Capillary Hemangioma of the Testis: A Case Report and Literature Review

Introduction/Objective Testicular capillary hemangioma is a rare benign vascular tumor and typically occurs in patients younger than 20 years. Study suggests that the mean age of these patients is usually 25.1 ± 22.7 years. We report a case of a 63-year-old man who underwent an uncomplicated radical orchiectomy for scrotal irritation and testicular fullness. Methods/Case Report Clinically he was found to have a large testicular mass. Ultrasound showed cystocele and an intratesticular tumor. Increased LDH was also found. Gross examination showed a single large cystic cavity containing yellow-colored fluid and a well-circumscribed tan-brown nodule measuring 2.5 × 1.8 × 1.0 cm within the testicular parenchyma. There was no extension into the tunica albuginea. Microscopic examination showed groups of capillaries of varying sizes in a lobular arrangement with bland spindle-like endothelial cells lining these capillary structures. The circumscribed vascular lesion was well-demarcated from the testicular parenchyma by a fibrous 0.1-cm pseudocapsule. The benign nature of this lesion was suggested by the lack of any mitotic activity, anaplasia, or dysplasia. Immunohistochemical staining was strongly positive for endothelial markers (CD31 and CD 34), and negative for mesothelial (WT1) and lymphatic markers (D2-40), excluding an adenomatoid tumor. Based on these characteristic morphological and immunohistochemical findings, the diagnosis of testicular capillary hemangioma was made. After 6 months of follow-up, the patient was well without any clinical evidence of recurrence. Results (if a Case Study enter NA) NA Conclusion While rarity of testicular capillary hemangioma impedes significant changes in how we approach adult testicular masses, the possibility of a benign tumor should always be in mind to consider. This is especially pertinent when patients fall outside the typical age range for germ-cell tumors, and for patients with a solitary testicular mass.

A subset of arachnoid granulations in humans drain to the venous circulation via intradural lymphatic vascular channels

OBJECTIVE The discovery of dural lymphatics has spurred interest in the mechanisms of drainage of interstitial fluid from the CNS, the anatomical components involved in clearance of macromolecules from the brain, mechanisms of entry and exit of immune components, and how these pathways may be involved in neurodegenerative diseases and cancer metastasis. In this study the authors describe connections between a subset of arachnoid granulations (AGs) and the venous circulation via intradural vascular channels (IVCs), which stain positively with established lymphatic markers. The authors postulate that the AGs may serve as a component of the human brain’s lymphatic system. METHODS AGs and IVCs were examined by high-resolution dissection under stereoscope bilaterally in 8 fresh and formalin-fixed human cadaveric heads. The superior sagittal sinus (SSS) and adjacent dura mater were immunostained with antibodies against Lyve-1 (lymphatic marker), podoplanin (lymphatic marker), CD45 (panhematopoietic marker), and DAPI (nuclear marker). RESULTS AGs can be classified as intradural or interdural, depending on their location and site of drainage. Interdural AGs are distinct from the dura, adhere to arachnoid membranes, and occasionally open directly in the inferolateral wall or floor of the SSS, although some cross the infradural folds of the dura’s inner layer to meet with intradural AGs and IVCs. Intradural AGs are located within the leaflets of the dura. The total number of openings from the AGs, lateral lacunae, and cortical veins into the SSS was 45 ± 5.62 per head. On average each cadaveric head contained 6 ± 1.30 intradural AGs. Some intradural AGs do not directly open into the SSS and use IVCs to connect to the venous circulation. Using immunostaining methods, the authors demonstrate that these tubular channels stain positively with vascular and lymphatic markers (Lyve-1, podoplanin). CONCLUSIONS AGs consist of two subtypes with differing modes of drainage into the SSS. A subset of AGs located intradurally use tubular channels, which stain positively with vascular and lymphatic markers to connect to the venous lacunae and ultimately to the SSS. The present study suggests that AGs may function as a component of brain lymphatics. This finding has important clinical implications for cancer metastasis to and from the CNS and may shed light on mechanisms of altered clearance of macromolecules in the setting of neurodegenerative diseases.

