Waldenström's macroglobulinemia pathophysiology: Difference between revisions
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*Mast cell hyperplasia is common and may stimulate tumor cell proliferation and monoclonal IgM secretion. | *Mast cell hyperplasia is common and may stimulate tumor cell proliferation and monoclonal IgM secretion. | ||
*Gene expression profiling has indicated that lymphoid cells of WM more closely resemble those of chronic lymphocytic leukemia than those of myeloma.<ref name="pmid16804116">{{cite journal| author=Chng WJ, Schop RF, Price-Troska T, Ghobrial I, Kay N, Jelinek DF et al.| title=Gene-expression profiling of Waldenstrom macroglobulinemia reveals a phenotype more similar to chronic lymphocytic leukemia than multiple myeloma. | journal=Blood | year= 2006 | volume= 108 | issue= 8 | pages= 2755-63 | pmid=16804116 | doi=10.1182/blood-2006-02-005488 | pmc=1895596 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=16804116 }} </ref> | *Gene expression profiling has indicated that lymphoid cells of WM more closely resemble those of chronic lymphocytic leukemia than those of myeloma.<ref name="pmid16804116">{{cite journal| author=Chng WJ, Schop RF, Price-Troska T, Ghobrial I, Kay N, Jelinek DF et al.| title=Gene-expression profiling of Waldenstrom macroglobulinemia reveals a phenotype more similar to chronic lymphocytic leukemia than multiple myeloma. | journal=Blood | year= 2006 | volume= 108 | issue= 8 | pages= 2755-63 | pmid=16804116 | doi=10.1182/blood-2006-02-005488 | pmc=1895596 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=16804116 }} </ref> | ||
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[[File:Atypical B cell.png|thumb|300px|none|High-power field of peripheral blood smear revealing a large, atypical B cell with mild cytoplasmic expansion, coarse chromatin, multiple distinct nucleoli and peripheral vacuolation.[https://openi.nlm.nih.gov/detailedresult.php?img=PMC2944189_1752-1947-4-300-2&query=waldenstrom+macroglobulinaemia&it=xg&req=4&npos=17 Source: Charakidis M. et al, Department of Haematology-Oncology, Royal Hobart Hospital, Tasmania, 7000, Australia.]]] | |||
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[[File:WM.png|thumb|300px|none|Medium-power field of bone marrow aspirate demonstrating a population of small atypical lymphocytes admixed with normal cells of erythroid, myeloid and lymphoid lineage.[https://openi.nlm.nih.gov/detailedresult.php?img=PMC2944189_1752-1947-4-300-3&query=waldenstrom+macroglobulinaemia&it=xg&req=4&npos=18 Source: Charakidis M. et al, Department of Haematology-Oncology, Royal Hobart Hospital, Tasmania, 7000, Australia.]]] | |||
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[[File:Rouleaux formation.png|thumb|300px|none|(A) Rouleaux formation, plasmacytoid cells, and lymphoid cells in the PBF (Leishman, ×1000). (B) Uni-binucleated plasmacytoid cells in the PBF (Leishman, ×1000).[https://openi.nlm.nih.gov/detailedresult.php?img=PMC3443994_CRIM.PATHOLOGY2012-271407.001&query=waldenstrom+macroglobulinaemia&it=xg&req=4&npos=49 Source: Sethi B. et al, Department of Pathology, Hamdard Institute of Medical Sciences and Research, New Delhi, India.]]] | |||
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[[File:Bm aspirate.png|thumb|300px|none| (A) Plasmacytoid cells in the bone marrow aspirates (Leishman, ×1000). (B) Tetranucleated plasmacytoid/plasma cell and lymphoid cell in the bone marrow aspirates (Leishman, ×1000). [https://openi.nlm.nih.gov/detailedresult.php?img=PMC3443994_CRIM.PATHOLOGY2012-271407.002&query=waldenstrom+macroglobulinaemia&it=xg&req=4&npos=50 Source: Sethi B. et al, Department of Pathology, VCSGGMS & RI Srinagar, Pauri Garhwal, Uttarakhand, India.]]] | |||
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[[File:Splenic infiltrate.png|thumb|300px|none| Low-power magnification of the splenic tissue. This slide displays significant distortion and diffuse infiltration of the splenic parenchyma by lymphoid cells. Of particular note is the expansion of the white pulp by this infiltrate. [https://openi.nlm.nih.gov/detailedresult.php?img=PMC2944189_1752-1947-4-300-8&query=waldenstrom+macroglobulinaemia&it=xg&req=4&npos=22 Source: Charakidis M. et al, Department of Haematology-Oncology, Royal Hobart Hospital, Tasmania, 7000, Australia.]]] | |||
