Salivary gland tissues and derived primary and metastatic neoplasms: unusual pitfalls in the work-up of sellar lesions. A systematic review.

PURPOSE: Salivary gland (SG) tissue and derived neoplasms may occur in the sellar region. As the current literature is mostly limited to case reports, the puzzling case of an inflammatory SG removed by transsphenoidal surgery (TS) and mimicking a prolactinoma prompted us to perform the first systematic review of these unusual conditions. METHODS: A systematic literature search was conducted according to the PRISMA guidelines. Forty-four individual cases-non-neoplastic enlarged salivary glands (NNESG, n = 15), primary benign (n = 7) and malignant (n = 8) ectopic salivary tumours (ST) and sellar metastasis from eutopic primary ST (n = 14)-were suitable for the analysis of clinical, radiological and pathological characteristics. Therapeutic outcome was reviewed as a secondary endpoint. RESULTS: All cases were diagnosed after surgery. NNESG commonly affected young and/or female patients, typically leading to headaches and hyperprolactinemia and originating close to the neurohypophysis. Submucosal SG should be excluded before concluding to an intrasellar NNESG after TS. No gender or age predominance was found for primary ectopic ST, which present as large tumors, with histological phenotypes similar to common ST. Hypopituitarism and diabetes insipidus were more frequent in ST than in NNESG. NNESG and benign ectopic ST rarely recur. Malignant ectopic ST should be distinguished from secondary localizations of eutopic ST reaching the sella by contiguity or metastatic spread; both share a frequent unfavorable outcome. CONCLUSION: Sellar neoplasms derived from SG are rare but misleading conditions and pituitary dysfunction is likely to be more common than currently reported. Appropriate pathological evaluation and multidisciplinary approach are required.

Pituitary metastasis from renal cell carcinoma: case report and review of the literature.

Pituitary metastasis(PM) from renal cell carcinoma(RCC) is rare, and is easy to be misdiagnosed. Here, we present a case of pituitary metastasis from clear-cell renal cell carcinoma(ccRCC) which was difficult to distinguish from other sellar region tumors. In addition, we systematically review the literature to find the characteristics of different tumors of the sellar region. It provides a new idea for the diagnosis of sellar region tumors in the clinic.

Metastatic Spread to the Pituitary.

The pituitary fossa is an uncommon site for metastatic tumor spread. Metastatic lesions to the sellar area derived mostly from breast, lung, renal, prostate, and colon cancers, and rarely from other solid and hematologic malignancies. Almost every cancer has been reported as a source of pituitary metastasis. Pituitary metastasis can involve both the anterior and posterior lobes, but the neuro-hypophysis is mainly involved. Clinical manifestations include diabetes insipidus, hypopituitarism, headache, visual disturbances, ophthalmoplegia, and also compression of adjacent structures by aggressive tumor masses. Metastatic spread to the pituitary from a distant primary malignancy is commonly associated with metastases to other tissues and poor prognosis, unless efficient systemic targeted medical treatment is available for the primary cancer (melanoma, lymphoma).

Current status and treatment modalities in metastases to the pituitary: a systematic review.

BACKGROUND: Metastases to the pituitary (MP) are uncommon, accounting for 0.4% of intracranial metastases. Through advances in neuroimaging and oncological therapies, patients with metastatic cancers are living longer and MP may be more frequent. This review aimed to investigate clinical and oncological features, treatment modalities and their effect on survival. METHODS: A systematic review was performed according to PRISMA recommendations. All cases of MP were included, excepted primary pituitary neoplasms and autopsy reports. Descriptive and survival analyses were then conducted. RESULTS: The search identified 2143 records, of which 157 were included. A total of 657 cases of MP were reported, including 334 females (50.8%). The mean ± standard deviation age was 59.1 ± 11.9 years. Lung cancer was the most frequent primary site (31.0%), followed by breast (26.2%) and kidney cancers (8.1%). Median survival from MP diagnosis was 14 months. Overall survival was significantly different between lung, breast and kidney cancers (P < .0001). Survival was impacted by radiotherapy (hazard ratio (HR) 0.49; 95% confidence interval (CI) 0.35-0.67; P < .0001) and chemotherapy (HR 0.58; 95% CI 0.36-0.92; P = .013) but not by surgery. Stereotactic radiotherapy tended to improve survival over conventional radiotherapy (HR 0.66; 95% CI 0.39-1.12; P = .065). Patients from recent studies (≥ 2010) had longer survival than others (HR 1.36; 95% CI 1.05-1.76; P = .0019). CONCLUSION: This systematic review based on 657 cases helped to better identify clinical features, oncological characteristics and the effect of current therapies in patients with MP. Survival patterns were conditioned upon primary cancer histologies, the use of local radiotherapy and systemic chemotherapy, but not by surgery.

