brief overview of the ovarian neoplasm

1. An Overview Of Ovarian
Neoplasm
Dr. Gaurav Kumar
Dr. Sumaira Qayoom
KING GEORGES MEDICAL UNIVERSITY

2. Classification of ovarian neoplasm
• 4 major groups
1- Surface epithelial tumors
2- Sex cord - Stromal tumors
3- Germ cell tumors
4- Metastatic tumors

3. Surface epithelial tumors
• Serous tumor
• Mucinous tumor
• Seromucinous tumor
• Endometriod tumor
• Clear cell tumor
• Brenner tumor

4. Sex cord- stromal tumor
• Granulosa cell tumor
• Fibroma – Thecoma group tumor
• Sertoli - Leydig cell tumor
• Steroid cell tumor

5. Germ cell tumor
• Dysgerminoma
• Yolk sac tumor
• Embryonal tumor
• Choriocarcinoma
• Teratoma

6. Risk factors
• Patient characteristics
• Increasing age
• Family history of breast carcinoma
• Genetic factors
• BRCA 1/2 mutations
• HNPCC syndrome
• Environmental factors
• Obesity
• High fat diet

7. Contd..
• Reproductive factors
• Nulliparity
• Early menarche
• Late menopause
• Infertility
• Polycystic ovarian syndrome
• Endometriosis
• OCPs
• HRT

8. Tumor markers

9. Gross based approach of ovarian mass
Gross appearance Probable diagnosis
Smooth walled cyst with serous/mucinous
content
Serous/ Mucinous cystadenoma
Cyst with thick hemorrhagic content Endometriosis
Cyst with hair, teeth with pultaceous material Teratoma
Solid mass with surface nodularity carcinoma
Solid, fibrous with mucinous cyst Fibroma/thecoma
Bilateral solid multinodular ovaries Krukenberg tumor

10. Histomorphological approach
• Where is the tumor arising?
Central location -- think GCTs and SCST.
Surface of ovary -- think surface epithelial tumor.
If no surface is apparent... possibly obliterated by tumor.
• Spindle cell morphology?
Consider sex cord stromal tumors.
• Nests of cells?
Consider Brenner tumour.
• Gland-like structures?
Endometrioid carcinoma.
Granulosa cell tumour.

11. Surface epithelial tumors
• Classified into 6 types on the basis of cell
types
• Each types classified into 3 subtypes –
benign
borderline and
malignant

12. • Benign tumors
• Epithelium with benign nuclear features and
differentiated cytoplasm, No stratification
• No invasion
Benign tumors
adenofibromacystadenoma cystadenofibroma
cystic Cystic + solid
Atleast 25% solid
solid

13. • Borderline tumors
• Cytologic atypia
• No invasion
• Distinction between borderline and malignant
tumor is the presence of invasion in the
malignant

14. • Serous borderline tumor(SBOT) - Cystic serous
tumor with >10 % BOT architecture
• Serous cystadenoma with focal
proliferation(atypia) - Cystic serous tumor with
BOT fraction <10 %
• Microinvasive SBOT- ≥ 1 invasive foci is ≤5mm
foci in greatest dimension

15. Familial ovarian cancer syndrome
Hereditary breast & ovarian
cancer syndrome (HBOCS)
• High grade serous
carcinoma
• BRCA 1/2
Hereditary nonpolyposis colorectal
cancer syndrome (Lynch syndrome)
• Clear cell carcinoma
• Endometroid carcinoma

16. Serous tubular
intraepithelial carcinoma
Epithelial atypia in FT
Germline mutation in
BRCA1/2
No Germline mutation in
BRCA1/2
Normal FT
Detachment of FT
epithelium & lodged on
the surface

18. Serous tumors
• Benign
• Cystadenoma
• Adenofibroma
• Surface papilloma
• Borderline
• Serous BOT/ Atypical proliferating tumor
• SBOT, micropapillary type/ serous low grade carcinoma
• Malignant
• Serous low grade carcinoma
• Serous high grade carcinoma

19. Benign serous tumors

21. Borderline serous tumor

22. Histological criteria for serous
borderline tumor
• Epithelial hyperplasia in the form of
• Stratification
• Tufting
• Cribriform
• Micropapillary arrangements
• Atypia (mild to moderate)
• Detached cell clusters
• Minimal mitotic activity
• Absence of destructive stromal invasion

