L11 - Gynaecopathology: genetics driven cancers of the ovary and fallopian tube (Dr Francesca Maggiani) Flashcards
- Revising the anatomy and histology of the ovary - Understanding pathogenesis of ovarian and tubal cancer (Mullerian origin cancers) - Describing the different cancers as by the recent reviewed classification (the disappearing serous carcinoma of the ovary) (139 cards)
1
Q
What is the primary focus of ovarian tumour classification in modern medicine?
A
The focus is on genetically driven cancers of the ovary and fallopian tube, as many ovarian cancers originate from other organs or from Müllerian-type epithelium, including the fallopian tube and endometrium.
2
Q
What is the significance of the WHO Blue Book in ovarian tumour classification?
A
It provides the standard classification of tumours of the female genital tract, helping in understanding their origins and characteristics.
3
Q
What are the anatomical and embryological features of the ovary?
A
The ovary is the female gonad, present bilaterally in the pelvis. While separate from the fallopian tubes, it is located very close to the fimbrial end of the tube.
4
Q
what is a gonad
A
primary reproductive gland that produces reproductive cells (gametes)
5
Q
What is the role of the fimbrial end of the fallopian tube?
A
It acts like a funnel, allowing the passage of the oocyte from the ovary into the fallopian tube, so it can be fertilised.
6
Q
What are some conditions that affect the fallopian tube and impact fertility?
A
Infections: Can cause adhesions inside the tube, blocking sperm-oocyte interaction.
Structural abnormalities: Can prevent the fertilized oocyte from moving into the uterus, leading to ectopic pregnancy.
7
Q
what is one of the main reasons for infertility
A
infections
8
Q
What is an ectopic pregnancy?
A
It is a pregnancy where the embryo implants in the fallopian tube instead of the uterus.
9
Q
Why are ectopic pregnancies a medical emergency
A
Since the fallopian tube is very narrow (~4mm thick), the growing placental tissue can rupture the tube, leading to massive internal bleeding and requiring emergency medical intervention.
10
Q
Why is pregnancy status crucial in diagnosing women with acute abdominal pain?
A
A ruptured ectopic pregnancy can cause severe internal bleeding. Therefore, in women of reproductive age presenting with severe abdominal pain, pregnancy must be considered
11
Q
What is the typical size and shape of the ovary in a fertile woman?
A
The ovary is usually ovoid in shape and measures up to 4 cm in diameter during the reproductive years.
12
Q
What happens to the size of the ovary with age and atrophy
A
With age and atrophy, it can shrink to 1–2 cm.
13
Q
What is the external lining of the ovary made up of
A
Mesothelium (so-called ovarian surface epithelium)
14
Q
How does the number of oocytes change in a lifetime
A
A woman is born with all the eggs she will ever have and these eggs don’t regenerate but decline throughout her reproductive life:
A fetus has ~6-7 million oocytes
at birth : ~1-2 million
Puberty : ~500,000
menopausal : ~1000 - 0
15
Q
How can ovarian size be affected by pathology?
A
- Polycystic Ovary Syndrome (PCOS)
- Benign ovarian disease
16
Q
How do Polycystic Ovary syndrome (PCOS) and benign ovarian disease affect ovarian pathology
A
- Polycystic Ovary Syndrome (PCOS): Leads to enlarged ovaries with multiple follicles.
- Benign ovarian disease: Can also result in increased ovarian size due to follicular cysts.
17
Q
What are the main structural components of the ovary?
A
- Cortex: The outer layer, containing most of the oocytes at different maturation stages.
- Medulla: The inner core, consisting of stromal cells for structural support.
- Hilum: The central part where the vascular supply enters and distributes.
18
Q
What type of epithelium covers the ovary?
A
The ovary is covered by mesothelium, the same tissue that lines the abdominal and chest cavities. This modified mesothelium is also called the ovarian surface epithelium.
19
Q
What is the ovary composed of
A
It is composed mainly of stromal cells that support the maturing germ cells ( covered by a monolayer modified mesothelium) 3
20
Q
How does the number of oocytes change over a woman’s lifetime
A
A female is born with a fixed number of oocytes, which does not increase. The number gradually declines throughout life due to natural atresia and ovulation.
21
Q
What is atresia
A
the degeneration of those ovarian follicles which do not ovulate during the menstrual cycle.
