HER2-directed therapy in metastatic vulvar empd—a report of two cases and narrative review
Case Report

HER2-directed therapy in metastatic vulvar empd—a report of two cases and narrative review

Grace Gorecki1# ORCID logo, Bana Antonios2#, Srinishant Rajrajan1, Kalaivani Babu1, John Nakayama3, Christie Hilton2

1Internal Medicine Institute, Allegheny Health Network, Allegheny General Hospital, Pittsburgh, PA, USA; 2Allegheny Health Network Cancer Institute, Pittsburgh, PA, USA; 3Division of Gynecologic Oncology, Allegheny Health Network, Pittsburgh, PA, USA

Contributions: (I) Conception and design: G Gorecki, B Antonios; (II) Administrative support: J Nakayama, C Hilton; (III) Provision of study materials or patients: J Nakayama, C Hilton; (IV) Collection and assembly of data: G Gorecki, B Antonios, S Rajrajan, K Babu; (V) Data analysis and interpretation: None; (VI) Manuscript writing: All authors; (VII) Final approval of manuscript: All authors.

#These authors contributed equally to this work as co-first authors.

Correspondence to: Grace Gorecki, MD. Internal Medicine Institute, Allegheny Health Network, Allegheny General Hospital, 314 E North Ave. Suite 344, Pittsburgh, PA 15212, USA. Email: grace.gorecki@ahn.org; gracegorecki19@gmail.com.

Background: Extramammary Paget’s disease (EMPD) is a rare malignancy of the skin arising in apocrine gland-rich areas, most commonly the vulva, scrotum, and perianal region. Often misdiagnosed due to resemblance to benign dermatologic conditions, EMPD presents diagnostic and therapeutic challenges. While localized disease usually has a favorable prognosis after surgery, metastatic EMPD is rare, with poor outcomes and limited options. Recent molecular profiling has identified human epidermal growth factor receptor 2 (HER2) overexpression as a potential therapeutic target. We present a clinical series of HER2-positive EMPD treated with targeted therapies and review the literature to assess their role in disease control and outcomes.

Case Description: We report two cases of metastatic HER2-amplified vulvar EMPD treated with HER2-directed agents, including trastuzumab, pertuzumab, trastuzumab emtansine (T-DM1), and trastuzumab deruxtecan (T-DXd), and integrate our findings into a narrative review of reported cases. Both patients achieved clinical benefit from HER2-targeted therapy with disease control across sequential regimens.

Conclusions: We describe one of the first documented real-world cases of vulvar EMPD treated with T-DXd, showing a meaningful clinical response. HER2-positive metastatic vulvar EMPD may respond to targeted therapy, and T-DXd appears promising for disease control. Molecular HER2 testing should be incorporated into the diagnostic workup to guide therapy selection in this rare malignancy.

Keywords: Extramammary Paget’s disease (EMPD); human epidermal growth factor receptor 2-directed therapy (HER2-directed therapy); metastatic EMPD; case report

Received: 31 August 2025; Accepted: 18 November 2025; Published online: 22 January 2026.

doi: 10.21037/acr-2025-230

Highlight box

Key findings

• We present two cases of metastatic vulvar extramammary Paget’s disease (EMPD) with human epidermal growth factor receptor 2 (HER2) amplification, both treated with HER2-directed therapies.

• One patient achieved clinical benefit from trastuzumab deruxtecan, representing one of the first real-world reports of its use in vulvar EMPD.

• Our review integrates published cases and a narrative review of the therapeutic role of HER2 testing in EMPD.

What is known and what is new?

• EMPD is a rare malignancy with limited therapeutic options in the recurrent or metastatic setting. HER2 amplification has been described in a subset of EMPD cases, with case reports of response to HER2-targeted therapies.

• This report details of trastuzumab deruxtecan (T-DXd) in vulvar EMPD and provides a comprehensive synthesis of reported HER2-targeted treatment outcomes.

What is the implication, and what should change now?

• HER2 testing should be incorporated into the diagnostic evaluation of patients with recurrent or metastatic vulvar EMPD.

• HER2-directed therapies, including trastuzumab deruxtecan, should be considered in treatment planning for HER2-positive cases.

• Further collaborative research and prospective data collection are warranted to define the role of targeted therapy in EMPD.

