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
8. GERM CELL TUMOURS
Origin- germ cells (totipotent) which migrate to ovary
from yolk sac .
Frequency-15-20%
Age group- children & young adults
~95% are benign.
The younger the patient, more chances of malignancy
Dr Aksharaditya Shukla
10. Dysgerminoma
Dysgerminoma is the most
common malignant germ cell
neoplasia of the ovary, and is
similar to seminoma which
is the testicular counterpart
<1% of all ovarian tumors
≈5% of malignant ovarian
tumors
Usually young <30 years of
age.
≈5% arise in abnormal gonads:
a) pure or mixed gonadal
dysgenesis (from a
gonadoblastoma),
b) testicular feminization
(androgen insensitivity)
syndrome
More common on right.
Bilateral in 15% of cases.
Metastases commonly in:
* contralateral ovary
* retroperitoneal nodes
* peritoneal cavity:
(associated with
decreased survival rate).
Exceptionally associated
with hypercalcemia
Extremely radiosenstive.
Dr Aksharaditya Shukla
11. DYSGERMINOMA
Often: large:
may be >1000g
encapsulated
Smooth, often convoluted surface
Cut surface
solid
gray
Cut surface of ovarian dysgerminoma.
The multinodular solid quality and the
tan color are characteristic features.
Foci of hemorrhage and
necrosis: not as common or
prominent as in other malignant
germ cell tumors.
Typical lobulated outer
aspect of ovarian
dysgerminoma
Dr Aksharaditya Shukla
12. Dysgerminoma
Diffuse insular or trabecular pattern.
Tumor cells: uniform
* nuclei: Central large
nucleoli:
- one or more
- prominent
* cytoplasm:
-abundant
- clear to finely
- contains:
+ glycogen
+ sometimes fine droplets of fat
* cell membrane prominent
fibrous strands infiltrated by lymphocytes
(most T-cell type5)
May be:
* focal necrosis
* hyaline changes in vessels
* germinal centers
* granulomatous fociDr Aksharaditya Shukla
13. Special Stains and Immunohistochemistry
of dysgerminoma
Tumor cells reactive for:
-PLAP
-CD117 (c-KIT)
Often keratin (erratically and focally)
Sometimes
-GFAP
-Desmin
Dr Aksharaditya Shukla
14. Yolk Sac Tumor
Malignant germ cell tumor of the ovary developed as a result of
differentiation of primitive malignant germ cell
elements in the direction of yolk sac or vitelline
structures.
Usually children and young adults:
* Median age 19 years
* ≈25% prepubertal at diagnosis
Vaginal bleeding in 1%
Serum AFP level invariably elevated
Chorionic gonadotropin levels normal.
Highly aggressive, and associated with other germ cell tumour
Dr Aksharaditya Shukla
15. Yolk Sac Tumor
Average diameter
15cm
External surface:
* smooth
* glistening
Cut surface:
* variegated
* partially cystic
* often large foci of
hemorrhage and
necrosis
Component of benign
cystic teratoma in
≈15% of cases
Gross appearance of yolk sac tumor. The cut surface is
remarkably heterogeneous due to extensive hemorrhage,
necrosis, and cystic degeneration
Dr Aksharaditya Shukla
16. YOLK SAC TUMOR
Many histologic variants occur,
including the reticular,
endodermal sinus (papillary),
polyvesicular–vitelline,
hepatoid, and glandular
patterns.
The endodermal sinus pattern
is the second most common
pattern(after reticular).
This pattern features
characteristic Schiller–
Duvall bodies (rounded
papillae containing a single
central vessel and lined by
columnar tumor cells) .
Dr Aksharaditya Shukla
17. YOLK SAC TUMOR
PAS-positive hyaline droplets
* intracytoplasmic and
extracellular
* nearly always present
High-power view of ovarian yolk
sac tumor. Numerous hyaline
globules are seen in the cytoplasm
of the tumor cells lining the
papillae
Dr Aksharaditya Shukla
18. Yolk Sac Tumor
Some show
differentiation
toward hepatic,
intestinal, and
parietal yolk sac
structures
Yolk sac tumor with
endometrioid features
Dr Aksharaditya Shukla
19. Special Stains and
Immunohistochemistry
Yolk sac tumor:
stains positive for : pankeratin
negative for : keratin 7:
(in contrast with endometrioid and clear cell ovarian ca)
stains positive for -WT-1:
( in contrast with serous ovarian carcinoma)
Hyaline droplets:
- usually stain for α-fetoprotein
- may also contain:
- α1-antitrypsin
- basement membrane components:
#type IV collagen
# laminin
Dr Aksharaditya Shukla
20. Embryonal carcinoma
Rare and the least differentiated of the ovarian germ cell
tumors.
