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.

Biologic therapy for amyloid A amyloidosis secondary to rheumatoid arthritis treated with interleukin 6 therapy: Case report and review of literature.

INTRODUCTION: Secondary amyloidosis is a rare complication of rheumatoid arthritis (RA) that is histologically characterized by the deposition of amyloid fibrils in target organs, such as the kidneys and gastrointestinal tract. Controlling the inflammatory response is essential to prevent organ dysfunction in amyloid A (AA) amyloidosis secondary to RA, and no clear treatment strategy exists. PATIENT CONCERNS AND DIAGNOSIS: A 66-year-old woman with RA, who had been treated with disease-modifying anti-rheumatic drugs for 1 year, presented with recurrent abdominal pain and prolonged diarrhea. Endoscopy showed chronic inflammation, and colon tissue histology confirmed AA amyloidosis. INTERVENTIONS AND OUTCOMES: After tocilizumab therapy was begun, her diarrhea and abdominal pain subsided, and articular symptoms improved. Biologic drugs for RA have been used in patients with secondary AA amyloidosis, including tumor necrosis factor and Janus kinase inhibitors, interleukin 6 blockers, and a T cell modulator. Here, we systematically review existing case reports and compare the outcomes of RA-related AA amyloidosis after treatment with various drugs. CONCLUSION: The data indicate that biologic drugs like tocilizumab might be treatments of choice for AA amyloidosis secondary to RA.

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.

Nutritional counseling improves quality of life and preserves body weight in systemic immunoglobulin light-chain (AL) amyloidosis.

OBJECTIVE: Malnutrition is associated with mortality and impaired quality of life (QoL) in systemic immunoglobulin light-chain (AL) amyloidosis. The aim of this study was to determine whether nutritional counseling is beneficial to patients with AL. METHODS: In this intervention study (ClinicalTrials.gov Identifier: NCT02055534), 144 treatment-naïve outpatients with AL were randomized to usual care (UC; n = 72) and nutritional counseling (NC; n = 72). RESULTS: In the randomized population, although patients in the NC group maintained a stable body weight (weight loss [WL] = 0.6 kg; 95% confidence interval [CI], -1.0 to 2.1; P = 0.214), those in the UC group demonstrated a significant decrease (WL = 2.1 kg; 95% CI, 0.2-4.1; P = 0.003). However, the difference in weight between groups was not significant (mean WL difference = 1.6 kg; 95% CI, -0.7 to 3.9; P = 0.179). Patients in the NC group demonstrated more satisfactory energy intake (≥75% of estimated requirements, odds ratio, 2.18; 95% CI, 1.04-4.57; P = 0.048) and a significant increase in the mental component summary of QoL (Short form-36) at 12 mo (mean difference, 8.1; 95% CI, 2.3-13.9; P = 0.007), which was restored to a mean score of 53 (95% CI, 50-53), over the healthy population norms. NC was also associated with better survival (crude hazard ratio, 0.57; 95% CI, 0.35-0.94; P = 0.028). CONCLUSIONS: In outpatients with AL, NC was helpful in preserving body weight, effective in improving mental QoL, and associated with better survival.

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 marked decline in the incidence of renal replacement therapy for amyloidosis associated with inflammatory rheumatic diseases - data from nationwide registries in Finland.

Risk for amyloidosis in rheumatic diseases is associated with a long-lasting inflammation. To assess possible changes in the incidence of terminal uraemia due to amyloidosis associated with rheumatic diseases on a nationwide basis, we scrutinised the files of the Finnish Registry for Kidney Diseases for patients suffering from amyloidosis associated with rheumatoid arthritis (RA), ankylosing spondylitis (AS) or juvenile idiopathic arthritis (JIA) over the period 1995-2008. The registry has an estimated 97-99% coverage of all patients accepted for renal replacement therapy (RRT) in the country. Data on the consumption of antirheumatic drugs were collected from two sources: the Social Insurance Institution's Drug Reimbursement Register, and the Sales Register of the National Agency for Medicines from the above period. Altogether 264 cases were identified. Two hundred twenty-nine of them had RA, 15 AS and 20 JIA. When the total annual number of new admissions to RRT varied between 20 and 37 at the end of 1990s, it was under half of that from 2002 onwards. Over this period, the number of users of low-dose methotrexate (MTX) has increased 3.6-fold, the drug being the most frequently used disease modifying anti-rheumatic drug in Finland. The present nationwide series is the first to show that the incidence of end-stage renal disease due to amyloidosis associated with rheumatic diseases is decreasing. An obvious reason for this is intensive anti-rheumatic drug therapy.

Toll-like receptors expression and signaling in glia cells in neuro-amyloidogenic diseases: towards future therapeutic application.

