L15 – Soft Tissue Tumours: How Rare Entities Are Now a Pilot for the Medicine of Tomorrow Flashcards
What defines “soft tissue” in the context of tumour pathology?
Soft tissue refers to mesenchymal tissues—including adipose, muscle, nerves, vessels, and fibrous tissue—that form the body’s supportive framework.
Besides extremities, where else can soft tissue tumours arise?
They can develop in organs and the skin because these regions contain substantial mesenchymal tissue.
What is the scope of the WHO classification for soft tissue tumours?
It categorises tumours based on differentiation into adipocytic, fibroblastic/myofibroblastic, fibrohistiocytic, vascular, pericytic, smooth muscle, skeletal muscle, chondro-osseous, peripheral nerve sheath tumours, and tumours of uncertain differentiation.
What percentage of benign soft tissue tumours are reported to be superficial?
Approximately 99% of benign soft tissue tumours are superficial.
What size limitation is typical for most benign soft tissue tumours?
About 95% are less than 5 cm in size.
How are soft tissue sarcomas generally distributed in clinical practice?
They are rare; their incidence is low compared to benign counterparts, and they often present with distinct size and depth characteristics.
What constitutes adipocytic tumours?
These are tumours derived from adipose tissue, ranging from benign lipomas to malignant liposarcomas.
What is the most common malignant adipocytic tumour?
Atypical lipomatous tumour, also known as well-differentiated liposarcoma, which accounts for 40–45% of liposarcomas.
What key genetic alteration is associated with well-differentiated liposarcomas?
They characteristically display ring or giant marker chromosomes with amplification of genes (e.g. MDM2) from the 12q13–15 region.
How is dedifferentiated liposarcoma distinguished from its well-differentiated counterpart?
Dedifferentiated liposarcoma occurs in a subset of cases (around 10%) and shows areas of high-grade non-lipogenic sarcoma, often in retroperitoneal sites.
What percentage of adult sarcomas does myxoid liposarcoma represent?
Myxoid liposarcoma represents about 5% of adult sarcomas.
Which chromosomal translocation is most frequently found in myxoid liposarcoma?
The recurrent t(12;16)(q13;p11.2) translocation, resulting in the FUS-DDIT3 fusion gene.
What is the significance of the rare t(12;22)(q13;q12) rearrangement?
It is found in a small percentage (approximately 2%) of myxoid liposarcomas and results in an EWSR1-DDIT3 fusion gene.
What tissue do smooth muscle tumours originate from?
They arise from smooth muscle, which can be found in vessel walls or the erector pili muscles of the skin.
How are cutaneous smooth muscle tumours typically characterised?
They are usually superficial, small, often multiple, and can be painful; some are linked to immunodeficiency and EBV infection.
What is leiomyosarcoma and where is it commonly located?
Leiomyosarcoma is a malignant smooth muscle tumour often found in the extremities, retroperitoneum, and large vessels such as the inferior vena cava.
What diagnostic criteria are used for leiomyosarcoma in soft tissue?
Criteria include mitotic figures per 10 high-power fields, tumour size, depth, and the presence of necrosis, with thresholds varying by site.
What distinguishes a rhabdomyoma from a rhabdomyosarcoma?
Rhabdomyoma is a benign tumour of mature skeletal muscle, whereas rhabdomyosarcoma is malignant and shows immature myogenic differentiation.
Which subtype of rhabdomyosarcoma is most prevalent in children?
Embryonal rhabdomyosarcoma is the most common subtype in the paediatric and adolescent populations.
What histological features are typical of embryonal rhabdomyosarcoma?
They often consist of primitive mesenchymal cells with myogenic differentiation, sometimes positive for MyoD1 or myogenin.
Name some familial syndromes associated with rhabdomyosarcoma.
Syndromes include Costello syndrome, neurofibromatosis type 1, Noonan syndrome, Beckwith-Wiedemann syndrome, Dicer syndrome, Li-Fraumeni syndrome, and Gorlin syndrome.
What is alveolar rhabdomyosarcoma and its associated genetic fusion?
Alveolar rhabdomyosarcoma is a high-grade sarcoma often found in older children and adolescents, with ~60% of cases harbouring the PAX3-FOXO1 fusion gene.
What proportion of alveolar rhabdomyosarcoma cases show the PAX7-FOXO1 fusion?
Approximately 20% of cases have the PAX7-FOXO1 fusion.
What is the primary aim of the 1000 Genomes Project?
