Borderline Ovarian Tumors
Dr. Deepak.P (2nd year PG)
Moderators: Dr. Sri Vani(Prof)
Dr. Anunayi (Asso. Prof)
Dr. Shiva Chaitanya (Asst.Prof)
Objectives
• History
• WHO classification
• Borderline tumors
History
• Taylor in 1929 as “semi-malignant” ovarian tumors with
peritoneal involvement but surprisingly good prognosis.
• International Federation of Gynecology and Obstetrics
(FIGO) in 1971 as tumors of “low malignant potential”.
• WHO in 1973 recognised these tumors.
• 2014 WHO Classification of Tumours of the Female
Genital Organs uses the term “borderline tumor”
interchangeable with “atypical proliferative tumor”
• “tumor of low malignant potential” is no longer
recommended
• The WHO Histological Classification for ovarian tumors
separates ovarian neoplasms according to the most probable
tissue of origin:
• Surface epithelial (65%),
• Germ cell (15%),
• Sex cord-stromal (10%),
• Metastases (5%),
• Miscellaneous
• Surface epithelial tumors are further classified by cell type
and atypia
• Most of malignant are surface epithelial tumours(90%)
• Surface epithelial - stromal tumors
– Serous tumors:
• Benign (cystadenoma)
• Borderline tumors (serous borderline tumor)
• Malignant (serous adenocarcinoma)
– Mucinous tumors, endocervical-like and intestinal type:
• Benign (cystadenoma)
• Borderline tumors (mucinous borderline tumor)
• Malignant (mucinous adenocarcinoma)
– Endometrioid tumors:
• Benign (cystadenoma)
• Borderline tumors (endometrioid borderline tumor)
• Malignant (endometrioid adenocarcinoma)
– Clear cell tumors:
• Benign
• Borderline tumors
• Malignant (clear cell adenocarcinoma)
– Transitional cell tumors:
• Brenner tumor
• Brenner tumor of borderline malignancy
• Malignant Brenner tumor
• Transitional cell carcinoma (non-Brenner type)
Benign v/s Borderline v/s Malignant
Serous Borderline Tumour(SBT)/Atypical
Proliferative Serous Tumour(APST)
• Non invasive tumors
• 10–15% of all serous epithelial tumours of ovary
• Display greater epithelial proliferation and cytological
atypia than benign tumors
• But less than low grade serous carcinoma(LGSC)
• Mean age of patients -42 years
• KRAS and BRAF mutation: 50% cases
• Histological spectrum of borderline tumors
• Tumors at lower end- behave benign-
hierarchical pattern- APST
• Tumors at other end- low grade carcinoma-
complex non hierarchical pattern, delicate
micropapillae - non invasive micropapillary
serous carcinoma (MPSC).
• Papillae with hierarchical branching:
• –– The large papillae divide and give rise to
smaller papillae which again divide to produce
much smaller papillae.
• –– Papillary tufts are frequently detached
from the tip and float in the cyst
• Tangentially cut papillae may simulate stromal
invasion
• There will be no stromal invasion.
• The lining epithelial cells of the papillae and
cyst are cuboidal to columnar.
• Mild to moderate nuclear enlargement,
pleomorphism and
hyperchromasia.
Essential Diagnostic Criteria
• Complex hierarchical branching papillary pattern
• Nuclear atypia: cuboidal to columnar lining
epithelial cells show mild to moderate nuclear
enlargement and pleomorphism
• No stromal invasion
• Hobnail appearance frequently present
• If confluent growth present: it measures less
than 5 mm area (microinvasion)
SBT/APST with Focal Micropapillary features
Subtype of SBT(5-15% of SBT)
Display foci of Micro papillae arranged in Non
Hierarchical branching pattern
Simulates Non Invasive LGSC
Lack nuclear atypia of Non Invasive LGSC
Measure <5mm in confluent growth
Microinvasion
• Microinvasion may be found in 25% of cases
• Single or Clusters of cells in stroma with abundant
eosinophilic cytoplasm similar to cells on the surface of
papillae
• Measure <5mm in greater dimension
• ER,PR Negative, Low Ki67 index
• 1.Usual Type of Microinvasion (Eosinophilic Type)
• 2. Microinvasive Carcinoma
Features of Microinvasion
• Irregular outline of cell clusters/ micropapillae
• Cell clusters surrounded by clear space
• Desmoplastic reaction.
• D2-40 immunostaining demonstrates clear
space as a lymphatic space
• Higher frequency of bilaterality, exophytic
growth, and peritoneal implants.
Implants
• Because women with extra ovarian spread
have a good prognosis, the peritoneal lesions
are classified as implants instead of metastasis
• Non invasive: just stuck to peritoneal surface.
• Invasive: invading the underlying tissue such
as omentum and bowel wall.
Implants associated with SBT/APST
• Peritoneal implants: 30–40% cases of SBT
• Papillary group, glands or small clusters or single cells with nuclear
atypia surrounded by dense fibrous stroma.
Non invasive implants- Confined to the surface of organ
• Epithelial type
• Display hierarchical branching papillae or detached clusters of
cells
• Associated with Non fibrotic stroma
• Desmoplastic type
• Clusters of cells embedded in reactive or dense fibrous stroma
that overshadows epithelial component
Invasive implants-infiltrating the underlying tissue
• Overall 12% of SBT shows invasive implants
• The papillae/glands/isolated clusters of cells within
the stroma having irregular margin
• Micropapillae formation
• Island of cells surrounded by clear space
• Higher chances of recurrence and more aggressive in
behaviour
Pelvic lymph nodes associated with SBT/APST
Noted in 23% cases of SBT
Sinusoidal spaces of lymph node is involved by the cluster of
cells with abundant eosinophilic cytoplasm
Contain variety of lesions
• Eosinophilic cells in LN interpreted as senescent cells
• Endosalpingosis
• Non invasive implants –Resembling primary ovarian
SBT/APST
These do not affect the survival, no prognostic value.
