mesothelial inclusion cyst peritoneal pathology outlines
mesothelial inclusion cyst peritoneal pathology outlines - Pleura & peritoneum
Peritoneum
Peritoneal malignant mesothelioma
Author: Yin P. Hung, M.D., Ph.D.
Editor-in-Chief: Debra Zynger, M.D.
Topic Completed: 23 May 2019
Minor changes: 26 December 2019
Copyright: 2002-2019, PathologyOutlines.com, Inc.
PubMed Search: Peritoneal malignant mesothelioma[title]
Yin P. Hung, M.D., Ph.D.
Page views in 2019: 27
Page views in 2020 to date: 3,162
Table of Contents
Definition / general | Essential features | Terminology | ICD coding | Epidemiology | Sites | Etiology | Clinical features | Diagnosis | Radiology description | Radiology images | Prognostic factors | Case reports | Treatment | Gross description | Gross images | Microscopic (histologic) description | Microscopic (histologic) images | Cytology description | Positive stains | Negative stains | Electron microscopy description | Molecular / cytogenetics description | Sample pathology report | Differential diagnosis | Board review style question #1 | Board review answer #1 | Board review style question #2 | Board review answer #2
Cite this page: Hung Y. Peritoneal malignant mesothelioma. PathologyOutlines.com website. http://www.pathologyoutlines.com/topic/pleuraperitmesotheliomageneral.html. Accessed August 4th, 2020.
Definition / general
Tumor that originates from the serosal lining of the peritoneal cavity
Essential features
Peritoneal malignant mesothelioma shows weaker association with asbestos exposure and more likely involves women / young patients than pleural malignant mesothelioma
Histologic variants (epithelioid, biphasic and sarcomatoid) impart prognostic information with treatment implications
Loss of BAP1 expression is seen in 40 - 60% of peritoneal malignant mesothelioma, not sensitive but fairly specific for the diagnosis of malignant mesothelioma in the appropriate histologic context
Terminology
Peritoneal mesothelioma
Malignant peritoneal mesothelioma
Diffuse malignant peritoneal mesothelioma
Abdominal mesothelioma
ICD coding
ICD-10:
C45.1 - mesothelioma of peritoneum
ICD-0:
9050/3 - malignant mesothelioma
9051/3 - sarcomatoid / desmoplastic malignant mesothelioma
9052/3 - epithelioid malignant mesothelioma
9053/3 - biphasic malignant mesothelioma
Epidemiology
Accounts for ~10% of all mesotheliomas
Incidence: ~300 new cases annually in the United States
Presents with a wide age range and no apparent sex predilection (Cancer Causes Control 2009;20:935, Bull World Health Organ 2011;89:716, Clin Epidemiol 2016;8:743)
Sites
Involves the serosal lining in the peritoneal cavity, often of multiple intra-abdominal organs
Generally diffuse, rarely solitary / localized (Am J Surg Pathol 2005;29:866)
Etiology
Associated with exposure to asbestos fibers in a subset of patients, typically with a long latency (median ~32 years); the association is weaker than in pleural mesothelioma (J Clin Oncol 1983;1:386, J Occup Med 1992;34:718, Arch Pathol Lab Med 2018;142:753)
Rarely associated with exposure to non asbestos mineral fibers: erionite, fluoro-edenite and others (Arch Pathol Lab Med 2018;142:753)
Rarely associated with prior exposure to therapeutic radiation for other malignancy with a latency of years to decades (J Clin Oncol 1983;1:695, Cancer 1988;61:2019, Arch Pathol Lab Med 2018;142:753)
Rarely associated with recurrent peritonitis / chronic serosal inflammation secondary to Crohn disease, endometriosis or Familial Mediterranean Fever (J Clin Pathol 2017;70:228, J Clin Pathol 2018;71:971, Arch Pathol Lab Med 2018;142:753)
Rarely associated with germline mutations and characteristic gene rearrangements (see molecular/cytogenetics section below)
Clinical features
More likely to affect women and young patients as compared to pleural malignant mesothelioma (Cancer Causes Control 2009;20:935)
