Neoplasia Practice Questions

Q: What is the most common tumor suppressor gene involved in carcinogenesis?

p53. ***p53*** [1][2] - The **p53 gene** is widely recognized as the most common tumor suppressor gene associated with various cancers, particularly due to its role in apoptosis and cell cycle regulation [1][2]. - Mutations in **p53** are found in over **50%** of human tumors, highlighting its critical role in cancer genesis [2]. *Rb* - While the **Rb gene** is significant in preventing retinoblastoma and other cancers, it is less commonly mutated overall compared to p53 [1]. - Rb primarily regulates the **cell cycle**, particularly the transition from G1 to S phase, but its involvement in cancer is more limited in scope [2]. *p16* - **p16** acts as an inhibitor of cyclin-dependent kinases but is primarily associated with specific cancers such as melanoma, not broadly across all cancers. - It serves as a cell cycle checkpoint but is not as ubiquitous a tumor suppressor as p53. *p73* - Although **p73** shares structural similarities with p53 and has roles in apoptosis, it is not as frequently implicated in cancer development. - Its functions are more related to developmental processes and it does not have the same high mutation rates seen in tumors as p53. **References:** [1] Kumar V, Abbas AK, et al.. Robbins and Cotran Pathologic Basis of Disease. 9th ed. Neoplasia, pp. 297-298, 302-304. [2] Cross SS. Underwood's Pathology: A Clinical Approach. 6th ed. (Basic Pathology) introduces the student to key general principles of pathology, both as a medical science and as a clinical activity with a vital role in patient care. Part 2 (Disease Mechanisms) provides fundamental knowledge about the cellular and molecular processes involved in diseases, providing the rationale for their treatment. Part 3 (Systematic Pathology) deals in detail with specific diseases, with emphasis on the clinically important aspects., pp. 227-228.

Q: Immunohistochemical marker for sentinel node biopsy in breast carcinoma?

Cytokeratin. ***Cytokeratin*** - **Cytokeratin** is a specific marker for **epithelial cells**, including those of breast carcinoma, making it ideal for detecting micrometastases in lymph nodes. - Immunohistochemistry with cytokeratin antibodies can identify even small clusters of tumor cells not visible on routine hematoxylin and eosin (H&E) staining. *Vimentin* - **Vimentin** is a filament protein characteristic of **mesenchymal cells**, such as fibroblasts and endothelial cells, not epithelial carcinoma cells. - While some carcinomas can exhibit **epithelial-mesenchymal transition (EMT)** and express vimentin, it is not the primary or most specific marker for detecting breast carcinoma cells in lymph nodes. *Calretinin* - **Calretinin** is a marker typically used to identify **mesothelial cells** and is often employed in the diagnosis of **mesothelioma**. - It is not expressed by breast carcinoma cells and would not be useful for detecting metastatic disease in sentinel lymph nodes. *CD45* - **CD45** (Leukocyte Common Antigen) is a specific marker for **hematopoietic cells**, including lymphocytes, macrophages, and other immune cells. - It is used to identify and distinguish lymphoid infiltrates but is not expressed by breast carcinoma cells, making it unsuitable for this purpose.

Q: In breast carcinoma, prognosis depends best upon -

Axillary lymph node status. ***Axillary lymphnode status*** - The presence and number of **positive axillary lymph nodes** are the **most significant prognostic factor** in breast carcinoma, as they directly indicate the extent of regional spread [1]. - Involvement of axillary lymph nodes is strongly predictive of a **higher risk of distant metastasis** and generally a poorer prognosis [2]. *Estrogen receptor status* - **Estrogen receptor (ER) status** is an important **predictive marker** for response to hormonal therapy, but it is not the best single indicator of overall prognosis in metastatic disease [2]. - While ER-positive tumors generally have a better prognosis and respond to endocrine therapy, the presence of metastasis itself dictates much of the prognosis. *Size of tumour* - **Tumor size** is a significant prognostic factor for **primary breast cancer**, with larger tumors generally having a worse prognosis [1]. - However, in the context of **metastasis**, the spread to lymph nodes or distant sites becomes a more critical determinant of overall prognosis than the original tumor size. *Site of tumour* - The **site of the primary tumor within the breast** generally has **little independent prognostic value** once metastasis has occurred or is being evaluated. - While certain locations might be associated with variations in lymph node drainage, the actual **lymph node status** is what directly reflects metastatic spread and prognosis. **References:** [1] Kumar V, Abbas AK, et al.. Robbins and Cotran Pathologic Basis of Disease. 9th ed. The Breast, pp. 1070-1072. [2] Cross SS. Underwood's Pathology: A Clinical Approach. 6th ed. Common Clinical Problems From Liver And Biliary System Disease, pp. 458-459.

