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Clinical Pathology in Action > L7 – Gynaecopathology: Hormonally-Driven Tumours of the Uterus > Flashcards

L7 – Gynaecopathology: Hormonally-Driven Tumours of the Uterus Flashcards

1
Q

What are the typical features of the normal endometrial lining?

A

The endometrium is a cyclically regenerating mucosa with a proliferative basal layer and secretory functional layer.

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2
Q

How is endometrial carcinoma generally classified?

A

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).

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3
Q

Which demographic is most affected by endometrial carcinoma?

A

It predominantly affects postmenopausal women, with the majority of cases occurring in women aged 60–70.

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4
Q

What is the precursor lesion for Type I endometrial carcinoma?

A

Atypical hyperplasia or endometrial intraepithelial neoplasia (EIN) is the recognised precursor.

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5
Q

What are the key risk factors for endometrial carcinoma?

A

Risk factors include morbid obesity, chronic anovulation, late menopause, tamoxifen use, and a history of unopposed oestrogen exposure.

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6
Q

How does oestrogen influence the development of endometrioid carcinoma?

A

Excess oestrogen stimulates endometrial proliferation, increasing the risk of atypical hyperplasia and subsequent malignant transformation.

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7
Q

What is the significance of hereditary syndromes in endometrial cancer?

A

Syndromes such as Lynch syndrome contribute to a higher risk of endometrial carcinoma due to germline mutations in mismatch repair genes.

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8
Q

Why is the distinction between Type I and Type II endometrial carcinoma clinically relevant?

A

It guides treatment decisions and provides prognostic information, with Type I generally having a better prognosis.

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9
Q

What histological patterns are seen in endometrioid carcinoma?

A

They include confluent or back-to-back glands, cribriform or microacinar patterns, and occasional papillary formations.

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10
Q

How do Type II carcinomas differ histologically from Type I?

A

Type II carcinomas, such as serous papillary and clear cell carcinomas, display high-grade nuclear atypia, papillary architecture, and more aggressive features.

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11
Q

What new molecular classification has emerged for endometrial carcinoma?

A

The integrated classification by TCGA divides tumours into groups based on POLE mutations, MMR deficiency, low copy number, and p53 abnormalities.

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12
Q

How does molecular profiling impact prognosis in endometrial carcinoma?

A

Molecular subtypes correlate with outcomes; for example, POLE-mutated tumours have an excellent prognosis, while p53 mutant tumours have a poor prognosis.

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13
Q

What is the primary symptom leading to the diagnosis of endometrial carcinoma?

A

Postmenopausal bleeding is the most common presenting symptom.

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14
Q

Which factors are assessed to stage endometrial carcinoma?

A

Factors include myometrial invasion, lymphovascular space invasion, and the presence of extrauterine spread.

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15
Q

How does the depth of myometrial invasion influence prognosis?

A

Greater invasion correlates with higher risk of metastasis and poorer survival rates.

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16
Q

What treatment options are available for endometrial carcinoma?

A

Treatment usually involves surgical management (hysterectomy with bilateral salpingo-oophorectomy) supplemented by radiotherapy, chemotherapy, or hormonal therapy as appropriate.

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17
Q

What molecular markers help differentiate Type I from Type II endometrial carcinomas?

A

Type I often exhibits PTEN, KRAS, and PIK3CA mutations, while Type II frequently shows TP53 mutations.

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18
Q

How does chronic anovulation contribute to endometrial carcinoma development?

A

Prolonged unopposed oestrogen exposure leads to continuous endometrial proliferation and increased mutation risk.

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19
Q

What role does endometrial intraepithelial neoplasia (EIN) play in carcinogenesis?

A

EIN represents a clonal expansion of atypical glands that is a direct precursor to invasive endometrioid carcinoma.

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20
Q

How can imaging modalities like MRI aid in endometrial carcinoma staging?

A

They help assess myometrial invasion depth and extrauterine spread, guiding surgical planning.

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21
Q

What is the prognostic significance of lymphovascular space invasion in uterine cancers?

A

Its presence is linked to higher metastatic potential and a poorer prognosis.

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22
Q

What factors influence the decision to use adjuvant therapy in endometrial cancer?

A

Tumour stage, grade, depth of myometrial invasion, and molecular profile are critical in treatment planning.

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23
Q

How does tamoxifen use affect endometrial cancer risk in breast cancer patients?

A

Tamoxifen acts as an oestrogen agonist in the endometrium, increasing the risk of hyperplasia and carcinoma.

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24
Q

What are the typical features of the normal endometrial lining?

