The role of neutrophil-lymphocytes ratio (NLR) in the prognosis of CIN2+ 2 recurrence after excisional treatment.

OBJECTIVES: The main risk factor involved in CIN2+ recurrence after treatment is the HPV persistent infection. The dysregulation of the immune system permits only HR-HPVs to become persistent infections, to promote cancer development and to increase the risk of recurrence after treatment. Therefore, there is a shift to a Th2-type cytokine pattern during the carcinogenesis pathway; for this reason, the neutrophil-lymphocytes ratio (NLR) could be a marker of this immunological change. The study aims to analyse the predictive role of NLR in the recurrence of High-grade CIN (CIN2+) after excisional treatment in a real-world life setting of patients treated for CIN2+ Design: cross-sectional study Participants/Materials, Setting, Methods: We examined a retrospective database of 444 patients, who attended the Colposcopy Service of our Department from 2011 to 2020 due to an abnormal screening pap smear and we compared the clinical characteristics to NLR performed at the time of diagnosis. All analysed patients were treated according to an established protocol (colposcopy every 6 months for the first two years, and every year for the over three years,) and HPV-DNA test and cervical biopsy were performed at entry and the end of follow-up. All patients underwent a blood sample examination, including complete white blood cell counts and collecting neutrophil and lymphocyte values expressed as 103/ml. Results The sensitivity (SE) and specificity (SP) of the NLR cut-off point of 1.34 for the diagnosis of CIN2+ recurrence were 0.76 and 0.67, respectively. We found that CIN2+ recurrences were significantly higher in patients with NLR < 1.34 (3.7% vs. 0.6%, p = 0.033) and the 5-year recurrence-free survival was higher in patients with NLR ≥ 1.34 (97% vs. 93%, p=0.030). Limitations First, the retrospective analysis and low incidence of recurrence may limit the conclusions. Second, for the retrospective design of the study, we did not take into consideration the patient's comorbidities and habits (smoking), that may influence the NLR. On the other hand, the median duration of follow-up in our study was 26 months (IQR 22-31), which fully reflects the incidence of recurrences. Conclusions It is well known that CIN2+ lesions are sustained by deregulation of the immune system caused by persistent HPV infection, which may lead to cervical cancer. Among the actors underlying dysregulation of immunity, lymphocytes are involved in the permission of persistent infection and for this reason, NRL could be a reliable and cost-effective biomarker in predicting the risk of recurrence, especially for high-grade cervical lesions.

Retrospective Investigation of Human Papillomavirus Cervical Infection and Lymphoma Incidence: A Clinical and Pathological Evaluation.

OBJECTIVE: Human papillomavirus (HPV) persistence is considered the main risk factor for neoplastic progression, and evidence suggests that regulatory T cells play an important role in the failure of viral elimination. Regulatory T cells may be involved in maintaining a microenvironment favourable for viral persistence and neoplasticity, through a deregulation of the local immune response. The association between altered immune function and the development of chronic infections, cancer (solid and haematological), and autoimmune diseases is documented in the literature. The purpose of this retrospective analysis was to evaluate the possible correlation between HPV cervical infection and lymphoma incidence in women attending colposcopy due to an abnormal Pap smear during a period of 15 years. DESIGN: This is a cross-sectional study. PARTICIPANTS: We investigated retrospectively the incidence of haematological diseases in women aged 21-84 with an abnormal Pap smear who referred to our centre between 2004 and 2019. SETTING: This study was conducted at the university hospital. METHODS: In our analysis, we included women with diagnoses of HL and NHL after the detection of abnormal Pap smears and HPV infections. We excluded patients with a diagnosis of lymphoma preceding the date of the abnormal Pap smear and HPV test. RESULTS: We divided the patients into two groups in order to analyse the standard incidence ratio (SIR): HL patients (19/7,064, 0.26%) and NHL patients (22/7,064, 0.31%). In our sample, we reported a significant risk of developing lymphoma compared to the general population, both for HL and NHL disease, at age <45 years. Regarding HL, the SIR of disease in women <45 years was 4.886 (95% CI 2.775-9.6029) and in women between 45 and 59 years was 2.612 (95% CI 0.96-7.108804). On the other hand, for NHL in women <45 years, we reported an SIR of about 3.007 (95%, CI 1.273-7.101575), in women aged 45-59 years, the SIR was 4.291 (95% CI 2.444-7.534399), and in women aged 60-74 years, the SIR was 3.283 (95% CI 1.054-10.22303). LIMITATIONS: This retrospective analysis was conducted in a single centre in Northern Italy and did not consider all interregional differences existing in the country in terms of HPV genotypes, ethnicity, and population characteristics. Regarding the analysis of SIR for HL and NHL, we did not divide the disease into subtypes because of the small sample of cases. Finally, we considered in our analysis only women with an abnormal Pap smear and not the general population. CONCLUSIONS: Women with chronic and persistent HPV infections may have a higher relative risk of developing lymphoma. This possible association may be caused by the deregulation of the immune system response against HPV and the failure of viral clearance, especially in younger women.

