A Rare Case of Subcutaneous Amyloidoma Associated with Localized Lymphoplasmacytic Lymphoma: Diagnostic Challenges and Treatment Considerations.

BACKGROUND AL amyloidomas are solitary, localized, tumor-like deposits of immunoglobulin light-chain-derived amyloid fibrils in the absence of systemic amyloidosis. A rare entity, they have been described in various anatomical sites, typically in spatial association with a sparse lymphoplasmacytic infiltrate, ultimately corresponding to a clonal, malignant, lymphomatous disorder accounting for the amyloidogenic activity. Most frequently, the amyloidoma-associated hematological disorder corresponds to either a solitary plasmacytoma or an extranodal marginal zone lymphoma of MALT. Much rarer is the association with lymphoplasmacytic lymphoma, which by itself is usually a bone marrow-bound disorder with systemic burden. The almost anecdotic combination of an amyloidoma and a localized lymphoplasmacytic lymphoma deserves attention, as it entails a thorough diagnostic workup to exclude systemic involvement and a proportionate therapeutic approach to avoid overtreatment. A review of the literature provides an insight on pathogenesis and prognosis, and can assist both pathologists and clinicians in establishing optimal patient management strategies. CASE REPORT We herein report the incidental finding of a subcutaneous amyloidoma caused by a spatially related, similarly localized lymphoplasmacytic lymphoma diagnosed in a 54-year-old female patient with no other disease localizations and a complete remission following 2 subsequent surgical excisions. CONCLUSIONS Whatever the specific combination of an amyloidoma and the related hematological neoplasm, a multidisciplinary collaboration and a comprehensive clinical-pathological staging are warranted to exclude systemic involvement and identify patients with localized diseases who would benefit from local active treatment and close follow-up.

Diagnostic and Therapeutic Implications of Pulmonary Lymphoma Associated With Nodular Amyloidosis.

Pulmonary localization of B-cell lymphoma associated with deposits of amyloid material is a rare finding in the thoracic disease spectrum. This report describes a rare case of nodular pulmonary amyloidosis in a 50-year-old patient. He underwent left upper lobectomy for mucosa-associated lymphoid tissue lymphoma that originated from bronchial lymphoid tissue.

Applications of the real-time quaking-induced conversion assay in diagnosis, prion strain-typing, drug pre-screening and other amyloidopathies.

INTRODUCTION: The development of in vitro protein misfolding amplification assays for the detection and analysis of abnormally folded proteins, such as proteinase K resistant prion protein (PrPres) was a major innovation in the prion field. In prion diseases, these types of assays imitate the pathological conversion of the cellular PrP (PrPC) into a proteinase resistant associated conformer or amyloid, called PrPres. Areas covered: The most prominent protein misfolding amplification assays are the protein misfolding cyclic amplification (PMCA), which is based on sonication and the real-time quaking-induced conversion (RT-QuIC) technique based on shaking. The more recently established RT-QuIC is fully automatic and enables the monitoring of misfolded protein aggregates in real-time by using a fluorescent dye. Expert commentary: RT-QuIC is a very robust and highly reproducible test system which is applicable in diagnosis, prion strain-typing, drug pre-screening and other amyloidopathies.

Insular carcinoma arising on a background of follicular carcinoma, thyrolipomatosis and amyloid goitre.

A 67-year-old man was referred with a history of a right-sided neck lump and dysphonia, secondary to a lesion in the thyroid gland. After undergoing a total thyroidectomy, he was found to have an exceedingly rare combination of follicular carcinoma, insular carcinoma, thyrolipomatosis and an amyloid goitre in his thyroid gland. He subsequently underwent further radioactive iodine ablation and has been in remission. He was also later incidentally diagnosed with systemic amyloidosis, which explained the amyloid deposition in his thyroid gland.

The Efficacy of Q-Switched ND:YAG 1064 nm Laser in Recalcitrant Macular Amyloidosis: A Case Report.

