DATASETS AND CLINICAL STAGING
Dr Oreoluwa Suleiman
January 2025
• Principles of cancer staging
OUTLI NE
• Different staging systems in use
• Examples of staging of specific cancers
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
Choose from the options below:
FIGO
AJCC 8th edition
UICC TNM 8th edition
UICC
ypT3N0M0
pT2N0M0
pT0N0M0
cT3N0M0
• 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
• FIGO
• Organisation that develops TNM staging
• UICC
• Staging system used for Melanoma staging currently in the UK
• UICC TNM 8th edition
• 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
• pT1mi – microinvasion <1 mm
• pT1a – 1<5 mm
• pT1b – 5<10 mm
• pT1c – 10<20 mm
• pT2 2-5cm, pT3 >5cm
• pT4 – skin / chest wall involved
• Grading
• Tubules, pleomorphism, mitoses
• Lymph node
• Metastasis - >2mm
• micrometastasis
• >0.2mm to <2mm
• ITC (isolated tumour cells)
• <0.2mm
BREAST
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. Type of tumour
2. Hormone status
3. Tumour size
4. 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
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,
• E.g. extension to sternothyroid muscles or perithyroid soft tissues
• pT4a Tumour invades beyond thyroid capsule and invades any of: subcutaneous soft tissues,
• E.g. larynx, trachea, oesophagus, recurrent laryngeal nerve
• pT4b Tumour invades prevertebral fascia, mediastinal vessels, or encases carotid artery.
STRAP MUSCLES OF THE NECK
THYROID AND NECK STRUCTURES
CONT…
• For clinical staging of papillary/follicular thyroid carcinoma
• Age important criteria (> 55 years poorer prognosis)
• 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
GASTROINTESTINAL NEUROENDOCRINE TUMOUR
• Well-differentiated (poorly differentiated are staged as per carcinoma)
• Grading
• 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 stages of tumour can be confirmed on macroscopic examination of colorectal tumour?
• pT1
• pT2
• pT3
• pT4a
• pT4b
ANSWER
GASTROINTESTINAL STROMAL TUMOUR
• Lasota and Miettinen
Prediction of tumour behaviour based on:
• Tumour size (<2cm)
• Mitoses – per 5mm² (<5)
• Site of tumour – gastric, duodenum etc
• CD117, DOG-1
• 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
• Head of pancreas, Duodenum, CBD, 2/3rd of stomach
• Transection margin in Whipple’s resection:
• Gastric, Duodenal, CBD, Pancreas
• Dissected margin
• 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
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
• +/- vascular invasion
• pT1b – single tumour >2 cm
• 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) including diaphragm or perforates visceral peritoneum
TUMOUR AT THE GASTROOESOPHAGEAL
• Siewert type:
JUNCTION
• 1–5 cm above the gastro-oesophageal junction (Type 1) - oesophageal
• • at the junction (Type 2) - gastric
• 2–5 cm below the junction (Type 3) - gastric
TUMOUR AT THE GASTRO-
OESOPHAGEAL JUNCTION – TNM 8TH 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 para-aortic 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 prognostic factor
• pT 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: <0.8 b: 0.8 1.0
a: Without ulceration
b: With ulceration
2 1.01 2.0
a: without ulceration
b: with ulceration
3 2.01 4.0
a: without ulceration
b: with ulceration
4 >4.0 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
• No detectable evidence of distant metastases
• M1a
• Metastases to skin, subcutaneous, or distant lymph nodes
• M1b
• Metastases to lung
• M1c
• Metastases to all other non-CNS sites
• M1d
• CNS mets
CLARK LEVELS
• 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.There is ulceration of the epidermis over the tumour site. 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 peri-renal 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 SYSTEM
• Grade 1: Nucleoli are inconspicuous and basophilic at ×400 magnification.
• Grade 2: Nucleoli are clearly visible at ×400 (x40) magnification and eosinophilic.
• Grade 3: Nucleoli are clearly visible at ×100 (x10)magnification.
• Grade 4: Extreme pleomorphism or rhabdoid and/or sarcomatoid morphology.
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 - Clinically inapparent tumour not palpable or visible by imaging)
• 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 (Tumour confined within prostate)
• 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) including microscopic bladder neck involvement;
• pT3b Tumour invades seminal vesicle(s)
• T4 Tumour is fixed or invades adjacent structures other than seminal vesicles external sphincter, rectum, levator muscles, or pelvic wall
BLADDER TUMOUR
• pTX Primary tumour cannot be assessed
• pT0 No evidence of primary tumour
• pTa Non-invasive papillary carcinoma
• pTis Carcinoma in situ:‘flat tumour’
• pT1 Tumour invades subepithelial connective tissue
• pT2 Tumour invades muscularis propria
• pT2a Tumour invades muscularis propria (inner half)
• pT2b Tumour invades muscularis propria (outer half)
BLADDER TUMOUR CONT’D
pT3 Tumour invades perivesical tissue
• pT3a Microscopically
• pT3b Macroscopically (extravesical mass)
• pT4 Invades any of the following: prostate stroma, seminal vesicles, uterus, vagina, pelvic wall, abdominal wall
• pT4a Tumour invades prostate stroma, seminal vesicles, uterus or vagina
• pT4b Tumour invades pelvic wall or abdominal wall
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
CONT
• pT2
• a – 3 ≤ 4 cm
• b – 4 ≤ 5 cm
• Or: involves main bronchus (not the carina), invades visceral pleura, associated obstructive pneumonitis
• pT3
• 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
• 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?
• 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
• A tumour at within 5 cm gastroesophageal junction without extension into the oesophagus –
• Gastric cancer
• A liver biopsy with clinical suspicion of metastasis but no evidence of metastasis on histology
• cM0
• An endometrial tumour shows morphology of serous carcinoma comprising of 20% solid area .What is the tumour grade?
• High grade
• An ovarian tumour showing morphology of serous carcinoma with 15 mitoses/10 hpf.
• High grade
• A prostate carcinoma on needle core biopsy shows cribriform architecture with fused glands
• 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