There are many different histological types of soft tissue sarcoma. The most common are:
- Gastrointestinal stromal tumor (GIST)
Liposarcoma is one of the most frequently appearing sarcomas. There are many different subtypes of liposarcoma important to recognize because of varying biology.
|Operation specimen with a well differentiated liposarcoma. Click to enlarge.
||Photomicrograph of a well differentiated liposarcoma. Click to enlarge.
||Photomicrograph of a dedifferentiated liposarcoma. Click to enlarge
Well differentiated liposarcoma
|Operation specimen from the posterior abdominal wall demonstrating a liposarcoma growing around the kidney. Click to enlarge.
Well differentiated liposarcoma is a tumor looking almost like a lipoma. The diagnosis is based on the finding of relatively mature fat cells with marked variation in cytoplasmic size. There are often atypical multivacuolated lipoblasts or atypical spindle cells in fibrous areas. The tumor can be lipoma-like, sclerosing, inflammatory or spindle celled. Differential diagnosis is lipoma, although lipoma is very seldom located in the posterior abdominal wall in contrast to in the extremities.
Cytogenetic investigation is useful in the differential diagnosis of these tumors. Ring- or giant cell marker chromosomes derived from chromosome 12 q indicate well differentiated liposarcoma. MDM2 or CDK4 in chromosome 12 is amplified in these tumors. The majority of the well differentiated liposarcoma do not metastasize, although larger tumor more frequently recur.
Dedifferentiated liposarcoma include two distinct growth patterns, one partly well differentiated liposarcoma and the other looking more like a malignant fibrous histiosarcoma or fibrosarcoma. The dedifferentitated component is usually high grade malignant. Dedifferentiation can either be detected in the primary tumor or in a later occurring recurrences. These tumor types are more frequent in the posterior abdominal wall compared to the extremities. Cytogenetically they demonstrate the same findings as in well differentiated liposarcoma.
Gastrointestinal stromal tumor (GIST)
GIST is a cellular tumor in the gastro-intestinal tract with spindle, epitheloid or pleomorphic tumor cells that express KIT (CD117). This tumor originate from the mesenchymal stem cells that produce interstitial Cajal-cells (pacemaker cells). This is the most common mesenchymal tumor in the GI-tract, but comprise only 2,2% of all GI-tumors or 13,9% of small intestinal tumors. GANT (GI autonom nerve tumor) is considered to be a variant of GIST.
The most frequent location for GIST is the stomach (55-65%), small intestine (20-30%), Colon/rectum (5-8%), esophagus and other locations (2-3%).
Before GIST was well recognized it was diagnosed as leiomyoma, leiomyoblastoma or leiomyosarcoma.
Since histological appearance do not correlate well to biological behavior malignancy grading is not used with GIST, instead a risk evaluation according the following table is performed.
|Risk evaluation in GIST
Mitotic count (in 50 lf.)
||< 2 cm
||< 5 cm
||> 10 cm
||Any mitotic count
Immunohistochemical investigation in GIST tumor usually demonstrate positive reaction for KIT (CD117) (95%), CD34 (70-80%), smooth muscle actin (SMA) 20-40% or Caldesmon (80%). Desmine and protein S-100 is usually negative in GIST. It is recommended to include an immunhistochemical panel with CD117, vimentin, desmine, actin, SMA, CD34, protein S-100, and AE1/AE3 when investigating spindle cell tumor in the abdomen.
|Operation specimen from the stomach with GIST. Click to enlarge.
||Operations specimen from the rectum with a GIST. Click to enlarge.
|Photomicrograph of GIST. Click to enlarge.
Mutations in GIST
Majority of GIST has activating mutations in KIT, that codes for a tyrosinkinase receptor. Mutation produce a ligand
|Photomicrograph demonstrating immunohistochemical positively for KIT (CD117) in a GIST. Click to enlarge.
independent activation of tyrosinkinase that induce uncontrolled cell growth. In about 5% of all GIST there is a mutation in the related tyrosinkinase PDGFRA. Mutation in KIT and PDGFRA genes can rather well predict the response to treatment with tyrosinsinhibitor imatinib.
Primary mutations in KIT is seen in exon 9,11,13 or 17. The most frequent is seen in exon 11(about 70%), while about 10-20% is in exon 9. Exson 9 mutations is more frequent in small intestine and seldom seen in stomach GIST. It has been shown that GIST with mutations in exon 11 respond better to imatinib than those with mutations in exon 9.
About 5% of GIST is immunohistochemically negative for KIT (CD117). A majority of these have mutations in PDGFRA in exon 12,14 or 18. PDGFRA mutations are strongly related to GIST located in the stomach and with epitheloid morphology. GIST with exon 18 mutations is most frequent in these cases (80%) and point mutations that produce D842V is known to be associated with resistance to imatinib.
In some GIST no mutations can be detected (wild type). These respond poorly to imatinib treatment.
Patients with GIST that initially respond to imatinib treatment might subsequently over time develop resistance. the resistance is associated with new mutations in the tumor cells (secondary mutations).
Mutation analysis can be performed on frozen, fixed or paraffin-embedded material. The result of such analysis can of importance for deciding type of therapy.
Leiomyosarcoma in the posterior abdominal wall (retroperitoneum) or in the abdominal cavity are often well circumscribed tumors. Microscopically they demonstrate spindle or epitheloid cells with atypia and partly cigar-formed nuclei. Immunohistochemical investigation demonstrate positivity for smooth muscle actin (SMA), actin, or desmine, but negative for CD117 and CD34.
|Operation specimen from the posterior abdominal wall with a leiomyosarcoma probably originating from a large vein. Click to enlarge.
||Photomicrograph of leiomyosarcoma. Click to enlarge.
The most common gynecologic sarcoma is leiomyosarcoma and endometriestroma sarcoma in the uterus. Other types of sarcoma can also appear and be located in all gynecological organs.
The criteria for malignancy grading of uterine sarcomas differ from soft tissue sarcomas and gastro-intestinal sarcoma.
Evaluation of operation specimens
When a soft tissue sarcoma is diagnosed the following information should be included in the pathology report:
- Histological diagnosis
- Malignancy grade /mitoc count
- Tumor size (three dimensions or largest diameter)
- Vessel invasion
- Necrosis (percentage area with necrosis)
- Growth pattern (infiltrative growth or not)
- Tumor localization and infiltration of surrounding tissue'
- Resection borders
- Result of additional special investigations (immunohistochemical or molecular, genetical.