Update on molecular genetics, diagnosis, staging, sentinel lymph … · 2019. 9. 5. · Hanly 2001...

Merkel cell carcinoma

Update on molecular genetics,

diagnosis, staging, sentinel lymph

node processing

Michael T. Tetzlaff MD, PhDAssociate Professor

Departments of Pathology (Section of Dermatopathology) and Translational and

Molecular Pathology

The University of Texas MD Anderson Cancer Center

Houston Texas

Disclosure of Relevant Financial Relationships

I report no relevant financial relationships.

I have served on Advisory Boards for Novartis LLC, Myriad Genetics and Seattle Genetics, but

these are all unrelated to the topics I will present today.

Merkel Cell Carcinoma

• Diagnosing Merkel Cell Carcinoma

• Histopathologic mimics

• Immunohistochemical studies that aid in the diagnosis

• Pitfalls: CK20-negative and combined morphologies

• Demographics of the disease

• Who gets Merkel cell carcinoma and why?

• Molecular genetics of Merkel cell carcinoma

• Staging Merkel cell carcinoma: Updates to 8th Edition AJCC

• Prognostic biomarkers in Merkel cell carcinoma

• Therapeutic advances in Merkel cell carcinoma

• Biomarkers predictive of response

Case 1

• 52 year old Caucasian woman

• No past medical history

• Rapidly enlarging erythematous

papule

• Right malar cheek

Cam5.2 CK20

CHG Synaptophysin

CD45 (LCA) TTF-1

Case 2

• 76 year old Caucasian man

• Rapidly enlarging red-blue papule

• Left proximal pretibial region

CK20Pan-CK

CHG Synaptophysin

TTF-1NF

Diagnosis: MERKEL CELL CARCINOMA

MERKEL CELL CARCINOMA, ULCERATED

TUMOR SIZE: 3.1 x 1.75 MM

TUMOR THICKNESS: 1.75 MM

MITOTIC COUNT: 39/MM2

PATTERN OF GROWTH: PUSHING

LYMPHOCYTIC INFILTRATE: NON-BRISK

VASCULAR INVASION: PRESENT

INVASION BEYOND SUBCUTANEOUS TISSUE

(BONE, MUSCLE, FASCIA, OR CARTILAGE):

NOT IDENTIFIED

ASSOCIATED MALIGNANCY: NOT IDENTIFIED

SURGICAL MARGINS: CARCINOMA PRESENT

AT DEEP TISSUE EDGE

MERKEL CELL CARCINOMA

TUMOR SIZE: AT LEAST 5.8 X 2.9 MM

TUMOR THICKNESS: AT LEAST 6.0 MM

MITOTIC COUNT: 25/MM2

PATTERN OF GROWTH: NOT AVAILABLE

LYMPHOCYTIC INFILTRATE: NON-BRISK

VASCULAR INVASION: NOT IDENTIFIED

INVASION BEYOND SUBCUTANEOUS TISSUE

(BONE, MUSCLE, FASCIA, OR CARTILAGE):

NOT AVAILABLE

ASSOCIATED MALIGNANCY: NOT IDENTIFIED

SURGICAL MARGINS: CARCINOMA PRESENT

AT PERIPHERAL AND DEEP TISSUE EDGES.