22
Q
What are the key structures visible in a mature ovarian follicle
A
- Oocyte: The egg cell, ready for ovulation.
- Zona Pellucida: A glycoprotein layer surrounding the oocyte.
- Cumulus Oophorus: Granulosa cells that support the oocyte.
- Antrum: A fluid-filled cavity in the follicle.
- Theca Interna: A cell layer producing hormones for follicle maturation.
- Follicular Epithelium (Granulosa Cells): Cells that provide hormonal and metabolic support.
23
Q
What does the cortex of the ovary contain?
A
The cortex houses immature oocytes in follicles at different stages of development.
24
Q
What does a mature follicle look like before ovulation?
A
It has a large antrum, a well-developed cumulus oophorus, and an oocyte ready for release during ovulation.
25
How common is ovarian cancer in women ( what ranking is it given)
It is the 8th most common cancer in women
26
What is the geographic variation of ovarian cancer
It varies geographically
27
Why are fewer ovarian malignant cases now being found despite more tumours being found?
The new classification system reclassifies some previously malignant tumors as borderline tumors, which have a more indolent (less aggressive) behavior.
28
What genetic predispositions increase the risk of ovarian cancer?
- BRCA1 and BRCA2 mutations
- Lynch syndrome (hereditary nonpolyposis colorectal cancer, HNPCC)
- Other genetic syndromes, including:
* Peutz-Jeghers syndrome
* Cowden syndrome
* Coffin-Siris syndrome
* Li-Fraumeni syndrome
29
What is the germline mutation in Peutz-Jeghers syndrome?
STK11
30
What is the germline mutation in Cowden syndrome?
PTEN
31
What is the germline mutation in Coffin-Siris syndrome
ARID1A
32
What is the germline mutation in Li-Fraumeni syndrome?
TP53 / p53
33
What are protective factors against ovarian cancer?
- Oral contraceptive pill (OCP) use
- High parity (having multiple pregnancies)
- Breastfeeding
- Tubal ligation
- Hysterectomy
34
how do protective factors reduce the risk of ovarian cancer
These factors likely reduce hormonal stimulation and the number of ovulatory cycles, which may lower cancer risk.
35
Why is ovarian cancer often diagnosed late?
Ovarian cancer can grow silently for a long time, often without symptoms until it is large or aggressive. Unlike bowel or lung cancer, it does not cause early noticeable symptoms.
36
How has the use of imaging techniques affected ovarian cancer detection?
The increased use of imaging (CT scans, ultrasounds) has led to more incidental findings of ovarian tumors, even when they are still asymptomatic.
37
What unexpected effects has COVID-19 related lung imaging had on tumour detection?
CT scans for respiratory function monitoring have incidentally detected more kidney tumours, and further ovarian tumours.
38
What is an extreme case of ovarian tumor growth?
Some ovarian tumors can reach 30 cm in size, often cystic and fluid-filled, remaining undetected for a long time due to the spacious nature of the pelvis.
39
What are the key risk factors for ovarian cancer?
Genetic factors
Medical history
Family history of ovarian, breast, or colorectal cancer
40
what are genetic risk factors for ovarian cancer
BRCA1, BRCA2, Lynch syndrome, mismatch repair gene mutations
41
What are examples of medical history which increases the risk factor for ovarian
Endometriosis, Polycystic Ovarian Syndrome (PCOS)
42
What is the most common type of ovarian tumor?
Surface epithelial-stromal cell tumors, accounting for 65-70% of all ovarian tumors and 90% of malignant ovarian tumors.
43
At what age do surface epithelial-stromal cell tumors typically occur?
They are found in women over 20 years old, spanning the entire fertile period, though some subtypes are more common after age 60.
44
What are the 4 main origins of ovarian tumours ( used for classification)
1. Surface epithelial cells ( surface epithelial stromal cell tumours)
2. Germ cell
3. Sec cord stroma
4. Metastasis to ovaries
45
What are the main histological subtypes of surface epithelial-stromal tumors?
