Datasets and clinical staging Dr J Stevenson Consultant Cellular Pathologist St Helens & Knowsley Teaching Hospitals
Outline
Principles of cancer staging
Different staging systems in use
Examples of staging of specific cancers
TNM staging system
Cancer staging system Developed and maintained by UICC (International Union Against Cancer) The TNM system is an expression of the anatomic extent of disease and is based on the assessment of 3 components
T- extent of primary tumour N- lymph node M- distant metastases
Latest edition - 8th edition (TNM 7 may still be in use)
TNM staging system
T: size or direct extent of the primary tumuor Tx – cannot assess primary tumour T0 - no signs of tumour Tis- Carcinoma in-situ T1 to T4- depend on size or extent of primary tumour
TNM staging system
Prefix used: c- clinical staging; e.g. cT3 p- pathological staging on resection specimen y- neoadjuvant chemotherapy r- recurrent tumour after disease free interval a –classification determined at autopsy
TNM staging system
Other prognostic parameters Grade of tumour – G1-3 Completeness of resection
Rx- residual tumour cannot be assessed R0- no residual tumour at margins R1- microscopic residual tumour R2-macroscopic residual tumour
Lymphovascular invasion L- lymphatic invasion V- venous invasion
Other organisations
AJCC (American Joint Committee on Cancer) Skin cancer staging in the UK (although now UICC TNM 8) FIGO (International Federation of Gynaecology and Obstetrics) Gynaecological tumours Ann Arbor Staging Lymphoma International Staging System for Neuroblastoma (INSS) and International Neuroblastoma Risk Group (INRG) Neuroblastoma
EMQ Choose from the options below:
FIGO AJCC 8th edition UICC TNM 8th edition UICC ypT3N0M0 pT2N0M0 pT0N0M0 cT3N0M0
EMQ
System used for staging of endometrial tumour Organisation that develops TNM staging Staging system used for Melanoma staging currently in the UK Colorectal tumour which had received neoadjuvant therapy and on resection infiltrates beyond muscularis propria without lymph node involvement or metastases In MDT, the stage used before resection of breast carcinoma clinically measuring 55mm
EMQ
System used for staging of endometrial tumour
Organisation that develops TNM staging
FIGO UICC
Staging system used for Melanoma staging currently in the UK
UICC TNM 8th edition
EMQ
Colorectal tumour which had received neoadjuvant therapy and on resection infiltrates beyond muscularis propria without lymph node involvement or metastases ypT3N0M0 In MDT, the stage used before resection of breast carcinoma clinically measuring 55mm cT3N0M0
Datasets
Published by The Royal College of Pathologists
Defines minimum standard for reporting of common cancers
Evidence based
Consistency in reporting
Datasets
The Working Group on Cancer Services (WGCS) production of guidelines and datasets for the reporting of cancers
WGCS recommendations for histopathologists reporting cancer:
Use of dataset Nominate lead pathologist Participate in EQA Should be a core member of MDT UKAS accredited laboratory
Datasets Provide: communication with clinicians to achieve optimal patient management clinical audit of pathology services accurate and consistent data recording for the Cancer Services and Outcomes Dataset (COSD) comparison between cancer services.
Datasets
Core-items recorded by Cancer Registries and National Cancer Outcomes and Services Dataset (COSD) Essential to record these items
Non-core items
recorded to improve the clarity of reports, because of particular local interest, for monitoring clinical trials or for research.
Specific examples
Breast
Tumour size – most important for staging pTis – DCIS, LCIS or Paget’s disease pT1 up to 2cm
pT2 2-5cm, pT3 >5cm pT4 – skin / chest wall involved Grading
pT1mi – microinvasion <1 mm pT1a – 1<5 mm pT1b – 5<10 mm pT1c – 10<20 mm
Tubules, pleomorphism, mitoses
Lymph node
Metastasis - >2mm micrometastasis >0.2mm to <2mm ITC (isolated tumour cells) <0.2mm
Reporting categories for breast biopsy
B1 : Normal breast – breast parenchyma present or not B2: FA, FCC, Sclerosing Adenosis, Fat necrosis, Abscess, Duct ectasia B3 Papilloma, Radial scar, Phyllodes B4 Suspicious B5 B5a – in-situ; B5b – invasive; B5c – not assessable
MCQ
Which of these is the most important parameter in breast cancer staging? 1. 2. 3. 4.
Type of tumour Hormone status Tumour size Tumour grade
Answer
Tumour size
MCQ
A sentinel lymph node in wide local excision specimen has tumour cells measuring 1.8mm in maximum dimension. Which of the category does this fall into?