Macular amyloidosis typically presents as small, dusky-brown or greyish pigmented macules, the result of altered keratin deposition. Treatment of these hyperpigmented regions with topical and systemic therapies remains challenging, however Q-Switched neodymi- um-doped yttrium aluminum garnet (ND:YAG) laser has proven to be an effective treatment modality to reduce hyperpigmentation. In this case report we investigated the ef cacy of Q-Switched Nd:YAG laser treatment on a 34-year old woman with recalcitrant macular amyloidosis who failed to respond to over-the-counter bleaching creams. The patient was treated with 7 treatment sessions of Q- Switched Nd:YAG laser at one month intervals. According to our photographic analysis and patient self-assessment, the patient ap- peared to improve with each treatment session. Post-recurrence of the lesion after reaction to Triluma ( uocoinolone actetonide 0.01%, hydroquinone 4%, tretinoin 0.05%), the patient has been continuing to respond well to a second round of treatment with Q-switched Nd:YAG laser at 1064 nm. J Drugs Dermatol. 2016;15(11):1456-1458..

Acquired factor X deficiency developed four years after autologous transplantation in a patient with multiple myeloma associated with systemic AL amyloidosis.

We describe a case of acquired factor X deficiency after high-dose melphalan with autologous stem cell transplantation (HDM/ASCT) for multiple myeloma (MM) with systemic AL amyloidosis. A 68-year-old woman with renal amyloidosis was diagnosed as having MM in 2007. She achieved a partial response after VAD (vincristine, adriamycin, dexamethasone) therapy and HDM/ASCT. In December 2011, coagulation tests revealed a prolonged prothrombin time (PT) of 17.6 sec and she was administered vitamin K. In January 2012, she received low anterior resection with colostomy for rectal cancer. She received fresh frozen plasma (FFP) infusion but the perioperative bleeding tendency persisted. In February 2012, she was referred from surgery for colostomy closure. She showed no progression of MM and had prolonged PT, corrected by mixing with normal plasma. Factor X activity was markedly decreased. She was diagnosed as having an acquired factor X deficiency and was given FFP infusion for colostomy closure. Although acquired factor X deficiency after HDM/ASCT for MM with systemic AL amyloidosis is rare, we should be aware of the possibility of this disease in MM patients with a bleeding tendency.

A first step beyond traditional boundaries: destination therapy with the SynCardia total artificial heart.

The SynCardia total artificial heart is currently used as a bridge to transplantation therapy in cases of irreversible, acute or chronic, biventricular heart failure. We describe the implementation of this technology in the context of destination therapy in a patient with an end-stage heart failure on grounds of primary amyloidosis.

MetAmyl: a METa-predictor for AMYLoid proteins.

The aggregation of proteins or peptides in amyloid fibrils is associated with a number of clinical disorders, including Alzheimer's, Huntington's and prion diseases, medullary thyroid cancer, renal and cardiac amyloidosis. Despite extensive studies, the molecular mechanisms underlying the initiation of fibril formation remain largely unknown. Several lines of evidence revealed that short amino-acid segments (hot spots), located in amyloid precursor proteins act as seeds for fibril elongation. Therefore, hot spots are potential targets for diagnostic/therapeutic applications, and a current challenge in bioinformatics is the development of methods to accurately predict hot spots from protein sequences. In this paper, we combined existing methods into a meta-predictor for hot spots prediction, called MetAmyl for METapredictor for AMYLoid proteins. MetAmyl is based on a logistic regression model that aims at weighting predictions from a set of popular algorithms, statistically selected as being the most informative and complementary predictors. We evaluated the performances of MetAmyl through a large scale comparative study based on three independent datasets and thus demonstrated its ability to differentiate between amyloidogenic and non-amyloidogenic polypeptides. Compared to 9 other methods, MetAmyl provides significant improvement in prediction on studied datasets. We further show that MetAmyl is efficient to highlight the effect of point mutations involved in human amyloidosis, so we suggest this program should be a useful complementary tool for the diagnosis of these diseases.

Solitary amyloidosis of the sigmoid colon featuring submucosal tumor caused hematochezia.

A previously a healthy 64-year-old woman complained of a two-week history of hemorrhaging upon defecation. The laboratory and urinalysis findings were normal, and no serum or urine M components were detectable on protein electrophoresis. An air contrast barium enema revealed an elevated lesion measuring -20 mm in diameter with a smooth surface and a depression in the sigmoid colon. Colonoscopy revealed a red colored and congested tumor. The exposed surface of the submucosal tumor (SMT) center was somewhat yellow in color and covered with fuzz. All other portions of the colon were normal. The endoscopy and double-contrast barium revealed a normal upper gastrointestinal tract and a normal small intestine, respectively. A histopathological evaluation of a biopsy specimen obtained from the SMT suggested amyloid deposition. However, the other biopsy specimens of the esophagus, stomach, duodenal bulb, second portion of the duodenum, terminal ileum and other portions of the colon demonstrated no amyloid deposition. Colonoscopic ultrasonography (US) revealed the hypoechoic, homogeneous SMT to be mainly localized within the submucosa. An endoscopic submucosal resection (EMR) of the solitary amyloidosis was performed and the immunohistopathology revealed the entire SMT to consist of amyloid light chain kappa amyloid deposition. We considered that the US followed by EMR contributed to the precise diagnosis of solitary amyloidosis and the treatment of hematochezia caused by a solitary area of amyloidosis within the sigmoid colon.

