scholarly journals Massive Hepatomegaly Secondary to Amyloidosis with Normal Liver Chemistries

2020 ◽  
Vol 14 (2) ◽  
pp. 271-278
Author(s):  
Sarah Doe-Williams ◽  
Lee J. Hixson ◽  
David C. Pfeiffer

Amyloid light chain (AL) amyloidosis is a disease of misfolded, fibrous proteins, either kappa or lambda subtype, that can be deposited into one or more organs, caused by a proliferation of plasma cells. The liver is uncommonly the main organ system affected and rarely the only organ affected by amyloid deposition. With hepatic involvement, the most common presenting findings are hepatomegaly and elevation of serum alkaline phosphatase. We report a case of a 50-year-old male who presented to our gastroenterology clinic with marked hepatomegaly secondary to hepatic amyloidosis, in concert with bone marrow involvement and nephrotic syndrome. Biopsies in conjunction with Congo red staining demonstrated 95% replacement of hepatic structure and 80% replacement of bone marrow with amyloid deposition. Despite these findings, liver chemistries, renal function, and blood count were normal. Our case presents not only the rare finding of primary hepatic amyloidosis but also an atypical presentation of this disorder. Although rare, AL amyloidosis should be in a differential diagnosis of any patient who presents with unexplained hepatomegaly, nephrotic-range proteinuria, heart failure with preserved ejection fraction, fatigue, weight loss or a history of monoclonal gammopathy of undetermined significance.

2020 ◽  
Vol 92 (7) ◽  
pp. 85-89
Author(s):  
L. P. Mendeleeva ◽  
I. G. Rekhtina ◽  
A. M. Kovrigina ◽  
I. E. Kostina ◽  
V. A. Khyshova ◽  
...  

Our case demonstrates severe bone disease in primary AL-amyloidosis without concomitant multiple myeloma. A 30-year-old man had spontaneous vertebral fracture Th8. A computed tomography scan suggested multiple foci of lesions in all the bones. In bone marrow and resected rib werent detected any tumor cells. After 15 years from the beginning of the disease, nephrotic syndrome developed. Based on the kidney biopsy, AL-amyloidosis was confirmed. Amyloid was also detected in the bowel and bone marrow. On the indirect signs (thickening of the interventricular septum 16 mm and increased NT-proBNP 2200 pg/ml), a cardial involvement was confirmed. In the bone marrow (from three sites) was found 2.85% clonal plasma cells with immunophenotype СD138+, СD38dim, СD19-, СD117+, СD81-, СD27-, СD56-. FISH method revealed polysomy 5,9,15 in 3% of the nuclei. Serum free light chain Kappa 575 mg/l (/44.9) was detected. Multiple foci of destruction with increased metabolic activity (SUVmax 3.6) were visualized on PET-CT, and an surgical intervention biopsy was performed from two foci. The number of plasma cells from the destruction foci was 2.5%, and massive amyloid deposition was detected. On CT scan foci of lesions differed from bone lesions at multiple myeloma. Bone fragments of point and linear type (button sequestration) were visualized in most of the destruction foci. The content of the lesion was low density. There was no extraossal spread from large zones of destruction. There was also spontaneous scarring of the some lesions (without therapy). Thus, the diagnosis of multiple myeloma was excluded on the basis based on x-ray signs, of the duration of osteodestructive syndrome (15 years), the absence of plasma infiltration in the bone marrow, including from foci of bone destruction by open biopsy. This observation proves the possibility of damage to the skeleton due to amyloid deposition and justifies the need to include AL-amyloidosis in the spectrum of differential diagnosis of diseases that occur with osteodestructive syndrome.


2020 ◽  
Vol 144 (8) ◽  
pp. 967-973 ◽  
Author(s):  
Sara Javidiparsijani ◽  
Maria M. Picken