Toll-like receptors (TLRs) are known to be expressed by innate immune response cells and to play a critical role in their activation against foreign pathogens. It was recently suggested that TLRs have an important role in the crosstalk between neurons and glial cells in the central nervous system (CNS). TLR signaling was reported to be associated with a yin-yang effect in the CNS. While TLR signaling was linked to neurogenesis, it was also found to be involved in the pathogenesis of neurodegenerative diseases. This paper will focus on TLR signaling in glial cells in neurodegenerative diseases such as Alzheimer's disease, prion diseases, amyotrophic lateral sclerosis, and Parkinson's disease. Understanding the pattern of TLR signaling in the glial cells may lead to the identification of new targets for therapeutic application.

Allogeneic and autologous transplantation for haematological diseases, solid tumours and immune disorders: current practice in Europe 2009.

The European Group for Blood and Marrow Transplantation regularly publishes special reports on the current practice of haematopoietic SCT for haematological diseases, solid tumours and immune disorders in Europe. Major changes have occurred since the first report was published. HSCT today includes grafting with allogeneic and autologous stem cells derived from BM, peripheral blood and cord blood. With reduced-intensity conditioning regimens in allogeneic transplantation, the age limit has increased, permitting the inclusion of older patients. New indications have emerged, such as autoimmune disorders and AL amyloidosis for autologous HSCT and solid tumours, myeloproliferative syndromes and specific subgroups of lymphomas for allogeneic transplants. The introduction of alternative therapies, such as imatinib for CML, has challenged well-established indications. An updated report with revised tables and operating definitions is presented.

Successful treatment of lichen amyloidosus associated with atopic dermatitis using a combination of narrowband ultraviolet B phototherapy, topical corticosteroids and an antihistamine.

Lichen amyloidosus (LA) is a type of primary localized cutaneous amyloidosis characterized by multiple pruritic discrete hyperkeratotic papules with amyloid deposition in the papillary dermis. Clinical regression is usually difficult to achieve, even after treatment. In this study, we report a case of an adult man with LA associated with atopic dermatitis (AD) which was successfully treated with narrowband ultraviolet B (NB-UVB) phototherapy, topical corticosteroids and an oral antihistamine. This case suggests that NB-UVB phototherapy may be a useful adjuvant for LA associated with AD.

Calreticulin expression in the clonal plasma cells of patients with systemic light-chain (AL-) amyloidosis is associated with response to high-dose melphalan.

In high doses with stem-cell transplantation, melphalan is an effective but toxic therapy for patients with systemic light-chain (AL-) amyloidosis, a protein deposition and monoclonal plasma cell disease. Melphalan can eliminate the indolent clonal plasma cells that cause the disease, an achievement called a complete response. Such a response is usually associated with extended survival, while no response (a less than 50% reduction) is not. Gene-expression studies and a stringently supervised analysis identified calreticulin as having significantly higher expression in the pretreatment plasma cells of patients with systemic AL-amyloidosis who then had a complete response to high-dose melphalan. Calreticulin is a pleiotropic calcium-binding protein found in the endoplasmic reticulum and the nucleus whose overexpression is associated with increased sensitivity to apoptotic stimuli. Real-time PCR and immunohistochemical staining also showed that expression of calreticulin was higher in the plasma cells of those with a complete response. Furthermore, wild-type murine embryonic fibroblasts were significantly more sensitive to melphalan than calreticulin knock-out murine embryonic fibroblasts. These data have important implications for understanding the activity of melphalan in plasma-cell diseases and support further investigation of calreticulin and its modulation in patients with systemic AL-amyloidosis receiving high-dose melphalan.

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.

Successful treatment of lichen amyloidosis with combined bath PUVA photochemotherapy and oral acitretin.

Lichen amyloidosis (LA) is a chronic, pruritic skin disorder characterized by brownish-grey papules on extensor surfaces of legs and rarely on the trunk. Thioflavin T-positive amyloid deposits are found in the papillary dermis of affected skin, which is the only organ involved. A variety of therapeutic regimens for lichen amyloidosis have been described; however, in many cases with only limited effect. We report on two patients with lichen amyloidosis with typical clinical symptoms not responding to local treatment. A combined regimen with bath psoralen ultraviolet A (PUVA) and oral acitretin was initiated, resulting in nearly complete resolution of the papules and impressive relief from the severe pruritus. The beneficial response has persisted for 8 months. The suggested combined therapy with bath PUVA photochemotherapy and oral acitretin represents an efficacious and practical treatment modality for lichen amyloidosis with long-lasting effects.

The effect of high-flux hemodialysis on dialysis-associated amyloidosis.

Amyloidosis is an important cause of mortality and morbidity in patients with end-stage renal disease (ESRD) undergoing hemodialysis (HD). In this study, depending on the idea that the clearance of middle and high molecular weight toxins could be improved, we aimed to investigate the effect of high-flux dialyzer on clearance of beta-2 microglobulin (beta2-MG) and calcium (Ca) phosphorus (P) metabolism in patients under HD treatment. Forty-eight patients with ESRD under chronic HD treatment were included in the study. All patients were randomized into two groups, and HD was performed with low-flux or high-flux dialyzer for 6 months. In the high-flux group, the reduction of beta2-MG and P levels during dialysis was significantly higher when compared with the low-flux group (p<0.001). During the follow-up period, while beta2-MG levels decreased significantly in the high-flux group (p<0.05), there was an increase in the low-flux group (p<0.05). As a result, our findings suggest that use of high-flux dialyzer can be an efficient alternative in terms of controlling the clearance of beta2-MG and impaired Ca and P metabolism. These beneficial effects of high-flux dialyzers are probably mediated by the improved clearance of middle and high molecular weight toxins.

