Pseudoxanthoma elasticum with null cell adenoma of the pituitary gland: A case report with multimodal imaging study.

Abstract

A 57-year-old male without known medical history presented with progressive vision loss in the right eye. His best-corrected visual acuity (BCVA) was 20/25 and 20/20 for the right and left eyes, respectively. Slit-lamp exam results were unremarkable. Fundoscopy revealed a patch of macular hemorrhage in the right eye (Figure 1A) and “peau d'orange” appearance in both eyes (Figure 1B). Fluorescein angiography showed macular neovascularization (MNV) in the right eye (Figure 1C), comet's tail (Figure 1D) and angioid streaks (Figure 1E) in both eyes. Optical coherence tomography (OCT) angiography showed subretinal hemorrhage and type 2 MNV (Figure 1F,G). Over the next 3 years, BCVA for his right eye deteriorated gradually to counting fingers and OCT angiography revealed an exacerbated MNV despite aflibercept treatment (Figure 1H,I). A presumptive diagnosis of pseudoxanthoma elasticum (PXE) was made based on fundoscopic findings. The patient had no conspicuous cutaneous lesions compatible with PXE, and skin biopsies revealed no elastorrhexis immunohistochemically. Genetic examination revealed ABCC6 heterozygous mutations: c.3490C>T (p.Arg1164Ter) in exon 24 and c.2542delA (p.Met848CysfsTer83) in exon 19. Systemic workup was performed for intermittent chest pain, shortness of breath, and dizziness. Coronary angiogram (Figure 1J) found coronary artery stenosis and intravascular OCT of the coronary artery revealed intima thickening with neovascularization (Figure 1K). Angioplasty with stenting was implemented to restore blood flow (Figure 1L,M). Magnetic resonance imaging of the brain demonstrated a pituitary tumor, which was resected and confirmed to be a pituitary adenoma. Immunohistochemical studies revealed immunonegativity for adenohypophyseal hormones and positive nuclear staining for PIT-1 and SF-1 but not T-Pit (Figure 1N-Q). Therefore, it was classified as a null cell adenoma according to the 2017 World Health Organization classification. The current case featured multiorgan involvement of PXE, including MNV (Figure 1A,C,F-I), coronary artery homogeneous stenosis (Figure 1J-K), and pituitary adenoma (Figure 1N-Q). The diagnosis was based on molecular testing since skin biopsies showed no cutaneous involvement. The mutation variants were already documented and were confirmed to be related to PXE1, 2; however, the correlation between the pituitary null cell adenoma and PXE was still unclear since this is the first report to reveal the pathological details of possible PXE-related pituitary adenoma. PXE is an autosomal recessive disease induced by mutations of the ABCC6 gene, which typically causes ectopic calcification mostly in the skin and eyes.3 Phenotypic presentations may vary greatly and some patients lack skin manifestations.4 PXE-associated pituitary tumor was rarely reported and without comprehensive genetic and pathologic data.5 Since studies on phenotype–genotype correlation in PXE are still lacking, this study may lay ground for further research. In conclusion, PXE may involve the eye, skin, cardiovascular system, and pituitary gland. The association of PXE with pituitary tumor is rare and it is possible that the pituitary null cell adenoma is a coincident finding in cases with PXE. Genetic testing for ABCC6 may be a diagnostic clue for patients with solitary visual complaints and future studies need to be performed to elucidate the role of ABCC6 mutations in pituitary adenoma. We thank Drs. Chaw-Ning Lee, Chao-Kai Hsu, Hsin-Yu Huang (Department of Dermatology, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University), Dr. E-Jian Lee (Division of Neurosurgery, Department of Surgery, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University), and Ms. Haui-Wen Hsu and Yu-Shan Chang (Department of Medicine, College of Medicine, National Cheng Kung University) for a critical reading of the manuscript. This study is supported by a grant from National Cheng Kung University Hospital, Tainan, Taiwan (Grant/Award Number: NCKUH-11006018 to J. H. Hung). The study was approved by the Institutional Review Board of National Cheng Kung University Hospital (A-EC-110-005).