Role of autophagy and ferroptosis in the development of endometriotic cysts (Review).

It is considered that the etiology of endometriosis is retrograde menstruation of endometrial tissue. Although shed endometrial cells are constantly exposed to a challenging environment with iron overload, oxidative stress and hypoxia, a few cells are able to survive and continue to proliferate and invade. Ferroptosis, an iron­dependent form of non­apoptotic cell death, is known to play a major role in the development and course of endometriosis. However, few papers have concentrated on the dynamic interaction between autophagy and ferroptosis throughout the progression of diseases. The present review summarized the current understanding of the mechanisms underlying autophagy and ferroptosis in endometriosis and discuss their role in disease development and progression. For the present narrative review electronic databases including PubMed and Google Scholar were searched for literature published up to the October 31, 2023. Autophagy and ferroptosis may be activated at early stages in endometriosis development. On the other hand, excessive activation of intrinsic pathways (e.g., estrogen and mechanistic target of rapamycin) may promote disease progression through autophagy inhibition. Furthermore, suppression of ferroptosis may cause further progression of endometriotic lesions. In conclusion, the autophagy and ferroptosis pathways may play a dual role in disease initiation and progression. The present review discussed the temporal transition of non­apoptotic cell death regulation during disease progression from retrograde endometrium to early lesions to established lesions.

Placental Transmogrification of the Lung Presenting as Cystic-Solid Mass: A Case Report.

The gradually progressive solitary cystic-solid mass of chest CT scans is highly suggestive of lung cancer. We report a case of a 29-year-old woman with a persistent cystic-solid lesion in the right upper lobe. A chest CT scan showed a 35 mm × 44 mm × 51 mm focal cystic-solid mass in the anterior segment of the right upper lobe. The size of lesion had increased over 3 years, especially for the solid component. The right upper lobe pneumonectomy was performed. Postoperative pathological examination showed placental transmogrification of the lung, which is a rare cause of pulmonary cystic lesion.

A 10-year retrospective study of the risks and peculiarities in pediatric patients with (para)gonadal tumors and cysts.

INTRODUCTION: Gonadal pediatric tumors are rare, ranking fourth (6%) among pediatric tumors, by Surveillance, Epidemiology, and End Results Program (https:∕∕seer.cancer.gov∕). They have vague symptoms, leading to late discovery, but early detection and identifying its risk factors result in favorable prognosis and reduction of its incidence respectively. PATIENTS, MATERIAL AND METHODS: A 10-year retrospective study identified peculiarities and risk factors in 210 children till age 17 with (para)gonadal tumors. RESULTS: Stress, pollution (agricultural chemicals, insecticides and metal mine), obesity, breastfeeding ≤5 months, malformations [mainly non-genetic related 67∕87 (77%), especially eye malformation - 64%], hormone, smoking, positive heredo-genetic history, rural residence area, abnormal birth weight, and menstruation disorders showed an increased gonadal malignancy risk; relative risk ratio (RR): 1.33, 1.30, 1.34, 1.11, 1.65, 1.16, 1.36, 1.10, 1.00, 1.08 and 1.15 folds, respectively. RR for histopathological subtypes: immature teratoma (IT) (pollution - 1.75, Rhesus positive - 3.41), dysgerminoma (menstruation disorders - 2.80), granulosa cell tumor (stress - 2.10, menstruation disorders - 2.80), mucinous cystadenomas (obesity - 2.84, no postnatal vaccine - 3.71), mature teratomas (stress - 2.35, malformations - 2.18) and serous cystadenomas (breastfeeding ≤5 months - 2.53), dependent variables being mixed germ cell tumors (GCTs) and cysts. Children presenting with bleeding (73%), abdominal distention (62%), elevated tumor markers (91%), (multilocular) solid tumor (88% and 100%), tumor size >10 cm (65%), GCTs (74%), death (100%), metastases (100%), viruses (77%), loss of appetite (68%), and weight (85%), had gonadal malignant tumors, especially mixed GCTs and IT. CONCLUSIONS: Avoiding these risk factors will prevent and reduce gonadal pediatric tumors. Investigating children presenting with the listed peculiarities, especially if exposed to the mentioned risk factors, will enable early gonadal tumor identification, successful patient management, and favorable prognosis.

Presacral Tailgut Cyst.

