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OVARIAN TUMORS-II
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.
Dr Aksharaditya Shukla
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
Dr Aksharaditya Shukla
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
 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
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
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
Dr Aksharaditya Shukla
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
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
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
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
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
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
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
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
Yolk Sac Tumor
 Some show
differentiation
toward hepatic,
intestinal, and
parietal yolk sac
structures
 Yolk sac tumor with
endometrioid features
Dr Aksharaditya Shukla
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
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
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
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
Special Stains and Immunohistochemistry of embryonal
carcinoma
 Syncytiotrophoblast-like tumor cells
immunoreactive for hCG.
 CD30 and cytokeratin
Dr Aksharaditya Shukla
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
Choricarcinoma
 Typical admixture of
syncytial and
cytotrophoblastic
elements in a
necrotic and
hemorrhagic
background
 Choriocarcinoma arising in a
dermoid cyst
Dr Aksharaditya Shukla
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
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
Thanks
 Presented By: Dr Aksharaditya Shukla
Resident, Department Of Patholgy
MGM Medical College & M.Y. Hospital, Indore
Dr Aksharaditya Shukla
OVARIAN TUMOURS II
 Moderator: Dr Poonam Nanwani
Asst. Prof. Department Of Pathology
MGM Medical College & M.Y. Hospital, Indore
Dr Aksharaditya Shukla
Dr Aksharaditya Shukla
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
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
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
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
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
 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
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
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
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
Struma Ovarii
 Color and
consistency of
thyroid tissue, but
often cystic
Dr Aksharaditya Shukla
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
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
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
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
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
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
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
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
 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
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
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
Coffee-bean( longitudnally grooved) nuclei in adult type
of ovarian granulosa cell tumor
Dr Aksharaditya Shukla
 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
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
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
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
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
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
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
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
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
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
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
Immunohistochemistry of Fibromas
 diffusely positive for vimentin
Dr Aksharaditya Shukla
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
Gross Pathology
 Hypercalcemic-type
Small Cell Carcinoma
 Large and solid
 Areas of necrosis and
hemorrhage
Dr Aksharaditya Shukla
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
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
Thanks
 Presented By: Dr Aksharaditya Shukla
Resident, Department Of Patholgy
MGM Medical College & M.Y. Hospital, Indore
Dr Aksharaditya Shukla

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Ovary slide share 2

  • 1. OVARIAN TUMORS-II Dr Aksharaditya Shukla Resident, Department Of Pathology MGM Medical College & M.Y. Hospital, Indore
  • 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
  • 52. Coffee-bean( longitudnally grooved) nuclei in adult type of ovarian granulosa cell tumor 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
  • 64. Immunohistochemistry of Fibromas  diffusely positive for vimentin 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
  • 66. Gross Pathology  Hypercalcemic-type Small Cell Carcinoma  Large and solid  Areas of necrosis and hemorrhage 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

  1. Ocps, salphingooprectomy pregnancy before 25 yrs are associated with decreased risk. abdominal enlargement, pressure on adjacent organs.
  2. Gross appearance of struma ovarii. The thyroid tissue is represented by the solid areas.
  3. Struma ovarii. The thyroid tissue, which has a microscopically unremarkable appearance, is sharply delimited from the ovarian stroma