Q: Grade of tumor denotes

Degree of differentiation. ***Degree of differentiation*** - The grade of a tumor is primarily defined by the **degree of differentiation** of the cancer cells, indicating how much the tumor cells resemble normal cells [2]. - Grading helps predict the **aggressiveness** of cancer and its behavior in the body. *Vascular invasion* - Vascular invasion refers to the presence of cancer cells within blood vessels and is more associated with tumor **stage** rather than the **grade**. - It indicates the potential for cancer to metastasize, but it does not reflect the differentiation of cells. *Stage of disease* - The stage of disease encompasses the extent of tumor spread and includes aspects such as **size** and **lymph node involvement**, rather than the cellular characteristics of differentiation. - Staging is about **how advanced** the cancer is, while grading focuses on the **appearance** of the tumor cells. *Degree of anaplasia* - Anaplasia refers to the loss of differentiation and organization of cells [1][2], which can relate to tumor **grade**, but it is not synonymous with grading itself. - While higher grades indicate greater anaplasia, not all anaplastic tumors are graded the same due to other factors influencing classification. **References:** [1] Kumar V, Abbas AK, et al.. Robbins and Cotran Pathologic Basis of Disease. 9th ed. Neoplasia, pp. 278-280. [2] Kumar V, Abbas AK, et al.. Robbins and Cotran Pathologic Basis of Disease. 9th ed. Neoplasia, pp. 276-278.

Q: Paraneoplastic syndrome Hypercalcemia of malignancy is produced due to ectopic production of which hormone by solid tumors like squamous cell carcinoma?

PTHrP. ***PTHrP*** - **Parathyroid hormone-related protein (PTHrP)** is the most common cause of **humoral hypercalcemia of malignancy**, particularly in **solid tumors** such as squamous cell carcinoma (lung, head and neck), renal cell carcinoma, and breast cancer. - It mimics the actions of parathyroid hormone (PTH), leading to increased **bone resorption** and **renal calcium reabsorption**. - PTHrP binds to the same PTH receptor and activates similar signaling pathways, resulting in elevated serum calcium levels. *Calcitonin* - **Calcitonin** is a hormone that **lowers blood calcium levels** by inhibiting osteoclast activity and increasing renal calcium excretion. - Ectopic production of calcitonin (seen in medullary thyroid carcinoma) would cause **hypocalcemia**, not hypercalcemia. *PGE2* - **Prostaglandin E2 (PGE2)** can contribute to **local bone resorption** in some malignancies through stimulation of osteoclast activity. - However, its role is less prominent and typically involves **local osteolytic** mechanisms rather than systemic humoral effects like PTHrP. *Parathormone* - **Parathormone (PTH)** is produced by the parathyroid glands; true ectopic PTH production by tumors is **extremely rare**. - The primary mechanism of humoral hypercalcemia of malignancy in solid tumors is almost exclusively due to **PTHrP**, not PTH itself.

Q: Which syndrome is associated with an inherited mutation of the p53 tumor suppressor gene?

