Search

This article discusses a study that aimed to establish a correlation between sonographic and histopathologic patterns in severe Human Cytomegalovirus (HCMV)-related lesions in fetuses. The researchers collected cases of fetuses with HCMV and severe neurosonographic alterations and examined the brain tissue samples obtained from postmortem examinations. They found that there were two main periventricular sonographic patterns, which corresponded to two different histopathologic patterns. The study suggests a relationship between these patterns and calls for further investigations to understand the timeline, development, and neurological correlations of these lesions in newborns. [Extracted from the article]

Abstract The spleen is an infrequent site for metastatic lesions, and solitary splenic metastases from squamous cell carcinoma of the esophagus are very rare: only 4 cases have been reported thus far. These lesions are whitish nodules that are macroscopically and radiologically similar to primary splenic lymphomas. We report a case of metachronous splenic metastases from esophageal cancer and multiple splenic abscesses, which developed nine months after apparently curative esophagectomy without adjuvant chemotherapy. The patient underwent splenectomy dissection followed by adjuvant chemotherapy, but liver and skin metastases developed, and the patient died 9 months later.

An osteoma is a slow-growing, benign lesion comprising mature bone tissue. Osteomas rarely occur in maxillary bones, with the exception of the maxillary sinuses. Various possible etiologies have been proposed, including congenital anomalies, chronic inflammation, muscular activity, embryogenetic changes, and trauma. Here we present a case of an osteoma of the buccal plate of the mandible at the site where a sports-related traumatic injury occurred 15 years earlier. Both conventional and 3-dimensional x-ray examinations were used for diagnosis and preoperative evaluation of the possible involvement of the adjacent anatomic structures. The lesion was treated surgically without complications and the patient made a complete recovery. Histologic tests confirmed the preoperative diagnosis. A review of the international literature is also presented. [ABSTRACT FROM AUTHOR]

Competing Interests: Conflicts of interest The authors declare no conflicts of interest.

Cryptococcoid Sweet syndrome (cSS) is a recently described clinical and histological variant of Sweet syndrome (SS). Its cutaneous presentation is similar to the classical form of SS but it includes atypical findings, such as capsular and yeast-like structures on microscopy that are reminiscent of Cryptococcus species. However, in cSS, fungal staining and cultural examination are negative, whereas myeloperoxidase (MPO) staining on biopsy specimens is typically positive. Due to the rarity and the diagnostic challenge represented by this disease, its extracutaneous involvement, and the latency in its diagnosis, this condition is frequently associated with poor prognosis. In this study, we report the case of a cSS patient with a positive outcome., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Volonté, Fiandrino, Vassallo, Barruscotti, Giorgini, Tomasini and Brazzelli.)

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.

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., (Copyright © 2024 Società Italiana di Anatomia Patologica e Citopatologia Diagnostica, Divisione Italiana della International Academy of Pathology.)

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.

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 aimed 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: This study wascross-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 2 years and every year for over 3 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: Firstly, 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., (© 2024 S. Karger AG, Basel.)

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., (© 2024 S. Karger AG, Basel.)

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., (Copyright © 2023 Elsevier Inc. All rights reserved.)

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., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

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., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Michelerio, Tomasini, Fiandrino, De Amici, Varettoni, Defrancesco, Cavalloni, Brazzelli, Derlino, Paulli, Arcaini and Vassallo.)

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.

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.

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., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier Masson SAS. All rights reserved.)

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., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Gardella, Dominoni, Scatigno, Cesari, Fiandrino, Orcesi and Spinillo.)

Introduction: Glypican-3 (GPC3) is an oncofetal protein involved in cellular signaling, strongly expressed in the placenta, absent or diminished in postnatal life, but often increased in human malignancies. Germline loss-of-function variants of GPC3 gene are associated with Simpson-Golabi-Behmel syndrome type 1 (SGBS1), a rare recessive X-linked overgrowth disease characterized by typical facial features, congenital abnormalities, and an increased risk of developing childhood cancers., Methods: A clinical suspicion of SGBS1 was postulated for a newborn with prenatal history of overgrowth and polyhydramnios, presenting with neonatal weight and length >99th percentile, coarse facies, iris and retinal coloboma, supernumerary nipples, and splenomegaly. While waiting for whole-genome sequencing (WGS) results, we investigated placental GPC3 immunohistochemical expression in the proband, in three additional cases of SGBS1, and disorders commonly associated with fetal macrosomia and/or placentomegaly., Results: WGS in the proband identified a likely pathogenic maternally inherited missense variant in GPC3: c.1645A > G, (p.Ile549Val), and GPC3 immunohistochemistry demonstrated full-thickness loss of stain of the placental parenchyma. The same pattern ("null") was also present in the placentas of three additional cases of SGBS1, but not in those of unaffected controls., Discussion: Immunohistochemical expression of GPC3 in the placenta is highly reproducible. Our findings showed that a "null pattern" of staining is predictive of SGBS1 and represents a valuable aid in the differential diagnosis of fetal macrosomias, allowing targeted genetic testing and earlier diagnosis., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

