Female Genital and Breast Pathology MCQs

Pathology · 100 free questions with answers & explanations.

  1. A 45-year-old woman is found on routine mammography to have microcalcifications. Biopsy reveals atypical ductal hyperplasia (ADH). Compared to women without ADH, her relative risk of developing invasive breast cancer is approximately:
  2. A 35-year-old woman has a cervical biopsy showing dysplastic cells confined to the lower two-thirds of the epithelium without surface maturation. HPV genotyping shows high-risk HPV 16. This is best classified as:
  3. The most common histological type of ovarian carcinoma arising from high-grade serous tubal intraepithelial carcinoma (STIC) of the fimbriated end of the fallopian tube, with TP53 and BRCA1/2 mutations, is:
  4. Paget disease of the nipple presents with eczematous skin changes and is characterized histologically by large cells with clear cytoplasm within the epidermis. These intraepidermal Paget cells stain positive for:
  5. A 55-year-old postmenopausal woman has a 2.5 cm breast lump. Core biopsy shows infiltrating lobular carcinoma (ILC). Which molecular alteration is the hallmark of ILC and explains its characteristic 'Indian file' growth pattern and diffuse infiltration without forming a mass?
  6. A 30-year-old woman has a 3 cm vulvar lesion with VIN III (high-grade squamous intraepithelial lesion). HPV typing shows HPV-16 positive. Which protein product of HPV-16 is primarily responsible for p16 overexpression seen on IHC of this lesion?
  7. A 35-year-old BRCA1-positive woman elects for risk-reducing salpingo-oophorectomy (RRSO). Pathological examination of the fallopian tube using the SEE-FIM (sectioning and extensively examining the fimbriated end) protocol reveals a serous tubal intraepithelial carcinoma (STIC) at the fimbria. This finding is clinically significant because:
  8. A 55-year-old postmenopausal woman has a breast mass. Core biopsy shows infiltrating carcinoma with tubule formation in >75% of the tumor, mild nuclear pleomorphism, and <5 mitoses/10 HPF. Nottingham grading would assign this tumor a grade of:
  9. HER2 (ERBB2) overexpression in breast cancer is used to guide trastuzumab therapy. Per ASCO/CAP 2018 guidelines, HER2 IHC result of 2+ (equivocal) mandates which confirmatory test, and what defines HER2 positivity by that test?
  10. Endometrial carcinomas are categorized by the Cancer Genome Atlas (TCGA) into four molecular subtypes. A 45-year-old woman has grade 3 endometrial carcinoma with ultramutated phenotype (>100 mutations/Mb) and mutations in POLE (DNA polymerase epsilon). This TCGA molecular subtype has which prognosis?
  11. A 55-year-old with invasive ductal carcinoma (no special type) undergoes molecular profiling showing ER+, PR+, HER2 amplified (IHC 3+). Per 2018 ASCO/CAP guidelines, HER2 positivity by IHC 3+ is defined as:
  12. A 28-year-old woman with BRCA1 germline mutation is found to have a breast carcinoma. The typical histological subtype enriched in BRCA1-mutant breast cancers and its IHC profile is:
  13. A 32-year-old woman with cervical carcinoma in situ (CIN 3/HSIL) shows diffuse p16 block staining on IHC. The mechanism of p16 overexpression in HPV-driven dysplasia is:
  14. A 55-year-old postmenopausal woman has a breast mass. Core biopsy shows a tumor with sheets of large cells with abundant eosinophilic cytoplasm; IHC reveals ER+, PR+, HER2−, and Ki-67 of 5%. Oncotype DX recurrence score is 12. According to the 2021 St. Gallen consensus, which category does this tumor most likely fall into?
  15. Cervical intraepithelial neoplasia (CIN) grading is determined by the proportion of dysplastic cells from the basal layer upward. CIN 3 is distinguished from CIN 2 by which histological criterion?
  16. A 32-year-old woman with a phyllodes tumor of the breast. Histological features include stromal overgrowth, marked stromal cellularity with > 10 mitoses/10 HPF, and infiltrative margins. This would be classified as:
  17. A 32-year-old woman with a BRCA1 germline mutation undergoes risk-reducing salpingo-oophorectomy. The pathologist performs a SEE-FIM (Sectioning and Extensively Examining the Fimbria) protocol and identifies a microscopic lesion: p53 signature in fimbrial tubal epithelium followed by serous tubal intraepithelial carcinoma (STIC). STIC represents the putative origin of which cancer?
