Ovarian tumors I

OVARIAN TUMORS-I
Dr Aksharaditya Shukla
Resident, Department Of Pathology
MGM Medical College & M.Y. Hospital, Indore

Ovarian tumours
 Tumour of the ovary are common form of
neoplasia in women
 Accounts for 3% of all cancers in females
 80% are benign
 More common in older white women of
northern European ancestry
 90% of malignancies are carcinoma, 80% have
spread beyond the ovary at diagnosis.

Risk factors for carcinoma
 Nulliparity
 Family history
 Childhood gonadal dysgenesis
 Clomiphene
 Hereditary non polyposis colon cancer
 BRCA1 and BRCA2 mutations
 CA-125 present in 80% of serous and endometrioid
tumours
 Cytogenetics-gain of 12 & 8
 loss of chr X,22 18,17,14,13,12 & 8 ,
 benign/borderline tumor exhibit trisomy12

Classification of ovarian tumours
 Novak's classification (1967) has advantage of
being simple but has certain obvious drawbacks,
since it depends primarily on two
fundamental factors; benign or malignant
and solid or cystic.
 Thus the borderline tumors, solid tumors with cystic
degeneration and predominantly cystic tumors with
solid areas fall into grey zone.

 In 1971, the cancer committee of International
Federation of Gynecology and Obstetrics (FIGO)
proposed a histological classification of common primary
epithelial ovarian tumors. Although this classification
covered only epithelial tumors, it was a step in the
direction of uniformity in classification and it also
included the group of tumors of "low potential
malignancy".
 A significant stride in the direction of a
histogenesis-based classification system was made in
1973 with the publication of the World Health
Organization (WHO) Classification of Ovarian Tumors.
This classification system was updated in 1999 and
recently in 2003.

WHO classification of ovarian
tumours
1. SURFACE EPITHELIAL TUMOURS
2. GERM CELL TUMOURS
3. SEX CORD STROMAL TUMOURS
4. GERM CELL SEX CORD STROMAL TUMOURS
5. TUMOUR OF THE RETE OVARII
6. MISCELLANEOUS TUMOURS
7. TUMOUR LIKE CONDITIONS
8. LYMPHOID AND HEMATOPOETIC TUMOURS
9. SECONDARY TUMOURS

1. Serous tumours
2. Mucinous tumours
3. Endometroid tumours including variants of
squamous differentiation
4. Clear cell tumours
5. Transitional tumours
6. Squamous cell tumours
7. Mixed epithelial tumours
8. Undifferentiated and unclassified tumours.
SURFACE EPITHELIAL TUMOURS

 ¼ of all ovarian tumors
 Adults
 30-50% bilateral
 60% benign,15%
borderline,25% malignant
 Papillary formation present
 M/E: cuboidal to columnar
cells lining wall of cysts and
papillae
 Psammoma bodies 30%
Serous tumors

 BENIGN
a) Cystadenoma
b) Papillary cystadenoma
c) Surface papilloma
d) Adenofibroma and
cystadenofibroma
 BORDERLINE
a) Papillary cystic tumour
b) Surface papillary tumour.
c) Cystadenofibroma
 MALIGNANT
a) Adenocarcinoma
b) Surface papillary
carcinoma
c) Adenocarcinofibroma
(SEROUS TUMORS)

 Cystic masses usually
unilocular, containg
clear but sometimes
viscid fluid
 Multiloculated smooth
glistening cyst wall
with no epithelial
thickening or papillary
Serous cystadenoma- gross

Serous cystadenoma
 Cuboidal to columnar
cells are seen lining wall
of the cysts and papillae
in better differentiated
tumors.

 Borderline serous cystadenoma
 Age:20-50yrs
 Bilaterality-
30%
 Prognosis-
100% 5yr
survival
 GROSS-
increased
papillary
projections
within cyst

Borderline serous tumor.
 Entirely increased
complexity of stromal
papilla with
stratification and
nuclear atypia.
 But there is no
infiltrative growth into
the stroma.

 Epithelial
stratification
(2-3 layers).
 ↑ complexity of
stromal papillae.
 No stromal invasion

Serous Cystadenocarcinoma
 Age:40-70 yr
 Bilaterality-~66%
 Marker- CK7
 Prognosis-70%
5 yr survival
 GROSS-
- irregular
tumour mass
- ↑ solid/ papillary
- necrosis/
haemorrhage

 Complex papillary
architecture.
 Malignant cells in
glandular pattern.
 Nuclear atypia.
 High mitotic activity.
 Stratification.
 Stromal invasion
Serous Cystadenocarcinoma

Papillary serous cystadenocarcinoma of the ovary
. Microscopic features include stratification of low columnar epithelium lining
the inner surface of the cyst and a few psammoma bodies. The stroma shows invasion
by clusters of anaplastic tumour cells.

