Presentation Of AL Amyloidosis Research Articles

Recurrent Massive Gastrointestinal Bleeding as a first presentation of AL Amyloidosis in a 76-Year-Old Patient

Background: Light chain or AL amyloidosis is a systemic disease that occasionally involves the gastrointestinal tract, but very rarely presents as gastrointestinal bleeding without evidence of systemic involvement. In such cases recognition of amyloidosis as the cause of bleeding is essential in order to rapidly initiate effective treatment to stop the bleeding. Case presentation: We describe a 76-year-old patient who presented with recurrent massive gastrointestinal bleeding as the initial manifestation of AL amyloidosis. One episode necessitated emergency right colectomy, and histopathological analysis of the resected bowel revealed diffuse amyloid infiltration. This finding prompted further investigations, which demonstrated elevated plasma lambda light chain levels, and 10% monoclonal plasma cells in the bone marrow. Treatment with bortezomib, dexamethasone, and daratumumab was initiated and no further gastrointestinal bleeding occurred. Conclusion: The diagnosis of amyloidosis involving the gastrointestinal tract should be considered in adult patients with unexplained recurrent gastrointestinal bleeding.

Emerging from the shadows: A rare case of gastrointestinal AL amyloidosis presenting as hematemesis

We document a unique presentation of light chain (AL) amyloidosis in a 62-year-old man exhibiting as acute hematemesis and chronic abdominal discomfort. Esophagogastroduodenoscopy disclosed marked thickening of gastric and duodenal folds, gastroduodenal nodularity, and friable ulcerations. Biopsy confirmed amyloidosis. Subsequent investigations ratified a diagnosis of systemic AL amyloidosis with cardiac involvement. Initiation of the cyclophosphamide, bortezomib, and dexamethasone (CyBorD) regimen, along with tafamidis and doxycycline for cardiac pathology, led to substantial improvement of abdominal symptoms. This case highlights the variability in amyloidosis presentations and the importance of early diagnosis.

173 AL Amyloidosis Presenting as Asymptomatic Nephrotic Range Proteinuria in a Patient With Long Standing Diabetes Mellitus

173 AL Amyloidosis Presenting as Asymptomatic Nephrotic Range Proteinuria in a Patient With Long Standing Diabetes Mellitus

AL Amyloidosis Presenting with Yellow Discolouration of the Skin with Dermoscopic Findings.

AL Amyloidosis Presenting with Yellow Discolouration of the Skin with Dermoscopic Findings.

S2203 A Rare Case of Amyloid-Induced Colonic Pseudo-Obstruction

Introduction: Colonic pseudo-obstruction is a rare complication of AL Amyloidosis that is described as a diffuse colonic dilation without underlying mechanical cause. In AL Amyloidosis, extracellular protein deposits disrupt tissue structure and function. Manifestations of colonic involvement of AL Amyloidosis include chronic diarrhea, weight loss, abdominal pain, and pseudo-obstruction. Here we present a patient with worsening abdominal pain and distention, found to have colonic pseudo-obstruction likely from AL Amyloidosis. Her symptoms improved with colonic decompression and with the utility of prokinetic agents. Case Description/Methods: A 79-year-old female presented with 3 days of progressively worsening abdominal pain and distention, with associated constipation. Her past medical history was significant for anemia, AL-Amyloidosis diagnosed 4 months prior to arrival, and PEG placement 3 weeks prior to arrival due to worsening dysphagia secondary to macroglossia. Vital signs were normal. She did not appear in acute distress and was hemodynamically stable. Pertinent examination findings included abdominal distention, decreased bowel sounds, and diffuse abdominal tenderness. Pertinent labs included WBC 5.6 k/uL, albumin 2.1 g/dL, AST 39 U/L, ALT 43 U/L, ALP 196 U/L, and total bilirubin 0.3 mg/dL. Clostridium difficile, giardia lamblia, salmonella, and stool occult blood were negative. CT abdomen and pelvis revealed gaseous distention of the transverse colon and diffuse colonic wall thickening, as displayed in figure 1. Colonoscopy revealed diffuse dilation of the transverse colon, with components of inflammation including friability and loss of vascularity. Decompression was successfully performed through the colonoscope. The patient tolerated the procedure well and had marked improvement of abdominal distention and pain. Her percutaneous tube feeds were reinitiated and tolerated well. (Figure) Discussion: Colonic pseudo-obstruction is a rare complication of AL Amyloidosis that is caused by deposits of protein in extracellular tissue. AL Amyloidosis is a multisystem disease that rarely presents with colonic manifestations. However, colonic manifestations may be the sole presentation of AL Amyloidosis. Colonic pseudo-obstruction remains a clinical challenge and can lead to bacterial overgrowth and malnutrition. Here we demonstrate successful air decompression of a colonic pseudo-obstruction due to AL Amyloidosis. We hope to increase awareness of AL Amyloidosis as an etiology colonic pseudo-obstruction.Figure 1.: CT Abdomen Pelvis reveals diffuse gaseous distention of the transverse colon with bowel wall thickening.

