Commentary Pitfalls of Mohs micrographic surgery Ronald P. Rapini, MD Houston, Texas This articlediscusses some of the pitfalls and disadvantages of Mohs micrographic surgery forthe excision ofskincancer. These include (1) frozen section quality; (2) interpretationof frozen sections; (3) holes in fragmented tissue margins; (4) tissue orientation problems; (5) excessively narrow or wide margins; (6) transection of the tumor itself; (7) problems with multifocal tumor; and (8) the tedious, time-consuming natureoftheprocedure. Despitethese problems, the importance ofthe procedure in the treatmentof cutaneous neoplasms should not be underestimated. (J AM ACAD DERMATOL 1990;22:681-6.) The Mohs micrographic surgical technique for excision of skin cancers is an important modality that is often useful for difficultlesions. The details of the technique and its advantages have been extensivelydiscussed.l? Mohs surgery involves excision of the skin cancer in thin layers so that the lateral and deep margins can be examined in the same plane by horizontal frozen sections." A map of the tumor is prepared, and individual margins are color-coded so that accurate orientation of the excisedtissueis possible. This article discusses some of the disadvantages or pitfalls of the Mohs technique, many of which have received little attention and are poorly understood by physicians who have not had training in the procedure.
Frozen section quality The high (95% to 99%) cure rates reported with Mohs surgery indicate that most Mohs surgeons must not have major problems with quality of their frozen sections or with other matters discussed herein. Nevertheless, some problems with frozen sections are bound to occur from time to time.5 Good-quality frozen sections are obtained only when the tissue is kept adequately frozen from -10° to - 300 C. If tissue is frozen too slowly, ice crystals can leave holes in the tissue. Usually the heat extractor in the cryostat, Freon aerosol spray, liquidnitrogen, or dry ice is used for rapid freezing. Closedunit cryostat machines are usually more efficient at keeping tissue cold than the more widelyused opentop units, but handling the tissue may be more dif-
From the Departments of Dermatology and Pathology, University of Texas Medical School. Reprint requests: Ronald P. Rapini, MD, Departments of Dermatology and Pathology, University of Texas Medical School, 6431 Fannin, MSB 1.204, Houston, TX 77030.
ficult in the closed units. A minority of Mohs surgeons use a microtome with carbon dioxide instead of a cryostat. Because the knives in such microtomes are not kept as cold as the tissue, sections tend to adhere to the knife, and good sections aredifficultto obtain." Problems with warm knives and curling tissue can also occur in open-top cryostats but can be remedied by the use of Freon spray." Adequate freezing may be more difficultwhen the tissue layer is thicker than 3 mm. If the tissue tends to fragment during sectioning, it may be because the tissue is too cold. Skilled technicians can often obtain sections 4 to 5 JLm in diameter, whereas less-experienced ones produce inferior,thicker sections. Use of a dull knife, improper knife angle, or too warm a temperature all may produce tissue compression. Even the best technicians cannot consistently section tissue larger than 2 X 2 em without producing "incomplete sections" with incomplete margins or holes in them. 8 Folds in the tissue, which may obscure tumor, occasionallyoccur in frozen sections regardless of the skillof the technician. 8 Some problems can be solved by requesting deeper sections,but excessive "facing of the block" may remove the true margin and produce a false-positive margin by cutting deeper into the tissue towards the tumor. I One of the major problems with frozen sections is that good sections through adipose are difficult to obtain. Sections tend to develop holes readily, and the tissue often falls off the slide. Fortunately, most basal cell carcinomas (the tumors most frequently treated by the Mohs technique) find adipose to be a relativelyunfavorablestroma for growth. If tumor is present in the fat, it usually produces or induces its ownstroma sothat sectionsthat demonstrate tumor are usually obtainable. Better sections through adipose can be obtained by cutting thicker sections at 10 to 20 urn,1 avoidingan alcohol fixative, cutting at a lower temperature, and by washing the slides
Journal of the American Academy of Dermatology
'\, Fig. 1. Nodular aggregates of inflammatory cells in a poor-quality frozen section such as this one may resemble or obscure a neoplasm. (Hematoxylin-eosin stain; X150.)
carefully during the staining procedures so that the tissue will not fall off the slide.? Despite these maneuvers, poor sections are still frequent when adipose is involved. Formalin-fixed, paraffin-embedded sections are of better quality than most frozen sections and are sometimes the only way to ensure that no tumor is present in deep margins that involve adipose.? Such sections are less likely to fragment, and tumors with difficult histologic features are easier to evaluate.!? Unfortunately, the disadvantages include a higher chance of misorientation after transporting the specimen to the laboratory and a delay in obtaining the result. For this reason, paraffin-embedded sections are underused by most Mohs surgeons, but they can be useful in certain difficult situations.
