Dermatopathology Clues in Pigmentary Disorders

  • Riti Bhatia
  • M. Ramam
Part of the Updates in Clinical Dermatology book series (UCD)


Pigmentary disorders are a group of diseases characterized by a reduction, increase or alteration of pigment in the skin. On biopsy, hypopigmented lesions typically show a reduction of melanin in basal epidermal cells with an accompanying reduction in the number of melanocytes in some conditions. Hyperpigmented lesions show an increase in basal layer melanin with some melanophages in the upper dermis. However, these findings are shared by many different disorders and are not of much diagnostic value.

The focus in this chapter is on histopathological clues that can help make a diagnosis. These clues fall into three groups. There may be abnormalities related to components of the pigment system (melanocytes, melanin) as seen in dermal melanocytosis, vitiligo, carbon baby syndrome and hereditary melanosome transfer disorders. The second group includes pigmentary disorders with non-melanin pigment in the skin such as tattoos, pigmented purpuric dermatoses, talon noir, argyria, drug-induced pigmentation and ochronosis. The third and largest group consists of disorders with findings not related to the pigmentary system but distinctive enough to allow a diagnosis. These include lichen planus pigmentosus, connective tissue disorders, lichen sclerosus, Dowling-Degos disease, epidermodysplasia verruciformis, indeterminate leprosy and clear cell papulosis, among others.


Dermatopathology clues Melanocytosis Melanocytes Melanin Melanophages Hyperpigmentation Hypopigmentation Skin pigmentation 


  1. 1.
    Hirayama T, Suzuki T. A new classification of Ota’s naevus based on histopathological features. Dermatologica. 1991;183:169–72.CrossRefGoogle Scholar
  2. 2.
    Kang W, Lee E, Choi GS. Treatment of Ota’s nevus by Q-switched alexandrite laser: therapeutic outcome in relation to clinical and histopathological findings. Eur J Dermatol. 1999;9:639–43.PubMedGoogle Scholar
  3. 3.
    Hori Y, Ouhara K, Miimura M, et al. Electron microscopy: ultrastructural observations of the extracellular sheath of dermal melanocytes in nevus of Ota. Am J Dermatopathol. 1982;4:245–51.CrossRefGoogle Scholar
  4. 4.
    Page DG, Swirsky JA, Kaugars GE. Nevus of Ota with associated palatal involvement. Oral Surg Oral Med Oral Pathol. 1985;59:282–4.CrossRefGoogle Scholar
  5. 5.
    Wilcox JC. Melanomatosis of skin and central nervous system. Am J Dis Child. 1939;57:391.CrossRefGoogle Scholar
  6. 6.
    Rathi SK. Bilateral nevus of ota with oral mucosal involvement. Indian J Dermatol Venereol Leprol. 2002;68:104.PubMedGoogle Scholar
  7. 7.
    Sun CC, Lü YC, Lee EF, Nakagawa H. Naevus fusco-caeruleus zygomaticus. Br J Dermatol. 1987;1:545–53.CrossRefGoogle Scholar
  8. 8.
    Hori Y, Kawashima M, Oohara K, Kukita A. Acquired, bilateral naevus of Ota-like macules. J Am Acad Dermatol. 1984;10:961–4.CrossRefGoogle Scholar
  9. 9.
    Bhat RM, Pinto HP, Dandekeri S, Ambil SM. Acquired bilateral nevus of ota-like macules with mucosal involvement: a new variant of Hori’s nevus. Indian J Dermatol. 2014;59:293–6.CrossRefGoogle Scholar
  10. 10.
    Barnhill RL. Dermal melanocytoses, blue nevi, and related conditions. In: Barnhill RL, editor. Pathology of melanocytic nevi and melanoma. Boston: Butterworth-Heinemann; 1995. p. 131–52.Google Scholar
  11. 11.
    Kerl H, Massi D. Melanotic macules, simple lentigo and lentiginous melanocytic naevus. In: Leboit PE, editor. Pathology and genetics of skin tumours. Lyon: IARC; 2006. p. 103–4.Google Scholar
  12. 12.
