Cyst Lumen Research Articles

Simultaneous resolution of arachnoid cyst and chronic subdural hematoma after middle meningeal artery embolization: illustrative case.

Arachnoid cysts are cerebrospinal fluid-filled spaces that are typically congenital and treated conservatively or with fenestration when symptomatic. Chronic subdural hematomas (cSDHs) can arise in the presence of arachnoid cysts due to fragile leptomeningeal vessels or veins within the cyst wall or cyst lumen, leading to bleeding and subsequent hematoma formation. Middle meningeal artery (MMA) embolization is regularly used for the treatment of cSDH as an alternative to craniotomy and evacuation. Here, the authors present the first known report of the simultaneous resolution of an arachnoid cyst and cSDH following MMA embolization in an adult. A 24-year-old male presented to the emergency department with 1 month of worsening headaches. Imaging revealed the presence of a cSDH and ipsilateral arachnoid cyst. The cSDH was treated with MMA embolization using coils exclusively. Follow-up imaging 4 months after embolization demonstrated simultaneous resolution of both the hematoma and the arachnoid cyst. MMA embolization has been used for the treatment of cSDH. In cases in which the hematoma is related to an arachnoid cyst, MMA embolization can also lead to the concurrent resolution of both pathologies. https://thejns.org/doi/10.3171/CASE24192.

#2834 Analysis of cyst hetero- and homogeneity to unravel common pathways in autosomal dominant polycystic kidney disease

Abstract Background and Aims Autosomal dominant polycystic kidney disease (ADPKD) is the most common inherited kidney disease, with a prevalence of 1 in ca. 1000 individuals and accounting for 10% of the European dialysis population. It is most frequently (75-80%) caused by mutations in the PKD1 gene encoding Polycystin-1. Besides systemic manifestations such as liver cysts, hypertension and cardiac abnormalities, the most prominent phenotype is the gradual development of kidney cysts, leading to kidney enlargement and a decline in kidney function leading to end-stage kidney disease at an average age of ca. 50 years. The cysts arise from tubular epithelial cells in the nephron that start to dedifferentiate, proliferate and eventually secrete fluid into the cyst lumen promoting its swelling. This process is molecularly regulated by changes in Ca2+, cAMP, PKA and PI3K-Akt-mTOR signaling, among others. The renal cysts are further characterized by ciliary dysfunction, altered signal transduction, loss of polarity, apoptosis, mitochondrial abnormalities, metabolic reprogramming, inflammation, oxidative stress and epigenetic changes. However, the exact sequence of events and their relative importance in the process of cyst formation remains unclear. Therefore, we analyzed the transcriptomic cyst hetero- and homogeneity to identify the pathways that were different, but also shared among individual cysts. Method We performed RNA-Seq analysis on 40 individual cystic membranes of nephrectomized kidneys of 4 PKD1 patients. We included 4 samples of macroscopically healthy tissue from 2 ADPKD kidneys (histologically confirmed to have microcysts) and 4 samples from 4 healthy kidneys. Principal component, cluster and trajectory analysis was performed to explore cyst heterogeneity. Adjacent pieces of cystic membrane were analyzed for histology (H&E, Sirius Red) or stained with FITC-tagged Lotus Tetragonolobus Lectin (LTL) or Dolichos Biflorus Agglutinin (DBA), a proximal and distal tubular marker, respectively. Results Although the cysts clearly separated from the healthy tissues in the analyses, there was also a distinct heterogeneity observed among the cysts that was independent of patient, gender, cyst size, location or fluid color. Pathway analysis revealed that these changes were characterized by a gradual increase of interstitial (remodeling) and inflammation markers, and a gradual decrease in differentiation markers (e.g. development, intercellular junctions, basement membrane) along the trajectory pseudotime. We could identify 6 clusters of cystic samples, with 2 clusters deviating from the main trajectory. With respect to tubular/epithelial dedifferentiation, the decrease in proximal tubular markers already occurred in microcystic tissue and was stronger compared to the other tubular segments. Consequently, none of the analyzed cystic membranes stained positive for LTL, while others showed clear staining for DBA. Microcysts on the other hand stained positive for LTL or DBA. Several cysts showed RNA marker expression of multiple tubular segments. Indeed, smaller macrocysts (diameter in the mm range) were lined by both LTL- and DBA-positive regions. Conclusion By analyzing transcriptomic hetero- and homogeneity among individual cysts, the molecular alterations in ADPKD progression can be tracked down and determined whether they occur similarly in all cysts or at different levels. Our data also suggest that loss of proximal tubular markers in macrocysts is more prominent compared to the decrease in distal markers. Finally, inner cyst walls can consist of cyst-lining cells of multiple origins.

