The susceptibility of brain to secondary formation from lung cancer primaries is a well-known phenomenon. In contrast, the molecular basis for invasion and metastasis to the brain is largely unknown. ...In the present study, 31 brain metastases that originated from primary lung carcinomas were analyzed regarding over expression of Dishevelled-1 (DVL1), Dishevelled-3 (DVL3), E-cadherin (CDH1) and beta-catenin (CTNNB1). Protein expressions and localizations were analyzed by immunohistochemistry. Genetic alterations of E-cadherin were tested by polymerase chain reaction (PCR)/loss of heterozygosity (LOH). Heteroduplex was used to investigate mutations in beta-catenin. DVL1 and DVL3 showed over expression in brain metastasis in 87.1% and 90.3% of samples respectively. Nuclear staining was observed in 54.8% of cases for DVL1 and 53.3% for DVL3. The main effector of the Wnt signaling, beta-catenin, was up-regulated in 56%, and transferred to the nucleus in 36% of metastases. When DVL1 and DVL3 were up-regulated the number of cases with nuclear beta-catenin significantly increased (p=0.0001). Down-regulation of E-cadherin was observed in 80% of samples. Genetic analysis showed 36% of samples with LOH of the CDH1. In comparison to other lung cancer pathologies, the diagnoses adenocarcinoma and small cell lung cancer (SCLC) were significantly associated to CDH1 LOH (p=0.001). Microsatellite instability was detected in one metastasis from adenocarcinoma. Exon 3 of beta-catenin was not targeted. Altered expression of Dishevelled-1, Dishevelled-3, E-cadherin and beta-catenin were present in brain metastases which indicates that Wnt signaling is important and may contribute to better understanding of genetic profile conditioning lung cancer metastasis to the brain.
Tumor suppressor gene AXIN1 is an inhibitor of Wnt signaling pathway. It down-regulates the pathway's main signaling effector molecule, beta-catenin, in an AXIN-based destruction complex. In the ...present study we investigated the involvement of AXIN1 in intracranial meningioma.
Loss of heterozygosity and microsatellite instability analyses were performed. The consequences of genetic changes on protein expression levels were studied in the same patients by immunohistochemistry.
Allelic deletions of AXIN1 gene were found in 21.1% of meningiomas. Microsatellite instability was also observed in 5.3% of cases. Weak or lack of AXIN1 expression was found in 21.9% of meningiomas. We found strong statistical correlations between cytoplasmic localization of AXIN1 and its weak expression and also between the simultaneous cytoplasmic and nuclear localizations and moderate and strong expression levels (p<0.000). The findings on AXIN1 were compared to concomitant expression of APC, beta-catenin and E-cadherin in the same patients by Chi-Square tests and Pearson's correlations. Analysis revealed that AXIN1 genetic changes were significantly associated to lack of the expression of APC and presence of mutant APC proteins (p<0.018). Moderate and strong cytoplasmic and nuclear AXIN1 expressions were positively correlated to strong expression of E-cadherin (p<0.05).
Our findings on genetic changes and expression levels of AXIN1 bring novel data on its involvement in meningeal brain tumors and reveal AXIN1's relation to specific Wnt molecules.
Spontaneous resolution of nonfunctioning pituitary adenoma after hemorrhagic apoplexy is a rare clinical entity of unknown etiology and is defined as disappearance of a tumor without any specific ...treatment. Here we present a 54-year-old male patient who presented with acute onset of severe headache, vomiting, photophobia, and sonophobia. He was referred to brain computed tomography, which showed a 16x12x16 mm tumor mass located in the sellar region with signs of hemorrhage. Endocrinologic evaluation was consistent with under-function of pituitary gonadotropic cells. Magnetic resonance imaging (MRI) performed ten days later was consistent with hemorrhagic apoplexy of the pituitary adenoma. The patient's symptoms resolved after conservative treatment with dexamethasone, but he was scheduled for elective pituitary surgery. Preoperative MRI was performed one month after the first one and disclosed normal pituitary gland without any signs of adenoma. Our case is remarkable due to the fact that spontaneous remission of pituitary adenoma occurred within the first month, which is the shortest interval reported to date. Our case highlights the importance of conservative therapy as the first-line treatment for pituitary apoplexy in the absence of neurological impairment, since spontaneous remission may occur in a short time interval. Key words: Pituitary neoplasms; Pituitary apoplexy; Adenoma; Empty sella syndrome; Neoplasm regression, spontaneous; Remission, spontaneous
Empty Sella in the Making Kirigin Biloš, Lora Stanka; Kruljac, Ivan; Radošević, Jelena Marinković ...