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., (© 2022 S. Karger AG, Basel.)

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., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Erosive pustular dermatosis of the scalp (EPDS) is an uncommon, pustular, idiopathic disorder typically occurring on the scalp of the elderly, whose diagnosis requires close clinicopathologic correlations. Recently, the primary histopathologic characteristic of EPDS has been identified in some biopsies from hair-bearing scalp lesions as a sterile, vesiculo-pustule involving the infundibulum of hair follicles. To further delineate the clinicopathologic spectrum of the disease, we led a retrospective study of 50 patients (36 males and 14 females) with a diagnosis of EPDS between 2011 and 2021, reviewing clinical and histopathological data. Androgenetic alopecia was present in 32 patients. Triggering factors were present in 21 patients. The vertex was the most common location; one patient also had leg involvement. Two cases were familial. Disease presentation varied markedly from tiny, erosive, scaly lesions to crusted and hemorrhagic plaques, mimicking pustular pyoderma gangrenosum (PPG). Biopsies of patients with severe androgenetic or total baldness produced specimens showing nonspecific pathologic changes (39/50), while in 11 patients with a hair-bearing scalp histopathologic examination, changes were specific. The clinicopathologic similarities between EPDS and PPG suggest that EPDS should be included in the spectrum of autoinflammatory dermatoses. Clinicians could consider the possibility of associated disorders rather than managing EPDS as a sui generis skin disorder.

Background: We evaluated the rates of placental pathologic lesions and their relationship with two-year neurodevelopmental outcomes in very-low-birth-weight (VLBW) infants., Methods: This is a cohort observational study comprising 595 VLBW infants during 2007 to 2015. Neurodevelopmental assessment was carried out at 24 months corrected age., Results: In univariate analysis the rates of survival with normal neurodevelopmental outcomes were lower in pregnancies with severe histologic chorioamnionitis (38 of 43, 88.4% when compared with 305 of 450, 67.8%), severe maternal vascular malperfusion (MVM) (17 of 37, 45.9% when compared with 326/492, 66.3%), and intravillous hemorrhage (37 of 82, 45.1% when compared with 306 of 449, 68.1%). In logistic models, severe MVM (adjusted odds ratio [adj. OR] = 0.45, 95% confidence interval [CI] = 0.22 to 0.92), severe fetal vascular malperfusion (FVM) (adj. OR = 0.46, 95% CI = 0.22 to 0.45), and intravillous hemorrhage (adj. OR = 0.38, 95% CI = 0.22 to 0.62) were associated with lower rates of infant survival with normal neurodevelopmental outcome. FVM (adj. OR = 0.46, 95% CI = 0.21 to 0.97) and intravillous hemorrhage (adj. OR = 0.37, 95% CI = 0.22 to 0.62) were also the only placental lesions that were independent predictors of a lower rate of intact survival in stepwise analysis for prognostic factors of the entire cohort., Conclusions: Placental pathologic findings such as severe MVM, FVM, and intravillous hemorrhage are significant predictors of neonatal survival and subsequent adverse neurodevelopmental outcomes. Data on the placental pathology could be useful in the neurodevelopmental follow-up of VLBW infants., (Copyright © 2021 Elsevier Inc. All rights reserved.)

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., (© The Author(s) 2020. Published by Oxford University Press on behalf of the British Society for Rheumatology.)

