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Current trends in treating malignant melanoma
Current trends in treating malignant melanoma Lemuel Bowden, MD
In the broad field of neoplastic disease, malignant melanoma occupies a unique position. It can be immediately visualized, requiring no special diagnostic tools, because of its customary location on the surface of the body. It is by all odds the most aggressive and deceptive of the various malignant tumors of the skin. It arises in many instances from a preexisting benign nevus,I an extremely common lesion of the skin. It very rarely occurs with its characteristic malignant capabilities prior to puberty. Finally, it is enjoying unwarranted prominence because of effective publicity accorded the “pigmented mole” by lay organizations active in the field of cancer. Malignant melanoma is a relatively uncommon neoplasm, which accordLemuel Bowden,
MD, i s
a consultant, Tumor Serv-
ice, Memorial Hospital: an attending surgeon at Doctors Hospital: and associate attending surgeon at Beekman Downtown Hospital, all in New York City. H e i s a graduate of Harvard College and Harvard Medical School.
a4
ing to the Dorn-Cutler figures,? is found in about three people per 100,000 in the United States. It occurs with slightly greater frequency in the female than in the male. It slowly increases in frequency from the time of puberty onward. Individuals of North European ancestry are more commonly afflicted than are those of Mediterranean descent, presumably because of characteristics of complexion rather than because of racial or national origin. The “strawberry blond” individual, with light red hair and very sensitive fair skin, is the one most likely to develop melanoma (Fig 1); following with decreasing frequency is the natural blonde with yellow hair, blue eyes and fair skin; the intermediate types, the brunette with black hair, dark eyes and olive skin, and finally the Negro. The incidence rate for the white race is about six times that for the black race. Those melanomas which do occur in the Negro are almost wholly confined to the least
AORN Journal
Fig I : ”Strawberry blond” with melanoma of skin of left anterior thorax.
Fig 2: Right, extensive melanoma in sole o f left foot of Negro male.
pigmented areas of the skin, specifically the nail beds and the soles of the feet. (Fig 2). For the purpose of this presentation the terms malignant melanoma, melanocarcinoma and melanoma may be used interchangeably as applying to the same malignant lesion of the skin and mucous membranes. Diagnosis: The key to diagnosis is a suspicion that a pigmented lesion of the skin or mucous membrane may be a melanoma, particularly if it has shown recent growth or other change in characteristics. Such lesions should be completely and promptly excised. The diagnosis should be established by histological study. If the surgeon is reasonably sure, or just highly suspicious, that such a lesion is a melanoma, then the patient should be hospitalized for a total excision of the lesion with frozen section diagnosis. If the diagnosis is sustained, then definitive surgical treatment can be carried out
March 1973
under the same general anesthesia, just as is routinely done for breast tumors. Sometimes even the most experienced pathologists cannot make a positive diagnosis with frozen section. In this event further surgery is cancelled and treatment is delayed for 24 to 48 hours, or until paraffin sections have been prepared and the pathologist has had ample time to give a conclusive report. Renewed interest in the pathological features of melanoma has included careful evaluation of the degree or extent of dermal invasion, called “micro staging.”3 Correlation of this information with the patient’s subsequent course has enabled clinicians to predict with reasonable accuracy which melanomas may be managed by local surgery and which require more radical or more extensive surgery. General aspects of treatment: Permanent control of malignant mela-
85
noma has heretofore been accomplished only by aggressive surgical treatment. Depending upon the location of the melanoma, its microscopic characteristics, and the presence or absence of regional lymph node metastasis, such potentially curative surgery may consist of wide excision, usually with skin graft, wide excision with regional node dissection, or amputation. Many experienced clinicians ' * 5 add regional isolation perfusion with a chemotherapeutic agent to the definitive treatment of a melanoma arising in the skin or an extremity. Obviously, the type of treatment accorded a melanoma will vary with the extent of the malignant process. It is becoming customary to stage malignant melanoma in accordance with ultimate pathological findings, as follows: Stage I: The malignant melanoma is localized to its primary site, with no regional node metastases, and with no distant metastases. Stage 11: The malignant melanoma is found with regional node metastases, but with no distant metastases. Stage 111: The malignant melanoma is disseminated with distant visceral metastases or with multiple cutaneous and nodal metastases. The treatment, as well as the prognosis, varies strikingly with the stage of the disease. Treatment of stage I melanoma: When an excisional biopsy of a melanoma reveals that the lesion is truly superficial and involves the basal or junctional layer of the epidermis with no extension into the true dermis, then a wide excision of the area,
86
