Localized Amyloid Deposits Research Articles

Extranodal Marginal Zone Lymphoma of Mucosa Associated Lymphoid Tissue (MALT LYMPHOMA) With Extensive Plasma Cell Differentiation and Localized Amyloid Deposition.

Extranodal marginal zone lymphoma of mucosa-associated lymphoid tissue (MALT) lymphoma is a mature and clinically indolent B cell lymphoma composed of heterogeneous cell population. Plasma cell differentiation is commonly seen in MALT lymphomas. However, plasmacytic differentiation along with localized amyloid deposition in the lungs is an extremely rare. We encountered a unique case of Extranodal MALT lymphoma with extensive plasmacytic differentiation and amyloid deposition. A 78-year-old female with past history of Gastric MALT lymphoma, status post chemotherapy presented in outpatient clinic. PET scan revealed an incidental 9 mm nodule in left lung, and subsequently underwent biopsy. Histology showed sheets of heterogeneous neoplastic cells including small lymphocytes, monocytoid cells, and abundant number of plasma cells (Fig A) in the background of hyalinization (Fig B). Immunohistochemical (IHC) reveals lymphoma cells are positive for CD20 (Fig C) and CD43, and plasma cells showed lambda restriction (Fig D). Furthermore, Congo Red stain of eosinophilic background showed positive birefringence upon polarization, consistent with Amyloid. Great caution is required in differentiating these cases from lymphoplasmacytic lymphoma as the histologic and IHC features can significantly overlap, and studies have also suggested that plasmacytic differentiation in these cases represent precursor neoplasm of plasma cells. Amyloid depositions in MALT lymphomas are rare and organ confined but can lead to local complications and cause considerable morbidity. Therefore, it is necessary to be aware of the association between MALT lymphoma with extensive plasma cell differentiation and amyloid deposition, as close clinical follow up is recommended.

Bilateral localized primary parotid gland amyloidosis: A rare entity with literature review.

Amyloidosis of the salivary glands is a rare occurrence. Due to non-specific clinical presentation, the diagnosis can be overlooked. Here we present a case of a localized bilateral parotid glands AL kappa-light chain amyloid deposition without systemic involvement, as well as a literature review. Fine needle aspiration (FNA) of a right parotid lesion was performed with rapid on-site evaluation (ROSE). Slides showed characteristic amyloid staining with Congo red and typical Apple-green birefringence under polarized light microscopy. Amyloid in the head and neck can be misinterpreted as other materials such as colloid, keratin, necrosis, hyaline degeneration especially when the condition is not suspected.

Cutaneous Ossifying Amyloidoma

Amyloidoma, otherwise known as tumoral amyloidosis, is a localized deposition of amyloid (AL-type or AA type) without systemic amyloidosis. It is the rarest form of tissue amyloid deposition, and up to 7% of amyloidomas develop systemic amyloidosis.Cutaneous AL-type amyloidoma is considered by many authors as an unusual variant of primary cutaneous marginal zone lymphoma. Although cutaneous amyloidoma can form calcifications, ossification is extremely unusual, with only 1 case previously published to date.We report the case of a 75-year-old woman with voluminous and strikingly ossifying AL-type amyloidoma in the left pretibial skin. Her medical history included excision of hepatic hydatidic cysts 25 years prior and diffuse large B-cell lymphoma of the left parotid gland 8 years prior treated with chemotherapy and radiotherapy with complete response. After the diagnosis of amyloidoma, an extension study with cervical, chest, abdominal, and pelvic TC was performed, with no additional lesions found. Serum and protein electrophoresis revealed elevations in kappa light chain and IgA immunoglobulin levels but did not reveal monoclonal bands. In situ hybridization for immunoglobulin light chains showed monotypic kappa expression in plasma cells infiltrating the amyloidoma.Extensive ossification in amyloidomas can make diagnosis difficult; therefore, we describe an interesting case of this histopathologically peculiar amyloidoma.

