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OVARIAN TUMORS-III
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
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
Sertoli stromal cell tumors
Sertoli leydig cell
tumour group
(androblastoma).
a) well differentiated
b) intermediate
differentiation
c) poorly differentiated
(sarcomatoid)
d) retiform
 2. Sertoli cell tumour.
 3. Stromal leydig cell
tumour
Dr Aksharaditya Shukla
Sertoli leydig cell tumor
 Young patients (average 25 years)
 50% shows signs of androgen excess i.e
defeminisation
(breast atrophy, loss of subcutaneous Fat)
 Later masculinisation appears
Dr Aksharaditya Shukla
Sertoli leydig cell tumor
 Mixture of variable
proportions of cells
morphologically
resembling male sertoli
and leydig cells.
 0.1% of ovarian neoplasms.
 Grossly predominantly
solid.
 Variegated appearance of
cut surface of ovarian
Sertoli–Leydig cell tumor.
Dr Aksharaditya Shukla
Microscopic pattern
 Well differentiated
(meyer’s type I)
Tubules lined by
sertoli like cells
seperated by
variable number of
leydig like cells
 Well-differentiated
(Meyer’s type I) Sertoli–Leydig cell
tumor.
Dr Aksharaditya Shukla
Microscopic patterns of SLCT
 Intermediate
(meyer’s type II)
Formation of cords,
sheets sertoli like
cells seperated by
spindle stromal cells
Dr Aksharaditya Shukla
Microscopic patterns of SLCT
 Poorly
differentiared
(meyer’s type III)
Composed of
masses of spindle
shaped cells
arranged in
“sacomatoid”
pattern
Dr Aksharaditya Shukla
Special Stains and Immunohistochemistry of
SLCT
 Testosterone and estradiol both in sertoli and
leydig cells
 Areas of sertoli cell differentiation are Keratin+
 Gonadal stromal components- inhibin+
Dr Aksharaditya Shukla
Sex Cord Tumor with Annular Tubules
(Sex cord stromal tumours of mixed or unclassified cell types )
 A distinctive variant of sex
cord stromal-tumor with
features of Sertoli and
granulosa cell
differentiation, divided in
two subsets including those
associated with Peutz-
Jeghers syndrome and those
without such association
 33% associated with Peutz–
Jeghers syndrome
 Symptoms suggestive of
hyperestrinism in ≈50%
 Gross Pathology
 If associated with Peutz–
Jeghers syndrome typically:
- multifocal
- bilateral
- small (or even
microscopic)
- calcified
- benign
 * If unassociated with Peutz–
Jeghers syndrome:
- unilateral
- often large
- ≈22% of cases clinically
malignantDr Aksharaditya Shukla
Sex cord tumor with
annular tubules
 Combines:
- features suggestive
of granulosa cell
tumor
- pattern of growth
reminiscent
sertoli cells
 Simple and complex
annular tubules
containing eosinophilic
hyaline bodies, often
calcified.
- morphologic
hallmark
 Sex cord tumor with annular tubules. The
patient had Peutz–Jeghers syndrome
Dr Aksharaditya Shukla
Steroid cell tumor
(Sertoli stromal cell tumors)
 Syn. Lipid, lipoid cell tumor
 Heterogeneous group of
tumors composed entirely of
cells with morphologic
features indicative of steroid
hormone secretion.
 Any age
 Most associated with a
virilizing syndrome
(defeminization and
amenorrhea)
 Sometimes:
- Cushing's syndrome
-associated with
endometrioid carcinoma
Dr Aksharaditya Shukla
Gross Pathology
 Usually unilateral
 Composed of yellow or
yellowish brown nodules
separated by fibrous
trabeculae
 Malignant tumors tend to:
- be larger (≥06cm in
diameter)
- have foci of necrosis and
hemorrhage
 Cut surface of ovarian lipid cell
tumor.