usually with split-thickness skin grafting, is the treatment of choice. Such wide excision should include removal of an ellipse or disc of skin, subcutaneous tissue, and fascia with a minimal margin of five centimeters on all sides of the melanoma. An excision of this magnitude must be somewhat compromised when a melanoma of the head and neck area is treated, but the excision must be wide enough to ensure that local recurrence of the melanoma will not develop. For excisions of this magnitude, closure by skin grafting is needed. For invasive stage I melanoma located on an extremity, some experienced clinicians add regional perfusion to their treatment a t the time of axillary or groin dissection. They report between a 10% and 15% increase in the five-year control of the malignant process by this additional procedure over that which might otherwise be e ~ p e c t e d . ~Accurate .~ comparisons between series of patients treated with surgery and perfusion and those treated with surgery alone are difficult because of inherent factors in the selection of treatment, and because of the lack of uniformity in classifying the stages of melanoma from one medical center to another. Subungual melanoma of the fingers or toes, which is usually fully invasive but may still be localized to the nailbed, is treated by digital amputation, usually as a ray amputation of a finger for better cosmetic result, (Fig 3), and as a metatarso-phalangeal disarticulation of a toe for better support and weight bearing. Again, regional node dissection with or without perfusion therapy is combined with the digital amputation.
AORN Journal
Fig 3: Above, a subungual melanoma of right index finger of white female. Right, the same patient’s postoperative appearance fol‘lowing ray amputation of index finger.
Treatment of stage I1 melanoma: When excisional biopsy reveals that the melanoma is fully invasive, then equally wide excision with skin grafting is performed. In addition, a regiowtl lymph node dissection is performed whether or not these nodes are palpable. If microscopic foci of melanoma are found in the lymph nodes, then by definition the patient is necessarily reclassified as having stage 11melanoma. If lymph nodes in the neck, axilla, or groin show metastatic melanoma from a primary lesion in the skin of the head and neck, of upper extremity and thorax, or of lower extremity and trunk respectively, then aggressive surgical treatment requires that these lymph node areas be completely dissected in continuity with wide excision and graft of the primary site. When the primary melanoma lies close to the regional node basin, this procedure of dissection in continuity presents no particular technical problem. When the primary melanoma lies at considerable distance from its regional node area,
March 1973
as in a melanoma of the sole of the foot with groin metastases, then a wide excision with node dissection in continuity is unreasonable. Current surgical practice in such instances is to perform discontinuous procedures such as wide excision with graft of the primary site and then appropriate regional node dissection. Sometimes a malignant melanoma will have been treated previously by local excision and graft only. If regional node metastases appear many months later, then only node dissection is required. When a distant primary site is untreated, or if local recurrence of melanoma occurs in a distant primary site, and regional node metastases are present, then wide excision and graft of the primary site with discontinuous node dissection has certain inherent disadvantages and dangers. The likelihood of early development of metastases between the two surgically treated areas is great. (Fig 4). This is the phenomenon of “in transit” metastasis. Tumor emboli extruded into lymph channels from
87
the primary site would normally be trapped in the regional nodes. With simultaneous node dissection, they have no place to go. They remain instead in the intervening static lymph channels where they become lodged and where they begin to flourish. This unfortunate sequence of events occurs in about 20% t o 30% of all patients so treated. Two approaches to prevent or overcome this problem are employed. The first is to combine regional chemotherapy by perfusion with the regional node dissection. The other is to employ radical exarticulation such as interscapulothoracic amputation, hip-joint disarticulation, or hemipelvectomy to remove the entire condemned extremity. Chemotherapy is reported5 to salvage a significant number of patients by preventing the development of in-transit metastases. Amputation prevents intransit metastasis by removing the entire extremity. In our experience amputation has been successful in salvaging about one-third of the patients so treated.6 Treatment of stage I11 melanoma: Sometimes a patient's melanoma appears to be controlled by surgical treatment as described above for many months. Then he will be found to have a solitary metastasis in his brain, lung, or liver. When such a situation develops, and when further investigation confirms that the metastasis is in fact solitary, an aggressive surgical attack must be made on this metastasis. Even though by definition the patient will have stage I11 melanoma, certain patients can survive for many months. Cure is even possible by surgical resection of a truly solitary late metastasis. This is well documented in pulmonary resection for metastatic melanoma,' less
88
Fig 4: The small pigmented nodules in the skin represent "in transit" metastases in a white male who had previously undergone excision and graft of a melanoma on medial aspect of right heel with discontinuous radical groin dissection.
