Merkel Cell Carcinoma

Updated by Anna O. Likhacheva

BACKGROUND

What is the annual incidence of Merkel cell carcinoma (MCC) in the U.S.?

~500 cases/yr of MCC in the U.S.

What is the median age of Dx for MCC?

The median age of Dx is 75 yrs (90% >50 yrs). MCC presents earlier in immunosuppressed pts.

What is the cell type of origin for MCC?

Neuroendocrine (dermal sensory cells)—aka primary small cell cancer, trabecular cell, or anaplastic cancer of the skin.

What virus is associated with MCC?

Merkel cell polyomavirus (detected in 43%–100%)

What is the prognosis of MCC as compared to other skin cancers?

Of skin cancers, MCC has the worst prognosis (even worse than melanoma).

What % of pts have LN involvement at Dx?

20% have LN involvement at Dx.

DMs develop in what % of pts with MCC?

50%–60% of MCC pts develop DMs.

Is MCC a radiosensitive or radioresistant tumor?

MCC is considered radiosensitive.

What demographic group does MCC affect predominantly?

Elderly whites males are primarily affected by MCC (male:female ratio, 2:1).

Where do most MCCs arise anatomically?

H&N region (50%) > extremities (33%)

MCC tumors at which sites have a particularly poor prognosis?

Vulva and/or perineum MCC is associated with a particularly poor prognosis.

To what tumor type is the histologic appearance of MCC similar?

The histologic appearance of MCC is similar to small cell carcinoma of the lung.

What are the histologic subtypes of MCC?

Histologic subtypes of MCC:

1. Small cell

2. Intermediate cell

3. Trabecular

What histologic subtype of MCC has the best prognosis?

Trabecular MCC has the best prognosis.

What are 2 important prognostic factors in MCC?

Prognostic factors in MCC:

1. Thickness/DOI

2. LN status

WORKUP/STAGING

What is the workup for MCC?

MCC workup: H&P, CBC, CMP, CT C/A/P, and MRI or PET for H&N primaries to assess nodal status

What imaging is required at a min for MCC staging?

CT chest/abdomen is required for staging.

What markers should be included in the immuno panel?

CK-20 (specific for MCC) and TTF-1 (specific for lung and thyroid)

Why obtain chest imaging at staging?

To r/o the possibility of small cell lung cancer with mets to the skin as an etiology, especially when CK-20–.

Outline the informal staging system commonly utilized by various institutions for MCC.

Informal staging system for MCC:

Stage I: localized

Stage II: LN+

Stage III: DMs

Outline the 7^th edition (2011) AJCC TNM staging.

T1: ≤2 cm

T2: >2 cm and ≤5 cm

T3: >5 cm

T4: invades bone, muscle, fascia, or cartilage

N1a: micromets

N1b: macromets (clinically detectable, path confirmed)

N2: in-transit mets (between primary and nodal basin or distal to primary)

M1a: mets to skin, SQ tissue, or distant LN

M1b: mets to lung

M1c: mets to all other visceral sites

What is the definition of in-transit mets or N2 Dz per the latest AJCC classification?

N2 Dz is defined as tumor distinct from the primary tumor and either between the primary and the nodal basin or distal to the primary.

Outline the latest AJCC stage groupings for MCC.

Stage IA: T1pN0

Stage IB: T1cN0

Stage IIA: T2–3pN0

Stage IIB: T2–3cN0

Stage IIC: T4N0

Stage IIIA: any TN1a

Stage IIIB: any TN1b–2

Stage IV: M1

TREATMENT/PROGNOSIS

What is the Tx paradigm for MCC?

MCC Tx paradigm: surgery (WLE or Mohs) with sentinel LN Bx +/– LND +/– adj RT +/– adj chemo

What are some commonly used chemo agents for MCC?

Agents used in MCC: cisplatin/carboplatin +/– etoposide

What surgical margins are recommended for WLE?

1–2 cm (NCCN 2014)

When is adj RT indicated for MCC?

Historically, adj RT has been included in the Tx course for the majority of MCC pts. A study by Allen PJ et al. (JCO 2005) suggested that adj RT was of no benefit in margin– pts with surgically staged low-risk nodal Dz. A SEER analysis of 1665 cases showed adj RT to be associated with better OS. (Mojica P et al., JCO 2007) Strong indications for RT include:

1. Tumor >2 cm

2. +/Close margins

3. Angiolymphatic invasion

4. LN+ or no LN evaluation

5. Immunocompromised pts

Per the NCCN, what RT doses are commonly used for MCC?

Commonly used total doses for MCC:

Negative margins: 50–56 Gy

Positive margins: 56–60 Gy

Gross residual or unresectable: 60–66 Gy

Clinically negative LN: 46–50 Gy

Clinically positive LN: 60–66 Gy

What RT margins are typically used for MCC?

For MCC, the typical RT margin is 5 cm around the primary tumor (i.e., not the scar).

When are regional LNs covered in the RT volume for MCC?

Regional LNs are typically covered for all MCC pts. Retrospective data suggest that the inclusion of regional LNs in the RT field is associated with superior outcomes. (Eich HT et al., Am J Clin Oncol 2002; Jabbour J et al., Ann Surg Oncol 2007) However, the role of LN coverage in sentinel LN Bx–or LND– pts is controversial.

What is the evidence for concurrent CRT after surgery for MCC?

Data on concurrent CRT for MCC are limited. Phase II trials have shown that CRT is tolerable (Poulsen MG et al., IJROBP 2006), but no trials have established superior efficacy over RT alone.

What is the historical LF rate after surgery alone and with adj RT?

Historical rates are 45%–75% with surgery alone and 15%–25% with adj RT.

Estimate the 3-yr OS for MCC by informal staging.

3-yr OS by informal staging:

Stage I (localized): 70%–80%

Stage II (LN+): 50%–60%

Stage III (DM): 30%

After recurrence, can Merkel cell be retreated?

Yes. Multimodality surgery +/– RT +/– chemo is recommended, with improved survival over single modality for recurrent Dz. (Eng TY et al., IJROBP 2004)

TOXICITY

What specific follow-up studies do MCC pts require?

Frequent CXR imaging, consideration of serum neuron-specific enolase testing for recurrence, and total skin exam for life (high rates of 2^nd skin cancers)

What follow-up intervals are recommended by the NCCN for MCC?

NCCN recommended follow-up schedule: H&P and clinically indicated imaging q3–6mos for 2 yrs, and q6–12mos thereafter.

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