Introduction

Extramammary Paget’s disease (EMPD) is a rare neoplasm primarily affecting apocrine gland-rich areas of the skin. The annual incidence of vulvar EMPD is estimated at 0.36 per 100,000 person-years with a notable rise observed over the past two decades (1). The mean age at diagnosis typically ranges from 60 to 70 years (2). It typically manifests as a chronic eczematous rash that may transform into erythematous plaques that ulcerate over time. Recurrence is not uncommon, and data on effective systemic therapies for invasive or metastatic disease are limited to small case series and individual reports (3). Here, we add two cases of vulvar EMPD to the literature.

The population affected by EMPD has exponentially increased over the last few decades (1). EMPD can present as a primary disease or as a secondary manifestation of underlying malignancy, with secondary EMPD accounting for 10–30% of cases (4). Localized EMPD is generally associated with a favorable prognosis. Metastatic disease is rare but carries a poor prognosis and increased mortality (5). In this patient cohort, there is no established consensus on the optimal systemic treatment approach. Vulvar EMPD accounts for less than 1–2% of all vulvar malignancies and typically presents as a chronic, pruritic, eczematous lesion often mistaken for benign dermatologic conditions, leading to diagnostic delays (6).

Surgical excision remains the mainstay of treatment. Achieving negative surgical margins has been associated with improved outcomes (7); however, this can be particularly challenging when excising lesions near the genital and perineal regions. While some studies recommend a 1–2 cm surgical margin, there is no consensus on the optimal margin width, and its impact on reducing local recurrence remains unclear (2,4,8,9).

For patients who are not surgical candidates, alternative modalities such as radiotherapy, photodynamic therapy, and topical imiquimod may be employed. Systemic therapy is typically reserved for advanced or metastatic cases and includes combined chemotherapy and targeted human epidermal growth factor receptor 2 (HER2) therapy. Radiation therapy has occasionally been used in EMPD for local control in nonsurgical candidates (10).

Conventional chemotherapy (single-agent or combination) has been utilized in metastatic EMPD. Combination chemotherapy is typically reserved for patients with good performance status, with reported regimens in the literature including low-dose 5-fluorouracil/cisplatin, cisplatin and epirubicin, paclitaxel and epirubicin, or multi-agent combinations such as mitomycin, vincristine, carboplatin, and 5-fluorouracil (11-13). However, reported complete response rates with conventional chemotherapy remain low, typically ≤10% across published series (11-13). Trastuzumab deruxtecan (T-DXd) is an antibody-drug conjugate targeting HER2 that is FDA approved for HER2-positive metastatic breast cancer (14). T-DXd has the ability to target low levels of HER2 expression and has revolutionized breast cancer care (15).

Given the rarity of EMPD (vulvar or other sites) literature is limited and there is a lack of standardized treatment guidelines. At present, case-based evidence is an essential guide for clinical decision-making (4,8). We present this article in accordance with the CARE reporting checklist (available at https://acr.amegroups.com/article/view/10.21037/acr-2025-230/rc).

Case presentation

Case 1

A 68-year-old White female was diagnosed with vulvar EMPD and underwent a vulvectomy with negative surgical margins. Two years later, she experienced a local recurrence of vulvar EMPD and required a second vulvectomy with rotational skin flap reconstruction, which again achieved clear margins. Immunohistochemistry of the neoplastic cells was positive for cytokeratin (CK)7 and monoclonal carcinoembryonic antigen (CEA) but negative for CK5/6, CK20, and S-100, findings consistent with the diagnosis. Approximately three years later, she presented with gross hematuria. Further evaluation, including cystourethroscopy, revealed an extensive recurrence of EMPD (pathologically confirmed) involving the mons, bilateral rotational flaps, the lower third of the vagina, the urethra, and the proximal vesical neck. Bladder and urethral biopsies confirmed a poorly differentiated carcinoma with morphology consistent with her known EMPD. A positron emission tomography (PET) scan demonstrated extensive metastatic disease to liver and lymph nodes. She was started on systemic chemotherapy with carboplatin [area under the curve (AUC) 5] and paclitaxel (175 mg/m2). Interval PET scan after three and six cycles showed a partial response. She developed a hypersensitivity reaction to carboplatin and was subsequently maintained on single-agent weekly paclitaxel (60 mg/m2). After 12 weeks of paclitaxel, her disease remained stable on PET imaging. Following a year of chemotherapy with ongoing stable disease, she took a treatment break due to worsening peripheral neuropathy.

