MUCOSAL MELANOMA OF THE HEAD AND NECK Scott J. Stern, MD, and Oscar M. Guillamondegui, MD
Forty-two patients with mucosal melanoma of the head and neck were treated at the M. D. Anderson Cancer Center from 1944- 1989. Their records were evaluated regarding: location of the primary, stage of the disease at presentation, type of treatment, location of recurrences, and overall survival. These patients received the majority of their therapy at M. D. Anderson Cancer Center. The treatment consisted of surgery, radiotherapy, chemotherapy, immunotherapy, or a combination of these. The 5-year survival rate was 40%. Twenty-four of 27 patients who died with metastatic melanoma had local or regional disease concomitantly. Forty percent of patients were free of disease at 5 years; however, only 26% had long-term survival. Although the majority of patients eventually succumbed to their disease, local and regional control was obtained initially in 92% of the group. These data indicate that prolonged survival is possible with mucosal melanoma of the head and neck; however, recurrence or metastasis remain possible many years after the initial diagnosis. HEAD 81NECK 1991; 13:22-27
Mucosal melanoma of the head and neck is frequently considered a fatal disease. Most published reports document a dismal 5-year survival rate of 10% t o 15%. Although many different treatment protocols have been tried, most experi-
From the Department of Head and Neck Surgery The University of Texas M. D. Anderson Cancer Center, Houston, Texas. Presented at the 72nd Annual Meeting of the American Radium Society, April 21 -25, 1990, Scottsdale, Arizona. Address reprint requests to Dr. Guillamondegui at the Department of Head and Neck Surgery, M. D. Anderson Cancer Center, 1515 Holcombe Blvd.. Box 069, Houston, TX 77030. Accepted for publication June 25, 1990 CCC 0148-6403/91/01022- 06 $04.00 0 1991 John Wiley & Sons, Inc.
22
Mucosal Melanoma
ence is anecdotal and limited to very few patients. The purpose of this study is to review the outcome of patients with mucosal melanoma of the head and neck over a span of 45 years, and to determine patterns of recurrences and survival. MATERIALS AND METHODS
Sixty-seven patients have registered at The University of Texas M. D. Anderson Cancer Center since 1944 with the diagnosis of mucosal melanoma of the head and neck. The primary tumor sites were the nasal cavity, including the nasopharynx and paranasal sinuses, and the oral cavity, including all structures anterior to the faucial pillars. Of the initial 67 patients, 49 received all or the majority of their treatment at M. D. Anderson Cancer Center. Eighteen patients were seen only in consultation, and did not receive further therapy. Seven patients were registered since 1985; as follow-up was less than 5 years, they were excluded from the analysis. Forty-two patients were evaluable and available to be followed for 5 years or until death. The subjects were evaluated regarding the location of the primary tumor, stage of the disease at the time of presentation, location and interval of recurrence, and survival. They were also stratified according to initial symptomatology, therapy received prior to admission at M. D. Anderson Cancer Center and therapy obtained at this hospital. The therapeutic modalities used included surgery, radiotherapy, chemotherapy, immunotherapy, or any combination of these. The timing
HEAD & NECK
JanuaryIFebruary 1991
and nature of each intervention was noted in order to classify the specific therapy as primary, salvage, curative, or palliative in intent. Statistical analyses were performed using log-rank tests, and survival data was calculated using the Kaplan-Meier method. Only those patients admitted prior to 1985 were included in the survival calculations.
Table 2. Presenting symptoms of 42 patients with mucosal melanoma of the head and neck.