Case 1 Case 2

Aggressive Epidermal MalignanciesMerkel Cell Carcinoma












Pos Total Pos Total Pos Total

Kervarrec 2018 PMID: 30349028 94 103 10 95 73 97

Stanoszek 2018 PMID: 30239030 46 55 42 55

Bobos 2006 PMID: 16625069 13 13 0 13 12 13

Hanly 2001 PMID: 10728812 20 21 0 21

Sidropoulos 2011 PMID: 21571955 35 40 1 40

Cheuk 2001 PMID: 11175640 23 23 0 23

Moll 1992 PMID: 1371204 15 15

Schmidt 1998 PMID: 9700371 43 56 25 40

Llombart 2005 PMID: 15910593 15 20 0 20

Sur 2007 PMID: 17885674 14 15 0 15

Ordonez 2000 PMID: 10976695 16 18 0 18

Leech 2001 PMID: 11533085 10 11 0 11

Chan 1997 PMID: 9042291 33 34

McCalmont 2010 PMID: 20642632 80 100 95 100

Johannson 1990 PMID: 1698390 17 25

Shah 1993 PMID: 7678934 9 9

Metz 1998 PMID: 9717649 6 6 4 6

Yang 2004 PMID: 14984578 19 22 0 22

Jensen 2000 PMID: 11127923 23 26

Kurokawa 2003 PMID: 12727026 6 6

Chu 2000 PMID: 11007036 7 9

Acebo 2005 PMID: 16164706 9 10 8 8

Byrd-Gloster 2000 PMID: 10665914 16 21 0 21

Nicholson 2000 PMID: 10937047 18 27

Scott and Helm 1999 PMID: 10027519 9 10

Totals 570 661 11 299 285 353

Total Percentage

CK20 TTF-1 NF

80.73.786.2 NF

TTF1

CK20

Pos Total Pos Total Pos Total Pos Total Pos Total

Bobos 2006 PMID: 16625069 4 13 12 13 13 13 10 13 9 13

Sidropoulos 2011 PMID: 21571955 2 40 29 40 39 40

Llombart 2005 PMID: 15910593 20 20 19 20

Sur 2007 PMID: 17885674 4 15 15 15 11 15 13 15 15 15

Jensen 2000 PMID: 11127923 6 26

Kurokawa 2003 PMID: 12727026 6 6 5 6 6 6 6 6

Acebo 2005 PMID: 16164706 5 10 6 8 6 8

Totals 21 104 33 34 84 102 93 102 30 34

Total Percentage 20.2 97.1 82.4 91.2 88.2

CK7 NSE CHG Synaptophysin CD56

CHG SYN

Differential diagnosis of Merkel cell carcinoma

Diagnosis Morphology IHC

Basal cell carcinoma • Peripheral palisading

• Clefting

• Mucinous tumor

associated stroma

• MCPy-T-antigen negative

• BCC: CK5/6+ and CK20-

• MCC: CK20+ and CK5/6-

Melanoma • Pigmented

• Intraepidermal extension

common

• S100+, MART-1+, Sox-10+, HMB-45+,

MITF+

• Cytokeratin-

Lymphoma/Leukemia • Dishesive • Positive for lymphoid markers

• Negative for cytokeratins

Metastatic

neuroendocrine

carcinoma (SCLC)

• Overlapping • TTF-1+

• CK7+ (20% of MCCs also positive)

• CDX-2+

• MCPy-T-antigen negative

Basal cell carcinoma may mimic Merkel cell carcinoma

Stromal retractionPeripheral palisading Mucinous stroma

MCC may exhibit some morphologic features

that closely overlap with those of BCC

Merkel cell carcinoma may show overlapping

morphology with Basal cell carcinoma

BCC

MCC

CK20 CK5/6

Immunohistochemical studies for CK5/6 and CK20

help to distinguish BCC from MCC

Differential diagnosis of MCC: Melanoma

S100 CK20

Mart-1

Rare examples

of S100+ in MCC

2% (3/146)

Differential diagnosis of MCC: MelanomaImmunohistochemical studies support the distinction