Approximately after 6 months of being off systemic therapy, follow-up imaging raised concerns for disease progression and local recurrence in the vulvar area. Next-generation sequencing identified a HER2-neu (ERBB2) +3 amplification, along with somatic mutations of BRCA2, TP53, EGFR, TS, and TUBB3 genes. Molecular profiling also confirmed microsatellite instability (MSI)-stable disease with a tumor mutational burden of 8 mut/Mb.

Given the highly amplified HER2-neu status, she was started on trastuzumab. Although she initially showed a positive response, her disease unfortunately progressed with new pulmonary nodules after about 6 months. Treatment was then modified to include weekly paclitaxel in combination with trastuzumab. Disease stability was maintained for 6 months, but paclitaxel was eventually discontinued due to ongoing peripheral neuropathy. At this point, therapy was switched to trastuzumab and pertuzumab, along with a brief rechallenge of paclitaxel as her neuropathy showed signs of improvement. She achieved a positive response, but paclitaxel had to be discontinued again after a few cycles due to worsening neuropathy. Despite this, her disease remained stable on dual HER2 blockade with trastuzumab and pertuzumab for approximately 18 months.

Restaging scans later revealed an enhancing soft tissue lesion in the perineal region, concerning local recurrence, but no evidence of distant metastases. Consequently, her treatment was changed to ado-trastuzumab emtansine (ado-T-DM1), which controlled her disease for about a year. Disease progression followed, with the emergence of a notable vulvar mass extending to the posterior bladder and rectum, accompanied by adjacent lymphadenopathy and significant lymphedema. Palliative pelvic radiation was planned but was not well tolerated. Systemic therapy was then switched to fam-T-DXd. Her functional status declined and she received only one cycle before passing away due to rapid disease progression, almost 12 years after her initial diagnosis. A detailed timeline summarizing systemic therapies and clinical responses for case 1 is shown in Figure 1.

Figure 1 Longitudinal systemic treatment timeline for case 1, showing duration on each therapy and reasons for treatment discontinuation. T-DM1, trastuzumab emtansine; T-DXd, trastuzumab deruxtecan.

Case 2

A 65-year-old White female with a personal history of endometrial cancer was initially diagnosed with EMPD of the vulva and treated with a radical vulvectomy and inguinal lymphadenectomy, achieving negative surgical margins. She developed several episodes of locally recurrent disease, which were treated with surgical resection 12 years after initial diagnosis. A PET scan revealed mild fluorodeoxyglucose uptake in the inguinal lymph nodes without evidence of distant metastatic disease. She subsequently underwent a bilateral complete vulvectomy and declined lymph node dissection.

Six months later, she presented with new-onset hematuria. A CT scan of the abdomen and pelvis demonstrated new right-sided hydronephrosis and suspicious tumor infiltration around the ureterovesical junction, along with a lytic lesion in the left ischium concerning for metastatic disease. She underwent cystoscopy and pelvic examination with biopsies from the urethra and urinary bladder, which confirmed metastatic carcinoma consistent with a vulvar primary, along with local recurrence of EMPD in the bilateral vulva.

Restaging PET imaging revealed fluorodeoxyglucose (FDG)-avid vulvar and vaginal disease, pelvic nodal involvement, and evidence of hepatic, osseous, and bilateral pulmonary nodal metastatic disease. Immunohistochemical staining showed that the tumor cells were strongly and diffusely positive for CK7 and GATA-3, with rare, scattered staining for CK5/6 and p40. Malignant cells also were positive for HER2 overexpression (3+), which was confirmed by next-generation sequencing identifying ERBB2 alterations. Additional mutations in MSH2, PIK3CA, and a somatic BRCA2 mutation were also detected. The tumor demonstrated MSI-high status with a tumor mutational burden of 37.7 mut/Mb.

Following a multidisciplinary discussion between the medical oncology and gynecologic oncology teams, the patient was started on a taxane-based chemotherapy regimen with paclitaxel (175 mg/m2) and trastuzumab every 3 weeks. After three cycles, restaging computed tomography (CT) scans of the chest, abdomen, and pelvis showed evidence of disease progression. Therapy was subsequently switched to T-DXd. After three cycles of this treatment, restaging imaging demonstrated a notable decrease in the size of some metastatic lesions and stable disease in the remainder. All procedures performed in this study were in accordance with the ethical standards of the institutional and/or national research committee(s) and with the Declaration of Helsinki and its subsequent amendments. Publication of this case report was waived from patients consent according to Allegheny Health Network institutional review board.

