This document contains an academic review of a patient case involving a 51-year-old woman with abdominal pain and distention, decreased urine output, and weight loss. Clinical findings revealed a mass in the right iliac region. Radiological findings from ultrasound and CT scan showed cystic masses in both ovaries suspicious for malignancy. The patient underwent staging laparotomy and chemotherapy. Pathological examination of surgical specimens found high grade papillary serous cystadenocarcinoma of both ovaries with tumor deposits in the omentum and one fallopian tube. Ovarian cyst fluid was also positive for malignant cells. The case report discusses the histopathological findings and staging of ovarian cancer.

1. ACADEMIC REVIEW
By
Dr. Varughese George
29/08/2017

2. Case History
Present history
51 year old lady (P3L2A1) presented with history of
• abdominal pain and distention for 15 days.
• decreased urine output for 3 months.
• loss of weight for 6 months.
Past history
• Generalised itching and is on regular medications since Dec
2016.
• Underwent LSCS 23 years ago, not sterilised.
• Last child birth was 18 years ago.
• Attained menopause 11/2 years ago.

3. Clinical Findings
On examination,
P/A
• Soft, tense, tenderness present in right iliac fossa, lumbar and
suprapubic region.
• A mass of size 6 x 8 cm with irregular borders is palpable in
the right iliac region extending to the suprapubic region.
• The mass is
– tender on palpation
– soft to hard in consistency
– not mobile (fixed)

4. Clinical Findings
P/S
• Cervix - stuck to the anterior vaginal wall.
P/V
• Uterus - anteverted, bulky and mobile.
• Anterior right lateral fornical fullness present
• Tenderness present
• Other fornices are free.

5. Radiological Findings
USG Abdomen
• Pelvis - Multiloculated cyst of size 12.1 x 9.1 cm arising from the
right ovary.
• Right kidney - Mild hydronephrosis.
• Advised
• CA 125 – 605 U/ml (0-35 U/ml)
• CT Abdomen.
CT Abdomen
• Large multiseptated cystic masses in both ovaries with mild
omental and mesenteric stranding noted on both sides –
? malignant mass lesions.
• Suggested clinical and histopathology correlation.

6. Treatment Plan
• Patient underwent staging laparotomy under
spinal and epidural anesthesia.
• This was followed by six cycles of
chemotherapy (cisplatin and paclitenel) three
weeks apart.

7. PAP Smear Report
• Non-specific Inflammatory smear.
• Negative for Intraepithelial Lesion/Malignancy.

8. Gross Examination
• Received uterus and cervix with
attached bilateral adnexa.
• The uterus and cervix measures
9x5x4cm.
• The external surface of the uterus
is unremarkable.
• The external surface of the cervix
is hypertrophied and everted.
• The cut section of the uterus and
cervix shows
– endocervical canal measuring
2.5cm
– endometrial canal measuring
4.5cm
– endometrial thickness
measuring 0.6cm.

9. Gross Examination
• One of the attached ovary is partially
cystic measuring 11x7x2.5cm.
• The external surface is bosselated
with capsular breach measuring 4cm
with multiple papillary excrescences
and areas of congestion.
• On cut section,
– 3ml of mucinous fluid was
exuded.
– shows multiloculated cyst
measuring 6.5x6cm and solid
areas measuring 3.8x3cm.
– The solid areas shows grey white
areas with papillary excrescences.
– The cyst wall thickness varies
from 0.5 to 1cm.
• The attached tube measures 3cm in
length. On cut section, the lumen is
identified.
One of the attached ovary

10. Gross Examination
The other attached ovary
• The other attached ovary
measures 7.5x7.0x1.8cm.
• The external surface is congested
with multiple papillary
excrescences and capsular breach
measuring 1cm.
• On cut section, 2ml of mucinous
fluid was exuded.
• shows predominantly cystic area
and partially solid areas
alltogether measuring 7 x 4.5cm
with multiloculations and
papillary excrescences.
• The cyst wall thickness varies from
0.2 to 0.4cm with focal areas of
calcification.
• The attached tube measures 2cm.
On cut section, the lumen is
identified.

11. Gross Examination
• Also received container labelled omentum.
• Received two grey yellow fibrofatty tissue masses,
the largest measuring 15x8x2cm and the smallest
measuring 7.5x3.5x0.5cm.
• The cut section of the largest fibrofatty tissue mass
shows grey white areas measuring 14.5 x 3 cm.