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[[File:Wrights stain.png|thumb|300px|none|Photomicrograph showing hypercellular bone marrow smears with the presence of mostly bare nuclei, few lymphoid cells, and plasmacytic cells (Wright's stain, ×1,000).[https://openi.nlm.nih.gov/detailedresult.php?img=PMC3786287_br-48-230-g001&query=waldenstrom+macroglobulinaemia&it=xg&req=4&npos=24 Source: Pujani M. et al, Department of Pathology, Hamdard Institute of Medical Sciences and Research, New Delhi, India.]]] | |||
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[[File:Splenic lymphoid infiltrate.png|thumb|300px|none|High-power magnification of splenic lymphoid infiltrate. This slide demonstrates that the infiltrate consists of small- and medium-sized atypical lymphocytes, which display dense chromatin clumping and prominent nucleoli.[https://openi.nlm.nih.gov/detailedresult.php?img=PMC2944189_1752-1947-4-300-9&query=waldenstrom+macroglobulinaemia&it=xg&req=4&npos=23 Source: Charakidis M. et al, Department of Haematology-Oncology, Royal Hobart Hospital, Tasmania, 7000, Australia.]]] | |||
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[[File:Bone marrow infiltrate.png|thumb|300px|none|Photomicrograph showing hypercellular marrow with diffuse infiltration by lymphoid cells, plasmacytoid lymphocytes, a few plasma cells, and mast cells (hematoxylin and eosin stain, ×1,000); inset photomicrograph showing strong cytoplasmic positivity for CD20 in the majority of the lymphoid cells (immunohistochemical stain for CD20, ×400).[https://openi.nlm.nih.gov/detailedresult.php?img=PMC3786287_br-48-230-g002&query=waldenstrom+macroglobulinaemia&it=xg&req=4&npos=25 Source: Pujani M. et al, Department of Pathology, Hamdard Institute of Medical Sciences and Research, New Delhi, India.]]] | |||
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[[File:GM. kidneys.png|thumb|300px|none| Light Microscopy. There is marked, global, homogeneous, eosinophilic thickening of the glomerular basement membrane with segmental accentuation. Homogeneous, eosinophilic globules are seen in the lumen of occasional capillary loops. The capillary lumina appear reduced in diameter but no inflammatory or proliferative changes are observed. The periglomerular interstitial space shows lymphocytic infiltration. Focal interstitial deposition of homogeneous eosinophilic material is present in the right upper corner of the picture (H&E × 400). [https://openi.nlm.nih.gov/detailedresult.php?img=PMC2600791_1757-1626-1-333-1&query=waldenstrom+macroglobulinaemia&it=xg&req=4&npos=31 Source: Castro H. et al, Department of Medicine, Division of General Internal Medicine, University of Miami/Jackson Memorial Medical Center, Miami, Florida, USA.]]] | |||
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[[File:Kidneys.immunoflorescence.png|thumb|250px|none|Immunofluorescence. Global granular and homogeneous deposition of IgG along the glomerular basement membrane. Notice the presence of IgG containing globules in rare capillary loops. They seem to correspond to the eosinophilic globules seen by light microscopy and large electron dense deposits detected by electron microscopy (FITC labeled anti-IgG × 400).[https://openi.nlm.nih.gov/detailedresult.php?img=PMC2600791_1757-1626-1-333-2&query=waldenstrom+macroglobulinaemia&it=xg&req=4&npos=32 Source: Castro H. et al, Department of Medicine, Division of General Internal Medicine, University of Miami/Jackson Memorial Medical Center, Miami, Florida, USA.]]] | |||
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[[File:Kidneys. EM.png|thumb|250px|none|Electron Microscopy. There is marked thickening of the glomerular basement membrane due to the presence of numerous electron dense deposits located at different levels. The deposits vary in size, tend to be spherical in shape and blend together. Under higher magnifications, they did not exhibit a fibrillary or micro-tubular substructure. Notice a thin subendothelial layer of duplicated basement membrane, also containing electron dense deposits, with cellular interposition. The capillary lumen appears significantly reduced in diameter. Also notice electron dense deposits present in the basement membrane of Bowman's capsule on the right upper corner (Uranyl acetate & lead citrate × 35,000).[https://openi.nlm.nih.gov/detailedresult.php?img=PMC2600791_1757-1626-1-333-3&query=waldenstrom+macroglobulinaemia&it=xg&req=4&npos=33 Source: Castro H. et al, Department of Medicine, Division of General Internal Medicine, University of Miami/Jackson Memorial Medical Center, Miami, Florida, USA.]]] | |||