Li-Fraumeni syndrome. ***Li-Fraumeni syndrome*** - This syndrome is characterized by an inherited mutation in the **TP53 tumor suppressor gene**, which encodes the p53 protein. - Individuals with Li-Fraumeni syndrome have a significantly increased risk of developing various cancers at a young age, including **osteosarcoma**, soft tissue sarcomas, breast cancer, brain tumors, and adrenocortical carcinoma. *Familial adenomatous polyposis syndrome* - This syndrome is caused by an inherited mutation in the **APC tumor suppressor gene**, not p53. - It is characterized by the development of hundreds to thousands of **colorectal adenomatous polyps**, which inevitably progress to colorectal cancer if untreated. *Retinoblastoma syndrome* - This syndrome is caused by an inherited mutation in the **RB1 tumor suppressor gene**, not p53. - It primarily affects the eye, leading to the development of **retinoblastoma**, a malignant tumor of the retina, often in childhood. *Osteosarcoma syndrome* - While osteosarcoma is a common cancer type seen in Li-Fraumeni syndrome, "Osteosarcoma syndrome" itself is not a distinct inherited syndrome specifically defined by a p53 mutation. - **Osteosarcoma** can arise from various genetic predispositions, including Li-Fraumeni syndrome, but it's not the sole defining characteristic of a p53-related syndrome.

Q: Anaplasia is

Lack of differentiation. ***Lack of differentiation*** - Anaplasia refers to a **loss of differentiation** in cells, making them more primitive and less specialized [1]. - It is often seen in **malignant tumors**, indicating a poor prognosis and aggressive behavior [1]. *Morphological changes* - While anaplasia involves **morphological changes**, this term is too broad and can relate to various cellular alterations, not exclusively anaplasia [1]. - Anaplasia specifically emphasizes **lack of differentiation**, distinct from general changes in cell appearance [1]. *Changing one type of epithelium to another* - This describes a process known as **metaplasia**, where one adult cell type transforms into another, not anaplasia. - Anaplasia signifies a **de-differentiation** rather than a change to a different epithelial type [1]. *Nuclear chromatin* - While changes in **nuclear chromatin** can occur in anaplastic cells, this does not define anaplasia itself [1]. - Anaplasia primarily refers to **loss of cell differentiation**, making this option insufficient to describe the concept [1]. **References:** [1] Kumar V, Abbas AK, et al.. Robbins and Cotran Pathologic Basis of Disease. 9th ed. Neoplasia, pp. 276-280.

Q: Which is the most common type of male breast cancer?

Invasive Ductal Carcinoma. ***Invasive Ductal Carcinoma*** - This is by far the most common type of breast cancer in men, accounting for approximately **80-90%** of all male breast cancer cases. - It originates in the **milk ducts** and then invades the surrounding breast tissue. *Invasive Lobular Carcinoma* - This type of cancer originates in the **milk-producing glands (lobules)**. - It is **extremely rare** in men due to the underdeveloped and non-functional lobules in the male breast. *Mucinous Carcinoma* - This is a **rare subtype** of invasive ductal carcinoma characterized by cancer cells that produce **mucin**. - It accounts for only a small percentage of male breast cancers, typically **2-3%** of cases. *Inflammatory Breast Cancer* - This is a **rare and aggressive** form of breast cancer characterized by rapid onset of redness, swelling, and warmth in the breast, often mistaken for an infection. - Although it can occur in men, it is not the most common type and represents a very small fraction of male breast cancer diagnoses.

Q: Which of the following is not associated with Carney's triad?

Atrial myxoma. ***Atrial myxoma*** - Atriomyxoma is not part of **Carney's triad**, which primarily includes **paraganglioma**, **chondroma**, and **gastrointestinal stromal tumors (GIST)**. - Carney's triad is a rare genetic condition associated with **multiple neoplasms**, and atrial myxomas are cardiac tumors, not part of this triad. *Paraganglioma* - Paragangliomas are tumors derived from **neuroendocrine cells**, and they are one of the key components of **Carney's triad**. - They typically arise in **chromaffin tissue**, which is involved in catecholamine secretion. *Chondroma* - Chondromas are benign tumors of **cartilage**, also recognized as a component of **Carney's triad**. - They are often found in the **bones** or soft tissues, but they are part of the neoplasms associated with this condition. *GIST* - Gastrointestinal stromal tumors (GISTs) are significant neoplasms linked to **Carney's triad**, arising from **interstitial cells of Cajal** in the GI tract. - They are characterized by specific mutations and can be a source of gastrointestinal symptoms in affected individuals.

