Non-neoplastic Polyps of the Gallbladder: A Clinicopathologic Analysis of 447 Cases.

There is no systematic histopathologic analysis of non-neoplastic polyps in the gallbladder. In this study, in addition to a computer search for cases designated as "polyp," a systematic review of 2533 consecutive routinely sampled archival and 203 totally submitted prospective cholecystectomies were analyzed for >2 mm polyps (cut-off was based on radiologic sensitivity). A total of 447 non-neoplastic polyps were identified. The frequency was 3% in archival cases and 5% in totally submitted cases. Only 21 (5%) were ≥1 cm. The average age was 52 years, and the female to male ratio was 3.1. Two distinct categories were delineated: (1) injury-related polyps (n=273): (a) Fibro(myo)glandular polyps (n=214) were small (mean=0.4 cm), broad-based, often multiple (45%), almost always (98%) gallstone-associated, and were composed of a mixture of (myo)fibroblastic tissue/lobular glandular units with chronic cholecystitis. Dysplasia seen in 9% seemed to be secondary involvement. (b) Metaplastic pyloric glands forming polypoid collections (n=42). (c) Inflammatory-type polyps associated with acute/subacute injury (11 granulation tissue, 3 xanthogranulomatous, 3 lymphoid). (2) Cholesterol polyps (n=174) occurred in uninjured gallbladders, revealing a very thin stalk, edematous cores devoid of glands but with cholesterol-laden macrophages in 85%, and cholesterolosis in the uninvolved mucosa in 60%. Focal low-grade dysplasia was seen in 3%, always confined to the polyp, unaccompanied by carcinoma. In conclusion, non-neoplastic polyps are seen in 3% of cholecystectomies and are often small. Injury-related fibromyoglandular polyps are the most common. Cholesterol polyps have distinctive cauliflower architecture, often in a background of uninjured gallbladders with cholesterolosis and may lack the cholesterol-laden macrophages in the polyp itself. Although dysplastic changes can involve non-neoplastic polyps, they do not seem to be the cause of invasive carcinoma by themselves.

Muscle invasion in oral tongue squamous cell carcinoma as a predictor of nodal status and local recurrence: just as effective as depth of invasion?

Tumor depth of invasion (DOI) is a histologic feature that consistently correlates with lymph node metastasis; however, there are many difficulties with accurately assessing DOI. The aim of this study was to identify a simpler and more reproducible method of determining DOI, by using skeletal muscle invasion as a surrogate marker of depth. Oral tongue squamous cell carcinoma American Joint Committee on Cancer (AJCC) stage T1 cases were identified in the Emory University Department of Pathology database. 61 cases, with a minimum of 2 years of follow-up, were included in the study. Cases were examined histologically to assess muscle invasion and DOI. The two methods of measurement were analyzed to determine the positive predictive value (PPV) of DOI or muscle invasion for both nodal disease and local recurrence. Cases with muscle invasion had a 23.3% PPV of occult lymph node metastasis. Cases with DOI of greater than 3 mm had a 29.7% PPV of occult lymph node metastasis. Cases with muscle invasion had a 43.7% PPV of local tumor recurrence. Cases with maximum DOI of greater than 3 mm had a 40.4% PPV of tumor recurrence. Although the PPV of muscle invasion in regards to nodal status was slightly less than DOI, it represents a more easily reproducible parameter which could guide surgeons in determining if the case warrants an elective neck dissection in a cN0 (clinically negative) neck. Interestingly, the PPV of local recurrence was higher with muscle invasion than DOI, and may represent an important indicator for extent of resection.

In vitro and in vivo effects of repifermin (keratinocyte growth factor-2, KGF-2) on human carcinoma cells.

PURPOSE: Repifermin (keratinocyte growth factor-2, KGF-2) is a growth factor that selectively induces epithelial cell proliferation, differentiation and migration. The objective of this study was to assess the effect of repifermin on in vitro tumor cell proliferation and in vivo tumor growth using a variety of human carcinoma cell lines with differing growth rates and levels of KGF receptor (KGFR) expression. METHODS: Potential effects of repifermin on in vitro cell proliferation were evaluated by alamarBlue and/or [(3)H]-thymidine incorporation assays under a range of serum conditions. In vivo tumor growth was evaluated by implanting KGFR(+) carcinomas subcutaneously into nude mice and measuring tumor growth over time in mice injected intravenously (i.v.) or intraperitoneally (i.p.) with repifermin or placebo. RESULTS: In vitro, none of the 30 human carcinoma cell lines tested demonstrated a substantial increase in proliferation in response to repifermin over the concentration range 0.01 to 1000 ng/ml. In vivo results showed no significant tumor growth-promoting activity when single- or multiple-cycle intravenous injections of repifermin (1 mg/kg) were given to athymic nude mice inoculated with human KGFR(+) tumors of the pharynx (Detroit 562, FaDu), colon (Caco-2), salivary gland (A-253) or tongue (SCC-25, CAL 27). In addition, repifermin (0.2 or 2 mg/kg) injected i.p. for 2 weeks had no effect on the growth of eight other human carcinomas including those of the ovary (NIH:OVCAR-3, SK-OV 3, PA-1), bladder (SCaBER), epidermis (A 431), lung (SW 900), breast (MDA-MB-231) and cervix (SiHa). CONCLUSIONS: Repifermin had no in vitro or in vivo proliferative effects on KGFR(+) human epithelial-like tumors. This failure to stimulate tumor cell growth highlights the ability of repifermin to specifically target normal epithelial tissue. This is critical to the safety profile of repifermin, since it is currently in phase II clinical trials for the treatment of cancer patients with mucositis resulting from chemo- or radiotherapy.