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Simple Summary The prognosis for advanced Extramammary Paget's disease (EMPD) is almost always poor. HER2-targeted antibody-drug conjugates (ADCs) such as trastuzumab emtansine and trastuzumab deruxtecan have proven to be effective against HER2-positive breast cancers; however, no studies have addressed HER2-targeted ADCs as treatments for EMPD. We examine the efficacy of ADCs against an EMPD patient-derived xenograft (PDX) model harboring pathogenic ERBB2 mutations. Treatment with trastuzumab emtansine or trastuzumab deruxtecan was found to significantly regress EMPD-PDX tumors in only seven days, with no recurrence observed for 10 weeks. Our results suggest that HER2-targeted ADCs could be novel and promising treatment options for patients with EMPD, especially in cases with the ERBB2-mutation or ERBB2-overexpression. Extramammary Paget's disease (EMPD) is an adenocarcinoma that develops mainly in the genital region of older adults. The prognosis for advanced EMPD is almost always poor; thus, novel therapeutic strategies need to be developed. HER2-targeted antibody-drug conjugates (ADCs) such as trastuzumab emtansine and trastuzumab deruxtecan have proven effective against HER2-positive breast cancers; however, no studies have addressed HER2-targeted ADCs as treatments for EMPD. We examine the efficacy of ADCs against an EMPD patient-derived xenograft (PDX) model harboring pathogenic ERBB2 mutations and investigate the expression levels of HER2 using EMPD clinical samples. Trastuzumab emtansine or trastuzumab deruxtecan was administered intravenously to tumor-bearing NOD/Scid mice. Treatment with trastuzumab emtansine or trastuzumab deruxtecan was found to significantly regress EMPD-PDX tumors in only seven days, with no recurrence observed for 10 weeks. EMPD tumors extracted 48 h after drug administration revealed the TUNEL-positive ratio to be significantly higher for the HER2-targeted ADC-treated tumors than for the control tumors. EMPD patients' clinical sampl

Simple Summary The prognosis for advanced Extramammary Paget's disease (EMPD) is almost always poor. HER2-targeted antibody-drug conjugates (ADCs) such as trastuzumab emtansine and trastuzumab deruxtecan have proven to be effective against HER2-positive breast cancers; however, no studies have addressed HER2-targeted ADCs as treatments for EMPD. We examine the efficacy of ADCs against an EMPD patient-derived xenograft (PDX) model harboring pathogenic ERBB2 mutations. Treatment with trastuzumab emtansine or trastuzumab deruxtecan was found to significantly regress EMPD-PDX tumors in only seven days, with no recurrence observed for 10 weeks. Our results suggest that HER2-targeted ADCs could be novel and promising treatment options for patients with EMPD, especially in cases with the ERBB2-mutation or ERBB2-overexpression. Extramammary Paget's disease (EMPD) is an adenocarcinoma that develops mainly in the genital region of older adults. The prognosis for advanced EMPD is almost always poor; thus, novel therapeutic strategies need to be developed. HER2-targeted antibody-drug conjugates (ADCs) such as trastuzumab emtansine and trastuzumab deruxtecan have proven effective against HER2-positive breast cancers; however, no studies have addressed HER2-targeted ADCs as treatments for EMPD. We examine the efficacy of ADCs against an EMPD patient-derived xenograft (PDX) model harboring pathogenic ERBB2 mutations and investigate the expression levels of HER2 using EMPD clinical samples. Trastuzumab emtansine or trastuzumab deruxtecan was administered intravenously to tumor-bearing NOD/Scid mice. Treatment with trastuzumab emtansine or trastuzumab deruxtecan was found to significantly regress EMPD-PDX tumors in only seven days, with no recurrence observed for 10 weeks. EMPD tumors extracted 48 h after drug administration revealed the TUNEL-positive ratio to be significantly higher for the HER2-targeted ADC-treated tumors than for the control tumors. EMPD patients' clinical sampl

Simple Summary The prognosis for advanced Extramammary Paget's disease (EMPD) is almost always poor. HER2-targeted antibody-drug conjugates (ADCs) such as trastuzumab emtansine and trastuzumab deruxtecan have proven to be effective against HER2-positive breast cancers; however, no studies have addressed HER2-targeted ADCs as treatments for EMPD. We examine the efficacy of ADCs against an EMPD patient-derived xenograft (PDX) model harboring pathogenic ERBB2 mutations. Treatment with trastuzumab emtansine or trastuzumab deruxtecan was found to significantly regress EMPD-PDX tumors in only seven days, with no recurrence observed for 10 weeks. Our results suggest that HER2-targeted ADCs could be novel and promising treatment options for patients with EMPD, especially in cases with the ERBB2-mutation or ERBB2-overexpression. Extramammary Paget's disease (EMPD) is an adenocarcinoma that develops mainly in the genital region of older adults. The prognosis for advanced EMPD is almost always poor; thus, novel therapeutic strategies need to be developed. HER2-targeted antibody-drug conjugates (ADCs) such as trastuzumab emtansine and trastuzumab deruxtecan have proven effective against HER2-positive breast cancers; however, no studies have addressed HER2-targeted ADCs as treatments for EMPD. We examine the efficacy of ADCs against an EMPD patient-derived xenograft (PDX) model harboring pathogenic ERBB2 mutations and investigate the expression levels of HER2 using EMPD clinical samples. Trastuzumab emtansine or trastuzumab deruxtecan was administered intravenously to tumor-bearing NOD/Scid mice. Treatment with trastuzumab emtansine or trastuzumab deruxtecan was found to significantly regress EMPD-PDX tumors in only seven days, with no recurrence observed for 10 weeks. EMPD tumors extracted 48 h after drug administration revealed the TUNEL-positive ratio to be significantly higher for the HER2-targeted ADC-treated tumors than for the control tumors. EMPD patients' clinical sampl