S2545 AL Amyloidosis Presenting as Isolated Gastric Lesion Found on Endoscopy in Patient With Recurrent Emesis

S2545 AL Amyloidosis Presenting as Isolated Gastric Lesion Found on Endoscopy in Patient With Recurrent Emesis

Clinical case report: Nephrotic syndrome as presentation of AL amyloidosis, a rare association in our setting

BACKGROUND: Amyloidosis is a heterogeneous group of diseases with multi-organ involvement and different clinical manifestations; one of them is nephrotic syndrome. Amyloidosis results from the extracellular deposit of fibrillar proteins that form the amyloid substance; amyloidogenic proteins resistant to proteolysis infiltrate tissues extracellularly and are capable of severely altering their structure and function. Amyloid deposits in the renal parenchyma can be observed in the mesangium, capillary wall, interstitium, and arterial vessels. Its diagnosis requires a biopsy of the comprised organs. CASE REPORT: 53-year-old male patient, presented with the incidental finding of microalbuminuria. The only clinical manifestations were mild lower limbs edema and foamy urine. Laboratory tests showed: hypoalbuminemia, hypercholesterolemia, hypertriglyceridemia and nephrotic- range proteinuria. With pure nephrotic syndrome diagnosis a renal biopsy was performed, leading to the histopathological diagnosis of amyloidosis. EVOLUTION: Nephroprotective measures were instituted and the extent of systemic involvement was studied, we diagnosed congestive heart failure and amyloid deposition in the digestive system. The patient initially received treatment based on Cyclophosphamide, Bortezomib and dexamethasone, with no renal or haematological response after four cycles of treatment, so treatment was changed to Bortezomib and Bendamustine. CONCLUSION: It is vitally important to have a high index of suspicion and to make an early diagnosis of the disease through a biopsy with Congo red staining. The treatment depends on the type of amyloidosis, its opportune start allows to increase survival rate, as well as, to avoid the deposit of amyloid in other organs.

Hepatic AL Amyloidosis Without Significant Light Chain Elevation in a Patient Treated with CyBorD Plus Daratumumab

Patient: Female, 60-year-old Final Diagnosis: Amyloid light-chain amyloidosis • hepatic amyloidosis Symptoms: Abdominal pain • anemia • emesis Medication: — Clinical Procedure: Bone marrow biopsy • exploratory laparotomy • hepatectomy • stem cell transplant Specialty: Hematology • Oncology Objective: Unusual clinical course Background:Immunoglobulin light chain (AL) amyloidosis is a plasma cell disorder in which excess light chain deposits in tissues, resulting in organ dysfunction and damage. Typically, AL amyloidosis presents as a systemic disease affecting multiple organs, and most patients have elevated serum free light chains. However, the presentation of AL amyloidosis is highly variable. The purpose of this case report is to raise awareness of the atypical presentations of AL amyloidosis in order to facilitate more rapid diagnosis, which has the potential to prevent additional organ damage when appropriate therapy is provided.Case Report:We describe a case of AL amyloidosis with amyloid deposition confined to the liver and bone marrow and lack of significant serum light chain elevation. The patient initially presented with a spontaneous hepatic hematoma, and was ultimately found to have hepatic AL amyloidosis, with monoclonal plasma cells in the bone marrow and monoclonal protein on serum protein electrophoresis. Our patient responded to treatment with cyclophosphamide-bortezomib-dexamethasone, the anti-CD38 antibody daratumumab, and autologous stem cell transplant, resulting in hematological and organ response.Conclusions:AL amyloidosis can present with end-organ damage confined to isolated organs, and it can present without the expected elevation in serum light chains. Such patients can benefit from appropriate treatment, including traditional chemotherapy, daratumumab, and stem cell transplant. As effective treatments for AL amyloidosis are now available, prompt diagnosis has the potential to limit end-organ damage and potentially improve patient outcomes.

