L14 - Soft tissue tumours: how rare entities are now a pilot for the medicine of tomorrow (Dr Francesca Maggiani)

Question 1

What are sarcomas?

Answer 1

Sarcomas are rare tumors that arise from mesenchymal tissues, such as fat, muscle, nerves, and blood vessels.

Question 2

How do sarcomas differ from epithelial and haematological malignancies

Answer 2

Unlike epithelial malignancies (carcinomas, adenocarcinomas) and haematological malignancies (leukaemia’s, lymphomas), sarcomas are derived from connective and structural tissues rather than epithelial or blood-forming cells.

Question 3

Where can mesenchymal tumours be found in the body?

Answer 3

🏥 Mesenchymal tumors can be found in two main locations:

1. Associated with organs – Example: Leiomyoma of the uterus (benign smooth muscle tumor) and Leiomyosarcoma (malignant form).
2. In soft tissue – Found in nerves, blood vessels, adipose (fat) tissue, fibrous tissue, skeletal muscle, and smooth muscle.

Question 4

Why are mesenchymal tumours often handled by tertiary referral centres?

Answer 4

🏛️ Because mesenchymal tumors are rare, they require specialized expertise for diagnosis and treatment. Tertiary referral centers focus on these specific tumors, making it easier to conduct research, specialized training, and controlled studies on their diagnosis and treatment.

Question 5

What is the role of genetics in the diagnosis and treatment of mesenchymal tumours

Answer 5

🧬 Advances in genetics have significantly changed how mesenchymal tumors are diagnosed and treated. Initially, tumors were identified based on morphology (appearance under a microscope), but now, genetic profiling helps classify tumors more accurately, leading to better-targeted treatments.

Question 6

What are the primary types of soft tissue that can develop mesenchymal tumours?

Answer 6

💡 Soft tissue of mesenchymal origin includes:
1️⃣ Adipose tissue (fat)
2️⃣ Skeletal muscle
3️⃣ Nerves
4️⃣ Blood vessels
5️⃣ Fibrous tissue

⚠️ Note: Soft tissue is also present within organs and skin, so mesenchymal tumors can develop in these areas as well.

Question 7

What are the different categories of soft tissue tumours in the WHO classification?

Answer 7

📚 The WHO classification of soft tissue tumors includes:
1️⃣ Adipocytic tumors (related to fat cells)
2️⃣ Fibroblastic and myofibroblastic tumors (derived from fibroblasts or myofibroblasts)
3️⃣ Fibrohistiocytic tumors (containing both fibroblast and immune-like cells)
4️⃣ Vascular tumors (originating from blood vessel cells)
5️⃣ Pericytic tumors (arising from pericytes, which surround blood vessels)
6️⃣ Smooth muscle tumors (from smooth muscle tissue, such as in blood vessels)
7️⃣ Skeletal muscle tumors (from voluntary muscle tissue)
8️⃣ Chondro-osseous tumors (forming bone or cartilage)
9️⃣ Peripheral nerve sheath tumors (from nerves)
🔟 Tumors of uncertain differentiation (poorly classified due to ambiguous features)

Question 8

How are soft tissue tumours identified and diagnosed?

Answer 8

🔬 Diagnosis follows a multi-step approach:
1️⃣ Morphology – Examining tumor appearance under a microscope.
2️⃣ Immunohistochemistry – Using specific markers to confirm tissue origin.
3️⃣ Genetics – In some cases, genetic testing is necessary for classification.

⚠️ If morphology and immunohistochemistry give ambiguous results, the tumor may be classified under tumors of uncertain differentiation.

Question 9

Where are superficial soft tissue tumours commonly found?

Answer 9

🏥 Superficial soft tissue tumors are usually located in the dermis or subcutaneous fat.

Question 10

what are key characteristics for superficial soft tissue tumours?

Answer 10

✅ 99% are superficial
✅ 95% are smaller than 5 cm
✅ Often found in the skin, chest wall, trunk, retroperitoneum, and limbs
✅ Can be challenging to diagnose due to overlapping features with melanocytic and epithelial tumors

Question 11

How do tumour types relate to location, age and symptoms?

