PReferentially Expressed Antigen in MElanoma (PRAME):preliminary communication on a translational tool able to early detect Oral Malignant Melanoma (OMM)

: Oral malignant melanoma (OMM) has a prevalence less than 1% of all melanomas and it commonly develops on the oral mucosa following a slow and unspecific transformation of unstable melanocytic lesions, often resulting in a diagnostic delay. The marker PReferentially Expressed Antigen in MElanoma (PRAME) seems to be a valid tool to investigate the biological and histological nature of cutaneous melanocytic lesions, but to date its use to characterize pigmented lesions in the oral cavity is largely unexplored. The aim of this study was to create preliminary knowledge on the PRAME expression in OMM, and to compare its expression respect to other dysplastic pigmented lesions of the oral cavity. Interestingly, PRAME has been demonstrated to be reliable in the clinical conditions investigated in our pilot study; in fact, it has clearly differentiated the cases of Melanoma, which showed diffuse and intense positivity (score 6+/7+) to PRAME, from the other melanocytic nevi, which resulted to be mainly negative to PRAME. This means a better differential diagnosis, a reliable early diagnosis and a proper clinical/surgical management of the oncological lesions. In conclusion, PRAME can be a valid qualitative marker for differential diagnosis, not only in cutaneous melanomas, but also in malignant melanoma of the entire head and neck area

The Tumor-Specific Expression of L1 Retrotransposons Independently Correlates with Time to Relapse in Hormone-Negative Breast Cancer Patients

Background: Long-Interspersed Nuclear Element (L1) retrotransposons are silenced in healthy tissues but unrepressed in cancer. Even if L1 reactivation has been associated with reduced overall survival in breast cancer (BC) patients, a comprehensive correlation with clinicopathological features is still missing. Methods: Using quantitative, reverse-transcription PCR, we assessed L1 mRNA expression in 12 BC cells, 210 BC patients and in 47 normal mammary tissues. L1 expression was then correlated with molecular and clinicopathological data. Results: We identified a tumor-exclusive expression of L1s, absent in normal mammary cells and tissues. A positive correlation between L1 expression and tumor dedifferentiation, lymph-node involvement and increased immune infiltration was detected. Molecular subtyping highlighted an enrichment of L1s in basal-like cells and cancers. By exploring disease-free survival, we identified L1 overexpression as an independent biomarker for patients with a high risk of recurrence in hormone-receptor-negative BCs. Conclusions: Overall, L1 reactivation identified BCs with aggressive features and patients with a worse clinical fate

Upgrading Treatment and Molecular Diagnosis in Endometrial Cancer-Driving New Tools for Endometrial Preservation?

One emerging problem for onco-gynecologists is the incidence of premenopausal patients under 40 years of age diagnosed with stage I Endometrial Cancer (EC) who want to preserve their fertility. Our review aims to define a primary risk assessment that can help fertility experts and onco-gynecologists tailor personalized treatment and fertility-preserving strategies for fertile patients wishing to have children. We confirm that risk factors such as myometrial invasion and The International Federation of Gynecology and Obstetrics (FIGO) staging should be integrated into the novel molecular classification provided by The Cancer Genome Atlas (TCGA). We also corroborate the influence of classical risk factors such as obesity, Polycystic ovarian syndrome (PCOS), and diabetes mellitus to assess fertility outcomes. The fertility preservation options are inadequately discussed with women with a diagnosis of gynecological cancer. A multidisciplinary team of gynecologists, oncologists, and fertility specialists could increase patient satisfaction and improve fertility outcomes. The incidence and death rates of endometrial cancer are rising globally. International guidelines recommend radical hysterectomy and bilateral salpingo-oophorectomy as the standard of care for this cancer; however, fertility-sparing alternatives should be tailored to motivated women of reproductive age, establishing an appropriate cost-benefit balance between childbearing desire and cancer risk. New molecular classifications such as that of TCGA provide a robust supplementary risk assessment tool that can tailor the treatment options to the patient's needs, curtail over- and under-treatment, and contribute to the spread of fertility-preserving strategies