Prognosis of SBT
• SBT confined to ovary behaves as a benign fashion
• Five year survival is 95–100%
• Peritoneal non-invasive implants may have
adhesion and recurrence
• No adverse prognosis in case of lymph nodal
implants
• Death occur only in those cases that progress to
low grade serous carcinoma.
Differential diagnosis
• Benign serous tumours
–– Less than 10% area show borderline changes
• Serous adenocarcinoma
–– Definite stromal invasion present
• Struma ovarii with papillary structure
–– Typical thyroid follicle present
IHC of SBT/APST
• Various epithelial markers are expressed
– CK(AE1/AE3,CAM 5.2)
– EMA
– BER-EP4
– WT1
– PAX8
• High levels of ER,PR
• negative for p53 and p16
Mucinous Borderline Tumour/Atypical
Proliferative Mucinous Tumour
• Definition: This tumour is characterized by
proliferation of atypical mucinous epithelial
cells that is more than the benign mucinous
neoplasms in absence of any stromal invasion.
• It constitutes of 15% of all ovarian mucinous
tumours
• Represents 70% of all borderline tumours of
ovary in Asian countries
• Mean age: 45 years
• KRAS mutation (50–75%)
• No germline mutation of BRCA 1 and BRC1 2
Gross
• There are two types of APMT:
-the gastrointestinal type (80%)
-the endocervical-like (mullerian, or
seromucinous) type (20%)
• Intestinal type are further divided:
-With atypia only
-With intraepithelial carcinoma
-With microinvasion
• Cysts and glands are lined by Tall columnar mucin
secreting epithelial cells
• Stratification of the epithelial cells: <3 layer
• Nuclei show mild to moderate enlargement and
pleomorphism and Prominent nucleoli
• Goblet cells, Paneth cells and neuroendocrine cells in
intestinal type of MBT
• Endocervical type mucinous cells in endocervical MBT
• Often associated with pseudomyxoma ovarii (acellular
pools of mucin)( (20% cases)
MBT/APMT with intraepithelial
carcinoma
Features of MBT/APMT
Foci of marked nuclear atypia confined to
epithelium
MBT/APMT with Microinvasion
Small foci of stromal invasion measuring
<5mm in greatest dimension
Composed of single cells, glands,
clusters/nests of mucinous epithelial cells,
small foci of confluent glandular or cribriform
growth with mild to moderate atypia
MBT/APMT associated with Mural Nodules
• Associated with sarcoma like mural nodules
• Well circumscribed nodules
• Contain Multinucleated cells of epulis type, atypical
spindle cells & inflammatory cells
• Represent reaction to hemorrhage or mucin of cyst
IHC
• CK7-typically diffuse
• CK20-variable positivity
• CDX2-variable
• ER,PR-almost negative
• PAX8-upto 50-60% of tumours
Endometrioid Borderline Tumour/Atypical
Proliferative Endometrioid Tumour
• Rare neoplasm
• Incidence: 2-3% of borderline tumors of ovary
• Mean age: 50 year
• Mass in lower abdomen
• Mean size is 10 cm
• Predominantly solid and partly cystic
• Cut section: Cyst contains fluid, haemorrhage and necrotic
foci
• Solid/cystic tumour composed of crowded glands lined by
atypical endometrioid type cells with no stromal invasion
Adenofibromatous
• Adenofibroma in the background
• Crowded back to back glands
• Mild to moderate atypia with epithelial stratification
• Cribiform pattern due to bridging of epithelial proliferation
• Squamous metaplasia common
Intracystic
• Without adenofibroma in background
• Back to back proliferation or papillary pattern
• Protruding into cystic structure
Clear Cell Borderline Tumour/APCCT
• Very rare
• Only 0.2% of all ovarian epithelial neoplasm
• Less than 1% of all borderline neoplastic
lesions of ovary
• Mean age is 60–68 years
• Benign course
• Multiple glands
• Focal crowding present
• Glandular epithelium shows cuboidal or
hobnail type of cells
• Epithelial cells have mild nuclear enlargement
and pleomorphism
• Stratification of the lining cells of the glands
• Focal endometriosis may be present
Borderline Brenner Tumour
• ‘Proliferating’’ or ‘‘Borderline’’Transitional cell
or Brenner tumor.
• mean age is 59 years.
• Prognosis- benign course
• Arrangement: Nests, cystic and papillary
• The papillae arise from the cyst wall
• Lining of the papillae is made of transitional cells
with mild to moderate nuclear atypia
• Multiple nests of transitional cells in the stroma.
• The nest are more closely spaced and relatively
large than the benign counterpart
• Benign Brenner component is also present
Seromucinous Borderline Tumour/Atypical
Seromucinous Tumour
• Histopathology
• Architectural features similar to SBT/APST
• Complex papillary architectural with hierarchical
branching pattern
• Larger papillae have oedematous stroma containing
neutrophils
• Lined by variable admixture of more often Serous
cells,Mucinous cells, (endocervical type)
• Less often Endometroid, Transitional, Squamous cells
References
• World Health Organization Classification of Tumours 4th
Edition
• Blaustein’s Pathology of the Female Genital Tract 6th Edition
• Color Atlas of Female Genital Tract Pathology Pranab dey
• Robbins & Cotran Pathologic Basis of Disease 9th Edition
• Ovarian borderline tumors in the 2014 WHO classification:
evolving concepts and diagnostic criteria Steffen
Hauptmann et al 2017
• Pathology of female reproductive tract -Robboy
THANK YOU