 Diagrammatic representation of general histologic criteria
to distinguish benign, borderline (atypical proliferating)
and malignant surface epithelial tumours of the ovary.

In some serous neoplasm fibroblastic stromal
component is unduly prominent
 Grossly as white , nodular foci in an otherwise cystic
neoplasm
1. Benign (common) adenofibroma &
cystadenofibroma
2. Borderline
3. Malignant adenofibrocarcinoma
cystadenofibrocarcinoma

Ovarian cystadenofibroma
 Well differentiated glands are
embedded within a dense
fibrous stroma

 Benign surface papillomas
 Intermediate borderline surface
papillary tumors
 Malignant serous surface papillary
tumors
Some serous neoplasms grow exophytically on the
surface of ovary , with little involvement of
underlying organ

 Papillomatous outer
surface of the ovary.
 Minimal enlargement of
the ovary.
Serous surface papillary carcinoma

Serous surface papillary carcinoma
 There is hardly any
infiltration of the
stroma.
 Mostly bilateral,
highly aggressive,
with peritoneal
spread at the time of
surgery.

Serous psammocarcinoma
 A rare form of serous
adenocarcinoma.
 Involve ovarian surface
 Massive psammoma body
formation.
 Low grade cytologic
features.
 Abundant psammoma bodies
in at least 75% of the papillae.

Immunohistochemistry of serous tumors
keratin profile
 CK 7+/ CK20-
 Also CK8, CK18, CK19, EMA, S100
 WT-1 stains diffusely most serous carcinomas

Ovarian implants
 Deposits of ovarian tumours on peritoneal surface.
 Entire peritoneum may contain tumour nodules<1 cm.
 Seen in 1/3 patients with serous borderline and malignant
tumours.
 Affect prognosis.
 Unencapsulated serous tumors of the ovarian surface
are more likely to extend to the peritoneal surfaces

 Less common. About 25%.
 Bilateral 10%-20% (clonal).
 80% are benign or borderline type.
MUCINOUS TUMORS

 BENIGN
a) cystadenoma
b) adenofibroma and
c) cystadenofibroma
 BORDERLINE
a) intestinal type
b) endocervical type
 MALIGNANT
a) adenocarcinoma
b) adenocarcinofibroma
 MUCINOUS CYSTIC
TUMOUR WITH
MURAL NODULES
 MUCINOUS CYSTIC
TUMOUR WITH
PSEUDOMYXOMA
PERITONEI
(MUCINOUS TUMORS)

Mucinouscystadenoma
 Larger then serous
 Cystic
 Multiloculated
 Fluid is viscous material of
mucoid nature present.

Mucinous cystadenoma
 These benign
cysts are lined by
a single layer of
tall columnar
mucinous
epithelium
without cilia.

Mucinous cystadenoma of the ovary.
The cyst wall and the septa are lined by a single layer of tall columnar mucin-
secreting epithelium with basally-placed nuclei and large apical mucinous
vacuoles.

 Intestinal type (80%)
 Endocervical type (20%)
Borderline mucinous tumors

Borderline mucinous cystadenoma
 Age:40-70yr
 Bilaterality-
5-10%
 GROSS-
-multiloculated
cysts
-papillae

Borderline mucinous tumor
(intestinal type)
 Epithelial lining with a
“picket fence appearance”
 Intestinal-type lining which
may be several layers thick
 Mild to moderate nuclear
atypia is present
 But destructive stromal
invasion with an associated
desmoplastic stromal
response ABSENT
 Goblet cells.
 Intestinal enzymes lipase ,
trypsin)
 But No evidence of
hormone excess
 Lining of mucinous cystadenoma

Borderline mucinous tumor
(endocervical type)
 Associated with
endometriosis
 Lining of tall non-
ciliated cells
 Basally located nuclei
 Abundant
intracellular mucin
 Endocervical lined
tumors are more
likely to be bilateral
and have associated
peritoneal implants

Malignant Mucinous tumors
 Age -40-70 yrs.
 Bilaterality- 5-15%.
 The neoplasm is
predominantly solid, but
some mucin-containing
cystic spaces can still be
appreciated.
 Thickened cyst wall.
 Areas of hemorrhage and
necrosis

Malignant Mucinous tumors
 Cell atypia
 Increased layering
 Gland complexity
 Papillae
 Areas of stromal
invasion
Complex architecture and obvious
nuclear atypia in mucinous
cystadenoma

STROMAL INVASION in MUCINOUS TUMORS
 Unquestionable carcinoma
stromal invasion
 Uncertain invasion .
atypical epithelium < 4 cells thick - borderline
atypical epithelium > 4 cells thick - carcinoma

