questionable accuracy. For example, Fine, Marshall, and Horn” and Epker and Henny14 report the same case but give different sites of origin. Eight tumors were presented as single case reports,3* 5* 20, 24*16*2g, 31,32 two were reported together with fifteen parotid ACTS, and ten were included in papers describing minor salivary gland tumors in genera1.8, IO, 14, 17, 19, 22, 23, 26, 27, 28 Th e rarity of acinic cell tumors in minor salivary glands can be appreciated by the fact that (I) these ten tumors were incorporated in reports totaling 348 benign and 8 10 malignant tumors and (2) there were no examples in an additional twenty-two papers (not referenced) describing 154 benign and 751 malignant tumors. In view of the paucity of reported ACTS in minor salivary glands, we deemed it appropriate (and possibly valuable) to study and report the cases in our files and compare findings with what is known of those from the major glands. MATERIALS
AND METHODS
A search of the files at the University of Southern California School of Dentistry and the California Tumor Tissue Registry at Los Angeles County/USC Medical Center was conducted to find tumors that satisfied the following criteria: (1) possessed histopathologic characteristics that would identify the lesion as an ACT if origin was parotid gland,‘, “a 3o (2) could not be better classified as another type of salivary gland tumor, (3) had an adequate history to ensure that the tumor was unassociated with parotid or submandibular glands, (4) lacked histopathologic evidence of parotid or submandibular gland
222
Oral Surg. August, I978
Abrams and Melrose
Table I. Acinic cell tumors of minor salivary glands Age Author
Year
Site
(years)
Duration
Gorlin and Chaudbryts
1957
34
M
Tongue
-
Burbank, Docketty, and Devine’ Fine, Marshall, and Horn”* Baden and Wallet?
1959 1960 1965
63 50 75
M F F
Sublingual Tongue Tongue Floor of mouth
Unknown 4 yr.
Luccioli, Clement, and Palme? Rosenfeld and associatesz6 Suzuki and Hendersot? Epker and Hennyr4*
1965 1966 1968 1969
70 45 50
M M F
Pharynx Mouth, N.O.S. Floor of mouth Palate
1 yr. 8-10 mo. -
Hjertman and Enerothrg Belinfante and Verne5
1970 1970
80
F
Palate Buccal mucosa
1 mo.
Manace and Goldmar?
1971
47
F
10 mo.
Wertheimer and Georgen32
1971
72
F
Fechner, Bentinck, and AskewtG TrodahFr
1972 1972
63 51
M M
Right nasal cavity, maxillary sinus, ethmoidal sinus Lower canine-premolar vestibule Lung, lower right lobe Upper lip
Spiro and associates’s
1973
Ito and associate?”
1970
25
F
Gingiva Nasal cavity Left posterior mandible
Coates and associates’” Main and associatesz3 Sharkey”?
1975 1976 1977
62 29
M F
Palate Tongue
19
F
Unknown
Case 2 Case 3 Case 4 Case 5
Unknown 43 45 35
F M M F
Mandible, left third molar area Palate Lower lip Buccal mucosa Soft palate
Case 6
65
M
Anterior buccal mucosa
1 yr.
Case 7 Case 8
59 75
F F
Anterior buccal mucosa Soft palate
1 mo. Unknown
Case 9
65
M
Lower lip
4 yr.
Abrams and Melrose Case 1
*Same case, location reported differently. N.E.D.-No D.O.D.-Died of disease.
Unknown 2-3 yr.
3% yr.
-
-
evidence of disease. D.O.C.-Died
5 mo.
Unknown 1 yr. Unknown Unknown
of other causes.
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Acinic cell tumors of minor salivary gland origin
Signs and symproms
Therapy
-
-
Nonulcerated swelling Asymptomatic, nonulcerated, firm, movable, brown-red nodule, 1.3 x 0.6 cm. Mass Asymptomatic, 5 cm. diameter mass Nonulcerated swelling Rapidly growing asymptomatic, 2.5 cm. fixed mass Nonulcerated, polypoid mass and nasal obstruction Asymptomatic, firm, movable, 2 X 1 cm. mass Discovered on chest radiographs Moderately soft, well-demarcated mass, 2.2 cm. diameter Increasing painful mass beneath intact mucosa; radiolucency from mandibular foramen to first premolar -
Painful, well-demarcated radiolucency below impacted third molar Painful ulcerated swelling Slightly tender soft swelling Asymptomatic, firm, movable mass Asymptomatic, bluish nodule, 1.O cm.diameter Asymptomatic, 3 x 3 cm. hard mass Tender swelling 5 x 5 cm. mass filling much of nasopharynx Asymptomatic, 1.O cm. nodule
Excision; radium implantation Excision
Surgery-N.O.S. Excision Wide excision and radium implantation Excision Surgical resection
Lobectomy Resection
Block resection
-
223
Follow-up
Local recurrence and distant met. 4 years P.O. N.E.D.-20 yr. None N.E.D.-2 yr. None Recurrence, D.O.D.-6 N.E.D.-15 yr. N.E.D.-2 yr. N.E.D.-8 yr. None N.E.D.-2 N.E.D.-13
yr. mo.
N.E.D.-6
mo.
N.E.D.-2 None
yr.
None None N.E.D.-3
mo.
yr.
N.E.D.-8 yr. None 1 recurrence; alive 7 yr. posttreatment
En bloc resection
N.E.D.-3%
Excision and irradiation Wide local excision Wide local excision Excision with border of normal tissue Excision
N.E.D.-4 N.E.D.-4 N.E.D.-1 N.E.D.-3
yr. yr. yr. yr.
N.E.D.-2
yr.
Excision Irradiation- 5;4 11 rads
N.E.D.-4 N.E.D.-3
yr. yr. D.O.C.
Excision
N.E.D.-10
yr.
yr. D.O.C.
224
Oral Surg. August, I978
Abrams and Melrose
Fig. 1. Case I. A 19-year-old a dentigerous cyst.
woman
with a central intraosseous
Fig. 2. Case 6. A 65year-old man with an asymptomatic, and lip with protrusion into the mouth (A) and swelling
ACT simulating
the radiographic
appearance
hard ACT originating of the face (B).
in the anterior
buccal mucosa
of
origin. This quest produced nine cases that we believe qualify as ACT originating from minor salivary glands. Sections stained with hematoxylin and eosin from all cases were studied. RESULTS Clinical
features
Clinical data on each of these nine cases are presented in Table I. This was a disease of adults, with a fairly broad age range and an average age of 5 I years. There was no sex predominance. Location was variable, with the palate and buccal mucosa each accounting for three cases, the lower lip for two, and the mandible for one. The mandibular tumor was a completely intraosseous, 2.5 by I .5 cm., well-demarcated radiolucency with no connection whatsoever to the overlying soft tissue. It was situated inferior to the impacted third molar tooth (Fig. 1). Most were asymptomatic swellings, but four patients complained of tenderness or
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Acinic cell tumors of minor salivary gland origin
Fig. 3. Case 6. Photomicrograph composed of well-differentiated
225
of section of the ACT displayed in Fig. 2 featuring predominantly solid growth acinic cells. (Hematoxylin and eosin stain. Original magnification, X 100.)
