2. 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.
Dr Aksharaditya Shukla
3. 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
Dr Aksharaditya Shukla
5. 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.
Dr Aksharaditya Shukla
6. 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.
Dr Aksharaditya Shukla
7. 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
Dr Aksharaditya Shukla
9. 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
Dr Aksharaditya Shukla
10. 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
SURFACE EPITHELIAL TUMOURS
(SEROUS TUMORS)
Dr Aksharaditya Shukla
11. Cystic masses usually
unilocular, containg
clear but sometimes
viscid fluid
Multiloculated smooth
glistening cyst wall
with no epithelial
thickening or papillary
Serous cystadenoma- gross
Dr Aksharaditya Shukla
12. Serous cystadenoma
Cuboidal to columnar
cells are seen lining wall
of the cysts and papillae
in better differentiated
tumors.
Dr Aksharaditya Shukla
14. Borderline serous tumor.
Entirely increased
complexity of stromal
papilla with
stratification and
nuclear atypia.
But there is no
infiltrative growth into
the stroma.
Dr Aksharaditya Shukla
16. Serous Cystadenocarcinoma
Age:40-70 yr
Bilaterality-~66%
Marker- CK7
Prognosis-70%
5 yr survival
GROSS-
- irregular
tumour mass
- ↑ solid/ papillary
- necrosis/
haemorrhage
Dr Aksharaditya Shukla
17. Complex papillary
architecture.
Malignant cells in
glandular pattern.
Nuclear atypia.
High mitotic activity.
Stratification.
Stromal invasion
Serous Cystadenocarcinoma
Dr Aksharaditya Shukla
18. 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.
Dr Aksharaditya Shukla
19. Diagrammatic representation of general histologic criteria
to distinguish benign, borderline (atypical proliferating)
and malignant surface epithelial tumours of the ovary.
Dr Aksharaditya Shukla
20. 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
Dr Aksharaditya Shukla
22. 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
Dr Aksharaditya Shukla
23. Papillomatous outer
surface of the ovary.
Minimal enlargement of
the ovary.
Serous surface papillary carcinoma
Dr Aksharaditya Shukla
24. Serous surface papillary carcinoma
There is hardly any
infiltration of the
stroma.
Mostly bilateral,
highly aggressive,
with peritoneal
spread at the time of
surgery.
Dr Aksharaditya Shukla
25. 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.
Dr Aksharaditya Shukla
26. Immunohistochemistry of serous tumors
keratin profile
CK 7+/ CK20-
Also CK8, CK18, CK19, EMA, S100
WT-1 stains diffusely most serous carcinomas
Dr Aksharaditya Shukla
27. 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
Dr Aksharaditya Shukla
28. Less common. About 25%.
Bilateral 10%-20% (clonal).
80% are benign or borderline type.
MUCINOUS TUMORS
Dr Aksharaditya Shukla
29. 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
SURFACE EPITHELIAL TUMOURS
(MUCINOUS TUMORS)
Dr Aksharaditya Shukla
30. Mucinouscystadenoma
Larger then serous
Cystic
Multiloculated
Fluid is viscous material of
mucoid nature present.
Dr Aksharaditya Shukla
31. Mucinous cystadenoma
These benign
cysts are lined by
a single layer of
tall columnar
mucinous
epithelium
without cilia.
Dr Aksharaditya Shukla
32. 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.
Dr Aksharaditya Shukla
33. Intestinal type (80%)
Endocervical type (20%)
Borderline mucinous tumors
Dr Aksharaditya Shukla
35. 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
Dr Aksharaditya Shukla
36. 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
Dr Aksharaditya Shukla
37. 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
Dr Aksharaditya Shukla
38. Malignant Mucinous tumors
Cell atypia
Increased layering
Gland complexity
Papillae
Areas of stromal
invasion
Complex architecture and obvious
nuclear atypia in mucinous
cystadenoma
Dr Aksharaditya Shukla
41. 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
Dr Aksharaditya Shukla
43. 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
Dr Aksharaditya Shukla
44. 1. Serous tumours
2. Mucinous tumours
Endometroid tumours including variants
of squamous differentiation
3. Clear cell tumours
4. Transitional tumours
5. Squamous cell tumours
6. Mixed epithelial tumours
7. Undifferentiated and unclassified tumours
SURFACE EPITHELIAL TUMOURS
Dr Aksharaditya Shukla
45. 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.
Dr Aksharaditya Shukla
46. 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.
