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

摘要

A 55-year-old male presented to our outpatient clinic with a 1-year history of a growing reddish lesion in his genital area. Physical examination showed a solitary, stinging, reddish, well-demarcated, 2.5-cm nodule arising from ill-defined erythematous patches [Figure 1]a on his left scrotum. Several palpable lymph nodes in the left inguinal area were also observed. The blood biochemistry was normal. Incisional biopsy revealed poorly differentiated adenocarcinoma [Figure 1]b with apocrine features (upper right inset). The patient underwent debulking surgery, following which numerous Paget's cells were found in the biopsy specimen [Figure 1]c. Immunohistochemistry revealed that the tumor was positive for CK7, GCDFP-15, and HER2/neu [DAKO score 3+, 50%; [Figure 1]d but negative for CK20, CDX2, TTF-1, and PSA. Staging computed tomography (CT) scan revealed multiple hepatic [size, up to 5.4 cm; [Figure 2]a and bony metastases. In addition, bilateral inguinal and para-aortic lymph node metastases were observed. The patient's tumor specimen was sent for comprehensive genomic profiling utilizing next-generation sequencing (NGS), which identified HER2 amplification with copy number of 63, and additional mutations in KRAS, RICTOR, and PARP1 (Foundation Medicine Inc., Cambridge, Massachusetts, USA). The patient was diagnosed with Stage IV HER2-amplified metastatic extramammary Paget's disease (EMPD).[1] Anti-HER2 trastuzumab in combination with paclitaxel and radiotherapy was provided, but disease progressed after 1 year. We changed the antineoplastic agents to ado-trastuzumab emtansine (T-DM1; 3.6 mg/kg), which was provided every 3 weeks for a 21-day cycle. After 1 year of treatment with T-DM1, follow-up CT showed a good response with significant reductions in the size and number of the liver metastases [size, up to 1.4 cm; [Figure 2]b. Regression of the tumor was observed in bilateral inguinal regions and para-aortic spaces. HER2 amplification was not detectable in follow-up liquid biopsy by NGS (Foundation Medicine Inc., Cambridge, Massachusetts, USA). At the time of this report, he has been in active treatment and continues to have clinical response.