Pkd1RC/RC mice demonstrate remodeling of purinergic receptors in ADPKD cysts

Polycystic kidney diseases (PKD) are characterized by development of multiple cysts, dilations of nephron segments, which replace normal tissues and lead to kidney insuffciency. To identify new gene pathways affected by cyst development in collecting ducts, we used a bulk RNAseq approach comparing gene expression of normal microdissected cortical collecting ducts (n=3 mice) vs cysts microdissected from Pkd1 RC/RC mice (n=4). Bulk-RNA analysis identified 18,000 genes and allowed statistical comparison of over 15,000 genes. Our data reveals that although cysts originate from normal collecting ducts, cystic epithelium show 2692 down-regulated and 2278 up-regulated genes (p<0.05 pAdj. FDR). Ingenuity Pathways Analysis identifies the following intracellular mechanisms mostly affected by transition: Rac and Rho signaling, fibrosis signaling, epithelial-to-mesenchymal transition, cytoskeleton rearrangement and ERK/MAPK signaling. Several of the differentially expressed genes were identified in GWAS of PKD, chronic kidney diseases and hypertension. Our previous publication reported that development of cysts in an autosomal recessive model of PKD is associated with a shift of P2Y to P2X receptor abundance. In the current study we found that in the autosomal dominant Pkd1 RC/RC mice purinergic signaling undergoes similar remodeling. The most abundant ionotropic receptors with reduced expression were P2ry2 -2.25; P2ry4 -1.37, log2 fold change, whereas ionotropic receptors P2rx5 and P2rx7 increased expression (2.88 and 1.53, log2 fold change, respectively). Additionally, analysis detected elevated abundance of P2ry6 and P2ry12 RNA level. We used a model of cystogenesis to test how P2X signaling affects growth of cysts formed by mpkCCDcl4 cells in Matrigel. Stimulation of P2X receptors with α,βMe-ATP significantly increases cyst growth. We hypothesize that the physiological significance of the predominant P2X signaling in the cysts include their role in regulation of ATP release via pannexin-1 channels. Abnormal ATP accumulation in the cyst space was shown earlier to contribute in cystogenesis and we previously showed that pannexin-1 mediates ATP release to the cyst lumen. Co-immunoprecipitatation experiments in mpkCCDcl4 cells revealed that P2X5 and P2X7 receptors bind pannexin-1 whereas P2Y6 and P2Y12 do not interact with pannexin-1. Interestingly, stimulation of cystogenesis with α,βMe-ATP was accompanied by increased abundance of pannexin-1. Lack of functional P2X5 in humans prioritizes P2X7 receptors as a therapeutic target in ADPKD. We conclude that development of ADPKD cysts involves massive transcriptome remodeling of collecting ducts which include a shift in purinergic signaling that facilitates pathogenic pannexin-1 hyperactivity. DK123266 and DK131114. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Bile duct hamartoma in a dog

An 11-year-old female Collie presented with a significantly increased abdominal circumference. Computed tomography of the abdomen revealed that the left lateral lobe of the liver contained a large mass, which was excised via laparotomy. Histologically, many small, dilated, cystic luminal structures were anastomosed and connected to a net-like structure. Immunohistochemistry revealed cytokeratin 19-immunopositive areas, representing bile duct structures in the cystic lumen. Based on these results, the tumour was diagnosed as a bile duct hamartoma. To our knowledge, this is the first report of a bile duct hamartoma in a dog.

Defining the Functional Influence of Endothelial Cell–Expressed Oncogenic Activating Mutations on Vascular Morphogenesis and Capillary Assembly

This study sought to define key molecules and signals controlling major steps in vascular morphogenesis, and how these signals regulate pericyte recruitment and pericyte-induced basement membrane deposition. The morphogenic impact of endothelial cell (EC) expression of activating mutants of Kirsten rat sarcoma virus (kRas), mitogen-activated protein kinase 1 (Mek1), phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha (PIK3CA), Akt serine/threonine kinase 1 (Akt1), Ras homolog enriched in brain (Rheb) Janus kinase 2 (Jak2), or signal transducer and activator of transcription 3 (Stat3) expression versus controls was evaluated, along with EC signaling events, pharmacologic inhibitor assays, and siRNA suppression experiments. Primary stimulators of EC lumen formation included kRas, Akt1, and Mek1, whereas PIK3CA and Akt1 stimulated a specialized type of cystic lumen formation. In contrast, the key drivers of EC sprouting behavior were Jak2, Stat3, Mek1, PIK3CA, and mammalian target of rapamycin (mTor). These conclusions are further supported by pharmacologic inhibitor and siRNA suppression experiments. EC expression of active Akt1, kRas, and PIK3CA led to markedly dysregulated lumen formation coupled to strongly inhibited pericyte recruitment and basement membrane deposition. For example, activated Akt1 expression in ECs excessively stimulated lumen formation, decreased EC sprouting behavior, and showed minimal pericyte recruitment with reduced mRNA expression of platelet-derived growth factor-BB, platelet-derived growth factor-DD, and endothelin-1, critical EC-derived factors known to stimulate pericyte invasion. The study identified key signals controlling fundamental steps in capillary morphogenesis and maturation and provided mechanistic details on why EC activating mutations induced a capillary deficiency state with abnormal lumens, impaired pericyte recruitment, and basement deposition: predisposing stimuli for the development of vascular malformations.

