Comprehensive Management of Head and Neck Tumors Stanley E Thawley, William R Panje, John G Batsakis, Robert D Lindberg Chapter 46: Controversies Regarding Therapy of Tumors of the Salivary Glands John Conley Controversies in the treatment of salivary gland tumors are to be expected, and, hopefully, will ultimately prove productive. Controversies may be a manifestation of the highest type of analytical thought, or be merely an expression of opposing views or a derivative of confusion. They can lead to brilliant precepts and acceptable consensus or nonproductive quarreling. I will attempt to analyze some features of their genesis in salivary gland tumors, the significance of these differences, and their possible evolution. All rational treatment programs should be preceded by an investigative and diagnostic analysis that establishes the reason and the style of management. There is certainly no fixed dictum regarding only one type of treatment. One would therefore expect nuances in management, depending on the therapist's analysis, professional background, and emotional attitudes regarding the disease and its treatment. This type of individual freedom in any therapeutic program introduces variations that will, hopefully, eventually lead to the truth. Controversies in therapy are the direct derivative of our reaction to the problems associated with neoplasia in salivary glands. The anatomy, the diagnosis, the biologic behavior, new surgical techniques, new concepts of management, irradiation, and chemotherapy generate discrepancies in results and the reporting of these results so that a variety of opinions may emerge. These differences naturally lead to controversies which are debated and ultimately settled by empiricism. Controversies are usually relative, contemporary, and personal, and most are ultimately relegated to oblivion. Biopsy There are some controversies in the method of diagnosis of these tumors. No one disputes the essentiality of the history and physical examination, but the question of biopsy has evolved through open incisional biopsy to needle aspiration biopsy to lateral lobectomy with frozen section diagnosis, which in some instances is an excisional biopsy. One would naturally expect some difference of opinion in such a broad approach. It is obvious that no single diagnostic procedure is applicable every time, nor is it expected to be eternally infallible. Open incisional biopsy is rarely performed today and is reserved for certain problem cases that defy routine methods of diagnosis. A possibly malignant tumor of the deep lobe in a teen-age girl who has questionable early facial paresis, and when the family group insists on a definitive pretherapeutic diagnosis, may necessitate an open biopsy if needle aspiration biopsy has proved to be inconclusive. Aspiration biopsy has the advantage of penetrating the tumor without incision and, hopefully, harvesting sufficient germane tissue to justify an accurate histologic diagnosis. The 1
difficulties with this technique are associated with the not infrequent pleomorphic structure of the tumor, the possibility that a representative portion of tumor may not be retrieved, and that the pathologist may not be able to establish the correct diagnosis or may request additional tissue for study purposes. If the pathologist's interpretation is incorrect and the patient receives treatment complying with this inaccuracy, there will certainly be controversy. In spite of these potential hazards, aspiration biopsy may be very helpful. It has the capability of differentiating benign from malignant tumors and identifying inflammatory disease under ideal circumstances. The responsibility for error or misjudgment with this technique rests with those who use it and who are sensitive to its strengths and weaknesses. It will obviously not solve all problems, but it can solve some. The technique of lateral lobectomy has become a standard operation in the management of parotid tumors. It is particularly useful in tumors located in the lateral lobe, and it is indeed both diagnostic and curative for all benign tumors and many low-grade malignant tumors localized in this portion of the gland. It has the advantage of exposure and protection of the facial nerve and of removing the major portion of the parotid gland while preserving the nerve. It establishes technical and biologic security, and supplies the pathologist with sufficient tissue for immediate frozen section examination. There is, of course, always the possibility that a frozen section diagnosis may be ambiguous. If it is, the surgeon has the option of waiting for the final definitive diagnosis and then advising the patient as to what should be done, or proceeding with conservative surgery immediately, without mutilation, to gain the maximum effectiveness during the primary operation. One word should be said regarding microscopic diagnosis of salivary gland tumors. It is a product of the training, interest, and experience of a pathologist or a group of pathologists. If the microscopic sections are examined by only one pathologist in a hospital that has a small volume of salivary gland tumors, there will be little controversy but perhaps an increased chance for misinterpretation. In large medical centers, there may be a consensus after a conference and discussion. In some instances, the responsible surgeon or patient may wish a second opinion. Both must be aware that a change of diagnosis or opinion can occur in over 10 per cent of the complicated cases and that this is not a fault, but a fact. Treatment Today there is general agreement that salivary gland tumors require treatment. For decades, however, it was not uncommon for the physician to advise the patient "not to operate a salivary gland tumor until it bothered him." This naïve concept of management has been replaced by treatment of all of these tumors, in light of the fact that approximately 25 per cent in the parotid gland, 50 per cent in the submandibular gland, and 65 per cent in the minor salivary glands are malignant. There is rarely ulceration of the skin or mucous membrane. These threatening data leave little choice beyond an attempt to accurately diagnose and then institute a therapeutic program. Sialography, technetium scanning, and response to conservative treatment, combined with clinical evaluation, inevitably lead to the proposition of a histologic diagnosis when tumor is suspected. Because of the difficulties encountered in certain histopathologic types of tumors in salivary glands, a variety of concepts of management have developed. These concepts include observation, conservative surgery, radical surgery, rehabilitative surgery, in combination with irradiation, irradiation alone, chemotherapy, and combinations of these modalities. 2
