Australas J. Dermatol 1991; 32: 159-164
RE VIEW ARTICLE
MOHS MICROGRAPHIC SURGERY FOR SKIN CANCER DAVIDF. LESLIEAND HUBERT T. GREENWAY Maroochydore, Queensland and La Jolla, Cailfornia SUMMARY
Mohs Micrographic Surgery is a technique offering superior treatment for skin cancer with cure rates of 99% for primary and 94.4% for recurrent BCC, greater than 94% for SCC. As developed by Dr Frederic M o b , the technique originally involved application of a chemical fixative. Mohs' fresh tissue technique is now usual, with immediate horizontal frozen sectioning of the entire margins of excised tissue, mapping and microscopic identification of remaining tumour, then repeat excisions, mapping and examination until a tumour-freeplane is demonstrated throughout. Thisprovides maximal conservation of uninvolved tissue structures, and allows more confident repair of a cancerfree surgical defect. Mohs Micrographic Surgery is becoming more widely available in Australasia; concurrentlj indicationsfor the technique are widening, as are the research interests, training opportunities, and professional organization of Mohs Practitioners. Very high, and increasing, incidence and prevalence of skin cancer in Australasia, and factors tending to contribute to this, suggest that Mohs Micrographic Surgery has an expanding role to play in Australasia. Key words: Skin cancer, Mohs micrographic surgery, dermatologic surgery. INTRODUCTION Surgical removal of cancerous growths under histologic control is a familiar concept. The technique developed by Dr Frederic Mohs of Wisconsin' is based on a unique intimacy between removal and control; it has now developed into a refined management technique, under the name of Mohs Micrographic Surgery (MMS), with proven superior results in the management of a range of tumours, including many of the commoner types of skin cancer. Maximum available cure rates in certain applications, maximum conservation of uninvolved tissue, and the developing availability of the technique within Australasia, make an appreciation of MMS desirable for all those involved in the management of visible tumours. David F. Leslie, FACD. Dermatologist, Maroochydore, Queensland. Hubert T. Greenway, FACMMSCO. Director, Mohs Surgery and Cutaneous Laser Unit, Department of Dermatology, Scripps Clinic and Research Foundation, La Jolla, California. Address for correspondence: Dr D.F. Leslie, PO Box 1067, Maroochydore, Queensland 4558.
RESULTS Mohs Micrographic Surgery has produced its best results in the treatment of Basal Cell Carcinoma (BCC) - published studies showing rigorous five year recurrence rates, when summarized, indicate figures of 1% for BCCs treated initially by MMS and 5.6% for recurrent (previously treated) lesions following MMS. Comparable figures for other management modalities are: 10.1 and 17.4070, respectively, for surgical excision; 7.7 and 40.0% for curettage and electrodessication; 8.7 and 9.8% for radiotherapy; and 7.5% (and 13.0% on preliminary data published) for cryos~rgery.~.~ MMS has been particularly valuable when used in a multi-disciplinary team approach for the more difficult tumours, as with plastic surgical repair of complex postMMS defects.' It offers less advantage for lowrisk superficial BCCs on the trunk and limbs, and for small BCCs (less than 0.5cm diameter) excepting the morpheaform type, for which it is the treatment of choiceS because of subclinical extensions which may average more than 7 mms.6 For cutaneous Squamous Cell Carcinoma (SCC), whilst prognosis remains adversely affected by 159
DAVIDF. LESLIEAND HUBERT T. GREENWAY
site, tumour size, prior treatment, histopathologic differentiation, etc., published results of MMS compare favourably overall (94% success rates’) including at recognized high risk sites on the lips (94.1% 5 year cure’) and the external ear (97.1% 5 year cures). INDICATIONS MMS has been successfully used for a wide range of cutaneous neoplasms (Thble 1). It is of particular value where tissue conservation concerns are critical, eg. in sebaceous carcinoma of the eyelid^;^ similarly it has been useful in extramammary Paget’s Disease despite recognized discontinuous modes of spread by these tumours. CHEMOSURGERY - FIXEDTISSUETECHNIQUE The concept was developed by Mohs in the early ’ ~ O S ,then a medical student working as a Zoology Research Assistant, following his observation of histologic fixation of skin cancer in rats following injection of a zinc chloride solution. He subsequently developed a technique involving controlled in situ fixation in his patients’ tumours by application of a complex zinc chloride fixative, followed by removal of the fixed layer, segmentation, marking and careful mapping then the preparation of horizontal frozen histology sections allowing examination of the entire margins of removal, and identification of the sites of silent outgrowths of cancer remaining in the tumour bed. Further layers could be fixed where required and removed serially, until a cancer-free plane had been demonstrated throughout. This technique, which Mohs called Chemosurgery: offered both a high chance of cure and maximum conservation of uninvolved tissue - and these remain the touchstones of MMS today.
TABLE1 Indications for Mohs Micrographic Surgery (Skin Cancer) 1.
