Growth of Cutibacterium acnes is common on osteosynthesis material of the shoulder in patients without signs of infection.

Background and purpose - Cutibacterium acnes, formerly known as Propionibacterium acnes, is often isolated from deep tissues of the shoulder. It is recognized as an important causative agent of foreign-material associated infections. However, the incidence and significance of its detection in tissues from patients without clinical evidence for infection is unclear. We assessed the incidence of C. acnes colonization of osteosynthesis material in asymptomatic patients, and evaluated the short-term outcome in relation to the microbiological findings. Patients and methods - We microbiologically analyzed osteosynthesis material of 34 asymptomatic patients after surgery on the clavicle. Material obtained from 19 asymptomatic patients after osteosynthesis of the fibula served as a control group. Patients were clinically followed up for 3-24 months after removal of the osteosynthesis material. Results - Bacteria were recovered from devices in 29 of 34 patients from the clavicle group. 27 of 29 positive samples grew C. acnes. Isolation of C. acnes was more common in male than in female patients. No bacterial growth was observed on foreign material from patients in the fibula group. All patients remained asymptomatic at follow-up. Interpretation - Growth of C. acnes is common on osteosynthesis material of the shoulder, especially in males. Samples were positive irrespective of clinical signs of infection. Therefore, detection of C. acnes in this clinical setting is of questionable clinical significance. The high positivity rate in asymptomatic patients discourages routine sampling of material in cases without clinical evidence for infection.

Minimally invasive autopsy by using postmortem endoluminal and transluminal endoscopy and EUS.

BACKGROUND: Virtual autopsy by using CT imaging has been introduced as an alternative to conventional autopsy and has resulted in an increase in acceptance of autopsy by relatives. Because direct inspection and tissue acquisition is not possible by imaging alone, various endoscopic techniques can be considered of complementary usefulness. OBJECTIVES: We present the first series of sequential endoscopic techniques including natural orifice transluminal access for minimally invasive autopsy. SETTING: University hospital, legal medicine department. SUBJECTS: Twenty deceased subjects. INTERVENTION: Various flexible endoscopic modalities including EUS, with biopsy or EUS-guided FNA, were attempted. This included transluminal intra-abdominal endoscopic exploration with tissue sampling in a few cases. MAIN OUTCOME MEASUREMENTS: Completeness of inspection of the luminal and extraluminal cavity as well as tissue acquisition. RESULTS: Complete upper GI endoscopy was performed in 17 of 20 and EUS in 8 of 8 cases. In addition, transgastric intra-abdominal endoscopy was successfully performed in 5 cases. Adequate histology from biopsy and EUS-guided puncture could be obtained in case of short time intervals post mortem. In 1 case, a rupture of the gastric cardia with bleeding was diagnosed as a significant unexpected finding. New minor pathological findings were revealed on EGD (6/17), GI EUS (3/8), and transgastric inspection (4/5). LIMITATIONS: Limited number of cases for all procedures. CONCLUSION: Minimally invasive autopsy by using multiple endoscopic techniques for imaging and tissue acquisition is feasible. The significant value of this technique, in combination with virtual autopsy compared with classic autopsy, warrants further evaluation.

A 64-year progression of an intradiploic epidermoid of the frontal skull: illustrative case.

BACKGROUND: Epidermoid cyst tumors can arise as intradiploic tumors in the frontal skull bones around the fontanel in childhood but are mostly found at the frontal or frontotemporal base of the brain or in the cerebellopontine angle. Therefore, finding a symptomatic intradiploic lesion in the convexity in late adulthood is uncommon. Intradiploic epidermoids can cause complications as they grow, by eroding and perforating their surroundings, and in cases of destruction of the wall of a pneumatized sinus, they can cause pneumocephalus. OBSERVATIONS: In the present case, a female patient presented with a skull lesion that had grown progressively over 64 years, resulting in spontaneous pneumocephalus. Surgery with subsequent cranioplasty was performed. The histological examination confirmed the presence of an intradiploic epidermoid. LESSONS: This case highlights that complete resection of the lesion with subsequent cranioplasty is recommended before symptoms and reconstructive challenges due to the enormous size of the defect. This case serves as a reminder that intradiploic epidermoids, although uncommon, will expand throughout life and can cause significant complications such as pneumocephalus after decades. Timely surgical interventions after diagnosis are recommended to prevent further complications and to achieve a successful outcome in terms of complete resection and reconstruction.