- Serous tumors (most common malignant type)
- Mucinous tumors
- Endometrioid tumors
- Clear cell tumors
- Brenner tumors
- Cystadenofibroma
46
What are the main subtypes of germ cell tumours
- teratoma
- Dysgerminoma
- Endomermal sin tumour
- Choriocarcinoma
47
what is the overal frequency and what proportion of maligant ovarian tumours are surface epithelial cells, germ cell tumours, sex cord-stromal tumours or have metastasised to the ovaries
1. Surface epithelial cells : 65-70% / 90%
2. Germ cell tumors : 15-20% / 3-5%
3. Sex cord-stromal tumors : 5-10% / 2-3%
4. Metastasis to overies : 5% / 5%
48
In what age groups are affected by surface epithelial cells, germ cell tumours, sex cord-stromal tumours or have metastasised to the ovaries
1. Surface epithelial cells : 20+
2. Germ cell tumors : 0 - 25+
3. Sex cord-stromal tumors : all ages
4. Metastasis to overies : variable
49
What is a key point about mucinous ovarian tumors?
Most mucinous carcinomas in the ovary are actually metastasis, often originating from the colon (large bowel) or stomach rather than being primary ovarian cancers.
50
What are the two most common malignant ovarian tumors?
1. Low-grade serous carcinoma
2. High-grade serous carcinoma (most common and aggressive form)
51
What are the three main differences between a low grade and a high grade serous ovarian carcinoma
1. Morphology
2. Prognosis
3. Genetics
52
How des the morphology of low-grade and high-grade serous ovarian carcinomas differ?
Low-grade serous carcinoma has well-differentiated, monomorphic cells, while high-grade serous carcinoma has pleomorphic, highly atypical cells.
53
which type of serous ovarian carcinoma has a better prognosis?
Low-grade serous carcinoma has a better prognosis, while high-grade serous carcinoma is more aggressive.
54
Which genetic mutations are commonly associated with low-grade vs high-grade serous carcinomas?
Low-grade serous carcinomas are often linked to BRAF or KRAS mutations
while
High-grade serous carcinomas are strongly associated with TP53 mutations
55
What is a low-grade serous carcinoma?
Low-grade serous carcinoma is a slow-growing, well differentiated ovarian cancer with a papillary growth pattern, mild nuclear atypia and low mitotic activity. It is often bilateral, contains calcification and may present with peritoneal implants
56
At what age does low-grade vs high grade serous carcinomas typically occur
Low-grade = 5th and 6th decade of life
high-grade = mean age of diagnosis is 63 years
(similar ages)
57
Are both low-grade and high-grade serous carcinomas bilateral?
yes (bilateral = affecting both ovaries
58
what is the typical growth pattern of low-grade vs high grade serous carcinomas?
low-grade = fine papillary nodular growths (finger-like)
high grade = mixture of solid and cystic (fluid filled) growth with exophytic (grows outwards) solid or papillary (finger like) components
59
How does necrosis differ between low-grade and high-grade serous carcinoma?
Low-grade has little to no necrosis, whereas high-grade frequently shows extensive necrosis.
60
What structural features distinguish low grade and high grade serous carcinomas?
Low grade = central fibrous stroma with a serpentine-like protrusion (known as a "Medusa's head" pattern) with frequent calcification
High grade = no medusa's head pattern with variable body calcification and can completely involve the fallopian tubes making it seem unrecognisable
61
How does tumour spread appear in high-grade serous carcinoma
In 30% of cases, the ovary appears normal in size, with only small implants or surface nodules <1cm.
62
What are the histological differences between low-grade and high-grade serous carcinomas?
Low-grade: Mild atypia, monomorphic nuclei, infrequent mitotic figures.
High-grade: High mitotic activity, pleomorphic nuclei, large nucleoli, frequent necrosis.
63
What was the traditional hypothesis about the origin of serous ovarian tumors?
They were thought to originate from the ovarian surface epithelium (mesothelial cells) that undergo metaplastic changes to acquire Müllerian differentiation
64
What is Müllerian differentiation in the context of serous ovarian tumors?
It refers to the transformation of ovarian surface epithelium into tissue resembling the fallopian tube, uterus, and genital tract.
65
What is the current understanding of the origin of serous ovarian carcinomas?
Many high-grade serous carcinomas originate from the fallopian tube rather than the ovarian surface epithelium. This discovery changed how tumors are studied and classified.
66
Why was the fallopian tube previously not well-studied in ovarian cancer cases?
he fallopian tube was removed along with the ovary, but only small sections were analyzed. The primary focus was on the large ovarian mass, rather than the small fallopian tube tissue, leading to a lack of detailed study.