Symptom
Number (%) of patients
RESULTS
Nasal obstruction Epistaxis Serous otitis media Dysphagia Neck disease Asymptomatic mass or pigmented lesion
24 (57) 22 (52) 2 (5) 2 (5) 2 (5) 19 (45)
Forty-two patients were included in this analysis. There were 23 men and 19 women. Their ages ranged from 23 to 89 years, with a median of 60;60% of the patients were between 55 and 75 years of age. Twenty-five patients had received no treatment prior to their admission to M. D. Anderson Cancer Center; the remaining patients had either an excisional biopsy or definitive therapy prior to their admission. The melanomas were classified as follows: stage 1, local disease, 31 patients (74%); stage 2,regional disease, 5 patients (12%); and stage 3, distant metastases, 6 patients (14%). After 1960, all patients were examined by a multidisciplinary group of physicians including head and neck surgeons, radiotherapy oncologists, and medical oncologists. Prior to 1960,surgery was the primary treatment in almost every case; chemotherapy and radiotherapy were generally used only for palliation. Twenty-three patients presented with primary tumors in the nasal cavity or paranasal sinuses; 19 had oral cavity melanomas (Table 1). The presenting symptoms are shown in Table 2; the median time from diagnosis to physician intervention was 8 months. Thirty-three patients (79%) received surgical treatment at some point in the course of their
disease; irradiation was used as the primary therapy in 5 patients. The total tumor dose varied between 50 and 65 Gy. Daily fraction size was 2 Gy in all cases, and the first echelon of nodal drainage pathways was included in the treatment fields. Chemotherapy was used after an excisional biopsy as “primary therapy” in 1 patient. Radiotherapy was used for salvage or as an adjuvant treatment in 8 patients; chemotherapy, immunotherapy, or both were similarly used in 29 patients. Sixty-five percent of the patients were alive 2 years after diagnosis; 48% (20) were alive 5 years after diagnosis, and 40% (17) of patients were disease-free at 5 years (Figures 1 and 2). The median time interval from the initial diagnosis to the first recurrence was 13.5 months. The median follow-up time was 46 months. Although the recurrence-free survival figures were relatively good 5 years after treatment, there was a steady decline in survival in years 5 through 10 as 26% (11)of patients were alive 10 years after diagnosis. In this group of surviving patients, 9 subjects never developed recurrences. Among the 42 patients evaluated, 17 patients had recurrence at the primary site, 7 had re-
Table 1. Site of the primary tumor in 42 patients with mucosal melanoma of the head and neck.
Site Nasal cavity Ethmoid Maxillary antrum Nasopharynx Septum and/or turbinates Oral cavity Retromolar trigone Maxillary alveolus Mandibular alveolus Hard/soft palate Oral tongue
Mucosal Melanoma
Number of patients 23 (total) 2 6 3 12 19 (total)
1 6 3 7 2
0.21
0.0
1 0
12
24
36 48 60 Month8 from Diagnoais
72
84
FIGURE 1. Cumulative survival of patients with mucosal melanoma of the head and neck.
HEAD & NECK
JanuarylFebruary 1991
23
1 . o n
4 I
0.0
.O
I\
K--
-'-\
- MD Anderson (11-25)
I
f h 0.0
I . . . . . . . 0
12
24
36 40 60 Months from Diognosis
72
0.0
J0
I
12
24
36
18
60
84
72
Months from Diognorir
04
FIGURE 4. Cumulative survival by place of initial treatment
FIGURE 2. Recurrence-free survival of patients with mucosal melanoma.
gional recurrences, and 27 develoepd distant metastases (median follow-up time, 7 years). A statistically significant difference in survival was determined by comparing the type of initial therapy; patients who were initially treated by a surgical resection alone had better 5-year survival rates ( p = 0.01, Figure 3). It should be noted that 2 of 5 patients treated with radiotherapy alone were alive and free of disease at 5 years; however, the limited number of patients in this group does not allow a statistical evaluation. Death was usually due to local or regional recurrence combined with metastatic disease; of 27 patients who died with metastases, 24 had local or regional disease as well. Nasal cavity or sinus melanomas appeared to have a slightly better prognosis in this series (data not shown). There was no difference in survival between patients who were initially treated outside M. D. Anderson Cancer Center and those who received all of their treatment there (Figure 4). There also was no statistically
E
Be n
..I 0.0 4 0
I. A 32-year-old white woman presented in 1952 with a pigmented lesion on the left maxillary alveolus. She underwet a local excision of this lesion, and a diagnosis of mucosal melanoma
Care
E
c
E
n
12
24
36 40 60 Months from Diognosis
72
i
04
FIGURE 3. Cumulative survival by type of initial treatment. By the log-rank test, p = 0.017.
24
significant difference in the frequency of melanoma recurrence in patients treated initially outside M. D. Anderson and those who received their entire treatment there (p = 0.063, Figure 5). The time interval to first recurrence was not influenced by the type of surgery performed. Elective neck dissections were not performed during the study period; 7 therapeutic neck dissections were performed after regional recurrence or at the time of the initial surgery, and this did not affect local and regional control rates or patient survival. Forty percent of the patients who underwent a neck dissection after the appearance of clinically positive adenopathy survived at least 5 years. The 5-year disease-free survival rates for patients presenting with NO or N+ necks were 35% and 30%, respectively. To illustrate the variable nature of this disease process, 2 representative cases will be presented.
Mucosal Melanoma
Oe2 0.0
t
40
- MD Anderson (n-25)
-- Outside ( ~ 1 7 ) 12
24
36 40 60 Months from Oiognosis
72
I
04
FIGURE 5. First recurrence by place of initial treatment. By the log-rank test, p = 0.063.
