José Miguens | Universidade de Lisboa (original) (raw)

Papers by José Miguens

Acta Médica Portuguesa, 2016

PubMed, Feb 28, 2001

Ependymomas account for 3 to 9% of all neuroepithelial tumors and, although occurring most often ... more Ependymomas account for 3 to 9% of all neuroepithelial tumors and, although occurring most often within the ventricular system, they may arise from the extraventricular parenchyma as well. Several histologic patterns of these neoplasm are well known, but little attention has been devoted to a variant composed of giant elements. We describe the case of a 13-year-old girl experiencing a 3-month history of partial seizures in whom cranial magnetic resonance imaging showed an extraventricular, right parietotemporal neoplasm, adherent to the overlying dura mater. Histologic, immunohistochemical and ultrastructural findings were consistent with those of a high-grade ependymoma. The tumor was characterized by the presence of a major component of pleomorphic giant cells, as also seen in pleomorphic xantoastrocytoma, subependymal giant cell astrocytoma and glioblastoma multiforme. Similar elements have been described in two filum terminale and one supratentorial, intraventricular ependymoma, respectively. Histologic and evolutional data of those and of our own case suggest that isolated giant cells are not necessarily linked to a bad prognosis in ependymomas.

Neuro-oncology, Sep 1, 2018

many variables, including pre-operative neurological function, tumour histology and extent of res... more many variables, including pre-operative neurological function, tumour histology and extent of resection. Emphasis remains on surgical treatment due to the limited adjunctive therapeutic options and poor drug penetration. MATERIAL AND METHODS: 49 patients were identified from a surgical database. Variables collected included pre-and post-operative Frankel Grade and Modified McCormick Scale assessments, tumour histology, extent of resection and length of follow up. Chi-Squared, Kaplan-Mier Survival and Mann-Whitney U-Tests were completed. RESULTS: Ependymoma, Haemangioblastoma and Pilocytic Astrocytoma were the commonest tumour histologies. In total 21 different histological tumours were identified in the series. There was a statistically significant relationship between identification of the tumour plane and extent of resection (p<0.01), along with the extent of resection and recurrence (p<0.01). Compared to the other histological subtypes, ependymoma's demonstrated a significantly greater extent of resection (p=0.02). There was a significant relationship between the grade of tumour and progression free survival (p<0.01). We did not find a significant relationship between pre-and post-operative neurological function and survival. CONCLUSION: Tumour plane and the extent of tumour resection are significant determinants of progression free survival. Ependymoma, whilst being the commonest histology in our series were also the most resectable. Whilst complete resection reduces the rate of recurrence, tumour grade is the most important predictor of outcome.

Journal of Endocrinology and Metabolism, Feb 1, 2022

Cushing's disease (CD) remains a diagnostic and therapeutic challenge. Different subtypes may be ... more Cushing's disease (CD) remains a diagnostic and therapeutic challenge. Different subtypes may be recognized that will offer insight in this complex situation. We describe an atypical case that we assume is a common variation albeit with no previous formal description. A young female patient presented with minimal clinical features of CD, but increased adrenocorticotropic hormone (ACTH) and cortisol levels, with maintained circadian rhythm that was not suppressed either after the rapid dexamethasone or the prolonged low-dose dexamethasone tests, but suppressed with the prolonged high-dose dexamethasone test and presented a flat ACTH and cortisol response after the corticotropin-releasing hormone (CRH) test. A diffuse enlarged pituitary gland with thickened pituitary stalk was present and a mixed corticotroph adenoma was removed. CD persisted despite now normal pituitary morphology, except for pituitary stalk widening. Plasma levels of CRH were low and no abnormalities were found in the coding region or flanking introns of glucocorticoid receptor (GCR) gene (NR3C1). Somatostatin receptors were not present in the octreoscan, and treatment with cabergoline or somatostatin analogs was ineffective. Morbidity and mortality are increased in CD even in patients successfully treated and in remission. Despite early success in over 80% of the patients, in the long term CD recurs in almost 50% of the patients. Defining subtypes of CD may help elucidate mechanisms of the disease. We purpose a new variant that we assume is common. Furthermore adaptation to chronic hypercortisolism is present.

