Oral SURGERY Oral MEDICINE AND&d
Operative oral surgery Mucoepidermoid carcinomaof buccal mucosa Report of a case
Franklin D. Niver, D.M.D., Stuart Strong, M.D., and Max L. Guodman, M.D., Boston, Mass. BOSTON AND
he buccal mucosa, a nonkeratinized, stratified squamous epithelium with mixed salivary glands in the submucosa, is an uncommon site of salivary gland tumors. Mucoepidermoid carcinomas of salivary gland origin are relatively infrequent and, because of their bizarre histologic appearances, present problems in pathologic diagnosis and clinical management. The patient in the case to be presented here died of widespread metastases from mucoepidermoid carcinoma of the buccal mucosa. Some of the interesting obsetiations derived from the study of this case are the rapidly fulminating progress of the disease and the rare histologic features of the tumor. The predominance of adenocarcinomatous elements in the tumor may account for this patient’s rapid clinical course and the diffuse metastasis. REVIEW OF LITERATURE
The insidious clinical course of many oral mucous gland tumors may foster complacency on the part of both the patient and the consulted dentist or 1
physician. In the series of fifty-four accessory salivary gland tumors investigated by Vellios and Shafer,’ five (9 per ccntj nrosc in the buccnl mucosa and four of these were benign. Failure to eA;dlish the diagnosis early results in tllcl employment of inadequate procedures and invites recurrence. The prognosis for tumors of the minor salivary glands is worse than -for those of the major salivary glands because of the higher incidence of malignant versus benign tumor types. McFarland2 states that one of the few positive statements that may be made regardin g salivary gland t,umors is that lesions with a malignant histologic picture and rapid growth for which the patient, undergoes surgical treatment within a year have a poor prognosis. In the report by Bhaskar and Brrnier,‘j the majority of tumors that terminated fatally causetl death within one year of initial therapy. Fatal mncoepidermoid tumors were those in which the tumor was not classically mueoepidermoid but showed many features of the adenocarcinomas or squamous-cell carcinomas! namely, rapid growth, metastasis, or brain extension. Metastases from malignant mucoepidermoid carcinomas, when they occur, develop early in the course of the disease. The commonly involved sites include the lungs, liver, and bones.” Other reported sites arc the heart, retroperitonenl region, diaphragm, pleura, skeletal muscles, adrenal glands, lymph nodes, and skin.3. 5, GRegional mctastases have been reported in two thirds of the cases, with distant metastases found in one third of the cases brought to autopsy. Mucoepiclermoid tumors recurred at the rate of 60 per cent after therap>T, while 25 per cent, of the lesions were inoperable at the time of diagnosis.‘, 8 Tumors of minor salivary glands are often covered with intact epithelium. If ulceration is present, it is usually small in extent compared to the total bulk of the tumor. This is in contrast to squamous-cell carcinoma of the oral cavity in which ulceration is nearly always present and usually extends over most of the area involved by the tumor.” Kearly all tumors found in the buccal and labial mucosa arise as primary new growths from normal mucosal structures. lo Metastatic tumors to the jaws account for 1 per cent of all oral malignancies, while those metastatic to the buccal mucosa account for only 0.1 per cent.ll When metastases are found, the surface epithelium is not involved and the pattern of the tumor is foreign for the site. Undifferentiated carcinoma of the lung commonly metastasizes throughout the body, but oral metastases are unusual. Lesions which may metastasize to the jaws and mouth include adenocarcinoma of the breast and gastrointestinal tract and hypernephroma.12 ORIGIN
There now seems to be general agreement as to the origin of the mucoepidermoid carcinoma. The intercalated ducts are proliferative zones, and the low cuboidal epithelium of these ducts posseses the potential plasticity to differentiate into serous, mucous, oxyphilic granular, clear-cell, sebaceous, and squamous types of epithelium. The transformation of columnar and squamous epithelial cells into mucous cells is by no means a degenerative process; it is, rather, a metaplasia of the pleuripotential cells of the glandular ducts.13 It has been
suggested that the tumors more specifically arise from t.hose portions of the duct system that are proximal to the lobules, since at this point the lining cells of the salivary ducts become eosinophilic and cells of this character are not present in mucoepidermoid tumors. That the tumors do originate from the mucous and salivary glands may be considered only highly probable. HISTOPATHOLOGY
