Neoplasia Practice Questions

Q: TTF-1 is a tumor marker for which of the following?

Small cell carcinoma. ***Small cell carcinoma*** - **Thyroid transcription factor 1 (TTF-1)** is a nuclear transcription protein expressed in lung and thyroid neoplasms - It is positive in **85-90% of small cell lung carcinomas**, making it a key immunohistochemical marker [1] - TTF-1 helps differentiate small cell carcinoma from other neuroendocrine tumors and extrapulmonary small cell carcinomas [1] *Adenocarcinoma* - TTF-1 is also **strongly positive in 75-80% of lung adenocarcinomas** - It is a primary marker for lung adenocarcinoma, often used with **Napsin A** and **Cytokeratin 7 (CK7)** *Thymoma* - Thymomas are neoplasms of the **thymus gland** and typically express **cytokeratins** but **not TTF-1** - Characteristic markers include **CD5**, **CD117**, and epithelial markers *Melanoma* - Melanomas are cancers of **melanocytes** and express melanocytic markers like **S-100**, **HMB-45**, **Melan-A**, and **SOX10** - **TTF-1** is not expressed in melanoma and helps exclude lung primary when evaluating metastatic disease **References:** [1] Cross SS. Underwood's Pathology: A Clinical Approach. 6th ed. Common Clinical Problems From Respiratory Tract Disease, pp. 337-338.

Q: A 49 year old female presents with a breast lump. Which of the following findings is in accordance with basal-like breast cancer?

ER-, PR-, HER2-. ***ER-, PR-, HER2-*** - **Basal-like breast cancer** is characterized by its **triple-negative** status, meaning it does not express estrogen receptor (ER), progesterone receptor (PR), or human epidermal growth factor receptor 2 (HER2) [1]. - This specific immunophenotype is crucial for diagnosis and influences treatment strategies, as these cancers do not respond to therapies targeting these receptors [1]. *ER+, PR-, HER2-* - This profile describes a **hormone-sensitive** cancer (ER positive) but without PR or HER2 expression. - While it responds to endocrine therapies, it is distinct from basal-like cancer due to its ER positivity. *ER-, PR-, HER2+* - This profile indicates a cancer that is **HER2-positive**, meaning it overexpresses HER2, and can be targeted with anti-HER2 therapies like trastuzumab. - This is a separate molecular subtype of breast cancer often referred to as HER2-enriched, which is distinct from basal-like [2]. *ER+, PR+, HER2-* - This is the most common subtype, known as **luminal A** or **luminal B** depending on grade and Ki-67 expression, characterized by sensitivity to endocrine therapy [2]. - This hormone receptor-positive and HER2-negative profile is very different from the triple-negative basal-like breast cancer. **References:** [1] Kumar V, Abbas AK, et al.. Robbins and Cotran Pathologic Basis of Disease. 9th ed. The Breast, pp. 1064-1066. [2] Kumar V, Abbas AK, et al.. Robbins and Cotran Pathologic Basis of Disease. 9th ed. The Breast, p. 1060.

Q: The image below shows the life cycle of a virus. Which of the proteins of the virus act as oncogenes?

E6, E7. ***E6, E7*** - The **E6** and **E7** proteins of high-risk human papillomaviruses (HPVs) are considered **oncogenes** because they interfere with critical tumor suppressor pathways [1][2]. - **E6** promotes the degradation of **p53**, a tumor suppressor protein, while **E7** inactivates **retinoblastoma protein (pRb)**, leading to uncontrolled cell proliferation and increased risk of malignant transformation [2]. *L1, L2* - **L1** and **L2** are **late proteins** (structural proteins) that form the **viral capsid** (outer shell) of the HPV virion. - They are essential for assembling new viral particles but do not directly contribute to the oncogenic process by disrupting host cell cycle regulation. *E1, E2, E5* - **E1** is involved in **viral DNA replication**, acting as a helicase and ATPase. - **E2** regulates **viral gene expression** and DNA replication, while **E5** is a small transmembrane protein that can contribute to cell growth but is generally considered less potent in oncogenesis than E6 and E7, and its exact role varies by HPV type. *E1, E2* - **E1** is critical for **viral DNA replication**, and **E2** regulates viral gene transcription and DNA replication. - While important for the viral life cycle, neither E1 nor E2 are the primary drivers of oncogenesis in the way E6 and E7 are, as they do not directly target key tumor suppressor proteins like p53 and pRb. **References:** [1] Kumar V, Abbas AK, et al.. Robbins and Cotran Pathologic Basis of Disease. 9th ed. The Female Genital Tract, pp. 1007-1008. [2] Kumar V, Abbas AK, et al.. Robbins and Cotran Pathologic Basis of Disease. 9th ed. Neoplasia, pp. 334-335.

Q: Which of the following conditions is associated with perineural invasion?

