Cancer Cytopathology最新文献

Background: Fine-needle aspiration (FNA) biopsy is increasingly used for the diagnosis of hepatocellular masses. Because distinguishing well differentiated hepatocellular carcinoma (HCC) from other well differentiated hepatocellular lesions (e.g., large regenerative nodules or focal nodular hyperplasia) requires an assessment of architectural features, this may be challenging on FNA when intact tissue fragments are not sampled. Poorly differentiated HCC and intrahepatic cholangiocarcinoma (ICC) may exhibit overlapping pathologic features. Molecular testing can be helpful, because mutations in TERT promoter and CTNNB1 (β-catenin) are characteristic of HCC, whereas mutations in BAP1, IDH1/IDH2, and PBRM1 may favor ICC. The goal of this study was to assess the role of next-generation sequencing (NGS) in further subclassifying indeterminate liver lesions sampled by FNA.

Methods: A retrospective review of liver cytology cases with NGS on cell block material was performed. Age, radiologic features, background hepatic disease and treatment, outcome, and NGS data were obtained from the electronic medical record.

Results: Twelve FNA biopsies that had cell blocks from clinically suspected primary hepatic masses were identified. The presence of a TERT promoter mutation supported a diagnosis of HCC for one well differentiated neoplasm. For three patients, the presence of mutations, such as IDH1, CDKN2A/CDKN2B, and BRAF, supported a diagnosis of ICC. Of the eight poorly differentiated carcinomas, NGS helped refine the diagnosis in six of eight cases, with one HCC, three ICCs, and two that had combined HCC-ICC, with two cases remaining unclassified.

Conclusions: Molecular diagnostics can be helpful to distinguish HCC and ICC on FNA specimens, although a subset of primary hepatic tumors may remain unclassifiable.

Background: The third edition of The Bethesda System (TBS) subclassifies the atypia of undetermined significance (AUS) category on the basis of the presence of nuclear atypia (AUS-Nuclear). This approach is supported by studies showing significant differences in the risk of malignancy (ROM) between AUS-Nuclear and those without (AUS-Other). Although aspirates of follicular neoplasms (FNs) are characterized by marked architectural atypia, TBS recognizes the infrequent occurrence of FNs with mild nuclear atypia (FN-Nuclear). Furthermore, limited studies have shown significant differences in ROM between FN-Nuclear and those without (FN-Other). This study explored potential differences in ROM, molecular-derived risk of malignancy (MDROM), and molecular alterations between FN-Nuclear and FN-Other.

Methods: A retrospective database search identified 93 FN aspirates. Cytology slides, molecular reports, and histologic follow-ups were reviewed. Both groups' benign call rate (BCR), positive call rate (PCR), MDROM, and ROM were computed and compared.

Results: Eighty-six percent of aspirates (80 of 93) comprised FN-Other, whereas 14% (13 of 93) were FN-Nuclear. The BCR and PCR for FN-Other were 51% and 49%, respectively. In contrast, they were 23% and 77% for FN-Nuclear, respectively. The MDROM significantly differed between FN-Other (30%) and FN-Nuclear (56%) (p < .05). HRAS mutation was the most common molecular alteration in FN-Nuclear, whereas mutations in NRAS/KRAS and copy number alterations were more common in FN-Other. The ROM1/ROM2 in FN-Other and FN-Nuclear were 16%/31% and 54%/88%, respectively.

Conclusions: These results reveal that FN-Nuclear exhibits significantly higher MDROM and ROM than FN-Other, which provides support for a subclassification scheme for FNs based on the presence of nuclear atypia.

For Vera Gorbunova, PhD, professor of biology and medicine at the University of Rochester in New York, the moment of serendipity initially seemed like a nuisance. Dr Gorbunova’s laboratory studies why certain animals, such as the extremely long-lived, hairless, and so-ugly-they’re-cute subterranean dwellers known as naked mole-rats, are extraordinarily resistant to cancer. The unusual rodents from eastern Africa have a eusocial colony structure reminiscent of honeybees and can live more than 40 years in captivity, roughly 10-fold longer than mice.

