The Importance of Metabolic Factors in Endometrial Cancer: Evaluating the Utility of the Triglyceride-to-Glycemia Index and Triglyceride-to-High-Density Lipoprotein Ratio As Biomarkers.

Introduction Endometrial cancer (EC) is the most common gynecological malignancy in developed countries worldwide. Its incidence is rising, making it a significant public health concern. The relationship between lipids, hyperglycemia, and anthropometric risk factors in the development of EC has gained increasing attention in recent years. Understanding the role of dyslipidemia as a part of metabolic syndrome is crucial for developing effective prevention and treatment strategies for EC. We investigate the association between dyslipidemia, hyperglycemia, and EC. This study aims to elucidate the potential contribution of altered lipid profiles and chronic hyperglycemia to endometrial carcinogenesis. By analyzing patients with benign and malignant endometrial pathologies, we seek to identify novel biomarkers and unravel the underlying mechanisms by which these metabolic factors influence the risk of developing EC. Material and methods Our retrospective unicentric study included 390 patients (192 diagnosed with EC and 198 with endometrial hyperplasia), in which we compared the clinical and biochemical characteristics, with a particular focus on lipid profiles and glycemic indices sampled 24-48 hours before surgery. The data obtained from the medical records were analyzed using statistical methods to compare selected metabolic factors between EC and endometrial hyperplasia. Results Our analysis revealed statistically significant differences in metabolic health and lipid profiles between patients diagnosed with EC and those with endometrial hyperplasia. The EC group exhibits trends towards higher levels of triglycerides (TG) and glycated hemoglobin, alongside a higher BMI. Notably, high-density lipoprotein cholesterol levels were lower in the EC group. Conclusion Although the triglycerides-to-fasting blood glucose index and the triglycerides-to-high-density lipoprotein cholesterol ratio did not demonstrate sufficient discriminatory power for predicting myometrial invasion depth in this study, further exploration of cost-effective emerging biomarkers warrants investigation in future studies.

Metabolic Syndrome and Survival Outcomes in Endometrial Cancer.

Menopause, through attributable estrogen level decline and the corresponding increase in circulating androgens, significantly elevates a woman's risk for cardiometabolic diseases, including metabolic syndrome (MetS), type 2 diabetes, and cardiovascular disease. Metabolic syndrome itself is a cluster of interconnected risk factors, and among them, central obesity is a well-established factor for the development of endometrial cancer (EC), the most common gynecologic malignancy. This research investigates the impact of metabolic syndrome on survival rates among patients with endometrial cancer. The goal is to assess whether having metabolic syndrome or its individual components influences disease-free survival (DFS), overall survival (OS), cancer-specific survival, and recurrence rates. Understanding this link is crucial for determining risk levels and could help tailor treatment approaches for better long-term outcomes in endometrial cancer care.

Arteriovenous Fistula: The Case of a Rare Complication after Minimal Percutaneous Nephrostomy and Brief Review.

Percutaneous renal surgery, although much less invasive than other procedures, is subject to several complications, which can occur at any time during the course of treatment, starting from the performance of the minimal nephrostomy procedure. We present an extremely rare vascular complication of percutaneous nephrostomy represented by arteriovenous fistula that occurred in a 24-year-old patient known to have right ureteropelvic junction obstruction operated with the absence of double-J catheter permeability and grade II-III hydronephrosis for which minimal percutaneous nephrostomy was urgently fitted. The arteriovenous fistula was resolved by supraselective artery embolization.

The Role of Obesity in the Etiology and Carcinogenesis of Endometrial Cancer.

Endometrial cancer, the most common gynecological malignancy, presents a complex public health challenge. While its incidence rises alongside the obesity epidemic, a well-established risk factor for endometrial cancer development, the impact of obesity on survival after diagnosis remains unclear. This review aims to explore the complex relationship between obesity and endometrial cancer's development and survival rates, examining evidence from both epidemiological and clinical studies. It also aims to explore the proposed biological mechanisms by which excess adipose tissue promotes carcinogenesis and contributes to endometrial cancer progression and its negative effects on treatment outcomes. Furthermore, we analyzed the impact of body mass index, inflammation, hormonal imbalances, and their potential effects on endometrial cancer survival rates.

