Treatment Of Pituitary Carcinomas Research Articles

Pituitary carcinoma with multiple metastases: A case report and literature review

Pituitary carcinoma is traditionally defined as a tumor of adenohypophyseal cells that metastasizes systemically or craniospinally. They account for approximately 0-2% of all pituitary tumors. Their diagnosis and treatment is challenging. We report the case of a woman who was initially diagnosed with adenoma and scheduled for surgery. An MRI of the brain three weeks later showed metastatic lesions. The patient died ten days after surgery due to adrenal crisis. The development of pituitary carcinoma is extremely unusual. It could be misdiagnosed with an invasive pituitary adenoma. Until recently, treatment of pituitary carcinoma was mainly palliative and did not appear to increase overall survival.

Clinical features of pituitary carcinoma: analysis based on a case report and literature review.

Pituitary carcinoma (PC) is an extremely rare tumor of the adenohypophysis, which manifests as craniospinal dissemination and/or systemic metastasis. The diagnosis of PC is particularly difficult, as the clinical diagnosis only can be made after the metastasis is found. Owing to the complex diagnostic process and less effective treatments, the clinical prognosis of PC is usually very poor. Hence, it is of great significance to illustrate the diagnosis and treatment course of PC. In this case report, we described a 48-year-old male patient who was diagnosed with pituitary adenoma (PA) initially and then was diagnosed with PC eventually after spinal cord metastasis was found, and we illustrated the treatment course as well. Furthermore, we summarized all the published case reports until now and provided a comprehensive review of the diagnosis, treatment, prediction, and clinical outcome of PC. We found that most PC patients had adrenocorticotropic hormone/prolactin (ACTH/PRL)-secreting tumors, Ki-67 ≥ 10%, and P53 positivity, which may have the potential to predict the transformation from PA to PC; surgery excision combined with temozolomide (TMZ) and radiotherapy is helpful to prolong the survival of PC patients.

Recent Therapeutic Advances in Pituitary Carcinoma.

Pituitary carcinoma (PC) is a rare, aggressive malignancy that comprises 0.1-0.2% of all pituitary tumors. PC is defined anatomically as a pituitary tumor that metastasizes outside the primary intrasellar location as noncontiguous lesions in the central nervous system or as metastases to other organs. Similar to pituitary adenoma, PC originates from various cell types of the pituitary gland and can be functioning or nonfunctioning, with the former constituting the majority of the cases. Compression of intricate skull-based structures, excessive hormonal secretion, impaired pituitary function from therapy, and systemic metastases lead to debilitating symptoms and a poor survival outcome in most cases. PC frequently recurs despite multimodality treatments, including surgical resection, radiotherapy, and biochemical and cytotoxic treatments. There is an unmet need to better understand the pathogenesis and molecular characterization of PC to improve therapeutic strategies. As our understanding of the role of signaling pathways in the tumorigenesis of and malignant transformation of PC evolves, efforts have focused on targeted therapy. In addition, recent advances in the use of immune checkpoint inhibitors to treat various solid cancers have led to an interest in exploring the role of immunotherapy for the treatment of aggressive refractory pituitary tumors. Here, we review our current understanding of the pathogenesis, molecular characterization, and treatment of PC. Particular attention is given to emerging treatment options, including targeted therapy, immunotherapy, and peptide receptor radionuclide therapy.

Synergism of Checkpoint Inhibitors and Peptide Receptor Radionuclide Therapy in the Treatment of Pituitary Carcinoma.

ContextAggressive pituitary tumors that have progressed following temozolomide have limited treatment options. Peptide receptor radionuclide therapy and immunotherapy may have a complementary role in the management of these tumors.MethodsWe provide follow-up data on a previously reported patient with a hypermutated recurrent tumor. The patient in this report provided written informed consent for tumor sequencing and review of medical records on an institutional review board–approved research protocol (NCT01775072).ResultsThis patient with a corticotroph pituitary carcinoma with alkylator-induced somatic hypermutation has remained on treatment with ipilimumab and nivolumab for 3.5 years and remains clinically well. After an initial partial response to checkpoint inhibitors, she has had several recurrences that have undergone immunoediting of subclonal mutations, which have been effectively treated with continuation of immunotherapy, surgery, external beam radiation, and 177Lu-DOTATATE. Following external beam radiotherapy (RT), she had radiographic evidence of an abscopal response at a distant site of disease suggesting a synergism between checkpoint inhibitors and RT. Following treatment with 177Lu-DOTATATE, the patient had a partial response with a 61% reduction in volume of the target lesion.ConclusionIn patients with aggressive pituitary tumors, treatment with checkpoint inhibitors may trigger an abscopal response from RT. With appropriate selection, an additional efficacious treatment, 177Lu-DOTATATE, may be available for a limited number of patients with aggressive pituitary tumors, including patients who have progressed on temozolomide and exhibit increased somatostatin receptor expression on 68Ga-DOTATATE positron emission tomography.

