The 21st Korea-Taiwan-Japan
Joint Meeting for Gynecological Pathology
Sendai, October 28, 2017

Special lecture

Peritoneal lesions

Takako Kiyokawa, MD
Department of Pathology, The Jikei University Schoolof Medicine, Tokyo, Japan
E-mail: kiyokawa@jikei.ac.jp

Contents
1. Mesothelial lesions

2. Műllerian lesions
3. Mesenchymal tumors

4. Miscellaneous primary tumors
5. Secondary tumors

6. Other tumor-like lesions

Contents
1. Mesothelial lesions

2. Műllerian lesions
3. Mesenchymal tumors

4. Miscellaneous primary tumors
5. Secondary tumors

6. Other tumor-like lesions

Mesothelial lesions
Neoplasia• Malignant mesothelioma• Well-differentiated papillary mesothelioma• Adenomatoid tumor
Non-neoplastic lesions• Peritoneal inclusion cyst
• Mesothelial hyperplasia

Malignant mesothelioma• Rare 7/1000,000 population• M:F=7:3• Increase of death of disease x3/20yrs
Total
MaleFemale

Data by Ministryof welfare and5
labor of JApan

Peritoneal mesothelioma• 10％ of all malig mesothelioma• M:F=7:3 (Japanese mesothelioma registry)
M:F=1.5:1 (Hillerdal G. Br J Dis Chest. 1983;77:321343)• Heavy asbestos exposure is a higher risk fordevelopment of peritoneal mesothelioma in menAsbestos exposure in brief period is a higher
risk for plueral mesothelioma
Antman KH. Chest. 1993;103:373S-376S• Half of the pts with no history of asbestos
exposure6

Female peritoneal mesothelioma
Age：17-92（mean 47.4）yrs (n=75cases) No association with asbestos exposure

Abdominal discomfort, distention, weight loss

Most cases are epithelioid type（tubular>
papillary> solid, mixed）
 Tumor cells: polygonal, cuboidal/low columnar,
eosinophilic cytoplasm, mild to moderate nuclear
atypia, mitoses may be infrequent

Minor foci may resemble WDPM

Baker PM, et al. Am J Clin Pathol. 2005;123:724-737.
7

Malignant mesothelioma

Female peritoneal mesothelioma
Immunohistochemistry
Positive

Negative

Recommended
calretinin
WT-1
D2-40
CK5/6
MOC-31
Ber-EP4
PAX8*
ER*, PgR*
Caludin 4Others
CK7
Pan CKCEA
TTF-1

Loss of BAP 1 in only 50% of peritoneal mesothelioma 9Asbestos-Related Health Damage
Relief System in Japan• Act took effect on March 27, 2006
• Provides relief benefit (medical care expenses) tosufferers of the designated diseases and to thebereaved of those DOD• Diseases covered by the benefits: The following
diseases caused by asbestos
1)Mesothelioma2)Malignant neoplasm of lung and bronchus
3)Asbestosis with heavy respiratory dysfunction4)Diffuse pleural thickening with heavy
respiratory dysfunction

Results of female pts applied withperitoneal mesothelioma
Submission of pathology slides: 221 Pts
March 31, 2006～ March 31, 2017

Non-certified
51 （23%）

Others6 （3%）

Certified
164 （74%）

Panel diagnosis in non-certified pts （51）March 31, 2006～ March 31, 2017

Benign （10%）
Non-Gyn Malig
15（29%）Gyn Malig
31（61%）

Well-differentiated papillary
mesothelioma• Gross: Papillary, well circumscribed tumor,0.1-2cm, 50% multiple• Micro: papillary, wide fibrous stroma, blandnuclei, rare mitosis, inv<0.5cm• dDx: malignant mesothelioma• 23 -75 years (median, 47 y; mean, 48.6 y)• No hx of asbestos exposure• Incidental finding• Favorable prognosis

Daya D, et al. Cancer. 1990;65:292-296.
Malpica A, et al. Am J Surg Pathol. 2012;36:117-127.