Biomarker-Based Screening of Organ Dysfunction in Patients with MGUS Allows Early Diagnosis of AL Amyloidosis

Introduction. Despite availability of newer effective therapies, approximately 30% of patients with AL amyloidosis still die within 1 year from diagnosis due to advanced, irreversible cardiac involvement at presentation. In 40% of patients the diagnosis is made more than 1 year after the onset of symptoms, and, once amyloid organ involvement becomes symptomatic, organ dysfunction is often already advanced (Kourelis et al. AJH 2014, Lousada et al. Adv Ther 2015). Biomarkers [(N terminal pro natriuretic peptide (NT-proBNP) for the heart, albuminuria for the kidney, and alkaline phosphatase (ALP) for the liver] can detect organ involvement before symptoms appear and can facilitate early diagnosis. Moreover, increased circulating free light chains (FLC) precede the presentation of AL amyloidosis by 4 years or more (Weiss et al. JCO 2014). Thus, we advocated the screening with biomarkers of amyloid organ involvement of all patients with monoclonal gammopathy of undetermined significance (MGUS) and abnormal FLC ratio (Merlini et al. Hematology Am Soc Hematol Educ Program 2012, Merlini et al. Blood 2013). Here we present the clinical features and outcome of patients with MGUS diagnosed with AL amyloidosis while asymptomatic during biomarker-based screening.Methods. The prospectively-maintained database of the Pavia Amyloidosis Research and Treatment Center was systematically searched for patients diagnosed with AL amyloidosis during biomarker-based screening of MGUS. Patients who had amyloid-related symptoms at the time of diagnosis were excluded. The diagnosis of AL amyloidosis was established on abdominal fat or organ biopsy in all cases, and typing by immuno-electron microscopy confirmed that the amyloid fibrils were formed by a light chain of the same isotype as the monoclonal protein.Results. Thirteen patients were identified between January 2012 and December 2016. Six were males and their median age was 67 years (range 38-79 years). The median time from the identification of MGUS to diagnosis of AL amyloidosis was 4.2 years (range 0.7-19.8 years). The monoclonal components were IgAl in 1 patient, IgDl in 1, IgGk in 1, IgGl in 7, and IgMl in 3. The median dFLC value was 67 mg/L (range 21-283 mg/L). The biomarker found abnormal during follow-up was proteinuria (median 1.01 g/24h, range 0.7-1.32 g/24h, predominantly albumin) in 8 patients, elevated NT-proBNP in 8 (median 789 ng/L, range 441-2935 ng/L), and ALP in 1 (509 U/L, upper reference limit 279 U/L). In 4 patients more than 1 biomarker was elevated. Cardiac troponin I was <0.1 ng/mL in all but 1 of the 7 patients with heart involvement, resulting in cardiac stage II in 7 subjects and IIIa in 1. Median left ventricular wall thickness at echocardiography was 13.2 mm (range 10.0-14.4 mm) and median ejection fraction was 62% (range 50-70%) in patients with elevated NT-proBNP. Estimated glomerular filtration rate was >50 mL/min in all patients with proteinuria, resulting in renal stage I in all cases. All the patients are alive and none required dialysis after a median follow-up of 30 months. Eight patients received cyclophosphamide / bortezomib / dexamethasone (CyBorD), 2 (diagnosed in 2009) melphalan / dexamethasone (MDex), and 3 bortezomib / rituximab / dexamethasone. Ten patients obtained complete or very good partial (CR/VGPR) response plus organ response (OR) after upfront treatment. The remaining 3 subjects received second-line therapy, bortezomib /dexamethasone, lenalidomide / dexamethasone, and autologous stem cell transplant and reached CR/VGPR plus OR after rescue treatment.Discussion. Biomarker-based screening for amyloid organ involvement in patients with MGUS allowed pre-symptomatic diagnosis of systemic AL amyloidosis at early stages, resulting in excellent outcomes in all cases, including those who fail to respond to upfront therapy. Larger, prospective studies are warranted to assess the impact of this approach. DisclosuresPalladini:Prothena: Honoraria, Other: Travel grant; Celgene: Other: Travel grants; Jannsen-Cilag: Membership on an entity's Board of Directors or advisory committees. Varettoni:Jannsen: Consultancy, Other: travel expenses.

