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Dermatopathology: Practical & Conceptual

October – December 2010 | Volume 16, No. 4

Chapter 4: Atlas of lesions diagnosed as primary acquired melanosis

Ackerman, A. Bernard; Böer, Almut

Editor’s note

In a previous issue of this journal an introduction to this series of articles on primary acquired melanosis of the conjunctiva was published. In it, the structure and content of this work is given and the motivation of the authors is explained. [1] The table of contents of the series is as follows:

Introduction

Chapter 1: Anatomy and histology of the eyelid and conjunctiva

Chapter 2: History of melanoma in situ

Chapter 3: History of primary acquired melanosis

Chapter 4: Atlas of lesions diagnosed as primary acquired melanosis

Chapter 5: Examples from our own experience

Afterword

Chapters 1-3 of this series appeared in preceding issues of this journal. [2-6] The following contribution represents Chapter 4 of this work.

Almut Böer-Auer, M.D.

Editor-in-Chief

Chapter 4: Introduction

The review of articles devoted to the subject of primary acquired melanosis presented in chapter 3 of this work included also a reassessment of figures published in these articles. As pictures tell much more than words can do, at least to morphologists, this chapter provides a selection of photomicrographs, sometimes accompanied by clinical pictures, of lesions diagnosed by authors of articles as primary acquired melanosis. Readers are invited to analyze the images and to come to their own conclusion on the matter under discussion here. Comparison of photomicrographs reproduced from articles with those of our own cases as presented in the following chapter 5 of this work is encouraged!

Atlas of lesions diagnosed as primary acquired melanosis

Fig. 1

This figure reproduced from the article by Zeidler (1929) is a drawing of a lesion diagnosed as melanocytic nevus, but the changes histopathologic are those of melanoma in situ. In time, the neoplasm metastasized. Reproduced from: Zeidler M. Melanosis conjunctivae. Graefes Arch. 1929;122:629. [7]

Figs. 2 A-C

Pictured here are what Reese called “early and advanced cancerous melanosis,” the changes actually being those of “invasive” melanoma in each instance. Reproduced from: Reese AB. Precancerous melanosis and the resulting malignant melanoma (cancerous melanosis) of conjunctiva and skin of lids. Arch Ophthalmol. 1943; 29:737-746. [8]

Figs. 3A and B

This patient was diagnosed as having diffuse melanosis of the conjunctiva, but the changes are those of melanoma in situ. Reproduced from: Grosse H. Melanoma and melanosis of the conjunctiva. Albrecht Von Graefes Arch Ophthalmol. 1953;154(4):368-80. [9]

Figs. 4A-E

These photomicrographs of what Greer (1956) diagnosed as precancerous melanosis (A-D) demonstrate different features of melanoma in situ of the conjunctiva. The earliest changes are seen to consist of just a proliferation of single melanocytes in the basal layer. In advanced stages, single melanocytes are seen in suprabasal layers. Only in Fig. 4E, a diagnosis of melanoma was made by the author because subepithelial tissue was affected by the process of melanoma. Reproduced from: Greer CH. Precancerous melanosis of the conjunctiva. Aust N Z J Surg. 1956;25(4):258-63. [10]

Fig. 5

Manschot illustrated in his article of 1966 what he called intraepithelial and malignant melanoma. He did not employ the nomenclature of “precancerous and cancerous melanosis.” The changes pictured are those of melanoma in situ and of melanoma involving the lamina propria. Reproduced from: Manschot WA. Congenital ocular melanosis, conjunctival naevus, conjunctival melanosis, conjunctival melanoma. Ophthalmologica. 1966;152(6):495-505. [11]

Fig. 6

Just as Manschot, Jay, in 1968, also employed the term intraepithelial melanoma in lieu of “precancerous melanosis.” The changes pictured are those of melanoma in situ. Reproduced from: Jay B. Pigmented lesions of the conjunctiva. II. Br J Ophthalmol. 1968;52(1):70-1. [12]

Figs. 7A-D

The lesion pictured here was diagnosed by Kaufer (1969) as “acquired cancerous melanosis. The changes are those of melanoma in situ together with melanoma involving the lamina propria. Reproduced from: Kaufer G. Nevus, acquired melanosis and melanomas of the conjunctiva. Current status and personal experience with stress in the clinical pathological correlation. Arch Oftalmol B Aires. 1969;44(7):177-84. [13]

