A Clinicopathologic Study of Head and Neck Malignant Peripheral Nerve Sheath Tumors

Abstract

Head and neck high grade malignant peripheral nerve sheath tumors (HN-MPNSTs) are rare highly aggressive soft tissue sarcomas that show overlapping morphologic and immunophenotypic features with melanoma and other high grade sarcomas, resulting in diagnostic challenges, particularly in sporadic settings. Recent discoveries have implicated loss of function mutations in the polycomb repressive complex 2 (PRC2) components, including EED or SUZ12 genes, as one of the leading pathogenetic mechanisms in high grade MPNST. MPNSTs with PRC2 loss are associated with complete loss of trimethylation at lysine 27 of histone H3 (H3K27me3), which emerged as a reliable immunohistochemical marker in the diagnosis of sporadic and radiation induced MPNST. As the diagnosis of MPNST in the HN is particularly challenging to distinguish from melanoma and other sarcoma types, we carried out a clinicopathologic analysis on HN-MPNST patients managed at our institution over a 20-year period (1997–2016), using the latest diagnostic criteria including H3K27me3 staining and other molecular investigations. The overall survival of HN-MPNST was compared with other HN soft tissue sarcomas. The diagnosis of HN-MPNST was confirmed in 13 patients (seven males and six females), with a mean age of 31 years; with 3 (23%) patients being of pediatric age. The most common site was the neck soft tissue (77%). Two-thirds of patients (n = 9) had stigmata of NF1, three had prior radiotherapy and only one developed a de novo MPNST. All except one tumor (86%) tested showed loss of H3K27me3 expression, including all non-NF1 patients. The 2 and 5-year DSS rates were 50 and 30%. The 2-year DFS rate was 21%. Adverse predictors on DSS included adult age (p = 0.011), prior-history of RT (p = 0.003) and recurrence (p = 0.003). Compared to other molecularly confirmed subsets of HN sarcomas (Ewing and Ewing-like sarcoma, rhabdomyosarcoma and synovial sarcoma), HN-MPNST had the worst overall survival (p < 0.0001). We conclude that HN-MPNSTs are highly aggressive sarcomas associated with an unfavorable outcome and the utility of H3K27me3 IHC stains in the evaluation of MPNST is a reliable ancillary diagnostic adjunct.

http://ift.tt/2tQFJAN

A Clinicopathologic Study of Head and Neck Malignant Peripheral Nerve Sheath Tumors

Abstract

Head and neck high grade malignant peripheral nerve sheath tumors (HN-MPNSTs) are rare highly aggressive soft tissue sarcomas that show overlapping morphologic and immunophenotypic features with melanoma and other high grade sarcomas, resulting in diagnostic challenges, particularly in sporadic settings. Recent discoveries have implicated loss of function mutations in the polycomb repressive complex 2 (PRC2) components, including EED or SUZ12 genes, as one of the leading pathogenetic mechanisms in high grade MPNST. MPNSTs with PRC2 loss are associated with complete loss of trimethylation at lysine 27 of histone H3 (H3K27me3), which emerged as a reliable immunohistochemical marker in the diagnosis of sporadic and radiation induced MPNST. As the diagnosis of MPNST in the HN is particularly challenging to distinguish from melanoma and other sarcoma types, we carried out a clinicopathologic analysis on HN-MPNST patients managed at our institution over a 20-year period (1997–2016), using the latest diagnostic criteria including H3K27me3 staining and other molecular investigations. The overall survival of HN-MPNST was compared with other HN soft tissue sarcomas. The diagnosis of HN-MPNST was confirmed in 13 patients (seven males and six females), with a mean age of 31 years; with 3 (23%) patients being of pediatric age. The most common site was the neck soft tissue (77%). Two-thirds of patients (n = 9) had stigmata of NF1, three had prior radiotherapy and only one developed a de novo MPNST. All except one tumor (86%) tested showed loss of H3K27me3 expression, including all non-NF1 patients. The 2 and 5-year DSS rates were 50 and 30%. The 2-year DFS rate was 21%. Adverse predictors on DSS included adult age (p = 0.011), prior-history of RT (p = 0.003) and recurrence (p = 0.003). Compared to other molecularly confirmed subsets of HN sarcomas (Ewing and Ewing-like sarcoma, rhabdomyosarcoma and synovial sarcoma), HN-MPNST had the worst overall survival (p < 0.0001). We conclude that HN-MPNSTs are highly aggressive sarcomas associated with an unfavorable outcome and the utility of H3K27me3 IHC stains in the evaluation of MPNST is a reliable ancillary diagnostic adjunct.

