ArticleFrontiers in medicine2026
Metastatic extramammary Paget's disease successfully treated by trastuzumab deruxtecan: a rare case report.
Article in Frontiers in medicine, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
Background: Metastatic extramammary Paget's disease (mEMPD) is a rare cancer with a poor prognosis. Approximately 40% of cases overexpress the Her2/neu protein, making it a critical therapeutic target for precision-based systemic treatment. Case presentation: A 73-year-old man presented with a chronic erythematous patch on the left supra-pubic and scrotal area that had been slowly enlarging over months. A tender right groin mass developed recently. Imaging revealed right inguinal lymphadenopathy with necrosis, para-aortic lymph node involvement, bladder wall lesions, and right hydronephrosis. A skin biopsy confirmed the diagnosis of extramammary Paget's disease (EMPD), and invasive EMPD was subsequently confirmed through the excision of metastatic lymph nodes in the right groin. The immunochemical stains of the carcinoma reveal low Her2/neu expression (++/+++). Next-generation sequencing (NGS) demonstrated a high tumor mutation burden (30Muts/Mb), along with ERBBR2, PIK3CA, and PTEN mutations. Initially, he received trastuzumab and pembrolizumab. However, there was no clinical response. Then, he was treated with trastuzumab deruxtecan (anti-Her2/neu antibody-drug conjugates, ADC). A partial response was noted clinically and radiologically, including the regression of lymphadenopathy and bladder lesion. EMPD with low Her2/neu expression and high TMB may benefit more from anti-Her2/neu ADC rather than from immune checkpoint inhibitors combined with anti-Her2/neu antibodies. Discussion: HER2-targeted strategies, including trastuzumab-docetaxel and T-DM1, show high efficacy in mEMPD. This paradigm shift toward molecularly driven, customized treatments optimizes clinical outcomes while maintaining patient performance status in this rare malignancy.
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