Figs. 8A-F

Two patients were diagnosed by Elas (1974) as having melanoma that developed in “precancerous melanosis.” In both, other melanocytic neoplasms appeared, they being well circumscribed neoplasms unassociated with an intraepithelial component. Although the authors considered those neoplasms to be benign, more likely they represent local metastases of melanoma (Figs. 8C and F). Reproduced from: Elsas FJ, et al. Benign pigmented tumors, arising in acquired conjunctival melanosis. Am J Ophthalmol. 1974;78(2):229-32. [14]

Figs. 9A-I

Photomicrographs 9A and 9F show unequivocal melanoma in situ of eyelid skin, Figures 9B, 9C, and 9G picture proliferations of abnormal melanocytes of what almost certainly is melanoma in situ of the conjunctiva, and Figures 9D, 9H, and 9I portray melanomas in the lamina propria. The effort of Bernardino and coworkers (1976) to integrate these melanomas according to Clark’s “histogenetic classification” failed because the criteria histopathologic for diagnosis of melanoma are the very same irrespective of anatomic site, including skin and conjunctiva. Reproduced from: Bernardino VB et al. Malignant melanomas of the conjunctiva. Am J Ophthalmol. 1976;82(3):383-94. [15]

Figs. 10A and B

A patient diagnosed as having primary acquired melanosis with atypia which Gonder (1980) considered to represent the “radial growth phase” of conjunctival melanoma. The changes shown are those of melanoma in situ of the conjunctiva and of skin. Reproduced from: Gonder JR et al. Idiopathic acquired melanosis. Ophthalmology. 1980;87(8):835-40. [16]

Fig. 11

A patient diagnosed as having melanoma arising in primary acquired melanosis has melanoma clinically and melanoma in the lamina propria histopathologically. Reproduced from: Pialat J et al. Reese’s conjunctival melanosis. Two anatomicoclinical observations wit ultrastructural study in one case. J Fr Ophtalmol. 1982;5(12):805-11. [17]

Fig. 12A and B

A patient diagnosed as having acquired precancerous melanosis later developed melanoma, but the changes pictured here are those of melanoma in situ. Reproduced from: Desjardins L and Shields JA. Malignant melanoma of the conjunctiva arising from precancerous melanosis, prognosis and treatment. J Fr Ophtalmol. 1983;6(5):515-20. [18]

Figs. 13A-E

These illustrations appeared in an article by Jakobiec in 1984. Changes diagnosed as primary acquired melanosis included marked pleomorphism of melanocytes increased in number. The changes pictured are diagnostic of melanoma in situ. Reproduced from: Jakobiec FA. The ultrastructure of conjunctival melanocytic tumors. Trans Am Ophthalmol Soc. 1984;82:599-752. [19]

Figs. 14A-D

These pale photomicrographs show what was diagnosed by the author as primary acquired melanosis. Even though the authors noted that the proliferation of melanocytes simulated “carcinoma in situ” (their Figure 5), they did not conclude the changes they pictured here were those of melanoma in situ. Nevertheless, the changes are those of melanoma in situ. Reproduced from: Folberg R et al. Primary acquired melanosis of the conjunctiva. Hum Pathol. 1985;16(2):129-35. [20]

Figs. 15A-E

These figures show what the author considers to be primary acquired melanosis, but the histopathologic changes are those of melanoma in situ. Reproduced from: Jakobiec FA et al. Clinicopathologic characteristics of premalignant and malignant melanocytic lesions of the conjunctiva. Ophthalmology. 1989;96(2):147-66. [21]

Figs. 16A and B

A patient with xeroderma pigmentosum diagnosed as having primary acquired melanosis but the changes pictured are those of melanoma in situ. Reproduced from: Paridaens AD et al. Premalignant melanosis of the conjunctiva and the cornea in xeroderma pigmentosum. Br J Ophthalmol. 1992;76(2):120-2. [22]

Figs. 17A and B

A patient diagnosed as having primary acquired melanosis with atypia, but who has melanoma in situ. Reproduced from: Frucht-Pery J and Pe’er J. Use of mitomycin C in the treatment of conjunctival primary acquired melanosis with atypia. Arch Ophthalmol. 1996;114(10):1261-4. [23]