Kervarrec 2018 PMID: 30349028 mulitple types 4 65 37 63 3 69

Stanoszek 2018 PMID: 30239030 multiple types 25 61 2 61

Bobos 2006 PMID: 16625069 SCLC 1 13 11 13 0 13

Hanly 2001 PMID: 10728812 SCLC 11 33 28 33

Sidropoulos 2011 PMID: 21571955 SCLC 0 36 27 36

Cheuk 2001 PMID: 11175640 SCLC 0 52 43 52

Cheuk 2001 PMID: 11175640 Extrapulmonary NEC 2 50 21 50

Moll 1992 PMID: 1371204 SCLC 3 15

Schmidt 1998 PMID: 9700371 SCLC 0 18 0 22

Ordonez 2000 PMID: 10976695 SCLC 1 28 27 28

Ordonez 2000 PMID: 10976695 Extrapulmonary NEC 1 36 4 36

Leech 2001 PMID: 11533085 SCLC 0 20 10 10

Chan 1997 PMID: 9042291 SCLC 1 37

Chan 1997 PMID: 9042291 Extrapulmonary NEC 1 52

Johannson 1990 PMID: 1698390 SCLC 0 58

Shah 1993 PMID: 7678934 SCLC 0 28

Shah 1993 PMID: 7678934 Extrapulmonary NEC 0 9

Metz 1998 PMID: 9717649 SCLC 0 22 0 22

Yang 2004 PMID: 14984578 SCLC 0 9 9 9

Chu 2000 PMID: 11007036 SCLC 0 7

Byrd-Gloster 2000 PMID: 10665914 SCLC 1 36 35 36

Nicholson 2000 PMID: 10937047 SCLC 0 5

Scott and Helm 1999 PMID: 10027519 SCLC 0 6

Totals all cases 51 601 252 366 5 282

Total Percentage all cases

Totals SCLC 18 337 190 217 0 143

Total Percentage SCLC

Total Extrapulmonary NEC 4 138 25 86 0 9

Total Percentage Extrapulmonary NEC

NFTTF-1CK20

CK20

2.9 29.1 0.0

0.087.65.3

TTF-1 NF

CK20 TTF-1 NF

8.5 68.9 1.8


Kervarrec 2018 PMID: 30349028 94 103 10 95 73 97

Stanoszek 2018 PMID: 30239030 46 55 42 55

Bobos 2006 PMID: 16625069 13 13 0 13 12 13

Hanly 2001 PMID: 10728812 20 21 0 21

Sidropoulos 2011 PMID: 21571955 35 40 1 40

Cheuk 2001 PMID: 11175640 23 23 0 23

Moll 1992 PMID: 1371204 15 15

Schmidt 1998 PMID: 9700371 43 56 25 40

Llombart 2005 PMID: 15910593 15 20 0 20

Sur 2007 PMID: 17885674 14 15 0 15

Ordonez 2000 PMID: 10976695 16 18 0 18

Leech 2001 PMID: 11533085 10 11 0 11

Chan 1997 PMID: 9042291 33 34

McCalmont 2010 PMID: 20642632 80 100 95 100

Johannson 1990 PMID: 1698390 17 25

Shah 1993 PMID: 7678934 9 9

Metz 1998 PMID: 9717649 6 6 4 6

Yang 2004 PMID: 14984578 19 22 0 22

Jensen 2000 PMID: 11127923 23 26

Kurokawa 2003 PMID: 12727026 6 6

Chu 2000 PMID: 11007036 7 9

Acebo 2005 PMID: 16164706 9 10 8 8

Byrd-Gloster 2000 PMID: 10665914 16 21 0 21

Nicholson 2000 PMID: 10937047 18 27

Scott and Helm 1999 PMID: 10027519 9 10

Totals 570 661 11 299 285 353

Total Percentage

CK20 TTF-1 NF

80.73.786.2

SCLC

Distinguishing MCC from Small Cell Carcinoma of the LungImmunohistochemical studies for CK20, TTF-1 and NF

MCC

CK20CK20

TTF-1TTF-1

Differential diagnosis of MCC: Lymphoma/LeukemiaMCC may (aberrantly) express B-cell markers, TdT and CD56

• MCC may stain positively for

hematolymphoid markers:• 70% of MCCs are TdT+

• 94% of MCCs are Pax-5+

MCC

TdT Pax5

Sur M 2007 8/15 ---

Sidiropoulos M 2011 28/40 ---Kohle R 2013 21/27 24/27Zur Hausen A 2013 15/21 21/21

Total72/103

70%

45/48

94%

CD56 positivity of MCCs is an additional pitfall, as CD56 may also highlight

NK/T-cell lymphomas and Blastic plasmacytoid dendritic cell neoplasm

Demographics of Merkel cell carcinoma

• Risk factors for MCC are advanced age

and immunosuppression• Elderly

• Accumulation of mutations from ultraviolet light

• Organ transplantation, HIV+, CLL

• Merkel cell polyomavirus (MCPyV)

• Older Caucasian men

• Head and neck• 70% of patients >70 years old

• 62% of patients male

• 43% of patients head and neck

Image courtesy of Isaac Brownell MD PhD

Merkel cell carcinoma incidence is increasing

• SEER database study of 6600 cases of

MCC from 2000-2013 in the United States

95.2%

56.5%

15.5%

Overall incidence of MCC rising Especially among older patients

J Am Acad Dermatol. 2018. 78(3):457-463.

Most Merkel cell carcinomas are driven by

polyomavirus infection

• Merkel cell polyomavirus

integrated in the genome of

~70-80% of MCCs.

Detecting Merkel cell carcinoma polyomavirus in tissue?Immunohistochemistry may be the most sensitive and specific

• MCPyV- vs MCPyV+o Increased PFS

o Reduced MSS

• MCPyV status NOT

independent of stage.