Pink-on-pink: hepatocellular carcinoma metastatic to oncocytic carcinoma of the thyroid.

Hepatocellular carcinoma typically metastasizes within the liver and may involve extrahepatic sites such as the lungs, adrenal glands, and bones at advanced stages. However, hepatocellular carcinoma metastasis to the thyroid is very uncommon and tumor-to-tumor metastasis from a hepatocellular cancer to a thyroid neoplasm is extremely rare. In this report, we present a case of a 70-year-old man with a hepatocellular carcinoma metastasizing to oncocytic thyroid carcinoma, emphasizing the importance of clinical history and of a multidisciplinary approach, as well as the usefulness of site-specific immunohistochemical markers, in diagnosing and managing cases of Rosai's metastasis, especially when donor and recipient neoplasms share similar histologic features.

Placental fetal vascular malperfusion, neonatal neurologic morbidity, and infant neurodevelopmental outcomes: a systematic review and meta-analysis.

OBJECTIVE: This study aimed to evaluate the association of placental fetal vascular malperfusion lesions with neonatal brain injury and adverse infant neurodevelopmental outcomes. DATA SOURCES: PubMed and Medline, Scopus, and Cochrane databases were searched from inception to July 2022. STUDY ELIGIBILITY CRITERIA: We included cohort and case-control studies reporting the associations of fetal vascular malperfusion lesions with neonatal encephalopathy, perinatal stroke, intracranial hemorrhage, periventricular leukomalacia, and infant neurodevelopmental and cognitive outcomes. METHODS: Data were analyzed by including fetal vascular malperfusion lesions as an exposure variable and brain injuries or neurodevelopmental impairment as outcomes using random-effects models. The effect of moderators, such as gestational age or study type, was assessed by subgroup analysis. Study quality and risk of bias were assessed by applying the Observational Study Quality Evaluation method. RESULTS: Out of the 1115 identified articles, 26 were selected for quantitative analysis. The rates of neonatal central nervous system injury (neonatal encephalopathy or perinatal stroke) in term or near-term infants were more common among fetal vascular malperfusion cases (n=145) than among controls (n=1623) (odds ratio, 4.00; 95% confidence interval, 2.72-5.90). In premature deliveries, fetal vascular malperfusion lesions did not influence the risk of intracranial hemorrhage or periventricular leukomalacia (odds ratio, 1.40; 95% confidence interval, 0.90-2.18). Fetal vascular malperfusion-associated risk of abnormal infant neurodevelopmental outcome (314 fetal vascular malperfusion cases and 1329 controls) was modulated by gestational age being higher in term infants (odds ratio, 5.02; 95% confidence interval, 1.59-15.91) than in preterm infants (odds ratio, 1.70; 95% confidence interval, 1.13-2.56). Abnormal infant cognitive development and mental development were more common among fetal vascular malperfusion cases (n=241) than among controls (n=2477) (odds ratio, 2.14; 95% confidence interval, 1.40-3.27). The type of study (cohort vs case-control) did not influence the association between fetal vascular malperfusion and subsequent infant brain injury or abnormal neurodevelopmental outcome. CONCLUSION: The findings of cohort and case-control studies indicate a considerable association between fetal vascular malperfusion placental lesions and increased risk of brain injury in term neonates, and neurodevelopmental impairment in both term and preterm infants. A diagnosis of placental fetal vascular malperfusion should be taken into consideration by both pediatricians and neurologists during the follow-up of infants at risk of adverse neurodevelopmental outcomes.

Clinical Correlates of Placental Pathologic Features in Early-Onset Fetal Growth Restriction.

