COMMENTARY

Vitiligo: To Biopsy or Not To Biopsy?

María Eugenia Mazzei Weiss, MD

he histopathologic diagnosis of is classi- these histologic findings, it is common to find spongiosis, cally understood as the absence of mononuclear superficial perivascular inflammatory infil- T and in the skin biopsy.1 It is difficult for a trate, and melanophages in biopsies of vitiligo.3 pathologist to establish the absolute absence of melano- Given that ensuring the absence of melanocytes is cytes and melanin in a skin biopsy. Therefore, we need to central to diagnosis and melanocytes can be difficult to take into consideration many variables when we face the identify or differentiate from repositioned Langerhans possibility to biopsy a vitiligo lesion. cells in the basal layercopy with hematoxylin and eosin stain, The basis of the clinical diagnosis of vitiligo is the immunohistochemical techniques must be performed appearance of achromic lesions in periorificial and acral every time we are dealing with vitiligo biopsies. Although areas; however, sometimes it is difficult to differentiate there are no studies comparing the diagnostic value of between an achromic or hypochromic lesion. Although the different immunohistochemical techniques in vitiligo, Wood light is of great help in these circumstances, it still dihydroxyphenylalaninenot (DOPA) seems to be a good can be difficult to make the diagnosis with certainty. option, as it will only mark active melanocytes. Human In other cases, the lesions do not present a classic melanoma black 45 (HMB-45), anti-TYRP1 (Mel-5), and distribution of vitiligo, and other differential diagnoses antimelanoma gp 100 antibody (NKI/beteb) also have are considered. For example, if we see a single hypochro- been used. Some authors recommend the use of pan mel- mic or achromic lesion in a young child, then theDo main anoma because it includes 3 markers—HMB-45, tyrosi- differential diagnosis would be achromic . If there nase, and Mart-1. Currently, SRY-related HMG-box10 are multiple lesions, then we may consider progres- (SOX10) seems to be a good option, as it is a nuclear sive macular hypomelanosis, postinflammatory hypopig- marker that makes it easier to differentiate melanocytes mentation, and hypopigmented mycosis fungoides. In from pigmented keratinocytes.4 genital lesions, the differential diagnosis between initial Establishing a complete absence of melanocytes in lichen sclerosus and vitiligo also can be considered. the lesions or finding there are melanocytes but they Finally, we must always bear in mind that both sarcoid- are inactivated is key to evaluating the pathogenesis of osis and Hansen disease can appear as achromic or hypo- vitiligo and directly affects the histologic diagnosis and chromic lesions. eventually even the treatment. Le Poole et al5 used a panel The histologic diagnosisCUTIS of vitiligo in a completely of 17 monoclonal antibodies and a polyclonal antibody in constituted lesion implies the total loss of melanocytes lesions of 12 patients with vitiligo without identifying the and melanin in the epidermis. Additional histologic find- presence of melanocytes. They concluded that there are ings are described at the edge of the advanced border, no melanocytes in lesions of vitiligo.5 such as the presence of melanocytes that have increased In a subsequent study with a larger number of in size with large dendrites and lymphoid infiltrate. In per- patients, Kim et al2 found melanocytes that marked with ilesional skin, vacuolated keratinocytes and Langerhans NKI/beteb and Mart-1 in 12 of 100 patients with vitiligo. cells have increased in number and repositioned in the They also showed melanocytes by electron microscopy in basal layer, with visible degeneration of nerves and sweat lesional skin of 1 of 3 patients with vitiligo.2 Tobin et al6 glands. Lymphocytes also can be found in contact with the managed to grow melanocytes from skin with vitiligo and melanocytes.2 It is important to note that in addition to confirmed the presence of melanin in basal keratinocytes

From the Clínica Dermatológica, Hospital de Clínicas, Facultad de Medicina, Universidad de la República Oriental del Uruguay, Montevideo. The author reports no conflict of interest. Correspondence: María Eugenia Mazzei Weiss, MD, Clínica Dermatológica, Hospital de Clínicas, Av Italia 2870, Montevideo Uruguay, CP11600 ([email protected]).