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[[File:EM. kidneys.png|thumb|250px|none|Electron Microscopy. This field illustrates a large subendothelial and several, much smaller, subepithelial electron dense deposits. This pattern is similar to that originally described in MPGN type III and also often seen in proliferative lupus GN. Notice the duplication of the glomerular basement membrane with cellular interposition. The duplicated segment also contains electron dense deposits. Occasionally giant, subendothelial, globular electron dense deposits reduced the capillary loop to a pin-point lumen. Probably they correspond to the globules seen by light and fluorescence microscopy (Uranyl acetate and lead citrate × 40,000).[https://openi.nlm.nih.gov/detailedresult.php?img=PMC2600791_1757-1626-1-333-4&query=waldenstrom+macroglobulinaemia&it=xg&req=4&npos=34 Source: Castro H. et al, Department of Medicine, Division of General Internal Medicine, University of Miami/Jackson Memorial Medical Center, Miami, Florida, USA.]]] | |||
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[[File:Renal biopsy.immunofloresence.png|thumb|250px|none| Renal biopsy. (A) Immunofluorescent microscopic study showed 2+ reaction for IgM. (B) On the electron microscopic (EM) findings (× 20,000), there are subendothelial (arrow) and mesangial electron dense deposits revealing microtubular structures (25 nm in average diameter).[https://openi.nlm.nih.gov/detailedresult.php?img=PMC3102879_jkms-26-824-g001&query=waldenstrom+macroglobulinaemia&it=xg&req=4&npos=40 Source: Kim YL. et al, Department of Internal Medicine, Eulji University College of Medicine, Seoul, Korea]]] | |||
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===Immunohistochemistry=== | ===Immunohistochemistry=== | ||
Revision as of 02:14, 16 February 2019
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Waldenström's macroglobulinemia Microchapters |
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Differentiating Waldenström's macroglobulinemia from other Diseases |
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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]Associate Editor(s)-in-Chief: Sara Mohsin, M.D.[2]Roukoz A. Karam, M.D.[3] Mirdula Sharma, MBBS [4]
Overview
Waldenström macroglobulinemia is an uncontrolled clonal proliferation of terminally differentiated B lymphocytes (plasma cells), which are normally involved in humoral immunity. Genes involved in the pathogenesis of Waldenström macroglobulinemia include MYD88-L265P, and CXCR4.
Pathophysiology
- Waldenström macroglobulinemia arises from terminally differentiated B lymphocytes, which are normally involved in humoral immunity.
- It is understood that Waldenström macroglobulinemia is mediated by 2 major factors:
- The secretion of IgM paraprotein
- Causes symptoms of hyperviscosity syndrome
- The infiltration of tissues with neoplastic lymphoplasmacytic cells
- Mainly the bone marrow, spleen,and lymph nodes
- Sometimes the liver, gastrointestinal tract, lungs, kidneys, skin, eyes, and central nervous system
- The secretion of IgM paraprotein
Genetics
- The exact pathogenesis of Waldenström macroglobulinemia is not completely understood; however, its familial pattern of involvement supports the role played by genetic factors in the pathogenesis of this disease.[1][2]
- Development of Waldenström macroglobulinemia is the result of multiple genetic mutations.[3]
- Somatic mutations as well as chromosomal abnormalities play a part in the pathogenesis of this disease:
- A mutation of the MYD88 gene (L265P) has been found in more than 90% of patients with Waldenström macroglobulinemia, while it has rarely presented in patients with other types of mature B-cell tumors.[4][5][6][7][8][9][10][11]
- MYD88: The activating point mutation of MYD88 augments growth and survival of both normal and neoplastic B cells by preventing apoptosis. Point mutation of MYD88 leads to leucine to proline substitution in codon 265 (L265P) of MYD88 and produces constantly overactive protein causing proliferation of malignant cells that should normally undergo apoptosis.
