Neoplasia Practice Questions

Q: Most common secondary tumor associated with Retinoblastoma is

Osteosarcoma. ***Osteosarcoma*** - **Osteosarcoma** is the most common secondary malignancy associated with retinoblastoma, especially in patients with the **hereditary form** of the disease who have a germline mutation in the *RB1* tumor suppressor gene [1]. - Patients treated with **radiation therapy** for retinoblastoma are at an increased risk of developing osteosarcoma within the radiation field, as well as other secondary cancers. *Neuroblastoma* - **Neuroblastoma** is a childhood cancer that develops from immature nerve cells (neuroblasts) found in several areas of the body, most commonly the **adrenal medulla**, but it is not typically associated as a secondary malignancy of retinoblastoma. - While both are childhood cancers, there is **no direct genetic or etiological link** that makes neuroblastoma a common secondary tumor to retinoblastoma. *Pineoblastoma* - **Pineoblastoma** is a rare, aggressive tumor of the pineal gland and is associated with **trilateral retinoblastoma**, a specific presentation where bilateral retinoblastoma is accompanied by an intracranial tumor of the pineal region. - Although it occurs in conjunction with retinoblastoma in some cases, it is a specific presentation rather than the **most common secondary malignancy** overall. *Osteochondroma* - An **osteochondroma** is a benign (non-cancerous) bone tumor, often growing near the ends of long bones [2]. - It is a common benign bone tumor in children and adolescents, but it is **not a malignancy** and is not typically associated with retinoblastoma as a secondary cancer [1]. **References:** [1] Kumar V, Abbas AK, et al.. Robbins and Cotran Pathologic Basis of Disease. 9th ed. Bones, Joints, and Soft Tissue Tumors, pp. 1200-1202. [2] Cross SS. Underwood's Pathology: A Clinical Approach. 6th ed. Common Clinical Problems From Osteoarticular And Connective Tissue Disease, pp. 671-673.

Q: Which of the following markers is typically elevated in small cell lung carcinoma?

Chromogranin. ***Chromogranin*** - **Chromogranin A** is a **neuroendocrine marker** frequently elevated in small cell lung carcinoma (SCLC), which has neuroendocrine features. - SCLC cells originate from **neuroendocrine cells** in the bronchial epithelium and exhibit characteristics of these cells. *Cytokeratin* - **Cytokeratins** are **intermediate filaments** primarily found in **epithelial cells** and are commonly expressed in non-small cell lung carcinomas (NSCLC). - While some SCLC cells can express certain cytokeratins, it is not considered a specific or typically elevated marker for SCLC diagnosis compared to neuroendocrine markers. *Desmin* - **Desmin** is an **intermediate filament** characteristic of **muscle cells** (smooth, skeletal, and cardiac muscle). - Its presence is associated with muscle-derived tumors like **rhabdomyosarcoma** and **leiomyosarcoma**, not lung carcinomas. *Vimentin* - **Vimentin** is an **intermediate filament** expressed in **mesenchymal cells** (e.g., fibroblasts, endothelial cells) and is often associated with mesenchymal tumors. - While some epithelial tumors can undergo epithelial-to-mesenchymal transition and express vimentin, it is not a primary diagnostic marker for SCLC.

Q: Among the following, keratin (cytokeratin) immunohistochemistry is MOST specifically used as a tumor marker for

