A Matched Molecular and Clinical Analysis of the Epithelioid Haemangioendothelioma Cohort in the Stafford Fox Rare Cancer Program and Contextual Literature Review.

BACKGROUND: Epithelioid haemangioendothelioma (EHE) is an ultra-rare malignant vascular tumour with a prevalence of 1 per 1,000,000. It is typically molecularly characterised by a WWTR1::CAMTA1 gene fusion in approximately 90% of cases, or a YAP1::TFE3 gene fusion in approximately 10% of cases. EHE cases are typically refractory to therapies, and no anticancer agents are reimbursed for EHE in Australia. METHODS: We report a cohort of nine EHE cases with comprehensive histologic and molecular profiling from the Walter and Eliza Hall Institute of Medical Research Stafford Fox Rare Cancer Program (WEHI-SFRCP) collated via nation-wide referral to the Australian Rare Cancer (ARC) Portal. The diagnoses of EHE were confirmed by histopathological and immunohistochemical (IHC) examination. Molecular profiling was performed using the TruSight Oncology 500 assay, the TruSight RNA fusion panel, whole genome sequencing (WGS), or whole exome sequencing (WES). RESULTS: Molecular analysis of RNA, DNA or both was possible in seven of nine cases. The WWTR1::CAMTA1 fusion was identified in five cases. The YAP1::TFE3 fusion was identified in one case, demonstrating unique morphology compared to cases with the more common WWTR1::CAMTA1 fusion. All tumours expressed typical endothelial markers CD31, ERG, and CD34 and were negative for pan-cytokeratin. Cases with a WWTR1::CAMTA1 fusion displayed high expression of CAMTA1 and the single case with a YAP1::TFE3 fusion displayed high expression of TFE3. Survival was highly variable and unrelated to molecular profile. CONCLUSIONS: This cohort of EHE cases provides molecular and histopathological characterisation and matching clinical information that emphasises the molecular patterns and variable clinical outcomes and adds to our knowledge of this ultra-rare cancer. Such information from multiple studies will advance our understanding, potentially improving treatment options.

Yaws Osteoperiostitis Treated with Single-Dose Azithromycin.

AbstractThe etiologic agent of yaws, Treponema pallidum subsp. pertenue, causes a multistage infection transmitted by nonsexual contact with the exudates from active lesions. Bone lesions in the form of osteoperiostitis are common and occur in numerous bones simultaneously in early stages. Although a multinational eradication campaign with mass administration of intramuscular benzathine benzylpenicillin in the 1950s greatly reduced its global incidence, a resurgence of yaws has occurred since around 2000 in western and central Africa and the Pacific Islands. The finding that a single oral dose of azithromycin (30 mg/kg) was as effective as benzathine benzylpenicillin prompted renewed interest by World Health Organization in 2012 toward eradication of this infection by 2020. We previously reported the excellent response to benzathine benzylpenicillin therapy for yaws osteoperiostitis. Herein, we document a confirmed case of yaws with osteoperiostitis successfully treated with single-dose azithromycin and discuss the pathology of yaws periostitis and comment on the implications of this in light of the new campaign toward yaws eradication.

Collagenous ileitis: a study of 13 cases.

Collagenous ileitis (CI), characterized by subepithelial collagen deposition in the terminal ileum, is an uncommon condition. The few cases reported to date have been associated with collagenous colitis (CC) or lymphocytic colitis. Thirteen cases of CI retrieved over a 9-year period were retrospectively studied. There were 7 female and 6 male patients, with an age range of 39 to 72 years (mean, 64 y). Two groups were identified: (1) CI associated with collagenous or lymphocytic disease elsewhere in the gastrointestinal tract and (2) CI as an isolated process. Diarrhea was the presenting symptom in 11 cases. Most patients had no regular medication use. Subepithelial collagen thickness ranged from 15 to 100 µm (mean, 32 µm) and involved 5% to 80% of the subepithelial region of the submitted biopsies. Six cases had >25 intraepithelial lymphocytes (IELs)/100 epithelial cells, and villous blunting was observed in 11 cases. Chronic inflammation of the lamina propria was present in 9 cases, and focal neutrophil infiltration was identified in 3 cases. In biopsies taken from other sites, 7 of 13 colonic biopsies showed CC, 4 of 9 gastric biopsies showed collagenous gastritis, and 2 of 10 duodenal biopsies were abnormal with collagenous sprue (n=1) and partial villous atrophy and increased IELs (n=1) (both celiac disease related). Resolution of the subepithelial collagen deposition was found in the 1 case in which follow-up of terminal ileal biopsies were taken. There was partial or complete resolution of symptoms in 6 of 9 patients for whom follow-up information was available.

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.