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GIST Prognosis: Risk Of Recurrence or Aggressive Behavior

 

Several different schemes have been used to estimate the risk of recurrence,  also called malignant potential, for gastrointestinal stromal tumor (GIST).  Your pathology report may use one or more of the following categorizations.

  • NIH risk scheme - applies to primary tumors that have not yet metastasized
  • NCCN risk classification - applies to primary tumors that have not yet metastasized
  • AJCC Staging - applies to both primary and metastatic GIST

Note that bcause these classifications were developed using data for GIST in adults, they may not be appropriate for use with the very rare pediatric GIST cases.

 

NIH consensus risk scheme for GIST

Developed at a consensus conference of experts and published in 2002 (CDM Fletcher et al), this scheme divides GISTs into risk groups based solely on tumor size and mitotic count.  Four risk groups were defined as shown below.  This risk table was based on expert experience and opinion, as there were only limited data to support the categories at that point in time.

 

Risk of Aggressive Behavior in GISTs (from Fletcher et al, 2002, Human Pathology 33(5):459-65, used with permission of Elsevier)


 
Size (largest dimension) Mitotic Count
very low risk <2 cm <5 / 50 HPF
low risk 2-5 cm < 5 / 50 HPF
intermediate risk
 
<5 cm
 
6-10 / 50 HPF
 
5-10 cm < 5 / 50 HPF
 
high risk

 
>5 cm
 
> 5 / 50 HPF
>10 cm
 
any mitotic rate
 

 

NCCN Risk Classification for GIST

An improved risk scheme for GIST was developed by pathologists Miettinen and Lasota at the Armed Forces Institute of Pathology (AFIP), based on thousands of GIST samples available in the AFIP files.  The Miettinen and Lasota scheme has been adapted and endorsed by the National Comprehensive Cancer Network (NCCN) Task Force on GIST (see their 2010 report).  This approach evaluates tumor risk based partly on the organ where the GIST originates.  Gastric (stomach) GISTs of a given size and mitotic rate are less likely to recur than similar tumors from other sections of the GI tract.


 

Risk classification for primary GIST by mitotic index, size, and tumor site. Adapted from Miettinen and Lasota, Seminars in Diagnostic Pathology 2006: 23(2) 70-83.  Used with the permission of Elsevier. 

 Tumor Parameters      Risk of Progressive Disease a
 Mitotic
 Index
 Size Stomach  Duodenum  Jejunum
 or Ileum
 Rectum
 
 ≤ 5 per
 50 hpf
 
 
 ≤ 2cm  none  none  none  none
 > 2 ≤ 5cm  very low
(1.9%)
 low
 (8.3%)
 low
 (4.3%)
 low
 (8.5%)
 > 5 ≤ 10 cm  low
 (3.6%)
 insufficient
 data
 moderate
 (24%)
 insufficient
 data
 > 10 cm  moderate
 (10%)
 high
(34%)
 high
 (52%)
 high
 (57%)
 
 > 5 per
 50 hpf
 
 
 ≤ 2 cm  none b  insufficient
 data
 high b  high
 (54%)
 > 2 ≤ 5 cm  moderate
 (16%)
 high
 (50%)
 high
 (73%)
 high
 (52%)
 > 5 ≤ 10 cm  high
 (55%)
 insufficient
 data
 high
 (85%)
 insufficient
 data
 > 10 cm  high
 (86%)
 high
 (86%)
 high
 (90%)
 high
 (71%)
 a defined as metastasis or tumor-related death
 b denotes small number of cases
 Data based on longterm followup of 1055 gastric, 629 small intestinal, 144 duodenal, and 111 rectal GISTs.

 


American Joint Committee on Cancer (AJCC) Staging for GIST

The AJCC is a joint effort by several professional organizations to define classifications for various cancer types for standardized description and treatment decisionmaking.  The AJCC defines cancer staging as follows:   "Staging describes the extent or severity of an individual's cancer based on the extent of the original (primary) tumor and the extent of spread in the body."
You can read more about staging at the AJCC website.