To characterise human genetic variation by sequencing whole genomes from diverse populations.
How does whole genome sequencing (WGS) benefit cancer research?
WGS detects germline and somatic mutations, copy number changes, and structural variants, guiding personalised treatment strategies.
What additional goal does the 100,000 Genomes Project have compared to earlier projects?
It seeks to identify rare variants and further correlate genetic polymorphisms with disease phenotypes for improved personalised medicine.
What does a Circos plot illustrate in cancer genomics?
It visually represents chromosomal structural variants and copy number alterations across the genome.
Why are soft tissue tumours considered ideal candidates for pilot genomic studies in the NHS?
Their rarity, well-documented genetic abnormalities, and treatment challenges make them suitable for targeted whole genome sequencing initiatives.
How does identifying specific genetic mutations in soft tissue tumours affect clinical management?
It enables targeted therapies and more precise prognostication, improving patient outcomes.
What impact does dedifferentiation have on the prognosis of liposarcomas?
Dedifferentiation typically indicates a more aggressive tumour with a poorer prognosis.
What are peripheral nerve sheath tumours and how do they fit into the soft tissue tumour classification?
They are tumours originating from the nerve sheath and are classified within the broader WHO categorisation of soft tissue tumours.
What challenges arise when diagnosing tumours of uncertain differentiation?
Their lack of specific histological or molecular markers complicates diagnosis and treatment planning.
How does tumour size influence the treatment of soft tissue sarcomas?
Larger tumours may be more aggressive and often require extensive surgical resection and adjuvant therapy.
What role do imaging techniques play in managing soft tissue tumours?
They assess tumour size, depth, and relation to adjacent structures, which is crucial for surgical planning.
How might future genomic profiling change the treatment landscape for soft tissue tumours?
It promises personalised therapies that target specific genetic alterations, potentially leading to better outcomes and fewer side effects.
What defines “soft tissue” in the context of tumour pathology?
Soft tissue refers to mesenchymal tissues—including adipose, muscle, nerves, vessels, and fibrous tissue—that form the body’s supportive framework.
Besides extremities, where else can soft tissue tumours arise?
Soft tissue tumours can also develop in organs and the skin because these regions contain substantial mesenchymal tissue.
What is the scope of the WHO classification for soft tissue tumours?
The WHO classification categorises soft tissue tumours based on differentiation into adipocytic, fibroblastic/myofibroblastic, fibrohistiocytic, vascular, pericytic, smooth muscle, skeletal muscle, chondro-osseous, peripheral nerve sheath tumours, and tumours of uncertain differentiation.
What percentage of benign soft tissue tumours are reported to be superficial?
Approximately 99% of benign soft tissue tumours are superficial.
What size limitation is typical for most benign soft tissue tumours?
About 95% of benign soft tissue tumours are less than 5 cm in size.
How are soft tissue sarcomas generally distributed in clinical practice?
Soft tissue sarcomas are rare; their incidence is low compared to benign counterparts, and they often present with distinct size and depth characteristics.
What constitutes adipocytic tumours?
Adipocytic tumours are derived from adipose tissue, ranging from benign lipomas to malignant liposarcomas.
What is the most common malignant adipocytic tumour?
The most common malignant adipocytic tumour is the atypical lipomatous tumour, also known as well-differentiated liposarcoma, which accounts for 40–45% of liposarcomas.
What key genetic alteration is associated with well-differentiated liposarcomas?
Well-differentiated liposarcomas characteristically display ring or giant marker chromosomes with amplification of genes (e.g. MDM2) from the 12q13–15 region.
How is dedifferentiated liposarcoma distinguished from its well-differentiated counterpart?
Dedifferentiated liposarcoma occurs in a subset of cases (around 10%) and shows areas of high-grade non-lipogenic sarcoma, often in retroperitoneal sites.
What percentage of adult sarcomas does myxoid liposarcoma represent?
Myxoid liposarcoma represents about 5% of adult sarcomas.
Which chromosomal translocation is most frequently found in myxoid liposarcoma?
The recurrent t(12;16)(q13;p11.2) translocation, resulting in the FUS-DDIT3 fusion gene, is most frequently found in myxoid liposarcoma.
What is the significance of the rare t(12;22)(q13;q12) rearrangement?
The rare t(12;22)(q13;q12) rearrangement results in an EWSR1-DDIT3 fusion gene and is found in approximately 2% of myxoid liposarcomas.
