Buschke-Lowenstein Tumors: A Review and Proposed Classification System.

ABSTRACT: Buschke-Lowenstein (B-L) tumors or giant condylomata are large fungating lesions that are caused by human papillomavirus (HPV) and develop in the anogenital region. Although uncommon, physicians and surgeons who treat sexually transmitted diseases or other diseases involving the anogenital area will encounter these patients. The purpose of this study is to review the current literature regarding these lesions. We evaluated every published study in PubMed and Embase from 1925 to 2020, concentrating on the clinical data included in each report, such as presentation and treatment. We also evaluated each work for any definition used and found that there is no accepted definition for these lesions. As such, we provide an inclusive, workable definition. In addition, there are many misconceptions about B-L that continue to be propogated as more case reports are published every year. After evaluating every published case, we refute the fact that these lesions have a high mortality or a high malignancy rate. Furthermore, we refute that these lesions are synonymous with verrucous carcinoma. In addition to a definition, we also propose a simple grading system that we hope can be used to assist in the study and management of these patients moving forward. Although the literature is very heterogenous regarding B-L, they are caused by HPV and are distinct from verrucous carcinoma. Because of the majority of information is based on case reports, the literature concentrates on treatment, but more work is clearly needed to delineate the association with specific HPV types and optimal management of this disease.

Primary hyperoxaluria: spectrum of clinical and imaging findings.

Primary hyperoxaluria is a rare autosomal recessive inborn error of metabolism with three known subtypes. In primary hyperoxaluria type 1, the most common of the subtypes, a deficiency in the hepatic enzymes responsible for the metabolism of glycoxylate to glycine, leads to excessive levels of glyoxylate, which is converted to oxalate. The resultant elevation in serum and urinary oxalate that characterizes primary hyperoxaluria leads to calcium oxalate crystal deposition in multiple organ systems (oxalosis). We review the genetics, pathogenesis, variable clinical presentation and course of this disease as well as its treatment. Emphasis is placed on the characteristic imaging findings before and after definitive treatment with combined liver and renal transplantation.

2-Acetylcyclopentanone, an enolate-forming 1,3-dicarbonyl compound, is cytoprotective in warm ischemia-reperfusion injury of rat liver.

We have previously shown that 2-acetylcyclopentanone (2-ACP), an enolate-forming 1,3-dicarbonyl compound, provides protection in cell culture and animal models of oxidative stress. The pathophysiology of ischemia-reperfusion injury (IRI) involves oxidative stress, and, therefore, we determined the ability of 2-ACP to prevent this injury in a rat liver model. IRI was induced by clamping the portal vasculature for 45 minutes (ischemia phase), followed by recirculation for 180 minutes (reperfusion phase). This sequence was associated with substantial derangement of plasma liver enzyme activities, histopathological indices, and markers of oxidative stress. The 2-ACP (0.80-2.40 mmol/kg), administered by intraperitoneal injection 10 minutes prior to reperfusion, provided dose-dependent cytoprotection, as indicated by normalization of the IRI-altered liver histologic and biochemical parameters. The 2-ACP (2.40 mmol/kg) was also hepatoprotective when injected before clamping the circulation (ischemia phase). In contrast, an equimolar dose of N-acetylcysteine (2.40 mmol/kg) was not hepatoprotective when administered prior to reperfusion. Our studies to date suggest that during reperfusion the enolate nucleophile of 2-ACP limits the consequences of mitochondrial-based oxidative stress through scavenging unsaturated aldehyde electrophiles (e.g., acrolein) and chelation of metal ions that catalyze the free radical-generating Fenton reaction. The ability of 2-ACP to reduce IRI when injected prior to ischemia most likely reflects the short duration of this experimental phase (45 minutes) and favorable pharmacokinetics that maintain effective 2-ACP liver concentrations during subsequent reperfusion. These results provide evidence that 2-ACP or an analog might be useful in treating IRI and other conditions that have oxidative stress as a common molecular etiology.

Cutaneous ciliated cyst: a case report with focus on mullerian heterotopia and comparison with eccrine sweat glands.

Cutaneous ciliated cyst is an exceedingly rare, benign lesion most commonly found in the dermis or subcutis of the lower extremities of young female patients in their second and third decades. The pathogenesis of the cyst is unknown. We report a cutaneous ciliated cyst in the lower extremity of a 13-year-old female patient. On histologic examination, clusters of eccrine sweat glands were observed adjacent to the cyst. Upon comparison of the immunohistochemical profile of the cutaneous ciliated cyst and the eccrine sweat glands, they appeared almost completely unrelated. The histologic, immunohistochemical, and ultrastructural findings of this case and the literature provide evidence in favor of the Mullerian heterotopia theory.

GRB7 Expression and Correlation With HER2 Amplification in Invasive Breast Carcinoma.