PB2155: B-CELL NON-HODGKIN’S LYMPHOMAS ASSOCIATED WITH AMYLOIDOSIS

Background: Different types of B-NHLs (MZL, LPL, B-CLL/SLL, FL, MCL, DLBCL) may show plasmacytic differentiation and may produce AL amyloid locally or as a part of systemic amyloidosis. Case reports of coincidence of B-NHL and non-AL amyloidosis were also reported, therefore correct diagnostic workflow to type amyloid deposits should include three main steps 1. special histological staining (Congo red and/or Saturn red), 2. immunoprofiling and proteomic analysis (LMD-LC/MS). Nomenclature classification distinguishes 36 amyloidogenic proteins and more are expected (ISA 2020). Aims: Analysis of amyloid deposits irrespective of origin and localization is appealing for diagnostic and experimental precising which brings new insights in pathogenesis, classification and correct therapy due to a possibility of combination or hybrid amyloid deposits, and concurrent B-NHL may be detected. Methods: Amyloid deposits were detected in variable FFPE tissues stained with Congo red and/or Saturn red with consequent immunohistochemical analysis (IHC) and proteomic analysis with the use of laser capture microdissection and liquid chromatography/tandem mass spectrometry (LMD-LC/MS/MS). Concurent B-NHLs (excl. multiple myeloma, plasmocytoma and MGUS) were diagnosed due to characteristic morphology (HE, PAS, Giemsa), immunoprofile (primary antibodies with appropriate dilution - CD3, CD5, CD10, CD20, CD21, CD23, CD30, CD138, Bcl-2, Bcl-6, MUM1/IRF4, PAX5, cyclin D1 and/or SOX11, c-Myc, Ki67) and detected clonal rearrangement of IgVH (BIOMED-2). Results: In our file with 329 amyloid positive specimens concurent B-NHLs were found in 14 specimens. 7 specimens were signed as highly suspected for B-NHL with plasmacytic differentiation and immunoglobulin light chain restriction but without evidence of IgVH clonal rearrangement. The most common B-NHL associated with localised amyloidosis was ENMZL MALT-type (10 cases, 1 case with hybrid amyloidosis AL kappa/AH IgG1), in 4 specimens LPL was detected. In all cases with IHC and/or LCM-LC/tandem MS analysis AL type of amyloid was detected including 2 cases with hybrid amyloidosis AL/AH and AL/AApoAIV, and in 1 case local AL amyloid deposition was produced after a therapy for B-NHL. Summary/Conclusion: M-protein produced by B-NHL may be low or high according to a localised or systemic AL involvement resp., localised amyloid deposition is commonly associated with ENMZL MALT-type, both localised and systemic amyloidosis may be found out in LPL. Our category of highly suspected B-NHL with plasmacytic differentiation is literary sign as “AL amyloidosis with a localized B-cell neoplasia of undetermined significance” or as “AL amyloidosis with a an associated predominant kappa or lambda light chain expressing plasma cell population without evidence for clonality”. In our file (7 cases) only kappa/lambda immunohistochemically detected monotypy was recorded without an evidence of IgVH clonal rearrangement (somatic hypermutation of IgVH may be expected). The possibility of senescence evolution in B-NHL after a therapy may also bring local AL deposits (1 case in our cohort). Coincidence or association of non-AL amyloidosis (ATTRwt, ATTRv, AA and other) with B-NHL was described mainly in single case reports and extends the differential diagnosis. In a such cases both methods (IHC and LCM-LC/tandem MS) are suitable for correct amyloid typing, although LMD-LC/tandem MS brought more promising results than IHC.

Tracheobronchial Amyloidosis: A Case Report

Amyloidosis is a spectrum of diseases, in which various proteins which are a usual component of plasma are deposited as insoluble beta-pleated sheets extracellularly, disrupting the function of various organs. Amyloid light-chain amyloidosis occurs due to the deposition of proteins, derived from immunoglobulin light chains, routinely manifesting with multisystem involvement. Pulmonary involvement is seen in about 50% of cases [1]. Three common patterns of amyloidosis on computed tomography (CT) chest are tracheobronchial, nodular parenchymal, and diffuse alveolar septal variety. Here we report a case of amyloidosis involving tracheobronchial tree due to localized deposition of amyloid. Knowledge about pulmonary amyloidosis is important due to nonspecific findings in the CT chest and its poor prognosis.

