Detailed Morphologic Evaluation of Breast Papillary Lesions on Core Biopsy Is Critical for Accurate Classification and Clinical Management: The Experience of an Academic Institute.

BACKGROUND: Distinguishing between a breast intraductal papilloma and a papillary lesion with atypia or malignancy can be very challenging on core biopsy. There has been a long ongoing debate over whether or not it is necessary for breast papillary lesions diagnosed on core biopsies to be surgically excised, and the upgrading rate after excision varies. METHOD AND/OR RESULT: This study was carried out in a subspecialized academic pathology department, with well-formed criteria established among the faculty for the categorization of breast papillary lesions, with emphasis on the morphology evaluation of cellular features. A total of 320 breast core biopsies with follow-up excisions were identified. Of these, 286 cases had concordant results between the biopsy and excision, giving a concordance rate of 89.4%, with 98% concordance (143/146) in benign papilloma, 100% (111/111) in papillary carcinoma, and 51% (32/63) in papilloma with atypia. Of the upgraded cases, two were upgraded from benign to atypical, 11 from atypia to malignancy, and only one from benign to malignant. The overall average upgrading rate was 4.4% (14/320), with the critical upgrading (from benign to atypia or malignancy) rate of 0.94% (3/320). Downgrading was only identified in the group of papilloma with atypia, with 20 of 63 cases downgraded to benign papilloma on excision. CONCLUSION: Our study indicates that surgical excision may not be necessary for all papillary lesions after detailed evaluation of the morphology on core biopsies. Assessing the morphological features of the epithelial cells is critical for the accurate classification and clinical management of papillary lesions.

Binding of pro-prion to filamin A disrupts cytoskeleton and correlates with poor prognosis in pancreatic cancer.

The cellular prion protein (PrP) is a highly conserved, widely expressed, glycosylphosphatidylinositol-anchored (GPI-anchored) cell surface glycoprotein. Since its discovery, most studies on PrP have focused on its role in neurodegenerative prion diseases, whereas its function outside the nervous system remains unclear. Here, we report that human pancreatic ductal adenocarcinoma (PDAC) cell lines expressed PrP. However, the PrP was neither glycosylated nor GPI-anchored, existing as pro-PrP and retaining its GPI anchor peptide signal sequence (GPI-PSS). We also showed that the PrP GPI-PSS has a filamin A-binding (FLNa-binding) motif and interacted with FLNa, an actin-associated protein that integrates cell mechanics and signaling. Binding of pro-PrP to FLNa disrupted cytoskeletal organization. Inhibition of PrP expression by shRNA in the PDAC cell lines altered the cytoskeleton and expression of multiple signaling proteins; it also reduced cellular proliferation and invasiveness in vitro as well as tumor growth in vivo. A subgroup of human patients with pancreatic cancer was found to have tumors that expressed pro-PrP. Most importantly, PrP expression in tumors correlated with a marked decrease in patient survival. We propose that binding of pro-PrP to FLNa perturbs FLNa function, thus contributing to the aggressiveness of PDAC. Prevention of this interaction could provide an attractive target for therapeutic intervention in human PDAC.

Hepatic angiomyolipoma.

Hepatic angiomyolipoma is a rare, benign, hepatic mesenchymal neoplasm found in both males and females, and most commonly in adult females. Angiomyolipoma occurs most commonly in the kidneys. The liver represents the second most frequent site of involvement. Hepatic angiomyolipomas are composed of varying amounts of smooth muscle cells, adipose tissue, and vessels. The smooth muscle cell component is the most specific to the diagnosis. The smooth muscle cells can have varying morphologies and are positive for homatropine methylbromide-45 but are negative for hepatocyte paraffin 1 and S100 protein. The definitive diagnostic study remains the histologic examination of the surgically resected lesion coupled with immunohistochemical stains. The differential diagnosis includes hepatocellular carcinoma, hepatic adenoma, leiomyoma, hepatoblastoma, melanoma, and gastrointestinal stromal tumor. The immunohistochemical staining pattern differentiates this lesion from other malignant and benign liver lesions. If the diagnosis of hepatic angiomyolipoma has been made, it can be followed conservatively or surgically resected.

The clinical significance of focal enhanced gastritis in adults with isolated ileitis of the terminal ileum.

BACKGROUND: Isolated chronic ileitis in the terminal ileum, without accompanying chronic colitis, is not an uncommon finding present in biopsy specimens from patients being evaluated for chronic diarrhea. Among the many entities that should be included in the differential diagnosis are Crohn's disease and nonsteroidal antiinflammatory drugs (NSAIDs)-induced enterocolitis. In high-prevalence Crohn's disease populations, focal enhanced or active gastritis (FEG) may be a good predictor of Crohn's disease; however, this criterion may not apply in a general clinical setting. Our goal was to determine if FEG is a pathological marker of Crohn's disease in patients with isolated chronic ileitis in the terminal ileum. METHODS: We examined 46 consecutive cases of isolated chronic ileitis with concurrent stomach biopsies. These patients did not have evidence or previous history of inflammatory bowel disease. The diagnostic criteria of chronic ileitis included crypt distortion and inflammation, plasmacytosis in the lamina propria, ulceration, and/or pyloric gland metaplasia. RESULTS: Of the 46 cases reviewed, 25 (54%) cases were diagnosed with Crohn's disease later, confirmed by clinical manifestations and/or biopsies with a follow-up of up to 4 years. The stomach biopsies of these patients were either normal or demonstrated a spectrum of histological findings, including FEG, chronic gastritis with or without Helicobacter pylori organisms, chemical gastropathy, and normal tissues. FEG was more commonly present in Crohn's disease patients (36%) than in non-Crohn's disease patients (5%) (P < 0.01). CONCLUSIONS: The presence of FEG is a good indicator for the diagnosis of Crohn's disease in adult patients with isolated chronic ileitis.