Pituitary carcinoma: The University of Texas MD Anderson Cancer Center experience.

2068 Background: Pituitary carcinoma (PC) is a rare and aggressive neuroendocrine tumor diagnosed once a pituitary adenoma (PA) becomes metastatic. Although no standard treatment currently exists, surgery, radiation (XRT) and/or chemotherapy are most commonly used. Recently, treatment with temozolomide (TMZ) has shown promising results, although the lack of prospective trials limits accurate outcome assessment. Methods: We describe a single-center multidisciplinary team experience in managing PC patients over a 13-year period (Oct, 2003 to Jan, 2017). Results: A total of 17 patients (9 males) were seen. Median age at diagnosis of PC was 44 years (range 16-82 years) and the median time from PA to PC conversion was 6 years (range 1-29 years). Median follow-up time: 28 months (range 8-158 months) with 7 reported deaths. The majority of PC was hormone-secreting (HS) subtype (n = 12): ACTH (n = 5), PRL (n = 4), FSH/LH (n = 2), GH (n = 1). After PC diagnosis, all pituitary tumors were locally invasive, all underwent at least one resection (mean 2.3) and all received at least one course of XRT alone (IMRT = 76%, SRS = 29%, IMPT = 12%) or concurrent with chemotherapy (18%). Immunohistochemistry showed high Ki-67 labeling index ( > 3%) in 9 (53%) cases. Most cases (n = 14) had metastases to the CNS, 35% of those had combined CNS and systemic foci. Ten (59%) cases underwent focal treatment of metastases, 90% of which underwent XRT. The most common chemotherapy used was TMZ [n = 14 (82%): single agent (n = 10); TMZ+capecitabine (n = 5); concurrent TMZ+XRT (n = 3); concurrent TMZ+XRT with adjuvant TMZ (n = 1)]. The median longest progression-free survival (LPFS) was 18 months (range 4-45 months). TMZ was associated with the chemotherapy-related LPFS in 9 (75%) cases. The 2, 3 and 5 year survival rate was 65%, 53% and 35%, respectively. All patients surviving > 5 years were treated with TMZ (n = 5, 2 survived > 10 years). Two refractory cases are currently on PD-1 inhibitor agent. Eighty percent of non-functioning PC were alive at last follow-up (HS-PC, 58%). Recurrence occurred in 11 (65%) cases. Conclusions: Treatment of PC requires a multidisciplinary approach. Multimodality therapy with surgery, radiation and TMZ was associated with higher survival rates and longer PFS.

Genetic aspects of pituitary carcinoma: A systematic review.

Background:Pituitary carcinoma (PC) is a rare type of malignant intracranial neoplasm defined as distant metastasis of pituitary adenoma (PA). Although PC incidence is low because only 0.1% to 0.2% of PAs ultimately develop into PCs, the prognosis is poor and 66% of patients die within the first year. Existing therapeutic measures, including surgical removal, chemotherapy, and radiotherapy, have limited effectiveness. The lack of efficacy of current treatments is largely caused by the limited understanding of the molecular pathogenesis of PA and the malignant transformation to PC. Therefore, the aim of this systematic review was to summarize published research regarding gene and protein expression in PC to clarify the molecular mechanisms underlying PC genesis and development and identify new candidate diagnostic biomarkers and therapeutic targets for potential use in personalized treatment of PC.Methods:We followed the PRISMA guidelines to plan and conduct this systematic review. PubMed, Embase, and Web of Science databases were searched for relevant studies conducted before December 16, 2015 describing the association of PC with gene expression at the mRNA and protein levels. MeSH terms combined with free terms were used to retrieve the references.Results:In total, 207 records were obtained by primary search, and 32 were included in the systematic review. Compared with normal pituitary gland and/or PA, 30 and 18 genes were found to have higher or lower expression, respectively, in PCs using different analytical methods. Among them, we selected 9 upregulated and 7 downregulated genes for further analysis based on their identification as candidate treatment targets in other cancers, potential clinical application, or further research value.Conclusion:Previous studies demonstrated that many genes promote PC malignant transformation, angiogenesis, invasion, metastasis, and recurrence. Although most of these genes and proteins have not been fully analyzed with regard to their downstream mechanisms or potential diagnostic and therapeutic application, they have the potential to become candidate PC biomarkers and/or molecular targets for guiding personalized treatment. Modern advanced technologies should be utilized in future research to identify more candidate genes for PC pathogenesis, as precisely targeted gene therapies against PC are urgently required.

