FMGE 2025 - Pathology Practice Questions

Q: HPV infection is most commonly associated with which type of cancer?

Oropharyngeal cancer. ***Oropharyngeal cancer*** - HPV (particularly HPV-16 and HPV-18) is strongly associated with oropharyngeal cancers, especially those affecting the **base of tongue and tonsils** [2], [3] - HPV-positive oropharyngeal cancers represent a distinct epidemiological entity with **better prognosis** compared to tobacco/alcohol-related cases - Among the options listed, oropharyngeal cancer is the **only HPV-associated malignancy** [3] - Note: Cervical cancer is the **most common HPV-related cancer overall** (not listed in options) [1], [3] *Incorrect: Esophageal cancer* - Primarily associated with **tobacco, alcohol, Barrett's esophagus, and chronic GERD** - Not significantly associated with HPV infection *Incorrect: Lung cancer* - Main risk factors include **smoking, radon exposure, asbestos, and air pollution** - No established HPV association *Incorrect: Stomach cancer* - Associated with **H. pylori infection, dietary factors (nitrosamines), and chronic gastritis** - Not linked to HPV infection **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 Lung, pp. 739-741. [3] 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.

Q: A 25-year-old man presents with headaches, visual disturbances, and hypertension. MRI brain shows a cerebellar hemangioblastoma, and abdominal imaging reveals multiple cysts in the kidneys along with a solid renal mass suggestive of renal cell carcinoma. His father had similar findings and died from a brain tumor in his 40s. Which of the following chromosomal abnormalities is most likely associated with his condition?

Deletion on chromosome 3p. ***Deletion on chromosome 3p*** - This clinical presentation of **cerebellar hemangioblastoma**, **renal cell carcinoma (clear cell type)**, and multiple renal and pancreatic cysts in a familial context is highly characteristic of **Von Hippel-Lindau (VHL) disease**. [1] - VHL disease is caused by an inherited or sporadic inactivation (deletion or mutation) of the **VHL tumor suppressor gene** located on the short arm of chromosome 3 (**3p25.3**). [2] *Deletion on chromosome 13q* - Deletion of the **RB1 gene** on chromosome 13q is associated with **retinoblastoma** and an increased risk of **osteosarcoma**, not VHL disease. - The clinical picture of headaches, cerebellar mass, and renal cell carcinoma is distinct from the typical presentation of RB1-associated disorders. *Deletion on chromosome 17p* - Deletion or mutation of the **TP53 gene** on chromosome 17p is primarily associated with **Li-Fraumeni syndrome**, which increases the risk for a variety of cancers, including sarcomas, breast cancer, and adrenocortical carcinoma, but less commonly VHL-related tumors. - This deletion is not the genetic locus for the VHL tumor suppressor gene. *Trisomy of chromosome 12* - Trisomy 12 is a common chromosomal anomaly found in B-cell chronic lymphocytic leukemia (**CLL**) and some benign tumors like **uterine leiomyomas**. - It is an inappropriate anomaly for a familial syndrome presenting with hemangioblastoma and renal cell carcinoma. **References:** [1] Cross SS. Underwood's Pathology: A Clinical Approach. 6th ed. Common Clinical Manifestations Of Central And Peripheral Nervous System Disease, pp. 724-725. [2] Kumar V, Abbas AK, et al.. Robbins and Cotran Pathologic Basis of Disease. 9th ed. The Kidney, pp. 958-959.

Q: Mutation in which of the following genes is most commonly associated with medullary thyroid carcinoma?

RET. ***RET***- The **RET proto-oncogene** mutation is the defining genetic feature of medullary thyroid carcinoma (MTC), which arises from parafollicular C-cells. [1] - Germline mutations in **RET** are responsible for hereditary forms of MTC, including **Multiple Endocrine Neoplasia type 2 (MEN 2A and 2B)**, making it the most critical diagnostic marker. [1] *RAS* - Mutations in the **RAS family** of genes (NRAS, HRAS, KRAS) are highly prevalent in **follicular thyroid carcinoma (FTC)** and follicular variants of papillary thyroid carcinoma (PTC). - These mutations are typically associated with a less aggressive tumor phenotype compared to RET or BRAF alterations. *BRAF* - The **BRAF V600E mutation** is the most common genetic alteration found in **papillary thyroid carcinoma (PTC)**, specifically the classical and tall cell variants. - The presence of **BRAF V600E** often correlates with increased risk of aggressive features, such as lymph node metastasis and extrathyroidal extension in PTC. *TP53* - **TP53** is a tumor suppressor gene whose mutations are primarily seen in highly aggressive, **anaplastic (undifferentiated) thyroid carcinoma (ATC)**. - Mutations in **TP53** indicate a progression from well-differentiated tumors and are associated with a very poor prognosis. **References:** [1] Kumar V, Abbas AK, et al.. Robbins and Cotran Pathologic Basis of Disease. 9th ed. The Endocrine System, pp. 1139-1140.