Herein, we present a case of extramammary Paget’s disease with brain metastasis that was diagnosed pathologically for the first time in Japan. Moreover, invasive extramammary Paget’s disease (with distant metastasis) highly resistant to treatment. Only for brain metastasis, we may control the tumor by surgical resection and stereotactic radiosurgery (SRT) for the treatment of intracranial metastases was assessed. An 76-year-old man was diagnosed with extramammary Paget’s disease of the vulva at nearby hospital. Surgical resection and sentinel lymph node dissection were then performed, and the patient received che-motherapy because multiple lymph node metastases were suspected. The patient’s response to chemotherapy was poor, and he was in the state of Progressive Disease. He complained of dyslexia and was referred to another hospital when he was 81 years old. Plain magnetic resonance imaging (MRI) was conducted, and two brain tumors in the vicinity of the left cerebellar tent were suspected. In our hospital, gadolinium contrast-enhanced MRI was performed and showed a tumor in the cerebel-lum (left posterior temporal lobe) and another tumor under the tent (left cerebellar hemisphere). Significant edema was also noted. Based on these findings, the intracranial lesion was diagnosed as metastatic brain tumor. The pathological diagnosis was brain metastasis from extramammary Paget’s disease. Postoperative intracranial residual disease was treated with stereotactic radiosurgery. MRI showed that the size of the cerebellar lesions decreased, and no recurrence of cerebral lesions was observed. SRT for extracranial lymph node metastases was performed. Mass reduction and SRT may be the best way to treat brain metastasis from extramammary Paget’s disease.

Extramammary Paget disease (EMPD) is a rare malignant neoplasm of apocrine sweat glands that is morphologically and histologically identical to Paget disease of the breast. The primary lesion is usually a solitary, well-demarcated, erythematous, scaly plaque that may contain crust, erosions, or ulcerations. The vulva is the most common site, but any area containing apocrine sweat glands may be involved. We present a case of triple extramammary Paget disease of the groin and bilateral axillae in a diabetic patient whose axillary lesions appeared consistent with acanthosis nigricans. This case demonstrates the need to consider EMPD in the evaluation of acanthosis of the axilla given its ability to mimic more common conditions.

Extramammary Paget disease (EMPD) is a rare malignant neoplasm of apocrine sweat glands that is morphologically and histologically identical to Paget disease of the breast. The primary lesion is usually a solitary, well-demarcated, erythematous, scaly plaque that may contain crust, erosions, or ulcerations. The vulva is the most common site, but any area containing apocrine sweat glands may be involved. We present a case of triple extramammary Paget disease of the groin and bilateral axillae in a diabetic patient whose axillary lesions appeared consistent with acanthosis nigricans. This case demonstrates the need to consider EMPD in the evaluation of acanthosis of the axilla given its ability to mimic more common conditions.

The histopathologic characteristics of reactions caused by the many novel anticancer agents are under-recognized. We report a case of a 67-year-old female with locally advanced metastatic breast cancer, who initially presented with an extensive reticulated erythematous patch on the trunk caused by intravascular metastases confirmed by a skin biopsy. Owing to disease progression, she was started on ixabepilone, a mitotic inhibitor. While receiving ixabepilone, another skin biopsy was obtained and initially interpreted as extramammary Paget's disease. However, the biopsy showed metaphase arrest of numerous keratinocytes in the basilar and suprabasilar epidermis. Atypical epithelial cells were only present in the intravascular spaces similar to the initial biopsy. Given the temporal association between the initiation of ixabepilone therapy and the epidermal mitotic arrest, a diagnosis of chemotherapy reaction to ixabepilone was rendered. Ixabepilone is an analog of epothilone, a microtubule stabilizer causing mitotic arrest of the cell cycle approved for the treatment of metastatic and locally advanced treatment-resistant breast cancer. The demonstration of epidermal mitotic arrest caused by ixabepilone is without precedent. The case emphasizes the importance of considering a chemotherapy reaction in the histologic differential diagnosis of epidermal mitotic arrest in a cancer patient receiving chemotherapy.