Primary ovarian
carcinoma Metastasis
 Unilateral
 Size>10 cm
 Smooth external surface
 Expansile pattern of
invasion
 Complex papillary
pattern
 Without discrete
nodularity
 Bilateral
 H/O extraovarian primary
mucinous adenocarcinoma
 Surface implants
 Infilterative pattern of stromal
invasion
 Nodular invasive pattern
 Ovarian hilar involvement
 Vascular invasion
 Primary sites-45%GI,20%
pancreas,
Mucinous cystadenocarcinoma primary Vs metastasis

Pseudomyxoma peritonei
 Mucinous tumors (like serous tumors) may involve
the peritoneal surface with collection of extensive
mucinous material resembling cystic contents
within the peritoneal cavity.
 Is a rare condition
 Seen with primarily borderline or malignant
neoplasms.
 Major complication:
 Extensive interadherence and adhesion of the viscera,
producing a matting together of the abdominal contents and
intestinal obstruction

Immunohistochemistry of Mucinous tumors
 CEA
 EMA (particularly if
malignant)
 MUC5AC
 Dpc4
 CK7+ (always)
 CK20+ (50 %)
Intestinal Type
Immunohistochemically
endocrine cells contain:
 5-
hydroxytryptamine
(serotonin)
 ACTH
 gastrin
 somatostatin

1. Serous tumours
2. Mucinous tumours
Endometroid tumours including variants
of squamous differentiation
4. Transitional tumours
5. Squamous cell tumours
6. Mixed epithelial tumours
7. Undifferentiated and unclassified tumours

ENDOMETROID TUMORS
 10-25% of all primary
ovarian carcinomas
 Coexistent endometriosis
in 10-20%
 Grossly, endometroid
carcinoma may present as
cystic or solid mass
 Contents are hemorrhagic
 Visible papillary
formations absent.
 Good prognosis.

ENDOMETROID TUMORS
Villous papillary structures
and/or tubular glands
composed of a stratified layer of
epithelial cells with smooth
luminal borders.
 Destructive stromal invasion is
present.
 Resembles appearance of
endometrial carcinoma, with
centrally placed nuclei.


ENDOMETROID TUMOR
Adenoacanthoma
 Well-differentiated
endometrioid ovarian
carcinoma with
extensive squamous
metaplasia.
 Foci of squamous
metaplasia in 50%.
 May be peritoneal
keratin granulomas
 Well-differentiated endometrioid ovarian
carcinoma with extensive squamous metaplasia

Endometrioid (cyst) adenofibroma

Immunohistochemistry of endometroid
carcinoma
 Keratin
 EMA
 Vimentin
 CEA usually negative or weak

1. Serous tumours
2. Mucinous tumours
Clear cell tumours
4) Transitional tumours
5) Squamous cell tumours
6) Mixed epithelial tumours
7) Undifferentiated and unclassified tumours

Clear cell tumors
 Frequency- <5%.
 Epithelial tumors of the ovary in
which most or all of the cells
have clear cytoplasm; most
are malignant with rare benign
and borderline variants.
 Often associated with
endometriosis and endometrial
Ca.
 The tumor is predominantly
cystic mixed solid and cystic
masses. But often contain mixed
nodules.
 Clear cell carcinomas are always
high grade. Poor prognosis,Dr Aksharaditya Shukla

 Growth patterns:
tubular–cystic
papillary
solid sheet
Have abundant clear
cytoplasm and
significant nuclear
atypia.
Clear cell tumor

Clear cell tumors
 Clear cell carcinoma of ovary. Note the high nuclear grade and the hobnail
configuration
 Tumor cells: large, Clear
 Nuclei: some protrude into lumina, resulting in hobnail configuration ,cytoplasm:
clear &often contains:
 Glycogen, mucin, fat,may be PAS-positive diastase-resistant hyaline globules

Clear cell carcinoma
Clear cell carcinoma of ovary showing short papillae with hyalinized
cores lined by highly atypical cells.

Clear cell carcinoma
(oxyphilic variant) Clear cell adenofibroma

Special Stains and Immunohistochemistry
of Clear cell tumors
 Hyaline globules
negative for α-fetoprotein
 Tumor cells:
 always reactive for:
 keratin (CK7, CK5/6, CAM 5.2
 EMA
 CEA
 CD15 (Leu-M1)
 vimentin
 bcl-2
 p53
 CA-125
 Variably reactive for:
 estrogen and progesterone
receptors:
 much greater expression of ER
than PR
 ER exclusively of β rather than
αtype
 HER2/neu
 α-fetoprotein
 negative for:
 CK20
 also reactive for:
 hepatocyte nuclear factor-1β:
 transcription factor involved
with liver differentiation

1. Serous tumours
2. Mucinous tumours
Transitional tumours
5) Squamous cell tumours
6) Mixed epithelial tumours
7) Undifferentiated and unclassified tumours

