Showing papers on "Primary systemic amyloidosis published in 2019"
TL;DR: Clinical effects of driver somatic mutations on the outcomes of patients with myelodysplastic syndromes treated with allogeneic hematopoietic stem-cell transplantation and the BMT-AZA prospective study are presented.
Abstract: 1. Bejar R, Stevenson KE, Caughey B, Lindsley RC, Mar BG, Stojanov P, et al. Somatic mutations predict poor outcome in patients with myelodysplastic syndrome after hematopoietic stemcell transplantation. J Clin Oncol. 2014;32:2691–8. 2. Lindsley RC, Saber W, Mar BG, Redd R, Wang T, Haagenson MD, et al. Prognostic Mutations in Myelodysplastic Syndrome after Stem-Cell Transplantation. N Engl J Med. 2017;376:536–47. 3. Della Porta MG, Galli A, Bacigalupo A, Zibellini S, Bernardi M, Rizzo E et al. Clinical effects of driver somatic mutations on the outcomes of patients with myelodysplastic syndromes treated with allogeneic hematopoietic stem-cell transplantation. J Clin Oncol. 2016;34:3627–37, JCO673616. 4. Voso MT, Leone G, Piciocchi A, Fianchi L, Santarone S, Candoni A, et al. Feasibility of allogeneic stem-cell transplantation after azacitidine bridge in higher-risk myelodysplastic syndromes and low blast count acute myeloid leukemia: results of the BMT-AZA prospective study. Ann Oncol. 2017;28:1547–53. 5. Papaemmanuil E, Gerstung M, Malcovati L, Tauro S, Gundem G, Van Loo P, et al. Clinical and biological implications of driver mutations in myelodysplastic syndromes. Blood. 2013;122: 3616–27. 6. Yoshizato T, Nannya Y, Atsuta Y, Shiozawa Y, Iijima-Yamashita Y, Yoshida K, et al. Genetic abnormalities in myelodysplasia and secondary acute myeloid leukemia: impact on outcome of stem cell transplantation. Blood. 2017;129:2347–58. 7. Craddock CF, Houlton AE, Quek LS, Ferguson P, Gbandi E, Roberts C, et al. Outcome of azacitidine therapy in acute myeloid leukemia is not improved by concurrent vorinostat therapy but is predicted by a diagnostic molecular signature. Clin Cancer Res. 2017;23:6430–40. 8. Russler-Germain DA, Spencer DH, Young MA, Lamprecht TL, Miller CA, Fulton R, et al. The R882H DNMT3A mutation associated with AML dominantly inhibits wild-type DNMT3A by blocking its ability to form active tetramers. Cancer Cell. 2014;25: 442–54. 9. Balasubramanian SK, Aly M, Nagata Y, Bat T, Przychodzen BP, Hirsch CM, et al. Distinct clinical and biological implications of various DNMT3A mutations in myeloid neoplasms. Leukemia. 2018;32:550–3. 10. Jongen-Lavrencic M, Grob T, Hanekamp D, Kavelaars FG, Al Hinai A, Zeilemaker A, et al. Molecular minimal residual disease in acute myeloid leukemia. N Engl J Med. 2018;378:1189–99. 11. Winkelmann N, Schafer V, Rinke J, Kaiser A, Ernst P, Scholl S, et al. Only SETBP1 hotspot mutations are associated with refractory disease in myeloid malignancies. J Cancer Res Clin Oncol. 2017;143:2511–9. 12. Welch JS, Petti AA, Miller CA, Fronick CC, O’Laughlin M, Fulton RS, et al. TP53 and decitabine in acute myeloid leukemia and myelodysplastic syndromes. N Engl J Med. 2016;375: 2023–36. 13. Sallman DA, Komrokji R, Vaupel C, Cluzeau T, Geyer SM, McGraw KL, et al. Impact of TP53 mutation variant allele frequency on phenotype and outcomes in myelodysplastic syndromes. Leukemia. 2016;30:666–73.
