Introduction:
Sarcomas are rare cancers which develop in the bones and soft tissues, including fat, muscles, blood vessels, nerves, deep skin tissues and fibrous tissues.
The incidence is approx 1% of all Cancer and is seen across all the age groups. Patients should preferably be treated in specialized centres by a multidisciplinary team comprising of sarcoma specialists including surgical, orthopaedic, medical oncologists, radiologists, pathologists, oncology nursing as well as rehabilitation services.
FAQ for Pathology in Sarcomas:
1. What is pathology, and why is it important in diagnosing sarcoma?
Pathology is the study of the cause, the pathogenesis, the morphological changes and functional derangement in cells, tissues and organs that underlie disease. It is based on the analogy: “To defeat the enemy (Sarcoma/Cancer), one should know (Pathology) the enemy”
2. What is the difference between blocks and slides?
The tissue biopsy taken is initially kept in chemical (Formalin) to prevent decays and later processed in other chemicals and finally tissue is made to merge in wax medium (Paraffin wax blocks). Subsequently, this tissue block can be cut into multiple very thin section/slice (4-8 microns; thinner than onion peel) and taken on transparent glass slide which is then stained by colour , which can be further studied for histology examination under the microscope for diagnosis. Block contains the tissue in wax medium, while glass slide is having one very thin section of tissue.
3. Why are blocks important, and how are they used in sarcoma diagnosis?
Blocks contain the preserved tumor tissue which can be safely stored for many years. They can be utilized immediately for making diagnosis and even years later if some new predictive tests comes which promises an effective therapeutic target
4. How does a pathologist diagnose sarcoma from a biopsy or surgical specimen?
Pathologist diagnose the sarcoma/cancer by evaluating the histology of cells and tissues section (Biopsy) on glass slide under the microscope, which is a basic test. Once a pathologist confirms the diagnosis of sarcoma, then it is classified as per recent WHO (World Health Organization) classification, so that a standard term for diagnosis is used worldwide.
5. What tests are performed on my biopsy to confirm sarcoma?
After performing the above mentioned basic histopathology test, pathologist may need to confirm and subtype a sarcoma by performing specialized tests like Immunohistochemistry (IHC), FISH (Fluorescent In-Situ Hybridization) and Next Generation Sequencing(NGS). These test not only confirm the diagnosis but also guides for the effective therapeutic selection of drugs and therapeutic regime
6. What is NGS (Next-Generation Sequencing)?
NGS are new technologies which have contributed to developments in sarcoma research. NGS is used for DNA and RNA sequencing and variant/mutation detection. NGS can sequence hundreds and thousands of genes. Genes are made of DNA and are located on chromosomes in the nucleus of cells. A gene is a segment of DNA that contains information for making proteins or controlling other genes.
7. Why is NGS recommended for sarcoma patients?
NGS can help to diagnose and classify the sarcomas as per WHO Classification which may at times difficult to diagnose using traditional basic methods. It can help to identify mutations that can be targeted with drugs. Based upon the mutation, patient can be recruited in clinical trials like immunotherapy and targeted drugs. NGS can also help identify germinal mutations that may be hereditary and hence can provide information useful for genetic counseling to the patient and relatives
8. How many blocks are typically created after surgery, and how many are needed for an accurate diagnosis?
There is no specific number however number of blocks are made depending on the size of the tumor, heterogeneous areas within the tumor etc. The minimum numberof blocks made are 1 section/cm of the largest dimension of the tumor.
9. What is immunohistochemistry (IHC), and why is it used in sarcoma diagnosis?
IHC is a technique used in surgical pathology for histological classification of tumor and utilizes antibodies targeted against certain antigens. Immunohistochemistry (IHC) plays a vital role in the diagnosis and management of sarcoma. Traditional IHC stains are used to identify specific proteins in tumour cells indicating a specific histological differentiation (e.g. desmin, myogenin and Myo D1 expression in tumours with skeletal muscle differentiation, SMA for smooth muscle differentiation etc ). Recently, mutation specific molecular IHC (like SS18 for Synovial Sarcoma, DDIT3 for myxoid liposarcoma, CAMTA1 for hemangioendothelioma etc ) have emerged as the game changer in the diagnosis, as they can be done faster and cheaper than molecular testing, and also have far more accessibility across various labs which may not have high-end molecular techniques.