What tissue do smooth muscle tumours originate from?
Smooth muscle tumours arise from smooth muscle, which can be found in vessel walls or the erector pili muscles of the skin.
How are cutaneous smooth muscle tumours typically characterised?
Cutaneous smooth muscle tumours are usually superficial, small, often multiple, and can be painful; some are linked to immunodeficiency and EBV infection.
What is leiomyosarcoma and where is it commonly located?
Leiomyosarcoma is a malignant smooth muscle tumour commonly found in the extremities, retroperitoneum, and large vessels such as the inferior vena cava.
What diagnostic criteria are used for leiomyosarcoma in soft tissue?
Diagnostic criteria for leiomyosarcoma in soft tissue include mitotic figures per 10 high-power fields, tumour size, depth, and the presence of necrosis, with thresholds varying by site.
What distinguishes a rhabdomyoma from a rhabdomyosarcoma?
A rhabdomyoma is a benign tumour of mature skeletal muscle, whereas rhabdomyosarcoma is malignant and shows immature myogenic differentiation.
Which subtype of rhabdomyosarcoma is most prevalent in children?
Embryonal rhabdomyosarcoma is the most common subtype in the paediatric and adolescent populations.
What histological features are typical of embryonal rhabdomyosarcoma?
Embryonal rhabdomyosarcoma typically consists of primitive mesenchymal cells with myogenic differentiation, sometimes positive for MyoD1 or myogenin.
Name some familial syndromes associated with rhabdomyosarcoma.
Syndromes associated with rhabdomyosarcoma include Costello syndrome, neurofibromatosis type 1, Noonan syndrome, Beckwith-Wiedemann syndrome, Dicer syndrome, Li-Fraumeni syndrome, and Gorlin syndrome.
What is alveolar rhabdomyosarcoma and its associated genetic fusion?
Alveolar rhabdomyosarcoma is a high-grade sarcoma often found in older children and adolescents, with ~60% of cases harbouring the PAX3-FOXO1 fusion gene.
What proportion of alveolar rhabdomyosarcoma cases show the PAX7-FOXO1 fusion?
Approximately 20% of alveolar rhabdomyosarcoma cases have the PAX7-FOXO1 fusion.
What is the primary aim of the 1000 Genomes Project?
The primary aim of the 1000 Genomes Project is to characterise human genetic variation by sequencing whole genomes from diverse populations.
How does whole genome sequencing (WGS) benefit cancer research?
Whole genome sequencing (WGS) benefits cancer research by detecting germline and somatic mutations, copy number changes, and structural variants, guiding personalised treatment strategies.
What additional goal does the 100,000 Genomes Project have compared to earlier projects?
The 100,000 Genomes Project seeks to identify rare variants and further correlate genetic polymorphisms with disease phenotypes for improved personalised medicine, compared to earlier projects.
What does a Circos plot illustrate in cancer genomics?
A Circos plot in cancer genomics visually represents chromosomal structural variants and copy number alterations across the genome.
Why are soft tissue tumours considered ideal candidates for pilot genomic studies in the NHS?
Soft tissue tumours are considered ideal candidates for pilot genomic studies in the NHS due to their rarity, well-documented genetic abnormalities, and treatment challenges.
How does identifying specific genetic mutations in soft tissue tumours affect clinical management?
Identifying specific genetic mutations in soft tissue tumours enables targeted therapies and more precise prognostication, improving patient outcomes.
What impact does dedifferentiation have on the prognosis of liposarcomas?
Dedifferentiation typically indicates a more aggressive tumour with a poorer prognosis.
What are peripheral nerve sheath tumours and how do they fit into the soft tissue tumour classification?
Peripheral nerve sheath tumours originate from the nerve sheath and are classified within the broader WHO categorisation of soft tissue tumours.
What challenges arise when diagnosing tumours of uncertain differentiation?
Tumours of uncertain differentiation lack specific histological or molecular markers, which complicates diagnosis and treatment planning.
How does tumour size influence the treatment of soft tissue sarcomas?
Larger soft tissue sarcomas may be more aggressive and often require extensive surgical resection and adjuvant therapy.
What role do imaging techniques play in managing soft tissue tumours?
Imaging techniques assess tumour size, depth, and relation to adjacent structures, which is crucial for surgical planning.
How might future genomic profiling change the treatment landscape for soft tissue tumours?
Future genomic profiling promises personalised therapies that target specific genetic alterations, potentially leading to better outcomes and fewer side effects.