Clinical Correlations between Serological Markers and Endometrial Cancer.

Background: Endometrial cancer is associated with changes in blood cell counts and with high levels of inflammatory markers, thus reflecting the tumor's impact on various biological processes and suggesting their potential as biomarkers for endometrial cancer diagnosis, prognosis, and treatment response. The neutrophil-to-lymphocyte ratio, platelet-to-lymphocyte ratio, and monocyte-to-lymphocyte ratio in peripheral blood sampled preoperatively from patients have been reported to be independently associated with the prognosis of different types of malignancies. Objectives: This study aimed to compare several blood markers-red blood cells, white blood cells, platelet parameters, neutrophil-to-lymphocyte ratio, platelet-to-lymphocyte ratio, monocyte-to-lymphocyte ratio, C-reactive protein, and fibrinogen-in patients with benign or malignant endometrial tumors. Material and methods: Our retrospective study included 670 patients (192 diagnosed with endometrial cancer and 478 with endometrial hyperplasia), and we compared the serological parameters discussed above with those sampled the day before surgery. Results: Analysis of complete blood count indices revealed no significant differences in red blood cell or total white blood cell parameters between the endometrial cancer group and the endometrial hyperplasia group. However, a distinct pattern emerged in the white blood cell differential. The endometrial cancer group showed a statistically significant decrease in lymphocyte count compared with the endometrial hyperplasia group. In contrast, the endometrial cancer group showed significantly higher mean platelet counts and increased mean platelet volume compared with controls. Furthermore, the endometrial cancer group demonstrated a marked inflammatory response, as evidenced by significantly elevated levels of C-reactive protein, fibrinogen, neutrophil-to-lymphocyte ratio, platelet-to-lymphocyte ratio, and monocyte-to-lymphocyte ratio compared with the endometrial hyperplasia group. Conclusions: The current research revealed statistically significant differences in multiple serological biomarkers between the two groups. These findings support the initial hypothesis regarding the potential utility of these biomarkers in endometrial cancer diagnosis, prognosis, and treatment response, highlighting the existence of biomarkers affordable for analysis under any health system, regardless of the country's level of development.

Unveiling the Therapeutic Horizon: HPV Vaccines and Their Impact on Cutaneous Diseases-A Comprehensive Review.

Human papillomavirus (HPV) encompasses a diverse array of viruses, comprising approximately 200 serotypes that affect humans. While the majority of HPV strains are associated with benign skin or mucous membrane growths, a subset is implicated in severe health conditions, such as cervical, anal, vulvar, and vaginal cancers. Despite the established effectiveness of HPV vaccines in preventing cervical and anal carcinomas in particular, their therapeutic potential in addressing cutaneous diseases linked to diverse HPV strains remains an intriguing area of investigation. This narrative review critically examines the existing literature to assess the viability of HPV immunization as a therapeutic intervention for prevalent cutaneous conditions. These include genital and extragenital cutaneous warts, epidermodysplasia verruciformis, and keratinocyte carcinomas. The findings suggest a promising dual role for HPV vaccines in preventing and treating dermatologic conditions while emphasizing future research directions, including the immunization perspective against ß-HPVs. Moreover, the presence of conflicting study outcomes underscores the imperative for larger-scale, randomized trials with well-matched control groups to validate the efficacy of HPV immunization in the dermatologic context. This review contributes valuable insights into the evolving landscape of HPV-vaccine applications in the field of dermatology.

The Intersection of Dermatological Dilemmas and Endocrinological Complexities: Understanding Necrobiosis Lipoidica-A Comprehensive Review.