Symptoms can be nonspecific and depend on the extent of involvement
Presentation includes most commonly abdominal pain, distension or ascites; rarely incidental or with new hernia, bowel obstruction or perforation (Tumori 2003;89:269, Ann Gastroenterol 2018;31:659)
Morbidity / mortality primarily due to locoregional spread with extra-abdominal metastasis rare
Median overall survival of 3 - 7 years with a 5 year survival rate of 40 - 60% with treatment (Ann Gastroenterol 2018;31:659)
Diagnosis
Radiologic assessment of disease extent by computed tomography (CT) or magnetic resonance imaging (MRI)
Cytologic analysis of peritoneal fluid, though this is not entirely sensitive
Definitive diagnosis is most commonly based on histologic analysis of surgical specimen from laparoscopic / open or core needle biopsy
Peritoneal malignant mesothelioma, particularly the sarcomatoid variant, is difficult to diagnose and requires multiple immunohistochemical markers to exclude mimics
Since no single immunohistochemical marker is entirely sensitive and specific for the diagnosis, a panel of at least 2 positive markers and 2 negative markers is recommended (Hum Pathol 2017;67:160)
Radiology description
Multiple nodular lesions involving omentum and the mesentery, peritoneal thickening and accumulation of ascites (Anticancer Res 2016;36:1067)
Radiology images
Images hosted on other servers:
Missing Image
Omental caking
Prognostic factors
Improved survival has been associated with the following:
Age < 60 years (J Clin Oncol 2003;21:4560, Ann Surg Oncol 2018;25:2159, Ann Surg Oncol 2018;25:2018)
Female gender (Ann Surg Oncol 2018;25:2159, Ann Surg Oncol 2018;25:2018)
Epithelioid variant (J Clin Oncol 2009;27:6237, Pathology 2014;46:604, Ann Surg Oncol 2018;25:2018)
Complete cytoreduction (J Clin Oncol 2003;21:4560, J Clin Oncol 2009;27:6237, Ann Surg Oncol 2015;22:1686, J Gastrointest Oncol 2017;8:915)
Lack of lymph node metastasis (J Clin Oncol 2009;27:6237, J Gastrointest Oncol 2017;8:915)
Low peritoneal cancer index (PCI) (Cancer 2011;117:1855, J Gastrointest Oncol 2017;8:915)
Absence of loss of chromosomal region 9p21 / CDKN2A (Mod Pathol 2010;23:531, JAMA Oncol 2018;4:235)
Worse survival has been noted to be associated with the following, although more data is needed for definitive conclusion:
BAP1 molecular or expression status (J Thorac Oncol 2017;12:724)
Elevated mitotic count (Clin Cancer Res 2005;11:3303, Histopathology 2016;68:729)
High nuclear grade (Am J Surg Pathol 2016;40:1243)
Solid pattern in epithelioid variant (Histopathology 2016;68:729)
Case reports
19 year old woman with abdominal pain and cachexia (epithelioid) (Cold Spring Harb Mol Case Stud 2019;5:a003566)
35 year old woman with omentum caking (epithelioid, deciduoid) (BMC Clin Pathol 2017;17:13)
40 year old woman with abdominal pain and distension (epithelioid) (Gastroenterology Res 2019;12:48)
61 year old woman with abdominal distension and ascites (epithelioid, clear cell pattern) (Pathol Res Pract 2017;213:580)
63 year old woman with abdominal pain (epithelioid, clear cell pattern with VHL mutation) (Hum Pathol 2019;83:199)
81 year old man with refractory ascites (biphasic) (Intern Med 2017;56:861)
Treatment
Cytoreductive surgery, often combined with hyperthermic intraoperative chemotherapy, generally recommended for treating epithelioid variant (and some biphasic) but not sarcomatoid variant (Ann Surg Oncol 2015;22:1686, Ann Surg Oncol 2018;25:667)
Chemotherapy types: hyperthermic intraoperative chemotherapy (HIPEC), early postoperative intraperitoneal chemotherapy (EPIC), long term intraperitoneal (IP) chemotherapy and systemic chemotherapy (Eur J Cancer 2016;65:69, Eur J Surg Oncol 2017;43:1228)
Radiation
Immunotherapy: clinical trial on using tremelimumab (anti-CTLA4 monoclonal antibody) and durvalumab (PD-L1 blockade) ongoing (Lancet Respir Med 2018;6:451)