well recognized in neurosurgical extirpation of an intracranial metastasis,x and least well accepted in hepatic resection for metastatic melanoma. In stage I11 melanoma, furthermore, surgery may be required purely for palliation of a life threatening complication of widespread metastases. For example, uncontrolled melanoma has an affinity for metastasizing to the wall of the intestine. Here it may cause acute bowel ob-
AORN Journal
Fig 5:
Surgical
specimen
of
opened distal ileum and cecum, showing
intusrusception
pro-
duced by submucosal metastasis of malignant melanoma.
struction. Emergency laparotomy with appropriate bowel resection is the only way of managing this complication. (Fig 5 ) Occasionally uncontrolled melanoma will metastasize t o the bone. Just as with bone metastases in cancer of the breast, prostate, lung, or thyroid, judicious roentgentherapy to the involved area may afford relief of pain for an unpredictable period of time, despite the fact that melanoma is generally cm&kred to be insensitive to raentgentherapy. By far the majority of patients with stage III melanoma are totally incurable, and yet may not be very symptomatic for varying periods of time. Sooner or later symptoms will become prominent, and palliative treatment must be directed toward symptomatic relief to make the patient’s remaining life worthwhile. Systemic chemotherapy will occasionally produce some degree of
March 1973
growth restraint of metastases of melanoma. It has definite value in psychologically supporting the patient. The physician is at least “doing something.” Furthermore, if drugs are employed and combined wisely, the patient may have little adverse reaction to their use. The most hopeful development for treatment of the patient with vanced melanoma has appeared adin
recent yeam. Those of us caring for patients with advanced cancer, and with melanoma patients in particular, infrequently have observed a patient who will seem to live with his incurable tumor in relative comfort for a long period of time. Even more infrequently we have seen an occasional patient who appears to have resolved his tumor “spontaneously.” The assumption has been that these individuals have had some elusive and unmeasurable resistance or immunity to the tumor.
89
With the hope of increasing resistance to the neoplasm, Morton and coworkers9 injected BCG vaccine directly into nodules of recurrent melanoma in eight patients with stage 111 melanoma, and found some degree of regression of the nodules in five of the eight patients. Many centers are now engaged in studies on immunotherapy in cancer; and selected patients, often with advanced melanoma, are being so treated.lnJ1 Investigators in immunotherapy are employing two approaches to the treatment of human beings with cancer. They use nonspecific stimulation of immune response or will use administration of tumor-specific antibodies, if and when these can be produced. Nonspecific i m m u n o t h e r a p y is based on the fact that many patients with advanced cancer lose their natural or acquired immunity to many antigens. Researchers assume that if a patient with advanced cancer has a depleted antibody response to simple antigenic stimulation such as tuberculin, as is widely used in the simple tuberculin skin test, then merely improving the patient’s general antibody response may slow the inexorable progress of the cancer. A relatively harmless antigen, such as BCG, will thus be administered either into the tumor or subcutaneously, usually at weekly intervals. Researchers intend to stimulate the patient’s depleted or absent immune reaction, and hopefully slow the progress of the cancer. Specific immunotherapy is more involved. Basically it consists of pairing two individuals of similar blood type who have advanced cancer of similar histogenesis. Each of these patients is believed to have
90
lost all naturally occurring resistance or immunity to his tumor. By inoculation with a vaccine prepared from one patient’s tumor into the other patient, it is hoped that antibodies to the similar tumor of the other individual can be produced. Evidence indicates that these antibodies are located on the white blood cells. Accordingly, after some 10 to 14 days a suspension of white blood cells is prepared from the recipient of the tumor inoculate and infused back into the donor. Results in this type of experimental treatment are by no means constant or predictable, but when successful they may be quite dramatic. Summary: Malignant melanoma, though not a frequently occurring tumor, is the most aggressive of the readily visualized lesions of the integument. The key to diagnosis is suspicion that any pigmented lesion exhibiting growth or change in color or consistency may be m e 1 a n o m a. Prompt identification of such a lesion by excisional biopsy and histological study is mandatory. Both the treatment of melanoma and its prognosis depend upon the stage of the disease. For stage I and stage I1 melanoma, aggressive surgical treatment is indicated. Regional perfusion w i t h chemotherapeutic agents may be added to the radical surgery for melanomas of the extremities. State I11 melanoma is usually incurable, and surgical treatment is indicated only for the infrequent patient with solitary distant metastasis, or for palliation of certain complications of disseminated metastases. Other methods of treatment, including roentgentherapy, chemotherapy, and in recent years immuno-
AORN Journal
therapy are employed for many patients with stage I11 melanoma, and almost always prove to be palliative rather than curative. Immunotherapy
would seem, nevertheless, to offer hope for substantially better results as this new approach to cancer therapy becomes better understood.