Interpretation of frozen sections One of the main advantages of the Mohs techniqueis that the surgeon often interprets the frozen sections. Special attention can be paid to margins of most concern, and there is less chance of orientation problems from miscommunication with a pathologist. Transport of a specimen in gauze with saline solution to a remote laboratory may produce artifacts and create holes in the tissue.s Most pathologists are not accustomed to orienting skin sections horizontally (sometimes called parallel) as opposed to vertically (sometimes called perpendicular). Some Mohs surgeons have said that only a true Mohs surgeon can accurately orient and interpret horizontal sections, and pathologists and dermatopathologists have expressed the concern that some Mohs surgeons may not have adequate training or certifica-
tion in pathology. 5,6 There may be some conflict of interest when a surgeon interprets his own biopsy specimens.? The diagnosis of unusual or difficult tumors, such as Merkel cell tumors, melanocytic neoplasms, adnexal tumors, spindle cell tumors, soft tissue sarcomas, meningiomas, or metastases may require the skill of an experienced pathologist. 6, II Regardless of the skill of the person who interprets horizontal frozen sections, problems still arise. Cross sections or tangential sections of hair follicles, sweat glands, or blood vessels may resemble basal cell carcinoma.': 5,12,13 Nodular aggregates oflymphocytes may resemble or obscure a neoplasm'- 12,13 (Fig. 1). Deeper sections often help to resolve these problems.' but if the block is too deeply sectioned, the true margin is lost. The finding of tumor creates a false-positive margin. In addition, the fact that a basaloid aggregate connects to an adnexal structure does not prove that it is not basal cell carcinoma because basal cell carcinoma may arise from adnexal structures (Fig. 2). Toluidine blue staining may help to identify basal cell carcinoma because of the mucopolysaccharides within and around this tumor.I but mucopolysaccharides can sometimes be abundant around normal adnexal structures. Other special stains (such as immunoperoxidase or dihydroxyphenylalanine oxidase) have generally proved impractical for routine use during Mohs surgery.v 14
Holes in fragmented tissue margins After the tumor is debulked, Mohs surgery involves excision of a thin layer of tissue around the defect, representing the margin that is submitted for frozen sections." Considerable practice is needed to
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Pitfalls of Mohs micrographic surgery 683
Fig. 2. Basal cell carcinoma (arrows) arising from hair follicle. The fact that a basaloid aggregate connects to an adnexal structure does not always prove that it is a benign portion of that structure. (Hematoxylin-eosin stain; frozen section; X75.)
obtain good layers without fragmentation of the tissue, especially if there is a problem with bleeding. Layers that are too thick will not freeze well,thereby giving poor sections. Layers that are too thin may fragment, leaving "buttonholes" through the tissue where the margin will not be checked. Adequate layers may be difficult to obtain in certain anatomic sites (such as embryonic fusion planes),13 especially when one part of the layer contains cartilage and another contains adipose, for example. Fragmentation is common in layers through periosteum or adipose. If the tissue is soft and friable, taking smaller specimens may be the only way to avoid losing part of the margin. 1
Tissue orientation problems As Mobs surgery involves many steps for orienting, mapping, inking, freezing, and interpreting frozen sections, there are many chances for human error as well as technical problerns.P The surgeon should do the inking so that there is less chance of it being placed on the wrong margins. Despite meticulous technique, sometimes the ink is not visible on the sections. Some types of ink are better than others. If the specimen is too wet or if too much ink is used, ink may run or smear over the wrong portions of the specimen. Obviously, if the ink is present in the wrong place, or if the map is incorrect, the wrong area may be interpreted as positive for tumor and reexcised. Orientation problems are less frequent when the surgeon and pathologist are the same person." If sections are removed to a remote site for examination, there is a higher chance for