A tailgut cyst is a rare benign polycystic congenital lesion in presacral or retrorectal space, when there is failure of involution of tailgut. Clinical presentation may be with or without symptoms of different types related to obstruction, infection, or rarely malignancy. Symptoms may be misleading and atypical, so understanding of characteristics of tailgut cysts is important for precise and early diagnosis to be made for proper treatment and to avoid complications and malignant transformation. Magnetic resonance imaging pelvis was used as diagnostic imaging investigation, but the final confirmation was only done by histopathology. Definitive treatment is surgery, though various surgical approaches are described, surgery is tailored which will suit the individual patient's anatomy and suspected diagnosis of mass. This case review used PubMed and Web of Science databases to search for the studies. We found around 176 articles and selected 77 articles in our survey, with 8 reviews, 31 case reports, and 31 case reports and reviews.

RésuméUn kyste intestinal est une lésion congénitale polykystique bénigne rare dans l'espace présacré ou rétrorectal, en cas d'échec de l'involution de l'intestin grêle. La présentation clinique peut être accompagnée ou non de symptômes de différents types liés à une obstruction, une infection ou, plus rarement, une tumeur maligne. Les symptômes peuvent être trompeurs et atypiques, c'est pourquoi il est important de comprendre les caractéristiques des kystes de l'intestin grêle pour établir un diagnostic précis et précoce afin d'établir un traitement approprié et d'éviter les complications et la transformation maligne. L'imagerie par résonance magnétique du bassin a été utilisée comme examen d'imagerie diagnostique, mais la confirmation finale n'a été faite que par histopathologie. Le traitement définitif est la chirurgie, bien que diverses approches chirurgicales soient décrites, la chirurgie est adaptée à l'anatomie de chaque patient et au diagnostic suspecté de masse. Cette revue de cas a utilisé les bases de données PubMed et Web of Science pour rechercher les études. Nous avons trouvé environ 176 articles et sélectionné 77 articles dans notre enquête, avec 8 revues, 31 rapports de cas et 31 rapports de cas et critiques.

ACG Clinical Guideline: Focal Liver Lesions.

Focal liver lesions (FLLs) have become an increasingly common finding on abdominal imaging, especially asymptomatic and incidental liver lesions. Gastroenterologists and hepatologists often see these patients in consultation and make recommendations for management of multiple types of liver lesions, including hepatocellular adenoma, focal nodular hyperplasia, hemangioma, and hepatic cystic lesions including polycystic liver disease. Malignancy is important to consider in the differential diagnosis of FLLs, and healthcare providers must be familiar with the diagnosis and management of FLLs. This American College of Gastroenterology practice guideline uses the best evidence available to make diagnosis and management recommendations for the most common FLLs.

Defective mesenchymal Bmpr1a-mediated BMP signaling causes congenital pulmonary cysts.

Abnormal lung development can cause congenital pulmonary cysts, the mechanisms of which remain largely unknown. Although the cystic lesions are believed to result directly from disrupted airway epithelial cell growth, the extent to which developmental defects in lung mesenchymal cells contribute to abnormal airway epithelial cell growth and subsequent cystic lesions has not been thoroughly examined. In the present study using genetic mouse models, we dissected the roles of bone morphogenetic protein (BMP) receptor 1a (Bmpr1a)-mediated BMP signaling in lung mesenchyme during prenatal lung development and discovered that abrogation of mesenchymal Bmpr1a disrupted normal lung branching morphogenesis, leading to the formation of prenatal pulmonary cystic lesions. Severe deficiency of airway smooth muscle cells and subepithelial elastin fibers were found in the cystic airways of the mesenchymal Bmpr1a knockout lungs. In addition, ectopic mesenchymal expression of BMP ligands and airway epithelial perturbation of the Sox2-Sox9 proximal-distal axis were detected in the mesenchymal Bmpr1a knockout lungs. However, deletion of Smad1/5, two major BMP signaling downstream effectors, from the lung mesenchyme did not phenocopy the cystic abnormalities observed in the mesenchymal Bmpr1a knockout lungs, suggesting that a Smad-independent mechanism contributes to prenatal pulmonary cystic lesions. These findings reveal for the first time the role of mesenchymal BMP signaling in lung development and a potential pathogenic mechanism underlying congenital pulmonary cysts.