Gross description
Multiple omental / serosal nodules and thickened peritoneum
Gross images
Images hosted on other servers:
Missing Image
Adhesion of abdominal organs
Microscopic (histologic) description
Unequivocal indicator of malignancy: invasion into adipose tissue or stromal invasion (Am J Surg Pathol 2000;24:1183, Arch Pathol Lab Med 2018;142:89)
Histologically classified into epithelioid, biphasic and sarcomatoid variants with implications on prognosis and treatment planning
Epithelioid mesothelioma is characterized by epithelioid to round tumor cells, which are often more monotonous than what are seen in most carcinomas
Sarcomatoid mesothelioma is characterized by spindled tumor cells
Biphasic mesothelioma is characterized by the presence of both epithelioid and sarcomatoid components, each comprising at least 10% of the tumor
In epithelioid mesothelioma, architectural / cytologic features that can be seen are diverse; histologic patterns most commonly seen are tubular, papillary and solid and more rarely micropapillary, trabecular, acinar, adenomatoid-like, clear cell, deciduoid, adenoid cystic-like, signet ring cell, small cell and rhabdoid (Arch Pathol Lab Med 2013;137:647)
In sarcomatoid mesothelioma, histologic patterns include conventional, desmoplastic, lymphohistiocytoid and those with heterologous differentiation (Arch Pathol Lab Med 2013;137:647, Am J Surg Pathol 2015;39:1568)
Microscopic (histologic) images
Contributed by Yin P. Hung, M.D., Ph.D.
Missing Image
Epithelioid variant, solid growth
Missing Image
Calretinin
Missing Image
WT1
Missing Image
Epithelioid variant, infiltrative growth
Missing Image
Typically uniform tumor cells
Missing Image
AE1 / AE3
Missing Image
Calretinin
Missing Image
WT1
Missing Image
Biphasic variant
Missing Image
AE1 / AE3
Cytology description
Large clusters to sheets of fairly monotonous mesothelial tumor cells
Limitation of cytologic diagnosis: rarely definitive, since tissue invasion is difficult to assess
Positive stains
Mesothelial markers: calretinin, WT1 and D2-40 (podoplanin), CAIX (J Clin Pathol 2016;69:706, Arch Pathol Lab Med 2018;142:236, Arch Pathol Lab Med 2018;142:89)
Keratins such as AE1 / AE3, CAM 5.2 and broad spectrum pankeratin
Keratin 5 / 6: expressed in most epithelioid mesotheliomas (rarely adenocarcinomas)
Mesothelin, thrombomodulin, HBME1
GATA3: expressed in a large subset of sarcomatoid mesothelioma (also in breast and urothelial carcinoma)
Negative stains
Epithelial markers: claudin4, BerEP4, MOC31, B72.3, CEA
TTF1
BAP1: complete loss of BAP1 expression in 40 - 60% (lost in < 1% of carcinomas and not in reactive mesothelial proliferation) (Am J Surg Pathol 2015;39:977, Hum Pathol 2016;51:9, J Thorac Oncol 2017;12:724)
PAX8: expression in 10 - 20% (Hum Pathol 2018;72:160, Am J Surg Pathol 2017;41:1675, Arch Pathol Lab Med 2018;142:89)
Electron microscopy description
Microvilli and desmosomes
Molecular / cytogenetics description
BAP1 somatic mutations in 40 - 70% (J Transl Med 2015;13:122, Mod Pathol 2017;30:246, J Thorac Oncol 2017;12:724)
Copy number loss of BAP1 in 3p21, CDKN2A in 9p21 and NF2 in 22q12 in 20 - 40% (Mod Pathol 2010;23:531, Hum Pathol 2016;55:72)
Somatic mutations in SETD2, DDX3X and others in a subset (Mod Pathol 2017;30:246)
Germline mutations in BAP1, ATM or other regulators in DNA repair in a subset (J Clin Oncol 2018;36:2863, J Pediatr Hematol Oncol 2018;40:e511)
EWSR1-ATF1 or FUS-ATF1 gene fusion in rare cases (Am J Surg Pathol 2017;41:980)
ALK gene rearrangement in rare cases but enriched in young patients (JAMA Oncol 2018;4:235)
Sample pathology report
Peritoneum and omentum, resection:
Malignant mesothelioma, epithelioid variant, 5.0 cm in greatest dimension
Surgical margins, negative for tumor
Comment: The tumor cells are positive for WT1, calretinin and D2-40, and are negative for claudin4, PAX8, MOC31 and CEA.