Cell reports medicine, May 1, 2022

Neurocirugía, Nov 1, 2017

Background: Lumbosacral and coccygeal skin covered appendages are a rare malformation, considered... more Background: Lumbosacral and coccygeal skin covered appendages are a rare malformation, considered human-tails. Case report: The authors describe the case of a full term newborn girl with lumbar skin appendage and a normal neurologic examination. The magnetic resonance of the spine revealed a dermal sinus continuous with the skin appendage and with extension into to the spinal canal. Due to the infection risk, a surgery was performed on the third day of life, with dermal sinus ligation and appendage removal. At 12 months of follow-up the girl has a normal neurologic examination. Conclusions: With the description of this case the authors aim to emphasize that although rare, lumbar skin appendages can be associated with spinal dysraphism and other lesions, requiring extensive work-up and long-term surveillance.

PubMed, Jun 7, 2002

Benign fibrous histiocytomas (BFHs) are tumors with fibroblastic and histiocytic components witho... more Benign fibrous histiocytomas (BFHs) are tumors with fibroblastic and histiocytic components without histological anaplasia. Intracerebral lesions are exceptional and to our knowledge a spinal location was not yet described. We describe 2 cases of BFHs of the neural axis: the first, a 22-month-old boy with Down's syndrome, presented with a paraparesis and the magnetic resonance (MR) of the spine disclosed an intradural extramedullary, thoracic mass, totally resected; the second, a 13-year-old boy with left partial motor seizures, in whom the MR of the brain showed an intracerebral, right frontal tumor, also surgically removed. Both patients are free of recurrence, 6 years and 15 months after surgery, respectively. Histological examination and immunoreactivity for vimentin and histiocytic markers favored the diagnosis of BFH. It is likely that these tumors may originate from spinal dura mater mesenchymal stem cells and from the intracerebral perivascular pial sheath or the brain vessel walls themselves, respectively. Other benign, isolated, intracranial fibrohistiocytic neoplasms, namely the juvenile xanthogranuloma, can harbor a clinical, morphological and immunohistochemical profile overlapping the one of the BFH. Intracranial germ cell tumors may be associated with Down's syndrome, although harboring an unusual, non-pineal and non-chiasmatic location. One can speculate that a similar, still unknown genetic mechanism responsible for this association, could also induce the growth of other type of tumors in patients with this syndrome. BFHs should be added to the differential diagnosis of intracerebral or spinal dural attached tumors. Furthermore, we propose to name these intracranial tumors "benign isolated fibrohistiocytic tumors of the CNS".

PubMed, Jul 27, 2023

Background: The prevalence of thyrotropin-secreting pituitary adenomas, most being macroadenomas,... more Background: The prevalence of thyrotropin-secreting pituitary adenomas, most being macroadenomas, is one to two cases per million inhabitants. Their differential diagnosis may be challenging, especially for microadenomas. Case description: We present the case of a 50-year-old male with progressive neck enlargement, hot sudorific hands, anorexia, diarrhea, and weight loss over the preceding three months. Laboratory evaluation revealed high thyroid hormones, predominantly high free triiodothyronine of 7.74 pg/mL (reference range 2.3-4.2), with a non-suppressed thyroid stimulating hormone (TSH) of 1.73 µIU/mL (reference range 0.55-4.78). A high level of suspicion directed additional evaluation that revealed a high total alpha-subunit of glycoprotein hormones (αGS) and αGS/TSH ratio. Magnetic resonance imaging revealed a six mm pituitary lesion. A microthyrotropinoma was diagnosed, and long-acting octreotide was initiated before surgery for symptomatic control. Endoscopic transnasal transsphenoidal tumor resection was performed months later. The patient was in remission one year after surgery with no pituitary deficits. Conclusions: Reaching an accurate diagnosis on time is crucial for deciding the optimal therapeutic approach and preventing and decreasing the frequency of endocrine and neurological complications. HIPPOKRATIA 2022, 26 (4):157-160.