pain. Size varied from 1.O to 5.0 cm. in diameter. None of the tumors had metastasized (Fig. 2). Histomorphologic
features
The histomotphologic characteristics seen in these tumors of minor salivary gland origin were essentially the sameas those which have been describedpreviously in major glands.‘, 12*15,3oThe tumors were composed, in varying proportions, of one or more of four cell types. These were designatedas acinic cells, intercalated-duct cells, vacuolated cells, and nonspecific glandular cells. Acinic cells resembledthe polyhedral cells of normal acini and contained abundant, finely granular cytoplasm possessinga basophilic hue of varying intensity (Figs. 3 and 4). Nuclei were generally small and hyperchromatic; however, in three tumors the nuclei of someacinic cells were larger and contained a single basophilic nucleolus-like condensation. Acinic cells were presentin all tumors and were the predominant constituents in six cases. Vacuolated cells-those characterized by either one or two large vacuoles or by multiple, extremely small ones-were seenin eight casesand were moderately abundant in three (Fig. 5). Cells were often distendedand seemedto have coalescedfrequently into groupsof small cysts separatedby a syncytial network of cytoplasm imparting a latticelike pattern. Nuclei were usually somewhatlarger than those of acinic cells. It is possiblethat these vacuolated cells are acinic cells which have been altered by a tissue-processing artifact. Intercalated duct cells were never the predominant cell type but were readily observed in six tumors (Fig. 6). These cuboidal cells with limited amphophilic cytoplasm and distinct borders were frequently scrambled with acinic cells and possessedsimilar-
226
Abrams and Melrose
Fig. 4. Case 8. Photomicrograph of uniform but faintly staining acinic cells in a solid growth ACT of the soft palate. (Hematoxylin and eosin stain. Original magnification, x 100.)
pattern
from
an
appearing nuclei. Cells of this type were sometimesarrangedin ductlike patterns. Ducts lined by two distinct cell types (epithelial and myoepithelial) commonly encountered in mixed tumors were not visualized in acinic cell tumors. Cells lacking specific features necessaryto categorize them into one of the first three groups were designated as nonspecific glandular cells and were present in moderate quantities in only three cases.These cells featured the most nuclear atypia and the only unequivocal mitotic activity. Cytoplasm was faintly eosinophilic or amphophilic and contained no granules. Cells characterized by nonstainablecytoplasm with distinct nondistendedcell borders were too infrequently seento justify a legitimate category of “clear cells.” The occasional examples appear to represent poorly stained varieties already described, with cytoplasm faintly stained as a result of faulty laboratory manipulations. There were a variety of growth patterns. A solid parenchymatous mass was the predominant morphologic trait in six tumors (Figs. 3 and 4). A significant microcystic configuration resulting from cell rupture and coalescenceof vacuoles was prominent in three casesbut was noted to somedegreein all tumors. Papillary-cystic morphology was a major component in one tumor and was presentto a slight extent in two additional cases. A follicular growth pattern resemblingthyroid follicles occurred in three tumors (Figs. 8 and 9, A). The follicular spacescontained homogeneousproteinaceous-appearingmaterial bounded by cuboidal or slightly elongated cells. There were no encapsulatedtumors. Three, including the intraosseousone (Case I), were blatantly infiltrative (Fig. 7). Apparent perineural invasion was discovered in only one instance (Case 5). Stroma tended to be sparseand generally consisted of narrow bands of moderately densefibrous connective tissue separatingtumor masses.
Volume 46 Number 2
Acinic cell tumors of minor salivary gland origin
227
Fig. 5. Case 9. Photomicrograph of portion of a lower lip ACT composed of vacuolated cells. (Hematoxylin and eosin stain. Original magnification X 100.)
There was calcification in only one tumor (Case6). This consistedof scatteredsmall, round, darkly basophilic calcospheritesresembling psammomabodies. The unique central ACT of the mandible (Case I) was prominently infiltrative and composedmostly of acinic-type cells with small dark nuclei, but a moderate number of intercalated duct cells were present (Fig. 9). Solid and microcystic tumor extended between bone trabeculae. Focal areasfeatured blood pigment and cholesterol depositsassociated with foreign body reaction and chronic inflammation, a feature frequently seenin other cases.Mitoses were rare. Therapy
and follow-up
data
Seven tumors were treated solely by surgical excision. Included in this group was en bloc surgical resectionfor the ACT of the mandible. Surgical excision followed by irradiation was the therapeutic method for one tumor of the palate (Case2), and a secondACT of the soft palate (Case8) was managedonly by cobalt-60 irradiation to a total of 5,411 rads. Follow-up data were obtained in all cases.There were neither recurrencesnor metastasisin any case. Follow-up duration ranged from 1to 10 years, with a meanof 3.8 years. DISCUSSION Incidence
The nine new cases reported here plus the twenty examples uncovered from the literature produced a total of such meager proportions that one must view occurrence of acinic cell tumors from minor glands as most uncommon, if not rare. Indeed, acceptance of all twenty previously reported cases as legitimate ACTS may be overly generous becauseten were included in papersdescribing large seriesof glandular tumors and the few listed in the acinic cell category were not illustrated. Also, the two lesionsof minor
220
Abrams
and Melrose
Fig. 6. Case 4. Photomicrograph of an ACT from the buccai mucosa featuring many intercalated duct type cells and a microcystic pattern. (Hematoxylin and eosin stain. Original magnification, x 100.)
gland lineage reported by Gorlin and Chaudhry18in their group of ACTS were not illustrated. Two of the single casereport?, *Oare poorly illustrated examplesbut are included here becausethey may be legitimate. Therefore, our searchdetected only six caseswhich appear to be unequivocal examples of ACT.33 16,24,2g,31,32 Clinical
features
It appearsthat ACTS of minor salivary glands have no characteristicsrelated to age, sex, symptoms, or signsthat would provide the clinician with clues asto the nature of the diseaseprior to biopsy. A ratio of 5 : 4 in favor of asymptomatic to painful swellings is fairly consistentwith data reported on major salivary gland ACTS.’ No significant differencesbetween casesfrom the literature and thosereported here were noted with regardto age and sex data, and female predominancenoted in casesof parotid origin*, l*, l5 was missingwith theseaccessorygland tumors. However, there was minor conflict in location as evidenced by the lack of tumors from the tongue and floor of the mouth, regions that also tend to be involved to a moderatedegreeby salivary gland tumors in general.g*23,28 Except for possibly the buccal mucosa and palate, no one site of origin seemedto predominate. It is obvious from Table I that a wide variety of siteshave been afflicted by ACTS. Certainly, the most unusual location is the mandible. Although central jaw origin for salivary gland tumors is well recognized,7 to our knowledge, intraosseousgenesisof an ACT has been reported only once before in the English-language literature.*O Such an occurrence might be anticipated, but the rarity of that phenomenonis also reasonablein view of the paucity of intraoral acinic cell tumors. Both central ACTS were painful mandibular lesions. Our casefeatured a radiolucency associatedwith the crown of an impacted third molar tooth, while the tumor reported by
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Acinic cell tumors of minor salivary gland origin
Fig. 7. Case 4. Photomicrograph main mass and tumor nification, X 100.)
