Guidelines for reporting histopathology of cervical carcinoma Naveena Singh, Consultant Pathologist
Introduction Cancer management is multidisciplinary Histopathology report has a MAJOR impact on management Main determinant of treatment and prognosis is STAGE Cervical cancer is clinically staged Preclinical cancers are entirely within the remit of the pathological report Parameters other than stage also influence management
Introduction Treatment options: Surgery Lymphadenectomy Radiotherapy Chemoradiation Sentinel node sampling Intensity-modulated RT Intrarterial NAC followed by surgery Choice of treatment Appropriate for stage Fertility LIMIT treatment complications 16 14 12 10 8 6 4 2 0 Symptomatic Screen detected
Treatment of cervical cancer Approaches FIGO Ia1 Cone biopsy (LLETZ) Simple hysterectomy FIGO Ia1 with LVSI Radical Hysterectomy/Radical trachelectomy with PLND FIGO Ia2: Radical Hysterectomy/Radical trachelectomy with PLND Brachytherapy +/- external beam pelvic radiation therapy American Cancer Society, 2012
Treatment of cervical cancer Approaches FIGO Ib1 Radical Hysterectomy/Radical trachelectomy with PLND and PALND; +/- adjuvant RT or chemort Brachytherapy +/- external beam pelvic radiation therapy FIGO Ib2 Radical chemoradiotherapy +/- surgery Radical Hysterectomy/Radical trachelectomy with PLND and PALND; +/- adjuvant RT or chemort if node +ve FIGO II+ Radical chemoradiotherapy American Cancer Society, 2012
Treatment of cervical cancer Change in approach in recent years Radical chemoradiotherapy is becoming the treatment of choice of all stages over Ia2 Surgery first choice in specific settings for fertility conservation (trachelectomy) As two stage procedure in node negative cases; no adverse prognostic features Radical hysterectomy has become a rare specimen!
Reporting specimens for cervical cancer Cancer specimens should be reported in standard format RCPath datasets list core macroscopic and microscopic items In cervix cancer these are different for excision and radical surgical specimens
90% by April 2014
Reporting specimens for cervical cancer: Excision specimens CORE MACROSCOPIC ITEMS: Type of specimen Measurements of each piece
Reporting specimens for cervical cancer: Excision specimens CORE MICROSCOPIC ITEMS Invasive malignancy: Type Differentiation/grade Distribution of invasive component: Unifocal/Multifocal Tumour size Maximum thickness/depth of invasion Presence of invasive foci present in 3/more sequential tissue slices of tissue
Reporting specimens for cervical cancer: Excision specimens Excision status: Incomplete/ Complete/Not assessable If complete excision, distance to closest resection margin in mm Specify margin: ectocervical/endocervical/deep radial Other features: Presence and grade of CIN/CGIN/SMILE Excision of intraepithelial neoplasia Lymphovascular space invasion
Reporting specimens for cervical cancer: Excision specimens Cone biopsy Pin out to fix Slice in neat parallel slices Embed all ONE SLICE PER CASSETTE!
Reporting specimens for cervical cancer: Excision specimens Cone biopsy, alternative method Slice proximal portion in neat parallel transverse slices Distal either radially or bread slices ONE SLICE PER CASSETTE!