Differential diagnosis
Metastatic adenocarcinoma
Variable histologic overlap
Typically expresses other epithelial markers: claudin4, BerEP4, polyclonal CEA, MOC31 and B72.3
Rarely express keratin 5 / 6 and mesothelial markers (calretinin and D2-40), though WT1 is commonly expressed in carcinomas of Müllerian primary and CAIX is expressed in renal cell carcinoma, clear cell type
Expression of PAX8 favors renal or gynecologic origin and TTF1 favors lung origin
Sclerosing peritonitis
Reactive proliferation of stromal myofibroblasts, often associated with adjacent linear arrangement of mesothelial cells, chronic inflammation, surface fibrin deposition and occasionally entrapped fat
Associated with various conditions including luteinized thecomas (Am J Surg Pathol 1994;18:1)
Distinction can be challenging, particularly in small biopsies, cases with tangential sectioning or fat entrapment (Am J Surg Pathol 2000;24:1183)
Well differentiated papillary mesothelioma
Most commonly in the peritoneum, rarely pleura and other sites
Histology: papillae with myxoid cores, each lined by a single mesothelial cell layer
Invasion is typically not present (Am J Surg Pathol 2014;38:990)
Overall more indolent than peritoneal malignant mesothelioma (Ann Surg Oncol 2019;26:852)
Recurrent mutations in TRAF7 or CDC42 (Mod Pathol 2019;32:88)
Adenomatoid tumor of genital type
Benign mesothelial tumor that arises mostly commonly near the genital tract
Histology: a microcystic low power appearance with poor margination and tubules / cords of epithelioid cells with characteristic cytoplasmic vacuolation
Associated with immunosuppressive state in some cases (Histopathology 2018;73:1013)
Recurrent mutations in TRAF7 (Mod Pathol 2018;31:660)
Multicystic peritoneal inclusion cyst
Also known as multilocular inclusion cyst
Histology: multiple cysts of various sizes, each with thin fibrous walls lined by flattened mesothelial cells (Cancer 1989;64:1336)
TNS3-MAP3K3 or ZFPM2-ELF5 gene fusion in rare cases (Cancer Lett 2015;357:502)
Epithelioid hemangioendothelioma
Rare distinctive malignant vascular tumor
Most commonly involves liver, lung / pleura, bone or soft tissue
Histology: cord-like pattern, myxohyaline matrix, epithelioid cells with intracytoplasmic vacuoles
Immunohistochemistry: typically positive for CAMTA1 and endothelial markers (ERG, CD31, CD34 and D2-40) but negative for calretinin and WT1 (Am J Surg Pathol 2016;40:94)
WWTR1-CAMTA1 gene fusion in most cases, YAP1-TFE3 fusion in rare cases (Sci Transl Med 2011;3:98ra82, Genes Chromosomes Cancer 2011;50:644, Genes Chromosomes Cancer 2013;52:775)
Board review style question #1
Which of the following is true regarding peritoneal malignant mesothelioma?
All cases are associated with asbestos exposure
Compared to pleural mesothelioma, peritoneal mesothelioma more likely involves women and children
Copy number loss of CDKN2A and NF2 is detected in all cases
Histologic subtyping has no prognostic value
The presence of intact BAP1 protein expression rules out malignancy entirely
Board review answer #1
B. Compared to pleural mesothelioma, peritoneal mesothelioma more likely involves women and children
Comment Here
Reference: Peritoneal malignant mesothelioma
Board review style question #2
Missing Image Missing Image
Which of the following is true regarding the two images (the tumor and the corresponding BAP1 immunostain) illustrated?
This indicates germline BAP1 mutation(s) in all cases
This is a metastatic adenocarcinoma
This is a reactive mesothelial proliferation
This is a sarcomatoid malignant mesothelioma
This is an epithelioid malignant mesothelioma
Board review answer #2
E. This is an epithelioid malignant mesothelioma
Comment Here
Reference: Peritoneal malignant mesothelioma
Back to top
Home > Pleura & peritoneum > Peritoneal malignant mesothelioma
Peritoneum
Peritoneal malignant mesothelioma
Author: Yin P. Hung, M.D., Ph.D.