INTRODUCTION: The purpose of this study was to evaluate the association between placental pathologic features of maternal (MVM) or fetal (FVM) vascular malperfusion and clinical characteristics, sonographic findings and neonatal outcome in a cohort of pregnancies complicated by early-onset (diagnosed before 32 weeks of gestational age) fetal growth restriction (FGR). METHODS: A prospective cohort study included 250 singleton early-onset FGR pregnancies diagnosed, followed up and delivered at a single center. Placental pathologic lesions were classified according to standard recommendations. Logistic regression and Cox analysis were used to evaluate outcomes adjusting for confounders. RESULTS: Overall features of severe placental MVM and FVM were observed in 29.6% (74/250) and 12.8% (32/250) of the subjects, respectively. Severe placental MVM lesions were more common among subjects with umbilical artery Doppler Pulsatility Index >95th than ≤95th percentile (50/120 as opposed to 24/130, Adj odds ratio [OR] = 3, 95% CI = 1.6-5.4) and Cerebroplacental ratio <5th than ≥5th percentile (48/115 as opposed to 26/135, Adj OR = 2.7, 95% CI = 1.5-4.9). Mean time from FGR diagnosis to delivery was shorter among subjects with severe MVM (25.5 days, 95% CI = 20.6-30.2, Adj. OR = 1.9, 95% CI = 1.9, 95% CI = 1.4-2.5) when compared to both those with mild/moderate MVM (36.5 days [95% CI = 27.2-45, p = 0.04]) or no MVM (39.4, 95% CI = 35.4-43.4, p < 0.001). Finally, severe FVM was associated with an increased risk of perinatal/neonatal death or severe brain lesions (9/28 in subjects with perinatal/neonatal death/brain lesions as compared to 23/222 in controls, Adj OR = 3, 95% CI = 1.05-8.6) or severe adverse neonatal outcomes (13/46 in subjects with severe adverse outcome as compared to 19/204 among controls, Adj OR = 3.2, 95% CI = 1.2-8.5). CONCLUSIONS: In early-onset FGR, placental pathologic features of MVM and FVM are, in different regards, associated to severity of clinical picture, abnormal Doppler markers of placental and fetal circulation and of neonatal outcome, respectively.

Role of placental inflammatory mediators and growth factors in patients with rheumatic diseases with a focus on systemic sclerosis.

OBJECTIVES: Pregnancy in SSc is burdened with an increased risk of obstetric complications. Little is known about the underlying placental alterations. This study aimed to better understand pathological changes and the role of inflammation in SSc placentas. Leucocyte infiltration, inflammatory mediators and atypical chemokine receptor 2 (ACKR2) expression in SSc placentas were compared with those in other rheumatic diseases (ORD) and healthy controls (HC). METHODS: A case-control study was conducted on eight pregnant SSc patients compared with 16 patients with ORD and 16 HC matched for gestational age. Clinical data were collected. Placentas were obtained for histopathological analysis and immunohistochemistry (CD3, CD20, CD11c, CD68, ACKR2). Samples from four SSc, eight ORD and eight HC were analysed by qPCR for ACKR2 expression and by multiplex assay for cytokines, chemokines and growth factors involved in angiogenesis and inflammation. RESULTS: The number of placental CD3, CD68 and CD11 cells was significantly higher in patients affected by rheumatic diseases (SSc+ORD) compared with HC. Hepatocyte growth factor was significantly increased in the group of rheumatic diseases patients (SSc+ORD) compared with HC, while chemokine (C-C motif) ligand 5 (CCL5) was significantly higher in SSc patients compared with ORD and HC. CCL5 levels directly correlated with the number of all local inflammatory cells and higher levels were associated with histological villitis. CONCLUSIONS: Inflammatory alterations characterize placentas from rheumatic disease patients and could predispose to obstetric complications in these subjects.

Placental features of fetal vascular malperfusion and infant neurodevelopmental outcomes at 2 years of age in severe fetal growth restriction.