• CM2B4 IHCo Best sensitivity (88.2%)

and specificity (94.3%)

In comparison to MCPyV-positive MCCs (n=7):

• MCPyV-negative MCCs (n=8)

• A significantly higher mutational burden

• A UV-type mutational signature

Mutational signature of MCC depends on MCPyV statusMCPyV-negative tumors have high uv-induced mutational burden

In comparison to MCPyV-positive MCCs

(n=12):

• MCPyV-negative MCCs (n=19)

• Arise on chronic uv-exposed sites

• Show a much higher mutational burden

Mutational signature of MCC depends on MCPyV statusMCPyV-negative tumors have high uv-induced mutational burden

Mechanisms of Merkel cell carcinomagenesisCommon pathways abrogated by distinct mechanisms:

Virus or uv-induced mutations

Viral inactivation

of RB and TP53

related pathways

Mutational

inactivation of

TP53 and RB

MCPyV

+ MCC

MCPyT

MCPyV

- MCC

Starett et al. MBio. 2017 Jan 3;8(1). pii: e02079-16.

Geographic distribution of MCPyV+ MCC often different from MCPyV- MCC.

MCPyT

Staging Merkel cell carcinoma:

Survival associates with stage at presentation

Cases with follow-up

and complete staging

n=9,387

• Survival directly correlates

with disease burden• Local disease > Nodal metastases

> Distant metastases

cN0 or pN0

AJCC 8th Edition clinical staging of Merkel cell carcinomaT-category (based on clinical measurement) has not changed

• T-category based on clinical measurement• Tumor size (and extent of invasion) define T-category

• Gross and histologic measurements can be used but subject to underestimation

T Category T criteria

TX Primary tumor cannot be identified

T0 No primary tumor

T1 Tumor ≤ 2 cm in greatest dimension

T2 Tumor > 2 cm but ≤ 5 cm in greatest dimension

T3 Tumor > 5 cm

T4 Tumor invades fascia, muscle cartilage, or bone



n=9,387

Increasing tumor

diameter:

OS (p=0.003)

DSS (p=0.008)

Cancer. 2015. 121: 3252-60.

cN0 or pN0

• T-category based on clinical measurement• Tumor size (and extent of invasion) define T-category

• Gross and histologic measurements can be used but subject to underestimation

T Category T criteria

TX Primary tumor cannot be identified

T0 No primary tumor

T1 Tumor ≤ 2 cm in greatest dimension

T2 Tumor > 2 cm but ≤ 5 cm in greatest dimension

T3 Tumor > 5 cm

T4 Tumor invades fascia, muscle cartilage, or bone



n=9,387

AJCC 8th Edition clinical staging of Merkel cell carcinomaT-category (based on clinical measurement) has not changed

Histopathologic features of Merkel cell carcinoma that

correlate with outcome: What do we report and why?

Retrospective review of 156

patients with MCC with median

follow up 51 months (range: 3-224

months)

• Among patients with lymph node negative

early stage MCC (Stage I and II)• Pattern of growth (Nodular versus infiltrative)

• Deepest anatomic compartment of involvement

• Tumor thickness (< vs ≥ 5 mm)

• Lymphovascular invasion

• Tumor infiltrating lymphocytes (absent vs present)

Histopathologic features of Merkel cell carcinoma that

correlate with outcome: What do we report and why?

AJCC 8th Edition clinical staging of Merkel cell

carcinoma regional metastasesN-category based on clinical evidence of regional metastases

Definitive surgical management

Clinical staging• Clinical measurement of

primary MCC

• Clinical assessment of

metastasis +/- pathologic

confirmation

Pathologic staging• Clinical measurement of

primary MCC

• Pathologic confirmation

• Nodal metastases (pN)

• Distant metastases (pM)

N Category Clinical N criteria

cNX Regional lymph nodes cannot be assessed

cN0 No evidence of lymph node metastasis

cN1 Clinically detected regional lymph node metastasis

cN2 Clinically detected in-transit metastasis without lymph node metastasis

cN3 Clinically detected in-transit metastasis AND lymph node metastasis

Based on clinical assessment of metastatic nodal disease


carcinoma regional metastasesN-category based on clinical evidence of metastases

Imaging studies are not required for every patient• If thorough history and physical exam do not reveal metastatic disease (N0 M0).

