------------------------------------------------------------------------------- TITLE: MOHS MICROGRAPHIC SURGERY SOURCE: Dept. of Otolaryngology, UTMB, Grand Rounds DATE: SEPTEMBER 14, 1994 RESIDENT PHYSICIAN: Kathleen R. Mcdonald M.D. FACULTY: Karen H. Calhoun M.D. DATABASE ADMINISTRATOR: Melinda McCracken, M.S. ------------------------------------------------------------------------------- "This material was prepared by resident physicians in partial fulfillment of educational requirements established for the Postgraduate Training Program of the UTMB Department of Otolaryngology/Head and Neck Surgery and was not intended for clinical use in its present form. It was prepared for the purpose of stimulating group discussion in a conference setting. No warranties, either express or implied, are made with respect to its accuracy, completeness, or timeliness. The material does not necessarily reflect the current or past opinions of members of the UTMB faculty and should not be used for purposes of diagnosis or treatment without consulting appropriate literature sources and informed professional opinion." Introduction: There are more than 600,000 new cases of skin cancer occurring annually in the United States. Most tumors arise on the sun-exposed regions of the head and neck. The median delay for diagnosis between first onset and definitive treatment is 3 years. Skin cancer most commonly affects fair-skinned, red-heads and blondes who have had significant exposure to ultraviolet light, especially if significant sunburn occurred in childhood. With significant enough sun exposure all caucasians and some other skin types are at significant risk. Basal cell carcinoma is the predominant histologic type and accounts for about 90% of all cutaneous neoplasm in the head and neck region. This is followed by squamous cell carcinoma. Malignant melanoma is less common yet needs to be mentioned due to it malignant tendency. More than 90% of these are seen by physicians and cured by the primary therapeutic modality. Due to the location on the face, especially the nose, lip, ear and periorbital area, the most conservative yet complete excision is the desired result to prevent recurrence. The technique of Mohs surgery has been developed to use serial excisions with microscopic examination of the specimen to attain a complete excision. Historical Background: In 1932 while working as a cancer research assistant at University of Wisconsin, a medical student Frederic E. Mohs developed a technique of excising cutaneous cancers using a chemical fixative, zinc chloride, under microscopic control. With the use of 20% zinc chloride solution the microscopic features of the tissues were preserved as if they had been immersed in a fixative solution. Clinical trial began in 1936 using the technique of "chemosurgery". In 1941 Mohs went on to publish his work on the caustic escharotic agent, zinc chloride, which was enabling him to excise the cancerous lesion in a relatively blood-free field, rendering it suitable for sections. The procedure consisted of an overnight application of zinc chloride paste. The following day a saucer shaped sample was taken and carefully mapped. The exact area which showed persistent disease would be require reapplication and future excision the following day until complete excision was attained. The remaining fixed tissue would slough off in the next few days. This procedure showed a high cure rate but resulted in severe pain upon application of the paste and was very time consuming. The fresh tissue technique of Mohs micrographic surgery was introduced for tumors on the eyelid by Dr Mohs in 1953 and later popularized by Theodore Tromovitch. In 1970's Theodore Tromovitch presented his results with the fresh-tissue Mohs surgery to the American College of Chemosurgery which gave this surgery the needed attention which was lacking despite the superiority over conventional means. In 1974, Tromovitch and Stegman published results showing comparable results using the fresh tissue technique compared to the fixed. This technique was much less painful for the patient and allowed for multiple stages of excision to be carried out on a single day. In 1991 the AMA reported 56,791 tumors treated by Mohs micrographic surgery. Indications: There are many variables to consider when determining the type of surgery to preform for neoplasm. Certain types of locally invasive malignant cutaneous tumors and tumors arising in specific anatomical locations such as the nose or ears have a relatively