nodules
of an ACT of the buccal mucosa characterized extending toward skeletal muscle. (Hematoxylin
229
by a pseudocapsule between the and eosin stain. Original mag-
Ito and associates20 was more anterior and lesssuggestiveof an odontogenic process.This lesion was also described, both grossly and microscopically, as encapsulated, a feature absent from all nine new cases reported here and contrary to the obvious infiltrative growth of our mandibular tumor. The patients with thesetwo central jaw lesions are the youngest (25 and 19 years) of all reported casesof ACT. Both were treated by en bloc resection, and neither tumor recurred during 3 years of follow-up observation. Histomorphologic
features
The histomorphologic characteristics of ACT of minor salivary glands were as variable as those of the parotid gland. Although a solid growth pattern predominatedin most of our cases,microcystic and, to a lesserextent, papillary-cystic configurations were also noted. ACTS may also display a follicular pattern resembling tissueof thyroid origin, a characteristic recognized previously in those of major salivary gland lineage.‘, 15,23We agree with Azzopardi2 that the presenceof “clear cells” in ACTS is uncommon and in most instances probably represents fixation and processing artifacts. Ultrastructural studiestend to support that view. l1 Cells with distinct bordersand no stainablecytoplasm were so sparse in well-prepared tissue sections that a category devoted to them was considered to be unjustified. Indeed, it is our impressionthat clear cells are seenmuch more frequently in mucoepidermoid tumors. The frequent and sometimesabundantlymphoid tissuefound in associationwith ACTS of parotid gland was absent from all casesreported here and was not described in the literature. This might be related to the absenceof normally occurring lymphoid tissue in most minor salivary gland-bearing areas. However, except for the Warthin tumor and sebaceouslymphadenoma, no other parotid gland tumor contains lymphoid tissue as
230
Oral Surg. August, 1978
Abrams and Melrose
Fig. 8. Case 5. Photomicrograph stain. Original magnification,
X
of follicular 100.)
pattern from an ACT of the soft palate. (Hematoxylin
and eosin
frequently as the ACT. Thus, the absenceof this component in minor gland ACTS may indicate the presenceof subtlebiochemical-immunologic disparitiesbetweenmorphologically similar tumors originating in different sites or from glands of divergent structure. Laminated concretions, another finding of moderately frequent occurrence in parotid ACTS, were noted in only one of our casesas small psammoma-likebodies and were not described in any case from the literature. In our experience these calcospheritescan be discovered occasionally in other types of salivary gland tumors, so they are not diagnostic of a specific tumor. Clincopathologic
correlation
and prognosis
Except for the finding that the papillary-cystic growth pattern seemsto be most prominent in palatal tumors, correlation between clinical features and histomorphology was unrewarding. Presentingclinical charactersticsappear to be unrelated to proportions of cell types, mitotic activity, nuclear and cellular atypia, and growth patterns; since no tumor hassofar recurred, correlation betweenhistomorphology and prognosisis meaningless. All tumors were unencapsulated,but this seemsto have little effect on prognosis. Irrespective of therapeutic manipulation, ACTS usually behave in a relatively benign fashion. In only one case so far reported did a patient definitely die of the tumor.22 Treatment in that instance was irradiation, a modality consideredto be ineffective in the managementof ACTS. However, even that assumptionmight be disputed, becausethe treatment of one of our cases(Case8) wasirradiation, and that patient died of other causes 3 years later without tumor recurrence. Actually, irradiation is usedtoo infrequently for its effectiveness to be adequately evaluated. A secondpatient mentioned in the literature had distant metastasisat the time of the report and may have died of tumor.‘* When data on surgical managementare known, it appearsthat excision generally includes a border of normal-appearing tissue. So far this therapy seemsto have been adequatefor cure in sixteen of seventeenoral casessummarized here. Enucleation was
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2
Acinic cell tumors of minor salivary gland origin
231
Fig. 9. Ca se 1, Photomicrographs of the central ACT of the mandible. A, Predominantly folk&r pattt :rn. B, Cord Isofa fell-differentiated acinic cells and vacuolated cells. (Hematoxylin and eosin stain. Original I mag ;nification, x lO( 1.)
liste :d as therapy in only one case, and follow-up con1clusic3ns.32 Nomenclature
of 6 months is too brief for act :urate
232
OralSurg.
Abrams ana’ Melrose
August, I978
neoplastic change, and because acinic cells originate from duct cells in normal gland development, This is speculation; referring to a precise cell of origin as if it were known is unscientific, if not nonsense. Nomenclature can be important to the patient, because type of treatment is often based solely upon the presence or absence of the word “carcinoma” in the label and not on an understanding of the biologic characteristics of the tumor, no matter how comprehensively these have been described. To us and to others, “acinic cell tumor” (“acinous” or “acinar,” if you prefer) seems to be the best designation and will likely result in the most appropriate treatment for the patient. 4~ls, 23*3o On the basis of what has been reported so far, it appears that ACTS of minor salivary gland origin should be removed with a generous border of normal tissue-treatment also appropriate for mixed tumors and low-grade mucoepidermoid tumors. Only one patient so far reported has succumbed to the disease, and this was following irradiation as exclusive therapy. It may be that those tumors of minor salivary gland lineage are biologically “less dangerous” than their counterparts in the parotid gland, but even in major glands it seems that the critical primary factor affecting the likelihood of recurrence is appropriate initial therapy.’ Incisional biopsy, enucleation, and in vivo abuse of the neoplasm significantly compromise prognosis. Certainly, ACTS are not totally innocuous. There have been thirty-two deaths due to neoplasm out of 259 major salivary gland ACTS reported in papers describing significant numbers of cases.4 But these are fairly old data, with the most recent major publication dated 1966.12 Most patients described in these reports were treated more than 20 years ago. Thus, lack of appreciation for the proper and currently well-recognized surgical approach to parotid tumors may account for some past therapeutic failures. In addition, large series of major salivary gland tumors are often reported from cancer centers, institutions which frequently treat the larger, sometimes recurrent, and therapeutically complex cases. Many minor salivary gland tumors are removed in outpatient clinics and in dentists’ and physicians’ offices. They tend to be relatively small tumors requiring a more simple therapeutic approach and are often not available for statistical analysis. The new cases of ACT reported here and many of those gleaned from the literature were apparently managed in such a milieu. This could account for a more favorable prognosis. Unfortunately, pathologists have yet to identify distinguising histologic features by which the occasional tumor having a more ominous potential can be recognized. However, this inability no more justifies labeling all acinic cell lesions “carcinoma” than it would to designate all squamous carcinomas of the tongue “tumors” is justified because some patients survive. The authors express their appreciation
to Drs. Weldon
Bullock,
Milton
Feinberg,
William
Volume 46 Number2
4,
Acinic celltumors ofminor salivary gland origin233
Batsakis, I,6,:Tumors ofthe Head and Neck, Baltimore, 1974, Tht Williams &Mkins Company, pp,
17-20. 5. Belinfante,L. S., and Verne, D.: IntraoralAcinic Cell Adenocarcinoma:Report of Case, I. Oral Surg. 28: 617-618, 1976. 6. Bhaskar, S. N.: Acinic Cell Carcinoma of Salivary Glands: Report of 21 Cases, ORAL SURG. 17: 62-74, 1964. 7. Browand, 8. 9. IO. I I. 12.
