Учебники / Textbook and Color Atlas of Salivary Gland Pathology - DIAGNOSIS AND MANAGEMENT Carlson 2008

Figure 10.3d. Due to the relative inability to dissect this tumor bed entirely transorally, a decision was made to perform a combined transcutaneous and transoral approach to the tumor ablation with an Attia double osteotomy of the mandible. Wide transcutaneous access was accomplished for this tumor surgery.

Figure 10.3f. Bone plates were placed on the mandible in preparation for the osteotomy. The plates were then removed and an Attia double osteotomy of the mandible was performed that involved a horizontal resection of the mandible superior to the mandibular foramen and a vertical resection of the mandible anterior to the mental foramen.

Figure 10.3e. Dissection of the mandible was performed in a subperiosteal fashion, while maintaining as much periosteum and muscle as possible on the lateral surface of the mandible.

Figure 10.3g. Superior reflection of the mandibular segment was then able to be accomplished.

Figure 10.3h. Refl ection of the medial surface of the medial pterygoid muscle permitted entry into the parapharyngeal space with identification of the tumor.

Figure 10.3i. With the great vessels of the neck protected, the tumor ablation continued intraorally with development of the tumor dissection surrounding the pseudocapsule.

Figure 10.3j. The combination of transcutaneous access and transoral access permitted safe delivery of the specimen.

Figure 10.3k. Histopathology identified a pleomorphic adenoma with tumor present in the pseudocapsule, but with negative margins.

Figure 10.3l. Following delivery of the specimen, the plates are replaced on the mandible and closure occurred.

effective dissection of the tumor bed and protection of the great vessels in the neck may be indicated.

Pleomorphic adenomas are known to occur in other minor salivary gland sites, including the lip, buccal mucosa, and tongue. Lip tumors accounted for 297 cases in the AFIP files, of which a majority occurred in the upper lip. Lower lip pleomorphic adenomas are very rare. The buccal mucosa accounted for 126 cases in the AFIP series. The surgery required for removal of pleomorphic adenomas in the lip and buccal mucosa involves an excision of the tumor and associated minor salivary gland tissue. The plane of dissection is “peri-pseudocapsular” in nature. This ensures an anatomic barrier of fascia surrounding the tumor. These tumor surgeries are curative as long as tumor spillage does not occur intraoperatively. Subtherapeutic ablation of these tumors in the form of an enucleation will certainly predispose the patient to persistent disease. Such recurrences are noted to be multifocal in nature as originally described in the major salivary glands (Foote and Frazell 1953).

Malignant pleomorphic adenomas of salivary gland origin are uncommon neoplasms. The broad heading, malignant mixed tumor, includes three different clinical and pathologic entities: carcinoma ex-pleomorphic adenoma, carcinosarcoma, and metastasizing pleomorphic adenoma. Carcinoma ex-pleomorphic adenoma, perhaps the most commonly referenced malignant pleomorphic adenoma, is a pleomorphic adenoma in which a second neo-

Figure 10.3m. The 6-month postoperative view of the palate is noted. This surgery was curative for this patient’s tumor. Reprinted with permission from Carlson ER, Schimmele SR. 1998. The management of minor salivary gland tumors of the oral cavity. In: Surgical Management of Salivary Gland Disease, The Atlas of the Oral and Maxillofacial Surgery Clinics of North America 6. Philadelphia: W.B. Saunders, pp. 75–98.

plasm develops from the epithelial component that fulfills the criteria for malignancy. These features include invasiveness, destruction of normal tissues, cellular anaplasia, cellular pleomorphism, atypical mitoses, and abnormal architectural patterns (Wenig and Gnepp 1991). The AFIP data showed 326 cases of carcinoma ex-pleomorphic adenoma, which accounted for 2.4% of their 13,749 cases. A significant majority of these were located in the parotid gland (64.4%); however, these malignancies occurred in the minor salivary glands, as well. The palate accounted for 36 of 57 cases in the minor glands, with the upper lip (6 cases), tongue (4 cases), and cheek (4 cases) also represented. A review of this tumor shows that preoperative duration of a benign pleomorphic adenoma is the main determining factor regarding malignant transformation. Specifically, the incidence of malignancy progressively increases from 1.6% for tumors present for less than 5 years to 9.4% for tumors present for periods longer than 15 years (Wenig and Gnepp 1991). The other predisposing condition for the development of this malignancy is recurrence of a benign pleomorphic adenoma. This fact supports a curative approach to the pleomorphic adenoma from the outset, with abandonment of the subtherapeutic enucleation of these tumors in the parotid gland or minor salivary gland tissues.

The prognosis for this malignancy is generally considered dismal, with 71% of patients exhibiting metastatic disease during the course of their disease.