misorientation. It is particularly important for the pathologist to section from the deep side of the tissue rather than from the other side. Perhaps the biggest challenge in Mohs surgery is to get the entire 360-degree epidermal margin in the same plane with the rest of the tissue.P: 15 The Mohs margin is analogous to half of a peeled orange, after the tumor has been debulked from the center (Fig. 3). It is important for the Mohs surgeon to excise the margin at approximately 45 degrees so that the epidermis can be forced into the same plane as the deeper tissue.16 Although it may be somewhat of an exaggeration of the problem, Fig. 4 demonstrates the difficulty in persuading the epidermis to cooperate. Cartilage and thick specimens may be nearly impossible to compress into a flat layer, whereas adipose may be too easy to compress. I? Even worse, the orange peel may fall apart! Just try peeling an orange and then try compressing the peel flat! Numerous techniques and devices have been advocated to solve this problem. 18 The most common techniques for flattening the specimen include the use of a flat scalpel handle, a glass microscope slide, the heat extractor in the cryostat, the Miami Special (sponge forceps with two attached copper plates),'? or a special tissue press. I 9 Despite meticulous efforts, it is uncommon to view 100% of the epidermal margin 20, 21 (Fig. 5). It has been found that sections considered to be "complete" may include only 75% to 85% of the epidermal edge and that 10% of the sections include even less than that. 17 In a recent survey of 130 Mohs surgeons, only 50% to 73% of them (depending on the method used) claimed to
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Fig. 3. Mohs margin is similar to half of a peeled orange. Tumor has been debulked from center and black-inked rim represents epidermal margin. obtain sections with 90% to 100% of the epidermal edge present. 22 Deeper sections can be used to search for the epidermal edge, 12, 13 but the true margin is lost by cutting too far into the block. Another solution is to thaw the block and to reorient the epidermal edge. 13,17 Many dermatologists have the misconception that Mohs surgery is the only method that evaluates 100% of the surgical margin.f 23 Actually, vertical (perpendicular) sections through the peripheral margins of an ellipse, combined with horizontal (parallel) sections through the deep margin, can provide as close to a 100% examination of the margins as Mohs surgery." In fact, Mohs surgery may be a poor choice for evaluating margins of in situ tumors (limited to the epidermis) as compared with vertical peripheral sections. Although most pathology laboratories routinely use random vertical sectioning (such as the breadloaf method), which samples only a small portion of the margin, special arrangements can usually be made for peripheral sectioning if there is good communication with the pathologist. Such arrangements have their own pitfalls. In particular, it is common for technicians to section from the wrong side of a peripheral section, giving false-positive margins, and the geometry of small fusiform ("elliptic") specimens may make peripheral sectioning difficult.
Excessively wide or narrow margins A major advantage of the Mohs fresh-tissue technique is that narrow margins are often obtained with maximal tissue conservation. The Mohs surgeon removes margins from around the main tumor mass in successive stages that are often approximately 3 mm in thickness. Such narrow margins rely heavily on frozen sections to indicate clear margins, If there is any problem with frozen section quality or
Fig. 4. When orange is sectioned, it may fall apart. There is difficulty in gettingit to lie flat so that blackepidermal margin will be in same plane as rest of margin during sectioning, interpretation, there is a possibility of residual tumor because in most cases little extra normal tissue is sacrificed around the tumor mass as insurance. A major problem with the Mohs method of checking surgical margins is that the closeness of the tumor to the surgical margin in horizontal frozen sections cannot be assessed because the tumor is not seen in the sections. After the tumor is debulked, the first layer is taken and sent for frozen section. If no tumor is seen, the Mohs surgeon has no idea whether he is around the tumor by a few microns or by a kilometer. In fact, unless a preoperative biopsy is taken, there is no proof that there was ever tumor there at all! Of course, this problem does not occur if frozen sections are positive because the Mohs surgeon will know how close subsequent sections are to the initial positive section. In addition, the surgeon can always thaw the tissue margin and orient it vertically to see how close the tumor is to the deep or lateral edge, or vertical sections through the debulked tumor can be requested. In some instances Mohs surgery may actually produce an excessively wide margin. Although the tumor has been completely removed, a margin may appear to be a false-positive when the technician "faces the block"; a technician should be trained to get a complete section as soon as possible without cutting too deeply into the block. Extra layers of tissue may also be unnecessarily removed by the inexperienced Mohs surgeon if he chases nodular aggregates of inflammatory cells or adnexal structures (they may resemble a basal cell carcinoma) or benign fibroblasts in an area of fibrosis (they may resemble a dermatofibrosarcoma protuberans),IO.24
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Pitfalls of Mohs micrographic surgery
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Fig. 5. Poor-quality frozen section of Mohs surgical margin with incomplete representation of epidermal edge (arrows). (Hematoxylin-eosin stain; X15.)