http://ift.tt/2tQFJAN

A Clinicopathologic Study of Head and Neck Malignant Peripheral Nerve Sheath Tumors

Abstract

Head and neck high grade malignant peripheral nerve sheath tumors (HN-MPNSTs) are rare highly aggressive soft tissue sarcomas that show overlapping morphologic and immunophenotypic features with melanoma and other high grade sarcomas, resulting in diagnostic challenges, particularly in sporadic settings. Recent discoveries have implicated loss of function mutations in the polycomb repressive complex 2 (PRC2) components, including EED or SUZ12 genes, as one of the leading pathogenetic mechanisms in high grade MPNST. MPNSTs with PRC2 loss are associated with complete loss of trimethylation at lysine 27 of histone H3 (H3K27me3), which emerged as a reliable immunohistochemical marker in the diagnosis of sporadic and radiation induced MPNST. As the diagnosis of MPNST in the HN is particularly challenging to distinguish from melanoma and other sarcoma types, we carried out a clinicopathologic analysis on HN-MPNST patients managed at our institution over a 20-year period (1997–2016), using the latest diagnostic criteria including H3K27me3 staining and other molecular investigations. The overall survival of HN-MPNST was compared with other HN soft tissue sarcomas. The diagnosis of HN-MPNST was confirmed in 13 patients (seven males and six females), with a mean age of 31 years; with 3 (23%) patients being of pediatric age. The most common site was the neck soft tissue (77%). Two-thirds of patients (n = 9) had stigmata of NF1, three had prior radiotherapy and only one developed a de novo MPNST. All except one tumor (86%) tested showed loss of H3K27me3 expression, including all non-NF1 patients. The 2 and 5-year DSS rates were 50 and 30%. The 2-year DFS rate was 21%. Adverse predictors on DSS included adult age (p = 0.011), prior-history of RT (p = 0.003) and recurrence (p = 0.003). Compared to other molecularly confirmed subsets of HN sarcomas (Ewing and Ewing-like sarcoma, rhabdomyosarcoma and synovial sarcoma), HN-MPNST had the worst overall survival (p < 0.0001). We conclude that HN-MPNSTs are highly aggressive sarcomas associated with an unfavorable outcome and the utility of H3K27me3 IHC stains in the evaluation of MPNST is a reliable ancillary diagnostic adjunct.

http://ift.tt/2tQFJAN

Paraneoplastic pemphigus seen in 4 patients with hematologic malignancies formerly treated with rituximab

Abstract

Paraneoplastic pemphigus (PNP) is a peculiar variant of pemphigus with pathognomonic clinical, histological, and immunological features. It is typically associated with hematologic malignancies (84%), such as non-Hodgkin lymphomas (NHL) (most common), chronic lymphocytic leukemia (CLL), Castleman disease, thymoma, Waldenström's macroglobulinemia, Hodgkin lymphoma, and monoclonal gammopathy, as well as non-hematological neoplasms, such as epithelial carcinomas, mesenchymal sarcomas, and malignant melanoma.