REFERENCES
I. A C Allen, "A Reorientation of the Histogenesis
Years Clinical Experience." Annals of Surgery, I75
and Clinical Significance of Cutaneous Nevi and Melanoma,'' Cancer, 2 (1949), 28-56.
( I972), 900-9 17. 6. CJ McPeak, et al, "Amputation for Melanoma
2. HF Darn and SJ Cutler, Morbidity from Cancer in the United States, Public Health Monograph No. 56, Washington, DC, 1959, p60.
o f the Extremity," Surgery, 54 (1963). 426-431. 7. WG Cohen, €xcirion o f Melanoma Metastases t o Lung: A n Analysis o f 29 Cases. To be published.
3. VJ McGovern, "The Classification o f Melanoma and i t s Relationship with Prognosis." Pathology, 2 ( l970), 85-89. 4.
JS Stehlin, Jr, Perfusion of €xtremities for
Cancer,
Proc
6th
National
Cancer
(Philadelphia: JB Lippincott Co,
Conference
1970), p p 617-
620. 5. ET Krementz and RF Ryan, "Chemotherapy o f Melanoma o f the Extremities by Perfusion: Fourteen
8. L Bowden, Unpublished data. 9. DL Morton, e t al- "Immunological Factors which Influence Response t o lmmunotherapy in Malignant Melanoma," Surgery, 68 ( 1970), 158-164.
10. LJ Humphrey, e t al. "lmmunotherapy for the Patient with Cancer," Annals of Surgery, 173 ( l 9 7 l ) , 47-54. I I . ET Krementz, e t al, "Clinical Experiences i n lmmunotherapy o f Cancer," Surgery, Gynecology, and Obstetrics, I 3 3 ( 1971 ) , 209-2 17.
New +ransplan+ era predic+ed A leading biologist predicted a new era of transplants of organs and tissues will be opened through prenatal surgery t o modify the original tissue type of the individual. Dr Bentley Glass, professor o f biology at the State University of New York, Stony Brook, t o l d the clinical congress of the American College of Surgeons this may become possible by prenatal introduction of appropriate foreign tissue. "We have long known there i s an early period during development when the immunological and histocompatibility mechanisms have not yet emerged and that the fused chorionic circulation o f the dizygotic twins sometimes permits a mutual transfer o f blood forming cells,'' he said. "In this way, individuals are produced who are genetic mosaics. Like monozygotic twins, they are mutually acceptable as donors and recipients of grafts." In his lecture, "Genetics and Surgery," Dr Glass said the implanting cells of different genes i n an embryo may not produce a universal recipient but should make the individual receptive t o a wide genetic variety of grafts or transplants. Surgeons o f the future will be involved in operations on cells rather than organs and tissues, Dr Glass forecast. The notion o f modifying individuals already has inspired widespread fears of tyrants controlling population. "In my own view, however, the development of such techniques i s more likely t o involve, at least initially, a widened freedom o f individual choice," the speaker said. "Given the technical possibility, there will very likely always be some persons, perhaps otherwise doomed t o childlessness, who will want t o adopt prenatally an embryo o f selected ancestry, perhaps one identical in genotype t o some ideal of their cwn or an earlier time-say, a Martin Luther King or a Sophia Loren."