Unusual ectopic ACTH syndrome in a patient with orbital neuroendocrine tumor, resulted false-positive outcome of BIPSS:a case report.

BACKGROUND: Cushing's syndrome has been described as a complex endocrine disorder characterized with high cortisol concentration. Correct and early diagnosis of Cushing's syndrome is challenging. According to the latest guideline, bilateral inferior petrosal sinus sampling (BIPSS) is considered to be the gold standard for the differential diagnosis. However, in some unusual cases, this method may be false positive. Here, we presented a rare case of orbital neuroendocrine tumor secreting adrenocorticotrophic hormone with false positive inferior petrosal sinus sampling. CASE PRESENTATION: A 48-year-old woman was admitted to West China Hospital of Sichuan University, presenting with fatigue, whole body edema for 1 year, alopecia and skin pigmentation for 5 months. Hormonal profiles including plasma cortisol and adrenocorticotrophic hormone (ACTH) measurements and low-dose dexamethasone inhibition test suggested that the patient had Cushing's syndrome. However, during tumor location phase, the results of high-dose dexamethasone inhibition test (HDDST) contradicted desmopressin (DDAVP) stimulation test. Thus, BIPSS was employed, and its results indicated a pituitary origin. Interestingly, MRI of sellar region showed an innocent pituitary but caught a serendipitous lesion in the lateral rectus muscle of left eye, which was later proved to be an orbital neuroendocrine tumor secreting ACTH by pathological and immunohistochemical results. ACTH level of the patients was < 0.1 ng/L and cortisol level was 51.61 nmol/L 1 week after surgery. At 24 months follow-up, the patient appeared stable with no complaints nor any symptoms of Cushing's syndrome, including moon face, purple striate and central obesity. The patient's life quality also improved significantly. CONCLUSION: We reported a rare case of endogenous Cushing's syndrome due to ectopic ACTH secreting from an orbital neuroendocrine tumor. This unique case of orbital EAS suggests that orbital venous blood backflow, owning to abnormal anatomic structures, may possibly lead to false positive BIPSS results.

[Hypovascular Pituitary Metastasis from Poorly Differentiated Lung Adenocarcinoma:Report of One Case].

Pituitary metastasis is a rare intracranial malignant tumor originated from other malignant tumors at other parts of the body.Pituitary metastases are typically hypervascular,while hypovascular pituitary metastasis is rare.Radiologically,hypovascular pituitary metastasis is difficult to be distinguished from pituitary adenoma.This article reports one case of pathologically confirmed hypovascular pituitary metastasis,with the main diagnostic clues including history of malignant tumor,presence of normal pituitary in the intrasellar region,and isointensity on T1 and T2 sequence.

Clinical management of a pituitary gland metastasis from clear cell renal cell carcinoma.

In very few years, several treatments have significantly improved the prognosis of patients with metastatic renal cell carcinoma (RCC). Despite this, the clinical outcomes of specific subgroups of patients including those with central nervous metastases still remain poor. In this population, a very infrequent and poorly described site of metastases is the pituitary gland. Because of the important endocrinal function and the anatomic site of this specific organ, clinical management of this complication requires several additional precautions compared with other central nervous metastases. Here, we describe a case of a single pituitary metastasis from clear cell RCC in a patient who showed a surprising progression-free survival and overall survival to sunitinib first-line treatment. Because of the uncommon clinical course of the disease of our patient and the atypical site of metastases, we want also to underline the importance of further investigation of molecular pathways associated with a favorable prognosis in patients with metastatic clear cell RCC.