Squamous cell carcinoma (SCC). ***Squamous cell carcinoma (SCC)*** - While **keratin (cytokeratin)** is an intermediate filament protein found in **all epithelial tumors**, the question asks which tumor it is **most specifically** used to identify among the given options. - **High molecular weight keratins** (CK5/6, CK14) are particularly characteristic of **squamous differentiation** and SCC. - When differentiating between epithelial and non-epithelial tumors from this list, keratin expression definitively identifies SCC as epithelial in origin. - Pan-cytokeratin staining is routinely used to confirm epithelial differentiation in poorly differentiated carcinomas. *Adenocarcinoma* - Adenocarcinomas are also **epithelial tumors** and do express cytokeratins (typically **low molecular weight keratins** like CK7, CK8, CK18, CK19). - However, adenocarcinomas are better characterized by **glandular differentiation** and expression of specific markers like CEA, MUC1, or organ-specific markers. - The keratin profile differs from SCC, with adenocarcinomas showing predominantly low MW keratins. *Rhabdomyosarcoma (RMS)* - RMS is a **mesenchymal tumor** derived from skeletal muscle precursors and is **keratin-negative**. - RMS expresses **muscle-specific markers**: desmin, myogenin, MyoD1, and muscle-specific actin. - The absence of keratin helps distinguish RMS from epithelial malignancies. *Choriocarcinoma (CC)* - Choriocarcinoma is a **germ cell/trophoblastic tumor** that may show variable keratin expression. - The definitive marker for choriocarcinoma is **human chorionic gonadotropin (hCG)**, not keratin. - Diagnosis relies on hCG levels and histologic identification of syncytiotrophoblasts and cytotrophoblasts, not keratin staining.

Q: Which of the following tumors is most commonly associated with perineural spread?

Adenoid cystic carcinoma. ***All of the above*** - Perineural spread is associated with multiple tumor types, including **adenoid cystic carcinoma** and **mucoepidermoid carcinoma**, confirming each can exhibit this feature [1]. - This spread presents significant clinical implications, as tumors that migrate along nerve sheaths tend to show **aggressive behavior** and increased risk of recurrence. *Adenoid cystic carcinoma* - While it is known to have perineural invasion as a feature, it is not the only tumor associated with this mechanism [1]. - This carcinoma often presents with **slow-growing masses** and a characteristic **cribriform pattern** histologically, but does not encompass all cases. *Keratoacanthoma* - Typically presents as a **rapidly growing squamous cell carcinoma** variant with a **central keratin plug** and does not commonly exhibit perineural invasion. - It shows a benign course compared to tumors associated with perineural spread. *Mucoepidermoid carcinoma* - This tumor also can demonstrate **perineural invasion**, but it is just one of several tumor types known for this characteristic [1]. - Its risk of perineural spread highlights its **diverse histological features**, yet it is not representative of all cases. **References:** [1] Kumar V, Abbas AK, et al.. Robbins and Cotran Pathologic Basis of Disease. 9th ed. Head and Neck, pp. 753-755.

Q: What is the target gene that is affected by the E6 gene product of HPV, leading to malignant transformation?

p53 gene (tumor suppressor gene). ***p53 gene (tumor suppressor gene)*** - The **E6 gene product of HPV** inactivates the **p53 tumor suppressor protein**, which normally functions to halt cell growth or induce apoptosis in response to DNA damage [1], [2]. - Degradation of p53 by E6 leads to **uncontrolled cell proliferation** and genomic instability, contributing significantly to malignant transformation [1]. *C-myc gene (proto-oncogene)* - While **c-myc** is a proto-oncogene involved in cell growth and proliferation, it is not the primary target directly affected by the HPV E6 protein. - Activation of c-myc can be a secondary event in carcinogenesis, but it's not the direct mechanism by which E6 promotes malignancy. *N-myc gene (proto-oncogene)* - **N-myc** is another proto-oncogene, often associated with neuroblastoma, and is not a direct target of the HPV E6 oncoprotein. - Its role in HPV-induced cancers is not central to the mechanism of E6. *RAS gene (involved in signaling)* - The **RAS gene** is a proto-oncogene encoding proteins involved in cell signaling pathways that regulate cell growth and differentiation [2]. - Mutations in RAS are common in various cancers, but the HPV E6 protein does not primarily target or inactivate the RAS gene or its protein products for malignant transformation. **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. 301-304.

Q: Which HPV oncoprotein initiates cervical carcinogenesis primarily by inactivating the p53 tumor suppressor?