Congenital disorders are medical conditions that are present from birth. Although many congenital disorders are rare, they can have a severe impact on the quality of life of those affected. For example, congenital pulmonary airway malformation (CPAM) is a rare congenital disorder that occurs in around 1 out of every 25,000 pregnancies. In CPAM, abnormal, fluid-filled sac-like pockets of tissue, known as cysts, form within the lungs of unborn babies. After birth, these cysts become air-filled and do not behave like normal lung tissue and stop a baby's lungs from working properly. In severe cases, babies with CPAM need surgery immediately after birth. We still do not understand exactly what the underlying causes of CPAM might be. CPAM is not considered to be hereditary ­ that is, it does not appear to be passed down in families ­ nor is it obviously linked to any environmental factors. CPAM is also very difficult to study, because researchers cannot access tissue samples during the critical early stages of the disease. To overcome these difficulties, Luo et al. wanted to find a way to study CPAM in the laboratory. First, they developed a non-human animal 'model' that naturally forms CPAM-like lung cysts, using genetically modified mice where the gene for the signaling molecule Bmpr1a had been deleted in lung cells. Normally, Bmpr1a is part of a set of the molecular instructions, collectively termed BMP signaling, which guide healthy lung development early in life. However, mouse embryos lacking Bmpr1a developed abnormal lung cysts that were similar to those found in CPAM patients, suggesting that problems with BMP signalling might also trigger CPAM in humans. Luo et al. also identified several other genes in the Bmpr1a-deficient mouse lungs that had abnormal patterns of activity. All these genes were known to be controlled by BMP signaling, and to play a role in the development and organisation of lung tissue. This suggests that when these genes are not controlled properly, they could drive formation of CPAM cysts when BMP signaling is compromised. This work is a significant advance in the tools available to study CPAM. Luo et al.'s results also shed new light on the molecular mechanisms underpinning this rare disorder. In the future, Luo et al. hope this knowledge will help us develop better treatments for CPAM, or even help to prevent it altogether.

Lack of inflammation or immune response in cyst tissue of patients with symptomatic non-hydrocephalic pineal cysts.

Pineal cysts are frequently encountered as incidental findings in magnetic resonance imaging, usually devoid of symptoms, yet some patients exhibit symptomatic manifestations possibly associated with the cyst, even in the absence of hydrocephalus. The etiology of these symptoms remains contentious. This study aims to investigate the presence of lymphatic endothelial cell (LEC) markers and indications of inflammation or immune response within the pineal cysts of patients experiencing symptomatic non-hydrocephalic presentations. Eight patients who underwent surgical excision of their cysts were included in the study. Immunohistochemistry was utilized to assess the expression of LYVE-1, PDPN, and VEGFR3 as LEC markers, alongside IL-6 and CD3 for indications of inflammation or immune activity. Our analysis revealed an absence of inflammatory markers or immune response. However, a distinct expression of VEGFR3 was observed, likely localized to neurons within the pineal cyst tissue. We propose that these VEGFR3+ neurons within the pineal cyst may contribute to the headache symptoms reported by these patients. Further investigations are warranted to substantiate this hypothesis.

Chronic active and atrophic gastritis as significant contributing factor to the development of gastric cystica profunda.

Gastric cystica profunda (GCP) is an uncommon but underestimated gastric lesion. Its precancerous potential determines its significance. In addition to previous mucosa injury due to operations, biopsy or polypectomy, chronic active and atrophic gastritis may also lead to the development of GCPs. By carefully examining the stomach and taking biopsy samples from the susceptible regions, the stage of atrophy can be determined. Chronic atrophic gastritis is a risk factor for cancer evolvement and it can also contribute to GCPs formation. GCPs frequently occur close to early gastric cancers (EGCs) or EGC can arise from the cystic glands. Endoscopic resection is an effective and minimally invasive treatment in GCP.

Features of Remyelination after Transplantation of Olfactory Ensheathing Cells with Neurotrophic Factors into Spinal Cord Cysts.

This paper shows for the first time that co-transplantation of human olfactory ensheathing cells with neurotrophin-3 into spinal cord cysts is more effective for activation of remyelination than transplantation of cells with brain-derived neurotrophic factor and a combination of these two factors. The studied neurotrophic factors do not affect proliferation and migration of ensheathing cells in vitro. It can be concluded that the maximum improvement of motor function in rats receiving ensheathing cells with neurotrophin-3 is largely determined by activation of remyelination.

Dissecting microenvironment in cystadenomas and hepatic cysts based on single nucleus RNA-sequencing data.

