Letters to the Editor

Lentigo Maligna Melanoma and Excisional Biopsy Techniques

TO THE EDITOR: As physicians who are on the receiving end of consultations from our primary care colleagues, we read with interest Dr. Rose's article, "Recognizing Neoplastic Skin Lesions: A Photo Guide."¹ While the article contains illustrative photographs and much useful information, two issues relating to the diagnosis and treatment of malignant melanoma did not reflect current dermatologic recommendations.

The first issue concerns the discussion of lentigo maligna (Hutchison's melanotic freckle). By including it in the discussion of blue nevi, congenital nevi and dysplastic nevi, which may all be true precursors of melanoma, the article suggests that lentigo maligna is some sort of premalignant lesion whose progress should be followed until "one or more nodules" signal its change to an invasive lesion. Lentigo maligna is considered by most dermatologists to be a melanoma in situ and prompt and complete excision is recommended before it becomes invasive, at which point it is then called lentigo maligna melanoma. Furthermore, Figure 18 is mislabeled as "lentigo maligna," a preinvasive melanoma, rather than as lentigo maligna melanoma. This may confuse the reader, since the caption calls attention to the "nodules signaling invasiveness." In our opinion, Figure 18 is not a classic example of either lentigo maligna or lentigo maligna melanoma, which can be difficult to distinguish clinically from a solar lentigo or flat seborrheic keratosis. A high index of suspicion is often necessary to prevent a delayed or missed diagnosis of lentigo maligna.

The second, more important contention is with Dr. Rose's discussion of biopsy techniques. He writes, "If a cosmetically acceptable result would be difficult to obtain . . . punch biopsy of several areas may be performed, including the margins and any raised areas." Histologically, melanomas are diagnosed more by the overall architecture of the entire lesion than by the cytologic abnormality of individual melanocytes. Even the best dermatopathologists have difficulty diagnosing melanoma in a collection of 2- and 3-mm skin punches.

General pathologists, who service the skin pathology for most family physicians, would have even more difficulty making an accurate diagnosis in this scenario. Furthermore, the ugliest part of a pigmented lesion may not be the most diagnostic. In fact, in the case of a congenital or acquired melanocytic neoplasm that has undergone malignant transformation, the "raised area" may be the only normal area of the lesion. Without adequate sample size, the patient may be subjected to unnecessary mutilating surgery or, even worse, may be falsely reassured into simply observing a potentially lethal melanoma. If the physician is unable to perform an adequate biopsy in his or her office because the lesion is too big, the patient should be referred to someone whose office is better prepared to take care of it.

We do not agree that "multiple punch biopsies of selected areas . . . is an acceptable method for reaching a diagnosis." An excisional biopsy is critical for the diagnosis of cutaneous melanoma because both the prognostic information and the surgical therapy are based directly and primarily on the depth of the invasion as measured in the biopsy specimen. Dr. Rose fails to mention the well-established relationship between melanoma thickness and mortality. The sampling errors that are inherent with multiple punch biopsies prevent accurate depth determination. This can deny patients the benefit of essential prognostic counseling and impede proper management of the melanoma. Current standards of care for the surgical margins of melanoma excision are based directly on melanoma thickness. If referral for excisional biopsy is not an option, then the largest possible elliptical incisional biopsy, both through the most ominous or nodular area and including the border, is less than ideal, but may be acceptable.

JEFFREY J. MEFFERT, LTCOL, USAF, MC
JOHN G. ALBERTINI, CAPT, USAF, MC
San Antonio Uniformed Services Health Education Consortium
Brooke Army Medical Center
Fort Sam Houston, TX 78234-6200

REFERENCE

1. Rose L. Recognizing neoplastic skin lesions: a photo guide. Am Fam Physician 1998;58:873-84.

IN REPLY: I am pleased that my article has provoked some constructive feedback. In an article that focused on recognition and early diagnosis of skin neoplasia, the section on biopsy and surgery was exceedingly brief.

Squamous cell carcinoma (SCC) is often quite invasive. In its "Guidelines for Care for Cutaneous Squamous Cell Carcinoma,"¹ the American Academy of Dermatology (AAD) recommends biopsy before or at the time of definitive therapy. Associated lymph nodes should be sought and biopsied. Recommendations for therapy include the following:

• Curettage and electrosurgery for small primary lesions on areas of skin exposed to the sun.
• Cryosurgery for primary lesions, especially when other forms of surgery are refused or contraindicated.
• Laser surgery.
• Excision with adequate lateral and deep margins for both primary and recurrent lesions.
• Mohs' micrographic surgery, especially for recurrent lesions or more aggressive primary lesions.
• Ionizing irradiation in selected patients for some recurrent cancers and for palliation of inoperable cancers. Irradiation may aggravate verrucous carcinoma.

