Merkel Cell Carcinoma

Question 1

What is the annual incidence of Merkel cell carcinoma (MCC) in the United States?

Answer 1

∼500 cases/yr of MCC in the United States. Higher in Australia and NZ.

Question 2

What is the median age of Dx for MCC?

Answer 2

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

Question 3

What is the cell type of origin for MCC?

Answer 3

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

Question 4

What virus is associated with MCC?

Answer 4

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

Question 5

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

Answer 5

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

Question 6

What % of pts have LN involvement at Dx?

Answer 6

∼25% have LN involvement at Dx.

Question 7

DMs develop in what % of pts with MCC?

Answer 7

50%–60% of MCC pts develop DMs. ∼10% DM rate at presentation.

Question 8

Is MCC a radiosensitive or radioresistant tumor?

Answer 8

MCC is considered radiosensitive.

Question 9

What demographic group does MCC affect predominantly?

Answer 9

Elderly white males are primarily affected by MCC (M:F, 2:1). Immunocompromised pts, 24-fold increase risk in transplant pts.

Question 10

Where do most MCCs arise anatomically?

Answer 10

H&N region (∼45%) > UEs (∼25%) > LEs (∼15%) > trunk (∼10%) > other (∼5%–10%)

Question 11

MCC tumors at which sites have a particularly poor prognosis?

Answer 11

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

Question 12

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

Answer 12

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

Question 13

What is the most important prognostic factor in MCC?

Answer 13

LN status at presentation.

Question 14

What clinical features are common in MCC?

Answer 14

1. Asymptomatic
2. Expand (grow) rapidly
3. Immune suppression
4. Older than 50 yo
5. UV exposed area in fair skin individual

Question 15

What is the workup for MCC?

Answer 15

MCC workup: H&P (focused on skin and regional nodes), CBC, CMP, CT
N/C/A/P, PET/CT, ± MRI Brain

Question 16

What markers should be included in the immuno panel?

Answer 16

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

Question 17

Why obtain chest imaging at staging?

Answer 17

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

Question 18

Outline the informal staging system commonly utilized by various institutions for MCC, and approximate 5-yr OS.

Answer 18

Stage I: localized (5-yr OS 51%)
Stage II: LN+ (5-yr OS 35%)
Stage III: DMs (5-yr OS 14%)

Question 19

Outline the 8th edition AJCC TNM staging.

Answer 19

T1: ≤2 cm
T2: >2 cm and ≤5 cm
T3: >5 cm
T4: invades bone, muscle, fascia, or cartilage
N1: regional LN mets
N1a: clinically occult mets on LND; N1a(sn) if detected on SLN Bx
N1b: clinically/radiographically evident mets
N2: in-transit mets (b/t primary and nodal basin or distal to primary) without LN mets
N3: in-transit mets (b/t primary and nodal basin or distal to primary) with LN mets
M1a: mets to skin, SQ tissue, or distant LN
M1b: mets to lung
M1c: mets to all other visceral sites

Question 20

What is the definition of in-transit mets or N2/N3 Dz per the 8th edition AJCC classification?

Answer 20

“In-transit” is defined as tumor distinct from the primary tumor and either b/t the primary and the nodal basin or distal to the primary.

Question 21

Outline the latest AJCC stage groupings for MCC.

Answer 21

Clinical:
Stage I: T1N0
Stage IIA: T2–3N0
Stage IIB: T4N0
Stage III: any TN1–3
Stage IV: M1

Pathologic:
Stage I: T1N0
Stage IB: T1cN0
Stage IIA: T2–3N0
Stage IIB: T4N0
Stage IIIA: T0N1b
Stage IIIA: any TN1a(sn) or N1a
Stage IIIB: any TN1b–3
Stage IV: M1

Question 22

What is the Tx paradigm for MCC?

Answer 22

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

Question 23

In which group of pts is an SLNB more likely to be unreliable?

Answer 23

SLNB in the H&N region is more likely to be unsuccessful; in these cases RT to the regional draining nodes should be considered.

Question 24

What surgical margins are recommended for WLE?

Answer 24

1–2 cm (NCCN 2018)

Question 25

When is adj RT indicated for MCC?

Answer 25

Historically, adj RT has been included in the Tx course for the majority of MCC pts. A study by Allen 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 1,665 cases showed adj RT to be associated with better OS. (Mojica 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

Question 26

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

Answer 26

Commonly used total doses for MCC:
Negative margins: 50–56 Gy
Microscopically+ margins: 56–60 Gy
Gross residual or unresectable: 60–66 Gy
No LN Bx or LND, clinically node–: 46–50 Gy
No LN Bx or LND, clinically node+: 60–66 Gy
SLN–, no LND: Observe
SLN+, no LND: 50–56 Gy
LND+: 50–60 Gy

Question 27

What RT margins and techniques are typically used for MCC?

Answer 27

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

Question 28

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

Answer 28

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 sup 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

Question 29

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

Answer 29

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 sup efficacy over RT alone.

Question 30

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

Answer 30

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

Question 31

After recurrence, can Merkel cell be retreated?

Answer 31

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

Question 32

Are there any effective systemic therapies for metastatic MCC?

Answer 32

Yes, PD-L1 inhibitor Avelumab has been approved by the FDA. Carboplatin/etoposide is 1st-line chemo

Question 33

What specific f/u studies do MCC pts require?

Answer 33

Frequent CXR imaging, complete LN exam, and total skin exam for life (high rates of 2nd skin cancers

Question 34

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

Answer 34

NCCN recommended f/u schedule: H&P and clinically indicated imaging q3–6mos for 3 yrs, and q6–12mos thereafter.

Question 35

What are the major toxicities in pts receiving CRT for MCC?

Answer 35

Skin (grade 3–4) toxicity is ∼60% and neutropenia is ∼40%. (Poulsen M et al., IJROBP 2001)