A dendritic cell sarcoma cell line, U-DCS, was established from a dendritic cell sarcoma in a 53-year-old Caucasian male patient. Since its establishment, U-DCS has maintained stable phenotypic characteristics in vitro and has a doubling time of approximately 2 days under standard culture conditions. U-DCS is growing with typical dendritic cell morphology in tissue and expresses the dendritic cell sarcoma immunophenotypic markers S100 protein, MHCI, MHCII, and vimentin. Expression analysis revealed transcripts for the toll-like receptors TLR3, -4, -9 and DDX58 (RIG-I), but not for TLR2. U-DCS shows functional features of dendritic cells with the ability of phagocytosis and antigen-specific T cell stimulation. Karyotype-, CGH-, and mFISH analysis point to a chromosomal instability and a hypotetraploid karyotype with approximately 130 chromosomes. U-DCS is the first immortalized human dendritic cell sarcoma cell line and has some morphological and functional features of dendritic cells without dependency on growth factors.

The generation, differentiation, survival and activation of B cells are coordinated by signals emerging from the B cell antigen receptor (BCR) or its precursor, the pre-BCR. The adaptor protein SLP65 (also known as BLNK) is an important signaling factor that controls pre-B cell differentiation by down-regulation of PI3K signaling. Here, we investigated the mechanism by which SLP65 interferes with PI3K signaling. We found that SLP65 induces the activity of the small GTPase RHOA, which activates PTEN, a negative regulator of PI3K signaling, by enabling its translocation to the plasma membrane. The essential role of RHOA is confirmed by the complete block in early B cell development in conditional RhoA-deficient mice. The RhoA-deficient progenitor B cells showed defects in activation of immunoglobulin gene rearrangement and fail to survive both in vitro and in vivo. Reconstituting the RhoA-deficient cells with RhoA or Foxo1, a transcription factor repressed by PI3K signaling and activated by PTEN, completely restores the survival defect. However, the defect in differentiation can only be restored by RhoA suggesting a unique role for RHOA in B cell generation and selection. In full agreement, conditional RhoA-deficient mice develop increased amounts of autoreactive antibodies with age. RHOA function is also required at later stage, as inactivation of RhoA in peripheral B cells or in a transformed mature B cell line resulted in cell loss. Together, these data show that RHOA is the key signaling factor for B cell development and function by providing a crucial SLP65-activated link between BCR signaling and activation of PTEN. Moreover, the identified essential role of RHOA for the survival of transformed B cells offers the opportunity for targeting B cell malignancies by blocking RHOA function.

It is well recognized that the AP-1 transcription factor BATF3 is constitutively expressed in Hodgkin/Reed-Sternberg (HRS) cells, but its potential as a diagnostic marker for classical Hodgkin lymphoma (cHL) has not yet been addressed. In this study, we performed immunohistochemistry and analyzed the BATF3 expression in lymphoma cells on 218 lymphoma samples belonging to 14 different lymphoma entities. We observed varying degrees of BATF3 expression in nearly half of the cases (n = 100) with BATF3 expression being a constitutive feature of cHL (n = 53) and anaplastic large cell lymphoma (ALCL). By scoring BATF3 expression (BATF3-score) we observed constitutively high BATF3-scores in cHL and ALCL and low to moderate BATF3-scores in all other entities examined. Western blot analysis confirmed BATF3 protein expression in cell lysates from cHL cell lines (n = 7). Thus, BATF3 can be considered a useful IHC marker for the diagnosis of cHL as it is highly sensitive and sufficiently specific when analyzed by BATF3-scoring.

We present a case report of a patient with laparoscopic surgery of a deep infiltrating endometriosis with a complicative course. In addition to a postoperatively diagnosed ureteral fistula with local inflammation, acute perforation and ultimately lethal bleeding from the adjacent external iliac artery occurred more than 3 weeks after surgery. To the best of our knowledge, a case with the same constellation has not yet been published. A literature review on the rare and comparable complication of a ureteroarterial fistula is discussed in connection with the case.

Zusammenfassung Einleitung Kleinzellige neuroendokrine Karzinome (KNK) des Larynx sind eine seltene Tumorentität mit schlechter Prognose bei einer 5-Jahres-Überlebensrate nach Standardtherapie mit primärer Radiochemotherapie (pRCT) von 5 %. Methoden Es erfolgte eine systematische Literaturrecherche auf PubMed mit den Suchbegriffen „small cell neuroendocrine carcinoma“ und „head and neck“ sowie die Aufarbeitung von Patientenfällen aus unserer Klinik. Ergebnisse Die Recherche ergab keine großen randomisierten kontrollierten Studien zur Standardtherapie. Bisherige Therapiestrategien basieren auf den Erfahrungen bei kleinzelligen Karzinomen der Lunge. 0,5 % aller KNK treten im Kopf-Hals-Bereich auf. In unserer Klinik wurden in 12 Jahren 9 KNK diagnostiziert, 2 davon mit laryngealer Manifestation. Wir berichten über einen 29-jährigen Patienten mit Erstdiagnose (ED) eines Larynx-KNK im Frühjahr 2018. Im Staging zeigten sich zervikale Lymphknotenmetastasen, eine Fernmetastasierung wurde ausgeschlossen. Es erfolgte eine pRCT mit Cisplatin/Etoposid mit darauffolgender Komplettremission. Im Re-Staging 6 Monate nach ED zeigten sich Metastasen-suspekte Lungenherde. Unter 6 Zyklen palliativer Systemtherapie mit Cyclophosphamid, Adriamycin und Vincristin kam es zu einer partiellen Remission. Nach 12 Monaten erfolgte bei Progress die Therapieumstellung auf den PD-1-Antikörper Nivolumab. Der Patient verstarb 22 Monate nach ED an einer tumorbedingten Massenblutung mit Verlegung der Atemwege. Schlussfolgerung Bisher existieren keine Studienergebnisse über den Einsatz von Nivolumab als Third-Line-Therapie bei KNK. Die Analyse einer NTRK-Fusion (neurotrophe Tyrosin-Rezeptor-Kinase) oder einer Folatrezeptor-Expression sollte erwogen werden zur Evaluation einer Tropomyosin-Rezeptor-Kinase-Inhibitor- oder einer Radionuklidtherapie.