Dermatology MCQ - Infiltrative and Neoplastic Disorders - Photochemotherapy lentigo PUVA lentigo

A 62-year-old man with a 25-year history of plaque psoriasis, previously managed with prolonged courses of oral photochemotherapy (PUVA), is noted on follow-up to have numerous irregularly shaped, dark brown macules scattered across his trunk. These lesions have persisted for many years since his last treatment. Which of the following best describes the most significant histopathological and clinical concern associated with these lesions?

A. They demonstrate epidermal atrophy and a marked reduction in melanocytes, increasing the risk of aggressive squamous cell carcinoma.
B. They are characterized by melanocytic atypia and an increased number of single melanocytes, and are associated with a significantly elevated risk of melanoma.
C. They show nests of cytologically atypical melanocytes at the dermo-epidermal junction, which is a hallmark of invasive malignant melanoma.
D. They are benign, showing only hyperkeratosis and papillomatosis without any increase in melanocyte number or atypia.
E. They represent a post-inflammatory hyperpigmentation with pigmentary incontinence and a sparse dermal lymphocytic infiltrate.

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Correct Answer: B. They are characterized by melanocytic atypia and an increased number of single melanocytes, and are associated with a significantly elevated risk of melanoma.

Answer and Explanation

The correct answer is B. This question describes the classic presentation of PUVA lentigines. The key clinical clue is the history of high-dose or long-term PUVA therapy. The most significant concern with these lesions is not just their appearance but their well-documented association with an increased risk of malignant melanoma.

Histopathologically, PUVA lentigines often show:

• An increased number of large, hyperchromatic (atypical) melanocytes, which can be singly dispersed or form small nests.

• The rete ridges may be elongated, similar to a solar lentigo, but the presence of cytologic atypia in the melanocytes is the critical distinguishing feature.

• These atypical features are why PUVA lentigines are considered a significant risk marker.

Why the Other Options are Incorrect:

• A. They demonstrate epidermal atrophy and a marked reduction in melanocytes...: This is incorrect. While PUVA does cause epidermal atrophy and increases the risk of squamous cell carcinoma (SCC), the lesions described are specifically lentigines, which are defined by an increase in melanocytes, not a reduction. The SCC risk, while real, is a separate issue from the lentigines themselves.

• C. They show nests of cytologically atypical melanocytes... a hallmark of invasive malignant melanoma: This is incorrect because it describes invasive melanoma. While PUVA lentigines can show atypia and nests, the diagnosis of invasive melanoma requires the presence of melanocytes invading into the dermis, which is not a defining feature of the lentigo itself. However, these lesions are precursors that can progress to melanoma.

• D. They are benign, showing only hyperkeratosis and papillomatosis...: This describes a seborrheic keratosis. PUVA lentigines are not considered entirely benign due to the associated melanocytic atypia and increased melanoma risk.

• E. They represent a post-inflammatory hyperpigmentation...: While hyperpigmentation can occur after inflammation, PUVA lentigines are a distinct, persistent proliferation of melanocytes, not simply dermal pigment deposition (pigmentary incontinence) from a resolved inflammatory process.

Additional High-Yield Information for Exams:

• Histopathology: The key features are large, hyperplastic, and often cytologically atypical melanocytes within elongated rete ridges. The atypia can range from mild to severe, sometimes making distinction from melanoma in situ (lentigo maligna) very difficult.

• Associated Conditions & Prognosis:

  • This is a critical exam point: The development of PUVA lentigines is a marker of high cumulative PUVA exposure and is associated with a significantly increased risk of cutaneous melanoma. This risk increases with the total number of PUVA treatments.

  • They are also associated with an increased risk of non-melanoma skin cancer, particularly SCC.

  • The lentigines themselves are persistent and may not fade after discontinuing PUVA.

• Differential Diagnosis: The main differential includes:

  • Solar Lentigo: Lacks significant melanocytic atypia.

  • Lentigo Maligna / Melanoma in situ: Can be histologically indistinguishable from a severely atypical PUVA lentigo. A thorough clinical history of PUVA exposure is essential.

• Management & Rationale:

  • Rationale: The primary goal is surveillance and early detection of melanoma. These patients require lifelong, high-risk skin surveillance.

  • First-line: Regular and rigorous full-body skin examinations, often with sequential digital dermatoscopy to monitor for changes in these atypical lentigines.

  • Biopsy: Any lentigo that shows clinical change (e.g., increase in size, irregular color variation, shape change) should be biopsied.

  • Treatment: Treatment of the lentigines for cosmetic reasons is secondary to surveillance. If treatment is pursued (e.g., with cryotherapy or laser), the lesion should be biopsied first to rule out melanoma.