Metastatic cSCC Diagnostic Work-Up and Risk Assessment

Gregory A. Daniels, MD:Today we’re discussing a case of a 79-year-old gentleman who visits his dermatologist with a large ulcerative lesion near the clavicle. He reports that the lesion was there for approximately 5 months while he was living in Florida for the winter. The lesion was biopsied. It was felt and found to be a cutaneous squamous cell carcinoma. The standard excision was performed with 4 mm margins with postoperative margin determination to be negative.

The patient did well for several years until re-presenting in May of 2018 when he shows up to his dermatologist now with lesions that are surrounding the area where the original lesion was, including signs that there was dermal spread and regional lymph node involvement.

Imaging at the time that the patient presented to his dermatologist with the recurrence found that there was subcutaneous fat involvement and parotid lymph node involvement. Biopsy confirmed that these areas were involved with a poorly differentiated cutaneous squamous cell cancer. It was staged as a stage IV, felt to be the original lesion was a T3, and now we had N2 involvement.

The patient was felt to be best suitable for systemic therapy, and he was started on cemiplimab.

My initial impression of this case is that as we know, cutaneous squamous cell cancers are the second most common skin cancer presented in the United States. It happens in elderly patients more often, typically a white male. So, despite not knowing the race of this gentleman, the occurrence makes sense in that he’s 79 years old, presented with a lesion, and was taken care of primarily.

He recurred 2 years later. Why did he recur 2 years later? He likely had some risk factors that aren’t well defined in the case. For example, we don’t know the original size of the lesion. We do know that it was on the clavicle area and that it was resected to negative margins, but we don’t know if it was in to the subcutaneous fat at that time, or if there was perineural invasion.

I’d want to know that information, and I’m suspicious of that, given that 2 years later he presents in this pattern where he has dermal involvement and lymph node involvement of the tumor. I’d also want to know this gentleman’s current health condition. Does he have diabetes? Maybe he has other comorbidities such as CLL [chronic lymphocytic leukemia]. Then to the extreme, is he a transplant patient? I’m sure that would have been mentioned in the case, but not here.

The general work-up for a patient presenting with regional involvement, in this case, this gentleman had palpable lymph nodes. I’d be concerned about the extent of the involvement, even systemic involvement. Besides the usual history and physical, a work-up should include looking for signs and symptoms. I’d also consider routine scans. In this case, I’d consider CT [computed tomography] scans in the chest, abdomen, and pelvis. If there’s any concern, sometimes I’ll even consider imaging of the brain.

General health should be assessed. That would be considering liver and kidney status. Are there underlying comorbidities such as HIV or hepatitis that I should be worried about too as I’m starting to think about the systemic plan for this gentleman?

I think the work-up has changed a little bit over the years. I mentioned HIV and hepatitis C. These risk groups also factor in to some of the systemic therapies that we’re considering such as PD-1 [programmed cell death protein 1] blockade or other cytotoxic chemotherapies. But, the general evaluation of looking at signs and symptoms and the scans that I mentioned have been standard for some time.

For high-risk features, we divide cutaneous squamous cell cancer into low-risk and high-risk groups. High-risk features would include locations such as in the center of the face, on the hands, or on the genitals. For the size of the tumor, how extensive it is in terms of its depth of invasion or the anatomic structures that it goes through? We also consider factors such as the patient. Is this a high-risk patient? For example, do they have derangements of their immune system? Is there an underlying DNA repair deficiency? All of these will factor into what the risk of recurrence is.

We rely a lot on the pathologist or dermatopathologist to give us these variables back—has there been perineural invasion, what the size of these nerves might be that are involved, as well as the differentiation state of the tumor. Is it a poorly differentiated or a well differentiated tumor? These factor in to the clinical assessment of the patient. Unfortunately, today we really don’t have good molecular prognostic factors, such as in breast cancer, where we might be able to risk-stratify patients. So, we rely on these clinical factors.

Transcript edited for clarity.

Case: A 79-Year-Old Male With Metastatic CSCC

April 2016

• A 79-year-old male presented to dermatologist with a large ulcerative lesion on clavicle; he reported lesion first appeared 5 months ago while living in Florida for the winter
• Diagnosed with localized cutaneous squamous cell carcinoma
• Standard surgical excision performed with 4 mm clinical margins; postoperative margins negative

May 2018

• Patient returns to dermatologist for follow-up c/o multiple lesions on shoulder and neck around the site of prior excision
• PE:
  • Multiple visible, ulcerated lesions, approximately 2-3cm in diameter; suspected tumor depth >5mm
  • Multiple palpable nodes ~2cm
• Imaging confirmed 7 mm invasion into subcutaneous fat; parotid nodal involvement
• Biopsy confirmed cutaneous squamous cell carcinoma, poorly-differentiated
• Diagnosis: Metastatic cutaneous squamous cell carcinoma
• Stage IV: T3N2M0
• Patient started on cemiplimab