Considered to be homologous to the embryonal carcinoma of
adult testis.
Young age group (median age 15 years):
47% prepubertal at diagnosis, 43% of whom present with
precocious puberty
Vaginal bleeding in 33%
Amenorrhea in 7%
Hirsutism in 7%
Serum α-fetoprotein levels often elevated
Chorionic gonadotropin levels invariably high:
results in consistently positive pregnancy tests
Dr Aksharaditya Shukla
21. Embryonal carcinoma
Median diameter
17cm.
External surface:
smooth and
glistening.
Cut surface:
predominantly
solid and
variegated.
extensive areas of
necrosis and
hemorrhage.
Gross appearance of embryonal
carcinoma of ovary.
Dr Aksharaditya Shukla
22. Embryonal carcinoma
Similar appearance to
embryonal carcinoma of
adult testis.
Solid sheets and nests of
large primitive cells:
occasionally forming
papillae and abortive
glandular structures.
Frequently
syncytiotrophoblast-like
tumor cells scattered
among smaller cells
Microscopic appearance of embryonal
carcinoma of ovary
Dr Aksharaditya Shukla
23. Special Stains and Immunohistochemistry of embryonal
carcinoma
Syncytiotrophoblast-like tumor cells
immunoreactive for hCG.
CD30 and cytokeratin
Dr Aksharaditya Shukla
24. Choriocarcinoma
Malignant tumor of the ovary with trophoblastic
differentiation composed of syncytiotrophoblast,
cytotrophoblast and intermediate trophoblast.
Exceedingly rare.
May be associated with mature cystic teratoma of
contralateral ovary.
Dr Aksharaditya Shukla
25. Choricarcinoma
Typical admixture of
syncytial and
cytotrophoblastic
elements in a
necrotic and
hemorrhagic
background
Choriocarcinoma arising in a
dermoid cyst
Dr Aksharaditya Shukla
26. Special Stains and Immunohistochemistry
Usually immunohistochemical reactivity
for hCG.
Keratin 7 said to represent a marker for
subset of trophoblastic cells.
LK26 (a folate-binding protein):
- consistently expressed
Dr Aksharaditya Shukla
27. References
ROSAI AND ACKERMAN`S SURGICAL PATHOLOGY
DIAGNOSTIC SURGICAL PATHOLOGY- STERNBERG
PATHOLOGIC BASIS OF DISEASE– ROBBINS AND
COTRAN
ANDERSON`S PATHOLOGY
CURRAN`S ATLAS OF PATHOLOGY
WWW.WEBPATH.COM
Dr Aksharaditya Shukla
28. Thanks
Presented By: Dr Aksharaditya Shukla
Resident, Department Of Patholgy
MGM Medical College & M.Y. Hospital, Indore
Dr Aksharaditya Shukla
29. OVARIAN TUMOURS II
Moderator: Dr Poonam Nanwani
Asst. Prof. Department Of Pathology
MGM Medical College & M.Y. Hospital, Indore
Dr Aksharaditya Shukla
31. Immature Malignant Teratoma
Malignant ovarian
germinal tumor composed
of mixture of immature
embryonal and mature
adult tissue derived from
all three germ layers.
Usually children and
adolescents.
May be:
* solid throughout
* solid with multiple
minute cysts
* predominantly cystic
Gross appearance of
ovarian immature
teratoma
Dr Aksharaditya Shukla
32. Immature teratoma
Mixture of embryonal and adult
tissues derived from all three
germ layers:
* any type of tissue
* main component usually
neuroepithelial
* mesodermal elements also
common
* sometimes predominantly
composed of endodermal
derivatives, including
-esophagus
- liver
-intestinal structures
This is immature teratoma containing
immature neuroepithelium forming
rosettes
immature teratoma
containing immature
neuroepithelium forming
rosettes.
