Branchioma is an uncommon benign neoplasm with an adult male predominance, typically occurring in the lower neck region. Different names have been used for this entity in the past (ectopic hamartomatous thymoma, branchial anlage mixed tumor, thymic anlage tumor, biphenotypic branchioma), but currently, the term branchioma has been widely accepted. Branchioma is composed of endodermal and mesodermal lineage derivatives, in particular epithelial islands, spindle cells, and mature adipose tissue without preexistent thymic tissue or evidence of thymic differentiation. Twenty-three branchiomas were evaluated morphologically. Eighteen cases with sufficient tissue were assessed by immunohistochemistry, next-generation sequencing (NGS) using the Illumina Oncology TS500 panel, and fluorescence in situ hybridization (FISH) using an RB1 dual-color probe. All cases showed a biphasic morphology of epithelial and spindle cells with intermingled fatty tissue. Carcinoma arising in branchioma was detected in three cases. The neoplastic cells showed strong AE1/3 immunolabeling (100%), while the spindle cells expressed CD34, p63, and SMA (100%); AR was detected in 40-100% of nuclei (mean, 47%) in 14 cases. Rb1 showed nuclear loss in ≥ 95% of neoplastic cells in 16 cases (89%), while two cases revealed retained expression in 10-20% of tumor cell nuclei. NGS revealed a variable spectrum of likely pathogenic variants (n = 5) or variants of unknown clinical significance (n = 6). Loss of Rb1 was detected by FISH in two cases. Recent developments support branchioma as a true neoplasm, most likely derived from the rudimental embryological structures of endoderm and mesoderm. Frequent Rb1 loss by immunohistochemistry and heterozygous deletion by FISH is a real pitfall and potential confusion with other Rb1-deficient head and neck neoplasms (i.e., spindle cell lipoma), especially in small biopsy specimens.
- MeSH
- branchiom * patologie MeSH
- dospělí MeSH
- hybridizace in situ fluorescenční MeSH
- lidé MeSH
- molekulární biologie MeSH
- nádory brzlíku * MeSH
- nádory glandulární a epitelové * MeSH
- nádory měkkých tkání * patologie MeSH
- nádory sítnice * MeSH
- retinoblastom * genetika patologie MeSH
- thymom * MeSH
- Check Tag
- dospělí MeSH
- lidé MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
Branchioma (previously called ectopic hamartomatous thymoma, branchial anlage mixed tumor, or thymic anlage tumor) is a rare lower neck lesion with an adult male predominance and an uncertain histogenesis. Except for 4 cases, all branchiomas described in the literature were benign. Recently, HRAS mutation was detected in one case, but still little is known about the molecular genetic background of this rare entity. We herein report the histological, immunohistochemical, and molecular genetic analysis of a branchioma with a nested/organoid (neuroendocrine-like) morphology in a 78-year-old man. Histology revealed classical branchioma areas merging with nested/organoid cellular component lacking conventional features of malignancy. Immunohistochemistry was positive for high-molecular-weight cytokeratins. CD34 was expressed in the spindle cell component. Moreover, the tumor cells showed near-complete loss of retinoblastoma (RB1) expression (<1% of cells positive). All neuroendocrine markers (synaptophysin, chromogranin, and INSM1) were negative. Next-generation sequencing (TSO500 Panel) revealed 5 pathogenic/likely pathogenic mutations including 1 mutation in KRAS and 2 different mutations in each of MSH6 and PTEN. FISH and DNA sequencing were negative for RB1 gene alterations. To our knowledge, this is the first report of a branchioma showing misleading nested/organoid morphology and the first report on Rb1 immunodeficiency in this entity, in addition to multiple gene mutations revealed by NGS.