Endocrine Abstracts, May 3, 2017

Neuro-oncology advances, 2023

Background. Despite current improvements in systemic cancer treatment, brain metastases (BM) rema... more Background. Despite current improvements in systemic cancer treatment, brain metastases (BM) remain incurable, and there is an unmet clinical need for effective targeted therapies. Methods. Here, we sought common molecular events in brain metastatic disease. RNA sequencing of thirty human BM identified the upregulation of UBE2C, a gene that ensures the correct transition from metaphase to anaphase, across different primary tumor origins. Results. Tissue microarray analysis of an independent BM patient cohort revealed that high expression of UBE2C was associated with decreased survival. UBE2C-driven orthotopic mouse models developed extensive leptomeningeal dissemination, likely due to increased migration and invasion. Early cancer treatment with dactolisib (dual PI3K/mTOR inhibitor) prevented the development of UBE2C-induced leptomeningeal metastases. Conclusions. Our findings reveal UBE2C as a key player in the development of metastatic brain disease and highlight PI3K/mTOR inhibition as a promising anticancer therapy to prevent late-stage metastatic brain cancer. Key Points • High levels of UBE2C in BM correlate with patients' worse outcome. • UBE2C promotes leptomeningeal dissemination in vivo. • PI3K/mTOR inhibition prevents this late-stage complication of cancer. UBE2C promotes leptomeningeal dissemination and is a therapeutic target in brain metastatic disease

Neuro-oncology advances, Aug 1, 2021

Andrologia, May 11, 2017

Disorders of sex development generally present in the neonatal period with ambiguity of external ... more Disorders of sex development generally present in the neonatal period with ambiguity of external genitalia. We report a very old male patient presenting at 75 years because of panhypopituitarism and a large nonsecreting pituitary macroadenoma secondary to long-standing primary hypogonadism due to 46,XX sex reversal disorder now first diagnosed. Sex development disorders may go unrecognised for the entire life span, despite infertility and long-standing primary gonadic failure may lead to uncommon complications.

Journal of Pediatric infectious diseases, 2010

The Burkholderia cepacia complex (Bcc) compris-es nine related ubiquitous bacteria that are prese... more The Burkholderia cepacia complex (Bcc) compris-es nine related ubiquitous bacteria that are present in moist environments, such as in soil and fresh water, and in certain urban areas. They are regarded as human op-portunistic pathogens, mostly as agents of nosocomial ...

Childs Nervous System, Apr 23, 2016

Introduction Despite being the second most frequent tumor in children, pediatric central nervous ... more Introduction Despite being the second most frequent tumor in children, pediatric central nervous system (CNS) tumors are rare, and the published European epidemiological data is limited. Our goal is to present the first surgical series of pediatric CNS tumors in Portugal and to review other similar worldwide series. Methods Retrospective review of all patients younger than 19 years old, operated to a CNS tumor in the Neurosurgery Department at Hospital de Santa Maria (Lisbon, Portugal) between January 2004 and December 2014. Demographic data, tumor location, clinical data, histopathology, and surgical treatment were analyzed and compared to surgical series of pediatric CNS tumors published in PubMed indexed journals over the last 20 years. Results We performed 253 surgeries in 215 patients, with a male:female ratio of 1.2:1 and a mean age of 9.2 years old. Primary brain tumors accounted for 95 % of all tumors and had more often a supratentorial location. Tumors of neuroepithelial tissue, particularly astrocytic tumors, embryonal tumors, neuronal and mixed neuronal-glial tumors, and oligodendrogliomas accounted for 81 % of cases. A grosstotal resection was achieved in most cases. There was no mortality, and the overall morbidity was low. Conclusions The demography, topography, and clinical presentation of the tumors and the surgical results of this series are comparable to other European ones. We found a higher incidence of neuronal and mixed neuronal-glial tumors and oligodendrogliomas and a slight lower incidence of ependymomas. Our results should encourage further national multi-institutional studies to better characterize these tumors in the pediatric population.

ABSTRACTDespite current improvements in systemic cancer treatment, brain metastases (BM) remain i... more ABSTRACTDespite current improvements in systemic cancer treatment, brain metastases (BM) remain incurable, and there is an unmet clinical need for effective targeted therapies. Here, we sought common molecular events in brain metastatic disease. RNA sequencing of thirty human BM identified the upregulation of UBE2C, a gene that ensures the correct transition from metaphase to anaphase, across different primary tumor origins. Tissue microarray analysis of an independent BM patient cohort revealed that high expression of UBE2C was associated with decreased survival. UBE2C-driven orthotopic mouse models developed extensive leptomeningeal dissemination, likely due to increased migration and invasion. Early cancer treatment with dactolisib (dual PI3K/mTOR inhibitor) prevented the development of UBE2C-induced leptomeningeal metastases. Our findings reveal UBE2C as a key player in the development of metastatic brain disease and highlight PI3K/mTOR inhibition as a promising anticancer thera...

Endocrine Abstracts, 2017