Localized amyloidosis: a survey of 35 French cases.

Since the prognosis of localized amyloidosis remains unclear, we conducted a survey to define the characteristics and the course of this disease. The charts of 35 patients with either laryngeal (14 patients), tracheobronchial (10 patients), colonic (1 patient), or lower urinary tract amyloidosis (10 patients) were analyzed. The average age at diagnosis was 52.7+/-12 years (range 33-73 years). The amyloid protein type was specified to be amyloid light chain (AL) in 15 cases. All patients had undergone additional biopsies (accessory salivary glands, rectal, fat pad and bone marrow aspirates) to rule out a systemic disease. Symptomatic treatments included endoscopic excision and laser therapy. Colchicine and chemotherapy with prednisone and melphalan were prescribed with limited success. During a mean follow-up period of 6.1+/-5.3 years no patient developed a systemic form of amyloidosis. Six deaths were reported, one related to the disease because of a fatal airway hemorrhage. We suggest that immunolabeling studies should be more routinely performed. There was no risk of developing a systemic disease from local amyloid deposits in our survey. However, local evolution can be life-threatening. Such patients should be referred to specialist centers for further evaluation. Management requires close follow-up to exclude recurrence and to determine the appropriate symptomatic treatment.

Primary amyloidosis presenting as small bowel encapsulation.

Amyloidosis is a pathological process which encompasses a spectrum of diseases that result from extracellular deposition of pathological fibrillar proteins. Clinical presentations vary depending on the organs involved. There is no documented case of amyloidosis presenting as small bowel encapsulation. A previously healthy 62-year-old man developed a small bowel obstruction in 1997. At surgery, a peculiar membrane encasing his entire small bowel was discovered. This appeared to have no vascularity and was removed without difficulty, exposing a grossly normal bowel. Histopathology revealed thick bands of collagen overlying the peritoneal surface, which was congo red positive and showed apple green birefringence. The findings were consistent with encapsulating peritonitis due to amyloidosis. There was no history or symptoms of any chronic inflammatory condition and he became symptom-free postoperatively. An abdominal fat pad biopsy failed to demonstrate amyloidosis. Endoscopic duodenal biopsies revealed classical primary amyloidosis. Quantitative immunoglobulins, lactate dehydrogenase, C3, C4 and beta-2 microglobulin were normal. Protein electrophoresis identified monoclonal paraprotein, immunoglobulin G lambda 3.7 g/L. Bone marrow biopsy and aspirate revealed only a mild plasmacytosis (5% to 10%). Echocardiogram and skeletal survey were normal. He had mild proteinuria. Complete blood count, C-reactive protein, calcium, albumin and total protein were normal. No specific therapy was instituted. In January of 1998 the patient remained asymptomatic with no gastrointestinal, cardiovascular or constitutional symptoms. He had developed nephrotic range proteinuria (3.95 g/24 h), microalbuminuria, hypoalbuminemia and a renal biopsy consistent with renal amyloidosis. In 1999 there was an increase in the monoclonal paraprotein (6.2 g/L). The remaining investigations were normal except for an echocardiogram which showed left ventricular hypertrophy but a normal ejection fraction and no diastolic dysfunction. He went on to have high-dose chemotherapy and an autologous stem cell transplant in September, 2000. He has subsequently developed renal insufficiency. To our knowledge this is the first reported case of primary amyloidosis presenting as small bowel obstruction from encapsulating peritonitis.

Music therapy for mood disturbance during hospitalization for autologous stem cell transplantation: a randomized controlled trial.

BACKGROUND: High-dose therapy with autologous stem cell transplantation (HDT/ASCT) is a commonly used treatment for hematologic malignancies. The procedure causes significant psychological distress and no interventions have been demonstrated to improve mood in these patients. Music therapy has been shown to improve anxiety in a variety of acute medical settings. In the current study, the authors determined the effects of music therapy compared with standard care on mood during inpatient stays for HDT/ASCT. METHODS: Patients with hematologic malignancy admitted for HDT/ASCT at two sites (Memorial Sloan-Kettering Cancer Center and Ireland Cancer Center in Cleveland, Ohio) were randomized to receive music therapy given by trained music therapists or standard care. Outcome was assessed at baseline and every 3 days after randomization using the Profile of Mood States. RESULTS: Of 69 patients registered in the study, follow-up data were available for 62 (90%). During their inpatient stay, patients in the music therapy group scored 28% lower on the combined Anxiety/Depression scale (P = 0.065) and 37% lower (P = 0.01) on the total mood disturbance score compared with controls. CONCLUSIONS: Music therapy is a noninvasive and inexpensive intervention that appears to reduce mood disturbance in patients undergoing HDT/ASCT.