The influence of DNA repair on neurological degeneration, cachexia, skin cancer and internal neoplasms: autopsy report of four xeroderma pigmentosum patients (XP-A, XP-C and XP-D)

BACKGROUND: To investigate the association of DNA nucleotide excision repair (NER) defects with neurological degeneration, cachexia and cancer, we performed autopsies on 4 adult xeroderma pigmentosum (XP) patients with different clinical features and defects in NER complementation groups XP-A, XP-C or XP-D. RESULTS: The XP-A (XP12BE) and XP-D (XP18BE) patients exhibited progressive neurological deterioration with sensorineural hearing loss. The clinical spectrum encompassed severe cachexia in the XP-A (XP12BE) patient, numerous skin cancers in the XP-A and two XP-C (XP24BE and XP1BE) patients and only few skin cancers in the XP-D patient. Two XP-C patients developed internal neoplasms including glioblastoma in XP24BE and uterine adenocarcinoma in XP1BE. At autopsy, the brains of the 44 yr XP-A and the 45 yr XP-D patients were profoundly atrophic and characterized microscopically by diffuse neuronal loss, myelin pallor and gliosis. Unlike the XP-A patient, the XP-D patient had a thickened calvarium, and the brain showed vacuolization of the neuropil in the cerebrum, cerebellum and brainstem, and patchy Purkinje cell loss. Axonal neuropathy and chronic denervation atrophy of the skeletal muscles were observed in the XP-A patient, but not in the XP-D patient. CONCLUSIONS: These clinical manifestations and autopsy findings indicate advanced involvement of the central and peripheral nervous system. Despite similar defects in DNA repair, different clinicopathological phenotypes are seen in the four cases, and therefore distinct patterns of neurodegeneration characterize XP-D, XP-A and XP-C patients

Early-Onset Stroke and Vasculopathy Associated with Mutations in ADA2

We observed a syndrome of intermittent fevers, early-onset lacunar strokes and other neurovascular manifestations, livedoid rash, hepatosplenomegaly, and systemic vasculopathy in three unrelated patients. We suspected a genetic cause because the disorder presented in early childhood

Incidental Findings on Brain Magnetic Resonance Imaging From 1000 Asymptomatic Volunteers

CONTEXT Previous reports have discussed incidental disease found on brain magnetic resonance imaging (MRI) scans that had been requested for an unrelated clinical concern or symptom, resulting in a selection bias for disease. However, the prevalence of unexpected abnormalities has not been studied in a healthy population. OBJECTIVE To evaluate the prevalence of incidental findings on brain MRI scans obtained for a healthy, asymptomatic population without selection bias. DESIGN, SETTING, AND PARTICIPANTS Retrospective analysis of brain MRI scans obtained between May 17, 1996, and July 25, 1997, from 1000 volunteers who participated as control subjects for various research protocols at the National Institutes of Health. All participants (age range, 3-83 years; 54.6% male) were determined to be healthy and asymptomatic by physician examination and participant history. MAIN OUTCOME MEASURE Prevalence of abnormalities on brain MRI by category of finding (no referral necessary, routine referral, urgent referral [within 1 week of study], and immediate referral [within 1 to several days of study]). RESULTS Eighty-two percent of the MRI results were normal. Of the 18% demonstrating incidental abnormal findings, 15.1% required no referral; 1.8%, routine referral; 1.1%, urgent referral; and 0%, immediate referral. In subjects grouped for urgent referral, 2 confirmed primary brain tumors (and a possible but unconfirmed third) were found, demonstrating a prevalence of at least 0.2%. CONCLUSION Asymptomatic subjects present with a variety of abnormalities, providing valuable information on disease prevalence in a presumed healthy population. A small percentage of these findings require urgent medical attention and/or additional studies

Endolymphatic Sac Tumor Showing Increased Activity On \u3csup\u3e68\u3c/sup\u3eGa Dotatate Pet/Ct

Endolymphatic sac tumors (ELSTs) are rare tumors arising from the epithelium of the endolymphatic sac and duct that can be either sporadic or associated with von Hippel-Lindau (VHL) disease. We report a case of a VHL patient with histologically proven residual ELST who underwent 68Ga DOTATATE PET/CT showing increased activity (SUVmax, 6.29) by the ELST. The presented case of a VHL-associated ELST with increased 68Ga DOTATATE uptake indicates cell-surface expression of somatostatin receptors by this tumor, suggesting the potential application of somatostatin receptor imaging using 68Ga DOTA-conjugated peptides in the workup and management of these patients

