L7 – Gynaecopathology: Hormonally-Driven Tumours of the Uterus Flashcards
What are the typical features of the normal endometrial lining?
The endometrium is a cyclically regenerating mucosa with a proliferative basal layer and secretory functional layer.
How is endometrial carcinoma generally classified?
It is broadly classified into Type I (low-grade, oestrogen-related, typically endometrioid carcinoma) and Type II (high-grade, non-oestrogen-related, such as serous and clear cell carcinomas).
Which demographic is most affected by endometrial carcinoma?
It predominantly affects postmenopausal women, with the majority of cases occurring in women aged 60–70.
What is the precursor lesion for Type I endometrial carcinoma?
Atypical hyperplasia or endometrial intraepithelial neoplasia (EIN) is the recognised precursor.
What are the key risk factors for endometrial carcinoma?
Risk factors include morbid obesity, chronic anovulation, late menopause, tamoxifen use, and a history of unopposed oestrogen exposure.
How does oestrogen influence the development of endometrioid carcinoma?
Excess oestrogen stimulates endometrial proliferation, increasing the risk of atypical hyperplasia and subsequent malignant transformation.
What is the significance of hereditary syndromes in endometrial cancer?
Syndromes such as Lynch syndrome contribute to a higher risk of endometrial carcinoma due to germline mutations in mismatch repair genes.
Why is the distinction between Type I and Type II endometrial carcinoma clinically relevant?
It guides treatment decisions and provides prognostic information, with Type I generally having a better prognosis.
What histological patterns are seen in endometrioid carcinoma?
They include confluent or back-to-back glands, cribriform or microacinar patterns, and occasional papillary formations.
How do Type II carcinomas differ histologically from Type I?
Type II carcinomas, such as serous papillary and clear cell carcinomas, display high-grade nuclear atypia, papillary architecture, and more aggressive features.
What new molecular classification has emerged for endometrial carcinoma?
The integrated classification by TCGA divides tumours into groups based on POLE mutations, MMR deficiency, low copy number, and p53 abnormalities.
How does molecular profiling impact prognosis in endometrial carcinoma?
Molecular subtypes correlate with outcomes; for example, POLE-mutated tumours have an excellent prognosis, while p53 mutant tumours have a poor prognosis.
What is the primary symptom leading to the diagnosis of endometrial carcinoma?
Postmenopausal bleeding is the most common presenting symptom.
Which factors are assessed to stage endometrial carcinoma?
Factors include myometrial invasion, lymphovascular space invasion, and the presence of extrauterine spread.
How does the depth of myometrial invasion influence prognosis?
Greater invasion correlates with higher risk of metastasis and poorer survival rates.
What treatment options are available for endometrial carcinoma?
Treatment usually involves surgical management (hysterectomy with bilateral salpingo-oophorectomy) supplemented by radiotherapy, chemotherapy, or hormonal therapy as appropriate.
What molecular markers help differentiate Type I from Type II endometrial carcinomas?
Type I often exhibits PTEN, KRAS, and PIK3CA mutations, while Type II frequently shows TP53 mutations.
How does chronic anovulation contribute to endometrial carcinoma development?
Prolonged unopposed oestrogen exposure leads to continuous endometrial proliferation and increased mutation risk.
What role does endometrial intraepithelial neoplasia (EIN) play in carcinogenesis?
EIN represents a clonal expansion of atypical glands that is a direct precursor to invasive endometrioid carcinoma.
How can imaging modalities like MRI aid in endometrial carcinoma staging?
They help assess myometrial invasion depth and extrauterine spread, guiding surgical planning.
What is the prognostic significance of lymphovascular space invasion in uterine cancers?
Its presence is linked to higher metastatic potential and a poorer prognosis.
What factors influence the decision to use adjuvant therapy in endometrial cancer?
Tumour stage, grade, depth of myometrial invasion, and molecular profile are critical in treatment planning.
How does tamoxifen use affect endometrial cancer risk in breast cancer patients?
Tamoxifen acts as an oestrogen agonist in the endometrium, increasing the risk of hyperplasia and carcinoma.