Basal Cell Carcinoma 1. Recurrent lesions 2. Subgroups of primary lesions: a. With clinical features, ie. morphoeic, infiltrating, multicentric lesions, those demonstrating rapid growth or aggressive behaviour, or large size. b. In critical anatomic locations including central third of the face, nasolabial fold, periorbital and canthal areas, pre-auricular cheek, auricle, postauricular sulcus, hands, feet, genitalia. c. With high risk histologic features on biopsy, ie. infiltrating or morphoeic; sclerotic, metatypical, keratotic lesions, and tumours with neural or perivascular involvement. d. Incompletely removed lesions. 3. Collision tumours, ie. anatomically overlapped 4. Lesions involving deep tissue or bone 5. Patient preference
11. Squamous Cell Carcinoma (SCC)
1. Lesions which fit the above categories as recommended for BCC 2. Irradiation-affected lesions 3. Mucosal lesions 4. Bowen’s Disease in certain locations 111. Other tumours 1. Keratoacanthomas (aggressive or mutilating)
2. Adenocystic carcinoma of the skin 3. Sebaceous carcinoma 4. Microcystic adenoid carcinoma 5. Dermatofibrosarcoma 6. Extramammary Paget’s Disease 7. Aggressive fibrohistiocytoma 8. Merkel cell carcinoma 9. Hemangioendothelioma 10. Leiomyosarcoma 11. Penile Erythroplasia of Queyrat 12. Verrucous carcinoma IV. Other lesions, in major multidisciplinary and academic Clinics 1. Tumours involving deep structures 2. Oral and central facial lesions including SCC of the floor of the mouth, tongue, palate, tonsillar pillar, paranasal sinuses 3. Melanoma in selected cases 4. Lesions in combination with other modalities under study, ie. retinoids, monoclonal antibodies, etc. 5 . Lesions of educational value to Fellows in approved training programs
DEVELQPMENT OF FRESH TISSUETECHNIQUE Being referred many advanced or “inoperable” cases, Mohs treated numerous cancers of the mouth, nasal sinuses, larynx, parotid gland, genitalia, some cases of melanoma and rarer cutaneous tumours - and published vigorously!’ Many wounds were allowed to heal by second intention, the fixative having stimulated formation of healthy granulation tissue. He developed great experience and high cure rates, and in 1978 V. Miscellaneous 1. Other circumstances where Micrographic control is was able to publish five-year end results showing desirable and appropriate cure in 99.3% of 7,574 BCCs, and 94% of 2,349 160
MOHSMICROGRAPHIC SURGERY FOR SKIN CANCER SCCs!’ However, in the early 1950s, Mohs began PRACTICAL CONCERNS deleting the chemical fixative, initially when Frozen section quality, fragmented tissue treating eyelid carcinomas. This “fresh tissue margins, tears, tissue orientation, interpretation technique” was not immediately accepted:’ but of frozen sections, and the taking of excessively Mohs reported five year cure rates of 100% for wide or narrow margins, are technical but real 66 BCCs and 4 SCCs of the eyelids in 1969” and challenges - that they are well managed by most Dermatologists Tromovitch and Stegman report- MMS Surgeons is reflected in the high cure rates ed good results using the fresh-tissue technique achieved!* lbmours exhibiting multi-focal growth, in 1970 and 197q3Mohs reported success in 3,450 the more aggressive carcinomas, and of 3,466 patients with BCC in 1976!4 The fresh discontinuous tumour remnants in old scar, tissue technique has become synonymous with require particularly careful application of MMS Mohs Micrographic Surgery, the fixed tissue technique but the advantages, particularly tissue technique being reserved for some cases of bone sparing in critical sites, remain. Tmsection of the involvement, the Acquired Immunodeficiency tumour itself when using fresh-tissue MMS is of Syndrome’ and selected cases of M e l a n ~ m a . ” ’ ~little concern in BCC but not in melanoma. The The American College of Chemosurgery was pitfalls are well canvassed by Rapini.19 founded in 1967, and in 1986, became the Misconceptions, some stemming from confusion American College of Mohs Micrographic Surgery between fixed and fresh tissue MMS persist, and and Cutaneous Oncology. are addressed by Zitelli.20 The time interval Standard MMS practice now involves, typically between Mohs layers is usually between 40 and under local anaesthesia and in an office or 60 minutes, and fewer than 10% of cases require ambulatory surgery facility, initial debulking of the tumour with curette or scalpel (providing a more than three layers for tumour eradication2’ specimen for vertical frozen sections and comparison with any prior biopsy), then careful removal of the tumour periphery as a saucershaped layer, so as to allow examination of the whole of the outermost surface on horizontal frozen sections. The wound is dressed and the patient returns to a waiting area whilst the tissue is processed. The “Mohs layer”, carefully orientated with respect to the tumour bed, is divided into segments and marked with a standard system of dyes and this is carefully recorded on a map of the tumour bed prepared by the Mohs Surgeon. Thin frozen sections, typically four to eight microns thick, are prepared in the cryostat, stained histochemically, and mounted for microscopic examination. Immunohistologial staining has become useful for some situationst7The Mohs Surgeon then examines the slides, correlating histologic features with the clinical setting, identifies and then maps out the remaining tumour foci. The patient is recalled and further layers taken where required, the steps being repeated until a tumour-free plane is reached; arrangements are then made for repair of the surgical defect and follow-up. With fresh tissue MMS, the resulting clean and tumour-free surgical defect is usually repaired promptly by direct closure, flap or graft as appropriate. Prior inter-specialty consultation and repair by specially-skilled reconstructive surgeons represents optimal management in complex cases.4
BASICREFERENCES The literature contains excellent reviews;’ 1.22.23 Dr Mohs’ text3 remains a valuable reference, as is a new text by Mikhail,24and standard texts on cutaneous surgery25and onco10gy*26 ACADEMIC ASPECTS MMS Practitioners are represented by the h e r i C a n College Of Mohs Micrographic Surgery and Cutaneous OncologY (ACMMSCO), Currently with 260 members. The Journal of Dermatologic Surgery and Oncology, Published monthly and now in its 17th indexed annual volume (Elsevier) serves as the Official publication O f the ACMMSCO (and three other Dermatologic Surgery Societies). The College is academically active: at the March 1991 annual meeting, Papers were presented on cutaneous tumour types, laboratory techniques and basic science, and on operative techniques, and repair techniques for post-Mohs defects. Issues of current concern addressed included HPV carcinogenesis, reduction and management of surgical complications, the impact of Medicare (USA) policies, and Mohs surgeonkonsultant interactions. MMS practitioners are involved in developing alternative therapies, notably intra-lesional alpha-2b interferon for BCC,2.7.28 currently showing 80% success rate at one year in a multi-centre, doubleblind, histological evaluation study, and laser