Expression of Lymphatic Markers in the Berger’s Space and Bursa Premacularis

We previously reported that the bursa premacularis (BPM), a peculiar vitreous structure located above the macula, contains numerous cells expressing markers of lymphatic endothelial cells, such as podoplanin and LYVE-1. Herein, we examined the expression of lymphatic markers in the Berger’s space (BS), BPM, and vitreous core (VC). BS, BPM, and VC specimens were selectively collected in macular hole and epiretinal membrane patients during vitrectomy and were then immunostained with antibodies for podoplanin, LYVE-1, and fibrillin-1 and -2. By visualization using triamcinolone acetonide, the BS was recognized as a sac-like structure with a septum located behind the lens as well as BPM. Those tissues adhered to the lens or retina in a circular manner by means of a ligament-like structure. Immunostaining showed intense expression of podoplanin and LYVE-1 in the BS. Both BS and BPM stained strongly positive for fibrillin-1 and -2. The VC was faintly stained with antibodies for those lymph-node markers. Our findings indicate that both BS and BPM possibly belong to the lymphatic system, such as lymph nodes, draining excess fluid and waste products into lymphatic vessels in the dura mater of the optic nerve and the ciliary body, respectively, via intravitreal canals.

PROX1 IMMUNOHISTOCHEMICAL ANALYSIS OF PEDIATRIC VASCULAR ANOMALIES, A POSIBLE PROGNOSTIC AND THERAPEUTIC FACTOR OF HEMANGIOMAS?

Infantile and congenital hemangiomas still a challenge for both the pediatric surgeon and the pediatrician. The treatment of hemangiomas must be individualized according to: the type of lesion, location, size, depth, stage of growth and evolution of the lesion. To date, none of the available therapies is considered standard therapy. Currently, personalized therapy is not widely applied in Romania, not being included in the usual therapy protocols in any of the types of hemangioma. This is a starting point for the identification of new specific therapeutic targets that preserve normal endothelial cells and determine the regression of hemangioma, especially recurrent ones and those with an increased proliferation rate. Another controversial and unexplained aspect, consequently unexploited from a therapeutic point of view is represented by the expression and role of lymphatic markers in infantile and congenital hemangiomas.

P03.08 Omental fat in ovarian cancer potentially induces lymphangiogenesis

BackgroundOvarian cancer metastasis occurs by direct multifocal seeding in the peritoneum as well as by migration through the lymphatic system. High grade ovarian carcinoma patients present with distant metastases. Significant risk factors for the development of those are stage, grade, and lymph node involvement. An increase of the number of lymphatic vessels is shown in ovarian tumors and these vessels seem implicated in tumor progression. While the tropism of ovarian cancer cells for fat is well described, the potential impact of a fatty microenvironment on the dissemination of tumor cells via lymphatic vessels has, to our knowledge, never been investigated yet. In this study, we examined the effect of omental fat on lymphangiogenesis in ovarian carcinoma.Materials and MethodsTo examine the effect of omental fat on lymphangiogenesis in OC we used a cohort of 80 human specimens. We analysed lymphatic vessels histologically with D2-40 and Lyve-1 markers. We also developed a healthy fat tissue explant culture model and treated explants with ascites of patient with OC before analysis. We analysed by fluorescence stainings the co expression of adipose derived stem cells (ASCs) and lymphatic markers in these explants.ResultsWe observed a higher density of tumor-associated vessels, especially lymphatic vessels in OC in contact with the omentum; mainly localized along the adipose tissue. We also measured a higher secretion of VEGF-C in tissues with fat compared to tissues without fat. Healthy fat tissues treated with ascites show an increase of number of ASCs, some of them express lymphatic markers such as D2-40 and Lyve-1. In a clinical trial of patients with OC treated by Bevacizumab, we observed a decrease of the number of lymphatic vessels in correlation with a decrease of the inflammation around the fat tissue.DiscussionWe saw an increase in the number of lymphatic vessels in ovarian carcinoma infiltrating fat. These vessels are principally distributed around the fat. We also observed an increase of proliferating ASC expressing lymphatic marker in fat explants treated with ascites. In a clinical trial of patients treated with Bevacizumab, we see a decrease of the lymphatic vessels. This decrease is linked with a decrease in the number of Inflammatory cells. These results together show that the fat tissue can play an important role in the lymphangiogenesis in the ovarian carcinoma. Furthermore, in the dissemination of metastasis through the body. We will next investigate the mechanisms underlying this phenomenon and try to understand all factors implicated in this process.Disclosure InformationB.M.A. Lenoir: None. V. Starrach: None. D. Ferber: None. M. Suarez-Carmona: None. S. Schott: None. I. Zörnig: None. D. Jäger: None. N. Halama: None.