23. • Divided into 2 types
– Typical (90%)
• Classic branching
papillary architecture
• Epithelial tufts overlying
the papillae
– Micropapillary (10%)
• Diffuse proliferation of
tumor cells in elongated
thin micropapillae
• Length 5 times the width
• Arising directly from
papillae

24. Malignant serous tumor
• Nuclear atypia
• Mitotic activity
• Stratification
• Glandular complexity
• Papillary fronds
• Stromal invasion

25. • Stromal invasion can be
– Single cells or in compact nests
– Micropapillae and complex papillary fronds
– Inverted micropapillae
– Cribriform
– Glandular
– Solid
LOW GRADE vs HIGH GRADE
• Mild to moderate nuclear atypia (<3 fold variation
in size and shape)
• Mitosis – <12 /10 HPF

27. Low grade serous carcinoma High grade serous carcinoma

28. HGSC with slit like spaces
HGSC with gland formation
Pattern in HGSC
a. Papillary
b. Micropapillary
c. Slit like
d. Glandular
e. Microcystic
f. Transitional

29. Mucinous tumors
• Less common (20%)
• Bilateral 10-20%
• Predominantly benign and borderline
• Viscous mucoid material
• Epithelium- intestinal (goblet cells)

31. Mucinous cystadenoma Mucinous borderline tumor
Mucinous carcinoma

32. IHC
Serous tumor
• CK7/20 (+/-)
• WT1 +
• P16 +
• ER +
• p53 +
• PAX 8 +
Mucinous tumor
• CK7/20 (+/+ or -)
• p16 (v)
• ER (-/focal positive)
• CEA+
• Endocrine cells:
– Serotonin
– ACTH
– Gastrin
– somatostatin

33. Seromucinous tumor
• Previously considered as a variant of mucinous
tumor
• Also called endocervical type mucinous tumor
• Serous part- papillary architecture
• Mucinous part- tall non ciliated cells with
basally located nuclei and abundant mucin
• ARID1A mutation

34. Seromucinous borderline
tumor
With prominent edema in
stroma
Prominent
intracellular mucin

35. Endometroid tumor
• Benign
• Endometriosis cyst
• Endometroid cystadenoma
• Endometroid cystadenofibroma
• Borderline
• Endometroid borderline tumor
• Malignant
• Endometroid carcinoma

36. • 10%
• Grossly- cystic or solid
• Hemorrhagic> serous/mucinous
• Papillae- generally absent
• Microscopically- similar to endometroid
adenocarcinoma

37. Villoglandular pattern Villi and gland lined by endometroid epithelum

38. • Endometrial carcinoma
resembling sex cord
stromal tumor
– small and tubular
neoplastic glands
– Old aged patients
– Absence of endocrine
manifestations
– Foci of squamous
metaplasia
– Negativity for inhibin
50% of tumor – foci of squamous
metaplasia

39. Clear cell tumor
• <5%
• Cells have clear
cytoplasm, majority are
malignant
• a/w endometriosis &
endometrial CA
• Predominantly cystic
with solid
• Higher grade

40. High nuclear grade, hobnail pattern
Nuclei protrude into lumina
Clear Cytoplasm - Glycogen, mucin or fat
PAS + diastase resistance hyaline globules

41. Oxyphilic cytoplasm Stromal hyalinization

42. Brenner tumor
• Benign
• Brenner tumor
• Borderline
• Borderline brenner tumor/ atypical proliferating
brenner tumor
• Malignant
• Malignant brenner tumor

43. • Resembles transitional cell neoplasm of
urinary tract
• 1-2%
• ~50 yrs
• Sometimes sign of hyperestronism
(postmemopausal bleeding or endometrial
hyperplasia)
• Strong association with mucinous tumor

45. Malignant brenner Borderline brenner

47. Malignant mixed mullerian tumor
• Resembles grossly and microscopically resembles
in every respect of its uterine counterpart
• Homologous variety – nonspecific malignant
stroma
• Heterologous variety – malignant heterologous
elements
• Hyaline droplets containing alpha 1 Antitrypsin in
cytoplasm of tumor cells
• Also called carcinosarcoma

48. • Carcinomatous :
– Serous
– Endometroid
– Squamous
– Clear cell
• Sarcomatous:
– Chondrosarcoma
– Osteosarcoma
– Rhabdosarcoma

49. Germ cell tumor
• Origin: germ cell
• 15-20%
• Children & young adult
• Younger the patient, more likely the GCT is
malignant

