Phase II Trial of Chemopreventive Effects of Levonorgestrel on Ovarian and Fallopian Tube Epithelium in Women at High Risk for Ovarian Cancer: An NRG Oncology Group/GOG Study.

A large body of epidemiologic evidence has shown that use of progestin-containing preparations lowers ovarian cancer risk. The purpose of the current study was to gather further preclinical evidence supporting progestins as cancer chemopreventives by demonstrating progestin-activation of surrogate endpoint biomarkers pertinent to cancer prevention in the genital tract of women at increased risk of ovarian cancer. There were 64 women enrolled in a multi-institutional randomized trial who chose to undergo risk-reducing bilateral salpingo-oophorectomy (BSO) and to receive the progestin levonorgestrel or placebo for 4 to 6 weeks prior to undergoing BSO. The ovarian and fallopian tube epithelia (FTE) were compared immunohistochemically for effects of levonorgestrel on apoptosis (primary endpoint). Secondary endpoints included TGFß isoform expression, proliferation, and karyometric features of nuclear abnormality. In both the ovary and fallopian tube, levonorgestrel did not confer significant changes in apoptosis or expression of the TGFß1, 2, or 3 isoforms. In the ovarian epithelium, treatment with levonorgestrel significantly decreased the proliferation index. The mean ovarian Ki-67 value in the placebo arm was 2.027 per 100 cells versus 0.775 per 100 cells in the levonorgestrel arm (two-sided P value via Mann-Whitney U test = 0.0114). The karyometric signature of nuclei in both the ovarian and FTE deviated significantly from normal controls (women at average risk of ovarian cancer), but was significantly less abnormal in women treated with levonorgestrel. These karyometric data further support the idea that progestins may clear genetically abnormal cells and act as chemopreventive agents against ovarian and fallopian tube cancer.

Encrusted Cystitis Secondary to Corynebacterium glucuronolyticum in a 57-Year-Old Man Without Predisposing Factors.

Encrusted cystitis is a rare condition characterized by encrustation of the bladder mucosa with associated chronic inflammation induced by urea-splitting bacterial infection--most commonly, Corynebacterium urealyticum. Moreover, it usually occurs in immunocompromised patients, especially recipients of renal transplants or patients with a history of previous urological procedures. Due to the rarity of the entity and the slow growth of Corynebacterium species, appropriate treatment is often delayed due to difficulties in diagnosis and resistance to numerous antibiotics. We report a case of encrusted cystitis caused by Corynebacterium glucuronolyticum, another urea-splitting microbe, in a 57-year-old previously healthy Caucasian man with no known predisposing factors. The timely diagnosis and management in this otherwise healthy patient was facilitated by characteristic imaging, cystoscopy, and histologic findings confirmed by results of prolonged urine cultures and 16S ribosomal RNA (rRNA) gene sequencing of the microbe.

Multifocal and multicentric glioblastoma with leptomeningeal gliomatosis: a case report and review of the literature.

Glioblastoma (GBM) rarely presents as an infratentorial tumor in adults. The authors present a case of concomitant supratentorial and infratentorial GBM in an adult. A 72-year-old man presented with headache, nausea, vomiting, and lightheadedness. Initial MR images revealed enhancing masses in the right cerebellum and right posterior periventricular region. The patient underwent a suboccipital craniotomy and resection of the cerebellar lesion. Final histopathology was consistent with glioblastoma. The patient went on to receive standard radiation treatment for GBM with concurrent and adjuvant temozolomide. However, the patient experienced clinical deterioration within a few days after starting radiotherapy. He and his family decided to forego treatment and pursue palliative care. The patient expired three months after the initial diagnosis. Autopsy findings supported the diagnosis of GBM with leptomeningeal gliomatosis and involvement of the cerebrum, cerebellum, and spinal cord. The authors review the literature and propose that the pathogenesis of multiple and multicentric GBM may involve neural stem cells within the subventricular zone or could result from tumor dissemination along established CNS routes, such as white matter tracts and CSF pathways.

An audit of dermatopathology requisitions: hand written vs. electronic medical record data entry accuracy.

