Pseudomyxoma Peritonei

Mucinous Peritoneal Surface Metastasis

S.C. Bruin

Clinical Research Fellow NKI-AVL

The Netherlands

• PMP is used for a wide range of disease entities

• Ongoing discussion around PMP

–Definitions site of origin

–Histopathology

PMP

• Ronnett: Mucinous material within the peritoneal cavity associated with a mucinous tumor

• Sugarbaker: PMP is a rare disease that results from a primary mucinous appendicealneoplasm

• Bradley: PMP is a clinical term for gelatinous ascites, usually secondary to an appendicealtumor. The pathologic classification has been plagued with controversy and confusing terminology

• Glehen: PMP is a rare disease, usually diagnosed after the discover of "jelly belly" by laparotomy

Definition PMP

What is a Jelly Belly?

• Primary lesion• Appendiceal

• Colorectal

• Appendiceal and colorectal

• Pseudomyxoma peritonei

–Colonic Carcinomatosis??

HIPEC literature reports

• PMP is thought to be mainly associated with a mucinous epithelial neoplasm of the appendix

Primary lesion Appendix

Gobletcellcarcinoma

Signetringcell carcinoma

Mucinous adenocarcinoma

Cystadenocarcinoma

Appendiceal mucinous tumor of uncertain malignant potential

Cystadenoma

Adenoma (serrated)

Appendiceal neoplasms associated with mucinous peritoneal disease

Site of origin

Why not the colon?

• There is confusing nomenclature surrounding PMP

Histopathology

Non-aggressive Aggressive

Histopathology

Low grade, High gradeBradley, Miner, Butterworth, Murphy

Grade 1, 2 and 3Cariker, Gough, Loungnarrath

DPAM, PMCA-i, PMCARonnett

Grading of mucinous peritoneal lesions according to different authors

Peritoneal Lesion

Primary

What do we know?

Cytoreduction plus HIPEC

• Improves survival

Survival predictors

• Completeness of cytoreduction

• Number of affected regions

• Histological characteristics

Aim study

• Correlate clinical-pathologic characteristics to survival

Histological revision

• 269 patients treated with HIPEC

• Colon AND appendiceal

• Evaluated histopathological features

–Extracellulair mucus–Mitotic activity–Cellularity–Cytologic atypia

Histological classification PSM

Peritoneal Carcinomatosis(PCA)

Peritoneal MucinousCarcinomatosis (PMCA)

Disseminated PeritonealAdeno Mucinosis (DPAM)

non-mucinous

mucinous

NON-MUCINOUS

MUCINOUS

Extracel Mucus Mitosis None Little Lots None Little Lots

None None

Sporadic 9

Abundant 60

1-50% None 1

Sporadic 4

Abundant 20

50-90% None

Sporadic 1 2

Abundant 15

>90% None 20 38 3

Sporadic 43 13 1 3

Abundant 6 13 17

Few

Nuclear atypia

Cellularity

Many

Nuclear atypia

Disseminated Peritoneal Adeno Mucinosis DPAM

DPAM

MUCINOUS

NON-MUCINOUS

Extracel Mucus Mitosis None Little Lots None Little Lots

None None

Sporadic 9

Abundant 60

1-50% None 1

Sporadic 4

Abundant 20

50-90% None

Sporadic 1 2

Abundant 15

>90% None 20 38 3

Sporadic 43 13 1 3

Abundant 6 13 17

Few

Nuclear atypia

Cellularity

Many

Nuclear atypia

Peritoneal Mucinous Carcinomatosis PMCA

Disseminated Peritoneal Adeno Mucinosis DPAM

PMCA

MUCINOUS

NON-MUCINOUS

Extracel Mucus Mitosis None Little Lots None Little Lots

None None

Sporadic 9

Abundant 60

1-50% None 1

Sporadic 4

Abundant 20

50-90% None

Sporadic 1 2

Abundant 15

>90% None 20 38 3

Sporadic 43 13 1 3

Abundant 6 13 17

Few

Nuclear atypia

Cellularity

Many

Nuclear atypia

Peritoneal Carcinomatosis PCA

Peritoneal Mucinous Carcinomatosis PMCA

Disseminated Peritoneal Adeno Mucinosis DPAM

PCA

MUCINOUS

NON-MUCINOUS

Extracel Mucus Mitosis None Little Lots None Little Lots

None None

Sporadic 9

Abundant 60

1-50% None 1

Sporadic 4

Abundant 20

50-90% None

Sporadic 1 2

Abundant 15

>90% None 20 38 3

Sporadic 43 13 1 3

Abundant 6 13 17

Few

Nuclear atypia

Cellularity

Many

Nuclear atypia

Peritoneal Carcinomatosis PCA

Peritoneal Mucinous Carcinomatosis PMCA

Disseminated Peritoneale Adeno Mucinosis DPAM

PMCA-intermediate PMCA-I

Conclusion

• PSM from colon and appendicealtumors can be classified into

4 distinguishable groups:

»DPAM» PMCA-i

»PMCA

»PCA

Primary tumor location and type of PSM

71%

DPAM PMCA-i PMCA PCA

9%14%

6%

Appendix

2% 5%

30%

63%

Colon

• PSM from primary colon tumors in 37% mucinous

• DPAM most frequently from a primary appendix tumor

• 29% of primary appendix tumors non-DPAM

P<0,001 univariate

64%

24%

33%

Survival prediction by pathology

Survival analysis

• Significant factors mulitivariate analysis

–Histological Classification (p<0,0001)–Gender (p<0,014)–Number of regions (p<0,008)–Result cytoreduction (p<0,0001)

–HIPEC as first treatment on PSM (p<0,007)–Tumor location (p<0,025)

• Combined in a Nomogram Score

Survival DPAM Male

5424

78

0

57%

54

Survival DPAM Female

0

45

75%

2322

Survival PMCA Male

24 61

85

37%

24 42

66

59%

Survival PMCA Female

PCA

PCA

17 74

91

28%

Summary

• PSM are often mucinous

• DPAM better OS than PMCA and PMCA better than PCA

• Female patients better survival than male in mucinous PSM

• Non-mucinous tumors worse survival

Conclusion

• Histological classification of colorectal AND appendiceal PSM gives prognosticinformation

• PSM should be classified by a standardized protocol

• HIPEC Nomogram provides a tool for individual patient risk assessment

Acknowledgements

Vic Verwaal

Andrew Vincent

Laura van ’t Veer

Loes van Velthuysen