Treatments that were still being evaluated by the AAD included photodynamic therapy, intralesional injection with interferon, and retinoids, both oral and topical.¹

For the treatment of a small basal cell carcinoma that is growing slowly, easily accessible and less than 1 cm in diameter, any of the treatment modalities listed for squamous cell carcinoma may be used. Larger, more aggressive lesions, those that have ulcerated, nodular basal cell carcinoma and infiltrating (morpheaform) lesions should be excised with a safe margin.²

Hutchison's freckle (lentigo maligna) was considered to be a premalignant lesion in the AAD guidelines. Many older patients with this lesion will have it for many years without experiencing an invasive malignant change. Lentigo maligna is now classified as a carcinoma in situ, which should be excised. Some dermatologists prefer to use cryotherapy, chemocautery or dermabrasion.³

When the appearance or behavior of any lesion suggests that it may be a malignant melanoma, there is no role for punch or wedge biopsy. The lesion should be removed with an adequate margin. If excision would require special skills or equipment not available to the primary physician, the patient should be referred. Sometimes, a pigmented lesion that would be difficult to excise completely has a low possibility of malignancy. We hate to excise a benign lesion when excision will create a significant scar or require plastic surgery procedures, but most dermatologists believe that any suspicious lesion should be excised completely. Only a minority of dermatologists will use a variety of biopsy techniques to make the diagnosis.^4-6 It is important that a biopsy or an excision be at least 4 mm deep to allow staging of any malignant changes.

For complete excision of any large malignant skin lesions or those in difficult situations, Mohs' micrographic surgery is recommended.

LEWIS C. ROSE, M.B.B.S.
University of Texas Health Science Center at San Antonio
7703 Floyd Curl Dr.
San Antonio, TX 78284

REFERENCES

1. Guidelines of care for cutaneous squamous cell carcinoma. Committee on Guidelines of Care. Task Force on Cutaneous Squamous Cell Carcinoma. J Am Acad Dermatol 1993;28:628-31.
2. Drake LA, Ceilley RI, Cornelison RL, Dobes WA, Dorner W, Goltz RW, et al. Guidelines of care for basal cell carcinoma. The American Academy of Dermatology Committee on Guidelines of Care. J Am Acad Dermatol 1992;26:117-20.
3. Cohen LM. Lentigo maligna and lentigo maligna melanoma. J Am Acad Dermatol 1995;33:923-36.
4. Slade J, Marghoob AA, Salopek TG, Rigel DS, Kopf AW, Bart RS. Atypical mole syndrome: risk factor for cutaneous malignant melanoma and implications for management. J Am Acad Dermatol 1995; 32:479-94.
5. Salopek TG, Slade J, Marghoob AA, Rigel DS, Kopf AW, Bart RS, et al. Management of cutaneous malignant melanoma by dermatologists of the American Academy of Dermatology. I. Survey of biopsy practices of pigmented lesions suspected as melanoma. J Am Acad Dermatol 1995;33:441-50.
6. Guidelines of care for malignant melanoma. Committee on Guidelines of Care. Task Force on Malignant Melanoma. J Am Acad Dermatol 1993; 28:638-41.

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Potentially Fatal Natural Remedies

TO THE EDITOR: The "it can’t hurt me" attitude many people have toward botanical remedies is widespread,¹ yet the medical literature records more than 100 fatal encounters with herbs (Table 1).^1-82

TABLE 1 Organ Systems Affected by Potentially Fatal Natural Remedies Brain • Arnica2 • Citronella oil3 • Eucalyptus oil4 • Goldenseal5 • Hemlock6-10 • Indian tobacco4,11 • Herbs contaminated with lead12,13 • Nutmeg4 • Pokeweed14,15 • Mildewed sugar cane16 • Yagjinhua17 • Angel's Trumpet18,19 • Neem20 • Tree tobacco15 • Thornapple or Jimson weed21,22 Heart • Ephedrine containing herbal products23 • Monkshood24-28 • Yellow oleander29-31 • Pink oleander32-33 • South American "mutis"34 • Chan-su aphrodisiac (also known as "rock hard," "stone," "love stone"and "black stone")35 • Squill36 • Rhododendron37 • Chaparral38 • Mail-order diet pills39 • Mistletoe40 (possibly) Liver • Lupin beans41 • Mate´ tea42 • Nutmeg11 • White chameleon43-45 • Comfrey46 • Pennyroyal oil47,48 • Huan glian49,50 • "Spiritual water"51 • Germander52 • Thread-leafed groundsel53 • Heliotrope1 • Chinese herbal remedies54 • Crotalaria spp55 • Chaparral38 • Skullcap1 (possibly) Kidney • Rhubarb leaves4 • Squirting cucumber56 • South African traditional remedies containing Liliiflorae sona57 • Cantharidin beetle powders58-60 • Hemlock61 Gastrointestinal tract • Jequirity seeds or rosary peas62 • Castor beans63 • Philodendron64 Miscellaneous • Clove cigarettes4 • Golden seal4 • Alfalfa (listeriosis)65 • Royal Jelly (anaphylaxis)66,67 • Akee (hypoglycemia)68 • Tanning tablets [beta-carotene and canthaxanthin] (aplastic anemia)69 • Podophyllum70-72 • Wintergreen oil73 • Yew74,75 • Black pepper76,77 • Chinaberry4 • Hemlock water dropwort78,79 • Holly4 • Apple seed (cyanide poisoning)80 • Apricot kernels (cyanide poisoning)81 • Climbing lily 82