BACKGROUND: Necrobiosis lipoidica (NL) is a rare granulomatous skin disorder with a predilection for females, often associated with diabetes mellitus (DM). This paper aims to comprehensively review the literature on NL, focusing on its association with DM, thyroid disorders, and the metabolic syndrome. METHODS: A systematic search was conducted in English-language literature from inception to October 2023, utilizing PubMed. We identified 530 studies and selected 19 based on clinical significance, statistical support, and relevance to the paper's goals. RESULTS: The coexistence of NL and DM is prevalent, with rates ranging from 11% to 65.71%. NL may precede DM diagnosis and a correlation between NL and increased daily insulin requirements has been observed in such patients. NL is suggested as a potential prognostic marker for DM complications; however, recent studies question this association, highlighting the need for further research. Studies in the context of NL and Thyroid Disease indicate a correlation, especially with autoimmune thyroiditis. Regarding NL and Metabolic Syndrome, the prevalence of metabolic syndrome among NL patients is notably higher than in the general population. Additionally, DM patients with ulcerated NL commonly exhibit hypertension or obesity, raising questions about the potential influence of hypertension and obesity on NL ulcerations. CONCLUSION: Additional research is required to untangle the complex connections between NL and various comorbidities.

Thyroid Disorders in Systemic Sclerosis: A Comprehensive Review.

Systemic sclerosis, also referred to as scleroderma, is a chronic autoimmune disease that affects both internal organs and the skin. Systemic sclerosis predominantly affects female patients and can coexist with other disorders, including those affecting the thyroid gland. Common symptoms such as fatigue and weight changes can be attributed to either systemic sclerosis or thyroid disease. In this comprehensive review, an extensive analysis is conducted using research from 2002 to 2022, sourced from PubMed. The main focus of this exploration is to understand the intricate relationship between thyroid disorders and systemic sclerosis. We obtained these results by analyzing a number of 32285 patients included in 21 original studies. The existing evidence suggests that there is a higher incidence of elevated TSH levels and hypothyroidism in patients with systemic sclerosis, particularly in females, compared to the general population. This remains true even when comparing patients from iodine-deficient regions. Additionally, there is an increased occurrence of hyperthyroidism in the context of systemic sclerosis, which negatively impacts the prognosis of these patients. Furthermore, thyroid antibodies, predominantly anti-thyroid peroxidase (anti-TPO) antibodies, and autoimmune disorders are more commonly observed in individuals with systemic sclerosis. Although thyroid nodules are not specifically linked to the disease, when considering thyroid volume, it is observed that the thyroid gland in systemic sclerosis patients has a decreased volume, possibly due to fibrosis. Conversely, other studies have revealed that patients without autoimmune thyroid diseases (AITDs) are more likely to have a history of digital ulcers, pulmonary fibrosis detected by computed tomography scan, and a requirement for immunosuppressive medication. The majority of the studies did not establish a connection between thyroid disease in these patients and the occurrence of the limited or diffuse forms of systemic sclerosis, as well as the presence of digital ulcers, calcinosis, pulmonary arterial hypertension, scleroderma renal crisis, Raynaud phenomenon, and various other clinical manifestations.

Vulvar Lichen Sclerosus: Navigating Sex Hormone Dynamics and Pioneering Personalized Treatment Paradigm.

Vulvar lichen sclerosus (VLS) is a frequently overlooked inflammatory disorder affecting the skin and mucous membranes of the vulva. With a propensity for atrophy, severe scarring, functional impairment, and malignant evolution, VLS is a disease that recurs frequently; early diagnosis, rapid treatment, and ongoing patient follow-up are essential. Potent topical corticosteroids (TCSs) are now widely recognized as the most effective treatment for achieving remission in VLS, but considering the potential complications of long-term treatment with potent TCSs, understanding the evolution of VLS during puberty becomes particularly crucial in determining the necessity for aggressive or more conservative therapeutic interventions. Emerging treatments, including PRP (platelet-rich plasma), stem cell therapy, and energy-based lasers like fractional CO2 and Nd-YAG, are being investigated to identify more effective VLS treatments than ultrapotent topical corticosteroids. However, more research is needed to assess the efficacy and safety of these new medicines. Topical clobetasol 0.05% ointment daily for 4-12 weeks is the gold standard for treating VLS. This article is a narrative review of the English-language medical literature from 2017 to November 2023, following three main sections concerning VLS: studies of the evolution amid pubertal hormonal changes; studies of the outcomes of personalized conventional therapies; and studies addressing the spectrum of innovative modalities for VLS.

