Sarcomas in the head and neck area are rare diseases with an incidence of under 1% of all head and neck malignant tumours. Osteosarcomas or osteogenic sarcomas consist of neoplastic cells that ...produce osteoid bone or immature bone. Sarcomas develop more in the mandible than the maxilla. The exact diagnosis of different types of sarcomas is based on the immunohistochemical investigation. These rare tumours are of mesenchymal origin; osteosarcomas and chondrosarcomas are the most common types—Ewing’s sarcomas. The use of proton beam radiotherapy in the treatment of osteosarcoma of the maxilla is rarely reported in the literature. We present a case of successfully treated (surgery and proton beam radiotherapy) poorly differentiated highly aggressive osteosarcoma in the ethmoids and maxillary sinus and morbidity after the treatment. We were presented with a case of a 65-year-old man with anaesthesia and palsy of the right face. The stomatology department performed the extraction of a tooth. One month later, the wound was still open. The histology showed an osteogenic sarcoma in the area of the wound. The oncologist and maxillofacial surgeons in a catchment hospital recommended a nonsurgical approach. Hence, we performed a radical maxillectomy and ethmoidectomy, after which we continued with proton bean radiotherapy. The patient is now five years after therapy without signs of sarcoma; however, he has blindness in the right eye and reduced vision in the left eye, as well as gliosis of the brain, vertigo, tinnitus, trismus, and ancylostomiases. Head and neck osteosarcomas treatment is considered a complex multidisciplinary task. It is currently argued that there is no clear therapeutic protocol for successful treatment. Innovations in treatment modalities such as proton beam radiotherapy appear to have potential, although their effects on long-term morbidity and survival outcomes are still undetermined. We present a rare case report of an osteosarcoma of the maxilla involving an innovative, successful treatment procedure combining surgical excision followed by proton beam radiotherapy. This treatment approach may enable maximum tumour control. This protocol has not been adequately described in the world literature for this diagnosis.
Sox2 is one of the transcription factors responsible for the maintenance of stem cell phenotype. It has been implicated as a marker of stem cells in normal pituitaries and pituitary neuroendocrine ...tumours. To explore the clinical significance of Sox2 expression in histological sections, we performed immunohistochemical detection of Sox2 in 113 pituitary neuroendocrine tumours from 109 patients with acromegaly. In 11 tumours, we performed double immunostaining for Sox2, annexin A1 and S100 protein. Tumours were characterised using the WHO classification system. Proliferative activity and invasion were assessed. The amount of immunoreactive cells was evaluated and correlated with tumour size and biochemical features (levels of IGF1, GH, prolactin, βTSH). Sox2
+
cells were identified in 35/38 normal pituitaries adjacent to the tumours. In 36 tumours (33%), ≥ 1% of the cells expressed Sox2, in 24 cases (22%), Sox2
+
cells comprised < 1% and 49 cases (45%) were negative. We found no significant differences between Sox2
+
and Sox2
−
groups with respect to the age, initial levels of GH, IGF1, prolactin, βTSH, tumour size, invasion, proliferative activity or histological features. We observed a positive correlation between Sox2
+
cell count and βTSH immunoreactive cells (
r
= 0.459,
p
< 0.001) that was further verified by multivariate analysis. Using double stain, the majority of Sox2
+
cells coexpressed annexin A1 (average 89%) and S100 protein (average 76.2%) and showed morphological features of folliculo-stellate cells. Sox2
+
cells are thus commonly present in growth hormone–producing tumours and normal pituitaries, and their amount does not have any prognostic significance. Most of these cells represent a subpopulation of folliculo-stellate cells, pointing out to their role as a possible stem cell population.
Aims
In somatotroph pituitary neuroendocrine tumours (adenomas), a pattern of cytokeratin (CK) 18 expression is used for tumour subclassification, with possible clinical implications. Rare ...somatotroph tumours do not express CK 18. We aimed to characterise this subset clinically and histologically.
