NEVI: A PROBLEM OF MISDIAGNOSIS*

NEVI: A PROBLEM OF MISDIAGNOSIS* MARTIN SWERDLOW, M.D. Department of Pathology J Michael Reese Hospital, Chicago, Illinois The recurring discrepancy between the clinical and pathologic diagnosis of nevus or pigmented mole in our routine surgical specimens constantly impressed us. The term nevus or mole as used here denotes a benign tumor of nevus cells or cells derived from dopa-positive melanoblasts or potential melanoblasts.,7 This study was made to determine just how frequently and with what lesions nevi were confused in our general hospital. The importance of determining this is more than merely academic because the injudicious treatment of the mole or nevus may result in the development of a malignant melanoma. There is, it is true, far from uniform agreement that irritation, let alone a single trauma, can stimulate the development of melanomas in' nevi; yet this untoward result of mistreatment is emphatically stressed by numerous authorities. Webster 5 believes that the junctional type of nevus is potentially malignant and may become so if subjected to trauma. He recommends, if such nevi are irritated or changed and must be treated, wide excision and deep electrocoagulation as the only really acceptable methods of treatment; otherwise he recommends that these lesions be left untreated. He states that it is certainly true that pigmented nevi are removed in countless numbers by cosmeticians, general practitioners and dermatologists, using such modalities as electrolysis, solid carbon dioxide, caustic chemicals and superficial desiccation, and the percentage of cases in which such procedures are followed by the development of a malignant neoplasm must be very small. He feels, however, that he would rather not have even one such instance occur as a result of his ministrations and therefore he does not use these superficial methods of treatment for pigmented nevi under any circumstances. Traub 3 writes that junctional nevi, if treated at all, should be widely excised and that radiation, freezing and chemical methods are entirely contraindicated. He also states, however, that the common mole or dermal nevus is always benign and therefore may be treated with superficial desiccation. We take exception to this view because, first, malignant melanoma arising in a dermal nevus has been described by Montgomery and Kernohan, 9 and secondly, if it is true that melanomas arise in the junctional component of nevi, as many today believe,, * 9i 3-5 then we will show below, as others have shown, that an appreciable percentage of dermal nevi are compound or mixed, i.e., have a junctional component and are therefore also potentially malignant. Traub 3 himself points out the fact that dermal nevi are frequently mixed, and, most important, that they can be recognized only by the microscope. Ormsby and Montgomery 0 recommend deep removal of flat or junctional nevi, if treated, and state that melanomas * Received for publication, June 3, 95. Aided by a grant from the Estate of Addie M. Lang. f This department is in part supported by the Michael Reese Research Foundation. 054 Downloaded from https://academic.oup.com/ajcp/article-abstract///054/78 on 8 January 08

DIAGNOSIS OF NEVUS 055 may develop in benign, incompletely removed nevi. Sutton and Sutton also recommend wide excision of nevi. Pack and Livingston, as quoted by Becker, point to the one malignant melanoma that occurs for the thousands of nevi removed and treated without mishap, but state that the malignant transformation of an apparently quiet nevus, after incomplete desiccation, occurred with unpleasant frequency in their cases. They recommend complete surgical excision with scalpel or endothermic cutting current. Beerman 3 states that surgical ex- TABLE MICROSCOPIC DIAGNOSIS OF 55 LESIONS DIAGNOSED CLINICALLY AS.NEVI OR PIGMENTED MOLES MICROSCOPIC DIAGNOSIS Pigmented nevus Basal-cell carcinoma Seborrheic keratosis Squamous-cell (hard) papilloma. Pigmented neurofibroma Capillary hemangioma Epidermal cyst Sclerosing hemangioma Neurofibrosarcoma Cavernous hemangioma Fibroma Sebaceous adenoma Lentigo Chronic perifolliculitis Xanthomatous histiocytoma... Fibrolipoma Senile keratosis Bowen's keratosis Scar Foreign-body granuloma Pigmented myoblastoma Hyperkeratosis Syringocystadenoma Subepidermal fibrosis Chronic dermatitis 33S 0 4S S S cision is the method of choice for the treatment of pigmented nevi. He also states that the partial removal by superficial figuration, electrolysis, solid carbon dioxide or caustics, although apparently satisfactory in the hands of many dermatologists, in his experience has the potentiality of the subsequent development of melanoma in a small percentage of cases. He condemns the use of x- rays and radium in the treatment of nevi. Webster, Stevenson and Stout write that a majority of malignant melanomas start from preexisting moles, and that a large percentage of these arise from moles stimulated either by physicians or patients. Figi condemns the common practice by both physicians and patients Downloaded from https://academic.oup.com/ajcp/article-abstract///054/78 on 8 January 08