Contribution of <sup>99m</sup>Tc-DPD Scintigraphy in the Diagnosis of Cardiac Amyloidosis in Black Africans

Cardiac amyloidosis presents a picture of hypertrophic cardiomyopathy with heart failure with preserved ejection fraction. It is largely underdiagnosed, especially in black Africans, and therefore falls under the category of heart disease classified as idiopathic. Light chain amyloidosis (AL) is mainly found in Caucasian subjects and the mutant variant of transthyretin (TTRm) in negroid subjects. Numerous studies have shown that ATTRm was found predominantly in black American and black British patients. In African countries the entity of idiopathic heart failure is quite important because of lack of diagnosis, ETT, MRI and immuno-histochemistry are expensive or not available. We can probably assume that the proportion of cardiac amyloidosis is quite important in black Africans. The question is if 99mTc-DPD really easy to perform, can probably help to investigate in the nuclear medicine department in Africa. No large-scale study has been able to demonstrate the prevalence or not of cardiac amyloidosis in black-African subjects and by extension reduce this nosological entity of idiopathic heart disease. The 99mTc-DPD scintigraphy using Perrugini’s visual sore allows localization and classification of amyloid damage. The mechanism of binding of 99mTc-DPD to amyloid fibril deposits is not well known, its binding to TTR-type (mutated or wild type) amyloidosis is greater than the AL variant. In the diagnostic algorithm, endomyocardial biopsy is the gold standard but remains invasive, ETT with the strain allows a presumptive diagnosis and remains an operative examination dependent and is not reproducible. Cardiac MRI allows some localization of amyloid deposits but still remains less sensitive than scintigraphy. In addition, performing the whole-body MRI is very restrictive (time, antenna change and cost). The aim of this literature review was to show the superiority of 99mTc-DPD scintigraphy compared to other diagnostic modalities and to consider its use given its simplicity when it comes to usage in Sub-Saharan Africa to diagnose the disease. cardiac amyloidosis and by extension reduce the number of cases of heart disease classified as idiopathic and thus allow early and appropriate management.

A Case of Laryngeal Mucosa Associated Lymphoid Tissue Lymphoma Mimicking Laryngeal Amyloidosis

Laryngeal amyloidosis is a rare disorder characterized by localized amyloid deposition and carries an excellent prognosis. On the other hand, mucosa associated lymphoid tissue (MALT) lymphoma is the most common type of marginal zone lymphoma. MALT lymphoma has a poorer prognosis compared to laryngeal amyloidosis due to more frequent local recurrence, distant metastasis and malignant changes. Despite the differences, as both are found in the form of benign mass and have slow progression, accurate diagnosis is necessary. This report deals with the case of a patient with voice change accompanied by a mass, in which the initial biopsy did not include enough specimen for an accurate diagnosis. However, in the second attempt, an adequate sample was obtained, hence the final diagnosis of laryngeal MALT lymphoma. Based on our recent experience and a review of related literature, we report a case of laryngeal MALT lymphoma mimicking laryngeal amyloidosis.

Using digital whole-slide images to evaluate renal amyloid deposition and its association with clinical features and outcomes of AL amyloidosis.