Twelve cases of pituitary metastasis: a case series and review of the literature.

PURPOSE: The pituitary gland is an unusual site for metastatic spread, but as patients with metastatic malignancy are living longer, it may become more prevalent. Compression of important anatomy adjacent to the sella may produce disabling symptoms and endocrine derangement, leading to significant morbidity. METHODS: An ambispective review of patient records between 2013 and 2017 from three neurosurgical centres was performed. After identifying cases, further investigation was performed to evaluate patient demographic, symptoms at presentation, radiological and histological findings, management, and outcome. RESULTS: Our investigation identified 12 patients with pituitary metastasis. The average age of the cases was 63.4 years, with breast (n = 4) and lung (n = 4) being the most common primary cancers. In half the cases there was a history of metastatic disease, while in one-quarter of cases, pituitary symptoms were the first sign of malignancy. Adenohypophyseal dysfunction (83%), diabetes insipidus (DI) (75%), headache (67%) and visual field defects (67%) were the most common findings at presentation. Glucocorticoid replacement increased the sensitivity for diagnosis of DI. All cases were contrast enhancing on MRI and the endoscopic trans-sphenoidal approach was preferred for biopsy and debulking. CONCLUSIONS: The pituitary should not be overlooked as a site of metastasis and sellar symptoms may be the first presentation of neoplastic disease. Any biochemical or clinical sign of pituitary pathology in a patient with known cancer should raise suspicion for sellar metastasis. Moreover, the development of DI or ophthalmoplegia from any pituitary lesion is suggestive of metastatic disease even in patients with no known primary.

Pituitary Metastasis in a Patient with Pulmonary Adenocarcinoma Presenting with a Disturbance of Consciousness.

BACKGROUND: Brain metastases are one of the main causes of morbidity and mortality of patients with oncological disease. In non-small cell lung carcinoma (NSCLC), the risk of CNS secondary development is 30-50%. An unusual diagnostic and therapeutic problem is the finding of suspicious pituitary lesions. Obtaining a differential diagnosis relies on evaluating the clinical course of the disease (visual disturbances, diabetes insipidus (DI), weakness etc.), and performing endocrinological examinations and imaging analyses (CT, but mainly MRI). Sometimes, however, definitive resolution of the problem requires histological assessment of the tumor. CASE REPORT: A 65-year-old patient with a newly diagnosed metastatic lung adenocarcinoma was admitted to our department for a first cycle of chemotherapy consisting of cisplatin and navelbine. However, at the beginning of hospitalization, the patient developed qualitative disturbances in consciousness and disorientation. Emergency CT of the CNS revealed a tumor of the pituitary gland, and a subsequent MRI showed intraseller and suprasellar masses making contact with the optic chiasma. An endocrinological examination revealed panhypopituitarism. Pituitary metastasis of NSCLC was confirmed by tumor histology using the trans-sphenoid approach. CONCLUSION: Lung and breast carcinomas are among the most common cancers to metastasize to the pituitary gland. The incidence of pituitary metastases is reported to be 0.4-28.1%. Clinically, they are mostly silent, but may manifest as endocrine disorders, such as DI, hypothyroidism, and hypocorticism, or as visual disturbances due to compression of the optic nerve. Management depends on the establishment of a correct diagnosis. Key words: hypopituitarism - magnetic resonance imaging - pituitary neoplasm - radiosurgery - targeted therapy The authors declare they have no potential confl icts of interest concerning drugs, products, or services used in the study. The Editorial Board declares that the manuscript met the ICMJE recommendation for biomedical papers. Submitted: 26. 4. 2018 Accepted: 27. 6. 2018.

