Photodynamic diagnosis-guided treatment of Erythroplasia of Queyrat with ALA-PDT

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Erythroplasia of Queyrat (EQ) is a rare form of squamous cell carcinoma (SCC) in situ, commonly affecting the glans penis, penis shaft, and coronary sulcus.¹ It clinically presents as well-marginated erythematous velvety plaques, which can transform into invasive SCC without treatment. Photodynamic diagnosis (PDD) is a fluorescence-based imaging technique useful for diagnosing and monitoring non-pigmented cutaneous neoplasms. Here, we report a case of EQ successfully treated with aminolaevulinic acid photodynamic therapy (ALA-PDT) assisted by PDD technology.

A 55-year-old male patient presented with raised, itchy lesions over his glans penis for 4 years. The patient underwent circumcision twice without complete lesional resolution. Instead, the lesion increased in size and developed painful erosions and crusting. Tests for Human Papillomavirus (HPV), Human Immunodeficiency Virus (HIV), and syphilis were negative, and ultrasonography detected no inguinal lymphadenopathy. Dermatological examination revealed a 2.0 cm × 1.5 cm erythematous plaque on the right glans with ulcerations and purulent discharge [Figure 1]. Histopathology confirmed EQ [Figures 2a-c]. The patient declined surgery and, after informed consent, underwent PDD-guided ALA-PDT.

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Figure 1:

Erythematous crusted and plaque with erosions on the glans at first presentation.

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Figure 2a:

The epidermis demonstrates hyperkeratosis, acanthosis with spongiosis, accompanied by serous exudation and crust formation. (Haematoxylin & eosin 100x).

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Figure 2b:

The superficial dermis demonstrates vascular dilation with a dense lymphoplasmacytic infiltrate, accompanied by fibrinoid degeneration of vascular walls. (Haematoxylin & eosin, 200x).

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Figure 2c:

The keratinocytes were markedly heterogeneous with loss of polarity, increased mitoses, and large, deeply stained nuclei that did not break through the basement membrane. (Haematoxylin & eosin, 400x).

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Pre-treatment, saline-soaked gauze removed scabs. A 20% ALA solution (Shanghai Fudan Zhangjiang Biomedical Co., Ltd., Shanghai, China) was applied to the lesion with a 1cm margin using sterile gauze, then occluded for 4 hours with light protection. After 4 hours, the gauze was removed and PDD was performed using a blue light source (6.50 mW/cm² ± 20%) in a dark chamber. Brick-red fluorescence was observed inside and around the lesion. [Figure 3a]. The fluorescence boundary was derived by extracting the red fluorescence layer using Image J (version 1.54; National Institutes of Health, USA) software [Figure 3b]. Based on PDD findings, the lesion was irradiated using an LED-IB photodynamic therapy instrument (LED-IB, 633 nm, 80 mW/cm², Wuhan Yage Optoelectronics Technology Co., Ltd., China) for 20 minutes at a distance of approximately 10 cm. The actual irradiation area included the lesion in the red light therapeutic zone at a distance of 10 cm from the lesion (defined based on the aminolevulinic acid Photodynamic Therapy Operating Guidelines) and the irradiation area exceeded the lesional by 5 cm. Treatment was administered once weekly. During the procedure, the patient experienced mild skin swelling and burning pain. No long-term adverse effects, such as hyperpigmentation or scar formation, were observed. After four treatments, the lesion showed substantial resolution [Figure 4a]. Repeat PDD examination revealed a significantly reduced and lighter fluorescent area [Figure 4b]. Dermatopathological examination of the most prominently fluorescent (brick-red) lesion site showed decreased atypia and inflammation [Figure 5a-c]. For areas with residual erythema and mild fluorescence, ALA penetration depth was enhanced for complete removal of the lesion. Two months later, the patient underwent three additional ALA-PDT sessions at weekly intervals. One month after the final treatment, the lesion had largely resolved. No recurrence was observed during a 5-month follow-up period. This patient is currently under follow-up.

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Figure 3a:

Before the first treatment, the Photodynamic diagnosis showed brick-red fluorescence in the lesion and the surrounding skin.

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Figure 3b:

The fluorescence boundary was derived by extracting the red fluorescence layer using Image J (version 1.54; National Institutes of Health, USA) software.

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Figure 4a:

Aspect of the glans penis after four times of treatment.

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Figure 4b:

After 4 times of ALA-PDT treatments, the PDD showed that the brick-red area decreased, and the colour became lighter.

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Figure 5a:

The epidermis exhibits mild acanthosis with features of lichenoid interface dermatitis. (Haematoxylin & eosin,100x).

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Figure 5b:

The superficial dermis demonstrates vascular dilation with a focal lymphocytic infiltrate and scattered neutrophils. (Haematoxylin & eosin, 200x).

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Figure 5c:

The epidermis shows minimal keratinocyte atypia with relatively preserved basal cell layer architecture. (Haematoxylin & eosin, 400x).

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EQ has a 10-33% risk of progressing to invasive SCC, emphasizing the need for early treatment.² First-line Mohs surgery may compromise genital function and aesthetics.³ ALA-PDT, utilizing protoporphyrin IX (PpIX)-mediated fluorescence, offers a non-invasive alternative. Most case reports indicate that PDT is effective in treating EQ. Some studies have reported efficacy rates of 36-83% for PDT with relapse-free follow-up periods of up to 51 months.⁴ While histopathology remains the gold standard, PDD is a non-invasive diagnostic tool that allows for the intuitive identification of tumour margins, localisation of lesion sites, visualisation of foci invisible to the naked eye, and a more accurate assessment of tumour characteristics before treatment.⁵ However, a 4-hour PpIX incubation period improves patient compliance. Additionally, fluorescence may extend beyond the actual pathologic area (e.g., involvement of the scrotum in [Figure 3a]), which may be caused by the accumulation of protoporphyrin IX (PpIX) in the inflamed tissues.⁶ In practice, we observe the lesional boundaries under white light to avoid treatment of nonpathological tissues. In this case, after four PDT sessions, PDD showed a significant reduction in the brick-red fluorescence area with a lighter colour. Histopathological examination revealed a significant reduction in cellular atypia, along with a decreased number of dermal neutrophils and lymphocytes in the dermis, consistent with the PDD findings. Both results indicated improvement in the patient’s condition. This first report of PDD-guided PDT for EQ shows promise, but the 5-month follow-up period is relatively short; long-term monitoring is necessary to assess recurrence risks and larger long-term studies are needed to validate efficacy.