Odontogenic Keratocyst in an Edentulous Patient: Report of an Unusual Case

The purpose of this study was to report a rare case of an odontogenic keratocyst occurring in the edentulous jaw area. A 64-year-old man presented with a painful swelling of the right posterior mandibular vestibule that prevented him from wearing a complete lower denture. Upon intraoral clinical examination, the patient was totally edentulous and had two removable complete dentures. He had a fistula in the vestibular mucosa of edentulous site 48 that was painful upon palpation. Radiological examination revealed an unilocular radiolucent lesion with a continuous peripheral sclerotic border, centered on both the mandibular angle and right branch. Differential diagnosis mainly included a residual cyst and an odontogenic cystic tumor. The biopsy and the excisional material allowed a diagnosis of an odontogenic keratocyst to be made, the cyst being lined by a uniform parakeratinized squamous epithelium, corrugated in places, showing intercellular edema in places, with a well differentiated basal cell layer ranging from cuboidal to columnar in shape, a relatively thin, inflammation-free fibrous wall, and a cyst lumen that contained varying amounts of desquamated keratin. In this case, the surgical risk was represented by paresthesia of both the inferior alveolar and the lingual nerves. The lesion was enucleated without any complications, and the follow-up after 1 year did not reveal any nerve functional damage. Our case underlines the importance for the clinicians to consider a keratocyst in the differential diagnosis of cyst-like lesions presenting in an edentulous area.

Appearance of retinal arterial macroaneurysms in patients using swept-source optical coherence tomographic angiography

BackgroundRetinal arterial macroaneurysm (RAM) is a common clinical disease leading to vision loss in elderly individuals. The appropriate interpretation of swept-source optical coherence tomographic angiography (SS-OCTA), a noninvasive examination, is easy and convenient for detecting the status of RAMs and guiding treatment.MethodsThe objectives of this study were to describe the morphologic characteristics of RAMs using SS-OCTA and to observe whether there are differences in the morphologies of RAMs between SS-OCTA and fundus fluorescein angiography (FFA), before and after treatment. We retrospectively evaluated twenty-two eyes of 22 patients who were diagnosed with RAMs. All patients underwent a complete ophthalmologic examination, including a review of medical records, best-corrected visual acuity (BCVA), fundus photography, FFA and SS-OCTA. RAMs were recorded by SS-OCTA before any treatment or observation decisions were made. The morphologic findings of the RAMs on SS-OCTA were investigated.ResultsOn SS-OCTA, RAMs can show local dilatation or an irregular linear blood flow signal, and the dilated cystic lumen may show thrombosis with a low reflection signal. After treatment, the shape of the RAMs will show reactive changes. The findings on SS-OCTA are not very consistent with those on FFA.ConclusionsThe same RAM may have different manifestations on OCTA and FFA, and OCTA can more conveniently reflect the changes in blood flow signals and treatment response of RAMs.

First record of molecular and pathological investigations of physalopterid larvae infection in northern palm squirrel Funambulus pennantii.

Around 100 reported species of Physaloptera commonly infect mammals, reptiles, birds, and amphibians. The identification of Physaloptera species solely on morphological characteristics is difficult, especially in the case of larval and congeneric infections. The present study is an attempt to identify molecularly and to perform phylogeny and pathology of natural Physaloptera larval infection in northern palm squirrels. The molecular confirmation of the recovered parasitic stages was performed by targeting the nuclear 18S rRNA gene sequence. Phylogenetic analysis and evolutionary divergence of the present study isolate with GenBank™ archived Physaloptera sequences were performed. The cysts (containing the larval stages) were subjected to histopathological examination. Morphological identification of the larval stages revealed the presence of pseudolabia, two spines, and a collar-like projection at the anterior end. Histopathology of the cysts revealed transverse sections of parasites in the lumen along with the thickened cystic wall, infiltration of mononuclear cells, fibrous tissue proliferation in the wall, and cellular debris in the cystic lumen. The molecularly confirmed and sequenced present study isolate was submitted to GenBank™ under the accession number LC706442. Blast analysis revealed 96.82-98.64% nucleotide homology of the present study isolate to the GenBank™ archived Physaloptera sequences. The isolate of the present study was monophyletic with Physaloptera sp. and P. praeputialis recovered from the cats of Haryana, India. Also, evolutionary divergence studies revealed no difference among these sequences. The present study evinced the most probable role of the northern palm squirrel Funambulus pennantii as an aberrant or second intermediate host for P. praeputialis.