67
what is the difference between a nuclei and a nucleoli
The nucleus is a larger, membrane bound organelle that actually houses the nucleolus (not membrane bound) which is a spherical structure found in the cell's nucleus with a primary function of producing and assembling the cell's ribosomes.
68
What histological feature differentiates borderline tumors from invasive carcinomas?
- Depth of invasion: If tumor invasion is less than 5mm, it is classified as borderline.
- If it invades deeper than 5mm, it is classified as low-grade serous carcinoma.
69
what are serous ovarian carcinomas
A serous ovarian carcinoma is a type of ovarian cancer that originates from the serous membrane lining the ovary, and is often referred to as "high-grade serous carcinoma" which is the most common and aggressive form of epithelial ovarian cancer
70
How do serous ovarian carcinomas spread?
- Peritoneal dissemination (spreading within the abdominal cavity).
- Can metastasize to lymph nodes even when appearing histologically mild
71
Why do serous tumors often have calcifications?
Any tumor that forms papillary structures tends to accumulate calcium over time
72
What type of calcifications are commonly seen in serous tumours?
Psammoma bodies, which are round, laminated calcified structures found in papillary tumors.
73
Why do psammoma bodies form
cellular necrosis results in calcium phosphate being deposited around the cellular debris forming layers (similar to an onion). over time these layers accumulate resulting in the characteristic laminated appearance
74
How does the presence of calcifications help in diagnosing serous tumors?
Microcalcifications on imaging (e.g., CT or ultrasound) may indicate a papillary tumor.
Histologically, the presence of psammoma bodies supports the diagnosis of serous carcinoma or other papillary tumors.
75
What does the presence of tumor in lymph nodes indicate?
Even though low-grade serous carcinoma is not highly atypical, the presence of lymph node metastases confirms it as a carcinoma and not just a borderline lesion.
76
What is the most common cause of death among ovarian cancer patients?
High-grade serous carcinoma (HGSC) is responsible for the majority of deaths caused by ovarian tumors due to its aggressive nature and late-stage diagnosis.
77
What genetic mutation is the primary driver of high-grade serous carcinoma?
TP53 mutations are the hallmark of high-grade serous carcinoma, making p53 staining a key diagnostic tool.
78
How does p53 immunohistochemistry help diagnose high-grade serous carcinoma?
The p53 mutation is a key driver of high-grade serous carcinoma (HGSC). This mutation plays a crucial role in the development of the tumor. therefore a strong, diffuse staining or complete absence of staining suggests a TP53 mutation and hence are characteristics of HGSC
79
What is the role of WT1 in HGSC
WT1 is positive in high-grade serous carcinoma (HGSC) that originates from the ovary or fallopian tube.
80
How does WT1 help differentiate between ovarian and endometrial tumours?
WT1 is negative in uterine serous carcinoma (a type of endometrial cancer), helping distinguish it from ovarian HGSC.
81
What is the most common type of mucinous carcinoma found in the ovary?
Metastatic mucinous carcinoma, making up 77% of ovarian mucinous carcinomas
they most commonly come from the gastrointestinal (GI) tract (e.g., colorectal, appendix, pancreas
82
What percentage of mucinous ovarian tumors are primary ovarian mucinous carcinomas?
Only 23% are primary ovarian mucinous carcinomas.
83
What are the key features of primary ovarian mucinous carcinoma?
- 77% of ovarian mucinous carcinomas are metastases, 23% are ovarian primaries originating from borderline mucinous tumours
- Unilateral (metastatic ones are often bilateral).
- Large, multiloculated cystic mass filled with mucin.
- May arise from a borderline mucinous tumor
84
What is seromucinous carcinoma of the ovary?
A rare type of ovarian carcinoma with mixed serous and mucinous features.
85
What are the histological characteristics of clear cell carcinoma of the ovary?
Large, polygonal cells with clear or pink cytoplasm.
High nuclear atypia and hobnail cells.
Often associated with endometriosis.
86
In which population is clear cell carcinoma of the ovary most common?
Highest incidence in Japan, accounting for 25% of ovarian carcinomas.
87
What is a significant risk factor for clear cell carcinoma of the ovary?
Endometriosis—clear cell carcinoma frequently arises in the setting of endometriotic cysts.
88
What percentage of primary ovarian carcinomas are endometrioid carcinoma?
About 10% of primary ovarian carcinomas.
89
What are the key associations of endometrioid carcinoma of the ovary?