Dr Aksharaditya Shukla
47. 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
Dr Aksharaditya Shukla
50. 1. Serous tumours
2. Mucinous tumours
3. Endometroid tumours including variants of
squamous differentiation
Clear cell tumours
4) Transitional tumours
5) Squamous cell tumours
6) Mixed epithelial tumours
7) Undifferentiated and unclassified tumours
SURFACE EPITHELIAL TUMOURS
Dr Aksharaditya Shukla
51. 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
53. 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
Dr Aksharaditya Shukla
54. Clear cell carcinoma
Clear cell carcinoma of ovary showing short papillae with hyalinized
cores lined by highly atypical cells.
Dr Aksharaditya Shukla
56. 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
Dr Aksharaditya Shukla
57. 1. Serous tumours
2. Mucinous tumours
3. Endometroid tumours including variants of
squamous differentiation
4. Clear cell tumours
Transitional tumours
5) Squamous cell tumours
6) Mixed epithelial tumours
7) Undifferentiated and unclassified tumours
SURFACE EPITHELIAL TUMOURS
Dr Aksharaditya Shukla
58. Benign
a) Brenner
b) Metaplastic variant
Borderline
brenner
(proliferating variant)
Malignant
a) Transitional cell
carcinoma (non-
Brenner type).
b) Malignant Brenner
tumour
Transitional tumours
Dr Aksharaditya Shukla
59. 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
Dr Aksharaditya Shukla
60. 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
Dr Aksharaditya Shukla
61. 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.
Dr Aksharaditya Shukla
63. 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
Dr Aksharaditya Shukla
64. Borderline Brenner
papillary fronds
nuclear atypia
resemble pattern of
low-grade (I or II)
transitional carcinoma
of urinary bladder
Highly proliferating
(borderline) Brenner tumor
Dr Aksharaditya Shukla
65. 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
Dr Aksharaditya Shukla
66. Malignant Brenner tumor
Stromal invasion
Recognized mainly
because of
association with a
typical benign,
metaplastic,
proliferating, or
borderline component.
Areas of nuclear
atypia.
Dr Aksharaditya Shukla
67. 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.
Dr Aksharaditya Shukla
69. 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
Dr Aksharaditya Shukla
70. 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
Dr Aksharaditya Shukla
71. Malignant Mixed Müllerian Tumor
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
Dr Aksharaditya Shukla
73. Malignant Mixed Müllerian Tumor
Heterogenous Type
Showing skeletal muscle and fibrous element.
Malignant mixed müllerian tumor of ovary exhibiting
heterologous foci in the form of skeletal muscle
Dr Aksharaditya Shukla
74. 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.
Dr Aksharaditya Shukla
75. To be continue…
Presented By: Dr Aksharaditya Shukla
Resident, Department Of Patholgy
MGM Medical College & M.Y. Hospital, Indore
Dr Aksharaditya Shukla
Editor's Notes
Ocps, salphingooprectomy pregnancy before 25 yrs are associated with decreased risk. abdominal enlargement, pressure on adjacent organs.
Cystic masses usually unilocular, containg clear but sometimes viscid fluid
Multiloculated smooth glistening cyst wall without epithelial thickening or papillary projections
Lined by flattened epithelium similar to that of fallopian tube
Ciliated/non-ciliated
Multilayered epithelium
malignant cells in glandular pattern
Stromal invasion
Gross-
Uni-/ multiloculated cysts (filled with mucinous material
Piling up of malignant epithelium
Papillary formation
Origin- diff. towards endometrial epithelium Mostly malignant
Age group- V-VI decade
Bilaterality- 15-30%
Good prognosis
GROSS-
-Solid /cystic / combination
-Cyst content- haemorrhagic usually
Psammoma bodies exceptional
Columnar lining with centrally placed nucleus
Uncommon pattern
Frequency-~5%
Benign/borderline-rare
Mostly present as adenofibroma.The tumor is predominantly cystic, but it contains several mural nodules
Age- V-VI decade
Bilaterality- 10%
Poor prognosis
Association with endometriosis & endometrial carcinoma
GROSS-
- spongy, often cystic
- unilocular cysts with solid nodules
Bilaterality- 6%, GROSS-
- Mostly solid
- well
circumscribed
- On cut- firm,
white/yellowish
white
Brenner tumor of ovary showing solid and cystic epithelial cells embedded within fibrous tissueTumour cells -oval nuclei
-distinct nucleolus
-longitudinal groove
Borderline Brenner tumor showing solid area with papillary formations, associated with a large cystic space
The nuclear atypia is evident. Other areas of the tumor had the typical appearance of Brenner tumor
in larger amounts in stromal cells if hyperestrinism
Malignant mixed müllerian tumor of ovary exhibiting heterologous foci in the form of bone and cartilage
Malignant mixed müllerian tumor of ovary exhibiting heterologous foci in the form of skeletal muscle