BACKGROUND: Placental pathologic lesions suggesting maternal or fetal vascular malperfusion are common among pregnancies complicated by intrauterine growth restriction. Data on the relationship between pathologic placental lesions and subsequent infant neurodevelopmental outcomes are limited. OBJECTIVE: This study aimed to assess the relationship between placental pathologic lesions and infant neurodevelopmental outcomes at 2 years of age in a cohort of pregnancies complicated by intrauterine growth restriction. STUDY DESIGN: An observational cohort study included singleton intrauterine growth restriction pregnancies delivered at ≤34 weeks' gestation and with a birthweight of ≤1500 g at a single institution in the period between 2007 and 2016. Maternal and neonatal data were collected at discharge from the hospital. Infant neurodevelopmental assessment was performed every 3 months during the first year of life and every 6 months in the second year. Penalized logistic regression was used to test the association of maternal vascular malperfusion and fetal vascular malperfusion with infant outcomes adjusting for confounders. RESULTS: Of the 249 pregnancies enrolled, neonatal mortality was 8.8% (22 of 249). Severe and overall maternal vascular malperfusion were 16.1% (40 of 249) and 31.7% (79 of 249), respectively. Severe maternal vascular malperfusion was associated with an increased risk of neonatal mortality (adjusted odds ratio, 3.3; 95% confidence interval, 1.2-9.5). Among the 198 survivors after a 2-year neurodevelopmental follow-up evaluation, the rate of major and minor neurodevelopmental sequelae was 57.1% (4 of 7) among severe fetal vascular malperfusion (adjusted odds ratio, 24.5; 95% confidence interval, 4.1-146), 44.8% (13 of 29) among overall fetal vascular malperfusion (adjusted odds ratio, 5.8; 95% confidence interval, 5.1-16.2), and 7.1% (12 of 169) in pregnancies without fetal vascular malperfusion. Infants born from pregnancies with fetal vascular malperfusion also had lower 2-year general quotient, personal-social, hearing and speech, and performance subscales scores than those without fetal vascular malperfusion. Finally, in the presence of fetal vascular malperfusion, the likelihood of a 2-year infant survival with normal neurodevelopmental outcomes was reduced by more than 70% (adjusted odds ratio, 0.29; 95% confidence interval, 0.14-0.63). Noticeably, 10 of the 20 subjects with a 2-year major neurodevelopmental impairment (3 of 4 with severe fetal vascular malperfusion) had little or no abnormal neurologic findings at discharge from neonatal intensive care unit. CONCLUSION: In preterm intrauterine growth restriction, placental fetal vascular malperfusion is correlated with an increased risk of abnormal infant neurodevelopmental outcomes at 2 years of age even in the absence of brain lesions or neurologic abnormalities at discharge from the neonatal intensive care unit. In the case of a diagnosis of fetal vascular malperfusion, pediatricians and neurologists should be alerted to an increased risk of subsequent infant neurodevelopmental problems.

The relationship of human papillomavirus infection with endocervical glandular involvement on cone specimens in women with cervical intraepithelial neoplasia.

OBJECTIVE: The aim of study was to evaluate the association of endocervical gland involvement (EGI) on histological samples with high risk (HR) human papillomavirus (HPV) infection and with the persistence/recurrence rate of cervical intraepithelial neoplasia (CIN) after treatment. METHODS: A total of 1301 subjects who had conization procedures after cervical punch biopsies (533 persistent CIN1, 768 CIN2+ including 20 microinvasive cervical cancer) were enrolled in the study. HPV genotypes were identified using the INNO-LiPA HPV genotyping assay on cervical scraping. Logistic regression and Cox regression analyses were used to evaluate the association of EGI on the persistence/recurrence rate of CIN after treatment. RESULTS: The rate of EGI on final histology was 46.3% (602/1301). HPV 16 was the only HR-HPV significantly associated with increasing rates of EGI (231/602 as compared to 211/699, p = 0.002). EGI was also associated with an excess of multiple HR-HPV infections (237/602 as compared with 225/699, p = 0.006). After correction for confounders, the odds ratio of EGI among women infected by HPV 16 was 1.41 (95% CI = 1.12-178). CIN2+ lesions were diagnosed in 40.5% (283/699) of EGI negative subjects and 86.7% (522/602, p < 0.001 compared to negative subjects) of EGI positive subjects.After a median of 25 months of follow-up (IQR = 15-47) of 1090 treated women, the persistence of HPV 16 during follow-up was 38.1% (93/217, p = 0.03 compared to EGI negative) among EGI positive and 32% (58/181) among controls. After corrections for potential confounders, the odds ratio of CIN2+ persistence and or recurrence was higher among EGI positive (OR = 2.35, 95% CI = 1.16-4.77) than negative controls. CONCLUSION: EGI on histological samples is associated with increased rates of HPV 16, multiple high risk-HPV infections and CIN2+ lesions. EGI positive subjects also had an increased CIN recurrence/persistence after treatment compared to controls.

Pathologic placental lesions in early and late fetal growth restriction.

