Gastric-type mucinous adenocarcinoma of the uterine cervix with neoadjuvant therapy mimicking clear cell carcinoma

Gastric-type mucinous adenocarcinoma, an uncommon subtype of cervical carcinoma, is characterized by a distinct morphology and immunophenotype. Herein, we report a case of a 71-year-old woman who received neoadjuvant radiotherapy and chemotherapy after cervical biopsy revealed moderately differentiated invasive endocervical adenocarcinoma. Subsequently, the outside patient underwent radical hysterectomy with bilateral salpingo-oophorectomy. The post-neoadjuvant therapy hysterectomy specimen showed tumor cells with clear cytoplasm, hyperchromatic nuclei with irregular contours, which mimicked clear cell carcinoma. However, immunohistochemical staining showed that these tumor cells were positive for carcinoembryonic antigen, cytokeratin 7 (diffuse), and cytokeratin 20 (patchy), After review of the pretreatment cervical biopsy specimen, the tumor was favored to represent a gastric-type mucinous adenocarcinoma of the cervix. Pathologists should be aware of this rare tumor and its post-neoadjuvant therapy morphologic changes, which can make diagnosis more challenging.     

Tumoral calcinosis in postmenopausal women in urban India: an etiopathologic evaluation of 64 cases

Tumoral calcinosis (TC) is a distinct pathologic entity of obscure etiology, characterized by soft tissue calcium deposition. We analyzed 64 cases retrieved from surgical records over the last 15 years, to assess the disease pattern and recognize the various stages of the evolution of this lesion. In our study, most patients were women (53/64 cases), 47 of whom were postmenopausal, aged 51-70 years, belonging to lower socioeconomic strata, and involved with household chores. The hip was the most frequently affected site. Repeated trauma probably triggered calcium chelation and deposition at this site. Histologically, 10 cases belonged to stage II and 54 cases to stage III. Fully developed lesions showed chips of calcium surrounded by thick fibrosis, mimicking calcified parasite like the Guinea worm. Precursor lesions seen at the periphery of the main lesion suggests a possible etiological role for trauma. Postmenopausal hormonal imbalance, along with poor nutrition and repeated trauma led to TC in our women population. Awareness of its evolution can lead to a better understanding of the disease with possible therapeutic implications.     

Polymorphisms in apoptosis- and proliferation-related genes, ionizing radiation exposure, and risk of breast cancer among U.S. Radiologic Technologists.

BACKGROUND: Although genes involved in apoptosis pathways and DNA repair pathways are both essential for maintaining genomic integrity, genetic variants in DNA repair have been thought to increase susceptibility to radiation carcinogenesis, but similar hypotheses have not generally been raised about apoptosis genes. For this reason, potential modification of the relationship between ionizing radiation exposure and breast cancer risk by polymorphic apoptosis gene variants have not been investigated among radiation-exposed women. METHODS: In a case-control study of 859 cases and 1,083 controls within the U.S. Radiologic Technologists cohort, we assessed breast cancer risk with respect to 16 candidate variants in eight genes involved in apoptosis, inflammation, and proliferation. Using carefully reconstructed cumulative breast dose estimates from occupational and personal diagnostic ionizing radiation, we also investigated the joint effects of these polymorphisms on the risk of breast cancer. RESULTS: In multivariate analyses, we observed a significantly decreased risk of breast cancer associated with the homozygous minor allele of CASP8 D302H [rs1045485, odds ratio (OR), 0.3; 95% confidence interval (95% CI), 0.1-0.8]. We found a significantly increased breast cancer risk with increasing minor alleles for IL1A A114S (rs17561); heterozygote OR 1.2 (95% CI, 1.0-1.4) and homozygote OR 1.5 (95% CI, 1.1-2.0), P(trend) = 0.008. Assuming a dominant genetic model, IL1A A114S significantly modified the dose-response relationship between cumulative personal diagnostic radiation and breast cancer risk, adjusted for occupational dose (P(interaction) = 0.004). CONCLUSION: The U.S. Radiologic Technologists breast cancer study provided a unique opportunity to examine the joint effects of common genetic variation and ionizing radiation exposure to the breast using detailed occupational and personal diagnostic dose data. We found evidence of effect modification of the radiation and breast cancer dose-response relationship that should be confirmed in studies with more cases and controls and quantified radiation breast doses in the low-to-moderate range.     

Correlating nanoscale titania structure with toxicity: a cytotoxicity and inflammatory response study with human dermal fibroblasts and human lung epithelial cells.

Nanocrystalline titanium dioxide (nano-TiO(2)) is an important material used in commerce today. When designed appropriately it can generate reactive species (RS) quite efficiently, particularly under ultraviolet (UV) illumination; this feature is exploited in applications ranging from self-cleaning glass to low-cost solar cells. In this study, we characterize the toxicity of this important class of nanomaterials under ambient (e.g., no significant light illumination) conditions in cell culture. Only at relatively high concentrations (100 microg/ml) of nanoscale titania did we observe cytotoxicity and inflammation; these cellular responses exhibited classic dose-response behavior, and the effects increased with time of exposure. The extent to which nanoscale titania affected cellular behavior was not dependent on sample surface area in this study; smaller nanoparticlulate materials had effects comparable to larger nanoparticle materials. What did correlate strongly to cytotoxicity, however, was the phase composition of the nanoscale titania. Anatase TiO(2), for example, was 100 times more toxic than an equivalent sample of rutile TiO(2). The most cytotoxic nanoparticle samples were also the most effective at generating reactive oxygen species; ex vivo RS species generation under UV illumination correlated well with the observed biological response. These data suggest that nano-TiO(2) samples optimized for RS production in photocatalysis are also more likely to generate damaging RS species in cell culture. The result highlights the important role that ex vivo measures of RS production can play in developing screens for cytotoxicity.