Collision tumor of the thyroid - a challenge during the COVID-19 pandemic.

Some of the patients with anaplastic thyroid carcinomas have a coexistent differentiated thyroid cancer, sustaining the hypothesis that this cancer may develop from more differentiated tumors. We describe a case with a collision tumor of the thyroid, defined as a neoplastic lesion composed of two distinct cell populations, with distinct borders. The patient presented during the COVID-19 pandemic with dysphonia, dyspnea, multinodular goiter and a painless, rapidly enlarging, left cervical swelling. She had been first time diagnosed with left nodular goiter in 2007, with an indication for surgery, which she declined. After partial excision of the left latero-cervical adenopathy, the pathological analysis showed massive lymph node metastasis from anaplastic thyroid cancer. A total thyroidectomy was done; the postoperative pathological exam identified a papillary thyroid microcarcinoma in the right lobe and an anaplastic thyroid cancer in the left lobe. Postoperatively, levothyroxine treatment was started and the patient was referred to radiotherapy. This case highlights the importance of urgent management of some cases with compressive multinodular goiter, even during the COVID-19 pandemic.

VEGF, VEGF165b and EG-VEGF expression is specifically related with hormone profile in pituitary adenomas.

Vascular endothelial growth factor (VEGF), its inhibitory splice variant, VEGF165b and Endocrine Gland derived VEGF (EG-VEGF) have a controversial role in pituitary gland. We aim to study VEGF, VEGF165b and EG-VEGF expression in pituitary adenomas. A significant correlation was found between growth hormone (GH) and VEGF secretion (P=0.024). For prolactinomas, VEGF and prolactin expression, had a P-value of 0.02 for Kendall coefficient and a P-value of 0.043 for the Spearman coefficient. VEGF-mRNA amplification was detected in both tumor cells and folliculostellate cells. VEGF165b was positive in 16.66% of pituitary adenomas. EG-VEGF was significantly correlated with prolactin (P=0.025) and luteinizing hormone (P=0.028). Our data strongly support VEGF, VEGF165b and EG-VEGF as important players of pituitary adenomas tumorigenesis. Particular hormonal milieu heterogeneity, special vascular network with an unusual reactivity to tumor growth correlated with variability of VEGF, VEGF165b and EG-VEGF secretion may stratify pituitary adenomas in several molecular groups with a direct impact on therapy and prognosis.

The "game" of glial fibrillary acidic and S100 proteins in pituitary adenomas: two players or several?

INTRODUCTION: S100 protein and GFAP expression in pituitary adenomas tumour cells is not well known; few correlations with other prognostic or therapeutic factors have previously been reported in pituitary adenomas. We aim to elucidate their involvement in the pathogenesis of pituitary adenomas and to establish the correlation of their expression with different growth factors and growth factor receptors known to have a prognostic and/or therapeutic role. MATERIAL AND METHODS: Sixty-one cases of pituitary adenomas were immunohistochemically assessed for the expression of GFAP and S100 protein in both tumour cells and FS cells, in close relationship with hormone profile, and correlated with vascular endothelial growth factor (VEGF) and epidermal growth factor receptor (EGFR) expression, previously studied by our team. RESULTS: GFAP and S100 protein were expressed both in tumour cells and FS cells. Differences between morphology, distribution, and density of GFAP+ FS cells and S100+ FS cells were observed according to the hormone profile of pituitary adenomas. GFAP and S100 protein expression in tumour cells was significantly related to hormone profile of pituitary adenomas and also with VEGF and EGFR expression. CONCLUSIONS: GFAP and S100 protein expressions in tumour cells from pituitary adenomas are influenced by hormone profile. Our re-sults support the presence of two molecular subtypes of FS cells GFAP+/VEGF+/S100 respectively and another one that is GFAP-/S100+/EGFR+ simultaneously with the classical variant GFAP+/S100+. It is possible that S100+/EGFR+ pituitary adenomas represent a group of pituitary adenomas with an aggressive behaviour and a high ability of invasion and recurrence.

High Ki-67 expression is associated with prolactin secreting pituitary adenomas.

Pituitary adenomas represent the third most common primary intracranial tumor in neurosurgical practice. To understand the biological behaviour of the pituitary adenomas previous studies have determined the tumor proliferation rate using monoclonal antibodies targeted against the Ki-67 antigen. The aim of this study was to correlate the Ki-67 index with hormonal profiles of pituitary adenomas. The study included 50 pituitary adenomas. For histopathologic evaluation, the sections were stained with routine hematoxylin and eosin method. Additional paraffin sections from each tumor were immunostained using primary antibodies against the following pituitary hormones: somatotropin (STH), prolactin (PRL), adrenocorticotrophic hormone (ACTH), thyroid-stimulating hormone (TSH), follicle-stimulating hormone (FSH), and luteinizing hormone (LH). To detect the expression of Ki-67 we used a mouse anti-human monoclonal antibody (clone K2). The percentage of Ki-67 positive nuclei (Ki-67 labeling index) was assessed by counting approximately 1000 nuclei of the tumor cells at ×400 magnification. Out of the 50 tumor samples, 31 (62%) pituitary adenomas showed proliferative activity, and the proliferation rate was variable in this group. The overall mean Ki-67 labeling index was 1.59 ± 1.47, ranging from 0.3% to 6.6%. In 5 cases, the Ki-67 index was >3%, all of them being prolactinomas. The Ki-67 index was higher in PRL-secreting adenomas (mean ± SD was 3.37 ± 1.80, range 0.9 - 6.6%). Our study provides the evidence that a higher Ki-67 value is associated with pituitary adenomas that secrete PRL (prolactinomas and mixed STH/PRL-secreting adenomas).

Endocrine Gland-Derived Vascular Endothelial Growth Factor/Prokineticin-1 in Cancer Development and Tumor Angiogenesis.

A lot of data suggests endocrine gland-derived vascular endothelial growth factor (EG-VEGF) to be restricted to endocrine glands and to some endocrine-dependent organs. Many evidences show that EG-VEGF stimulates angiogenesis and cell proliferation, although it is not a member of the VEGF family. At the time, a lot of data regarding the role of this growth factor in normal development are available. However, controversial results have been published in the case of pathological conditions and particularly in malignant tumors. Thus, our present paper has been focused on the role of EG-VEGF in normal tissues and various malignant tumors and their angiogenic processes.

Geographic-Related Differences of Pituitary Adenomas Hormone Profile: Analysis of Two Groups Coming from Southeastern and Eastern Europe.

We compared the immunoprofile of pituitary adenomas from Romania and Moldova. One hundred and eighty cases coming from Romania (94 cases, group 1) and Moldova (86 cases, group 2) were assessed by immunohistochemistry regarding all six basic hormones expressed in pituitary adenomas. Specific differences and similarities were found and stated for both groups. In group 1, 70% of cases were pituitary adenomas positive for one hormone, 13% were plurihormonal, while 17% were negative. In group 2, 50,3% of the cases expressed only one hormone and 12,5% were negative for all hormones. The highest difference was observed for plurihormonal adenomas, found in about 37,2% of cases for group 2 (2.86 times higher for group 2 compared with group 1). A higher incidence of GH-secreting adenomas characterized group "1," while group "2" had the highest percent of LH-secreting adenomas, 55% of cases being positive. Triple association was noticed in 4.25% of cases of group 1 and in 8,13% out of total cases, from group 2. Four-hormone association was found only in group 2, noticed in 15,56% of the cases. The present paper highlights strong evidences of a particular and different immunoprofile of pituitary adenomas coming from Romania and Moldova.