• If there is clinical suspicion for or evidence of metastatic disease, and radiographic

studies confirm this, then cN (1, 2, 3) or cM1 (a, b, c)


carcinoma regional metastasesN-category based on pathologic evidence of regional metastases



primary MCC


metastasis +/- pathologic

confirmation


primary MCC




Based on pathologic evidence of metastatic disease

N Category Pathologic N criteria

pNX Regional lymph nodes cannot be assessed

pN0 No evidence of lymph node metastasis (negative SLNB, etc)

pN1a (sn) Clinically occult lymph node metastasis on SLN biopsy (NO completion LND)

pN1a Clinically occult lymph node metastasis on SLN biopsy (WITH completion LND)

pN1b Clinically detected lymph node metastasis, pathologically confirmed

pN2 In-transit metastasis without lymph node metastasis

pN3 In-transit metastasis plus lymph node metastasis


carcinoma regional metastasesN-category based on pathologic evidence of metastases

8th Edition AJCC staging of Merkel cell carcinomaClinical versus pathologic staging highlights important survival differences

cN0 only (pNX)

Patients with clinically evident

regional MCC metastases have

worse survival compared to those

with clinically occult involvement

of the regional lymph nodes

Patients presenting with MCC metastases

to lymph nodes without a known primary

MCC have better survival compared to

those with known primary MCC

• Approximately 35% of patients with MCC present with regional

lymph node metastases

Mol Clin Oncol. 2015. 3(2):299-302.

The sentinel node is the most common site for

clinically occult Merkel cell carcinoma metastases

• H&E

• Pan-Cytokeratin IHC

• Unstained slide

200mm

Among patients with negative SLN following examination of initial H&E:

Approximately 20-30% of patients with lymph node metastases are identified after

examination of additional tissue levels and IHC for pan-Cytokeratin or CK20

IHC for PanCK

or CK20

• 5/23 SLN+ (22%)

• 4/10 patients (40%)

• 10 patients

• 23 SLNBs

• All negative on 1st H&E



• H&E


• Unstained slide

200mm



Among patients with negative SLN following examination of initial H&E:

Approximately 20-30% of patients with lymph node metastases are identified after

examination of additional tissue levels and IHC for pan-Cytokeratin or CK20

Sentinel lymph node assessment in MCCPositivity on initial H&E stained tissue sections spans a spectrum of

disease burden

• H&E


• Unstained slide

200mm

Sentinel lymph node assessment in MCCImmunohistochemical studies facilitate the detection of clinically

occult lymph node involvement

• H&E


• Unstained slide

200mm

Sentinel lymph node assessment in MCCImmunohistochemical studies facilitate the detection of clinically

occult lymph node involvement

No minimal size threshold defined for metastatic deposits of Merkel cell

carcinoma to qualify as positive

• H&E


• Unstained slide

200mm

Extent of disease burden in lymph node status correlates with survival

• Clinically evident lymph node positive disease fares worst

• Pathological node negative disease fares best

SLN is a critical prognostic tool for patients with MCC:

Pathologically negative patients fare the best

59%

26%

76%

42%

Prognostic factors in Merkel cell carcinoma: p63

• n= 47 pts with MCC

• 25 p63+

• 22 p63-CK20

CHG SYN

p63

n= 70 pts with MCC

• 43 p63+

• 27 p63-

Assessed for association between

survival:

• Age

• Gender

• Anatomic site

• Tumor size

• Tumor thickness

• Cell size

• LVI

• Mitotic figures

• TILS

• Pattern of growth

• Stage

• p63

• p53

• Ki-67 (MIB1)

• MCPyV status

Stage I-II MCC

Stage I Stage II Stage III Stage IV

No significant correlation with p63 status within a given stage

?


• 42 p63+

• 86 p63-

All patients

Prognostic factors in Merkel cell carcinoma: p63

Prognostic factors in Merkel cell carcinoma: Integrity of the immune system

• Advanced patient age and male sex associate with worse

prognosis(Laryngoscope. 2012. 122:1283-90.)

• Immunosuppression is a risk factor for developing MCC and correlates

with worse outcome independent of stage.


• n= 430 immunocompetent

• n= 41 immunosuppressed

• n=21 CLL/hematologic malignancy

• n=5 HIV/AIDS

• n=15 iatrogenic

• transplant

• autoimmune

Prognostic factors in Merkel cell carcinoma: Tumor associated immune infiltrate correlates with survival

Prognostic factors in Merkel cell carcinoma: Composition, density and distribution of the tumor

associated immune infiltrate correlates with survival

• n=62 MCCs and IHC CD3, CD8, PD-1, and PD-L1

• Quantified with Aperio automated image analysis

• Does the composition, density and/or distribution of

the associated immune infiltrate associate with

survival in MCC?

CD3 IHC CD3-quantified/mm2

Response to anti-PD-1 in Merkel cell carcinoma

56% objective response rate to PD-1 inhibitor among stage IIIb or IV MCC

patients who had not received prior systemic therapy—independent of MCPyV

status or the relative expression of PD-L1.