Few data are available quantifying the proportion of amyloid deposition in renal biopsy specimens. The aim of the study is to investigate the correlation between the proportion of amyloid deposition in renal biopsy and clinical characteristics of Chinese patients with immunoglobulin light-chain amyloidosis (AL amyloidosis). 259 patients diagnosed with renalAL amyloidosis between 2003 and 2015 were studied retrospectively. We developed a digital, automated quantification method to evaluate amyloid deposits in glomeruli, vessels and interstitium on digital whole-slide images (WSIs). The associations between the proportion of amyloid-positive area in the renal biopsy and clinical manifestations were analyzed. The proportion (%) of amyloid-positive area in glomeruli, vessels, interstitium and the whole renal tissue were 11.81 ± 11.38, 14.14 ± 14.05, 3.34 ± 5.36 and 4.25 ± 5.77, respectively. The proportion of amyloid deposition in glomeruli, vessels and interstitium was positively correlated with serum creatinine (Scr), estimated glomerular filtration rate (eGFR) and urinary retinol binding protein (RBP). The proportion of glomerular amyloid deposition, age, urinary N-acetyl-b-D-glucosaminidase (NAG) and urinary RBP could independently predict the risk for overall death. The proportion (%) of amyloid-positive area in blood vessels, interstitium and the whole renal tissue, Scr, and urinary RBP were independent risk factors associated with renal survival. A novel digital analysis algorithm was firstly developed to quantify the proportion of amyloid deposits in renal tissues based on digitalWSIs. The degree and localization of amyloid deposits in the kidney evaluated by digitalWSIs may have predictive value in assessing risk of outcome of AL amyloidosis.

Lactoferrin amyloid presenting as a mural nodule in a pancreatic cystic lesion prompting pancreatoduodenectomy: a case report

BackgroundAmyloid deposition in pancreas is rare. Lactoferrin amyloid deposition has not been reported in pancreas, till date. Presence of enhancing mural nodule in a cyst on imaging is a worrisome feature for malignancy, and warrants surgical resection in a surgically fit candidate, as per Fukuoka guidelines for management of cystic lesions in pancreas.Case reportWe report a case of localized amyloidosis presenting as a mural nodule in a 1.6 cm cyst located in the head of pancreas, which led to pancreatoduodenectomy in a 69 year old woman. Histological evaluation revealed a simple mucinous cyst with localized lactoferrin amyloid deposition corresponding to the mural nodule identified on imaging.ConclusionsWe report the first case of localized lactoferrin amyloid deposition in pancreas that presented as a mural nodule in a cystic lesion and prompted pancreatoduodenectomy. This unique case illustrates that on rare occasion mural nodule in a cyst can be benign. It adds amyloid deposition to the differential diagnosis of mural nodules in pancreatic cystic lesions seen on imaging.

Proteomic analysis shows that the main constituent of subepidermal localised cutaneous amyloidosis is not galectin-7

Lichen or macular localised cutaneous amyloidoses have long been described as keratinic amyloidoses and believed to be due to the deposition of cytokeratin peptides originating from epidermis in the dermal papillae. However, recently it was suggested that galectin-7 is the causative protein for this type of amyloidosis. This was based on the detection of galectin-7 in a biopsy from a patient diagnosed with Bowen’s disease and localised cutaneous amyloidosis. In this study we report mass spectrometry-based proteomic analysis of the protein composition of localised cutaneous amyloid deposits from seven patients using laser microdissection and show that basal keratins are the main constituents of the amyloid deposits. Galectin-7 was not present in the dermal amyloid deposits and was only present in the overlying Congo red negative epidermis.

Local and systemic light chain amyloidosis in patients with rheumatic diseases

In patients with chronic inflammatory rheumatic diseases various types of amyloidosis diseases can occur. If amyloidosis is suspected a differentiation between local and systemic amyloid deposits needs to be made as well as between AL, AA and other forms of amyloidosis. The aim is the characterization of local and systemic AL amyloidosis in rheumatic diseases, demonstration of diagnostic algorithms and prognostic factors as well as a discussion of the treatment options. The cohort of patients with amyloidosis at the amyloidosis center in Heidelberg is presented and compared to other amyloidosis cohorts as well as a discussion of the treatment options. A monoclonal gammopathy can be observed in many patients with various rheumatic diseases. In patients with Sjogren's syndrome nodular cutaneous deposits of local AL amyloid can be observed; however, the occurrence of systemic AL amyloidosis has so far been reported only in a few isolated cases of patients with rheumatic diseases. In patients with rheumatic diseases, the development of a mostly local AL amyloidosis must also be considered in addition to AA amyloidosis. An early diagnosis is crucial to prevent further deterioration of organ function in patients with clinical indications of a systemic amyloidosis. The differentiation between AA and AL amyloidosis is essential in order to initiate a targeted treatment.