161
DAVIDF. LESLIEAND HUBERTT. GREENWAY ~ u r g e r y , ’ ~despite . ~ ~ limitations of laser surgery increase in biologically effective irradiance levels unique to the MMS setting.j’ A new scalpel is predicted for immunosuppressive effects of handle type facilitating removal of a Mohs layer sunlight for each 1% decrease in ozone levels.46 free of surface irregularities has been devel~ped.’~ Immunosuppression in humans is associated with Many Mohs surgeons also practice in other areas substantially increased skin cancer development, of Dermatologic Surgery, e.g. laser, dermabra- particularly SCC, and with an adversely affected sion, chemical peeling, acne surgery, prognosis,47and solar immunosuppression may sclerotherapy. contribute to skin cancer in There are also significant and increasing numbers of MELANOMA patients whose immune systems are suppressed The role of MMS in melanoma management by necessary treatment following organ transis still controversial. Mohs has published plantation, by oncology drug regimens, and by favourable results.”” However, his most recent HIV infection. figures, with Clark Levels I1 to V showing a 65.2% 5-year cure rate (Level I1 89070, Level V OF SKINCANCER SURGICAL CLEARANCE 38%), contain only 155 determinate casesJ4The - THE CHALLENGE issues have been addressed by Zitelli.3JAustralia Overall therefore, the management of skin and New Zealand have well documented high cancer will remain a major medical problem in levels of Melanoma incidence, and largely attriAustralasia in the foreseeable future. Currently, butable to the influences of the Queensland Melanoma Project and the Sydney Melanoma BCC is by far the commonest of these (BCC: Unit, well standardized surgical management with SCC ratio of 4.5 to l).‘* Histologic analysis of high care rates.36Mortality is still rising slightly a large series of BCCs treated by an experienced in most parts of the country, but this is in the face Australian Plastic Surgeon contained more than of dramatically rising incidence.j7 Melanoma is 20% of types other than papulonodular and the major cause of cancer death in young adult superficial multi-focal varieties; the author Autralians;” significant improvement in control stressed the value of horizontal sections, and the of this problem seems most likely to come from subclinical extension in those types of BCCs which are more aggressive, and more prone to prevention programs. rec~rrence.~~ Histological analysis of 1,039 BCCs excised, in an American series, showed surgically SKIN CANCER RATESIN AUSTRALIA clear margins reported in greater than 90% of The adult Australian population has very high nodular and superficial lesions, 91.4% of microdocumented levels of prevalence of non- nodular, 73.5% of infiltrative and 66.6% of melanoma skin cancer (consistently 5 % morpheic lesions.5o Confidence in histology appro^.),'^,^^.^' with annual incidence of these reports of surgical clearance however, must be tumours reported as high as 2,389 per 100,OOO per tempered by a clear understanding of the methods annum for men/1,908 per 100,000 per annum for used for checking surgical margins - conventional women.‘’ Many older Australians have personal “bread loaf” vertical sections leave much of the experience of these tumours - 14% prevalence at surgical margins unexamined!8 ages 60 to 69, plus 37% without tumours giving a history of prior removal of such.j9 Two of every MOHSMICROGRAPHIC SURGERY three Australians, at the present rate of incidence, IN AUSTRALIA will develop at least one skin cancer during their life.43 These figures are probably still rising, The introduction of MMS to Australia foldespite active prevention programs co-ordinated lowed the visit of Dr Perry Robins to the Skin by the Anti-Cancer Council of Victoria, with the and Cancer Foundation at Darlinghurst in 1978, hope of consequent future reductions. after which Drs Lance Cains and William Land commenced MMS there; others have followed SKINCANCER- FUTURE INFLUENCES and presently there are five Mohs Surgeons pracThe effects of ozone depletion are of particular ticing in Sydney, one in Perth, one in Auckland, concern in southern parts of but and two in Queensland. Others are currently effects upon skin cancer development are hard to training in the United States. One Fellowship Based on a murine model, a 0.6% training position in Sydney is in the process of 162
MOHS MICROGRAPHICSURGERY FOR SKIN CANCER
accreditation to the ACMMSCO. Formal qualification in MMS is now available through the Fellowship program of the ACMMSCO, and certification by examination is now available through the American Board of Mohs Micrographic Surgery and Cutaneous Oncology. In Australia as in America, most have entered the field from Dermatology. Mohs himself worked in a surgical department from 1940, publishing initially in surgical journals; he has written recently of the greater enthusiasm for the method shown by Dermatologists, and made a plea that Otolaryngologists, Head and Neck Surgeons, Oculoplastic Surgeons, Plastic Surgeons and other surgical specialists not be discouraged from entering the field!’ As Mohs Micrographic Surgery becomes more widely available, more patients in Australasia will be able to benefit from its demonstrated advantages. ACKNOWLEDGEMENT Dr Leslie’s study with Dr Greenway in La Jolla, California was assisted by the Florance Bequest, administered by the Australasian College of Dermatologists.
REFERENCES I
1
I
. J
6
7
(I
9
0
Mohs FE. Chemosurgery, a microscopically controlled method of cancer excision. Arch Surg 1941; 42: 279-295. Rowe DE, Carroll RJ, Day CL. Long-term recurrence rates in previously untreated (primary) basal cell carcinoma: Implications for patient follow-up. J Dermatol Surg Oncol 1989; 15: 315-328. Rowe DE, Carroll RJ, Day CL. Mohs Surgery is the treatment of choice for recurrent (previously treated) basal cell carcinoma. JDermatol Surg Oncol1989; 15: 424-431. Riefkohl R, Pollack S, Georgiade GS. A rationale for the treatment of difficult basal cell and squamous cell carcinomas of the skin. Ann PIast Surg 1985; 15: 99-104. Lang PG, Maize JC. Histologic evaluation of recurrent BCC and treatment implications. J Amer Acad DermatoI 1986; 14: 186-196. Salasche SJ, Ammonette RA. Morpheaform basal cell epitheliomas; a study of subclinical extensions in a series of 51 cases. J Dermatol Surg Oncol 1981; 7: 387-394. Mohs FE. Chemosurgery, microscopically controlled surgery for skin cancer. Springfield, 11: Charles C Thomas, 1978, pp 1-29. Mohs FE, Larson PO, Iriondo M. Micrographic surgery for the microscopically controlled excision of carcinoma of the external ear. J Amer Acad Dermatol 1988; 19: 729-737. Ratz JL, Liu-Duong S, Kulwin DR. Sebaceous carcinoma of the eyelid treated with Mohs Surgery. J Amer Acad Dermatol 1986; 1 4 668-673. Mohs FE, Lathrop TG.Modes of spread of cancer of skin. Arch Dermatol 1951; 66: 427-439.
