Successful and long-term response to trastuzumab plus paclitaxel combination therapy in human epidermal growth factor receptor 2-positive extramammary Paget's disease: A case report and review of the literature

Abstract

A 58-year-old woman with a histologically confirmed diagnosis of vulvar extramammary Paget's disease (EMPD) was referred to our hospital due to locally advanced and relapsed EMPD. The patient had undergone surgical resection three times for relapsed vulvar EMPD over a period of 12 years, but developed locally advanced and unresectable EMPD. As pathological examination indicated that the lesion was positive for human epidermal growth factor receptor 2 (HER2) on immunohistochemical staining, the patient was treated with trastuzumab plus paclitaxel. The primary tumor mass and lymph node metastasis regressed successfully with combined trastuzumab and paclitaxel therapy, and the disease has been stable for >2 years after the initiation of treatment. These observations suggest that HER2 status must be determined in patients with advanced and/or metastatic extramammary Paget's disease and therapy with HER2 inhibitors should be considered as an option for the treatment of HER2-positive EMPD.

Keywords: breast cancer; chemotherapy; human epidermal growth factor receptor 2; paclitaxel; trastuzumab.

Figure 1.

Giant, slightly raised erythematous and hemorrhagic granular lesions in the perineum and a mass in the inner thigh were observed on physical examination.

Figure 2.

Changes in computed tomography (CT) findings (A and B) before and (C and D) after treatment with trastuzumab and paclitaxel. CT prior to therapy revealed (A) enlargement of the inguinal lymph nodes and (B) a mass in the perineum (arrows). (C and D) CT after therapy revealed disappearance of the inguinal lymph nodes and improvement of the mass in the perineum (arrows).

Figure 3.

(A) Histological findings of vulvar excision specimens at initial presentation showed infiltration by hypertrophic cells with enlarged nuclei, proliferating as they replace the basal side of the epidermis (hematoxylin and eosin staining). (B) Immunohistological examination revealed that the tumor cells were positive for cytokeratin 7. All magnifications, ×40.

Figure 4.

(A) Histological findings of biopsy specimens from the vulvar tumor revealed proliferation of hypertrophic cells with enlarged nuclei, with an irregular part on the basal side of the proliferation foci (hematoxylin and eosin staining). The immunohistochemical findings revealed the specimens to be positive for (B) cytokeratin 7 and (C) human epidermal growth factor 2, and negative for (D) estrogen and (E) progesterone receptors (all magnifications, ×200).

Figure 5.

Human epidermal growth factor 2 (HER2) gene amplification by fluorescence in situ hybridization. Red signal, HER2 gene; green signal, chromosome 17 centromere (CEP17) (×600). The HER2 signal numbers and the signal numbers of CEP17 were counted and the HER2/CEP17 signal ratio was calculated as 2.1, which was considered to be positive in the present case.