Reporting specimens for cervical cancer: Excision specimens CORE MICROSCOPIC ITEMS Invasive malignancy: Type Differentiation/grade Distribution of invasive component: Unifocal/Multifocal Tumour size Maximum thickness/depth of invasion Presence of invasive foci present in 3/more sequential tissue slices of tissue Excision status: Incomplete/ Complete/Not assessable If complete excision, distance to closest resection margin in mm Specify margin: ectocervical/endocervical/deep radial Other features: Presence and grade of CIN/CGIN/SMILE Excision of intraepithelial neoplasia Lymphovascular space invasion
Reporting specimens for cervical cancer: Recognising stromal invasion Can be subtle Not all features seen in every case: Absence or loss of sharply-defined basement membrane Small, angulated buds of atypical squamous epithelial cells Arise from surface epithelium with CIN3, or from gland crypts Single or multiple Continuous with the dysplastic epithelium or detached. Hypermature appearance, typically with more abundant eosinophilic cytoplasm Nuclei are pleomorphic, may contain nucleoli or exhibit altered nuclear polarity. May show dyskeratosis
Reporting specimens for cervical cancer: Recognising stromal invasion Stromal reaction: inflammatory, oedematous, desmoplastic, rarely absent Loss of the orderly basal epithelial palisade in the atypical epithelial buds. Different patterns of stromal invasion: spray bud pattern, which comprises tiny nests of hypermature squamous cells confluent pattern invasive tongues Clinical outcome is strongly influenced by the depth of invasion but not by the pattern of invasion
Cyclin D1 Epithelial mesenchymal transition: Phenotypic and functional change in Ca cells Mesenchymal ch tics: loss of cohesiveness, stromal invasion, resistance to anoikis, intravasation, intravascular survival, low proliferation IHC: Loss of E-cadherin and beta-catenin Acquisition of vimentin Cyclin D1 expression
Reporting specimens for cervical cancer: Tumour type Squamous carcinoma Adenosquamous carcinoma Adenocarcinoma Neuroendocrine carcinoma Other, specify
Reporting specimens for cervical cancer: Tumour type WHO Classification: Squamous tumours and precursors Squamous carcinoma, not otherwise specified Keratinizing Non-keratinizing Basaloid Verrucous Warty Papillary Lymphoepithelioma-like Squamotransitional Early invasive (microinvasive) squamous cell carcinoma: THE USE OF THESE TERMS IS NOT RECOMMENDED Squamous intraepithelial neoplasia Poorly differentiated tumours Absent intercellular bridges and keratinisation, many mucin producing cells = adenoca p63 is useful to confirm squamous diffn Exclude Neuroendocrine ca
Reporting specimens for cervical cancer: Tumour type WHO classification: Glandular tumours and precursors Adenocarcinoma Mucinous adenocarcinoma Endocervical type Intestinal Signet-ring cell Minimal deviation Villoglandular Endometrioid adenocarcinoma Clear cell adenocarcinoma Serous adenocarcinoma Mesonephric adenocarcinoma Early invasive adenocarcinoma: NOT RECOMMENDED WITHOUT STAGE Adenocarcinoma in situ
Reporting specimens for cervical cancer: Tumour type WHO Classification: Other epithelial tumours Adenosquamous carcinoma Glassy cell carcinoma variant Adenoid cystic carcinoma Adenoid basal carcinoma Neuroendocrine tumours Carcinoid tumour Atypical carcinoid Small cell carcinoma Large cell neuroendocrine carcinoma Undifferentiated carcinoma
Reporting specimens for cervical cancer: Tumour differentiation/grade Well/Grade 1 Moderate/Grade 2 Poor/Grade 3 Not assessable/gx very early lesions N/A neuroendocrine carcinomas SCC: Controversial prognostic factor in cervical carcinoma Variety of grading systems Grading systems using multiple parameters show more consistent correlation with behaviour: Stendahl system or invasive front grading Modified Broders used most universally Base on keratinisation, cytonuclear atypia and mitotic activity AdenoCa: No agreed system, nuclear grade most appropriate
Reporting specimens for cervical cancer: Distribution of invasive component: Unifocal/Multifocal HPV has potential to produce field change More than one focus of neoplastic transformation may arise Multifocal stromal invasion can be detected in up to 12% of carcinomas Important not to overstage multiple FIGO stage IA1 or IA2 tumours as FIGO stage IB
Reporting specimens for cervical cancer: Distribution of invasive component: Unifocal/Multifocal Multifocal disease: foci separated by blocks of uninvolved cervical tissue (cut levels!) foci on separate cervical lips foci situated far apart from each other in the same section. Individual foci may be attached to, or discontinuous from, the epithelium Each focus of invasion is measured separately Staging based on dimensions of largest focus