1287: AL Amyloidosis Presenting as Syncope With Hemorrhagic Shock due to Splenic Rupture

Keller, Daniel1; Stern, Jeffrey2; Mytinger, Andrea2; Anand, Rahul2; Miller, Kristin2 Author Information

Chronic Swelling of the Submandibular Glands and Sicca Syndrome: An Unusual ENT Presentation of AL Amyloidosis

Amyloidosis is a sistemic disease characterized by accumulation in the extracellular and perivascular spaces of insoluble fibrillar proteins (amyloid), which determines the impairment of the function of the affected tissues. Clinically it can mimic conditions. In the case report we reported the case of a clinical overlap with Sjogren's syndrome.

AL-Amyloidosis presenting with painful mononeuropathy multiplex and bilateral cranial nerve 3 palsies (4349)

AL-Amyloidosis presenting with painful mononeuropathy multiplex and bilateral cranial nerve 3 palsies (4349)

Systemic AL amyloidosis presenting as progressive hepatic failure with coagulopathy: An autopsy case report

Introduction: Systemic AL amyloidosis is defined as extracellular deposition of insoluble immunoglobulin light chains, amyloid fibril protein AL, in at least one vital organ. Here we report a case of systemic AL amyloidosis presenting as progressive hepatic failure with coagulopathy.

PB2138 LIGHT CHAIN (AL) AMYLOIDOSIS: A SINGLE CENTRE EXPERIENCE AND THE EFFECTIVENESS OF BORTEZOMIB BASED THERAPY AS FIRST LINE THERAPY

Background:Amyloidosis is a heterogenous disease characterised by deposition of amyloid fibrils in soft tissue. Light chain (AL) amyloidosis is the most common form of systemic amyloidosis and is a complication of plasma cell dyscrasia. It can affect a wide range of organs including kidneys, heart, nervous system, liver, gastrointestinal tract and spleen which make the diagnosis difficult. Kidneys are the most commonly affected organ in AL amyloidosis and most patients present with nephrotic range proteinuria.In light chain amyloidosis, clonal plasma cells use proteasome to cope with misfolded light chain induced proteotoxicity, and the proteasome inhibitor bortezomib is a potential targeted therapy. Studies have demonstrated that Cyclophosphamide, Bortezomib, Dexamethasone (CyBorD) is a useful, highly effective upfront option.Aims:A retrospective study to evaluate the experience of a single centre, Waitemata District Health Board on the source of referral, biopsy source and the effectiveness of Bortezomib‐based therapy with long term follow up.MethodsDatabase at Waitemata District Health Board was searched for newly diagnosed patients with amyloidosis between 2001 and 2018. 55 out of 70 cases reported to New Zealand Cancer Registry were included. The source of referral, light chain subtype, disease association and biopsy source were analysed.43 patients who received Bortezomib based therapy as first line had been identified. The haematological response was assessed according to the International Society of Amyloidosis criteria. The duration to complete remission and relapse rates were also analysed.Results:55 patients were diagnosed with AL amyloidosis between 2001 and 2018. Half of the patients were referred by renal service (49%) and 11/55 (20%) were from cardiology service. Two third (38/55) of the patients had lambda light chains. Vast majority (87%) had either MGUS or smouldering myeloma.Half of the patients were diagnosed from renal biopsy. Other sites of diagnostic biopsy sample include bone marrow, lymph node, cardiac, GI tract, liver and tongue. Congo red stain was done on 39/50 bone marrow trephine samples and 16 of them (41%) were positive (8 muscular layer, 1 cortical bone, 7 marrow interstitium). Rectal biopsies were done on 10 patients with 7 positive result (70%).Of the 43 patients who received Bortezomib based therapy as first line treatment, 14 (32.6%) achieved complete response within 30 days of commencing treatment. Three patients (21.4%) relapsed with median time to relapse of 3.6 years. 15 patients (34.9%) achieved complete response after 30 days of commencing therapy and 5 patients (33.3%) relapsed with median time of 2 years. Five patients achieved very good partial response (VGPR), six patients with limited or no response.Summary/Conclusion:Renal disease is the most common presentation of AL amyloidosis followed by cardiac involvement. 2/3 of patients have elevated serum free lambda light chain and most of them have either MGUS or smouldering myeloma on bone marrow biopsy. Diagnoses are mostly made on renal biopsy but rectal biopsy seems to be sensitive for diagnosis of amyloidosis infiltration as well. Bortezomib based therapy appeared to be effective treatment as first line therapy with 79% achieving good haematological response with sustainable remission status. Ongoing follow up and larger cohort will be required for more conclusive results.

