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Primary malignant melanoma of the oral cavity
Primary malignant melanoma of the oral cavity DEPARTMENT NEWCASTLE
OF l’ATHOLO(;Y,
DENTAL
SCHOOL, UNIVERSITY
OF
UPON TYNE
I’rinmry mnliynant melanoma of the oral cavity is an uncommon tumor. Six cases which represent the authors experience with this lesion over a 14.year period are presented. The literature is reviewed, and tlw ultimately poor prognosis is commented upon.
P
limary malignant melanoma of the mouth represents less than 2 per cent of all malignant melanomas,1-4 approximately the same ratio that exists between oral malignancies of all kinds and those occurring elsewhere in the body. Anneroth ant1 associates,” citing fourteen cases in Sweden, found that these represented only 0.2 per cent of cases. This may be tluc to the fact that malignant melanoma is much more common in very fair-skinned persons” but is also apparently related to exposure to sunlight, a factor not effective in the mouth. The disease is rare, and although Chauclhry and associates’ were able to review 105 cases, these had been spread over a hundred years. Reports have become more common with the great increase in publications of all kinds, but 14 years were required to collect the six cases reported here, a period during which we could expect to see 400 cases of carcinoma of the mouth. Pigmentation of the oral mucosa, like that of the skin, is commonly reported to precede malignant melanoma. Chaudhry and associates found an incidcn~e of about 30 per cent and, since pigmentation of the mouth might well escape notice, this is probably a low estimate. Racial pigmentation probably bears a negative relationship to melanoma, with the disease appearing to be much more common in Caucasians than in Negroes,” a common site in whom is the relatively unpigmented sole of the foot. AGE AND
SEX
Moore and Martin found that the average age of patients who suffered from malignant melanoma of the upper respiratory tract and mouth was 59 years, and 553
Oral April,
Surg. 1975
none of their patients was under 30. Chaudhry and associates reported an average age of 50.5 years, 90 per cent being over 30. The youngest of our six patients was 49, and the oldest was 80. Chaudhry and associates found that oral tumors were almost twice as common in males; whereas Moore and Martin, in their smaller series, had fourteen male and twelve female patients. Our own six patients were all females. It is of interest that Pack and associates,“i in their extensive investigation of malignant melanoma in all sites, found exactly the same numbers, 372, of each sex. SITE
Four fifths of all oral lesions occur in the upper jaw. It follows that only isolated cases are reported in other parts of the mouth, although lesions may extend from the palate and maxillary alveolar process to involve adjacent structures. CLINICAL
APPEARANCE
Patients may seek treatment because of bleeding or because they have been alarmed by a pigmented patch on the oral mucosa. The lesion may be an obvious swelling, or it may take the form of a black or brown discoloration of variable extent, partly elevated, or ulcerated. Pain is not a common symptom, so that the lesion may reach a considerable size before it is observed or considered worthy of attention. Not all oral melanomas are obviously pigmented, as the following case histories show, and one of our cases presented as a nonpigmented swelling that arose in an extensive area of black pigmentation of the palate. Involvement of lymph nodes is common. .In Chaudhry’s cases, more than half had clinical evidence of regional lymph node metastases, and 20 per cent had clinical or radiographic evidence of generalized metastases. HISTOLOGY
The presence of junctional activity is a helpful feature in the diagnosis of primary malignant melanoma, since it indicates the probable source of the tumor cells, more particularly if it, is possible to connect the cells in the junctional situation with those in the tumor. The cells ma.y resemble melanocytes or may be spindle shaped, suggestive of a sarcoma. They may mimic squamous cells and suggest squamous carcinoma. Sometimes they are very anaplastic. The most helpful feature in doubtful cases is the presence of melanin, which can be bleached to distinguish it from other pigments, particularly hemosiderin, which can be stained by the Prussian blue reaction. Melanin may be seen in the tumor cells, in histiocytes, or lying free in the tumor. Sometimes it is absent or present in only small quantities in the primary lesion but may still be an obvious feature in metastases. It is perhaps noteworthy in the six cases reported here that pigment, when present, was largely confined to the overlying or adjacent epithelium and subepithelial connective tissue. TREATMENT
Excision of the local lesion or its destruction by diathermy may arrest the local disease but usually will not prevent the development of secondary deposits.