INTRODUCTION: The purpose of the study was to evaluate the differences in individual histopathologic placental lesions in pregnancies complicated by early-onset (<32 weeks at diagnosis) and late-onset (≥32 weeks at diagnosis) fetal growth restriction (FGR). MATERIAL AND METHODS: A cohort study of 440 singleton pregnancies complicated by FGR, diagnosed according to standard ultrasonographic criteria, followed up and delivered at the same institution between 2010 and 2016. Placental lesions were classified according to the Amsterdam Placental Workshop Consensus Criteria. Pathologic examination of placentas from 113 healthy singleton term pregnancies served as controls. Binary and multinomial logistic regression models were used to evaluate the independent association of placental lesions with the type of FGR. RESULTS: In our cohort the prevalences of early and late FGR were 37.3% (164/440) and 62.7% (276/440), respectively. The overall rates of preeclampsia (69/164 vs 59/276, P < 0.01) and absent/reversed umbilical artery pulsatility indices (61/164 vs 14/276, P < 0.001) were higher among early FGR than late FGR. Placental characteristics from early and late FGR pregnancies differed mainly in regard to maternal vascular malperfusion scores rather than fetal scores, with preeclampsia found to be a cofactor modulating the rates and severity of associated lesions. In the binary logistic analysis, recent infarcts (OR 2.44, 95% CI 1.2-5), distal villous hypoplasia (OR 1.8, 95% CI 1.0-3.2), atherosis (OR 2.71, 95% CI 1.35-5.47), persistent endovascular trophoblasts (OR 1.67, 95% CI 1.03-2.7), and a reduced fetal/placental weight score (OR 0.27, 95% CI 0.2-0.38) were independently associated with an increased likelihood of early FGR compared with late FGR. The sensitivity, specificity, and area under the curve of the model were 60% (95% CI 51.2-66.2), 89.1% (95% CI 84.9-92.3), and 0.81 (95% CI 0.77-0.85), respectively, suggesting a fair to good predictive value. CONCLUSIONS: Individual placental lesions suggestive of increased rates of ischemia, defective remodeling of spiral arteries, peripheral hypoxia interfering with villus development, and reduced placental efficiency were significantly more common in early FGR than late FGR.

Spleen endothelial cells from patients with myelofibrosis harbor the JAK2V617F mutation.

Increased microvessel density contributes to abnormal BM and spleen microenvironment in myelofibrosis (MF). Taking advantage of the JAK2V617F mutation as a marker of malignancy, in the present study, we investigated whether splenic endothelial cells (ECs) obtained from capillaries by laser microdissection or from fresh spleen tissue by cell culture or cell sorting harbored such mutation in patients bearing the mutation in their granulocytes and undergoing splenectomy for therapeutical reasons. To extend the analysis to the ECs of large vessels, endothelial tissue from the splenic vein was also studied. We found JAK2V617F(+) ECs in 12 of 18 patients also bearing the mutation in their granulocytes. In 3 patients, the mutation was found in at least 2 different EC samples obtained by laser microdissection, cell culture, or cell sorting. The mutation was detected in the splenic vein ECs of 1 of 6 patients investigated. In conclusion, we provide evidence that some ECs from the spleen and splenic veins of patients with MF bear the JAK2V617F mutation. We suggest that splenic ECs are involved in the process of malignant transformation in MF.

Giant Morpheaform Basal Cell Carcinoma Mimicking Scarring Alopecia: Exception Prone to Neglect.

A 74-year-old woman in good general health presented with a 5-year history of progressive hair loss over several years, interpreted as female androgenetic alopecia (AGA), and was treated with topical 5% Minoxidil without improvement. The patient's relevant medical history revealed infiltrating, triple-negative apocrine carcinoma of the right breast four years before, treated by quadrantectomy, radiation, lymphadenectomy and chemotherapy, with no recurrence at the last follow-up. On examination, there was an asymptomatic 15 × 15 cm firm and whitish area of scarring alopecia on the central scalp. Dermoscopy revealed multiple arborizing vessels and many telangiectasia. The clinical considerations included mainly cutaneous metastasis of breast carcinoma (alopecia neoplastica), pseudopelade of Broque and morpheaform basal cell carcinoma (BCC). A histopathologic examination revealed characteristic changes of morpheaform BCC with basaloid islands and cords of atypical basaloid cells diffusely infiltrating the dermis, embedded in a sclerotic and hypervascularized stroma. Secondary alopecia neoplastica due to morpheaform BCC on the scalp is an exceedingly rare entity, possessing subtle clinical features that may mimic both scarring and non-scarring alopecia. Delayed recognition may contribute to aggressive behavior and extensive local destruction. Treatment with hedgehog inhibitors in locally advanced BCC of the scalp, both in adjuvant and neoadjuvant modalities, is promising.