Discussion

A structured literature review was performed using PubMed and Google Scholar to identify English-language reports of HER2-positive EMPD published between January 2010 and August 2025. We present two cases of vulvar EMPD that were treated with surgery and chemotherapy but progressed to metastasis. In both patients, the cancerous cells were HER2-positive and one patient was successfully stabilized with a taxane-based chemotherapy regimen. Both cases illustrate the utility of testing for HER2 mutations when developing the treatment plan. Emerging studies have demonstrated that HER2 overexpression is relatively common in EMPD, though at a lower and more variable frequency compared to mammary Paget’s disease (16). As more cases of EMPD are reported and standardized treatment protocols are developed, we recommend the incorporation of HER2 testing to the process.

HER2 overexpression is reported in 80–90% of cases of mammary Paget’s disease, whereas the reported ranges are much broader in EMPD, extending from 15% to 60% of cases (17,18). Tanaka et al. (19) found HER2 overexpression by immunohistochemistry in 18% of invasive EMPD cases, with ERBB2 amplification confirmed in all HER2 3+ cases. Deeply invasive EMPD showed higher frequencies of HER2 2+/3+ expression and ERBB2 amplification, and these tumors were more likely to be associated with lymph node metastases (19). Given the role of HER2 expression in many cases of EMPD, the consideration of HER2-targeted therapies is supported.

The first clinical case of targeting metastatic HER2-positive EMPD was reported by Hanawa et al. (20). They used a humanized monoclonal antibody targeting HER2 (trastuzumab) in combination with taxane-based chemotherapy, which is the standard of care for HER2-positive metastatic breast cancer (15,20). Initially administered as a single agent in the first-line setting, trastuzumab produced a limited response (20). However, upon the addition of weekly paclitaxel, their patient experienced a significant cutaneous response and a reduction in the size of metastatic lesions (20).

The utility of taxane-based therapies was also demonstrated in a retrospective study of 37 patients with recurrent, unresectable, or metastatic EMPD (3). Among those who received first-line systemic chemotherapy, platinum-based regimens were the most used, while a smaller subset was treated with taxane-based monotherapy (3). While both approaches demonstrated clinical benefit, taxane-based therapy was associated with a higher objective response rate and disease control rate compared to platinum-based regimens (3). Additionally, patients treated with taxane-based chemotherapy experienced a longer progression-free survival, and overall survival outcomes appeared favorable, though the median had not yet been reached at the time of analysis (3).

T-DM1 is an antibody-drug conjugate that combines the anti-HER2 monoclonal antibody trastuzumab with the cytotoxic agent DM1. It was approved as a second-line treatment for metastatic HER2-positive breast cancer in patients who progressed on trastuzumab and chemotherapy (15). Two published case reports have described T-DM1 as a second-line option in HER2-amplified metastatic EMPD after progression on trastuzumab-based chemotherapy (21,22). One patient with primary vulvar EMPD achieved 6 months of disease stabilization on T-DM1 (22); a patient with primary scrotal EMPD maintained tumor control for 12 months (21). Our first patient likewise experienced significant benefit from T-DM1 at a dose of 3.6 mg/kg, achieving about 12 months of disease control as fourth-line therapy following progression on single and dual HER2 blockade.

In both cases we report on, the combination treatment of trastuzumab and paclitaxel was employed. This approach proved effective in our first patient, who received trastuzumab (loading dose of 8 mg/kg followed by 6 mg/kg every 3 weeks) as a second-line treatment following disease progression and intolerance to cytotoxic chemotherapy. She initially responded to single-agent trastuzumab, and upon further progression, the addition of weekly paclitaxel achieved disease control for approximately 6 months. In contrast, our second patient did not respond to this combination strategy when used as first-line therapy, highlighting the heterogeneity and aggressive nature of HER2-positive EMPD.

Others have also reported on using HER2 as a chemotherapy target. Sohn et al. (3) identified 12 patients with HER2 overexpression in their study. Among them, six received a combination of chemotherapy and anti-HER2 therapy in either the first- or second-line setting (3). This group demonstrated an overall response rate (ORR) of 100% and a median progression-free survival of 13.31 months (3). The study suggested that combining trastuzumab with chemotherapy was associated with improved survival outcomes compared to trastuzumab monotherapy or conventional chemotherapy alone (3). Hirai et al. (23) likewise reported outcomes for 13 patients with metastatic HER2-positive EMPD treated with a combination of docetaxel and trastuzumab (23). Although they did not specify the line of therapy in which this regimen was administered, an analysis after three treatment cycles showed an ORR of 76.9%, including five patients who achieved a complete response (23).