Phaeohyphomycotic cyst.

Phaeohyphomycosis is a term used for a rare opportunistic infection caused by a group of dematiaceous fungi which contains melanin in their cell walls. In 1974, the term phaeohyphomycosis was first coined by Ajello for an entity caused by pigmented fungi.1 Four clinical forms of phaeohyphomycosis exist: i) cutaneous, ii) subcutaneous, iii) systemic, and iv) cerebral. Among these, the subcutaneous form (phaeohyphomycotic cyst) is the most common subtype which usually presents as nodular swelling mainly over the distal extremities, which may be misdiagnosed as epidermal inclusion cyst, ganglion or lipoma. These fungi are present in the soil, where they infect mostly farmers and persons working in fields and farms. It was also highlighted that these infections are seen mostly in immunocompromised individuals and are byproducts of antimicrobial, steroid, and immunosuppressive therapy for various illnesses, including cancer, autoimmune diseases, and transplant cases.1 The pigment giving the characteristic brownish-black appearance to the fungi is melanin, which prevents phagocytosis and hence acts as a virulence factor.2 This group has more than 120 species and 70 genera.3 They have a broad spectrum of clinical manifestations, including superficial and deep fungal infections, sinus involvement, and disseminated forms, including lung and brain abscesses. The incidence ranges from 1-3.1 per 100,000 patients.4 The gold standard method for diagnosis is histopathological examination and culture. Fontana-Masson stain is of immense help in identifying these dematiaceous fungi in tissue as it highlights the melanin pigment in the cell walls. Figure 1 refers to a 59-year-old farmer man who presented with nodular swelling over the dorsum of the left hand for the last 9 months. Initially, the swelling was of peanut size, which gradually progressed to the present size of 5x3x2cm. The lesion was painless, well-defined, and freely mobile. The joint was not affected. He is on medication for type II diabetes mellitus and hypertension. He underwent Whipple's surgery for periampullary carcinoma. He was treated for proximal sensory-motor axonal neuropathy and tuberculosis three years back. Because of isoniazid-induced hepatitis, the patient received a modified anti-tuberculous regime for 9 months, after which he developed gastric ulceration with hematemesis and melena. On endoscopic biopsy, he was found to have chronic active gastritis with Helicobacter pylori infection. In addition, the patient had severe iron deficiency and hypoalbuminemia due to malabsorption. After treatment, he completely recovered at the time of hospital discharge. Figure 1 Phaeohyphomycotic cyst. A - A well-encapsulated and unilocular cyst measuring 4.5x2.2x1.8cm in size (scale bar = 2.5cm); The cyst lumen contains homogenous and translucent gelatinous soft material; B - Multinucleated giant cells showing fungal profile with septate, branching and globose swelling (H&E; x200); C - Periodic Acid-Schiff stain showing bright magenta positivity (PAS stain; x200); D - Fontana Masson stain giving brownish black color due to melanin in the fungal cell walls (x200).: Thus, the nodular swelling was wholly excised and sent for histopathological examination. Grossly, a well-encapsulated mass measuring 4.5x2.2x1.8 cm was submitted for histological analysis (Figure 1A). The external aspect appeared intact, yellowish-white, and congested. A unilocular cyst was identified on serial slicing with a capsular thickness of 0.1-0.2cm. The cut surface was soft in consistency with homogenous and gelatinous translucent material within the lumen. On light microscopy, an outer thick fibrous capsule layer was identified. Just beneath this capsular layer was the vascularized granulation tissue, proliferating fibroblasts, numerous multinucleated foreign and Langhan’s giant cells, and variable lymphoplasmacytic cell infiltrate. Also, abundant basophilic mucoid material with a background of many degenerated cells. These giant cells engulfed pigmented fungal profiles that depicted branching, septate and globose swelling (Figure 1B). Periodic Schiff-Acid stain gave bright magenta color to these fungi (Figure 1C), whereas Fontana Masson stain gave brownish black color due to melanin in the fungal cell walls (Figure 1D). Given the morphology, a diagnosis of a phaeohyphomycotic cyst was rendered. On follow-up, the patient is doing well, and has not received any antifungal agent. The leading treatment choice in non-invasive subcutaneous phaeohyphomycosis is local excision.