BACKGROUND: At our institution, dermatopathology case requisitions are received in hand written form or via electronic medical record (EMR). Categories for requisition data entry include patient demographics, physician name and procedure site/date. Systematic data entry problems potentially cause considerable documentation error, propagate inaccurate patient information and potentially delay billing/revenue collection. METHOD: We compared dermatopathology data entry errors on hand written requisitions to data entry errors using the EMR. A total of 11,475 requisitions (8545 hand written and 2930 EMR) were included in the study (the time frame was 4/1/2011-9/30/2011). RESULTS: For hand written requisitions, there were 258 data entry errors on 8545 specimens (3.0%). For requisitions entered via EMR, there were 113 errors on 2930 specimens (3.9%). Container labeling, which is a hand written process with both requisition methods, was the most common source of error. CONCLUSIONS: Currently, even with an EMR, containers are at least partially hand labeled and 96% of EMR errors occurred during this process. Other EMR data entry errors are extremely uncommon (4/2930 cases). This suggests introduction of a labeling process entirely linked to EMR data entry could nearly eliminate data entry errors. Although this study focused solely on dermatopathology cases, the findings can be extrapolated to all types of specimens.

AlphaB-crystallin: a novel marker of invasive basal-like and metaplastic breast carcinomas.

Basal-like tumors are a newly recognized estrogen receptor (ER) negative and HER2 negative breast cancer subtype that express basal epithelial genes and are associated with poor survival. Metaplastic carcinomas are thought to belong within the basal-like group. We have recently demonstrated that the small heat shock protein alphaB-crystallin is commonly expressed in basal-like tumors and contributes to their aggressive phenotype. The current study examined the rates and patterns of alphaB-crystallin expression in whole tissue sections of human breast, including normal tissue, proliferative lesions, in situ and invasive carcinomas (ER positive, HER2 positive, basal-like, and metaplastic cancers). In normal breast tissue, proliferative lesions and in situ carcinomas, alphaB-crystallin expression was restricted to the myoepithelial cell compartment of ductal and lobular units. Most basal-like and metaplastic carcinomas demonstrated cytoplasmic expression of alphaB-crystallin (81% and 86%, respectively). Conversely, no staining for alphaB-crystallin was observed in nonbasal-like (ie, ER positive or HER2 positive) breast carcinomas. Taken together, our results indicate that alphaB-crystallin is a sensitive (81%) and specific (100%) marker for basal-like breast carcinomas. Moreover, the high rates of expression of alphaB-crystallin in metaplastic breast carcinomas (86%) suggest that these tumors may represent a histologically distinctive subset of basal-like breast tumors with a similar underlying molecular etiology.

Metastatic basal cell carcinoma: complete response to chemotherapy and associated pure red cell aplasia.

Basal cell carcinoma (BCC) is usually a benign and indolent cancer cured in greater than 95 percent of cases. Nevertheless, it can be locally destructive or occasionally metastasize to distant organs. We report a case of BCC metastatic to the lungs, occurring 17 years after the primary BCC was noticed, that responded to carboplatin and paclitaxel on 3 occasions. The patient also developed pure red cell aplasia (PRCA). Work-up did not reveal underlying thymoma or infectious, rheumatologic, or lymphoproliferative disorders. Parvovirus serologies were negative, and antibodies against erythropoetin were not detected. There was no history of exposure to drugs associated with PRCA. Bone marrow biopsy on 2 different occasions did not show evidence of myelodysplasia. PRCA may represent an unusual paraneoplastic syndrome associated with BCC as reported with other carcinomas. This is the first report of PRCA associated with metastatic BCC or the drugs carboplatin and paclitaxel, which were used to treat it. The literature on chemotherapy for metastatic BCC is reviewed.

High-risk human papillomavirus detection: a split-sample comparison of hybrid capture and chromogenic in situ hybridization.