Mohs FE. Origin and progress of Mohs micrographic surgery, in Mikhail GR (Ed) Mohs Micrographic Surgery. Philadelphia, 1991 WB Saunders, p 6. I* Mohs FE. Cancer of eyelids. Bull A m Coil Chemosurgery 1970; 3: 10-11. I3 Tromovitch TA, Stegman SJ. Microscopically controlled excision of skin turnours: Chemosurgery (Mohs) fresh tissue technique. Arch Dermatol 1974; 110: 231-232. I4 Mohs FE. Chernosurgery for skin cancer. Fixed tissue and fresh tissue techniques. Arch Dermatol1976; 112: 211-215. I1 Hruza GJ, Snow SN. Basal cell carcinoma in a patient with acquired immunodeficiency syndrome: treatment with Mohs micrographic surgery fixed tissue technique. J Dermatol Surg Oncol 1989; 15: 545-551. 14 Mohs FE. Chemosurgery for melanoma. Arch Dermatol 1977; 133: 285-291. I7 Penneys NS. Immunoperoxidase methods and advances in skin biology. J A m Acad Dermatol 1984; 11: 784. la Rapini RPI Comparison of methods for checking surgical margins. J Am Acad Dermatol 1990, 23: 288-294. l9 Rapini RP. Pitfalls of Mohs micrographic surgery. J Am Acad Dermatol 1990; 2 2 681-686. *O Zitelli JA. Mohs surgery: concepts and misconceptions. Znt J Dermatol 1985; 24: 541-548. Swanson NA. Mohs surgery: techniques, indications, applications, and the future. Arch Dermatol 1983; 119: 761-763. *’ Cottel WI, Bailin P, Albom MJ, et al. Essentials of Mohs micrographic surgery. J Dermatol Surg Oncol 1988; 14: 11-13. * I Roenigk RK, Roenigk HH. Current surgical managements of skin cancer in dermatology. J Dermatol Surg Oncol 1990, 16: 136-151. *‘ Mikhail GR (Ed). Mohs micrographic surgery. Philadelphia, 1991 WB Saunders. *’ Bennett RG. Fundamentals of cutaneous surgery. St Louis, CV Mosby 1988, pp 650-654. ’‘ Albom MJ, Swanson NA, in Friedman RJ (Ed) Cancer of the Skin. Philadelphia, 1991 WB Saunders. *’ Greenway HT, Cornell RC. Interferon: Coming of age. Arch Dermatol 1990; 126: 1080-1082. Cornell RC, Greenway HT, Tbcker SB, et al. Intralesional interferon therapy for BCC. JAmer Acad Dermatol1989; 23: 694-700. Garden JM, Geronemus RG. Dermatological laser surgery. J Dermatol Surg Oncol 1990; 16: 156-158. Geronemus RE, Reyes B. Laser surgery in the treatment of skin cancer, in: Friedman RJ (Ed) Cancer of the Skin. Philadelphia, 1991 WB Saunders. Bailin PL, Ratz JL, Lutz-Nagey L. CO’ laser modification of Mohs surgery. JDermatol Surg Oncoll981; 7: 621-623. ” Siege1DM. A new scalpel handle for the cutaneous surgeon. J Derrnatol Surg Oncol 1989; 15: 125. l 3 Mohs FE. Chemosurgery for melanoma. Arch Dermatol 1977; 113: 285-291. ” Zitelli JA, Mohs FE, Larson P, Snow SN. Mohs micrographic surgery for melanoma. Dermatol CIin 1989; 7: 833-834. Zitelli JA. Mohs surgry for Melanoma, in Mikhail GR (Ed) Mohs micrographic surgery. Philadelphia, 1991 WB Saunders. l6 Kelly JW. The management of early skin cancers in the 90s. Aust Family Phys 1990; 19: 17144729. 3 7 Hatton WM. Melanoma in Western Australia. Transactions of the Menzies Foundation 1989; 15: 165-167 (Melb.). II
163
DAVIDF. LESLIEAND HUBERT T.GREENWAY I'
I'
'O
'I
42
McCarthy WH. Enhancing the prospects for reduction of the incidence of mortality of melanoma. Transactions of the Menzies Foundation 1989; 15: 233-237. Green A, et al. Skin cancer in a Queensland population. J Amer Acad Dermatol 1988; 1 9 1045-1052. Kricker A, et al. Skin cancer in Geraldton, Western Australia (a survey of incidence and prevalence). Med J AUSt 1990; 152: 399-407. Marks R, Ponsford MW, Selwood TS,et al. Non-melanotic skin cancer and solar keratoses in Victoria. Med J Aust 1983; 2 619-622. Green A, Battistuta D. Incidence and determinants of skin cancer in a high risk Australian population. Int J Cancer 1990; 4 6 356-361.
'I
Marks R, J o k y D, Dorevitch AP, et al. The incidence of non-melanotic skin cancers in an Australian population: results of a five year prospective study. Med J Aust 1989; 150 475-478,
"
"
46
Refshauge, Sir W (Ed). Transactions of the Menzies Foundation: the Ozone Layer and Health. 1989; Vol 15 (Melbourne). De Fabo EC, Noonan FP, Frederick IE. Biologically effective doses of sunlight for immune suppression at various latitudes and their relationship to changes in stratospheric ozone. Photochem Photobiol 1991; 52: 811-817.
'' Emmett AJ, O'Rourke MG (Eds). Malignant skin tumours.
''
London 1982, Churchill Livingstone. De Fabo ED, Noonan FP. Photoimmunology: ultraviolet radiation effects on the immune system, in Zola H (Ed) Laboratory Methods in Immunology Vol I1 1990, CRC press Bocaraton (Florida). Emmett AJ. Surgical analysis and biological behaviour of 2,277 basal cell carcinomas. Aust NZ J Surg 1990; 6 0 855-863.
'O
Proffitt MH, Fahey DW, Kelly KK, et al. High latitude ozone loss outside the Antartic ozone hole. Nature 1989; 342 233-237.
164
Sexton MD, et al. Histologic pattern analysis of BCC. J Am Acad Dermatol 1990; 23: 1118-1126.