Editor-in-Chief: Debra Zynger, M.D.
Topic Completed: 23 May 2019
Minor changes: 26 December 2019
Copyright: 2002-2019, PathologyOutlines.com, Inc.
PubMed Search: Peritoneal malignant mesothelioma[title]
Yin P. Hung, M.D., Ph.D.
Page views in 2019: 27
Page views in 2020 to date: 3,162
Table of Contents
Definition / general | Essential features | Terminology | ICD coding | Epidemiology | Sites | Etiology | Clinical features | Diagnosis | Radiology description | Radiology images | Prognostic factors | Case reports | Treatment | Gross description | Gross images | Microscopic (histologic) description | Microscopic (histologic) images | Cytology description | Positive stains | Negative stains | Electron microscopy description | Molecular / cytogenetics description | Sample pathology report | Differential diagnosis | Board review style question #1 | Board review answer #1 | Board review style question #2 | Board review answer #2
Cite this page: Hung Y. Peritoneal malignant mesothelioma. PathologyOutlines.com website. http://www.pathologyoutlines.com/topic/pleuraperitmesotheliomageneral.html. Accessed August 4th, 2020.
Definition / general
Tumor that originates from the serosal lining of the peritoneal cavity
Essential features
Peritoneal malignant mesothelioma shows weaker association with asbestos exposure and more likely involves women / young patients than pleural malignant mesothelioma
Histologic variants (epithelioid, biphasic and sarcomatoid) impart prognostic information with treatment implications
Loss of BAP1 expression is seen in 40 - 60% of peritoneal malignant mesothelioma, not sensitive but fairly specific for the diagnosis of malignant mesothelioma in the appropriate histologic context
Terminology
Peritoneal mesothelioma
Malignant peritoneal mesothelioma
Diffuse malignant peritoneal mesothelioma
Abdominal mesothelioma
ICD coding
ICD-10:
C45.1 - mesothelioma of peritoneum
ICD-0:
9050/3 - malignant mesothelioma
9051/3 - sarcomatoid / desmoplastic malignant mesothelioma
9052/3 - epithelioid malignant mesothelioma
9053/3 - biphasic malignant mesothelioma
Epidemiology
Accounts for ~10% of all mesotheliomas
Incidence: ~300 new cases annually in the United States
Presents with a wide age range and no apparent sex predilection (Cancer Causes Control 2009;20:935, Bull World Health Organ 2011;89:716, Clin Epidemiol 2016;8:743)
Sites
Involves the serosal lining in the peritoneal cavity, often of multiple intra-abdominal organs
Generally diffuse, rarely solitary / localized (Am J Surg Pathol 2005;29:866)
Etiology
Associated with exposure to asbestos fibers in a subset of patients, typically with a long latency (median ~32 years); the association is weaker than in pleural mesothelioma (J Clin Oncol 1983;1:386, J Occup Med 1992;34:718, Arch Pathol Lab Med 2018;142:753)
Rarely associated with exposure to non asbestos mineral fibers: erionite, fluoro-edenite and others (Arch Pathol Lab Med 2018;142:753)
Rarely associated with prior exposure to therapeutic radiation for other malignancy with a latency of years to decades (J Clin Oncol 1983;1:695, Cancer 1988;61:2019, Arch Pathol Lab Med 2018;142:753)
Rarely associated with recurrent peritonitis / chronic serosal inflammation secondary to Crohn disease, endometriosis or Familial Mediterranean Fever (J Clin Pathol 2017;70:228, J Clin Pathol 2018;71:971, Arch Pathol Lab Med 2018;142:753)
Rarely associated with germline mutations and characteristic gene rearrangements (see molecular/cytogenetics section below)
Clinical features
More likely to affect women and young patients as compared to pleural malignant mesothelioma (Cancer Causes Control 2009;20:935)
Symptoms can be nonspecific and depend on the extent of involvement