B. C., and Waldron, C. A.: Central Mucoepidermoid Tumors of the Jaws: Report of Nine Cases and Review of the Literature, ORAL SURG. 40: 63 I-643, 1975. Burbank, P. M., Dockerty, M. B., and Devine, K. D.: Clinicopathologic Study of 43 Cases of Glandular Tumors of the Tongue, Surg. Gynecol. Obstet. 109: 573-582, 1959. Chaudhry, A. P., Vickers, R. A., and GorIin, R. J.: Intraoral Minor Salivary Gland Tumors: An Analysis of 1,414 Cases, ORAL SURG. 14: 1194-1226, 1961. Coates, H. L. C., Devine, K. D., DeSanto, L. W., and Weiland, L. H.: Glandular Tumors of the Palate. Sing. Gynecol. Obstet. 140: 589-593, 1975. Echevarria, R. A.: Ultrastructure of the Acinic Cell Carcinoma and Clear Cell Carcinoma of the Parotid Gland, Cancer 20: 563-571, 1967. Eneroth, C.-M., Jakobsson, P. A., and Blanck, C.: Acinic Cell Carcinoma of the Parotid Gland, Cancer 19: 1761-1772,
13. 14. 15. 16. 17 18.
1966.
Eneroth, C.-M., Silfverswtd, C., and Zetterberg, A.: Malignancy of Acinic Cell Tumours Elucidated by Microspectrophotometric DNA Analysis, Acta Otolaryngol. (Stockh.) 77: l26- 130, 1974. Epker, B. N., and Henny, F. A.: Clinical, Histopathologic, and Surgical Aspects of Intraoral Minor Salivary Gland Tumors: Review of 90 Cases, 1. Oral Surg. 27: 792-804, 1969. Evans, R. W., and Cruickshank, A. H.: Epithelial Tumors of the Salivary Glands, Philadelphia, 1970, W. B. Saunders Co., pp. 98-119. Fechner, R. E.. Bentinck, R. B., and Askew, J. B.: Acinic Cell Tumor of the Lung: A Histologic and Ultrastructural Study, Cancer 29: 501-508, 1972. Fine, G., Marshall, R. B., and Horn, R. C.: Tumors of the Minor Salivary Glands, Cancer 13: 653-669, 1960. Gorlin, R. J., and Chaudhry, A.: Acinic Cell Tumor of Major and Minor Salivary Glands, 3. Oral Surg. 15:
304-306, 1957. 19. Hjertman, L., and Eneroth, 20. Ito, H., Soda, T., Asakura, 21
Tumor of the Mandible: Kay, S., and Schatzki, 235-244,
22 23 24
37 ,
28. 29. 30. 3 I. 32.
1972.
Luccioli, G. M., Clement, H., and Palmer, J. D.: An Analysis of 50 Carcinomas of the Salivary Glands, Can. J. Surg. 8: 389.399, 1965. Main, J. H. P., Orr, J. A., McGurk, F. M., McComb, R. J., and Mock, D.: Salivary Gland Tumors: Review of 643 Cases, J. Oral Path. 5: 88-102, 1976. Manace, E. D., and Goldman, J. L.: Acinic Cell Carcinoma of the ParanasaI Sinuses, Laryngoscope 81: 1072-1082,
2.5 26
C.-M.: Tumours of the Palate, Acta Otolaryngol. 263~ 179- 182, 1970. A., Nakajima, T., Kobayashi, Y., and Miyazawa, M.: Central Acinic Cell Report of a Case, Bull. Tokyo Med. Dent. Univ. 17: 239-247, 1970. P. F.: Ultrastructure of Acinic Cell Carcinoma of the Parotid Gland, Cancer 29:
1971.
Rivilin, R. S.: Acinic Cell Adenocarcinoma of the Parotid Gland, Am. J. Sury. 100: 639-642, 1960. Rosenfeld, L., Sessions, D. G., McSwain, B., and Graves, H.: Malignant Tumors of Salivary Gland Origin: 37 Year Review of 184 Cases, Ann. Surg. 163: 726-735, 1966. Sharkey, F. E.: Systematic Evaluation of the World Health Organization Classification of Salivary Gland Tumors, Am. J. CIin. Path. 67: 272-278, 1977. Spiro, R. H., Koss, L. G., Hajdu, S. I., and Strong, E. W.: Tumors of Minor Salivary Origin-A Clinicopathologic Study of 492 Cases, Cancer 31: I 17.129, 1973. Suzuki, H.. and Henderson, R.: Acinic Cell Carcinoma of the Sublingual Gland, Arch. Otolaryng. 87: 146-149, 1968. Thackray, A. C.. and Lucas, R. B.: Tumors of the Major Salivary Glands. In Atlas of Tumor Pathology, Series 2, Fascicle IO. Washington, D. C., 1974, Armed Forces Institute of Pathology, pp. 81-90. Trodahl, J. N.: Case for Diagnosis: Acinic Cell Adenocarcinoma of the Lip, Milit. Med. 137: 234, 1972. Wertheimer, F. W., and Georgen, G. J.: Intraoral Acinic Cell Adenocarcinoma. ORAL SUKG. 32: 923-926. 1971.
Reprint
requests
to:
Dr. Albert M. Abrams School of Dentistry Universitv of Southern
California
CHARLES E. TOMICH, D.D.S., M.S.D. Academy of Oral Pathology
American
Indiana University School of Dentistry I 121 West Michigan Street Indianapolis, Indiana 46202
Acinic cell tumors of minor salivary gland origin Albert M. Abrams, D.D.S., Los Angeles, CalijY DEPARTMENT SOUTHERN
OF PATHOLOGY,
MS.,
and Raymond
SCHOOL
OF DENTISTRY,
J. Melrose,
D.D.S.,
UNIVERSITY
OF
CALIFORNIA
Acinic cell tumors of minor salivary glands are most uncommon. Search of the English language literature revealed twenty previously reported cases. Nine additional cases are newly described. Most patients presented with asymptomatic swellings, but pain and tenderness were experienced by some. Sites of involvement were variable, with the palate, tongue, and floor of the mouth being the most commonly afflicted. One new case occurred centrally within the mandible. There was no sex predominance. A spectrum of histomorphologic characteristics included solid, microcystic, papillary cystic, and follicular patterns composed of acinic, intercalated duct, vacuolated, and nonspecific glandular cells. Follow-up data on ten cases from the literature and the nine new cases revealed that one patient died of tumor, one was alive with distant metastases, and one had been successfully treated for local recurrence. The patient representing the single fatality was treated by irradiation only. Surgical excision with a border of normal tissue seems to be effective treatment. The use of “carcinoma” as an appropriate designation for this neoplasm is questioned.
A cinic cell tumors (ACT) representa well-established, albeit uncommonentity in the classification of neoplasmsof salivary gland origin. Most of what is known about this tumor has been derived from studiesof those occurring in major glands, and characteristics have been well documentedduring the past 25 years.‘, 12**j* 2sAlthough data vary, acinic cell tumors compriseabout 2.5 percent of parotid tumors4*13*3oand 17to 19percent of parotid gland malignant neoplasms.4 Women are afflicted more often than men; occurrence in children is consideredto be rare.2 This investigation was supported in part by the California Tumor Tissue Registry, Los Angeles County/USC Medical Center, and by Grant IR25CAl9270-02 awarded by the National Cancer Institute, Department of Health, Education and Welfare.
