Reproductive Pathology Practice Questions

Q: Molecular classification of breast cancer is based on?

Gene expression profiling. ### Explanation **Correct Answer: D. Gene expression profiling** **1. Why Gene Expression Profiling is Correct:** The molecular classification of breast cancer (Perou and Sorlie classification) is based on **microarray-based gene expression profiling**. This technique analyzes the mRNA levels of hundreds of genes simultaneously to categorize tumors into distinct biological subtypes. This classification is superior to traditional morphology because it reflects the underlying genetic driver of the tumor, providing better prognostic and therapeutic insights. The four main molecular subtypes are: * **Luminal A:** High ER/PR, low Ki-67 (Best prognosis). * **Luminal B:** ER+, but may have lower PR or higher Ki-67/HER2+. * **HER2-enriched:** Overexpression of the HER2 gene. * **Basal-like:** Usually "Triple Negative" (ER-, PR-, HER2-); worst prognosis. **2. Why Other Options are Incorrect:** * **A. Serum hormone levels:** Breast cancer behavior is determined by the receptors *on the tumor cells*, not the circulating levels of hormones in the blood. * **B. Expression of hormone receptors (ER/PR):** While we use Immunohistochemistry (IHC) for ER/PR/HER2 in clinical practice as a **surrogate** for molecular classification, the *actual* molecular classification is defined by gene expression, not protein expression. * **C. In-vitro response to chemotherapy:** Chemosensitivity is a result of the molecular subtype, not the basis for the classification itself. **3. Clinical Pearls for NEET-PG:** * **Surrogate Markers:** In routine labs, we use **IHC** (protein expression) to approximate molecular subtypes because gene profiling (Oncotype DX/MammaPrint) is expensive. * **Luminal A** is the most common subtype and has the best prognosis. * **Basal-like** tumors are often associated with **BRCA1** mutations. * **Ki-67** is a marker of cellular proliferation; high Ki-67 (>20%) distinguishes Luminal B from Luminal A.

Q: Which proteins of Human Papillomavirus (HPV) play a role in the pathogenesis of cervical cancer?

E6 and E7. ### Explanation The pathogenesis of cervical cancer is primarily driven by the integration of high-risk Human Papillomavirus (HPV) DNA (most commonly types 16 and 18) into the host genome. This integration leads to the over-expression of two key viral oncoproteins: **E6 and E7**. **1. Why E6 and E7 are correct:** These proteins disrupt the host cell cycle by neutralizing tumor suppressor proteins: * **E6 (Six-P):** Binds to and degrades the **p53** protein via ubiquitin-mediated proteolysis. Loss of p53 prevents apoptosis and allows the accumulation of DNA mutations. * **E7 (Seven-R):** Binds to and inactivates the **Retinoblastoma (Rb)** protein. This releases the E2F transcription factor, pushing the cell prematurely into the S-phase of the cell cycle. * *Mnemonic:* **E6** affects **p53**; **E7** affects **Rb**. **2. Why other options are incorrect:** * **E3, E4, E5, E8, E10:** While other early (E) proteins exist, they are not the primary drivers of malignancy. **E4** is involved in viral release and is a marker of productive infection. **E5** enhances growth factor signaling but is often lost when the virus integrates into the host genome. E8 and E10 are not significant in the context of human oncogenesis. **3. NEET-PG High-Yield Pearls:** * **HPV 16** is the most common type associated with Squamous Cell Carcinoma. * **HPV 18** is more frequently associated with Adenocarcinoma. * **L1 Protein:** This is the major capsid protein used to develop HPV vaccines (e.g., Gardasil). * **Koilocytosis:** The hallmark cytological finding of HPV infection (perinuclear halo with nuclear wrinkling/raisinoid appearance). * **Screening:** The primary screening tool is the Pap smear, but HPV DNA testing is now preferred for primary screening in women over 30.

Q: What is the most common testicular tumor in prepubertal individuals?

Yolk sac tumor. **Explanation:** The correct answer is **Yolk sac tumor** (also known as Endodermal Sinus Tumor). In the prepubertal population, yolk sac tumors account for approximately 70–80% of all germ cell tumors (GCTs), making them the most common testicular malignancy in children (typically occurring before age 3). **Why the correct answer is right:** * **Yolk Sac Tumor:** These are non-seminomatous germ cell tumors (NSGCT) that characteristically produce **Alpha-Fetoprotein (AFP)**, which serves as a reliable diagnostic and prognostic marker. Histologically, they are identified by the presence of **Schiller-Duval bodies** (glomeruloid-like structures). In children, they usually present as a pure form and have a very favorable prognosis compared to the adult variant. **Why the other options are incorrect:** * **Embryonal cell carcinoma:** These are aggressive tumors typically seen in adults (ages 20–30) as part of mixed germ cell tumors; they are rare in prepubertal children. * **Seminoma:** This is the most common testicular tumor in **adults** (4th decade). It is virtually never seen in prepubertal children. * **Teratoma:** While the second most common GCT in children, prepubertal teratomas are usually **benign** (unlike post-pubertal teratomas, which are considered malignant). **High-Yield Clinical Pearls for NEET-PG:** * **Most common overall testicular tumor in children:** Yolk sac tumor. * **Most common benign testicular tumor in children:** Teratoma. * **Most common testicular tumor in elderly (>60 years):** Lymphoma (Secondary). * **Tumor Marker:** AFP is elevated in Yolk sac tumors but **never** in pure Seminomas. * **Reinke Crystals:** Pathognomonic for Leydig cell tumors.