Trisomy 22 Mosaicism from Prenatal to Postnatal Findings: A Case Series and Systematic Review of the Literature.

BACKGROUND: Among aneuploidies compatible with life, trisomy 22 mosaicism is extremely rare, and only about 25 postnatal and 18 prenatal cases have been described in the literature so far. The condition is mainly characterized by facial and body asymmetry, cardiac heart defects, facial dysmorphisms, growth failure, delayed puberty, and variable degrees of neurodevelopmental delay. PROBLEM: The scattered information regarding the condition and the dearth of data on its natural history and developmental outcomes restrict genetic counseling, particularly in prenatal settings. Moreover, a prompt diagnosis is frequently delayed by the negative selection of trisomic cells in blood, with mosaicism percentage varying among tissues, which often entails the need for further testing. Purpose/topic: The aim of our work is to provide assistance in prenatal and postnatal genetic counseling by systematically delineating the current knowledge of the condition. This entails defining the prenatal and postnatal characteristics of the condition and presenting novel data from three cases, both prenatally and postnatally. Additionally, we report the developmental outcomes observed in two new patients.

Twenty-one cases of blastic plasmacytoid dendritic cell neoplasm: focus on biallelic locus 9p21.3 deletion.

Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is a rare and aggressive malignancy derived from precursors of plasmacytoid dendritic cells. We analyzed 21 cases with array-based comparative genomic hybridization (aCGH). Complete or partial chromosomal losses largely outnumbered the gains, with common deleted regions involving 9p21.3 (CDKN2A/CDKN2B), 13q13.1-q14.3 (RB1), 12p13.2-p13.1 (CDKN1B), 13q11-q12 (LATS2), and 7p12.2 (IKZF1) regions. CDKN2A/CDKN2B deletion was confirmed by FISH. This scenario argues for disruption of cell cycle at G(1)/S transition, representing a genetic landmark of BPDCN, and possibly contributing to its pathogenesis. Statistical analysis of overall survival in our series highlighted an association of poor outcome with biallelic loss of locus 9p21.3. We suggest that, in the absence of reliable parameters for predicting prognosis in BPDCN other than age, tumor stage, and/or clinical presentation, simple methods, such as FISH for CDKN2A/CDKN2B, could help to identify the most aggressive cases.

Low-Grade Cervical Intraepithelial Neoplasia (CIN1) Evolution: Analysis of Opportunistic Preventive Vaccination Role.

BACKGROUND: Low-grade cervical lesions have a high percentage of clearance in young women, even if 71-82% of low-grade intraepithelial lesion/atypical squamous cells of undetermined significance (LSIL/ASCUS) reported a High-Risk Human Papillomavirus (HR-HPV) infection, which correlates with an increased risk of Cervical Intraepithelial Neoplasia (CIN)2+. The immunogenic effect of the anti-HPV vaccine appears to be significant. The aim of the study is to evaluate the effect, two years after the diagnosis, of the anti-HPV preventive vaccination on patients with low-grade cervical lesions. METHODS: We collected clinical, colposcopic, histological, and virological data from patients aged 21-45 years who attended the colposcopy service of the department of Obsetrics and Gynecology of IRCCS Foundation Policlinico San Matteo, Pavia, Italy. In the 2005-2019 period and had a low-grade pap-smear. RESULTS: We enrolled 422 women consecutively, divided into two groups (vaccinated and not vaccinated) for the retrospective analysis. The rate of persistence and progression of CIN were higher in the not-vaccinated group (p = 0.019). The relative risk (RR) to develop CIN2+ during follow-up vs. the the CIN1 persistence was 1.005 (95% Confidence Interval-CI 0.961-1.051) vs. 0.994 (95% CI 0.994-1.018) for age, 3.472 (95% CI 1.066-11.320) vs. 1.266 (95% CI 0.774-2.068) for non-vaccinated, 0.299 (95% CI 0.088-1.018) vs. 0.518 (95% CI 0.242-1.109) for HIV status negative, respectively. Analyzing the time to negativity, the odds ratio (OR) was 1.012 (95% CI 1-1.024) for age and 1.591 (95% CI 1.223-2.069) for vaccination; on the other hand, considering the relationship between the time to negative and the HPV genotypes contained in the 9-valent HPV vaccines, the OR was 1.299 (95% CI 1.026-1.646) for at least one of these at recruitment and 0.631 (95% CI 0.471-0.846) at follow-up. Furthermore, the presence of at least one of the HPV genotypes targeted by the HPV nonavalent vaccine is a key indicator of the risk of progression to CIN2+: OR was 3.443 (95% CI 1.065-11.189) for the presence of at least one HPV genotype at enrollment and 5.011 (95% CI 1.899-13.224) for the presence of at least one HPV genotype at follow-up, respectively. CONCLUSIONS: We reported in a retrospective study the benefit of anti-HPV vaccination in promoting negativity and increasing low-grade cervical lesions regression.