Well-differentiated papillary mesothelioma

14Adenomatoid tumor• Adults• Incidental finding• Benign• Gross: Small, firm nodules• Micro: cells with cytoplasmic
vacuoles/eosinophilic abundant cytoplasm, blandround to oval nuclei, rare mitosis; anastomosing
gland-like spaces>solid nests• Immnohx: cytokeratin+, vimentin+, WT1+,
calretinin, CK5/6, thrombomodulin+• dDx: metastatic carcinoma

Adenomatoid tumor

Infarcted adenomatoid tumor• Solitary solid mass 1.1-3.5cm• Necrosis in the center of the tumor• Proliferation of fibroblasts,
myofibroblasts• Tumor cells often arranged in a solid nest
( 4 males and one female-paratubal mass)
Skinnider BF, et al. Am J Surg Pathol 2004; 28: 77-83

Peritoneal inclusion cyst
• Cyst-forming mesothelial proliferation• Rare• Women of reproductive age• Unilocular>>>multilocular• Multilocular cyst
up ∅20cm, ass w previous surgery,endometiosis, inflammatory process• Most of them reactive rather than neoplastic

Peritoneal inclusion cyst
• AKA– Multilocular peritoneal inclusion cyst
– Mesothelial inclusion cyst
– Benign cystic mesothelioma*– Multicystic mesothelioma** Not recommended (WHO2014)

2cmPeritoneal
inclusion cyst

Mesothelial hyperplasia• Salpingitis, peritonitis, pelvic endometriosis,
etc• Grossly unidentifiable• Stratification, papillary, enlarged mesothelialcells• Mesothelial entrapment in the peritoneal
stroma/ovarian stroma• dDx : invasive carcinoma (adenocarcinoma),malignant mesothelioma

Entrapped hyperplastic
mesothelial
18歳，女性cells
in the endometriotic
卵巣内膜症性嚢胞cyst

Contents
1. Mesothelial lesions2. Műllerian lesions
3. Mesenchymal tumors

4. Miscellaneous primary tumors
5. Secondary tumors

6. Other tumor-like lesionsMűllerian-type neoplasia• Serous carcinoma: high-grade>>>low-grade• Serous borderline tumor• Műllerian adenosarcoma• Endometrioid stromal sarcoma• Carcinosarcoma• Endometrioid carcinoma• Clear cell carcinoma• Mucinous carcinoma

High-grade serous carcinoma

Classical criteria for peritoneal
serous carcinoma
Carcinoma in the peritoneum• Both ovaries are either normal in size orenlarged by a benign process• The bulk of the tumor in the extrovarian sites
is greater than on the ovarian surface• Microscopically ovaries reveal
1) No tumor2)Tumor confined to the surface epithelium3)Tumor is <5x5mm in the ovarian substanceOrigin of “ovarian or peritoneal ”
high-grade serous carcinoma
Tubal origin

Paradigm shift• Studies using RRSO in women with
BRACA1/2 mutation• Examination of fallopian tubes by SEEFIM protocol, perspective studies
Traditional model• No precursor lesion• Arise from surface epithelial inclusion cyst
• Decision of primary site based on tumor volumefimbriated end of tube

Protocol for Sectioning andExtensively Examining theFIMbriated end (SEE-FIM)
Medeiros F, et al. Am J Surg
Pathol 30;230-236, 2006

Serous intraepithelial carcinoma (STIC)• Intraepithelial proliferation of atypicalcells identical to HGSC in the tube

• 50-60%of extrauterine HGSC
• RRSO tubes of women with BRCA1/2mutation• >90% in fimbria• Possible to spread to peritoneum and ovary• Imhx: abberant expression of p53

Criteria for peritoneal high-grade
serous carcinoma 2014（WHO 2014)• Carcinoma in the peritoneum• Both ovaries and fallopian tubes are grossly
and microscopically normal or enlarged only bya normal process