- Monoclonal gammopathy of undetermined significance patients found to have MYD88 L265P mutation have significantly higher risk of progression to Waldenström macroglobulinemia or to other lymphoproliferative disorders.
- Less commonly (30-35%), nonsense or frameshift mutations in the C-X-C chemokine receptor type 4 (CXCR4) 5338X gene have also been reported in patients with Waldenström macroglobulinemia.[12]
- Patients with Waldenström's macroglobulinemia with co-existing mutation of MYD88 & CXCR4 are more likely to have hyper-viscosity syndrome and bone marrow involvement.[3]
- Somatic hypermutation in IGHV/IG gene rearrangement.[13]
- ARIDA mutations.
- A mutation of the MYD88 gene (L265P) has been found in more than 90% of patients with Waldenström macroglobulinemia, while it has rarely presented in patients with other types of mature B-cell tumors.[4][5][6][7][8][9][10][11]
Cytogenetics
- Many cytogenetic abnormalities were reported in Waldenström macroglobulinemia patients including:
- Deletion (genetics) of the long arm of chromosome 6q21-22.1 (most common,50%).[14]
- Deletion of long arm of chromosome 10, 12 0r 20.
- t(9;14)(p13;q32)(50%).[13]
- Trisomy 4(20%).[13]
- Trisomy 5.
- Monosomy 8.[15]
- Deletions of regions of 13q14 that include MIRN15A and MIRN16-1.[16]
- t(11;18)(q21;q21) involving API-malt1.[16]
- t(8;14).
- t(14;18).
Epigenetics
- Three most common epigenetic causes are DNA methylation, histone acetylation, and non-coding RNAs such as miRNAs.[17]
- Up-regulation of miRNAs 155, 184, 206, 363, 494, and 542-3p occurs in Waldenström macroglobulinemia; among which miRNA-155 has a crucial role in tumor cell growth and proliferation in Waldenström macroglobulinemia.
- Gene transcription through histone acetylation occurs following increased expression of miRNA-206 and reduced expression of miRNA-9.
Associated Conditions
Several studies showed an increased incidence of following second cancers in patients with Waldenström macroglobulinemia:[18]
- Diffuse large B-cell lymphoma
- Myelodysplastic syndrome/Acute myeloid leukemia
- Brain tumor
- Renal MALT lymphoma [19]
Microscopic Pathology
WM/LPL is a form of an indolent (slowly growing) non-hodgkin lymphoma. LPL is called so because the lymphoma cells have the characteristics of both lymphocytes and plasma cells. After a detailed clinicopathological assessment and review of the published literature, the following diagnostic criteria was proposed for WM:[20]
- IgM monoclonal gammopathy of any concentration.
- Bone marrow infiltration by:[21][22][23]
- Small lymphocytes with clumped chromatin, inconspicuous nucleoli, and sparse cytoplasm.
- Well-formed plasma cells.
- Plasmacytoid lymphocytes (have cytologic features intermediate between above 2 extremes), in following patterns:[24][25]
- Diffuse.
- Interstitial.
- Nodular.
- Paratrabecular.
- Nodular-interstitial.
- Mixed paratrabacular-nodular.
- Following lymphoid organs are involved in WM:
- Bone marrow.
- Lymph nodes(nodal involvement is characterized by paracortical and hilar infiltration with frequent sparing of the subscapular and marginal sinuses).
- Spleen.
- WM has two histologic subtypes:[25]
- Lymphoplasmacytoid (73%).
- Lymphoplasmacytic (27%).
- The cytologic composition and the degree of plasmacytic differentiation varies from case to case.
- The bone marrow contains variable numbers of pleomorphic lymphoid cells.
- Dutcher bodies may be seen in plasma cells, as intracytoplasmic inclusions positive for periodic acid Schiff.
- Mast cell hyperplasia is common and may stimulate tumor cell proliferation and monoclonal IgM secretion.
- Gene expression profiling has indicated that lymphoid cells of WM more closely resemble those of chronic lymphocytic leukemia than those of myeloma.[26]
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Immunohistochemistry
Malignant cells in Waldenström macroglobulinemia have following immunophenotypic characteristics:[23] [3]
- Express pan B-cell antigens surface with following immunophenotype:[27][28][20]
- Variable expression of:
- Following aren't expressed:
- IgM positive (mostly).