Another HER2-targeting treatment is pertuzumab. Pertuzumab is a monoclonal antibody that binds to a different domain of the HER2 receptor, inhibiting its dimerization with other members of the HER family. When combined with trastuzumab and docetaxel, this dual HER2 blockade significantly improved overall survival in patients with HER2-positive metastatic breast cancer, as demonstrated in the CLEOPATRA trial (15). This combination has since become the standard of care in this setting (14), but reports of this dual HER2-targeting approach in EMPD remain exceedingly scarce. One report described an 80-year-old man with a bulky inguinal EMPD lesion and metastatic inguinal and retroperitoneal lymphadenopathy who achieved an almost complete response after three cycles of pertuzumab plus trastuzumab, underwent surgical resection, and remained disease-free for over a year of follow-up (24). Another involved a 65-year-old man with metastatic scrotal EMPD who attained a complete response following first-line treatment with trastuzumab, pertuzumab, and paclitaxel, maintaining remission for approximately 14 months (25).

Given the utility of pertuzumab in breast cancer patients, we incorporated pertuzumab alongside trastuzumab in our first patient and achieved disease stabilization for nearly 18 months. To our knowledge, ours is only the third documented case of such a durable response to combined pertuzumab and trastuzumab in EMPD.

Our second case illustrates a metastatic HER2-amplified EMPD with clinical benefit from T-DXd, given at a dose of 5.4 mg/kg, achieving a favorable response after three cycles of treatment. T-DXd delivers a potent chemotherapy payload directly into HER2-expressing cells and produces a bystander effect, offering deeper and more durable responses than trastuzumab or T-DM1. While we had intended to offer this therapy to our first patient, her rapid disease progression unfortunately precluded the opportunity to initiate T-DXd, and she ultimately succumbed to the disease (26,27). A consolidated summary of previously published HER2-positive EMPD cases is provided in Table 1.

Table 1

Summary of published HER2-positive metastatic EMPD cases and therapeutic outcomes

Study No. of cases Primary site(s) Age (years) HER2 status Treatment Response Duration of response (months)
Current study, 2025 2 Vulva 65, 68 IHC 3+, ERBB2 amplified Sequential HER2 therapy: trastuzumab → trastuzumab + paclitaxel → pertuzumab + trastuzumab → T-DM1 → T-DXd PR, SD 12–18 (case 1); PR/SD ongoing (case 2)
Hanawa et al., 2011 (20) 1 Vulva 70 IHC 3+ Trastuzumab → trastuzumab + paclitaxel PR ≈11
Chen et al., 2020 (21) 1 Scrotum 55 IHC 3+ T-DM1 SD ≈15
Hsieh et al., 2018 (22) 1 Vulva 65 IHC 3+ T-DM1 SD ≈6
Sola-Ortigosa et al., 2022 (24) 1 Groin 80 IHC 3+ Trastuzumab + pertuzumab (dual HER2 blockade) CR ≈12
Nowicka-Matus et al., 2023 (25) 1 Scrotum 65 IHC 3+ Paclitaxel + trastuzumab + pertuzumab → HP maintenance CR ≈14

CR, complete response; EMPD, extramammary Paget’s disease; HER2, human epidermal growth factor receptor 2; IHC, immunohistochemistry; PR, partial response; SD, stable disease; T-DM1, trastuzumab emtansine; T-DXd, trastuzumab deruxtecan.

Conclusions

This report underscores the clinical heterogeneity and therapeutic complexity of HER2-amplified metastatic EMPD. Despite its rarity, emerging evidence supports the efficacy of HER2-targeted strategies in selected patients, mirroring successes observed in breast cancer. Our experience demonstrates that trastuzumab-based regimens, dual HER2 blockade, and antibody-drug conjugates such as T-DM1 and T-DXd can provide meaningful disease control, even in heavily pretreated patients. These findings highlight the importance of routine HER2 testing and molecular profiling in EMPD to inform personalized treatment approaches. Continued investigation and inclusion of EMPD in basket trials will be crucial to expanding therapeutic options and improving long-term outcomes.