Carcinosarcoma, also known as true malignant pleomorphic adenoma, is a tumor defined by histologic evidence of malignancy in both the epithelial and stromal elements of the tumor. These tumors are more rare than the carcinoma ex-pleo- morphic adenoma, accounting for only 8 cases in the AFIP registry, and none occurred in the minor salivary glands. Other cases presented in the literature do identify the existence of this diagnosis in the minor salivary glands.

Metastasizing mixed tumor is a histologically benign pleomorphic adenoma, but located in distant sites. The pleomorphic adenomas are known to arise in major as well as minor salivary glands, and the metastatic foci have been identified in the cervical lymph nodes, spine, and liver (Wenig and Gnepp 1991). Data on the interval from removal of the primary tumor to the identification of the first metastasis is 1.5–51 years, with an average of 16.6 years.

Canalicular Adenoma

The canalicular adenoma is a benign tumor that has a significant predilection for the upper lip (Figure 10.4). In the past, this tumor was

Figure 10.4a. A freely moveable, indurated, submucosal mass of the upper lip in an elderly woman, highly suggestive of a canalicular adenoma.

more commonly referred to as a “monomorphic adenoma.” Gardner recommended that the term monomorphic adenoma be used as a nosologic group of epithelial salivary gland tumors that are not pleomorphic adenomas (Gardner and Daley 1983). The canalicular adenoma and basal cell adenoma identify specific forms of monomorphic

Figure 10.4b. Based on this assumption, an incisional biopsy is not required. A pericapsular dissection and excision of this mass was performed in association with surrounding minor salivary gland tissue, thereby allowing for delivery of the specimen.

Figure 10.4c. The histopathology of the specimen con- fi rms the clinical impression of canalicular adenoma. Reprinted with permission from Carlson ER, Schimmele SR. 1998. The management of minor salivary gland tumors of the oral cavity. In: Surgical Management of Salivary Gland Disease, The Atlas of the Oral and Maxillofacial Surgery Clinics of North America 6. Philadelphia: W.B. Saunders, pp. 75–98.

230 Tumors of the Minor Salivary Glands

Figure 10.5a. A freely moveable, indurated, submucosal mass of the buccal mucosa is noted in this patient.

adenomas (Daley, Gardner, and Smout 1984). The canalicular adenoma classically occurs in the upper lip in elderly women (Kratochvil 1991). In fact, canalicular adenomas typically affect an older population compared to pleomorphic adenomas (Ord 1994). The canalicular adenoma is typically an asymptomatic, slow-growing, and freely moveable mass that uncommonly exceeds 2 cm in widest diameter. It may resemble mucoceles, which are uncommonly located in the upper lip. Of the 121 canalicular adenomas in the AFIP files, 89 of them occurred in the upper lip. The second most common site was the buccal mucosa (Auclair, Ellis, and Gnepp et al. 1991). The tumor is encapsulated such that an excision of the tumor in any anatomic site in a pericapsular fashion represents a curative surgery provided that tumor spillage does not occur (Figure 10.5). The canalicular adenoma is multifocal in 20% of cases (Ord 1994). If recurrence is believed to have occurred, it might actually represent a new primary tumor (Melrose 1994).

Figure 10.5d. A benign neoplastic process occupies a high position on the differential diagnosis such that a mucosal-sparing excision of the mass with transoral access is able to be performed without first obtaining an incisional biopsy.

h

Figure 10.5e. A pericapsular dissection is performed.

Figure 10.5f. This dissection permits delivery of the specimen. Stenson’s duct was intimately attached to the tumor and therefore sacrificed with the tumor.

Figures 10.5g and 10.5h. Histopathology identified canalicular adenoma (g) with an uninvolved capsule (h).

Figure 10.5i. The appearance of the site is noted to be well healed at 9 months postoperatively. Reprinted with permission from Carlson ER. 1995. Salivary gland pathol- ogy—clinical perspectives and differential diagnosis. In: The Comprehensive Management of Salivary Gland Pathology, Oral and Maxillofacial Surgery Clinics of North America 7. Philadelphia: W.B. Saunders, pp. 361–386.

232 Tumors of the Minor Salivary Glands

SURGICAL TREATMENT OF MALIGNANT MINOR SALIVARY GLAND TUMORS

The malignant diagnoses in the minor salivary glands are more diverse than their benign counterparts. These malignant diagnoses may be low grade or high grade, and most represent histopathologic diagnostic challenges. As with the benign minor salivary gland tumors, surgery represents the hallmark of therapy for malignant minor salivary gland tumors, and the principles of surgery have not changed significantly over the past several decades (Bell et al. 2005). In addition to eradication of the primary malignancy, consideration should be given for neck dissection in very specific circumstances, as well as postoperative radiation therapy in this cohort of patients.