Answer 11

🎯 While not absolute, there are patterns in tumour presentation:
✔️ Certain tumours are age-specific (e.g., common in children, young adults, or older adults)
✔️ Some tumours affect a wide age range (22–95 years)
✔️ Tumours can be linked to specific locations in the body (e.g., head & neck, limbs, gastrointestinal tract, retroperitoneum)
✔️ Some tumours are associated with germline mutations (syndromic conditions), while others have no known genetic link

Question 12

What is the age distribution for sarcomas, and where are they commonly found?

Answer 12

📊 Sarcomas most commonly occur in the sixth and seventh decades of life (50s–70s).
📍 Common locations:
1️⃣ Chest wall, trunk, retroperitoneum (largest group)
2️⃣ Limbs
3️⃣ Head and neck
4️⃣ Gastrointestinal tract
5️⃣ Skin (difficult to diagnose due to similarities with melanocytic and epithelial tumors)

Question 13

What is the most common type of soft tissue sarcoma?

Answer 13

🧬 Liposarcoma is one of the most common types of soft tissue sarcomas. However, the classification is continuously evolving, allowing for more precise subtyping of rare soft tissue tumors.

Question 14

What makes rare soft tissue tumours difficult to diagnose?

Answer 14

🔍 Rare soft tissue tumours may have specific genetic mutations that define them. If a key mutation is not found, diagnosis can be challenging. Some tumours remain unclassified due to their infrequency and incomplete genetic profiling.

Question 15

What is the key genetic feature of soft tissue tumours?

Answer 15

🧬 Chromosomal translocations are a hallmark of soft tissue tumours. These translocations fuse two genes together, triggering tumour growth. This differs from carcinomas, which typically have mutations activating cell proliferation pathways.

Question 16

What are the key genetic differences between carcinomas and sarcomas?

Answer 16

🧬 Carcinomas usually have point mutations activating specific pathways, while sarcomas are often caused by chromosomal translocations, where two genes fuse to create an abnormal protein that drives tumor growth.

Question 17

What is an example of a translocation associated with sarcomas?

Answer 17

🔗 The EWSR1 gene is commonly involved in sarcomas. A key example is EWSR1-FLI1 (t[11;22]), which is diagnostic for Ewing sarcoma, a small, undifferentiated tumour seen in children and young adults.

Question 18

Why do different sarcomas sometimes share the same translocation

Answer 18

🔄 Some sarcomas with different morphology and behaviour can have the same translocation but with different fusion partners. This suggests that additional genetic factors influence tumor characteristics beyond just the translocation itself.

Question 19

What are other common genes involved in sarcoma translocations?

Answer 19

🧬 Besides EWSR1, other frequently involved genes include:
✔️ FUS
✔️ WT1
✔️ ERG

Question 20

How does tumor classification improve with modern research?

Answer 20

🏷️ New classifications allow for more precise identification of tumor subtypes. As genetic testing improves, we can distinguish rare tumors by their unique mutations and abnormal translocations making diagnosis and treatment more accurate

Question 21

How do carcinomas and sarcomas differ in their genetic changes?

Answer 21

🔬 Carcinomas often have mutations that activate cell proliferation pathways, while sarcomas are typically driven by chromosomal translocations, which fuse two genes together and lead to tumor formation.

Question 22

What makes Ewing sarcoma unique in terms of histology and genetics?

Answer 22

🏥 Ewing sarcoma is a small, round, undifferentiated tumor that resembles embryonic cells. It is characterized by the EWSR1-FLI1 translocation (t[11;22]), which is diagnostic for this tumor.

Question 23

Why do some sarcomas with different behaviors share the same genetic translocation?

Answer 23

🔄 The same translocation can occur in different tumors, but their behavior and morphology vary. This suggests that additional genetic or environmental factors contribute to the specific tumor type and its aggressiveness.

Question 24

Why are sarcomas challenging to diagnose clinically?

Answer 24

🏥 Sarcomas are often rare, highly variable, and can mimic other tumor types (e.g., epithelial or melanocytic tumors). They may also alter surrounding tissue, making clinical and histological diagnosis difficult.

Question 25

What factors influence where a sarcoma develops in the body?

Answer 25

📍 Sarcomas can arise anywhere, but their location is influenced by: ✔️ Age (e.g., Ewing sarcoma in younger patients) ✔️ Tissue type (e.g., liposarcoma in fatty tissue) ✔️ Genetic mutations (e.g., EWSR1 in soft tissue and bone)

Question 26

What are the challenges of diagnosing sarcomas in the skin?