Hypofractionated stereotactic radiosurgery for pituitary metastases.

Pituitary metastases (PMs) are uncommon, representing only 1% of pituitary lesions. The diagnosis of PMs can be challenging and an optimal management remains to be determined. Here, we present a pilot clinical study on the efficacy and safety of hypofractionated stereotactic radiosurgery (SRS) with an optimized dosimetric plan in treating PMs. Between June 2013 and December 2014, seven consecutive patients (4 men and 3 women; median age 62 years) had been diagnosed with PMs based on their characteristic clinical and radiological features and subsequently treated using hypofractionated SRS. Primary cancers originated from the lung (n = 5) or the breast (n = 2). All patients presented with diabetes insipidus (DI). Anterior pituitary and visual dysfunction were combined in 4 and 3 patients, respectively. On magnetic resonance imaging (MRI), PMs involved the pituitary stalk and/or the posterior lobe in all patients. SRS of a cumulative marginal dose 31 Gy with dose-volume constraints for the optic apparatus was delivered in 5 daily fractions. As results, tumor was locally controlled in all patients with substantial responses on MRI (including complete remission in 4 patients). The median survival time was 14 months (range, 6-24 months) after SRS. DI and visual dysfunction improved in all patients, although anterior pituitary dysfunction did not recover. No patients experienced any deterioration in visual, pituitary, or other cranial nerve functions. These results suggest a promising role of hypofractionated SRS in treating PMs in terms of both tumor control and functional outcomes.

Gastrointestinal stromal tumor metastases to the pituitary: a rare entity.

Gastrointestinal stromal tumors (GISTs) are rare, but represent the most common mesenchymal tumor of the gastrointestinal tract. The paucity of intracranial metastasis makes treatment strategies difficult. This manuscript presents the first documented case report of a GIST that presented clinically with pituitary symptoms due to a pituitary metastasis.

[A Case of Central Diabetes Insipidus That Was Caused by Pituitary Metastasis of Lung Adenocarcinoma and Was Controlled by Radiation Therapy].

BACKGROUND: Pituitary metastasis of lung cancer is rare; however, it often causes diabetes insipidus. Although the majority of such patients are treated with radiation therapy, it remains unclear whether diabetes insipidus can be controlled by radiation therapy. CASE: A 72-year-old man was admitted to our hospital for hemosputum, headache, and polyuria. A chest CT scan showed a 3.0 cm mass in the left upper lobe of his lung. Bronchofiberscopy results confirmed the pathological diagnosis of lung adenocarcinoma. Based on the findings from PET-CT, head MRI, and endocrine tests, the diagnosis of lung adenocarcinoma( cT1bN0M1b, stage IV)accompanied with central diabetes insipidus caused by pituitary metastasis was made. Oral administration of desmopressin reduced urine volumes; however, chemotherapy for achieving stable disease in the primary tumor was ineffective in controlling the symptoms of diabetes insipidus. Chemotherapy was discontinued after 4 months because of severe hematological toxicity. During 2 months after the cessation of chemotherapy, polyuria worsened and, therefore, radiation therapy for pituitary metastasis was started. Following the radiation therapy, an apparent reduction in urine volume was observed. CONCLUSION: Our experience of this case suggests that radiation therapy for pituitary metastasis should be considered at the time when diabetes insipidus becomes clinically overt.

[Metastatic Pituitary Disorders]. / Metastatické postizení hypofýzy.