Mucoepidermoid Carcinoma

The mucoepidermoid carcinoma is the second most common tumor of the salivary glands overall, the most common salivary gland malignancy overall, and the most common minor salivary gland malignancy (Auclair and Ellis 1991). During the greater than 60 years since its first description, this neoplasm has generated significant debate regarding the possible existence of a benign variant, the optimal number of grades, and the proper treatment for certain minor salivary gland lesions. The term “mucoepidermoid tumor” was first introduced by Stewart, Foote, and Becker in 1945 in their publication of 45 cases (Stewart, Foote, and Becker 1945). In this report, only two grades were utilized, including relatively favorable (benign) and highly unfavorable (malignant) tumors. The authors indicated that the adjective “benign” was rarely ever applicable in an absolute sense and as used in their report did not imply innocent behavior. It did indicate, however, that the authors had not observed metastasis from these tumors. The designation “malignant” indicated a histologic structure that was associated with the ability to produce regional lymph node and distant metastases. This notwithstanding, the authors explicitly referred to and separated the benign and malignant tumors in their series of 45 cases in this report, of which there were 26 “benign” tumors and 19 “malignant” tumors. In 1953 this grading scheme was modified to include three grades due to the development of metastases related to tumors previously referred to as benign (Foote and Frazell

1953). These investigators accepted all of these tumors as malignant, and clinical and pathologic correlation suggested that separation into low-, intermediate-, and high-grade malignant subgroups might be useful, mainly due to histologically overlapping qualities. The designation of intermediate grade was recognized as behaving more like the low-grade tumors than the high-grade tumors. Interestingly, despite the authors’ recognition that all of these tumors were malignant, the designation “mucoepidermoid tumor” persisted throughout their paper. Subsequent studies were undertaken to more objectively determine if a benign variant existed. One such study investigated 23 mucoepidermoid carcinomas with a malignant course, such as evidence of local extension of tumor outside the capsule, local recurrences, histologically verified metastases, or death due to the tumor (Eneroth et al. 1972). Fifteen patients showed local recurrences, 13 showed histologically verified metastases, and 22 patients died of their disease. In 7 of the 23 cases the histology revealed highly or moderately differentiated structures, and in 3 of these cases the primary tumor as well as the lymph node metastases were highly differentiated. Six of the 23 patients had tumors in the palate, with 2 of these patients developing recurrences, 1 with lymph node metastases, and 5 of the patients died due to their disease. The authors concluded by stating that well-differentiated metastases in cases with a malignant course contradicted the existence of a benign variety of mucoepidermoid carcinoma, such that all of these neoplasms should be considered cancers (Eneroth et al. 1972).

Of the 712 mucoepidermoid carcinomas occurring in the minor salivary glands in the AFIP registry, 305 (43%) of them were noted in the palate, 93 (13%) in the buccal mucosa, and 58 (8%) in the lip, with 37 specifically designated as the upper lip and 12 specifically designated as the lower lip (Auclair, Ellis, and Gnepp et al. 1991). While the AFIP data is generally recognized as being representative of the incidence of most salivary gland tumors, some authors have identified the mucoepidermoid carcinoma to be more common in minor salivary gland sites than in major salivary gland sites (Plambeck, Friedrich, and Schmelzle 1996).

Histologic grading of mucoepidermoid carcinomas is an important exercise. Histologic grade connotes biologic aggressiveness and prognosis and also provides the surgeon with important

information with which to plan surgical treatment (Brandwein, Ivanov, and Wallace et al. 2001; Evans 1984). Mucoepidermoid carcinomas are composed of three cell types: mucous secreting, epidermoid, and intermediate. The intermediate cell is appropriately named because it is likely the progenitor of the two other cells (Batsakis and Luna 1990). Three grading schemes have found general acceptance among pathologists, and differences in biologic behavior could be demonstrated as a function of grade, even though clinical stage has also been considered an important prognosticator. Indeed, Brandwein, Ivanov, and Wallace et al. (2001) found that only 5% of low-grade mucoepidermoid carcinomas of the major glands, and only 2.5% of low-grade mucoepidermoid carcinomas of the minor glands, metastasized to regional lymph nodes or resulted in death. Spiro indicated that survival of patients with minor salivary gland carcinoma is significantly influenced by the clinical stage and the histologic grade, but the applicability of grading to survival was limited to patients with mucoepidermoid carcinoma or adenocarcinoma in their study (Spiro, Thaler, and Hicks et al. 1991). They determined that staging was important in all patients regardless of the histologic diagnosis.

The mucoepidermoid carcinoma is the most common salivary gland malignancy in children (Auclair, Ellis, and Gnepp et al. 1991; Luna, Batsakis, and El-Naggar 1991; Ord 1994; Rogerson 1995). Although most of these tumors are noted in the parotid gland, the palate is the second most common site of involvement. Most appear to occur in teenagers, and the majority are low-grade or intermediate-grade histology. Mucoepidermoid carcinoma in children appears to follow a more favorable course with cure rates of 98–100% (Ord 1994).