Radiotherapy sometimes appears to be almost ineffective but may be the only practicable form of treatment in some eases. In view of the overwhelming frequency of metastases, doubt has been east on the value of block dissection.4 Some writers advise this treatment, however, perhaps in the hope that the almost inevitable metastases are confincd to the cervical lymph nodes. From the figures quoted below, it is clear that treatment has only a small chance of permanent SUCcess. Occasionally, however, patients have received prolonged benefit from rc[seated local measures. One patient described by Conley and Pack! had been livilrg free of malignant melanoma for 9 years subsequcllt to four local rcsfctions. PROGNOSIS
Oral lesions have a much poorer prognosis than do skin lesions. Only three of Chaudhry’s 105 patients were known to have survived for 5 years, and Moore and Martin reported only one S-year cure in twenty-six cases. In contrast to these depressing figures, C’onlcy and Pack reported a S-year cure rate of 35 per cent in 116 patients with melanoma of the head and neck; Lehman and associates’” reported a 13 per cent survival rate in forty-two cases of skin lesions; and Pack and associates* reported a 21.4 per cent s-year cure rate in 575 patients with melanoma of all sites. The reasons L’or the tliffcrentc between oral and other lesions are probably late diagnosis ancl difficulty in treatment of the former. REPORT OF SIX CASES
Five of the following cases of primary malignant melanoma of the oral cavity were examined clinically at the Dental Hospital or the IIental Department of the Royal Victoria Infirmary, Newcastle upon Tyne, and one at the (:cncral Hospital, Newcastle upon Tyne. The histologic examinations were carried out at one or another of these institutions and the material was rc-cxaminetl by us for the present purpose.” CASE 1
This 80-year-old etlentulous Wyman attendetl in September, 1951, having ol)serve(l a (liscoloration of the mouth subsequent to a small injury 2 months previously. Examination revealed numerous black spots on the patient’s face an(l intense black pigmentation of most of the hart1 palate and of the anterior part of the alveolar process. The pigment,ecl area was sharply tlemarcate(1 from the surrountling normal tissue (Fig. 1). ln the maxillary 1.5 cm. in diameter, coverecl ]I> incisor region there was a soft, pe(lunculate~1 swelling, mucous membrane of normal pink appe~~ranec. The ecarvio:ll lymph nodes \\(‘I‘(! enlarged. A biopsy of the black mucosa showetl junctional activity anI1 melanin. In February, 1955, the unpigrnentetl oral swelling became ulceratell, ant1 l,iopsy showetl that it was composed of clear cells resembling melanocytes. Some of the overlying epithelium showetl junctional activit)continuous with the tumor, which was partly pigmenterl. Over the next 3 years the oral lesion slowly enlnrgd and hecnmc~ irregul:ir and somewhat lobulatetl in contour. It started to blee(l at fairly frequent intervals, but otherwise neither the primary lesion nor the gradually enlarging cervical notlex causetl any trouble. In view of the slow progress of the oral lesion, its relatively trouble-free nature, ant1 the “\Ve are grateful for the help of our colleagues pres(Jnt :ln(] past in these llospit;l]s and wish particularly to thank the following who nllowed us access to their ease notcxs: Mr. J. I). K. Dawes, Mr. J. R. G. Edwards, Dr. R. G. B. Evans, Mr. R. Finney, Professor G. IA. Howe, Mr. G. Hutchinson, Mr. K. I. Munro Black, Mr. C. .J. I,. Thurgar, an,] professor B. I:. Tomlinson
556
Jacksott and Simpson
Oral April,
P’iy. 1. Case 1. The intensely pigmented area of the palate is sharply demarcated surrounding mucosa. Contained within it is a clinically nonpigmented swelling.