Context.— Amyloidoses are rare but heterogeneous disorders for which diagnosis is contingent upon the detection of deposits by Congo red stain and amyloid protein typing determines the treatment options. Objective.— To address the reporting of bone marrow (BM) involvement by amyloid in relation to the spatial distribution of deposits and to explore whether the location of deposits may have clinical relevance. Design.— We examined 66 BM biopsies positive for amyloid with regard to the location and type of amyloid, the percentage and clonality of plasma cells, other organ involvement, and relevant clinical information. Results.— In 21 cases, amyloid deposits involved BM stroma, whereas 45 cases were nonstromal. All cases of stromal involvement were typed as amyloid light chain (AL) amyloidosis (or presumed AL), whereas nonstromal involvement was associated with at least 3 types of amyloidosis: AL, amyloid transthyretin (ATTR), and amyloid A (AA). The initial diagnosis of amyloidosis was made in a BM specimen in 21 of 66 cases (31.8%). Plasma cells ranged from 1% to 80% (mean, 13.4%; median, 8%; <10% in 44 of 66 specimens [66.6%]) and were monoclonal in 58 of 66 cases (87.8%), and in 54 of 66 cases (81.8%) amyloid deposits were documented in at least one other organ. Conclusions.— This study demonstrates that there is significant heterogeneity in the spatial distribution of amyloid in BM biopsy specimens with medullary, extramedullary, purely vascular, or combined involvement. Whereas stromal deposits were associated exclusively with AL, nonstromal and purely vascular deposits were seen in at least 3 types of systemic amyloidosis (AL, AA, and ATTR). We discuss the reporting of BM biopsy tissue positivity for amyloid deposits.


2019 ◽  
Vol 4 ◽  
pp. I 30-30
Author(s):  
Hui-Wen Wang ◽  
Rong Tang ◽  
Xiang-Cheng Xiao ◽  
Wei Liu ◽  
Morie A. Gertz ◽  
...  

1994 ◽  
Vol 12 (7) ◽  
pp. 1415-1421 ◽  
Author(s):  
S M Sanal ◽  
F W Flickinger ◽  
M J Caudell ◽  
R M Sherry

PURPOSE To evaluate the value of magnetic resonance imaging (MRI) in detecting bone marrow metastases in patients with breast cancer. PATIENTS AND METHODS Twenty-three patients with breast cancer in various stages (stage IV, 11; stage III, five; stage II, seven) were evaluated for bone marrow involvement. MRIs of marrow from lumbar spine, pelvis, and proximal femora were obtained with a 1.5-Tesla unit. All patients underwent bilateral bone marrow aspirations and biopsies for histologic evaluation and immunostaining with monoclonal antibody (MoAB) against low-molecular weight cytokeratin (CAM 5.2). Marrow MRI findings were compared with technetium 99m bone scans. Patients with stage II or III disease were monitored for clinical outcome. Possible correlation of MRI findings with serum alkaline phosphatase level was explored. RESULTS Fourteen of 23 patients showed MRI abnormalities suggestive of metastatic marrow disease (stage IV, nine; stage III, two; stage II, three). In six patients with abnormal MRIs, histology and MoAB immunostaining confirmed marrow involvement (stage IV, five; stage III, zero; stage II, one). In the other eight patients with MRI abnormalities, neither of these methods confirmed the presence of marrow metastasis. Four of five operable breast cancer (stage II-III) patients with an abnormal initial MRI showed additional abnormalities on follow-up examination and developed metastatic disease within 5 to 18 months demonstrable by conventional clinical methods. Conversely, none of the operable patients with negative MRIs developed recurrent disease at 3 to 16 months (Student's t test, P = .01). Nine patients with a normal MRI had no evidence of marrow involvement with histologic or MoAB immunostaining (stage IV, two; stage III, two; stage II, five). Of 14 patients with abnormal MRIs, bone scans were normal in seven and failed to show corresponding abnormalities in six. Elevated serum alkaline phosphatase levels showed a direct relationship with abnormal bone scans indicating extensive bony involvement, but failed to correlate with positive marrow MRIs. CONCLUSION MRI is a promising new technique to detect occult marrow involvement in breast cancer patients. There is a good correlation between abnormal marrow MRI and early development of clinical metastatic disease in patients with stage II to III disease.


Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 1350-1350
Author(s):  
Simrit Parmar ◽  
Mubeen Khan ◽  
Gabriela Rondon ◽  
Nina Shah ◽  
Qaiser Bashir ◽  
...  

