Case of the Month

1
Case of the Month

• Dr Emma Sheldon
• Consultant Histopathologist
• Mid Staffordshire NHS Foundation Trust

2
Clinical Details

• 46 year old female
• Glandular abnormality initially reported on
  cervical smear
• Previous cone biopsy showed high grade CGIN
  extending to endocervical resection margin.

3
Macro

• Uterine corpus with attached cervix 85 x 45 x
  35mm with separate ovaries and fallopian tubes
  one ovary measured 35x20x15mm with attached
  fallopian tube 55mm in length and the second
  ovary measured 35x23x16mm with attached fallopian
  tube 40mm in length.
• Endometrium 3mm, myometrium 16mm.

4
Cervix
5
Cervix
6
Cervix
7
Cervix
8
Cervix
9
Cervix
10
Cervix
11
Cervix
12
Cervix
13
Cervix
14
Cervix
15
Cervix
16
Cervix (PASD)
17
Cervix (PASD)
18
Cervix (PASD)
19

• Cervix showed extensive high grade CGIN
  (intestinal type) with some areas showing
  expansion of glands, cribriform glands and
  extension along the lower uterine segment (but
  not into myometrium) in keeping with subtle
  invasion
• Also well-defined more obvious focus of invasive
  adenocarcinoma composed of small narrow cords of
  cells containing PAS-positive diastase-resistant
  mucin

20
Ovary
21
Ovary
22
Ovary
23
Ovary
24
Ovary
25
Ovary
26
Ovary
27
Ovary
28
Ovary
29
Ovary
30
Ovary
31
Ovary
32
Ovary (PASD)
33

• Both ovaries contained multiple cystic tubules
  lined by atypical columnar epithelium with
  crowded hyperchromatic nuclei and goblet cells
• More concentrated on the surface of the ovaries
  as nodular collections, with overlying adhesions

34
CK7

• Cervix ()

• Ovary ()

35
CK20

• Cervix (focal )

• Ovary (focal )

36
CEA

• Cervix ()

• Ovary ()

37
CA-125

• Cervix ()

• Ovary ()

38
Oestrogen receptor

• Cervix (-)

• Ovary (-)

39
Vimentin

• Cervix (-)

• Ovary (-)

40
p16
Ovary
Cervix
41
CDX-2
Cervix
Ovary
42
Diagnosis

• Invasive endocervical adenocarcinoma with
  background high grade CGIN and bilateral ovarian
  metastases

43
Key Message

• Endocervical adenocarcinomas, including
  microinvasive forms and some not recognizably
  invasive, have the potential to metastasize to
  the ovaries extension into the lower uterine
  segment/corpus endometrium may be a risk factor,
  with retrograde uterine/transtubal spread as a
  possible mechanism

44
Discussion

• Majority endocervical adenocarcinomas are
  HPV-related
• Difficulty in recognising subtle patterns of
  invasion within extensive high grade CGIN (and
  therefore in measuring the invasive component)

45

• Ability of some minimally invasive
  adenocarcinomas to metastasize to ovaries BUT
  often misinterpreted representing primary ovarian
  mucinous/endometrioid borderline tumours or
  carcinomas

46

• Minimally invasive endocervical adenocarcinomas
  and those in which definite invasion cannot be
  recognized have the ability to metastasize (NB
  lower uterine segment/corpus extension of tumour
  may be a risk factor for ovarian metastases, with
  retrograde uterine/transtubal spread as a
  possible mechanism)

47

• Difficulty recognising an ovarian neoplasm
  representing a metastasis as may have smooth
  capsule and lack destructive stromal invasion
  therefore mimicking a borderline tumour
• More typical indicators of ovarian metastases are
  bilaterality, smaller size, cortical involvement,
  nodularity and infiltrative growth

48

• HPV DNA detection (in situ hybridization and PCR)
  may be useful, as if both the cervical and
  ovarian tumours contain the same HPV type is
  evidence that the ovarian tumour represents a
  metastasis from the cervical adenocarcinoma
  rather than representing a separate primary
  tumour

49

• IHC Use of p16, ER and PR may be useful as most
  endocervical adenocarcinomas
• are p16ER-/PR-
• HOWEVER rarely higher grade primary ovarian
  tumours and metastatic carcinomas unrelated to
  high risk HPV may also exhibit diffuse/strong p16
  expression

50
References

• Endocervical Adenocarcinomas with Ovarian
  Metastases Analysis of 29 cases with emphasis on
  minimally invasive cervical tumours and the
  ability of the metastasis to simulate primary
  ovarian neoplasms
• B M. Ronnett, A Yemelyanova, R Vang, B Gilks, D
  Miller, P Gravitt and R Kurman
• AM J Surg Pathol 2008321835-1853)