However, sometimes such sacrifice of extra tissue may be necessary because a nodular aggregate of inflammatory cells may obscure a tumor, and all methods of checking margins require some sacrifice of normal tissue. Because they often cannot see the relation of the tumor to the margin in horizontal frozen sections, some Mohs surgeons excise extra tissue in cases of aggressive tumors. Although this may be indicated in some cases, there needs to be a balance between the cosmetic result and an acceptable cure rate. A related Concern is whether the treatment may sometimes be worse than the disease.P Although basal cell carcinoma may rarely infiltrate to the brain, occasional selected elderly patients may be better off keeping their basal cell carcinoma or having it irradiated rather than having an entire cheek or nose removed by Mohs surgery. The decision regarding these options can only be made after the patient and/or family is completely informed of the expected cure rates and consequences of persistent tumor. Of course, many of these patients with extensive tumor would not have found themselves in such a predicament if they had had definitive treatment such as Mohs surgery at an earlier stage.
Transection of the tumor itself Mohs surgery (in the classic form where the tumor is debulked by curettage) violates the precept of many tumor surgeons that cutting into the tumor itself should be avoided; instead, one should surround and conquer the enemy by excising adequately around it on the first cut. This is really not a legitimate concern in the case of basal cell carcinoma
because it almost never metastasizes and is difficult to transplant. However, most physicians believe that Mohs surgery is a poor choice of therapy for a malignant melanoma]; if it is done at all, the fixed tissue technique should be used. I If a Mohs surgeon is concerned about cutting into a tumor and spreading it, this can be avoided by making sure the initial debulking of the tumor sacrifices a margin of normal tissue to keep from transecting the tumor.
Problems with multifocal tumors If tumor is present in more than one place, the Mohs surgeon may obtain a clear margin around one portion ofthe tumor while not realizing that the other portion of tumor exists. For this reason, there may be problems with certain tumors that are often multifocal, such as Paget's disease" or sebaceous carcinoma. Sometimes basal cell carcinoma may persist within two discontinuous portions of a previously treated area, or two primaries may be present in close apposition. In this situation, Mohs surgery may fail to remove both portions of the tumor, 13, 15,20 but other methods of treatment may not fare much better. Assuming the persistent tumor islands are present only in the scar in the case of previous treatment, often Mohs surgery will be successful as long as the surgeon removes the entire scar instead of being confined only to the apparent area of the tumor.P
Tedious, time-consuming nature of the procedure These problems are generally well known. Most authors argue that Mohs surgery is not needed for
most routine, uncomplicated skin cancers, but some Mohs surgeons treat the majority of tumors in this manaer.' Selected cases may require up to several hundred frozen sections and may take more than 1 day. 1, 8 Although the use of local anesthesia instead of general anesthesia is usually listed as an advantage of the Mohs technique, it can become uncomfortableforthepatient. Nevertheless, the prospect of tissue conservation and the careful margin check afforded by Mohs surgery may make this worthwhile for the patient. Another problem is that reconstruction may involve a separate procedure and a separate bill, especially when the surgeon doing the repair is not the Mohs surgeon.I" Repair may not be optimal because of necrosis, dessication, infection, or swelling if reconstruction is delayed too long. However, if repair is done immediately (often by the Mohs surgeon himself), these problems are avoided. It is important not to misconstrue this article as an attack on the Mohs technique. Mohs micrographic excision of skin cancer has been an important advance that is useful in treating many lesions that are poorly treated by other techniques. The advantages of Mohs surgery have been appropriately stressed in the literature, and I have not listed them in detail because they are well known. I hope that this article provides insight into the often unmentioned pitfalls of the Mohs technique from the vantage point of someone who is active in both dermatopathology and Mohs surgery. As with any technique, all these pitfalls can be minimized with training and experience,' but even the most skilled Mohs surgeons and histology technicians occasionally encounter the problems discussed herein. Controversies regarding the training needed to become skilled in Mohs surgery are beyond the scope of this discussion.27-29 The best skin cancer surgeon is one who recognizes the advantages and disadvantages of the multiple techniques at his or her disposal.l" including Mohs surgery, electrodessication and curettage, primary excision, cryotherapy, radiotherapy, and perhaps even intralesional interferon.