higher statistical frequency of recurrence following treatment with conventional methods such as local excision, curettage and electrodesiccation, cryotherapy, and radiation when compared to Mohs micrographic surgery. Aggressive tumors have a tendency to have finger-like projections that may be left behind even though the area appears to be free of tumor. Certain types of basal cell carcinoma like the morpheaform and sclerosing have a high incidence of this. The technique allows perineural invasion, penetration into surrounding fat, bone, cartilage or muscle to be detected and removed. Wide-margin surgical excision to completely excise these tumors is usually not possible in the head and neck. Mohs micrographic surgery uses thin sections and precise mapping allowng only the affected area to be excised and preserving the unaffected tissue with tumor-free margins. Mohs in the treatment of choice for any recurrent tumor. Recurrent tumor cells often grow in unexpected patterns along scars, undermining borders or under repair flaps. Tissue sparing is an asset of Mohs surgery and this is vitally important in areas such as the nasolabial folds, Medial and lateral canthi, nose, ear and vermillion borders of the lip. Skin cancer: Cancer of the skin comprises one of the most frequently treated malignancies of the head and neck. Twenty five percent of all patients with skin cancers have more than one lesion at the time of diagnosis. Some systemic disorders are prone to developing skin cancer i.e., albinism, xeroderma pigmentosa and nevoid basal cell carcinoma syndrome. Basal cell carcinoma is a locally aggressive skin cancer that often has fingers of tissue growth out into the surrounding tissue. Basal cell carcinomas is the most common malignant tumor affecting humans (400,000 new cases in the US per year.) It characteristically occurs in the light exposed areas. The greatest percentage of tumors are seen on the face (29%) and the nose (25%). Basal cell carcinomas present as a slow growing nodular pearly gray raised lesion with surrounding translucent border of telangiectatic vessels. They may be smooth, ulcerated, or they may crust over eventually being covered by a smooth layer of epithelium, giving a false impression of healing. This repeated cycles of healing and recurrent ulceration eventually lead to extensive local tissue destruction and hence, the histoical term, rodent ulcer. Other types of BCCA exist which are more aggressive such as morpheaform or sclerosing, Adenoid, cystic, and basosquamous. Microscopically the picture show buds of deeply basophilic cells protruding from the epidermis or extending into the dermis, forming large nests. Robins in his 15 years of experience found that there is a greater incidence of BCCA in men compared to women. They commonly present in the age range of 60-65 years, but appear to be more aggressive if presenting at ages less than 50. The size of the lesion upon diagnosis was 2-2.9 cm in diameter(50%). The most common locations were the nose and periorbital area. Squamous cell carcinoma is the second most common group of skin cancer accounting for 150,000 new cases per year. Squamous cell carcinoma typically arises on the face due to the high amount of sun exposure. Its gross appearance is usually a localized hyperkeratosis, which is usually produces increasing amounts of keratin. Microscopic examination reveals atypical keratinocytic hyperplasia involving all the epidermal layers. Invasion is seen when there is extension of the atypical keratinocytes into the underlying connective tissue. Lip lesion have the highest rate of metastasis in squamous cell carcinoma. Technique: Fixed-tissue technique: This technique uses the escharotic agent zinc chloride to fix the tissue and allow microscopic controlled excision of cancerous lesion in a relatively blood-free field, rendering it suitable for sections. The healing is by secondary intention where the fixed tissue remaining was allowed to slough. The fixed tissue technique is preferred in certain circumstances such as with vascular tumors, tumors arising in vascular areas and also tumors involving bone. It has also been used in the treatment of osteomyelitis and tumors that have penetrated bone. Fresh-tissue technique: The fresh-tissue technique is the most commonly used. The patient is surgically prepped and draped and the area is anesthetized with a local anesthetic of 1% lidocaine and epinephrine (1:100,000 to 1: 400,000) for vasoconstriction. After allowing 10 minutes for maximum