Diagnosis and Treatment of Pituitary Carcinoma

The early diagnosis and treatment of pituitary carcinoma is difficult. The diagnosis is often delayed, and the confirmation of a diagnosis requires the presence of distant subarachnoid,brain or systemic metastasis from the primary pituitary tumor in the sella and also needs the evidences of pathology and imaging of the primary pituitary carcinoma and metastases. Treatment of pituitary carcinoma includes surgery, radiation therapy ,hormone therapy, chemotherapy, and molecularly targeted therapy; however, these methods are mainly palliative and can not prolong the survival. The prognosis remains poor. Efforts should be made to develop more effective diagnosis and treatment options.

Meta-analysis of temozolomide treatment of pituitary carcinomas and aggressive adenomas

e13014 Background: Most pituitary tumors are benign and cured surgically. Pituitary carcinomas (PC) and aggressive pituitary adenomas (APA) are rare variants, but often recur and respond poorly to ...

Treatment of pituitary carcinomas and atypical pituitary adenomas: a review.

Atypical pituitary adenomas (APAs) are aggressive tumors, harboring a Ki-67 (MIB-1) staining index of 3% or more, and positive immunohistochemical staining for p53 protein, according to the World Health Organization (WHO) classification in 2004. Pituitary carcinomas (PC) usually develop from progressive APAs and predominantly consist of hormone-generating tumors, defined by the presence of disseminations in the cerebrospinal system or systemic metastases. Most of the cases with these malignant pituitary adenomas underwent surgeries, irradiations and adjuvant medical treatments, nevertheless, the therapies are mainly palliative. Recently, the efficacy of temozolomide (TMZ), an orally administered alkylating agent, has been reported as an alternative medical treatment. However, some recent studies have demonstrated a significant recurrence rate after effective response to TMZ. Further clinical and pathological researches of malignant pituitary adenomas will be required to improve the outcome of patients with these tumors.

Pituitary carcinoma with fourth ventricle metastasis: treatment by excision and Gamma-knife radiosurgery

Pituitary carcinomas, which are rare, generally present with craniospinal and systemic metastases. Although several treatments exist, the prognoses of patients with pituitary carcinomas are extremely poor to date. In this report, the authors describe the case of a 23-year-old male who had undergone trans-sphenoidal surgery and radiotherapy for an invasive prolactinoma. Seven years later, he presented with a new 4th ventricle metastasis from the pituitary lesion, and it was diagnosed with a pituitary carcinoma. He underwent resection and Gamma-knife radiosurgery (GKRS). The tumor has been well controlled for over 3 years. To our knowledge, there have been no reports of the effects of GKRS in patients with pituitary carcinomas. GKRS might have considerable effects in the treatment of pituitary carcinomas.

Molecular status of pituitary carcinoma and atypical adenoma that contributes the effectiveness of temozolomide

There have been several reports of temozolomide (TMZ) treatment of pituitary carcinomas and atypical adenomas. O(6)-methyl-guanine-DNA methyltransferase is not the sole molecule determining the sensitivity to TMZ in pituitary carcinomas and atypical adenomas. The Japan Society of Hypothalamic and Pituitary Tumors study suggests that MSH6, one of mismatch repair pathway enzyme, fulfills a contributory role to the efficacy of TMZ treatment for pituitary carcinomas and atypical adenomas. The preserved MSH6 function might be essential for the responsiveness to TMZ treatment in pituitary carcinomas and atypical adenomas.