Al amyloidosis.

UNLABELLED: DEFINITION OF THE DISEASE: AL amyloidosis results from extra-cellular deposition of fibril-forming monoclonal immunoglobulin (Ig) light chains (LC) (most commonly of lambda isotype) usually secreted by a small plasma cell clone. Most patients have evidence of isolated monoclonal gammopathy or smoldering myeloma, and the occurrence of AL amyloidosis in patients with symptomatic multiple myeloma or other B-cell lymphoproliferative disorders is unusual. The key event in the development of AL amyloidosis is the change in the secondary or tertiary structure of an abnormal monoclonal LC, which results in instable conformation. This conformational change is responsible for abnormal folding of the LC, rich in ß leaves, which assemble into monomers that stack together to form amyloid fibrils. EPIDEMIOLOGY: AL amyloidosis is the most common type of systemic amyloidois in developed countries with an estimated incidence of 9 cases/million inhabitant/year. The average age of diagnosed patients is 65 years and less than 10% of patients are under 50. CLINICAL DESCRIPTION: The clinical presentation is protean, because of the wide number of tissues or organs that may be affected. The most common presenting symptoms are asthenia and dyspnoea, which are poorly specific and may account for delayed diagnosis. Renal manifestations are the most frequent, affecting two thirds of patients at presentation. They are characterized by heavy proteinuria, with nephrotic syndrome and impaired renal function in half of the patients. Heart involvement, which is present at diagnosis in more than 50% of patients, leading to restrictive cardiopathy, is the most serious complication and engages prognosis. DIAGNOSTIC METHODS: The diagnosis relies on pathological examination of an involved site showing Congo red-positive amyloid deposits, with typical apple-green birefringence under polarized light, that stain positive with an anti-LC antibody by immunohistochemistry and/or immunofluorescence. Due to the systemic nature of the disease, non-invasive biopsies such as abdominal fat aspiration should be considered before taking biopsies from involved organs, in order to reduce the risk of bleeding complications. DIFFERENTIAL DIAGNOSIS: Systemic AL amyloidosis should be distinguished from other diseases related to deposition of monoclonal LC, and from other forms of systemic amyloidosis. When pathological studies have failed to identify the nature of amyloid deposits, genetic studies should be performed to diagnose hereditary amyloidosis. MANAGEMENT: Treatment of AL amyloidosis is based on chemotherapy, aimed at controlling the underlying plasma clone that produces amyloidogenic LC. The hematological response should be carefully checked by serial measurements of serum free LC. The association of an alkylating agent with high-dose dexamethasone has proven to be effective in two thirds of patients and is considered as the current reference treatment. New agents used in the treatment of multiple myeloma are under investigation and appear to increase hematological response rates. Symptomatic measures and supportive care is necessary in patients with organ failure. Noticeably, usual treatments for cardiac failure (i.e. calcium inhibitors, ß-blockers, angiotensin converting enzyme inhibitors) are inefficient or even dangerous in patients with amyloid heart disease, that should be managed using diuretics. Amiodarone and pace maker implantation should be considered in patients with rhythm or conduction abnormalities. In selected cases, heart and kidney transplantation may be associated with prolonged patient and graft survival. PROGNOSIS: Survival in AL amyloidosis depends on the spectrum of organ involvement (amyloid heart disease being the main prognosis factor), the severity of individual organs involved and haematological response to treatment.

Effects of the main green tea polyphenol epigallocatechin-3-gallate on cardiac involvement in patients with AL amyloidosis.

