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

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

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

Correlations between milk and plasma levels of amino and carboxylic acids in dairy cows.

The objective of this study was to investigate the relationship between the concentrations of 19 amino acids, glucose, and seven carboxylic acids in the blood and milk of dairy cows and their correlations with established markers of ketosis. To that end, blood plasma and milk specimens were collected throughout lactation in two breeds of dairy cows of different milk yield. Plasma concentrations of glucose, pyruvate, lactate, α-aminobutyrate, β-hydroxybutyrate (BHBA), and most amino acids, except for glutamate and aspartate, were on average 9.9-fold higher than their respective milk levels. In contrast, glutamate, aspartate, and the Krebs cycle intermediates succinate, fumarate, malate, and citrate were on average 9.1-fold higher in milk than in plasma. For most metabolites, with the exception of BHBA and threonine, no significant correlations were observed between their levels in plasma and milk. Additionally, milk levels of acetone showed significant direct relationships with the glycine-to-alanine ratio and the BHBA concentration in plasma. The marked decline in plasma concentrations of glucose, pyruvate, lactate, and alanine in cows with plasma BHBA levels above the diagnostic cutoff point for subclinical ketosis suggests that these animals fail to meet their glucose demand and, as a consequence, rely increasingly on ketone bodies as a source of energy. The concomitant increase in plasma glycine may reflect not only the excessive depletion of protein reserves but also a potential deficiency of vitamin B6

Pleomorphic Adenoma of External Auditory Canal: Case Report of First Endoscopic Resection and Literature Review

Ceruminous pleomorphic adenoma is a very rare, mostly benign tumor originating from the ceruminal glands in the external auditory canal. Histologically, it is a mixed tumor with epithelial and stromal parts of different proportions, and is recognized today by the World Health Organization (WHO) as a ceruminous adenoma. Similar to the pleomorphic adenoma of salivary glands, recurrence or malignant degeneration with cellular atypia and metastasis can occur on rare occasions. Here, we describe an 87-year old female patient with a growing spherical mass in the right external auditory canal. After exclusive endoscopic tumor resection, a ceruminous pleomorphic adenoma was histologically diagnosed. Due to the absence of nuclear pleomorphism, no increased mitotic rate, no perineural invasion and no fusion transcripts of the MYB or MYBL1 gene loci, an adenoid cystic carcinoma could be excluded. The postoperative course was without any evidence of complications. A literature review identified 44 articles with 49 patients that were considered. Hearing loss and ear sensations were the most commonly reported symptoms. Most cases underwent an excision via an endaural or retroauricular approach. Recurrences were described in four patients, three of which had a malignant transformation. Keywords: Pleomorphic adenoma; ceruminal gland tumor; ceruminous adenoma; endoscopic ear surgery; external auditory canal

Poorly differentiated thyroid carcinoma : An underdiagnosed entity.

Poorly differentiated thyroid carcinomas (PDTCs) are a rare subtype of thyroid carcinomas that are biologically situated between well-differentiated papillary/follicular thyroid carcinomas and anaplastic thyroid carcinomas (ATCs).The diagnosis of conventional as well as oncocytic poorly differentiated thyroid carcinoma is difficult and often missed in daily routine. The current WHO criteria to allow the diagnosis of PDTCs are based on the results of a consensus meeting held in Turin in 2006. Even a minor poorly differentiated component of only 10%of a given carcinoma significantly affects patient prognosis and the oncocytic subtype may even have a worse outcome. Immunohistochemistry is not much help and is mostly used to exclude a medullary thyroid carcinoma with calcitonin and to establish a follicular cell of origin via thyroglobulin staining.Due to the concept of stepwise dedifferentiation, there is a vast overlap of different molecular alterations like BRAF, RAS, CTNNB1, TP53 and others between different thyroid carcinoma subtypes. A distinctive molecular tumor profile is therefore currently not available.PDTCs have a unique miRNA signature, which separates them from other thyroid carcinomas. The average relapse free survival is less than one year and about 50% of patients die of the disease. Modern tyrosine kinase inhibitors offer in conjunction with powerful molecular diagnostic new chances in these difficult to treat carcinomas

[Poorly differentiated thyroid carcinoma : An underdiagnosed entity. German version].

Poorly differentiated thyroid carcinomas (PDTCs) are a rare subtype of thyroid carcinomas that are biologically situated between well-differentiated papillary/follicular thyroid carcinomas and anaplastic thyroid carcinomas (ATCs).The diagnosis of conventional as well as oncocytic poorly differentiated thyroid carcinoma is difficult and often missed in daily routine. The current WHO criteria to allow the diagnosis of PDTCs are based on the results of a consensus meeting held in Turin in 2006. Even a minor poorly differentiated component of only 10% of a given carcinoma significantly affects patient prognosis and the oncocytic subtype may even have a worse outcome. Immunohistochemistry is not much help and is mostly used to exclude a medullary thyroid carcinoma with calcitonin and to establish a follicular cell of origin via thyroglobulin staining.Due to the concept of stepwise dedifferentiation, there is a vast overlap of different molecular alterations like BRAF, RAS, CTNNB1, TP53 and others between different thyroid carcinoma subtypes. A distinctive molecular tumor profile is therefore currently not available.PDTCs have a unique miRNA signature, which separates them from other thyroid carcinomas.The average relapse free survival is less than one year and about 50% of patients die of the disease. Modern tyrosine kinase inhibitors offer in conjunction with powerful molecular diagnostic new chances in these difficult to treat carcinomas