CeruminousSyringocystadenoma papilliferum: An Extremely Rare Neoplasm of the External Ear

Abstract Introduction/Objective Syringocystadenoma papilliferum (SCAP) is a rare benign adnexal tumor derived from the apocrine or the eccrine sweat glands on the face or the scalp. Ceruminous glands are modified apocrine glands in the external auditory canal and produce cerumen that helps the ear canal against physical damage and microbial invasion. Neoplastic transformation of these glands is even rarer among these benign tumors. Methods/Case Report Here we report a case of a 29-year-old female with a three-month history of progressively worsening right-sided ear pain, muffled hearing, aural fullness, and right-sided shooting aches. She reported that her ear felt sensitive to touch and was painful if she lay on it. Previous treatments included steroids and oral antibiotics without any improvement in symptoms. A physical exam revealed a right narrow ear canal with a cystic mass to the superior lateral canal wall. A CT Temporal Bone showed a 1 cm oval soft tissue lesion in the lateral osseous portion of the right external auditory canal with no underlying osseous erosions identified. This is nonspecific, and neoplasm cannot be excluded. The decision was made for excision. The mass ruptured during excision with dishwater appearing fluid. Microscopic examination showed papillae lined by bilayered glandular epithelium projecting into a cystic lumen. Well defined myoepithelial cell layer is appreciated. Decapitation secretions and plasma cells are noted to be present in the stroma. A final diagnosis of Syringocystadenoma papilliferum is made. Results (if a Case Study enter NA) NA. Conclusion Ceruminous Syringocystadenoma papilliferum is an extremely rare benign tumor of the ceruminous glands of the external ear. Complete excision is the treatment of choice

Identification of an Electrogenic 2Cl−/H+ Exchanger, ClC5, as a Chloride-Secreting Transporter Candidate in Kidney Cyst Epithelium in Tuberous Sclerosis

Kidney cyst expansion in tuberous sclerosis complex (TSC) or polycystic kidney disease (PKD) requires active secretion of chloride (Cl-) into the cyst lumen. In PKD, Cl- secretion is primarily mediated via the cystic fibrosis transmembrane conductance regulator in principal cells. Kidney cystogenesis in TSC is predominantly composed of type A intercalated cells, which do not exhibit noticeable expression of cystic fibrosis transmembrane conductance regulator. The identity of the Cl--secreting molecule(s) in TSC cyst epithelia remains speculative. Based on RNA-sequencing analysis studies, we examined the expression of FOXi1, the chief regulator of acid base transporters in intercalated cells, along with localization of Cl- channel 5 (ClC-5), in kidneys of various models of TSC. Our results in Tsc2+/- mice show that the expansion of kidney cysts corresponds to the induction of Foxi1 and correlates with the strong appearance of ClC-5 and H+-ATPase on the apical membrane of cyst epithelia. In various mouse models of TSC, Foxi1 is robustly induced in the kidney, and ClC-5 appears along with H+-ATPase on the apical membrane of cyst epithelia. Expression of ClC-5 was also detected on the apical membrane of cyst epithelia in humans with TSC but was absent in humans with autosomal dominant PKD or in a mouse model of PKD. These results indicate that ClC-5 is expressed on the apical membrane of cyst epithelia and is a likely candidate mediating Cl- secretion into the kidney cyst lumen in TSC.

