Grading Systems

Question 1

What is the grading system used for invasive breast carcinomas and what are the components?

Answer 1

The Modified Scarff-Bloom-Richardson-Nottingham System

Three components assigned a score of 1-3 each and added together:
1. Tubule formation
Score 1: >75%
Score 2: 10-75%
Score 3: <10%

2. Nuclear Pleomorphism
   Score 1: Mild: Minimal nuclear variation in size and shape (<1.5x size of benign epithelial cells nuclei), even chromatin, inconspicuous nucleoli
   Score 2: Moderate: (1.5 - 2x size of benign epithelial cell nuclei), visible but small nucleoli
   Score 3: Marked: (>2x size of benign epithelial cell nuclei), often prominent nucleoli
3. Mitotic count per 10hpf (0.56)
   Score 1: < /=12
   Score 2: 13 - 24
   Score 3: >/= 25

Nottingham Score:
3-5: Well differentiated
6-7: Moderately differentiated
8-9: Poorly differentiated

Question 2

How do we grade breast ductal carcinoma in-situ?

Answer 2

Ductal Carcinoma in situ is graded based on the nuclear features, of which 6 components are assessed:

1. Nuclear pleomorphism
   Grade I: Monotonous (monomorphic)
   Grade II: Intermediate
   Grade III: Markedly pleomorphic
2. Size (Compared to size of RBC or normal duct epithelial cell nucleus)
   Grade I: 1.5 - 2x
   Grade II: 2-2.5x
   Grade III: >2.5x
3. Chromatin
   Grade I: Usually diffuse, finely dispsered chromatin
   Grade II: Intermediate
   Grade III: Usually vesicular with irregular chromatin distribution
4. Nucleoli
   Grade I: Only occasional
   Grade II: Intermediate
   Grade III: Prominent, often multiple
5. Mitoses:
   Grade I: Only occasional
   Grade II: Intermediate
   Grade III: May be frequent
6. Orientation:
   Grade I: Polarized towards luminal spaces
   Grade II: Intermediate
   Grade III: Usually not polarized towards the luminal space

**Importance is grading is to help predict likeliness of progression or recurrence

Question 3

How are prostate biopsies and resections graded?

Answer 3

Prostate biopsies are graded using the Gleason Score and WHO/ISUP grade groups.

Gleason score is based on the glandular architecture divided in 3 main pattern groups (3-5)

Pattern 3:
Discrete, well formed glands separated by intervening stroma

Pattern 4:
- Poorly formed glands
- Fused or back-to-back glands with no intervening stroma
- Cribriform glands (ISUP defines as a confluent sheets of contiguous malignant epithelial cells with multiple glandular lumina that are easily visible at low power objective (x10)
- Glomeruloid pattern

Pattern 5:
- Single cells pattern
- Forming cords
- Signet rings
- Comedonecrosis
- Sheets

For prostate biopsy:
The most common and the worst pattern:

For prostate resection:
The most common and second most common pattern

WHO/ISUP Grade Groups:
Grade group 1: 6 (3+3)
Group group 2: 7 (3+4)
Group group 3: 7 (4+3)
Group group 4: 8 (4+4, 3+5)
Group group 5: 9 or 10 (5+4, 5+5)

Question 4

What is the system used for grading endometroid carcinoma?

Answer 4

FIGO Grading System (International Federation of Gynecology and Obstetrics)

Based on % of nonsquamous or nonmorular solid growth pattern

Grade 1: </= 5%
Grade 2: 6-50%
Grade 3: >50%

** Notable nuclear atypia inappropriate for architecture grade, raises the grade by 1

NCCN:
FIGO grade 1 and 2: Low grade carcinomas
FIGO grade 3: High grade carcinoma

Question 5

How is colon adenocarcinoma graded?

Answer 5

Based on glandular formation:

Grade 1 - Well differentiated: >95%
Grade 2 - Moderately differentiated: 50-95%
Grade 3 - Poorly differentiated: <50%
Grade 4 - Undifferentiated: No gland formatiom or mucin; no squamous or neuroendocrine differentiation)

Question 6

What system is used to grade soft tissue tumours?

Answer 6

Federation Nationale des Centres de Lutte Contre le Cancer (FNCLCC)

FNCLCC grading system composed of three components:

1. Tumour differentiation
   - Scored 1, 2 or 3 based on resemblance of normal tissue
   (eg. Well differentiated liposarcoma - 1 ; Myxoid liposarcoma - 2 ; Dedifferentiated or Pleomorphic Liposarcoma - 3)
2. Mitotic count: (per 10hpf)
   1 point: 0 - 9 mitoses
   2 points: 10 - 19 mitoses
   3 points: >/= 20 mitoses
3. Tumour necrosis:
   0 points: No necrosis
   1 point: <50% necrosis
   2 points: >/= 50% necrosis

Grade: sum of total points:
Grade 1: 2-3 points
Grade 2: 4-5 points
Grade 3: 6-8 points

Question 7

What system is used to grade renal carcinomas?

Answer 7

WHO/ISUP (2022) grading system:
Based on the nucleoli

Grade 1: Absent of inconspicuous at x40
Grade 2: Eosinophilic and visible at x40
Grade 3: Eosinophilic and prominent at x10