Answer 26

⚠️ In the skin, mesenchymal tumors must be distinguished from: ✔️ Melanocytic tumors (e.g., melanoma) ✔️ Epithelial tumors (e.g., carcinoma) ✔️ Soft tissue tumors affecting the dermis Overlapping features can make diagnosis complex and require genetic testing.

Question 27

what are lipoma

Answer 27

🟡 Lipoma is the most common benign mesenchymal tumor, composed of mature adipose (fat) tissue.

Question 28

How do lipomas typically apear

Answer 28

It typically appears as a soft, mobile lump under the skin, enclosed in a thin, shiny capsule.

Question 29

How do lipomas appear under the microscope?

Answer 29

🔬 Lipomas contain large, empty-appearing fat cells (adipocytes) with small, peripheral nuclei. They show no mitotic activity, minimal atypia, and are well-circumscribed.

Question 30

What are the clinical features of lipomas?

Answer 30

🏥 Lipomas are usually: ✔️ Soft, painless lumps under the skin ✔️ Well-circumscribed with a thin capsule ✔️ Yellowish in appearance due to fat content ✔️ Found in subcutaneous fat, often on the trunk, neck, or limbs

Question 31

What is a spindle cell lipoma?

Answer 31

🔍 A spindle cell lipoma is a benign fat tumour seen mostly in elderly men, often in the neck or shoulder. It has spindle-shaped cells and mild atypia but remains non-cancerous.

Question 32

What is the immunohistochemistry marker for a spindle cell lipoma

Answer 32

✔️ CD34+ immunohistochemistry marker

Question 33

What is an angiolipoma, and why is it painful?

Answer 33

❤️ Angiolipoma is a benign fat tumor with numerous blood vessels, often found in the wrists or arms. It can be painful due to thrombi (blood clots) forming in its blood vessels. Ut is common in young adults

Question 34

What is a hibernoma, and where does it occur?

Answer 34

🟤 Hibernoma is a benign fat tumor made of brown fat, a type of fat typically found in embryos. It occurs in unusual locations like the back (near the scapula) or deeper tissues.

Question 35

What is hibernoma associated with?

Answer 35

✔️ Associated with UCP1 expression (a marker of brown fat)

Question 36

How do lipomas differ from malignant fat tumors?

Answer 36

⚠️ Unlike liposarcomas, lipomas are: ✔️ Well-circumscribed ✔️ Uniform in fat cell size ✔️ Lacking mitotic activity ✔️ Not infiltrative into surrounding tissues

Question 37

What are the key differences between a lipoma and a liposarcoma?

Answer 37

Lipoma (Benign) vs. ⚠️ Liposarcoma (Malignant): - Growth: Lipomas grow slowly, while liposarcomas can grow rapidly. - Capsule: Lipomas have a well-defined, thin capsule; liposarcomas are poorly circumscribed and may infiltrate surrounding tissue. - Fat Cells: Lipomas contain uniform, mature fat cells; liposarcomas have atypical lipoblasts with nuclear atypia. - Mitotic Activity: Lipomas have little to no mitotic activity, while liposarcomas show increased mitotic activity. - Necrosis: Rare in lipomas but can be present in aggressive liposarcomas. - Symptoms: Lipomas are usually painless; liposarcomas may cause pain or compress nearby structures. - Location: Lipomas are typically superficial (subcutaneous fat), whereas liposarcomas are often deep-seated in soft tissues.

Question 38

What is a Well-Differentiated Liposarcoma (Atypical Lipomatous Tumour)?

Answer 38

✅ A well-differentiated liposarcoma is a low-grade malignant tumour that arises from fat cells. It is the most common malignant adipocytic tumour, accounting for 40-45% of all liposarcomas.

Question 39

Who is affected by Liposarcomas

Answer 39

👥This tumour primarily occurs in adults between the ages of 40 and 60 and is very rare in children.

Question 40

Where do liposarcomas occur

Answer 40

It is commonly found in the retroperitoneum, limbs, and other soft tissues.

Question 41

What are the genetic characteristics of liposarcomas

Answer 41

It is characterized by amplification of the MDM2 gene, which plays a role in tumour development.