BACKGROUND: Amyloid light chain (AL) amyloidosis is a rare disease with poor prognosis and limited therapeutic alternatives. Recently, one clinical case with cardiac involvement, as well as a compelling evidence of green tea polyphenol, epigallocatechin-3-gallate (EGCG), inducing the formation of benign aggregation products that do not polymerize into fibrils were published. This is a report of the cardiac effects of green tea consumption in these patients. METHODS: Patients with known cardiac involvement in AL amyloidosis were examined by routine cardiovascular examinations that took place every 3-6 months. Of 59 patients with cardiac involvement, 11 revealed a decrease of at least 2 mm of interventricular wall thickness, after initiation of regular green tea consumption (GT). A matched historic control group (n = 22) was selected. Comprehensive echocardiography was conducted at every control examination and analyzed offline by two independent examiners. RESULTS: GT patients showed an improvement in New York Heart Association (NYHA) class from a median of 3 (25th, 75th percentiles: 2, 3) to 2 (2, 3), P = 0.038. Septal thickness decreased from 18 (18, 20) to 16 (16, 17) mm, P = 0.021. Left ventricular mass index decreased from 175 (154, 180) to 133 (128, 154) g/m(2), P = 0.007. Comparing both groups, an increase in left ventricular ejection fraction could be found in the GT group, 65 (51, 73) versus 53 (47, 59)%, P = 0.012. These changes could not be observed in the control group. CONCLUSION: Consumption of green tea polyphenol EGCG in patients with cardiac involvement with AL amyloidosis causes a significant decrease in left ventricular wall thickness and mass, as well as an improvement in NYHA functional classification and left ventricular ejection fraction.

[Antidementia drugs]. / Antidementiva.

The pharmacological treatment of dementias aims to improve cognitive deficits, activities of daily living and behavioural and psychiatric symptoms. The weighting of theses therapeutic aims varies with disease progression. Behavioural symptoms may dominate especially in the more severe stages of the disease and may further deteriorate global functional level of the patient. Today there is no causal therapy for Alzheimer's disease (AD). Based on preclinical disease models novel therapeutic approaches are under development that target the beta-amyloid and tau protein metabolism. Some of them aim to inhibit the formation, aggregation and toxicity of beta-amyloid peptides or promote their clearance from the brain. Others inhibit the formation of neurofibrillary tangles or have neuroprotective effects. Active or passive immunisation against beta-amyloid may be a very specific and effective approach. The efficacy of acetylcholine esterase inhibitors (AchEI) in the treatment of mild to moderate AD is well documented. They are first line therapeutics in the treatment of the disease and lead to a delay of symptomatic progression. Memantine is effective in the treatment of moderate to severe stages of AD. The evidence for the treatment of vascular dementia is comparatively weak. However, positive effects have been shown for all available AchEI and memantine. Non pharmacological therapy is an indispensable part of the treatment of dementia patients and should be adapted to the individual needs of the patient in the respective stage of the disease. The efficacy of antipsychotics in the treatment of behavioural and psychiatric symptoms of dementia is limited. These drugs are associated with increased morbidity and mortality in dementia patients. Therefore, their application should be based on a critical and individual evaluation of risks and benefits.

Effect of dietary unsaturated fatty acids on senile amyloidosis in senescence-accelerated mice.

Effects of dietary oils on aging were investigated in senescence-accelerated mice. For 26 weeks, mice were fed purified diets containing 4% olive oil, safflower oil, perilla oil, or fish oil. Serum total, high-density lipoprotein cholesterol, and apolipoprotein A-II (ApoA-II) were significantly lower in the fish oil group than in the perilla oil group, and these were significantly lower than in the olive oil or safflower oil group. The olive oil and safflower oil groups had significantly fewer ApoA-II amyloid fibril (AApoAII) deposits and anti-single-strand DNA (ssDNA) antibodies than the fish oil or perilla oil group, and the fish oil diet induced significantly more AApoAII deposits and anti-ssDNA antibodies than did the perilla oil diet. Survival decreased earlier in the fish oil group than in the other groups (as seen in the survival curve). The results suggest that greater the degree of unsaturation of dietary fatty acids, greater is the tendency for accelerated senescence.