 Benign
a) Brenner
b) Metaplastic variant
 Borderline
brenner
(proliferating variant)
 Malignant
a) Transitional cell
carcinoma (non-
Brenner type).
b) Malignant Brenner
tumour
Transitional tumours

Brenner Tumor and Transitional Cell
Carcinoma
 Resemble those of transitional cell neoplasms of
the urinary tract.
 1–2% of all ovarian neoplasms.
 Average age at presentation ≈50 years:
 Sometimes signs of hyperestronism, such as
postmenopausal uterine bleeding from
endometrial hyperplasia.
* Slow rate of growth
* Rarely ascites

Benign Brenner
tumour
 Grossly, these tumors have
a white to tan-yellow
whorled cut surface, but
may show cystic spaces and
calcification
 unilateral
 firm
 May be associated with:
 mucinous cystadenoma
 exceptionally struma ovarii
 also transitional cell tumors
of urinary bladder

Brenner Tumor
Epithelial cells:
solid and cystic nests
 Resemble transitional
epithelium(urothelium).
 Surrounded by abundant
stroma.
 Cysts with eosinophilic
fluid in a fibrotic stroma.
 Tumour cells -oval nuclei,
distinct nucleolus,
longitudinal groove.
 Brenner tumor of ovary showing solid
and cystic epithelial cells embedded
within fibrous tissue.

Metaplastic Brenner tumor
* Unduly prominent cystic formations.
* Florid mucinous changes.
* Papillary fronds and nuclear atypia absent.

Borderline Brenner tumor
 Pattern of proliferating
Brenner tumor with
greater atypia
(equivalent to grade I or
II transitional cell
carcinoma).
 Stromal invasion
cannot be demonstrated
 Borderline Brenner tumor showing
solid area with papillary formations,
associated with a large cystic space

Borderline Brenner
 papillary fronds
 nuclear atypia
 resemble pattern of
low-grade (I or II)
transitional carcinoma
of urinary bladder
 Highly proliferating
(borderline) Brenner tumor

Borderline Brenner tumor
 Nuclei:
 oval
 Small but distinct
nucleolus,
longitudinal
grooves
 clear cytoplasm:
 The epithelial nests of Brenner tumor are
composed of cells with oval nuclei, many of
which exhibit longitudinal grooves

Malignant Brenner tumor
Stromal invasion
Recognized mainly
because of
association with a
typical benign,
metaplastic,
proliferating, or
borderline component.
Areas of nuclear
atypia.

Transitional cell carcinomas of ovary
(non-brenner type)
 (TCCs) of the ovary resemble other epithelial
carcinomas with solid and cystic areas.
 Closely resemble TCC of the bladder.
 By definition, no Brenner tumor component is
present.
 Ovarian TCC is graded using the criteria for TCC of
the urothelial tract.

TCC ovary
Papillary cores lined by stratified, cytologically atypical
epithelium
Benign brenner component absent
Stratified malignant transitional epithelium

Special Stains and Immunohistochemistry of
Brenner tumors and TCC
Cytoplasm of tumor cells:
immunoreactive for:
- keratin
- EMA
- CEA:
+ also in lumen of cysts
* May contain:
glycogen, mucin, lipid
Steroidogenic enzymes usually absent

Malignant Mixed Müllerian Tumor
 Resembles grossly in every respect its more common uterine counterpart.
 The neoplasm is large, variegated, solid and cystic, with hemorrhagic
and necrotic areas
Gross appearance of malignant mixed
müllerian tumor of ovary. The
neoplasm is large, variegated, solid and
cystic, with hemorrhagic and necrotic
areas

 Carcinomatous component
may appear:
 Serous
 Endometrioid
 Squamous
 Clear cell (mesonephroid)
 Sarcoma-like elements may
have appearance of:
 Chondrosarcoma
(most common)
 Osteosarcoma
 Rhabdomyosarcoma
 Angiosarcoma
 Malignant mixed müllerian tumor of ovary
exhibiting heterologous foci in the form of
bone and cartilage

Non-specific malignant
stroma
Endometrioid
component
Clear cell component
Homologous type

Heterogenous Type
 Showing skeletal muscle and fibrous element.
 Malignant mixed müllerian tumor of ovary exhibiting
heterologous foci in the form of skeletal muscle

Special Stains and Immunohistochemistry
of MMMT
 Often hyaline droplets containing α1-antitrypsin
in cytoplasm of tumor cells.
 Prognosis: Extremely poor.
 Most reliable prognostic criterion is initial tumor
stage
 Most tumors have already extended outside ovary at surgery.

To be continue…
 Presented By: Dr Aksharaditya Shukla
Resident, Department Of Patholgy
MGM Medical College & M.Y. Hospital, Indore

Ovarian tumors I

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