Ophthalmologic Oncology Conjunctival Melanomas NIGAR NIKI ARIF, M.D., AND PAUL HENKIND, M.D., PH.D.
T here is no known biologic difference between the
melanocytes in the conjunctiva and those in the skin. Presumably then, there is no distinction between nevi and the melanomas that develop from them. However, the literature on the subject of malignant melanoma in the eyes is confusing and we wish to make a critique and update on it. In 1976, a retrospective study by Bernardino et al.1 of 23 conjunctival melanomas revealed that the three most common types of melanoma seen in skin, namely, lentigo maligna melanoma, superficial spread ing malignant melanoma, and nodular malignant melanoma were also identifiable in the conjunctiva. This was a significant contribution to the study of con junctival malignant melanomas, a disease entity that has been poorly understood because of its rarity and the imprecise terminology used in discussing it. Invasive conjunctival malignant melanomas are commonly extensions from intraepithelial melanomas, but may develop de novo in the conjunctiva or may reflect malignant change in preexisting nevi. The per centages that arise from each of these ways has not been firmly established; reports about them vary widely. Bernardino et al. found that three out of their 23 cases arose de novo and 16 either arose from or were admixed with intraepithelial melanomas. Lentigo maligna melanoma and superficial spreading melanoma are of particular interest because of their intraepithelial radial growth phase. They appear first as flat, hyperpigmented lesions that may spread hori zontally for extended periods of time before becoming vertically invasive. Reese2 lumped the early phase of both entities under the heading “ precancerous Dr. Arif is a resident, Department of Ophthalmology, Montefiore Hospital and Medical Center, Albert Einstein College of Medicine, Bronx, New York. Dr. Henkind is Professor and Chairman, Department of Ophthal mology, Montefiore Hospital and Medical Center, Albert Einstein College of Medicine, Bronx, New York. Address reprint requests to Dr. Nigar N. Arif, Department of Ophthalmology, Montefiore Hospital and Medical Center, 111 East 210th Street, Bronx, N.Y. 10467.
melanosis of the conjunctiva.” Once the vertical, inva sive phase began, it was then termed “ cancerous melanosis.” This grouping together of two forms of intraepithelial melanoma led to confusion, since the natural course of each may differ widely. Although most of what is presently known about Hutchinson’s freckle and superficial spreading malig nant melanoma has been defined in terms of the skin, much of this information is applicable to the conjunc tiva. In lentigo maligna, the lesion is flat, irregular in shape, and hyperpigmented; it may wax and wane; frequently it remains noninvasive for many years. Lids and conjunctiva may be involved simultaneously as they were in the very first case described by Hutchin son in 18923. Initially, there is an area of increased pigmentation within the epithelium and the melano cytes appear swollen and prominent. Subsequently, there is a linear proliferation of these abnormal cells and they take on a “ palisade” appearance. In the skin, the abnormal melanocytes usually involve the external sheath of the hair follicle as well. However, when and if invasion occurs, metastasis is rare.4 Superficial spreading malignant melanoma may de velop in middle life on any cutaneous surface or mu cous membrane, including the conjunctiva. Melano cytes invade in a pagetoid pattern and generally are uniform in size and shape. In the skin, the malignancy may be differentiated from a junctional nevus by melanocytic proliferation on and between re te pegs. Although it may look like a senile freckle clinically, it usually increases in diameter to about 2.5 cm and tends to invasion earlier than does a lentigo maligna melanoma4 (Figs. 1, 2A-2C). Differentiation of lentigo maligna melanoma from in vasive superficial spreading malignant melanoma as they occur in the conjunctivae is difficult both clini cally and histologically, the latter because conjunctival tissue is so thin. According to Bernardino et al. \ al though there is no single histologic criterion for differ entiating the two, the impression of a “ wild” melanoma with surrounding dispersion of abnormal melanocytes, particularly cells of pagetoid character,
J. Dermatol. Surg. Oncol. 5:5 May 1979