Were it not for liver transplantation,^38,83,84 renal transplantation,⁸³ dialysis^85-88 and other heroic medical measures,⁸⁹ many more people might have died as a result of using natural remedies and green plants. Because natural remedies pose as dietary supplements, these products currently escape systematic study by the U.S. Food and Drug Administration. In South Africa, 51.7 percent of fatal poisonings result from the use of traditional herbal preparations.⁹⁰ Recently in the United States, the proportion of deaths from outpatient medication errors and "undetermined poisonings" has more than doubled.⁹¹

TABLE 2 Advice for Patients Who Self-Medicate with Herbs Look at the label on the medication for scientific names of ingredients, quantity of active ingredients, name and address of producer, batch and lot numbers, date of manufacture and date of expiration. Learn about the efficacy and toxicity of the product and the reliability of the producer. Distrust information from those who gain from its sales. Seek out objective, credible information. Avoid use in infants and young children, avoid use if pregnant, lactating or trying to conceive, and avoid abuse or overdosage. Be wary of variations from batch to batch and of other ways (misidentification, substitution, contamination, adulteration) that commonly cause a mismatch between what the label claims and what the product actually contains. Inform your doctor about all of your self-medications. Stop taking the medication if an adverse reaction occurs.

Like the flourishing sales of botanicals, there is increasing recognition that herbs can be toxic. Ellenhorn’s Medical Toxicology, for example, lists 86 references published prior to 1980, 164 articles between 1980 and 1989, and 248 papers between 1990 and 1995. Clearly, plants can kill as well as cure. Patients who choose to self-medicate with natural remedies should not be told that "it probably can’t hurt you" (Table 2).^1,4,67 The facts must be checked first.

ALAN T. MARTY, M.D.
Deaconess Resource Center for Healthy Living
600 Mary St.
Evansville, IN 47747

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38. Sheikh NM, Philen RM, Love LA. Chaparral-associated hepatotoxicity. Arch Intern Med 1997;157:913-9.
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40. Krenzelok EP, Jacobsen TD, Aronic JM. Mistletoe exposures–the kiss of death? J Toxicol Clin Toxicol 1995;33:475-86.
41. Lowen RJ, Alam FK, Edgar JA. Lupin bean toxicity. Med J Aust 1995;162:256-7.
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43. Georgiou M, Sianidou L, Hatzis T, Papadatos J, Koutselinis A. Hepatotoxicity due to Atractylis gummifera-L. J Toxicol Clin Toxicol 1988;26:487-93.
44. Nogue S, Sanz P, Botey A, Esforzado N, Blanche C, Alvarez A. Acute kidney failure caused by Atractylis gummifera-L poisoning [French]. Presse Med 1992;21:130.
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46. Roulet M, Laurini R, Rivier L, Calame A. Hepatic veno-occlusive disease in a newborn infant of a women drinking herbal tea. J Pediatr 1988;112:433-6.
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58. Hundt HK, Steyn JM, Wagner L. Post-mortem serum concentration of cantharidin in a fatal case of cantharides poisoning. Hum Exp Toxicol 1990;9:35-40.
59. Cheng KC, Lee HM, Shum SF, Yip CP. A fatality due to the use of cantharides from Mylabris phalerata as an abortifacient. Med Sci Law 1990;30:336-40.
60. Burnett JW, Calton GJ, Morgan RJ. Blister beetles: "Spanish fly." Cutis 1987;40:22.
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65. Farber JM, Carter AO, Varughese PV, Ashton FE, Ewan EP. Listeriosis traced to the consumption of alfalfa tablets and soft cheese. N Engl J Med 1990;322:338.
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Corrections

Question 10 of the September 1, 1998 "Clinical Quiz" (page 647), pertaining to the article "External Cephalic Version" (page 731), was incorrectly worded. The question should read as follows: "Which of the following steps would be appropriate before external cephalic version is attempted?" The correct answers remain A, B and D.

An item in "Family Practice International" (September 1, 1998, page 780), titled "Malaria Prophylaxis in Travelers," gives an incorrect address for a Centers for Disease Control and Prevention Web page. The correct Internet address for obtaining information about malaria prophylaxis in travelers is as follows: http://www.cdc.gov/travel/.

The answer to Question 6 in the July 1998 "Clinical Quiz" (page 34), pertaining to the article "Indications for Anticoagulation in Atrial Fibrillation" (page130), is incorrect as the question is currently worded. The correct answers to the question as it is published are B and C. However, if the scenario had involved a patient 75 years of age, the answer might more clearly be C alone. Medication in the 65- to 75-year-old age group has been a point of controversy, and most physicians preferentially choose warfarin over aspirin unless there is a contraindication to its use.

Question 10 in the September 15, 1998 "Clinical Quiz" (page 849), pertaining to the article "Management of Female Sexual Assault" (page 920), is unclearly worded. The question would have been better stated this way: "Which of the following is/are not recommended as part of the physical examination of a patient who has been sexually assaulted?" The correct answer is D.

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