Dr. Manisha Thakuria
“The lack of a pathognomonic appearance is often what precludes an early diagnosis of this cancer,” Dr. Thakuria, a dermatologist at Brigham and Women’s Hospital, Boston, said during a virtual forum on cutaneous malignancies jointly presented by Postgraduate Institute for Medicine and the Global Academy for Medical Education. “MCCs can vary in appearance in their color, from pink to red to purple, or sometimes they have no color at all. They can be exophytic and obvious, or subtle, deeper tumors. These tumors are generally firm and nontender and are characterized by rapid growth, which is usually but not exclusively the feature that prompts biopsy.”
The typical patient with MCC is elderly, with an average age of 75 years. It affects males more than females by an approximately 2:1 ratio and tends to occur in fair-skinned individuals, although MCC does develop in skin of color. “While the majority of patients with this disease are immunocompetent, immunosuppressed patients are overrepresented in this disease, compared with the general population,” she said.
The clinical differential diagnosis is broad and includes both malignant and benign tumors, which requires a high index of suspicion. Most primary lesions are located on the head and neck, lower limb, and upper limb, but they may appear in non–sun exposed areas, such as the buttocks, as well.
One prospective study of 195 MCC patients found that 56% of clinicians presumed that these tumors were benign at the time of biopsy, and 32% were thought to have a cyst or acneiform lesion. The study authors summarized key clinical features of MCC with the acronym AEIOU: A stands for asymptomatic or nontender; E stands for expanding rapidly, usually over a duration less than 3 months; I stands for immunosuppression; O stands for patient older than age 50 years; and U stands for UV exposed skin location. The researchers found that 89% of the patients studied met three or more of the AEIOU criteria.
Dr. Thakuria, codirector of the Merkel Cell Carcinoma Center of Excellence at the Dana-Farber/Brigham and Women’s Cancer Center and assistant professor of dermatology at Harvard University, both in Boston, shared the following tips for dermatologic evaluation when MCC is suspected:
- Measure and record the clinical diameter of the lesions. “This helps you determine the T staging later, and from there can help you decide on proper treatment,” she said.
- Inspect and palpate the surrounding skin to look for in-transit metastases. “This may actually upstage the patient.”
- For a subcutaneous nodule, hub your punch biopsy. “These tumors can be centered in the deep dermis or fat,” Dr. Thakuria said. “If you really suspect MCC and you don’t get a result on your first biopsy, you may want to consider doing a second deeper biopsy, perhaps even a telescoping biopsy. This is especially true if your first biopsy was via shave technique and showed normal skin.”
- Refer to surgical oncology and radiation oncology ASAP. “You want to call them to ensure speedy consultation, within 1 week if possible,” she said. “Remember that all clinically node-negative MCCs warrant consideration of sentinel lymph node biopsy, regardless of tumor size. Upstaging will occur in 25%-32% of patients.”
Staging workup includes a full skin and lymph node exam to identify in-transit metastases and regional lymphadenopathy. “Palpation is key,” Dr. Thakuria said. “Next, you want to do some form of radiographic examination, so either a scalp to toes PET/CT or CT scan of the chest, abdomen, and pelvis. Finally, sentinel lymph node biopsy is going to be important if you have a clinically node-negative patient but you want to pathologically stage the person appropriately.” Although not formally part of the staging workup, she recommends ordering an AMERK test at diagnosis. AMERK detects antibodies to a Merkel cell polyomavirus oncoprotein, which is a marker of disease status present in about half of MCC patients. It falls with the treatment of cancer and rises with recurrence.
Discussing prognosis with MCC patients “can be challenging and uncomfortable, but even more so if you’re unfamiliar with some of the nuances of the terminology that is used,” Dr. Thakuria said. “Patients who go to Google are often going to encounter overall survival numbers, which are going to be worse than disease-specific numbers in any disease because they take into account death from any cause. This effect is heightened in MCC because this is cancer of predominately older adults, so there are other competing causes of death in this population, which drags down the overall survival estimates.”
Another point to remember when discussing survival with patients is that advances in immunotherapy are not necessarily reflected in national databases. “This is important, because usually in any cancer there’s a 5- to 10-year lag in survival information,” she said. “The last 5 years have brought an incredible change to MCC because of the advent of immunotherapy. Now we’re seeing incredible responses [in the clinic], but we’re not yet seeing those reflected in our survival tables.”
According to an analysis of prognostic factors from 9,387 MCC cases, nodal status is one of most important predictors of lower survival at 5 years, compared with having local disease: 35% versus 51%, respectively. Among patients with macroscopic lymph nodes, having known primary disease is associated with a lower survival at 5 years, compared with having unknown primary disease (27% vs. 42% at five years).
Dr. Thakuria concluded her presentation by recommending a three-step plan for surveillance, starting with a full skin and lymph node exam every 3-6 months for the first 3 years and every 6-12 months thereafter. Second, she advised routine imaging for high risk patients (American Joint Committee on Cancer stage 2 and above) and symptom-directed imaging for low-risk patients. Finally, she recommended the AMERK test every 3 months for the first 2-3 years in patients who were seropositive at diagnosis. A rising titer may be an early indicator of recurrence.
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Dr. Thakuria reported having no financial disclosures.