Surg. 1975
from the
advanced age of the patient, the decision was made to only irradiate the cervical nodes. This treatment had little effect. The patient eventually developed a cough, which may have been caused by secondary deposits in the lungs, although circumstances preventetl proof of this being obtained. She died in January, 1958, 3$$ years after the oral lesion was first observed; death was attributed to the tumor. CASE 2
This 49-year-old woman was first seen in December, 1956, when she stated that she had noticed a brown spot on the palate 2 weeks after an episode of soreness of the mouth. She was wearing 5-year-old dentures. Examination revealed an extensive area of pigmentation on the left side of the palate and alveolar process. Histologically, the lesion appeared to be a benign melanoma, but it recurred three times in the next 7 years. On the last of these occasions, in January, 1964, it appeared as a soft swelling on the right maxillary alveolar process, extending from the midline to the premolar region, together with two nodules, each 1 cm. in tliameter, in the labial sulcus. Biopsy showed junctional nevus and a malignant melanoma composed of densely aggregated spindle cells with little pigmentation, The tumor was irradiated. Nine months later there was a further recurrence and also bilateral enlargement of the cervical lymph notles. Further irradiation was given, apparently effectively, but the patient died in April, 1965, with the cause of death being given as malignant melanoma and secondary deposits. Although the patient lived for 8 years from the time she was first examined, death occurred only 14 months after the lesion was pronounced to be malignant. CASE 3
In September, 1956, this 54-year-old woman complained of soreness of the left maxillary gingivae, and in llecember she observed a swelling which grew slowly at first but more rapidly later. E:xaminatiou in April, 1957, revealed an oval mass 5 by 2 cm. extending along the edentulous alveolar ridge in the upper left premolar and molar region. It was of rounded form am1 attached by a thick pedicle and had a tleshy appearance. There was tenderness over the right malar eminence, extending to the infraorbital region, and the patient stated that during the previous week she had suflerecl from attacks of stabbing pain. Radiographs of the sinuses showed no abnormality. Biopsy showed a tumor composed mainly of short, variously orientated spindle ceils, partly anaplastic and underlying densety packed, squamous epithelium which demonstrated considerable junctional activity. Ko pigmentation
Volume 39 Number 4
Primary
maligsawt
melanoma
of oral cavity
557
Fig. 1. Case 6. Centrally on the palate there is a soft, pigmented swelling with an ulcerated surface. There are also diffuse areas of pigmentation of the edentulous alveolar ridge.
was seen either in this tissue or in a lymph node removed later. The patient was suffering from marked cardiac disability, and treatment was delayed for several weeks, after which the lesion was excised. Shortly afterward, enlarged nodes were observed in the right side of the neck and submandibular region. These were irradiated and they regressed markedly. In February, 1958, a large node in the right submandibular region was excised and found to contain tumor that resembIed the more anaplastic part of the primary lesion. In August, 1958, the patient complained of several severe attacks of epistaxis and of increasing discomfort in the right cheek. There was a recurrent lesion in the right maxillary antrum. A month later she had considerable pain in the right maxillary and zygomatic evidence of pulregions. There was a palpable node in the right neck, and radiographic monary metastases. In November, 1958, the bulk of the maxillary lesion was removed because of severe pain. The patient died 4 months later with melanoma of the palate and secondary lesions in the lungs and mediastinum. She had suffered a great deal of pain and was troubled continually by the primary lesion, but in spite of her cardiac defect she lived for 2rh years from the time she first noticed the lesion. CASE 4
This E&year-old woman, who was edentulous and wearing 16-year-old dentures, complained of bleeding from the left maxillary gingivae of 3 weeks’ duration. Examination in July, 1963, revealed an ulcerated, nonpigmented, pedunculated swelling situated on the edentulous alvelolar ridge in the left maxillary incisor and canine region and extending into the labial sulcus. No lymphadenopathp was observed. The lesion was excised and histologically consisted of spindle cells with many mitosee. No pigment was seen, but the presence of junctional activity in the overlying epithelium and the apparent continuity of this abnormality with the tumor indicated that this was a malignant melanoma. Two weeks later the alveolar process and palate were excised from the right canine to the left mol’ar region. After another 6 weeks, some more tissue was removed from the margins of the wound, and a large left submandibular node was observed. A block dissection of the left side of the neck was carried out and pigmented melanoma was found in the lymph nodes. The patient remained well for several months, but in August, 1964, she was hospitalized with a pleural effusion in which was found cytologic evidence of malignant melanoma. She died in September, 1964, 14 months from the time she was first seen. Death was attributed to pleural effusion and melanotic metastases.