    Wayte DM, Helwig EB. Halo nevi. Cancer. 1968;22:69–90.CrossRefGoogle Scholar
  13. 13.
    Menasche G, Ho CH, Sanal O, Feldmann J, Tezcan I, Ersoy F, et al. Griscelli syndrome restricted to hypopigmentation results from a melanophilin defect (GS3) or a MYO5A F-exon deletion (GS1). J Clin Invest. 2003;112:450–6.CrossRefGoogle Scholar
  14. 14.
    Menasche G, Feldmann J, Huodusse A, Desaymard C, Fischer A, Goud B, et al. Biochemical and functional characterization of Rab27a mutations occurring in Griscelli syndrome patients. Blood. 2003;101:2736–42.CrossRefGoogle Scholar
  15. 15.
    Pastural E, Barrat FJ, Dufoureq-Lagelouse R, Certain S, Sanal O, Jabade N, et al. Griscelli disease maps to chromosome 15q21 and is associated with mutations in the myosin Va gene. Nat Genet. 1997;16:289–92.CrossRefGoogle Scholar
  16. 16.
    Griscelli C, Durandy A, Guy Grand D, Daguillard F, Herzog C, Prunieras M. A syndrome associating partial albinism and immunodeficiency. Am J Med. 1978;65:691–702.CrossRefGoogle Scholar
  17. 17.
    Sanal O, Yel L, Kucukali T, Gilbert-Barnes E, Tardieu M, Texcan I, et al. An allelic variant of Griscelli disease: presentation with severe hypotonia, mental-motor retardation, and hypopigmentation consistent with Elejalde syndrome (neuroectodermal melanolysosomal disorder). J Neurol. 2000;247:570–2.CrossRefGoogle Scholar
  18. 18.
    LePoole IC, Van den Wijingaard RM, Westerhof W, Dutrieux RP, Das PK. Presence or absence of melanocytes in vitiligo lesions: an immunohistochemical investigation. J Invest Derma. 1993;100:816–22.CrossRefGoogle Scholar
  19. 19.
    Sharquie KE, Mehenna SH, Naji AA, Al-Azzawi H. Inflammatory changes in vitiligo: stage I and II depigmentation. Am J Dermatopathol. 2004;26:108–12.CrossRefGoogle Scholar
  20. 20.
    Attili VR, Attili SK. Lichenoid inflammation in vitiligo--a clinical and histopathologic review of 210 cases. Int J Dermatol. 2008;47:663–9.CrossRefGoogle Scholar
  21. 21.
    Wańkowicz-Kalińska A, van den Wijngaard RM, Tigges BJ, Westerhof W, Ogg GS, Cerundolo V, et al. Immunopolarization of CD4+ and CD8+ T cells to Type-1-like is associated with melanocyte loss in human vitiligo. Lab Investig. 2003;83:683–95.CrossRefGoogle Scholar
  22. 22.
    Yaghoobi R, Omidian M, Bagherani N. Vitiligo: a review of the published work. J Dermatol. 2011;38:419–31.CrossRefGoogle Scholar
  23. 23.
    Moellmann G, Klein-Angerer S, Scollay DA, Nordlund JJ, Lerner AB. Extracellular granular material and degeneration of keratinocytes in the normally pigmented epidermis of patients with vitiligo. J Invest Dermatol. 1982;79:321–30.CrossRefGoogle Scholar
  24. 24.
    Ruiz-Maldonado R, Tamayo L, Fernandez-Diaz J. Universal acquired melanosis: the carbon baby. Arch Dermatol. 1978;114:775–8.CrossRefGoogle Scholar
  25. 25.
    Abdallah MA, Abdallah MMA, Abdallah MA-R. Foreign body reactions. In: Bolognia JL, Jorizzo JL, Schaffer JV, editors. Dermatology. 3rd ed. England: Saunders Elsevier; 2012. p. 1573–83.Google Scholar
  26. 26.
    Ploysangam T, Breneman DL, Mutasim DF. Cutaneous pseudolymphomas. J Am Acad Dermatol. 1998;38:877–95.CrossRefGoogle Scholar
  27. 27.