220
0030-4220178102460220.$01.40/O
0
1978 The C. V. Mosby
Co.
Volume 46 Number 2
Acinic cell tumors of minor salivary gland origin
221
Because histopathologic features are often markedly similar to normal serous cells, some investigators believe that tumors are derived from acinar cells.“* I5321*3oHowever, the presence of intercalated duct-type cells and the considerable variety of histomorphologic patterns suggest tumor origin from the more pluripotential duct cells, as do the serous cells in normal gland development.‘, 6 In spite of a fairly broad spectrum of microscopic features, attempts at correlating histomorphologic characteristics with clinical features, anticipated behavior, and prognosis have been unsuccessful .*, 12*3o Attempts to identify and separate a benign variety from those possessing malignant potential so far have failed, even with the use of microspectrophotometric DNA analysis. I3 Compared to many other salivary gland malignancies, patients with ACT have a relatively good prognosis (over 80 percent) on the basis of .5-year follow-up’5; however, long-term studies indicate a more ominous outlook, as recorded by the finding of Eneroth, Jakobsson, and Blanck12 of 56 percent survival at the end of 20 years. Not only are prognostic predictions risky, but sites of metastasis to include lung, bone, and brain in addition to lymph nodes suggest a potential for occasional hematogenous spread. I, I,3 Local recurrences tend to be multiple,15 a fact which may reflect more on variegated treatment than on tumor biology.’ Current custom seems to advocate the term “acinic cell tumor,” rather than the more menacing “acinic cell carcinoma,” as the most appropriate designation for a neoplasm which, in a vast majority of instances, behaves in a benign fashion.4, “3 3o But the unpredictable nature of the disease convinces others that “carcinoma” is a more meaningful label. “* 27 Recent experiences stimulated a search of the English-language literature in quest of information on ACT of minor salivary gland derivation. Twenty previously reported examples were discovered (Table I). Details of case characteristics were generally sparse and of questionable accuracy. For example, Fine, Marshall, and Horn” and Epker and Henny14 report the same case but give different sites of origin. Eight tumors were presented as single case reports,3* 5* 20, 24*16*2g, 31,32 two were reported together with fifteen parotid ACTS, and ten were included in papers describing minor salivary gland tumors in genera1.8, IO, 14, 17, 19, 22, 23, 26, 27, 28 Th e rarity of acinic cell tumors in minor salivary glands can be appreciated by the fact that (I) these ten tumors were incorporated in reports totaling 348 benign and 8 10 malignant tumors and (2) there were no examples in an additional twenty-two papers (not referenced) describing 154 benign and 751 malignant tumors. In view of the paucity of reported ACTS in minor salivary glands, we deemed it appropriate (and possibly valuable) to study and report the cases in our files and compare findings with what is known of those from the major glands. MATERIALS
AND METHODS
A search of the files at the University of Southern California School of Dentistry and the California Tumor Tissue Registry at Los Angeles County/USC Medical Center was conducted to find tumors that satisfied the following criteria: (1) possessed histopathologic characteristics that would identify the lesion as an ACT if origin was parotid gland,‘, “a 3o (2) could not be better classified as another type of salivary gland tumor, (3) had an adequate history to ensure that the tumor was unassociated with parotid or submandibular glands, (4) lacked histopathologic evidence of parotid or submandibular gland
222
Oral Surg. August, I978
Abrams and Melrose
Table I. Acinic cell tumors of minor salivary glands Age Author
Year
Site
(years)
Duration
Gorlin and Chaudbryts
1957
34
M
Tongue
-
Burbank, Docketty, and Devine’ Fine, Marshall, and Horn”* Baden and Wallet?
1959 1960 1965
63 50 75
M F F
Sublingual Tongue Tongue Floor of mouth
Unknown 4 yr.
Luccioli, Clement, and Palme? Rosenfeld and associatesz6 Suzuki and Hendersot? Epker and Hennyr4*
1965 1966 1968 1969
70 45 50
M M F
Pharynx Mouth, N.O.S. Floor of mouth Palate
1 yr. 8-10 mo. -
Hjertman and Enerothrg Belinfante and Verne5
1970 1970
80
F
Palate Buccal mucosa
1 mo.
Manace and Goldmar?
1971
47
F
10 mo.
Wertheimer and Georgen32
1971
72
F
Fechner, Bentinck, and AskewtG TrodahFr
1972 1972
63 51
M M
Right nasal cavity, maxillary sinus, ethmoidal sinus Lower canine-premolar vestibule Lung, lower right lobe Upper lip
Spiro and associates’s
1973
Ito and associate?”
1970
25
F
Gingiva Nasal cavity Left posterior mandible
Coates and associates’” Main and associatesz3 Sharkey”?
1975 1976 1977
62 29
M F
Palate Tongue
19
F
Unknown
Case 2 Case 3 Case 4 Case 5
Unknown 43 45 35
F M M F
Mandible, left third molar area Palate Lower lip Buccal mucosa Soft palate
Case 6
65
M
Anterior buccal mucosa
1 yr.
Case 7 Case 8
59 75
F F
Anterior buccal mucosa Soft palate
1 mo. Unknown
Case 9
65
M
Lower lip
4 yr.
Abrams and Melrose Case 1
*Same case, location reported differently. N.E.D.-No D.O.D.-Died of disease.
Unknown 2-3 yr.
3% yr.
-
-
evidence of disease. D.O.C.-Died
5 mo.
Unknown 1 yr. Unknown Unknown
of other causes.
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Acinic cell tumors of minor salivary gland origin
Signs and symproms
Therapy
-
-
Nonulcerated swelling Asymptomatic, nonulcerated, firm, movable, brown-red nodule, 1.3 x 0.6 cm. Mass Asymptomatic, 5 cm. diameter mass Nonulcerated swelling Rapidly growing asymptomatic, 2.5 cm. fixed mass Nonulcerated, polypoid mass and nasal obstruction Asymptomatic, firm, movable, 2 X 1 cm. mass Discovered on chest radiographs Moderately soft, well-demarcated mass, 2.2 cm. diameter Increasing painful mass beneath intact mucosa; radiolucency from mandibular foramen to first premolar -
Painful, well-demarcated radiolucency below impacted third molar Painful ulcerated swelling Slightly tender soft swelling Asymptomatic, firm, movable mass Asymptomatic, bluish nodule, 1.O cm.diameter Asymptomatic, 3 x 3 cm. hard mass Tender swelling 5 x 5 cm. mass filling much of nasopharynx Asymptomatic, 1.O cm. nodule
Excision; radium implantation Excision
Surgery-N.O.S. Excision Wide excision and radium implantation Excision Surgical resection
Lobectomy Resection
Block resection
-
223
Follow-up
Local recurrence and distant met. 4 years P.O. N.E.D.-20 yr. None N.E.D.-2 yr. None Recurrence, D.O.D.-6 N.E.D.-15 yr. N.E.D.-2 yr. N.E.D.-8 yr. None N.E.D.-2 N.E.D.-13
yr. mo.
N.E.D.-6
mo.
N.E.D.-2 None
yr.
None None N.E.D.-3
mo.
yr.