MORPHOLOGICAL JUSTIFICATION OF IMMUNOREHABILITATION THERAPY OF CHRONIC NASOPHARYNGITIS ASSOCIATED WITH EBV

Adenotomy, the most widespread surgery in children, which does not solve the problem of symptoms in 19-26% patients. The main reasons are related diseases of nasopharynx, therefore, the indications for surgical intervention must be considered after evaluating the efficacy of conservative treatment. The relevant conservative treatment of CNP associated with EBV infection must include adequate immunorehabilitation effect on nasopharynx epitheliocytes, since the interaction of local immune response and cells infected with Epstein-Barr virus can lead to the control of virus infection.
 Objective of research: to establish the specific features of morphological changes in respiratory epithelium of pharyngeal tonsil in patients with chronic nasopharyngitis associated with EBV.
 Materials and methods. There was carried out the research of surgical material obtained as a result of endoscopic surgical intervention including the removal of hypertrophic part of pharyngeal tonsil in 15 patients diagnosed with chronic nasopharyngitis associated with EBV. The diagnosis was made on the ground of a typical clinical picture and determination of immunoglobulin M, G classes to Epstein-Barr virus in the blood.
 Results. It has been shown that intraepithelial lymphocytic and histiocytic infiltration can be determined morphologically and the edema of loose connective tissue, full blood vessels of the microcirculatory channel can be determined subepithelially which is the morphological sign of the chronic inflammation process.
 The identified structural reconstruction of epithelium reflects the development of virus-induced degenerative processes, namely, koilocytosis and spongiosis. The virus-induced changes in epithelium in the form of koilocytosis can be observed both in covering epithelia and in metaplastic epithelium, which demonstrates the persistence of viral infection in chronic inflammation.
 It has been found that on the background of chronic inflammation the cystic formations in the thickness of the lymphoid tissue are forming and the amphophilic masses of mucus can be visualized on the surface of epitheliocytes with hypersecretory changes, as well as similar mucous masses can be identified in the lumen of cysts of lymphoid tissue. The changes in epithelium in the form of koilocytosis can be seen in the epithelial crypts and cysts as well as indicating that the persistence of infection is viral.
 Conclusions:
 
 In CNP associated with EBV, the morphological changes of respiratory epithelium of nasopharynx are indications of both non-specific inflammatory processes (hyperplasia, metaplasia of epithelium, hypersecretory changes in cells, intraepithelial inflammatory cell infiltration), and specific for viral infections processes (koilocytosis, spongiosis, lymphocytes with wide cytoplasm).
 Structural changes are indications of the development of degenerative virus-induced processes (koilocytosis, spongiosis) combined with reactive changes in epithelial cells (hyperplasia, hypersecretion) that happen both in the surface epithelium and in the crypts with cyst formations.
 There can be seen phenomena of significant hypersecretory activities of epithelium including the accumulation of mucus on the surface of cells as well as in the lumen of crypts and cysts.

Testicular Epidermoid Cyst: A Rare Case Report.

Introduction an importanceTesticular epidermoid cysts (TECs) are rare benign testicular neoplasms. Recently, testicular epidermoid cysts (TECs) are listed as teratoma of prepubertal type, however it is still difficult to differentiate the epidermoid cyst from malign testicular tumor. Therefore, we would like to report testicular epidermoid cyst at our institution.Case presentationA 67-year-old man from Indonesia, presented with chronical painless mass of testis since one year ago. On physical examination obtained normal penile structure with descended testicles, palpable intrascrotal mass with size of 10 × 7 × 5 cm, firm consistency, immobile, without any tenderness, and no lymphadenophaty in groin. Scrotal USG showed intratesticular mass, homogenous parenchym, showed no vascularization during Doppler examination. Histopathological examination revealed the specimen of right scrotum with size of 12.5 cm × 8.5 cm × 6.1 cm with red-brownish colored, during lamellation, obtained encapsulated mass with size of 12.2 cm × 7.9 cm × 6 cm, hollowed space filled with porridge-like texture with capsule thickness of 0.1–0.3 cm.Clinical discussionEpidermoid cysts are benign lesions occurring on the skin usually, however, it rarely occurs in intratesticular area. Most of the cases (60%) presented with the typical onion-ring phenomenon. Histopathological findings commonly revealed typical well-defined cyst lined by a fibrous membrane. No skin appendages are found in the cyst's lumen and no germ cell neoplasm (GCN) is present in the adjacent testicular parenchyma.ConclusionAll testicular masses are considered malignant until proven otherwise. It is necessary to do accurate diagnosis for the prevention of unnecessary radical orchiectomy.

Kidney stone formation in a novel murine model of polycystic kidney disease.

Individuals with autosomal dominant polycystic kidney disease have a higher incidence of stone formation than the general population. However, there are no cystic animal models known to develop stones. Cystic mice compound heterozygous for hypomorphic Pkd1V and Pkd1RC alleles develop cystic kidneys within a few weeks of birth but live beyond 20 wk of age, allowing for the study of cystic comorbidities including stone formation. Cystic Pkd1V/RC mice were euthanized at 3, 13, or 26 wk of age, and their kidneys were analyzed by microcomputed tomography (µCT) for stone formation. Mice had occasional mineral aggregates that could be detected by µCT analysis at 3 wk of age. At 13 or 26 wk of age, numerous white masses were visible beneath the kidney surface. µCT analysis confirmed the masses to be large mineral stone deposits throughout the renal cortex, with mineral content increasing with age. Staining of histological sections with alizarin red and von Kossa suggested that the stone deposits were composed primarily of calcium and phosphate. Microdissection confirmed stones localized within cyst lumens. Analysis of individual stones by µCT and infrared spectroscopy confirmed apatite mineral composition. Urinalysis revealed elevated levels of phosphate and citrate at 3 wk of age and lower pH and elevated levels of calcium and citrate at 13 wk of age, suggesting altered phosphate and calcium homeostasis as a potential cause of mineralization and renal stone formation. This is the first animal model exhibiting overt kidney stone formation in the context of cystic kidney disease.NEW & NOTEWORTHY Compound heterozygous Pkd1V/RC mice were found to form calcium phosphate-containing stones within cysts of the renal cortex by 13 wk of age. This is the first polycystic kidney disease animal model exhibiting spontaneous stone formation. A growing body of evidence suggests a link between renal stone formation and cystic kidney disease. This mouse model may be useful for studying the interplay between stone and cyst formation and the functional role of polycystins in mineral homeostasis.