A

The endometrium is a cyclically regenerating mucosa with a proliferative basal layer and secretory functional layer.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
25
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).
26
Which demographic is most affected by endometrial carcinoma?
It predominantly affects postmenopausal women, with the majority of cases occurring in women aged 60–70.
27
What is the precursor lesion for Type I endometrial carcinoma?
Atypical hyperplasia or endometrial intraepithelial neoplasia (EIN) is the recognised precursor.
28
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.
29
How does oestrogen influence the development of endometrioid carcinoma?
Excess oestrogen stimulates endometrial proliferation, increasing the risk of atypical hyperplasia and subsequent malignant transformation.
30
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.
31
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.
32
What histological patterns are seen in endometrioid carcinoma?
They include confluent or back-to-back glands, cribriform or microacinar patterns, and occasional papillary formations.
33
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.
34
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.
35
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.
36
What is the primary symptom leading to the diagnosis of endometrial carcinoma?
Postmenopausal bleeding is the most common presenting symptom.
37
Which factors are assessed to stage endometrial carcinoma?
Factors include myometrial invasion, lymphovascular space invasion, and the presence of extrauterine spread.
38
How does the depth of myometrial invasion influence prognosis?
Greater invasion correlates with higher risk of metastasis and poorer survival rates.
39
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.
40
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.
41
How does chronic anovulation contribute to endometrial carcinoma development?
Prolonged unopposed oestrogen exposure leads to continuous endometrial proliferation and increased mutation risk.
42
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.
43
How can imaging modalities like MRI aid in endometrial carcinoma staging?
They help assess myometrial invasion depth and extrauterine spread, guiding surgical planning.
44
What is the prognostic significance of lymphovascular space invasion in uterine cancers?
Its presence is linked to higher metastatic potential and a poorer prognosis.
45
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.
46
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.
47
What are the two histological layers of the endometrium?
The two layers are the stratum basalis (basal layer) and stratum functionalis (functional layer).
48
How does the menstrual cycle affect the endometrium?
The endometrium thickens under oestrogen influence and sheds when hormonal stimulation ceases.
49
What is the stratum functionalis?
The stratum functionalis is the upper layer of the endometrium that regenerates and is shed during menstruation.
50
What are common symptoms of endometrial cancer?
Common symptoms include abnormal uterine bleeding, particularly postmenopausal or irregular bleeding.
51
Why is postmenopausal bleeding a critical symptom?
Postmenopausal bleeding often signals underlying malignancy and requires urgent investigation.
52
What is the main difference between Type I and Type II endometrial carcinoma?
Type I carcinomas are oestrogen-driven and typically low-grade, whereas Type II are unrelated to oestrogen and more aggressive.
53
What histological feature differentiates typical endometrium from hyperplasia?
Normal endometrium shows regularly spaced glands with minimal atypia, while hyperplasia shows glandular crowding.
54
What are the features of atypical endometrial hyperplasia?
Atypical hyperplasia shows crowded glands with cytological atypia and sometimes mitotic activity.
55
How can hormonal therapy reverse atypical hyperplasia?
Progesterone therapy or intrauterine devices like Mirena can induce regression of atypical hyperplasia.
56
What histological features distinguish endometrioid carcinoma?
Endometrioid carcinoma shows crowded glands with loss of intervening stroma and frequent mitotic figures.
57
What is the significance of lymphovascular invasion in endometrial cancer?
Lymphovascular invasion is associated with higher risk of metastasis and worsens prognosis.
58
How does serous carcinoma differ from endometrioid carcinoma?
Serous carcinoma shows high-grade nuclear atypia, papillary structures, and aggressive behaviour, unlike typical endometrioid carcinoma.
59
What molecular alteration is characteristic of serous carcinoma?
TP53 mutation is a hallmark of serous carcinoma.
60
What is the role of p53 immunohistochemistry in endometrial cancer diagnosis?
p53 immunohistochemistry shows either strong diffuse positivity or complete negativity in serous carcinoma.
61
What are key features of clear cell carcinoma of the endometrium?
Clear cell carcinoma shows large, clear cytoplasm cells arranged in solid sheets and papillae.
62
Which immunohistochemical markers help identify clear cell carcinoma?
Markers like Napsin A and AMACR are typically positive in clear cell carcinoma.
63
What mutation is associated with POLE-mutated endometrial cancers?
POLE mutations lead to hypermutated tumours with strong immune responses and good prognosis.
64
What are the four molecular subtypes of endometrial carcinoma based on TCGA?
The four subtypes are POLE-mutated, MMR-deficient, copy-number low (endometrioid-like), and p53-abnormal (serous-like).
65
How does mismatch repair (MMR) deficiency affect endometrial cancer prognosis?
MMR-deficient tumours often have better responses to treatment compared to p53-abnormal cancers.
66
What is Lynch syndrome’s connection to endometrial cancer?
Lynch syndrome involves inherited defects in DNA mismatch repair genes and increases endometrial cancer risk.
67
Why is genetic testing important alongside histology in endometrial cancer?
Genetic testing refines prognosis and treatment decisions beyond what histology alone provides.
68
What diagnostic methods are used to sample endometrial tissue?
Pipelle biopsy and hysteroscopic-directed biopsy are common sampling methods.
69
What factors may cause an inadequate endometrial biopsy?
Inadequate samples may occur if the endometrium is inaccessible or if there is insufficient tissue.
70
What is the clinical relevance of endometrial thickness measurement on ultrasound?
Increased endometrial thickness in postmenopausal women (>4 mm) is suspicious for pathology.
71
What is the difference between polyps and endometrial carcinoma regarding sampling?
Polyps may cause bleeding and can sometimes harbour carcinoma, necessitating careful evaluation.
72
Why is accurate clinical information critical for pathology interpretation?
Lack of detailed clinical history can lead to misinterpretation of biopsy adequacy and results.
73
What are precursors of serous carcinoma called?
Precursors are termed serous endometrial intraepithelial carcinoma (SEIC).
74
Why is early diagnosis important for endometrial carcinoma prognosis?
Early diagnosis improves survival by allowing treatment before myometrial invasion or metastasis.
75
What role do hormonal factors play in endometrial carcinogenesis?
Oestrogen exposure without progesterone leads to endometrial proliferation and potential malignancy.
76
How do tamoxifen and prior pelvic radiation relate to endometrial cancer?
Tamoxifen acts like oestrogen in the endometrium, increasing cancer risk; radiation can also trigger genetic mutations.
77
How does obesity contribute to the risk of endometrial carcinoma?
Obesity leads to increased peripheral oestrogen production and chronic endometrial stimulation, raising cancer risk.

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