March 1973
91
In the broad field of neoplastic disease, malignant melanoma occupies a unique position. It can be immediately visualized, requiring no special diagnostic tools, because of its customary location on the surface of the body. It is by all odds the most aggressive and deceptive of the various malignant tumors of the skin. It arises in many instances from a preexisting benign nevus,I an extremely common lesion of the skin. It very rarely occurs with its characteristic malignant capabilities prior to puberty. Finally, it is enjoying unwarranted prominence because of effective publicity accorded the “pigmented mole” by lay organizations active in the field of cancer. Malignant melanoma is a relatively uncommon neoplasm, which accordLemuel Bowden,
MD, i s
a consultant, Tumor Serv-
ice, Memorial Hospital: an attending surgeon at Doctors Hospital: and associate attending surgeon at Beekman Downtown Hospital, all in New York City. H e i s a graduate of Harvard College and Harvard Medical School.
a4
ing to the Dorn-Cutler figures,? is found in about three people per 100,000 in the United States. It occurs with slightly greater frequency in the female than in the male. It slowly increases in frequency from the time of puberty onward. Individuals of North European ancestry are more commonly afflicted than are those of Mediterranean descent, presumably because of characteristics of complexion rather than because of racial or national origin. The “strawberry blond” individual, with light red hair and very sensitive fair skin, is the one most likely to develop melanoma (Fig 1); following with decreasing frequency is the natural blonde with yellow hair, blue eyes and fair skin; the intermediate types, the brunette with black hair, dark eyes and olive skin, and finally the Negro. The incidence rate for the white race is about six times that for the black race. Those melanomas which do occur in the Negro are almost wholly confined to the least
AORN Journal
Fig I : ”Strawberry blond” with melanoma of skin of left anterior thorax.
Fig 2: Right, extensive melanoma in sole o f left foot of Negro male.
pigmented areas of the skin, specifically the nail beds and the soles of the feet. (Fig 2). For the purpose of this presentation the terms malignant melanoma, melanocarcinoma and melanoma may be used interchangeably as applying to the same malignant lesion of the skin and mucous membranes. Diagnosis: The key to diagnosis is a suspicion that a pigmented lesion of the skin or mucous membrane may be a melanoma, particularly if it has shown recent growth or other change in characteristics. Such lesions should be completely and promptly excised. The diagnosis should be established by histological study. If the surgeon is reasonably sure, or just highly suspicious, that such a lesion is a melanoma, then the patient should be hospitalized for a total excision of the lesion with frozen section diagnosis. If the diagnosis is sustained, then definitive surgical treatment can be carried out
March 1973
under the same general anesthesia, just as is routinely done for breast tumors. Sometimes even the most experienced pathologists cannot make a positive diagnosis with frozen section. In this event further surgery is cancelled and treatment is delayed for 24 to 48 hours, or until paraffin sections have been prepared and the pathologist has had ample time to give a conclusive report. Renewed interest in the pathological features of melanoma has included careful evaluation of the degree or extent of dermal invasion, called “micro staging.”3 Correlation of this information with the patient’s subsequent course has enabled clinicians to predict with reasonable accuracy which melanomas may be managed by local surgery and which require more radical or more extensive surgery. General aspects of treatment: Permanent control of malignant mela-
85
noma has heretofore been accomplished only by aggressive surgical treatment. Depending upon the location of the melanoma, its microscopic characteristics, and the presence or absence of regional lymph node metastasis, such potentially curative surgery may consist of wide excision, usually with skin graft, wide excision with regional node dissection, or amputation. Many experienced clinicians ' * 5 add regional isolation perfusion with a chemotherapeutic agent to the definitive treatment of a melanoma arising in the skin or an extremity. Obviously, the type of treatment accorded a melanoma will vary with the extent of the malignant process. It is becoming customary to stage malignant melanoma in accordance with ultimate pathological findings, as follows: Stage I: The malignant melanoma is localized to its primary site, with no regional node metastases, and with no distant metastases. Stage 11: The malignant melanoma is found with regional node metastases, but with no distant metastases. Stage 111: The malignant melanoma is disseminated with distant visceral metastases or with multiple cutaneous and nodal metastases. The treatment, as well as the prognosis, varies strikingly with the stage of the disease. Treatment of stage I melanoma: When an excisional biopsy of a melanoma reveals that the lesion is truly superficial and involves the basal or junctional layer of the epidermis with no extension into the true dermis, then a wide excision of the area,
86