- IgG positive (few).
- IgA (rare).
- IgD negative (lack).
References
- ↑ Royer RH, Koshiol J, Giambarresi TR, Vasquez LG, Pfeiffer RM, McMaster ML (2010). "Differential characteristics of Waldenström macroglobulinemia according to patterns of familial aggregation". Blood. 115 (22): 4464–71. doi:10.1182/blood-2009-10-247973. PMC 2881498. PMID 20308603.
- ↑ Treon SP, Hunter ZR, Aggarwal A, Ewen EP, Masota S, Lee C; et al. (2006). "Characterization of familial Waldenstrom's macroglobulinemia". Ann Oncol. 17 (3): 488–94. doi:10.1093/annonc/mdj111. PMID 16357024.
- ↑ 3.0 3.1 3.2 Ngo VN, Young RM, Schmitz R, Jhavar S, Xiao W, Lim KH, Kohlhammer H, Xu W, Yang Y, Zhao H, Shaffer AL, Romesser P, Wright G, Powell J, Rosenwald A, Muller-Hermelink HK, Ott G, Gascoyne RD, Connors JM, Rimsza LM, Campo E, Jaffe ES, Delabie J, Smeland EB, Fisher RI, Braziel RM, Tubbs RR, Cook JR, Weisenburger DD, Chan WC, Staudt LM (2011). "Oncogenically active MYD88 mutations in human lymphoma". Nature. 470 (7332): 115–9. doi:10.1038/nature09671. PMID 21179087.
- ↑ Treon, Steven P.; Xu, Lian; Yang, Guang; Zhou, Yangsheng; Liu, Xia; Cao, Yang; Sheehy, Patricia; Manning, Robert J.; Patterson, Christopher J.; Tripsas, Christina; Arcaini, Luca; Pinkus, Geraldine S.; Rodig, Scott J.; Sohani, Aliyah R.; Harris, Nancy Lee; Laramie, Jason M.; Skifter, Donald A.; Lincoln, Stephen E.; Hunter, Zachary R. (2012). "MYD88 L265P Somatic Mutation in Waldenström's Macroglobulinemia". New England Journal of Medicine. 367 (9): 826–833. doi:10.1056/NEJMoa1200710. ISSN 0028-4793.
- ↑ Varettoni M, Arcaini L, Zibellini S, Boveri E, Rattotti S, Riboni R; et al. (2013). "Prevalence and clinical significance of the MYD88 (L265P) somatic mutation in Waldenstrom's macroglobulinemia and related lymphoid neoplasms". Blood. 121 (13): 2522–8. doi:10.1182/blood-2012-09-457101. PMID 23355535.
- ↑ Shi M, Spurgeon S, Press R, Olson S, Fan G (2015). "MYD88 mutation analysis of a rare composite chronic lymphocyte leukemia and lymphoplasmacytic lymphoma by flow cytometry cell sorting". Ann Hematol. 94 (11): 1941–4. doi:10.1007/s00277-015-2460-6. PMID 26231802.
- ↑ Yang G, Zhou Y, Liu X, Xu L, Cao Y, Manning RJ; et al. (2013). "A mutation in MYD88 (L265P) supports the survival of lymphoplasmacytic cells by activation of Bruton tyrosine kinase in Waldenström macroglobulinemia". Blood. 122 (7): 1222–32. doi:10.1182/blood-2012-12-475111. PMID 23836557.
- ↑ Ngo VN, Young RM, Schmitz R, Jhavar S, Xiao W, Lim KH; et al. (2011). "Oncogenically active MYD88 mutations in human lymphoma". Nature. 470 (7332): 115–9. doi:10.1038/nature09671. PMC 5024568. PMID 21179087.
- ↑ Mori N, Ohwashi M, Yoshinaga K, Mitsuhashi K, Tanaka N, Teramura M; et al. (2013). "L265P mutation of the MYD88 gene is frequent in Waldenström's macroglobulinemia and its absence in myeloma". PLoS One. 8 (11): e80088. doi:10.1371/journal.pone.0080088. PMC 3818242. PMID 24224040.