The three basic cellular components of the mucoepidermoid tumors are the mucous, epidermoid, and intermediate cells; the latter resemble certain cells of salivary gland ducts and are smaller than the two main cell types.149I5 The more malignant forms of the tumor are characterized by a predominance of epidermoid cells, the absence of microcysts, a sheetlike arrangement of cells, the absence of tubular or papillary features seen in the benign form, the absence of large mucous pools, and the absence of interstitial inflammation.l’j The highly malignant tumors have abundant squamous differentiation, with formation of epithelial pearls, pseudoglandular formation, and perincural lymphatic invasi0n.l’ They are uniformly infiltrative and are rarely encapsulated.14j 1s The histologic pattern is partly the result of the invasive squamous epithelial columns in which mucus-secreting cells develop, with the result that cysts filled with mucus and surrounded by goblet cells are often developed.ls> I9 Intermediate cells are seldom the dominant cell type, but it seems that they are capable of differentiation into mucous cells or into epidermoid and then squamous cells, since observations reveal all sorts of transitional structural relationships. This explains the pleomorphism of the mucocpidermoid group as a whole. Microscopically, the highly malignant tumors may resemble squamous-cell carcinomas.Zo It has been suggested that a certain number of rather anaplastic and diffuse cancers of the salivary glands are basically mucoepidermoid but have become so overgrown that the mucous element is no longer discernible.15, 24 Epidermoid, squamous, basal, mucus-secreting, clear, and finely granular eosinophilic cells have been identified in varying combinations, depending upon the degree of cell differentiation. Mitoses were infrequent or absent, whereas perineural lymphatic invasion was common. INCIDENCE
Recent studies indicate a greater incidence of malignant tumors among the minor salivary glands than in the major salivary glands.22 The incidence of mucoepidermoid carcinoma has been variously reported as 2 to 11 per cent of the tumors of both major and minor salivary glands; the incidence in minor salivary glands ranges from 11 to 30 percent.9, 16yI9923-26 There has been no satisfactory evidence to relate the occurrence of mucoepidermoid carcinomas to sex. 15,I8 With regard to age, Stewart, Foote, and BeckerI found that 65 per cent of the tumors occurred in patients over 40 years of age while 9.0 per cent of these tumors occurred in patients over 50 years. This differs slightly from the findings of Foote and Fraze1114 and Skorpil,ls who reported the highest incidence of mucoepidermoid tumors in the fourth and fifth decades.3
Fig. 1. Buccal duct opening.
O.S.,O.M. & 02.
mucosa of right
Pig. 8. Facial aspect of lesion at time of surgical intervention. excisional margin of tumor and of restorative Estlander flap.
CASE REPORT The patient presented with a chief complaint of a painful ulcer of the right cheek. This had been present for 3 months and was asymptomatic except for pain during mastication. The patient had smoked one to two packs of cigarettes per day for the past 56 years and had consumed one pint of alcoholic beverage per day for the past 20 years. The lesion consisted of a 3 cm. indurated, localized, white, fissured, necrotic ulcer below the right oral commissure with extension of the granular tumor backward on the buccal mucosa to the parotid duct opening (Figs. 1 and 2). The gingiva was not involved, and there were no palpable lymph nodes. This was a Stage II lesion (T,N,M,*). A biopsy of the lesion led to a diagnosis of squamous-cell carcinoma (Fig. 3). A week later the remaining mandibular teeth were removed and the tumor was excised, followed by *American
for Cancer Staging
and End Result Reporting.
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carcinonta of buccal mucoaa
Fig. 3. Biopsy specimen of lesion with epidermoid elements present. Pig. 4. Representative section of excised tumor mass depicting both epidermoid components. Fig. 5. Section of tumor with prominent keratin pearl formation.
immediate reconstruction with an Estlander flap. The final diagnosis was malignant mucoepidermoid carcinoma (Fig. 4). In 2 months, the patient developed multiple lymph node enlargements in the right neck and a 3 cm. mass firmly attached to the lower surface of the. mandibular symphysis. Radiographs of the chest and jaws were negative for metastasis. Cobalt therapy (5,900 rads) was administered to these glands over a B-week period. Two months after radiation there were no palpable lymph nodes and no evidence of recurrence of the primary tumor. Within a short period of time, however, the patient was rehospitalized for severe, progressive shortness of breath. Response to palliative therapy was slight, and the patient’s mental and physical status deteriorated rapidly. He died 6 months after surgical excision of the tumor. Pathology
The excised tumor mass consisted of a stony hard, gray-white, homogeneous tissue with an ulcerated, granular mucosal surface. Microscopically, the tumor was a nonencapsulated, in-
Pig. 6. Section from vr~t~tel)ml 1m11c ~I:II’I’OLI \\itlr Ineinsl:\t ic, coccus oi’ mucocpidermoid carcinoma. Note prominent glandular fornxrtious. Pig. 7. Section of myocardium vviH1 metastatic: fows of’ Jtluc~oc,~,iti(,~1111,id carcinoma. Prom inent acinar arrangements arc present.
lesion with lymphatic cell types with keratin
The tumor consisted of epidermoid and interpermeation. pearls and mucus-secreting cells in acinar arrangements (Fig.