Adenoid cystic carcinoma. ***Adenoid cystic carcinoma*** - **Adenoid cystic carcinoma** is the **most notoriously characterized** by its strong propensity for **perineural invasion**, which contributes to its high recurrence rate and poor prognosis [1]. - This invasion allows the tumor cells to spread along nerve sheaths, extending beyond the visible tumor margins, often for considerable distances. - It is the **classic example** of perineural invasion among salivary gland tumors [1]. *Mucoepidermoid tumor* - While mucoepidermoid tumors can be locally aggressive, **perineural invasion** is not a characteristic feature that defines this tumor type. - They are more commonly associated with cystic degeneration and mucin production. *Pancreatic cancer* - **Pancreatic adenocarcinoma** does show **significant perineural invasion** (present in 70-90% of cases) and is an important feature contributing to its poor prognosis and pain symptoms. - However, in the context of this question, **adenoid cystic carcinoma** is considered the **most characteristic** or **prototypical** example of perineural invasion, particularly among head and neck neoplasms. - Both are associated with perineural invasion, but adenoid cystic carcinoma is the textbook example. *Pleomorphic adenoma* - A **pleomorphic adenoma** is a benign mixed tumor of the salivary glands and usually does not exhibit **perineural invasion** [2]. - Malignant transformation into a carcinoma ex pleomorphic adenoma can occur, but the benign form primarily grows as an encapsulated mass [2]. **References:** [1] Kumar V, Abbas AK, et al.. Robbins and Cotran Pathologic Basis of Disease. 9th ed. Head and Neck, pp. 753-755. [2] Kumar V, Abbas AK, et al.. Robbins and Cotran Pathologic Basis of Disease. 9th ed. Head and Neck, pp. 751-753.

Q: What is the correct statement about thymoma?

Thymoma is the most common neoplasia of the thymus.. ***Thymoma is the most common neoplasia of the thymus.*** [1] - **Thymoma** is the most common primary tumor of the thymus, accounting for approximately **40-50% of anterior mediastinal masses** in adults. - It is a slow-growing tumor originating from the **epithelial cells** of the thymus [1]. *Chest X-ray is the investigation of choice for the diagnosis of thymoma.* - While a **chest X-ray** may show a widened mediastinum or an anterior mediastinal mass, it is not the investigation of choice for definitive diagnosis or staging [2]. - **CT scan** of the chest with contrast is the preferred imaging modality for evaluating thymomas, providing better anatomical detail and assessing invasiveness [2]. *Thymoma is typically asymptomatic and rarely causes any symptoms.* - Approximately **30-50% of patients with thymoma are asymptomatic** at diagnosis, with the tumor discovered incidentally on imaging [2]. - However, the remaining **50-70% of patients present with symptoms** related to **mass effect** (e.g., chest pain, dyspnea, cough) or **paraneoplastic syndromes** like myasthenia gravis, pure red cell aplasia, or hypogammaglobulinemia [2]. - Therefore, it is incorrect to say thymoma "rarely" causes symptoms. *Thymoma is primarily located in the posterior mediastinum.* - **Thymoma** is characteristically located in the **anterior mediastinum**, which is the most common site for thymic tissue. - Tumors primarily found in the posterior mediastinum are more commonly **neurogenic tumors**. **References:** [1] Cross SS. Underwood's Pathology: A Clinical Approach. 6th ed. Common Clinical Problems From Diseases Of The Urinary And Male Genital Tracts, pp. 571-574. [2] Cross SS. Underwood's Pathology: A Clinical Approach. 6th ed. Common Clinical Problems From Diseases Of The Urinary And Male Genital Tracts, pp. 572-574.

Q: Which of the following is an Anti-apoptotic gene?

MCL-1. ***MCL-1*** - **MCL-1 (myeloid cell leukemia sequence 1)** is a pro-survival protein belonging to the **Bcl-2 family**, which inhibits apoptosis by binding to and sequestering pro-apoptotic proteins [1]. - Its overexpression is frequently observed in various cancers, contributing to **chemoresistance** and tumor survival [2]. *BAK* - **BAK (Bcl-2 antagonist killer 1)** is a **pro-apoptotic protein** that belongs to the Bcl-2 family. - Upon activation, BAK undergoes **oligomerization** on the mitochondrial outer membrane, leading to its permeabilization and the release of pro-apoptotic factors into the cytoplasm. *BIN* - **BIN1 (Bridging Integrator 1)** is a **tumor suppressor gene** that can promote apoptosis in certain contexts, particularly when associated with DNA damage or cellular stress. - It is not primarily known as an anti-apoptotic gene but rather as a protein involved in **membrane dynamics** and cellular signaling, with roles in endocytosis and cytoskeletal regulation. *NOX-Q* - **NOX-Q** is not a commonly recognized or established gene in the context of apoptosis regulation. - The **NOX (NADPH oxidase) family** of enzymes is primarily involved in the production of **reactive oxygen species (ROS)**, which can either induce or inhibit apoptosis depending on the cellular context and concentration. **References:** [1] Kumar V, Abbas AK, et al.. Robbins and Cotran Pathologic Basis of Disease. 9th ed. Neoplasia, p. 310. [2] Kumar V, Abbas AK, et al.. Robbins and Cotran Pathologic Basis of Disease. 9th ed. Neoplasia, pp. 310-311.