N.E.D.-8 yr. None 1 recurrence; alive 7 yr. posttreatment
En bloc resection
N.E.D.-3%
Excision and irradiation Wide local excision Wide local excision Excision with border of normal tissue Excision
N.E.D.-4 N.E.D.-4 N.E.D.-1 N.E.D.-3
yr. yr. yr. yr.
N.E.D.-2
yr.
Excision Irradiation- 5;4 11 rads
N.E.D.-4 N.E.D.-3
yr. yr. D.O.C.
Excision
N.E.D.-10
yr.
yr. D.O.C.
224
Oral Surg. August, I978
Abrams and Melrose
Fig. 1. Case I. A 19-year-old a dentigerous cyst.
woman
with a central intraosseous
Fig. 2. Case 6. A 65year-old man with an asymptomatic, and lip with protrusion into the mouth (A) and swelling
ACT simulating
the radiographic
appearance
hard ACT originating of the face (B).
in the anterior
buccal mucosa
of
origin. This quest produced nine cases that we believe qualify as ACT originating from minor salivary glands. Sections stained with hematoxylin and eosin from all cases were studied. RESULTS Clinical
features
Clinical data on each of these nine cases are presented in Table I. This was a disease of adults, with a fairly broad age range and an average age of 5 I years. There was no sex predominance. Location was variable, with the palate and buccal mucosa each accounting for three cases, the lower lip for two, and the mandible for one. The mandibular tumor was a completely intraosseous, 2.5 by I .5 cm., well-demarcated radiolucency with no connection whatsoever to the overlying soft tissue. It was situated inferior to the impacted third molar tooth (Fig. 1). Most were asymptomatic swellings, but four patients complained of tenderness or
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Acinic cell tumors of minor salivary gland origin
Fig. 3. Case 6. Photomicrograph composed of well-differentiated
225
of section of the ACT displayed in Fig. 2 featuring predominantly solid growth acinic cells. (Hematoxylin and eosin stain. Original magnification, X 100.)
pain. Size varied from 1.O to 5.0 cm. in diameter. None of the tumors had metastasized (Fig. 2). Histomorphologic
features
The histomotphologic characteristics seen in these tumors of minor salivary gland origin were essentially the sameas those which have been describedpreviously in major glands.‘, 12*15,3oThe tumors were composed, in varying proportions, of one or more of four cell types. These were designatedas acinic cells, intercalated-duct cells, vacuolated cells, and nonspecific glandular cells. Acinic cells resembledthe polyhedral cells of normal acini and contained abundant, finely granular cytoplasm possessinga basophilic hue of varying intensity (Figs. 3 and 4). Nuclei were generally small and hyperchromatic; however, in three tumors the nuclei of someacinic cells were larger and contained a single basophilic nucleolus-like condensation. Acinic cells were presentin all tumors and were the predominant constituents in six cases. Vacuolated cells-those characterized by either one or two large vacuoles or by multiple, extremely small ones-were seenin eight casesand were moderately abundant in three (Fig. 5). Cells were often distendedand seemedto have coalescedfrequently into groupsof small cysts separatedby a syncytial network of cytoplasm imparting a latticelike pattern. Nuclei were usually somewhatlarger than those of acinic cells. It is possiblethat these vacuolated cells are acinic cells which have been altered by a tissue-processing artifact. Intercalated duct cells were never the predominant cell type but were readily observed in six tumors (Fig. 6). These cuboidal cells with limited amphophilic cytoplasm and distinct borders were frequently scrambled with acinic cells and possessedsimilar-
226
Abrams and Melrose
Fig. 4. Case 8. Photomicrograph of uniform but faintly staining acinic cells in a solid growth ACT of the soft palate. (Hematoxylin and eosin stain. Original magnification, x 100.)
pattern
from
an
appearing nuclei. Cells of this type were sometimesarrangedin ductlike patterns. Ducts lined by two distinct cell types (epithelial and myoepithelial) commonly encountered in mixed tumors were not visualized in acinic cell tumors. Cells lacking specific features necessaryto categorize them into one of the first three groups were designated as nonspecific glandular cells and were present in moderate quantities in only three cases.These cells featured the most nuclear atypia and the only unequivocal mitotic activity. Cytoplasm was faintly eosinophilic or amphophilic and contained no granules. Cells characterized by nonstainablecytoplasm with distinct nondistendedcell borders were too infrequently seento justify a legitimate category of “clear cells.” The occasional examples appear to represent poorly stained varieties already described, with cytoplasm faintly stained as a result of faulty laboratory manipulations. There were a variety of growth patterns. A solid parenchymatous mass was the predominant morphologic trait in six tumors (Figs. 3 and 4). A significant microcystic configuration resulting from cell rupture and coalescenceof vacuoles was prominent in three casesbut was noted to somedegreein all tumors. Papillary-cystic morphology was a major component in one tumor and was presentto a slight extent in two additional cases. A follicular growth pattern resemblingthyroid follicles occurred in three tumors (Figs. 8 and 9, A). The follicular spacescontained homogeneousproteinaceous-appearingmaterial bounded by cuboidal or slightly elongated cells. There were no encapsulatedtumors. Three, including the intraosseousone (Case I), were blatantly infiltrative (Fig. 7). Apparent perineural invasion was discovered in only one instance (Case 5). Stroma tended to be sparseand generally consisted of narrow bands of moderately densefibrous connective tissue separatingtumor masses.
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Acinic cell tumors of minor salivary gland origin
227
Fig. 5. Case 9. Photomicrograph of portion of a lower lip ACT composed of vacuolated cells. (Hematoxylin and eosin stain. Original magnification X 100.)
There was calcification in only one tumor (Case6). This consistedof scatteredsmall, round, darkly basophilic calcospheritesresembling psammomabodies. The unique central ACT of the mandible (Case I) was prominently infiltrative and composedmostly of acinic-type cells with small dark nuclei, but a moderate number of intercalated duct cells were present (Fig. 9). Solid and microcystic tumor extended between bone trabeculae. Focal areasfeatured blood pigment and cholesterol depositsassociated with foreign body reaction and chronic inflammation, a feature frequently seenin other cases.Mitoses were rare. Therapy
and follow-up
data
Seven tumors were treated solely by surgical excision. Included in this group was en bloc surgical resectionfor the ACT of the mandible. Surgical excision followed by irradiation was the therapeutic method for one tumor of the palate (Case2), and a secondACT of the soft palate (Case8) was managedonly by cobalt-60 irradiation to a total of 5,411 rads. Follow-up data were obtained in all cases.There were neither recurrencesnor metastasisin any case. Follow-up duration ranged from 1to 10 years, with a meanof 3.8 years. DISCUSSION Incidence
The nine new cases reported here plus the twenty examples uncovered from the literature produced a total of such meager proportions that one must view occurrence of acinic cell tumors from minor glands as most uncommon, if not rare. Indeed, acceptance of all twenty previously reported cases as legitimate ACTS may be overly generous becauseten were included in papersdescribing large seriesof glandular tumors and the few listed in the acinic cell category were not illustrated. Also, the two lesionsof minor
220
Abrams
and Melrose
Fig. 6. Case 4. Photomicrograph of an ACT from the buccai mucosa featuring many intercalated duct type cells and a microcystic pattern. (Hematoxylin and eosin stain. Original magnification, x 100.)