    Slater DN, Durrant TE. Tattoos: light and transmission electron microscopy studies with x-ray microanalysis. Clin Exp Dermatol. 1984;9:1365–2230.CrossRefGoogle Scholar
  28. 28.
    Angeloni VL, Salasche SJ, Ortiz R. Nail, skin, and scleral pigmentation induced by minocycline. Cutis. 1987;40:229–33.PubMedGoogle Scholar
  29. 29.
    Dereure O. Drug-induced skin pigmentation. Epidemiology, diagnosis and treatment. Am J Clin Dermatol. 2001;2:253–62.CrossRefGoogle Scholar
  30. 30.
    Job CK, Yoder L, Jacobson RR, Hastings RC. Skin pigmentation from clofazimine therapy in leprosy patients: a reappraisal. J Am Acad Dermatol. 1990;23:236–41.CrossRefGoogle Scholar
  31. 31.
    Trimble JW, Mendelson DS, Fetter BF, Ingram P, Gallagher JJ, Shelburne JD. Cutaneous pigmentation secondary to amiodarone therapy. Arch Dermatol. 1983;119:914–8.CrossRefGoogle Scholar
  32. 32.
    Argenyi ZB, Finelli L, Bergfeld WF, Tuthill RJ, McMahon JT, Ratz JL, et al. Minocycline-related cutaneous hyperpigmentation as demonstrated by light microscopy, electron microscopy and X-ray energy spectroscopy. J Cutan Pathol. 1987;14:176–80.CrossRefGoogle Scholar
  33. 33.
    Johansson EA, Kanerva L, Niemi KM, Lakomaa EL. Generalised argyria with low ceruloplasmin and copper levels in the serum. A case report with clinical and microscopic findings and a trial of penicillamine treatment. Clin Exp Dermatol. 1982;7:169–76.CrossRefGoogle Scholar
  34. 34.
    Pariser RJ. Generalized Argyria clinicopathologic features and histochemical studies. Arch Dermatol. 1978;114:373–7.CrossRefGoogle Scholar
  35. 35.
    Hori Y, Miyazawa S. Argyria: electron microscope and x-ray microanalysis. J Electron Microsc (Tokyo). 1977;26:193–201.Google Scholar
  36. 36.
    al-Talib RK, Wright DH, Theaker JM. Orange-red birefringence of gold particles in paraffin wax embedded sections: an aid to the diagnosis of chrysiasis. Histopathology. 1994;24:176–8.CrossRefGoogle Scholar
  37. 37.
    Zala L, Hunziker T, Braathen LR. Pigmentation following long-term bismuth therapy for pneumatosis cystoides intestinalis. Dermatology. 1993;187:288–9.CrossRefGoogle Scholar
  38. 38.
    Crissey JT, Peachy JC. Calcaneal petechiae. Arch Dermatol. 1961;83:501.CrossRefGoogle Scholar
  39. 39.
    Hafner J, Haenseler E, Ossent P, et al. Benzidine stain for the histochemical detection of hemoglobin in splinter hemorrhage (subungual hematoma) and black heel. Am J Dermatopathol. 1995;17:362–7.CrossRefGoogle Scholar
  40. 40.
    Cox NH, Piette WW. In: Burns DA, Breathnach SM, Cox NH, Griffiths C, editors. Textbook of dermatology, vol. 3. 8th ed. Oxford: Blackwell Scientific Publications; 1998. p. 2327–77.Google Scholar
  41. 41.
    Zawar VP, Mhaskar ST. Exogenous ochronosis following hydroquinone for melasma. J Cosmet Dermatol. 2004;3:234–6.CrossRefGoogle Scholar
  42. 42.
    Phillips JI, Isaacson C, Carman H. Ochronosis in black South Africans who used skin lighteners. Am J Dermatopathol. 1986;8:14–21.CrossRefGoogle Scholar
  43. 43.
    Albers SE, Brozena SJ, Glass LF, Fenske NA. Alkaptonuria and ochronosis: case report and review. J Am Acad Dermatol. 1992;27:609–14.CrossRefGoogle Scholar
  44. 44.