- MeSH
- branchiom * patologie MeSH
- lidé MeSH
- nádory měkkých tkání * MeSH
- nádory sítnice * MeSH
- organoidy patologie MeSH
- represorové proteiny MeSH
- retinoblastom * genetika patologie MeSH
- senioři MeSH
- Check Tag
- lidé MeSH
- mužské pohlaví MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- kazuistiky MeSH
- MeSH
- diferenciální diagnóza MeSH
- dítě MeSH
- enukleace oka metody MeSH
- geny retinoblastomu genetika MeSH
- lidé MeSH
- nádory oka diagnostické zobrazování diagnóza klasifikace patologie MeSH
- oční paraneoplastické syndromy diagnóza klasifikace MeSH
- oftalmoskopie metody MeSH
- retinoblastom * chirurgie diagnóza klasifikace patologie MeSH
- uveitida diagnóza MeSH
- Check Tag
- dítě MeSH
- lidé MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- Publikační typ
- kazuistiky MeSH
- MeSH
- dítě MeSH
- hemangiom klasifikace patologie MeSH
- lidé MeSH
- melanom klasifikace patologie MeSH
- nádory oka * chirurgie klasifikace patologie radioterapie terapie MeSH
- oftalmologické chirurgické výkony klasifikace MeSH
- radioterapie klasifikace MeSH
- retinoblastom dějiny diagnóza farmakoterapie klasifikace patologie MeSH
- Check Tag
- dítě MeSH
- lidé MeSH
- Publikační typ
- přehledy MeSH
- MeSH
- chromozomální aberace klasifikace MeSH
- chromozomální poruchy genetika klasifikace patologie MeSH
- dědičné nemoci očí * genetika klasifikace patologie MeSH
- genetická terapie MeSH
- genetické nemoci vázané na chromozom X genetika MeSH
- genetické poradenství etika metody MeSH
- glaukom genetika MeSH
- lidé MeSH
- multifaktoriální dědičnost MeSH
- oční nemoci genetika klasifikace vrozené MeSH
- repetitivní sekvence nukleových kyselin MeSH
- retinoblastom genetika patologie MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- přehledy MeSH
INTRODUCTION: Advanced intraocular retinoblastoma can be cured by enucleation, but spread of retinoblastoma cells beyond the natural limits of the eye is related to a high mortality. Adjuvant therapy after enucleation has been shown to prevent metastasis in children with risk factors for extraocular retinoblastoma. However, histological criteria and adjuvant treatment regimens vary and there is no unifying consensus on the optimal choice of treatment. METHOD: Data on guidelines for adjuvant treatment in European retinoblastoma referral centres were collected in an online survey among all members of the European Retinoblastoma Group (EURbG) network. Extended information was gathered via personal email communication. RESULTS: Data were collected from 26 centres in 17 countries. Guidelines for adjuvant treatment were in place at 92.3% of retinoblastoma centres. There was a consensus on indication for and intensity of adjuvant treatment among more than 80% of all centres. The majority of centres use no adjuvant treatment for isolated focal choroidal invasion or prelaminar optic nerve invasion. Patients with massive choroidal invasion or postlaminar optic nerve invasion receive adjuvant chemotherapy, while microscopic invasion of the resection margin of the optic nerve or extension through the sclera are treated with combined chemo- and radiotherapy. CONCLUSION: Indications and adjuvant treatment regimens in European retinoblastoma referral centres are similar but not uniform. Further biomarkers in addition to histopathological risk factors could improve treatment stratification. The high consensus in European centres is an excellent foundation for a common European study with prospective validation of new biomarkers.