E6. ***E6*** - **E6 oncoprotein is the HPV protein that specifically targets and degrades p53** through ubiquitin-mediated proteolysis [2]. - **p53 degradation** prevents apoptosis and allows cells with damaged DNA to survive and proliferate, a critical early step in malignant transformation [3]. - E6 works synergistically with E7 in cervical carcinogenesis, but **E6 is uniquely responsible for p53 inactivation** [1]. *E3* - HPV does not have a clinically significant E3 oncoprotein in the context of cervical cancer pathogenesis. - This is not a major viral oncoprotein involved in malignant transformation. *E5* - **E5 oncoprotein** plays a minor role in early infection by enhancing growth factor receptor signaling. - It does **not target p53** and is often lost during viral integration, making it less critical for malignant progression. *E7* - **E7 oncoprotein targets the retinoblastoma protein (Rb)**, not p53 [1]. - Rb inactivation releases E2F transcription factors, driving cell cycle progression [1]. - E7 and E6 work together, but **E7's specific target is Rb, not p53** [1]. **References:** [1] Kumar V, Abbas AK, et al.. Robbins and Cotran Pathologic Basis of Disease. 9th ed. Neoplasia, pp. 334-335. [2] Kumar V, Abbas AK, et al.. Robbins and Cotran Pathologic Basis of Disease. 9th ed. The Female Genital Tract, pp. 1006-1007. [3] Kumar V, Abbas AK, et al.. Robbins and Cotran Pathologic Basis of Disease. 9th ed. Neoplasia, pp. 303-304.

Q: Which of the following viruses is NOT known to be associated with human cancers?

Parvovirus B-19. ***Parvovirus B-19*** - Parvovirus B-19 is primarily associated with **fifth disease** in children and causes symptoms like rash and anemia, not cancer. - Unlike the other viruses listed, it has no established link to **human malignancies** [2]. *Papilloma virus* - Certain strains of **human papillomavirus (HPV)** are known to cause **cervical** and other cancers, making it a significant carcinogen [1][2]. - HPV is associated with the development of **kinetic lesions** that can progress to cancer. *Hepatitis B virus* - Hepatitis B virus is a well-established cause of **hepatocellular carcinoma** due to chronic liver inflammation and cirrhosis [2][3]. - It can lead to **viral oncogenesis** through integration into the host genome [3]. *Epstein Barr virus* - Epstein Barr virus (EBV) is linked to several cancers, including **Burkitt lymphoma** and **nasopharyngeal carcinoma** [2][4]. - It plays a role in immune evasion leading to **B-cell transformation**, which can result in malignancy [4]. **References:** [1] Kumar V, Abbas AK, et al.. Robbins and Cotran Pathologic Basis of Disease. 9th ed. Neoplasia, pp. 334-335. [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. 219-220. [3] Kumar V, Abbas AK, et al.. Robbins and Cotran Pathologic Basis of Disease. 9th ed. Neoplasia, pp. 336-337. [4] Kumar V, Abbas AK, et al.. Robbins and Cotran Pathologic Basis of Disease. 9th ed. Neoplasia, pp. 335-336.

Q: A patient with a history of increased lethargy and significant loss of weight, found to have elevated carcinoembryonic antigens (CEA) in laboratory examination, may have all of the following conditions, except:

Osteogenic sarcoma. ***Osteogenic sarcoma*** - While osteogenic sarcoma is a serious malignancy, it is **not typically associated with elevated carcinoembryonic antigen (CEA)** levels. - CEA is primarily a marker for **adenocarcinomas** and does not usually rise in bone or soft tissue sarcomas. *Lung cancer* - **Elevated CEA** is a common finding in many types of lung cancer, particularly **adenocarcinoma of the lung**. - Lung cancer can cause symptoms like **lethargy** and **significant weight loss** due to systemic effects of the malignancy [1], [3]. *Breast cancer* - **CEA levels can be elevated** in a significant proportion of patients with breast cancer, especially in advanced or metastatic disease. - Like other advanced cancers, breast cancer can present with **lethargy** and **unexplained weight loss** [1], [3]. *Colon cancer* - **Elevated CEA** is a well-established and widely used tumor marker for **colon cancer**, both for diagnosis and monitoring of disease recurrence [2], [4]. - Colon cancer, particularly in later stages, often leads to systemic symptoms such as **lethargy**, fatigue, and **significant weight loss** [1].

Q: Which of the following conditions is not typically associated with an underlying malignancy?

