Cancer-associated fibroblasts are a useful cytological finding for diagnosing pancreatic ductal adenocarcinoma.

INTRODUCTION: Cancer-associated fibroblasts (CAFs) are activated fibroblasts or myofibroblasts that play a crucial role in the invasiveness of pancreatic ductal adenocarcinoma (PDAC). In this study, the cytological features and diagnostic significance of CAFs based on pancreatic duct brushing cytology (PDBC) were evaluated. METHODS: The prevalence of fibrous stroma (FS) including CAFs on PDBC in 42 PDAC cases and 33 benign cases was retrospectively investigated. The average nuclear size of fibroblasts was compared between PDAC and benign cases to distinguish CAFs from normal FS. RESULTS: Overall, FS was observed in 25 PDAC cases (60%) and eight benign cases (24%). The average nuclear size of FS in PDAC cases was significantly larger than that in benign cases. From the receiver operating characteristics analysis, the cut-off value of the nuclear size of FS for the diagnosis of PDAC was defined as 10.22 µm. FS with nuclei over 10.22 µm in size in PDAC cases had clear prominent nucleoli. In contrast, FS in benign cases had no clear nucleoli. Thus, CAFs on PDBC were considered to be FS with nuclei over 10.22 µm in size and prominent nucleoli. The presence of CAFs on PDBC had 100% positive predictive value and specificity for the diagnosis of PDAC. CONCLUSIONS: This study suggested that CAFs on PDBC could be distinguished from normal FS by large nuclear size (over 10.22 µm) and prominent nucleoli and that CAFs on PDBC may be used for the diagnosis of PDAC.

Fine needle aspiration cytology of ductal adenoma of the breast with intracellular mucin: a report of three cases.

BACKGROUND: Ductal adenoma of the breast is a benign lesion that can mimic both the clinical and cytopathologic features of carcinoma. Benign breast lesions with intracellular mucin are extremely rare, and ductal adenoma with intracellular mucin has not previously been reported. Here we present three cases of ductal adenoma of the breast with foci of intracellular mucin. CASES: Three patients were admitted to Tokai University School of Medicine Hospital and underwent fine needle aspiration cytology and histologic examination by excisional biopsy or partial resection. Fine needle aspiration cytology was performed using a 23-gauge needle, and smears were immediately fixed in ethanol and stained as Papanicolaou preparations. Epithelial cells formed cohesive clusters, consisting of biphasic luminal and myoepithelial cells accompanied by apocrine metaplasia with occasional high nuclear atypia. All three cases showed intracellular mucin, in varying amounts, which led to their being overdiagnosed as malignant lesions. CONCLUSION: To avoid overdiagnosis of ductal adenomas as malignant lesions, it is important to recognize that both intracytoplasmic mucin and atypical apocrine features can be usual cytologic findings of this disease.

Lower HER-2/chromosome enumeration probe 17 ratio in cytologic HER-2 fluorescence in situ hybridization for breast cancers: three-dimensional analysis of intranuclear localization of centromere 17 and HER-2 signals.

BACKGROUND: Fluorescence in situ hybridization (FISH) is the gold standard for assessing HER-2 status for breast cancers, and paraffin-embedded tissue sections are used routinely for HER-2 FISH. Cytologic samples also are used, but to the authors' knowledge, little is known regarding the reliability of these samples. The objective of this study was to elucidate the usefulness of cytologic specimens for HER-2 FISH testing. METHODS: Histologic and cytologic specimens from 32 patients with invasive ductal carcinoma of the breast were subjected to comparative analysis of HER-2 status by FISH. FISH was performed by using a PathVysion HER-2 DNA Probe Kit according the manufacturer's instructions. The signal ratios of chromosome enumeration probe 17 (CEP17) and HER-2 were estimated and compared. In 15 cytologic specimens, the distance between signals (HER-2 and CEP17) and the nearest nuclear membrane were measured by using 3-dimensional image analysis and confocal microscopy. RESULTS: Cytologic and histologic FISH results were compared. Signal ratios of HER-2/CEP17 were lower in cytologic specimens from 26 of 32 patients compared with the histologic material. Three-dimensional image analysis demonstrated that the distance between the CEP17 signal and the nuclear membrane was shorter than the distance between the HER-2 gene and the nuclear membrane. CONCLUSIONS: The current results demonstrated that CEP17 could be lost more easily through histologic sectioning compared with the cytology results, because CEP17 is closer to the nuclear membrane. FISH analysis in cytologic specimens produced more accurate HER-2/CEP17 ratios, because the whole nucleus was subjected to FISH testing, compared with matched histologic specimens.