HEAD & NECK
January/February 1991
was obtained. She received no further treatment until 1954, where a local recurrence was similarly excised. Two other local recurrences were resected in 1956 and 1957, respectively. There was no evidence of disease until 1969, when a fourth local recurrence was treated by palatectomy. In 1973, a right subdigastric node was excised; this proved to be metastatic melanoma. A second node appeared in 1973 on the left side of the neck; this was treated successfully with radiotherapy. In May of 1974, pulmonary metastases were noted. The patient died of metastatic disease in February 1975, 23 years after initial diagnosis. At the time of death, there was no locoregional disease. An 82-year-old black man presented in July of 1961 with a 1-year history of a bleeding, pigmented lesion on the left mandibular alveolus. Biopsy confirmed the diagnosis of mucosal melanoma, and the patient underwent resection of the floor of mouth in continuity with a marginal mandibulectomy. In October of 1961, the patient presented with left subdigastric and perivascular nodal metastases. A radical neck dissection was performed; 6 nodes were positive for metastatic melanoma. The patient died in 1978 of a myocardial infarction at the age of 99; he was free of disease at the time of his death.
Case 2.
DISCUSSION
Mucosal melanoma of the head and neck is a relatively rare disease. Most reports in the literature include very few patients, and the experience in this subject has been limited. In general, the treatment of mucosal melanoma has not been uniform; thus, the results are difficult t o interpret.’-3 Reported 5-year survival rates of - ~ ; investigators 10% to 15% are ~ o m m o n ~many feel that there are no long-term survivors with this d i ~ e a s e .The ~ relatively hidden location of mucosal melanomas of the head and neck usually delays diagnosis, and curative therapy is often impossible. The evaluation of the patient with mucosal melanoma of the head and neck is straightforward. A complete history and physical examination gives the most information. Depending on the location of the tumor, appropriate radiologic studies (plain films, sinus tumor survey, computed tomographic scans) are obtained. As the vast majority of patients present with local disease, the investigation for metastatic disease
Mucosal Melanoma
should only include a chest radiograph and liver function tests. If these are normal, no further evaluation is necessary. Abnormalities in the physical examination or on the screening tests mentioned will direct further diagnostic studies. Early clinical diagnosis of mucosal melanoma of the head and neck is rare. The symptoms that prompt the patient to seek a physician’s care are usually indicative of advanced d i ~ e a s e . ”In ~ ,na~ sal cavity or paranasal sinuses primary lesions, the presenting symptom is usually epistaxis or nasal obstr~ction.~ Patients with oral cavity melanomas rarely have symptoms; in fact, the presence of a pigmented mass is usually the only reason for physician interventi~n.’.~ Histologic diagnosis of mucosal melanoma is seldom accomplished using routine stains. Special stains (the Fontana silver stain and the Prussian blue stain) are only about 75% a ~ c u r a t eImmunocytochemistry .~ has become the diagnostic method of choice.8 The S-100 stain and, more recently, the monoclonal antibody HMB-45 have shown better specificity in the diagnosis of undifferentiated neoplasm^.^,^ Histologic staging, used in the Clark system for cutaneous melanoma, has little utility for melanoma of the upper aerodigestive tract.g The depth of invasion of primary mucosal melanoma has been studied in some detail; there are reports that demonstrate a better prognosis for thin lesions.lo Unfortunately, standardized measurements have not been made, and most series are small. The only clinical finding that has definite prognostic significance is the presence of distant metastases at the time of diagnosis. The prognosis does not seem to be affected by anatomical site of origin, age, or sex of the patient.” The vast majority of patients with local disease undergo surgery as the initial treatment modality.12 In the past, radiotherapy was used only in patients with uncertain surgical margins or with locally recurrent or unresectable d i ~ e a s e .It~ has been demonstrated that local control may be increased by adjuvant radiotherapy, especially in patients with questionable surgical margins.13 The role of elective neck dissection for the control of subclinical regional disease is unclear. As the status of the regional lymph nodes does not appear to affect survival, dissection of the NO neck is probably not warranted.13-15 Whether radiotherapy or surgery should be used t o control the N+ neck is controversial; however, if one can extrapolate from cutaneous melanoma of the head and neck,
HEAD & NECK
JanuarylFebruary 1991
25