Presentation includes most commonly abdominal pain, distension or ascites; rarely incidental or with new hernia, bowel obstruction or perforation (Tumori 2003;89:269, Ann Gastroenterol 2018;31:659)
Morbidity / mortality primarily due to locoregional spread with extra-abdominal metastasis rare
Median overall survival of 3 - 7 years with a 5 year survival rate of 40 - 60% with treatment (Ann Gastroenterol 2018;31:659)
Diagnosis
Radiologic assessment of disease extent by computed tomography (CT) or magnetic resonance imaging (MRI)
Cytologic analysis of peritoneal fluid, though this is not entirely sensitive
Definitive diagnosis is most commonly based on histologic analysis of surgical specimen from laparoscopic / open or core needle biopsy
Peritoneal malignant mesothelioma, particularly the sarcomatoid variant, is difficult to diagnose and requires multiple immunohistochemical markers to exclude mimics
Since no single immunohistochemical marker is entirely sensitive and specific for the diagnosis, a panel of at least 2 positive markers and 2 negative markers is recommended (Hum Pathol 2017;67:160)
Radiology description
Multiple nodular lesions involving omentum and the mesentery, peritoneal thickening and accumulation of ascites (Anticancer Res 2016;36:1067)
Radiology images
Images hosted on other servers:
Missing Image
Omental caking
Prognostic factors
Improved survival has been associated with the following:
Age < 60 years (J Clin Oncol 2003;21:4560, Ann Surg Oncol 2018;25:2159, Ann Surg Oncol 2018;25:2018)
Female gender (Ann Surg Oncol 2018;25:2159, Ann Surg Oncol 2018;25:2018)
Epithelioid variant (J Clin Oncol 2009;27:6237, Pathology 2014;46:604, Ann Surg Oncol 2018;25:2018)
Complete cytoreduction (J Clin Oncol 2003;21:4560, J Clin Oncol 2009;27:6237, Ann Surg Oncol 2015;22:1686, J Gastrointest Oncol 2017;8:915)
Lack of lymph node metastasis (J Clin Oncol 2009;27:6237, J Gastrointest Oncol 2017;8:915)
Low peritoneal cancer index (PCI) (Cancer 2011;117:1855, J Gastrointest Oncol 2017;8:915)
Absence of loss of chromosomal region 9p21 / CDKN2A (Mod Pathol 2010;23:531, JAMA Oncol 2018;4:235)
Worse survival has been noted to be associated with the following, although more data is needed for definitive conclusion:
BAP1 molecular or expression status (J Thorac Oncol 2017;12:724)
Elevated mitotic count (Clin Cancer Res 2005;11:3303, Histopathology 2016;68:729)
High nuclear grade (Am J Surg Pathol 2016;40:1243)
Solid pattern in epithelioid variant (Histopathology 2016;68:729)
Case reports
19 year old woman with abdominal pain and cachexia (epithelioid) (Cold Spring Harb Mol Case Stud 2019;5:a003566)
35 year old woman with omentum caking (epithelioid, deciduoid) (BMC Clin Pathol 2017;17:13)
40 year old woman with abdominal pain and distension (epithelioid) (Gastroenterology Res 2019;12:48)
61 year old woman with abdominal distension and ascites (epithelioid, clear cell pattern) (Pathol Res Pract 2017;213:580)
63 year old woman with abdominal pain (epithelioid, clear cell pattern with VHL mutation) (Hum Pathol 2019;83:199)
81 year old man with refractory ascites (biphasic) (Intern Med 2017;56:861)
Treatment
Cytoreductive surgery, often combined with hyperthermic intraoperative chemotherapy, generally recommended for treating epithelioid variant (and some biphasic) but not sarcomatoid variant (Ann Surg Oncol 2015;22:1686, Ann Surg Oncol 2018;25:667)
Chemotherapy types: hyperthermic intraoperative chemotherapy (HIPEC), early postoperative intraperitoneal chemotherapy (EPIC), long term intraperitoneal (IP) chemotherapy and systemic chemotherapy (Eur J Cancer 2016;65:69, Eur J Surg Oncol 2017;43:1228)
Radiation
Immunotherapy: clinical trial on using tremelimumab (anti-CTLA4 monoclonal antibody) and durvalumab (PD-L1 blockade) ongoing (Lancet Respir Med 2018;6:451)
Gross description
Multiple omental / serosal nodules and thickened peritoneum