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should suggest malignant melanoma of the superficial spreading type. On the other hand, a malignant melanoma with a more benign cytology of pleomorphic cells and hyperpigmentation in the basal layer of the epithelium, is more characteristic of lentigo maligna melanoma. Although no indubitable data on survival rates from conjunctival superficial spreading malignant melanoma and lentigo maligna melanoma is available, all five pa tients with lentigo maligna melanoma in Bernardino’s study were alive after 8-20 years, while half of those with superficial spreading melanoma (5 out of 10) were dead of metastatic disease within 4-11 years after rec ognition of the lesion. In Reese’s study2 of 62 cases of “ cancerous melanosis” a mortality rate of 40% was found. The significance of that rate is unclear because no differentiation was made between lentigo maligna melanoma and superficial spreading malignant melanoma. However, the mortality rate found by Reese is much greater than is the experience from len tigo maligna melanoma (reported as 10%4a) and proba bly reflects that of many cases of invasive superficial spreading malignant melanoma. Although it is difficult to correlate data on cutaneous and conjunctival condi tions, it is our impression too that lentigo maligna in conjunctivae is as benign there as it is in skin and su perficial spreading malignant melanoma may also be as malignant in conjunctivae as it is in skin. Nodular melanomas in the conjunctivae usually arise de novo, and are more common near the limbus. They appear to have a better prognosis than similar melanomas in the skin. This may be due to their greater visibility, early detection, and quicker man agement when in eyes than when in skin. Conditions requiring differential diagnosis from in traepithélial melanomas are junctional nevus, nevus of Ota, melanosis oculi, acquired benign melanoses, and lesions simulating melanoses. Principles of management of conjunctival mel anomas are yet to be clearly defined. Blodi3 advises that lentigo maligna affecting the lids be treated by local excision with adequate margins of normal tissue. Henkind and Friedman5 advise local excision of these pigmented conjunctival lesions when not fixed to un derlying structures. Reese6proposes that for extensive “ cancerous melanosis” excision of all conjunctivae and substantia propria affected be done and followed in two weeks by dissection of regional lymphatics. Ac cording to Manschot7 exenteration is indicated only when a lesion is extensive or after widespread recur rence following radiotherapy. Radiotherapy alone may be effective, but data is not convincing.
370
J. Dermatol. Surg. Oncol. 5:5 May 1979
Malignant melanomas of the conjunctivae, both in traepithélial and invasive, are of importance to the dermatologist as well as to the ophthalmologist. One reason is that conjunctival lesions may extend to in volve the surrounding skin and the patient may be come aware of and seek attention first for the cutane ous change. Another reason is that the biological similarity between the melanocytes of the skin and conjunctivae makes any advance in the understanding of either applicable in part or in whole to the other.
REFERENCES 1. Bernardino, V. B., Jr., Naidoff, M. A., and Clark, W. H., Jr. Malignant melanomas of the conjunctiva. Am. J. Ophthalmol. 82:383-394, 1976. 2. Reese, A. B. Precancerous and cancerous melanosis. Am. J. Ophthalmol. 61:1272-1277, 1966. 3. Blodi, F. C., and Widner, R. R. The melanotic freckle (Hutchin son) of the lids. Surv. Ophthalmol. 13:23-30, 1968. 4. Henkind, P., and Benjamin, J. V. Conjunctival melanocytic le sions: natural history. Trans. Ophthalmol. Soc. U.K. 97:373377, 1977. 4a. Jakobiec, F., Rootman, J., and Jones, I. Secondary and meta static tumors of the orbit. In: Duane, T., ed. Clinical Ophthal mology. Hagerstown, Harper & Row, 1976, Vol. 2, p. 20. 5. Henkind, P., and Friedman, A. H. External ocular pigmenta tion. Int. Ophthalmol. Clin. 1:87-111, 1971. 6. Reese, A. B. Tumors of the Eye. 3rd ed., Hagerstown, Harper & Row, 1976, pp. 250-275. 7. Manschot, W. Melanotic lesions of the conjunctiva. Mod. Probl. Ophthalmol. 14:344-348, 1975.
ARI F A N D H E N K I N D
FIGURE 1. Typical appear ance o f an intraepithelial ma lignant melanoma o f the con junctiva and lid. There is dif fuse hyperpigmentation involv ing the caruncle, plica, tarsal and htdbar conjunctiva, and the skin o f the lower lid.
FIGURE 2A. An intraepithelial malignant melanoma in a 57-year-old, white woman with a 25-year history o f progrèssive ocular pigmentation. Biopsy revealed an intraepithelial superficial spreading malignant melanoma.
FIGURE 2B. The condition in the patient shown in Fig. 2A one year later,
FIGURE 2C. Recurrence o f lesion in the patient shown in Fig. 2A. Biopsy now revealed superficial spreading malignant melanoma in vertical growth phase.