27 citations
TL;DR: 3 cases of LC-associated amyloidosis presenting with alopecia are reported, whereby there was evidence of a systemic plasma cell dyscrasia in 2 of the patients, one of whom developed multiple myeloma.
Abstract: Primary systemic amyloidosis has a varied clinical presentation, making it one of the great masqueraders of other disease entities in clinical medicine. The association of amyloidosis with alopecia is uncommon with at least 22 cases reported in the literature mostly in the setting of systemic amyloidosis. Alopecia in these patients occurs either as the initial presentation of the systemic amyloidosis or it happens during the disease course. The occurrence of amyloid alopecia associated with light chain (LC) restricted plasmacytic infiltrates in the absence of systemic amyloidosis, however, it is not well known. We report 3 cases of LC-associated amyloidosis presenting with alopecia, whereby there was evidence of a systemic plasma cell dyscrasia in 2 of the patients, one of whom developed multiple myeloma. None of the patients had systemic amyloidosis. Skin presentation in the patient with multiple myeloma was characterized by a diffuse form of alopecia affecting the entire scalp, eyebrow, and axillary and pubic hair in contrast to the localized form of alopecia noted in the other 2 patients. The mechanism by which LC-associated amyloidosis eventuates in this pattern of nonscarring alopecia potentially reflects the affinity of this form of amyloid for dermatan sulfate. Dermatan sulfate is found at highest concentrations within the adventitial dermis of the superficial to mid isthmic portions of the anagen hair follicles likely interfering with the hair cycle and induces early hair follicle involution. The result is a pattern of alopecia that can clinically and to some extent pathologically resemble either androgenetic alopecia or alopecia areata.
5 citations
TL;DR: A case of gastrointestinal involvement in primary systemic amyloidosis (PSA) in a patient complaining of diarrhea and weight loss is reported.
Abstract:
The amyloidosis is a group of rare diseases caused by extracellular deposition of amyloid. It may affect multiple organs with protean manifestations, thus often causing delayed or incorrect diagnoses. We report a case of gastrointestinal involvement in primary systemic amyloidosis (PSA) in a patient complaining of diarrhea and weight loss. The diagnosis was confirmed by endoscopic biopsies of upper digestive tract and by multidisciplinary evaluation for systemic involvement.
4 citations
TL;DR: Diagnosis and therapeutic approach in a 25-year-old female patient diagnosed with urinary bladder amyloidosis and the exclusion of primary systemic amyloidsosis due to a completely different treatment method are presented.
Abstract: Amyloidosis is a heterogeneous group of protein misfolding diseases caused by extracellular deposition
of abnormal beta-fibrils resistant to proteolysis. The most common type is light-chain amyloidosis
(AL amyloidosis) which can be systemic or localized. Localized amyloidosis mostly affects the
respiratory airways, genitourinary tract, gastrointestinal system or skin. We present diagnostic and
therapeutic approach in a 25-year-old female patient diagnosed with urinary bladder amyloidosis.
The main complaint was macroscopic hematuria occurring periodically for 2 years. Abdominal
and pelvic computed tomography revealed single 25-mm-thick soft-tissue lesion of the left bladder
wall. Histopathological examination of the lesion biopsied during transurethral resection of bladder
tumor showed amyloid deposits with strong positive immunostaining for transthyretin, weaker for
light chain (AL) and weak for serum amyloid A (AA). Serum protein electrophoresis and immunofixation
did not reveal monoclonal protein. X-rays of flat bones presented without lytic lesions. There
were no amyloid deposits both in trephine biopsy and subcutaneous fat biopsy. Primary systemic
AL amyloidosis was excluded. According to the results of (99m)Tc-DPD scintigraphy and genetic
analysis of transthyretin gene (TTR), the ATTRm amyloidosis was also excluded. Consultative histopathological
analysis of the bladder biopsy made in the National Amyloidosis Center in London
revealed amyloid deposits stained to lambda light chains, confirming the diagnosis of localized AL
lambda bladder amyloidosis. The patient was qualified for surgical treatment. Partial resection of
the bladder wall with no need for left ureter transplantation was performed. Primary localized bladder
amyloidosis is a very rare entity. In the diagnostic approach the most important is the exclusion
of primary systemic amyloidosis due to a completely different treatment method.
