Pigmented skin lesions: are they all of melanocytic origin? A histopathological perspective

Original Article Pigmented skin lesions: are they all of melanocytic origin? A histopathological perspective Rajesh Singh Laishram, Barida Ginia Myrthong, Sharmila Laishram, Rachel Shimray, Arun Kumar K, Durlav Chandra Sharma Department of Pathology, Regional Institute of Medical Sciences, Lamphelpat, Imphal, Manipur State, India Abstract Objective To study the pattern of pigmented skin lesions in Manipur. Patients and methods This was a retrospective analysis of pigmented skin lesions received at the Department of Pathology, RIMS, Imphal Manipur. Pigmented skin lesions which were histologically reported from January 2005 to December 2012 were reviewed and analysed according to age, gender, site of occurrence and histological types. Results A total of 183 pigmented skin lesions were histologically reported during the period under review in 57 male and 126 female patients with a male to female ratio of 1: 2.21. Maximum of the cases were seen in the age group of 21 to 30 years, with the youngest patient being 4 years and the oldest being 77 years. It was found that the most common site was the face (51.4%) followed by the arms (8.9%). Melanocytic nevi were the most common pigmentary lesion which accounted for 74.3% of the cases followed by melanoma (9.8%) and seborrheic keratosis(6%). Conclusion In this study the commonest benign pigmented lesion was melanocytic nevi and melanoma had the highest incidence from among the malignant lesions. Key words Pigmented skin lesions, melanocytic nevi, melanoma. Introduction Skin lesions account for about 15% of a general practitioners workload. The skin is the protective interface between the potentially injurious external environment and the vulnerable organs and tissues of the body. 1 Address for correspondence Dr. Rajesh Singh Laishram Department of Pathology, Regional Institute of Medical Sciences Lamphelpat, Imphal, Manipur State, Pin-795004 India E mail: rajeshlaishr@gmail.com Mobile: +919436039201 Pigmented skin lesions are a very common presenting problem; while majority (about 90%) are benign, a small minority are melanomas. 2 Many pigmented skin lesions can mimic clinically melanocytic lesions including malignant melanoma. A histopathological interpretation by pathologist is helpful in the diagnosis and management of these lesions. The prevalence of nevi is related to the age, race and perhaps genetic and environmental factors. A few nevi are present since early childhood and the greatest number is observed in the middle age following which it gradually decreases with time. 3 284

The incidence of melanoma is increasing worldwide and is now responsible for 2% of all skin cancers and 1% of all skin cancer deaths in the UK. Australia and New Zealand lead the world with about 50 cases per 100,000 population per year. 3 It is relatively uncommon in India and in Manipur, a state in North Eastern India it constitutes about 2.13% of all diagnosed cancer. 4 All the pigmented lesions are not to be considered as malignant. The benign melanocytic and other nonmelanocytic pigmented skin lesions should also be considered. This study was undertaken to document the pattern of pigmented skin lesions with reference to age, gender, site of occurrence and histological types in Manipur. Patients and methods This was a retrospective study of all the histologically diagnosed pigmented skin lesions received at the Department of Pathology, RIMS, Imphal from January 2005 to December 2012. Regional Institute of Medical Sciences (RIMS) is the major referral centre in Manipur, a small state in North Eastern India. Ethical approval was obtained from the institutional ethical committee. The clinical data (age, sex and site) were obtained from the histopathology request forms. All the histology slides had been routinely stained with hematoxylin and eosin (H&E) and special stains like Masson-Fontana were employed whenever necessary. Pigmented skin lesions which were histologically reported during the study period were reviewed and analysed according to age, gender, site of occurrence and histological types. Results A total of 183 histologically diagnosed pigmented skin lesions were reported in as many patients during the period under review of which 57 were males and 126 were females. The results were divided into benign and malignant lesions. Out of the 183 cases, 158 (86.3%) were benign and 25 (13.7%) were malignant. Among the benign cases, melanocytic nevi accounted for the majority of them with 136 (74.3%) cases followed by seborrheic keratosis with 11 (6%) cases (Table 1). Melanoma accounted for maximum of the malignant pigmented lesions with 18 (9.8%) cases followed by pigmented basal cell carcinoma (BCC) with 7 (3.9%) cases. The commonest site of the lesions was the face with 94 (51.4%) cases followed by the upper limbs with 26 (14.2%) cases and lower limbs with 20 (10.9%) cases (Table 2). Table 3 shows that the incidence of melanocytic nevi was highest in the third decade of life after Table 1 Frequency of various pigmented skin lesions (n=183). Diagnosis N (%) Benign pigmented lesions 1. Melanocytic nevi 136 (74.4%) Intradermal nevus (n=102) Junctional nevus (n=9) Compound nevus (n=21) Pigmented cell nevus (n=3) Halo nevus (n=1) 2. Seborrheic keratosis 11 (6.0) 3. Lentigo simplex 3 (1.6) 4. Lichen planus pigmentosus 3 (1.6) 5. Actinic lentigo (solar lentigo) 4 (2.2) 6. Melanoacanthoma 1 (0.5) Malignant pigmented lesions 1. Melanoma 18 (9.8) 2. Pigmented basal cell carcinoma 7 (3.9) Table 2 Sites of lesions (n=183). Sites N (%) Face 94 (51.4%) Upper limb 26 (14.2%) Lower limb 20 (10.9%) Neck 19 (10.4%) Trunk 17 (9.3%) Scalp 7 (3.8%) 285