What is the primary challenge viruses face when entering a host cell?
Ensuring stability outside while rapidly disassembling inside the host.
How do viruses ensure stability outside the host while remaining capable of disassembly inside the host?
They remain structurally stable but utilize host factors to disassemble upon entry.
What entry mechanism do Adenoviruses and Influenza viruses commonly use?
Clathrin-mediated endocytosis.
What role does the ubiquitin system play in viral entry?
It labels proteins for degradation and regulates viral and cellular interactions.
What cellular structures act as transport highways for viruses?
Microtubules.
Which motor protein transports viruses toward the nucleus?
Dynein.
What is the genome type of Adenovirus?
Linear double-stranded DNA.
How does Adenovirus escape the endosome?
Through pH-dependent activation of viral proteins.
What viral protein is essential for Adenovirus endosomal escape?
Protein 6.
What process allows Adenovirus to reach the nucleus?
By traveling along microtubules using dynein motors.
Which viral proteins are ubiquitinated to facilitate transport to the nucleus?
Key structural proteins of the virus.
What are the main glycoproteins involved in Influenza virus attachment and entry?
Hemagglutinin (HA) and neuraminidase (NA).
How does Influenza virus dismantle its structure upon entry?
Through acidification in the endosome, triggering fusion.
Which host factor assists Influenza virus in uncoating its genome?
HDAC6.
How do Influenza genes enter the nucleus?
Using importin and transportin proteins.
Why is nuclear transport crucial for Influenza virus replication?
Influenza replicates inside the nucleus, requiring nuclear entry of its RNA.
How quickly do Adenovirus and Influenza complete their journey from entry to nuclear import?
Typically within 20 to 30 minutes.
How does ubiquitination benefit viruses during entry and transport?
It helps viruses degrade host restriction factors and facilitates movement.
Why is it important to understand the mechanisms viruses use to reach the nucleus?
It provides insight into viral replication and potential drug targets.
What potential therapeutic strategies could target viral nuclear transport?
Blocking host factors involved in viral transport or disassembly.
What are the typical features of the normal endometrial lining?
The endometrium is a cyclically regenerating mucosa with a proliferative basal layer and secretory functional layer.
How is endometrial carcinoma generally classified?
It is broadly classified into Type I (low-grade, oestrogen-related, typically endometrioid carcinoma) and Type II (high-grade, non-oestrogen-related, such as serous and clear cell carcinomas).
Which demographic is most affected by endometrial carcinoma?
It predominantly affects postmenopausal women, with the majority of cases occurring in women aged 60–70.
What is the precursor lesion for Type I endometrial carcinoma?
Atypical hyperplasia or endometrial intraepithelial neoplasia (EIN) is the recognised precursor.
What are the key risk factors for endometrial carcinoma?
Risk factors include morbid obesity, chronic anovulation, late menopause, tamoxifen use, and a history of unopposed oestrogen exposure.
How does oestrogen influence the development of endometrioid carcinoma?
Excess oestrogen stimulates endometrial proliferation, increasing the risk of atypical hyperplasia and subsequent malignant transformation.
What is the significance of hereditary syndromes in endometrial cancer?
Syndromes such as Lynch syndrome contribute to a higher risk of endometrial carcinoma due to germline mutations in mismatch repair genes.
Why is the distinction between Type I and Type II endometrial carcinoma clinically relevant?
It guides treatment decisions and provides prognostic information, with Type I generally having a better prognosis.
What histological patterns are seen in endometrioid carcinoma?
They include confluent or back-to-back glands, cribriform or microacinar patterns, and occasional papillary formations.
How do Type II carcinomas differ histologically from Type I?
Type II carcinomas, such as serous papillary and clear cell carcinomas, display high-grade nuclear atypia, papillary architecture, and more aggressive features.
What new molecular classification has emerged for endometrial carcinoma?
The integrated classification by TCGA divides tumours into groups based on POLE mutations, MMR deficiency, low copy number, and p53 abnormalities.
How does molecular profiling impact prognosis in endometrial carcinoma?