Activation of Notch3 in Renal Tubular Cells Leads to Progressive Cystic Kidney Disease.

Background: Polycystic kidney disease (PKD) is a genetic disorder affecting millions of people worldwide that is characterized by fluid-filled cysts and leads to end-stage renal disease (ESRD). The hallmarks of PKD are proliferation and dedifferentiation of tubular epithelial cells, cellular processes known to be regulated by Notch signaling. Methods: We found increased Notch3 expression in human PKD and renal cell carcinoma biopsies. To obtain insight into the underlying mechanisms and the functional consequences of this abnormal expression, we developed a transgenic mouse model with conditional overexpression of the intracellular Notch3 (ICN3) domain specifically in renal tubules. We evaluated the alterations in renal function (creatininemia, BUN) and structure (cysts, fibrosis, inflammation) and measured the expression of several genes involved in Notch signaling and the mechanisms of inflammation, proliferation, dedifferentiation, fibrosis, injury, apoptosis and regeneration. Results: After one month of ICN3 overexpression, kidneys were larger with tubules grossly enlarged in diameter, with cell hypertrophy and hyperplasia, exclusively in the outer stripe of the outer medulla. After three months, mice developed numerous cysts in proximal and distal tubules. The cysts had variable sizes and were lined with a single- or multilayered, flattened, cuboid or columnar epithelium. This resulted in epithelial hyperplasia, which was observed as protrusions into the cystic lumen in some of the renal cysts. The pre-cystic and cystic epithelium showed increased expression of cytoskeletal filaments and markers of epithelial injury and dedifferentiation. Additionally, the epithelium showed increased proliferation with an aberrant orientation of the mitotic spindle. These phenotypic tubular alterations led to progressive interstitial inflammation and fibrosis. Conclusions: In summary, Notch3 signaling promoted tubular cell proliferation, the alignment of cell division, dedifferentiation and hyperplasia, leading to cystic kidney diseases and pre-neoplastic lesions.

Isolated tubal torsion associated with hydrosalpinx

Background: Isolated tubal torsion associated with hydrosalpinx is a rare pathology. Our aim was to analyze clinical and imaging features. Case: A 15-year-old girl was admitted to the gynecological emergency department with lower abdominal pain. She was virgin and did not have gynecological examination. In ultrasonography a 10 cm cystic lumen was observed in the right tube. Right salpingectomy was performed. In the pathological examination, there was ischemic changes due to torsion. Conclusion: Isolated tubal torsion is extremely rare in early adolescent period. Early surgical intervention after diagnosis is important for fertility.

Cisto epidérmico: relato de caso raro em criança de 5 meses

ABSTRACT The epidermal cyst is a rare, benign lesion, usually asymptomatic and slowly enlarging, more frequently located in the submandibular region. Its etiology is believed to be associated with the epithelial residual tissues retained in the midline during the closure of the first and second brachial arches, in the third and fourth weeks of intra-uterine life. Its clinical characteristics are of a rubbery consistency to palpation, well defined borders, with the absence of skin appendages within their squamous epithelium lined walls. The final diagnosis is confirmed through histopathological examination with stratified squamous epithelium findings in the cystic fluid lumen or keratin. The treatment is usually surgical and without recurrence and the final diagnosis is confirmed through histopathological examination. This paper aims to present a case report of a congenital epidermal cyst in a 5-month-old female patient located in the mouth floor near the sublingual gland duct. The case was treated with excisional biopsy and after follow-up, there was no recurrence.