World neurosurgery,
August 2019, 2019-Aug, 2019-08-00, 20190801, Volume:
128
Journal Article
Peer reviewed
Pituitary apoplexy may occur when a large tumor compresses or outgrows its nutrient supply, resulting in ischemic necrosis and hemorrhage. Although once deemed a neurosurgical emergency, increasing ...evidence suggests that conservative management of pituitary apoplexy leads to favorable neuro-ophthalmologic and endocrinologic outcomes as well. Spontaneous remission after pituitary apoplexy has been described in functioning pituitary adenomas, but it is a rare occurrence in nonfunctioning tumors.
We report a man that presented with pituitary apoplexy of a nonfunctioning pituitary macroadenoma that was managed conservatively and treated hormonally for hypopituitarism during a 2-year follow-up period, with serial neuroimaging demonstrating significant tumor volume reduction with almost complete resolution resulting in partial empty sella. In addition, a short literature review was performed pertaining to the management of pituitary apoplexy with emphasis on a more conservative approach.
A subset of patients with pituitary apoplexy without altered consciousness and nonprogressive or mild ophthalmologic deficits may be managed conservatively; however, lifelong periodic assessment, preferably by a specialized multidisciplinary pituitary team, is essential until clinical outcomes become clear.
- A rare case of necrotizing hypophysitis (NH) in a 52-year-old man presenting with pituitary apoplexy and sterile meningitis is described. This case indicates that the diagnosis of NH could be made ...without biopsy, based on concomitant presence of diabetes insipidus, hypopituitarism and radiologic features of ischemic pituitary apoplexy. Conservative management of pituitary apoplexy should be advised in NH. Additionally, this is the first report of a case of sterile meningitis caused by ischemic pituitary apoplexy.
Purpose: Increasing evidence exists that hyperprolactinemia alters metabolic profile. The mechanism of this effect is unknown. We aimed to investigate the differences between the metabolic profile of ...patients with prolactinomas and nonfunctional pituitary adenomas and to evaluate the impact of other pituitary hormones on their metabolic profile. Methods: Our retrospective study included 86 consecutive patients with prolactinomas and nonfunctional adenomas (29 prolactinomas and 57 adenomas). Body mass index (BMI), blood pressure, serum prolactin, growth hormone (GH), insulin-like growth factor I (IGF-I), adrenocorticotropic hormone (ACTH), cortisol, urinary free cortisol, triiodothyronine (T3), thyroxine (T4), thyroid-stimulating hormone (TSH), dehydroepiandrosterone-sulfate (DHEA-S), testosterone in men, triglycerides, total cholesterol, HDL (high-density lipoprotein) cholesterol, LDL (Low-density lipoprotein) cholesterol, alanine-transaminase, aspartate-transaminase, fasting glucose, and C-reactive protein (CRP) were obtained for all patients. Regression analyses were performed on log-transformed data. Results: After adjustment for age, gender, and tumor size, prolactinomas were associated with higher BMI (OR 5.61, 95%CI 1.70-9.51, p = 0.005), LDL cholesterol (OR 3.60, 95%CI 1.35-5.93, p = 0.015), DHEA-S (OR 1.97, 95%CI 1.23-3.72, p = 0.026), and lower GH levels (OR 0.43, 95%CI 0.03-0.84, p = 0.037). In a linear multivariate regression, the association between DHEA-S, GH, and prolactin remained significant even after adjustment for BMI. GH and IGF-I were associated with BMI and LDL cholesterol, but the association diminished after adjustment for serum prolactin. Conclusions: Prevalence of obesity is four times higher in patients with prolactinomas than in patients with nonfunctional adenomas. Higher DHEA-S and lower GH levels in patients with prolactinomas may have an important role in prolactin-induced metabolic effects. Further studies are needed.