Dr Aksharaditya Shukla
Steroid cell tumor
 Masses of large rounded or
polyhedral cells
 Composed entirely of cells with
features indicative of steroid
hormone secretion:
 cytoplasm:
+ abundant
+ eosinophilic
+ may be vacuolated
+ often positive for fat
stains
 Malignant tumors tend to
exhibit:
- nuclear atypia
- mitotic activity
Dr Aksharaditya Shukla
Special Stains and Immunohistochemistry
 * Immunohistochemically:
- reactivity for:
+ vimentin in 75%
+ keratin in 50%
+ actin in ≈33%8
 consistent reactivity for:
- inhibin
- A103
- Mart-1
Dr Aksharaditya Shukla
GERM CELL SEX CORD STROMAL
TUMOURS
a) Gonadoblastoma
b) Mixed germ cell sex cord stromal tumour
Dr Aksharaditya Shukla
Gonadoblastoma
 Tumor composed of a combination of germ cells and sex-cord cells that
arises almost exclusively in dysgenetic gonads.
 Usually sexually abnormal:
 commonly gonadal dysgenesis and carrying Y chromosome, i.e.:
- XY gonadal dysgenesis
- XO–XY mosaicism
- but not XX gonadal dysgenesis1
 estimated 25% risk of neoplasia in these dysgenetic gonads
 Also documented in:
* phenotypically and chromosomally normal females, even during
pregnancy
* ataxia–telangiectasia
Dr Aksharaditya Shukla
Gross Pathology
 Usually small
 Often impossible to
determine nature of gonad
bearing tumor:
- sometimes identified as:
+ a streak(many become
apparent only on
microscopic examination)
+ cryptorchid testis
 Never a normal ovary
 * ≈36% bilateral
 Streak gonad microscopically shown to
contain gonadoblastoma. The tumor
was barely apparent grossly.
Dr Aksharaditya Shukla
Gonadoblastoma
 Admixture of:
 primitive germ cells:
 resembling those of
dysgerminoma
 sex cord–stromal cells:
 resembling
morphologically and
immunohistochemical
ly immature Sertoli
and granulosa cells
 Commonly:
 hyalinization:
 when abundant may
be obvious on plain
abdominal radiograph
 calcification
 Ovarian gonadoblastoma. Note the sharply outlined
tumor nests and the heavy calcification
Dr Aksharaditya Shukla
Special Stains and Immunohistochemistry
 Hyaline material reacts strongly with anti-laminin
antibodies,
Dr Aksharaditya Shukla
Metastatic tumors
 Malignant secondary tumors
involving ovaries originated in
other organs.
 * ≈7% of lesions presenting as
primary ovarian tumors are
metastatic
* >50% bilateral
* Most common sources:
- stomach
- large bowel
- appendix
- breast
- uterus (corpus and cervix)
- lung
- skin (melanoma)
 Metastases From Breast Carcinoma
* Immunoreactive for GCDFP-15:
- important in differential diagnosis
with primary ovarian carcinoma, which
is generally negativeDr Aksharaditya Shukla
Metastases From Adenocarcinoma of Large Bowel
Dr Aksharaditya Shukla
Krukenberg Tumors
 Usually:
* >40 years of age
* bilateral
* metastatic origin
 Usual primary sources:
* stomach:
- diffuse gastric carcinoma (linitis plastica) used to be most
common
* large bowel, Appendix, Breast
 May be:
* retroperitoneal lymph node metastases
* peritoneal implants
Dr Aksharaditya Shukla
Gross Pathology
 Krukenberg Tumor
 Moderate solid
multinodular
enlargement of the
ovaries.
 Typical gross appearance of
Krukenberg tumors of ovary. The
involvement is bilateral and the
tumors are characterized by a
multinodular outer appearance
Dr Aksharaditya Shukla
Krukenberg Tumor
 * Diffuse infiltration by signet
ring cells
- signet ring cells.
* Tumor emboli >50% of cases
Krukenberg tumor of ovary.