Endometriosis (common precursor lesion).
Can be synchronous with endometrial carcinoma (found in uterus & ovary).
More common in the Asian population than in Caucasians.
90
what was the traditional hypothesis about the origin of high-grade serous carcinoma (HGSC) of the ovary?
It was thought to arise from metaplastic changes in the surface epithelium of the ovary, which originates from mesothelial cells.
91
Why was the traditional ovarian surface epithelium hypothesis for HGSC questioned?
- HGSC does not retain mesothelial markers.
- There is no evidence of metaplastic changes or low-grade dysplasia transitioning to cancer.
- There are no hybrid forms between mesothelial tumors and HGSC.
- Similar mesothelial linings in other organs (e.g., testis) do not develop similar tumors.
92
Controversies in Ovarian Surface Epithelium and Tumors
1. Ovarian Surface Epithelial Carcinomas (OSE) Characteristics: Serous, endometrioid, clear cell, mucinous, seromucinous, transitional tumors do not resemble OSE.
Metaplasia:
2. Metaplasia of OSE is difficult to demonstrate and almost never observed. No intermediate or hybrid phenotypes of OSE metaplasia tumors.
3. Mesotheliomas: Real mesotheliomas are rare in the ovaries.
4. Molecular Markers: Most ovarian tumors do not express OSE molecular markers.
5. Testis Tumors: Analogous surface (tunica albuginea) tumors in the testis are rare.
93
What genetic mutations are commonly associated with hereditary ovarian and fallopian tube cancers?
BRCA1 and BRCA2 mutations, which increase the risk of:
- Breast cancer
- Ovarian cancer (primarily HGSC)
- Fallopian tube cancer
- Endometrial cancer (to a lesser extent)
94
What led to the shift in focus from the ovary to the fallopian tube as the origin of HGSC?
- Prophylactic surgeries (removal of ovaries and fallopian tubes) in BRCA-mutated patients revealed small precancerous lesions in the fallopian tubes.
- Histological and genetic similarities between fallopian tube lesions and HGSC.
- Tubal ligation/removal is protective, reducing the risk of HGSC.
95
What is the precursor lesion for high-grade serous carcinoma (HGSC)?
Serous tubal intraepithelial carcinoma (STIC), found in the fimbrial end of the fallopian tube.
96
What are the common origins of endometrioid carcinoma and clear cell carcinoma of the ovary?
Endometriosis is the primary precursor for both types.
97
How does endometriosis contribute to endometrioid and clear cell carcinoma?
Endometriosis creates a chronic inflammatory environment.
Leads to genetic mutations (e.g., ARID1A, PTEN, PIK3CA) promoting tumorigenesis.
Endometriotic cysts can transform into malignant tumors over time.
98
Where do high-grade serous carcinomas (HGSC) tend to be found in the fallopian tube?
HGSCs are typically found in the fimbria, the last part of the fallopian tube near the ovaries. They can also appear in smaller proportions in the ampulla or isthmus. In some cases, they can be bilateral (10-20%) or multifocal.
99
What is the relationship between serous tubal intraepithelial carcinoma (STIC) and high-grade serous carcinoma (HGSC)?
STIC and HGSC share overlapping molecular alterations such as p53, p16, FAS, RSF1, CCNE1, and centrosome amplification, indicating a clonal relationship between the two.
100
How can the risk of high-grade serous carcinoma be reduced in BRCA patients?
BRCA patients can reduce the risk by opting for bilateral mastectomy and removal of the fallopian tube. The ovaries may also be removed, but this leads to menopause. Removing just the fallopian tubes may be sufficient.
101
What effect does tubal ligation or fallopian tube removal have on the risk of certain ovarian cancers?
Tubal ligation or the removal of the fallopian tube lowers the risk of ovarian endometrioid carcinoma, clear cell carcinoma, and high-grade serous carcinoma, as these cancers may originate from endometrial or endometriotic foci.
102
What are the typical cells of origin for most ovarian cancers?
extra-ovarian Müllerian epithelia (endometrium or fallopian tube epithelium) / Overial surface epithelium (OSE)
103
What is the primary site of origin for most ovarian cancers?
Primary site of origin: extra-ovarian Müllerian epithelia (endometrium or fallopian tube epithelium) or ovary (endometriosis or fallopian tube epithelium seeded on the ovary as inclusion cysts)
104
How do cells from extra-ovarian sites contribute to ovarian cancer?