12. Microscopical Examination
• Section studied from both lips of cervix show
features of chronic papillary endocervicitis.
• Sections studied from the corpus –
– Endometrium - Proliferative phase.
– Myometrium – Adenomyosis
– (H&E,x4)

13. Microscopical Examination
(H&E, x4) (H&E, x4)
Papillary
fashion
Nuclear
stratificatonMicropapillary
pattern

14. Microscopical Examination
(H&E, x10)
Fibrovascular
stalk

15. Microscopical Examination
(H&E, x10)
Fibrovascular Stalk
Papillary branching with
nuclear stratification

16. Microscopical Examination
Complex branching
(H&E, x4)

17. Microscopical Examination
Stromal Invasion
(H&E, x10)

18. Microscopical Examination
(H&E, x40)
Mitotic figures
Vesicular nucleus
Hyperchromatic nucleus

19. Microscopical Examination
(H&E, x40) (H&E, x40)

20. Microscopical Examination
(H&E, x4) (H&E, x4)
Calcification
Areas of
necrosis

21. Microscopical Examination
(H&E, x4) (H&E, x4)
Tumor
Emboli
Tumor
Emboli

22. Microscopical Examination
(H&E, x4) (H&E,x4)

23. Microscopical Examination
(H&E, x4)
Capsular Invasion

24. Microscopical Examination
Tumor deposits on the wall of the Fallopian tubes
(H&E, x4)
Tumor deposits

25. Microscopical Examination
(H&E, x10)
Psamomma
bodies

26. Microscopical Examination
Tumor deposits in the omentum
(H&E, x4) (H&E, x4)

27. Microscopical Examination
• Sections studied from both the ovarian masses show
cystic areas lined by tumor cells projecting into the
lumen in form of complex branching papillae with
central fibrovascular core having hierarchical pattern
lined by columnar cells with nuclear stratification and
vesicular nuclei.
• Large areas of hemorrhage and necrosis are seen.
• The wall of the cyst shows invasion by solid nests and
sheets of tumor cells having scanty to moderate
eosinophilic cytoplasm, enlarged vesicular nuclei with
pleomorphism. There are 12-15 mitoses/hpf.
• Focal areas with micropapillae formation, calcification
and psammoma bodies are seen.

28. Microscopical Examination
• Tumor emboli is present.
• Section studied from foci of capsular breach of both
ovaries show tumor deposits and invasion of capsule.
• Section studied from one side Fallopian tube shows
dense lymphocytic infiltration, few psammoma bodies
are seen in the sub-mucosa.
• Section studied from other side Fallopian tube is
unremarkable.
• Section from omentum shows deposits of tumor cells
arranged in the form of solid nests, complex papillae
with central fibrovascular core.

29. IMPRESSION
• High Grade Papillary Serous Cystadenocarcinoma
of Bilateral Ovaries with Capsular Breach and
Invasive Epithelial Implants in the Omentum.
• One of the Fallopian tubes shows foci of
calcification in the sub-mucosa.
• pT1C
• Score II ( Universal Grading System)
• Cervix - Chronic papillary endocervicitis.
• Corpus – Endometrium - Proliferative phase.
Myometrium - Adenomyosis.

30. Physical Examination of Ovarian Cyst Fluid
Received ovarian cyst fluid.
Volume – 3 ml
Blood mixed fluid
No coagulum was seen

31. Microscopical Examination of Ovarian Cyst
Fluid
(H&E, x4) (H&E, x4)
scattered and tightly
cohesive three-
dimensional clusters
of pleomorphic cells
Tightly cohesive
three- dimensional
clusters of
pleomorphic cells

32. Microscopical Examination of Ovarian Cyst
Fluid
(H&E, x10)
A tightly cohesive three-
dimensional cluster of
pleomorphic cells

33. Microscopical Examination of Ovarian Cyst
Fluid
(H&E, x40) (H&E, x40)
hyperchromatic nucleus

34. Microscopic Examination
• Highly cellular smear showed scattered and
tightly cohesive three- dimensional clusters of
pleomorphic cells having
– hyperchromatic nucleus
– high nuclear to cytoplasm ratio
– few having irregular nuclear membrane in a
background of inflammatory cells and
hemorrhage.

35. IMPRESSION
Ovarian cyst fluid was positive for malignant
cells

36. DISCUSSION

37. 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.