Presence of intracellular
mucin
Dr Aksharaditya Shukla
 Features favoring primary
ovarian tumor:
* expansile (pushing)
pattern of invasion
* complex papillary
architecture
* size over 10cm
* smooth external surface
* benign- and borderline-
appearing foci
 Ovarian metastases tend to
be:
* cystic
* well differentiated
* mucin-producing
* associated with necrosis
and hemorrhage
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

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Ovarian Tumor Classification

  • 1. OVARIAN TUMORS-III 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. 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
  • 9. Sertoli stromal cell tumors Sertoli leydig cell tumour group (androblastoma). a) well differentiated b) intermediate differentiation c) poorly differentiated (sarcomatoid) d) retiform  2. Sertoli cell tumour.  3. Stromal leydig cell tumour Dr Aksharaditya Shukla
  • 10. Sertoli leydig cell tumor  Young patients (average 25 years)  50% shows signs of androgen excess i.e defeminisation (breast atrophy, loss of subcutaneous Fat)  Later masculinisation appears Dr Aksharaditya Shukla
  • 11. Sertoli leydig cell tumor  Mixture of variable proportions of cells morphologically resembling male sertoli and leydig cells.  0.1% of ovarian neoplasms.  Grossly predominantly solid.  Variegated appearance of cut surface of ovarian Sertoli–Leydig cell tumor. Dr Aksharaditya Shukla
  • 12. Microscopic pattern  Well differentiated (meyer’s type I) Tubules lined by sertoli like cells seperated by variable number of leydig like cells  Well-differentiated (Meyer’s type I) Sertoli–Leydig cell tumor. Dr Aksharaditya Shukla
  • 13. Microscopic patterns of SLCT  Intermediate (meyer’s type II) Formation of cords, sheets sertoli like cells seperated by spindle stromal cells Dr Aksharaditya Shukla
  • 14. Microscopic patterns of SLCT  Poorly differentiared (meyer’s type III) Composed of masses of spindle shaped cells arranged in “sacomatoid” pattern Dr Aksharaditya Shukla
  • 15. Special Stains and Immunohistochemistry of SLCT  Testosterone and estradiol both in sertoli and leydig cells  Areas of sertoli cell differentiation are Keratin+  Gonadal stromal components- inhibin+ Dr Aksharaditya Shukla
  • 16. Sex Cord Tumor with Annular Tubules (Sex cord stromal tumours of mixed or unclassified cell types )  A distinctive variant of sex cord stromal-tumor with features of Sertoli and granulosa cell differentiation, divided in two subsets including those associated with Peutz- Jeghers syndrome and those without such association  33% associated with Peutz– Jeghers syndrome  Symptoms suggestive of hyperestrinism in ≈50%  Gross Pathology  If associated with Peutz– Jeghers syndrome typically: - multifocal - bilateral - small (or even microscopic) - calcified - benign  * If unassociated with Peutz– Jeghers syndrome: - unilateral - often large - ≈22% of cases clinically malignantDr Aksharaditya Shukla
  • 17. Sex cord tumor with annular tubules  Combines: - features suggestive of granulosa cell tumor - pattern of growth reminiscent sertoli cells  Simple and complex annular tubules containing eosinophilic hyaline bodies, often calcified. - morphologic hallmark  Sex cord tumor with annular tubules. The patient had Peutz–Jeghers syndrome Dr Aksharaditya Shukla
  • 18. Steroid cell tumor (Sertoli stromal cell tumors)  Syn. Lipid, lipoid cell tumor  Heterogeneous group of tumors composed entirely of cells with morphologic features indicative of steroid hormone secretion.  Any age  Most associated with a virilizing syndrome (defeminization and amenorrhea)  Sometimes: - Cushing's syndrome -associated with endometrioid carcinoma Dr Aksharaditya Shukla
  • 19. Gross Pathology  Usually unilateral  Composed of yellow or yellowish brown nodules separated by fibrous trabeculae  Malignant tumors tend to: - be larger (≥06cm in diameter) - have foci of necrosis and hemorrhage  Cut surface of ovarian lipid cell tumor. Dr Aksharaditya Shukla