  18. A 35-year-old woman undergoes core biopsy of a palpable breast mass. Histology shows tubular carcinoma — small, well-formed tubules with open lumens, low nuclear grade, and no stromal desmoplasia. Which is the characteristic IHC profile expected in this special type breast carcinoma?
  19. A 55-year-old postmenopausal woman presents with postmenopausal bleeding. Endometrial biopsy shows complex hyperplasia with marked nuclear atypia, crowded glands, and mitotic activity. According to the WHO 2020 classification, this lesion is now classified as:
  20. A 52-year-old woman undergoes mastectomy for invasive lobular carcinoma. Compared to invasive ductal carcinoma (IDC NST), lobular carcinoma has a distinct growth pattern of single-file infiltrating cells. The molecular basis for this distinctive infiltrative pattern is:
  21. The 2019 WHO classification of endometrial carcinoma identifies four molecular subtypes with distinct prognoses. Which molecular subtype has the best prognosis despite high histological grade?
  22. A cervical biopsy shows koilocytes, dysplastic cells confined to the lower 2/3 of the epithelium with preservation of the superficial zone, and no surface maturation. This is classified as:
  23. A 32-year-old woman has breast biopsy for a palpable mass showing columnar cell change with flat epithelial atypia (FEA). Molecular profiling demonstrates loss of 16q and gain of 1q. FEA is considered a precursor of which breast carcinoma subtype?
  24. A 40-year-old woman has a cervical biopsy showing CIN 3 with p16 block positivity and high-risk HPV (type 16) on genotyping. The molecular mechanism by which HPV E7 oncoprotein causes S-phase entry in infected cells is:
  25. A 55-year-old postmenopausal woman has endometrial carcinoma with microsatellite instability (MSI-H), POLE mutation, and TP53 wild-type. According to the ProMisE molecular classification of endometrial carcinoma, which group does this tumor belong to, and what is the prognostic implication?
  26. A 38-year-old woman has a 2.5 cm breast mass. Histology shows infiltrating tumor cells arranged in solid nests without tubule formation, with nuclear pleomorphism (grade 3 nuclei) and >10 mitoses/10 HPF. ER, PR, HER2 IHC are all negative on two separate assays. What is the molecular subtype, and which genetic association is most important to screen for?
  27. Endometrial carcinoma is now classified by The Cancer Genome Atlas (TCGA) into four molecular subgroups. Which molecular subgroup has the BEST prognosis despite often showing high-grade morphology?
  28. A 32-year-old BRCA1 mutation carrier undergoes surveillance breast MRI which detects a 1.2 cm mass. Excision biopsy shows high-grade triple-negative invasive ductal carcinoma (ER–, PR–, HER2–) with pushing borders, central necrosis, and tumor-infiltrating lymphocytes. What is the molecular basis for the characteristic triple-negative, high-grade, basal-like phenotype seen in BRCA1-associated breast cancers?
  29. A Pap smear from a 28-year-old shows koilocytic cells with nuclear enlargement, hyperchromasia, irregular nuclear membranes, and perinuclear halos. HPV genotyping returns HPV 16 positive. Which molecular mechanism of HPV 16 E7 oncoprotein accounts for it being more carcinogenic than HPV 6 E7?
  30. The 2020 WHO Classification of Female Genital Tumours introduced the p53 mutant signature as a key molecular marker. High-grade serous carcinoma (HGSC) of the ovary shows p53 mutation in >96% of cases. The four molecular subtypes of ovarian cancer from TCGA (2011) that correlate with prognosis are: immunoreactive, mesenchymal, differentiated, and proliferative. The subtype with BEST prognosis is:
  31. On breast core needle biopsy, a 45-year-old woman's specimen shows cells with large nuclei, prominent nucleoli, and high mitotic rate filling distended ducts with central necrosis and periductal stromal fibrosis. There is no stromal invasion identified. The Ki-67 proliferation index is 80%. ER/PR are negative. HER2 is 3+. This lesion is best classified as:
  32. A 58-year-old postmenopausal woman has an endometrial biopsy showing high-grade serous endometrial carcinoma. IHC shows p53 strong diffuse positivity ('block staining') in virtually all tumor cells and loss of mismatch repair proteins (MLH1/PMS2). According to the 2023 FIGO molecular classification of endometrial cancer, which molecular subtype does this represent?
  33. A 48-year-old woman undergoes sentinel lymph node biopsy for a 1.8 cm invasive breast carcinoma. The SLN shows a 0.3 mm cluster of tumour cells detected on IHC (AE1/AE3+) in the subcapsular sinus. According to the AJCC 8th edition TNM staging, how is this SLN finding classified?