Molecular subtypes correlate with outcomes; for example, POLE-mutated tumours have an excellent prognosis, while p53 mutant tumours have a poor prognosis.
What is the primary symptom leading to the diagnosis of endometrial carcinoma?
Postmenopausal bleeding is the most common presenting symptom.
Which factors are assessed to stage endometrial carcinoma?
Factors include myometrial invasion, lymphovascular space invasion, and the presence of extrauterine spread.
How does the depth of myometrial invasion influence prognosis?
Greater invasion correlates with higher risk of metastasis and poorer survival rates.
What treatment options are available for endometrial carcinoma?
Treatment usually involves surgical management (hysterectomy with bilateral salpingo-oophorectomy) supplemented by radiotherapy, chemotherapy, or hormonal therapy as appropriate.
What molecular markers help differentiate Type I from Type II endometrial carcinomas?
Type I often exhibits PTEN, KRAS, and PIK3CA mutations, while Type II frequently shows TP53 mutations.
How does chronic anovulation contribute to endometrial carcinoma development?
Prolonged unopposed oestrogen exposure leads to continuous endometrial proliferation and increased mutation risk.
What role does endometrial intraepithelial neoplasia (EIN) play in carcinogenesis?
EIN represents a clonal expansion of atypical glands that is a direct precursor to invasive endometrioid carcinoma.
How can imaging modalities like MRI aid in endometrial carcinoma staging?
They help assess myometrial invasion depth and extrauterine spread, guiding surgical planning.
What is the prognostic significance of lymphovascular space invasion in uterine cancers?
Its presence is linked to higher metastatic potential and a poorer prognosis.
What factors influence the decision to use adjuvant therapy in endometrial cancer?
Tumour stage, grade, depth of myometrial invasion, and molecular profile are critical in treatment planning.
How does tamoxifen use affect endometrial cancer risk in breast cancer patients?
Tamoxifen acts as an oestrogen agonist in the endometrium, increasing the risk of hyperplasia and carcinoma.
What is the primary challenge viruses face when entering a host cell?
Ensuring stability outside while rapidly disassembling inside the host.
How do viruses ensure stability outside the host while remaining capable of disassembly inside the host?
They remain structurally stable but utilize host factors to disassemble upon entry.
What entry mechanism do Adenoviruses and Influenza viruses commonly use?
Clathrin-mediated endocytosis.
What role does the ubiquitin system play in viral entry?
It labels proteins for degradation and regulates viral and cellular interactions.
What cellular structures act as transport highways for viruses?
Microtubules.
Which motor protein transports viruses toward the nucleus?
Dynein.
What is the genome type of Adenovirus?
Linear double-stranded DNA.
How does Adenovirus escape the endosome?
Through pH-dependent activation of viral proteins.
What viral protein is essential for Adenovirus endosomal escape?
Protein 6.
What process allows Adenovirus to reach the nucleus?
By traveling along microtubules using dynein motors.
Which viral proteins are ubiquitinated to facilitate transport to the nucleus?
Key structural proteins of the virus.
What are the main glycoproteins involved in Influenza virus attachment and entry?
Hemagglutinin (HA) and neuraminidase (NA).
How does Influenza virus dismantle its structure upon entry?
Through acidification in the endosome, triggering fusion.
Which host factor assists Influenza virus in uncoating its genome?
HDAC6.
How do Influenza genes enter the nucleus?
Using importin and transportin proteins.
Why is nuclear transport crucial for Influenza virus replication?
Influenza replicates inside the nucleus, requiring nuclear entry of its RNA.
How quickly do Adenovirus and Influenza complete their journey from entry to nuclear import?
Typically within 20 to 30 minutes.
How does ubiquitination benefit viruses during entry and transport?
It helps viruses degrade host restriction factors and facilitates movement.
Why is it important to understand the mechanisms viruses use to reach the nucleus?
It provides insight into viral replication and potential drug targets.
What potential therapeutic strategies could target viral nuclear transport?
Blocking host factors involved in viral transport or disassembly.