REFERENCES 1. Mohs FE. Chemosurgery: microscopically controlled surgery for skin cancer. Springfield, Ill: C Thomas, 1978. 2, Mohs FE. Chemosurgery: microscopically controlled surgery for skin cancer-past, present and future. J Dermatol Surg Oncol 1978;4:41-53. 3. Swanson NA. Mohs surgery: technique, indications, applications, and the future. Arch DermatoI1983;119:761-73. 4. Cottel WI, Bailin PL, Albom MJ, et al. Essentials of Mohs micrographic surgery: position paper. J Dermatol Surg Oncol1988;14:1l-3.
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5. Cockerell CJ. Mohs' surgery. Let's make a good thing better. Am J DermatopathoI1985;7:587-8. 6. Silva EG, Kraemer BB, eds. Intraoperative pathologic diagnosis: frozen section and other techniques. Baltimore: Williams & Wilkins, 1987. 7. Picoto AM, Picoto A. Technical procedures for Mohs fresh tissue surgery. J Dermatol Surg OncoI1986;12:134-8. 8. Bennett RG. Mohs' surgery: new concepts and applications. Dermatol Clin 1987;5:409-28. 9. Breuninger H, Schaumberg-Lever G. Control of excisional margins by conventional histopathology techniques: an alternative to the Mohs' technique. J Cutan Pathol 1986;13:437. 10. Robinson JK. Dermatofibrosarcoma protuberans resected by Mohs' surgery (chemosurgery). J AM ACAD DERMATOL 1985;12:1093-8. 11. Gross DA, Field LM. Cooperative frozen section surgery. J Dermatol Surg OncoI1987;13:1085-8. 12. Cott RE, Wood MG, Johnson BL. Use of curettage and shave excision in office practice. JAM ACAD DERMATOL 1987;16:1243-51. 13. Dzubow LM. Chemosurgical report. Recurrence (persistence) of tumor following excisionby Mobs surgery. J Dermatol Surg Oncol 1987;13:27-30. 14. Vigneswaran N, Haneke E, Peters KP. Peanut agglutinin immunohistochemistry of basal cell carcinoma. J Cutan PathoI1987;14:147-53. 15. Zitelli JA. Mohs surgery: concepts and misconceptions. Int J Dermatol 1985;24:541-8. 16. Tromovitch TA, Stegman SJ. Microscopic-controlled excision of cutaneous tumors. Chemosurgery, fresh tissue technique. Cancer 1978;41:653-8. 17. Hanke CW, Menn H, O'Brien JJ. Frozen section processing with the Miami Special. J Dermatol Surg Oneol 1983;9:260-2. 18. Carter VH. A new method for preparing tissue blocks for cryostat sectioning. J Dermatol Surg Oncol1985; 11:687-9. 19. Gormley DE. Evaluation of a method for controlled tissue embedding for histologic evaluation of tumor margins. Am J Dermatopatbol1987;9:308-15. 20. Davidson TM, Nahum AM, Haghighi P, et al. The biology of head and neck cancer. Detection and control by parallel histologic sections. Arch Otolaryngol1984;ll0:193-6. 21. Dzubow LM. False-negative tumor-free margins following Mohs surgery. J Derrnatol Surg OncoI1988;14:600-2. 22. Hanke CW, Lee MW. Cryostat use and tissue processing in Mohs micrographic surgery. J Dermatol Surg Oncol 1989;15:29-32. 23. Abide JM, Nahai F, Bennett RG. The meaning of surgical margins. Plast Reconstr Surg 1984;73:492-6. 24. Hobbs ER, Wheeland RG, Bailin PL, et a1. Treatment of dermatofibrosarcoma protuberans with Mohs micrographic surgery. Ann Surg 1988;207:102-7. 25. Wagner RF, Cottel WI. Multifocal recurrent basal cell carcincoma following primary tumor treatment by electrodessication and curettage. J AM ACAD DERMATOL 1987;17:1047-9. 26. Older JJ. Eyelid tumors: clinical diagnosis and surgical treatment. New York: Raven Press, 1987:49. 27. Braun M. Being certain the cancer is out. J Dermatol Surg Oneal 1987;13:1058-60. 28. Wirtzer AS. Mohs surgeons and the ACC. J Dermatol Surg Oncol 1987;13:105-6. 29. Bernstein G. Training in Mohs surgery [Editorial]. 1 Dermatol Surg Oncol 1986;12:669. 30. Albright SD. Treatment of skin cancer using multiple modalities. J AM ACAD DERMATOL 1982;7:143-71.