Conundrum for Psoriasis and Thyroid Involvement.

Strategies concerning thyroid anomalies in patients confirmed with psoriasis, either on clinical level or molecular levels, and their genetic findings remain an open issue. Identification of the exact subgroup of individuals that are candidates to endocrine assessments is also controversial. Our purpose in this work was to overview clinical and pathogenic data concerning psoriasis and thyroid comorbidities from a dual perspective (dermatologic and endocrine). This was a narrative review of English literature between January 2016 and January 2023. We included clinically relevant, original articles with different levels of statistical evidence published on PubMed. We followed four clusters of conditions: thyroid dysfunction, autoimmunity, thyroid cancer, and subacute thyroiditis. A new piece of information in this field was the fact that psoriasis and autoimmune thyroid diseases (ATD) have been shown to be related to the immune-based side effects of modern anticancer drugs-namely, immune checkpoint inhibitors (ICP). Overall, we identified 16 confirmatory studies, but with heterogeneous data. Psoriatic arthritis had a higher risk of positive antithyroperoxidase antibodies (TPOAb) (25%) compared to cutaneous psoriasis or control. There was an increased risk of thyroid dysfunction versus control, and hypothyroidism was the most frequent type of dysfunction (subclinical rather than clinical), among thyroid anomalies correlated with >2-year disease duration, peripheral > axial and polyarticular involvement. With a few exceptions, there was a female predominance. Hormonal imbalance included, most frequently, low thyroxine (T4) and/or triiodothyronine (T3) with normal thyroid stimulating hormone (TSH), followed by high TSH (only one study had higher total T3). The highest ratio of thyroid involvement concerning dermatologic subtypes was 59% for erythrodermic psoriasis. Most studies found no correlation between thyroid anomalies and psoriasis severity. Statistically significant odds ratios were as follows: hypothyroidism: 1.34-1.38; hyperthyroidism: 1.17-1.32 (fewer studies than hypo); ATD: 1.42-2.05; Hashimoto's thyroiditis (HT): 1.47-2.09; Graves' disease: 1.26-1.38 (fewer studies than HT). A total of 8 studies had inconsistent or no correlations, while the lowest rate of thyroid involvement was 8% (uncontrolled studies). Other data included 3 studies on patients with ATD looking for psoriasis, as well as 1 study on psoriasis and thyroid cancer. ICP was shown to potentially exacerbate prior ATD and psoriasis or to induce them both de novo (5 studies). At the case report level, data showed subacute thyroiditis due to biological medication (ustekinumab, adalimumab, infliximab). Thyroid involvement in patients with psoriasis thus remained puzzling. We observed significant data that confirmed a higher risk of identifying positive antibodies and/or thyroid dysfunction, especially hypothyroidism, in these subjects. Awareness will be necessary to improve overall outcomes. The exact profile of individuals diagnosed with psoriasis who should be screened by the endocrinology team is still a matter of debate, in terms of dermatological subtype, disease duration, activity, and other synchronous (especially autoimmune) conditions.

Women's Sexual Dysfunctions Following Stem Cell Transplant and the Impact on Couple Relationship.

