Pigmentation skin disorders: Pathology review

21 year old Holly comes to her primary care provider's office complaining of pigment changes on her skin for the past year. She denies any history of trauma or recent inflammation of the skin. Her past medical history is significant for autoimmune thyroiditis. Physical examination shows several sharply demarcated depigmented patches on the dorsum of both her hands and wrists. On the same day, 30 year old Maria comes due to some tan spots that recently appeared on her cheeks. Maria tells you she is pregnant and of hispanic descent. Physical examination reveals that no other body area is involved. Based on the initial presentation, Holly and Maria seem to have some form of pigmentation skin disorder. All right, so the skin is divided into three main layers, the epidermis, dermis, and hypodermis. Melanocytes are located in the stratum basale layer of the epidermis and they produce a pigment called melanin from tyrosine. Melanin is then taken up by surrounding keratinocytes, and it contributes to the color of our skin, hair, and eyes. Now, what’s high yield is that melanin acts as a natural sunscreen that absorbs and dissipates, or scatters, UV radiation from the sun or other sources such as tanning booths, preventing it from damaging the keratinocytes. Now, as keratinocytes in the stratum basale mature, they migrate into the next layers of the epidermis, called the stratum spinosum, stratum granulosum, stratum lucidum, and finally, the stratum corneum, which is the uppermost and thickest epidermal layer.

Before we dive into the various disorders, there are several high yield terms to describe skin lesions. So, macules are flat, well circumcised lesions up to 1 centimeter in diameter, while patches are similar to a macule but are larger than 1 centimeter. Papules are raised bumps that are up to 1 centimeter in diameter, while plaques are like papules but larger than 1 centimeter. Okay, now, let’s start with pigmentation skin disorders. First, there’s hypopigmentation, which refers to any form of decreased or lost skin pigmentation compared to the baseline skin color. Sometimes, this can progress to depigmentation, in which there’s total absence of all pigment. These are in contrast to hyperpigmentation, which refers to darkening or increase in the natural color of the skin. Let’s start with hypopigmentation disorders. One of the most common and well known disorders is vitiligo, which is characterized by well defined, irregular shaped macules or patches of skin depigmentation. Lesions can range in size from millimeters to centimeters, and can sometimes expand and merge with other lesions over time. Vitiligo can affect any area of the body, but the most commonly affected body areas include the face, genitals, and body surfaces subjected to repeated trauma like the hands, wrists, and extensor forearms. Vitiligo can be classified according to the location affected. The most common type is non segmental vitiligo, which occurs at various locations that are often symmetrical on both sides of the face and body, and can affect any age group. On the other hand, segmental vitiligo occurs in segments along a single spinal nerve or dermatome typically on only one side of the body, and mostly affects children. Now, the exact cause of vitiligo isn’t known, but it is thought to be an autoimmune disorder where immune cells attack and destroy melanocytes. For your exams, remember that this is why vitiligo is often associated with other autoimmune disorders, like systemic lupus erythematosus and autoimmune thyroiditis. Now, the diagnosis of vitiligo is mainly clinical, and a Wood’s lamp may be used for diagnostic aid. Regarding treatment, topical corticosteroids are commonly used as first line therapy of smaller or more limited vitiligo, and if not effective then topical calcineurin inhibitors can be used. On the other hand, when the affected area is large, systemic immunosuppressants, UV phototherapy, skin bleaching, and in severe cases, skin grafts, can all be tried. Whatever the course of therapy, sunscreen is recommended to supplement the protection melanin would have provided.

Next, there’s albinism, which is caused by an autosomal recessive gene mutation encoding any one of the enzymes needed to produce melanin, typically tyrosinase. The result is a dysfunctional or deficient enzyme that drastically decreases the amount of melanin that’s made within normal melanocytes. Albinism can also occur if there are mutations in proteins responsible for the transport of tyrosine. Now, a decrease or absence of melanin can reduce or obliterate pigmentation of the skin, hair, and eyes, causing them to appear lighter in color or completely white. Diagnosis of albinism is mainly clinical, and definitive diagnosis can be made with genetic testing. Those with albinism are at an increased risk of skin cancers, so it’s recommended that they get frequent monitoring for skin changes. In addition, they can develop vision impairment, so they should get regular ocular examinations. Treatment generally includes strict protection of the skin with sunscreen, and the eyes by wearing tinted glasses. For your test, it’s important to know that albinism can be linked to Chediak Higashi syndrome, which is a rare autosomal recessive disorder that results in impaired lysosomal trafficking and phagocytosis. Individuals affected by this syndrome present a characteristic tetrad of hypopigmentation, recurrent infections, coagulation defects, and neurologic problems.

Moving on to hyperpigmented skin lesions, the most frequent ones are melanocytic nevi, also known as moles, which are benign proliferations of melanocytes. Now, melanocytic nevi can be classified as congenital or acquired. Congenital melanocytic nevi are typically present at birth or may appear within the first few months of life. One of the characteristic features of congenital nevi is that they usually have hair growing out of them. On the other hand, acquired melanocytic nevi appears throughout life due to predisposing factors like familial tendency, sun exposure, and skin type, with higher nevus counts seen in individuals with lightly pigmented skin. The most common moles or nevi are called nevocellular nevus, which are benign tumors of melanocytes, which increase in number and cluster as nests along the junction of the epidermis and underlying dermis, also known as the dermal-epidermal junction. These are known as junctional nevi and typically present as flat macules. Now, if nevus cells extend down into the dermis, they create what’s known as compound nevi. And eventually, these cells might break free from the dermal-epidermal junction, leaving off only the dermal component. These are the so called intradermal nevi and typically have a papular appearance. These common nevocellular nevi tend to be small and symmetric with a homogeneous surface, evenly pigmented, round or oval shape, regular outline, and sharply demarcated border. In contrast to common nevi, there are also atypical nevi, which tend to be larger and more asymmetric, with pigment variability, and irregular borders. Now, keep in mind that both congenital and acquired nevi are at risk of turning into malignant melanoma, but atypical nevi carry a higher risk, so they can be considered precursors to melanoma. However, most melanocytic nevi remain benign throughout the lifetime of a person and require no treatment other than observation. For a definitive diagnosis of suspicious nevi, to rule out malignant melanoma, an excisional biopsy may be performed.