Taking this information into consideration, we can understand that if our differential diagnosis is a dermatosis that requires the evaluation of the number of melanocytes as a fundamental diagnostic clue (eg, postinflammatory hypopigmentation), the biopsy will probably not be useful. On the other hand, when our differential diagnosis has characteristic diagnostic findings independent of the number of melanocytes or the presence of melanin, the biopsy will be useful (eg, hypopigmented mycosis fungoides).
Thus, we can understand why the histologic differentiation between vitiligo, pityriasis alba, postinflammatory hypopigmentation, and progressive macular hypopigmentation is difficult. The histology images of these 4 diseases may show different degrees of melanocyte and melanin decrease, spongiosis, and in the superficial dermis melanophages and mononuclear inflammatory infiltrate.7
Nevus depigmentosus also may generate diagnostic confusion with vitiligo. Although it is unilateral and usually congenital, it can appear as late as 3 years of age, leading to an initial clinical differential diagnosis of vitiligo. The histologic findings in this nevus also overlap with vitiligo. The characteristic findings are presence of melanocytes and decreased pigment in the keratinocytes compared with perilesional skin. Therefore, a biopsy is not a solution to this diagnostic dilemma.8
In all the differentials named, the solution to the diagnostic doubt is not based on the histologic findings but on the clinical evolution of the patients. In cases of vitiligo, the lesions will become more evident in the evolution. They will eventually disappear in pityriasis alba, postinflammatory hypopigmentation, and progressive macular hypopigmentation and will remain unchanged in nevus depigmentosus. It is important, especially when we are dealing with concerned parents/guardians, to convey the importance of assessing the evolution of the disease as the main diagnostic procedure. Even though a biopsy is minimally invasive, it is usually stressful on children, it may leave sequelae, and above all it will not contribute to the diagnosis in this clinical context.
There are other clinical circumstances in the scenario of hypochromic or achromic lesions in which the biopsy will be useful: If we consider an initial genital lichen sclerosus vs vitiligo. In lichen sclerosus the biopsy will show dermal hyalinosis and interphase changes; absence of both will support vitiligo. If we need to differentiate hypopigmented mycosis fungoides from vitiligo, we will find an infiltrate of pleomorphic lymphocytes in the epidermis and dermis in the former and an absence of these findings in vitiligo. Finally, if we find granulomas in a biopsy of an achromic or hypopigmented lesion, we may be dealing with hypopigmented sarcoidosis or Hansen disease.
It also is important to choose the best site to perform the biopsy to have the best chance at diagnosing vitiligo histologically. As already described, in the edges and in the perilesional skin we can find remnant melanocytes, Langerhans cells, and interphase changes that do not allow us to clearly evaluate the main change that is the loss of melanocytes and melanin. In fact, a biopsy of the edge of a vitiligo macula can lead to confusion. For example, if the differential diagnosis is lichen sclerosus and the image we see in the biopsy of the edge of a vitiligo lesion is an interface reaction, we can interpret it as a finding that favors lichen sclerosus. In this way, it is better to biopsy the center of a well-constituted vitiligo lesion where we have the best chance to assess the absence of melanin and melanocytes.
The vitiligo differential diagnosis can be divided into 2 groups: entities that are difficult to differentiate from vitiligo histologically (ie, pityriasis alba, postinflammatory hypopigmentation, progressive macular hypopigmentation, nevus depigmentosus) and entities that are easily distinguishable from vitiligo histologically (ie, lichen sclerosus, mycosis fungoides, sarcoidosis, leprosy). If our differential diagnosis was found in the first group, the final diagnosis should be based on the evolution of the patient. If it was in the second group, a biopsy of the center of the lesion will be useful and may allow us to reach a definitive diagnosis.