BACKGROUND: Pituitary metastases are a rare complication of generalized cancer. Metastases to the pituitary gland occur in only 1% of patients operated on for sellar tumor. The most common presenting symptom in patients with pituitary metastases is diabetes insipidus, whereas this is rare in those with pituitary adenoma. MATERIAL AND METHODS: This publication presents the cases of two patients with pituitary metastases and a systematic review of the literature. English-language publications related to pituitary metastases and published from 1957 to 2016 were identified using the PubMed database. RESULTS: A total of 131 publications containing information about 259 patients (121 female and 138 male; mean age, 57.3 years) were identified. The most often metastasized breast carcinoma (24.6%) and lung carcinoma (23.8%), followed by thyroid carcinoma (11.3%), renal cell carcinoma (7.8%), hepatocellular carcinoma (4.3%), colorectal carcinoma (3.5%), and malignant melanoma (3.5%). The most frequent initial symptoms were manifestations of diabetes insipidus (39.6%), anterior pituitary deficiency (44.9%), perimeter disorders (51.6%), headache (37.6%), cranial nerve palsy (33.5%), and pseudoprolactinemia (16.7%). Radiotherapy (67.8%) and surgical treatment (63.9%) were the most frequently used treatment. CONCLUSION: The average survival time from the onset of metastatic disease was 11.8 months. Surgical therapy alone or in combination with radiation therapy does not prolong survival, but alleviates symptoms and improves quality of life.Key words: pituitary metastasis - diabetes insipidus - hypopituitarism - transsphenoidal surgery The authors declare they have no potential conflicts of interest concerning drugs, products, or services used in the study. The Editorial Board declares that the manuscript met the ICMJE recommendation for biomedical papers.Submitted: 13. 1. 2017Accepted: 4. 4. 2017.

Pituitary metastasis: is there still a place for neurosurgical treatment?

Pituitary metastases are uncommon, ranging from 1 to 5 % of all metastases. Between 10 and 30 % of pituitary lesions are symptomatic responsible for diabetes insipidus, visual field defect or cranial nerve palsy. Primary sites are lung or breast in two-thirds of cases. There is no current reference concerning treatment of such lesions. Overall survival is poor and depends on primary site. Although the role of surgery is currently limited, discussion is warranted in several indications for diagnostic or symptomatic purposes. We report two cases of symptomatic pituitary metastases in a context of breast cancer and review the litterature concerning the role of surgery and other treatment modalities.

[Leptomeningeal Dissemination in Patients with Pituitary Metastasis from Breast Cancer].

Pituitary metastases are uncommon complications of systemic cancer and account for only 1% of pituitary lesions. Breast cancer is one of the most common tumors to metastasize to the pituitary gland. A multidisciplinary approach that calls for close collaboration among oncologists, neurosurgeons, radiologists, and endocrinologists is mandatory for diagnosis and treatment of pituitary metastasis. From 2002 through 2013, 6 patients with pituitary metastases were treated at Shizuoka Cancer Center Hospital. The patients' age at presentation ranged from 45 to 75 years (average 59 years). Five of 6 patients had symptoms: anterior pituitary insufficiency in 4, diabetes insipidus in 3, and visual deficits in 2 patients. Five patients had other metastases at the time of presentation. Local irradiation to the metastatic lesion was adopted in 4, and whole brain irradiation was in 2 patients. In all cases, local control was achieved after irradiation, however, the pituitary insufficiency did not recover. Two of 4 patients treated with local irradiation suffered from meningeal dissemination within 5 months after treatment, and died at 8 and 11 months after diagnosis of pituitary metastasis, respectively. The patients treated with whole brain irradiation had longer survival periods. Early diagnosis, endocrinological management, and radiation therapy improve the quality of life in patients suffering from pituitary metastasis. Whole brain irradiation may be favorable in order to prevent meningeal dissemination.

[Atypical presentation of a breast cancer pituitary metastasis]. / Découverte fortuite d'une métastase hypophysaire d'un cancer du sein : cas clinique.

Pituitary metastasis occur in 1-5 % of patients with cancer. We report the discovery of a unique pituitary metastasis of breast cancer. A 67 years old woman was treated in 2003 for local adenocarcinoma. After bone metastatic relapse in 2008, the patient developed diplopia and diabetes insipidus. An MRI revealed a histologically proven metastatic pituitary nodule. Further explorations revealed failure of multiple endocrine axes. Pituitary metastases are relatively rare, but are probably under-diagnosed in the presence of advanced cancers with impaired general condition. This diagnosis should be considered in the context of cancer patients, with a recent history of diabetes insipidus, especially if the latter is associated with other neurological signs (ophthalmoplegia, cephallagia).