Methods and results
Clinical and pathological data for the study were derived from a previously published data set of a cohort of 110 patients with acromegaly. Data included serum levels of insulin‐like growth factor 1 (IGF1), growth hormone (GH), prolactin and thyroid‐stimulating hormone (TSH), tumour diameter, tumour invasion defined by Knosp grade and immunohistochemical data concerning the expression of Ki67, p53, E‐cadherin, somatostatin receptor (SSTR)1, SSTR2A, SSTR3, SSTR5 and D2 dopamine receptor. Additional immunohistochemical analysis (AE1/3, CK 8/18, vimentin, neurofilament light chain, internexin‐α) was performed. CK 18 was negative in 10 of 110 (9.1%) tumours. One of these tumours was immunoreactive with CK 8/18 antibody, while the remainder expressed only internexin‐α intermediate filament in patterns similar to CK 18 (perinuclear fibrous bodies). CK‐negative tumours showed no significant differences with respect to biochemical, radiological or pathological features. They showed significantly higher expression of SSTR2A compared to the sparsely granulated subtype and significantly lower expression of E‐cadherin compared to the non‐sparsely granulated subtypes of tumours. The tumours showed divergent morphology and hormonal expression: two corresponded to densely granulated tumours and three showed co‐expression of prolactin and morphology of either mammosomatotroph or somatotroph–lactotroph tumours. Four tumours showed morphology and immunoprofile compatible with plurihormonal Pit1‐positive tumours.
Conclusions
CK‐negative somatotroph tumours do not represent a distinct subtype of somatotroph tumours, and can be further subdivided according to their morphology and immunoprofile.
Endocrine disruptors (EDs) are ubiquitous substances both in the environment and everyday products that interfere with the hormonal system. Growing evidence demonstrates their adverse effects on the ...organism, including the reproductive system and the prostate, owing to their (anti)estrogenic or antiandrogenic effects. Since EDs can interact with steroid hormone actions on-site, understanding the levels of intraprostatic EDs in conjunction with steroids may hold particular significance. The aim of this study was to develop and validate a method for determining estrogens, various groups of EDs (bisphenols, parabens, oxybenzone and nonylphenol) and phytoestrogens in their unconjugated and conjugated forms in prostate tissue by liquid chromatography-tandem mass spectrometry, and subsequently analyze 20 human prostate tissue samples. The method enabled 20 compounds to be analyzed: estrogens (estrone, estradiol, estriol), bisphenols (bisphenol A- BPA, BPS, BPF, BPAF, BPAP, BPZ, BPP), parabens (methyl-, ethyl-, propyl-, butyl-, benzyl- paraben), oxybenzone, nonylphenol and phytoestrogens (daidzein, genistein, equol) with LLOQs between 0.017-2.86 pg/mg of tissue. The most frequently detected EDs in prostate tissues were propylparaben (conjugated and unconjugated forms in 100 % of tissues), methylparaben (unconjugated in 45 % and conjugated in 100 %), ethylparaben (unconjugated in 25 % and conjugated in 100 %), BPA (unconjugated in 35 % and conjugated in 60 %) and oxybenzone (both forms in 45 %). To the best of our knowledge, this is the first study detecting EDs, phytoestrogens and estriol conjugate (E3C) in the prostate. E3C was the most abundant estrogen in prostatic tissue. This highlights the need for further explorations into estrogen metabolism within the prostate.
