Lindsey A. Fitzgerald, MD

A 70-year-old veteran followed in clinic for metastatic castration-resistant prostate cancer (mCRPC) was found to have a new left axillary lymph node conglomerate on routine imaging, despite stable PSA on Enzalutamide therapy. Biopsy of the axillary mass showed metastatic neuroendocrine carcinoma, with a differential diagnosis of small cell carcinoma of unknown primary vs. Merkel Cell Carcinoma (MCC). Given his prostate cancer diagnosis and the rarity of MCC, small cell differentiation of prostate cancer was initially favored. However, the patient appeared well and subsequent PET/CT only showed two subcutaneous hypermetabolic lesions. These findings would be unusual with small cell differentiation of prostate cancer. A second biopsy of a subcutaneous lesion was most consistent with MCC, confirming our diagnosis.

At time of diagnosis, staging MRI Brain revealed 3 parenchymal brain lesions, presumed to be metastatic MCC. As per a landmark trial by Nghiem et al, the patient was started on Pembrolizumab 2 mg/kg every three weeks for treatment of metastatic MCC. Brain lesions were locally treated with stereotactic radiosurgery (SRS).

Although his mCRPC was under good control with Enzalutamide, this drug is associated with increased risk of seizures in clinical trial and is not recommended for those with predisposing seizure risk. In light of MCC brain metastases, we decided to switch mCRPC therapy to Darolutamide, an androgen receptor antagonist that has lower penetration of the blood-brain barrier and less incidence of seizures. He tolerated the combination of Darolutamide with Pembrolizumab well, with only a grade 1 acneiform rash.

After just 1 cycle of Pembrolizumab, the patient’s clinically-evident MCC drastically regressed. After 8 months of treatment, his MCC continues to respond clinically and radiographically. This case emphasizes the importance of not relying on “Occam’s razor” – that one should assume a single diagnosis for multiple findings. The simplest explanation of the patient’s left axillary mass biopsy would have been small cell differentiation of prostate cancer; however, this has proved to be a synchronous MCC, which portends a much more favorable prognosis with immunotherapy treatment. We also demonstrate a successful approach to concurrent treatment of metastatic MCC and mCRPC.

A 70-year-old veteran followed in clinic for metastatic castration-resistant prostate cancer (mCRPC) was found to have a new left axillary lymph node conglomerate on routine imaging, despite stable PSA on Enzalutamide therapy. Biopsy of the axillary mass showed metastatic neuroendocrine carcinoma, with a differential diagnosis of small cell carcinoma of unknown primary vs. Merkel Cell Carcinoma (MCC). Given his prostate cancer diagnosis and the rarity of MCC, small cell differentiation of prostate cancer was initially favored. However, the patient appeared well and subsequent PET/CT only showed two subcutaneous hypermetabolic lesions. These findings would be unusual with small cell differentiation of prostate cancer. A second biopsy of a subcutaneous lesion was most consistent with MCC, confirming our diagnosis.

At time of diagnosis, staging MRI Brain revealed 3 parenchymal brain lesions, presumed to be metastatic MCC. As per a landmark trial by Nghiem et al, the patient was started on Pembrolizumab 2 mg/kg every three weeks for treatment of metastatic MCC. Brain lesions were locally treated with stereotactic radiosurgery (SRS).

Although his mCRPC was under good control with Enzalutamide, this drug is associated with increased risk of seizures in clinical trial and is not recommended for those with predisposing seizure risk. In light of MCC brain metastases, we decided to switch mCRPC therapy to Darolutamide, an androgen receptor antagonist that has lower penetration of the blood-brain barrier and less incidence of seizures. He tolerated the combination of Darolutamide with Pembrolizumab well, with only a grade 1 acneiform rash.

After just 1 cycle of Pembrolizumab, the patient’s clinically-evident MCC drastically regressed. After 8 months of treatment, his MCC continues to respond clinically and radiographically. This case emphasizes the importance of not relying on “Occam’s razor” – that one should assume a single diagnosis for multiple findings. The simplest explanation of the patient’s left axillary mass biopsy would have been small cell differentiation of prostate cancer; however, this has proved to be a synchronous MCC, which portends a much more favorable prognosis with immunotherapy treatment. We also demonstrate a successful approach to concurrent treatment of metastatic MCC and mCRPC.

A 70-year-old veteran followed in clinic for metastatic castration-resistant prostate cancer (mCRPC) was found to have a new left axillary lymph node conglomerate on routine imaging, despite stable PSA on Enzalutamide therapy. Biopsy of the axillary mass showed metastatic neuroendocrine carcinoma, with a differential diagnosis of small cell carcinoma of unknown primary vs. Merkel Cell Carcinoma (MCC). Given his prostate cancer diagnosis and the rarity of MCC, small cell differentiation of prostate cancer was initially favored. However, the patient appeared well and subsequent PET/CT only showed two subcutaneous hypermetabolic lesions. These findings would be unusual with small cell differentiation of prostate cancer. A second biopsy of a subcutaneous lesion was most consistent with MCC, confirming our diagnosis.

At time of diagnosis, staging MRI Brain revealed 3 parenchymal brain lesions, presumed to be metastatic MCC. As per a landmark trial by Nghiem et al, the patient was started on Pembrolizumab 2 mg/kg every three weeks for treatment of metastatic MCC. Brain lesions were locally treated with stereotactic radiosurgery (SRS).

Although his mCRPC was under good control with Enzalutamide, this drug is associated with increased risk of seizures in clinical trial and is not recommended for those with predisposing seizure risk. In light of MCC brain metastases, we decided to switch mCRPC therapy to Darolutamide, an androgen receptor antagonist that has lower penetration of the blood-brain barrier and less incidence of seizures. He tolerated the combination of Darolutamide with Pembrolizumab well, with only a grade 1 acneiform rash.

After just 1 cycle of Pembrolizumab, the patient’s clinically-evident MCC drastically regressed. After 8 months of treatment, his MCC continues to respond clinically and radiographically. This case emphasizes the importance of not relying on “Occam’s razor” – that one should assume a single diagnosis for multiple findings. The simplest explanation of the patient’s left axillary mass biopsy would have been small cell differentiation of prostate cancer; however, this has proved to be a synchronous MCC, which portends a much more favorable prognosis with immunotherapy treatment. We also demonstrate a successful approach to concurrent treatment of metastatic MCC and mCRPC.