Reporting specimens for cervical cancer: Distribution of invasive component: Unifocal/Multifocal Report should: state clearly that the tumour is multifocal provide dimensions of each of the separate foci indicate how the FIGO stage has been ascertained Such cases should to be referred to cancer centres for review, and should be discussed at the MDM
Reporting specimens for cervical cancer: Tumour dimensions Two dimensions are required for FIGO stage: depth and maximum width Depth of invasion: Taken from the base of the epithelium (surface or glandular) from which the carcinoma arises If no obvious epithelial origin, from the tumour base (the deepest focus of tumour invasion) to the base of the nearest surface epithelium
Reporting specimens for cervical cancer: Tumour depth
Reporting specimens for cervical cancer: Tumour width Horizontal spread/width/lateral extent of unifocal tumours; tumour present in less than 3 blocks: Use the section with the greatest tumour width Measure from one lateral edge of the tumour to the other Measurement of width is not limited to the confluent component of the tumour
Reporting specimens for cervical cancer: Tumour width
Reporting specimens for cervical cancer: Tumour width Width of unifocal tumours; tumour present in 3 or more blocks: may exceed 7 mm in its third dimension, i.e. the carcinoma may be more than FIGO stage IA2 third dimension determined by: block thickness x number of contiguous blocks showing invasion
Reporting specimens for cervical cancer: Other microscopic core items: Excision Excision status: assessable Incomplete/ Complete/Not If complete excision, distance to closest excision margin in mm Specify margin: ectocervical/endocervical/deep radial
Reporting specimens for cervical cancer: Tumour differentiation/grade Presence and grade of CIN/CGIN/SMILE Excision of intraepithelial neoplasia Lymphovascular space invasion
Reporting specimens for cervical cancer: Radical hysterectomy specimens: CORE MACROSCOPIC ITEMS Vaginal cuff: presence and dimensions Dimensions of uterus Adnexa: presence and normal/abnormal Tumour: Present or not Maximum dimensions of tumour (mm) Position Macroscopic involvement of vagina Macroscopic involvement of parametrial/paracervical tissues
Reporting specimens for cervical cancer: Radical hysterectomy
Reporting specimens for cervical cancer: Radical hysterectomy
Reporting specimens for cervical cancer: Radical hysterectomy: CORE MICROSCOPIC ITEMS Type Differentiation/grade Tumour size: Maximum horizontal dimension Thickness/depth of invasion Minimum thickness of uninvolved cervical stroma (minimum tumour-free rim) Position of minimum tumour-free rim Closest radial resection margin (include paracervical tissue) Position of closest radial resection margin Vaginal involvement Distance from distal vaginal margin, position Paracervical involvement Parametrial involvement Lymphovascular invasion CIN/CGIN/SMILE
Reporting specimens for cervical cancer: Radical hysterectomy Minimum thickness of uninvolved cervical stroma (minimum tumour-free rim) Position of minimum tumour-free rim Closest radial resection margin (include paracervical tissue) Position of closest radial resection margin Vaginal involvement Distance from distal vaginal margin, position Paracervical involvement Parametrial involvement
Slice proximal portion in neat parallel transverse slices Slice distal portion including vaginal cuff radially
Reporting specimens for cervical cancer: Radical trachelectomy uterus vagina
Reporting specimens for cervical cancer: Radical trachelectomy
Reporting specimens for cervical cancer: Radical trachelectomy
Reporting specimens for cervical cancer: Radical trachelectomy
Reporting specimens for cervical cancer: Radical trachelectomy
Reporting specimens for cervical cancer: Lymphadenectomy Pelvic nodes: (obturator, internal, external and common iliac nodes) Positive/Negative/Not sampled Left/Right: Total number of nodes Number of positive nodes Extranodal spread: Yes No Para-aortic nodes: Positive/Negative/Not sampled Total number of nodes Number of positive nodes Extranodal spread: Yes No
Reporting specimens for cervical cancer: Lymphadenectomy Sample each node group separately (or as received) LN >5mm can be bisected or sliced perpendicular to longest axis LN< 5mm embed whole One node per cassette as far as possible or indicate clearly how many are embedded
Reporting specimens for cervical cancer Thank you Questions?