Ömer Faruk ELMAS, Mehmet GAMSIZKAN, Asuman KİLİTCİ, Necmettin AKDENİZ

Melanocytes as the source of the increased melanisation in pigmented epithelial tumours: a holistic approach

Background/aim: We aimed to elucidate the causes of the increased melanisation in basal cell carcinoma (BCC) and seborrheic keratosis (SK), and the role of melanocytes in this process. Materials and methods: This study was a retrospective-cohort study conducted in the pathology department of a university hospital between January 2019 and October 2020. Forty-nine SK and 30 pigmented BCC were included in our study. SRY-box transcription factor 10 (SOX10), CD68, and Masson–Fontana staining was used for analysis in all samples. A representative section of each specimen was photographed under ×400 magnification to facilitate the assessments of the morphology of the melanocytes and their following morphometric parameters: density, nuclear diameter, and distribution. The density of pigmented keratinocytes in the lesional epidermis was scored. The nuclear diameters of melanocytes located in the nonlesional epidermis, the density of the melanophages, and the presence or absence of ulceration and solar elastosis were also recorded. Results: The morphometric findings confirmed a statistically significant increase in melanocyte density in the BCC group compared with that in the SK group (p < 0.001). Moreover, the nuclear minor diameters in the melanocytes of the BCC sections were significantly higher than those in the SK specimens (p < 0.001). The epidermal melanocytes were distributed diffusely in almost all BCC specimens (96.7%), whereas they were mainly limited to the basal layer in the majority of the SK sections (59.2%). The number of epidermal melanised keratinocytes with a score of 3 was significantly higher in the SK group (n = 31; 63.2%) than in the BCC group (n = 6; 20%) (p = 0.001), and they were the main cells representing the pigmented appearance of the tumours. No significant difference was found between both tumour groups in terms of their melanophage density scores (p = 0.206). Conclusion: This study is the first step towards an objective quantification of the melanocytes in pigmented epithelial tumours and may provide a morphological background for future studies on these skin lesions.