38. 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

40. WHO Histologic 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

41. 1. Serous tumours
2. Mucinous tumours
3. Endometroid tumours including variants of
squamous differentiation
4. Clear cell tumours
5. Transitional tumours
6. Squamous cell tumours
7. Mixed epithelial tumours
8. Undifferentiated and unclassified tumours.
SURFACE EPITHELIAL TUMOURS

43. • ¼ of all ovarian tumors
• Adults
• 30-50% bilateral
• 60% benign,15% borderline,25%
malignant
• Papillary formation present
• M/E: cuboidal to columnar cells
lining wall of cysts and papillae
• Psammoma bodies 30%
Serous tumors

44.  BENIGN
a) Cystadenoma
b) Papillary cystadenoma
c) Surface papilloma
d) Adenofibroma and
cystadenofibroma
 BORDERLINE
a) Papillary cystic tumour
b) Surface papillary tumour.
c) Cystadenofibroma
 MALIGNANT
a) Adenocarcinoma
b) Surface papillary carcinoma
c) Adenocarcinofibroma
SURFACE EPITHELIAL TUMOURS
(SEROUS TUMORS)

45. • Cystic masses usually
unilocular, containg
clear but sometimes
viscid fluid
• Multiloculated smooth
glistening cyst wall with
no epithelial thickening
or papillary
Serous cystadenoma- gross

46. Serous cystadenoma
• Cuboidal to columnar cells
are seen lining wall of the
cysts and papillae in better
differentiated tumors.

47. • Borderline serous cystadenoma
• Age:20-50yrs
• Bilaterality-
30%
• Prognosis-
100% 5yr
survival
• GROSS-
increased
papillary
projections
within cyst

48. Borderline serous tumor.
• Entirely increased
complexity of stromal
papilla with stratification
and nuclear atypia.
• But there is no infiltrative
growth into the stroma.

49. • Epithelial
stratification
(2-3 layers).
• ↑ complexity of
stromal papillae.
• No stromal invasion

50. Serous Cystadenocarcinoma
• Age:40-70 yr
• Bilaterality-~66%
• Marker- CK7
• Prognosis-70%
5 yr survival
• GROSS-
- irregular tumour
mass
- ↑ solid/ papillary
- necrosis/
haemorrhage

51. • Complex papillary
architecture.
• Malignant cells in
glandular pattern.
• Nuclear atypia.
• High mitotic activity.
• Stratification.
• Stromal invasion
Serous Cystadenocarcinoma

52. Papillary serous cystadenocarcinoma
of the ovary
. Microscopic features include stratification of low columnar epithelium lining
the inner surface of the cyst and a few psammoma bodies. The stroma shows invasion by
clusters of anaplastic tumour cells.

53. • Papillomatous outer
surface of the ovary.
• Minimal enlargement of
the ovary.
Serous surface papillary carcinoma

54. Serous surface papillary carcinoma
• There is hardly any
infiltration of the
stroma.
• Mostly bilateral,
highly aggressive,
with peritoneal
spread at the time of
surgery.

55. Serous psammocarcinoma
• A rare form of serous
adenocarcinoma.
• Involve ovarian surface
• Massive psammoma body
formation.
• Low grade cytologic features.
• Abundant psammoma bodies in
at least 75% of the papillae.

56. Stage I (FIGO 2014)
Stage I Growth limited to ovaries
IA T1a N0 M0 Growth limited to one ovary; no tumour on the
external surface, capsule intact, no ascites
IB T1b N0 M0 Growth limited to both ovaries; no tumour on the
external surface, capsule intact, no ascites
IC T1c N0 M0 Tumor limited to one or both ovaries
IC1 Surgical spill
IC2 Capsule rupture before surgery
or tumor on ovarian surface
IC3 Malignant cells in the ascites
or peritoneal washings

57. Stage II (FIGO 2014)
Stage II Tumor involves 1 or both ovaries with pelvic
extension (below the pelvic brim) or primary
peritoneal cancer
IIA T2A N0 M0 Extension and/or implant on uterus and/or
Fallopian tubes
IIB T2B N0 M0 Extension to other pelvic intraperitoneal tissues