it is likely that surgery plus adjuvant radiotherapy provides the greatest benefit.12 Chemotherapy has generally been reserved for patients with systemic disease. Immunotherapy, either as primary or salvage treatment, has not improved survival or local-regional control rates in patients with mucosal melanoma. Surgical excision of the primary and regional melanoma has been associated with higher local and regional control and survival rates; however, this may reflect the fact that patients with unresectable disease undergo radiotherapy and chemotherapy primarily, thereby selecting more favorable patients for surgical inter~enti0n.l~ At the University of Texas M. D. Anderson Cancer Center, primary therapy for all resectable mucosal melanomas of the head and neck is surgery. If the lesion is small and margins are adequate, postoperative radiotherapy is not given. In general, postoperative radiotherapy is used in all patients with either microscopic or gross residual disease; only the primary and first echelon lymphatic drainage pathways are treated. Chemotherapy, given before or after the development of metastatic disease, has not impacted upon survival or local- regional control rates and is therefore not used as a primary therapeutic modality. For unresectable tumors, initial treatment with chemotherapy and/or radiotherapy is performed for palliation. If tumor shrinkage occurs, the lesion is resected. The cause of death is usually a combination of local recurrence and distant metastases.16The recent literature indicates that distant disease is associated with local recurrence in greater than
90% of cases.9J1,13,16,17 The average time to first local recurrence is 9 to 12 months; once local disease recurs, distant metastases are usually diagnosed within 3 months." Although local recurrence adversely affects survival, regional recurrence (in the absence of local or distant disease) probably does not. Many studies have demonstrated that therapeutic neck dissection after the appearance of regional disease is effective, and could be associated with prolonged s ~ r v i v a l . ~ ,Once ~ ~ , metastatic ~' melanoma is recognized, patients uniformly do poorly; the average duration of survival after metastases is 6 month^.'^.^^ Chemotherapy, even when used prophylactically, has not prevented the development of metastatic disease.13,1s Mucosal melanoma will remain a challenging clinical problem. Diagnosis is difficult and is often late in the course of the disease. Staging is imprecise and may not reflect tumor behavior. Patients who are seemingly cured may present with local or distant recurrence years after their initial therapy; therefore, constant vigilance is necessary with this malignancy. Surgery remains the mainstay of treatment; in fact, aggressive surgical control of local disease may result in prolonged disease-free survival. The role of primary or adjuvant radiotherapy remains unclear. Chemotherapy generally is reserved for proven metastatic disease. The extreme variability in the behavior of this neoplasm as evidenced by our case presentations is well-documented;although we have demonstrated improved survival by using aggressive surgical measures, death due to metastatic and locally recurrent disease remains a formidable clinical problem.
REFERENCES
1. Catlin D. Mucosal melanomas of the head and neck. AJR 1967;99:809-816. 2. Holdcraft J, Gallagher JC. Malignant melanomas of the nasal and paranasal sinus mucosa. Ann Otol Rhino1 Laryngol 1969;78:5- 19. 3. Hormia M, Vuori EEJ. Mucosal melanomas of the head and neck. J Laryngol Otol 1969;83:349-358. 4. Freedman HM, DeSanto LW, Devine KD, Weiland LH. Malignant melanoma of the nasal cavity and paranasal sinuses. Arch Otolaryngol 1973;97:322-325. 5. Conley J, Pack GT. Melanoma of the mucous membranes of the head and neck. Arch Otolaryngol 1974;99:315319. 6. Barton RT. Mucosal melanomas of the head and neck. Laryngoscope 1975;85:93-99. 7. Batsakis JD, Regezi JA, Solomon AR, Rice DH. The pathology of head and neck tumors-part 13: mucosal melanomas. Head Neck Surg 1982;4:404-412.
26
Mucosal Melanoma
8. Ordonez NG. Application of immunocytochernistry in the diagnosis of poorly differentiated neoplasms and tumors of unknown origin. Cancer Bull 1989;41:11-19. 9. Berthelson A, Anderson AP, Jensen TS, Hansen HS. Melanomas of the mucosa in the oral cavity and the upper respiratory passages. Cancer 1984;54:907- 912. 10. Iversen K, Robins RE. Mucosal malignant melanomas. A m J Surg 1980;139:660-664. 11. Blatchford SJ, Koopman CF, Coulthard SW. Mucosal melanoma of the head and neck. Laryngoscope 1986; 96:929-934. 12. Conley J, Hamaker RC. Melanoma of the head and neck. Laryngoscope 1977;87:760- 764. 13. Snow GB, Vander Waal I. Mucosal melanoma of the head and neck. Head Neck Surg 1978;1:24-30. 14. Shah JP, Huvos AG, Strong EW. Mucosal melanomas of the head and neck. A m J Surg 1977;134:531-535. 15. Snow GB, Van Der Esch EP, Van Slooter EA. Mucosal
HEAD 8. NECK
January/February 1991
melanomas of the head and neck. Otolayngol Clin North A m 1986;19:537-547. 16. Hoyt DL,Jordan T, Fisher SR. Mucosal melanoma of the head and neck. Arch Otolaryngol Head Neck Surg 1989;115:1096-1099. 17. Harwood AR, Cummings BJ. Radiotherapy for mucosal
Mucosal Melanoma
melanoma. Znt J Radiat Oncol Biol Phys 1982;8:11211126. 18. Eneroth CM, Lindberg C. Mucosal malignant melanomas of the head and neck. Acta Otolaryngol (Stockh) 1975;80:452-458.