550
Jackson and Simpson
Oral April,
Surg. 1975
CASE 5
This 69.year-old woman presented in July, 1964, with a small papillomatous lesion of the soft palate and a pigmented patch on the hard palate, 2.5 by 1.2 cm. She was unable to provide any history. The papillomatous lesion was excised and reported as a junctional nevus. In October, 1968, she returned with a small tumor in the upper incisor region and pigmented patches on the left hard palate. The tumor was excised and histologically was found to be a spindle-cell malignant tumor compatible in appearance with a malignant melanoma. There was no pigment, but the adjacent epithelium showed junctional activity. The palate and neck were irradiated, but a year later a pedunculated, fleshy swelling was observed on the alveolar process to the right of the midline, and there was a pigmented area to the left. In spite of radiotherapy, the lesion progressed and a mass developed in the left neck. Further irradiation produced some improvement in the cervical lesion, but the patient died in May, 1973, with persistent oral lesions and metastases in the liver. This patient survived for 4yz years from the time the malignant lesion was diagnosed, and for nearly 9 years after the diagnosis of a junctional nevus and the recognition of oral pigmentation. CASE 6
One month before this 72.year-old woman was examined, she observed what she thought was a blister on the palate. It appeared to burst and there was subsequent bleeding. Examination in December, 1968, showed that the patient was wearing 27-year-old dentures. In the center of the hard palate and extending to its posterior margin was a blue/black patch with a soft central elevation which appeared to be ulcerated (Fig. 2). There were two less intensely pigmented areas on the alveolar ridge in the right molar and premolar areas and another patch on the mucous surface of the upper lip. The regional lymph nodes were not palpable. Two days later, at which time there was a certain amount of bleeding from the raised part of the palatal lesion, a biopsy specimen was taken from the adjacent pigmented mucosa. Histologically, it showed considerable melanin pigmentation of the epithelium and subepithelial connective tissue. There was junctional activity, with many mitoses and intraepithelial spread of maligant melanoma, but no tumor mass was found in the tissue which was peripheral to the more active-appearing part of the lesion. The patient was treated lvith radiotherapy, but the oral lesion persisted and she developed cervical metastases. She died in October, 1969, with multiple secondary lesions, 16 months after she was first seen and less than a year after she first observed the oral lesion.
DISCUSSION
Diagnosis of primary malignant melanoma is not always easy. Pigmentation present over or surrounding the tumor immediately arouses suspicion, and even atypical patches of pigmentation alone do not usually go unnoticed but when this sign is absent there is obvious difficulty, and the benefits of hindsight are readily applicable to the later assessment of such material. The cases described here all showed some degree of junctional activity involving the overlying or adjacent epithelium. One tumor was composed of recognizable melanocytes, whereas the others consisted of spindle cells of varying thickness and, in the absence of both melanin and junctional activity, would have presented a considerable problem. Sections of multiple blocks were sometimes necessary to exclude spindle-cell sarcoma. In one case the presence of pigmented lymph node metastases was a helpful finding when the primary lesion showed no pigmentation. Although the tumor, once established, appears to be little affected by treat-
Volume 39 Number 4
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maligvlaat
meh10mff
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559
ment, it is not necessarily as rapidly fatal as its reputation might suggest. In spite of the unrelenting nature of their disease, four of the patients lived for several years relatively free of symptoms. SUMMARY
The natural history of malignant melanoma of the oral with reference to the findings of previous writers, and six reported. These demonstrate the considerable variations in of the disease while confirming the difficulty of treatment nature of the condition.
cavity is discussed additional cases are detail of the course and the inexorable
REFERENCES 1. Baxter,
2. 3. 4. 5. 6. 7. 8. 9. 10.
II.: Malignant Melanoma in the Coloured Races: Report of a Case Originating in the Mouth, Can. Med. Assoc. J. 41: 350-354, 1939. Morris, G. C., Jr., and Horn, R. C.: Malignant Melanoma in the Negro; Review of the Literature and Report of Nine Cases, Surgery 29: 223-230, 1951. Moore, S. E., and Martin, H.: Melanoma of the Upper Respiratory Tract and Oral Cavity, Cancer 8: 1167-1176, 1955. Milton, G. W., and Lane Brown, M. M.: Malignant Melanoma of the Nose and Mouth, Br. J. Surg. 52: 484-493, 1965. Anneroth, G., Carlson, 0. D., Eneroth, C. M., and Moberger, Cr.: Primary Melanoma in the Oral Mucous Membrane, Swedish Dent. J. 66: 27-37, 1973. Pack, G. T., Davis, J., and Oppenheim, A.: The Relation of Race and Complexion to the Incidence of Moles and Melanomas, Ann. N. Y. Acad. Sci. 100: 719-742, 1963. Malignant Melanoma of the Chaudhry, A. P., Hampel, A., and Gorlin, R. J.: Primary Oral Cavity, Cancer 11: 923.928, 1958. of Pack, G. T., Gerber, D. M., and Scharnagel, I. M.: End Results in the Treatment Malignant Melanoma, Ann. Surg. 136: 905-911, 1952. Conley, J. J., and Pack, G. T.: Melanoma of the Head and Neck, Surg. Gynecol. Obstet. 116: 15-28, 1963. Lehman, J. A., Cross, F. S., and Richey, G. D.: A Clinical Study of 49 Patients With Malignant Melanoma, Cancer 19: 611, 1966.