5). The pertinent autopsy findings included gray-white furnor masses involving the heart, lungs, hilar lymph nodes, diaphragm, liver, adrenal glands, kidneys, 11ones, and skcletnl muscles. There was no residual tumor in the huccal mucosa or the cervical lymph nodes. A second primary malignancy-adenocarcinoma of the prostate gland-was discovcrcd. The histologic appearance of the metastatic foci was slightly altered from the pattern of
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carcifloma of buccal mucosa
the primary lesion. The major elements were now adenomatous with a reduction in the epidermoid component (Figs. 6 and 7). The usual finding in the metastasis is an overgrowth of the epidermoid fraction, sometimes to the point of mimicking squamous-cell carcinoma. DISCUSSION
In evaluating the occurrence of this rare, highly malignant form of mucoepidermoid carcinoma, which in this case appears to have arisen from the minor salivary gland ducts of the buccal mucosa, other sources of origin must be considered. There is a possibility that this tumor represented a metastasis from a bronchogenic carcinoma which had features of both adenocarcinoma and squamous-cell carcinoma. Several facts negate this inference. First, there is the chronologic sequence of the patient’s symptoms of pain from an oral lesion for 3 months, regional nodal involvements 2 months after excision of the tumor with response of the nodes to radiation, and, finally, respiratory distress. Thus, the progression of the lesion from oral to cervical to thoracic regions is documented. Second, the extremely rare incidence of oral metastases from any primary site has been noted. The most common carcinomas which have oral metastases are those of the breast, gastrointestinal tract, and kidneys. Even in these cases, however, there is only a 1 per cent incidence of metastases to the jaws, with a 0.1 per cent incidence of oral soft-tissue metastases.Z4 Third, 65 per cent of all bronchogenic carcinomas are of the pure varieties and, although there arc mixed types, the mixture of adenocarcinoma with squamous-cell carcinoma has been reported in only 2.4 per cent of bronchogenic carcinomas.27 It could be stated that two rare primary lesions were present with identical histologic features and that both were present within the same relative period of time. In addition, the patient had a primary adenocarcinoma of the prostate, making the diagnosis of t,hree unrelated primary carcinomas improbable. The most likely explanation, therefore, is that the tumor was a primary lesion of the buccal mucosa which had metastasized widely. CONCLUSION
The poor prognosis of malignant tumors of minor salivary gland origin noted by previous authors is illustrated by the case of mucoepidermoid carcinoma reported here. Only 11 months elapsed from the onset of symptoms until death from widespread metastascs. It is possible that if the patient had sought treatment earlier the primary tumor could have been eradiacated before metastases had occurred and that the fatal outcome thus could have been avoided. SUMMARY
The incidence and origin of mucoepidermoid carcinoma of the buccal mucosa have been reviewed, and the poor prognosis of malignant tumors of minor salivary glands has been discussed. A case of mucoepidermoid carcinoma of the buccal mucosa, with a rapidly fatal outcome, has been presented.
3. Hhaskar, R. h., and I
C. V. &lo~lw
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a1111 hlillO1 I.ouis,
5. Mulligan, R. 1\1.: Metastasis dt’ Mixetl Tumors of the Salivary (ilantls, Arch. Path. 35: R.57 1943 6. Tailor, G. IV., ant1 Garcelon, G. G.: Tumors of Salivary Gland Origin, Sew Englantl .1. Med. 238: 76, 194% 7. Frazell, K. I,.: Clinical Bspects of Tumors of the Major Salivary- Glands, (lancer 7: 637, 1954. 8. Maclntgre, H. TV:.: Mucoepidermoid Carcinoma of the Salivary Blandr, Arch. Path. 56: 79, 1953. H. S.: Tumors of the Minor Salivaq 9. Brown, R. L., Bishop, E. I,., and Girardeau, Glands. Cancer 12: 40. 1959. 10. Traige;, J., and Ros&, M, B.: Mixed Tumor of the Cheek, ORAL SVRG., ORAL Msu. & ORAL PATH. 19: 711, 1965. Tumors Metastatic to Xouth and Jaws, ORAL 11. Illeper, I., and Shklar, G.: Ualignant STJRG., ORAL MED. R- ORAL PATII.
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12. Shklar, G., and Taylor, R.: Metastasis of Pulmonary Carcinoma Oral Surg. 23: 549, 1965. 13. Bauer, W. H., and Bauer, J. I).: Classification of Glandular Tumors Arch. Path. 55: 328, 1953. E. I,.: Tumors of the Major Salivary 14. Foote, F. W., and Frazell,
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25. At&bury, R. A., and Vazirani, S . .J.: Mucoepidtrrmoid Tumor of Minor Salivary Glauds; Report of a Case, Ortar, RURG., ORAL MED. & ORAL PATH. 10: 948, 19.57. %. Edwards, E. (+.: Tumors of the Minor Salivary Glantls, Am. J. ('Iin. Path. 34: 45.5, l!lGO. 27. \Villis, R,. A.: I’atholog~~ of ”I umors. St. I,ouis, 1948, The C. V. Jlosby Corupatly, p. :I(ii.