Sarcomas of the Larynx: One Institution's Experience and Treatment Protocol Analyses.

Soft tissue sarcomas in the head and neck are rare malignancies. They occur in this area in less than 1% of all malignant tumors. Some authors have described the development of sarcoma from the mesenchymal tissue in the larynx. The histological diagnosis of a sarcoma depends on the immunohistochemical investigation. In particularly difficult diagnoses, electron microscopy has to be used. The treatment recommendation depends on the histological type of sarcoma. We analysed and summarized data on the diagnostic criteria and therapy for sarcoma of the larynx presented in the literature. We present three new cases of laryngeal sarcoma and describe the analyses of the published diagnostic and treatment schedules of laryngeal sarcomas. We developed a treatment protocol recommendation for laryngeal sarcoma based on an analysis of literature data and case reports. This recommendation is based on histological type, staging, grading, size, and survival data.

Primary renal well-differentiated neuroendocrine tumour (carcinoid): next-generation sequencing study of 11 cases.

AIMS: Primary renal well-differentiated neuroendocrine tumour (NET) (hereafter referred to as renal NET) is rare, with ~100 cases having been reported in the literature. There are also limited data on the molecular-genetic background of primary renal NETs. METHODS AND RESULTS: We analysed 11 renal NETs by using next-generation sequencing (NGS) to identify characteristic genetic aberrations. All tumours were positive for synaptophysin, and also expressed insulinoma-associated protein 1 (10/11), chromogranin-A (8/11), and CD56 (3/11). Cytoplasmic positivity of CD99 was present in eight of 11 cases, and strong nuclear expression of α-thalassaemia/mental retardation syndrome X-linked (ATRX) was retained in all 11 cases. Molecular-genetic analysis of aberration of VHL gave negative results in all cases. Loss of heterozygosity on chromosome 3p21 was found in three of nine analysable cases. NGS was successful in nine cases, showing a total of 56 variants being left after the updated filtering process, representing an average of five variants per sample. All analysable cases were negative for ATRX and DAXX (death-domain associated protein X) mutations. The most frequently mutated genes were CDH1 and TET2, with three mutations in two cases. Mutations in AKT3, ROS1, PIK3R2, BCR and MYC were found in two cases. The remaining 41 genes were found to be mutated only in individual cases. In four cases, the mutations affected a subset of genes related to angiogenesis. CONCLUSIONS: Overall, the mutation profile of primary renal NETs is variable, and none of the studied genes or affected pathways seems to be specific for renal NET.

Sebaceous adenoma arising in mature cystic teratoma of the ovary. Case report.

We report the case of a 44-year-old female with sebaceous adenoma arising in mature cystic teratoma of the ovary. The patient had a tumor in the left ovary; 125 x 90 x 70 mm. Microscopically, the tumor consisted of structures typical of dermoid cysts. However, large areas of sebaceous proliferation were found. These areas were comprised of sebaceous nodules with features similar to a sebaceous adenoma of the skin. Immunohistochemically, the tumor showed "wild-type" expression of p53 and low proliferative activity (Ki-67 index < 5%). To verify the possibility of Muir-Torre syndrome we performed immunohistochemical examination of DNA mismatch repair proteins expression. However, all four proteins examined (MSH2, MSH6, MLH1, PMS2) were positive. Sebaceous adenoma arising in mature teratoma of the ovary is rare. To the best of our knowledge, only six cases have been reported in the literature to date.

Prognostic Importance of Cell Cycle Regulators Cyclin D1 (CCND1) and Cyclin-Dependent Kinase Inhibitor 1B (CDKN1B/p27) in Sporadic Gastric Cancers.

Background. Gastric cancer is known for a notable variety in the course of the disease. Clinical factors, such as tumor stage, grade, and localization, are key in patient survival. It is expected that molecular factors such as somatic mutations and gene amplifications are also underlying tumor biological behavior and may serve as factors for prognosis estimation. Aim. The purpose of this study was to examine gene amplifications from a panel of genes to uncover potential prognostic marker candidates. Methods. A panel of gene amplifications including 71 genes was tested by multiplex ligation-dependent probe amplification (MLPA) technique in 76 gastric cancer samples from a Caucasian population. The correlation of gene amplification status with patient survival was determined by the Kaplan-Meier method. Results. The amplification of two cell cycle regulators, CCND1 and CDKN1B, was identified to have a negative prognostic role. The medial survival of patients with gastric cancer displaying amplification compared to patients without amplification was 192 versus 725 days for CCND1 (P = 0.0012) and 165 versus 611 days for CDKN1B (P = 0.0098). Conclusion. Gene amplifications of CCND1 and CDKN1B are potential candidates to serve as prognostic markers for the stratification of patients based on the estimate of survival in the management of gastric cancer patients.

