Relationship Between Mast Cell Density and Various Histological Features in Melanocytic Lesions

  • Blagjica Lazarova Department of Pathology, Clinical Hospital, Faculty of Medical Sciences, Goce Delcev University,2000 Shtip, Republic of North Macedonia
  • Gordana Petrushevska Institute of pathology, Faculty of Medicine, Ss. Cyril and Methodius University, Skopje, Republic of North Macedonia
  • Dzengis Jashar Department of Histopathology and Cytology, Clinical Hospital Acibadem-Sistina, Skopje, North Macedonia
  • Zdenka Stojanovska Faculty of Medical Sciences, Goce Delcev University, Shtip, Republic of North Macedonia
DOI: https://doi.org/10.5937/scriptamed56-61302
Keywords: Mast cells, Melanocytic lesions, Nevus, pigmented, Skin, Secondary

Abstract


Background/Aim: Mast cells, derived from multipotent hematopoietic progenitors in the bone marrow, are immune cells typically found in varying concentrations within melanocytic lesions. Aim of this study was to investigate mast cell density (MCD) in 182 melanocytic lesions, with a particular focus on its association with demographic and histopathological characteristics.

Methods: MCD and secondary changes in melanocytic lesions were assessed histopathologically using paraffin-embedded tissue samples analysed under a Nikon Eclipse E400 microscope.

Results: MCD was significantly higher in lesions from females compared to males and in lesions located on the head and neck compared to those on the arm, trunk and leg. Nevi exhibited higher MCD than melanomas, with marked differences observed among specific lesion types. Histopathological analysis revealed that lesions devoid of clear cells and those exhibiting an angioadnexocentric pattern had significantly elevated MCDs. Furthermore, lesions characterised by prominent elastic fibres, mucin deposition and certain adjacent structural interactions demonstrated increased MCDs.

Conclusion: These findings underscore the complexity of mast cell functions in melanocytic lesions, offering valuable insights that may enhance diagnostic and therapeutic strategies.

References

Kaszuba A, Sławińska M, Żółkiewicz J, Sobjanek M, Nowicki RJ, Lange M. Mastocytosis and skin cancer: the current state of knowledge. Int J Mol Sci. 2023;24(12):9840. doi:10.3390/ijms24129840.

Ribatti D, Tamma R, Annese T, Crivellato E. The role of mast cells in human skin cancers. Clin Exp Med. 2021 Aug;21(3):355-360. doi: 10.1007/s10238-021-00688-x.

Segura-Villalobos D, Ramírez-Moreno IG, Martínez-Aguilar M, Ibarra-Sánchez A, Muñoz-Bello JO, Anaya-Rubio I, et al. Mast cell-tumor interactions: molecular mechanisms of recruitment, intratumoral communication and potential therapeutic targets for tumor growth. Cells. 2022;11(3):349. doi:10.3390/cells11030349.

Siiskonen H, Poukka M, Bykachev A, Tyynelä-Korhonen K, Sironen R, Pasonen-Seppänen S, et al. Low numbers of tryptase+ and chymase+ mast cells associated with reduced survival and advanced tumor stage in melanoma. Melanoma Res. 2015;25(6):479–85. doi:10.1097/CMR.0000000000000192.

Noto CN, Hoft SG, DiPaolo RJ. Mast cells as important regulators in autoimmunity and cancer development. Front Cell Dev Biol. 2021;9:752350. doi:10.3389/fcell.2021.752350.

Saxena S, Singh A, Singh P. Tumor associated mast cells: biological roles and therapeuticapplications. Anat Cell Biol. 2020;53(3):245–51. doi:10.5115/acb.19.181.

Alda S, Ceausu RA, Gaje PN, Raica M, Cosoroaba RM. Mast cell: a mysterious character in skin cancer. In Vivo. 2024;38(1):58–68. doi:10.21873/invivo.13410.

Yuan Z, Li Y, Zhang S, Wang X, Dou H, Yu X, et al. Extracellular matrix remodeling in tumor progression and immune escape: from mechanisms to treatments. Mol Cancer. 2023;22(1):48. doi:10.1186/s12943-023-01744-8.

Siiskonen H, Harvima IT. Mast cell chymase is in contact with melanoma cells in vivo and it detaches melanoma cells from the substratum in vitro. Transl Cancer Res. 2022;11(12):4315–25. doi:10.21037/tcr-22-1688.

Kannen V, Grant DM, Matthews J. The mast cell-T lymphocyte axis impacts cancer: Friend or foe? Cancer Lett. 2024 Apr 28;588:216805. doi: 10.1016/j.canlet.2024.216805.

Fernandez-Flores A, Cassarino DS. Unusual histopathological patterns in melanocytic nevi with some previously undescribed patterns. Am J Dermatopathol. 2016 Mar;38(3):167-85. doi:10.1097/DAD.0000000000000381.

Tran TAN. Melanocytic nevus with elastophilic features. Am J Dermatopathol. 2022 Sep 1;44(9):677-679. doi:10.1097/DAD.0000000000002207.

Zimmermann N, Abonia JP, Dreskin SC, Akin C, Bolton S, Happel CS, et al. Developing a standardized approach for assessing mast cells and eosinophils on tissue biopsies: A Work Group Report of the AAAAI Allergic Skin Diseases Committee. J Allergy Clin Immunol. 2021 Oct;148(4):964-83. doi: 10.1016/j.jaci.2021.06.030.