Time trends prevalence of human papillomavirus (HPV) genotypes including negative and untypable infections were analyzed during a 15-year period (2005-2019) among 5807 subjects with abnormal pap-smears and/or cervical intraepithelial neoplasia (CIN). The rates of HPV16 dropped by 13% every 3 years (Prevalence Ratio, PR = 0.87, 95% CI = 0.82-0.93) in the CIN1 biopsy, while HPV16 status was unchanged over time in the CIN2+ biopsy. In CIN1 lesions, there was a corresponding increase of HR-HPV types unrelated to nonavalent vaccine. The rates of HPV 18, 31, and 52, decreased by 35% (PR = 0.65, 95% CI = 0.54-0.79), 19% (PR = 0.81, 95% CI = 0.73-0.91), and 21% (PR = 0.79, 95% CI = 0.73-0.86) every 3-year interval in CIN2+, respectively. Overall, the prevalence of negative/untypable HPV specimens in the entire database increased from 9.6% (129/1349) in the period 2011-2013 to 17.6% (161/913) and 28.4% (224/790) in the 2014-2016 period and in the 2017-2019 period, respectively (PR = 1.69, 95% CI = 1.52-1.88). HPV 16 prevalence decreased significantly among subjects with low-grade cervical squamous lesions. A significant increase of both HPV types unrelated to nonavalent vaccination and negative/untypable HPV infections was reported. The prevalence of HPV types among subjects with abnormal pap smears in Northern Italy is changing. Many variables including demographic factors and possibly vaccination could be responsible for this modification.

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., Competing Interests: Declaration of Competing Interest The authors have no conflict of interest to declare., (Copyright © 2020 Elsevier Inc. All rights reserved.)

The aim is to evaluate the clinical consequences of coinfection between HPV 16 and other high-risk HPVs among women with a histological diagnosis of CIN or invasive cervical cancer. A total of 2985 women, with a diagnosis of either CIN or cancer (

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., (© 2019 Nordic Federation of Societies of Obstetrics and Gynecology.)

Introduction: Massive perivillous fibrin deposition (MPDD) is an uncommon placental lesion which has been associated with an increased risk of adverse pregnancy outcome in retrospective series. The purpose of the study was to evaluate the frequency and consequences of MPFD in pregnancies complicated by fetal growth restriction (FGR)., Materials and Methods: A cohort study of 355 pregnancies complicated by FGR diagnosed according to standard ultrasonographic criteria, enrolled, followed and delivered at a single obstetric unit. Pathological placental lesions were classified according to the Amsterdam Placental Workshop Consensus. Penalized logistic regression models were used to evaluate the association of MPFD with maternal risk factors, other pathological lesions and neonatal outcome., Results: The rates of moderate (25-50% of villi) and severe (>50% of villi) MPFD were 8.7% (31/355) and 3.1% (11/355), respectively. Compared to other FGR cases, MPFD pregnancies were characterized by higher placental volume (450 ± 144.5 SD as compared to 412.2 ± 151 cm 3 ,p < 0.001) and lower birthweight/placental weight ratio (5.32 ± 1.53 compared to 6.1 ± 1.52,p < 0.001). The rates of abnormal Doppler ultrasound studies of umbilical and middle cerebral artery were similar in MPFD subjects and controls. After correction for gestational age and birthweight, MPFD was associated with an increased risk of neonatal intraventricular hemorrhage (>grade II) (OR = 5.66,95% CI = 1.69-18.97), sepsis (OR = 5.9, 95% CI = 1.27-27.12), proven necrotizing enterocolitis (OR = 9.84,95% CI = 2.49-38.8) and overall severe adverse neonatal outcome (OR = 5.71,95% CI = 2.05-15.87)., Conclusions: Moderate-to-severe MPFD was relatively common among FGR pregnancies and was associated with morphometric modifications of placenta and with an increased risk of severe adverse neonatal outcome., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Lyme disease acrodermatitis chronica atrophicans is a tertiary form of Lyme borrelliosis. It occurs at least six months, but also up to several years, after a tick bite. This rare condition is probably underestimated because of the difficult diagnosis. Clinical presentations of acrodermatitis chronic atrophicans are quite variable depending upon the duration of the disease. Complimentary explorations are difficult to interpret and rarely specific. Only rare configurations allow formal diagnosis of Borrelia burgdoferi infection. We present a patient who exhibited an atypical clinical presentation of Lyme disease acrodermatitis chronic atrophicans. The clinical outcome was quite favorable with treatment, confirming the diagnosis. Such treatments, which are well tolerated and highly effective, are essential since an untreated disease can lead to potentially severe neurological involvement., (Copyright © 2014 Elsevier Masson SAS. All rights reserved.)

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.