Paget disease of bone. ***Paget disease of bone*** - While Paget disease of bone can rarely undergo **malignant transformation** into **osteosarcoma**, it is itself a disorder of excessive bone remodeling and **not directly an underlying malignancy** like the other Paget diseases [2]. - The primary concern in Paget disease of bone is metabolic bone changes and potential complications like fractures, rather than being a superficial manifestation of internal cancer [2]. *Paget disease of nipple* - This condition is almost always associated with an **underlying ductal carcinoma in situ** or invasive adenocarcinoma of the breast [1]. - The epidermal changes are a manifestation of malignant cells migrating from the underlying breast tissue [1]. *Paget disease of vulva* - While it can occur as a primary intraepithelial neoplasm (adenocarcinoma in situ), approximately 20-30% of cases are associated with an **underlying invasive adenocarcinoma**, either vulvar or originating from other sites such as the colon, bladder, or urethra. - Its presence necessitates a thorough search for associated malignancies. *Paget disease of anal region* - Similar to vulvar Paget disease, it can be a primary intraepithelial adenocarcinoma, but it frequently is associated with an **underlying adenocarcinoma** of the colon, rectum, or anal glands. - Evaluation for an internal malignancy is crucial when this diagnosis is made. **References:** [1] Kumar V, Abbas AK, et al.. Robbins and Cotran Pathologic Basis of Disease. 9th ed. The Breast, pp. 1061-1062. [2] Kumar V, Abbas AK, et al.. Robbins and Cotran Pathologic Basis of Disease. 9th ed. Bones, Joints, and Soft Tissue Tumors, pp. 1191-1194.

Question 1

Most common secondary tumor associated with Retinoblastoma is

Accepted Answer

Osteosarcoma

Answer

Pineoblastoma

Answer

Neuroblastoma

Answer

Osteochondroma

Question 2

Which of the following markers is typically elevated in small cell lung carcinoma?

Accepted Answer

Chromogranin

Answer

Cytokeratin

Answer

Desmin

Answer

Vimentin

Question 3

Among the following, keratin (cytokeratin) immunohistochemistry is MOST specifically used as a tumor marker for

Accepted Answer

Squamous cell carcinoma (SCC)

Answer

Adenocarcinoma

Answer

Rhabdomyosarcoma (RMS)

Answer

Choriocarcinoma (CC)

Question 4

Which of the following tumors is most commonly associated with perineural spread?

Accepted Answer

Adenoid cystic carcinoma

Answer

Mucoepidermoid carcinoma

Answer

Keratoacanthoma

Answer

Basal cell carcinoma

Question 5

What is the target gene that is affected by the E6 gene product of HPV, leading to malignant transformation?

Accepted Answer

p53 gene (tumor suppressor gene)

Answer

C-myc gene (proto-oncogene)

Answer

N-myc gene (proto-oncogene)

Answer

RAS gene (involved in signaling)

Question 6

Which HPV oncoprotein initiates cervical carcinogenesis primarily by inactivating the p53 tumor suppressor?

Accepted Answer

E6

Answer

E3

Answer

E5

Answer

E7

Question 7

Which of the following viruses is NOT known to be associated with human cancers?

Accepted Answer

Parvovirus B-19

Answer

Hepatitis B virus

Answer

Human Papillomavirus

Answer

Epstein-Barr virus

Question 8

A patient with a history of increased lethargy and significant loss of weight, found to have elevated carcinoembryonic antigens (CEA) in laboratory examination, may have all of the following conditions, except:

Accepted Answer

Osteogenic sarcoma

Answer

Lung cancer

Answer

Breast cancer

Answer

Colon cancer

Question 9

Which of the following conditions is not typically associated with an underlying malignancy?

Accepted Answer

Paget disease of bone

Answer

Paget disease of vulva

Answer

Paget disease of anal region

Answer

Paget disease of nipple

Question 10

Which of the following is NOT a precancerous condition associated with bladder carcinoma?

Accepted Answer

Aniline dyes

Answer

Chronic ulcer

Answer

Schistosomiasis

Answer

Tuberculosis of the bladder

Neoplasia — MCQs

Neoplasia — MCQs

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