2 citations
TL;DR: The patients hemogram, liver function tests, and renal function tests were normal; however, albumin‐to‐globulin ratio was reversed, and bone marrow aspiration revealed a predominance cutaneous amyloidosis.
Abstract: © 2019 Indian Dermatology Online Journal | Published by Wolters Kluwer Medknow A 65‐year‐old lady presented with asymptomatic soft‐to‐firm swelling of her bilateral eyelids for the past 4 years [Figure 1]. The lesions were initially discrete and had slowly become confluent in the past 1 year resulting in bulky and drooping upper eyelids. There were extensive purpura on her neck and arms [Figure 2]. Histopathology showed a dense homogenous acellular eosinophilic material throughout the papillary and reticular dermis with clefting and extensive red blood cell extravasation [Figures 3 and 4]. Congo red staining showed a characteristic apple green birefringence [Figure 5], diagnostic of cutaneous amyloidosis. The patients hemogram, liver function tests, and renal function tests were normal; however, albumin‐to‐globulin ratio was reversed. Skeletal survey was unremarkable. Bone marrow aspiration revealed a predominance
TL;DR: A 55‐year‐old male presented with asymptomatic nodular growth over nose since 6 months and final diagnosis of primary systemic amyloidosis was made.
Abstract: © 2019 Indian Dermatology Online Journal | Published by Wolters Kluwer Medknow A 55‐year‐old male presented with asymptomatic nodular growth over nose since 6 months. On examination it was ~5 cm, well‐defined, waxy thick brownish plaque extending from left ala of nose to tip of nose with skin overlying showed ridging and dilated pilosebaceous openings [Figure 1a]. On further follow‐up, we noticed periorbital ecchymosis, which was not present earlier, few waxy papules and nodules over scalp, lateral aspect of lower eyelids, purpura over neck and toe, finger and toe nails showing dystrophy, striations, and anonychia [Figure 1b], and tongue showing macroglossia. Histopathology showed eosinophilic deposits in the dermis [Figure 2a], which on special staining with Congo red showed apple green birefringence of fibrils under polarized light [Figure 2b]. On further investigation, 24 h urine protein levels were raised 793.80 mg/24 h and albumin and gamma band were present on electrophoresis. Therefore, final diagnosis of primary systemic amyloidosis was made.
TL;DR: This is a case report where an unusual extensive cutaneous and cardiac involvement provided the sign of widespread systemic deposition of amyloid protein which eventually led to the diagnosis of multiple myeloma.
Abstract: Amyloidosis refers to a group of disorders characterized by extracellular deposition of protein fibrils. Primary systemic amyloidosis is commonly due to an underlying plasma cell dyscrasia. Infiltrative amyloid cardiomyopathy is a rare cause of predominantly diastolic myocardial disease. Restrictive cardiomyopathy is the main finding in cardiac amyloidosis and results from the replacement of normal myocardial contractile elements by infiltration and interstitial deposits of amyloid, leading to alterations in cellular metabolism, calcium transport, receptor regulation, and cellular edema. Injury can also occur from circulating light chains in the absence of amyloid fibril formation. Cardiac amyloidosis should be considered in any patient presenting with congestive heart failure, preserved systolic function, and a discrepancy between a low QRS voltage on electrocardiography and an apparent left ventricular hypertrophy on sonogram. The pattern of left ventricular diastolic dysfunction changes during the course of amyloidosis and the classically described restrictive physiology occurs only in advanced stages of the disease. This is a case report where an unusual extensive cutaneous and cardiac involvement provided the sign of widespread systemic deposition of amyloid protein which eventually led to the diagnosis of multiple myeloma.