Stem cell transplant proved its efficacy in increasing the survival rate among young patients diagnosed with hematological malignancies. A transplant conditioning regimen is particularly destructive on the genital system, often determining premature ovarian failure, accompanied by vulvovaginal atrophy and sexual dysfunctions. The aims of the present study were, first, to evaluate sexual dysfunctions among transplanted women, using clinical examination and the female sexual function index (FSFI), and second, to determine their impact on a couple's relationship. A prospective observational comparative study was performed and included 38 patients who underwent allogenic stem cell transplant (SCT) procedures for different hematological malignancies and 38 healthy patients (control group). This study included baseline evaluation, one-year, and three-year follow-up visits. In addition to anamnesis and medically obtained information, FSFI was evaluated to determine the impact of gynecological damage in a subjective manner. In the study group, vulvovaginal atrophy was diagnosed in 76.32%, with subsequent sexual dysfunctions in 92.10% of patients, based on FSFI scoring. Even though the results improved throughout the study, at the last visit, mild vulvovaginal atrophy was diagnosed in 81.58% of patients, and the FSFI score was abnormal for 21.05%. When compared to the control group, both sexual dysfunctions and FSFI results were considerably impaired, with statistical significance. There is a confirmed negative impact of sexual dysfunctions and self-declared FSFI on couple/marital status and couple relationships, with statistical significance, at the last visit. In conclusion, anatomical, functional, and psychological difficulties are a reality of long-term survivors after a stem cell transplant. They should be addressed and assessed equally to other medical conditions, as they may determine serious consequences and impact the sexual quality of life and the couple's relationship.

Adapting surgical 'bundles' to prevent surgical site infections in obstetrics and gynecology (Review).

Surgical site infections (SSIs) are a complication in any surgical field and they are responsible for 38% of surgery-related patient deaths. Identifying appropriate prophylaxis and solutions to combat SSIs is of global interest. Several studies and reports on SSI raise awareness of this costly complication, both in terms of physical and mental suffering, and as a monetary burden. Knowing the risk factors and implementing strategies to reduce SSI risk represent an adequate approach to reduce SSI incidence. General risk factors of SSI are applicable in the obstetrics and gynecology field, alongside its specific characteristics, including immunological changes occurring during pregnancy, as well as disturbances of vaginal microbiota. The risk of SSI is determined by patient factors but also by preoperative, intraoperative and postoperative care. 'Bundle' prevention strategies have been smartly adopted and their efficiency has been demonstrated in colorectal surgery, cesarean deliveries and gynecological oncology surgeries. 'Bundle' measures may vary among studies, but they remain important prevention methods, which contribute to decreasing SSIs, which is a favorable outcome, and thus, are increasingly used as a routine practice. Therefore, healthcare personnel should aim for the early identification of risk factors to minimize the risk of SSI. All evidence-based methods for preventing and treating SSIs in all surgical fields should be considered to be integral components in order for the best care to be provided to patients.

Half abdomen tumor - giant retroperitoneal lipoma: a case report and review of the literature.

The pure retroperitoneal lipoma is a sporadic benign tumor originating from the mesenchymal tissue. There are only a few data in the literature. The technique available at this moment cannot establish a clear distinction between a benign adipose mass and a low-grade liposarcoma. This study presents the case of a 53-year-old man presenting computed tomography (CT) and magnetic resonance imaging (MRI) findings that revealed a giant retroperitoneal fatty tumor of 365∕210∕165 mm dimensions, suspected of malignancy. The patient's medical history, clinical data, and blood tests are more likely inclined to a benign condition. Liposarcoma couldn't be excluded preoperatively. The patient underwent an open surgical procedure respecting the oncological principles, with complete resection of 6400 g of retroperitoneal adipose tumor that also affected the surrounding organs' normal abdominal anatomy. The tumor was relatively well delimited without any signs of local invasion or infiltration. Three solid masses described on the MRI were identified upon dissection and sent separately for histological examination. The result indicated a giant retroperitoneal lipoma with benign characteristics. Facing imagistic difficulties to distinguish lipoma from liposarcoma clearly, and the inconclusiveness of fine-needle biopsies, oncological resection remains the only option as a diagnostic method and curative treatment.

Diagnostic Pitfall in Atypical Febrile Presentation in a Patient with a Pregnancy-Specific Dermatosis-Case Report and Literature Review.