Reprint requests to : Dr. D. Jackson Department of Pathology Dental School University of Newcastle upon Tyne Newcastle upon Tyne, England
OF l’ATHOLO(;Y,
DENTAL
SCHOOL, UNIVERSITY
OF
UPON TYNE
I’rinmry mnliynant melanoma of the oral cavity is an uncommon tumor. Six cases which represent the authors experience with this lesion over a 14.year period are presented. The literature is reviewed, and tlw ultimately poor prognosis is commented upon.
P
limary malignant melanoma of the mouth represents less than 2 per cent of all malignant melanomas,1-4 approximately the same ratio that exists between oral malignancies of all kinds and those occurring elsewhere in the body. Anneroth ant1 associates,” citing fourteen cases in Sweden, found that these represented only 0.2 per cent of cases. This may be tluc to the fact that malignant melanoma is much more common in very fair-skinned persons” but is also apparently related to exposure to sunlight, a factor not effective in the mouth. The disease is rare, and although Chauclhry and associates’ were able to review 105 cases, these had been spread over a hundred years. Reports have become more common with the great increase in publications of all kinds, but 14 years were required to collect the six cases reported here, a period during which we could expect to see 400 cases of carcinoma of the mouth. Pigmentation of the oral mucosa, like that of the skin, is commonly reported to precede malignant melanoma. Chaudhry and associates found an incidcn~e of about 30 per cent and, since pigmentation of the mouth might well escape notice, this is probably a low estimate. Racial pigmentation probably bears a negative relationship to melanoma, with the disease appearing to be much more common in Caucasians than in Negroes,” a common site in whom is the relatively unpigmented sole of the foot. AGE AND
SEX
Moore and Martin found that the average age of patients who suffered from malignant melanoma of the upper respiratory tract and mouth was 59 years, and 553
Oral April,
Surg. 1975
none of their patients was under 30. Chaudhry and associates reported an average age of 50.5 years, 90 per cent being over 30. The youngest of our six patients was 49, and the oldest was 80. Chaudhry and associates found that oral tumors were almost twice as common in males; whereas Moore and Martin, in their smaller series, had fourteen male and twelve female patients. Our own six patients were all females. It is of interest that Pack and associates,“i in their extensive investigation of malignant melanoma in all sites, found exactly the same numbers, 372, of each sex. SITE
Four fifths of all oral lesions occur in the upper jaw. It follows that only isolated cases are reported in other parts of the mouth, although lesions may extend from the palate and maxillary alveolar process to involve adjacent structures. CLINICAL
APPEARANCE
Patients may seek treatment because of bleeding or because they have been alarmed by a pigmented patch on the oral mucosa. The lesion may be an obvious swelling, or it may take the form of a black or brown discoloration of variable extent, partly elevated, or ulcerated. Pain is not a common symptom, so that the lesion may reach a considerable size before it is observed or considered worthy of attention. Not all oral melanomas are obviously pigmented, as the following case histories show, and one of our cases presented as a nonpigmented swelling that arose in an extensive area of black pigmentation of the palate. Involvement of lymph nodes is common. .In Chaudhry’s cases, more than half had clinical evidence of regional lymph node metastases, and 20 per cent had clinical or radiographic evidence of generalized metastases. HISTOLOGY
The presence of junctional activity is a helpful feature in the diagnosis of primary malignant melanoma, since it indicates the probable source of the tumor cells, more particularly if it, is possible to connect the cells in the junctional situation with those in the tumor. The cells ma.y resemble melanocytes or may be spindle shaped, suggestive of a sarcoma. They may mimic squamous cells and suggest squamous carcinoma. Sometimes they are very anaplastic. The most helpful feature in doubtful cases is the presence of melanin, which can be bleached to distinguish it from other pigments, particularly hemosiderin, which can be stained by the Prussian blue reaction. Melanin may be seen in the tumor cells, in histiocytes, or lying free in the tumor. Sometimes it is absent or present in only small quantities in the primary lesion but may still be an obvious feature in metastases. It is perhaps noteworthy in the six cases reported here that pigment, when present, was largely confined to the overlying or adjacent epithelium and subepithelial connective tissue. TREATMENT
Excision of the local lesion or its destruction by diathermy may arrest the local disease but usually will not prevent the development of secondary deposits.