Figs. 18A-F

This report of a patient by McNab of 1997 illustrates that one and the same melanoma may involve conjunctiva and nasal mucosa. Interestingly, the author used the nomenclature of primary acquired melanosis as a synonym of melanoma in situ when referring to intraepithelial melanoma of the conjunctiva, but called the same proliferation melanoma in situ straightforwardly where it affected nasal mucosa. Reproduced from: McNab AA and McKelvie P. Malignant melanoma of the lacrimal sac complicating primary acquired melanosis of the conjunctiva. Ophthalmic Surg Lasers. 1997;28(6):501-4. [24]

Figs. 19A and B

This patient of McLean published in 1998 was diagnosed with primary acquired melanosis. Pictures taken with a distance of 15 years both show melanoma in situ. Reproduced from: McLean IW. Differential diagnosis of the conjunctival melanoses. Ann Diagn Pathol. 1998;2(4):264-70. [25]

Fig. 20

Lesions diagnosed by the authors as primary acquired melanosis with and without atypia. Their Fig. 1c shows melanoma in situ, whereas their Fig. 1b seems to represent a pigmented epithelial lesion. The clinical lesion pictured in their Fig. 1a is typical of early melanoma of the conjunctiva. Reproduced from: Lommatzsch PK and Werschnik C. Malignant conjunctival melanoma. Clinical review with recommendations for diagnosis, therapy and follow-up. Klin Monatsbl Augenheilkd. 2002;219(10):710-21. [26]

Figs. 21A and B

A patient diagnosed histopathologically as having primary acquired melanosis. The histopathologic changes in their Figure 2A is melanoma in situ. Reproduced from: Yuen VH et al. Topical mitomycin treatment for primary acquired melanosis of the conjunctiva. Ophthal Plast Reconstr Surg. 2003;19(2):149-51. [27]

Figs. 22A and B

A patient diagnosed by the authors as having melanoma that arose in primary acquired melanosis, but the changes pictured in their Figures 5a-b are those of melanoma in situ. The nodule of melanoma seen as scanning power magnification is in continuity with the melanoma in situ. Reproduced from: Duchateau N et al. Nodular melanoma on primary acquired conjunctival melanosis. J Fr Ophtalmol. 2005;28(3):331-5. [28]

Figs. 23A-F

A patient diagnosed as having melanoma that began in primary acquired melanosis, but the findings in conjunctival epithelium both before and after treatment with mitomycin are those of melanoma in situ. Reproduced from: Colby KA and Nagel DS. Conjunctival melanoma arising from diffuse primary acquired melanosis in a young black woman. Cornea. 2005;24(3):352-5. [29]

Figs. 24A and B

Pigmented lesions that arose in pterygia diagnosed by Perra in 2006 as primary acquired melanosis with and without atypia. What is said to be “PAM without atypia” in their Figure 1 and “PAM with atypia” in their Figure 2 are both changes of melanoma in situ at different stages of the process. Reproduced from: Perra MT et al. Finding of conjunctival melanocytic pigmented lesions within pterygium. Histopathology. 2006;48(4):387-93. [30]

Figs. 25A and B

What the authors diagnosed as “primary acquired melanosis with atypia” is melanoma in situ. The one small high-power field of the lesion diagnosed as “primary acquired melanosis without atypia” does not permit a diagnosis with specificity to be rendered. It seems to be a pigmented epithelial lesion rather than a melanocytic proliferation. Reproduced from: Messmer EM et al. In vivo confocal microscopy of pigmented conjunctival tumors. Graefes Arch Clin Exp Ophthalmol. 2006;244(11):1437-45. [31]

Figs. 26A-D

What is pictured clinically as primary acquired melanosis in Figs 1 and 2 of the authors is melanoma just as melanoma is shown in clinical images of their Fig 4. What is diagnosed histopathologically as primary acquired melanosis in their Figures 3A-D is melanoma in situ. Changes in their Fig 3A are subtle, but melanocytes are typified by prominent and high reaching dendrites, a finding typical of early melanoma in situ of the conjunctiva. Reproduced from: Shields JA et al. Primary acquired melanosis of the conjunctiva: experience with 311 eyes. Trans Am Ophthalmol Soc. 2007;105:61-71. [32]