Question 42

How does a Well-Differentiated Liposarcoma behave?

Answer 42

Although it is technically malignant, a well-differentiated liposarcoma does not metastasize in most cases. However, it can be locally aggressive, meaning it may grow and invade nearby tissues

Question 43

what is the risk of recurrence in liposarcomas?

Answer 43

🔄 The risk of recurrence is high, particularly when the tumour is located in the retroperitoneum, where complete surgical removal is often difficult.

Question 44

What do liposarcomas look like under the microscope

Answer 44

🔬 This tumour consists of large fat cells with scattered atypical cells (lipoblasts), which have enlarged, irregular nuclei.

Question 45

How are liposarcomas treated?

Answer 45

💊 The main treatment is wide surgical excision, and in some cases, radiation therapy may be used to reduce the risk of recurrence.

Question 46

What is a dedifferentiated liposarcoma?

Answer 46

⚠️ A dedifferentiated liposarcoma is a more aggressive form of liposarcoma that arises from a previously well-differentiated liposarcoma.

Question 47

How often does dedifferentiation occur?

Answer 47

🔄 This transformation occurs in about 10% of cases, especially in tumours located in the retroperitoneum.

Question 48

In what age group is dedifferentiation of liposarcomas most common?

Answer 48

👴 more common in older adults, with a slight preference for men.

Question 49

what is a genetic feature of a dedifferentiated liposarcoma

Answer 49

🧬 Like well-differentiated liposarcoma, it involves MDM2 gene amplification, but additional genetic mutations contribute to its more aggressive behaviour.

Question 50

How does a dedifferentiated liposarcoma behave?

Answer 50

📈 A dedifferentiated liposarcoma grows more rapidly than a well-differentiated liposarcoma and has a higher risk of recurrence and metastasis.

Question 51

How does a dedifferentiated liposarcoma appear under the microscope

Answer 51

🧬 There is often a sharp transition from well-differentiated fat cells to high-grade, poorly differentiated tumour cells, which look very abnormal and aggressive.

Question 52

How are dedifferentiated liposarcomas treated?

Answer 52

🩺 Treatment involves surgical removal, but due to its aggressive nature, chemotherapy and radiation therapy are often required.

Question 53

Why is a retroperitoneal liposarcoma more dangerous?

Answer 53

📏 When a liposarcoma occurs in the retroperitoneum (the space at the back of the abdomen), it has room to grow without being detected early.

Question 54

Which organs may be displaced by retroperitoneal liposarcoma?

Answer 54

🩻 By the time it is diagnosed, the tumour is often very large and may displace organs such as the stomach, intestines, and kidneys.

Question 55

Why is surgical removal or retroperitoneal liposarcoma more challenging and risky?

Answer 55

🩸 The tumour is located near major blood vessels like the aorta and vena cava, making surgical removal much more challenging and risky. ⚠️ Even if it is initially well-differentiated, incomplete removal increases the risk of recurrence, and each recurrence increases the chance of it becoming a dedifferentiated liposarcoma, which can metastasize.

Question 56

Why is the same tumour (as a retroperitoneum) called an "Atypical lipomatous tumour" in soft tissue?

Answer 56

🦵 When this tumour occurs in the limbs or other soft tissue rather than the retroperitoneum, it is easier to detect and completely remove with surgery. Because of this it can be filly excised with good margins so has a lower risk of recurrence and does not usually metastasise. 🏥 In some countries, especially the United States, calling it an “Atypical Lipomatous Tumour” instead of “Well-Differentiated Liposarcoma” is done to avoid classifying the patient as having cancer, which could increase insurance costs. However, both terms describe the same tumour with the same genetics and morphology.

Question 57

What is Myxoid Liposarcoma?

Answer 57

✅ Myxoid Liposarcoma is a type of high-grade soft tissue sarcoma that arises from fat cells but has very few mature fat cells compared to other liposarcomas. Instead, it contains tiny primitive cells in a myxoid (gel-like) background.

Question 58

who is affected by Myxoid liposarcoma?

Answer 58

👥 It is more common in young adults, typically peaking in the 4th and 5th decades of life. Unlike many other sarcomas, there is no gender preference.

Question 59

Where does myxoid liposarcoma occur?