- MeSH
- adjuvantní chemoterapie metody MeSH
- adjuvantní radioterapie metody MeSH
- dítě MeSH
- enukleace oka MeSH
- kombinovaná terapie metody MeSH
- lidé MeSH
- nádory sítnice patologie terapie MeSH
- předškolní dítě MeSH
- prognóza MeSH
- protokoly antitumorózní kombinované chemoterapie terapeutické užití MeSH
- průzkumy a dotazníky MeSH
- retinoblastom patologie terapie MeSH
- rizikové faktory MeSH
- Check Tag
- dítě MeSH
- lidé MeSH
- předškolní dítě MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Geografické názvy
- Evropa MeSH
Retinoblastoma (Rb) is the most common primary malignant intraocular tumor in children which develops from the retinal stem cells. Systemic chemotherapy is the typical therapeutic treatment and though most children survive Rb, they often lose their vision, or the eye needs to be enucleated. Regarding to the pure availability of the target tumor by systemic chemotherapy, the local anticancer drug administration would be advantageous to increase the local drug concentration and minimize adverse side effects of chemotherapy. The present paper describes a new hydrogel implant enabled to deliver therapeutically active doses of low molecular weight hydrophilic antitumor drugs topotecan and vincristine. The hydrogel implant is proposed as bi-layered with an inner hydrophilic layer from 2-hydroxyethyl methacrylate (HEMA) serving as a reservoir of the chemotherapeutic agent and an outer hydrophobic layer from 2-ethoxyethyl methacrylate (EOEMA) acting as a barrier to protect the surrounding vascularized tissue against cytotoxicity of the delivered chemotherapeutics. The experiments with enucleated pig eyes demonstrated the ability of tested drugs to diffuse through sclera and reach the vitreous humor. HEMA-based hydrogels were examined in terms of sorption, release and transport properties, showing the possibility of adjusting the loading capacity and diffusion of the drugs by the degree of crosslinking. The EOEMA-based gels proved to be an inert for drug sorption and diffusion. A chorioallantoic membrane assay demonstrated excellent biocompatibility of unloaded hydrogels, and in vitro experiments confirmed significant cytotoxicity of drug-loaded hydrogels against a Rb cell line; 2 days for those topotecan-loaded and a minimum of 6 days for vincristine-loaded hydrogels. The bi-layered hydrogel implant can be considered promising for local administration of active agents to eye-globe for the treatment of Rb and also other ocular disorders.
- MeSH
- hydrogely chemie MeSH
- kinetika MeSH
- lidé MeSH
- methakryláty chemie MeSH
- nádorové buněčné linie MeSH
- nosiče léků chemie MeSH
- oči účinky léků metabolismus MeSH
- prasata MeSH
- protézy a implantáty MeSH
- retinoblastom metabolismus patologie MeSH
- stabilita léku MeSH
- topotekan chemie metabolismus farmakologie MeSH
- viabilita buněk účinky léků MeSH
- vinkristin chemie metabolismus farmakologie MeSH
- vysokoúčinná kapalinová chromatografie MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
In our routine and consultative pathology practices, we have repeatedly encountered an unusual subcutaneous fatty tumor with notable anisocytosis, single-cell fat necrosis, and patchy, often mild, adipocytic nuclear atypia. Because of the focal atypia, consultative cases have most often been received with concern for a diagnosis of atypical lipomatous tumor. Similar tumors have been described in small series under the designations "subcutaneous minimally atypical lipomatous tumors" and "anisometric cell lipoma." Sixty-six cases of this tumor type were collected and reviewed. Immunohistochemistry for p53, MDM2, CDK4, Retinoblastoma 1 (RB1) protein, CD34, S100, and CD163 was performed. Cases were tested for MDM2 gene amplification and RB1 gene deletion with fluorescence in situ hybridization (FISH) and for TP53 mutations by Sanger sequencing. Next-generation sequencing analysis using a panel of 271 cancer-related genes, including TP53, RB1, and MDM2, was also carried out. Our patient cohort included 57 male patients, 8 female patients, and 1 patient of unstated sex, who ranged in age from 22 to 87 years (mean: 51.2 y). All tumors were subcutaneous, with most examples occurring on the upper back, shoulders, or posterior neck (86.4%). Ten patients had multiple (2 to 5) lipomatous tumors, and the histology was confirmed to be similar in the different sites in 4 of them, including 1 patient who had a retinoblastoma