  • 20. Steroid cell tumor  Masses of large rounded or polyhedral cells  Composed entirely of cells with features indicative of steroid hormone secretion:  cytoplasm: + abundant + eosinophilic + may be vacuolated + often positive for fat stains  Malignant tumors tend to exhibit: - nuclear atypia - mitotic activity Dr Aksharaditya Shukla
  • 21. Special Stains and Immunohistochemistry  * Immunohistochemically: - reactivity for: + vimentin in 75% + keratin in 50% + actin in ≈33%8  consistent reactivity for: - inhibin - A103 - Mart-1 Dr Aksharaditya Shukla
  • 22. GERM CELL SEX CORD STROMAL TUMOURS a) Gonadoblastoma b) Mixed germ cell sex cord stromal tumour Dr Aksharaditya Shukla
  • 23. Gonadoblastoma  Tumor composed of a combination of germ cells and sex-cord cells that arises almost exclusively in dysgenetic gonads.  Usually sexually abnormal:  commonly gonadal dysgenesis and carrying Y chromosome, i.e.: - XY gonadal dysgenesis - XO–XY mosaicism - but not XX gonadal dysgenesis1  estimated 25% risk of neoplasia in these dysgenetic gonads  Also documented in: * phenotypically and chromosomally normal females, even during pregnancy * ataxia–telangiectasia Dr Aksharaditya Shukla
  • 24. Gross Pathology  Usually small  Often impossible to determine nature of gonad bearing tumor: - sometimes identified as: + a streak(many become apparent only on microscopic examination) + cryptorchid testis  Never a normal ovary  * ≈36% bilateral  Streak gonad microscopically shown to contain gonadoblastoma. The tumor was barely apparent grossly. Dr Aksharaditya Shukla
  • 25. Gonadoblastoma  Admixture of:  primitive germ cells:  resembling those of dysgerminoma  sex cord–stromal cells:  resembling morphologically and immunohistochemical ly immature Sertoli and granulosa cells  Commonly:  hyalinization:  when abundant may be obvious on plain abdominal radiograph  calcification  Ovarian gonadoblastoma. Note the sharply outlined tumor nests and the heavy calcification Dr Aksharaditya Shukla
  • 26. Special Stains and Immunohistochemistry  Hyaline material reacts strongly with anti-laminin antibodies, Dr Aksharaditya Shukla
  • 27. Metastatic tumors  Malignant secondary tumors involving ovaries originated in other organs.  * ≈7% of lesions presenting as primary ovarian tumors are metastatic * >50% bilateral * Most common sources: - stomach - large bowel - appendix - breast - uterus (corpus and cervix) - lung - skin (melanoma)  Metastases From Breast Carcinoma * Immunoreactive for GCDFP-15: - important in differential diagnosis with primary ovarian carcinoma, which is generally negativeDr Aksharaditya Shukla
  • 28. Metastases From Adenocarcinoma of Large Bowel Dr Aksharaditya Shukla
  • 29. Krukenberg Tumors  Usually: * >40 years of age * bilateral * metastatic origin  Usual primary sources: * stomach: - diffuse gastric carcinoma (linitis plastica) used to be most common * large bowel, Appendix, Breast  May be: * retroperitoneal lymph node metastases * peritoneal implants Dr Aksharaditya Shukla
  • 30. Gross Pathology  Krukenberg Tumor  Moderate solid multinodular enlargement of the ovaries.  Typical gross appearance of Krukenberg tumors of ovary. The involvement is bilateral and the tumors are characterized by a multinodular outer appearance Dr Aksharaditya Shukla
  • 31. Krukenberg Tumor  * Diffuse infiltration by signet ring cells - signet ring cells. * Tumor emboli >50% of cases Krukenberg tumor of ovary. Presence of intracellular mucin Dr Aksharaditya Shukla
  • 32.  Features favoring primary ovarian tumor: * expansile (pushing) pattern of invasion * complex papillary architecture * size over 10cm * smooth external surface * benign- and borderline- appearing foci  Ovarian metastases tend to be: * cystic * well differentiated * mucin-producing * associated with necrosis and hemorrhage Dr Aksharaditya Shukla
  • 33. 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
  • 34. 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.