Hepatic cystadenoma is a rare disease, accounting for about 5% of all cystic lesions, with a high tendency of malignant transformation. The preoperative diagnosis of cystadenoma is difficult, and some cystadenomas are easily misdiagnosed as hepatic cysts at first. Hepatic cyst is a relatively common liver disease, most of which are benign, but large hepatic cysts can lead to pressure on the bile duct, resulting in abnormal liver function. To better understand the difference between the microenvironment of cystadenomas and hepatic cysts, we performed single-nuclei RNA-sequencing on cystadenoma and hepatic cysts samples. In addition, we performed spatial transcriptome sequencing of hepatic cysts. Based on nucleus RNA-sequencing data, a total of seven major cell types were identified. Here we described the tumor microenvironment of cystadenomas and hepatic cysts, particularly the transcriptome signatures and regulators of immune cells and stromal cells. By inferring copy number variation, it was found that the malignant degree of hepatic stellate cells in cystadenoma was higher. Pseudotime trajectory analysis demonstrated dynamic transformation of hepatocytes in hepatic cysts and cystadenomas. Cystadenomas had higher immune infiltration than hepatic cysts, and T cells had a more complex regulatory mechanism in cystadenomas than hepatic cysts. Immunohistochemistry confirms a cystadenoma-specific T-cell immunoregulatory mechanism. These results provided a single-cell atlas of cystadenomas and hepatic cyst, revealed a more complex microenvironment in cystadenomas than in hepatic cysts, and provided new perspective for the molecular mechanisms of cystadenomas and hepatic cyst.

Cytological Features of Fibrin-associated Diffuse Large B-cell Lymphoma Arising in Retroperitoneal Pseudocyst: The First Case Report.

BACKGROUND/AIM: Fibrin-associated diffuse large B-cell lymphoma (FA-DLBCL) is frequently associated with the Epstein-Barr virus (EBV) and manifests as non-mass-forming microscopic lesions within fibrin-rich lesions. Herein, we describe the cytological features of FA-DLBCL. CASE REPORT: A 72-year-old man presented with a large retroperitoneal cystic mass that was treated by cyst aspiration and laparoscopic excision. Individually dispersed large, atypical cells in a necrotic background contained scant cytoplasm and hyperchromatic nuclei with irregular nuclear contours, frequent karyorrhectic debris, and mitotic figures. A fibrinous exudate with necrotic material attached to the inner surface of the cystic mass contained large, atypical cells that were individually scattered or arranged in small clusters. These were positive for cluster of differentiation 20 and Epstein-Barr virus-encoded RNA in situ hybridization. CONCLUSION: We cytologically characterized FA-DLBCL as large, atypical cells that were individually scattered or arranged in small clusters in a necrotic background. To the best of our knowledge, we revealed the cytological features of FA-DLBCL.

Malignancy and "Violated Neck" Rates in Consecutive Cohort of 79 Adult Patients With Solitary Cystic Neck Mass-Lessons Learned and Recommendations for Clinical Practice Guidelines.

OBJECTIVE: The neck region is a common site for solitary cystic neck mass (SCNM) of various etiologies, including congenital, inflammatory, and neoplastic. In adults, the primary focus is excluding malignancy. The objective of this study was to retrospectively analyze the accuracy of available diagnostic technologies for the differentiation of benign and malignant SCNM in adult patients. The study aimed to develop new clinical practice guidelines for evaluating and managing SCNM. METHODS: The primary predictive variables were the diagnostic utilities of fine-needle aspiration cytology (FNAC), ultrasound (U/S), multislice computed tomography, and magnetic resonance imaging. The study's endpoint was the overall diagnostic accuracy in differentiating between benign and malignant SCNM. The final diagnosis was based on histopathology. RESULTS: The study included 79 adult patients: 55 (69.62%) male and 24 (30.38%) female ( P <0.05). The mean age at presentation was 42.1 years (range: 18-84 years). Solitary cystic neck mass was distributed in the anterior neck region in 30 (37.97%) patients and the posterolateral neck regions in 49 (62.03%) patients ( P <0.05). The posterolateral neck regions had a significantly higher rate of malignant SCNM than the anterior neck region [19/49 (38.78%) versus 1/30 (3.33%)] ( P <0.05). There was no statistically significant difference between the U/S+FNAC and U/S+FNAC+multislice computed tomography and/or magnetic resonance imaging groups in differentiating benign and malignant SCNM (40/42 versus 36/37, P >0.05). "Violated neck" was recorded in 2 cases. CONCLUSION: A systematic investigation protocol should be applied to evaluate adult patients with SCNM.