Q: Hereditary non-polyposis colorectal cancer (HNPCC), also known as Lynch syndrome, is caused by mutations in which type of genes?

MMR. ***MMR*** - Hereditary non-polyposis colorectal cancer (**HNPCC**), also known as **Lynch syndrome**, is caused by germline mutations in **DNA Mismatch Repair (MMR)** genes [1]. - Defective MMR function, most commonly due to mutations in **MLH1**, **MSH2**, **MSH6**, or **PMS2**, leads to an accumulation of mutations throughout the genome, a state known as **microsatellite instability (MSI)**. *APC* - Mutations in the **APC** gene, a tumor suppressor, are the cause of **Familial Adenomatous Polyposis (FAP)**, a different hereditary colorectal cancer syndrome [1]. - FAP is characterized by the development of hundreds to thousands of colonic polyps, whereas HNPCC typically presents with fewer polyps that rapidly progress to carcinoma [1]. *MYC* - **MYC** is a **proto-oncogene** involved in cell cycle control and proliferation; its dysregulation contributes to the development of many cancers, but it is not the primary genetic cause of HNPCC. - It is not a DNA repair gene, but rather a transcription factor that, when overexpressed, promotes uncontrolled cell growth. *TERT1* - This likely refers to the **TERT** gene, which encodes **telomerase reverse transcriptase**, an enzyme essential for maintaining telomere length. - While reactivation of **telomerase** is a critical step for cellular immortalization in many cancers, inherited mutations in this gene are not the cause of Lynch syndrome. **References:** [1] Kumar V, Abbas AK, et al.. Robbins and Cotran Pathologic Basis of Disease. 9th ed. The Gastrointestinal Tract, pp. 817, 821-822.

Q: Basophilic stippling of red blood cells is most characteristically seen in which of the following conditions?

Lead poisoning. ***Lead poisoning*** - Lead inhibits several enzymes in the heme synthesis pathway and also inhibits **ribonuclease**, which is responsible for degrading residual ribosomal RNA (rRNA) in reticulocytes [1]. This leads to aggregation of ribosomes, appearing as coarse blue granules known as **basophilic stippling**. - While also seen in conditions like thalassemias and sideroblastic anemia, coarse basophilic stippling is a classic and highly characteristic finding in lead poisoning. *Iron deficiency anaemia* - The characteristic peripheral smear findings are **microcytic** and **hypochromic** red blood cells, which appear smaller and paler than normal [2]. - **Pencil cells** (elliptocytes) and **thrombocytosis** (an increased platelet count) are also commonly observed, but basophilic stippling is not a typical feature [2]. *Megaloblastic anemia* - This anemia, due to **vitamin B12** or **folate** deficiency, is characterized by **macro-ovalocytes** (large, oval red blood cells) and **hypersegmented neutrophils** on the peripheral smear [3]. - Other inclusions like **Howell-Jolly bodies** may be present, but basophilic stippling is not the defining feature. *Hereditary spherocytosis* - This is a genetic disorder affecting red blood cell membrane proteins, leading to the formation of **spherocytes** – small, round RBCs lacking central pallor. - The key findings are spherocytes on the smear and an increased **mean corpuscular hemoglobin concentration (MCHC)**, not basophilic stippling. **References:** [1] Kumar V, Abbas AK, et al.. Robbins and Cotran Pathologic Basis of Disease. 9th ed. Infectious Diseases, pp. 418-419. [2] Cross SS. Underwood's Pathology: A Clinical Approach. 6th ed. Common Clinical Problems From Blood And Bone Marrow Disease, pp. 590-591. [3] Cross SS. Underwood's Pathology: A Clinical Approach. 6th ed. Common Clinical Problems From Blood And Bone Marrow Disease, pp. 594-595.

Q: In Pap smear cytology, which of the following is the most appropriate fixative used to preserve cellular details immediately after smearing?