Approach to the patient with pituitary carcinoma

One patient confirmed as pituitary carcinoma by histopathology was retrospectively analyzed according to the great changes of tumor invasive growth in imaging examine and clinical characters. Clinically,pituitary carcinoma quickly grows,and the growth character of tumor is helpful in the diagnosis. Moreover,the treatment for pituitary carcinoma is different from pituitary adenoma.The rapid progress of pituitary adenoma indicates the possibility of primary carcinoma.More experience should be accumulated for the diagnosis and treatment of the disease. Key words: Pituitary carcinoma ; Invasive; Treatment ; Diagnosis

Pituitary carcinomas and aggressive pituitary tumours: merits and pitfalls of temozolomide treatment

Pituitary carcinomas are rare, accounting for about 0.2% of all pituitary tumours. They represent a challenge to clinical practice in both diagnosis and treatment. They may present initially as typical pituitary adenomas, with a delayed appearance of aggressive signs, or as aggressive tumours from the outset. Predicting the pituitary tumour behaviour remains difficult: increased mitotic, Ki-67 and P53 indices might be associated with tumour aggression. The treatment of pituitary carcinomas and aggressive pituitary tumours includes surgery, adjuvant medical treatment, external beam radiotherapy and chemotherapy. Until recently, the treatment of pituitary carcinomas was mainly palliative and did not seem to increase overall survival. Recent case reports have detailed the successful use of temozolomide, an orally administered alkylating agent used to treat malignant gliomas, in the management of pituitary carcinomas and aggressive pituitary tumours. The outcome of treatment might depend on the expression of O(6)-methylguanine-DNA methyltransferase (MGMT), a DNA repair enzyme that potentially interferes with drug efficacy. This review describes the clinical presentation and response to temozolomide in 44 patients with pituitary carcinomas or aggressive pituitary tumours reported in the literature. The results suggest that temozolomide should be considered a drug of major importance in the therapeutic algorithm of aggressive pituitary tumours and pituitary carcinomas. Because of the inconsistency of published data, MGMT expression should probably not be taken as a reason to deny these patients the potential benefit of temozolomide treatment, taking into account the paucity of other available treatments.

A Case of Nonfunctioning Pituitary Carcinoma That Responded to Temozolomide Treatment

Pituitary carcinoma is a rare malignancy and is difficult to manage. Pituitary carcinomas commonly produce either PRL or ACTH, but some do not produce pituitary hormones. The alkylating reagent temozolomide (TMZ) was recently shown to be effective as a treatment for pituitary carcinoma. Most of the published reports of TMZ use in pituitary carcinoma cases were against hormone-producing carcinomas. Only a few patients with a nonfunctioning pituitary carcinoma treated with TMZ have been reported. Here we describe our treatment of a patient with nonfunctioning pituitary carcinoma and a background of multiple endocrine neoplasia type 1. The pituitary carcinoma was accompanied by meningeal dissemination with cerebral and L1 spinal bone metastasis. The patient received continuous dosing of TMZ along with external radiation, followed by standard dosing of TMZ. There was an apparent antitumor response seen in MRI. MGMT, an enzyme antagonized by TMZ, was negative in the tumor. The therapeutic efficacy of TMZ and dosing schedules of TMZ in pituitary carcinoma are discussed.

Temozolomide: a novel treatment for pituitary carcinoma

Pituitary tumours account for about 15% of all intracranial neoplasms, and clinically evident local invasion takes place in 35–40% of cases. 1 Sellman WR Laws ER Scheithauer BW Carpenter SM The occurrence of dural invasion in pituitary adenomas. J Neurosurgery. 1986; 64: 402-407 Crossref PubMed Scopus (236) Google Scholar Pituitary carcinoma is tumour tissue that is not contiguous with the pituitary tissues or is found in other extracranial sites. The disorder is rare (accounting for about 0·1% of pituitary tumours), rapidly progressive, and largely unresponsive to current combination treatment of surgery, radiation, and systemic chemotherapy. 2 Kaltsas GA Nomikos P Kontogeorgos G et al. Diagnosis and management of pituitary carcinoma. J Clin Endocrinol Metab. 2005; 90: 3089-3099 Crossref PubMed Scopus (260) Google Scholar , 3 Ragel BT Couldwell WT Pituitary carcinoma: a review of the literature. Neurosurg Focus. 2004; 16: E7 Crossref PubMed Scopus (151) Google Scholar Consequently, most patients die within 1 year of diagnosis. Here, we report a case of pituitary carcinoma treated with temozolomide.