Abstract Abstract 1350 Background: Systemic Primary AL Amyloidosis is a rare but potentially fatal disease resulting from tissue deposits of amyloid fibrils derived from monoclonal immunoglobulin light chains. High-dose melphalan followed by autologous hematopoietic stem cell transplant (auto HCT) is associated with hematologic and organ responses and improved survival. Methods: In this retrospective analysis we identified 46 patients with primary AL amyloidosis who received auto HCT between 01/1998 to 05/2010 at MDACC. Organ responses were determined using Amyloidosis Consensus Criteria. Results: The median age at auto HSCT was 56 years (34-74) where 61% were males and 35% were older than 60 years of age. 61% had lambda light chain restriction and only 4% had cytogenetic abnormalities. Disease characteristics are summarized in Table 1. The median time from diagnosis to auto HCT was 6.6 months (2.2-29.4 months). 22 pts (47.8%) had one organ, 19 pts (41.3%) had 2 organ and 4 pts (8.7%) had 3 organ involvement. 11 pts (23.9%) had heart and 35 pts (76.1%) had kidney involvement. The median follow up from the time of diagnosis was 22.4 months and from time of auto HCT was 16.7 months. High dose Melphalan dose was 200mg/m2 in 24 pts (52%) and 140mg/m2 in 22 (47.8%). There were 4 early deaths and 4 pts whose follow up was less than 3 months and their response was not assessed. Out of the 38 evaluable patients, the post-transplant organ responses were as follows ≥PR 25(66%), ≥stable disease 35(92%) (Table2). The hematologic responses were: CR=5 (13%), ≥VGPR=10(26%), ≥PR=26 (68%), ≥SD=37(97%). One patient had progressive disease. There was a correlation between organ response and hematologic response (chi square;p<10-3). The day-100 treatment related mortality (TRM) was 8.7% and 1-yr TRM was 13%. The median progression-free (PFS) and overall survival (OS) from auto HCT was 73.8 months and not reached (from transplant). The median PFS and OS from diagnosis were 93 months and 59.8 months respectively. In multivariate analysis, heart involvement (p=0.01), female sex (p=0.011), age ≥60 years (p=0.002), bone marrow plasma cells≥10% (p=0.043) and Beta-2 microglobulin>3.5mg/l (p=0.02) were associated with poor OS. Improved OS correlated with organ response (52.6 vs 11.4 months; p=0.01) and hematologic response (52.6 vs.6.1months; p=0.002). Hemoglobin <10 g/dl (p=0.047), bone marrow plasma cells≥10% (p=0.043) and age≥60 years (p=0.075) were associated with shorter PFS. Hematologc response (p=0.48) and organ response (p=0.12) were not associated with improved PFS. Conclusion: In this analysis the outcome of patients with primary systemic AL amyloidosis was durable with auto HCT with acceptable mortality risk and improved survival. Disclosures: No relevant conflicts of interest to declare.


Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 5399-5399
Author(s):  
Assia Bassarova ◽  
Gunhild Trøen ◽  
Signe Spetalen ◽  
Francesca Micci ◽  
Anne Tierens ◽  
...  

Abstract Lymphoplasmacytic lymphoma and marginal zone lymphoma in the bone marrow: paratrabecular involvement as an important distinguishing feature Assia Bassarova, Gunhild Tr¿en, Signe Spetalen, Francesca Micci, Anne Tierens, Delabie Abstract Lymphoplasmacytic lymphoma (LPL) is a neoplasm of small B-lymphocytes, lymphoplasmacytoid and plasma cells involving bone marrow and sometimes lymph nodes and spleen. Lymphoplasmacytic lymphoma is often accompanied by Waldenström macroglobulinemia. Since the original description, Waldenström macroglobulinemia has become recognized as a distinct clinicopathological entity defined by serum IgM paraprotein and bone marrow involvement by lymphoplasmacytic lymphoma. Since serum IgM paraprotein in itself is not specific and can be seen in a variety of small B-cell lymphoproliferative disorders, notable chronic lymphatic leukemia and marginal zone lymphoma, as well as in rare cases of myeloma, the diagnosis of Waldenström macroglobulinemia rests largely upon the proper diagnosis of LPL in the bone marrow. The differential diagnosis between bone marrow involvement by lymphoplasmacytic lymphoma (LPL) and marginal zone lymphoma (MZL) is challenging because histology and immunophenotype of both diseases overlap. The diagnosis may be helped by demonstrating the MYD88 L265P mutation, seen in most LPL. However, the mutation is also present in MZL, although at a lower frequency. To better define the distinguishing features of LPL we studied a series of bone marrow trephine biopsies of 59 patients with Waldenström's macroglobulinemia (WM) without extramedullary involvement and compared the findings with bone marrow biopsies from 23 patients with well-characterized MZL who also had bone marrow involvement. H&E and immunoperoxidase-stained sections of bone marrow trephine biopsies as well as flow cytometry and classical cytogenetics performed on aspirations were reviewed. The study was complemented with MYD88L265P mutation analysis on the bone marrow trephine biopsies of all patients. The features are summarized in Table 1. The most distinguishing features of LPL with respect to MZL were focal paratrabecular involvement (p<0.001), the presence of lymphoplasmacytoid cells (p<0.001), Dutcher bodies (p<0.001), increased numbers of mast cells (p<0.001) and the MYD88L265P mutation (p<0.001). Other features such as sinusoidal infiltration and immunophenotype were not distinguishing. Table 1. Summary of the pathology features of lymphoplasmacytic and marginal zone lymphoma in bone marrow trephine biopsies Lymphoplasmacytic lymphoma Marginal zone lymphoma p Infiltration pattern* Paratrabecular Nodular non-paratrabecular Paratrabecular and non-paratrabecular Intrasinusoidal Diffuse 37% (10/27) 0% (0/27) 56% (15/27) 37% (10/27) 0% (0/27) 0% (0/16) 75% (12/16) 0% (0/16) 37% (6/16) 25% (4/16) <0,001 <0,001 <0,001 1 0,015 Cytology Small lymphoid cells Plasmacytoid cells Plasma cells Dutcher nuclear inclusions Mast cells 100% (59/59) 100% (59/59) 93% (55/59) 90% (53/59) 87% (49/56) 100% (23/23) 0% (0/23) 78% (18/23) 0% (0/23) 9% (2/23) - <0,001 0,108 <0,001 <0,001 Immunophenotype of the lymphoma CD20 CD138 (plasma cells) CD5 CD23 IgK IgL IgM IgG Focal CD21+ or CD23+ follicular dendritic cell network in the stroma 100% (59/59) 88% (50/57) 21% (12/52) 29% (15/51) 81% (48/59) 19% (11/59) 97% (57/59) 3% (2/59) 20% (10/51) 100% (23/23) 80% (12/15) 0% (0/23) 13% (5/23) 26% (5/19) 10% (2/19) 64% (7/11) 0% (0/11) 48% (11/23) - - 0,014 0,580 - - - - 0,024 MYD88 L265P mutation 96% (45/47) 20% (3/15) 0,001 *the analysis was only performed on bone marrow trephine biopsies showing less than 66% lymphoma infiltration In conclusion, LPL can reliably be distinguished from MZL in the bone marrow by using a combination of pathology characteristics. In contrast to other studies, our findings stress the diagnostic importance of paratrabecular infiltration in LPL. Disclosures No relevant conflicts of interest to declare.


