ABPath - American Board of Pathology Cytopathology Questions and Answers 1 — Questions and Answers
Question 1: A 32-year-old woman's liquid-based Pap test shows atypical squamous cells with a high nuclear-to-cytoplasmic ratio, irregular nuclear membranes, and hyperchromatic, coarse chromatin. The cells are arranged in sheets and as single cells with scant cytoplasm. According to the Bethesda System for Reporting Cervical Cytology, which of the following is the most likely diagnosis?
- Atypical Squamous Cells of Undetermined Significance (ASC-US)
- Low-grade Squamous Intraepithelial Lesion (LSIL)
- High-grade Squamous Intraepithelial Lesion (HSIL) (Correct answer)
- Reactive cellular changes associated with inflammation
Correct answer: High-grade Squamous Intraepithelial Lesion (HSIL)
The described cytomorphologic features—specifically the high nuclear-to-cytoplasmic ratio, significant nuclear hyperchromasia, and irregular nuclear contours—are the classic characteristics of a High-grade Squamous Intraepithelial Lesion (HSIL). LSIL typically presents with more cytoplasm and less severe nuclear atypia, often with koilocytic change. ASC-US is used when cellular changes are present but do not quantitatively or qualitatively meet the criteria for SIL. Reactive changes lack the marked nuclear atypia seen in HSIL.
Question 2: A 58-year-old male renal transplant recipient undergoes routine urine cytology. The specimen reveals numerous enlarged urothelial cells containing large, homogenous, ground-glass intranuclear inclusions that obscure the underlying chromatin. These cells are best known as "decoy cells." The presence of these cells is most strongly associated with an infection by which of the following viruses?
- Polyomavirus (BK virus) (Correct answer)
- Cytomegalovirus (CMV)
- Herpes Simplex Virus (HSV)
- Human Papillomavirus (HPV)
Correct answer: Polyomavirus (BK virus)
The described "decoy cells" are characteristic of Polyomavirus (most commonly BK virus) infection in urothelial cells. These viral inclusions are typically large, homogenous, and have a ground-glass appearance. This finding is particularly important in immunocompromised patients, such as renal transplant recipients, as it can signal viral reactivation and potential polyomavirus-associated nephropathy.
Question 3: A fine-needle aspiration of a 3 cm thyroid nodule from a 45-year-old female shows cellular smears with follicular cells arranged in syncytial-type clusters. The nuclei are enlarged and overlapping, with finely dispersed pale chromatin, prominent nuclear grooves, and occasional intranuclear cytoplasmic inclusions. These cytomorphologic features are most characteristic of which of the following?
- Follicular Adenoma
- Medullary Thyroid Carcinoma
- Anaplastic Thyroid Carcinoma
- Papillary Thyroid Carcinoma (Correct answer)
Correct answer: Papillary Thyroid Carcinoma
The combination of nuclear features including enlargement, overlapping, pale "Orphan Annie eye" chromatin, nuclear grooves, and intranuclear pseudoinclusions is the classic constellation of findings for Papillary Thyroid Carcinoma. Follicular neoplasms lack these specific nuclear changes, Medullary carcinoma typically shows plasmacytoid cells with salt-and-pepper chromatin, and Anaplastic carcinoma is characterized by marked pleomorphism and high-grade features.
Question 4: A 65-year-old patient with altered mental status undergoes a lumbar puncture. Cytologic examination of the cerebrospinal fluid (CSF) reveals a monomorphic population of large, atypical lymphoid cells with scant basophilic cytoplasm, irregular nuclear contours, prominent nucleoli, and apoptotic debris. Which of the following findings would be most definitive for a diagnosis of B-cell lymphoma?
- Positive CD45 and CD20 immunohistochemistry on the cell block
- A monotypic B-cell population with surface light chain restriction by flow cytometry (Correct answer)
- Numerous reactive lymphocytes and plasma cells in the background
- Positive Glial Fibrillary Acidic Protein (GFAP) staining in scattered cells
Correct answer: A monotypic B-cell population with surface light chain restriction by flow cytometry
While positive CD45 and CD20 stains confirm a B-lymphocyte lineage, they do not distinguish a malignant process from a reactive one. The definitive evidence for a B-cell lymphoma is the demonstration of clonality. This is best achieved by showing a monotypic population (i.e., expressing only kappa or only lambda light chains) via flow cytometry. Reactive processes are polyclonal. GFAP is a marker for glial cells and is not relevant.
Question 5: A 70-year-old female with a history of ER-positive invasive ductal carcinoma of the breast develops a large pleural effusion. Cytologic evaluation shows cohesive clusters of malignant cells. A cell block is prepared for ancillary studies to confirm the origin. Which of the following immunohistochemical markers is most specific for supporting a diagnosis of metastatic breast carcinoma in this context?
- WT-1
- Calretinin
- GATA3 (Correct answer)
- TTF-1
Correct answer: GATA3
GATA3 is a transcription factor that is a highly sensitive and specific marker for carcinomas of breast and urothelial origin. In the differential diagnosis of a malignant pleural effusion in a woman, which includes mesothelioma (positive for WT-1, Calretinin) and lung adenocarcinoma (positive for TTF-1), strong positivity for GATA3 is excellent evidence for metastatic breast carcinoma.
Question 6: A fine-needle aspiration is performed on a 3.5 cm solid mass in the head of the pancreas in a 68-year-old male. The cytology shows crowded, three-dimensional clusters of ductal cells with significant nuclear size variation, irregular nuclear membranes, and prominent nucleoli, suspicious for malignancy. Which of the following molecular alterations is most frequently associated with pancreatic ductal adenocarcinoma?
- KRAS gene mutation (Correct answer)
- BRAF V600E mutation
- EGFR mutation
- ALK gene rearrangement
Correct answer: KRAS gene mutation
Activating mutations in the KRAS oncogene are the most common and earliest genetic alteration found in pancreatic ductal adenocarcinoma (PDAC), occurring in over 90% of cases. Therefore, detecting a KRAS mutation provides strong ancillary evidence for the diagnosis. BRAF V600E is associated with melanoma and some colon/thyroid cancers, while EGFR mutations and ALK rearrangements are most famously associated with lung adenocarcinoma.
ABPath - American Board of Pathology Cytopathology Questions and Answers 1
A 32-year-old woman's liquid-based Pap test shows atypical squamous cells with a high nuclear-to-cytoplasmic ratio, irregular nuclear membranes, and hyperchromatic, coarse chromatin.
The cells are arranged in sheets and as single cells with scant cytoplasm.
According to the Bethesda System for Reporting Cervical Cytology, which of the following is the most likely diagnosis?