Answer 59

It most commonly affects the extremities, particularly the proximal thigh.

Question 60

Is Myxoid liposarcoma found in the retroperitoneum?

Answer 60

🚫 A primary retroperitoneal myxoid liposarcoma is extremely rare, but metastases to the retroperitoneum are more common.

Question 61

How does Myxoid Liposarcoma appear under the mucroscope?

Answer 61

🔬 This tumour is unique because it does not have the typical yellowish fat-rich appearance of most liposarcomas. Instead, it has: 🩸 Numerous blood vessels, arranged in a highly characteristic branching pattern. 🦠 Small, primitive tumour cells with minimal cytoplasm. 🫧 A myxoid (gel-like) background, giving the tumour its name. 🔄 Some signet ring lipoblasts, which are cells with a nucleus pushed to the side by fat droplets.

Question 62

What genetic abnormalities are found in Myxoid Liposarcoma?

Answer 62

🧬 Unlike other liposarcomas that involve MDM2 amplification, myxoid liposarcomas have specific gene fusions: 🔗 Most common: t(12;16)(q13;p11.2) → FUS-DDIT3 fusion 🧬 Rare (~2%) cases: t(12;22)(q13;q12) → EWSR1-DDIT3 fusion

Question 63

How can the genetic abnormalities in Myxoid Liposarcoma be detected?

Answer 63

🧪 translocations can be detected using fluorescence in situ hybridization (FISH) or more advanced genetic testing like next-generation sequencing (NGS).

Question 64

How does Myxoid Liposarcoma respond to treatment?

Answer 64

💡 One major advantage of myxoid liposarcoma is that it responds very well to radiotherapy. --> When treated with radiation, the tumour shrinks significantly, making surgical removal easier and less aggressive

Question 65

What can radiation induce to myxoid liposarcoma?

Answer 65

🧪 Radiation can also induce changes in the tumour, leading to: ✅ More mature fat cells (adipocytic differentiation) ✅ Fibrosis (scarring), which makes excision easier

Question 66

does myxoid liposarcoma metastasise?

Answer 66

⚠️ Yes, it is a high-grade tumour, so it has a risk of metastasis e.g. to the lung, bone and retroperitoneal. To make sure metastases doesn't occur, regular follow-ups are required.

Question 67

What improves myxoid liposarcoma outcomes?

Answer 67

👨‍⚕️ Early detection and treatment improve outcomes, especially when radiotherapy and surgery are combined.

Question 68

Where do smooth muscle tumours originate from?

Answer 68

Smooth muscle tumours can arise from: 🩸 Blood vessels – Often linked to vessel walls in deep and superficial tissues. 💇 Piloerector muscles – Found in the skin, responsible for goosebumps.

Question 69

Where do smooth myscle tumours typically occur in the body?

Answer 69

🩸 Blood vessels – Many smooth muscle tumours in superficial and deep soft tissues are linked to blood vessels. 💇 Skin (dermis) – They can arise from piloerector muscles, which are responsible for goosebumps. 🫁 Organs – These tumours can also form in the walls of internal organs, such as the uterus, intestines, or lungs.

Question 70

How do smooth muscle tumours appear?

Answer 70

They can have different growth patterns: 🟠 Well-circumscribed lumps – These are rounded and easy to distinguish from surrounding tissue. 🩸 Vessel-associated tumours – These grow around blood vessels. ⚠️ Infiltrative tumours – These spread into nearby tissues, making them harder to remove completely.

Question 71

Are there any risk factors for developing smooth muscle tumours?

Answer 71

⚠️ Some smooth muscle tumours have been linked to: 🦠 Epstein-Barr virus (EBV) infection 🦠 Immunosuppression, such as in organ transplant patients or those with HIV/AIDS 🧬 Genetic mutations, though less frequently

Question 72

What are the key features of cutaneous smooth muscle tumours?

Answer 72

🩹 Superficial – Found just under the skin. 🔵 Small & multiple – Often appear in clusters. ⚡ Painful – Can cause discomfort, unlike many other benign tumour

Question 73

Where do leiomyosarcomas typically arise from?

Answer 73

Leiomyosarcomas arise from smooth muscle cells, most commonly in the blood vessels or soft tissues

Question 74

Where are Leiomyosarcomas frequently found?