Growth factor receptor-bound protein 7 (GRB7) gene is located adjacent to the HER2 gene on the 17q12-21 amplicon, is often coamplified with HER2 in a subset of breast cancers, and has been implicated in resistance to anti-HER2 and antiestrogen therapy. This study investigated the correlation of GRB7 expression by immunohistochemistry with HER2 expression, HER2 amplification, increased chromosome 17 copy number, and other prognostic and predictive factors in invasive breast cancer, including histologic grade, pathologic stage, and ER, PR, and p53 status. Paraffin-embedded samples of 188 invasive breast carcinomas with documented HER2, ER, and PR testing were collected and divided into 3 groups: cases positive for HER2 overexpression/gene amplification (n=60), negative for HER2 overexpression (n=97), and cases with increased chromosome 17 copy number without HER2 amplification (n=31). GRB7 expression was evaluated on all 188 cases. In addition, p53 immunohistochemistry was performed on 13 HER2+/GRB7+ cases and 39 HER2+/GRB7- cases. GRB7 expression correlated strongly with HER2 overexpression. GRB7 expression was present in 20/60 (33.33%) of HER2+ cases, compared with 1/97 (1.03%) HER2- cases, and 1/31 (3.22%) increased chromosome 17 copy number cases (P<0.0001). In HER2+ cases, GRB7 expression was found to correlate significantly with a greater degree of HER2 amplification. The mean±SEM HER2 copy number was 21.14±2.59 in GRB7+ cases, compared with 9.8±1.38 in GRB7- cases (P=0.0001). GRB7 expression correlated significantly with ER negativity (P=0.012) and p53 positivity (P=0.03). GRB7 expression did not correlate with histologic grade, pathologic stage, or PR expression. Our data shows that GRB7 expression in invasive breast cancer correlates with markers of a more aggressive phenotype, including HER2 overexpression, a greater degree of HER2 amplification, ER negativity, and p53 positivity.

Accuracy and Reproducibility of Nuclear/Cytoplasmic Ratio Assessments in Urinary Cytology Specimens.

BACKGROUND: Evaluation of the nuclear to cytoplasmic ratio is commonly used for assessment of the presence of malignancy and for grading and typing of malignant neoplasms. Despite its widespread usage, little information exists regarding the accuracy and reproducibility of non-automated assessment. METHODS: Forty-seven cells obtained from Papanicolaou stained urine cytologies were assessed by quantitative image analysis for nuclear area and cell area. The nuclear/cytoplasmic ratio was calculated. Visual estimates of the N/C ratio were made by six pathologists. Statistical analysis was performed to determine accuracy, precision, and interrater reliability. RESULTS: True N/C ratios varied from 0.02 to 0.81. 27% of cases demonstrated a true N/C ratio between 0.5 and 0.7. Quantitative estimates of N/C ratios were less precise and less accurate at high N/C ratios. The coefficient of variation was 27%. The majority of raters demonstrated decreased accuracy and precision of estimates as N/C ratio increased. Overall classification accuracy was 73%. Accuracy of classification was 53% for cases with a true N/C ratio between 0.4 and 0.8. Absolute interrater agreement was 75%. Chance corrected agreement (kappa) was 0.54. CONCLUSIONS: Visual quantitation of N/C ratio showed only a fair correlation with actual N/C ratio with correlation decreasing with increasing N/C ratio. In the critical range, 0.5-0.7 N/C ratio both interobserver correlation and correlation with true N/C ratio may be insufficiently accurate for precise category assignment as used in the Paris System. Diagn. Cytopathol. 2017;45:107-112. © 2016 Wiley Periodicals, Inc.

Impact of Consensus Conference Review on Diagnostic Disagreements in the Evaluation of Cervical Biopsy Specimens.

OBJECTIVES: To determine the impact of consensus conferences on the frequency of discrepant cases in a surgical pathology practice. METHODS: The percentage of discrepancies in cases reviewed at a weekly consensus conference was calculated for the first and last months of a 13-month period. Both interrater agreement and agreement with the consensus diagnoses were assessed. A total of 309 diagnoses were performed for the first month and 518 for the last month. Both absolute and chance-corrected agreement were calculated for each period. RESULTS: Absolute agreement rate increased from 91.2% in the first month to 98.2% in the final month. Chance-corrected agreement increased from 0.80 in the first month to 0.97 in the final month. CONCLUSIONS: The consensus conference technique appears to be a useful method to reduce intradepartmental diagnostic discrepancies. Both absolute and chance-corrected agreement are improved by using consensus conferences.

An Intraventricular Schwannoma with Associated Hydrocephalus and Ventricular Entrapment: A Case Report.

Intraventricular schwannomas are rare primary brain tumors, with fewer than 25 cases reported in the literature. Here, we present the case of a 20-year-old male patient with a 2 year history of blurry vision and dysesthesia involving his right occiput and upper neck. Imaging demonstrated a homogeneously enhancing mass located within the atrium of the right lateral ventricle with associated right lateral ventricular entrapment. Pathology confirmed the tumor to be an intraventricular schwannoma. Imaging findings, presentation, complications, and treatment options for intraventricular schwannomas are described.