10. How do molecular or genetic tests (like FISH or PCR) help in diagnosing specific types of sarcoma?
Many sarcomas are associated with specific type of mutation, gene rearrangement which is the defining characteristic of a particular sarcoma like EWSR1-FLI1 fusion in Ewing Sarcoma, SS18-SSX1/2/3/4 fusion in synovial sarcoma etc. So the molecular tests demonstrates the defining mutation, hence not only confirms the diagnosis , but can also provide the effective targeted drug of choice, for eg ALK rearranged Epithelioid Inflammatory Myofibroflastic sarcoma shows good response to ALK inhibitors ( crizotinib, ceritinib etc.)
11. Why is it important to store pathology blocks and slides? What storage temperature is required for blocks?
Storage of slides and especially blocks is important, as tumor tissue is precious because it contains diagnostic, prognostic, therapeutic and molecular information. If the tumor is not responding to treatment as per the diagnosis, the blocks can be reviewed again for diagnosis or molecular testing. Regarding storage, few simple precautions are required like blocks have to stored in an air-tight plastic box of reasonable strength at room temperature and should be kept away from heat or direct sunlight.
12. Why might I be told to have my blocks reviewed at AIIMS or another specialized center if I already have a biopsy report from a private hospital ?
Many sarcoma look similar on Histopathology slide diagnosis, but different sarcoma have different management. Hence, it is very Important to have a precise and accurate diagnosis. Since sarcomas are rare cancer and expertise in sarcoma pathology is usually available in specialized/ tertiary cancer care centres, the blocks should preferably be reviewed at these centres.
13. What are sarcoma subtypes, and why is it important to identify them?
There is a long list of sarcoma subtype depending upon the histological and molecular classification of the tumor, hence they are classified as per recent WHO classification and it is very important for correct identification as different subtypes have different management. Some subtype may be sensitive to chemotherapy while other may be resistant.
14. What information is included in a pathology report, and how does it affect my treatment plan?
The pathology report includes histological description of tumor with final diagnosis (Histologcal subtype) along with Grade, margins status in case of resection specimen. Collectively all of these parameters decide the optimal plan and sequence of treatment
15. What does “tumor grade” mean in the context of sarcoma? How does it relate to prognosis and treatment?
Grade tells about the aggression of the sarcoma. The most widely used grading system is the French Federation of Cancer Centers Sarcoma Group (FNCLCC) system, which is based on three parameters: Differentiation, Mitotic activity, Necrosis; and are graded as 1 to 3. Grade 1 sarcoma are considered low grade; while grade 2/3 sarcoma are considered high grade.
16. What are clear surgical margins, and why are they important in sarcoma treatment?
Clear margins are adequate margins which comprises of normal tissue at the periphery of the tumor, taken during surgery. Clear and adequate margins significantly reduces the risk of recurrence and metastasis of sarcoma
17. How does pathology guide decisions about surgery, chemotherapy, or radiation?
Depending upon the histological subtype and grade, some sarcoma undergo upfront surgery while some sarcoma (Like Ewing Sarcoma) undergo first chemotherapy and then followed by surgery. Some high grade sarcoma may not require chemotherapy at all like mesenchymal chondrosarcoma. Similarly some sarcoma can be radiation sensitive while some may be radiation resistant. Hence accurate diagnosis and grading will subject the patient for optimum modality of treatment and prevent over treatment and under treatment
18. What role does a multidisciplinary team, including the pathologist, play in managing sarcoma?
Coordination between the multidisciplinary team provides optimum management to the sarcoma patients. Research studies have shown that sarcoma patients treated in high-volume centres with a multidisciplinary team have a significantly better survival and functional outcomes
19. If a biopsy result is inconclusive, what additional steps can be taken to ensure an accurate diagnosis?
Blocks should be reviewed at specialized sarcoma centers, and may be subjected to molecular testing as and when required for additional information for a conclusive diagnosis. If tissue is inadequate, a repeat biopsy may need to be considered.
Contributed by:
Dr Sunil Pasricha (MD Pathology, Fellowship Oncopathology)
Senior Consultant, Oncopathology, Rajiv Gandhi Cancer Institute & Research Centre, New Delhi