anesthesia and vasoconstriction, a curette is used to debulk the soft part of the lesion and to "feel' for tumor extensions. Frozen or permanent sections are not necessary if previous biopsy established the diagnosis. The planned excision is delineated on the skin with 2mm to 5mm margins of normal appearing skin is marked from the margin of the curetted tumor. For recurrent lesions, the whole scar, graft or flap is usually removed. The margin excised is proportional to the clinical size of the lesion. It is necessary to bevel inwardly the edge of the tissue at an angle of 45 degrees to the base of the surgical wound. This beveling enables the histotechnician to press flat the entire undersurface (base and peripheral rim) onto the cryostat objective holder to facilitate horizontal sectioning. To remove the next layer, the blade is held almost perpendicular to the skin to avoid missing the tumor located below the epidermal margin and conserve normal tissue. To allow for precise rotational orientation, asymmetric identifying marks are made on corresponding areas on the edge of the defect and the edge of the specimen. This can be done with the used of suture, staples or with scalpeled superficial hash marks. A two dimensional map of the wound is drawn for future reference and documentation. Spot bovie cauterization is done on small bleeding vessels with larger vessels requiring suture ligation. Oxidized cellulose (Oxycel) may be used in highly vascularized areas which are prone to bleeding. Oxycel is not used when primary closure or immediate plastic surgical repair contemplated. As the tissue is excised, or, after complete excision, the tissue is subdivided into sections that are small enough to fit on a glass slide. Each section is numbered and the subdivision is indicated on the map. The specimen is then cut into 1-cm pieces of various geometric shapes. Two adjacent edges of each tissue segment are color-coded, using laundry bluing and 50% mercurochrome to orient spatially the tissue as to left and right, and top and bottom. By convention, the blue dye is applied on the bottom edge opposite the epidermal rim. The specimens are numbered sequentially and this number and the color-coding are drawn on the map: a solid line representing red; and interrupted line, blue. The tissue specimens are taken to the cryostat and 6 to 8 micron thick horizontal frozen sections are obtained. The specimen is placed on the cryostat chuck with the more superficial tissue down and the deeper and most peripheral tissue edges teased upward so that the outer edge of the excised tissue is in the same plane as the deeper tissue. The prepared sections are stained with one of several stains, usually hematoxylin and Eosin. Others stains used are Periodic Acid-Schiff stain and Oil Red O stain. The staining technique of H&E closely duplicated those of more conventional paraffin-fixed slides. The PAS-diastase and ORO stains are not used routinely but are reserved for use when special information is need such as with extramammary Paget's, sebaceous carcinoma, apocrine and eccrine tumors and basal cell carcinoma with eccrine, sebaceous, or trichilemmal differentiation. Extramammary Paget's disease histopathologically show clear cells in the epidermis with mucopolysaccharide containing malignant cells. The tumor cells of extramammary Paget's disease exhibit PAS-positive and diastase-resistant mucopolysaccharides. This stain delineates the intraepidermal adenocarcinoma cells from other epidermal clear cells. Sebaceous carcinoma may appear as a poorly differentiated carcinoma in the skin with characteristic foamy cytoplasm. The use of ORO staining is positive for intracytoplasmic lipids and aids in differentiating this tumor from other poorly differentiated cutaneous carcinomas. Eccrine carcinoma contains abundant PAS-positive and diastase-labile glycogen while Apocrine carcinomas are PAS-positive and diastase-resistant. Occasional difficulty may arise in the interpretation of horizontal frozen sections of basal cell carcinoma especially in differentiating tumor from normal appendageal structures. The basal cell carcinoma with sebaceous differentiation will have ORO-positive intracytoplasmic lipids; trichilelemmal differentiation or eccrine differentiation will exhibit PAS-positive granules. After the slides are stained they are presented to the Mohs surgeon or pathologist for histologic examination. Using the color coded edges and the map of the excised tissue, residual tumor that is noted on the slide can be