Endobronchial Ultrasound-Guided Transbronchial Needle Aspiration (EBUS-TBNA) is a reliable and accurate method for the diagnosis of mediastinal metastases in patients with pulmonary and extrathoracic neoplasms. We report the cytopathologic findings of a case of metastatic signet-ring cell carcinoma with abundant extracellular mucin production in the mediastinal lymph nodes of a 41-year-old woman, who presented with nausea, abdominal pain, and weight loss. Imaging studies showed a renal mass, numerous lung nodules, and mediastinal and retroperitoneal lymphadenopathy. EBUS-TBNA of level 4R and 7 lymph nodes showed abundant, thick, "clean" mucus with entrapped ciliated bronchial cells, rare histiocytes, and fragments of cartilage. No neoplastic cells could be identified in Diff-Quik®-stained smears during the rapid on-site evaluation, but rare signet-ring cells were identified in the Papanicolaou-stained smears and cellblock sections. A distinctive feature of the aspirates was the presence of large branching (arborizing), "spidery" stromal fiber meshwork fragments. These stained metachromatically (magenta) with Romanowsky-type stains and cyanophilic to orangeophilic with Papanicolaou stains and showed occasional attached bland spindle cells, but had no capillary lumina or CD31-staining endothelial cells. The tumor cells were strongly and diffusely positive for CEA, CDX2, CK7, CK20, and MUC2, supporting the diagnosis of a metastatic signet-ring cell adenocarcinoma, most likely of gastrointestinal origin. We believe that the presence of the large spidery stromal fiber fragments is a useful clue to the presence of a mucinous neoplasm in EBUS-TBNA and allows the differentiation of the neoplastic mucus from contaminating endobronchial mucus.
Objectives
Many studies have shown poor reproducibility among pathologists for diagnosing dysplasia in Barrett’s esophagus (BE). Immunohistochemical stains (IHC) are not widely used due to overlapping expression patterns in reactive and dysplastic processes. We hypothesized that markers involved in cell-cycle (cyclin D1, Ki-67, P16), differentiation/cell-cell interaction (β-catenin, SATB2 CD44, OCT4) and senescence (γH2AX) would produce different results in reactive and dysplastic processes.
Methods
A micrograph album of 40 H&E and matching IHCs depicting optimally oriented lesions were evaluated independently by 3 pathologists. Expression was scored separately in the surface, isthmus, and base regions of the glands.
Results
Statistical analysis showed that surface Ki-67 expression showed the largest difference in expression and smallest P value (P < .001) for identifying dysplasia. At a cutoff level of 5% or less, negative predictive value (NPV) was 100%. κ correlation between pathologists improved from substantial to almost perfect (0.70-0.95) using ancillary surface Ki-67.
Conclusion
A case-control study with glass slides including all diagnostic categories using this parameter confirmed improved κ correlation among pathologists (0.29 vs 0.60), better correlation with outcomes (76% vs 69%), increased odd risks (15.3) for progression in positive cases, and an improvement in sensitivity (88% vs 64%) and NPV (88% vs 73%) compared to histology alone.
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