Histological Hallmarks of Malignant Melanoma

The histopathological diagnosis of malignant melanoma remains the gold standard to allow the patient to access the entire process of the diagnostic-therapeutic-assistance path. Despite the continuous search for markers that can assist in the diagnostic process, there are cases that remain complex to diagnose, and the presence of different criteria among dermatopathologists further complicates the issue. This section will focus on the state of the art of dermatopathological diagnostics of melanoma, starting from the morphological bases up to the latest acquisitions of immunohistochemistry for diagnostic purposes, and molecular biology for therapeutic purposes. Furthermore, we will focus on particularly “challenging” MM histotypes and on what are the current guidelines for a correct diagnosis

Turner Syndrome Mosaicism 45,X/46,XY with Genital Ambiguity and Duchenne Muscular Dystrophy:Translational Approach of a Rare Italian Case

Turner syndrome (gonadal dysgenesis with short stature and sterility) is characterized by chromosomal karyotype 45,X in 50% of cases or by mosaicism (45,X/46,XX and 45,X/46,XY) in 30–40% or X structural defects (deletions, long arm isochromosome, ring chromosome). When mosaic Turner syndrome (TS) occurs with a Y chromosome, there may be ambiguous genitalia. Duchenne muscular dystrophy (DMD) is an inherited neuromuscular disease with an X-Linked recessive pattern of inheritance that predominantly affects males, while females are usually asymptomatic. DMD has also been observed in groups of females affected by TS, not homozygous for the mutation. Here, we report a case of an Indian neonate born with ambiguous genitalia diagnosed prenatally by ultrasound who had a karyotype of 45,X/46,XY and who also had Duchenne muscular dystrophy caused by a de novo mutation in the DMD gene. Physical examination was normal without the typical dysmorphic features of TS with the exception of the genitourinary system showing ambiguous genitalia. Gender was assigned as female. At the age of three years, she had increasing difficulty walking, running, jumping and climbing stairs, proximal upper and lower extremity muscle weakness and a positive Gowers’ sign. In addition, the serum creatine kinase (CK) value was over 30X the upper limit of normal. This study shows that DMD can occur in females with TS having 45,X/46,XY mosaicism and that this coexistence should be considered in women affected by TS who start to develop potential typical symptoms such as motor or developmental delay

Histopathological Features of Tissue Alterations Induced by Cryolipolysis on Human Adipose Tissue

Background Adipose tissue cooling, under controlled conditions, induces physical effects on subcutaneous tissue called cryolipolysis (CLL), which has been proposed as a method to reduce noninvasively the amount of adipose tissue. Although CLL has been widely utilized in clinical practice and many favorable results have been reported in clinical studies, very few published studies have dealt with the effects of such therapies on human adipose tissue. Objectives The aim of this study was to evaluate, through histopathological examination, the in vivo effects of CLL on human adipose tissue. Methods Six patients to be submitted to abdominoplasty were enrolled in the study. Samples were taken from the surgical patch, respectively, 15 days (2 pts), 45 days (2 pts), and 60 days (2 pts) after a single standard session of CLL. Control samples were derived from the nontreated areas of the surgical patch. Results Disruption of the adipocytic membranes was evident in all treated areas, with a reduction of cell dissolution in the 60-day samples. Focal dissolution and homogenization of the collagen fibers was evident, resulting in the dissolution of the interlobular fibrous septa. A mild inflammatory response was observed in the 15- and 45-day samples. Neocapillarizzation was observed in the 45- and 60-day samples. Conclusions The lesions demonstrated in adipocytes confirm the theoretical premises of a usefulness of CLL in the treatment of localized adiposis. The alterations in the connective stroma could lead to a structural reorganization and consequently to the in vivo external appearance of the treated areas