Answer 74

They are frequently found in the extremities (arms and legs), the retroperitoneum (the area behind the abdominal organs), and sometimes in organs like the uterus. In rare cases, they can also occur in the bone, breast, colon, epididymis, or mediastinum (chest area).

Question 75

How can you tell a leiomyosarcoma apart from a benign smooth muscle tumour?

Answer 75

✅ A leiomyoma is a benign smooth muscle tumour that is well-circumscribed, grows slowly, and does not invade surrounding tissues. It has few mitotic figures (dividing cells) and lacks necrosis (cell death). ❌ A leiomyosarcoma, on the other hand, is malignant and shows higher mitotic activity, larger and irregular nuclei (atypia), and areas of necrosis. Unlike leiomyomas, they can spread to other tissues and often require aggressive treatment.

Question 76

What are the key microscopic features of a leiomyosarcoma?

Answer 76

🔬 Under the microscope, leiomyosarcomas have spindle-shaped cells with elongated nuclei and abundant eosinophilic (pink) cytoplasm. Atypia is present, meaning the nuclei look irregular and enlarged. The tumour also has increased mitotic figures, showing rapid cell division. If necrosis is present, it suggests a higher-grade tumour with more aggressive behaviour.

Question 77

What is the significance of tumour location in leiomyosarcoma?

Answer 77

📍 The location of an LMS plays a significant role in its behaviour and treatment options. Tumours in the retroperitoneum are particularly challenging because they have room to grow undetected before causing symptoms. They may also be difficult to remove completely due to their proximity to major blood vessels and organs. However, LMS in the limbs or superficial soft tissues is often detected earlier and can be excised with wider margins, improving the chances of complete removal.

Question 78

Why are some smooth muscle tumours classified as "uncertain malignant potential" (UMP)?

Answer 78

🤔 Some tumours do not clearly fit into either the benign or malignant category. These tumours might have some atypia (abnormal nuclei) but no necrosis, or they might show increased mitotic activity but otherwise look bland. Since it is difficult to predict their behaviour, they are classified as tumours of uncertain malignant potential (UMP). Patients with these tumours usually require careful monitoring to check for recurrence or aggressive behaviour over time.

Question 79

what are the malignant mitotic rates at different sites?

Answer 79

The number of mitotic figures (dividing cells) per 10 high-power fields (HPF) is crucial. - Soft tissue LMS: More than 1-2 mitoses/10 HPF. - Skin/subcutaneous LMS: More than 2 mitoses/10 HPF. - Retroperitoneal LMS: More than 5 mitoses/10 HPF, or 1-4 mitoses/10 HPF if necrosis is present and the tumour is larger than 7.5 cm.

Question 80

What is a rhabdomyoma?

Answer 80

A rhabdomyoma is a rare benign tumour of mature skeletal muscle.

Question 81

What are the different types of Rhabdomyoma?

Answer 81

👶 Fetal type – Occurs in infants and young children. 👩‍🦰 Adult type – Most common in men around 60 years old. 🖕Genital type – Found in the vulva, vagina, and other genital areas.

Question 82

Where are Rhabdomyomas (Skeletal muscle tumours) commonly found in the body?

Answer 82

👩‍🦰Head and neck region, especially the oral cavity. Less commonly found in other areas of the body.

Question 83

What are the key features of Rhabdomyoma

Answer 83

* Not associated with tuberous sclerosis. * Some cases may arise due to muscle degeneration and regeneration. * Very rare, with a male predominance (75%).

Question 84

What age group is affected by Rhabdomyosarcoma?

Answer 84

* Young children (~4-5 years old). * Teenagers and young adults. * Elderly patients (rarely).

Question 85

What are common locations for Rhabdomyosarcoma

Answer 85

* Head and neck (including orbit and perimeningeal areas). * Genitourinary tract (e.g., vagina, perianal region). * Extremities (arms and legs).

Question 86

What are the subtypes of rhabdomyosarcoma

Answer 86

1️⃣ Embryonal RMS (most common) – Often linked to TP53 mutations and p53 overexpression. Botryoid variant – Occurs in very young children. 2️⃣ Alveolar RMS – More aggressive, often seen in older children and teenagers. 3️⃣ Pleomorphic RMS – Mainly affects adults and has a poor prognosis.