Cauda equina neuroendocrine tumors (CENETs) are neoplasms of uncertain histogenesis with overlapping features between those of paragangliomas (PGs) and visceral neuroendocrine tumors (NETs). We have ...explored their biological relationship to both subsets of neuroendocrine neoplasms. The clinical and radiological features of a cohort of 23 CENETs were analyzed. A total of 21 cases were included in tissue microarrays, along with a control group of 38 PGs and 83 NETs. An extensive panel of antibodies was used to assess epithelial phenotype (cytokeratins, E-cadherin, EpCAM, Claudin-4, EMA, CD138), neuronal and neuroendocrine features (synaptophysin, chromogranin A, INSM1, neurofilaments, NeuN, internexin-α, calretinin), chromaffin differentiation (GATA3, Phox2b, tyrosine hydroxylase), and possible histogenesis (Sox2, T-brachyury, Oct3/4, Sox10). The cohort included 5 women (22%) and 18 men (78%). The average age at the time of surgery was 48.3 years (range from 21 to 80 years). The average diameter of the tumors was 39.27 mm, and invasion of surrounding structures was observed in 6/21 (29%) tumors. Follow-up was available in 16 patients (median 46.5 months). One tumor recurred after 19 months. No metastatic behavior and no endocrine activity were observed. Compared to control groups, CENETs lacked expression of epithelial adhesion molecules (EpCAM, CD138, E-cadherin, Claudin-4), and at the same time, they lacked features of chromaffin differentiation (GATA3, Phox2b, tyrosine hydroxylase). We observed no loss of SDHB. Cytokeratin expression was present in all CENETs. All the CENETs showed variable cytoplasmic expression of T-brachyury and limited nuclear expression of Sox2. These findings support the unique nature of the neoplasm with respect to NETs and PGs.
In somatotroph pituitary tumours, somatostatin analogue (SSA) therapy outcomes vary throughout the studies. We performed an analysis of cohort of patients with acromegaly from the Czech registry to ...identify new prognostic and predictive factors. Clinical data of patients were collected, and complex immunohistochemical assessment of tumour samples was performed (SSTR1‐5, dopamine D2 receptor, E‐cadherin, AIP). The study included 110 patients. In 31, SSA treatment outcome was evaluated. Sparsely granulated tumours (SGST) differed from the other subtypes in expression of SSTR2A, SSTR3, SSTR5 and E‐cadherin and occurred more often in young. No other clinical differences were observed. Trouillas grading system showed association with age, tumour size and SSTR2A expression. Factors significantly associated with SSA treatment outcome included age, IGF1 levels, tumour size and expression of E‐cadherin and SSTR2A. In the group of SGST, poor SSA response was observed in younger patients with larger tumours, lower levels of SSTR2A and higher Ki67. We observed no relationship with expression of other proteins including AIP. No predictive value of E‐cadherin was observed when tumour subtype was considered. Multiple additional factors apart from SSTR2A expression can predict treatment outcome in patients with acromegaly.
The trial was performed on 12 Texel lambs (6 males and 6 females) in selected flock. The lambs were slaughtered at the age of 180 days and samples of musculus longissimus lumborum et thoracis (MLLT) ...and musculus quadriceps femoris (QFM) were collected. The histochemical traits of fiber cross sectional area, diameter and perimeter were monitored. Subsequently the fiber type distribution was calculated and evaluated. The dataset was evaluated using SAS. Significantly higher pH value (+0.88; P < 0.01) was marked in females, while significantly higher L (*) attribute was observed in males. No differences between males and females were detected in histochemical evaluation. On the other hand significant differences (P < 0.05 to 0.01) were observed in fiber type distribution and cross sectional area parameters of MLLT and QMF muscles. In praxis the results are usable for meat scientists, sheep breeders or the meat industry.
The trial was performed on 12 Texel lambs (6 males and 6 females) in selected flock. The lambs were slaughtered at the age of 180 days and samples of musculus longissimus lumborum et thoracis (MLLT) ...and musculus quadriceps femoris (QFM) were collected. The histochemical traits of fiber cross sectional area, diameter and perimeter were monitored. Subsequently the fiber type distribution was calculated and evaluated. The dataset was evaluated using SAS. Significantly higher pH value (+0.88; P < 0.01) was marked in females, while significantly higher L* attribute was observed in males. No differences between males and females were detected in histochemical evaluation. On the other hand significant differences (P < 0.05 to 0.01) were observed in fiber type distribution and cross sectional area parameters of MLLT and QMF muscles. In praxis the results are usable for meat scientists, sheep breeders or the meat industry.
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