Genetically normal or mutated epithelial cells from the fallopian tube or endometrium can seed the ovary, often through inclusion cysts. These cells then acquire additional genetic changes, leading to neoplastic transformation.
105
What is the relationship between endometriosis and ovarian cancer?
Endometriosis is associated with an increased risk of ovarian cancer. Cells from the endometrium may seed the ovary, creating foci that can eventually lead to neoplastic changes.
106
What is the origin of mucinous carcinomas?
Mucinous carcinomas likely have different origins, including mature cystic teratomas (germ cell tumors) or extra-ovarian Müllerian epithelium (e.g., Brenner tumors or endometriosis).
107
What is observed when fallopian tubes are thoroughly analyzed in ovarian cancer?
Upon thorough examination of the fallopian tubes, small P53 patches may be found. These patches, while not typical, may appear slightly darker and exhibit increased activity when analyzed with P53 staining.
(These patches could show a higher proliferative index when using P67, but they are not tumors at this stage)
108
What are "signature P53 patches"?
Signature P53 patches are small foci in the fallopian tube that show increased P53 staining, indicating potential neoplastic transformation. They are not tumors but may represent early carcinoma stages. Over time, these patches can develop into serous tubal intraepithelial carcinoma (STIC), which may seed the ovaries and progress to high-grade serous carcinoma.
109
How do signature P53 patches potentially evolve into ovarian cancer?
If P53 patches are present along with characteristic morphological changes (potential key events to drive progression) , this could indicate an early carcinoma that may eventually evolve into high-grade serous carcinoma (HGSC).
110
hat are the alternative pathways for ovarian tumorigenesis?
- Other genetic mutations e.g. Potiagers Codon syndrome,
- Mutations in genes like KRAS, BRAF, HER2, and P10.
These mutations can lead to different pathways of tumorigenesis, with similar end stages, such as the presence of P53 mutation and morphological changes.
111
Why is it important to determine the origin of high-grade serous carcinoma (HGSC)?
If HGSC originates in the endometrium and is found in the ovary, it is classified as metastasis, affecting staging and treatment. If it arises in both the ovary and fallopian tube, it’s considered a primary tumor, not metastatic.
112
How do different mutations affect the classification of ovarian tumors?
Different mutations can lead to borderline tumors rather than full carcinomas. Understanding these mutations helps determine whether a tumor is benign, borderline, or malignant.
113
What is the biggest killer in terms of ovarian tumours
high grade serous (HGS) (70% of malignant tumours fall into this category with poor prognosis
114
Why does HGS have such poor prognosis
Because 80% of diagnosis are made at the advanced stage look at ovarian cancer prognosis sheet....
115
What is the connection between cancer and endometriosis?
Endometriosis is a condition where endometrial tissue grows outside of the uterus, and it is associated with an increased risk of developing ovarian cancers:
Endometrioid carcinoma (40% of cases).
Clear cell carcinoma (50-90% of cases).
Patients with endometriosis have a 3-10x increased risk of developing these cancers.
116
What are the typical molecular genetic alterations in cancers associated with endometriosis?
Common genetic alterations in these cancers include:
ARID1A
KRAS
MET
117
What is a "chocolate cyst" in the context of endometriosis?
ovarian cysts filled with blood due to menstrual shedding.. The cysts can appear cystic and contain dark, old blood, resembling chocolate in appearance.
118
How does endometriosis differ from adenomyosis?
Endometriosis refers to the presence of endometrial tissue outside the uterus, often in the abdominal cavity or ovaries.
Adenomyosis is the term used when endometrial tissue grows within the wall of the uterus (myometrium), not outside of it.
119
What is the current understanding of the incidence of primary mucinous ovarian carcinomas?
Primary mucinous ovarian carcinomas are less common than previously thought. The real incidence is lower than what was once estimated.
120
What is the possible origin of mucinous ovarian tumors?
Mucinous ovarian tumors may have a different origin compared to other ovarian cancers. The KRAS gene seems to be more involved in the development of mucinous tumors.
121
What pathways are shared between clear cell and endometrioid carcinomas?
Clear cell and endometrioid carcinomas seem to share certain pathways, particularly involving mutations such as PTEN (a tumor suppressor gene) and MMR (mismatch repair) deficiency.