J. Dermatol. Surg. Oncol. 5:5 May 1979
371
T here is no known biologic difference between the
melanocytes in the conjunctiva and those in the skin. Presumably then, there is no distinction between nevi and the melanomas that develop from them. However, the literature on the subject of malignant melanoma in the eyes is confusing and we wish to make a critique and update on it. In 1976, a retrospective study by Bernardino et al.1 of 23 conjunctival melanomas revealed that the three most common types of melanoma seen in skin, namely, lentigo maligna melanoma, superficial spread ing malignant melanoma, and nodular malignant melanoma were also identifiable in the conjunctiva. This was a significant contribution to the study of con junctival malignant melanomas, a disease entity that has been poorly understood because of its rarity and the imprecise terminology used in discussing it. Invasive conjunctival malignant melanomas are commonly extensions from intraepithelial melanomas, but may develop de novo in the conjunctiva or may reflect malignant change in preexisting nevi. The per centages that arise from each of these ways has not been firmly established; reports about them vary widely. Bernardino et al. found that three out of their 23 cases arose de novo and 16 either arose from or were admixed with intraepithelial melanomas. Lentigo maligna melanoma and superficial spreading melanoma are of particular interest because of their intraepithelial radial growth phase. They appear first as flat, hyperpigmented lesions that may spread hori zontally for extended periods of time before becoming vertically invasive. Reese2 lumped the early phase of both entities under the heading “ precancerous Dr. Arif is a resident, Department of Ophthalmology, Montefiore Hospital and Medical Center, Albert Einstein College of Medicine, Bronx, New York. Dr. Henkind is Professor and Chairman, Department of Ophthal mology, Montefiore Hospital and Medical Center, Albert Einstein College of Medicine, Bronx, New York. Address reprint requests to Dr. Nigar N. Arif, Department of Ophthalmology, Montefiore Hospital and Medical Center, 111 East 210th Street, Bronx, N.Y. 10467.
melanosis of the conjunctiva.” Once the vertical, inva sive phase began, it was then termed “ cancerous melanosis.” This grouping together of two forms of intraepithelial melanoma led to confusion, since the natural course of each may differ widely. Although most of what is presently known about Hutchinson’s freckle and superficial spreading malig nant melanoma has been defined in terms of the skin, much of this information is applicable to the conjunc tiva. In lentigo maligna, the lesion is flat, irregular in shape, and hyperpigmented; it may wax and wane; frequently it remains noninvasive for many years. Lids and conjunctiva may be involved simultaneously as they were in the very first case described by Hutchin son in 18923. Initially, there is an area of increased pigmentation within the epithelium and the melano cytes appear swollen and prominent. Subsequently, there is a linear proliferation of these abnormal cells and they take on a “ palisade” appearance. In the skin, the abnormal melanocytes usually involve the external sheath of the hair follicle as well. However, when and if invasion occurs, metastasis is rare.4 Superficial spreading malignant melanoma may de velop in middle life on any cutaneous surface or mu cous membrane, including the conjunctiva. Melano cytes invade in a pagetoid pattern and generally are uniform in size and shape. In the skin, the malignancy may be differentiated from a junctional nevus by melanocytic proliferation on and between re te pegs. Although it may look like a senile freckle clinically, it usually increases in diameter to about 2.5 cm and tends to invasion earlier than does a lentigo maligna melanoma4 (Figs. 1, 2A-2C). Differentiation of lentigo maligna melanoma from in vasive superficial spreading malignant melanoma as they occur in the conjunctivae is difficult both clini cally and histologically, the latter because conjunctival tissue is so thin. According to Bernardino et al. \ al though there is no single histologic criterion for differ entiating the two, the impression of a “ wild” melanoma with surrounding dispersion of abnormal melanocytes, particularly cells of pagetoid character,
J. Dermatol. Surg. Oncol. 5:5 May 1979
369
O P H T H A L M O L O G IC O N CO L O G Y
