Identification of a Novel TSC2 c.170G>A Missense Variant: A Case Report and Elaboration on the Yield of Targeted Options against Tuberous Sclerosis Complex Manifestations.

BACKGROUND: Tuberous sclerosis complex (TSC) is a rare genetic disease that affects multiple organs and affects the quality of life. Mutations in TSC1 and TSC2 genes are causing dysregulations in the mammalian target of the rapamycin (mTOR) pathway, inducing mostly benign but also malignant tumors, including renal cell carcinoma (RCC). The diagnosis of TSC, based on established clinical and genetic criteria, is essential for the optimal surveillance and management of patients. CASE PRESENTATION: With the current report, we present the case of two sisters who were consequently diagnosed with early-stage chromophobe-like RCC, possibly familial given their young age. The younger sister also had a previous diagnosis of differentiated thyroid carcinoma, for which she had been treated properly. Genetic testing of both revealed the same heterozygous TSC2 variant that is currently regarded as a variant of unknown significance, while both patients did not fulfill the clinical criteria for the diagnosis of TSC. Owing to these data, we opted to manage and surveil both sisters as TSC patients, while we also considered the specific TSC2 variant to be pathogenic - but of low penetrance - based on clinical judgment and functional analyses. Furthermore, we discussed the implementation of mTOR inhibitors for the treatment of TSC complications. CONCLUSION: As novel pathogenic variants of TSC genes are constantly being explored, the identification of TSC variants of unknown significance in combination with absent clinical diagnostic criteria cannot exclude a TSC diagnosis. We support the implementation of clinical judgment in assisting the diagnosis of TSC, as well as the enrollment of patients in clinical trials due to the rarity of the disease.

Genoprotective activity of the Pleurotus eryngii mushrooms following their in vitro and in vivo fermentation by fecal microbiota.

Pleurotus eryngii mushrooms are commercially cultivated and widely consumed due to their organoleptic properties, and the low caloric and high nutritional value. In addition, they contain various biologically active and health-promoting compounds; very recently, their genoprotective effect in Caco-2 cells after their fermentation by the human fecal microbiota was also documented. In the current study, the effect of P. eryngii pre- and post-fermentation supernatants in micronuclei formation was evaluated in human lymphocytes. In addition, the genoprotective properties of increasing concentrations of aqueous extracts from P. eryngii mushrooms (150, 300, 600 mg/kg) against the cyclophosphamide-induced DNA damage were studied in young and elderly female and male mice in bone marrow and whole blood cells. The ability of the highest dose (600 mg/kg) to regulate the main cellular signaling pathways was also evaluated in gut and liver tissues of female animals by quantifying the mRNA expression of NrF2, Nfkß, DNMT1, and IL-22 genes. P. eryngii post-fermentation, but not pre-fermentation, supernatants were able to protect human lymphocytes from the mitomycin C-induced DNA damage in a dose-dependent manner. Similarly, genoprotection was also observed in bone marrow cells of mice treated by gavage with P. eryngii extract. The effect was observed in all the experimental groups of mice (young and elderly, male and female) and was more potent in young female mice. Overexpression of all genes examined was observed in both tissues, mainly among the elderly animals. In conclusion, P. eryngii mushrooms were shown to maintain genome integrity through protecting cells from genotoxic insults. These beneficial effects can be attributed to their antioxidant and immunomodulatory properties, as well as their ability to regulate the cell's epigenetic mechanisms and maintain cell homeostasis.

Classification, histopathology and molecular pathology of thymic epithelial tumors: a review.

Thymic epithelial tumors represent 0.2-1.5% among all malignant neoplasms. They are slow-growing tumors with an overall recurrence rate around 10% and 90% of them are located in the anterior mediastinum. In this review we focused on the classification, histopathology, molecular pathology and prognosis of thymic epithelial tumors, mainly thymoma and thymic carcinoma.

Combined Use of Mammography and FNA Eliminates Pitfalls in the Management of Metaplastic Breast Carcinoma.

BACKGROUND: Due to its heterogeneity, metaplastic breast carcinoma (MBC) poses diagnostic dilemmas, leading to delayed treatment, thereby aggravating the prognosis. Over the years, there has been controversy regarding the role of fine-needle aspiration (FNA) cytology in timely diagnosis. CASE REPORT: A 54-year-old woman presented with a palpable mass in the upper outer quadrant of her right breast with corresponding mammographic findings and FNA was performed. The smears revealed small- and medium-sized cohesive clusters of malignant cells with atypical nuclei. Sporadically, there was a pleomorphic population of notably large mononuclear cells, with disturbance of nuclear/cytoplasmic ratio, and binucleated or multinucleated malignant cells. The presence of chondromyxoid substance with focally embedded cells in a magenta-colored substrate was predominant in the background. These features, along with the corresponding mammographic findings, allowed for high preoperative suspicion of MBC. Surgical resection followed immediately without neoadjuvant chemotherapy; the pathology report led to the definite diagnosis of MBC. DISCUSSION: MBC is a rare clinical entity with unfavorable prognosis, thus early diagnosis is imperative regarding its management. The effectiveness of FNA in the diagnostic algorithm has been questioned, with data from literature being rather contradictory. FNA seems to provide valuable information, which should always be interpreted in correlation with the clinical and mammographic findings. CONCLUSION: High preoperative suspicion of MBC with the combination of mammography and FNA cytology necessitated the surgical excision of the lesion as the principal treatment approach. Although the role of FNA in the diagnosis of MBC is debatable, its combination with clinical presentation and corresponding mammographic findings may prevent the administration of neoadjuvant chemotherapy in patients with ambiguous indications, given the poor response rate of this cancer subtype.