Purpose. In low-income countries, prolactinomas are difficult to manage with dopamine agonists (DA). We compared the effectiveness of DA in microprolactinomas as a first line treatment and as ...adjuvant therapy for residual macroprolactinomas treated surgically. Methods. Our retrospective study analyzed 78 patients, 38 with microprolactinomas and 40 with macroprolactinomas. Microprolactinomas were treated with DA. Macroprolactinomas were treated with microsurgical or endoscopic adenomectomies and adjuvant DA. Surgical remission was defined as normoprolactinemia three months postoperatively, and long-term remission as normoprolactinemia at the last control. Results. Surgical remission was achieved in 9 patients (23%). Postsurgical tumor mass was reduced by 50% (34–68). Residual macroprolactinoma size was greater than microprolactinoma size prior to treatment (10 mm versus 4 mm, P < 0.001 ). Both groups received similar doses of DA. Long-term remission occurred in 68% of microprolactinomas and 43% of macroprolactinomas ( P = 0.102 ). Prolactin (PRL) levels at the last control were similar in both groups (23.1 versus 32.9 mcg/L, P = 0.347 ). Conclusion. Comparable remission rates and PRL levels were reached in microprolactinomas and macroprolactinomas using similar doses of DA. Although complete tumor resection is the goal of surgery, our study suggests that even partial surgical removal has a role in treatment of prolactinomas since it may enhance the response to DA.
To analyze early remission, complications, and pituitary function recovery after pure endoscopic endonasal transsphenoidal surgery (PEETS), a novel method in pituitary adenoma treatment.
Testing of ...all basal hormone values and magnetic resonance imaging (MRI) were performed preoperatively and postoperatively (postoperative MRI only in nonfunctioning adenomas) in 117 consecutive patients who underwent PEETS in the period between 2007 and 2010. The series consisted of 21 somatotroph adenomas, 61 prolactinomas, and 4 corticotroph and 31 nonfunctioning adenomas. Sixty-three were macroadenomas and 54 were microadenomas. Remission was defined as hormonal excess normalization on the seventh postoperative day in functioning adenomas and as normal MRI findings approximately four months postoperatively in nonfunctioning adenomas. The presence of hypogonadism, growth hormone deficiency, and hypothyroidism was assessed on the seventh postoperative day. Hypocortisolism was assessed through necessity for replacement therapy within 18 months postoperatively.
Remission was achieved in 84% of patients: in 100% of microadenoma and 70% of macroadenoma patients (P<0.001, odds ratio OR, 28.16, 95% confidence interval CI, 1.61-491.36), respectively. Endocrinological complications occurred in 17.1% of patients: in 9% of microadenoma and 24% of macroadenoma patients (P=0.049, OR, 3.06; 95% CI, 1.03-9.08). Duration of empirical hydrocortisone replacement therapy was significantly shorter in microadenoma patients (P<0.001). Thirty-five percent of preoperatively present hormonal deficiencies improved after the surgery. Between tumor types there were no significant differences in remission, complications, and normal pituitary function recovery.
Patients with microadenomas had higher remission and lower complication rates following PEETS, emphasizing the necessity for early detection and treatment of pituitary adenomas. PEETS is a discussion-worthy method for microprolactinoma treatment.
Pituitary apoplexy (PA) typically results from infarction or hemorrhage in a pituitary adenoma, while PA in nonadenomatous pituitary gland is uncommon. Prothrombotic states have never been recognized ...as precipitating factors for PA. The authors report a case of an elderly female who received prophylactic fractionated heparin therapy due to sepsis, consequent rhabdomyolysis, and overt disseminated intravascular coagulation. On the seventh day of heparin therapy, she reported sudden vision loss, ptosis, diplopia, and severe headache. Severe thrombocytopenia and positive antibodies to the complex of platelet factor 4 and heparin confirmed heparin-induced thrombocytopenia type 2 (HIT). Magnetic resonance imaging disclosed a homogenous pituitary tumor mass with pronounced sphenoid sinus mucosa thickening and two hypointense zones within the tumor mass on contrast-enhanced images consistent with focal ischemic necrosis. The tumor was confirmed to be squamous cell carcinoma with no signs of necrosis. Ischemic necrosis was found within marginal pituitary tissue. This is the first reported case of ischemic PA associated with pituitary metastasis and the first case in which HIT triggered PA. Our case demonstrates that prothrombotic states such as HIT can precipitate ischemic PA. Pituitary metastasis can present with ischemic PA, but radiological features differ from those described in pituitary adenomas. Segregated low-signal intensity zones within the tumor mass on postcontrast images indicate partial infarction of the tumor, which could be a special feature of ischemic PA in pituitary metastasis and has never been described in pituitary adenomas. These are all novel findings and might enlighten the pathogenesis of PA.
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