gland lineage reported by Gorlin and Chaudhry18in their group of ACTS were not illustrated. Two of the single casereport?, *Oare poorly illustrated examplesbut are included here becausethey may be legitimate. Therefore, our searchdetected only six caseswhich appear to be unequivocal examples of ACT.33 16,24,2g,31,32 Clinical
features
It appearsthat ACTS of minor salivary glands have no characteristicsrelated to age, sex, symptoms, or signsthat would provide the clinician with clues asto the nature of the diseaseprior to biopsy. A ratio of 5 : 4 in favor of asymptomatic to painful swellings is fairly consistentwith data reported on major salivary gland ACTS.’ No significant differencesbetween casesfrom the literature and thosereported here were noted with regardto age and sex data, and female predominancenoted in casesof parotid origin*, l*, l5 was missingwith theseaccessorygland tumors. However, there was minor conflict in location as evidenced by the lack of tumors from the tongue and floor of the mouth, regions that also tend to be involved to a moderatedegreeby salivary gland tumors in general.g*23,28 Except for possibly the buccal mucosa and palate, no one site of origin seemedto predominate. It is obvious from Table I that a wide variety of siteshave been afflicted by ACTS. Certainly, the most unusual location is the mandible. Although central jaw origin for salivary gland tumors is well recognized,7 to our knowledge, intraosseousgenesisof an ACT has been reported only once before in the English-language literature.*O Such an occurrence might be anticipated, but the rarity of that phenomenonis also reasonablein view of the paucity of intraoral acinic cell tumors. Both central ACTS were painful mandibular lesions. Our casefeatured a radiolucency associatedwith the crown of an impacted third molar tooth, while the tumor reported by
Volume Number
46 2
Acinic cell tumors of minor salivary gland origin
Fig. 7. Case 4. Photomicrograph main mass and tumor nification, X 100.)
nodules
of an ACT of the buccal mucosa characterized extending toward skeletal muscle. (Hematoxylin
229
by a pseudocapsule between the and eosin stain. Original mag-
Ito and associates20 was more anterior and lesssuggestiveof an odontogenic process.This lesion was also described, both grossly and microscopically, as encapsulated, a feature absent from all nine new cases reported here and contrary to the obvious infiltrative growth of our mandibular tumor. The patients with thesetwo central jaw lesions are the youngest (25 and 19 years) of all reported casesof ACT. Both were treated by en bloc resection, and neither tumor recurred during 3 years of follow-up observation. Histomorphologic
features
The histomorphologic characteristics of ACT of minor salivary glands were as variable as those of the parotid gland. Although a solid growth pattern predominatedin most of our cases,microcystic and, to a lesserextent, papillary-cystic configurations were also noted. ACTS may also display a follicular pattern resembling tissueof thyroid origin, a characteristic recognized previously in those of major salivary gland lineage.‘, 15,23We agree with Azzopardi2 that the presenceof “clear cells” in ACTS is uncommon and in most instances probably represents fixation and processing artifacts. Ultrastructural studiestend to support that view. l1 Cells with distinct bordersand no stainablecytoplasm were so sparse in well-prepared tissue sections that a category devoted to them was considered to be unjustified. Indeed, it is our impressionthat clear cells are seenmuch more frequently in mucoepidermoid tumors. The frequent and sometimesabundantlymphoid tissuefound in associationwith ACTS of parotid gland was absent from all casesreported here and was not described in the literature. This might be related to the absenceof normally occurring lymphoid tissue in most minor salivary gland-bearing areas. However, except for the Warthin tumor and sebaceouslymphadenoma, no other parotid gland tumor contains lymphoid tissue as
230
Oral Surg. August, 1978
Abrams and Melrose
Fig. 8. Case 5. Photomicrograph stain. Original magnification,
X
of follicular 100.)
pattern from an ACT of the soft palate. (Hematoxylin
and eosin
frequently as the ACT. Thus, the absenceof this component in minor gland ACTS may indicate the presenceof subtlebiochemical-immunologic disparitiesbetweenmorphologically similar tumors originating in different sites or from glands of divergent structure. Laminated concretions, another finding of moderately frequent occurrence in parotid ACTS, were noted in only one of our casesas small psammoma-likebodies and were not described in any case from the literature. In our experience these calcospheritescan be discovered occasionally in other types of salivary gland tumors, so they are not diagnostic of a specific tumor. Clincopathologic
correlation
and prognosis
Except for the finding that the papillary-cystic growth pattern seemsto be most prominent in palatal tumors, correlation between clinical features and histomorphology was unrewarding. Presentingclinical charactersticsappear to be unrelated to proportions of cell types, mitotic activity, nuclear and cellular atypia, and growth patterns; since no tumor hassofar recurred, correlation betweenhistomorphology and prognosisis meaningless. All tumors were unencapsulated,but this seemsto have little effect on prognosis. Irrespective of therapeutic manipulation, ACTS usually behave in a relatively benign fashion. In only one case so far reported did a patient definitely die of the tumor.22 Treatment in that instance was irradiation, a modality consideredto be ineffective in the managementof ACTS. However, even that assumptionmight be disputed, becausethe treatment of one of our cases(Case8) wasirradiation, and that patient died of other causes 3 years later without tumor recurrence. Actually, irradiation is usedtoo infrequently for its effectiveness to be adequately evaluated. A secondpatient mentioned in the literature had distant metastasisat the time of the report and may have died of tumor.‘* When data on surgical managementare known, it appearsthat excision generally includes a border of normal-appearing tissue. So far this therapy seemsto have been adequatefor cure in sixteen of seventeenoral casessummarized here. Enucleation was
Volume 46 Number
2
Acinic cell tumors of minor salivary gland origin
231
Fig. 9. Ca se 1, Photomicrographs of the central ACT of the mandible. A, Predominantly folk&r pattt :rn. B, Cord Isofa fell-differentiated acinic cells and vacuolated cells. (Hematoxylin and eosin stain. Original I mag ;nification, x lO( 1.)
liste :d as therapy in only one case, and follow-up con1clusic3ns.32 Nomenclature
of 6 months is too brief for act :urate
232
OralSurg.