Talc Pleurodesis With Intense 18F-Fdg Activity But No 68Ga-Dota-Tate Activity On Pet/Ct

Talc pleurodesis (TP) is a technique, widely employed in the management of patients with persistent pleural effusions or pneumothoraces not amenable to other treatment options. It is well documented that talc deposits produce areas of highly increased F-FDG uptake, because of talc-induced inflammation. We present a case of a patient with history of TP who was evaluated with both F-FDG and Ga-DOTA-TATE. The hypermetabolic area seen on F-FDG-PET-CT in the region of talc placement showed no uptake by Ga-DOTA-TATE, suggesting the potential role of Ga-DOTA-TATE-PET-CT in elucidating F-FDG-postitive lesions in patients with history of both neuroendocrine malignancy and TP

Avascular Necrosis Of The Hips With Increased Activity On 68Ga-Dotatate Pet/Ct

Prolonged exposure to cortisol is one of the major causes of avascular bone necrosis (AVN). We report on a case of a woman with Cushing syndrome attributed to ectopic adrenocorticotropic hormone-secreting tumor who was evaluated with whole-body PET/CT study using Ga-DOTATATE. The scan showed increased activity by both femoral heads, corresponding to the margins of bilateral AVN seen on MRI. The presented data suggests AVN-induced reactive inflammatory alterations adjacent to the necrotic segment of the bone, which can be effectively targeted using radiolabeled somatostatin (SST) analogs

Kidney Tumor In A Von Hippel-Lindau (Vhl) Patient With Intensely Increased Activity On 68Ga-Dota-Tate Pet/Ct

Renal and pancreatic cysts and tumors are the most common visceral manifestations of von Hippel-Lindau (VHL) disease, a heritable multisystem cancer syndrome characterized by development of a variety of malignant and benign tumors. We report a case of a VHL patient with multiple renal cystic and complex cystic/solid lesions. The patient underwent Ga-DOTA-TATE-PET/CT showing intensely increased activity by a solid lesion which demonstrated enhancement on both CT and MRI scans, raising high suspicion for malignancy. The presented case indicates application of SSTR-imaging using Ga-DOTA-conjugated peptides in VHL-patients and emphasizes the need for cautious interpretation of renal parenchyma Ga-DOTATATE activity

Epididymal Cystadenomas In Von Hippel-Lindau Disease Showing Increased Activity On \u3csup\u3e68\u3c/sup\u3eGa Dotatate Pet/Ct

von Hippel-Lindau (VHL) disease is a familial cancer syndrome characterized by the development of a variety of malignant and benign tumors, including epididymal cystadenomas. We report a case of a VHL patient with bilateral epididymal cystadenomas who was evaluated with 68Ga DOTATATE PET/CT, showing intensely increased activity (SUVmax, 21.6) associated with the epididymal cystadenomas, indicating cell-surface overexpression of somatostatin receptors. The presented case supports the usefulness of somatostatin receptor imaging using 68Ga DOTA-conjugated peptides for detection and follow-up of VHL manifestations, as well as surveillance of asymptomatic gene carriers

Ectopic Acth And Crh Co-Secreting Tumor Localized By 68Ga-Dota-Tate Pet/Ct

Diagnosis of ectopic adrenocorticotropic hormone (ACTH) and corticotropin-releasing hormone (CRH) co-secreting tumors causing Cushing syndrome (CS) is challenging because these tumors are rare and their diagnosis is frequently confused with Cushing disease (CD), caused by the effect of CRH on the pituitary. We report a case of a 21-year-old male patient who was referred to our institution with persistent hypercortisolemia and CS after undergoing unnecessary transsphenoidal surgery (TSS). 68Ga-DOTA-TATE PET/CT revealed increased tracer uptake in the thymus, which was histologically proven to be a neuroendocrine tumor (NET) that stained positive for ACTH and CRH. Imaging with 18F-FDG PET/CT was not diagnostic