As part of its research, Dr Gorbunova’s laboratory grew naked mole-rat fibroblast cells, which make and secrete collagen and other components of the framework for connective tissues. Graduate students noticed that the cells also were secreting a viscous substance into the cell culture dish. The substance was so thick and gooey that it clogged the vacuum pump used to suck up the growing medium from the dishes. “When people complained about it, we all thought, ‘Well, there must be something interesting,’” Dr Gorbunova recalls.

After initial tests suggested that the viscous substance was not an overabundant protein, a Google search hinted at hyaluronic acid, a natural lubricant and cushion for skin and other sensitive body parts in humans and other animals. Sure enough, confirmatory tests revealed that the secretions were a very long form of hyaluronic acid made by the HAS2 gene.¹

From additional experiments, the laboratory found that this version of hyaluronic acid binds to a specific cell receptor and appears to trigger an anticancer response by arresting cell growth and division. “Basically, when there is a lot of high-molecular weight hyaluronic acid in the tissue, it reduces cell proliferation and it also slows down premalignant hyperplastic cells,” Dr Gorbunova says. In transgenic mice, the introduced HAS2 gene granted the animals more longevity and resistance to both spontaneous and induced tumors.² “They didn’t become completely resistant like naked mole-rats, which means there are additional mechanisms that are different in the mole-rat, but the incidence was reduced significantly,” she says.

From an evolutionary perspective, Dr Gorbunova doubts that anticancer activity was the original purpose of the naked mole-rats’ hyaluronic acid production. In a wide range of other tunnel-dwelling species, the researchers recently reported that all produced the same high-molecular-weight compound.³ “What we proposed is that it really becomes upregulated with adaptation to subterranean life,” she says. One possibility is that because underground animals are constantly rubbing against tunnel walls, the acid helps to reinforce their skin.

When the laboratory ramped up hyaluronic acid production in mice, the animals likewise acquired “very stretchy, elastic skin,” she says. “But then once it’s ov

Background: A standardized reporting system for bone and soft tissue tumor cytopathology has not yet been established. The objective of this study was to explore the potential utility of a classification modified from the Milan System for Salivary Gland Cytopathology and compared it with the upcoming World Health Organization (WHO) system for fine-needle aspiration of soft tissue lesions.

Methods: The authors reviewed 285 cytology cases of bone/joint (n = 173) and soft tissue (n = 112) lesions, scoring each within diagnostic categories. The results were compared with histologic diagnoses and the risk of malignancy (ROM) for each category, and diagnostic reliability was analyzed.

Results: All 285 cases were successfully classified into one of the following categories: nondiagnostic (6.3%), non-neoplastic (11.9%), atypia of uncertain significance (11.9%), benign neoplasm (5.6%), bone and soft tissue neoplasm of uncertain malignant potential (25.3%), suspicious for malignancy (1.4%), and malignant (37.5%). The ROM was 44.4% (eight of /18 cases) in nondiagnostic, 0% (zero of 34 cases) in non-neoplastic, 32.4% (11 of 34 cases) in atypia of uncertain significance, 0% (zero of 16 cases) in benign neoplasm, 16.7% (12 of 72 cases) in bone and soft tissue neoplasm of uncertain malignant potential, 75.0% (three of four cases) in suspicious for malignancy, and 100% (107 of 107 cases) in malignant categories. Using the WHO system, the proportion and ROM of the benign category (non-neoplastic and benign neoplasm) was 17.5% and 0%, respectively. Among benign and malignant lesions, the diagnostic accuracy, sensitivity, and specificity for detecting malignancy were 99.4%, 100%, and 98.0%, respectively.

Conclusions: The modified Milan system as well as the WHO system may be a useful cytopathologic classification tool for both bone and soft tissue lesions.

Background: This study evaluated the diagnostic effectiveness of the AIxURO platform, an artificial intelligence-based tool, to support urine cytology for bladder cancer management, which typically requires experienced cytopathologists and substantial diagnosis time.