Malignant tumors associated withendometriosis
Adenosarcoma
Clear cell Ca
Endom Ca
Serous Ca
Mucinous Ca
Serous BT
Mucinous BT
Total

Extraova (%) Ova (%)

Total(%)

3 (33.3)
4 (44.4)1
1
000
9 (100)3 (8.3)
13 (36.1)
9 (23.1)
6 (16.7)
13 (8.3)
136 (100)09 (33.3)
8 (29.7)
5 (18.5)
13 (11.1)
127 (100)

Stern RC et al. Int J Gynecol Pathol, 2001, 20:133-9Adenosarcoma (arising in pelvic endometirosis)

Adenosarcoma (arising in pelvic endometirosis)

Non-neoplastic Műllerian lesions• Endometriosis and its related lesions
Endosalpingiosis, endocervicosis, Műllerianosis• Ectopic decidua• Endometriosis with pregnancy effect• May mimic neoplastic process, both clinicallyand pathologicallyEndometriosis withdecidual change:-white flat elevatedlesion in the Douglas’
Pouch at c-section (preg38w)

Contents
1. Mesothelial lesions

2. Műllerian lesions
3. Mesenchymal tumors

4. Miscellaneous primary tumors
5. Secondary tumors

6. Other tumor-like lesions

Mesenchymal tumors• Extra-gastrointestinal stromal tumor• Solitary fibrous tumor• Desmoid tumor (abdominal fibromatosis)• Inflammatory myofibroblastic tumor• Calcifying fibrous tumor• Leiomyomatosis peritonealis disseminate• Liposarcoma• Others

Solitary Fibrous Tumor• Localized fibrous tumor with hemangiopericytoma-like vascular pattern• Originate from submesothelial fibroblast(CD34+)• Rare in the peritoneal cavity (usually in pleura)• Most with favorable prognosis; histology does
not predict malignant behavior• Doege-Potter syndrome
hypoglycemia (insulin-like GF 2)

38

Desmoid tumor (abdominalfibromatosis)• Invasive proliferation of fibroblastic spindle
cells in the abdominal wall/cavity• Adult; F>M• Sporadic cases; familial adenomatous
polyposis (10% of FAP), trisomy (#8,#20);
5q deletion• Local rec; no distant metastasis

2cm

Desmoid tumor (abdominal fibromatosis)

40

Inflammatory myofibroblastic tumor• Proliferation of myofibroblastic spindle cellswith lymphoplasmacytic infiltrate• Children, young adults• Presentation: mass, fever, growth failure,weight loss, anemia, thrombocytosis,
polyclonalhypergammaglabulinemia• Imhx: SMA+, desmin+• ALK gene rearrangement 60%• Local rec; metastasis- histology cannot
predict prognosis
Gynecologic Oncology Reports 12 (2015) :9–12

Calcifying fibrous tumor• Fibrous tumor with calcification, wellcircumscribed, abundant collagen,lymphoplasmacytic infiltration• Serosa of stomach, small intestine• Incidental finding• Young adults, adults

Contents
1. Mesothelial lesions

2. Műllerian lesions
3. Mesenchymal tumors

4. Miscellaneous primary tumors
5. Secondary tumors

6. Other tumor-like lesions

Desmoplastic small round cell tumor• Malignant tumor of unknown origin• Rare• Adolescents, young adults (15-30yrs)• Male >>Female (4:1)• Abdominal and/or pelvic peritoneum• t(11;22)(p13;q12)⇒EWS-WT1 fusion protein• Poor prognosis (OS 50%)

Desmoplastic small round cell tumor

高Ca型小細胞癌
DesminDesmoplastic smallround cell tumor
CAM5.2

Peritoneal ependymoma• Prognosis• Imhx: some difference from CNS ependymoma
ER 100% (10% in CNS epen)
PgR 80% (20% in CNS epen)
CK7 80% (10% in CNS epen)
GFAP 100% (100% in CNS)
Am J Surg Pathol 2008;32:710–718• Pathogenesis: controversial
Metaplasia,? teratoma? Aberrant tissue?
• dDX
serous carcinoma, malignant mesothelioma,
gliomatosis peritonei