Longitudinal molecular characterization of endoscopic specimens from colorectal lesions.

AIM: To compare molecular profiles of proximal colon, distal colon and rectum in large adenomas, early and late carcinomas. To assess feasibility of testing directed at molecular markers from this study in routine clinical practice. METHODS: A prospective 3-year study has resulted in the acquisition of samples from 159 large adenomas and 138 carcinomas along with associated clinical parameters including localization, grade and histological type for adenomas and localization and stage for carcinomas. A complex molecular phenotyping has been performed using multiplex ligation-dependent probe amplification technique for the evaluation of CpG-island methylator phenotype (CIMP), PCR fragment analysis for detection of microsatellite instability and denaturing capillary electrophoresis for sensitive detection of somatic mutations in KRAS, BRAF, TP53 and APC genes. RESULTS: Molecular types according to previously introduced Jass classification have been evaluated for large adenomas and early and late carcinomas. An increase in CIMP+ type, eventually accompanied with KRAS mutations, was notable between large adenomas and early carcinomas. As expected, the longitudinal observations revealed a correlation of the CIMP+/BRAF+ type with proximal location. CONCLUSION: Prospective molecular classification of tissue specimens is feasible in routine endoscopy practice. Increased frequency of some molecular types corresponds to the developmental stages of colorectal tumors. As expected, a clear distinction is notable for tumors located in proximal colon supposedly arising from the serrated (methylation) pathway.

Early Diagnosis of Cutaneous Mucormycosis Due to Lichtheimia corymbifera After a Traffic Accident.

A case report of cutaneous mucormycosis and obstacles to early diagnosis is presented. A 38-year-old male was involved in a car accident that led to amputation of both lower limbs. Subsequently, he developed fungal wound infection of the left lower limb stump. The infection was detected very early, although the diagnosis was difficult because only a small area was affected and histopathological examination was initially negative. The infection was proven by microscopy, culture and histopathology. The isolate was identified by sequencing of the rDNA ITS region gene (internal transcribed spacer region of ribosomal DNA) as Lichtheimia corymbifera. Liposomal amphotericin B and surgery were successful in management of the disease.

Improved specimen adequacy using jumbo biopsy forceps in patients with Barrett's esophagus.

AIM: To assess the sampling quality of four different forceps (three large capacity and one jumbo) in patients with Barrett's esophagus. METHODS: This was a prospective, single-blind study. A total of 37 patients with Barrett's esophagus were enrolled. Targeted or random biopsies with all four forceps were obtained from each patient using a diagnostic endoscope during a single endoscopy. The following forceps were tested: A: FB-220K disposable large capacity; B: BI01-D3-23 reusable large capacity; C: GBF-02-23-180 disposable large capacity; and jumbo: disposable Radial Jaw 4 jumbo. The primary outcome measurement was specimen adequacy, defined as a well-oriented biopsy sample 2 mm or greater with the presence of muscularis mucosa. RESULTS: A total of 436 biopsy samples were analyzed. We found a significantly higher proportion of adequate biopsy samples with jumbo forceps (71%) (P < 0.001 vs forceps A: 26%, forceps B: 17%, and forceps C: 18%). Biopsies with jumbo forceps had the largest diameter (median 2.4 mm) (P < 0.001 vs forceps A: 2 mm, forceps B: 1.6 mm, and forceps C: 2mm). There was a trend for higher diagnostic yield per biopsy with jumbo forceps (forceps A: 0.20, forceps B: 0.22, forceps C: 0.27, and jumbo: 0.28). No complications related to specimen sampling were observed with any of the four tested forceps. CONCLUSION: Jumbo biopsy forceps, when used with a diagnostic endoscope, provide more adequate specimens as compared to large-capacity forceps in patients with Barrett's esophagus.