The AJCC Cancer Staging Manual ,7th edition introduced staging criteria for GIST to be used starting in January 2010.  There had never been AJCC staging for GIST in the past, but pathology reports on new tumors and new biopsies from 2010 onward may use this scheme.  If you have a diagnosis from earlier than 2010, you could see where your tumor would fall in this new scheme, but there is no real new information here -- it employs the Miettinen and Lasota / NCCN criteria translated to the TNM (tumor, lymph nodes, and metastasis) system for describing the same information, backed by consensus of the AJCC.

All the AJCC staging schemes use "TNM" codes that stand for Tumor Node Metastasis. 

  • Tumor size yields a "T" category
  • Lymph node status yields an "N" category that is usually zero because lymph node spread is very rare in GIST (except in pediatric GIST)
  • The "M" category indicates whether the GIST has metastasized yet

Mitotic rate is combined with the TNM information to give a stage.  Mitotic rate is counted in an area of 5 square millimeters (5 mm2).  For microscopes with traditional field size, this equals 50 high power fields (50 HPF) at a magnification of 40x.  However, for microscopes with "wide-field optics" this equals just 25 fields to achieve the same 5 mm2.  Mitotic rate for GIST is classified as "low" for 0-5 mitoses and "high" for 6 or more mitoses per 5 mm2 .

 

Definitions of T, N, M, and Mitotic Rate for GISTs at all sites of origin. Used with the permission of the American Joint Committee on Cancer (AJCC), Chicago, Illinois. The original source for this material is the AJCC Cancer Staging Manual, Seventh Edition (2010) published by Springer Science and Business Media LLC, www.springer.com.

Primary Tumor (T)
 TX: Primary tumor cannot be assessed
 T0: no evidence for primary tumor
 T1: tumor 2 cm or less
 T2: tumor more than 2 cm but not more than 5 cm
 T3: tumor more than 5 cm but not more than 10 cm
 T4: tumor more than 10 cm in greatest dimension
Regional Lymph Nodes (N)
 NX: regional lymph nodes cannot be assessed
 N0: no regional lymph node metastasis
 N1: regional lymph node metastasis
Distant Metastasis (M)
 M0: no distant metastasis
 M1: distant metastasis
Mitotic Rate
 low mitotic rate: 5 or fewer per 50 HPF
 high mitotic rate: over 5 per 50 HPF

 

The final scheme is shown in the table below.  Staging is different for gastric and omental versus other GISTs, indicating a greater risk of recurrence for non-gastric GISTs.
 

Anatomic Stage / Prognostic Group for GIST by site of origin. Used with the permission of the American Joint Committee on Cancer (AJCC), Chicago, Illinois. The original source for this material is the AJCC Cancer Staging Manual, Seventh Edition (2010) published by Springer Science and Business Media LLC, www.springer.com.

Gastric GIST *
Group
T N M Mitotic Rate
 Stage IA  T1 or T2  N0  M0  low
 Stage IB  T3  N0  M0  low
 Stage II  T1
 T2
 T4
 N0
 N0
 N0
 M0  high
 high
 low
 Stage IIIA  T3  N0  M0  high
 Stage IIIB  T4  N0  M0  high
 Stage IV  any T
 any T
 N1
 any N
 M0
 M1
 any rate
 any rate
Small Intestinal GIST**
 Group 
 T  N  M  Mitotic Rate
 Stage I  T1 or T2  N0  M0  Low
 Stage II  T3  N0  M0  Low
 Stage IIIA  T1
 T4
 N0
 N0
 M0
 M0
 High
 Low
 Stage IIIB  T2
 T3
 T4
 N0
 N0
 N0
 M0
 M0
 M0

 High
 High
 High

 Stage IV  any T
 any T
 N1
 any N
 M0
 M1
 any rate
 any rate
 *  Note: also to be used for omentum
** Note: also to be used for esophagus, colorectal, mesentery, 
             and peritoneum

 

Stage 1 GISTs are low-risk tumors that are unlikely to recur after surgery, and Stage 4 GIST is metastatic disease that will likely benefit from treatment with molecularly targeted drugs such as imatinib mesylate (Gleevec).  The intermediate stages 2 and 3 correspond to moderate and high risk of recurrence for GIST.  Recommended treatment schemes for these tumor stages are evolving through active research, but treatment may also include targeted drugs. Genotyping of KIT and PDGFRA may be helpful in therapeutic selection and treatment approach.

 

Go to next section, Pathology Reports for GIST

 



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