Macrometastases Micrometastases Isolated tumour cells No evidence of metastases
Answer
Micrometastases
MCQ
A histology mastectomy specimen shows Paget’s disease of nipple but no evidence of invasive carcinoma. How will you stage it
pTx pT0 pT1 pTis
Answer
pTis
Thyroid
pTX Primary tumour cannot be assessed pT0 No evidence of primary tumour pT1a </=10 mm, limited to thyroid pT1b </=20 mm but >10 mm, limited to thyroid pT2 >20 mm, </=40 mm, limited to thyroid pT3 >40 mm, limited to thyroid or any tumour with minimal extrathyroidal extension,
pT4a Tumour invades beyond thyroid capsule and invades any of: subcutaneous soft tissues,
E.g. extension to sternothyroid muscles or perithyroid soft tissues
E.g. larynx, trachea, oesophagus, recurrent laryngeal nerve
pT4b Tumour invades prevertebral fascia, mediastinal vessels, or encases carotid artery.
Cont…
For clinical staging of papillary/follicular thyroid carcinoma
Age important criteria (> 55 years poorer prognosis)
MCQ
A thyroid tumour has histology of anaplastic carcinoma with infiltration into the recurrent laryngeal nerve. What is the tumour stage
pT0 pT1a pT1b pT2 pT3 pT4a pT4b
Answer
pT4a
Gastrointestinal neuroendocrine tumour
Well-differentiated (poorly differentiated are staged as per carcinoma) Grading Grade
Mitoses (per 10 hpf)
Ki67 index (%)
1
<2
<2
2
2-20
3-20
3
>20
>20
Staging varies depending on site of lesion, size and depth of invasion
Colorectum
TNM 8 pTis – limited to lamina propria pT1 – invades submucosa pT2 – invades muscularis propria pT3 – invades beyond muscularis propria pT4a – perforates visceral peritoneum pT4b – directly invades other organs or structures
Colorectum (cont…)
Node staging Nx – not assessed, N0 – no nodal mets pN1a – 1 node involved pN1b – 2 or 3 nodes involved pN1c – subserosal tumour deposits (without nodal mets) pN2a – 4-6 nodes involved pN2b – 7 or more nodes involved
Local excision of polyp
Kikuchi level Sessile tumour 1-3 (level of submucosal invasion)
Haggitt’s level Polypoid tumour 1-4 (Head, neck, stalk, beyond base)
MCQ
Which of the following stage of tumour can be confirmed on macroscopic examination of colorectal tumour?
pT1 pT2 pT3 pT4a pT4b
Answer
pT4a
Gastrointestinal stromal tumour
Lasota and Miettinen
CD117, DOG-1
Prediction of tumour behaviour Tumour size (<2cm) Mitoses – per 5mm² (<5) Site of tumour – gastric, duodenum etc Essential
Mutational analysis
C-kit – exon 9, 11, 13,17 PDGFRA – exon 12,14, 18
MCQ
A gastric tumour shows spindle cell morphology and is positive for CD117 and DOG-1. The tumour measures 1cm with 3 mitoses per 5mm². What is the risk of progressive disease according to Lasota and Miettinen criteria? None Low Moderate High
Answer
None
Pancreas
Kausch-Whipple’s pancreatoduodenectomy
Transection margin in Whipple’s resection:
Gastric, Duodenal, CBD, Pancreas
Dissected margin
Head of pancreas, Duodenum, CBD, 2/3rd of stomach
SMA/SMV (medial) and posterior margin
Minimum number of lymph nodes – 15 Staging differs depending on where the tumour has arisen from
Kausch-Whipple’s pancreatoduodenectomy
Liver biopsy
pM0 – does not exist pM1= distant metastasis proven microscopically, e.g.needle biopsy If a cM1 (e.g. liver met) is biopsied and is negative, it becomes cM0, not pM0
Liver Tumours
pT1a – single tumour <2 cm
pT1b – single tumour >2 cm
+/- vascular invasion without vascular invasion
pT2 – single tumour >2 cm with vascular invasion or multiple tumours all <5 cm pT3 – multiple tumours any >2 cm pT4 – Tumour invades major branch of portal/hepatic vein, invades adjacent organ (not gallbladder) inc diaphragm or perforates visceral peritoneum
Tumour at the gastro-oesophageal junction
Siewert type: 1–5 cm above the gastro-oesophageal junction (Type 1) - oseophageal at the junction (Type 2) - gastric 2–5 cm below the junction (Type 3) - gastric
Tumour at the gastro-oesophageal th junction – TNM 8 edition
A tumour in the stomach, the epicenter of which is within 2 cm of the oesophagogastric junction and also extends into the oesophagus is classified and staged according to the oesophageal scheme
All other tumours with an epicenter in the stomach <20 mm without extension into the oesophagus or greater than 2 cm from the oesophagogastric junction are staged using the gastric carcinoma scheme
Cervical carcinoma
FIGO I
FIGO IA Invasive carcinoma, diagnosed only by microscopy, with deepest invasion ≤ 5 mm and largest extension ≤ 7 mm