HEAD & NECK
January/February 1991
27
Forty-two patients with mucosal melanoma of the head and neck were treated at the M. D. Anderson Cancer Center from 1944- 1989. Their records were evaluated regarding: location of the primary, stage of the disease at presentation, type of treatment, location of recurrences, and overall survival. These patients received the majority of their therapy at M. D. Anderson Cancer Center. The treatment consisted of surgery, radiotherapy, chemotherapy, immunotherapy, or a combination of these. The 5-year survival rate was 40%. Twenty-four of 27 patients who died with metastatic melanoma had local or regional disease concomitantly. Forty percent of patients were free of disease at 5 years; however, only 26% had long-term survival. Although the majority of patients eventually succumbed to their disease, local and regional control was obtained initially in 92% of the group. These data indicate that prolonged survival is possible with mucosal melanoma of the head and neck; however, recurrence or metastasis remain possible many years after the initial diagnosis. HEAD 81NECK 1991; 13:22-27
Mucosal melanoma of the head and neck is frequently considered a fatal disease. Most published reports document a dismal 5-year survival rate of 10% t o 15%. Although many different treatment protocols have been tried, most experi-
From the Department of Head and Neck Surgery The University of Texas M. D. Anderson Cancer Center, Houston, Texas. Presented at the 72nd Annual Meeting of the American Radium Society, April 21 -25, 1990, Scottsdale, Arizona. Address reprint requests to Dr. Guillamondegui at the Department of Head and Neck Surgery, M. D. Anderson Cancer Center, 1515 Holcombe Blvd.. Box 069, Houston, TX 77030. Accepted for publication June 25, 1990 CCC 0148-6403/91/01022- 06 $04.00 0 1991 John Wiley & Sons, Inc.
22
Mucosal Melanoma
ence is anecdotal and limited to very few patients. The purpose of this study is to review the outcome of patients with mucosal melanoma of the head and neck over a span of 45 years, and to determine patterns of recurrences and survival. MATERIALS AND METHODS
Sixty-seven patients have registered at The University of Texas M. D. Anderson Cancer Center since 1944 with the diagnosis of mucosal melanoma of the head and neck. The primary tumor sites were the nasal cavity, including the nasopharynx and paranasal sinuses, and the oral cavity, including all structures anterior to the faucial pillars. Of the initial 67 patients, 49 received all or the majority of their treatment at M. D. Anderson Cancer Center. Eighteen patients were seen only in consultation, and did not receive further therapy. Seven patients were registered since 1985; as follow-up was less than 5 years, they were excluded from the analysis. Forty-two patients were evaluable and available to be followed for 5 years or until death. The subjects were evaluated regarding the location of the primary tumor, stage of the disease at the time of presentation, location and interval of recurrence, and survival. They were also stratified according to initial symptomatology, therapy received prior to admission at M. D. Anderson Cancer Center and therapy obtained at this hospital. The therapeutic modalities used included surgery, radiotherapy, chemotherapy, immunotherapy, or any combination of these. The timing
HEAD & NECK
JanuaryIFebruary 1991
and nature of each intervention was noted in order to classify the specific therapy as primary, salvage, curative, or palliative in intent. Statistical analyses were performed using log-rank tests, and survival data was calculated using the Kaplan-Meier method. Only those patients admitted prior to 1985 were included in the survival calculations.
Table 2. Presenting symptoms of 42 patients with mucosal melanoma of the head and neck.