RE VIEW ARTICLE
MOHS MICROGRAPHIC SURGERY FOR SKIN CANCER DAVIDF. LESLIEAND HUBERT T. GREENWAY Maroochydore, Queensland and La Jolla, Cailfornia SUMMARY
Mohs Micrographic Surgery is a technique offering superior treatment for skin cancer with cure rates of 99% for primary and 94.4% for recurrent BCC, greater than 94% for SCC. As developed by Dr Frederic M o b , the technique originally involved application of a chemical fixative. Mohs' fresh tissue technique is now usual, with immediate horizontal frozen sectioning of the entire margins of excised tissue, mapping and microscopic identification of remaining tumour, then repeat excisions, mapping and examination until a tumour-freeplane is demonstrated throughout. Thisprovides maximal conservation of uninvolved tissue structures, and allows more confident repair of a cancerfree surgical defect. Mohs Micrographic Surgery is becoming more widely available in Australasia; concurrentlj indicationsfor the technique are widening, as are the research interests, training opportunities, and professional organization of Mohs Practitioners. Very high, and increasing, incidence and prevalence of skin cancer in Australasia, and factors tending to contribute to this, suggest that Mohs Micrographic Surgery has an expanding role to play in Australasia. Key words: Skin cancer, Mohs micrographic surgery, dermatologic surgery. INTRODUCTION Surgical removal of cancerous growths under histologic control is a familiar concept. The technique developed by Dr Frederic Mohs of Wisconsin' is based on a unique intimacy between removal and control; it has now developed into a refined management technique, under the name of Mohs Micrographic Surgery (MMS), with proven superior results in the management of a range of tumours, including many of the commoner types of skin cancer. Maximum available cure rates in certain applications, maximum conservation of uninvolved tissue, and the developing availability of the technique within Australasia, make an appreciation of MMS desirable for all those involved in the management of visible tumours. David F. Leslie, FACD. Dermatologist, Maroochydore, Queensland. Hubert T. Greenway, FACMMSCO. Director, Mohs Surgery and Cutaneous Laser Unit, Department of Dermatology, Scripps Clinic and Research Foundation, La Jolla, California. Address for correspondence: Dr D.F. Leslie, PO Box 1067, Maroochydore, Queensland 4558.
RESULTS Mohs Micrographic Surgery has produced its best results in the treatment of Basal Cell Carcinoma (BCC) - published studies showing rigorous five year recurrence rates, when summarized, indicate figures of 1% for BCCs treated initially by MMS and 5.6% for recurrent (previously treated) lesions following MMS. Comparable figures for other management modalities are: 10.1 and 17.4070, respectively, for surgical excision; 7.7 and 40.0% for curettage and electrodessication; 8.7 and 9.8% for radiotherapy; and 7.5% (and 13.0% on preliminary data published) for cryos~rgery.~.~ MMS has been particularly valuable when used in a multi-disciplinary team approach for the more difficult tumours, as with plastic surgical repair of complex postMMS defects.' It offers less advantage for lowrisk superficial BCCs on the trunk and limbs, and for small BCCs (less than 0.5cm diameter) excepting the morpheaform type, for which it is the treatment of choiceS because of subclinical extensions which may average more than 7 mms.6 For cutaneous Squamous Cell Carcinoma (SCC), whilst prognosis remains adversely affected by 159
DAVIDF. LESLIEAND HUBERT T. GREENWAY
site, tumour size, prior treatment, histopathologic differentiation, etc., published results of MMS compare favourably overall (94% success rates’) including at recognized high risk sites on the lips (94.1% 5 year cure’) and the external ear (97.1% 5 year cures). INDICATIONS MMS has been successfully used for a wide range of cutaneous neoplasms (Thble 1). It is of particular value where tissue conservation concerns are critical, eg. in sebaceous carcinoma of the eyelid^;^ similarly it has been useful in extramammary Paget’s Disease despite recognized discontinuous modes of spread by these tumours. CHEMOSURGERY - FIXEDTISSUETECHNIQUE The concept was developed by Mohs in the early ’ ~ O S ,then a medical student working as a Zoology Research Assistant, following his observation of histologic fixation of skin cancer in rats following injection of a zinc chloride solution. He subsequently developed a technique involving controlled in situ fixation in his patients’ tumours by application of a complex zinc chloride fixative, followed by removal of the fixed layer, segmentation, marking and careful mapping then the preparation of horizontal frozen histology sections allowing examination of the entire margins of removal, and identification of the sites of silent outgrowths of cancer remaining in the tumour bed. Further layers could be fixed where required and removed serially, until a cancer-free plane had been demonstrated throughout. This technique, which Mohs called Chemosurgery: offered both a high chance of cure and maximum conservation of uninvolved tissue - and these remain the touchstones of MMS today.
TABLE1 Indications for Mohs Micrographic Surgery (Skin Cancer) 1.