Radiotherapy sometimes appears to be almost ineffective but may be the only practicable form of treatment in some eases. In view of the overwhelming frequency of metastases, doubt has been east on the value of block dissection.4 Some writers advise this treatment, however, perhaps in the hope that the almost inevitable metastases are confincd to the cervical lymph nodes. From the figures quoted below, it is clear that treatment has only a small chance of permanent SUCcess. Occasionally, however, patients have received prolonged benefit from rc[seated local measures. One patient described by Conley and Pack! had been livilrg free of malignant melanoma for 9 years subsequcllt to four local rcsfctions. PROGNOSIS
Oral lesions have a much poorer prognosis than do skin lesions. Only three of Chaudhry’s 105 patients were known to have survived for 5 years, and Moore and Martin reported only one S-year cure in twenty-six cases. In contrast to these depressing figures, C’onlcy and Pack reported a S-year cure rate of 35 per cent in 116 patients with melanoma of the head and neck; Lehman and associates’” reported a 13 per cent survival rate in forty-two cases of skin lesions; and Pack and associates* reported a 21.4 per cent s-year cure rate in 575 patients with melanoma of all sites. The reasons L’or the tliffcrentc between oral and other lesions are probably late diagnosis ancl difficulty in treatment of the former. REPORT OF SIX CASES
Five of the following cases of primary malignant melanoma of the oral cavity were examined clinically at the Dental Hospital or the IIental Department of the Royal Victoria Infirmary, Newcastle upon Tyne, and one at the (:cncral Hospital, Newcastle upon Tyne. The histologic examinations were carried out at one or another of these institutions and the material was rc-cxaminetl by us for the present purpose.” CASE 1
This 80-year-old etlentulous Wyman attendetl in September, 1951, having ol)serve(l a (liscoloration of the mouth subsequent to a small injury 2 months previously. Examination revealed numerous black spots on the patient’s face an(l intense black pigmentation of most of the hart1 palate and of the anterior part of the alveolar process. The pigment,ecl area was sharply tlemarcate(1 from the surrountling normal tissue (Fig. 1). ln the maxillary 1.5 cm. in diameter, coverecl ]I> incisor region there was a soft, pe(lunculate~1 swelling, mucous membrane of normal pink appe~~ranec. The ecarvio:ll lymph nodes \\(‘I‘(! enlarged. A biopsy of the black mucosa showetl junctional activity anI1 melanin. In February, 1955, the unpigrnentetl oral swelling became ulceratell, ant1 l,iopsy showetl that it was composed of clear cells resembling melanocytes. Some of the overlying epithelium showetl junctional activit)continuous with the tumor, which was partly pigmenterl. Over the next 3 years the oral lesion slowly enlnrgd and hecnmc~ irregul:ir and somewhat lobulatetl in contour. It started to blee(l at fairly frequent intervals, but otherwise neither the primary lesion nor the gradually enlarging cervical notlex causetl any trouble. In view of the slow progress of the oral lesion, its relatively trouble-free nature, ant1 the “\Ve are grateful for the help of our colleagues pres(Jnt :ln(] past in these llospit;l]s and wish particularly to thank the following who nllowed us access to their ease notcxs: Mr. J. I). K. Dawes, Mr. J. R. G. Edwards, Dr. R. G. B. Evans, Mr. R. Finney, Professor G. IA. Howe, Mr. G. Hutchinson, Mr. K. I. Munro Black, Mr. C. .J. I,. Thurgar, an,] professor B. I:. Tomlinson
556
Jacksott and Simpson
Oral April,
P’iy. 1. Case 1. The intensely pigmented area of the palate is sharply demarcated surrounding mucosa. Contained within it is a clinically nonpigmented swelling.