Symptom
Number (%) of patients
RESULTS
Nasal obstruction Epistaxis Serous otitis media Dysphagia Neck disease Asymptomatic mass or pigmented lesion
24 (57) 22 (52) 2 (5) 2 (5) 2 (5) 19 (45)
Forty-two patients were included in this analysis. There were 23 men and 19 women. Their ages ranged from 23 to 89 years, with a median of 60;60% of the patients were between 55 and 75 years of age. Twenty-five patients had received no treatment prior to their admission to M. D. Anderson Cancer Center; the remaining patients had either an excisional biopsy or definitive therapy prior to their admission. The melanomas were classified as follows: stage 1, local disease, 31 patients (74%); stage 2,regional disease, 5 patients (12%); and stage 3, distant metastases, 6 patients (14%). After 1960, all patients were examined by a multidisciplinary group of physicians including head and neck surgeons, radiotherapy oncologists, and medical oncologists. Prior to 1960,surgery was the primary treatment in almost every case; chemotherapy and radiotherapy were generally used only for palliation. Twenty-three patients presented with primary tumors in the nasal cavity or paranasal sinuses; 19 had oral cavity melanomas (Table 1). The presenting symptoms are shown in Table 2; the median time from diagnosis to physician intervention was 8 months. Thirty-three patients (79%) received surgical treatment at some point in the course of their
disease; irradiation was used as the primary therapy in 5 patients. The total tumor dose varied between 50 and 65 Gy. Daily fraction size was 2 Gy in all cases, and the first echelon of nodal drainage pathways was included in the treatment fields. Chemotherapy was used after an excisional biopsy as “primary therapy” in 1 patient. Radiotherapy was used for salvage or as an adjuvant treatment in 8 patients; chemotherapy, immunotherapy, or both were similarly used in 29 patients. Sixty-five percent of the patients were alive 2 years after diagnosis; 48% (20) were alive 5 years after diagnosis, and 40% (17) of patients were disease-free at 5 years (Figures 1 and 2). The median time interval from the initial diagnosis to the first recurrence was 13.5 months. The median follow-up time was 46 months. Although the recurrence-free survival figures were relatively good 5 years after treatment, there was a steady decline in survival in years 5 through 10 as 26% (11)of patients were alive 10 years after diagnosis. In this group of surviving patients, 9 subjects never developed recurrences. Among the 42 patients evaluated, 17 patients had recurrence at the primary site, 7 had re-
Table 1. Site of the primary tumor in 42 patients with mucosal melanoma of the head and neck.
Site Nasal cavity Ethmoid Maxillary antrum Nasopharynx Septum and/or turbinates Oral cavity Retromolar trigone Maxillary alveolus Mandibular alveolus Hard/soft palate Oral tongue
Mucosal Melanoma
Number of patients 23 (total) 2 6 3 12 19 (total)
1 6 3 7 2
0.21
0.0
1 0
12
24
36 48 60 Month8 from Diagnoais
72
84
FIGURE 1. Cumulative survival of patients with mucosal melanoma of the head and neck.
HEAD & NECK
JanuarylFebruary 1991
23
1 . o n
4 I
0.0
.O
I\
K--
-'-\
- MD Anderson (11-25)
I
f h 0.0
I . . . . . . . 0
12
24
36 40 60 Months from Diognosis
72
0.0
J0
I
12
24
36
18
60
84
72
Months from Diognorir
04
FIGURE 4. Cumulative survival by place of initial treatment
FIGURE 2. Recurrence-free survival of patients with mucosal melanoma.
gional recurrences, and 27 develoepd distant metastases (median follow-up time, 7 years). A statistically significant difference in survival was determined by comparing the type of initial therapy; patients who were initially treated by a surgical resection alone had better 5-year survival rates ( p = 0.01, Figure 3). It should be noted that 2 of 5 patients treated with radiotherapy alone were alive and free of disease at 5 years; however, the limited number of patients in this group does not allow a statistical evaluation. Death was usually due to local or regional recurrence combined with metastatic disease; of 27 patients who died with metastases, 24 had local or regional disease as well. Nasal cavity or sinus melanomas appeared to have a slightly better prognosis in this series (data not shown). There was no difference in survival between patients who were initially treated outside M. D. Anderson Cancer Center and those who received all of their treatment there (Figure 4). There also was no statistically
E
Be n
..I 0.0 4 0
I. A 32-year-old white woman presented in 1952 with a pigmented lesion on the left maxillary alveolus. She underwet a local excision of this lesion, and a diagnosis of mucosal melanoma
Care
E
c
E
n
12
24
36 40 60 Months from Diognosis
72
i
04
FIGURE 3. Cumulative survival by type of initial treatment. By the log-rank test, p = 0.017.
24
significant difference in the frequency of melanoma recurrence in patients treated initially outside M. D. Anderson and those who received their entire treatment there (p = 0.063, Figure 5). The time interval to first recurrence was not influenced by the type of surgery performed. Elective neck dissections were not performed during the study period; 7 therapeutic neck dissections were performed after regional recurrence or at the time of the initial surgery, and this did not affect local and regional control rates or patient survival. Forty percent of the patients who underwent a neck dissection after the appearance of clinically positive adenopathy survived at least 5 years. The 5-year disease-free survival rates for patients presenting with NO or N+ necks were 35% and 30%, respectively. To illustrate the variable nature of this disease process, 2 representative cases will be presented.
Mucosal Melanoma
Oe2 0.0
t
40
- MD Anderson (n-25)
-- Outside ( ~ 1 7 ) 12
24
36 40 60 Months from Oiognosis
72
I
04
FIGURE 5. First recurrence by place of initial treatment. By the log-rank test, p = 0.063.
