Giant ectopic liver, hepatocellular carcinoma and pachydermia-a rare genetic syndrome?

Ectopic liver is a very uncommon developmental anomaly that predisposes to the development of hepatocellular carcinoma. We describe the second documented case of a hepatocellular carcinoma developing in the primary liver of a patient with a rare and uncharacterized genetic symptom complex. Also present was the largest ectopic liver ever reported, measuring 12 cm in diameter which contained a solitary focus of metastatic hepatocellular carcinoma. The primary hepatocellular carcinoma is believed to have arisen in the native liver from a hepatic adenoma that was diagnosed 15 years earlier. The patient's uncharacterised condition featured prominent thick, yellow skin over the dorsum of the fingers, and was associated with follicular hyperkeratosis, abnormal plantar creases, digital clubbing, misshaped ears, a lingua plicata and an angioleiomyolipoma of the right kidney

A rare low-grade myofibroblastic sarcoma in lower jaw with the resemblance to benign lesions.

BACKGROUND Low-grade myofibroblastic sarcoma (LGMS) is a rare solid infiltrative soft tissue tumor with a predilection for the head and neck region. CASE PRESENTATION We report the diagnostic steps of a fast-growing lesion of the lower left jaw in a 45-year-old otherwise healthy woman. A first biopsy and subsequent histopathological examination showed potential differentials of a benign myofibroma, benign nodular fasciitis or an LGMS. This diagnostic overlap was a challenge for the decision of the further treatment approach. The treatment consisted of a segmental en bloc resection of the mandible including the second premolar, first and second molar. Histopathological examination of the resected tumor confirmed an LGMS. CONCLUSION The histopathologic resemblance of LGMS to a range of benign and reactive tumors may lead to misdiagnosis and mistreatment. The rarity of LGMS explains the lack of established treatment protocols. This case shows the importance of adequate clinical decisions, expertise in the histopathology of rare tumors and interdisciplinary exchange to achieve state-of-the-art patient management

Cribriform Morular Thyroid Carcinoma - Ultimobranchial Pouch-Related? Deep Molecular Insights of a Unique Case.

A 44-year-old female patient with a familial adenomatous polyposis (FAP) was diagnosed with a cribriform morular thyroid carcinoma (CMTC). We observed within the very necrotic tumor a small but distinct poorly differentiated carcinomatous component. As expected, next generation sequencing of both components revealed a homozygous APC mutation and in addition, a TERT promoter mutation. A TP53 mutation was found exclusively in the CMTC part, while the poorly differentiated component showed a clonal evolution, harboring an activating PIK3CA mutation and copy number gains of BRCA2, FGF23, FGFR1, and PIK3CB-alterations which are typically seen in squamous cell carcinoma. The mutational burden in both components was low, and there was no evidence for microsatellite instability. No mutations involving the mitogen-activated protein kinase (MAPK) pathway, typically seen in papillary thyroid carcinomas, were detected. Immunohistochemically, all tumor parts were negative for thyroglobulin, providing further evidence that this entity does not belong to the follicular epithelial cell-derived thyroid carcinoma group. CD5 was negative in the poorly differentiated component, making a relation to intrathyroidal thymic carcinoma rather unlikely. However, since this marker was seen in the morules, a loss in the poorly differentiated component and a relation to the ultimobranchial body cannot be excluded either. After total thyroidectomy and radioiodine ablation, the patient was disease-free with no residual tumor burden on 2-year follow-up

Hepatic teratoma and peritoneal gliomatosis: a case report

The hepatic teratoma is a very rare entity of which only 25 cases have been published so far. In our case the hepatic teratoma is associated with peritoneal gliomatosis, which is an indicator for an ongoing peritoneal spread of a teratoma. Wall calcifications and the homogeneity as well as the well defined border misled the radiologist to the diagnosis of an echinococcal cyst, which is the most common differential diagnosis, however the hepatic teratoma has to be taking into consideration when dealing with unclear hepatic cysts, although it is very rare

Lung tumour growth kinetics in SPC-c-Raf-1-BB transgenic mice assessed by longitudinal in-vivo micro-CT quantification

<p>Abstract</p> <p>Background</p> <p>SPC-c-Raf-1-BxB transgenic mice develop genetically induced disseminated lung adenocarcinoma allowing examination of carcinogenesis and evaluation of novel treatment strategies. We report on assessment of lung tumour growth kinetics using a semiautomated region growing segmentation algorithm.</p> <p>Methods</p> <p>156 non contrast-enhanced respiratory gated micro-CT of the lungs were obtained in 12 SPC-raf transgenic (n = 9) and normal (n = 3) mice at different time points. Region-growing segmentation of the aerated lung areas was obtained as an inverse surrogate for tumour burden. Time course of segmentation volumes was assessed to demonstrate the potential of the method for follow-up studies.</p> <p>Results</p> <p>Micro-CT allowed assessment of tumour growth kinetics and semiautomated region growing enabled quantitative analysis. Significant changes of the segmented lung volumes over time could be shown (<it>p </it>= 0.009). Significant group differences could be detected between transgenic and normal animals for time points 8 to 13 months (<it>p </it>= 0.043), when marked tumour progression occurred.</p> <p>Conclusion</p> <p>The presented region-growing segmentation algorithm allows in-vivo quantification of multifocal lung adenocarcinoma in SPC-raf transgenic mice. This enables the assessment of tumour load and progress for the study of carcinogenesis and the evaluation of novel treatment strategies.</p