Extra-CNS Ependymoma
Literature review

1 (8%)

Location （n=13)

1 (8%)ovary

1 (8%)

Paraovarian region
7 (54%)

1 (7%)

2 (15%)

LiverMediastinum

Smal bowel
Peritoneum
Verdun TP, et al. Pathol Res Pract 2015; 211: 268-70

Contents
1. Mesothelial lesions

2. Műllerian lesions
3. Mesenchymal tumors

4. Miscellaneous primary tumors
5. Secondary tumors

6. Other tumor-like lesions

Secondary tumors• Primary tumor: gyn, GI >>> pancreas,breast (lobular carcinoma)• Peritoneal implant of ovarian serous
borderline tumor• Gliomatosis peritonei

Peritoneal implant of ovarian serous
borderline tumor• Pts with ovarian serous borderline with peritoneal
lesion• WHO 2014
-implant: formally called non-invasive implantfavorable prognosis- low-grade serous carcinoma（LGSC): formallycalled non-invasive implant
Poor prognosis• …..invasive implant behave like LGSC they should
be designated as such. All other implants that are
non-invasive can be designated “implants”(WHO2014)

Pseudomyxoma peritonei• Clinical term :grossly evident peritoneal
involvement by mucoid material due toperitoneal spread of mucinous neoplasm• Origin: low-grade appendiceal mucinous
neoplasia >>>mucinous component of ovarian
mature cystic teratoma• Histology: dissecting mucin with fibrosis

Dissecting mucin withfibrosis with low-grade
mucinous tumor cells

Peritoneal lesions with mucin: Pathology
reportRE Scully et al. AFIP 3rd series,
fascicle 23Mucinous ascites
w LG mucinous tumor cells
w HG mucinous tumor cells

Ronnett et al. AJSP
1995; 19: 1390-1408

Organizing mucinous fluid
w LG mucinous tumor cells
w HG mucinous tumor cells

DPAM
PMCA

Dissecting mucin with fibrosis
w LG mucinous tumor cells
w HG mucinous tumor cells

DPAM
PMCA

DPAM :Disseminated peritoneal adenomucinosis
PMCA: Peritoneal mucinous carcinomatosis

Organizing mucinous fluid (with low-grade tumor cells)Gliomatosis peritonei• Benign mature glial implants on the peritoneal
surface• Rare complication of ova immature/mature
teratoma• Good prognosis (Grade 0)

Gliomatosis peritonei
Histogenesis• Peritoneal seeding of ovarian teratoma via
capsular rupturevs.
• Originate from peritoneal pluripotent cells
stimulated by GF in ovarian tumor(different genetic identity between peritoneal andova tumor)
Am J Pathol 2001; 159: 51-55
Hum Pathol 2004; 35: 685-688

with endometrisois

Int J Dev Biol 2012, 56:969-974
Korean J Pathol 2013, 47:587-591

Contents
1. Mesothelial lesions

2. Műllerian lesions
3. Mesenchymal tumors

4. Miscellaneous primary tumors
5. Secondary tumors

6. Other tumor-like lesions

Sclerosing peritonitis a/w ovarianluteinized thecoma• Reactive submesothelial mesenchymal
proliferation; ascites; encases the small bowel
to cause bowel obstraction• Premenopausal pts (mean 28yrs)• Bil ova lesions ; No endocrine manifestation• No rec or spread of the ovarian lesion• Pts may die of sclerosing peritonitis• Ovarian lesion may be non-neoplastic nature:
entrapped follicles and normal structureswithin the lesions → ‘‘thecomatosis’’ ？
Am J Surg Pathol 2008,32:1273-90

Peritoneal keratin granuloma• Response to deposition of keratin derived
from lesions in the female reproductive tract- ovarian teratoma- endometrial carcinoma with sq diff- cervical Sq CC (bulky)• may be confused with metastatic carcinoma