58. Stage III (FIGO, 2014)

59. Stage III Tumor involves 1 or both ovaries or fallopian tubes, or
primary peritoneal cancer, with cytologically or histologically
confirmed spread to the peritoneum outside the pelvis and/or
metastasis to the retroperitoneal lymph nodes
IIIB T3B N0/1 M0 Macroscopic peritoneal metastasis beyond the pelvis up to
2 cm in greatest dimension, with or without metastasis to the
retroperitoneal lymph nodes
IIIC T3C N0/1 M0 IIIC: Macroscopic peritoneal metastasis beyond the pelvis
more than 2 cm in greatest dimension, with or without
metastasis to the retroperitoneal lymph nodes (includes
extension of tumor to capsule of liver and spleen without
parenchymal involvement of either organ)
IIIA Positive retroperitoneal lymph nodes
and/or microscopic metastasis beyond the pelvis
IIIA1 T1/2 N1 M0 Positive retroperitoneal lymph nodes only (cytologically
or histologically proven):
IIIA1 (i)
IIIA1 (ii)
Metastasis up to 10 mm in greatest dimension
Metastasis more than 10 mm in greatest dimension
IIIA2 T3A N0/1 M0 Microscopic extrapelvic (above the pelvic brim) peritoneal
involvement with or without positive retroperitoneal
lymph nodes

60. Stage IV (FIGO, 2014)
Stage IV T any N any M1 Distant metastasis excluding peritoneal
metastases
IVA Pleural effusion with positive cytology
IVB Parenchymal metastases and metastases
to extra-abdominal organs (including
inguinal lymph nodes and lymph nodes
outside of the abdominal cavity)

61. Grading Systems
Minal, J., et al., Grading ovarian serous carcinoma using a two tier system: Does it have prognostic significance? International Journal of Biomedical and Advance
Research, 2015. 6(3): p. 269-274.

62. Immunohistochemistry of serous tumors
keratin profile
• CK 7+/ CK20-
• Also CK8, CK18, CK19, EMA, S100
• WT-1 stains diffusely most serous carcinomas

63. Ovarian implants
• Deposits of ovarian tumours on peritoneal surface.
• Entire peritoneum may contain tumour nodules<1 cm.
• Seen in 1/3 patients with serous borderline and malignant
tumours.
• Affect prognosis.
• Unencapsulated serous tumors of the ovarian surface are more
likely to extend to the peritoneal surfaces

64. Ovarian Implants
Benign implants:
• Tumor deposits formed by glandular and tubular
structures lined with benign-appearing epithelium
without the presence of endometrial stromal cells
surrounding the glandular structures of psammoma
bodies is not rare in this type of lesion.
• Benign implants are found in 22% of patients with LMP
serous tumors.
• This type of implant should be staged and treated as
stage I lesion.

65. Ovarian Implants
Non-invasive Implants:
• These implants are defined as tumor deposits with
histologic characteristics similar to those found in low
malignant potential tumors but without invasion of the
surrounding stroma and often with a subserosa
location.
• In these cases, it is believed that they are formed from
invaginations of mesothelial cells.
• Occasionally, they are intracystic.
• This type of implant is found in 37% of patients with
LMP serous tumors.

66. Ovarian Implants
Invasive Implants :
• This type of implant is found in 13% of patients with
LMP serous tumors.
• Tumor deposits similar to noninvasive implants, but
with invasion of the desmoplastic stroma by individual
tumor cells are defined as invasive. The margins of the
invasive implants are poorly demarcated.
• The invasive tumor resembles a well-differentiated
invasive serous adenocarcinoma.
• The desmoplastic stroma displays loose fibrous
connective tissue with an inflammatory response.

67. Invasive Implants :
• Implants from LMP serous tumors are found (from the
highest to the lowest frequency) pelvic peritoneum,
omentum, uterus, fallopian tubes, colon, appendix,
abdominal peritoneum, small intestine, periaortic
lymph nodes, liver capsule, and diaphragm.
• Patients with invasive implants have a less favorable
prognosis.
• More than one type of implant may be found in the
same patient

68. References
• Rosai and Ackerman's Surgical Pathology 10th Edition
• Fundamentals of Surgical Pathology 1st Edition
• Minal, J., et al., Grading ovarian serous carcinoma using a two tier system:
Does it have prognostic significance? International Journal of Biomedical
and Advance Research, 2015. 6(3): p. 269-274.
• Prat J, FIGO Committee on Gynecologic Oncology FIGO’s staging
classification for cancer of the ovary, fallopian tube, and peritoneum:
abridged republication. J Gynecol Oncol (2015) 26(2):87–9

69. THANK YOU