Structural and functional conservation of non-lumenized lymphatic endothelial cells in the mammalian leptomeninges

The vertebrate CNS is surrounded by the meninges, a protective barrier comprised of the outer dura mater and the inner leptomeninges, which includes the arachnoid and pial layers. While the dura mater contains lymphatic vessels, no conventional lymphatics have been found within the brain or leptomeninges. However, non-lumenized cells called Brain/Mural Lymphatic Endothelial Cells or Fluorescent Granule Perithelial cells (muLECs/BLECs/FGPs) that share a developmental program and gene expression with peripheral lymphatic vessels have been described in the meninges of zebrafish. Here we identify a structurally and functionally similar cell type in the mammalian leptomeninges that we name Leptomeningeal Lymphatic Endothelial Cells (LLEC). As in zebrafish, LLECs express multiple lymphatic markers, containing very large, spherical inclusions, and develop independently from the meningeal macrophage lineage. Mouse LLECs also internalize macromolecules from the cerebrospinal fluid, including Amyloid-β, the toxic driver of Alzheimer’s disease progression. Finally, we identify morphologically similar cells co-expressing LLEC markers in human post-mortem leptomeninges. Given that LLECs share molecular, morphological, and functional characteristics with both lymphatics and macrophages, we propose they represent a novel, evolutionary conserved cell type with potential roles in homeostasis and immune organization of the meninges.

Alzheimer disease and Apolipoprotein E4: meningeal brain lymphatics point to new clues in pathogenesis

ABSTRACTThe role of the lymphatic system in brain function and/or dysfunction has long been an enigma. However, recent reports that meningeal lymphatic vessels exist within the mouse and human brain, as well as evidence that mouse meningeal lymphatic vessels play a role in clearing the toxic amyloid-beta peptide connected with Alzheimer’s disease (AD), may herald novel diagnostic and therapeutic avenues. Here, we explore new evidence connecting the lymphatic system of the brain with AD. In particular, we focus on new findings showing that meningeal lymphatic vessels play a role in drainage of cerebrospinal fluid and egress of immune cells from the brain, and that disrupting this vessel system leads to accumulation of amyloid - beta peptide and cognitive dysfunction. We also discuss the hypothesis that apolipoprotein E isoform e4 (APO E4) ─ the leading genetic risk for developing AD ─ is involved in meningeal lymphatic vessel function. By reanalyzing previously published RNA-Seq data, we show that APO E4 knock-in microglia cells express lower levels of genes representing lymphatic markers (a phenomenon we call “attenuated lymphaticness”) and of genes in which functional missense mutations are linked to lymphedema. Accordingly, we propose the hypothesis that APO E4 is involved in the shrinkage of lymphatic vessels. This notion could lead, if verified by additional anatomic and mechanistic data, to the concept that APO E4-related AD (such as in late onset AD or trisomy 21-related AD) is related to lymphosclerosis coupled with lymphedema.

Absence of Intraocular Lymphatic Vessels in Uveal Melanomas with Extrascleral Growth

The aim of this study was to investigate the presence of intraocular lymphatic vessels in patients with uveal melanomas and extrascleral extension using a panel of lymphatic markers. The following immunohistochemical markers were analyzed: lymphatic vessel endothelial hyaluronic acid receptor-1 (LYVE-1), podoplanin (D2-40), prospero-related homeobox gene-1 (Prox-1), pan-endothelial marker cluster of differentiation 31 (CD31), and blood vessel endothelium-specific CD34. Lymphatic vessels were defined as a combination of staining of the following positive markers: LYVE-1, D2-40, Prox-1, and CD31; and no staining of the negative marker CD34. In total, 456 patients were enucleated; 16 of the 46 uveal melanomas with extrascleral extension were contained in stored paraffin tissue. Two samples of the 16 uveal melanomas showed focal positive intraocular vascular staining for LYVE-1 and co-expression of CD31 and CD34. Due to the lack of Prox-1 and D2-40, and positive expression of CD34, these cannot be classified as lymphatic vessels. In one case recruitment of an extraocular, intratumoral lymphatic vascular structure was observed in the periphery of the subconjunctival extrascleral extension. Intraocular lymphatic vessels are absent in uveal melanomas with extrascleral extension; however, we provide proof for recruitment of intratumoral lymphatics by uveal melanomas with extraocular extension from subconjunctival lymphatics that may explain the rare cases of regional lymphatic spread. A panel of antibodies is necessary to detect lymphatic vessels with high specificity.