PA6.1-7 | Neoplasia — Graded Quiz

A 60-year-old man undergoes resection of a 4 cm colonic mass. Gross examination shows a polypoid tumour with a broad stalk, smooth surface, and no infiltration of the muscularis propria. Histology reveals well-differentiated glandular structures with no nuclear pleomorphism, no mitoses, and an intact basement membrane. A second specimen from a 54-year-old woman shows a firm, irregular colonic mass with tethering to the mesentery. Histology shows poorly differentiated gland-like structures invading through the muscularis propria into pericolonic fat. Which SINGLE histological feature in specimen 2 defines malignancy as a categorical distinction from specimen 1?

A 48-year-old woman presents with a painless breast lump. Core biopsy shows a tumour with the following features: moderate nuclear pleomorphism, nuclear:cytoplasmic ratio 4:1, prominent nucleoli, scattered atypical mitoses, tumour giant cells, and loss of normal duct architecture. The pathologist grades this tumour as Grade 3 (poorly differentiated). A second patient has an identical-appearing breast primary, but on ultrasound her axillary lymph nodes are negative, while the first patient has 8/10 positive axillary nodes. Which pair of terms CORRECTLY captures the difference between the two patients, and which has worse prognosis?

A 35-year-old woman with germline BRCA1 mutation is counselled about her lifetime breast cancer risk. The oncologist explains that BRCA1 is a tumour suppressor gene. In a biopsy from a breast lump (which proves malignant), molecular testing shows loss of heterozygosity (LOH) at the BRCA1 locus, with the remaining allele carrying the germline mutation. Which genetic model BEST explains why BOTH copies must be lost for tumorigenesis, and which Hallmark of Cancer does BRCA1 loss primarily undermine?

A 52-year-old man presents with progressive right-sided weakness and headaches. MRI reveals multiple ring-enhancing lesions in the cerebral hemispheres. Further workup reveals a primary lung mass (2.1 cm), and core biopsy of the lung shows adenocarcinoma. A brain biopsy of one lesion also shows adenocarcinoma. The pathologist performs CK7/CK20 immunohistochemistry: CK7+/CK20−. Which concept BEST explains why the brain metastases show lung adenocarcinoma characteristics rather than brain tissue characteristics?

A 46-year-old rubber plant worker has a 2-year history of painless haematuria. Cystoscopy reveals a papillary urothelial carcinoma. His occupational history reveals 15 years of exposure to beta-naphthylamine. Which mechanism of chemical carcinogenesis BEST explains how an inhaled/skin-absorbed chemical causes bladder cancer specifically?

A 29-year-old HIV-positive woman (CD4 count 95/μL) with uncontrolled disease presents with an abnormal Pap smear showing high-grade squamous intraepithelial lesion (HSIL). Colposcopy biopsy shows CIN 3. HPV genotyping identifies HPV-18. The oncologist explains that HPV-18 causes cervical carcinoma through viral oncoprotein action. Which molecular mechanism CORRECTLY describes how HPV drives carcinogenesis in this patient?

A 66-year-old man with a 45 pack-year smoking history presents with proximal muscle weakness, weight loss (8 kg over 3 months), and a serum potassium of 2.8 mmol/L with metabolic alkalosis. CXR reveals a central hilar mass. Cortisol level at 08:00 is 1,800 nmol/L (normal <600), and dexamethasone suppression test (low-dose and high-dose) both fail to suppress cortisol. Sputum cytology shows small dark cells with scant cytoplasm and nuclear moulding. Which paraneoplastic syndrome is present, and which molecular mechanism drives it?

A pathologist examines a liver biopsy from a 65-year-old man with jaundice and a hepatic mass. IHC panel shows: CK7−, CK20−, AFP positive, HepPar-1 positive, Glypican-3 positive. The clinical team also finds serum AFP of 48,000 ng/mL. Which tumour does this IHC profile MOST accurately identify, and which risk factor in this patient population has the STRONGEST aetiological link?

A 70-year-old woman with known small-cell lung carcinoma (SCLC) presents with progressive truncal ataxia, dysarthria, and nystagmus over 8 weeks. MRI brain shows no metastases. Serum anti-Yo antibodies are negative; serum anti-Hu antibodies are detected at high titre. CSF shows mild lymphocytic pleocytosis and elevated protein. Which mechanism BEST explains her neurological syndrome, and how does it differ from direct brain invasion by SCLC?

A 58-year-old woman with previously resected colon adenocarcinoma is found on follow-up colonoscopy to have a new 1.8 cm sessile polyp. Molecular testing reveals: KRAS codon 12 mutation, APC loss-of-function mutation, and TP53 mutation. The polyp is excised and shows high-grade dysplasia without basement membrane breach. Three months later, the same site shows an invasive adenocarcinoma. Which concept BEST explains how this lesion progressed from high-grade dysplasia (no invasion) to invasive carcinoma in 3 months?

A 62-year-old man presents with a 7 kg weight loss, severe fatigue, and a palpable epigastric mass. CT abdomen reveals a 6 cm gastric mass with invasion of the lesser omentum. Multiple enlarged periportal lymph nodes and 2 hepatic lesions (each <2 cm) are seen. Biopsy confirms gastric adenocarcinoma (HER2 positive). Serum albumin is 22 g/L. Which combination MOST accurately predicts a worse prognosis, and why is cancer cachexia relevant to this prediction?

A 19-year-old man presents with a 3-week history of painless testicular swelling. Orchidectomy reveals a 4 cm tumour replacing the testis. Histology shows a uniform population of large cells with clear cytoplasm (glycogen-filled), central nuclei, prominent nucleoli, and a lymphocytic stroma with granuloma formation. IHC: PLAP+, OCT4+, CD117+, AFP−, β-hCG−. Which tumour is this, and which aetiological association is MOST strongly linked?