Columnar cell change with atypia (flat epithelial atypia) on breast core biopsy-outcomes following open excision.

Columnar cell change with atypia (CCCA) is a relatively recently recognized pathologic breast entity considered to be a risk factor for subsequent development of breast carcinoma. The aim of this study was to investigate the significance of finding CCCA on breast core biopsy, by establishing the frequency of other breast pathology on subsequently performed surgical excision specimens. All cases with CCCA as the most advanced lesion on core biopsy were reviewed. After excision, another advanced proliferative lesion was identified in 17 (33%) patients, including three patients (6%) with in situ or invasive carcinoma. An additional five patients (10%) were concurrently diagnosed with primary breast carcinoma at other sites. These findings indicate that when CCCA is found on core biopsy, open surgical biopsy of the relevant area should be performed and that workup of both breasts should be undertaken to exclude coexistent breast carcinoma at alternative sites.

Reactivation of embryonic nodal signaling is associated with tumor progression and promotes the growth of prostate cancer cells.

BACKGROUND: Nodal is a member of the transforming growth factor ß (TGFß) superfamily that directs embryonic patterning and promotes the plasticity and tumorigenicity of tumor cells, but its role in the prostate is unknown. The goal of this study was to characterize the expression and function of Nodal in prostate cancer and determine whether, like other TGFß ligands, it modulates androgen receptor (AR) activity. METHODS: Nodal expression was investigated using immunohistochemistry of tissue microarrays and Western blots of prostate cell lines. The functional role of Nodal was examined using Matrigel and soft agar growth assays. Cross-talk between Nodal and AR signaling was assessed with luciferase reporter assays and expression of endogenous androgen regulated genes. RESULTS: Significantly increased Nodal expression was observed in cancer compared with benign prostate specimens. Nodal was only expressed by DU145 and PC3 cells. All cell lines expressed Nodal's co-receptor, Cripto-1, but lacked Lefty, a critical negative regulator of Nodal signaling. Recombinant human Nodal triggered downstream Smad2 phosphorylation in DU145 and LNCaP cells, and stable transfection of pre-pro-Nodal enhanced the growth of LNCaP cells in Matrigel and soft agar. Finally, Nodal attenuated AR signaling, reducing the activity of a PSA promoter construct in luciferase assays and down-regulating the endogenous expression of androgen regulated genes. CONCLUSIONS: An aberrant Nodal signaling pathway is re-expressed and functionally active in prostate cancer cells.

Cystic neutrophilic granulomatous mastitis associated with Corynebacterium including Corynebacterium kroppenstedtii.

Granulomatous (lobular) mastitis is a rare inflammatory breast disease affecting parous reproductive-aged women. Once considered idiopathic, there is growing evidence of an association with corynebacteria infection, especially in the setting of a distinct histological pattern termed cystic neutrophilic granulomatous mastitis (CNGM). We describe 15 cases with histological features either confirming (n = 12) or suggesting (n = 3) CNGM, and concurrent microbiological evidence of Corynebacterium species. The organism was detected by culture or 16S rRNA gene sequencing of specimens obtained at surgery or fine needle aspiration. In seven cases, Gram-positive organisms were seen within vacuolated spaces. Speciation was performed in nine cases, with Corynebacterium kroppenstedtii subsequently identified. These cases provide further evidence in support of this association and in doing so highlight the importance of recognising these histological clues as well as the limitations of Gram stain and microbiological culture in detecting this previously under-recognised disease process.

Significance of minute focus of adenocarcinoma on prostate needle biopsy.

OBJECTIVES: To assess the radical prostatectomy findings in patients with a minute focus of adenocarcinoma on prostate needle biopsy in current practice in Australia. METHODS: A total of 58 patients with a 0.5-mm focus or less of Gleason score 6 adenocarcinoma on needle biopsy who had been treated by radical prostatectomy were selected. At each biopsy, 6 to 20 cores (mean 11, median 13) were taken. Significant tumors were those with a Gleason score of 6 or more and tumor volume of 0.5 cm3 or larger. RESULTS: The 58 patients (mean age 50 years, median 58, range 44 to 69) had a mean prostate-specific antigen (PSA) level of 6.9 ng/mL (range 0.7 to 16, median 6). Of the 58 men, 48 (82.75%) had pathologically significant tumor, with 8 (13.8%) showing extraprostatic extension. No statistically significant association was found between significant carcinoma and age, mean PSA level, PSA density greater than 0.15, prior negative biopsy, coexistent atypical glands, or the number of tissue cores per biopsy. A prostate weight greater than 40 g correlated significantly with insignificant cancer on both univariate (P = 0.03) and multivariate (P = 0.02) analyses. In 14 (29.2%) of 48 patients with significant tumor, the largest cancer focus in the radical prostatectomy was anterior, lateral, or anterolateral. In patients without atypical glands, 37 (78.72%) of 47 had significant carcinoma, a risk not significantly lower than that of the entire group. CONCLUSIONS: The results of our study have shown that in populations without PSA screening, a minute focus of prostate cancer on needle biopsy, even with extended biopsy cores, does not mean insignificant carcinoma in most cases. Patients with larger glands had a greater chance of insignificant cancer.