Acknowledgments

The authors thank Sarah Carey, MS, and Jacalyn Newman, PhD, of Allegheny Health Network’s Health System Publication Support Office (HSPSO) for their assistance in formatting the manuscript. The HSPSO is funded by Highmark Health (Pittsburgh, PA, United States of America), and all work was done in accordance with Good Publication Practice (GPP3) guidelines (http://www.ismpp.org/gpp3).

Footnote

Reporting Checklist: The authors have completed the CARE reporting checklist. Available at https://acr.amegroups.com/article/view/10.21037/acr-2025-230/rc

Peer Review File: Available at https://acr.amegroups.com/article/view/10.21037/acr-2025-230/prf

Funding: None.

Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://acr.amegroups.com/article/view/10.21037/acr-2025-230/coif). J.N. received research grants from GSK, Myriad and Tempus; consulting fees from AstraZeneca and Abbvie; and received honoraria for speakers from AstraZeneca, Esai and Merck. C.H. received research grants from GSK, Myriad and Tempus; consulting fees from AstraZeneca and Abbvie; and received honoraria from MJH and Curio Science. C.H. served as a speaker and the advisory board member for Astra Zeneca and Diiachi Sankyo; and also served as the advisory board member for Gilead and Tolmar. The other authors have no conflicts of interest to declare

Ethical Statement: The authors are accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved. All procedures performed in this study were in accordance with the ethical standards of the institutional and/or national research committee(s) and with the Declaration of Helsinki and its subsequent amendments. Publication of this case report was waived from patients consent according to Allegheny Health Network institutional review board.

Open Access Statement: This is an Open Access article distributed in accordance with the Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International License (CC BY-NC-ND 4.0), which permits the non-commercial replication and distribution of the article with the strict proviso that no changes or edits are made and the original work is properly cited (including links to both the formal publication through the relevant DOI and the license). See: https://creativecommons.org/licenses/by-nc-nd/4.0/.