This article is protected by copyright. All rights reserved.

http://ift.tt/2veBgeB

Hospitalization and outcomes attributed to epidermal necrolysis in United States: Predictors of Mortality

Abstract

Acute life-threatening mucocutaneous reactions characterized by extensive necrosis and detachment of the epidermis(epidermal necrolysis,EN) includes the spectrum of Stevens-Johnson syndrome (SJS, <10% body surface area), Toxic epidermal necrolysis (TEN, >20% BSA) and the SJS-TEN overlap(10-20%BSA). Prior older studies have revealed that the incidence of these rare conditions was estimated to be 1 to 6 cases per million person-years for SJS and 0.4 to 1.2 cases per million person-years for TEN. Current, large population based hospitalization outcomes attributed to EN in United States are lacking.

This article is protected by copyright. All rights reserved.

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Erforschung des Hautmikrobioms

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Fütter‑, Ess- und Schluckstörungen bei Säuglingen und Kindern

Zusammenfassung

Essen und Schlucken sind dynamische Prozesse, an denen mehr als 30 Muskeln in Koordination der orofazialen Muskulatur sowie der Muskulatur des Rachens, des Kehlkopfs und der Speiseröhre beteiligt sind. Saug‑, Such- und Würgreflex des Neugeborenen und des Säuglings verändern/differenzieren sich mit zunehmendem Alter, sodass der Ess‑, Kau- und Schluckvorgang beim Kleinkind differenziert und willentlich möglich sind. Ess‑, Fütter- und Schluckstörungen sind im Säuglings- und Kleinkindalter häufig schwierig zu unterscheiden. Essstörungen umfassen Nahrungsverweigerung, inadäquate Essgewohnheiten, Verhaltensauffälligkeiten bei der Nahrungsaufnahme, selektive und/oder einseitige Nahrungspräferenzen. Schluckstörungen beschreiben eine Beeinträchtigung der oralen, pharyngealen sowie ösophagealen Phase; alle oder einzelne Phasen können betroffen sein. Ursachen sind Verhaltens- oder Entwicklungsstörungen, Syndrome, neurologische Erkrankungen, Erkrankungen der Atemwege und/oder Ösophagitiden (mit oder ohne gastroösophagealen Reflux, eosinophile Ösophagitis) oder anatomische Fehlbildungen der oberen Speisewege. Ess‑/Schluckbeschwerden werden bei bis zu 25 % aller Kinder beschrieben; circa 40 % der frühgeborenen Kinder, bis zu 64–78 % der entwicklungsauffälligen Kinder und bis zu 99 % der Kinder mit schweren Zerebralparesen zeigen Schluckstörungen.

Die Diagnostik der Ess‑/Schluckstörung beinhaltet einen multifaktoriellen Ansatz. Die Anamnese erfasst das soziale Umfeld, die Eltern-Kind-Interaktion und die elterlichen Sorgen, die körperliche Untersuchung den aktuellen Gesundheitszustand mit Bestimmung von Gewicht, Körpergröße und Kopfumfang sowie eine ausführliche HNO-ärztliche-Diagnostik. Klinische Füttersituationen können Teil der Kindesbeobachtung sein oder Videoaufnahmen von dem Kind beim Füttern/Essen die Diagnostik ergänzen. Zur Beurteilung schluckdynamischer Prozesse sind die Videofluoroskopie und die fiberoptische Diagnostik des Schluckens (FEES) möglich. Bei sehr jungen Kindern ist die standardisierte FEES selten aussagekräftig, stattdessen sollte eine fiberoptische-endoskopische Schluckuntersuchung (FESU) mit „Leeraufnahme" und Videoaufnahme nach dem Schluckversuch erfolgen.

Die Therapie beginnt mit der Empfehlung einer angenehmen Fütterumgebung, von Hilfsmitteln (spezielle Löffel etc.) beim Essen, Kostform/Konsistenz, Körperhaltung beim Essen, alternativen/additiven Ernährungsmethoden (Gastrostomien, Nasogastralsonden) sowie orofazialen Stimulationsverfahren und Kompensationsverfahren bei kooperativen älteren Kindern.

Ein interdisziplinäres Team ist die Basis für eine umfassende Diagnostik und Therapieplanung.

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