05 SWERDLOW of removing moles with caustics of various types. He states that the fairly frequent application of chemical caustics to a simple mole has been followed by a rapidly progressing malignant lesion and he presents a case in point. He also states that failure to destroy the pigmented nevus completely with a single application is fraught with danger. He further states that it seems highly probable that in some cases a malignant lesion was already present at the time a caustic was applied but, even so, excision still offers a better chance of complete removal. Traub and Keil 4 state that the junctional type of nevi is potentially malignant, and that metastases may result from irritation or incomplete removal. Handley 8 states that chronic irritation and, more rarely, a single acute trauma CLINICAL DIAGNOSIS OF 454 TABLE LESIONS MICROSCOPICALLY DIAGNOSED AS NEVI CLINICAL DIAGNOSIS Pigmented nevus Papilloma Verruca vulgaris (wart) Fibroma Epidermal cyst Lipoma Lichen planus Neurodermatitis Squamous-cell carcinoma Pigmented hyperkeratosis Pigmented neurofibroma Dermoid cyst Hemangioma Soft corn Sebaceous cyst 338* 39 4 0 * These 33S lesions, clinically diagnosed as nevi, are the same lesions referred to in Table. and unwise irritant treatment are the main causes of malignancy in moles. The treatment of choice is complete excision. He aptly says that methods of treatment by the various superficial means amount to experiments in the conversion of innocent into malignant tumors. Similar opinions are held by others. 5 The purpose of this study then is to show how frequently nevi were confused with lesions, the usual treatment of which may be injudicious for nevi and might conceivably result in the tragedy of malignant melanoma. On the other hand, the somewhat radical treatment of choice for nevi may not be necessary for other lesions mistakenly called nevi. All lesions diagnosed as nevi or pigmented moles, either clinically or pathologically, during the past years were reviewed. In some instances the histologic diagnosis was not conclusive, and the patient's chart and/or the physician were consulted. All lesions diagnosed as melanoma, either clinically or Downloaded from https://academic.oup.com/ajcp/article-abstract///054/78 on 8 January 08

DIAGNOSIS OF NEVUS 057 pathologically, during this same period of time were also reviewed. The nevi were tabulated by variety, according to the classification listed by Allen. A review of both tables reveals that of a total of 7 lesions the diagnosis of nevus either clinically or pathologically was confused in almost half the cases, 49 per cent, and correct in only 5 per cent of the cases. The clinical diagnosis of nevus of 55 lesions was correct in only per cent of the lesions, and of 454 lesions diagnosed pathologically as nevi, the clinical diagnosis was correct in only 74 per cent. The greater error was in the direction of incorrectly diagnosing other lesions as nevi' rather than misdiagnosing actual nevi. This at least is prognostically more favorable for the patient. These figures do not compare with those of Becker, who found that of 70 lesions diagnosed clinically as nevi, 80 per cent were correct, and of 49 lesions diagnosed pathologically as nevi, 87 per cent were correct. This difference may possibly be explained by the experience of the examiners submitting the diagnoses. In Becker's series the diagnoses were made by dermatologists, dermatology TABLE 3 VARIETIES OF NEVI REVIEWED VARIETIES OF NEVI Intradermal nevi 47 Compound nevi SO Junctional nevi 8 Blue nevi 3 graduate students and a few general practitioners. In this series, the diagnoses were submitted by pi'actitioners in all specialties. Interestingly, the direction of error in Becker's series is similar to this study. Others ' 4 ' 4_ also mention lesions confused with nevi. The tables reveal that the most common lesions erroneously called nevi were seborrheic keratosis, squamous-cell (hard) papilloma, pigmented neurofibroma, basal-cell carcinoma and various varieties of hemangioma. The most common misdiagnoses of nevi were papilloma, verruca vulgaris and, interestingly, melanomas. The seborrheic keratosis is of especial interest because it was the single, most commonly confused lesion in both this series and Becker's, and because the treatment of choice for this lesion is definitely contraindicated for nevi. In our cases, this lesion occurred with almost equal frequency in males and females; the average age for both males and females was 5 years. The lesions also occurred, however, in much younger and in older people. The youngest patient was a 3-year-old man; the oldest, a 78-year-old woman. Seborrheic keratosis is excellently described by others 3 ' * 7 ' " as being a proliferation of basal epithelial cells in addition to having keratin cysts and plugs. In our sections, however, we were impressed by the proliferation of spinous and granular cells as well as the predominant basal-cell proliferation. Intercellular bridges were readily dis- Downloaded from https://academic.oup.com/ajcp/article-abstract///054/78 on 8 January 08