Table 3 Incidence of melanocytic lesions in different age groups (n=183) Age (years) Different melanocytic lesions Total (%) MN SK LS LPP SL Melanoacanthoma Melanoma Pigmented BCC <20 32 2 1 1 1 0 0 0 37 (20.2) 21-30 52 1 2 2 2 0 0 0 59 (32.2) 31-40 25 1 0 0 0 0 1 0 27 (14.7) 41-50 12 1 0 0 0 0 3 0 16 (8.7) 51-60 11 5 0 0 1 0 2 2 21 (11.5) 61-70 1 1 0 0 0 1 8 5 16 (8.7) >70 3 0 0 0 0 0 4 0 7 (3.8) Total 136 11 3 3 4 1 18 7 183 (100) BCC - Basal cell carcinoma, LPP - lichen planus pigmentosus, LS - lentigo simplex, MN - melanocytic nevi, SKseborrheic keratosis, SL solar lentigo. Table 4 Sex-wise distribution of the lesion Diagnosis Male Female Total Melanocytic nevi 44 92 136 Seborrheic keratosis 1 10 11 Lentigo simplex 0 3 3 Lichen planus pigmentosus 0 3 3 Actinic lentigo 1 3 4 Melanoacanthoma 1 0 1 Melanoma 7 11 18 Pigmented basal cell carcinoma 3 4 7 Total 57 (31.1%) 126 (68.9) 183 which it gradually tapered with age. Melanoma and pigmented BCC had the highest incidence in the sixth decade. The sex distribution of the various pigmented lesions is depicted in Table 4. Most of the lesions were more common in females except for melanoacanthoma where the only case was found in a male. Only cutaneous melanomas were included in the study. Maximum cases were seen in the lower extremities with six cases, two cases each in upper extremities and face. Six cases (60%) were of superficial spreading variety followed by two cases (20%) of nodular and acral lentiginous variety. Discussion Numerous pigmented skin lesions can defy clinical recognition and can mimic melanocytic lesions including melanoma. Such mimickers are seborrheic keratosis, pigmented BCC, actinic keratosis, dermatofibrosarcoma protuberans and rarely lesions like follicular cyst. 5 Many diagnoses are a complete surprise to the dermatologists and plastic surgeons. In the screening of 178 cases for malignant melanoma by Anderson et al. 6 13 (7.4%) cases were diagnosed as nonmelanoma lesions. In a study by Crasta et al. 5 in 30% of clinically diagnosed cases of melanoma, none had a histopathological diagnosis of melanoma. In this study, we found that maximum of the benign lesions were seen in the 3 rd decade of life which gradually decreased thereafter and this was comparable to studies done in Britain 7 and in Australia. 8 Rubegni et al. 9 in their study showed that melanocytic nevi were the highest among pigmented skin lesions which is comparable to our study. We also found that melanocytic nevi were seen more in females which is unlike the study done in Augsburg region (KORA) in Germany. 10 286