Dr Aksharaditya Shukla
33. Grading system for immature teratoma
(Norris et al)
Grade I
a. Abundance of mature tissues
b. Loose mesenchymal tissue with
occasional mitoses
c. Immature cartilage
d. Tooth anlage
Grade II
a) Fewer mature tissues
b) Rare foci of neuroepithelium
with common mitoses not
exceeding three low-
magnification (×10) fields in any
one slide
Grade III
a) Few or no mature tissues
b) Numerous neuroepithelial
elements merging with a cellular
stroma occupying four or more
low-magnification fields
Dr Aksharaditya Shukla
34. Special Stains and Immunohistochemistry
Glial fibrillary acidic protein (GFAP):
- helpful in identification of mature and
immature glial tissue
- also detectable in chondrocytes
* Long-chain polysialic acid moiety of neural cell
adhesion molecule:
- another marker of immature and mature neural tissue
Dr Aksharaditya Shukla
35. Mature Cystic Teratoma
Cystic germ cell tumors
composed of multiple mature
elements derived from
ectoderm, mesoderm and
endoderm.
Almost 20% of all ovarian
neoplasms:
Most common ovarian tumor
in childhood
88% unilateral
usually benign
Symptoms:
* relate to mass
* occasionally:
- hemolytic anemia
- virilization
* May coexist with:
- mucinous
cystadenoma
- Brenner tumor
- * Usually benign
Dr Aksharaditya Shukla
36. Usually multiloculated
Cystic content:
greasy
largely composed of:
keratin
sebum
hairs
commonly teeth
(tend to be in well-defined
nipple-like structure covered
with hair (Rokitansky's
protuberance)
Admixture of sebum and hair within
the cavity of an ovarian mature cystic
teratoma
Dr Aksharaditya Shukla
37. Mature cystic teratoma
#Cystic cavities lined by
mature epidermis
Extremely common:
* skin appendages
* neural (particularly glial)
tissue
Also:
* cartilage
* respiratory tissue
* gastrointestinal tract tissue
(- may be peptic ulcer
formation)
Mature cystic teratoma of ovary:
gastric mucosa of pyloric type
Dr Aksharaditya Shukla
38. Germ cell tumors (continued)
Monodermal
teratoma
a) Thyroid tumour group
Struma ovarii –benign or
malignant
b) Carcinoid group
-insular
-trabecular
-mucinous
-strumal carcinoid
c) Neuroectodermal tumour group
-ependymoma
-primitive neuroectodermal
tumour
-glioblastoma multiforme
-medulloblastoma
d) Carcinoma
e) Melanocytic group
f) Sarcoma group
g) Sebaceous tumour group
Dr Aksharaditya Shukla
39. Struma Ovarii
Ovarian teratoma composed exclusively or predominantly of
thyroid tissue
May show any of the pathologic changes seen in a normally
placed gland, including:
diffuse or nodular hyperplasia:
- may lead to
hyperthyroidism
- thyroiditis
-carcinoma:
( sometimes resulting in metastases)
Thyroid nature fully documented with biologic and
immunohistochemical studies for thyroid hormones
Dr Aksharaditya Shukla
40. Struma Ovarii
Color and
consistency of
thyroid tissue, but
often cystic
Dr Aksharaditya Shukla
41. Struma Ovarii
Dominant growth
of thyroid tissue in
a teratoma,
sometimes to
exclusion of other
components
Struma ovarii. The thyroid tissue,
which has a microscopically
unremarkable appearance, is sharply
delimited from the ovarian stroma
Dr Aksharaditya Shukla
42. Carcinoid Tumor (monodedrmal teratoma)
Primary well differentiated neuroendocrine tumor of the
ovary.
Carcinoid syndrome:
* more likely the larger tumor ( > 7 cm)
Sometimes severe constipation:
* presumably due to secretion of peptide YY
Dr Aksharaditya Shukla
43. carcinoid
Usually unilateral
Mean diameter 10 cm
External surface:
* smooth or bosselated
* predominantly solid
* firm
* tan to yellow
Cut surface of carcinoid
tumor of ovary showing
typical solid
appearance and white
to yellowish color
Cut surface of carcinoid tumor of ovary
showing typical solid appearance and white
to yellowish color
Dr Aksharaditya Shukla
44. Carcinoid (monodermal teratoma)
insular pattern of
growth similar to in
appendix and small
bowel
-trabecular appearance
similar to in rectum
- mucinous (goblet cell)
appearance similar to
those seen primarily in
appendix
Primary ovarian carcinoid tumor with a
trabecular pattern of growth
Dr Aksharaditya Shukla
45. 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 CONDITION
8. LYMPHOID AND HEMATOPOETIC
TUMOURS
9. SECONDARY TUMOURS.
SEX CORD STROMAL TUMOURS
Dr Aksharaditya Shukla
46. Granulosa stromal cell tumours
Sertoli stromal cell tumours
Sex cord stromal tumours of mixed or
unclassified cell types.