Differences of opinion are normative for such a complex set of situations occurring in the salivary glands. These controversies are reduced in scope by a general consensus that the majority of benign tumors are treated surgically, that the majority of malignant tumors of epithelial origin are also treated surgically, that all lymphomas and Hodgkin's neoplasms are treated by irradiation and chemotherapy, and that the majority of the pernicious, recurrent, and high-grade cancers are treated by a combination of surgery and irradiation. There are obvious exceptions and overlapping in all therapeutic trials. In general, the controversies do not dominate management and hopefully point the way to a more effective program. The basic surgical approach is by lateral lobectomy operation or removal of the submandibular or minor salivary gland combined with the advantage of frozen section information. The lateral lobectomy operation has proved effective in all benign tumors of the lateral lobe and isthmus and as a surgical preparation for benign tumors of the deep lobe and in some low-grade malignant tumors in the lateral lobe. This facilitates the tumors of the parotid gland. Excisional biopsy in all other salivary glands is usually curative for benign tumors, but always requires reoperation if the tumor proves to be malignant. It is in this latter circumstance that some physicians and some patients hope that the biopsy excision has cured the malignant tumor and prefer to "wait and see" what happens or to have irradiation. This decision, which is primarily based on wishful thinking, often proves disastrous. The alternative to this is to have discussed the possibility of malignancy in advance with the patient and to be prepared to carry out a radical ablation on the basis of a frozen section diagnosis or to reoperate after clarification with the patient. Some surgeons have expressed insecurity about accepting a frozen section diagnosis. There is always, of course, a possibility for error, and this responsibility must be measured by the surgeon in realistic terms that relate to the pathologist's experience and firmness upon open interrogation concerning the reliability of the diagnosis. If there is any doubt whatsoever on the part of the surgeon or the pathologist, the surgeon should not proceed with a mutilating operation without the patient's knowledge and consent. There is little difference of opinion regarding the treatment of benign tumors of the salivary glands. In the vast majority of cases, the benign tumor is removed along with the gland in which it arises. Some surgeons do not perform a lateral lobectomy in the parotid gland, but prefer enucleation. When this is performed outside the capsule, when the tumor is spheroid and compact without significant lobulations, and when it is removed without spillage, there is an equal chance of a low recurrence rate comparable to that associated with the lateral lobectomy technique. If these criteria, however, cannot be met, the incidence of recurrence will markedly increase. Under ideal circumstances, the rate of recurrence will be approximately 1 per cent. There is mild controversy and a slight misunderstanding regarding the management of recurrent benign mixed tumors in the parotid gland. The vast majority of these conditions are due to spillage and seeding during the primary operation. The incidence of local recurrence with the uncomplicated benign mixed tumor undergoing lateral lobectomy is in the neighborhood of 1 per cent. Before reoperating on anyone with a recurrent tumor, one should confirm the microscopic diagnosis of benignity and review the original operative report, if that is available. An assessment of the recurrent tumor will provide the information for the most rational reoperation. If there is a single focus of recurrence and the facial nerve is intact, 3
every effort should be made to conservatively remove the isolated tumor and preserve the nerve. If the more likely situation of multiple recurrences presents at the operative site, a conservative resection should again be considered, but the situation is obviously more complex. Recurrence rates for recurrent benign mixed tumor go up to 25 per cent after multiple failures at conservative attempts. When recurrent tumors have enmeshed the facial nerve and there are confluent masses of tumor about the area of the primary operation, the surgeon has few alternatives to an operation that would encompass the nerve. Under these circumstances, the facial nerve should be rehabilitated immediately by autogenous facial nerve grafting. Even with these aggressive efforts, the patient must be cautioned regarding the possibility of local recurrence. Some patients will not accept this type of operation and prefer either to remain under observation or to receive irradiation. Keeping a benign tumor under observation may please the patient for an indefinite period of time, but over a period of decades it always presents the slight possibility of the development of cancer and also of expanding to an inoperable status. Irradiation will retard the growth of the vast majority of these tumors, but carries the biologic risks associated with its use in the treatment of benign tumors. There is a substantial difference of opinion regarding certain specific aspects of the treatment of malignant tumors in the salivary glands. This difference is generated by the variations in the histologic and