Seborrheic keratosis was the second commonest benign lesion in this series; most of them were clinically diagnosed as melanoma. This was similar to the study in India, where seborrheic keratosis was the commonest lesion to be misdiagnosed clinically as melanoma. 5 Other pigmented nonmelanocytic lesions included in another study were seborrheic keratosis, solar lentigo, dermatofibroma and hemangioma. 11 Incidence of melanoma and its mortality rates are increasing in most countries throughout the world. 12 According to World Health Organisation (WHO), the number of melanomas cases worldwide is increasing faster than any other cancer. 13 Among the malignant lesions, malignant melanoma was the commonest lesion in the present series. It is relatively uncommon in India and it constitutes about 2.1% of all diagnosed cancer in Manipur, a state in North Eastern India. 4 The highest incidence is in sixth decades as seen in our series. 14,15 The slight female predominance is consistent with other studies. 16 However, one study reported a slight male predominance. 14,15 Superficial spreading melanoma was the commonest histological type in this series as expected because in India, superficial spreading melanoma and nodular melanoma are commonly found, 17 acral lentiginous being rare. 18 The incidence of pigmented BCC ranges from 6.7% to 8.5%. 19,20 Many BCC s histological patterns can have pigmentation except the morpheic type. Within the tumour mass, melanocytes are often hyperplastic and melanosomes are often confined to the melanocytes. However, they may be taken up by the malignant epithelial cells. 21 In the present series, we found seven cases of pigmented BCC clinically diagnosed as melanoma. Menzies et al. 11 had used surface microscopy to differentiate between pigmented BCC and malignant melanoma reinforcing the need for validation of the clinical diagnosis. The most common site was the face which is comparable to the study by Crasta et al. 5 It was reported from Japan that 86% of skin melanomas were found in lower limbs and most of these were seen in the sole which is comparable to our study. 22 We reported a female preponderance as substantiated by another paper. 16 In our study, melanocytic nevi were the most common benign lesion and melanoma from among the malignant lesions. It is a common observation that most of the pigmented moles are seen in sun exposed areas of the skin and melanomas on areas with many moles and relatively protected from the sun. Conclusion Even though most of the pigmented skin lesions are of melanocytic origin, some nonmelanocytic pigmented lesions should also be considered. Benign skin lesions comprise majority of the pigmented skin lesions with melanocytic nevi being the commonest, whereas in general melanoma is the third most common lesion. Histopathologic evaluation is crucial to avoid over diagnosis of melanoma and to provide reassurance to patients in benign lesions. References 1. Marks R, editor. Roxburgh s Common Skin Disease.17 th ed. London: Arnold; 2003. p.1-11. 2. Walter MF, Morris HC, Humphreys E et al. Protocol for the Mole Mate UK Trial: a randomised controlled trial of the Mole Mate system in the management of pigmented skin lesions in primary care. BMC Fam Pract. 2010;11:36. doi: 10.1186/1471-2296- 11-36. 3. Barnhills LR, Rabinovitz H. Benign melanocytic neoplasms. In: Bolognia 287

LJ, Jorizzo JL, Rapini RP, editors. Dermatology, Vol 2. Madrid, Spain: Mosby Elsevier; 2008. p. 1713-44. 4. Laishram RS, Banerjee A, Pukhrambam P et al. Pattern of skin malignancies in Manipur, India: a 5-year histopathological review. J Pak Assoc Dermatol. 2010;20:128-32. 5. Crasta J, Rameshkumar K. Pigmented lesions of nonmelanocytic origin- a pathological perspective. Indian J Dermatol. 2002;47:84-7. 6. Andersen WK, Silvers DN. Melanoma? It can t be melanoma- a subset of melanomas that defies clinical recognition. JAMA. 1991;266:3463-5. 7. Mackie R, English J, Aitchison T et al. The number and distribution of benign pigmented moles (melanocytic naevi) in a healthy British population. Br J Dermatol. 1985;113:167-74. 8. Nicholls EM. Development and elimination of pigmented moles and the anatomical distribution of primary malignant melanoma. Cancer. 1973;32:191-5. 9. Rubegni P, Cevenini G, Burroni M et al. Automated diagnosis of pigmented skin lesions. Int J Cancer. 2002;101:576-80. 10. Schafer T, Merkl J, Klemm E et al. The epidemiology of nevi and signs of skin aging in the adult general population: Results of the KORA-Survey 2000. J Invest Dermatol. 2006;126:1490-6. 11. Menzies SW, Westerhoff K, Rabinovitz H et al. Surface microscopy of pigmented basal cell carcinoma. Arch Dermatol. 2000;136:1012-6. 12. Marks R. Epidemiology of melanoma. Clin Exp Dermatol. 2000;25:459-63. 13. Lens MB, Dawes M. Global perspective of contemporary epidemiological trends of cutaneous malignant melanoma. Br J Dermatol. 2004;150:179-85. 14. Sharma K, Mohanti KB, Rath KG. Malignant melanoma: A retrospective series from a regional cancer centre in India. J Cancer Res Ther. 2009;5:173-80. 15. Chang DT, Amdur RJ, Morris CG et al. Adjuvant radiotherapy for cutaneous melanoma: Comparing hypofractionation to conventional fractionation. Int J Radiat Oncol Biol Phys. 2006;66:1051-5. 16. Wanebo HJ, Cooper PH, Young DV. Prognostic factors in head and neck melanoma. Effect of lesion location. Cancer. 1988;62:831-7. 17. Chopra A, Walia RL, Gupta S et al. Nodular malignant melanoma secondary to carcinoma rectum. Indian J Dermatol Venereol Leprol. 1997;63:327-9. 18. Khandpur S, Reddy BS. Acral lentiginous melanoma. Indian J Dermatol Venereol Leprol. 2000;66:37-8. 19. Malony M, Jones D, Sexton F. Pigmented basal cell carcinomainvestigation of 70 cases. J Am Acad Dermatol. 1992;27:74-8. 20. Betti R, Gualandri L, Cerri A et al. Clinical features and histologic pattern analysis of pigmented basal cell carcinoma in Italian population. J Dermatol. 1997;25:691-4. 21. Bleehen S. Pigmented basal cell epithelioma. Br J Dermatol. 1975;93:361-76. 22. Ohsumi T, Seiji M. Statistical study on malignant melanoma in Japan (1970-1976).Tohoku J Exp Med. 1977;121:355-64. 288