- ↑ Abeykoon JP, Paludo J, King RL, Ansell SM, Gertz MA, LaPlant BR; et al. (2018). "MYD88 mutation status does not impact overall survival in Waldenström macroglobulinemia". Am J Hematol. 93 (2): 187–194. doi:10.1002/ajh.24955. PMID 29080258.
- ↑ Steven P. Treon, Lian Xu, Guang Yang, Yangsheng Zhou, Xia Liu, Yang Cao, Patricia Sheehy, Robert J. Manning, Christopher J. Patterson, Christina Tripsas, Luca Arcaini, Geraldine S. Pinkus, Scott J. Rodig, Aliyah R. Sohani, Nancy Lee Harris, Jason M. Laramie, Donald A. Skifter, Stephen E. Lincoln & Zachary R. Hunter (2012). "MYD88 L265P somatic mutation in Waldenstrom's macroglobulinemia". The New England journal of medicine. 367 (9): 826–833. doi:10.1056/NEJMoa1200710. PMID 22931316. Unknown parameter
|month=ignored (help) - ↑ Zachary R. Hunter, Lian Xu, Guang Yang, Yangsheng Zhou, Xia Liu, Yang Cao, Robert J. Manning, Christina Tripsas, Christopher J. Patterson, Patricia Sheehy & Steven P. Treon (2014). "The genomic landscape of Waldenstrom macroglobulinemia is characterized by highly recurring MYD88 and WHIM-like CXCR4 mutations, and small somatic deletions associated with B-cell lymphomagenesis". Blood. 123 (11): 1637–1646. doi:10.1182/blood-2013-09-525808. PMID 24366360. Unknown parameter
|month=ignored (help) - ↑ 13.0 13.1 13.2 Yun S, Johnson AC, Okolo ON, Arnold SJ, McBride A, Zhang L; et al. (2017). "Waldenström Macroglobulinemia: Review of Pathogenesis and Management". Clin Lymphoma Myeloma Leuk. 17 (5): 252–262. doi:10.1016/j.clml.2017.02.028. PMC 5413391. PMID 28366781.
- ↑ Treon, S. P.; Hunter, Z. R.; Aggarwal, A.; Ewen, E. P.; Masota, S.; Lee, C.; Santos, D. Ditzel; Hatjiharissi, E.; Xu, L.; Leleu, X.; Tournilhac, O.; Patterson, C. J.; Manning, R.; Branagan, A. R.; Morton, C. C. (2006). "Characterization of familial Waldenström's macroglobulinemia". Annals of Oncology. 17 (3): 488–494. doi:10.1093/annonc/mdj111. ISSN 1569-8041.
- ↑ Roelandt F. J. Schop, W. Michael Kuehl, Scott A. Van Wier, Gregory J. Ahmann, Tammy Price-Troska, Richard J. Bailey, Syed M. Jalal, Ying Qi, Robert A. Kyle, Philip R. Greipp & Rafael Fonseca (2002). "Waldenstrom macroglobulinemia neoplastic cells lack immunoglobulin heavy chain locus translocations but have frequent 6q deletions". Blood. 100 (8): 2996–3001. doi:10.1182/blood.V100.8.2996. PMID 12351413. Unknown parameter
|month=ignored (help) - ↑ 16.0 16.1 Braggio E, Keats JJ, Leleu X, Van Wier S, Jimenez-Zepeda VH, Valdez R; et al. (2009). "Identification of copy number abnormalities and inactivating mutations in two negative regulators of nuclear factor-kappaB signaling pathways in Waldenstrom's macroglobulinemia". Cancer Res. 69 (8): 3579–88. doi:10.1158/0008-5472.CAN-08-3701. PMC 2782932. PMID 19351844.
- ↑ Waldenström macroglobulinemia. International Waldenström Macroglobulinemia foundation (2015)http://www.iwmf.com/sites/default/files/docs/WM_Review_Ghobrial_Jan2014.pdf Accessed on November 12, 2015
- ↑ Morra E, Varettoni M, Tedeschi A, Arcaini L, Ricci F, Pascutto C, Rattotti S, Vismara E, Paris L, Cazzola M (2013). "Associated cancers in Waldenström macroglobulinemia: clues for common genetic predisposition". Clin Lymphoma Myeloma Leuk. 13 (6): 700–3. doi:10.1016/j.clml.2013.05.008. PMID 24070824.