Lestarevic S, Savic S, Dejanovic M, Mijovic M, Mandic P, Marjanovic D, et al. The effect of aging on mast cell density in human skin: A comparative analysis of photoexposed and photoprotected regions. Folia Morphol (Warsz). 2025 doi: 10.5603/fm.102163.

Hart PH, Grimbaldeston MA, Hosszu EK, Swift GJ, Noonan FP, Finlay-Jones JJ. Age-related changes in dermal mast cell prevalence in BALB/c mice: functional importance and correlation with dermal mast cell expression of Kit. Immunology. 1999 Nov;98(3):352-6. doi:10.1046/j.1365-2567.1999.00897.x.

Abdel Hafez SMN. Age related changes in the dermal mast cells and the associated changes in the dermal collagen and cells: A histological and electron microscopy study. Acta Histochem. 2019 Jul;121(5):619-27. doi:10.1016/j.acthis.2019.05.004.

Damsky WE, Bosenberg M. Melanocytic nevi and melanoma: unraveling a complex relationship. Oncogene. 2017 Oct 19;36(42):5771-5792. doi:10.1038/onc.2017.189.

Bahri R, Kiss O, Prise I, Garcia-Rodriguez KM, Atmoko H, Martínez-Gómez JM, et al. Human melanoma-associated mast cells display a distinct transcriptional signature characterized by an upregulation of the complement component 3 that correlates with poor prognosis. Front Immunol. 2022 May 20;13:861545. doi:10.3389/fimmu.2022.861545.

Nielsen VW, Thomsen SF. The role of the mast cell in pigmentation disorders. Pigment Int. 2021;8(2):73-5. doi:10.4103/pigmentint.pigmentint_18_21.

Fu C, Chen J, Lu J, Yi L, Tong X, Kang L, et al. Roles of inflammation factors in melanogenesis (Review). Mol Med Rep. 2020 Mar;21(3):1421-30. doi:10.3892/mmr.2020.10950.

Asaki Y, Yoshida Y, Takahashi Y, Inoue S. Histamine induces melanogenesis and morphologic changes by protein kinase A activation via H2 receptors in human normal melanocytes. J Investig Dermatol. 2000;114(2):334-42. doi:10.1046/j.1523-1747.2000.00874.x.

Katayama I, Yang L, Takahashi A, Yang F, Wataya-Kaneda M. The two faces of mast cells in vitiligo pathogenesis. Explor Immunol. 2021;1(4):269-84. doi:10.37349/ei.2021.0001.

Ribatti D, Crivellato E. Mast cells, angiogenesis, and tumour growth. Biochim Biophys Acta. 2012;1822(1):2-8. doi:10.1016/j.bbadis.2010.11.010.

Derakhshani A, Vahidian F, Alihasanzadeh M, Mokhtarzadeh A, Lotfi Nezhad P, Baradaran B. Mast cells: A double-edged sword in cancer. Immunol Lett. 2019 May;209:28-35. doi:10.1016/j.imlet.2019.03.011.

Komi DEA, Redegeld FA. Role of Mast Cells in Shaping the Tumor Microenvironment. Clin Rev Allergy Immunol. 2020 Jun;58(3):313-25. doi:10.1007/s12016-019-08753-w.

Mulloy B, Lever R, Page CP. Mast cell glycosaminoglycans. Glycoconj J. 2017 Jun;34(3):351-61. doi:10.1007/s10719-016-9749-0.

Perdiki M, Bhawan J. Mucinous changes in melanocytic nevi and review of the literature. Am J Dermatopathol. 2008 Jun;30(3):236-40. doi:10.1097/DAD.0b013e318166f452.

Stillhard A, Cazzaniga S, Borradori L, Beltraminelli H. Pushing and loss of elastic fibers are highly specific for melanoma and rare in melanocytic nevi. Arch Dermatol Res. 2019 Mar;311(2):99-107. doi:10.1007/s00403-018-1885-x.

Imokawa G. Autocrine and paracrine regulation of melanocytes in human skin and in pigmentary disorders. Pigment Cell Res. 2004 Apr;17(2):96-110. doi:10.1111/j.1600-0749.2003.00126.x.

Ribatti D, Annese T, Tamma R. Adipocytes, mast cells and angiogenesis. Rom J Morphol Embryol. 2020 Oct-Dec;61(4):1051-1056. doi:10.47162/RJME.61.4.07.

Chen Y, Klonowski PW, Lind AC, Lu D. Differentiating neurotized melanocytic nevi from neurofibromas using Melan-A (MART-1) immunohistochemical stain. Arch Pathol Lab Med. 2012 Jul;136(7):810-5. doi:10.5858/arpa.2011-0335-OA.

Yamanaka-Takaichi M, Sugawara K, Sumitomo R, Tsuruta D. The Mast Cell-SCF-CB1 Interaction Is a Key Player in Seborrheic Keratosis. J Histochem Cytochem. 2020 Jul;68(7):461-71. doi:10.1369/0022155420938031.

Published
2025/12/31
Issue
Vol. 56 No. 6 (2025): Nov-Dec
Section
Original article
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