Giant intraperitoneal non-pancreatic pseudocyst: a case report.

INTRODUCTION: Non-pancreatic pseudocysts are rare lesions that typically form from the omentum and mesentery. These cysts have a thick fibrotic wall made up of fibrous tissue and may show signs of calcifications and inflammatory changes. The fluid inside them can vary, ranging from hemorrhage and pus to serous or sometimes chylous content. In most cases, these cysts appear as a result of trauma, surgery, or infection. CASE PRESENTATION: A 35-year-old male patient from Ethiopia presented with swelling in his lower abdomen that had been present for 2 years. Initially, the swelling was small but gradually increased in size. The patient experienced frequent urination but no pain or difficulty during urination, urgency, intermittent urination, or blood in the urine. The swelling was initially painless but became painful 2 months prior to his presentation. Abdominal computed tomography scans revealed a well-defined, lobulated peritoneal lesion measuring 16 × 12 × 10 cm, consisting primarily of fluid-filled cysts with a thick, enhancing wall and septa. Additionally, there was a large, heterogeneous enhancing soft tissue component measuring 8 × 6 cm. As a result, the cystic mass was surgically removed in its entirety with partial removal of the bladder wall, and the patient was discharged in an improved condition. CONCLUSION: Primary non-pancreatic pseudocysts are extremely rare lesions that must be differentiated from other possible causes of cystic lesions within the peritoneal or retroperitoneal regions. Surgeons should be aware of the potential occurrence of these lesions, which may have an unknown origin.

Phenotypes and outcome of diffuse pulmonary non-amyloid light chain deposition disease.

BACKGROUND: Light chain deposition disease (LCDD) is a very rare entity. Clinical manifestations of LCDD vary according to the organs involved. Data on pulmonary LCDD are scarce and limited to small series or case reports. This study aimed to describe the characteristics and outcome of diffuse pulmonary non-amyloid LCDD localized to the lungs. STUDY DESIGN AND METHODS: A multicenter retrospective cohort study was conducted. Clinical characteristics were collected, and chest CTs were centrally reviewed. The diagnosis of pulmonary non-amyloid LCDD was confirmed by immunohistochemistry. RESULTS: Thirty-one cases were identified (68% female), with a median age at diagnosis of 50 years (IQR 20). Baseline FEV1/FVC was < 0.70 in 45% of patients. Mean (± SD) FEV1 and DLCO were 86% ± 26.2 and 52% ± 23.9, respectively. CT revealed peculiar patterns of thin-walled cysts (58%) and thin-walled cystic bronchiectases (27%). Increased serum kappa light chain was found in 87% of patients. Histological analysis showed kappa light chain deposits in all patients, except one with lambda chain deposits. Median annual FEV1 decline was 127 ml (IQR 178) and median DLCO decline was 4.3% (IQR 4.3). Sixteen patients received immunomodulatory treatment or chemotherapy; serum light chain levels decreased in 9 cases (75%), without significant improvement in FEV1 (p = 0.173). Overall, 48% of patients underwent bilateral lung transplantation. Transplant-free survival at 5 and 10 years were 70% and 30%, respectively. An annual FEV1 decline greater than 127 ml/year was associated with increased risk of death or transplantation (p = 0.005). CONCLUSIONS: Diffuse pulmonary LCDD is characterised by female predominance, a peculiar imaging pattern with bronchiectasis and/or cysts, progressive airway obstruction and severe DLCO impairment, and poor outcome. Lung transplantation is a treatment of choice.

[Main Types of Cysts in Dermatopathology: Part 2]. / Principales tipos de quistes en dermatopatología: Parte 2.

This is the second article in a two-part series published in this journal, in which we examine the histopathological characteristics, as well as the differential diagnosis, of the main entities that present as cystic and pseudocystic structures in cutaneous biopsy. In this second article, we address ciliated cutaneous cysts, branchial cysts, Bartholin's cysts, omphalomesenteric cysts, thymic cysts, thyroglossal duct cysts, synovial cysts, and median raphe cysts, as well as mucocele, ganglion, and auricular and digital myxoid pseudocysts.