Les métastases hypophysaires surviennent chez 1 à 5 % des patients atteints de cancers. Nous rapportons ici la découverte fortuite d'une métastase hypophysaire d'un cancer du sein. Une patiente de 67 ans est prise en charge en 2003 pour un adénocarcinome mammaire localisé. Après une récidive métastatique osseuse en 2008, elle présente une diplopie et un diabète insipide. L'IRM cérébrale décèle une lésion hypophysaire dont l'origine métastatique est confirmée en anatomopathologie; une extension du bilan permet de diagnostiquer une insuffisance des multiples axes endocriniens. Les métastases hypophysaires sont des lésions relativement rares, mais qui restent probablement sous-diagnostiquées dans le contexte du cancer avancé avec altération majeure de l'état général. Ce diagnostic doit être évoqué en cas de découverte récente d'un diabète insipide, en particulier s'il est associé à des signes neurologiques (ophtalmoplégie ou céphalées).

Hypophyseal metastases: A report of three cases and literature review.

Metastatic tumours to the pituitary gland are rare. The most frequent are metastases from breast and lung. We describe three patients with metastatic tumours: (I) a 54-year-old patient with metastatic renal clear-cell carcinoma and consequent disturbances in visual acuity, cranial nerve paresis and panhypopituitarism, (II) a 60-year-old patient with a diffuse large B-cell lymphoma with panhypopituitarism and diabetes insipidus and (III) a 57-year-old patient with metastasis of breast cancer and panhypopituitarism, visual impairment and cranial nerve paresis. A transnasal endoscopic biopsy and resection of the tumour was performed in all patients, followed by the oncological treatment. Despite the rarity of the disease, it is important to suspect a metastatic pituitary tumour especially in the case of diabetes insipidus, ophthalmoplegia, rapid course of the disease and headaches. In 20-30% of patients, a metastasis to the pituitary is the first manifestation of a tumour of unknown origin. Surgical and adjuvant therapy may improve the quality of life. The survival is not affected, however, and the prognosis of the disease is usually poor.

Cancer metastases in the pituitary gland.

Metastases to the pituitary gland is a rare complication of systemic cancer in adults (does not practically occur in children). In 1857 L.Benjamin was the first who described a case of metastasis to the pituitary gland at autopsy of a patient with disseminated melanoma. Metastases in the pituitary gland are marked in 0,14-28,1% of all metastases to the brain in several series of autopsies. Many researchers consider that metastases in the pituitary gland are met in 1% of patients who underwent transsphenoidal surgery and 5% of autopsies.

Pituitary metastasis of hepatocellular carcinoma presenting with panhypopituitarism: a case report.

BACKGROUND: Metastasis to the pituitary gland is extremely rare and is often detected incidentally by symptoms associated with endocrine dysfunction. Breast and lung cancer are the most common primary metastasizing to pituitary gland. Metastasis from hepatocellular carcinoma to the pituitary gland is extremely rare, with only 10 cases having been previously reported. We present here the first case of pituitary metastasis of hepatocellular carcinoma presenting with panhypopituitarism diagnosed by magnetic resonance imaging. CASE PRESENTATION: We report the case of an 80-year-old Japanese woman who presented with the sudden onset of hypotension and bradycardia after having previously been diagnosed with hepatocellular carcinoma. Based on low levels of pituitary hormones, she was diagnosed with panhypopituitarism caused by metastasis of the hepatocellular carcinoma to the pituitary gland. Magnetic resonance imaging with arterial spin-labeling was effective in the differential diagnosis of the intrasellar tumor. The patient died despite hormone replacement therapy because of hypovolemic shock. CONCLUSION: Metastasis to the pituitary gland causes various non-specific symptoms, so it is difficult to diagnose. The present case emphasizes the importance of diagnostic imaging in identifying these metastases. Clinicians should consider the possibility of pituitary metastasis in patients with malignant tumors who demonstrate hypopituitarism.