- ↑ Chi PJ, Pei SN, Huang TL, Huang SC, Ng HY, Lee CT (2014). "Renal MALT lymphoma associated with Waldenström macroglobulinemia". J. Formos. Med. Assoc. 113 (4): 255–7. doi:10.1016/j.jfma.2011.02.007. PMID 24685302.
- ↑ 20.0 20.1 Owen RG (2003). "Developing diagnostic criteria in Waldenstrom's macroglobulinemia". Semin Oncol. 30 (2): 196–200. doi:10.1053/sonc.2003.50069. PMID 12720135.
- ↑ Morice WG, Chen D, Kurtin PJ, Hanson CA, McPhail ED (2009). "Novel immunophenotypic features of marrow lymphoplasmacytic lymphoma and correlation with Waldenström's macroglobulinemia". Mod Pathol. 22 (6): 807–16. doi:10.1038/modpathol.2009.34. PMID 19287458.
- ↑ Owen RG, Treon SP, Al-Katib A, Fonseca R, Greipp PR, McMaster ML; et al. (2003). "Clinicopathological definition of Waldenstrom's macroglobulinemia: consensus panel recommendations from the Second International Workshop on Waldenstrom's Macroglobulinemia". Semin Oncol. 30 (2): 110–5. doi:10.1053/sonc.2003.50082. PMID 12720118.
- ↑ 23.0 23.1 Ansell, Stephen M.; Kyle, Robert A.; Reeder, Craig B.; Fonseca, Rafael; Mikhael, Joseph R.; Morice, William G.; Bergsagel, P. Leif; Buadi, Francis K.; Colgan, Joseph P.; Dingli, David; Dispenzieri, Angela; Greipp, Philip R.; Habermann, Thomas M.; Hayman, Suzanne R.; Inwards, David J.; Johnston, Patrick B.; Kumar, Shaji K.; Lacy, Martha Q.; Lust, John A.; Markovic, Svetomir N.; Micallef, Ivana N.M.; Nowakowski, Grzegorz S.; Porrata, Luis F.; Roy, Vivek; Russell, Stephen J.; Short, Kristen E. Detweiler; Stewart, A. Keith; Thompson, Carrie A.; Witzig, Thomas E.; Zeldenrust, Steven R.; Dalton, Robert J.; Rajkumar, S. Vincent; Gertz, Morie A. (2010). "Diagnosis and Management of Waldenström Macroglobulinemia: Mayo Stratification of Macroglobulinemia and Risk-Adapted Therapy (mSMART) Guidelines". Mayo Clinic Proceedings. 85 (9): 824–833. doi:10.4065/mcp.2010.0304. ISSN 0025-6196.
- ↑ Owen RG, Barrans SL, Richards SJ, O'Connor SJ, Child JA, Parapia LA; et al. (2001). "Waldenström macroglobulinemia. Development of diagnostic criteria and identification of prognostic factors". Am J Clin Pathol. 116 (3): 420–8. doi:10.1309/4LCN-JMPG-5U71-UWQB. PMID 11554171.
- ↑ 25.0 25.1 Andriko JA, Aguilera NS, Chu WS, Nandedkar MA, Cotelingam JD (1997). "Waldenström's macroglobulinemia: a clinicopathologic study of 22 cases". Cancer. 80 (10): 1926–35. PMID 9366295.
- ↑ Chng WJ, Schop RF, Price-Troska T, Ghobrial I, Kay N, Jelinek DF; et al. (2006). "Gene-expression profiling of Waldenstrom macroglobulinemia reveals a phenotype more similar to chronic lymphocytic leukemia than multiple myeloma". Blood. 108 (8): 2755–63. doi:10.1182/blood-2006-02-005488. PMC 1895596. PMID 16804116.
- ↑ Dimopoulos MA, Gertz MA, Kastritis E, Garcia-Sanz R, Kimby EK, Leblond V; et al. (2009). "Update on treatment recommendations from the Fourth International Workshop on Waldenstrom's Macroglobulinemia". J Clin Oncol. 27 (1): 120–6. doi:10.1200/JCO.2008.17.7865. PMID 19047284.
- ↑ Vijay A, Gertz MA (2007). "Waldenström macroglobulinemia". Blood. 109 (12): 5096–103. doi:10.1182/blood-2006-11-055012. PMID 17303694.