Cytology: Diagnostic Principles and Clinical Correlates

Comprehensive review flashcards covering key diagnostic terms, cytomorphologic patterns, immunohistochemical profiles, and regulatory criteria in clinical cytopathology.

Minimum Squamous Cellularity (The Bethesda System)

The quantitative threshold required for an adequate cervical cytology sample: an estimated minimum of $5000$ well-visualized squamous cells for liquid-based preparations and $8000$ to $12{,}000$ cells for conventional smears.

Koilocyte

A squamous epithelial cell altered by human papillomavirus (HPV) infection, pathognomonically characterized by a large, sharply demarcated perinuclear cytoplasmic cavity with a dense peripheral rim and nuclear atypia.

HPV E6 and E7 Oncoproteins

Early viral oncoproteins of high-risk HPV where E6 binds and degrades p53 to inhibit apoptosis, and E7 binds to retinoblastoma protein (pRb) to disrupt cell-cycle arrest and induce S-phase entry.

Creola Bodies

Large, spherical, cohesive clusters of reactive, ciliated bronchial epithelial cells commonly observed in bronchial washings and sputum from patients with chronic airway diseases such as asthma.

EML4-ALK Translocation

An intrachromosomal rearrangement of chromosome 2p fusing the ALK kinase domain to EML4, detectable by split-apart interphase FISH probes, rendering non-small cell lung carcinomas sensitive to targeted tyrosine kinase inhibitors like crizotinib.

TTF-1 and p63 Algorithmic Staining in NSCLC

A first-line immunohistochemical panel to differentiate non-small cell lung carcinoma: TTF-1 positive/p63 negative favors adenocarcinoma ($\sim 90\%$ of cases), whereas TTF-1 negative/p63 strongly positive favors squamous cell carcinoma ($>95\%$ of cases).

Melamed-Wolinska Bodies

Round, red or green hyaline intracytoplasmic inclusions found within degenerating urothelial cells in urine and associated with metastatic transitional/urothelial cell carcinoma in pleural fluid.

Decoy Cells (Polyomavirus)

Urothelial cells infected with polyomavirus (BK or JC virus) featuring enlarged, hyperchromatic nuclei filled with glassy, homogeneous, basophilic viral inclusions that mimic high-grade urothelial carcinoma.

UroVysion Multi-Target FISH

A fluorescent in situ hybridization assay for detecting urothelial carcinoma in urine that utilizes centromeric probes to chromosomes 3, 7, and 17 and a locus-specific probe to the 9p21 band.

Mesothelial Windows

Narrow, slit-like translucent spaces separating adjacent benign mesothelial cells within cohesive clusters, created by interdigitating elongated, bushy surface microvilli.

Mesothelioma vs. Adenocarcinoma Staining Panel

An immunocytochemical panel for serosal effusions where calretinin (nuclear/cytoplasmic), WT1 (nuclear), and D2-40 (membranous) support mesothelioma, while CEA, MOC-31, Ber-EP4, B72.3, and TTF-1 support adenocarcinoma.

Primary Effusion Lymphoma (PEL)

A human herpesvirus 8 (HHV-8)–associated large B-cell neoplasm that primarily manifests as a malignant pleural, pericardial, or peritoneal effusion in immunocompromised patients without an associated tumor mass.

Ommaya Reservoir

A surgically implanted subcutaneous silicone reservoir connected to a ventricular cannula, used to instill intrathecal chemotherapeutic agents and periodically sample cerebrospinal fluid for cytology.

Mollaret Cells

Enlarged monocyte-macrophages with deep nuclear clefts imparting a footprint-like contour, detected in cerebrospinal fluid within the first 24 hours of recurring aseptic meningitis.

Collagen Balls

Spherical, acellular masses of mesothelial collagen surrounded by flattened benign mesothelial cells, found as an incidental finding in peritoneal washings.

Endosalpingiosis

A benign proliferation of tubal-type, ciliated epithelium and glands involving peritoneal and serosal surfaces, often associated with psammoma bodies, which mimics metastatic serous neoplasia.

