Advances
in immunohistochemistry and molecular pathology have
improved our understanding of various cancers. However,
adopting different styles and formats in histopathology
reporting in common cancers can cause confusion. Powsner
et al reported that clinicians misinterpreted the
pathology reports in 30% of cases. This has led The
Royal College of Pathologists, UK, and The college
of American Pathologists (CAP), USA, to propose the
use of minimum datasets in histopathology reporting
in cancers of various organs. This is to ensure the
uniformity in the information given in the report,
which is required for the patient management, comparison
of the data for cancer registries and epidemiological
purposes. The need and use of such minimum datasets
in gynaecological cancers is considered. The discussion
is focused on reporting the epithelial malignancies
e.g. carcinoma of the endometrium, cervix and the
ovaries. As epithelial malignancy of the ovary is
more common, only a brief mention of germ cell tumours
of the ovary and sex – cord stromal tumour of
the ovary is made.
ENDOMETRIAL CARCINOMA
The careful reporting of hysterectomy specimens removed
for endometrial cancers is important. In addition
to staging, the histological indicators of poor prognosis
include high histological tumor grade, unfavorable
tumour subtype, lower uterine segment involvement
by tumour, deep myometrial invasion, and myometrial
vascular space invasion.
Architectural grading of endometrioid Adenocarcinoma
(FIGO) is as follows :-
Grade I - 5% or less of the tumour shows
non squamous solid growth pattern
Grade II - between 5 and 50% of the
tumour exhibits non-squamous solid growth pattern
Grade III - More than 50% of the
tumour shows a non-squamous solid growth pattern
It is important to avoid areas with squamous differentiation
and evaluate the glandular areas.
Nuclear grading is proposed as follows :-
Grade I - Oval / elongated nuclei,
fine chromatin, small nucleoli, few mitoses
Grade II - Features between grade
I and III
Grade III- Enlarged/pleomorphic nuclei,
coarse chromatin , prominent nucleoli, many mitoses
Note : In an endometrioid Adenocarcinoma,
overall grade of the tumour should be raised by one
grade if it shows higher grade nuclear features. Serous
carcinomas, clear cell carcinomas, squamous carcinomas,
mixed mullerian tumors and undifferentiated carcinomas
are not graded, and are considered grade III tumours.
(unfavourable tumour type). Serous papillary and clear
cell carcinomas have a higher incidence of extrauterine
disease. Mucinous Adenocarcinoma arising primarily
in the endometrium can also be similarly graded.
Assessment of myometrial invasion :
The uterus should be cut in parallel slices coronally.
Measure maximum depth of myometrial invasion, which
should be recorded as tumor invading less than half
or more than half of the myometrial thickness for
the purpose of staging. Minimum distance of the tumour
from the serosal surface in millimeters should preferably
also be recorded. The main problems in estimation
of myometrial invasion are irregularity of the endomyometrial
junction and extension of the tumour into superficial
adenomyosis.
Lymph node examination
Regional nodal involvement is the most important prognostic
factor in carcinomas clinically confined to uterus.
Number of nodes involved and presence of extranodal
invasion should be recorded. Micrometastasis (<2
mm) should be noted. If lymph nodes are included in
the specimen, it is recommended that a full cross
section of each node is embedded. Lymph node metastasis
can be anticipated in 10-25% of clinical stage I neoplasms.
CERVICAL CARCINOMAS
Careful reporting of Wertheim’s hysterectomy
specimen is important. In addition to stage, the following
features have been shown to be important prognostic
factors in stage I to II cervical cancers; Tumour
size, Depth of invasion related to overall wall thickness,
Vascular space invasion and status of surgical margins
(both in-situ and invasive carcinoma should be noted).
Histological typing
Histological typing is more significant for non squamous
histologies, like poorly differentiated adenocarcinomas
and small cell neuroendocrine carcinomas. Hence taking
adequate sections is important. Certain rare variants
of adenocarcinomas like villoglandular adenocarcinomas
and adenoid basal carcinomas have excellent prognosis.
The squamous carcinomas can be subtyped as keratinising,
non keratinising, verrucous, warty and lymphoepithelioma
like.