biologic behavior of individual tumors, the teaching background of the surgeon or radiotherapist involved, and the emotional reactions of the patient to the problem. Most surgeons agree that all high-grade malignant tumors, all malignant tumors with preoperative facial paralysis or gross metastases, all large malignant tumors of the deep lobe or those that have invaded adjacent structures, and most recurrent malignant tumors require an aggressive ablative resection, usually including the total parotid, facial nerve, paraglandular structures, possibly the mandible, and some type of neck dissection. Neck dissection is, of course, more applicable in these types of tumors in the parotid gland and submandibular gland than in minor salivary glands. In cancers of the parotid gland, one may be forced to include the ear, a portion of the mastoid or temporal bone, the mandible, and infratemporal space contents. In such cancers arising in the submandibular gland, one may be obligated to carry out not only a neck dissection, but often resection of associated skin, a portion of the parotid, floor of the mouth, and a portion of the tongue. In such large resections, some type of regional flap is usually necessary to rehabilitate the wound. In such salivary gland cancers arising in the sinuses, palate, or oral cavity, large areas of not only the specific site of origin but also the adjacent tissue must often be sacrificed simultaneously. Most surgeons would also agree that the majority of these cases would be candidates for postoperative radiotherapy. The variability and aggressiveness of the different types of malignant tumors, their approximation to important aesthetic and functional structures, and the promise of therapeutic enhancement from postoperative irradiation have created a mixture of biologic insecurity and emotional hopefulness that has made the assessments of therapeutic options more difficult. The patient's involvement in the decisionmaking process is often influenced by the instinctual desire to maintain the integrity of the body and the "quality of life". These forces could understandably lead to controversy in a management program containing these variables. A consultation is always helpful. In low-grade malignant tumors of the salivary glands, there is a realistic possibility for some degree of conservatism. Low-grade mucoepidermoid and low-grade acinic cell cancers are candidates for some of these modifications. Small tumors that are readily 4
accessible surgically and have not approached or invaded adjacent structures, and tumors for which there has been a specific request to preserve the facial nerve or mandible or adjacent soft tissues and for which there is a planned intent to use postoperative irradiation as complementary treatment, also qualify for some type of conservation modification. There is no question that preserving all or some part of the facial nerve in malignant tumors of the parotid gland has gained considerable popularity. Many of these advocates propose "peeling" the cancer off the nerve sheath and preserving the integrity of the nerve regardless of the proximity, size, or biologic aggressiveness of the cancer. At times they may be willing to sacrifice a secondary or tertiary branch. These attitudes and judgments contain an increased risk, and this is compensated for by the use of postoperative irradiation. It is generally agreed today that the complementary use of irradiation in a combined program has great merit and will improve prognosis in certain cases. Saving the facial nerve in specific and hazardous circumstances may, indeed, be justified in a combined program. The decision for this type of management understandably contains the risks of spillage and gross subtotal resection of the cancer and the biologic possibility that any microscopic residual cancer may not respond to irradiation. The concept of conservation is emotionally very appealing and is being strongly advocated, but its ultimate role in therapy must await additional trials and data. An analysis of my experience with these variations in malignant tumors of the parotid gland indicated that 68 per cent of the patients had radical ablative surgery and 32 per cent had some type of conservation surgery. Approximately 32 per cent had preservation of some of the branches of the facial nerve, 26 per cent had facial nerve grafts, and 42 per cent had other types of reconstructive procedures. These results are summarized in the table. Table. Analysis of Surgical Results in Patients with Malignant Tumors of the Parotid Gland Patients (%) Types of Surgery Extent of surgery 68% Radical ablation 32% Some variety of conservation Results 26% Facial nerve graft 32% All or part of nerve intact 42% Not grafted, but other types of reconstruction (eg, masseter muscle, 12th cranial nerve, temporal muscle, use of alloplastic substance) There are obvious exceptions to the preceding philosophical concepts. Some patients will not accept mutilating procedures. Some radiotherapists are willing to treat a large variety of malignant tumors, and even some benign tumors, with irradiation as the primary method of management. Other radiotherapists approve of a reduction in the scope of the operation, with the hope that postoperative irradiation will eradicate any possible residual cancer. Some radiotherapists are reluctant to use irradiation in children because of the severe sequelae in arrested development, gross deformity, and biologic hazards. Some surgeons have not accepted radicality with any degree of enthusiasm and attempt to organize effective palliation in advanced cases. Many of these differences are reflections of philosophical and emotional 5
reactions to the complexity intrinsic in the management of some of these life-threatening and potentially deforming neoplasms. In dealing with a system of malignant tumors for which the cure rate varies from 20 to 95 per cent, it is realistic to have differences of opinion and controversy. There should never be a rigid protocol of therapy until the treatment advances to the stage at which a fixed protocol is justified. 6