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of lesions of stable vitiligo. From this evidence we can will find an infiltrate of pleomorphic lymphocytes in the conclude that the absence of melanocytes and melanin in epidermis and dermis in the former and an absence of the epidermis confirms the diagnosis of vitiligo; however, these findings in vitiligo. Finally, if we find granulomas the opposite is not true—that is, the presence of mela- in a biopsy of an achromic or hypopigmented lesion, nocytes or melanin in a skin biopsy does not rule out the we may be dealing with hypopigmented sarcoidosis or diagnosis of vitiligo. Hansen disease. Taking this information into consideration, we can It also is important to choose the best site to perform understand that if our differential diagnosis is a der- the biopsy to have the best chance at diagnosing vitiligo matosis that requires the evaluation of the number of histologically. As already described, in the edges and in melanocytes as a fundamental diagnostic clue (eg, postin- the perilesional skin we can find remnant melanocytes, flammatory ), the biopsy will probably Langerhans cells, and interphase changes that do not not be useful. On the other hand, when our differential allow us to clearly evaluate the main change that is the diagnosis has characteristic diagnostic findings indepen- loss of melanocytes and melanin. In fact, a biopsy of dent of the number of melanocytes or the presence of the edge of a vitiligo macula can lead to confusion. For melanin, the biopsy will be useful (eg, hypopigmented example, if the differential diagnosis is lichen sclerosus mycosis fungoides). and the image we see in the biopsy of the edge of a vit- Thus, we can understand why the histologic differen- iligo lesion is an interface reaction, we can interpret it as a tiation between vitiligo, , postinflammatory finding that favors lichen sclerosus. In this way, it is better hypopigmentation, and progressive macular hypopigmen- to biopsy the center of a well-constituted vitiligo lesion tation is difficult. The histology images of these 4 diseases where we have the best chance to assess the absence of may show different degrees of and melanin melanin and melanocytes. decrease, spongiosis, and in the superficial dermis melano- The vitiligo differentialcopy diagnosis can be divided into phages and mononuclear inflammatory infiltrate.7 2 groups: entities that are difficult to differentiate from Nevus depigmentosus also may generate diagnos- vitiligo histologically (ie, pityriasis alba, postinflammatory tic confusion with vitiligo. Although it is unilateral and hypopigmentation, progressive macular hypopigmenta- usually congenital, it can appear as late as 3 years of tion, nevus depigmentosus) and entities that are easily dis- age, leading to an initial clinical differential diagnosis of tinguishablenot from vitiligo histologically (ie, lichen sclerosus, vitiligo. The histologic findings in this nevus also overlap mycosis fungoides, sarcoidosis, leprosy). If our differential with vitiligo. The characteristic findings are presence of diagnosis was found in the first group, the final diagno- melanocytes and decreased pigment in the keratinocytes sis should be based on the evolution of the patient. If it compared with perilesional skin. Therefore, a biopsy is was in the second group, a biopsy of the center of the not a solution to this diagnostic dilemma.8 Dolesion will be useful and may allow us to reach a defini- In all the differentials named, the solution to the diag- tive diagnosis. nostic doubt is not based on the histologic findings but on the clinical evolution of the patients. In cases of vitiligo, REFERENCES the lesions will become more evident in the evolution. 1. Weedon D. Weedon´s Skin Pathology. 3rd edition. Churchill They will eventually disappear in pityriasis alba, postin- Livingston. 2009. flammatory hypopigmentation, and progressive macular 2. Kim YC, Kim YJ, Kang HY, et al. Histopathologic features in vitiligo. hypopigmentation and will remain unchanged in nevus Am J Dermatopathol. 2008;30:112-116. 3. Yadav AK, Singh P, Khunger N. Clinicopathologic analysis of stable depigmentosus. It is important, especially when we are and unstable vitiligo: a study of 66 cases. Am J Dermatopathol. dealing with concerned parents/guardians, to convey the 2016;38:608-613. importance of assessingCUTIS the evolution of the disease as 4. Alikhan A, Felsten LM, Daly M, et al. Vitiligo: a comprehensive over- the main diagnostic procedure. Even though a biopsy is view part i. introduction, epidemiology, quality of life, diagnosis, dif- minimally invasive, it is usually stressful on children, it ferential diagnosis, associations, histopathology, etiology, and work-up. J Am Acad Dermatol. 201165:473-491. may leave sequelae, and above all it will not contribute to 5. Le Poole IC, van der Wijngaard RM, Westerhof W, et al. Presence or the diagnosis in this clinical context. absence of melanocytes in vitiligo lesions: an immunohistochemical There are other clinical circumstances in the scenario investigation. J Invest Dermatol. 1993;100:816-822. of hypochromic or achromic lesions in which the biopsy 6. Tobin DJ, Swanson NN, Pittelkow MR, et al. Melanocytes are not absent will be useful: If we consider an initial genital lichen in lesional skin of long duration vitiligo. J Pathol. 2000;191:407-416. sclerosus vs vitiligo. In lichen sclerosus the biopsy will 7. Vargas-Ocampo F. Pityriasis alba: a histologic study. Int J Dermatol. 1993:32:870-873. show dermal hyalinosis and interphase changes; absence 8. Xu AE, Huang B, Li YW, et al. Clinical, histopathological and ultra- of both will support vitiligo. If we need to differenti- structural characteristics of naevus depigmentosus. Clin Exp Dermatol. ate hypopigmented mycosis fungoides from vitiligo, we 2008;33:400-405.

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