Popcorn Cells (L&H Cells)

The neoplastic monoclonal B-cell variants of nodular lymphocyte predominant Hodgkin lymphoma, characterized by polylobated, folded nuclei resembling popped corn kernels, with small nucleoli.

Tigroid Background

A reticular or striped background pattern on Romanowsky-stained smears caused by smeared, fragile cytoplasmic glycogen granules, classically associated with seminoma, dysgerminoma, and Ewing sarcoma.

Call-Exner Bodies

Small, rounded spaces filled with eosinophilic secretions or pyknotic debris surrounded in rosette-like fashion by neoplastic granulosa cells in adult-type granulosa cell tumors.

Hürthle Cell (Oncocyte)

A transformed follicular or salivary epithelial cell characterized by abundant, densely granular eosinophilic cytoplasm packed with mitochondria, an enlarged nucleus, and a prominent nucleolus.

Papillary Thyroid Carcinoma (PTC) Nuclear Features

The diagnostic nuclear constellation of PTC, including optically clear or pale 'powdery' chromatin, irregular nuclear contours with longitudinal nuclear grooves, and sharply demarcated intranuclear pseudoinclusions.

Atypia of Undetermined Significance (AUS / FLUS)

A Bethesda thyroid category reserved for aspirates with architectural and/or cytologic atypia insufficient for a neoplasm or suspicious for malignancy, associated with a $5\%$ to $15\%$ risk of cancer.

Warthin Tumor

A benign salivary gland tumor occurring almost exclusively in the parotid gland, cytologically characterized by an oncocytic epithelial sheet component, abundant mature lymphocytes, and amorphous granular debris.

Pleomorphic Adenoma (PA)

The most common benign salivary gland neoplasm, cytologically defined by a biphasic mixture of ductal epithelial cells, myoepithelial cells, and fibrillary, chondromyxoid, metachromatic matrix.

Verocay Bodies

Palisading rows of spindle-shaped Schwann cell nuclei flanking parallel acellular zones of fibrillar eosinophilic cytoplasmic processes in Antoni A regions of a schwannoma.

Cercariform Cells

Urothelial carcinoma cells characterized by elongated cytoplasmic tails with nucleated or vacuolated bulbous/flared ends, mimicking tadpoles or cercariae.

Pancreatic Neuroendocrine Tumor (PanNET)

A circumscribed neoplasm showing noncohesive plasmacytoid cells with eccentrically located round nuclei, 'salt and pepper' chromatin, and immunoreactivity for synaptophysin, chromogranin, and CD56.

Solid-Pseudopapillary Neoplasm (SPN)

A low-grade pancreatic neoplasm of young women featuring delicate pseudopapillary clusters with myxoid/hyalinized fibrovascular cores, foamy cells, and characteristic nuclear accumulation of $\beta$-catenin.

Squamoid Corpuscle

A discrete whorl of squamous differentiation in a background of primitive blastemal and acinar elements, pathognomonic for pancreatoblastoma.

Pseudomyxoma Peritonei

An extensive intraperitoneal accumulation of extracellular gelatinous mucin and muciphages, most commonly secondary to a low-grade mucinous appendiceal neoplasm rather than primary ovarian disease.

Physaliphorous Cells

Large, distinctive chordoma cells filled with multiple prominent cytoplasmic vacuoles that indent and traverse the cell, producing delicate, spidery cytoplasmic strands around the nucleus.

Negative Image Phenomenon (Mycobacteria)

A refractile, nonstaining rod-shaped appearance of mycobacterial bacilli in Romanowsky-stained smears, caused by the thick, lipid-rich cell wall that repels water-based stains.

CLIA '88 Cytotechnology Workload Limit

The federal statutory maximum of $100$ gynecologic and/or nongynecologic slides examined within any 24-hour period, requiring a minimum screening duration of $8$ hours ($12.5$ slides/hour).

Prospective 10% Rescreen

A federally mandated quality control requirement in the United States directing the prospective re-examination of at least $10\%$ of all gynecologic cytology cases originally interpreted as negative.

DOG1 (Discovered on GIST-1)

A calcium-activated chloride channel transmembrane protein that serves as a highly sensitive and specific immunohistochemical marker for gastrointestinal stromal tumors (GISTs), including c-kit-negative cases.