Pruritic urticarial papules and plaques of pregnancy (PUPPP) usually occurs in the third trimester of pregnancy in primiparous women. It is a self-limiting inflammatory disorder with a still unknown pathogenic mechanism. The abdominal wall overdistension, with a subsequent inflammatory response due to damage to the connective tissue, represents a pathogenesis explanation. Clinical features involve intensely pruritic urticarial rash with edematous, erythematous papules and plaques. The clinical picture and dermal biopsy establish the diagnosis. Topical corticosteroids and oral antihistamines are usually sufficient, but sometimes systemic corticosteroids are necessary. Maternal and fetal prognosis is excellent, and the lesions resolve after birth with no scarring or pigmentary change. We present a case of a 36-year-old patient with a 32-week pregnancy who was admitted with a generalized pruritic rash accompanied by fever. The final diagnosis was decided after multiple pathology exclusions. Treatment consisted of systemic corticoid therapy. The patient gave birth by cesarean section to a healthy newborn without dermatological lesions or other conditions. Adding more PUPPP cases to the literature portfolio will bring more awareness to this under-recognized and under-reported skin disorder. We trust this case will encourage other physicians to publish more cases of pregnancy-specific dermatoses.

Adrenocortical carcinoma: Pediatric aspects (Review).

Adrenocortical carcinoma (adrenal cortex-derived cancer), an orphan malignancy, is a very aggressive disease that affects both adults and children with an annual incidence of 1-2 adult and 0.2-0.38 pediatric cases/million (in the pediatric population it represents 0.2% of all cancers), with a female predominance. A total of 80-90% of cases have hormonal imbalances such as Cushing syndrome, virilization, and puberty anomalies. Precocious puberty (PP) of iso- or hetero-sexual pattern is independent of gonadotropin-releasing hormone (GnRH) (high testosterone/estrogens and low FSH/LH) but post-operative activation of GnRH may be expected (central PP). PP is accompanied by accelerated growth while Cushing syndrome by reduced growth velocity. Pure androgen-secreting tumors have been exceptionally described. A total of 50-80% of children have different genetic/epigenetic anomalies involving tumor protein p53 (most often, almost half of the cases; with a population cluster in Southern Brazilian children), insulin-like growth factor, multiple endocrine neoplasia type 1 (MEN1), PRKAR1A, dysfunctional alternative lengthening of telomeres. Hereditary syndromes associated to adrenocortical carcinoma include Li-Fraumeni, Beckwith-Wiedemann, MEN1, and Lynch. Recently, mutations in epidermal growth factor receptor have been reported in teenagers, suggesting the future use of tyrosine kinase inhibitors. Adrenalectomy is the first line therapy offering the best prognosis if complete tumor removal is achieved; genetic testing is recommended before surgery. Adjuvant therapies are less standardized in children (mitotane is a key adjuvant drug in addition with different regimes of chemotherapy such as etoposide, Adriamycin and cisplatin). A Ki-67 value of at least 15% is a predictor of poor outcome. Weiss score also serves as a prognostic factor, as well as the tumor size at diagnosis. The prognosis of adrenocortical carcinoma is poor with an overall 5-year survival rate of 55%; a Weiss score of at least 6 is associated with a 2-year survival rate of 35%. At present, pediatric adrenocortical carcinoma still represents a severe condition that requires prompt intervention and a multidisciplinary team. Further development of molecular markers is required for an improved understanding of the disease thus improving the protocols of approach and the prognostic.

A Challenging Diagnosis: Placental Mesenchymal Dysplasia-Literature Review and Case Report.