HEAD & NECK
January/February 1991
was obtained. She received no further treatment until 1954, where a local recurrence was similarly excised. Two other local recurrences were resected in 1956 and 1957, respectively. There was no evidence of disease until 1969, when a fourth local recurrence was treated by palatectomy. In 1973, a right subdigastric node was excised; this proved to be metastatic melanoma. A second node appeared in 1973 on the left side of the neck; this was treated successfully with radiotherapy. In May of 1974, pulmonary metastases were noted. The patient died of metastatic disease in February 1975, 23 years after initial diagnosis. At the time of death, there was no locoregional disease. An 82-year-old black man presented in July of 1961 with a 1-year history of a bleeding, pigmented lesion on the left mandibular alveolus. Biopsy confirmed the diagnosis of mucosal melanoma, and the patient underwent resection of the floor of mouth in continuity with a marginal mandibulectomy. In October of 1961, the patient presented with left subdigastric and perivascular nodal metastases. A radical neck dissection was performed; 6 nodes were positive for metastatic melanoma. The patient died in 1978 of a myocardial infarction at the age of 99; he was free of disease at the time of his death.
Case 2.
DISCUSSION
Mucosal melanoma of the head and neck is a relatively rare disease. Most reports in the literature include very few patients, and the experience in this subject has been limited. In general, the treatment of mucosal melanoma has not been uniform; thus, the results are difficult t o interpret.’-3 Reported 5-year survival rates of - ~ ; investigators 10% to 15% are ~ o m m o n ~many feel that there are no long-term survivors with this d i ~ e a s e .The ~ relatively hidden location of mucosal melanomas of the head and neck usually delays diagnosis, and curative therapy is often impossible. The evaluation of the patient with mucosal melanoma of the head and neck is straightforward. A complete history and physical examination gives the most information. Depending on the location of the tumor, appropriate radiologic studies (plain films, sinus tumor survey, computed tomographic scans) are obtained. As the vast majority of patients present with local disease, the investigation for metastatic disease
Mucosal Melanoma
should only include a chest radiograph and liver function tests. If these are normal, no further evaluation is necessary. Abnormalities in the physical examination or on the screening tests mentioned will direct further diagnostic studies. Early clinical diagnosis of mucosal melanoma of the head and neck is rare. The symptoms that prompt the patient to seek a physician’s care are usually indicative of advanced d i ~ e a s e . ”In ~ ,na~ sal cavity or paranasal sinuses primary lesions, the presenting symptom is usually epistaxis or nasal obstr~ction.~ Patients with oral cavity melanomas rarely have symptoms; in fact, the presence of a pigmented mass is usually the only reason for physician interventi~n.’.~ Histologic diagnosis of mucosal melanoma is seldom accomplished using routine stains. Special stains (the Fontana silver stain and the Prussian blue stain) are only about 75% a ~ c u r a t eImmunocytochemistry .~ has become the diagnostic method of choice.8 The S-100 stain and, more recently, the monoclonal antibody HMB-45 have shown better specificity in the diagnosis of undifferentiated neoplasm^.^,^ Histologic staging, used in the Clark system for cutaneous melanoma, has little utility for melanoma of the upper aerodigestive tract.g The depth of invasion of primary mucosal melanoma has been studied in some detail; there are reports that demonstrate a better prognosis for thin lesions.lo Unfortunately, standardized measurements have not been made, and most series are small. The only clinical finding that has definite prognostic significance is the presence of distant metastases at the time of diagnosis. The prognosis does not seem to be affected by anatomical site of origin, age, or sex of the patient.” The vast majority of patients with local disease undergo surgery as the initial treatment modality.12 In the past, radiotherapy was used only in patients with uncertain surgical margins or with locally recurrent or unresectable d i ~ e a s e .It~ has been demonstrated that local control may be increased by adjuvant radiotherapy, especially in patients with questionable surgical margins.13 The role of elective neck dissection for the control of subclinical regional disease is unclear. As the status of the regional lymph nodes does not appear to affect survival, dissection of the NO neck is probably not warranted.13-15 Whether radiotherapy or surgery should be used t o control the N+ neck is controversial; however, if one can extrapolate from cutaneous melanoma of the head and neck,
HEAD & NECK
JanuarylFebruary 1991
25