diagnosed at age 1. The tumors were generally well circumscribed. At low magnification, there was notable adipocytic size variation with single-cell fat necrosis in the background associated with reactive histiocytes. Adipocytic nuclear atypia was typically patchy and characterized by chromatin coarsening, nuclear enlargement, and focal binucleation or multinucleation. Focal Lochkern change was frequent. In most instances, the degree of atypia was judged to be mild, but in 3 instances, it was more pronounced. Spindle cells were sparse or absent, and when present, cytologically bland. Thick ropy collagen bundles were absent. In all cases, p53 immunoexpression was noted (range: 2% to 20% of adipocytic nuclei), characteristically highlighting the most atypical cells. Twenty of 50 cases had MDM2 immunoreactivity, usually in <1% of the neoplastic cells, but in 4 cases, up to 10% of the cells were positive. Of 32 cases tested, 22 showed a near total loss of RB1 immunoexpression, and the remainder showed partial loss. Three of 13 cases showed RB1 gene deletion in >45% of the cells by FISH (our threshold value for reporting a positive result) with an additional 3 cases being very close to the required cutoff value. MDM2 gene amplification was absent in all 60 cases tested, including those with the greatest MDM2 immunoexpression and most pronounced atypia. All 5 tested cases showed no TP53 mutation with Sanger sequencing. Because of material quality issues, next-generation sequencing analysis could be performed in only 3 cases, and this did not reveal any recurrent mutations. All tumors were managed by simple local excision. Follow-up was available for 47 patients (range: 1 to 192 mo; mean: 27 mo) and revealed 2 local recurrences and no metastases. Dysplastic lipoma is a distinctive atypical fatty tumor variant that has p53 overexpression and RB1 gene abnormalities and lacks MDM2 gene amplification by FISH. These tumors have a strong male predominance and a notable tendency to involve the subcutaneous tissue of the shoulders, upper back and posterior neck. Multifocality is frequent (18.9% of patients with follow-up information), and there is a rare association with retinoblastoma. This tumor warrants separation from ordinary lipoma with fat necrosis, fat-rich spindle cell lipoma and the conventional form of atypical lipomatous tumor that features MDM2 gene amplification.
- MeSH
- amplifikace genu * MeSH
- diferenciální diagnóza MeSH
- dospělí MeSH
- genetická predispozice k nemoci MeSH
- hybridizace in situ fluorescenční * MeSH
- imunohistochemie MeSH
- lidé středního věku MeSH
- lidé MeSH
- liposarkom * chemie genetika patologie MeSH
- mladý dospělý MeSH
- mnohočetné primární nádory * chemie genetika patologie MeSH
- mutace MeSH
- mutační analýza DNA MeSH
- nádorové biomarkery * analýza genetika MeSH
- nádorový supresorový protein p53 * analýza genetika MeSH
- prediktivní hodnota testů MeSH
- protoonkogenní proteiny c-mdm2 genetika MeSH
- retinoblastom * chemie genetika patologie MeSH
- retrospektivní studie MeSH
- senioři nad 80 let MeSH
- senioři MeSH
- tuková nekróza MeSH
- tukové buňky * chemie patologie MeSH
- ubikvitinligasy genetika MeSH
- upregulace MeSH
- vazebné proteiny retinoblastomu genetika MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mladý dospělý MeSH
- mužské pohlaví MeSH
- senioři nad 80 let MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- multicentrická studie MeSH
- práce podpořená grantem MeSH
- Geografické názvy
- Evropa MeSH
- MeSH
- abnormality očí * MeSH
- amblyopie diagnóza terapie MeSH
- diagnostické techniky oftalmologické MeSH
- konjunktivitida diagnóza etiologie terapie MeSH
- lidé MeSH
- nemoci novorozenců diagnóza etiologie terapie MeSH
- obstrukce slzovodu diagnóza terapie MeSH
- oči patologie MeSH
- retinoblastom diagnóza patologie terapie MeSH
- retinopatie nedonošených etiologie terapie MeSH
- strabismus terapie MeSH
- vrozené vady diagnóza etiologie MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- přehledy MeSH
- MeSH
- hemangiom diagnóza terapie MeSH
- lidé MeSH
- melanom diagnóza patologie terapie MeSH
- metastázy nádorů MeSH
- nádory oka * diagnóza patologie terapie MeSH
- nádory spojivky diagnóza patologie terapie MeSH
- nádory uvey diagnóza patologie terapie MeSH
- pigmentový névus diagnóza patologie MeSH
- retinoblastom diagnóza patologie terapie MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- přehledy MeSH