We describe a 22-year-old woman (2-gravid) case who was referred to our clinic at 18 weeks of gestation for a placenta with vesicular lesions discovered on prenatal examination routine. An ultrasound exam at 31 weeks of gestation showed numerous vesicular lesions, which gradually augmented as the pregnancy advanced. A live normal-appearing fetus was confirmed by intrauterine growth restriction (IUGR). The maternal serum ß-human chorionic gonadotropin level remained in normal ranges. At some point, a multidisciplinary medical consensus considered the termination of the pregnancy, but the patient refused to comply. At 33 weeks of gestation, preterm premature rupture of membranes (pPROM) occurred, and she spontaneously delivered a 1600 g healthy female baby with a good long-term outcome. Placental mesenchymal dysplasia (PMD) was retrospectively diagnosed after confronting the data from ultrasound, chorionic villus sampling (CVS), amniocentesis, pathological examination, and immunohistochemical stain. The lack of sufficient reports of PMD determines doctors to be cautious and reserved, approaching these cases more radically than necessary. We reviewed this disease and searched for all cases of PMD associated with healthy, live newborns.

Xanthogranulomatous Pyelonephritis Caused by Stenotrophomonas maltophilia-The First Case Report and Brief Review.

Xanthogranulomatous pyelonephritis (XGP) represents a rare and severe pathology secondary to chronic urinary obstruction and recurrent infections. Commonly, this condition leads to loss of kidney function, and frequently, surgical approach is the only optional treatment. Proteus mirabilis and Escherichia coli are the most frequent pathogens associated with XGP. The actual changes in the pathogen's characteristics increased the risk of newly acquired infections once considered opportunistic. Stenotrophomonas malthophilia is one of those agents more related to immunocompromised patients, presenting an increased incidence and modified antibiotic resistance profile in the modern era. This case report presents a healthy female patient with an underlying renal stone pathology diagnosed with XGP related to S. maltophilia urinary infection. After a complete biological and imagistic evaluation, the case was treated as pyonephrosis. Empirical antibiotic administration and a surgical approach were considered. A total nephrectomy was performed, but the patient's condition did not improve. The patient's status improved when specific antibiotics were administered based on the bacterial identification and antibiotic susceptibility pattern of drained perinephric fluid. Levofloxacin and Vancomycin were considered the optimal combination in this case. The histopathological examination revealed XGP secondary to chronic renal stone. The present study describes the first case of XGP related to an aerobic Gram-negative pathogen such as S. maltophilia, once considered opportunistic, in an apparently healthy female adult.

Aggressive prolactinoma (Review).

Aggressive prolactinoma (APRL) is a subgroup of aggressive pituitary tumors (accounting for 10% of all hypophyseal neoplasia) which are defined by: invasion based on radiological and/or histological features, a higher proliferation profile when compared to typical adenomas and rapidly developing resistance to standard medication/protocols in addition to an increased risk of early recurrence. This is a narrative review focusing on APRL in terms of both presentation and management. Upon admission, the suggestive features may include increased serum prolactin with a large tumor diameter (mainly >4 cm), male sex, early age at diagnosis (<20 years), and genetic predisposition [multiple endocrine neoplasia type 1 (MEN1), aryl hydrocarbon receptor interacting protein (AIP), succinate dehydrogenase (SDHx) gene mutations]. Potential prognostic factors are indicated by assessment of E-cadherin, matrix metalloproteinase (MMP)-9, and vascular endothelial growth factor (VEGF) status. Furthermore, during management, APRL may be associated with dopamine agonist (DA) resistance (described in 10-20% of all prolactinomas), post-hypophysectomy relapse, mitotic count >2, Ki-67 proliferation index ≥3%, the need for radiotherapy, lack of response in terms of controlling prolactin levels and tumor growth despite multimodal therapy. However, none of these as an isolated element serves as a surrogate of APRL diagnosis. A fourth-line therapy is necessary with temozolomide, an oral alkylating chemotherapeutic agent, that may induce tumor reduction and serum prolactin reduction in 75% of cases but only 8% have a normalization of prolactin levels. Controversies surrounding the duration of therapy still exist; also regarding the fifth-line therapy, post-temozolomide intervention. Recent data suggest alternatives such as somatostatin analogues (pasireotide), checkpoint inhibitors (ipilimumab, nivolumab), tyrosine kinase inhibitors (TKIs) (lapatinib), and mTOR inhibitors (everolimus). APRL represents a complex condition that is still challenging, and multimodal therapy is essential.