Q: A 32-year-old HIV-positive man presents with multiple flesh-colored, pedunculated lesions on his penis. Biopsy shows koilocytes and increased mitotic figures. Which of the following viral proteins is responsible for the cellular changes observed?

E6 and E7 proteins. ***E6 and E7 proteins*** - The presence of **koilocytes** and **increased mitotic figures** in penile lesions, particularly in an HIV-positive individual, strongly suggests **Human Papillomavirus (HPV)** infection leading to condyloma acuminata [2]. - **HPV E6 and E7 oncoproteins** are critical for HPV-induced cell proliferation and immortalization; E6 degrades **p53** (a tumor suppressor), and E7 inactivates **Rb protein** (retinoblastoma protein), leading to uncontrolled cell division and the observed cellular changes [1]. *Tax protein* - The **Tax protein** is associated with **Human T-lymphotropic virus type 1 (HTLV-1)**, which causes Adult T-cell Leukemia/Lymphoma and HTLV-1-associated myelopathy/tropical spastic paraparesis, not HPV-related lesions. - Tax acts as a transcriptional activator, promoting viral gene expression and cellular proliferation but through different mechanisms than HPV oncoproteins. *L1 protein* - The **L1 protein** is a major **capsid protein** of HPV and is used in HPV vaccines to induce protective antibodies. - While essential for viral structure and assembly, L1 itself does not directly cause the cellular proliferative changes or koilocytic atypia seen in infected cells; these are driven by the E6 and E7 oncoproteins. *EBNA-1* - **EBNA-1** (Epstein-Barr Nuclear Antigen 1) is a protein produced by the **Epstein-Barr virus (EBV)**, which is associated with various lymphomas (e.g., Burkitt lymphoma, Hodgkin lymphoma) and nasopharyngeal carcinoma. - It is crucial for the maintenance of the EBV episome in latently infected cells and does not cause penile lesions with koilocytes. **References:** [1] Kumar V, Abbas AK, et al.. Robbins and Cotran Pathologic Basis of Disease. 9th ed. The Female Genital Tract, pp. 1007-1008. [2] Kumar V, Abbas AK, et al.. Robbins and Cotran Pathologic Basis of Disease. 9th ed. The Lower Urinary Tract and Male Genital System, pp. 974-975.

Question 1

All of the following are major subtypes of breast cancer based on Gene array analysis EXCEPT:

Accepted Answer

Estrogen receptor positive

Answer

Luminal A and Luminal B

Answer

Triple negative

Answer

Her-2 receptor positive

Question 2

How do high-risk HPV types contribute to cervical carcinogenesis?

Accepted Answer

By integration into host genome and expression of E6/E7 oncoproteins

Answer

Through direct mutagenic effects on host DNA

Answer

Through chronic inflammation and oxidative damage

Answer

By inducing apoptosis resistance through capsid proteins

Question 3

A patient has a cerebellar mass, renal tumor, and a family history of similar conditions. Which of the following mutations is most likely present in the family?

Accepted Answer

VHL

Answer

Neurofibromatosis (NF1)

Answer

Tuberous Sclerosis Complex (TSC)

Answer

Li-Fraumeni syndrome

Question 4

TTF-1 is a tumor marker for which of the following?

Accepted Answer

Small cell carcinoma

Answer

Adenocarcinoma

Answer

Thymoma

Answer

Melanoma

Question 5

A 49 year old female presents with a breast lump. Which of the following findings is in accordance with basal-like breast cancer?

Accepted Answer

ER-, PR-, HER2-

Answer

ER+, PR-, HER2-

Answer

ER-, PR-, HER2+

Answer

ER+, PR+, HER2-

Question 6

The image below shows the life cycle of a virus. Which of the proteins of the virus act as oncogenes?

Accepted Answer

E6, E7

Answer

L1, L2

Answer

E1, E2, E5

Answer

E1, E2

Question 7

Which of the following conditions is associated with perineural invasion?

Accepted Answer

Adenoid cystic carcinoma

Answer

Mucoepidermoid tumor

Answer

Pancreatic cancer

Answer

Pleomorphic adenoma

Question 8

What is the correct statement about thymoma?

Accepted Answer

Thymoma is the most common neoplasia of the thymus.

Answer

Chest X-ray is the investigation of choice for the diagnosis of thymoma.

Answer

Thymoma is primarily located in the posterior mediastinum.

Answer

Thymoma is usually asymptomatic and only occasionally causes symptoms.

Question 9

Which of the following is an Anti-apoptotic gene?

Accepted Answer

MCL-1

Answer

BAK

Answer

BIN

Answer

NOX-Q

Question 10

A 32-year-old HIV-positive man presents with multiple flesh-colored, pedunculated lesions on his penis. Biopsy shows koilocytes and increased mitotic figures. Which of the following viral proteins is responsible for the cellular changes observed?

Accepted Answer

E6 and E7 proteins

Answer

Tax protein

Answer

L1 protein

Answer

EBNA-1

Neoplasia — MCQs

Neoplasia — MCQs

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