Ferritin-Mediated Iron Sequestration Stabilizes Hypoxia-Inducible Factor-1α upon LPS Activation in the Presence of Ample Oxygen

SummaryBoth hypoxic and inflammatory conditions activate transcription factors such as hypoxia-inducible factor (HIF)-1α and nuclear factor (NF)-κB, which play a crucial role in adaptive responses to these challenges. In dendritic cells (DC), lipopolysaccharide (LPS)-induced HIF1α accumulation requires NF-κB signaling and promotes inflammatory DC function. The mechanisms that drive LPS-induced HIF1α accumulation under normoxia are unclear. Here, we demonstrate that LPS inhibits prolyl hydroxylase domain enzyme (PHD) activity and thereby blocks HIF1α degradation. Of note, LPS-induced PHD inhibition was neither due to cosubstrate depletion (oxygen or α-ketoglutarate) nor due to increased levels of reactive oxygen species, fumarate, and succinate. Instead, LPS inhibited PHD activity through NF-κB-mediated induction of the iron storage protein ferritin and subsequent decrease of intracellular available iron, a critical cofactor of PHD. Thus, hypoxia and LPS both induce HIF1α accumulation via PHD inhibition but deploy distinct molecular mechanisms (lack of cosubstrate oxygen versus deprivation of co-factor iron)

VoiceS: voice quality after transoral CO2 laser surgery versus single vocal cord irradiation for unilateral stage 0 and I glottic larynx cancer-a randomized phase III trial [study protocol].

BACKGROUND Surgery and radiotherapy are well-established standards of care for unilateral stage 0 and I early-stage glottic cancer (ESGC). Based on comparative studies and meta-analyses, functional and oncological outcomes after both treatment modalities are similar. Historically, radiotherapy (RT) has been performed by irradiation of the whole larynx. However, only the involved vocal cord is being treated with recently introduced hypofractionated concepts that result in 8 to 10-fold smaller target volumes. Retrospective data argues for an improvement in voice quality with non-inferior local control. Based on these findings, single vocal cord irradiation (SVCI) has been implemented as a routine approach in some institutions for ESGC in recent years. However, prospective data directly comparing SVCI with surgery is lacking. The aim of VoiceS is to fill this gap. METHODS In this prospective randomized multi-center open-label phase III study with a superiority design, 34 patients with histopathologically confirmed, untreated, unilateral stage 0-I ESGC (unilateral cTis or cT1a) will be randomized to SVCI or transoral CO2-laser microsurgical cordectomy (TLM). Average difference in voice quality, measured by using the voice handicap index (VHI) will be modeled over four time points (6, 12, 18, and 24 months). Primary endpoint of this study will be the patient-reported subjective voice quality between 6 to 24 months after randomization. Secondary endpoints will include perceptual impression of the voice via roughness - breathiness - hoarseness (RBH) assessment at the above-mentioned time points. Additionally, quantitative characteristics of voice, loco-regional tumor control at 2 and 5 years, and treatment toxicity at 2 and 5 years based on CTCAE v.5.0 will be reported. DISCUSSION To our knowledge, VoiceS is the first randomized phase III trial comparing SVCI with TLM. Results of this study may lead to improved decision-making in the treatment of ESGC. TRIAL REGISTRATION ClinicalTrials.gov NCT04057209. Registered on 15 August 2019. Cantonal Ethics Committee KEK-BE 2019-01506

Targeting CD47 in Anaplastic Thyroid Carcinoma Enhances Tumor Phagocytosis by Macrophages and Is a Promising Therapeutic Strategy.

Background: Anaplastic thyroid carcinoma (ATC) is one of the most aggressive human cancers, with a median survival of only three to six months. Standard treatment options and even targeted therapies have so far failed to improve long-term overall survival. Thus, novel treatment modalities for ATC, such as immunotherapy, are urgently needed. CD47 is a "don't eat me" signal, which prevents cancer cells from phagocytosis by binding to signal regulatory protein alpha on macrophages. So far, the role of macrophages and the CD47-signal regulatory protein alpha signaling axis in ATC is not well understood. Methods: This study analyzed 19 primary human ATCs for macrophage markers, CD47 expression, and immune checkpoints by immunohistochemistry. ATC cell lines and a fresh ATC sample were assessed by flow cytometry for CD47 expression and macrophage infiltration, respectively. CD47 was blocked in phagocytosis assays of co-cultured macrophages and ATC cell lines. Anti-CD47 antibody treatment was administered to ATC cell line xenotransplanted immunocompromised mice, as well as to tamoxifen-induced ATC double-transgenic mice. Results: Human ATC samples were heavily infiltrated by CD68- and CD163-expressing tumor-associated macrophages (TAMs), and expressed CD47 and calreticulin, the dominant pro-phagocytic molecule. In addition, ATC tissues expressed the immune checkpoint molecules programmed cell death 1 and programmed death ligand 1. Blocking CD47 promoted the phagocytosis of ATC cell lines by macrophages in vitro. Anti-CD47 antibody treatment of ATC xenotransplanted mice increased the frequency of TAMs, enhanced the expression of macrophage activation markers, augmented tumor cell phagocytosis, and suppressed tumor growth. In double-transgenic ATC mice, CD47 was expressed on tumor cells, and blocking CD47 increased TAM frequencies. Conclusions: Targeting CD47 or CD47 in combination with programmed cell death 1 may potentially improve the outcomes of ATC patients and may represent a valuable addition to the current standard of care