Placental pathologic features in obesity.

INTRODUCTION: Obesity in pregnancy is associated with adverse long-term consequences both in the mother and in offspring. Maternal obesity induces a metabolic-inflammatory state that could impact on placental function and could mediate the adverse outcomes. The purpose of this study was to compare the major placental histological characteristics of non-diabetic obese women to lean controls, focusing on uncomplicated pregnancies. METHODS: Prospective case-control study comparing placental histopathological features between 122 non-diabetic obese women and 185 non-obese controls. The analysis was performed on overall subjects, then uncomplicated pregnancies from both groups were analyzed. Placenta pathologic findings were recorded according to standard classification. RESULTS: Both in overall analysis and among the subset of subjects with an uncomplicated pregnancy, obese subjects had higher risks of maternal vascular malperfusion (MVM) (respectively OR=2.2, 95%CI =1.3-3.7 and OR=4.2, 95%CI=2.1-8.5), fetal vascular malperfusion (FVM) (respectively OR=6.3, 95%CI=3.1-12.5 and OR=7.2, 95%CI=3-17.2), maternal and fetal inflammatory response placental lesions and villitis (VUE) (respectively OR=2.5, 95%CI=1.1-5.6 and OR=10.8, 95%CI=3.3-35.3) compared to controls. Among uncomplicated pregnancies and after adjustment for confounders, first trimester BMI was significantly associated with overall MVM, overall FVM, maternal inflammatory, fetal inflammatory response and VUE. DISCUSSION: Placentas from obese women showed a significantly higher risk of maternal and fetal vascular and inflammatory placental lesions, both in overall population and in the subgroup with uncomplicated pregnancies. The metabolic and inflammatory dysfunctions typical of obesity could have an impact on placental development and function, which could be a mediator of the detrimental effects of obesity on pregnancy outcome and on future health of the offspring.

Eosinophilic dermatosis of hematologic malignancy in patients with chronic lymphocytic leukemia/non-Hodgkin's B lymphoma: a single center prospective clinico-pathological study.

Background: The pathogenesis of eosinophilic dermatosis of hematologic malignancy (EDHM) is poorly understood. Previously thought to be a hypersensitivity reaction to insect bites, immune dysregulation and cytokine imbalance are now thought to be responsible. Its prognostic significance is unclear. Objective: To describe the clinical, pathological and immunological findings in a series of oncohematological patients with EDHM. Methods: An observational prospective cohort study of oncohematological patients receiving a diagnosis of EDHM between April 2017 and December 2018. Results: A total of 15 patients with EDHM (10 females and 5 males) were identified among 422 oncohematological patients. Disease presentation varied from firm erythematous papules to more polymorphic presentations. The lesions were most prevalent on the exposed sites, 8/15 patients recalled an insect bite. Lesion seasonality was reported in 13/15 patients. IgE levels were elevated in six patients, circulating IL-4 and IL-5 were within a normal range. Twelve out of 15 patients developed skin manifestations after chemotherapy. The infiltrate could be eosinophil-rich or lymphocytic-rich. Interestingly, the histopathologic findings were in accordance with arthropod bites. Conclusion: A role for insect bites in EDHM is supported by our findings. EDHM may be related to aggressive hematologic disease.

Photoinduced dermatitis and oral lichenoid reaction in a chronic myeloid leukemia patient treated with imatinib mesylate.