Question 87

What are diognostic features of rhabdomyosarcoma

Answer 87

🔬 Shows myogenic differentiation (positive for MyoD1 and myogenin). 🔬 Unlike some other sarcomas, no specific gene fusion is associated. 🔬 Often displays recurrent copy number changes in the genome.

Question 88

What is prognosis and treatment like for rhabdomyosarcom

Answer 88

* Anaplasia (abnormal cell structure) is linked to worse outcomes. * Requires aggressive treatment with surgery, chemotherapy, and/or radiation.

Question 89

What is botryoid embryonal rhabdomyosarcoma?

Answer 89

Botryoid embryonal rhabdomyosarcoma is a subtype of rhabdomyosarcoma that arises in mucosal-lined hollow organs.

Question 90

What are common locations for botryoid embryonal rhabdomyosarcoma?

Answer 90

📍Bladder 📍Biliary tract & extrahepatic bile ducts 📍Vagina 📍Upper respiratory tract (e.g., nasopharynx, sinuses) 📍Rarely found in the eyelid or anal region

Question 91

What are microscopic features for botryoid embryonal rhabdomyosarcoma?

Answer 91

🔬 Composed of small, round blue cells. 🔬 Cells cluster near the surface of the mucosa and become less dense deeper down. 🔬 Shows some pinkish cytoplasm, indicating myogenic differentiation (expressing myogenin).

Question 92

What is prognosis and treatment like for botryoid embryonal rhabdomyosarcoma?

Answer 92

Better prognosis compared to other rhabdomyosarcoma subtypes. Responds well to chemotherapy. Surgical excision is often necessary but can be highly invasive.

Question 93

Are rhabdomyosarcomas linked to genetic syndromes?

Answer 93

✅ Most cases of rhabdomyosarcoma occur sporadically, but some can be linked to inherited syndromes.

Question 94

what are genetic associations with rhabdomyosarcomas

Answer 94

🧬Most cases occur due to somatic mutations, with no inherited predisposition 🧬A small proportion arises in children with familial cancer syndromes, particularly those affecting the RAS or Hedgehog pathways

Question 95

What are some syndromes linked to rhabdomyosarcoma?

Answer 95

🧑‍⚕️ Costello syndrome (HRAS mutation) 🧑‍⚕️ Neurofibromatosis type 1 (NF1) – more commonly linked to neurogenic tumors 🧑‍⚕️ Noonan syndrome (PTPN11 & others) 🧑‍⚕️ Beckwith-Wiedemann syndrome (Chromosome 11p15 changes) 🧑‍⚕️ Dicer syndrome (DICER1 mutations) 🧑‍⚕️ Li-Fraumeni syndrome (TP53 mutations) 🧑‍⚕️ Gorlin syndrome (PTCH1 mutations)

Question 96

What is the 1000 genome project (2008-2015) ?

Answer 96

✅ Aimed to identify and characterize genetic variations in human genomes ✅ Sequenced 2600 individuals from 26 global populations ✅ Used low-coverage whole-genome sequencing, SNP arrays, and deep exome sequencing ✅ Helped uncover common genetic polymorphisms (≥1% frequency) across populations ✅ First large-scale genome sequencing project, creating a freely available database for research

Question 97

What is the 100,000 genomes project (UK, 2013 - 2018)

Answer 97

✅ Expanded genome sequencing to 100,000 whole genomes ✅ Focused on rare diseases and cancer genetics ✅ Integrated genomic data into the NHS, enabling personalized medicine ✅ Led to the first clinical diagnoses based on whole-genome sequencing ✅ Showed how genetic insights can guide treatment strategies

Question 98

Why are the 1000 and 100,000 genome projects important for sarcoma research?

Answer 98

📌 Sarcomas are rare, making it hard to study them in large numbers 📌Genomic data helps identify mutations that drive different sarcoma subtypes 📌Aids in targeted therapy, ensuring the best possible treatment for each patient

Question 99

What is Whole Genome Sequencing (WGS)?

Answer 99

🧬 Whole genome sequencing (WGS) is a technique used to determine the complete DNA sequence of an organism. It helps identify mutations that may contribute to diseases like cancer and genetic disorders.

Question 100

Why is WGS important for medical research?