    Findlay GH, Morrison JGL, Simson IW. Exogenous ochronosis and pigmented colloid milium from hydroquinone bleaching creams. Br J Dermatol. 1975;93:613–22.CrossRefGoogle Scholar
  45. 45.
    Khunger N, Kandhari R. Dermoscopic criteria for differentiating exogenous ochronosis from melasma. Indian J Dermatol Venereol Leprol. 2013;79:819–21.CrossRefGoogle Scholar
  46. 46.
    Bhutani LK, Bedi TR, Pandhi RK, Nayak NC. Lichen planus pigmentosus. Dermatologica. 1974;149:43–50.CrossRefGoogle Scholar
  47. 47.
    Seo JK, Lee HJ, Lee D, Choi JH, Sung H-S. A case of linear lichen planus pigmentosus. Ann Dermatol. 2010;22:323–5.CrossRefGoogle Scholar
  48. 48.
    Kumar YH, Babu AR. Segmental lichen planus pigmentosus: an unusual presentation. Indian Dermatol Online J. 2014;5:157–9.CrossRefGoogle Scholar
  49. 49.
    Laskaris GC, Papavasiliou SS, Bovopoulou OD, Nicolis GD. Lichen planus pigmentosus of the oral mucosa: a rare clinical variety. Dermatologica. 1981;162:61–3.CrossRefGoogle Scholar
  50. 50.
    Vega ME, Waxtein L, Arenas R, Hojyo T, Dominguez-Soto L. Ashy dermatosis and lichen planus pigmentosus: a clinicopathologic study of 31 cases. Int J Dermatol. 1992;31:90–4.CrossRefGoogle Scholar
  51. 51.
    Kanwar AJ, Dogra S, Handa S, Parsad D, Radotra BD. A study of 124 Indian patients with lichen planus pigmentosus. Clin Exp Dermatol. 2003;28:481–5.CrossRefGoogle Scholar
  52. 52.
    Kim YC, Davis MD, Schanbacher CF, Su WP. Dowling-Degos disease (reticulate pigmented anomaly of the flexures): a clinical and histopathologic study of 6 cases. J Am Acad Dermatol. 1999;40:462–7.CrossRefGoogle Scholar
  53. 53.
    Singh S, Khandpur S, Verma P, Singh M. Follicular Dowling Degos disease: a rare variant of an evolving dermatosis. Indian J Dermatol Venereol Leprol. 2013;79:802–4.CrossRefGoogle Scholar
  54. 54.
    Kanwar AJ, Kaur S, Rajagopalan M. Reticulate acropigmentation of Kitamura. Int J Dermatol. 1990;29:217–9.CrossRefGoogle Scholar
  55. 55.
    Lestringant GG, Masouyé I, Frossard PM, Adeghate E, Galadari IH. Co-existence of leukoderma with features of Dowling-Degos disease: reticulate acropigmentation of Kitamura spectrum in five unrelated patients. Dermatology. 1997;195:337–43.CrossRefGoogle Scholar
  56. 56.
    Hanneken S, Rütten A, Pasternack SM, Eigelshoven S, El Shabrawi-Caelen L, Wenzel J, et al. Systematic mutation screening of KRT5 supports the hypothesis that Galli-Galli disease is a variant of Dowling-Degos disease. Br J Dermatol. 2010;163:197–200.PubMedGoogle Scholar
  57. 57.
    Grosshans E, Geiger JM, Hanau D, Jelen G, Heid E. Early pigmentary changes in dowling-degos’ disease. J Cutan Pathology. 1984;7:77–87.CrossRefGoogle Scholar
  58. 58.
    Fajardo TT. Indeterminate leprosy: a 3 year study, clinical observations. Int J Lepr. 1971;39:94–5.Google Scholar
  59. 59.
    Vargas-Ocampo F. Pityriasis alba: a histologic study. Int J Dermatol. 1993;32:870–3.CrossRefGoogle Scholar
  60. 60.