References

  1. Kilts TP, Long B, Glasgow AE, et al. Invasive vulvar extramammary Paget's disease in the United States. Gynecol Oncol 2020;157:649-55. [Crossref] [PubMed]
  2. Nasioudis D, Bhadra M, Ko EM. Extramammary Paget disease of the vulva: Management and prognosis. Gynecol Oncol 2020;157:146-50. [Crossref] [PubMed]
  3. Sohn BS, Kim J, Kim M, et al. Treatment outcomes of advanced/metastatic extramammary Paget's disease in Korean patients: KCSG-RC20-06. Cancer Med 2023;12:15159-75. [Crossref] [PubMed]
  4. Ishizuki S, Nakamura Y. Extramammary Paget's Disease: Diagnosis, Pathogenesis, and Treatment with Focus on Recent Developments. Curr Oncol 2021;28:2969-86. [Crossref] [PubMed]
  5. Yao H, Xie M, Fu S, et al. Survival analysis of patients with invasive extramammary Paget disease: implications of anatomic sites. BMC Cancer 2018;18:403. [Crossref] [PubMed]
  6. Caruso G, Barcellini A, Mazzeo R, et al. Vulvar Paget's Disease: A Systematic Review of the MITO Rare Cancer Group. Cancers (Basel) 2023;15:1803. [Crossref] [PubMed]
  7. Bruce KH, Kilts TP, Lohman ME, et al. Mohs surgery for female genital Paget's disease: a prospective observational trial. Am J Obstet Gynecol 2023;229:660.e1-8. [Crossref] [PubMed]
  8. Hendi A, Brodland DG, Zitelli JA. Extramammary Paget's disease: surgical treatment with Mohs micrographic surgery. J Am Acad Dermatol 2004;51:767-73. [Crossref] [PubMed]
  9. Black D, Tornos C, Soslow RA, et al. The outcomes of patients with positive margins after excision for intraepithelial Paget's disease of the vulva. Gynecol Oncol 2007;104:547-50. [Crossref] [PubMed]
  10. Hata M, Koike I, Wada H, et al. Radiation therapy for extramammary Paget's disease: treatment outcomes and prognostic factors. Ann Oncol 2014;25:291-7. [Crossref] [PubMed]
  11. Hirai I, Tanese K, Nakamura Y, et al. Combination Cisplatin-Epirubicin-Paclitaxel Therapy for Metastatic Extramammary Paget's Disease. Oncologist 2019;24:e394-6. [Crossref] [PubMed]
  12. Oashi K, Tsutsumida A, Namikawa K, et al. Combination chemotherapy for metastatic extramammary Paget disease. Br J Dermatol 2014;170:1354-7. [Crossref] [PubMed]
  13. Tokuda Y, Arakura F, Uhara H. Combination chemotherapy of low-dose 5-fluorouracil and cisplatin for advanced extramammary Paget's disease. Int J Clin Oncol 2015;20:194-7. [Crossref] [PubMed]
  14. Bardia A, Hu X, Dent R, et al. Trastuzumab Deruxtecan after Endocrine Therapy in Metastatic Breast Cancer. N Engl J Med 2024;391:2110-22. [Crossref] [PubMed]
  15. Gupta R, Gupta S, Antonios B, et al. Therapeutic landscape of advanced HER2-positive breast cancer in 2022. Med Oncol 2022;39:258. [Crossref] [PubMed]
  16. Liu W, Iqbal J, Khoury T. Mammary Paget's disease and extra-mammary Paget's disease: two morphologically similar but biologically different diseases. J Cutan Pathol 2010;37:1145-9. [Crossref] [PubMed]
  17. Jia J, Mao L, Lin J, et al. Assessment of HER2 status in extramammary Paget disease and its implication for disitamab vedotin, a novel humanized anti-HER2 antibody-drug conjugate therapy. Front Med 2024;18:565-9. [Crossref] [PubMed]
  18. Mariano L, Nicosia L, Pupo D, et al. A Pictorial Exploration of Mammary Paget Disease: Insights and Perspectives. Cancers (Basel) 2023;15:5276. [Crossref] [PubMed]
  19. Tanaka R, Sasajima Y, Tsuda H, et al. Human epidermal growth factor receptor 2 protein overexpression and gene amplification in extramammary Paget disease. Br J Dermatol 2013;168:1259-66. [Crossref] [PubMed]
  20. Hanawa F, Inozume T, Harada K, et al. A Case of Metastatic Extramammary Paget's Disease Responding to Trastuzumab plus Paclitaxel Combination Therapy. Case Rep Dermatol 2011;3:223-7. [Crossref] [PubMed]
  21. Chen CY, Chiang CP, Lin LC, et al. Ado-trastuzumab emtansine (T-DM1) for a case of HER2-amplified metastatic extramammary Paget's disease of scrotum: Clinical next-generation sequencing for precision medicine. Dermatologica Sinica 2020;38:194-5.
  22. Hsieh GL, English DP, Tu P, et al. Case of Metastatic Extramammary Paget Disease of the Vulva Treated Successfully With Trastuzumab Emtansine. JCO Precis Oncol 2018;2:1-8. [Crossref] [PubMed]
  23. Hirai I, Tanese K, Nakamura Y, et al. Phase II clinical trial of docetaxel and trastuzumab for HER2-positive advanced extramammary Paget's disease (EMPD-HER2DOC). Oncologist 2024;29:e1201-8. [Crossref] [PubMed]
  24. Sola-Ortigosa J, Muñoz-Santos C, Hernández-Bronchud M, et al. Cutaneous Apocrine Adenocarcinoma of the Groin With Extramammary Paget Disease: Response to Dual HER2 Blockade With Trastuzumab and Pertuzumab. Actas Dermosifiliogr 2022;113:973-5. [Crossref] [PubMed]
  25. Nowicka-Matus K, Salkus G, Sønderkær M, et al. Scrotal Paget's Disease Associated With Human Epidermal Growth Factor Receptor 2-Overexpressing Metastatic Apocrine Carcinoma With Complete Response to Paclitaxel, Trastuzumab, and Pertuzumab. JCO Precis Oncol 2023;7:e2300173. [Crossref] [PubMed]
  26. Cortés J, Kim SB, Chung WP, et al. Trastuzumab Deruxtecan versus Trastuzumab Emtansine for Breast Cancer. N Engl J Med 2022;386:1143-54. [Crossref] [PubMed]
  27. Modi S, Saura C, Yamashita T, et al. Trastuzumab Deruxtecan in Previously Treated HER2-Positive Breast Cancer. N Engl J Med 2020;382:610-21. [Crossref] [PubMed]
doi: 10.21037/acr-2025-230
Cite this article as: Gorecki G, Antonios B, Rajrajan S, Babu K, Nakayama J, Hilton C. HER2-directed therapy in metastatic vulvar empd—a report of two cases and narrative review. AME Case Rep 2026;10:13.

Article Options

Download Citation

Share