51. Parameters Dysgerminoma Yolk sac tumor Embryonal
carcinoma
choriocarcinoma
Age Young, ~30 yrs Childern &
young adult ~19
yrs
Young , ~ 15 yrs Young to middle
age
Laterality Right, Bilateral
15%
U/L U/L U/L
Gross
cut surface
Solid & grey 15cm, smooth &
glistening
surface, partially
cystic
17cm, smooth &
glistening
surface, partially
cystic
Tan,
hemorrhagic
with necrosis
H/g & necrosis occasional predominant predominant predominant

52. Microscopy Dysgerminoma Yolk sac tumor Embryonal
carcinoma
choriocarcinoma
arrangement Well defined
nests, separated
by fibrous strand
Microcystic areas
l/b cuboidal cells
Solid sheets &
nests of large
primitive cells
Admixture of
cytotrophoblasts
and
syncytiotrophobl
asts
others • Prominent
nucleoli
• Clear
cytoplasm
• Infiltrated by
T
lymphocytes
• Schiller duval
bodies
• PAS + hyaline
globules
Can be arranged
in papillae,
Syncytiotrophobl
ast like cells
scattered in b/g
• Radiosensitiv
e
• a/w
hypercalcemi
a

53. Dysgerminoma

54. Yolk sac tumor

55. Embryonal carcinoma
Papillary pattern, sheets and nests of large primitive cells

56. Choriocarcinoma

57. SALL-4+
OCT-4
+
OCT 4 -
CD30+
PLAP+
SOX-2+
PLAP+
CD117+
βHCG +/-
Sox 2+AFP+
Glypican 3+
GATA-3+
Embryonal
Carcinoma
Dysgermin
oma
Immature
teratoma
Yolk sac
tumor
SALL-4 –
βHCG
GATA-3
Choriocarcino
ma

58. Immature malignant teratoma
• Malignant ovarian germinal tumor
• Mixture of embryonal & adult tissue (3 germ
layers)
• Main component – neuroepithelial
• Mesoderm also common

59. Grading
• Grade I: Benign
– rare foci of immature neuroepithelial tissue (<1LPF in
any slide)
• Grade II: Malignant
– Occasional foci of immature neuroepithelial tissue
with mitosis, (not exceeding 3 LPF in any slide)
• Grade III: Malignant
– Few / no mature tissue
– Numerous neuroepithelial elements merging with
stroma (4 or more LPF)

60. Mature cystic teratoma
• 20% of all ovarian neoplasm
• 88% unilateral
• Multiple mature elements
• Cystic: keratin, sebum, hairs
• Fetiform teratoma: resembling human organ
• Rokitansky’s protuberance: solid projection
from inner cystic wall (covered with hair)

61. • Ectodermal derivatives: 100%
• Mesodermal derivatives: 93%
• Endodermal derivatives: 71%
• May coexist with brenner tumor

62. Sex Cord stromal tumor
Parameter
s
Adult GCT Juvenile
GCT
Thecoma Fibroma Sertoli-
leydig cell
tumor
Steroid cell
tumor
Age Childbeari
ng
1st 2
decade
Menopaus
al group
After
puberty
Young Any age
A/w hyperestre
nism
Isosexual
precocity
Estrogenic
manifestati
on
Gorlin
syndrome
Meigs
syndrome
Androgen
excess,
reinke
crystalloid
Virlizing
syndrome
Gross Smooth
lobulated,
tan to
yellow
same Encapsulat
ed, solid,
YELLOW
color
Solid
lobulated
and white
Solid -
cystic
Yellow
IHC /
Special
stain
Oil red O,
FOXl2,
inhibin
vimentin Keratin,
SOX 9,
inhibin,
calretinin,
WT1
SF-1, Inhibin, calretinin
FOXL2, ER,PR

63. Parameters Adult GCT Juvenile
GCT
Thecoma Fibroma Sertoli-
leydig cell
tumor
Steroid cell
tumor
microscopy Grooving of
nuclei
No
grooving,
Large
tumor cells,
nuclear
atypia
Fascicles of
spindle
cells,
centrally
placed
nuclei, pale
pink
cytoplasm
Closely
packed
spindle
stromal
cells
Large
round cells,
eosinophili
c or
vacuolated
cytoplasm
pattern Microfollicu
lar,
macrofolllic
ular, solid
Diffuse,
macrofollic
ular
Storiform
pattern
Variant Cellular,
Mitotically
active
WD - tubules,
both sertoli
and leydig
cells
MD-
aggregates of
sertoli cells +
occ leydig
cells
PD-
sarcomatoid
Pure – no
leydig cells
Retiform-
coexist with
formation
resembling
rete of ovary
or testis
MEYER’S grading