Surg. 1975
from the
advanced age of the patient, the decision was made to only irradiate the cervical nodes. This treatment had little effect. The patient eventually developed a cough, which may have been caused by secondary deposits in the lungs, although circumstances preventetl proof of this being obtained. She died in January, 1958, 3$$ years after the oral lesion was first observed; death was attributed to the tumor. CASE 2
This 49-year-old woman was first seen in December, 1956, when she stated that she had noticed a brown spot on the palate 2 weeks after an episode of soreness of the mouth. She was wearing 5-year-old dentures. Examination revealed an extensive area of pigmentation on the left side of the palate and alveolar process. Histologically, the lesion appeared to be a benign melanoma, but it recurred three times in the next 7 years. On the last of these occasions, in January, 1964, it appeared as a soft swelling on the right maxillary alveolar process, extending from the midline to the premolar region, together with two nodules, each 1 cm. in tliameter, in the labial sulcus. Biopsy showed junctional nevus and a malignant melanoma composed of densely aggregated spindle cells with little pigmentation, The tumor was irradiated. Nine months later there was a further recurrence and also bilateral enlargement of the cervical lymph notles. Further irradiation was given, apparently effectively, but the patient died in April, 1965, with the cause of death being given as malignant melanoma and secondary deposits. Although the patient lived for 8 years from the time she was first examined, death occurred only 14 months after the lesion was pronounced to be malignant. CASE 3
In September, 1956, this 54-year-old woman complained of soreness of the left maxillary gingivae, and in llecember she observed a swelling which grew slowly at first but more rapidly later. E:xaminatiou in April, 1957, revealed an oval mass 5 by 2 cm. extending along the edentulous alveolar ridge in the upper left premolar and molar region. It was of rounded form am1 attached by a thick pedicle and had a tleshy appearance. There was tenderness over the right malar eminence, extending to the infraorbital region, and the patient stated that during the previous week she had suflerecl from attacks of stabbing pain. Radiographs of the sinuses showed no abnormality. Biopsy showed a tumor composed mainly of short, variously orientated spindle ceils, partly anaplastic and underlying densety packed, squamous epithelium which demonstrated considerable junctional activity. Ko pigmentation
Volume 39 Number 4
Primary
maligsawt
melanoma
of oral cavity
557
Fig. 1. Case 6. Centrally on the palate there is a soft, pigmented swelling with an ulcerated surface. There are also diffuse areas of pigmentation of the edentulous alveolar ridge.
was seen either in this tissue or in a lymph node removed later. The patient was suffering from marked cardiac disability, and treatment was delayed for several weeks, after which the lesion was excised. Shortly afterward, enlarged nodes were observed in the right side of the neck and submandibular region. These were irradiated and they regressed markedly. In February, 1958, a large node in the right submandibular region was excised and found to contain tumor that resembIed the more anaplastic part of the primary lesion. In August, 1958, the patient complained of several severe attacks of epistaxis and of increasing discomfort in the right cheek. There was a recurrent lesion in the right maxillary antrum. A month later she had considerable pain in the right maxillary and zygomatic evidence of pulregions. There was a palpable node in the right neck, and radiographic monary metastases. In November, 1958, the bulk of the maxillary lesion was removed because of severe pain. The patient died 4 months later with melanoma of the palate and secondary lesions in the lungs and mediastinum. She had suffered a great deal of pain and was troubled continually by the primary lesion, but in spite of her cardiac defect she lived for 2rh years from the time she first noticed the lesion. CASE 4
This E&year-old woman, who was edentulous and wearing 16-year-old dentures, complained of bleeding from the left maxillary gingivae of 3 weeks’ duration. Examination in July, 1963, revealed an ulcerated, nonpigmented, pedunculated swelling situated on the edentulous alvelolar ridge in the left maxillary incisor and canine region and extending into the labial sulcus. No lymphadenopathp was observed. The lesion was excised and histologically consisted of spindle cells with many mitosee. No pigment was seen, but the presence of junctional activity in the overlying epithelium and the apparent continuity of this abnormality with the tumor indicated that this was a malignant melanoma. Two weeks later the alveolar process and palate were excised from the right canine to the left mol’ar region. After another 6 weeks, some more tissue was removed from the margins of the wound, and a large left submandibular node was observed. A block dissection of the left side of the neck was carried out and pigmented melanoma was found in the lymph nodes. The patient remained well for several months, but in August, 1964, she was hospitalized with a pleural effusion in which was found cytologic evidence of malignant melanoma. She died in September, 1964, 14 months from the time she was first seen. Death was attributed to pleural effusion and melanotic metastases.
