Histological and clinical analysis of knee cyclops lesions.

BACKGROUND AND AIM: Cyclops Syndrome, first described by Jackson and Schaefer in 1990, is known as a complication of anterior cruciate ligament reconstruction (ACLR). However further researches have demonstrated that cyclops can be present even without symptoms and/or in absence of ACLR, simply configuring itself as a lesion in patients with rupture of the native ligament. METHODS: This is a retrospective cohort study in which we report our experience of 13 cyclops lesions found between 126 patients during a primary arthroscopic ACLR. Preoperative examination with tests of joint stability and range of movement measurement was performed and recorded. Accurate joint examination was performed during arthroscopy and the cyclops lesions found were removed and analyzed with haematoxylin-eosin coloration. Post-operative clinical examination was performed until 6 months of follow-up. RESULTS: Histological analysis showed proliferation of dense fibroelastic polypoid nodules with a macroscopically histological aspects of a "blue eye", hence the name Cyclops. At 6 months of follow-up after surgery, none of the patients reported pain at terminal extension or instability and they were all able to resume their previous activities. CONCLUSIONS: Our study confirmed that surgical reconstruction of the ACL is not the only condition in which the Cyclops Syndrome develops; in fact our histological analysis indicate that the Cyclops lesions develop like a reactive fibroproliferative process following the rupture of the native ACL fibers, as scar reaction to the trauma: for this reason an accurate arthroscopic detection of these Cyclops lesions is crucial during primary ACL reconstruction in order to obtain the best surgical outcomes.

Intra-patient Heterogeneity of BRAF and NRAS Molecular Alterations in Primary Melanoma and Metastases.

Mutations in MAPK signalling genes are driver events in melanoma, and have therapeutic relevance in the metastatic and adjuvant setting. This study evaluated the intra-patient heterogeneity of BRAF, NRAS and c-KIT mutational status between 30 primary melanomas and 39 related metastases, using molecular analysis and immunohistochemistry. BRAF mutations were identified in 46.7% of primary melanomas and 48.7% of metastases and NRAS mutations in 20% and 25.6%, respectively. Intra-patient heterogeneity was detected in 13.3% of patients for both BRAF and NRAS genes and was not associated with clinico-pathological characteristics of melanomas or metastases. High consistency was observed between immunostaining and molecular methods for BRAFV600E (k = 0.90; p < 0.001) and NRASQ61R (k = 0.87; p < 0.001). These findings demonstrate a relevant intra-patient heterogeneity between primary and metastatic lesions that is independent of clinical variables and methodological approach.

Dermoscopic similarity is an independent predictor of BRAF mutational concordance in multiple melanomas.

BACKGROUND: The association of clinical and dermoscopic features with BRAF mutational status has been poorly analysed in multiple primary melanomas (MPM). OBJECTIVE: To investigate whether concordance of BRAF mutational status is associated with dermoscopic similarity in multiple melanomas of the same patient. METHODS: Dermoscopic images and corresponding tissue sections of 124 melanomas from 62 patients with MPM were selected at four Italian Dermatology Departments. Similarity of dermoscopic appearance between multiple melanomas was evaluated according to the presence of the same prevalent dermoscopic feature. The BRAFV600 mutational status was analysed with allele-specific TaqManTM assays or pyrosequencing. Spearman's correlation and univariate and multivariate regression analysis were used for statistical analysis. RESULTS: A similar dermoscopic appearance was identified in 38.7% (24/62) of patients with MPM and was correlated with older age at first diagnosis (rho: 0.26; P: 0.042) and occurrence on sun-damaged skin (rho: 0.27; P: 0.037). The BRAFV600 mutation was detected in 39.5% (49/124) of the tumors and a concordant BRAF mutational status between melanomas in 33/62 (53.2%) MPM patients. Dermoscopically similar melanomas showed 5.7-fold higher odds to be concordant for BRAF mutational status compared to dissimilar lesions (OR: 5.7; 95% CI 1.7-19.5; P: 0.005). CONCLUSION: Dermoscopic similarity of multiple melanomas represents an independent clinical predictor of a concordant BRAF mutational status in MPM patients.

Different operators and histologic techniques in the assessment of germinal center-like structures in primary Sjögren's syndrome minor salivary glands.

OBJECTIVE: A standardization of minor salivary gland (MSG) histopathology in primary Sjögren's syndrome (pSS) has been recently proposed. Although there is strong agreement that germinal center (GC)-like structures should be routinely identified, due to their prognostic value, a consensus regarding the best protocol is still lacking. Aim of this study was to compare the performance of different histological techniques and operators to identify GC-like structures in pSS MSGs. MSG biopsies from 50 pSS patients were studied. METHODS: Three blinded operators (one pathologist and two rheumatologists with different years of experience in pSS MSG assessment) assessed 50 MSGs of which one slide was stained with haematoxylin and eosin (H&E) and consecutive slides were processed to investigate CD3/CD20, CD21 and Bcl-6 expression. RESULTS: By assessing 225 foci, the best agreement was between H&E-stained sections evaluated by the rheumatologist with more years of experience in pSS MSG assessment and CD3/CD20 segregation. In the foci with CD21 positivity, the agreement further increased. Bcl-6- foci could display a GC, detected with other staining, but not vice versa. CONCLUSION: GC assessment on H&E-stained sections should be performed with caution, being operator-dependent. The combination of H&E with CD3/CD20 and CD21 staining should be recommended as it is reliable, feasible, able to overcome the bias of operator experience and easily transferrable into routine practice.

