In the United States, prostate cancer is the most frequent malignancy in men and ranks second in terms of mortality. Although recurrent or metastatic disease can be managed initially with androgen ...ablation, most patients eventually develop castration-resistant disease within a number of years, for which conventional treatments (eg, chemotherapy) provide only modest benefits. In the last few years, immunotherapy has emerged as an exciting therapeutic modality for advanced prostate cancer, and this field is evolving rapidly. Encouragingly, the US Food and Drug Administration (FDA) has recently approved two novel immunotherapy agents for patients with advanced cancer: the antigen presenting cell-based product sipuleucel-T and the anti-CTLA4 (cytotoxic T-lymphocyte antigen 4) antibody ipilimumab, based on improvements in overall survival in patients with castration-resistant prostate cancer and metastatic melanoma, respectively. Currently, a number of trials are investigating the role of various immunological approaches for the treatment of prostate cancer, many of them with early indications of success. As immunotherapy for prostate cancer enters its golden age, the challenge of the future will be to design rational combinations of immunotherapy agents with each other or with other standard prostate cancer treatments in an effort to improve patient outcomes further.
Objective: To report a case of a catecholamine-secreting paraganglioma with possible tumor-dependent autoimmune diabetes mellitus.Methods: We present the imaging, laboratory, and pathologic findings ...and describe the clinical course of a patient with a norepinephrine-secreting aortic paraganglioma with succinate dehydrogenase deficiency who was concomitantly diagnosed with latent autoimmune diabetes of adults at the time of initial diagnosis. We performed immunohistochemistry on the paraganglioma tissue for glutamic acid decarboxylase-65 (GAD65).Results: A 55-year-old man was diagnosed with a retroperitoneal, norepinephrine-secreting paraganglioma. He was concomitantly found to have elevated serum glucose levels and positive anti-GAD65 antibodies, consistent with latent autoimmune diabetes of adults, and was started on a basal-bolus insulin regimen. Surgical removal of the tumor resulted in rapid improvement of his hypertension and glycemic control, eliminating the need for insulin therapy within 6 months. Approximately 18 months after surgery, he presented with worsening glycemic control, unintentional weight loss, and hypertension. His anti-GAD65 antibody titer increased dramatically compared to the initial evaluation, and imaging and lab results were consistent with recurrence of the paraganglioma with metastatic spread. Immunohistochemistry for GAD65 in the original paraganglioma tissue was negative. The patient is currently undergoing cytoreductive therapy, and his diabetes is well-controlled on basal-bolus insulin therapy.Conclusion: Paragangliomas can induce hyperglycemia through several mechanisms. However, here, we present a unique case of autoimmune diabetes in the setting of a paraganglioma, whose severity of hyperglycemia and autoimmune antibody titers appear to follow the timeline of paraganglioma treatment and recurrence, raising suspicion for a paraneoplastic syndrome.Abbreviations: CT = computed tomography; GAD65 = glutamic acid decarboxylase-65; IHC = immunohistochemistry; LADA = latent autoimmune diabetes of adults; SDH = succinate dehydrogenase
Decreased bone mineral density (BMD) has been documented in adults with Cushing disease (CD), and allelic variants of the vitamin D receptor (VDR) gene have been associated with osteopenia. Genetic ...factors play an important role in bone accrual and its response to various diseases; among them, the most studied are the allelic variants of the VDR gene. There is debate as to whether described variants in the VDR gene have an effect on BMD. In the current study, we sought to analyze whether BMD differences in patients with CD were associated with the Taq1 and Apa1 VDR allelotypes. The data showed lack of association between BMD and these widely studied VDR polymorphisms, suggesting that the effect of endogenous hypercortisolism on bone in the context of CD does not depend on VDR genotypes.
Odontogenic myxomas are rare benign neoplasms affecting the jaw. Myxomas of bones and other sites occur as part of Carney complex (CNC), a multiple neoplasia syndrome caused by mutations in the ...PRKAR1A gene, which codes for the regulatory subunit of protein kinase A (PKA). In the present study, 17 odontogenic myxomas from patients without CNC were screened for PRKAR1A mutations and PRKAR1A protein expression by immunohistochemistry (IHC). Mutations of the coding region of the PRKAR1A gene were identified in 2 tumors; both these lesions showed no or significantly decreased immunostaining of PRKAR1A in the tumor compared to that in the surrounding normal tissue. One mutation (c.725C>A) led to a nonconservative amino acid substitution in a highly conserved area of the gene (A213D); the other was a single base‐pair deletion that led to a frameshift (del774C) and a stop codon 11 amino acids downstream of the mutation site; both tumors were heterozygous for the respective mutations. Of the remaining tumors, 7 of the 15 without mutations showed almost no PRKAR1A in the tumor cells, whereas IHC showed that the protein was abundant in nontumorous cells. We concluded that PRKAR1A may be involved by its down‐regulation in the pathogenesis of odontogenic myxomas caused by mutations and/or other genetic mechanisms. Of the sporadic, nonfamilial tumors associated with PRKAR1A mutations, the odontogenic type was the first myxomatous lesion found to harbor somatic PRKAR1A sequence changes. Published 2005 Wiley‐Liss, Inc.
In the United States, prostate cancer is the most frequent malignancy in men and ranks second in terms of mortality. Although recurrent or metastatic disease can be managed initially with androgen ...ablation, most patients eventually develop castration-resistant disease within a number of years, for which conventional treatments (eg, chemotherapy) provide only modest benefits. In the last few years, immunotherapy has emerged as an exciting therapeutic modality for advanced prostate cancer, and this field is evolving rapidly. Encouragingly, the US Food and Drug Administration (FDA) has recently approved two novel immunotherapy agents for patients with advanced cancer: the antigen presenting cell-based product sipuleucel-T and the anti-CTLA4 (cytotoxic T-lymphocyte antigen 4) antibody ipilimumab, based on improvements in overall survival in patients with castration-resistant prostate cancer and metastatic melanoma, respectively. Currently, a number of trials are investigating the role of various immunological approaches for the treatment of prostate cancer, many of them with early indications of success. As immunotherapy for prostate cancer enters its golden age, the challenge of the future will be to design rational combinations of immunotherapy agents with each other or with other standard prostate cancer treatments in an effort to improve patient outcomes further.
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