PDF

___

1. Ali SA, Naaz I. Biochemical aspects of mammalian melanocytes and the emerging role of melanocyte stem cells in dermatological therapies. International Journal of Health Sciences 2018; 12 (1): 69-76.
2. Manaka I, Kadono S, Kawashima M, Kobayashi T, Imokawa G. The mechanism of hyperpigmentation in seborrhoeic keratosis involves the high expression of endothelin‐ converting enzyme‐1α and TNF‐α, which stimulate secretion of endothelin 1. British Journal of Dermatology 2001; 145 (6): 895-903. doi: 10.1046/j.1365-2133.2001.04521.x
3. Seiberg M. Keratinocyte–melanocyte interactions during melanosome transfer. Pigment Cell Research 2001; 14 (4): 236- 242. doi: 10.1034/j.1600-0749.2001.140402.x
4. Hara M, Yaar M, Byers HR, Goukassian D, Gonsalves J et al. Kinesin participates in melanosomal movement along melanocyte dendrites. Journal of investigative dermatology 2000; 114 (3): 438-443. doi: 10.1046/j.1523-1747.2000.00894.x
5. Agnarsdottir M, Sooman L, Bolander A, Strömberg S, Rexhepaj E et al. SOX10 expression in superficial spreading and nodular malignant melanomas. Melanoma Research 2010; 20 (6): 468- 478. doi: 10.1097/CMR.0b013e3283403ccd
6. Gamsizkan M, Buyucek S, Coskun SK, Sungur MA, Ozlu E et al. Can Numeric Maturation Value Be Used as a Prognostic Indicator and Diagnostic Tool in Cutaneous Melanomas? A Morphometric Study. Analytical and Quantitative Cytopathology and Histopathology 2019; 41 (5): 177-183.
7. Kilitçi A, Elmas ÖF, Demirbaş A, Gamsızkan M, Atasoy M et al. Refining diagnosis is the prerequisite for the correct treatment: The cytodiagnostic utility of SOX10 in the diagnosis of metastatic melanoma. Dermatologic Therapy 2020; e14657. doi: 10.1111/dth. 14657
8. Patterson JW. Weedon’s Skin Pathology E-Book. 4th ed. Philadelphia, PA, USA: Churchill Livingstone; 2016.
9. Konomi K, Imayama S, Nagae S, Terasaka R, Chijiwa K et al. Melanocyte chemotactic factor produced by skin metastases of a breast carcinoma. Journal of Surgical Oncology 1992; 50 (1): 62-66. doi: 10.1002/jso.2930500117
10. Akasaka T. Mobility of melanocytes and melanoma cells (in Japanese). DiagnosticTreatment Dermatology 1999; 21: 107.
11. Slominski A, Paus R, Wortsman J. On the potential role of proopiomelanocortin in skin physiology and pathology. Molecular and cellular endocrinology 1993; 93 (1): C1-C6. doi: 10.1016/0303-7207(93)90131-3
12. Lao LM, Kumakiri M, Kiyohara T, Kuwahara H, Ueda K. Sub‐ populations of melanocytes in pigmented basal cell carcinoma: a quantitative, ultrastructural investigation. Journal of Cutaneous Pathology 2001; 28 (1): 34-43. doi: 10.1034/j.1600- 0560.2001.280104.x
13. Medalie DA, Tompkins RG, Morgan JR. Characterization of a composite tissue model that supports clonal growth of human melanocytes in vitro and in vivo. Journal of Investigative Dermatology 1998; 111 (5): 810-816. doi: 10.1046/j.1523- 1747.1998.00368.x
14. Kippenberger S, Bernd A, Bereiter-Hahn J, Ramirez-Bosca A, Kaufmann R. The mechanism of melanocyte dendrite formation: the impact of differentiating keratinocytes. Pigment Cell Research 1998; 11 (1): 34-37. doi: 10.1111/j.1600- 0749.1998.tb00708.x
15. Gordon PR, Mansur CP, Gilchrest BA. Regulation of human melanocyte growth dendricity and melanization by keratinocyte derived factors. Journal of Investigative Dermatology 1989; 92 (4): 565-572. doi: 10.1111/1523-1747.ep12709595
16. Florell SR, Zone JJ, Gerwels JW. Basal cell carcinomas are populated by melanocytes and Langerhan’s cells. The American journal of dermatopathology 2001; 23 (1): 24-28.
17. Azzopardi JG, Eusebi V. Melanocyte colonization and pigmentation of breast carcinoma. Histopathology 1977; 1 (1): 21-30. doi: 10.1111/j.1365-2559.1977.tb01641.x
18. Bourlond A. Pigmented epidermotropic metastasis of a breast carcinoma. Dermatology 1994; 189: 46-49. doi: 10.1159/000246990
19. Poiares-Baptista A, De Vasconcelos AA. Cutaneous pigmented metastasis from breast carcinoma simulating malignant melanoma. International Journal of Dermatology 1988; 27 (2): 124-125. doi: 10.1111/j.1365-4362.1988.tb01291.x
20. Sau P, Solis J, Lupton GP, James WD. Pigmented breast carcinoma. A clinical and histopathologic simulator of malignant melanoma. Archives of Dermatology 1989; 125 (4): 536-539. doi:10.1001/archderm.1989.01670160084016
21. Garcia-Solano J, Garcia-Rojo B, Sanchez-Sanchez C, Montalban-Romero MS, Perez-Guillermo M. Basal cell carcinoma: cytologic and immunocytochemical findings in fineneedle aspirates. Diagnostic Cytopathology 1998;18 (6):403- 408. doi: 10.1002/(SICI)1097-0339(199806)18:6<403::AIDDC4>3.0.CO;2-9
22. Bhawan J. Non‐melanocytic mimics of melanocytic neoplasms. Histopathology 2012; 60 (5): 715-730. doi: 10.1111/j.1365-2559.2011.03815.x
23. Deppe R, Pullmann H, Steigleder GK. Dopa-positive cells and melanin in basal cell epithelioma (BCE). Archives of Dermatological Research 1976; 256: 79.
24. Kamil ZS, Tong LCB, Habeeb AA, Ghazarian D. Non Melanocytic Mimics of Melanoma Part-I: Intraepidermal Mimics. Journal of Clinical Pathology 2009; 62 (2): 120-127. doi: 10.1136/jcp.2008.060863
25. Brankov N, Prodanovic EM, Hurley MY. Pigmented basal cell carcinoma: increased melanin or increased melanocytes? Journal of Cutaneous Pathology 2016; 43 (12): 1139-1142. doi: 10.1111/cup.12819