Examining the Role of HIPPO/YAP and AMOT Dysregulation and Imbalance in Autosomal Dominant Polycystic Kidney Disease

Autosomal Dominant Polycystic Kidney Disease (ADPKD) is a genetic disorder, most commonly caused by mutations in Polycystin-1 and Polycystin-2 (PC1 and PC2), in which many large lumenal cysts develop in the kidney epithelium. The disease is progressive and ultimately leads to renal dialysis and/or kidney transplant given the lack of efficacious therapeutic intervention. Current research has implicated HIPPO/YAP pathway dysregulation and AMOT imbalance following defects in cell-cell adhesion and contact inhibition as the molecular basis for ADPKD. To test this hypothesis as to the minimum cellular changes necessary to produce cystogenesis, the Bacallao lab microinjected normal human kidney epithelial (HK2) cells in order to drive ectopic expression of Cadherin-8 (CAD-8). Our Imaging with confocal microscopy and subsequent image analysis indicates CAD-8, a cadherin abnormally expressed in renal epithelial cells of ADPKD patients, is sufficient to cause formation of cysts albeit with uncharacteristically small lumens compared to typical ADPKD cysts. However, these cells exhibit significantly larger cyst expansion when they are transduced for coexpression of CAD-8 and constitutively active YAP5SA. Cells modified for heterozygosity with respect to a defective PC1 gene (PKD) also exhibited significantly larger lumen cysts when transduced with YAP5SA reinforcing the role of Yap in lumen size control. Finally, PKD cells transduced with AMOTL1 exhibited significantly smaller lumen sizes. AMOTL1 belongs to a family of adapter proteins which bind and inhibit Yap activity thus showing conclusively that positive and negative modulation of Yap activity correlates with cyst lumen size expansion and reduction respectively.
 “This project was funded, in part, with support from the O’Brien Center for Advanced Renal Microscopic Analysis funded, in part by P30 DK079312 from the National Institutes of Health. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.”

Deep Learning-Based Microscopic Diagnosis of Odontogenic Keratocysts and Non-Keratocysts in Haematoxylin and Eosin-Stained Incisional Biopsies.

Background: The goal of the study was to create a histopathology image classification automation system that could identify odontogenic keratocysts in hematoxylin and eosin-stained jaw cyst sections. Methods: From 54 odontogenic keratocysts, 23 dentigerous cysts, and 20 radicular cysts, about 2657 microscopic pictures with 400× magnification were obtained. The images were annotated by a pathologist and categorized into epithelium, cystic lumen, and stroma of keratocysts and non-keratocysts. Preprocessing was performed in two steps; the first is data augmentation, as the Deep Learning techniques (DLT) improve their performance with increased data size. Secondly, the epithelial region was selected as the region of interest. Results: Four experiments were conducted using the DLT. In the first, a pre-trained VGG16 was employed to classify after-image augmentation. In the second, DenseNet-169 was implemented for image classification on the augmented images. In the third, DenseNet-169 was trained on the two-step preprocessed images. In the last experiment, two and three results were averaged to obtain an accuracy of 93% on OKC and non-OKC images. Conclusions: The proposed algorithm may fit into the automation system of OKC and non-OKC diagnosis. Utmost care was taken in the manual process of image acquisition (minimum 28–30 images/slide at 40× magnification covering the entire stretch of epithelium and stromal component). Further, there is scope to improve the accuracy rate and make it human bias free by using a whole slide imaging scanner for image acquisition from slides.

The chloride channel CFTR is not required for cyst growth in an ADPKD mouse model.

Autosomal dominant polycystic kidney disease (ADPKD) is characterized by the development of bilateral renal cysts which enlarge continuously, leading to compression of adjacent intact nephrons. The growing cysts lead to a progressive decline in renal function. Cyst growth is driven by enhanced cell proliferation and chloride secretion into the cyst lumen. Chloride secretion is believed to occur mainly by the cAMP-activated cystic fibrosis transmembrane conductance regulator (CFTR), with some contribution by the calcium-activated chloride channel TMEM16A. However, our previous work suggested TMEM16A as a major factor for renal cyst formation. The contribution of CFTR to cyst formation has never been demonstrated in an adult ADPKD mouse model. We used mice with an inducible tubule-specific Pkd1 knockout, which consistently develop polycystic kidneys upon deletion of Pkd1. Cellular properties, ion currents, and cyst development in these mice were compared with that of mice carrying a co-deletion of Pkd1 and Cftr. Knockout of Cftr did not reveal any significant impact on cyst formation in the ADPKD mouse model. Furthermore, knockout of Cftr did not attenuate the largely augmented cell proliferation observed in Pkd1 knockout kidneys. Patch clamp analysis on primary renal epithelial cells lacking expression of Pkd1 indicated an only marginal contribution of CFTR to whole cell Cl- currents, which were clearly dominated by calcium-activated TMEM16A currents. In conclusion, CFTR does not essentially contribute to renal cyst formation in mice caused by deletion of Pkd1. Enhanced cell proliferation and chloride secretion is caused primarily by upregulation of the calcium-activated chloride channel TMEM16A.