2013 ◽  
Vol 31 (15_suppl) ◽  
pp. 8516-8516
Author(s):  
Taxiarchis Kourelis ◽  
Morie Gertz ◽  
Martha Lacy ◽  
Francis Buadi ◽  
Suzanne R. Hayman ◽  
...  

8516 Background: There is consensus that light chain amyloidosis (AL) patients with CRAB criteria (abnormal calcium or renal function, anemia or lytic bone lesions) also have multiple myeloma (MM). These patients are typically excluded from AL trials; however, AL patients with >= 10% bone marrow plasma cells (BMPC) in the absence of CRAB are included in trials along with AL with < 10% BMPC. We postulated that the currently used dichotomy may be incorrect and examined the spectrum of AL with and without MM. Methods: We identified 1,272 patients with AL seen within 90 days of diagnosis, between January 1, 2000, and December 31, 2010. We defined the population of patients with coexisting MM based on the existence of CRAB (AL-CRAB-MM). Patients without CRAB were divided into two groups, AL-only (<10% BMPC) and AL-PC-MM (>=10% BMPC). Results: Among the 1,272 patients, 117 (9%) had AL-CRAB-MM, 476 (37%) had AL-PC-MM, and 679 (53%) had AL only. Their respective median overall survivals (OS) were 16.2, 15.8, and 28.4 months (p<0.0001). Autologous stem cell transplant (ASCT) was performed in 203 (30%), 138 (29%) and 23 (20%) patients respectively. Since the outcomes of AL-CRAB-MM and AL-PC-MM were similar, they were pooled for univariate and multivariate analyses. On multivariate analysis, AL-CRAB-MM and AL-PC-MM retained negative prognostic value independent of age, cardiac stage, prior autologous stem cell transplant (ASCT), beta 2 microglobulin, and dFLC. We next considered whether patients received ASCT as part of their treatment. For those patients who never received ASCT, the 5-year OS were 19%, 14%, and 31%, p<0.001, for AL-CRAB-MM, AL-PC-MM, and AL only respectively. In contrast, for those patients who received ASCT, the respective 5-year OS were 46%, 56%, and 73%, p<0.001. Conclusions: AL patients with >=10% BMPCs have a poor prognosis similar to patients with AL-CRAB-MM and should therefore be considered as AL with MM.