Strategies for the Molecular Imaging of Amyloid and the Value of a Multimodal Approach.

Protein aggregation has been widely implicated in neurodegenerative diseases such as Alzheimer's disease, frontotemporal dementia, Parkinson's disease, and Huntington disease, as well as in systemic amyloidoses and conditions associated with localized amyloid deposits, such as type-II diabetes. The pressing need for a better understanding of the factors governing protein assembly has driven research for the development of molecular sensors for amyloidogenic proteins. To date, a number of sensors have been developed that report on the presence of protein aggregates utilizing various modalities, and their utility demonstrated for imaging protein aggregation in vitro and in vivo. Analysis of these sensors highlights the various advantages and disadvantages of the different imaging modalities and makes clear that multimodal sensors with properties amenable to more than one imaging technique need to be developed. This critical review highlights the key molecular scaffolds reported for molecular imaging modalities such as fluorescence, positron emission tomography, single photon emission computed tomography, and magnetic resonance imaging and includes discussion of the advantages and disadvantages of each modality, and future directions for the design of amyloid sensors. We also discuss the recent efforts focused on the design and development of multimodal sensors and the value of cross-validation across multiple modalities.

Trigger Finger and Amyloid Cardiomyopathy, Usual Suspect; Amyloid Deposition

Objectives: The aim of this study was to investigate the amyloid deposition in patients with trigger finger disease, to analyze the factors affecting amyloid deposition. In addition, we aimed to research the presence of cardiac amyloidosis in patients with amyloid deposition in flexor pulleys. Methods: Consecutive 68 patients with trigger finger treated by open release between September 2018 and November 2019 in two different hospitals were included in this study. Idiopathic trigger fingers were solely included. Patients with systemic rheumatoid diseases, chronic renal failure under hemodialysis, gout, tuberculous synovitis and previously diagnosed systemic amyloidosis including familial amyloid poly- neuropathy or multiple myeloma, pregnant patients, patients who were previously had steroid injected injections were excluded. Demographic data, other concomitant diseases and previous carpal tunnel surgeries were recorded. Immunoperoxidase and immunofluorescence methods were used to determine the amyloid presence and subtype in pathological A1 pulley specimens. Patients with amyloid deposition in biopsy specimen were further evaluated for cardiac involvement of amyloidosis. Results: The study population consisted of 18 men and 50 women with a mean age of 57,6 ± 12,2 years. Of 68 patients with trigger finger, 6 (8,8%) showed amyloid deposition in the tenosynovial tissue; and all amyloid deposits were specifically immunolabeled only with the anti-TTR antibody. No evidence of cardiac amyloidosis is found in patients with localized amyloid deposition. Conclusion: Hand surgeons should be aware of the association trigger finger and amyloidosis and consider biopsy of tenosynovial tissue particularly in patients with older age, DM, prior carpal tunnel release surgery and multi-finger involvement. Tenosynovial biopsy is a low-risk procedure that may guide to cardiologic examination of patients with positive biopsy and it will contribute to early diagnosis of cardiac amyloidosis.

Trigeminal Amyloidoma: A Report of Two Cases and Review of the Literature.