Amiloidosis: enfermedad desafiante en su diagnóstico y tratamiento / Amyloidosis: diagnosis and treatment

La amiloidosis es una enfermedad sistémica caracterizada por el depósito de fibrillas amiloídeas en diversos órganos, lo que lleva a un deterioro y falla progresiva de éstos, afectando sustancialmente la sobrevida del paciente. Se analizaron los registros médicos de 34 pacientes egresados con diagnóstico de amiloidosis del Hospital Clínico de la Universidad de Chile en un período de 15 años. El promedio del tiempo entre la aparición de síntomas y el diagnóstico fue aproximadamente de seis meses. Los compromisos sistémicos de mayor relevancia fueron el renal y cardíaco, influyendo este último notablemente en la sobrevida. El laboratorio inmunológico tuvo un rol fundamental en identificar a los pacientes portadores de una paraproteína y de esta manera apoyar el diagnóstico. Es necesario plantearse este diagnóstico diferencial en todo paciente con compromiso sistémico de causa no clara y más aún cuando está asociado un trastorno mieloproliferativo.

Amyloidosis is a systemic disease characterized by the deposition of amyloid fibrils in many organs, leading to a progressive deterioration and failure of these, substantially affecting the survival of the patient. We present 34 medical records of patients that were hospitalized with the diagnosis of amyloidosis in the Hospital of the Universidad de Chile, over a period of fifteen years. The average time between the onset of symptoms and diagnosis was approximately six months. The most important systemic affectations were to the kidney and heart, the latter significantly influences survival. The immunology laboratory plays a fundamental role in identifying patients with paraprotein, thus supporting diagnosis. It is necessary to consider this differential diagnosis in all patients with systemic symptoms of no clear cause, especially when it is associated to a myeloproliferative disorder.

Creativity and dementia: emerging diagnostic and treatment methods for Alzheimer's disease.

Alzheimer's disease research is beginning to yield promising treatments and prevention strategies. Current Alzheimer's disease treatments benefit symptoms, but do not appreciably alter the basic disease process. The new generation of Alzheimer's disease medications, however, will likely include disease-modifying treatments, which will slow disease progression or stop it entirely. These new treatments pursue four points of intervention: increasing the clearance of amyloid-beta42 (Abeta42) proteins in the brain, blocking Abeta42 production, decreasing Abeta42 production, and decreasing Abeta42 aggregation. Neurogenerative therapies are being explored as well, suggesting future treatments may not only stop disease progression but also reverse it. Risk factors for developing Alzheimer's disease and factors associated with a lower risk of Alzheimer's disease have been identified. Future Alzheimer's disease management may come to resemble routine cardiovascular disease prevention and management, which involves the control of modifiable risk factors and the use of medications that decrease or stop underlying pathology. The hope is that such management will arrest the disease process before cognitive symptoms have begun. Like other neurologic illnesses, Alzheimer's disease has a profound impact on creativity. Alzheimer's disease attacks the right posterior part of the brain, which enables people to retrieve internal imagery and copy images. Alzheimer's disease patients may lose the ability to copy images entirely. However, people with Alzheimer's disease can continue to produce art by using their remaining strengths, such as color or composition instead of shapes or realism. Studying art and dementia is a model for identifying the strengths of psychiatric patients. Remarkably, art emerges in some patients even in the face of degenerative disease. In this expert roundtable supplement, Jeffrey L. Cummings, MD, offers an overview of recent advances in Alzheimer's disease research. Bruce L. Miller, MD, discusses creativity in patients with neurologic illnesses. Daniel D. Christensen, MD, discusses emerging Alzheimer's disease therapies. Debra Cherry, PhD, discusses the advocacy needs of Alzheimer's disease patients and their caregivers. In addition, Patricia Utermohlen, MA, provides a testimonial of the impact of Alzheimer's disease on an accomplished artist.

Secondary amyloidosis due to FMF.

Familial Mediterranean fever (FMF) is an ethnically restricted disease with an autosomal recessive inheritance characterized by recurrent attacks of fever, painful manifestations in the abdomen, chest and joints. The disease affects mainly non-Ashkenazi Jews, Armenians, Turks Arabs and other people of Mediterranean origin. The disease may present at any age, more than 80% of patients being symptomatic by the age of 20. Although the inflammatory attacks that characterize the disease may sometimes be debilitating, secondary (AA) amyloidosis remains the most serious manifestation of FMF causing considerable morbidity due mostly to nephropathic amyloidosis. The largest series of secondary amyloidosis in FMF have been reported from Turkey. The pathophysiological steps in progressing a patient from FMF to amyloidosis are not definitely known. Daily treatment with colchicine can prevent both the attacks and amyloid deposition but no effective alternative treatment exists for colchicine resistant cases. Meanwhile more population based epidemiological and genetic data should be gathered by worldwide collaborative studies to elucidate the link between FMF and amyloidosis and to develop alternative therapies.