mapped and traced back to the exact location of the residual tumor in the wound for further excision. Residual tumor is removed in successively numbered stages by modifying steps just to the location of the tumor until the surgical margins are entirely free of malignancy. In this manner, uninvolved tissue is preserved and the tumor is completely removed. The precise map of each stage accurately records the entire surgery and is retained as part of the patient's record. Wound Repair: There are several different methods used for wound repair. The one most often used especially with small superficial lesions healing by second intention or split thickness grafting is used. Since the malignancy is no likely to recur with this technique the use of flaps, full-thickness grafts and simple, intermediate, or complex closures give good cosmetic results. Early when most Mohs surgery used chemical cauterization the closure was by secondary intention because of the devitalized tissue that remained. Now that predominantly fresh frozen tissue technique only about 1/3 of the operative sites are closed by secondary intention. Many times the dermatologist will preform simple immediate closures. If the site is to complicated the ENT physician is used. When delayed closure is planned a semi-occlusive sterile dressing consisting of antibiotic ointment, Telfa, sterile cotton balls and flesh-colored micropore tape, is secured over the wound. To prevent desiccation of exposed bone, vaseline gauze is used. Primary closure may be done. A delay of 1 week to 10 days is acceptable for closure of larger lesions as long as proper wound care is performed. The patient is placed on the appropriate oral antibiotic immediately perioperative period, either erythromycin, a penicillinase-resistant penicillin, or cephalosporin. There are many local regional flaps that have been used. These will not be covered in this paper. Cure Rate: Fixed tissue technique has a well-established record for reliability. In the article by Mohs his series of 3,302 squamous cell carcinomas of the skin had a five year cure rate of 94.4%. This included a considerable amount of recurrent and advanced tumors. With the start of the fresh-tissue technique the five-year cure rates are 99% for primary basal cell carcinomas and 96% for recurrent basal cell carcinomas. Other treatment modalities fare poorly by comparison with surgical excision, 89.9% and 82.6% respectively; curettage and electrodesiccation, 92.3% and 60.0%; radiotherapy, 91.3 and 90.2%; cryotherapy 92.5%. The cure rate is dependent on size, type and location of the tumor. It has been found that younger patients (<50y/o) typically have more of an aggressive tumor with slightly lower cure rate 96.5% compared to 97.7% The smaller the BCCA the higher the cure rate with 1 cm lesions having a 5 year cure rate of 99.6 - 99% which drops to 92.2- 91% for lesions larger than 5 cm. The cure rate found also varies with the location. The areas for which high cure rates were achieved are the forehead, neck, cheeks, and extremities. The nose (97.4%), ear (95.2%), and the retroauricular (86%) are all difficult areas. The recurrence rates for treatment of primary basal cell carcinomas using all forms of treatment including Mohs showed that less than 1/3 of all recurrences appeared within the first year following treatment, only 50% appear within the first 2 years following treatment, and only 66% appear within the first three years. A five year follow up period is important to get accurate recurrence rate records. BCCA has a much higher recurrence rate after treating recurrent lesions than after treating the primary lesion. This is due to the fibrotic scar tissue forms at the site of the initial treatment, and the appearance of recurrent basal tumor cells is frequently squamified, lacy, and or morpheaform which are more aggressive behaving tumors. Primary squamous cell carcinoma has a 94-98% five- year cure rate was achieved by Mohs while an 84% cure rate was accomplished for recurrent squamous cell carcinomas. The size of the tumor is more influential on the cure rate of squamous cell carcinoma. Lesions less than 2 cm have 99% five year local control while lesions 2-3 cm result in 82% cure rate. Greater than 3 cm have only a 59% local control. Mohs has been used with malignant melanoma and is comparative to the conventional surgical excision. They show for Clarks level II, 100%; level III, 92%; level IV, 64%; and level V, 33%. Conclusion: Mohs micrographic surgery is an excellent