Q: Which of the following statements regarding male breast cancer is INCORRECT?

Lobular carcinoma is the commonest subtype.. **Explanation:** Male breast cancer is a rare malignancy, accounting for less than 1% of all breast cancers. The key to answering this question lies in understanding the anatomy of the male breast. **1. Why Option B is Incorrect (The Correct Answer):** In males, the breast tissue consists primarily of ducts and stroma but lacks well-developed **lobules** (the milk-producing units). Since lobules are absent or rudimentary, **Lobular Carcinoma is extremely rare** in men. Therefore, the statement that it is the "commonest subtype" is false. **2. Analysis of Other Options:** * **Option C (Ductal Carcinoma):** This is the **most common subtype**, accounting for approximately 85-90% of cases. Specifically, Invasive Ductal Carcinoma (NOS) is the most frequent histological finding. * **Option A (BRCA2 Mutations):** Genetic predisposition is a significant risk factor. While BRCA1 mutations are more common in female breast cancer, **BRCA2 mutations** are more strongly associated with male breast cancer, seen in roughly 4–10% of cases. * **Option D (Colloid Carcinoma):** Though rare, various histological subtypes seen in females, including colloid (mucinous), papillary, and medullary carcinomas, can occur in males. **Clinical Pearls for NEET-PG:** * **Most common presentation:** A painless, firm subareolar mass (due to the central location of ductal tissue). * **Risk Factors:** Klinefelter syndrome (highest risk), BRCA2 mutation, liver cirrhosis (hyperestrogenism), and radiation exposure. * **Receptor Status:** Male breast cancers are more likely to be **ER/PR positive** compared to female breast cancers. * **Staging & Treatment:** Staging is the same as in females. Modified Radical Mastectomy (MRM) is the standard surgical approach. Tamoxifen is the hormonal therapy of choice.

Question 1

Molecular classification of breast cancer is based on?

Accepted Answer

Gene expression profiling

Answer

Serum hormone levels

Answer

Expression of hormone receptors (ER/PR)

Answer

In-vitro response to chemotherapeutic agents

Question 2

Which of the following are predisposing features for germ cell tumor?

Accepted Answer

Cryptorchidism, Testicular feminizing syndrome, Klinefelter's syndrome, Right side more common than Left side

Answer

Testicular feminizing syndrome, Klinefelter's syndrome, Smoking, Right side more common than Left side

Answer

Cryptorchidism, Testicular feminizing syndrome, Klinefelter's syndrome, Smoking

Answer

Cryptorchidism, Testicular feminizing syndrome, Smoking, Right side more common than Left side

Question 3

A couple presents to a clinic for the work-up of infertility after 5 years of unprotected intercourse. The wife denies any medical problems and notes regular menstrual cycles. The husband reports a history of chronic sinusitis and lower respiratory tract infections. Physical examination of the woman is unremarkable. Examination of the man reveals dextrocardia. Further work-up of the husband will most likely reveal?

Accepted Answer

Immotile sperm

Answer

Azoospermia

Answer

Germinal cell aplasia

Answer

Isolated gonadotropin deficiency

Question 4

In a hydatidiform mole, blood cells do NOT develop due to a defect in which germ layer?

Accepted Answer

Mesoderm

Answer

Primary ectoderm

Answer

Endoderm

Answer

Trophoblast

Question 5

Which proteins of Human Papillomavirus (HPV) play a role in the pathogenesis of cervical cancer?

Accepted Answer

E6 and E7

Answer

E3 and E4

Answer

E5 and E6

Answer

E8 and E10

Question 6

What is the most specific marker for prostate cancer?

Accepted Answer

Prostate-specific antigen (PSA)

Answer

Prostatic acid phosphatase (PAP)

Answer

Placental alkaline phosphatase (PLAP)

Answer

Neuron-specific enolase (NSE)

Question 7

What is the first gene to be knocked out in the carcinogenesis of the endometrium?

Accepted Answer

PTEN

Answer

PI3KCA

Answer

KRAS

Answer

p53

Question 8

What is the most common testicular tumor in prepubertal individuals?

Accepted Answer

Yolk sac tumor

Answer

Embryonal cell carcinoma

Answer

Seminoma

Answer

Teratoma

Question 9

A 17-year-old pregnant girl in her 4th month of gestation presents with vaginal bleeding and passage of grapelike tissue fragments. Plasma human chorionic gonadotropin (hCG) is very high. Following ultrasound evaluation, dilatation and curettage is performed. Histologic examination shows diffuse trophoblastic proliferation and edema in all chorionic villi. Cytogenetic studies demonstrate a 46, XY karyotype. What is the approximate rate at which this condition progresses to choriocarcinoma?

Accepted Answer

2%

Answer

0.20%

Answer

20%

Answer

50%

Question 10

Which of the following statements regarding male breast cancer is INCORRECT?

Accepted Answer

Lobular carcinoma is the commonest subtype.

Answer

BRCA2 mutations are seen in approximately 6% of cases.

Answer

Ductal carcinoma is the most common subtype.

Answer

Colloid carcinoma can be seen.

Reproductive Pathology — MCQs

Reproductive Pathology — MCQs

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