Surgical treatment of the mucoepidermoid carcinoma of minor salivary gland origin is primarily a function of the anatomic site of the tumor and its histologic grade. Those arising in the palate are not only the most common but also the most variable insofar as surgical treatment is concerned. It is the histologic grade that is of utmost importance when determining treatment in the palate. Large series show that low-grade cancer is most common in this anatomic site (Pires et al. 2007). Incisional biopsy is clearly essential to establish the histopathologic diagnosis, as previously described. Computerized tomograms are essential in planning surgical treatment of palatal mucoepi-

dermoid carcinomas, as they assess the involvement of the underlying palatal bone. When the palatal bone does not appear to be involved by the cancer, a bone-sparing, periosteal sacrificing wide local excision with split thickness sacrifice of the soft palate musculature is the surgical treatment of choice (Figure 10.6). Similar to the surgery for the palatal pleomorphic adenoma, the periosteum serves as the anatomic barrier on the superior aspect of the tumor specimen, and tumor-free peri-

Figure 10.6a. A mass of the palate in a 45-year-old man.

Figure 10.6b. The extensive differential diagnosis, including benign and malignant entities, requires an incisional biopsy for diagnosis prior to performing definitive tumor surgery. The biopsy identifies low-grade mucoepidermoid carcinoma.

Figure 10.6c. A periosteal sacrificing, bone-sparing wide local excision with split thickness sacrifice of the soft palate is planned with 1 cm mucosal linear margins.

Figure 10.6d. A sharp dissection is performed with a periosteal elevator between the periosteum on the superior aspect of the tumor specimen and the overlying palatal bone.

Figure 10.6e. The specimen is delivered and oriented for the pathologist with sutures. Histopathology shows lowgrade mucoepidermoid carcinoma with negative margins.

Figure 10.6f. The association of the superior aspect of the tumor and the periosteum is noted histologically.

Figure 10.6g. The remaining tissue bed is temporarily covered with a palatal stent.

osteal frozen and permanent sections should be obtained so as to confirm this concept. When the periosteum has not been invaded by the cancer and all radial soft tissue margins are free of tumor, this surgery has a high frequency of cure.

The designation of an intermediate mucoepidermoid carcinoma of the palate may change the recommended surgical treatment of the tumor in this and other anatomic sites, with a more aggressive surgical procedure required for curative intent (Figure 10.7). This is particularly true if the designation of intermediate grade is made by the pathologist based on the worst microscopic pattern observed in the tumor. For example, a mucoepidermoid carcinoma that is predominantly low grade, but that shows a component of intermedi- ate-grade cancer, will likely be designated intermediate grade. The behavior of such a tumor is likely to be low grade in nature. This scenario is different from a cancer that is designated intermediate grade that shows a predominantly intermediate-grade pattern with intermixed low-grade cancer. The surgeon may wish to offer more aggressive surgical therapy in the form of a partial maxillectomy for the mucoepidermoid carcinoma of the palate that is predominantly intermediate grade on microscopic sections. While rare, a high-grade mucoepidermoid carcinoma of the palate would require a partial maxillectomy, and prophylactic surgical treatment of the neck in the case of an N0 neck, or a therapeutic neck dissection in the case of an N+ neck. Postoperative radiation

Figure 10.6h. Mucosalization of the exposed bone and soft palate musculature is noted at 9 months postoperatively. This surgery provided curative care for this patient’s tumor. Reprinted with permission from Carlson ER, Schimmele SR. 1998. The management of minor salivary gland tumors of the oral cavity. In: Surgical Management of Salivary Gland Disease, The Atlas of the Oral and Maxillofacial Surgery Clinics of North America 6. Philadelphia: W.B. Saunders, pp. 75–98.

therapy would also be administered in such circumstances.

Mucoepidermoid carcinoma of the buccal mucosa is the second most common minor salivary gland site affected. In contrast to benign neoplasms of this anatomic site, a mucosal-sacrificing tumor surgery is required, with attention to the sacrifice of surrounding submucosal anatomic barriers. The same is true of the lip (Figure 10.8).

Survival of patients with mucoepidermoid carcinomas of the minor salivary glands is clearly related to grade. Five-year survival rates have been estimated at 90% and 15-year survival rates have been estimated at 82% for low-grade mucoepidermoid carcinomas (Ord 1994).

Adenoid Cystic Carcinoma

Like the mucoepidermoid carcinoma, the adenoid cystic carcinoma is a very diverse tumor with three histologic variants. These have been described morphologically rather than by grade as is the case with the mucoepidermoid carcinoma, and include the tubular, cribriform, and solid variants. The adenoid cystic carcinoma is characteristically