32% (28/88) patients

with stage IV MCC who

failed at least one prior

systemic therapy

achieved rapid and

sustained response to

PD-L1 inhibitor—

independent of MCPyV

status or the relative

expression of PD-L1.

FDA approval for MCC

Response to anti-PD-L1 in Merkel cell carcinoma

Response to anti-PD-L1 in Merkel cell carcinoma

Response to anti-PD-L1 in Merkel cell carcinomaMultifactorial and includes spatial relationships of the TILS

Density of PD-1+ cells and PD-L1+ cells

significantly higher among responders

versus non-responders

Proximity of PD-1+ cells to PD-L1+ cells in a tumor

correlates with response to a-PD-1: Number of PD-1+

cells ≤ 20mm of PD-L1+ cell higher in R versus NR

Greater engagement of PD-1 with PD-L1 implies a greater likelihood that

inhibiting this interaction will exert a positive clinical effect.

Merkel cell carcinoma

• MCC is among the most aggressive forms of skin cancer• Risk factors are age, uv-exposure and immunosuppression

• MCC responds to immune checkpoint blockade• Thus far, independent of PD-L1 or MCPyV status

• Important parameters of the primary lesion• Size, extent of involvement of underlying structures

• Staging according to TNM criteria

• Depth, lymphocytic infiltrate, LVI, pattern of growth

• MCC is related to infection by Merkel cell polyoma virus• MCPyV-positive MCC lacks high mutational load

• Viral T-antigens impact on Rb and TP53-dependent processes

• MCPyV-negative MCC enriched for UV-mutations (in particular TP53 and RB)

• Prognostic biomarkers include:• Immune

• p63 expression by tumor cells

THANK YOU…..Department of Pathology, Section of

Dermatopathology, MDACC

• Victor G. Prieto, MD, PhD

• Carlos A. Torres-Cabala, MD

• Jonathan L Curry, MD

• Priyadharsini Nagarajan, MD, PhD

• Phyu Aung, MD, PhD

• Doina Ivan, MD

Steven Billings, MD

Isaac Brownell MD PhD

Paul Harms, MD PhD

Axel zur Hausen, MD, PhD

Jürgen Becker MD, PhD

• Described 5 cases of “trabecular carcinoma” of the skin

• Tumors consisted of ‘irregular, angular, anastomosing

trabeculae’ infiltrating among dermal collagen as cords

• Cells with oval, vesicular nuclei and indiscernible

cytoplasm

AJCC 7th Edition for Merkel cell carcinoma:Clinical and pathologic nodal status were considered together

*

*

*

*

With increasing application of sentinel lymph node biopsy (SLNB), this

system created a selection bias for stage IB and IIB (cN0 patients) to consist

of patients in whom SLNB was not performed due to underlying

comorbidities, and unclear if these comorbidities contribute to their survival.



primary MCC


metastatic disease (+/-

pathologic confirmation)


primary MCC




AJCC 8th edition more accurately distinguishes the prognostic

significance of the extent of nodal disease burden with less

emphasis on the extent of nodal evaluation.

AJCC 8th Edition for Merkel cell carcinoma:Clinical and pathologic nodal status considered separately



n=9,387

T1 (63%)

T2/3 (53%)

T4 (35%)

cN0 only

T1 (45%)

T2/3 (31%)

T4 (27%)

8th Edition AJCC establishes a more sensitive system for prognostication of

survival among pathologically node negative patients that is distinct from

clinically node negative patients.

8th Edition AJCC staging of Merkel cell carcinomaClinical versus pathologic node negative patient survival according to T-category

This underscores the importance of the sentinel lymph node.

721

patients

736 SLNBs

218 SLN+

(29.6%)

518 SLN-

(70.4%)

• Regional nodal relapse not

significantly different between

SLNB+ (11.2%) and SLNB- (8.7%)

patients

• Distant relapse far more frequent

among SLNB+ (17.6%) compared

to SLNB- (7.3%) patients

(p

MCC occasionally shows divergent differentiationThese tumors are not associated with MCPy-virus infection

• 44 cases of MCC combined with SCC:

• 0/44 MCPyV-negative

Update on molecular genetics, diagnosis, staging, sentinel lymph … · 2019. 9. 5. · Hanly 2001...

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Transcript of Update on molecular genetics, diagnosis, staging, sentinel lymph … · 2019. 9. 5. · Hanly 2001...