95% ethanol. ***95% ethanol*** - This is considered the **gold standard fixative** for conventional **Pap smear** cytology because it acts rapidly to precipitate proteins, effectively preserving cellular and **nuclear detail** crucial for diagnosis. - Immediate fixation in 95% ethanol (or proprietary sprays containing alcohol) is essential to prevent **air-drying artifact**, which can severely distort nuclear morphology and render the smear diagnostically inadequate [1]. *50% formaldehyde* - Formaldehyde is typically used for **tissue fixation** (histopathology) rather than cytology smears, and this concentration is too dilute for effective cellular preservation. - Formaldehyde is an **additive fixative**, which acts differently than the preferred precipitant fixatives (like ethanol) used on thin smears. *70% ethanol* - While an alcohol fixative, **95% ethanol** is the recommended concentration for optimum dehydration and quick stabilization of the cell structures in a Pap smear. - 70% concentration may not fix the cells rapidly enough, potentially leading to suboptimal **chromatin preservation** compared to the higher concentration. *10% buffered formalin* - This is the routine fixative used globally for large **surgical pathology** specimens (biopsies and resections). - Formalin is generally not the preferred immediate fixative for thin-layer cytology slides compared to quick-acting alcohol, which provides superior **nuclear clarity** for Papanicolaou staining. **References:** [1] Kumar V, Abbas AK, et al.. Robbins and Cotran Pathologic Basis of Disease. 9th ed. The Female Genital Tract, pp. 1010-1011.

Q: Which genetic syndrome is caused by a deletion of the short arm of chromosome 5 (5p deletion)?

Cri-du-chat syndrome. ***Cri-du-chat syndrome*** - This syndrome is classically defined by a partial terminal deletion of the short arm of chromosome 5, designated as **5p deletion**. - Key clinical features include severe **intellectual disability**, **microcephaly**, and the characteristic high-pitched, monotonic **cat-like cry** that gives the syndrome its name. *Edward syndrome* - Edward syndrome is caused by an extra copy of chromosome 18 (**Trisomy 18**) [1]. - Clinical findings are often severe, including **micrognathia**, overlapping fingers, and **rocker-bottom feet** [1]. *Patau syndrome* - Patau syndrome is caused by an extra copy of chromosome 13 (**Trisomy 13**) [1]. - It is associated with severe midline defects such as **holoprosencephaly**, **cleft lip and palate**, and **polydactyly** [1]. *Turner syndrome* - Turner syndrome is a sex chromosome abnormality resulting from the absence of one X chromosome (45,X), making it a form of **monosomy X** [2]. - It primarily affects females, causing features like **short stature**, primary **amenorrhea** due to streak ovaries, and a **webbed neck** [2]. **References:** [1] Kumar V, Abbas AK, et al.. Robbins and Cotran Pathologic Basis of Disease. 9th ed. Genetic Disorders, pp. 168-169. [2] Kumar V, Abbas AK, et al.. Robbins and Cotran Pathologic Basis of Disease. 9th ed. Genetic Disorders, pp. 175-177.

Q: FBN1 gene mutation is seen in which of the following genetic disorders?

Marfan syndrome. ***Marfan syndrome***- The **FBN1 gene** (located on chromosome 15) encodes the protein **fibrillin-1**, a major component of the extracellular matrix, deficiency of which leads to the clinical manifestations of Marfan syndrome.- **Fibrillin-1** is integral to the formation of elastic fibers; its defect causes issues in the skeletal, ocular, and cardiovascular systems [1].*Ehlers-Danlos syndrome*- This group of disorders is primarily caused by defects in **collagen synthesis** (e.g., **COL5A1**, **COL3A1**) or processing, leading to joint hypermobility and skin hyperextensibility [2].- It is not typically associated with the **FBN1** mutation.*Homocystinuria*- This disorder is an autosomal recessive metabolic error usually caused by a deficiency of the enzyme **cystathionine beta-synthase** (CBS) [3].- It involves abnormal metabolism of **methionine** and **cysteine**, leading to high levels of **homocysteine**, and is not linked to **FBN1**.*von Hippel-Lindau syndrome*- This is a predisposition syndrome caused by a mutation in the **VHL tumor suppressor gene** (located on chromosome 3).- It predisposes patients to various tumors, including **hemangioblastomas** and **renal cell carcinoma**, and has no association with **FBN1**. **References:** [1] Kumar V, Abbas AK, et al.. Robbins and Cotran Pathologic Basis of Disease. 9th ed. Genetic Disorders, pp. 153-154. [2] Kumar V, Abbas AK, et al.. Robbins and Cotran Pathologic Basis of Disease. 9th ed. Genetic Disorders, pp. 155-156. [3] Kumar V, Abbas AK, et al.. Robbins and Cotran Pathologic Basis of Disease. 9th ed. Genetic Disorders, pp. 150-151.