    Copeman PWM, Wilson-Jones EWJ. Pigmented hairy epidermal nevus (Becker). Arch Dermatol. 1965;92:249–51.CrossRefGoogle Scholar
  61. 61.
    Khaitan BK, Manchanda Y, Mittal R, Singh MK. Multiple Becker’s naevi: a rare presentation. Acta Derm Venereol. 2001;81:374–5.CrossRefGoogle Scholar
  62. 62.
    Alhusayen R, Kanigsberg N, Jackson R. Becker nevus on the lower limb: case report and review of the literature. J Cutan Med Surg. 2008;12:31–4.PubMedGoogle Scholar
  63. 63.
    Angelo C, Grosso MG, Stella P, et al. Becker’s nevus syndrome. Cutis. 2001;68:123–4.PubMedGoogle Scholar
  64. 64.
    Matsuoka LY, Wortsman J, Goldman J. Acanthosis nigricans. Clin Dermatol. 1993;11:21–5.CrossRefGoogle Scholar
  65. 65.
    Joshi R. Idiopathic eruptive macular pigmentation with papillomatosis: report of nine cases. Indian J Dermatol Venereol Leprol. 2007;73:402–5.CrossRefGoogle Scholar
  66. 66.
    Weedon D, Haneke E, Martinka M, et al. Acanthomas. In: Leboit PE, editor. Pathology and genetics of skin tumours. Lyon: IARC; 2006. p. 39–47.Google Scholar
  67. 67.
    Kurban AK, Malak JA, Afifi AK, Mire J. Primary localized macular cutaneous amyloidosis: histochemistry and electron microscopy. Br J Dermatol. 1971;85:52–60.CrossRefGoogle Scholar
  68. 68.
    Brownstein MH, Hashimoto K, Greenwald G. Biphasic amyloidosis: link between macular and lichenoid forms. Br J Dermatol. 1973;88:25–9.CrossRefGoogle Scholar
  69. 69.
    Moriwaki S, Nishigori C, Horiguchi Y, Imamura S, Toda K, Takebe H. Amyloidosis cutis dyschromica: DNA repair reduction in the cellular response to UV light. Arch Dermatol. 1992;128:966–70.CrossRefGoogle Scholar
  70. 70.
    Ngo JT, Trotter MJ, Haber RM. Juvenile-onset hypopigmented mycosis fungoides mimicking vitiligo. J Cutan Med Surg. 2009;13:230–3.CrossRefGoogle Scholar
  71. 71.
    Das JK, Gangopadhyay AK. Mycosis fungoides with unusual vitiligo-like presentation. Indian J Dermatol Venereol Leprol. 2004;70:304–6.PubMedGoogle Scholar
  72. 72.
    Werner B, Brown S, Ackerman AB. Hypopigmented mycosis fungoides is not always mycosis fungoides! Am J Dermatopathol. 2005;27:56–67.CrossRefGoogle Scholar
  73. 73.
    Attili VR, Attili SK. Vitiligoid lichen sclerosus: a reappraisal. Indian J Dermatol Venereol Leprol. 2008;74:118–21.CrossRefGoogle Scholar
  74. 74.
    Almeida HL Jr, Bicca Ede B, Breunig Jde A, Rocha NM, Silva RM. Scanning electron microscopy of lichen sclerosus. An Bras Dermatol. 2013;88:247–9.CrossRefGoogle Scholar
  75. 75.
    Elbendary A, Valdebran M, Parikh K, et al. Polarized microscopy in lesions with altered dermal collagen. Am J Dermatopathol. 2016;38:593–7.CrossRefGoogle Scholar
  76. 76.
    De Villiers WJ, Jordaan HF, Bates W. Systemic sclerosis sine scleroderma presenting with vitiligo-like depigmentation and interstitial pulmonary fibrosis. Clin Exp Dermatol. 1992;17:127–31.CrossRefGoogle Scholar
  77. 77.
    Smith ES, Hallman JR, DeLuca AM, Goldenberg G, Jorizzo JL, Sangueza OP. Dermatomyositis: a clinicopathological study of 40 patients. Am J Dermatopathol. 2009;31:61.CrossRefGoogle Scholar
  78. 78.