should suggest malignant melanoma of the superficial spreading type. On the other hand, a malignant melanoma with a more benign cytology of pleomorphic cells and hyperpigmentation in the basal layer of the epithelium, is more characteristic of lentigo maligna melanoma. Although no indubitable data on survival rates from conjunctival superficial spreading malignant melanoma and lentigo maligna melanoma is available, all five pa tients with lentigo maligna melanoma in Bernardino’s study were alive after 8-20 years, while half of those with superficial spreading melanoma (5 out of 10) were dead of metastatic disease within 4-11 years after rec ognition of the lesion. In Reese’s study2 of 62 cases of “ cancerous melanosis” a mortality rate of 40% was found. The significance of that rate is unclear because no differentiation was made between lentigo maligna melanoma and superficial spreading malignant melanoma. However, the mortality rate found by Reese is much greater than is the experience from len tigo maligna melanoma (reported as 10%4a) and proba bly reflects that of many cases of invasive superficial spreading malignant melanoma. Although it is difficult to correlate data on cutaneous and conjunctival condi tions, it is our impression too that lentigo maligna in conjunctivae is as benign there as it is in skin and su perficial spreading malignant melanoma may also be as malignant in conjunctivae as it is in skin. Nodular melanomas in the conjunctivae usually arise de novo, and are more common near the limbus. They appear to have a better prognosis than similar melanomas in the skin. This may be due to their greater visibility, early detection, and quicker man agement when in eyes than when in skin. Conditions requiring differential diagnosis from in traepithélial melanomas are junctional nevus, nevus of Ota, melanosis oculi, acquired benign melanoses, and lesions simulating melanoses. Principles of management of conjunctival mel anomas are yet to be clearly defined. Blodi3 advises that lentigo maligna affecting the lids be treated by local excision with adequate margins of normal tissue. Henkind and Friedman5 advise local excision of these pigmented conjunctival lesions when not fixed to un derlying structures. Reese6proposes that for extensive “ cancerous melanosis” excision of all conjunctivae and substantia propria affected be done and followed in two weeks by dissection of regional lymphatics. Ac cording to Manschot7 exenteration is indicated only when a lesion is extensive or after widespread recur rence following radiotherapy. Radiotherapy alone may be effective, but data is not convincing.
370
J. Dermatol. Surg. Oncol. 5:5 May 1979
Malignant melanomas of the conjunctivae, both in traepithélial and invasive, are of importance to the dermatologist as well as to the ophthalmologist. One reason is that conjunctival lesions may extend to in volve the surrounding skin and the patient may be come aware of and seek attention first for the cutane ous change. Another reason is that the biological similarity between the melanocytes of the skin and conjunctivae makes any advance in the understanding of either applicable in part or in whole to the other.
REFERENCES 1. Bernardino, V. B., Jr., Naidoff, M. A., and Clark, W. H., Jr. Malignant melanomas of the conjunctiva. Am. J. Ophthalmol. 82:383-394, 1976. 2. Reese, A. B. Precancerous and cancerous melanosis. Am. J. Ophthalmol. 61:1272-1277, 1966. 3. Blodi, F. C., and Widner, R. R. The melanotic freckle (Hutchin son) of the lids. Surv. Ophthalmol. 13:23-30, 1968. 4. Henkind, P., and Benjamin, J. V. Conjunctival melanocytic le sions: natural history. Trans. Ophthalmol. Soc. U.K. 97:373377, 1977. 4a. Jakobiec, F., Rootman, J., and Jones, I. Secondary and meta static tumors of the orbit. In: Duane, T., ed. Clinical Ophthal mology. Hagerstown, Harper & Row, 1976, Vol. 2, p. 20. 5. Henkind, P., and Friedman, A. H. External ocular pigmenta tion. Int. Ophthalmol. Clin. 1:87-111, 1971. 6. Reese, A. B. Tumors of the Eye. 3rd ed., Hagerstown, Harper & Row, 1976, pp. 250-275. 7. Manschot, W. Melanotic lesions of the conjunctiva. Mod. Probl. Ophthalmol. 14:344-348, 1975.
ARI F A N D H E N K I N D
FIGURE 1. Typical appear ance o f an intraepithelial ma lignant melanoma o f the con junctiva and lid. There is dif fuse hyperpigmentation involv ing the caruncle, plica, tarsal and htdbar conjunctiva, and the skin o f the lower lid.
FIGURE 2A. An intraepithelial malignant melanoma in a 57-year-old, white woman with a 25-year history o f progrèssive ocular pigmentation. Biopsy revealed an intraepithelial superficial spreading malignant melanoma.
FIGURE 2B. The condition in the patient shown in Fig. 2A one year later,
FIGURE 2C. Recurrence o f lesion in the patient shown in Fig. 2A. Biopsy now revealed superficial spreading malignant melanoma in vertical growth phase.
J. Dermatol. Surg. Oncol. 5:5 May 1979
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