058 SWERDLOW cernible as were cells containing keratohyaline granules. Seborrheic keratoses were also confused with melanomas and, as is illustrated below, in one instance the confusion resulted in somewhat radical treatment. The varieties of nevi are listed to show that an appreciable percentage of nevi has a junctional component. As mentioned above, even if it were true that dermal nevi or moles of the usual variety are always benign, they still should not be treated indiscriminately because of the possibility that they may have a junctional component, which many ' ' ' 3 ~ believe is the forerunner of the malig- TABLE 4 MICROSCOPIC DIAGNOSIS OF 57 LESIONS CLINICALLY DIAGNOSED AS MELANOMA MICROSCOPIC DIAGNOSIS Nevus Seborrheic keratosis... Hemangioma Neurofibrosarcoma Hyperkeratosis Epidermal cyst Chronic inflammation.. Blue nevus Neurofibroma Fat necrosis Verruca vulgaris (wart) 0 S 3 3 TABLE 5 CLINICAL DIAGNOSIS OP 7 MELANOMAS CLINICAL DIAGNOSIS Mole, pigmented Hard papilloma Fibroma Basal-cell carcinoma Squamous-cell carcinoma nant melanoma. Compound or dermal nevi with a junctional component accounted for 4 per cent of all nevi; if considered with the junctional nevi,. per cent of all nevi had a junctional component. These figures are irrespective of age. Allen reports an incidence of approximately per cent of 450 lesions; this brings his figures closer to those of this series which, however, are still somewhat higher. Tables 4 and 5 list the diagnoses confused with melanoma and are included to stress its confusion with nevi and to show that the malignant tumor of melanoblasts is also misdiagnosed and confused with lesions other than nevi. Although the number of lesions is small, it is at once apparent that melanomas Downloaded from https://academic.oup.com/ajcp/article-abstract///054/78 on 8 January 08

DIAGNOSIS OF NEVUS 059 are not only confused most commonly with nevi but with other lesions that require much less radical treatment. These tables also support Figi's" contention that a malignant lesion may already be present in what appears to be a benign nevus. The following cases are random examples of errors in the diagnosis of nevi or melanomas.. A 4-year-old white man had an elevated warty nodule (.0 by 0.3 cm.) over the right clavicle. The lesion was excised widely. Clinical diagnosis: pigmented mole; pathologic diagnosis, basal-cell carcinoma.. A 38-year-old white man had a "mole" on the left supraparotid region of the face. The lesion was present for months and suddenly increased in size. It was excised. Clinical diagnosis: nevus; pathologic diagnosis, seborrheic keratosis. 3. A 40-year-old white woman had an ulcerated, brown, nodular excrescence, measuring cm. in diameter and 4 mm. in height, on her right leg. The lesion was excised. Clinical diagnosis: melanoma; pathologic diagnosis, pigmented compound nevus. 4. A 39-year-old white woman had an irregular-shaped, brown, pigmented lesion (.0 by 0.8 cm.) on her back. The lesion was excised. Clinical diagnosis: pigmented mole; pathologic diagnosis, malignant melanoma. 5. A 78-year-old white woman had a small pigmented lesion on her abdomen for many years that became tender and grew in 3 weeks into a cauliflower-like, gray-black mass (3.0 by 3 cm.) on a broad base and ulcerated at the lateral border. Under general anesthesia, the lesion was widely excised with the subcutaneous fat, clown to the fascia. Clinical diagnosis: malignant melanoma; pathologic diagnosis, seborrheic keratosis.. A 40-yoar-old white woman had a dark gray, wartlike excrescence 4 mm. in height in the left inguinal region. The lesion was excised. Clinical diagnosis: nevus; pathologic diagnosis, hard papilloma. 7. A 30-year-old white woman had an elevated, pink tumor, mm. in greatest dimension, in the lumbar region that began to enlarge. The lesion was excised. Clinical diagnosis: growing pigmented mole; pathologic diagnosis, neurofibrosarcoma. S. A 4-year-old woman had a history of having a hard, black, raised mole removed from her right shoulder after it became inflamed and painful. The lesion had been present for many years. After removal of the lesion, she received several radiation treatments. The lesion, however, recurred with several surrounding smaller nodules. She then received more radiation therapy. The lesion of the shoulder enlarged to involve the whole shoulder. The patient died, and an autopsy was performed. The clinical course from the time of removal of the original lesion was approximately 5% months. The clinical impression was that of a malignant melanoma with widespread metastases, in spite of biopsies during the course of her disease that were interpreted elsewhere as basal-cell carcinoma. Necropsy revealed a basal-squamous cell carcinoma with ulceration and necrosis arising in the skin of the right shoulder with widespread metastases. SUMMARY In 7 lesions received as routine surgical specimens during an -year period and diagnosed either clinically or pathologically as nevi the sections were reviewed to determine how frequently and with what lesions nevi were confused clinically. It was found that nevi were confused with a variety of lesions in a significant percentage of cases. The awareness of this is of great importance because the treatment of many of the lesions is definitely contraindicated for nevi and may result in the tragedy of the malignant melanoma. On the other hand, the treatment of many lesions is less radical than that recommended for Downloaded from https://academic.oup.com/ajcp/article-abstract///054/78 on 8 January 08