BACKGROUND: Imatinib mesylate (IM) is a phenylaminopyrimidine that represents the first-line treatment for chronic myeloid leukemia (CML), Philadelphia chromosome-positive. It acts as a potent and selective inhibitor of the bcr-abl fusion protein by a competitive inhibition at the adenosine triphosphate-binding site of the enzyme, which leads to the inhibition of tyrosine phosphorylation of the proteins involved in bcr-abl signal transduction. IM is generally well tolerated and usually provokes only mild side effects consisting of nausea, myalgia, edema and muscle cramps. OBSERVATION: This is a report of a patient affected by CML, who developed a photoinduced dermatitis and an oral lichenoid reaction associated with IM treatment. The lesions were resolved, thanks to the withdrawal of the therapy, and they relapsed after the reintroduction of IM, confirming the drug-induced pathogenesis. CONCLUSION: Skin changes are the most common non-hematologic side effects to IM treatment and are usually dose dependent. In particular, patients with IM therapy reported a lightening and depigmentation of the skin, that may alter the skin protection against ultraviolet exposure, with a possible subsequent intolerance to sun exposure, as reported in our patient, and higher risk of skin cancer. They are frequently self-limited or easily managed; nevertheless, in some cases, the therapy needs to be discontinued or may only be continued with concomitant oral steroid.

SCN2A and arrhythmia: A potential correlation? A case report and literature review.

Variants in SCN2A, encoding the voltage-gated sodium channel Nav1.2, are commonly associated with developmental and epileptic encephalopathy. Although animal studies demonstrated a role for Nav1.2 in intraventricular conduction, heart anomalies have been only occasionally described in patients with SCN2A variants. In this report we trace the prenatal and neonatal history of a fetus/newborn with a de novo pathogenic variant in the SCN2A gene identified by prenatal trio whole-exome sequencing (WES). In addition to more typically SCN2A-associated neurological manifestations, the patient showed sustained tachyarrhythmia, potentially expanding the phenotypic spectrum associated with SCN2A variants and raising the question of whether cardiological assessment and prompt pharmacological intervention in SCN2A channelopathies to avoid heart complications might be beneficial. To the best of our knowledge, this represents the first clinical description of a SCN2A phenotype in a prenatal setting, as well as the first SCN2A diagnosis achieved by prenatal trio-WES approach.

What is known about neuroplacentology in fetal growth restriction and in preterm infants: A narrative review of literature.

The placenta plays a fundamental role during pregnancy for fetal growth and development. A suboptimal placental function may result in severe consequences during the infant's first years of life. In recent years, a new field known as neuroplacentology has emerged and it focuses on the role of the placenta in fetal and neonatal brain development. Because of the limited data, our aim was to provide a narrative review of the most recent knowledge about the relation between placental lesions and fetal and newborn neurological development. Papers published online from 2000 until February 2022 were taken into consideration and particular attention was given to articles in which placental lesions were related to neonatal morbidity and short-term and long-term neurological outcome. Most research regarding the role of placental lesions in neurodevelopment has been conducted on fetal growth restriction and preterm infants. Principal neurological outcomes investigated were periventricular leukomalacia, intraventricular hemorrhages, neonatal encephalopathy and autism spectrum disorder. No consequences in motor development were found. All the considered studies agree about the crucial role played by placenta in fetal and neonatal neurological development and outcome. However, the causal mechanisms remain largely unknown. Knowledge on the pathophysiological mechanisms and on placenta-related risks for neurological problems may provide clues for early interventions aiming to improve neurological outcomes, especially among pediatricians and child psychiatrists.

Pathologic Findings at Risk Reducing Surgery in BRCA and Non-BRCA Mutation Carriers: A Single-Center Experience.

Risk-reducing surgery (RRS) is recommended in BRCA-mutated carriers because of their increased risk of developing ovarian cancer, while its role is still discussed for women harboring mutations in non-BRCA homologous repair genes. The aim of this study was to retrospectively evaluate the occurrence of pathological findings in a high-risk population undergoing RRS in San Matteo Hospital, Pavia between 2012 and 2022, and correlate their genetic and clinical outcomes, comparing them with a control group. The final cohort of 190 patients included 85 BRCA1, 63 BRCA2, 11 CHEK2, 7 PALB2, 4 ATM, 1 ERCC5, 1 RAD51C, 1 CDH1, 1 MEN1, 1 MLH1 gene mutation carriers and 15 patients with no known mutation but with strong familial risk. Occult invasive serous carcinoma (HGSC) and serous tubal intraepithelial carcinoma (STIC) were diagnosed in 12 (6.3%) women, all of them BRCA carriers. No neoplastic lesion was diagnosed in the non-BRCA group, in women with familial risk, or in the control group. Oral contraceptive use and age ≤45 at surgery were both found to be favorable factors. While p53 signature and serous tubal intraepithelial lesion (STIL) were also seen in the control group and in non-BRCA carriers, STIC and HGSC were only found in BRCA1/2 mutation carriers.