Abrams ana’ Melrose
August, I978
neoplastic change, and because acinic cells originate from duct cells in normal gland development, This is speculation; referring to a precise cell of origin as if it were known is unscientific, if not nonsense. Nomenclature can be important to the patient, because type of treatment is often based solely upon the presence or absence of the word “carcinoma” in the label and not on an understanding of the biologic characteristics of the tumor, no matter how comprehensively these have been described. To us and to others, “acinic cell tumor” (“acinous” or “acinar,” if you prefer) seems to be the best designation and will likely result in the most appropriate treatment for the patient. 4~ls, 23*3o On the basis of what has been reported so far, it appears that ACTS of minor salivary gland origin should be removed with a generous border of normal tissue-treatment also appropriate for mixed tumors and low-grade mucoepidermoid tumors. Only one patient so far reported has succumbed to the disease, and this was following irradiation as exclusive therapy. It may be that those tumors of minor salivary gland lineage are biologically “less dangerous” than their counterparts in the parotid gland, but even in major glands it seems that the critical primary factor affecting the likelihood of recurrence is appropriate initial therapy.’ Incisional biopsy, enucleation, and in vivo abuse of the neoplasm significantly compromise prognosis. Certainly, ACTS are not totally innocuous. There have been thirty-two deaths due to neoplasm out of 259 major salivary gland ACTS reported in papers describing significant numbers of cases.4 But these are fairly old data, with the most recent major publication dated 1966.12 Most patients described in these reports were treated more than 20 years ago. Thus, lack of appreciation for the proper and currently well-recognized surgical approach to parotid tumors may account for some past therapeutic failures. In addition, large series of major salivary gland tumors are often reported from cancer centers, institutions which frequently treat the larger, sometimes recurrent, and therapeutically complex cases. Many minor salivary gland tumors are removed in outpatient clinics and in dentists’ and physicians’ offices. They tend to be relatively small tumors requiring a more simple therapeutic approach and are often not available for statistical analysis. The new cases of ACT reported here and many of those gleaned from the literature were apparently managed in such a milieu. This could account for a more favorable prognosis. Unfortunately, pathologists have yet to identify distinguising histologic features by which the occasional tumor having a more ominous potential can be recognized. However, this inability no more justifies labeling all acinic cell lesions “carcinoma” than it would to designate all squamous carcinomas of the tongue “tumors” is justified because some patients survive. The authors express their appreciation
to Drs. Weldon
Bullock,
Milton
Feinberg,
William
Volume 46 Number2
4,
Acinic celltumors ofminor salivary gland origin233
Batsakis, I,6,:Tumors ofthe Head and Neck, Baltimore, 1974, Tht Williams &Mkins Company, pp,
17-20. 5. Belinfante,L. S., and Verne, D.: IntraoralAcinic Cell Adenocarcinoma:Report of Case, I. Oral Surg. 28: 617-618, 1976. 6. Bhaskar, S. N.: Acinic Cell Carcinoma of Salivary Glands: Report of 21 Cases, ORAL SURG. 17: 62-74, 1964. 7. Browand, 8. 9. IO. I I. 12.
B. C., and Waldron, C. A.: Central Mucoepidermoid Tumors of the Jaws: Report of Nine Cases and Review of the Literature, ORAL SURG. 40: 63 I-643, 1975. Burbank, P. M., Dockerty, M. B., and Devine, K. D.: Clinicopathologic Study of 43 Cases of Glandular Tumors of the Tongue, Surg. Gynecol. Obstet. 109: 573-582, 1959. Chaudhry, A. P., Vickers, R. A., and GorIin, R. J.: Intraoral Minor Salivary Gland Tumors: An Analysis of 1,414 Cases, ORAL SURG. 14: 1194-1226, 1961. Coates, H. L. C., Devine, K. D., DeSanto, L. W., and Weiland, L. H.: Glandular Tumors of the Palate. Sing. Gynecol. Obstet. 140: 589-593, 1975. Echevarria, R. A.: Ultrastructure of the Acinic Cell Carcinoma and Clear Cell Carcinoma of the Parotid Gland, Cancer 20: 563-571, 1967. Eneroth, C.-M., Jakobsson, P. A., and Blanck, C.: Acinic Cell Carcinoma of the Parotid Gland, Cancer 19: 1761-1772,
13. 14. 15. 16. 17 18.
1966.
Eneroth, C.-M., Silfverswtd, C., and Zetterberg, A.: Malignancy of Acinic Cell Tumours Elucidated by Microspectrophotometric DNA Analysis, Acta Otolaryngol. (Stockh.) 77: l26- 130, 1974. Epker, B. N., and Henny, F. A.: Clinical, Histopathologic, and Surgical Aspects of Intraoral Minor Salivary Gland Tumors: Review of 90 Cases, 1. Oral Surg. 27: 792-804, 1969. Evans, R. W., and Cruickshank, A. H.: Epithelial Tumors of the Salivary Glands, Philadelphia, 1970, W. B. Saunders Co., pp. 98-119. Fechner, R. E.. Bentinck, R. B., and Askew, J. B.: Acinic Cell Tumor of the Lung: A Histologic and Ultrastructural Study, Cancer 29: 501-508, 1972. Fine, G., Marshall, R. B., and Horn, R. C.: Tumors of the Minor Salivary Glands, Cancer 13: 653-669, 1960. Gorlin, R. J., and Chaudhry, A.: Acinic Cell Tumor of Major and Minor Salivary Glands, 3. Oral Surg. 15:
304-306, 1957. 19. Hjertman, L., and Eneroth, 20. Ito, H., Soda, T., Asakura, 21
Tumor of the Mandible: Kay, S., and Schatzki, 235-244,
22 23 24
37 ,
28. 29. 30. 3 I. 32.
1972.
Luccioli, G. M., Clement, H., and Palmer, J. D.: An Analysis of 50 Carcinomas of the Salivary Glands, Can. J. Surg. 8: 389.399, 1965. Main, J. H. P., Orr, J. A., McGurk, F. M., McComb, R. J., and Mock, D.: Salivary Gland Tumors: Review of 643 Cases, J. Oral Path. 5: 88-102, 1976. Manace, E. D., and Goldman, J. L.: Acinic Cell Carcinoma of the ParanasaI Sinuses, Laryngoscope 81: 1072-1082,
2.5 26
C.-M.: Tumours of the Palate, Acta Otolaryngol. 263~ 179- 182, 1970. A., Nakajima, T., Kobayashi, Y., and Miyazawa, M.: Central Acinic Cell Report of a Case, Bull. Tokyo Med. Dent. Univ. 17: 239-247, 1970. P. F.: Ultrastructure of Acinic Cell Carcinoma of the Parotid Gland, Cancer 29:
1971.
Rivilin, R. S.: Acinic Cell Adenocarcinoma of the Parotid Gland, Am. J. Sury. 100: 639-642, 1960. Rosenfeld, L., Sessions, D. G., McSwain, B., and Graves, H.: Malignant Tumors of Salivary Gland Origin: 37 Year Review of 184 Cases, Ann. Surg. 163: 726-735, 1966. Sharkey, F. E.: Systematic Evaluation of the World Health Organization Classification of Salivary Gland Tumors, Am. J. CIin. Path. 67: 272-278, 1977. Spiro, R. H., Koss, L. G., Hajdu, S. I., and Strong, E. W.: Tumors of Minor Salivary Origin-A Clinicopathologic Study of 492 Cases, Cancer 31: I 17.129, 1973. Suzuki, H.. and Henderson, R.: Acinic Cell Carcinoma of the Sublingual Gland, Arch. Otolaryng. 87: 146-149, 1968. Thackray, A. C.. and Lucas, R. B.: Tumors of the Major Salivary Glands. In Atlas of Tumor Pathology, Series 2, Fascicle IO. Washington, D. C., 1974, Armed Forces Institute of Pathology, pp. 81-90. Trodahl, J. N.: Case for Diagnosis: Acinic Cell Adenocarcinoma of the Lip, Milit. Med. 137: 234, 1972. Wertheimer, F. W., and Georgen, G. J.: Intraoral Acinic Cell Adenocarcinoma. ORAL SUKG. 32: 923-926. 1971.
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requests
to:
Dr. Albert M. Abrams School of Dentistry Universitv of Southern
California