    Lutzner MA, Blanchet-Bardon C, Orth G. Clinical observations, virologic studies, and treatment trials in patients with epidermodysplasia verruciformis, a disease induced by specific human papillomaviruses. J Invest Dermatol. 1984;83:18s–25s.CrossRefGoogle Scholar
  79. 79.
    Yabe Y, Sadakane HJ. The virus of epidermodysplasia verruciformis: electron microscopic and fluorescent antibody studies. J Invest Dermatol. 1975;65:324–30.CrossRefGoogle Scholar
  80. 80.
    Elewski BE, Hughey LE, Sobera JO, Hay R. Fungal diseases. In: Bolognia JL, Jorizzo JL, Schaffer JV, editors. Dermatology. 3rd ed. England: Saunders Elsevier; 2012. p. 1251–84.Google Scholar
  81. 81.
    Landau M, Krafchik BR. The diagnostic value of café-au-lait macules. J Am Acad Dermatol. 1999;40:877–90.CrossRefGoogle Scholar
  82. 82.
    Pandhi RK, Bedi TR, Bhutani LK. Leucoderma in early syphilis. Br J Vener Dis. 1977;53:19–22.PubMedPubMedCentralGoogle Scholar
  83. 83.
    Fiumara NJ, Cahn T. Leukoderma of secondary syphilis: two case reports. Sex Transm Dis. 1982;9:140–2.CrossRefGoogle Scholar
  84. 84.
    Miranda MF, Bittencourt Mde J, Lopes Ida C, Cumino Sdo S. Leucoderma syphiliticum: a rare expression of the secondary stage diagnosed by histopathology. An Bras Dermatol. 2010;85:512–5.CrossRefGoogle Scholar
  85. 85.
    Frithz A, Lagerholm B, Kaaman T. Leukoderma syphiliticum: ultrastructural observations on melanocyte function. Acta Derm Venereol. 1982;62:521–5.PubMedGoogle Scholar
  86. 86.
    Kuo TT, Chan HL, Hsueh S. Clear cell papulosis of the skin. A new entity with histogenetic implications for cutaneous Paget’s disease. Am J Surg Pathol. 1987;11:827–34.CrossRefGoogle Scholar
  87. 87.
    Kumarasinghe SPW, Chin GY. Clear cell papulosis of the skin a case report from Singapore. Arch Pathol Lab Med. 2004;128:e149–52.PubMedGoogle Scholar
  88. 88.
    Kim YC, Mehregan DA, Bang D. Clear cell papulosis: an immunohistochemical study to determine histogenesis. J Cutan Pathol. 2002;29:11–4.CrossRefGoogle Scholar
  89. 89.
    Gupta V, Bhatia R, Ramam M, Khanna N. Hypopigmented macules and papules following the lines of Blaschko: a novel variant of Darier’s disease. Int J Dermatol. 2016;55:e623–5.CrossRefGoogle Scholar
  90. 90.
    Rowley MJ, Nesbitt LT Jr, Carrington PR, Espinoza CG. Hypopigmented macules in acantholytic disorders. Int J Dermatol. 1995;34:390–2.CrossRefGoogle Scholar
  91. 91.
    Tharp MD. Mastocytosis. In: Bolognia JL, Jorizzo JL, Schaffer JV, editors. Dermatology. 3rd ed. England: Saunders Elsevier; 2012. p. 1993–2002.Google Scholar
  92. 92.
    Clayton R, Breathnach A, Martin B, Feiwel M. Hypopigmented sarcoidosis in the negro. Report of eight cases with ultrastructural observations. Br J Dermatol. 1977;96:119–25.CrossRefGoogle Scholar
  93. 93.
    Ackerman AB, De Viragh PA, Chonchitnant N. Neoplasms with follicular differentiation. Philadelphia: Lea&Febiger; 1995. p. 553.Google Scholar

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© Government of India 2018

Authors and Affiliations

  • Riti Bhatia
    • 1
  • M. Ramam
    • 1
  1. 1.Department of Dermatology and VenereologyAll India Institute of Medical SciencesNew DelhiIndia

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