  34. A 40-year-old woman with BRCA2 germline mutation is diagnosed with triple-negative breast cancer (ER-/PR-/HER2-). On molecular subtyping (PAM50), the tumour is classified as 'basal-like'. Which IHC marker panel best identifies the basal-like subtype?
  35. A 45-year-old woman undergoes excision of a breast mass showing lobular carcinoma in situ (LCIS). Molecular analysis confirms E-cadherin loss. What is the mechanistic basis for the lack of cohesion in lobular neoplasia, and how does this differ from ductal carcinoma in situ (DCIS)?
  36. An endometrial biopsy shows glands with back-to-back architecture, minimal intervening stroma, nuclear atypia, and mitoses. There is no myometrial invasion. IHC: MLH1 and PMS2 are absent (MSH2 and MSH6 retained). Methylation analysis shows MLH1 promoter hypermethylation. What is the most likely molecular subtype of this endometrial carcinoma according to TCGA/ProMisE classification?
  37. A 55-year-old postmenopausal woman presents with a 2 cm breast mass. Core biopsy shows invasive lobular carcinoma (ILC). The molecular feature that distinguishes ILC from invasive ductal carcinoma at the cellular adhesion level is:
  38. The 2020 WHO classification of endometrial carcinoma introduced a molecular classification with four prognostically distinct subtypes. Which molecular subtype carries the worst prognosis and is characterized by TP53 mutations with copy number high (CN-high) pattern?
  39. A 35-year-old woman has cervical biopsy showing CIN 3 / high-grade squamous intraepithelial lesion (HSIL). HPV genotyping: HPV-16 positive. The oncogenic mechanism of HPV-16 in cervical carcinogenesis primarily involves:
  40. A breast tumor is ER-negative, PR-negative, and HER2-negative (triple-negative breast cancer, TNBC). Genomic profiling shows a BRCA1 germline mutation. What is the histological subtype most commonly associated with BRCA1-mutated TNBC and its characteristic molecular profile?
  41. Phyllodes tumor of the breast is classified as benign, borderline, or malignant based on histological criteria. Which single histological feature most reliably distinguishes malignant from borderline phyllodes tumor?
  42. A 32-year-old BRCA1 mutation carrier undergoes prophylactic mastectomy. Pathological examination of the specimen reveals lobular carcinoma in situ (LCIS). Which molecular alteration is characteristic of LCIS, and how does it relate to the impaired cell-cell adhesion seen?
  43. A 28-year-old woman with stage IB1 cervical squamous cell carcinoma undergoes radical hysterectomy. HPV-16 E6 protein is detected in the tumor. What is the mechanism by which HPV E6 protein promotes malignant transformation in cervical epithelium?
  44. A breast mass biopsy shows tubule formation >75%, mild nuclear pleomorphism, and 0-1 mitosis/10 HPF. The Nottingham histological grade is:
  45. Sertoli-Leydig cell tumor of the ovary secretes excess androgens causing virilization. It is classified under which WHO category of ovarian sex cord-stromal tumors?
  46. A postmenopausal woman with endometrial carcinoma shows deficient MLH1 and PMS2 immunostaining on mismatch repair (MMR) protein IHC, and methylation of the MLH1 promoter is detected. This is best classified as:
  47. A 35-year-old woman undergoes excisional biopsy of a breast mass showing sclerosing adenosis, apocrine metaplasia, and ductal hyperplasia without atypia. What is her relative risk for subsequent invasive breast carcinoma compared to the general population?
  48. A 28-year-old woman presents with an endometrial biopsy showing complex hyperplasia with atypia. What is the risk of concurrent or progression to endometrial carcinoma if untreated, and what is the recommended management?
  49. A HER2-enriched (HER2+, ER-, PR-) invasive breast carcinoma is diagnosed. HER2 overexpression is confirmed by FISH showing gene amplification. What is the mechanism of action of trastuzumab (Herceptin)?
  50. A 45-year-old woman undergoes core biopsy of a breast mass. Pathology shows large pleomorphic cells filling and distending ducts with central comedonecrosis and calcifications. Grade 3 DCIS is present. The comedonecrosis pattern of DCIS is most specifically associated with which molecular subtype of breast cancer?
  51. Endometrial carcinoma type II (serous carcinoma) differs from type I (endometrioid) in all of the following ways EXCEPT:
  52. On Pap smear, which cytological finding is MOST specific for high-grade cervical intraepithelial neoplasia (CIN 3)?
  53. A 55-year-old postmenopausal woman presents with vaginal bleeding. Endometrial biopsy shows glands with back-to-back architecture, cribriform pattern, and minimal intervening stroma (>50% replacement). This is BEST classified as:
  54. HER2 gene amplification in breast cancer is tested by FISH (fluorescence in situ hybridization). What HER2/CEP17 ratio on FISH indicates gene amplification?
