Joshi et al proposed histologic grading criteria for neuroblastomas in 1992 using mitotic rate and calcification status. This was modified in 1996 with the mitotic karyorrhexis index used in place of the mitotic index. This correlates with the Shimada classification but is easier to apply, since the degree of differentiation does not need to be determined.
Original (1992)
Histologic Features |
Grade |
mitotic rate low (<= 10/10 HPF), AND calcification present |
I |
mitotic rate low (<= 10/10 HPF), OR calcification present |
II |
mitotic rate high (> 10/10 HPF), AND calcification absent |
III |
Counting mitoses (Joshi, 1992, page 2200):
(1) count in most mitotically active area at x400 magnification
(2) 10 high powered fields counted on each of 4 sections from the tumor, with the maximum count used for grading
(3) features of mitosis (vs karyorrhexis): absent nuclear membrane, presence of hairy or spiky projections, and basophilic or clear cytoplasm
(4) doubtful structures are not counted
Modified (1996)
Histologic Features |
Grade |
mitotic karyorrhexis index low (<= 4%), AND calcification present |
I |
mitotic karyorrhexis index low (<= 4%), OR calcification present |
II |
mitotic karyorrhexis index NOT low (> 4%) AND calcification absent |
III |
where:
• mitotic karyorrhexis index (MKI) = number of cells showing mitotic activity or nuclear karyorrhexis in 5,000 cells (200 cells = 4%)
Features of karyorrhectic cells (Joshi, 1992, pages 2200-2201)
(1) condensed punctate or lobular nuclear material
(2) eosinophilic dense cytoplasmic staining
The MKI can be estimated (Joshi, 1996, page 1584-1585, Table III) by scanning an area for its cell density and counting the number of cells showing mitoses or karyorrhexis (MKC = mitotic or karyorrhectic cells)
Cell Density |
Tumor Cells per HPF |
Low MKI if number MKC |
High MKI if number MKC |
sparse |
100 |
<= 4 |
> 4 |
sparse |
200 |
<= 8 |
> 8 |
sparse to moderate |
300 |
<= 12 |
> 12 |
moderate |
400 |
<= 16 |
> 16 |
moderate |
500 |
<= 20 |
> 20 |
moderate to dense |
600 |
<= 24 |
> 24 |
dense |
700 |
<= 28 |
> 28 |
dense |
800 |
<= 32 |
> 32 |
dense |
900 |
<= 36 |
> 36 |
Prognostic Groups
Grade |
Age of Patient |
Prognosis |
I |
any age |
low risk (good) |
II |
<= 1 year of age |
low risk (good) |
II |
> 1 year of age |
high risk (poor) |
III |
any age |
high risk (poor) |
Note: In the abstract to Joshi 1996, it refers to grade II as low risk if < 1 year and high risk if >= 1 year. However, Tables 2 and 6 use <= 1year and > 1 year.
5 year survival in 1996:
• low risk group: 93%
• high risk group: about 48%
Specialty: Hematology Oncology, Surgery, general