Basal Cell Carcinoma 1. Recurrent lesions 2. Subgroups of primary lesions: a. With clinical features, ie. morphoeic, infiltrating, multicentric lesions, those demonstrating rapid growth or aggressive behaviour, or large size. b. In critical anatomic locations including central third of the face, nasolabial fold, periorbital and canthal areas, pre-auricular cheek, auricle, postauricular sulcus, hands, feet, genitalia. c. With high risk histologic features on biopsy, ie. infiltrating or morphoeic; sclerotic, metatypical, keratotic lesions, and tumours with neural or perivascular involvement. d. Incompletely removed lesions. 3. Collision tumours, ie. anatomically overlapped 4. Lesions involving deep tissue or bone 5. Patient preference
11. Squamous Cell Carcinoma (SCC)
1. Lesions which fit the above categories as recommended for BCC 2. Irradiation-affected lesions 3. Mucosal lesions 4. Bowen’s Disease in certain locations 111. Other tumours 1. Keratoacanthomas (aggressive or mutilating)
2. Adenocystic carcinoma of the skin 3. Sebaceous carcinoma 4. Microcystic adenoid carcinoma 5. Dermatofibrosarcoma 6. Extramammary Paget’s Disease 7. Aggressive fibrohistiocytoma 8. Merkel cell carcinoma 9. Hemangioendothelioma 10. Leiomyosarcoma 11. Penile Erythroplasia of Queyrat 12. Verrucous carcinoma IV. Other lesions, in major multidisciplinary and academic Clinics 1. Tumours involving deep structures 2. Oral and central facial lesions including SCC of the floor of the mouth, tongue, palate, tonsillar pillar, paranasal sinuses 3. Melanoma in selected cases 4. Lesions in combination with other modalities under study, ie. retinoids, monoclonal antibodies, etc. 5 . Lesions of educational value to Fellows in approved training programs
DEVELQPMENT OF FRESH TISSUETECHNIQUE Being referred many advanced or “inoperable” cases, Mohs treated numerous cancers of the mouth, nasal sinuses, larynx, parotid gland, genitalia, some cases of melanoma and rarer cutaneous tumours - and published vigorously!’ Many wounds were allowed to heal by second intention, the fixative having stimulated formation of healthy granulation tissue. He developed great experience and high cure rates, and in 1978 V. Miscellaneous 1. Other circumstances where Micrographic control is was able to publish five-year end results showing desirable and appropriate cure in 99.3% of 7,574 BCCs, and 94% of 2,349 160
MOHSMICROGRAPHIC SURGERY FOR SKIN CANCER SCCs!’ However, in the early 1950s, Mohs began PRACTICAL CONCERNS deleting the chemical fixative, initially when Frozen section quality, fragmented tissue treating eyelid carcinomas. This “fresh tissue margins, tears, tissue orientation, interpretation technique” was not immediately accepted:’ but of frozen sections, and the taking of excessively Mohs reported five year cure rates of 100% for wide or narrow margins, are technical but real 66 BCCs and 4 SCCs of the eyelids in 1969” and challenges - that they are well managed by most Dermatologists Tromovitch and Stegman report- MMS Surgeons is reflected in the high cure rates ed good results using the fresh-tissue technique achieved!* lbmours exhibiting multi-focal growth, in 1970 and 197q3Mohs reported success in 3,450 the more aggressive carcinomas, and of 3,466 patients with BCC in 1976!4 The fresh discontinuous tumour remnants in old scar, tissue technique has become synonymous with require particularly careful application of MMS Mohs Micrographic Surgery, the fixed tissue technique but the advantages, particularly tissue technique being reserved for some cases of bone sparing in critical sites, remain. Tmsection of the involvement, the Acquired Immunodeficiency tumour itself when using fresh-tissue MMS is of Syndrome’ and selected cases of M e l a n ~ m a . ” ’ ~little concern in BCC but not in melanoma. The The American College of Chemosurgery was pitfalls are well canvassed by Rapini.19 founded in 1967, and in 1986, became the Misconceptions, some stemming from confusion American College of Mohs Micrographic Surgery between fixed and fresh tissue MMS persist, and and Cutaneous Oncology. are addressed by Zitelli.20 The time interval Standard MMS practice now involves, typically between Mohs layers is usually between 40 and under local anaesthesia and in an office or 60 minutes, and fewer than 10% of cases require ambulatory surgery facility, initial debulking of the tumour with curette or scalpel (providing a more than three layers for tumour eradication2’ specimen for vertical frozen sections and comparison with any prior biopsy), then careful removal of the tumour periphery as a saucershaped layer, so as to allow examination of the whole of the outermost surface on horizontal frozen sections. The wound is dressed and the patient returns to a waiting area whilst the tissue is processed. The “Mohs layer”, carefully orientated with respect to the tumour bed, is divided into segments and marked with a standard system of dyes and this is carefully recorded on a map of the tumour bed prepared by the Mohs Surgeon. Thin frozen sections, typically four to eight microns thick, are prepared in the cryostat, stained histochemically, and mounted for microscopic examination. Immunohistologial staining has become useful for some situationst7The Mohs Surgeon then examines the slides, correlating histologic features with the clinical setting, identifies and then maps out the remaining tumour foci. The patient is recalled and further layers taken where required, the steps being repeated until a tumour-free plane is reached; arrangements are then made for repair of the surgical defect and follow-up. With fresh tissue MMS, the resulting clean and tumour-free surgical defect is usually repaired promptly by direct closure, flap or graft as appropriate. Prior inter-specialty consultation and repair by specially-skilled reconstructive surgeons represents optimal management in complex cases.4
BASICREFERENCES The literature contains excellent reviews;’ 1.22.23 Dr Mohs’ text3 remains a valuable reference, as is a new text by Mikhail,24and standard texts on cutaneous surgery25and onco10gy*26 ACADEMIC ASPECTS MMS Practitioners are represented by the h e r i C a n College Of Mohs Micrographic Surgery and Cutaneous OncologY (ACMMSCO), Currently with 260 members. The Journal of Dermatologic Surgery and Oncology, Published monthly and now in its 17th indexed annual volume (Elsevier) serves as the Official publication O f the ACMMSCO (and three other Dermatologic Surgery Societies). The College is academically active: at the March 1991 annual meeting, Papers were presented on cutaneous tumour types, laboratory techniques and basic science, and on operative techniques, and repair techniques for post-Mohs defects. Issues of current concern addressed included HPV carcinogenesis, reduction and management of surgical complications, the impact of Medicare (USA) policies, and Mohs surgeonkonsultant interactions. MMS practitioners are involved in developing alternative therapies, notably intra-lesional alpha-2b interferon for BCC,2.7.28 currently showing 80% success rate at one year in a multi-centre, doubleblind, histological evaluation study, and laser