Answer 100

🔎 WGS is a powerful tool in medical research because it helps detect genetic variations, including: 1️⃣ Single nucleotide polymorphisms (SNPs) – Small DNA changes. 2️⃣ Copy number variations (CNVs) – Changes in the number of gene copies. 3️⃣ Structural variants – Large-scale DNA alterations.

Question 101

How does WGS help in cancer diagnosis?

Answer 101

🏥 WGS allows doctors to analyze tumor DNA, identifying specific genetic abnormalities. This can help: Confirm or change a diagnosis. Identify targeted therapies. Predict how a tumor will behave.

Question 102

What makes fresh tissue analysis challenging?

Answer 102

🧪 Unlike traditional biopsies (which are preserved in formalin), fresh tissue samples must be processed immediately. This requires quick coordination between doctors, lab teams, and equipment.

Question 103

How has WGS changed the way biopsies are handled?

Answer 103

📦 Traditionally, biopsy samples were preserved in formalin and processed later. Now, with WGS, some tissue is immediately frozen and analyzed. 🚨 This requires rapid coordination between medical teams but leads to faster, more accurate diagnoses.

Question 104

What happens if a biopsy has limited tissue?

Answer 104

Sometimes, a biopsy does not contain enough high-quality DNA for sequencing. In these cases, doctors may: 🩺 Use alternative sequencing methods (like targeted panels). 🩺Rely on liquid biopsies to analyze tumor DNA from the blood.

Question 105

can WGS help in rare cancers?

Answer 105

🎯 Yes! Rare cancers, like alveolar rhabdomyosarcoma, have few cases, making research difficult. However, if WGS finds mutations that are also present in other cancers, existing treatments could be repurposed.

Question 106

❓ What is Next-Generation Sequencing (NGS)?

Answer 106

🚀 Next-Generation Sequencing (NGS) is an advanced technique that allows doctors to: - Analyze DNA and RNA more efficiently. - Detect translocations (which help diagnose tumors). - Identify additional mutations that could influence treatment.

Question 107

How can WSG improve early cancer detection

Answer 107

🩸 Some hospitals now use circulating tumor DNA (ctDNA) in blood to detect cancer earlier than traditional scans or biopsies. This liquid biopsy method is: ✅ Less invasive ✅ Faster ✅ More convenient for patients

Question 108

How does liquid biopsy compare to traditional scans?

Answer 108

📊 Traditional imaging (like CT scans) may miss tiny tumors. 🩸 Liquid biopsies can detect tumor DNA earlier, improving monitoring and treatment decisions

Question 109

How is WGS used beyond cancer research?

Answer 109

❓ How is WGS used beyond cancer research? 🌍 Genomics is transforming many areas of medicine, including: 👶 Newborn screening – Identifying rare diseases early. 🤰 Prenatal testing – Detecting fetal DNA in maternal blood for early diagnosis. 🧬 Rare disease research – Finding genetic causes of inherited conditions.

Question 110

How is WGS used in hospitals today?

Answer 110

🏥 Many hospitals now routinely sequence tumors to: Identify genetic mutations that guide treatment. Detect recurrence risks early. Improve diagnostic accuracy.

Question 111

What is personalised medicine?

Answer 111

🎯 Personalized medicine tailors treatments based on a patient's unique genetic profile. 🛠 Instead of a "one-size-fits-all" approach, doctors can: ✅ Match treatments to specific mutations. ✅ Avoid ineffective therapies. ✅ Improve patient outcomes.

Question 112

How does WGS help find a new drug target?

Answer 112

💊 If WGS identifies genetic mutations in a rare cancer that also appear in a common cancer, existing drugs may be repurposed. 🔬 This speeds up treatment development and reduces costs.

Question 113

How does WGS improve rare cancer treatments?

Answer 113

🔗 By identifying genetic links between rare and common cancers, WGS helps: Find shared drug targets. Improve early detection. Develop personalized therapies.

Question 114

What other medical areas use WGS?

Answer 114

🔬 WGS is used for more than just cancer! It helps in: 👶 Newborn screening – Identifying genetic conditions early. 🧬 Rare disease diagnosis – Finding inherited disorders. 🤰 Prenatal testing – Detecting fetal DNA for non-invasive genetic screening. 💊 Pharmacogenomics – Predicting how patients respond to medications.