Pathology

Role of Histopathologic Minimum Data Sets in the Management of Gynaecological Cancers.

 

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.

References :

1. Creasman WT, Morrow CP, Bunday BN, Homesly HD, Graham JE, Heller PB: Surgical pathologic spread pattersn of endometrial cancer. A Gynecologic Oncology Group Study. Cancer 1987;60:2035-41

2. Cross SS, Feeley KM, Angel CA. The effect of four interventions on the informational content of histopathology reports of resected colorectal carcinomas. J Clin Pathol 1998; 51: 481-482.

3. Fanning J, Evans MC, Peters AJ, Samuel M, Harmon ER, Bates JS: Endometrial Adenocarcinoma histological subtypes: clinical and pathological profile. Gynecol Oncol 1989;32: 288-91

4. Jaques SM, Qureshi F, Munkarah A, Lawrence WD. Interinstitutional surgical pathology review in gynecologic oncology. II. Endometrial cancer in hysterectomy specimens. Int J Gynecol Pathol 1998;17:42-45

5. Kamura T, Tsukamoto N, Tsuruchi N, et al. Multivariate analysis of the histopathologic prognostic factors of the cervical cancer in patients undergoing radical hysterectomy Cancer 1992;69:181-6

6. Kempson RL, Hendrickson MR. Ovarian serous borderline tumors: the citadel defended. Hum Pathol. 2000;31:525

7. Morrow CP, Bundy BN, Kurman RJ et al. Relationship between surgical pathological risk factors and outcome in clinical stage I and II carcinoma of the endometrium: a Gynecologic Oncology Group Study. Gynecol Oncol 1991;40:55-65

8. Powell DE. Low malignant potential tumours of the ovary: Does microinvasion matter? Hum Pathol 1996; 27: 517-518.

9. Powsner SM, Costa J, Homer RJ: Clinicians are from Mars and Pathologists are from Venus: clinician interpretation of pathology reports. Arch Pathol Lab Med 124:1040-46, 2000

10. Roman LD, Morris M, Mitchell MF, Eifel PJ, Burke TW, Atkinson EN. Prognostic factors for patients undergoing simple hysterectomy in the presence of invasive cancers of the cervix. Gynecol Oncol 1993;50:179-84

11. Seidman JD, Kurman RJ. Ovarian serous borderline tumors: a critical review of the literature with emphasis on prognostic indicators. Hum Pathol. 2000;31:539-557.

12. Silverberg SG. Histopathologic grading of ovarian carcinoma: a review and proposal. Int J gynecol Pathol 2000;19:27.

13. Sivridis E, Buckley CH, Fox H. The prognostic significance of lymphatic vascular space invasion in endometrial Adenocarcinoma Br. J Obstet Gynaecol 1987;94:991-4

14. WHO classification of Tumours. Pathology and Genetics: Tumours of the Breast and Female Genital Organs. Editors- Tavassoli F A, Devilee Peter, IARC press, Lyon 2003.

 
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