161
DAVIDF. LESLIEAND HUBERTT. GREENWAY ~ u r g e r y , ’ ~despite . ~ ~ limitations of laser surgery increase in biologically effective irradiance levels unique to the MMS setting.j’ A new scalpel is predicted for immunosuppressive effects of handle type facilitating removal of a Mohs layer sunlight for each 1% decrease in ozone levels.46 free of surface irregularities has been devel~ped.’~ Immunosuppression in humans is associated with Many Mohs surgeons also practice in other areas substantially increased skin cancer development, of Dermatologic Surgery, e.g. laser, dermabra- particularly SCC, and with an adversely affected sion, chemical peeling, acne surgery, prognosis,47and solar immunosuppression may sclerotherapy. contribute to skin cancer in There are also significant and increasing numbers of MELANOMA patients whose immune systems are suppressed The role of MMS in melanoma management by necessary treatment following organ transis still controversial. Mohs has published plantation, by oncology drug regimens, and by favourable results.”” However, his most recent HIV infection. figures, with Clark Levels I1 to V showing a 65.2% 5-year cure rate (Level I1 89070, Level V OF SKINCANCER SURGICAL CLEARANCE 38%), contain only 155 determinate casesJ4The - THE CHALLENGE issues have been addressed by Zitelli.3JAustralia Overall therefore, the management of skin and New Zealand have well documented high cancer will remain a major medical problem in levels of Melanoma incidence, and largely attriAustralasia in the foreseeable future. Currently, butable to the influences of the Queensland Melanoma Project and the Sydney Melanoma BCC is by far the commonest of these (BCC: Unit, well standardized surgical management with SCC ratio of 4.5 to l).‘* Histologic analysis of high care rates.36Mortality is still rising slightly a large series of BCCs treated by an experienced in most parts of the country, but this is in the face Australian Plastic Surgeon contained more than of dramatically rising incidence.j7 Melanoma is 20% of types other than papulonodular and the major cause of cancer death in young adult superficial multi-focal varieties; the author Autralians;” significant improvement in control stressed the value of horizontal sections, and the of this problem seems most likely to come from subclinical extension in those types of BCCs which are more aggressive, and more prone to prevention programs. rec~rrence.~~ Histological analysis of 1,039 BCCs excised, in an American series, showed surgically SKIN CANCER RATESIN AUSTRALIA clear margins reported in greater than 90% of The adult Australian population has very high nodular and superficial lesions, 91.4% of microdocumented levels of prevalence of non- nodular, 73.5% of infiltrative and 66.6% of melanoma skin cancer (consistently 5 % morpheic lesions.5o Confidence in histology appro^.),'^,^^.^' with annual incidence of these reports of surgical clearance however, must be tumours reported as high as 2,389 per 100,OOO per tempered by a clear understanding of the methods annum for men/1,908 per 100,000 per annum for used for checking surgical margins - conventional women.‘’ Many older Australians have personal “bread loaf” vertical sections leave much of the experience of these tumours - 14% prevalence at surgical margins unexamined!8 ages 60 to 69, plus 37% without tumours giving a history of prior removal of such.j9 Two of every MOHSMICROGRAPHIC SURGERY three Australians, at the present rate of incidence, IN AUSTRALIA will develop at least one skin cancer during their life.43 These figures are probably still rising, The introduction of MMS to Australia foldespite active prevention programs co-ordinated lowed the visit of Dr Perry Robins to the Skin by the Anti-Cancer Council of Victoria, with the and Cancer Foundation at Darlinghurst in 1978, hope of consequent future reductions. after which Drs Lance Cains and William Land commenced MMS there; others have followed SKINCANCER- FUTURE INFLUENCES and presently there are five Mohs Surgeons pracThe effects of ozone depletion are of particular ticing in Sydney, one in Perth, one in Auckland, concern in southern parts of but and two in Queensland. Others are currently effects upon skin cancer development are hard to training in the United States. One Fellowship Based on a murine model, a 0.6% training position in Sydney is in the process of 162
MOHS MICROGRAPHICSURGERY FOR SKIN CANCER
accreditation to the ACMMSCO. Formal qualification in MMS is now available through the Fellowship program of the ACMMSCO, and certification by examination is now available through the American Board of Mohs Micrographic Surgery and Cutaneous Oncology. In Australia as in America, most have entered the field from Dermatology. Mohs himself worked in a surgical department from 1940, publishing initially in surgical journals; he has written recently of the greater enthusiasm for the method shown by Dermatologists, and made a plea that Otolaryngologists, Head and Neck Surgeons, Oculoplastic Surgeons, Plastic Surgeons and other surgical specialists not be discouraged from entering the field!’ As Mohs Micrographic Surgery becomes more widely available, more patients in Australasia will be able to benefit from its demonstrated advantages. ACKNOWLEDGEMENT Dr Leslie’s study with Dr Greenway in La Jolla, California was assisted by the Florance Bequest, administered by the Australasian College of Dermatologists.
REFERENCES I
1
I
. J
6
7
(I
9
0
Mohs FE. Chemosurgery, a microscopically controlled method of cancer excision. Arch Surg 1941; 42: 279-295. Rowe DE, Carroll RJ, Day CL. Long-term recurrence rates in previously untreated (primary) basal cell carcinoma: Implications for patient follow-up. J Dermatol Surg Oncol 1989; 15: 315-328. Rowe DE, Carroll RJ, Day CL. Mohs Surgery is the treatment of choice for recurrent (previously treated) basal cell carcinoma. JDermatol Surg Oncol1989; 15: 424-431. Riefkohl R, Pollack S, Georgiade GS. A rationale for the treatment of difficult basal cell and squamous cell carcinomas of the skin. Ann PIast Surg 1985; 15: 99-104. Lang PG, Maize JC. Histologic evaluation of recurrent BCC and treatment implications. J Amer Acad DermatoI 1986; 14: 186-196. Salasche SJ, Ammonette RA. Morpheaform basal cell epitheliomas; a study of subclinical extensions in a series of 51 cases. J Dermatol Surg Oncol 1981; 7: 387-394. Mohs FE. Chemosurgery, microscopically controlled surgery for skin cancer. Springfield, 11: Charles C Thomas, 1978, pp 1-29. Mohs FE, Larson PO, Iriondo M. Micrographic surgery for the microscopically controlled excision of carcinoma of the external ear. J Amer Acad Dermatol 1988; 19: 729-737. Ratz JL, Liu-Duong S, Kulwin DR. Sebaceous carcinoma of the eyelid treated with Mohs Surgery. J Amer Acad Dermatol 1986; 1 4 668-673. Mohs FE, Lathrop TG.Modes of spread of cancer of skin. Arch Dermatol 1951; 66: 427-439.