Steroid cell tumours
SEX CORD STROMAL TUMOURS
Dr Aksharaditya Shukla
47. Granulosa stromal cell tumours
(SEX CORD STROMAL TUMOURS)
Granulosa cell
tumour group
a) Adult granulosa cell tumour.
b) Juvenile granulosa cell
tumour.
Thecoma fibroma
group
a) Thecoma (typical or
lutenised)
b) Fibroma
c) Cellular fibroma
d) Fibrosarcoma
e) Sclerosing stromal
tumours
f) Signet ring stromal tumour
g) Stromal tumour with minor
sex cord elements
h) Unclassified
Dr Aksharaditya Shukla
48. Granulosa Cell Tumor group
(sex cord stromal tumor)
Differentiation towards follicular granulosa cells that can
occur in adults (adult granulosa cell tumor) and in younger
patients (juvenile granulosa cell tumor).
Two distinct types:
* adult
* juvenile
Dr Aksharaditya Shukla
49. Adult Granulosa Cell Tumor
Usually childbearing age.
- 75% have hyperestrinism, which may result in:
+isosexual precocious puberty
+metrorrhagia in adults, including
postmenopausal women
Elevated serum inhibin and follicle regulatory proteins.
Dr Aksharaditya Shukla
50. AGCT
The tumors are usually large
(>10 cm) and unilateral.
The cut surface is soft and
yellow-tan with cysts and
hemorrhage.
encapsulated
smooth, lobulated outline
Cut surface:
-predominantly solid
May be:
cystic:
-filled with straw-colored
or mucoid fluid
-sometimes so prominent
as to simulat appearance
of a cystadenoma
Granulosa cell tumor with solid cut
surface.
Dr Aksharaditya Shukla
51. AGCT
Different histologic patterns
occur, including microfollicular,
macrofollicular, “watered-silk,”
gyriform, and diffuse.
However, all are composed of
round to oval granulosa cells
that have little cytoplasm and
round to angular nuclei with
longitudinal nuclear grooves
(coffee bean appearance)
There is minimal cytologic
atypia
Mitotic rate is low.
Dr Aksharaditya Shukla
53. The microfollicular
and diffuse
variants often
contain
characteristic
Call–Exner
bodies consisting
of a very small
collection of
eosinophilic
material lined by
well-differentiated
granulosa cells.
Dr Aksharaditya Shukla
54. Juvenile Granulosa Cell Tumor
More aggressive than adult
More likely to produce distant metastases
≈80% during first two decades
of life
* Usually presents with isosexual precocity
* Occasionally associated with:
- enchondromatosis (Ollier's disease)
- Maffucci's syndrome
Dr Aksharaditya Shukla
55. Juvenile Granulosa Cell
Tumor
Typical morphologic features
include:
diffuse or macrofollicular patterns
of growth (former
predominating)
- eosinophilic mucin-positive
intrafollicular secretion.
- larger tumor cells with
extensive luteinization
- paucity of nuclear grooves
- nuclear atypia
- variable but often high mitotic
activity.
On high power the tumor cells lack
the coffee-bean nuclei seen in the
adult type
The follicle-like spaces seen on low-power
examination are a common feature of this
neoplasm.
Dr Aksharaditya Shukla
56. Special Stains and Immunohistochemistry granulosa cell
tumors
Adult Granulosa Cell Tumor
* Immunohistochemically:
- steroid production:
+ by both theca and granulosa cells
with predominance of:
# estradiol in granulosa cell
# progesterone in luteinized theca
cells
- vimentin
- desmoplakin (desmosomal plaque
protein)
- inhibin (also JGCT)
follicle regulatory proteins
- CD99
keratin:
+ 33–50% of cases
+ typical dot-like distribution
+ mainly CK8 and CK18 types25,26
smooth muscle actin:
+ nearly all cases
S-100 protein: + ≈50% of cases
Strong immunoreactivity for inhibin in
granulosa cell tumor.