  55. Paget's disease of the nipple is characterized by large pale cells with prominent nucleoli within the nipple epidermis. These cells represent:
  56. A 28-year-old woman has a well-circumscribed, mobile, rubbery breast lump that increases in size during pregnancy. Biopsy shows a biphasic tumour with both epithelial (gland-forming) and stromal components, with the stroma being the neoplastic component. This is a:
  57. A 55-year-old woman has a breast mass. Core biopsy shows infiltrating carcinoma with positive ER/PR and HER2 overexpression (3+ IHC, FISH amplified). According to molecular classification, this tumour belongs to:
  58. In cervical intraepithelial neoplasia (CIN), the E6 oncoprotein of high-risk HPV (types 16/18) promotes carcinogenesis primarily by:
  59. BRCA1-associated breast cancers characteristically show triple-negative (ER-/PR-/HER2-) phenotype. Compared with sporadic breast cancer, BRCA1 tumors are more commonly of which histological grade and subtype?
  60. A 55-year-old post-menopausal woman has endometrial carcinoma with deep myometrial invasion and lymphovascular space invasion (LVSI). This is a Type I endometrial carcinoma. Its hallmark precursor lesion and associated molecular alteration are:
  61. Paget disease of the nipple presents as erythematous, eczematous nipple change with underlying breast carcinoma. The characteristic Paget cells on histology are:
  62. A 55-year-old woman presents with a breast mass. Core biopsy shows invasive carcinoma that is ER+, PR+, HER2−. Which molecular subtype does this correspond to?
  63. Endometriosis is defined as the presence of endometrial glands and stroma outside the uterus. The most widely accepted theory for its pathogenesis is:
  64. A 52-year-old post-menopausal woman undergoes biopsy of a breast lump. Histology shows malignant cells arranged in single-file rows (Indian file pattern) and targetoid periductal infiltration. Tumor cells are E-cadherin negative. The diagnosis is:
  65. A 28-year-old woman presents with progressive dysmenorrhea and infertility. Laparoscopy shows dark 'chocolate' cysts on the ovaries and implants on the uterosacral ligaments. Histologically, the implants must contain:
  66. A 30-year-old woman has a Pap smear showing high-grade squamous intraepithelial lesion (HSIL). Colposcopy-directed biopsy shows CIN 3. The HPV genotypes most commonly implicated and their target in carcinogenesis are:
  67. A 35-year-old woman with endometriosis has a 6-cm left ovarian cyst containing thick chocolate-brown fluid. Histologically the cyst wall is lined by endometrial-type glands and stroma with hemosiderin-laden macrophages. This lesion is called:
  68. Paget disease of the nipple is characterized histologically by the presence of large, pale, vacuolated malignant cells within the epidermis of the nipple. These cells originate from:
  69. Fibroadenoma of the breast is classified as an intracanalicular or pericanalicular type based on the growth pattern of stroma relative to ducts. Which molecular receptor profile do these benign tumors characteristically express?
  70. A 55-year-old woman has breast carcinoma with HER2 (ERBB2) gene amplification confirmed by FISH. HER2 overexpression drives tumor growth through which mechanism?
  71. Cervical intraepithelial neoplasia (CIN) progresses through grades 1-3 based on the extent of dysplastic cells occupying the epithelial thickness. CIN 3 (severe dysplasia/carcinoma in situ) is defined by dysplastic cells involving:
  72. A 35-year-old woman has a breast mass. Core biopsy shows invasive carcinoma with E-cadherin loss on immunohistochemistry. This loss of E-cadherin is most characteristic of which histological type?
  73. CIN (cervical intraepithelial neoplasia) grade 3 is defined as full-thickness atypia of squamous epithelium. Which HPV proteins are responsible for inactivating p53 and Rb in high-grade CIN?
  74. A 55-year-old woman has a stellate breast mass with microcalcifications on mammography. Core biopsy shows atypical epithelial cells in a cribriform pattern filling ducts with central comedonecrosis. No stromal invasion is seen. This lesion is classified as:
  75. A 30-year-old woman's cervical biopsy shows koilocytes and nuclear atypia confined to the basal and middle thirds, with normal surface maturation. The correct CIN grade and typical HPV association are:
  76. Which molecular pathway characterizes Type I (endometrioid) endometrial carcinoma?
  77. A 45-year-old woman undergoes mastectomy for an infiltrating ductal carcinoma. Pathology report notes: ER+, PR+, HER2−, Ki-67 15%, grade 2 (Nottingham). Which molecular subtype does this tumor belong to?