Mohs FE. Origin and progress of Mohs micrographic surgery, in Mikhail GR (Ed) Mohs Micrographic Surgery. Philadelphia, 1991 WB Saunders, p 6. I* Mohs FE. Cancer of eyelids. Bull A m Coil Chemosurgery 1970; 3: 10-11. I3 Tromovitch TA, Stegman SJ. Microscopically controlled excision of skin turnours: Chemosurgery (Mohs) fresh tissue technique. Arch Dermatol 1974; 110: 231-232. I4 Mohs FE. Chernosurgery for skin cancer. Fixed tissue and fresh tissue techniques. Arch Dermatol1976; 112: 211-215. I1 Hruza GJ, Snow SN. Basal cell carcinoma in a patient with acquired immunodeficiency syndrome: treatment with Mohs micrographic surgery fixed tissue technique. J Dermatol Surg Oncol 1989; 15: 545-551. 14 Mohs FE. Chemosurgery for melanoma. Arch Dermatol 1977; 133: 285-291. I7 Penneys NS. Immunoperoxidase methods and advances in skin biology. J A m Acad Dermatol 1984; 11: 784. la Rapini RPI Comparison of methods for checking surgical margins. J Am Acad Dermatol 1990, 23: 288-294. l9 Rapini RP. Pitfalls of Mohs micrographic surgery. J Am Acad Dermatol 1990; 2 2 681-686. *O Zitelli JA. Mohs surgery: concepts and misconceptions. Znt J Dermatol 1985; 24: 541-548. Swanson NA. Mohs surgery: techniques, indications, applications, and the future. Arch Dermatol 1983; 119: 761-763. *’ Cottel WI, Bailin P, Albom MJ, et al. Essentials of Mohs micrographic surgery. J Dermatol Surg Oncol 1988; 14: 11-13. * I Roenigk RK, Roenigk HH. Current surgical managements of skin cancer in dermatology. J Dermatol Surg Oncol 1990, 16: 136-151. *‘ Mikhail GR (Ed). Mohs micrographic surgery. Philadelphia, 1991 WB Saunders. *’ Bennett RG. Fundamentals of cutaneous surgery. St Louis, CV Mosby 1988, pp 650-654. ’‘ Albom MJ, Swanson NA, in Friedman RJ (Ed) Cancer of the Skin. Philadelphia, 1991 WB Saunders. *’ Greenway HT, Cornell RC. Interferon: Coming of age. Arch Dermatol 1990; 126: 1080-1082. Cornell RC, Greenway HT, Tbcker SB, et al. Intralesional interferon therapy for BCC. JAmer Acad Dermatol1989; 23: 694-700. Garden JM, Geronemus RG. Dermatological laser surgery. J Dermatol Surg Oncol 1990; 16: 156-158. Geronemus RE, Reyes B. Laser surgery in the treatment of skin cancer, in: Friedman RJ (Ed) Cancer of the Skin. Philadelphia, 1991 WB Saunders. Bailin PL, Ratz JL, Lutz-Nagey L. CO’ laser modification of Mohs surgery. JDermatol Surg Oncoll981; 7: 621-623. ” Siege1DM. A new scalpel handle for the cutaneous surgeon. J Derrnatol Surg Oncol 1989; 15: 125. l 3 Mohs FE. Chemosurgery for melanoma. Arch Dermatol 1977; 113: 285-291. ” Zitelli JA, Mohs FE, Larson P, Snow SN. Mohs micrographic surgery for melanoma. Dermatol CIin 1989; 7: 833-834. Zitelli JA. Mohs surgry for Melanoma, in Mikhail GR (Ed) Mohs micrographic surgery. Philadelphia, 1991 WB Saunders. l6 Kelly JW. The management of early skin cancers in the 90s. Aust Family Phys 1990; 19: 17144729. 3 7 Hatton WM. Melanoma in Western Australia. Transactions of the Menzies Foundation 1989; 15: 165-167 (Melb.). II
163
DAVIDF. LESLIEAND HUBERT T.GREENWAY I'
I'
'O
'I
42
McCarthy WH. Enhancing the prospects for reduction of the incidence of mortality of melanoma. Transactions of the Menzies Foundation 1989; 15: 233-237. Green A, et al. Skin cancer in a Queensland population. J Amer Acad Dermatol 1988; 1 9 1045-1052. Kricker A, et al. Skin cancer in Geraldton, Western Australia (a survey of incidence and prevalence). Med J AUSt 1990; 152: 399-407. Marks R, Ponsford MW, Selwood TS,et al. Non-melanotic skin cancer and solar keratoses in Victoria. Med J Aust 1983; 2 619-622. Green A, Battistuta D. Incidence and determinants of skin cancer in a high risk Australian population. Int J Cancer 1990; 4 6 356-361.
'I
Marks R, J o k y D, Dorevitch AP, et al. The incidence of non-melanotic skin cancers in an Australian population: results of a five year prospective study. Med J Aust 1989; 150 475-478,
"
"
46
Refshauge, Sir W (Ed). Transactions of the Menzies Foundation: the Ozone Layer and Health. 1989; Vol 15 (Melbourne). De Fabo EC, Noonan FP, Frederick IE. Biologically effective doses of sunlight for immune suppression at various latitudes and their relationship to changes in stratospheric ozone. Photochem Photobiol 1991; 52: 811-817.
'' Emmett AJ, O'Rourke MG (Eds). Malignant skin tumours.
''
London 1982, Churchill Livingstone. De Fabo ED, Noonan FP. Photoimmunology: ultraviolet radiation effects on the immune system, in Zola H (Ed) Laboratory Methods in Immunology Vol I1 1990, CRC press Bocaraton (Florida). Emmett AJ. Surgical analysis and biological behaviour of 2,277 basal cell carcinomas. Aust NZ J Surg 1990; 6 0 855-863.
'O
Proffitt MH, Fahey DW, Kelly KK, et al. High latitude ozone loss outside the Antartic ozone hole. Nature 1989; 342 233-237.
164
Sexton MD, et al. Histologic pattern analysis of BCC. J Am Acad Dermatol 1990; 23: 1118-1126.