Histological Grading
Both squamous carcinomas and adenocarcinomas should
be graded using a three tier system (CAP guidelines).
However, the prognostic value of grading of squamous
carcinomas is not fully clear.
Microinvasive squamous carcinoma and adenocarcinoma
(FIGO I A1) is usually recognized in a cone biopsy
or a large loop excision biopsy specimen, (rather
than a punch biopsy) wherein the lesion is seen in
its entirety. Invasive lesions included in stage IA1
are 3 mm or less in depth measured from the base of
the epithelium and up to 7 mm in horizontal axis.
An invasive lesion measuring up to 7 mm in horizontal
axis and between 3.1 to 5 mm in depth is included
in stage IA2.
N.B. If invasive foci are seen in 3 or more blocks,
the third dimension of the lesion may exceed 7 mm.
Ovarian carcinoma
The FIGO (International Federation of Obstetrics and
Gynecology) staging system is based on the extent
of the involvement of ovaries, tubes, omentum and
peritoneum; and is the most important parameter for
determination of further management and prognosis.
This staging system is based on both macroscopic and
microscopic assessment; hence adequacy of the sampling
of the tumour is crucial.
Indicators of poorer prognosis in ovarian carcinoma
are- Extra ovarian spread and omental involvement
(essential parameters of staging). Histologic distinction
of epithelial and non-epithelial tumors is crucial,
since in general, epithelial tumors have a less favorable
outcome than stromal tumors. There is some merit in
grading the epithelial tumours, since in patients
with invasive ovarian cancer, well-differentiated
ones have better prognosis than poorly differentiated
tumors stage for stage, especially in early stage
carcinoma.
The category of ‘borderline ovarian tumours’
is maintained in the current WHO classification. Borderline
tumours should be diagnosed after a rigorous exclusion
of destructive stromal invasion. Micropapillary pattern
when present should be separately identified. Mucinous
tumors require thorough sampling of the specimen,
especially the solid areas, ideally no less than 1
section per cm of maximum tumour diameter. Women with
borderline tumors (low malignant potential) have an
excellent prognosis even with extra-ovarian disease.
Borderline category is used in serous, mucinous, endometrioid,
and less often in clear cell and Brenner tumors. Ovarian
surface involvement as well as parenchymal invasion
should be commented upon.
Each tissue sent as an implant should be processed
and evaluated carefully for the stromal invasion.
The status of implant [invasive or non-invasive] should
be clearly mentioned.
The
appendix is usually removed in the context of a mucinous
tumour. It is important that the nature of the appendicial
involvement e.g. mucosal or serosal is recorded in
this situation.
Sex cord stromal tumours
They form about 8% of ovalian heoplasms. They can
be functional (oestrogenic drive to endometrium in
thecomas, granulosa cell tumours); virilisation in
Sertoli-Leydig Cell tumour. Prognosis relates to size
(more than or less than 5 cm size), most importantly
to stage of the disease and also atypia, mitoses and
bilaterality.
Germ cell tumours of ovary
A heterogeneous group of tumours reflecting the capacity
of multiple lines of differentiation of the main stem
cell system.
They account for approximately 30% of primary ovarian
tumours, 95% of which are mature cystic teratomas.
The remaining are malignant. Malignant germ cell tumours
commonly occur in children and adolescent females.
60% present with stage I disease (5 yr survival 90%)
with a five yr survival rate of 70-80% of all stages
of disease. Serum b HCG and AFP levels are useful
in postoperative monitoring and postoperative chemotherapy
is used for tumours other than stage I, grade I immature
teratoma.
General Recommendation
1) The histopathologist should be an integral part
of the multidisciplinary team.
2) Histopathologists reporting cancers should participate
in external quality assurance (EQA) scheme.
3) SNOMED coding system should be used (either 1979
or 1993)
4) The Royal College of Pathologists recommends use
of proformas for reporting cancers. Although, this
point is debatable, published audits have shown that
they are very effective in other cancers.
A detailed account and proformas are available at
www.rcpath.org/publications and www.cap.org.
Audit
An audit of the histopathology reports of endometrial,
cervical and ovarian carcinoma will be presented.
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