Cerebral amyloidomas, characterized by localized amyloid deposits in the nervous system in the absence of systemic disease, are rare. These typically consist of immunoglobulin light chain (AL)-type, predominantly lambda. Trigeminal nerve involvement is exceptionally rare with only 21 previously reported cases, three with bilateral disease. We report two additional cases of amyloid localized to Meckel's cave with secondary involvement of the trigeminal nerves bilaterally, with protein characterization by mass spectrometry. The patients, both females, 39 and 49-years-old, respectively, presented with the insidious onset of progressive trigeminal neuropathy, including pain and numbness with sensory loss, refractory to medical therapy. One patient experienced bilateral symptoms. Magnetic resonance imaging demonstrated abnormal thickening and contrast enhancement along Meckel's cave bilaterally in both cases. The clinical differential diagnosis included benign neoplasms and inflammatory disorders. At the time of biopsy, the trigeminal nerve was noted to be enlarged and multinodular in one case and associated with abnormal soft tan tissue in the other case. Microscopically, the nerve biopsies showed extensive Congo red-positive amyloid deposits. Liquid chromatography tandem mass spectrometry demonstrated that the amyloid was of (AL)-type in both cases (AL [kappa] in one case and AL [lambda] in the other). After extensive evaluation, there was no evidence of systemic involvement. Both patients received localized radiotherapy for their refractory symptoms. One patient has stable symptomatology and imaging. No follow-up is available for the other patient.

Tracheal amyloidosis presenting with hemoptysis

Amyloidosis is a generic term for a heterogeneous group of disorders associated with deposition of protein in an abnormal fibrillar form. The diverse spectrum of amyloid-related diseases is now recognised to include Alzheimer's disease, Type II diabetes and transmissible spongiform encephalopathies. Amyloidosis can be hereditary or acquired, localised or systemic and potentially lethal or merely an incidental finding. Tracheal amyloidosis refers to the deposition of localised amyloid deposits in the trachea. Localised tracheal amyloidosis is a rare form of amyloidosis with only a few hundred cases reported so far. We report here a case of a 65-year-old male presenting with haemoptysis.

Peripheral nervous system involvement in systemic amyloidosis

Peripheral nervous system involvement may be a main manifestation of systemic amyloidosis or occur in the later stages of the disease in the presence of multiple organ pathology. Focal, multiple mononeuropathy, radiculopathy, polyneuropathy, autonomic nervous system dysfunction, and myopathy develop depending on the localization of amyloid deposits in the peripheral nervous system. The most characteristic symptom in systemic amyloidosis is sensorimotor polyneuropathy accompanied in most cases by the involvement of autonomic nerve fibers in the pathological process. In cases of systemic amyloidosis, peripheral nervous system involvement is progressive, leading to disability, which makes the early diagnosis of the disease and its neurological manifestations and subsequent pathogenetic therapy relevant.

Localised foot and ankle amyloid deposition

BackgroundLocalised (transthyretin-associated) amyloid is commonly seen in articular/periarticular tissues of elderly individuals. Whether age-associated, amyloid deposition occurs in foot and ankle (F&A) tissues has not previously been investigated. In this study we assessed the nature and frequency of F&A amyloid deposition and determined whether it is associated with age and/or specific articular/periarticular F&A lesions. MethodsHistological sections of twenty five normal F&A articular/periarticular tissues (16–71 years) and a range of F&A lesions were stained by Congo Red. The amyloid protein was identified by immunohistochemistry and type of matrix glycosaminoglycans determined by Alcian Blue (critical electrolyte concentration) histochemistry. ResultsAmyloid deposits were found in the joint cartilage and capsule of 3/25 normal specimens (57, 62 and 78 years). Amyloid deposits were small, contained transthyretin, and found in areas of matrix degeneration associated with the presence of highly sulphated glycosaminoglycans. In patients older than 47 years, small amyloid deposits were noted in some F&A lesions, including osteoarthritis, Charcot arthropathy, bursa, ganglion, chondrocalcinosis, gout, calcific tendonitis and Achilles tendonitis. ConclusionSmall localised amyloid deposits in F&A tissues contain transthyretin and occur in areas of matrix degeneration associated with the presence of highly sulphated glycosaminoglycans; these deposits are age-associated and, although seen more commonly in some F&A lesions, are small and unlikely to be of pathogenic significance.