Methods: One cytopathologist and two cytotechnologists reviewed 116 urine cytology slides and corresponding whole-slide images (WSIs) from urology patients. They used three diagnostic modalities: microscopy, WSI review, and AIxURO, per The Paris System for Reporting Urinary Cytology (TPS) criteria. Performance metrics, including TPS-guided and binary diagnosis, inter- and intraobserver agreement, and screening time, were compared across all methods and reviewers.

Results: AIxURO improved diagnostic accuracy by increasing sensitivity (from 25.0%-30.6% to 63.9%), positive predictive value (PPV; from 21.6%-24.3% to 31.1%), and negative predictive value (NPV; from 91.3%-91.6% to 95.3%) for atypical urothelial cell (AUC) cases. For suspicious for high-grade urothelial carcinoma (SHGUC) cases, it improved sensitivity (from 15.2%-27.3% to 33.3%), PPV (from 31.3%-47.4% to 61.1%), and NPV (from 91.6%-92.7% to 93.3%). Binary diagnoses exhibited an improvement in sensitivity (from 77.8%-82.2% to 90.0%) and NPV (from 91.7%-93.4% to 95.8%). Interobserver agreement across all methods showed moderate consistency (κ = 0.57-0.61), with the cytopathologist demonstrating higher intraobserver agreement than the two cytotechnologists across the methods (κ = 0.75-0.88). AIxURO significantly reduced screening time by 52.3%-83.2% from microscopy and 43.6%-86.7% from WSI review across all reviewers. Screening-positive (AUC+) cases required more time than negative cases across all methods and reviewers.

Conclusions: AIxURO demonstrates the potential to improve both sensitivity and efficiency in bladder cancer diagnostics via urine cytology. Its integration into the cytopathological screening workflow could markedly decrease screening times, which would improve overall diagnostic processes.

Every year, roughly 1500–2000 women in the United States are diagnosed with a rare set of ovarian cancers known as granulosa cell tumors (GCTs), which carry a high risk of recurrence. Another 1300 individuals are diagnosed with adenoid cystic carcinomas (ACCs), which arise primarily in the salivary glands, commonly invade nerves, and metastasize to distant sites such as the lungs in approximately half of all cases.

Both cancers are rare enough that patients often struggled to connect with others facing the same malignancy until social media platforms such as Facebook helped them to connect through patient support groups. Such groups, in turn, have become critical resources for research efforts seeking to better understand the diseases and improve patient outcomes.

Amid the spate of recent warnings about the dangers of social media, including rampant misinformation, online groups have become the main vehicle for connecting patients and families affected by rare diseases. Physicians now regularly recommend Facebook groups to their patients, says Meghan Halley, PhD, MPH, a senior research scholar at the Stanford Center for Biomedical Ethics in Palo Alto, California. “It’s often the largest gathering of any patients with a particular very rare disease that’s available,” she says. “The extent to which the rare disease community has leveraged social media to identify other patients, share information, and provide social support is one of the few bastions of really good news in the social media space.”

Researchers have made good use of the space as well. In collaboration with the Granulosa Cell Tumor Survivor Sisters Facebook group, for example, a recent study based on an online survey of 743 patients revealed that 30% of respondents had recurrent disease, with one third of those recurrences occurring within 5 years of diagnosis.¹ The study represented one of the largest surveys yet of GCT patients’ treatment experiences. “Using naturally forming consumer groups may assist with developing the evidence base for care and supporting those living with GCT ovarian cancer,” the authors concluded.

Bioethicists such as Dr Halley, however, also have urged caution when relying on social media for bolstering research efforts. In a review of 120 social media–aided studies on rare noncancer diseases, she and her colleagues found that more than half relied exclusively on surveys, and the patient demographics, when reported, skewed toward female and White participants. “Despite its potential benefits in rare disease research, the use of social media is still methodologically limited, and the participants reached may not be representative of the rare disease population by gender, race, age, or rare disease type,” wrote the researchers.²

Rare cancers are tracked, in part, through the National Cancer Institute’s Surveillance, Epidemiology, and End Results (SEER) program. Classification, thou