Gross images
Images hosted on other servers:
Missing Image
Adhesion of abdominal organs
Microscopic (histologic) description
Unequivocal indicator of malignancy: invasion into adipose tissue or stromal invasion (Am J Surg Pathol 2000;24:1183, Arch Pathol Lab Med 2018;142:89)
Histologically classified into epithelioid, biphasic and sarcomatoid variants with implications on prognosis and treatment planning
Epithelioid mesothelioma is characterized by epithelioid to round tumor cells, which are often more monotonous than what are seen in most carcinomas
Sarcomatoid mesothelioma is characterized by spindled tumor cells
Biphasic mesothelioma is characterized by the presence of both epithelioid and sarcomatoid components, each comprising at least 10% of the tumor
In epithelioid mesothelioma, architectural / cytologic features that can be seen are diverse; histologic patterns most commonly seen are tubular, papillary and solid and more rarely micropapillary, trabecular, acinar, adenomatoid-like, clear cell, deciduoid, adenoid cystic-like, signet ring cell, small cell and rhabdoid (Arch Pathol Lab Med 2013;137:647)
In sarcomatoid mesothelioma, histologic patterns include conventional, desmoplastic, lymphohistiocytoid and those with heterologous differentiation (Arch Pathol Lab Med 2013;137:647, Am J Surg Pathol 2015;39:1568)
Microscopic (histologic) images
Contributed by Yin P. Hung, M.D., Ph.D.
Missing Image
Epithelioid variant, solid growth
Missing Image
Calretinin
Missing Image
WT1
Missing Image
Epithelioid variant, infiltrative growth
Missing Image
Typically uniform tumor cells
Missing Image
AE1 / AE3
Missing Image
Calretinin
Missing Image
WT1
Missing Image
Biphasic variant
Missing Image
AE1 / AE3
Cytology description
Large clusters to sheets of fairly monotonous mesothelial tumor cells
Limitation of cytologic diagnosis: rarely definitive, since tissue invasion is difficult to assess
Positive stains
Mesothelial markers: calretinin, WT1 and D2-40 (podoplanin), CAIX (J Clin Pathol 2016;69:706, Arch Pathol Lab Med 2018;142:236, Arch Pathol Lab Med 2018;142:89)
Keratins such as AE1 / AE3, CAM 5.2 and broad spectrum pankeratin
Keratin 5 / 6: expressed in most epithelioid mesotheliomas (rarely adenocarcinomas)
Mesothelin, thrombomodulin, HBME1
GATA3: expressed in a large subset of sarcomatoid mesothelioma (also in breast and urothelial carcinoma)
Negative stains
Epithelial markers: claudin4, BerEP4, MOC31, B72.3, CEA
TTF1
BAP1: complete loss of BAP1 expression in 40 - 60% (lost in < 1% of carcinomas and not in reactive mesothelial proliferation) (Am J Surg Pathol 2015;39:977, Hum Pathol 2016;51:9, J Thorac Oncol 2017;12:724)
PAX8: expression in 10 - 20% (Hum Pathol 2018;72:160, Am J Surg Pathol 2017;41:1675, Arch Pathol Lab Med 2018;142:89)
Electron microscopy description
Microvilli and desmosomes
Molecular / cytogenetics description
BAP1 somatic mutations in 40 - 70% (J Transl Med 2015;13:122, Mod Pathol 2017;30:246, J Thorac Oncol 2017;12:724)
Copy number loss of BAP1 in 3p21, CDKN2A in 9p21 and NF2 in 22q12 in 20 - 40% (Mod Pathol 2010;23:531, Hum Pathol 2016;55:72)
Somatic mutations in SETD2, DDX3X and others in a subset (Mod Pathol 2017;30:246)
Germline mutations in BAP1, ATM or other regulators in DNA repair in a subset (J Clin Oncol 2018;36:2863, J Pediatr Hematol Oncol 2018;40:e511)
EWSR1-ATF1 or FUS-ATF1 gene fusion in rare cases (Am J Surg Pathol 2017;41:980)
ALK gene rearrangement in rare cases but enriched in young patients (JAMA Oncol 2018;4:235)
Sample pathology report
Peritoneum and omentum, resection:
Malignant mesothelioma, epithelioid variant, 5.0 cm in greatest dimension
Surgical margins, negative for tumor
Comment: The tumor cells are positive for WT1, calretinin and D2-40, and are negative for claudin4, PAX8, MOC31 and CEA.