modality, but is probably not indicated for routine, small, nonrecurrent lesions. Rather, it should be strongly considered in cases involving treatment failures, large long-standing lesions, poorly differentiated squamous carcinomas, morpheaform basal cell carcinoma, tumors involving embryonic fusion planes, and tumors in the canthal regions and around functional areas where preservation of normal tissue is essential. The high rate of cure associated with Mohs surgery depends on tumor contiguity, and tumors that have micro-metastasized beyond surgical margins cannot be cured by any method of local primary tumor excision. Mohs is a method of 100% margin control giving a extremely high cure rate. Any tumor that is located in a vital area which is often the case with head and neck malignancy or has a high recurrence rate is a good candidate for Mohs surgery. The advantages of Mohs surgery are many. They consist of the fact that it is an outpatient surgery with very low risk to the patient. It minimizes the amount of normal tissue removed while giving us nearly 100% clear margins. This type of surgery gives us high cure rates despite the fact that the tumor is complicated and extensive. The problem that arises with Mohs surgery is that it requires the expertise of a qualified surgeon and trained staff. An experienced histology technician is required for on site frozen section. This technique is quite lengthy and painful so the patient must be cooperative and willing to wait between stages. The cost is usually less expensive that other acceptable treatment options. TABLE 1: Criteria for Mohs Micrographic Surgery Recurrent tumors Tumors locate in anatomic areas associated with a high risk of local recurrence. (nasolabial fold, pinna, medial and lateral canthi, periauricular area.) Tumors located in areas where tissue preservation is mandatory Tumors overlying the embryonic fusion planes Tumors located in areas where the highest cure rate is mandatory Aggressive tumors Large tumors Tumors with poorly defined clinical margins. Incompletely excised tumors Tumors arising in irradiated skin Tumors with perineural involvement Tumors with risk of metastasis Table 2: Indications for Mohs Micrographic Surgery Adenocystic carcinoma Angioendothelioma Angiosarcoma Atypical fibroxanthoma Basal cell carcinoma Bowen's disease Bowenoid papulosis Cylindroma Dermatofibrosarcoma protuberans Eccrine adenocarcinoma Erythroplasia of Queyrat Extramammary Paget's disease Hemangioendothelioma Keratoacanthoma Leiomyosarcoma Laryngeal carcinoma Malignant cylindroma Malignant fibrous histiocytoma Malignant Melanoma Malignant schwannoma Merkel cell carcinoma Microcystic adnexal carcinoma Osteomyelitis Sebaceous carcinoma Squamous cell carcinoma Verruca (recurrent) Verrucous carcinoma ------------------------------------------------------------------------ BIBLIOGRAPHY Bailey BJ. Head and Neck Surgery- Otolaryngology. Surgical reconstruction after Mohs surgery, JB Lippincott; Philadelphia. Ch 153 vol 2. 1993. Bailin PL. CO2 Laser Modification of Mohs Surgery. J Dermatol Surg Oncol 1981. &:8: 621-623. Bentley TJ. Histologic Evaluation of Horizontal Frozen Sections: Improved staining and special staining techniques. J Dermatol. Surg Oncol. 1982. 8:6:466-470. Cottel WI. Mohs' Surgery, Fresh-Tissue Technique: Our technique with a review. J Dermatol Surg Oncol. 1982. 8:7:576-85. Gates GA. Current Therapy in Otol- Head and Neck Surgery. Skin cancer. Mosby; St Louis. 1994. Lim JK. Microscopically controlled excision of skin cancer. Med J of Australia. 1992 vol 156. pg 486-88. Mohs RE. Chemosurgery for skin cancer: fixed-tissue and fresh-tissue technique. Arch Dermatol 1976: 112: 211- 215. Rassner G. Atlas of Dermatology. Tumors of the skin. Lea and Febiger; Philadelphia. Chapter 7, 1994. Robins P. Chemosurgery: my 15 years of experience. J Dermatol Surg Oncol 1981; 7: 779-789. Roenigk RK. Trends in the Presentation and Treatment of Basal Cell Carcinomas. J Dermatol Surg Oncol. 1986 12:8:860-4. Rowe DE. Mohs Surgery Is the Treatment of Choice for Recurrent (Previously Treated) Basal Cell Carcinoma. J Dermatol Surg Oncol. 1989. 15:4: 424-430. Rowe DE. Long-Term Recurrence Rates in Previously Untreated (Primary) Basal Cell Carcinoma: Implications for patient follow-up. J Dermatol Surg Oncol 15:3:315- 325. Rubin E. Pathology. The skin. JB Lippincott; Philadelphia. Ch 24. 1988. Chapter on Mohs from the UTMB Dept of Dermatology. Awaiting publishing. ------------------------------END----------------------------------------