usually with split-thickness skin grafting, is the treatment of choice. Such wide excision should include removal of an ellipse or disc of skin, subcutaneous tissue, and fascia with a minimal margin of five centimeters on all sides of the melanoma. An excision of this magnitude must be somewhat compromised when a melanoma of the head and neck area is treated, but the excision must be wide enough to ensure that local recurrence of the melanoma will not develop. For excisions of this magnitude, closure by skin grafting is needed. For invasive stage I melanoma located on an extremity, some experienced clinicians add regional perfusion to their treatment a t the time of axillary or groin dissection. They report between a 10% and 15% increase in the five-year control of the malignant process by this additional procedure over that which might otherwise be e ~ p e c t e d . ~Accurate .~ comparisons between series of patients treated with surgery and perfusion and those treated with surgery alone are difficult because of inherent factors in the selection of treatment, and because of the lack of uniformity in classifying the stages of melanoma from one medical center to another. Subungual melanoma of the fingers or toes, which is usually fully invasive but may still be localized to the nailbed, is treated by digital amputation, usually as a ray amputation of a finger for better cosmetic result, (Fig 3), and as a metatarso-phalangeal disarticulation of a toe for better support and weight bearing. Again, regional node dissection with or without perfusion therapy is combined with the digital amputation.
AORN Journal
Fig 3: Above, a subungual melanoma of right index finger of white female. Right, the same patient’s postoperative appearance fol‘lowing ray amputation of index finger.
Treatment of stage I1 melanoma: When excisional biopsy reveals that the melanoma is fully invasive, then equally wide excision with skin grafting is performed. In addition, a regiowtl lymph node dissection is performed whether or not these nodes are palpable. If microscopic foci of melanoma are found in the lymph nodes, then by definition the patient is necessarily reclassified as having stage 11melanoma. If lymph nodes in the neck, axilla, or groin show metastatic melanoma from a primary lesion in the skin of the head and neck, of upper extremity and thorax, or of lower extremity and trunk respectively, then aggressive surgical treatment requires that these lymph node areas be completely dissected in continuity with wide excision and graft of the primary site. When the primary melanoma lies close to the regional node basin, this procedure of dissection in continuity presents no particular technical problem. When the primary melanoma lies at considerable distance from its regional node area,
March 1973
as in a melanoma of the sole of the foot with groin metastases, then a wide excision with node dissection in continuity is unreasonable. Current surgical practice in such instances is to perform discontinuous procedures such as wide excision with graft of the primary site and then appropriate regional node dissection. Sometimes a malignant melanoma will have been treated previously by local excision and graft only. If regional node metastases appear many months later, then only node dissection is required. When a distant primary site is untreated, or if local recurrence of melanoma occurs in a distant primary site, and regional node metastases are present, then wide excision and graft of the primary site with discontinuous node dissection has certain inherent disadvantages and dangers. The likelihood of early development of metastases between the two surgically treated areas is great. (Fig 4). This is the phenomenon of “in transit” metastasis. Tumor emboli extruded into lymph channels from
87
the primary site would normally be trapped in the regional nodes. With simultaneous node dissection, they have no place to go. They remain instead in the intervening static lymph channels where they become lodged and where they begin to flourish. This unfortunate sequence of events occurs in about 20% t o 30% of all patients so treated. Two approaches to prevent or overcome this problem are employed. The first is to combine regional chemotherapy by perfusion with the regional node dissection. The other is to employ radical exarticulation such as interscapulothoracic amputation, hip-joint disarticulation, or hemipelvectomy to remove the entire condemned extremity. Chemotherapy is reported5 to salvage a significant number of patients by preventing the development of in-transit metastases. Amputation prevents intransit metastasis by removing the entire extremity. In our experience amputation has been successful in salvaging about one-third of the patients so treated.6 Treatment of stage I11 melanoma: Sometimes a patient's melanoma appears to be controlled by surgical treatment as described above for many months. Then he will be found to have a solitary metastasis in his brain, lung, or liver. When such a situation develops, and when further investigation confirms that the metastasis is in fact solitary, an aggressive surgical attack must be made on this metastasis. Even though by definition the patient will have stage I11 melanoma, certain patients can survive for many months. Cure is even possible by surgical resection of a truly solitary late metastasis. This is well documented in pulmonary resection for metastatic melanoma,' less
88
Fig 4: The small pigmented nodules in the skin represent "in transit" metastases in a white male who had previously undergone excision and graft of a melanoma on medial aspect of right heel with discontinuous radical groin dissection.