Peri-prostatovesicular smooth muscle tumors of undetermined malignant potential: a case report.

INTRODUCTION: Smooth muscle tumors of undetermined malignant potential (STUMPs) are atypical smooth muscle tumors, most of which derived from uterine tissue. STUMPs of male genitourinary system and of the male pelvic organs are uncommon. CASE DESCRIPTION: In this report, we describe the first case of peri-prostatovesicular STUMP that was treated with laparoscopic excision, in a young asymptomatic man. CONCLUSIONS: In most cases, the definitive diagnosis can be made only after surgical resection and accurate histological examination. The usefulness of adjuvant chemotherapy remains unclear, and a standardized follow-up protocol has not been described.

Which is the correlation between carcinoid tumor and Laparoscopic Sleeve Gastrectomy? A case series and literature review.

INTRODUCTION: Gastric Carcinoid Tumors (GCT) are very rare in general population, but some studies evidenced a higher incidence among bariatric surgery patients. Laparoscopic Sleeve Gastrectomy (LSG) is a widely accepted procedure for the surgical treatment of morbid obesity. LSG acts both in reducing food intake and interfering with hormonal balance in the gut-brain axis. In these patients, incidental GCT diagnosis can occur both during pre-bariatric surgery investigation and during post-operative follow-up. METHODS: We retrospectively analyzed the database of obesity patients submitted to LSG in two different centers to find out incidence of GCT in patients treated by surgery from May 2013 to March 2018. RESULTS: From the 560 obese consecutive patients underwent LSG, we recorded two cases of patients with GCT (0.36%): the case 1 was a patient who had a pre-operative diagnosis of GTC receiving a curative LSG which totally included the carcinoid in the resected portion; the case 2 was a patient that received a curative endoscopic resection 42 months after LSG. DISCUSSION: the predisposing factors that can correlate GCT with obesity and LSG and in particular the hormonal changes have been discussed. We illustrated our experience about the management of these tumors in obese patients. CONCLUSION: there are neither certain data which evidence a correlation between obesity and GCT, nor data to support the hypothesis of a higher incidence of GCT after bariatric surgery. Based on our experience in obese patients the finding of GCT in the pre-operatory phase is not an absolute contraindication for bariatric surgery.

Heterogeneity of BRAF, NRAS, and TERT Promoter Mutational Status in Multiple Melanomas and Association with MC1R Genotype: Findings from Molecular and Immunohistochemical Analysis.

Data on somatic heterogeneity and germline-somatic interaction in multiple primary melanoma (MPM) patients are limited. We investigated the mutational status of BRAF, NRAS, and TERT promoter genes in 97 melanomas of 44 MPM patients and compared molecular and immunohistochemical findings. We further evaluated the association of somatic alterations with the germline MC1R genotype. Mutations in BRAF gene were identified in 41.2% (40/97) of melanomas, in NRAS in 2.1% (2/97), and in TERT promoter in 19.6% (19/97). Distribution of BRAF mutations did not differ across multiple melanomas (P = 0.85), whereas TERT promoter changes decreased from first to subsequent melanomas (P = 0.04). Intrapatient discrepancy of BRAF mutations among multiple tumors was detected in 14 of 44 MPM patients (32%) and of BRAF/NRAS/TERT promoter genes in 20 of 44 (45%). We observed a high rate of agreement between allele-specific TaqMan assay and immunohistochemistry in BRAFV600E detection (κ = 0.83, P < 0.01) with 86 of 97 melanomas (88.7%) presenting similar BRAF status. Germline MC1R variants were identified in 81.4% (35/43) of MPM patients with no association of MC1R genotype with somatic mutations or with intrapatient concordance of somatic mutational profile. Our results support the genetic diversity of multiple melanomas and show that somatic heterogeneity is not influenced by inherited MC1R variants. Immunohistochemistry may be useful as an initial screening test.

Stemness Marker Detection in the Periphery of Glioblastoma and Ability of Glioblastoma to Generate Glioma Stem Cells: Clinical Correlations.

BACKGROUND: Recent studies suggested glioma stem cells (GSCs) are key contributors to therapeutic resistance of glioblastoma multiforme (GBM) and are responsible for GBM recurrence. METHODS: We characterized the phenotype of cancer cells in the core and periphery of 20 GBM tumors, correlating clinical outcome to the ability to form GSCs and distinguishing survival based on Ki-67 staining. RESULTS: Similar levels of methylguanine-deoxyribonucleic acid methyltransferase were found in the core and periphery of GBM tumors, whereas Ki-67 was reduced in the periphery. Similar levels of stemness markers in the periphery and in the core of all GBM cultures were found. Only cells expressing >30% SOX2 levels were able to produce neurospheres. Immunophenotypic analysis showed higher levels of stemness markers in GSC cultures than in all GBM primary cultures. GSC in vitro production and coexpression of Ki-67 >5% negatively correlated with outcome. CONCLUSIONS: Not all GBM cultures can generate GSCs, and this capacity is linked to >30% SOX2 levels. The ability to form spheres negatively correlated to survival, and the detection of >5% Ki-67 levels may be useful to identify patients at risk of disease progression. The presence of GSC-/SOX-2-/Ki-67- cells may be regarded as a new prognostic factor. The presence of stemness markers and methylguanine-deoxyribonucleic acid methyltransferase in the periphery of GBM tumors may be the reason for treatment failure and recurrence. Development of stem cell-targeted therapies and elaboration of more aggressive treatments represent an opportunity to eliminate the GBM source and the nidus of recurrence.