FIGO IA1 -Measured stromal invasion ≤ 3 mm and ≤ 7 mm FIGO IA2 -Measured stromal invasion of > 3 mm and not > 5 mm with an extension of not >7 mm
FIGO IB – clinically visible, confined to cervix or >7 mm microscopically FIGO IB1 – clinically visible <4 cm FIGO IB2 – clinically visible >4 cm
FIGO II – beyond uterus but not to pelvic wall or lower third vagina FIGO III – causes hydronephrosis
Endometrial carcinoma
Tumour grade Endometrioid Grade 1- <5% solid non-squamous component Grade 2- 6-50% Grade 3 ->50% Upgrading on nuclear characteristics – pleomorphism, mitoses, prominent nucleoli
Endometrial carcinoma
High grade carcinoma:
Serous carcinoma, clear cell carcinoma, undifferentiated carcinoma and carcinosarcoma
Endometrial staging
FIGO IA – no or less than half of myometrial invasion FIGO IB – invasion equal to or more than half of the myometrium FIGO II – cervical stromal involvement FIGO III – local or regional spread IIIA – serosa of corpus or adnexae IIIB – vaginal or parametrial involvement IIIC – pelvic or paraaortic node involvement FIGO IV – invades bladder/bowel
Ovarian carcinoma
Serous carcinoma
Low grade <12mitoses/10hpf No necrosis or multinucleate tumour cells Mild nuclear atypia
High grade >12mitoses/10hpf Necrosis or multinucleate tumour cells Marked nuclear atypia
Ovarian Carcinoma
FIGO I- tumour limited to ovaries IA – one ovary, capsule intact, no tumour on surface or peritoneal fluid IB – both ovaries IC – tumour limited to one or both ovaries with any of the following:
IC1 – surgical spill IC2 – capsule ruptured (before surgery) or tumour on surface IC3 – malignant cells in ascites/peritoneal washings
Ovarian carcinoma
FIGO II – one or both ovaries with pelvic extension or primary peritoneal carcinoma IIA – extension/implants on uterus/tubes/ovaries IIB – extension to other pelvic tissues inc bowel FIGO III – peritoneal deposit outside pelvis IIIA – 1i – LN met <10 mm; 1ii – LN met >10 mm IIIA2 – extrapelvic peritoneal spread IIIB – macroscopic peritoneal spread <2cm +/retroperitoneal LN spread IIIC – peritoneal mets beyond pelvic >2 cm +/retroperitoneal LN mets FIGO IV – distant metastasis A – pleural fluid B – parenchymal mets/extra-abdominal mets
Uterine Sarcoma
Leiomyosarcoma 2 of 3 features Severe
nuclear atypia Mitosis>10/10 hpf Coagulative necrosis
Uterine leiomyosarcoma Stage I Tumour limited to uterus IA ≤5 cm, IB >5 cm Stage II Tumour extends beyond the uterus, within the pelvis IIA Adnexal involvement,IIB Involvement of other pelvic tissues Stage III Tumour invades abdominal tissues (not just protruding into the abdomen) IIIA One site, IIIB > one site, IIIC Metastasis to pelvic and/or paraaortic lymph nodes Stage IV IVA Tumour invades bladder and/or rectum, IVB Distant metastasis
Melanoma
UICC TNM 8th Edition
Breslow thickness Increase thickness – increased risk of metastasis Thin melanoma - <1mm Extension to peri-appendeal sheath and microsatellites are not counted
Melanoma
Ulceration Important pT
prognostic factor
stage
full-thickness
epidermal defect (including absence of stratum corneum), evidence of reactive changes(i.e. fibrin deposition and neutrophils), and thinning, effacement or reactive hyperplasia of the surrounding epidermis in the absence of trauma or recent surgical procedure
Melanoma T
Thickness (mm) Ulceration status
1
a: Without ulceration
2
a: <0.8 b: 0.8-1.0 1.01–2.0
3
2.01–4.0
a: without ulceration b: with ulceration
4
>4.0
a: without ulceration b: with ulceration
b: With ulceration a: without ulceration b: with ulceration
Melanoma
T1a is restricted to melanomas with two criteria <0.8 mm thick Absence of ulceration
Melanoma
Micrometastases
diagnosed after sentinel lymph node biopsy and completion lymphadenectomy (if performed). They occur in the setting of no clinical abnormality.
Macrometastases
defined as clinically detectable nodal metastases confirmed by therapeutic lymphadenectomy or when nodal metastasis exhibits gross extracapsular extension. They occur in the setting of a clinical abnormality
Melanoma - metastases
M0
M1a
Metastases to lung
M1c
Metastases to skin, subcutaneous, or distant lymph nodes
M1b
No detectable evidence of distant metastases
Metastases to all other non CNS sites
M1d
CNS mets
MCQ
A patient has cutaneous melanoma with Breslow thickness of 0.7 mm with Clark level 2, mitotic rate 1mm², brisk tumour infiltrating lymphocytes, no lymphovascular invasion or perineural invasion. No evidence of ulceration. Margins are clear. Which is the most important staging criteria here?