it is likely that surgery plus adjuvant radiotherapy provides the greatest benefit.12 Chemotherapy has generally been reserved for patients with systemic disease. Immunotherapy, either as primary or salvage treatment, has not improved survival or local-regional control rates in patients with mucosal melanoma. Surgical excision of the primary and regional melanoma has been associated with higher local and regional control and survival rates; however, this may reflect the fact that patients with unresectable disease undergo radiotherapy and chemotherapy primarily, thereby selecting more favorable patients for surgical inter~enti0n.l~ At the University of Texas M. D. Anderson Cancer Center, primary therapy for all resectable mucosal melanomas of the head and neck is surgery. If the lesion is small and margins are adequate, postoperative radiotherapy is not given. In general, postoperative radiotherapy is used in all patients with either microscopic or gross residual disease; only the primary and first echelon lymphatic drainage pathways are treated. Chemotherapy, given before or after the development of metastatic disease, has not impacted upon survival or local- regional control rates and is therefore not used as a primary therapeutic modality. For unresectable tumors, initial treatment with chemotherapy and/or radiotherapy is performed for palliation. If tumor shrinkage occurs, the lesion is resected. The cause of death is usually a combination of local recurrence and distant metastases.16The recent literature indicates that distant disease is associated with local recurrence in greater than
90% of cases.9J1,13,16,17 The average time to first local recurrence is 9 to 12 months; once local disease recurs, distant metastases are usually diagnosed within 3 months." Although local recurrence adversely affects survival, regional recurrence (in the absence of local or distant disease) probably does not. Many studies have demonstrated that therapeutic neck dissection after the appearance of regional disease is effective, and could be associated with prolonged s ~ r v i v a l . ~ ,Once ~ ~ , metastatic ~' melanoma is recognized, patients uniformly do poorly; the average duration of survival after metastases is 6 month^.'^.^^ Chemotherapy, even when used prophylactically, has not prevented the development of metastatic disease.13,1s Mucosal melanoma will remain a challenging clinical problem. Diagnosis is difficult and is often late in the course of the disease. Staging is imprecise and may not reflect tumor behavior. Patients who are seemingly cured may present with local or distant recurrence years after their initial therapy; therefore, constant vigilance is necessary with this malignancy. Surgery remains the mainstay of treatment; in fact, aggressive surgical control of local disease may result in prolonged disease-free survival. The role of primary or adjuvant radiotherapy remains unclear. Chemotherapy generally is reserved for proven metastatic disease. The extreme variability in the behavior of this neoplasm as evidenced by our case presentations is well-documented;although we have demonstrated improved survival by using aggressive surgical measures, death due to metastatic and locally recurrent disease remains a formidable clinical problem.
REFERENCES
1. Catlin D. Mucosal melanomas of the head and neck. AJR 1967;99:809-816. 2. Holdcraft J, Gallagher JC. Malignant melanomas of the nasal and paranasal sinus mucosa. Ann Otol Rhino1 Laryngol 1969;78:5- 19. 3. Hormia M, Vuori EEJ. Mucosal melanomas of the head and neck. J Laryngol Otol 1969;83:349-358. 4. Freedman HM, DeSanto LW, Devine KD, Weiland LH. Malignant melanoma of the nasal cavity and paranasal sinuses. Arch Otolaryngol 1973;97:322-325. 5. Conley J, Pack GT. Melanoma of the mucous membranes of the head and neck. Arch Otolaryngol 1974;99:315319. 6. Barton RT. Mucosal melanomas of the head and neck. Laryngoscope 1975;85:93-99. 7. Batsakis JD, Regezi JA, Solomon AR, Rice DH. The pathology of head and neck tumors-part 13: mucosal melanomas. Head Neck Surg 1982;4:404-412.
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8. Ordonez NG. Application of immunocytochernistry in the diagnosis of poorly differentiated neoplasms and tumors of unknown origin. Cancer Bull 1989;41:11-19. 9. Berthelson A, Anderson AP, Jensen TS, Hansen HS. Melanomas of the mucosa in the oral cavity and the upper respiratory passages. Cancer 1984;54:907- 912. 10. Iversen K, Robins RE. Mucosal malignant melanomas. A m J Surg 1980;139:660-664. 11. Blatchford SJ, Koopman CF, Coulthard SW. Mucosal melanoma of the head and neck. Laryngoscope 1986; 96:929-934. 12. Conley J, Hamaker RC. Melanoma of the head and neck. Laryngoscope 1977;87:760- 764. 13. Snow GB, Vander Waal I. Mucosal melanoma of the head and neck. Head Neck Surg 1978;1:24-30. 14. Shah JP, Huvos AG, Strong EW. Mucosal melanomas of the head and neck. A m J Surg 1977;134:531-535. 15. Snow GB, Van Der Esch EP, Van Slooter EA. Mucosal
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melanomas of the head and neck. Otolayngol Clin North A m 1986;19:537-547. 16. Hoyt DL,Jordan T, Fisher SR. Mucosal melanoma of the head and neck. Arch Otolaryngol Head Neck Surg 1989;115:1096-1099. 17. Harwood AR, Cummings BJ. Radiotherapy for mucosal
Mucosal Melanoma
melanoma. Znt J Radiat Oncol Biol Phys 1982;8:11211126. 18. Eneroth CM, Lindberg C. Mucosal malignant melanomas of the head and neck. Acta Otolaryngol (Stockh) 1975;80:452-458.
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