Q: A mutation in the SOD1 gene is most commonly associated with which of the following conditions?

Amyotrophic lateral sclerosis (ALS). ***Amyotrophic lateral sclerosis (ALS)*** - **SOD1 (Superoxide dismutase 1)** gene mutations are responsible for approximately **20% of familial ALS** cases and 1-2% of sporadic cases - SOD1 enzyme normally protects cells from oxidative damage by converting superoxide radicals to hydrogen peroxide - Mutations lead to **toxic gain of function** causing motor neuron degeneration, affecting both upper and lower motor neurons [1] - Clinical features include progressive muscle weakness, fasciculations, spasticity, and bulbar symptoms [1] - This is one of the **most well-established genetic associations** in neurodegenerative disease *Parkinson's disease* - Associated with mutations in **SNCA (α-synuclein), LRRK2, and Parkin** genes, not SOD1 - Characterized by dopaminergic neuron loss in substantia nigra - Presents with bradykinesia, rigidity, resting tremor, and postural instability *Multiple sclerosis* - An **autoimmune demyelinating disease** with complex genetic susceptibility involving HLA-DRB1 and other immune-related genes - Not linked to SOD1 mutations - Presents with relapsing-remitting neurological symptoms and white matter lesions *Huntington's disease* - Caused by **CAG trinucleotide repeat expansion** in the huntingtin (HTT) gene on chromosome 4 - Autosomal dominant inheritance with anticipation - Presents with chorea, cognitive decline, and psychiatric symptoms

Question 1

HPV infection is most commonly associated with which type of cancer?

Accepted Answer

Oropharyngeal cancer

Answer

Esophageal cancer

Answer

Lung cancer

Answer

Stomach cancer

Question 2

A 25-year-old man presents with headaches, visual disturbances, and hypertension. MRI brain shows a cerebellar hemangioblastoma, and abdominal imaging reveals multiple cysts in the kidneys along with a solid renal mass suggestive of renal cell carcinoma. His father had similar findings and died from a brain tumor in his 40s. Which of the following chromosomal abnormalities is most likely associated with his condition?

Accepted Answer

Deletion on chromosome 3p

Answer

Trisomy of chromosome 12

Answer

Deletion on chromosome 17p

Answer

Deletion on chromosome 13q

Question 3

Mutation in which of the following genes is most commonly associated with medullary thyroid carcinoma?

Accepted Answer

RET

Answer

RAS

Answer

BRAF

Answer

TP53

Question 4

Hereditary non-polyposis colorectal cancer (HNPCC), also known as Lynch syndrome, is caused by mutations in which type of genes?

Accepted Answer

MMR

Answer

APC

Answer

TERT1

Answer

MYC

Question 5

A 25-year-old woman presents with lower abdominal discomfort. The surgical image is given below. What is the most likely diagnosis?

Accepted Answer

Mature cystic teratoma

Answer

Immature teratoma

Answer

Endometrioma

Answer

Serous cystadenoma

Question 6

Basophilic stippling of red blood cells is most characteristically seen in which of the following conditions?

Accepted Answer

Lead poisoning

Answer

Megaloblastic anemia

Answer

Hereditary spherocytosis

Answer

Iron deficiency anaemia

Question 7

In Pap smear cytology, which of the following is the most appropriate fixative used to preserve cellular details immediately after smearing?

Accepted Answer

95% ethanol

Answer

70% ethanol

Answer

10% buffered formalin

Answer

50% formaldehyde

Question 8

Which genetic syndrome is caused by a deletion of the short arm of chromosome 5 (5p deletion)?

Accepted Answer

Cri-du-chat syndrome

Answer

Edward syndrome

Answer

Turner syndrome

Answer

Patau syndrome

Question 9

FBN1 gene mutation is seen in which of the following genetic disorders?

Accepted Answer

Marfan syndrome

Answer

Homocystinuria

Answer

von Hippel-Lindau syndrome

Answer

Ehlers-Danlos syndrome

Question 10

A mutation in the SOD1 gene is most commonly associated with which of the following conditions?

Accepted Answer

Amyotrophic lateral sclerosis (ALS)

Answer

Parkinson's disease

Answer

Multiple sclerosis

Answer

Huntington's disease

FMGE 2025 — Pathology