Figs. 27A and B

Sugiura and colleagues attempted to forge criteria for differentiation between a “low risk” and a “high risk” type of primary acquired melanosis with atypia. What they picture in photomicrographs is melanoma in situ of the conjunctiva in all examples provided. Reproduced from: Sugiura M et al. Low-risk and high-risk histologic features in conjunctival primary acquired melanosis with atypia: Clinicopathologic analysis of 29 cases. Am J Surg Pathol. 2007;31(2):185-92. [33]

Fig. 28

In 2008, Maly and coworkers tried to provide criteria for grading of atypia in conjunctival melanocytic lesions. What they present in their photomicrographs B to G is diagnostic of melanoma in situ of the conjunctiva. The lesion pictured in their figure A is difficult to interpret but seems to represent a pigmented epithelial lesion rather than a melanocytic proliferation. Reproduced from: Maly A et al. Histological criteria for grading of atypia in melanocytic conjunctival lesions. Pathology. 2008;40(7):676-81. [34]

Conclusion

This selection of pictorial material from various articles was provided to enable readers to come to their own conclusion on the true nature of what as of today is called primary acquired melanosis of the conjunctiva by ophthalmologist and ophthalmopathologists. In our opinion, almost all examples given show features diagnostic of melanoma in situ.

Summary

In order to clarify the matter of what is called “primary acquired melanosis of the conjunctiva,” a comprehensive search of the literature was undertaken and presented in previous issues of this journal. This article presents a selection of the pictorial material provided by the authors of various articles in order to permit readers reassessment of the histopathologic features of what as of today is called primary acquired melanosis of the conjunctiva by ophthalmologist and ophthalmopathologists. Interpretation of the pictures is provided showing that almost all of the examples given show features diagnostic of melanoma in situ of the conjunctiva.

Almut Böer-Auer is a dermatopathologist at the Dermatologikum Hamburg, Germany. A. Bernard Ackerman, M.D., was Director emeritus at the Ackerman Academy of Dermatopathology in New York City. This article was reviewed by François Milette, M.D., and Diana Alvarez, M.D. Contact author via email: boer@dermatologikum.de .

References

1. Milette F, Ackerman AB. Primary acquired melanosis of the conjunctiva (PAM): Introduction to a series. Dermatopathology: Practical & Conceptual. 2009;15(2):10.

2. Alvarez D, Ackerman AB. Primary acquired melanosis of the conjunctiva (PAM): Chapter 1—Anatomic and histologic aspects of eyelid skin, eyelid margin, and conjunctiva. Dermatopathology: Practical & Conceptual. 2009;15(3):10.

3. Alvarez D, Ackerman AB. Primary acquired melanosis of the conjunctiva (PAM): Chapter 2— History of melanoma in situ. Dermatopathology: Practical & Conceptual. 2009;15(4):6.

4. Böer A. Primary acquired melanosis of the conjunctiva (PAM): Chapter 3—History of primary acquired melanosis—Part 1. Dermatopathology: Practical & Conceptual. 2010;16(1):6.

5. Böer-Auer A. Primary acquired melanosis of the conjunctiva (PAM): Chapter 3—History of primary acquired melanosis—Part 2. Dermatopathology: Practical & Conceptual. 2010;16(2):10.

6. Böer-Auer A. Primary acquired melanosis of the conjunctiva (PAM): Chapter 3—History of primary acquired melanosis—Part 3. Dermatopathology: Practical & Conceptual. 2010;16(3):4.

7. Zeidler M. Melanosis conjunctivae. Graefes Arch. 1929;122:629.

8. Reese AB. Precancerous melanosis and the resulting malignant melanoma (cancerous melanosis) of conjunctiva and skin of lids. Arch Ophthalmol 1943; 29:737-746.

9. Grosse H. Melanoma and melanosis of the conjunctiva. Albrecht Von Graefes Arch Ophthalmol. 1953;154(4):368-80.

10. Greer CH. Precancerous melanosis of the conjunctiva. Aust N Z J Surg. 1956;25(4):258-63.

11. Manschot WA. Congenital ocular melanosis, conjunctival naevus, conjunctival melanosis, conjunctival melanoma. Ophthalmologica. 1966;152(6):495-505.

12. Jay B. Pigmented lesions of the conjunctiva. II. Br J Ophthalmol. 1968;52(1):70-1.

13. Kaufer G. Nevus, acquired melanosis and melanomas of the conjunctiva. Current status and personal experience with stress in the clinical pathological correlation] Arch Oftalmol B Aires. 1969;44(7):177-84.

