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.
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Risk of Aggressive Behavior in GISTs (from Fletcher et al, 2002, Human Pathology 33(5):459-65, used with permission of Elsevier) |
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| 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.
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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. |
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| 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%) |
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| > 5 ≤ 10 cm | high (55%) |
insufficient data |
high (85%) |
insufficient data |
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| > 10 cm | high (86%) |
high (86%) |
high (90%) |
high (71%) |
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| a defined as metastasis or tumor-related death b denotes small number of cases |
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| 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.”
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 .
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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. |
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| 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.
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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. |
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| 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 ** N ote: also to be used for esophagus, colorectal, mesentery, and peritoneum |
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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