Spine Metastases in Immunocompromised Mice after Intracardiac Injection of MDA-MB-231-SCP2 Breast Cancer Cells.

Breast cancer cells frequently metastasize to bone, where their interaction with bone remodeling cell types enhances osteolytic bone destruction. Importantly, however, whereas skeletal analyses of xenograft models are usually restricted to hindlimb bones, human skeletal metastases are far more frequent in the spine, where trabecular bone mass is higher compared to femur or tibia. Here, we addressed whether breast cancer cells injected into immunocompromised mice metastasize to the spine and if this process is influenced by the amount of trabecular bone. We also took advantage of mice carrying the Col1a1-Krm2 transgene, which display severe osteoporosis. After crossing this transgene into the immunocompromised NSG background we injected MDA-MB-231-SCP2 breast cancer cells and analyzed their distribution three weeks thereafter. We identified more tumor cells and clusters of different size in spine sections than in femora, which allowed influences on bone remodeling cell types to be analyzed by comparing tumor-free to tumor-burdened areas. Unexpectedly, the Col1a1-Krm2 transgene did not affect spreading and metastatic outgrowth of MDA-MB-231-SCP2 cells, suggesting that bone tumor interactions are more relevant at later stages of metastatic progression.

Laryngeal Manifestation of Nodular Fasciitis: A Case Report and Literature Review.

Nodular fasciitis (NF) are non-neoplastic, fibroblastic lesions, typically located on the trunk and the extremities. The incidence of NF in the head and neck region is 13%-20%. However, a manifestation in the larynx of adult patients is extremely rare. Therefore, the occurrence of NF in this region can lead to diagnostic challenges and a high risk of misdiagnosis as well as potential mishandling when not aware of its possible laryngeal manifestation. Following emergency admission of a 41-year-old woman to the emergency department (ED) due to progressive dyspnea and inspiratory stridor a transnasal flexible laryngeal endoscopic examination revealed a left-lateral, subglottic mass. A subsequently performed CT demonstrated a 2.2 cm x 1.5 cm sized lesion of the subglottic larynx with profound stenosis of the lumen (Myer-Cotton grade III), no extraluminal extension, and no distant metastases. Histopathological processing of a tissue sample obtained by microlaryngoscopy and translaryngeal tracheoscopy revealed a spindle-cell lesion with immunohistochemical and molecular-pathogenic profile of NF. After tumor debulking and steroid infiltration (triamcinolone), a regrowth tendency quickly became apparent, which is why a tracheostomy had to be performed. Laryngectomy was rejected by the patient. After multiple transoral tumor reduction attempts, radiotherapy was performed according to an interdisciplinary tumor board decision to limit regrowth tendency. Subsequently, a substantial reduction of the tumor volume could be seen, although a discreet stenosis of the subglottic tracheal lumen persists in the follow-up. Laryngeal NF poses several challenges due to its rare occurrence in this location. This case report emphasizes the knowledge of this differential diagnosis and also depicts an interdisciplinary therapeutic approach aiming for function-preserving treatment of this benign but potentially relapsing pathology.

Musculoskeletal Soft-Tissue Sarcoma: Quality Assessment of Initial MRI Reports Shows Frequent Deviation from ESSR Guidelines.

Soft-tissue sarcomas (STS) are a rare subtype of soft-tissue mass and are frequently misinterpreted as benign lesions. Magnetic resonance imaging (MRI) is the primary recommended type of diagnostics. To assess the quality of primary radiology reports, we investigated whether recommended MRI report elements were included in compliance with European Society of Musculoskeletal Radiology (ESSR) guidelines. A total of 1107 patients were evaluated retrospectively, and 126 radiological reports on patients with malignant STS were assessed for ESSR quality criteria. One or more required sequences or planes were missing in 67% of the reports. In all 126 cases, the report recognized the mass as anomalous (100%). Sixty-eight percent of the reports mentioned signs of malignancy. The majority of reports (n = 109, 87%) articulated a suspected diagnosis, 32 of which showed a mismatch with the final diagnosis (25%). Thirty-two percent of the reports had a misinterpretation of the masses as benign. Benign misinterpretations were more common in masses smaller than 5 cm (65% vs. 27%). Thirty percent of the reports suggested tissue biopsy and 6% recommended referral to a sarcoma center. MRI reports showed frequent deviations from ESSR guidelines, and protocol guidelines were not routinely met. Deviations from standard protocol and reporting guidelines could put patients at risk for inadequate therapy.