14. Elsas FJ, Green WR, Ryan SJ. Benign pigmented tumors, arising in acquired conjunctival melanosis. Am J Ophthalmol. 1974;78(2):229-32.

15. Bernardino VB, Naidoff MA, Clark WH. Malignant melanomas of the conjunctiva. Am J Ophthalmol. 1976;82(3):383-94.

16. Gonder JR, Wagoner MD, Albert DM. Idiopathic acquired melanosis. Ophthalmology. 1980;87(8):835-40.

17. Pialat J, Grochowicki M, Dumas C, Rougier J. Reese’s conjunctival melanosis. Two anatomicoclinical observations wit ultrastructural study in one case. J Fr Ophtalmol. 1982;5(12):805-11.

18. Desjardins L, Shields JA. Malignant melanoma of the conjunctiva arising from precancerous melanosis, prognosis and treatment. J Fr Ophtalmol. 1983;6(5):515-20.

19. Jakobiec FA. The ultrastructure of conjunctival melanocytic tumors. Trans Am Ophthalmol Soc. 1984;82:599-752.

20. Folberg R, McLean IW, Zimmerman LE. Primary acquired melanosis of the conjunctiva. Hum Pathol. 1985;16(2):129-35.

21. Jakobiec FA, Folberg R, Iwamoto T. Clinicopathologic characteristics of premalignant and malignant melanocytic lesions of the conjunctiva. Ophthalmology. 1989;96(2):147-66.

22. Paridaens AD, McCartney AC, Hungerford JL. Premalignant melanosis of the conjunctiva and the cornea in xeroderma pigmentosum. Br J Ophthalmol. 1992;76(2):120-2.

23. Frucht-Pery J, Pe’er J. Use of mitomycin C in the treatment of conjunctival primary acquired melanosis with atypia. Arch Ophthalmol. 1996;114(10):1261-4.

24. McNab AA, McKelvie P. Malignant melanoma of the lacrimal sac complicating primary acquired melanosis of the conjunctiva. Ophthalmic Surg Lasers. 1997;28(6):501-4.

25. McLean IW. Differential diagnosis of the conjunctival melanoses. Ann Diagn Pathol. 1998;2(4):264-70.

26. Lommatzsch PK, Werschnik C. [Malignant conjunctival melanoma. Clinical review with recommendations for diagnosis, therapy and follow-up] Klin Monatsbl Augenheilkd. 2002;219(10):710-21.

27. Yuen VH, Jordan DR, Brownstein S, Dorey MW. Topical mitomycin treatment for primary acquired melanosis of the conjunctiva. Ophthal Plast Reconstr Surg. 2003;19(2):149-51.

28. Duchateau N, Meyer A, Hugol D, Allali J, Audouin J, Renard G, D’Hermies F. [Nodular melanoma on primary acquired conjunctival melanosis] J Fr Ophtalmol. 2005;28(3):331-5.

29. Colby KA, Nagel DS. Conjunctival melanoma arising from diffuse primary acquired melanosis in a young black woman. Cornea. 2005;24(3):352-5.

30. Perra MT, Colombari R, Maxia C, Zucca I, Piras F, Corbu A, Bravo S, Scarpa A, Sirigu P. Finding of conjunctival melanocytic pigmented lesions within pterygium. Histopathology. 2006;48(4):387-93.

31. Messmer EM, Mackert MJ, Zapp DM, Kampik A. In vivo confocal microscopy of pigmented conjunctival tumors. Graefes Arch Clin Exp Ophthalmol. 2006;244(11):1437-45.

32. Shields JA, Shields CL, Mashayekhi A, Marr BP, Benavides R, Thangappan A, Phan L, Eagle RC Jr. Primary acquired melanosis of the conjunctiva: experience with 311 eyes. Trans Am Ophthalmol Soc. 2007;105:61-71.

33. Sugiura M, Colby KA, Mihm MC Jr, Zembowicz A. Low-risk and high-risk histologic features in conjunctival primary acquired melanosis with atypia: Clinicopathologic analysis of 29 cases. Am J Surg Pathol. 2007;31(2):185-92.

34. Maly A, Epstein D, Meir K, Pe’er J. Histological criteria for grading of atypia in melanocytic conjunctival lesions. Pathology. 2008;40(7):676-81.