Bilateral amyloidoma of the trigeminal nerve causing a progressive trigeminal neuropathy: An unusual presentation of localised AL amyloidosis involving the peripheral nervous system

Bilateral amyloidoma of the trigeminal nerve causing a progressive trigeminal neuropathy: An unusual presentation of localised AL amyloidosis involving the peripheral nervous system

Gastrointestinal Polypoid Lesions and Hemorrhage as Presentation of Primary Systemic AL Amyloidosis: A Case Report

Gastrointestinal Polypoid Lesions and Hemorrhage as Presentation of Primary Systemic AL Amyloidosis: A Case Report

Exceptional Cause of Massive Lymph Node Enlargement: Primary Localized Amyloidosis

Amyloidosis is very rarely the cause of lymph node enlargement. In the localized form of the disease, amyloidosis commonly attains the bladder, the lung and the skin. Lymph node amyloid deposition is very unusual in the localized form of the disease. In particular, cervical and mediastinal sites are uncommon. We report an exceptional case of primary localized AL amyloidosis presenting as generalized lymph node enlargement. Our patient was initially treated by colchicine but in front of disease progression, a treatment with prednisone and melphalan was necessary for stabilization. Clinician should consider primary amyloidosis in the check-list of etiologies causing lymph node enlargement.

Incidental discovery of multiple myeloma, presenting as an amyloid tumor with plasmacytic elements of the thoracic wall

Multiple myeloma is characterized by monoclonal proliferation of bone marrow plasma cells causing multiple bone lesions and overproduction of a monoclonal protein (M-protein) that could deposit in tissues (amyloidosis). Dissemination of the multiple myeloma outside the bone is rare. We present a case of a 76 years old woman presenting with dry cough. Chest X-ray showed a giant tumor of the upper right lung. Contrast enhanced CT revealed a tumor that most probably originated from the structures of the thoracic wall. The transthoracic biopsy was inconclusive. The tumor was resected and the histopathological examination showed amyloid tumor of the thoracic wall with plasmacytic elements and lambda light chains deposits. A bone marrow aspiration was performed that found diffuse plasmacytic infiltrate of 20-60% and the serum proteins electrophoresis with immunofixation revealed elevated IgA and lambda light chains. The patient was diagnosed with IgA and lambda light chains multiple myeloma with consequent AL amyloidosis presenting as thoracic mass.

Vertebral compression fractures as the initial presentation of AL amyloidosis: case series and review of literature

The clinical presentation of AL amyloidosis is highly variable. In this series, we describe five cases of AL amyloidosis with vertebral compression fractures as initial presentation. All five patients had evidence of bone marrow replacement on magnetic resonance imaging and bone marrow biopsies demonstrating diffuse interstitial amyloid deposition. Hepatomegaly and elevated liver enzymes, consistent with liver involvement with amyloidosis, were also seen in each case. All five patients responded well to anti-plasma cell chemotherapy, with normalization of serum free light chain levels, reduction in alkaline phosphatase and improvement in pain and functional status. Although rare, AL amyloidosis should be considered in the differential diagnosis of selected patients with spontaneous vertebral compression fractures. Moreover, there seems to be an association of vertebral compression fractures with liver involvement in AL amyloidosis.

Nonsecretory Multiple Myeloma and AL Amyloidosis Presenting with Nephrotic Range Proteinuria.

Nonsecretory multiple myeloma (NSMM) is the absence of a detectable monoclonal protein in serum and urine of a multiple myeloma (MM) patient and immunoglobulin light chain (AL) amyloidosis is a significantly rare complication. A case of NSMM with AL amyloidosis and nephrotic range proteinuria is presented. Sharing clinical, therapeutic, and prognostic characteristics with MM, real challenge may be during initial diagnosis of NSMM and assessment of treatment response. In elderly patients with unexplained renal dysfunction, MM should be in the differential diagnosis and the absence of a monoclonal protein should not rule out MM but should remind us of the possibility of NSMM.