Differential diagnosis
Metastatic adenocarcinoma
Variable histologic overlap
Typically expresses other epithelial markers: claudin4, BerEP4, polyclonal CEA, MOC31 and B72.3
Rarely express keratin 5 / 6 and mesothelial markers (calretinin and D2-40), though WT1 is commonly expressed in carcinomas of Müllerian primary and CAIX is expressed in renal cell carcinoma, clear cell type
Expression of PAX8 favors renal or gynecologic origin and TTF1 favors lung origin
Sclerosing peritonitis
Reactive proliferation of stromal myofibroblasts, often associated with adjacent linear arrangement of mesothelial cells, chronic inflammation, surface fibrin deposition and occasionally entrapped fat
Associated with various conditions including luteinized thecomas (Am J Surg Pathol 1994;18:1)
Distinction can be challenging, particularly in small biopsies, cases with tangential sectioning or fat entrapment (Am J Surg Pathol 2000;24:1183)
Well differentiated papillary mesothelioma
Most commonly in the peritoneum, rarely pleura and other sites
Histology: papillae with myxoid cores, each lined by a single mesothelial cell layer
Invasion is typically not present (Am J Surg Pathol 2014;38:990)
Overall more indolent than peritoneal malignant mesothelioma (Ann Surg Oncol 2019;26:852)
Recurrent mutations in TRAF7 or CDC42 (Mod Pathol 2019;32:88)
Adenomatoid tumor of genital type
Benign mesothelial tumor that arises mostly commonly near the genital tract
Histology: a microcystic low power appearance with poor margination and tubules / cords of epithelioid cells with characteristic cytoplasmic vacuolation
Associated with immunosuppressive state in some cases (Histopathology 2018;73:1013)
Recurrent mutations in TRAF7 (Mod Pathol 2018;31:660)
Multicystic peritoneal inclusion cyst
Also known as multilocular inclusion cyst
Histology: multiple cysts of various sizes, each with thin fibrous walls lined by flattened mesothelial cells (Cancer 1989;64:1336)
TNS3-MAP3K3 or ZFPM2-ELF5 gene fusion in rare cases (Cancer Lett 2015;357:502)
Epithelioid hemangioendothelioma
Rare distinctive malignant vascular tumor
Most commonly involves liver, lung / pleura, bone or soft tissue
Histology: cord-like pattern, myxohyaline matrix, epithelioid cells with intracytoplasmic vacuoles
Immunohistochemistry: typically positive for CAMTA1 and endothelial markers (ERG, CD31, CD34 and D2-40) but negative for calretinin and WT1 (Am J Surg Pathol 2016;40:94)
WWTR1-CAMTA1 gene fusion in most cases, YAP1-TFE3 fusion in rare cases (Sci Transl Med 2011;3:98ra82, Genes Chromosomes Cancer 2011;50:644, Genes Chromosomes Cancer 2013;52:775)
Board review style question #1
Which of the following is true regarding peritoneal malignant mesothelioma?
All cases are associated with asbestos exposure
Compared to pleural mesothelioma, peritoneal mesothelioma more likely involves women and children
Copy number loss of CDKN2A and NF2 is detected in all cases
Histologic subtyping has no prognostic value
The presence of intact BAP1 protein expression rules out malignancy entirely
Board review answer #1
B. Compared to pleural mesothelioma, peritoneal mesothelioma more likely involves women and children
Comment Here
Reference: Peritoneal malignant mesothelioma
Board review style question #2
Missing Image Missing Image
Which of the following is true regarding the two images (the tumor and the corresponding BAP1 immunostain) illustrated?
This indicates germline BAP1 mutation(s) in all cases
This is a metastatic adenocarcinoma
This is a reactive mesothelial proliferation
This is a sarcomatoid malignant mesothelioma
This is an epithelioid malignant mesothelioma
Board review answer #2
E. This is an epithelioid malignant mesothelioma
Comment Here
Reference: Peritoneal malignant mesothelioma
Back to top
Home > Pleura & peritoneum > Peritoneal malignant mesothelioma
Comments
Post a Comment