Dr Aksharaditya Shukla
57. Thecoma
Postmenopausal women.
Symptoms of hyperestrogenism.
Most are unilateral and can measure up to 10 cm in
diameter.
Immunohistochemically, the tumor is positive for
inhibin expression. Oil Red O fat stains (which
require fresh tissue) highlight the intracellular lipid.
Dr Aksharaditya Shukla
58. Thecoma
Cut surface of thecoma showing a predominance of
yellow areas alternating with whitish foci
Usually unilateral
Variable size
Well-defined capsule
Firm consistency
Cut surface:
* largely or entirely solid
* may be cysts
Yellow color
Dr Aksharaditya Shukla
59. THECOMA
Fascicles of spindle cells with:
centrally placed nuclei
moderate amount of pale
cytoplasm.
Only mild atypia and rare mitoses
Intervening tissue may show:
-considerable collagen
deposition.
- focal hyaline plaque
formation.
Degree of cellularity varies
considerably
Some in young women are
heavily calcified
Bland microscopic appearance of
thecoma, with some variability in
cellularity.
Dr Aksharaditya Shukla
60. Special Stains and Immunohistochemistry
Oil red O: (require fresh tissue)
- abundant intracytoplasmic neutral fat
Positive for inhibin expression
Silver stains:
Estradiol usually limited to a small number of tumor cell
Dr Aksharaditya Shukla
61. FIBROMA
The most common type of sex-cord stromal tumor developing
from specialized ovarian stroma.
Common
Usually unilateral
Almost invariably after puberty
Fibromas are not hormonally functional
average of 5 cm in diameter
Sometimes in young women with basal cell nevus (Gorlin's)
syndrome.
Benign
May be ascites:
especially if large
sometimes with right-sided pleural effusion (Meigs' syndrome)
(disappears on removal of tumor).
Dr Aksharaditya Shukla
62. Gross Pathology
Solid
Lobulated
Firm
Uniformly white
Usually no adhesions
Average diameter 6cm
May be myxoid changes,
sometimes resulting in cystic
degeneration
Cut surface of ovarian
fibroma.
Outer aspect of ovarian
fibroma
Dr Aksharaditya Shukla
63. FIBROMA
Spindle stromal cells:
- closely packed
- arranged in 'feather-stitched'
or storiform pattern
- no atypia and few mitoses
May be:
- hyaline bands
- edema
If in basal cell nevus (Gorlin's)
syndrome:
- calcified
- usually bilateral
- often multinodular
Cellular fibroma. The tumor is
hypercellular, but
pleomorphism and mitotic
activity are minimal
Dr Aksharaditya Shukla
65. Small Cell Carcinoma
Poorly differentiated tumors,
composed mostly of small
cells, and subclassified into
hypercalcemic and pulmonary
type
Two types:
* hypercalcemic:
-most common
* pulmonary
Hypercalcemic-type Small
Cell Carcinoma
Young females
(average age 23 years)
Nearly always bilateral
Occasionally familial
Hypercalcemia:
- 67% of cases
- disappears following
removal
* High-grade malignancy
Dr Aksharaditya Shukla
67. Hypercalcemic-type Small Cell Carcinoma
Diffuse proliferation of small, closely
packed cells of carcinomatous
appearance with:
- scant cytoplasm
- small nuclei
May be:
- clusters of larger and more
pleomorphic cells,
some resembling luteinized cells:
+ if a large number referred to as
large variant
of small cell carcinoma
- cytoplasmic hyaline globules
- islands
- cords
- mucinous glands
- follicle-like structures
+ important clue to diagnosis
Small cell carcinoma, hypercalcemic type.
The presence of follicle-like formations is an
important diagnostic feature
Dr Aksharaditya Shukla
68. Pulmonary-type Small Cell Carcinoma
Resembles homonymous
lung tumor.
May be pure or associated
with endometrioid
carcinoma or other
patterns.
Ultrastructurally:
- neurosecretory-type
granule
Dr Aksharaditya Shukla
69. Thanks
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.
Gross appearance of struma ovarii. The thyroid tissue is represented by the solid areas.
Struma ovarii. The thyroid tissue, which has a microscopically unremarkable appearance, is sharply delimited from the ovarian stroma