Dermatology MCQ - Infiltrative and Neoplastic Disorders - Freckle / Ephelis

A 10-year-old child with red hair and fair skin presents with multiple, small (1-2 mm), light to dark brown macules scattered symmetrically across the nose and malar cheeks. The parents report that these spots become much more prominent during the summer months and seem to fade almost completely in the winter. Which of the following best describes the underlying pathophysiology of these lesions?

A. An increased number of melanocytes at the dermo-epidermal junction
B. An increased production and transfer of melanin by a normal number of melanocytes
C. A proliferation of melanocytes forming nests within the epidermis
D. The presence of large, dendritic melanocytes in the basal layer
E. The deposition of melanin in the papillary dermis within melanophages

Correct Answer: B. An increased production and transfer of melanin by a normal number of melanocytes

Explanation

The lesions described are classic for ephelides, or freckles. They are small, tan to brown macules that appear on sun-exposed skin, particularly in genetically predisposed individuals (often with MC1R gene variants), and are strongly influenced by UV exposure.

• Pathophysiology of Freckles: The key pathological feature of an ephelis is that the number of melanocytes is normal. However, these melanocytes are functionally hyperactive. Upon UV stimulation, they produce larger and more melanized melanosomes (the organelles containing melanin) and transfer them more efficiently to the surrounding keratinocytes. This results in the localized hyperpigmentation that characterizes a freckle. When UV exposure ceases, the melanocyte activity returns to baseline, and the freckles fade.

Why other options are incorrect

• A. An increased number of melanocytes at the dermo-epidermal junction: This is the hallmark of a lentigo simplex or solar lentigo (liver spot). In a lentigo, there is a linear increase in the density of melanocytes.

• C. A proliferation of melanocytes forming nests within the epidermis: This describes the pathology of a junctional nevus (if the nests are at the dermo-epidermal junction) or a compound nevus (if nests are in both the junction and the dermis).

• D. The presence of large, dendritic melanocytes in the basal layer: This is a characteristic finding in dermatosis papulosa nigra or seborrheic keratosis, where there is an increase in basaloid cells and often prominent melanocytes, but it is not the mechanism for freckles.

• E. The deposition of melanin in the papillary dermis within melanophages: This is known as dermal melanocytosis and is seen in conditions like a Mongolian spot, nevus of Ota, or post-inflammatory hyperpigmentation. It is not a feature of freckles.

Key Associations for Freckles (Ephelides)

• Clinical Features:

  • Appearance: Small, well-defined, tan to reddish-brown macules, typically 1-3 mm in diameter.

  • Distribution: Sun-exposed areas: face (especially nose and cheeks), shoulders, arms.

  • Key History: Appear or darken with sun exposure and fade significantly or disappear with sun avoidance. They often first appear in childhood.

• Histopathology: On biopsy, the epidermis may show slight hyperpigmentation of the basal layer, but the number of melanocytes is not increased. There is no elongation of the rete ridges (which is seen in a solar lentigo).

• Genetics: Strongly associated with variants in the Melanocortin-1 Receptor (MC1R) gene, which is also linked to fair skin, red hair, and an increased sensitivity to UV radiation and risk of melanoma.

• Differential Diagnosis:

  • Solar Lentigo (Liver Spot): Larger, darker, more uniform brown macules that do not fade significantly in winter; histology shows elongated rete ridges and an increased number of melanocytes.

  • Junctional Nevus: A melanocytic nevus that is usually darker, more raised, and stable in color regardless of sun exposure.

  • Lentigo Simplex: A small, dark brown to black macule that is not related to sun exposure and does not fade.

• Significance and Management:

  • Freckles themselves are entirely benign and require no treatment.

  • However, their presence is a clinical marker of significant cumulative sun exposure and skin sensitivity, indicating a higher risk for photoaging and skin cancers (both melanoma and non-melanoma).

  • Management centers on patient education about rigorous, lifelong sun protection, including sunscreen, hats, and sun-protective clothing.