Q: Which of the following is an oncogene?

RAS. ***RAS*** - RAS is an **oncogene**, not a tumor suppressor gene; it promotes cell proliferation and survival [1]. - Mutations in RAS lead to uncontrolled cell division, contributing to various cancers. *p53* - p53 is a crucial **tumor suppressor gene** responsible for regulating the cell cycle and preventing tumor formation [1,2]. - It functions by inducing apoptosis in cells with damaged DNA, preventing their proliferation [2]. *WT-1* - WT-1 is a **tumor suppressor gene** associated with Wilms' tumor and regulates kidney and gonadal development. - It plays a role in cell growth and differentiation, preventing tumorigenesis when functioning correctly. *Rb* - The Rb gene encodes the **retinoblastoma protein**, a key tumor suppressor that regulates the cell cycle by inhibiting cell division [1,2]. - Loss of Rb function is primarily associated with retinoblastoma and other cancers, indicating its critical role in tumor suppression [1,2]. **References:** [1] Kumar V, Abbas AK, et al.. Robbins and Cotran Pathologic Basis of Disease. 9th ed. Neoplasia, pp. 297-301. [2] Cross SS. Underwood's Pathology: A Clinical Approach. 6th ed. (Basic Pathology) introduces the student to key general principles of pathology, both as a medical science and as a clinical activity with a vital role in patient care. Part 2 (Disease Mechanisms) provides fundamental knowledge about the cellular and molecular processes involved in diseases, providing the rationale for their treatment. Part 3 (Systematic Pathology) deals in detail with specific diseases, with emphasis on the clinically important aspects., pp. 227-228.

Question 1

What is the most common tumor suppressor gene involved in carcinogenesis?

Accepted Answer

p53

Answer

Retinoblastoma (Rb)

Answer

Tumor protein p73 (p73)

Answer

Cyclin-dependent kinase inhibitor 2A (p16)

Question 2

Immunohistochemical marker for sentinel node biopsy in breast carcinoma?

Accepted Answer

Cytokeratin

Answer

Vimentin

Answer

Calretinin

Answer

CD45

Question 3

In breast carcinoma, prognosis depends best upon -

Accepted Answer

Axillary lymph node status

Answer

Size of tumour

Answer

Site of tumour

Answer

Estrogen receptor status

Question 4

Grade of tumor denotes

Accepted Answer

Degree of differentiation

Answer

Degree of anaplasia

Answer

Stage of disease

Answer

Vascular invasion

Question 5

Paraneoplastic syndrome Hypercalcemia of malignancy is produced due to ectopic production of which hormone by solid tumors like squamous cell carcinoma?

Accepted Answer

PTHrP

Answer

Calcitonin

Answer

PGE2

Answer

Parathormone

Question 6

Which syndrome is associated with an inherited mutation of the p53 tumor suppressor gene?

Accepted Answer

Li-Fraumeni syndrome

Answer

Familial adenomatous polyposis syndrome

Answer

Retinoblastoma syndrome

Answer

Osteosarcoma syndrome

Question 7

Anaplasia is

Accepted Answer

Lack of differentiation

Answer

Changing one type of epithelium to another

Answer

Nuclear chromatin

Answer

Morphological changes

Question 8

Which is the most common type of male breast cancer?

Accepted Answer

Invasive Ductal Carcinoma

Answer

Inflammatory Breast Cancer

Answer

Invasive Lobular Carcinoma

Answer

Mucinous Carcinoma

Question 9

Which of the following is not associated with Carney's triad?

Accepted Answer

Atrial myxoma

Answer

GIST

Answer

Chondroma

Answer

Paraganglioma

Question 10

Which of the following is an oncogene?

Accepted Answer

RAS

Answer

WT-1

Answer

Rb

Answer

p53

Neoplasia — MCQs

Neoplasia — MCQs

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