550
Jackson and Simpson
Oral April,
Surg. 1975
CASE 5
This 69.year-old woman presented in July, 1964, with a small papillomatous lesion of the soft palate and a pigmented patch on the hard palate, 2.5 by 1.2 cm. She was unable to provide any history. The papillomatous lesion was excised and reported as a junctional nevus. In October, 1968, she returned with a small tumor in the upper incisor region and pigmented patches on the left hard palate. The tumor was excised and histologically was found to be a spindle-cell malignant tumor compatible in appearance with a malignant melanoma. There was no pigment, but the adjacent epithelium showed junctional activity. The palate and neck were irradiated, but a year later a pedunculated, fleshy swelling was observed on the alveolar process to the right of the midline, and there was a pigmented area to the left. In spite of radiotherapy, the lesion progressed and a mass developed in the left neck. Further irradiation produced some improvement in the cervical lesion, but the patient died in May, 1973, with persistent oral lesions and metastases in the liver. This patient survived for 4yz years from the time the malignant lesion was diagnosed, and for nearly 9 years after the diagnosis of a junctional nevus and the recognition of oral pigmentation. CASE 6
One month before this 72.year-old woman was examined, she observed what she thought was a blister on the palate. It appeared to burst and there was subsequent bleeding. Examination in December, 1968, showed that the patient was wearing 27-year-old dentures. In the center of the hard palate and extending to its posterior margin was a blue/black patch with a soft central elevation which appeared to be ulcerated (Fig. 2). There were two less intensely pigmented areas on the alveolar ridge in the right molar and premolar areas and another patch on the mucous surface of the upper lip. The regional lymph nodes were not palpable. Two days later, at which time there was a certain amount of bleeding from the raised part of the palatal lesion, a biopsy specimen was taken from the adjacent pigmented mucosa. Histologically, it showed considerable melanin pigmentation of the epithelium and subepithelial connective tissue. There was junctional activity, with many mitoses and intraepithelial spread of maligant melanoma, but no tumor mass was found in the tissue which was peripheral to the more active-appearing part of the lesion. The patient was treated lvith radiotherapy, but the oral lesion persisted and she developed cervical metastases. She died in October, 1969, with multiple secondary lesions, 16 months after she was first seen and less than a year after she first observed the oral lesion.
DISCUSSION
Diagnosis of primary malignant melanoma is not always easy. Pigmentation present over or surrounding the tumor immediately arouses suspicion, and even atypical patches of pigmentation alone do not usually go unnoticed but when this sign is absent there is obvious difficulty, and the benefits of hindsight are readily applicable to the later assessment of such material. The cases described here all showed some degree of junctional activity involving the overlying or adjacent epithelium. One tumor was composed of recognizable melanocytes, whereas the others consisted of spindle cells of varying thickness and, in the absence of both melanin and junctional activity, would have presented a considerable problem. Sections of multiple blocks were sometimes necessary to exclude spindle-cell sarcoma. In one case the presence of pigmented lymph node metastases was a helpful finding when the primary lesion showed no pigmentation. Although the tumor, once established, appears to be little affected by treat-
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ment, it is not necessarily as rapidly fatal as its reputation might suggest. In spite of the unrelenting nature of their disease, four of the patients lived for several years relatively free of symptoms. SUMMARY
The natural history of malignant melanoma of the oral with reference to the findings of previous writers, and six reported. These demonstrate the considerable variations in of the disease while confirming the difficulty of treatment nature of the condition.
cavity is discussed additional cases are detail of the course and the inexorable
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2. 3. 4. 5. 6. 7. 8. 9. 10.
II.: Malignant Melanoma in the Coloured Races: Report of a Case Originating in the Mouth, Can. Med. Assoc. J. 41: 350-354, 1939. Morris, G. C., Jr., and Horn, R. C.: Malignant Melanoma in the Negro; Review of the Literature and Report of Nine Cases, Surgery 29: 223-230, 1951. Moore, S. E., and Martin, H.: Melanoma of the Upper Respiratory Tract and Oral Cavity, Cancer 8: 1167-1176, 1955. Milton, G. W., and Lane Brown, M. M.: Malignant Melanoma of the Nose and Mouth, Br. J. Surg. 52: 484-493, 1965. Anneroth, G., Carlson, 0. D., Eneroth, C. M., and Moberger, Cr.: Primary Melanoma in the Oral Mucous Membrane, Swedish Dent. J. 66: 27-37, 1973. Pack, G. T., Davis, J., and Oppenheim, A.: The Relation of Race and Complexion to the Incidence of Moles and Melanomas, Ann. N. Y. Acad. Sci. 100: 719-742, 1963. Malignant Melanoma of the Chaudhry, A. P., Hampel, A., and Gorlin, R. J.: Primary Oral Cavity, Cancer 11: 923.928, 1958. of Pack, G. T., Gerber, D. M., and Scharnagel, I. M.: End Results in the Treatment Malignant Melanoma, Ann. Surg. 136: 905-911, 1952. Conley, J. J., and Pack, G. T.: Melanoma of the Head and Neck, Surg. Gynecol. Obstet. 116: 15-28, 1963. Lehman, J. A., Cross, F. S., and Richey, G. D.: A Clinical Study of 49 Patients With Malignant Melanoma, Cancer 19: 611, 1966.
Reprint requests to : Dr. D. Jackson Department of Pathology Dental School University of Newcastle upon Tyne Newcastle upon Tyne, England