Loss of p16 and high Ki67 labeling index is associated with poor outcome in esophageal carcinoma.

The p16 tumor suppressor is coded by CDKN2A (9p21) and plays an important role during carcinogenesis and tumor progression in numerous tumor entities. The aim of our study was to evaluate the prognostic role of p16 expression and CDKN2A deletion in esophageal cancer (EC). Therefore, we analyzed p16 and KI67 expression by immunohistochemistry and 9p21 deletion by fluorescence in-situ hybridization on a tissue microarray including 398 adenocarcinomas (AC) and 293 squamous cell carcinomas (SCC) with clinical follow up-data. p16 positivity was found in 30.2% of AC and 13.9% of SCC and CDKN2A deletion in 32.1% of AC and 33.5% of SCC. In SCC p16 immunostaining correlated with low tumor stage (P = 0.014). In AC Ki67 positivity was associated with high tumor stage (P = 0.001), presence of lymph node metastasis (P = 0.009), high UICC stage (P = 0.001) and poor grading (P = 0.005). Overall survival (OS) was shorter for patients with high Ki67 labeling index (Ki67LI; P = 0.009) and negative p16 immunostaining (P = 0.026). In both histological tumor types, CDKN2A deletion showed no association with phenotype or outcome. Proportional cox-regression modeling revealed patients' age, tumor stage, lymph node metastasis and Ki67 labeling index as independent prognostic markers in AC. In SCC, only patients' age and tumor stage proved to be independent prognosticators. In summary, our study shows that loss of p16 expression and high Ki67LI is linked to shortened OS in AC. CDKN2A deletion shows no relevant association with tumor phenotype and patient outcome.

Increased Cytoplasmic CD138 Expression Is Associated with Aggressive Characteristics in Prostate Cancer and Is an Independent Predictor for Biochemical Recurrence.

Syndecan-1 (CD138) is a transmembrane proteoglycan expressed in various normal and malignant tissues. It is of interest due to a possible prognostic effect in tumors and its role as a target for the antibody-drug conjugate indatuximab ravtansine. Here, we analyzed 17,747 prostate cancers by immunohistochemistry. Membranous and cytoplasmic CD138 staining was separately recorded. In normal prostate glands, CD138 staining was limited to basal cells. In cancers, membranous CD138 positivity was seen in 19.6% and cytoplasmic CD138 staining in 11.2% of 12,851 interpretable cases. A comparison with clinico-pathological features showed that cytoplasmic CD138 staining was more linked to unfavorable tumor features than membranous staining. Cytoplasmic CD138 immunostaining was associated with high tumor stage (p < 0.0001), high Gleason grade (p < 0.0001), nodal metastases (p < 0.0001), positive surgical margin (p < 0.0001), and biochemical recurrence (p < 0.0001). This also holds true for both V-ets avian erythroblastosis virus E26 oncogene homolog (ERG) fusion positive and ERG fusion negative tumors although the cytoplasmic CD138 expression was markedly more frequent in ERG positive than in ERG negative tumors (p < 0.0001). Comparison with 11 previously analyzed chromosomal deletions identified a conspicuous association between cytoplasmic CD138 expression and 8p deletions (p < 0.0001) suggesting a possible functional interaction of CD138 with one or several 8p genes. Multivariate analysis revealed the cytoplasmic CD138 expression as an independent prognostic parameter in all cancers and in the ERG positive subgroup. In summary, our study indicates the cytoplasmic CD138 expression as a strong and independent predictor of poor prognosis in prostate cancer. Immunohistochemical measurement of CD138 protein may thus-perhaps in combination with other parameters-become clinically useful in the future.

Deletion of 3p13 is a late event linked to progression of TMPRSS2:ERG fusion prostate cancer.