Melanoma in patients with Li-Fraumeni syndrome (Review).

Li-Fraumeni syndrome (LFS) is a cancer-prone, autosomal dominant syndrome caused by underlying germline gene mutations of TP53, a tumor-suppressor gene encoding the p53 protein with a major role in apoptosis, DNA repair and cell cycle regulation. Cumulative cancer incidence for LFS patients by the age of 70 years is 80-100%, mostly involving adrenocortical carcinoma, brain tumors, bone and soft tissue sarcomas, leukemia and female breast cancer from the age of 20 years. Dominant negative TP53 variant is correlated with an increased tumorigenesis risk in LFS. Sporadic TP53 mutations are related to almost half of global cancers since p53 in addition to p73 protein represent essential players in anticancer cellular protection. Epidemiological aspects concerning skin cancers, especially malignant melanoma (MM), in LFS are less clear. A low level of statistical evidence demonstrates LFS cases with pediatric MM, multiple MM, spitzoid MM, atypical presentations, mucosal and uveal MM. Retrospective cohorts indicate a higher cumulative risk than the general population by the age of 70 years for MM and basal cell carcinoma. Non-syndromic and syndromic TP53 mutations are a major pathway of metastasis, including MM. In LHS, an important level of awareness involves skin cancers despite not being a part of the typical malignancy-containing picture. Additional data are crucially needed. However, at least one dermatologic control is a step in the multidisciplinary panel of surveillance of these patients; but in cases with benign and pre-malign pigmentations, serial dermatoscopy and full body photography are recommended for early melanoma detection in order to improve the prognosis and to reduce the overall malignancy burden.

Dermatological and endocrine elements in Carney complex (Review).

Carney complex (CΝC) is a very rare, autosomal dominant, hereditary syndrome. Seventy percent of individuals with CNC have germline inactivating or deleting mutations of the CNC1 gene [currently known as protein kinase cAMP-dependent type I regulatory subunit α (PRKAR1A), located at the 17q22-24 chromosome level], with 30% of cases presenting with phosphodiesterase gene mutations. A member of the lentiginosis family, dermatological features include: skin pigmentation, cutaneous/mucosal myxomas, usually diagnosed by the age of 20 years (neonatal presentation is exceptional, requiring a meticulous differential diagnosis). Melanocyte-derived tumors such as epithelioid blue nevi (with different levels of pigmentation) and pigmented epithelioid melanocytoma (previously 'animal-type melanoma') are often found. Myxomas, mesenchymal tumors with mostly a benign pattern, may be recurrent. Primary cutaneous melanotic schwannoma are atypical, while non-skin sites are frequent. Corticotropinomas or somatotropinomas are part of the hereditary syndrome-related pituitary adenomas (representing 5% of all). Primary pigmented nodular adrenocortical disease involves bilateral cortical hyperplasia causing Cushing syndrome (CS) at an earlier age than non-CNC cases; osteoporotic fractures seem more prevalent compare to CS of other etiologies. Typically benign, a few cases of adrenocortical carcinoma have been identified. A total of 5% of familial non-medullary thyroid cancer is syndromic, also including CNC. CNC-related thyroid frame includes: hyperthyroidism, follicular hyperplasia/adenomas, follicular carcinoma (usually aggressive, bilateral or multifocal). Large cell calcifying Sertoli cell tumors of the testes have malignant behavior in adults; in children these may induce precocious puberty. Two particular mammary tumors are found: myxoid fibroadenomas and breast myxomatosis. Cutaneous/subcutaneous lesions, pigmented or not, or any focal swelling of non-identified cause needs careful examination, since dermatological elements are among the earliest and most discernable by which to detect lesions in CNC, a systemic condition with multi-level endocrine involvement.