Clark level Breslow thickness Ulceration Mitoses
Answer
Ulceration
Skin – Squamous cell carcinoma
pT1 ≤20mm size pT2 20 ≤ 40 mm pT3 <40 mm
Or: minor bone erosion or perineural invasion (named nerve or ≥ 0.1 mm) or deep invasion (beyond SC fat or >6 mm)
pT4 axial skeleton invasion including skull base or foraminal involvement
Skin - BCC
High risk pathological factors Growth pattern: infiltrating/morphoeic and/or micronodular Basosquamous carcinoma Clark level 5 or beyond Perineural invasion Lymphovascular invasion present
Adult Kidney
Staging
pT1 –less than or equal to 7cm, confined to kidney. pT1a <= 4cm, pT1b >4cm
T2 - >7cm
Adult Kidney
Staging
T3a –Tumour grossly extends into the renal vein or its segmental (muscle containing) branches, or tumour invades perirenal and/or renal sinus fat. T3b – Tumour grossly extends into the vena cava below the diaphragm. T3c – Tumour grossly extends into the vena cava above the diaphragm or invades the wall of the vena cava.
T4
Tumour invades beyond Gerota fascia (including contiguous extension into the ipsilateral adrenal gland).
Adult Kidney
WHO/ISUP grading Nucleoli 1- none 2- 40hpf 3- 10hpf 4-bizarre cells
Prostate
Gleason grading Gleason score in radical prostatectomy
most prevalent and second most common grades and to mention the presence of a tertiary grade
Prostate
Gleason score in biopsy If only one grade is present, it is doubled (e.g. 3+3); If two grades are present, both are included by order of prevalence; If more than two grades are present, the third is included in the sum score if it is of higher grade
Prostate
pT1 (on biopsy or TURP) pT1a Tumour incidental histological finding in 5% or less of tissue resected pT1b Tumour incidental histological finding in more than 5% of tissue resected pT1c Tumour identified by needle biopsy (e.g. because of elevated PSA)
Prostate
pT2 pT2a Tumour involves one half of one lobe or less pT2b Tumour involves more than half of one lobe, but not both lobes pT2c Tumour involves both lobes pT3 pT3a Extracapsular extension (unilateral or bilateral) pT3b Tumour invades seminal vesicle(s)
Bladder tumour
pT2 – muscularis propria pT3b – gross invasion into perivesical tissue
Lung
Important parameters for staging
Tumour size (pT1 <3cm, pT2 3-7cm) Main bronchus involvement Visceral pleura involvement
pT1 mi – minimally invasive adenocarcinoma a – ≤ 1 cm b – 1 ≤ 2 cm c – 2 ≤ 3 cm
pT2
a – 3 ≤ 4 cm b – 4 ≤ 5 cm Or: involves main bronchus (not the carina), invades visceral pleura, associated obstructive pneumonitis
pT3
Cont…
5 ≤ 7 cm Or: separate tumour nodule in same lobe, or invades – parietal pleura, chest wall, phrenic nerve, parietal pericardium
pT4 - >7 cm or invaded anything else
EMQ
Gastric cancer Oesophageal cancer pM0 cM0 cM1 High grade Low grade Gleason grade 4 Gleason grade 3 Fuhrman grade 3 Fuhrman grade 4
EMQ
A tumour at within 5 cm gastroesophageal junction without extension into the oesophagus –
A liver biopsy with clinical suspicion of metastasis but no evidence of metastasis on histology
An endometrial tumour shows morphology of serous carcinoma comprising of 20% solid area . What is the tumour grade?
EMQ
An ovarian tumour showing morphology of serous carcinoma with 15 mitoses/10 hpf.
A prostate carcinoma on needle core biopsy shows cribriform architecture with fused glands
A conventional clear cell carcinoma of the kidney shows bizarre tumour cells. What is the grade of the tumour
EMQ
A tumour at within 5 cm gastroesophageal junction without extension into the oesophagus –
A liver biopsy with clinical suspicion of metastasis but no evidence of metastasis on histology
Gastric cancer
cM0
An endometrial tumour shows morphology of serous carcinoma comprising of 20% solid area . What is the tumour grade?
High grade
EMQ
An ovarian tumour showing morphology of serous carcinoma with 15 mitoses/10 hpf.
A prostate carcinoma on needle core biopsy shows cribriform architecture with fused glands
High grade
Gleason grade 4
A conventional clear cell carcinoma of the kidney shows bizarre tumour cells. What is the grade of the tumour
Fuhrman grade 4
Thank you