INTRODUCTION: Deletion of 3p13 is one of the most common alterations in prostate cancer preferentially occurring in tumors with TMPRSS2:ERG fusion. The cause for the striking association between 3p13 loss and ERG fusion is unknown. METHODS: Here, we made use of a preexisting heterogeneity prostate cancer tissue microarray including ten tissue spots from ten different tumor areas of 317 cancers to examine the spatial distribution of 3p13 deletions (determined by fluorescence in situ hybridization) in prostate cancer areas with and without ERG overexpression (determined by immunohistochemistry). RESULTS: 3p13 deletions were found in 61 of 299 (20.4%) and ERG positivity in 174 of 317 (54.9%) interpretable cancers. The likelihood of 3p13 loss was twice as high in ERG-positive cancers (39/152, 25.7%) than in ERG-negative cancers (17/124, 13.7%, P=0.010). At least three tissue spots were interpretable for 3p13 deletion status in 279 cancers: only these were used for heterogeneity assessment. Among these tumors, 58 (20.8%) had a 3p13 deletion and 221 (79.2%) were undeleted. The majority of 3p13-deleted cancers showed marked intratumoral heterogeneity. Areas with and without 3p13 loss were found in 50 (18%) of 279 cancers with three or more interpretable tissue spots, while only eight (3%) tumors had a homogeneous 3p13 loss. Comparison with ERG data revealed that ERG fusion usually precede 3p13 deletions. In total, 26 (66.7%) of 39 cancers with ERG and 3p13 alteration had only focal 3p13 deletions in an otherwise ERG-positive background. In contrast, none of the cancers showed a pattern that would be consistent with 3p13 deletion preceding ERG fusion. CONCLUSION: Our study identifies 3p13 deletion as a highly heterogeneous alteration in prostate cancer preferentially developing at rather late stages of progression in TMPRSS2:ERG fusion-positive tumors.

Molecular cancer phenotype in normal prostate tissue.

BACKGROUND: Insufficient sensitivity and specificity of prostate biopsies for cancer detection. OBJECTIVES: Based on evidence from our microarray analyses, we hypothesized that considerable molecular changes precede morphologically detectable malignant transformation of prostate epithelial tissues. The identification of such changes could lead to novel strategies in the clinical management of prostate cancer. DESIGN, SETTING, AND PARTICIPANTS: Histologically normal, fresh prostate tissue from prostate cancer patients, healthy donors, and cancer suspect patients with continuous negative biopsies were analyzed. MEASUREMENTS: To identify molecular changes between 29 tumor-free prostate tissues from healthy donors and 27 patients with proven prostate cancer, we performed a global microarray screening. Based on this screening as well as literature data, we selected a subset of 29 genes for validation by arrayed real-time reverse transcription-polymerase chain reaction (RT-PCR) using histologically tumor-free biopsy samples from 114 patients representing three prostate cancer risk groups. RESULTS AND LIMITATIONS: We identified five genes (FOS, EGR1, MYC, TFRC, and FOLH1), which displayed significant differential expression between morphologically normal prostate tissues from men of each of the three risk groups. These results were independent from age, prostate-specific antigen (PSA), frequency and timing of previous prostate biopsies, tissue composition, tumor stage, and tumor grade. In univariate logistic regression analyses, the transcript levels of these genes were found to be highly indicative for the presence or absence of cancer in the entire prostate. The study was designed as a proof of principle. The clinical relevance of our results has to be evaluated in a larger clinical setting. CONCLUSIONS: Our results suggest a measurable molecular cancer phenotype in histologically normal prostate tissue indicating the presence of prostate cancer elsewhere in the organ.

Marked gene transcript level alterations occur early during radical prostatectomy.

OBJECTIVES: Gene expression analyses have become an important approach to understand the biology of cancer. However, transcript level patterns and RNA quality could rapidly change in response to ischemic and mechanical stress. Studies have shown that this occurs both perioperatively and after surgical removal of organs. METHODS: To better understand the relative importance of perioperative and postoperative gene expression changes, we performed quantitative reverse transcription-polymerase chain reactions on the transcripts of 91 cancer-related genes from normal and cancerous prostate tissues from 10 patients at eight different time points during surgical manipulation and after removal of the prostate. RESULTS: The mRNA levels of 8 (EGR1, p21, KRT17, PIM1, S100P, TNFRSF, WFDC2, and TRIM29) of 91 genes changed significantly with time of surgery in normal and tumor tissue. Remarkably, all eight genes were up-regulated, a reaction that was most prominent during the early intraoperative period. Additional changes occurred but were much less prominent during the first postoperative hour. CONCLUSIONS: Our results substantially challenge the utility of immediate postoperative tissue sampling. At least for prostate cancer, the data suggest that preoperative tissue collection by core biopsies is optimal for studying molecular changes in normal and neoplastic prostate tissues.