64. Granulosa cell tumor
Adult granulosa cell tumor Juvenile granulosa cell tumor

65. Thecoma fibroma

66. Sertoli-leydig cell tumor
PD/ SarcomatoidWD

67. Steroid cell tumor

68. Primary and secondary ovarian tumors
• 7%
• 50% are bilateral
• Predominantly from Gastrointestinal tract
(stomach), colon, appendix, breast, uterus.
• Krukenberg tumor- usually B/L
Stomach (70%)
gross: solid multiodular enlargement
microscopic: signet ring cells

69. Primary ovarian mucinous tumor Mucinous tumors metastatic to ovary
Usually large (>15cm) Often small (<10cm)
U/L, multicystic with smooth capsule B/L, forming nodules with surface
A borderline component is present Borderline component absent
Growth is glandular and expansive Growth is infiltrative
Dirty necrosis (colorectal metastasis)
IHC Primary ovarian
adenocarcinoma
Metastatic
colorectal
carcinoma
CK7 Diffuse + +/-, focal
CK20 Usually negative
(except in mucinous
tumor)
Diffuse +
CDX2 variable Diffuse +
Diffuse CK7 and focal CK20 – ovarian primary
Focal CK7 and diffuse CK20 - colorectal primary

70. TNM staging
• pT1- limited to ovaries (one or both) or F.T(s)
pT1a: limited to one ovary (intact capsule) / FT
pT1b: limited to both ovaries (intact capsule)/ FT
pT1c: C1- surgical spill
C2- capsule ruptured before surgery or tumor on surface of ovary/ FT
C3- malignant cells in ascites/ peritoneal washing
• pT2- involving one or both ovary/FT with pelvic extension
pT2a: onto uterus/FT/Ovary
pT2b: onto other pelvic structure
• pT3: outside pelvic cavity
pT3a: microscopic extrapelvic peritoneal mets
pT3b: macroscopic peritoneal mets beyond pelvis (<2cm)
pT3c: macroscopic peritoneal mets beyond pelvis (>2cm)

71. • Regional Lymph Nodes (pN)
pN0: No regional lymph node metastasis
pN0(i+): Isolated tumor cells in regional lymph
node(s) no greater than 0.2 mm
pN1: Positive retroperitoneal lymph nodes only
(histologically confirmed)
pN1a: Metastasis up to and including 10 mm in
greatest dimension
pN1b: Metastasis more than 10 mm in greatest
dimension

72. Chemotherapy response criteria

73. References
• Rosai and Ackerman’s Surgical Pathology ,
11th Edition
• WHO classification of tumors of Breast and
Female Genital organ
• Meinhold-Heerlein, I., Fotopoulou, C., Harter,
P. et al. Arch Gynecol Obstet (2016) 293: 695.
https://doi.org/10.1007/s00404-016-4035-8

74. Question 1
True about brenner tumor ?
a) Contain squamous epithelium and adnexal
structures.
b) Contain fibrous tissue and transitional
epithelium.
c) May be associated with virilization
d) Most often are bilateral

75. 2- 40-year-old nulliparous woman with no
significant medical history presents with dyspnea
and abdominal distention for 1 month. The patient
has a right-sided hydrothorax, ascites, and a large
ovarian mass. Surgery is performed to remove the
ovarian mass, and the patient's ascites and pleural
effusion resolve promptly. What is the most likely
diagnosis?
a)Metastatic colon cancer
b)Metastatic lung cancer
c)Metastatic ovarian cancer
d)Meigs syndrome

76. Question 3
52-year-old patient
undergoes a biopsy of
the ovary, with the
results shown in
figure. Which of the
following additional
findings would you
most expect to see in
this patient?

77. a) Mature teratoma
b) Increased AFP level
c) Endometrial hyperplasia
d) Vaginal atrophy

78. Question 4
Sections from a solid-cystic uniliateral ovarian tumor in a
30-year old female show a tumor composed of diffuse
sheets of small cells with occasional nuclear grooving and
scant cytoplasm. No Call-Exner bodies are seen. The ideal
immunohistochemistry panel would include:
a) Vimentin, inhibin, CD45
b) Desmin, S-100, SMA, cytokeratin
c) Chromogranin, CD45, CD99
d) CD45, synaptophysin,

79. THANK YOU