00 SWERDLOW nevi, which, according to the predominant opinion in the literature, is wide excision if the nevus is irritated or shows evidences of change such as an increase in size or pigmentation, ulceration or surrounding inflammation. The single lesion most commonly confused with the nevus in this and other series was the seborrheic keratosis, which is also clinically confused with the malignant melanoma. In a significant percentage, dermal nevi have a junctional component that only becomes apparent on microscopic examination. The realization of this is of importance because some believe that dermal nevi always remain benign and therefore may be treated superficially. These lesions, however, should not be so treated because, even if it were true that dermal nevi always remain benign, there is always the possible presence of a junctional component that many believe to be the site of developing malignant melanomas. Lesions received as routine surgical specimens during an -year period and diagnosed either clinically or pathologically as melanomas were also reviewed. It was found that melanomas are also confused clinically with a variety of lesions, most commonly with the nevus. REFERENCES. ALLEN, A. C: A reorientation on the histogenesis and clinical significance of cutaneous nevi and melanomas. Cancer, : 8-S, 949.. BECKER, S. W.: Diagnosis and treatment of pigmented nevi; consideration of some of the pitfalls. Arch. Dermat. & Syph., 0: 44-5, 949. 3. BEERMAN, H.: Tumors of skin, Part : A review of recent literature. Am. J. M. Sc, : 480-504, 94. 4. CAHO, M. R., AND SZYMANSKI, F. J.: Seborrheic and senile keratoses. M. Clin. N. A., 35: 49-43, 95. 5. DELARIO, A. J.: The common non-vascular nevi and their treatment. Am. J. Surg., 77: 53-, 949.. Fioi, F. A.: Treatment of pigmented nevi of face and neck. S. Clin. North America, 3: 059-075, 943. 7. Fox, R. A.: Pigmented papilloma of skin. Arch. Path., 3: 95-00, 943. 8. HANDLEY, S.: Prognosis of simple moles and melanotic sarcoma. Lancet, : 40-40, 935. 9. MONTGOMERY, H., AND KERNOHAN, J. W.: Pigmented nevi, with special studies regarding a possible neuro-epithelial origin of the novus cell. J. Invest. Dermat., 3: 45-49, 940. 0. ORMSBY, O. S., AND MONTGOMERY, H.: Diseases of Skin. Ed.. Philadelphia: Lea & Febiger, 943, 30 pp... SACHS, W., MACKEE, G. M., AND SACHS, P. M.: Keratosis (seborrheic and senile). Arch. Dermat. & Syph., 9: 79-9, 949.. SUTTON, R. L., AND SUTTON, R. L., JR.: Diseases of the Skin. Ed. 0. St. Louis: C. V. Mosby Co., 939,. 549 pp. 3. TRAUB, E. F.: Nevi. M. Clin. N. A. 35: 30-33, 95. 4. TRAUB, E. F., AND KEIL, H.: "Common mole"; its clinicopathologic relations and question of malignant degeneration. Arch. Dermat. & Syph., 4: 4-5, 940. 5. WEBSTER, J. R.: The identification and management of the more common nevi. M. Clin. N. A., 33: 9-3S, 949.. WEBSTER, J. R., STEVENSON, T. W., AND STOUT, A. P.: Surgical treatment of malignant melanomas of the skin. S. Clin. North America, 4: 39-339,944. Downloaded from https://academic.oup.com/ajcp/article-abstract///054/78 on 8 January 08