122
What are the most common benign ovarian tumors, and what do they look like?
The most common benign ovarian tumors are cystadenomas. These tumors typically present as large cysts filled with fluid, often containing mucoid (jelly-like) material.
123
What are the two types of cystadenomas
Serous cystadenomas (clear fluid-filled)
Mucinous cystadenomas (mucoid or jelly-like fluid-filled)
124
What is the significance of the "borderline pattern" in ovarian tumors?
refers to a benign growth pattern, where the epithelium lining of the tumor is thicker or more florid than typical cystadenomas. these may have small patcges of tumour material outside the ovary.
125
What happens if borderline tumours are excised
While these were once considered malignant, we now understand that if excised, these tumors are self-limiting and will not grow or cause problems afterward.
126
How has the classification of borderline tumors changed over time?
They are now considered benign and are no longer labeled as potentially malignant as long as they are excised.
127
What are the growth patterns in mucinous ovarian carcinoma?
Mucinous ovarian carcinoma can show two types of growth patterns:
1. Expansile growth: This is a pushing growth pattern and is generally associated with a better prognosis.
2. Infiltrative growth: This growth pattern involves the carcinoma invading surrounding tissue, such as blood vessels or lymphatics, and is associated with a higher risk of metastasis.
128
What genetic abnormalities are commonly found in mucinous ovarian carcinoma?
often exhibits abnormalities in the KRAS gene.
As the tumor progresses, additional mutations are observed, including in the HER2 gene and P53, which are associated with higher proliferative indices and increased cellular atypia.
129
What is the relationship between KRAS mutations and ovarian cancer prognosis?
KRAS mutations are commonly found in mucinous ovarian tumors and are associated with different growth patterns. Expansile growth tends to have a better prognosis, while infiltrative growth has a higher risk of metastasis, particularly when combined with mutations in HER2 and P53.
130
Why is it important to identify whether an ovarian tumor has ruptured during surgery?
Rupture of ovarian tumors, particularly large and friable tumors, can lead to dissemination of tumor cells into the abdominal cavity, which complicates the staging and prognosis.
131
Why is it important for pathologists to know if the tumour ruptured before or during removal
This helps determine the extent of spread and ensures accurate pathological reporting.
132
What method can pathologists use to identify if a tumor is on the surface or has spread
- Inking: Pathologists can use China ink to mark the surface of the tumor sample. If the tumor is in contact with the ink, it is likely on the surface of the tumor.
- Distance measurement: Pathologists can measure the distance from the serosa to determine if there’s clearance and how much. This helps in staging and assessing potential spread.
133
What is the prognosis for high-grade serous ovarian carcinoma?
High-grade serous carcinoma (HGSC) is the most common and deadly form of ovarian cancer, accounting for 70% of ovarian malignancies.
134
Why is the prognosis for high grade serous ovarian carcinoma so poor
Prognosis is poor due to advanced stage at presentation, as the tumor often spreads within the pelvic cavity and can disseminate to other organs. Additionally, cancer cells can be found in abdominal fluid.
135
What is the prognosis for low-grade serous ovarian carcinoma?
Low-grade serous carcinoma (LGSC) has an intermediate prognosis.
The prognosis depends on the stage at presentation. It typically presents at an advanced stage, but the overall prognosis is better than high-grade serous carcinoma.
136
Why does endometrioid carcinoma typically have better outcomes compared to other ovarian carcinomas
Endometrioid carcinoma is generally more responsive to chemotherapy, providing more treatment options
137
How is ovarian cancer staged, and what does it imply for the prognosis?
Stage 1: The cancer is confined to the ovary.
Stage 2: Spread to the fallopian tubes or other pelvic organs.
Stage 3: Spread to the peritoneum, lymph nodes, or abdominal fluid.
Stage 4: Distant metastasis such as spread to the lungs or distant organs, which is associated with the worst prognosis.
138
What is the significance of ovarian cancer's ability to metastasize?
Ovarian cancer can spread through local dissemination, lymphatic spread, or hematogenous spread (via blood). this important to know for staging and determining prognosis
139
How do medical and scientific interpretations evolve in relation to ovarian tumors?
In medicine and science, new evidence may lead to changes in how diseases, such as ovarian tumors, are classified or treated.
The importance of being flexible and ready to adapt to new information is key, as outdated beliefs (e.g., tumor classification) may no longer be correct.