The American Society for Colposcopy and Cervical Pathology (ASCCP) has proposed high-risk human papillomavirus (HPV) testing as the "preferred" triage for women with atypical squamous cells of undetermined significance. We studied 401 atypical squamous cells of undetermined significance liquid-based cervicovaginal cytology split samples for HPV by chromogenic in situ hybridization (CISH) and by Hybrid Capture (HC) II (Digene, Gaithersburg, MD); 202 underwent HC II followed by CISH, and 199 underwent CISH followed by HC II. Of 401 vials, 101 (25.2%) were positive for HPV by 1 or more methods. HC II labeled 83 of 401 (20.7%) samples as positive, while 38 of 401 (9.5%) were positive by CISH. Positive attributes of CISH include the provision of a cytomorphologic link in assessing HPV positivity and comparative ease of use in laboratories without trained molecular diagnosticians. Greater efficacy and quantitative design are advantages of HC II. Comparing data by sequence of testing showed a lower likelihood of positive test results on the second ancillary test than on the first ancillary test, regardless of age or testing method (odds ratio, second/first = 0.58; P = .003). This finding suggests that liquid-based cervicovaginal cytology samples are not homogeneous throughout. Correlative studies with histology and polymerase chain reaction may clarify predictive values for both methods.

Upstaging of atypical ductal hyperplasia after vacuum-assisted 11-gauge stereotactic core needle biopsy.

BACKGROUND: Nonpalpable mammographic abnormalities are frequently evaluated by means of a stereotactic core needle biopsy. This technique is a very sensitive indicator of invasive cancer, but is less reliable to discriminate between ductal carcinoma in situ and atypical ductal hyperplasia (ADH). The objective of this study was to determine the correlation of the 11-gauge vacuum-assisted core needle biopsy to open biopsy when a diagnosis of ADH is obtained. HYPOTHESIS: The use of 11-gauge vacuum-assisted stereotactic core needle biopsy does not conclusively diagnose ADH. DESIGN: Retrospective analysis. SETTING: University-affiliated teaching hospital. PATIENTS: Mammographic findings were evaluated with an 11-gauge vacuum-assisted stereotactic core biopsy in 1750 patients. Seventy-seven patients were diagnosed as having ADH; of these, 65 underwent excisional biopsy. MAIN OUTCOME MEASURES: Pathological upstaging rate. RESULTS: Of the 65 patients who underwent excisional breast biopsy, 11 (17%) had their condition upstaged to a breast cancer diagnosis. These patients had presented at a later age than those who retained a benign diagnosis after excisional biopsy. The number of cores taken did not correlate with diagnostic accuracy. CONCLUSIONS: Of the 65 patients who underwent open biopsy for ADH in this series, only 83% had an accurate diagnosis. A diagnosis of ADH by stereotactic core needle biopsy should be followed by an open excisional biopsy.

Invasive micropapillary carcinoma of the breast is associated with chromosome 8 abnormalities detected by comparative genomic hybridization.

Invasive micropapillary carcinoma (IMC) of the breast is a rare variant of invasive ductal carcinoma (IDC) characterized by unique histology and an extremely high incidence of lymph node metastases (approximately 95%). Comparative genomic hybridization (CGH) was used to characterize DNA extracted from 16 archival IMC cases to identify clonal genetic changes associated with this unique and highly metastatic cancer subtype. The average number of chromosomal alterations per IMC tumor was 7.4 +/-2.9 (3.4 gains and 3.9 losses), fewer than the number that we have observed in IDCs not otherwise specified (9.5 +/-6.6), IDCs with erbB-2 gene amplification (12.6 +/-5.9), and invasive lobular carcinomas (8.2 +/-5.5). The mean number of changes in IMC was significantly higher than we have observed in the rarely metastasizing tubular subtype of IDC (3.9 +/-2.3, P = 0.001), but less than the more aggressive subset of erbB-2-amplified IDC (P = 0.02). Remarkably, 100% of IMCs demonstrated loss involving the short arm of chromosome 8 (8p). Six cases showed loss of the entire 8p arm, whereas in 10 cases the loss was limited to the distal portion (8p21-pter) with localized gain of proximal 8p (8p11-p12). A reciprocal gain of 8q was detected in 14 cases (88%). Other common alterations included loss of 17p in 50% of tumors and loss of 16q in 50% of IMC cases. Gains of 17q (38%), 1q (31%), and 16p (25%) were also commonly detected. In comparison, IDCs (not otherwise specified), IDCs of the tubular subtype, and invasive lobular carcinomas showed only modest 8p loss (33%, 28%, and 13%, respectively). This region of chromosome 8 may contain 1 or more genes whose loss leads to this particular histology and/or the lymphotrophic phenotype associated with this histopathologic pattern.