well recognized in neurosurgical extirpation of an intracranial metastasis,x and least well accepted in hepatic resection for metastatic melanoma. In stage I11 melanoma, furthermore, surgery may be required purely for palliation of a life threatening complication of widespread metastases. For example, uncontrolled melanoma has an affinity for metastasizing to the wall of the intestine. Here it may cause acute bowel ob-
AORN Journal
Fig 5:
Surgical
specimen
of
opened distal ileum and cecum, showing
intusrusception
pro-
duced by submucosal metastasis of malignant melanoma.
struction. Emergency laparotomy with appropriate bowel resection is the only way of managing this complication. (Fig 5 ) Occasionally uncontrolled melanoma will metastasize t o the bone. Just as with bone metastases in cancer of the breast, prostate, lung, or thyroid, judicious roentgentherapy to the involved area may afford relief of pain for an unpredictable period of time, despite the fact that melanoma is generally cm&kred to be insensitive to raentgentherapy. By far the majority of patients with stage III melanoma are totally incurable, and yet may not be very symptomatic for varying periods of time. Sooner or later symptoms will become prominent, and palliative treatment must be directed toward symptomatic relief to make the patient’s remaining life worthwhile. Systemic chemotherapy will occasionally produce some degree of
March 1973
growth restraint of metastases of melanoma. It has definite value in psychologically supporting the patient. The physician is at least “doing something.” Furthermore, if drugs are employed and combined wisely, the patient may have little adverse reaction to their use. The most hopeful development for treatment of the patient with vanced melanoma has appeared adin
recent yeam. Those of us caring for patients with advanced cancer, and with melanoma patients in particular, infrequently have observed a patient who will seem to live with his incurable tumor in relative comfort for a long period of time. Even more infrequently we have seen an occasional patient who appears to have resolved his tumor “spontaneously.” The assumption has been that these individuals have had some elusive and unmeasurable resistance or immunity to the tumor.
89
With the hope of increasing resistance to the neoplasm, Morton and coworkers9 injected BCG vaccine directly into nodules of recurrent melanoma in eight patients with stage 111 melanoma, and found some degree of regression of the nodules in five of the eight patients. Many centers are now engaged in studies on immunotherapy in cancer; and selected patients, often with advanced melanoma, are being so treated.lnJ1 Investigators in immunotherapy are employing two approaches to the treatment of human beings with cancer. They use nonspecific stimulation of immune response or will use administration of tumor-specific antibodies, if and when these can be produced. Nonspecific i m m u n o t h e r a p y is based on the fact that many patients with advanced cancer lose their natural or acquired immunity to many antigens. Researchers assume that if a patient with advanced cancer has a depleted antibody response to simple antigenic stimulation such as tuberculin, as is widely used in the simple tuberculin skin test, then merely improving the patient’s general antibody response may slow the inexorable progress of the cancer. A relatively harmless antigen, such as BCG, will thus be administered either into the tumor or subcutaneously, usually at weekly intervals. Researchers intend to stimulate the patient’s depleted or absent immune reaction, and hopefully slow the progress of the cancer. Specific immunotherapy is more involved. Basically it consists of pairing two individuals of similar blood type who have advanced cancer of similar histogenesis. Each of these patients is believed to have
90
lost all naturally occurring resistance or immunity to his tumor. By inoculation with a vaccine prepared from one patient’s tumor into the other patient, it is hoped that antibodies to the similar tumor of the other individual can be produced. Evidence indicates that these antibodies are located on the white blood cells. Accordingly, after some 10 to 14 days a suspension of white blood cells is prepared from the recipient of the tumor inoculate and infused back into the donor. Results in this type of experimental treatment are by no means constant or predictable, but when successful they may be quite dramatic. Summary: Malignant melanoma, though not a frequently occurring tumor, is the most aggressive of the readily visualized lesions of the integument. The key to diagnosis is suspicion that any pigmented lesion exhibiting growth or change in color or consistency may be m e 1 a n o m a. Prompt identification of such a lesion by excisional biopsy and histological study is mandatory. Both the treatment of melanoma and its prognosis depend upon the stage of the disease. For stage I and stage I1 melanoma, aggressive surgical treatment is indicated. Regional perfusion w i t h chemotherapeutic agents may be added to the radical surgery for melanomas of the extremities. State I11 melanoma is usually incurable, and surgical treatment is indicated only for the infrequent patient with solitary distant metastasis, or for palliation of certain complications of disseminated metastases. Other methods of treatment, including roentgentherapy, chemotherapy, and in recent years immuno-
AORN Journal
therapy are employed for many patients with stage I11 melanoma, and almost always prove to be palliative rather than curative. Immunotherapy
would seem, nevertheless, to offer hope for substantially better results as this new approach to cancer therapy becomes better understood.