Electron Microscopic Findings of Insulin-Induced Local Amyloidosis

Introduction: Insulin-induced local amyloidosis (ILA) was firstly described in 1983, but still underdiagnosed. Here we describe clinicopathological and electron microscopic findings of a case with ILA. Case: A 52-year-old male with type 2 diabetes mellitus for 14 years, on basal-bolus insulin (i.e., insulin lispro and glargine), had noticed 2x2 cm mass at injection site. MRI showed a fibrous mass at the subcutaneous tissue. Punch biopsy of the lesion revealed amyloid deposition surrounded by giant cells. Immunohistochemistry studies proved that amyloid material is insulin. Electron microscopic evaluation (EM) revealed both extra-, and intracellular amyloid fibrils (Figure 1A,B). Discussion: Local amyloid deposition due to insulin injection could be seen in both types of diabetes. Despite earlier reports were associated with porcine insulin, subsequent publications linked also with human insulin and recombinant insulin analogues. High doses of insulin and inappropriate insulin injections are the major risk factors. Extracellular amyloid deposits in ILA arises primarily from exogenous insulin, but the precise mechanism of pathogenicity remains to be established. There are only few case reports of ILA with EM. To the best of our knowledge, here in this case we have firstly showed intracellular accumulation of those amyloid fibrils as well as extracellular compartment, which might have further clinical implications. Disclosure S. Sendur: None. K. Katipoglu: None. O. Kockara: None. Ö. Gököz: None. F. Kaymaz: None. S. Dagdelen: None.

Cerebrovascular-Reactivity Mapping Using MRI: Considerations for Alzheimer's Disease.

Alzheimer’s disease (AD) is associated with well-established macrostructural and cellular markers, including localized brain atrophy and deposition of amyloid. However, there is growing recognition of the link between cerebrovascular dysfunction and AD, supported by continuous experimental evidence in the animal and human literature. As a result, neuroimaging studies of AD are increasingly aiming to incorporate vascular measures, exemplified by measures of cerebrovascular reactivity (CVR). CVR is a measure that is rooted in clinical practice, and as non-invasive CVR-mapping techniques become more widely available, routine CVR mapping may open up new avenues of investigation into the development of AD. This review focuses on the use of MRI to map CVR, paying specific attention to recent developments in MRI methodology and on the emerging stimulus-free approaches to CVR mapping. It also summarizes the biological basis for the vascular contribution to AD, and provides critical perspective on the choice of CVR-mapping techniques amongst frail populations.

Imitators of chronic pancreatitis: diffuse neuroendocrine tumour of the pancreas

We report a rare case of diffuse replacement of the pancreas with neuroendocrine tumour mimicking chronic pancreatitis. A 55-year-old female with no significant past medical history initially presented with abdominal pain in 2006. A CT of the abdomen and pelvis was performed, revealing diffuse pancreatic parenchymal calcifications with mild pancreatic ductal dilatation and no discrete mass. She was diagnosed with chronic pancreatitis and followed clinically until 2015, where she presented with recurrent abdominal pain. A repeat CT and MRI of the abdomen were performed which revealed new hypoenhancing masses within the pancreas, particularly in the pancreatic tail. There was a persistent background of pancreatic parenchymal calcifications. The possibility of pancreatic neuroendocrine tumour was raised, and an indium-111 Octreotide scan was recommended. Diffuse intense uptake was identified throughout the pancreas on the indium-111 imaging. Given the concern for neuroendocrine tumour, a total pancreatectomy was performed, with histopathology revealing replacement of the pancreas with coalescing well-circumscribed nodules. Many of the nodules had numerous calcifications and localized amyloid deposition. Immunohistochemical stains of the neoplastic cells were strong for neuroendocrine markers chromogranin A and synaptophysin. Overall the findings were consistent with numerous neuroendocrine tumours of the pancreas, Grade II, as per the 2010 WHO criteria for neuroendocrine tumours of the pancreas. Neuroendocrine tumours of the pancreas are lesions that arise from the islet cells, with an approximate incidence of five cases per million people per year. Only one other case report has been documented in the literature by Singh et al demonstrating diffuse pancreatic neuroendocrine tumour replacing the entire pancreas. As diffuse pancreatic neuroendocrine tumour can look similar on imaging to chronic pancreatitis or other infiltrative processes, we wanted to present this case and some of the more specific imaging findings in distinguishing these entities.