2016 ◽  
Vol 135 (3) ◽  
pp. 172-190 ◽  
Author(s):  
Eli Muchtar ◽  
Francis K. Buadi ◽  
Angela Dispenzieri ◽  
Morie A. Gertz

Immunoglobulin amyloid light-chain (AL) amyloidosis is the most common form of systemic amyloidosis, where the culprit amyloidogenic protein is immunoglobulin light chains produced by marrow clonal plasma cells. AL amyloidosis is an infrequent disease, and since presentation is variable and often nonspecific, diagnosis is often delayed. This results in cumulative organ damage and has a negative prognostic effect. AL amyloidosis can also be challenging on the diagnostic level, especially when demonstration of Congo red-positive tissue is not readily obtained. Since as many as 31 known amyloidogenic proteins have been identified to date, determination of the amyloid type is required. While several typing methods are available, mass spectrometry has become the gold standard for amyloid typing. Upon confirming the diagnosis of amyloidosis, a pursuit for organ involvement is essential, with a focus on heart involvement, even in the absence of suggestive symptoms for involvement, as this has both prognostic and treatment implications. Details regarding initial treatment options, including stem cell transplantation, are provided in this review. AL amyloidosis management requires a multidisciplinary approach with careful patient monitoring, as organ impairment has a major effect on morbidity and treatment tolerability until a response to treatment is achieved and recovery emerges.


Amyloid ◽  
2005 ◽  
Vol 12 (1) ◽  
pp. 33-40 ◽  
Author(s):  
Yasuhiro Shimojima ◽  
Masayuki Matsuda ◽  
Takahisa Gono ◽  
Wataru Ishii ◽  
Tomohisa Fushimi ◽  
...  

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 3177-3177 ◽  
Author(s):  
Yi L. Hwa ◽  
Shaji K. Kumar ◽  
Martha Q. Lacy ◽  
Morie A. Gertz ◽  
Francis Buadi ◽  
...  

Abstract Background: Previous studies have demonstrated inferior overall survival (OS) among patients with AL amyloidosis who have bone marrow plasmacytosis (BMPC) >10%. It is well recognized that AL patients who achieve the deepest hematologic responses have superior organ response and OS rate. Methods: We designed a study to determine if BMPC% affects CR rate post ASCT and whether pre-transplant induction therapy improves response rate and OS among patients with a higher baseline BMPC burden. Results: Among 415 AL patients who underwent ASCT at Mayo Clinic, Rochester within 12 months of diagnosis, 116 (28%) had BMPC>10% at diagnosis. The median age was 57.2 years. The median follow up for surviving patients was 67.3 months. There was no statistically significant difference in age, gender, time from diagnosis to transplant, or use of attenuated conditioning regimen between groups with high (>10%) and low (≤ 10%) bone marrow involvement. The high BMPC group tended to receive more induction chemotherapy before ASCT, and presented with greater value of albumin, beta-2 microglobulin and difference in serum free light chain (dFLC). A higher CR rate was observed in low BMPC group (44.6% versus 26.7%, p=0.0013). In patients with high BMPC, a higher CR rate (33.9% versus 17.7%, p<0.05) was seen in those who received pre-ASCT induction therapy compared with no induction therapy. Among 3 groups of patients who had: no pre-ASCT therapy; steroid only as induction; and induction chemotherapy, the 5-year OS rates were 50.5%, 40% & 67.5%, respectively, p<0.03. Conclusions: Lower bone marrow burden at diagnosis yielded a deeper response following ASCT. Compared to no therapy, patients who were treated with steroid only pre-ASCT had an inferior OS, but other induction regimens appeared to improve survival. These data would support the concept that using induction therapy prior to ASCT conditioning among patients with higher tumor burden may be of value. Figure 1. In BMPC > 10% at diagnosis, OS comparison between induction therapies pre-ASCT Figure 1. In BMPC > 10% at diagnosis, OS comparison between induction therapies pre-ASCT Figure 2. Figure 2. Figure 3. Figure 3. Disclosures Kumar: Celgene: Research Funding; Celgene, Millenium, Sanofi, Skyline, BMS, Onyx, Noxxon,: Other: Consultant, no compensation,; Sanofi: Research Funding; AbbVie: Research Funding; Millenium/Takeda: Research Funding; Onyx: Research Funding; Skyline, Noxxon: Honoraria; Janssen: Research Funding. Gertz:Celgene: Honoraria; millenium: Consultancy, Honoraria; Onyx: Honoraria; Novartis: Honoraria; Smith Kline: Honoraria.


Sign in / Sign up

Export Citation Format

Share Document