REFERENCES
I. A C Allen, "A Reorientation of the Histogenesis
Years Clinical Experience." Annals of Surgery, I75
and Clinical Significance of Cutaneous Nevi and Melanoma,'' Cancer, 2 (1949), 28-56.
( I972), 900-9 17. 6. CJ McPeak, et al, "Amputation for Melanoma
2. HF Darn and SJ Cutler, Morbidity from Cancer in the United States, Public Health Monograph No. 56, Washington, DC, 1959, p60.
o f the Extremity," Surgery, 54 (1963). 426-431. 7. WG Cohen, €xcirion o f Melanoma Metastases t o Lung: A n Analysis o f 29 Cases. To be published.
3. VJ McGovern, "The Classification o f Melanoma and i t s Relationship with Prognosis." Pathology, 2 ( l970), 85-89. 4.
JS Stehlin, Jr, Perfusion of €xtremities for
Cancer,
Proc
6th
National
Cancer
(Philadelphia: JB Lippincott Co,
Conference
1970), p p 617-
620. 5. ET Krementz and RF Ryan, "Chemotherapy o f Melanoma o f the Extremities by Perfusion: Fourteen
8. L Bowden, Unpublished data. 9. DL Morton, e t al- "Immunological Factors which Influence Response t o lmmunotherapy in Malignant Melanoma," Surgery, 68 ( 1970), 158-164.
10. LJ Humphrey, e t al. "lmmunotherapy for the Patient with Cancer," Annals of Surgery, 173 ( l 9 7 l ) , 47-54. I I . ET Krementz, e t al, "Clinical Experiences i n lmmunotherapy o f Cancer," Surgery, Gynecology, and Obstetrics, I 3 3 ( 1971 ) , 209-2 17.
New +ransplan+ era predic+ed A leading biologist predicted a new era of transplants of organs and tissues will be opened through prenatal surgery t o modify the original tissue type of the individual. Dr Bentley Glass, professor o f biology at the State University of New York, Stony Brook, t o l d the clinical congress of the American College of Surgeons this may become possible by prenatal introduction of appropriate foreign tissue. "We have long known there i s an early period during development when the immunological and histocompatibility mechanisms have not yet emerged and that the fused chorionic circulation o f the dizygotic twins sometimes permits a mutual transfer o f blood forming cells,'' he said. "In this way, individuals are produced who are genetic mosaics. Like monozygotic twins, they are mutually acceptable as donors and recipients of grafts." In his lecture, "Genetics and Surgery," Dr Glass said the implanting cells of different genes i n an embryo may not produce a universal recipient but should make the individual receptive t o a wide genetic variety of grafts or transplants. Surgeons o f the future will be involved in operations on cells rather than organs and tissues, Dr Glass forecast. The notion o f modifying individuals already has inspired widespread fears of tyrants controlling population. "In my own view, however, the development of such techniques i s more likely t o involve, at least initially, a widened freedom o f individual choice," the speaker said. "Given the technical possibility, there will very likely always be some persons, perhaps otherwise doomed t o childlessness, who will want t o adopt prenatally an embryo o f selected ancestry, perhaps one identical in genotype t o some ideal of their cwn or an earlier time-say, a Martin Luther King or a Sophia Loren."
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