  78. Endometrial carcinoma is classified into Type I and Type II categories. Which statement BEST differentiates Type II (serous) from Type I (endometrioid) endometrial carcinoma?
  79. Phyllodes tumor of the breast is a fibroepithelial lesion. Which histological feature MOST reliably distinguishes malignant phyllodes tumor from a cellular fibroadenoma?
  80. A breast biopsy shows ducts and lobules surrounded by a cellular spindle-cell stroma with a leaf-like cleft architecture. The correct diagnosis and its biological behaviour is:
  81. Paget's disease of the nipple is characterized by large, clear, mucin-containing cells in the epidermis of the nipple. These cells represent:
  82. A 35-year-old woman has a lumpectomy for a breast mass. Histology shows malignant epithelial cells filling and expanding the ductal lumens without basement membrane invasion. There is central comedo-type necrosis with calcification. What is this lesion?
  83. On Pap smear, koilocytic change (perinuclear halo with enlarged, raisinoid nuclei) is characteristic of infection by which organism?
  84. A 55-year-old postmenopausal woman has a breast mass. Core biopsy shows infiltrating malignant cells arranged in a single-file (Indian file) pattern with no gland formation. Cells are small and discohesive, with target-like intracytoplasmic mucin. E-cadherin immunostaining is negative. This is most consistent with:
  85. Gestational trophoblastic disease (GTD) includes hydatidiform moles and malignant tumors. Which chromosomal composition characterizes a complete hydatidiform mole?
  86. A 55-year-old woman with breast carcinoma has biopsy showing HER2/neu gene amplification by FISH (HER2:CEP17 ratio >2.0). HER2 overexpression drives tumour proliferation via which primary signalling mechanism?
  87. Endometrial hyperplasia without atypia carries a low risk of progression to endometrial carcinoma (<5%), while complex atypical hyperplasia carries ~25% risk. Which molecular alteration is the earliest molecular event in the endometrioid (type I) carcinogenesis pathway?
  88. A 22-year-old woman presents with a painless, firm, well-demarcated, rubbery 2 cm breast lump that moves freely on palpation. Biopsy shows a biphasic proliferation of both epithelial and stromal components with intracanalicular growth pattern. What is the diagnosis, and what hormonal influence promotes its growth?
  89. Phyllodes tumor of the breast is distinguished from fibroadenoma by which histological feature?
  90. Endometrial carcinoma type II (serous carcinoma) differs from type I (endometrioid) in which important molecular feature?
  91. The most specific immunohistochemical marker to distinguish invasive lobular carcinoma from invasive ductal carcinoma of the breast is:
  92. A 45-year-old woman has a lumpectomy for a breast mass. Histology shows tumor cells arranged in single-file lines ('Indian file' pattern) infiltrating the stroma, with discohesive cells and loss of E-cadherin expression. What is the most likely diagnosis?
  93. A 28-year-old woman has a Pap smear showing koilocytes (perinuclear halos with nuclear atypia) and is diagnosed with CIN I. Which molecular event in HPV-infected keratinocytes is primarily responsible for the characteristic koilocyte morphology?
  94. Paget disease of the nipple is characterized histologically by large cells with pale cytoplasm within the epidermis. Which statement about its pathogenesis is correct?
  95. A 35-year-old woman with endometriosis undergoes laparoscopy. Ectopic endometrial implants are found on the ovary forming a 'chocolate cyst' (endometrioma). The brown color of the cyst content is due to:
  96. A 35-year-old woman undergoes excisional biopsy of a breast mass. Histology shows lobular carcinoma in situ (LCIS). Compared to ductal carcinoma in situ (DCIS), LCIS is characterized by:
  97. Sertoli-Leydig cell tumor (arrhenoblastoma) of the ovary is associated with virilization. Which immunohistochemical marker, in addition to inhibin, is characteristically positive in this sex cord-stromal tumor?
  98. Endometrial adenocarcinoma type II (serous endometrial carcinoma) has distinct molecular features compared to type I (endometrioid). Which molecular alteration is characteristic of serous endometrial carcinoma?
  99. Paget disease of the nipple is associated with an underlying invasive or in-situ carcinoma in approximately what percentage of cases, and the malignant Paget cells spread from the underlying carcinoma via which route?
  100. In BRCA1 and BRCA2 hereditary breast and ovarian cancer syndrome, both BRCA proteins participate in which DNA repair pathway?
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