Pigmentation skin disorders: Pathology review

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Case Study0:00–0:51

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 in 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 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.

Physiology0:51–1:43

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 here 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 basal 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.

Pathology1:43–2:39

So macules are flat, well circumcised lesions up to one centimeter in diameter. While patches are similar to a macule but are larger than one centimeter, papules are raised bumps that are up to one centimeter in diameter.
While plaques are like papules but larger than one centimeter. Ok.
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.

Vitiligo2:39–4:36

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, wrist and extensor forearms, vitiligo can be classified according to the location affected.
The most common type is nonsegmental vitiligo, which occurs at various locations that are often symmetrical on both sides of the face and body.
And this 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's 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 woods lamp may be used for diagnostic aid. Regarding treatment, topical corticosteroids are commonly used as a first line therapy of smaller or more limited vitiligo.
And if those aren't 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.

Albinism4:36–6:06

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 as well. 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 Sh Yak Higashi syndrome, which is a rare autosomal recessive disorder that results in impaired lysosomal trafficking and phagocytosis.
Individuals affected with 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.

Melanocytic Nevi6:06–8:25

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 appear throughout life due to predisposing factors like familial tendency, sun exposure and skin type with higher nevus count 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 homogenous 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 next.
Another common hyperpigmented skin lesion is a elides better known as freckles elides are small, well demarcated light brown macules that develop in sun exposed skin areas such as the face, shoulders and chest due to UVB radiation which stimulates melanocytes to increase melanin production.

Ephelides8:25–9:25

Ils are most frequent in individuals with red or blonde hair and fair skin for your exams. It's important to remember that il present an increased epidermal melanin while the number of melanocytes is normal.
This makes il different from melanotic nevi, which are caused by an increase in the actual number of melanocytes that accumulate in a small area.
Diagnosis is clinical and they have no malignant risk whatsoever. So, no treatment is necessary.
However, for cosmetic reasons, there are some treatment options that can help lighten lesions to a minimal extent including topical depigmentation agents or laser treatment.
Next, there's melasma also known as chloasma, which typically consists of hyperpigmented macules most commonly on the cheeks for your test.

Melasma9:25–10:03

Remember that it's usually seen in individuals with darker skin complexion and it's associated with the use of oral contraceptive pills or oc ps and pregnancy.
In which case, it may be described as a mask of pregnancy. In fact, that's a key word to keep in mind for your exam diagnosis is clinical and treatment options include skin lightening agents, chemical peels and laser or light based therapy.

Seborrhoeic Keratosis10:03–11:17

Seborrheic keratoses are benign and slow growing lesions that most often pop up on certain parts of the body like the trunk, arms and face and become more frequent as people age.
They are well demarcated round or oval lesions that can appear in various colors and have a dull verrucous and slightly elevated surface exams tend to describe them as coin shaped, waxy in having atypical stuck on appearance, meaning that they look like a spot that you could peel away from the surface of the skin.
But what's particularly high yield is that a sudden onset of multiple seborrheic keratoses is called the lesser reloc sign.
And this suggests an underlying carcinoma, especially of the gastrointestinal tract. Definitive diagnosis can be made with a biopsy which shows a proliferation of keratinocytes that classically produce small cysts filled with keratin called horn cysts.
Since seborrheic keratoses are benign treatment is generally not required but removal for cosmetic reasons can be done with surgical excision, cryotherapy or electrodesiccation last but not least acanthosis nigricans is characterized by velvet like gray to brown hyperpigmented plaques due to epidermal hyperplasia of the stratum spinosum.

Acanthosis Nigricans11:17–12:35

Typically, acanthosis nigricans appear on the skin of intertriginous sites such as the neck, groin and axilla less frequently though it can appear in other skin sites or on mucosal surfaces.
What's super high yield is that acanthosis nigricans is often associated with a variety of underlying systemic disorders where there's insulin resistance.
These include obesity, diabetes, Mellitus Cushing's Syndrome and Polycystic Ovarian Syndrome. In rare cases, it can be associated with internal malignancy, especially gastric adenocarcinoma.
So, if a test question describes an older non obese individual with new onset acanthosis nigricans. Always consider the possibility of an occult malignancy diagnosis is clinical and individuals should be screened for underlying disorders.
Treatment involves addressing any associated underlying cause as well as topical treatments if desired, such as retinoids or laser therapy.
All right, there's a quick recap hypopigmented skin disorders include vitiligo in which destruction of melanocytes causes irregular patches of depigmentation and is associated with other autoimmune disorders and albinism where recessive gene mutations cause decreased melanin production with normal melanocyte number and result in reduced or no pigmentation of the skin, hair and eyes, hyperpigmented.

Review12:35–13:42

Skin lesions include melanocytic nevi or moles, which can be classified as congenital or acquired as well as common or atypical il or freckles, which are small, light brown macules that develop in areas of sun exposed skin melasma, which is hyperpigmented cheeks.
In those using oc PS or pregnant individuals. Seborrheic keratoses which are stuck on lesions in older individuals and sudden onset of multiple seborrhoic keratoses known as lesser relo sign may suggest malignancy and acanthosis nigricans which is skin thickening in the neck or axilla that can be associated with insulin resistance or malignancy.
Ok. Back to our cases, holley presented with well demarcated irregular patches of depigmentation and a history of autoimmune thyroiditis.

Summary13:42–14:11

This is classic for vitiligo and since the patches are symmetrical on the dorsum of both her hands and wrists, we're probably dealing with nonsegmental vitiligo On the other hand, Maria is a pregnant woman of Hispanic descent, complaining of those new tan spots on her cheeks.
Her clinical presentation is enough to make the diagnosis of