Transcript Differential Diagnosis Gastrointestinal Spindle Cell Tumors

Pathology Review
Gastrointestinal Stromal Tumors*
December 16, 2005 - Denver – Colorado
Francisco G. La Rosa MD
Pathologist, Assistant Professor
Department of Pathology, UCHSC
* In collaboration with S. Russell Nash, MD, PhD
UCDHSC at Fitzsimons
Mail Stop 8104, P.O. Box 6511
Phone:
Fax:
303 - 724 - 3782
413 - 410 – 4489
[email protected]
http://www.uchsc.edu/pathology/prostate
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Mucosa
Submucosa
Muscularis propria
Serosa
Normal Histology of the GI tract
Gastrointestinal Stromal Tumors (GIST) are a rare but important group of spindle cell
tumors arising within the gastrointestinal tract. For many years, these tumors were
misdiagnosed as leiomyomas, epithelioid leiomyomas, leiomyoblastomas,
leiomyosarcomas, and epithelioid leiomyoblastomas, depending upon the histologic
findings.
The cell of origin has been found to be a mesenchymal stem cell, and not the smooth
muscle cell as once thought. GISTs arise from the Interstitial Cajal Cells, that are
normally part of the autonomic nervous system of the intestine. They serve a
pacemaker function in controlling motility. Most of these tumors present with pain,
obstruction, a mass lesion, or bleeding.
Most (50-80%) GISTs arise because of a mutation in a gene called c-kit. This gene
encodes a transmembrane receptor for a growth factor termed scf (stem cell factor).
The c-kit/CD117 receptor is expressed on ICCs and a large number of other cells,
mainly bone marrow cells, mast cells, melanocytes and several others. In the gut,
however, a mass staining positive for CD117 is likely to be a GIST, arising from ICC
cells.
The pathologist is faced with the task of identifying prognostic factors that may
provide guidance for treatment and survival.
Differential Diagnosis
Gastrointestinal Spindle Cell Tumors
• Leiomyoma/Leiomyosarcoma
• Schwannoma/Malignant peripheral nerve
sheath tumor
• Solitary fibrous tumor
• Fibromatosis (desmoid tumor)
• Inflammatory myofibroblastic tumor
• Inflammatory fibroid polyp (in stomach)
• GISTs
GIST Sites
Stomach
50-60%
Small bowel
20-30%
Large bowel
10%
Esophagus
Mesentery, omentum,
retroperitoneum
5%
Rare
Gastric GIST - Tumoral nodules under the gastric mucosa
Gastric GIST
Stomach resection of 72 year old man with gastric leiomyosarcoma. Note that
normal mucosa is present at the right side of the photograph. The tumor
invades full-thickness and completely obliterates the gastric wall.
GIST tumor arising in small bowel. Note the mass lies underneath and is separate
from the bowel mucosal layer and there is no disruption of the overlying mucosa.
The deep location of the tumor makes it difficult to obtain endoscopic biopsies in
many cases.
Colonic GIST
Colonic GIST
Colonic GIST
Benign spindle cell GIST
Benign spindle cell GIST
Benign epithelioid GIST with multinucleated cells
Benign spindle cell GIST with extensive perinuclear vacuolization (typical feature)
Risk of Aggressive Behavior
in GI Stromal Tumors
Risk
Size
Mitoses
(per 50 hpf)
Very low
Low
< 2 cm
2-5 cm
<5
<5
Intermediate
<5
5-10
>5
6-10
<5
>5
>10
Any number
Any size
>10
High
From: Fletcher, CDM et al. 2002 Hum. Pathol. 33: 459-465
Histologic Features Suggesting
Malignant Behavior in GIST
•
•
•
•
•
Cell type: Epithelioid>Spindle Cell
Cellularity
Mitotic activity
Mucosal invasion
Tumor necrosis
From: Goldblum, JR 2002 Am. J. Clin. Pathol. 117Suppl: S49-S61
High cellularity and many mitoses suggest an aggressive behavior for this tumor.
Immunophenotypes
of Spindle Cell Tumors
Lesion
CD117 CD34 Desmin Actin
S100
GIST
+
+/-
-
-/+
-
Leiomyoma
-
-
+
+
-
Fibromatosis
-
-
-/+
+
-
Solitary fibrous T
-
+
-
-
-
Schwannoma
-
-/+
-
-
+
(pos = >75%)
( +/- = 50-75%)
(-/+ = 25-50%)
Actin = smooth muscle type
CD117 = sc-168 Santa Cruz Biotechnology
(neg = <25%)
CD117 staining in spindle cell GIST
Gastric leiomyoma with smooth muscle type spindle cells arranged in
fascicles and bundles. There is no perinuclear vacuolization.
Intra abdominal fibromatosis (desmoid like)
showing low cellularity and collagenous stroma.
Leiomyosarcoma – low power view shows increased cellularity and
cytological atypia.
High power view of leiomyosarcoma with marked cytological atypia.