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Revision as of 15:38, 4 February 2019

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Sara Mohsin, M.D.[2]

Synonyms and keywords: Waldenstrom's macroglobulinemia; Waldenstrom's disease; Primary macroglobulinemia; Hyperviscosity syndrome

Overview

Historical Perspective

In 1944, Jan G. Waldenstrom, a Swedish doctor of internal medicine, first discovered Waldenstrom macroglobulinemia(WM). He reported an unusal presentation of fatigue, lymphadenopathy, bleeding from nose and mouth, worsening anemia, elevated sedimentation rate, low serum fibrinogen levels (hypofibrinogenemia), hyperviscosity, and hypergammaglobulinemia in two patients due to increased levels of a class of an abnormal high molecular weight serum protein called macroglobulins.^[1]^[2]
In 1962, the first report on familiality in WM was published, and since then many cohort studies as well as small case-control studies have been published showing familial aggregation of WM.^[3]^[4]^[5]^[6]^[7]^[8]^[9]^[10]^[11] ^[12]^[13]^[14]^[15]
In 1994, a Revised European-American classification of lymphoid neaoplasms (REAL) was published by International Lymphoma Study Group which placed WM in the category of lymphoplasmacytic lymphoma (an indolent subtype of non-hodgkins lymphoma). The REAL classification is based on the morphology, immunophenotype, genetic features, and clinical features.^[16]^[17]
In 2001, WHO also classified the pathology of WM as lymphoplasmacytic lymphoma/Waldenstrom macroglobulinemia based on REAL classification.^[2]
In September 2002, a consensus group at the Second International Workshop on WM in Athens, Greece, defined WM as a distinct clinicopathologic entity with characteristics of bone marrow infiltration associated with IgM monoclonal gammopathy by WM.^[2]

The association between [important risk factor/cause] and [disease name] was made in/during [year/event].

In [year], [scientist] was the first to discover the association between [risk factor] and the development of [disease name].

In [year], [gene] mutations were first implicated in the pathogenesis of [disease name].

There have been several outbreaks of [disease name], including -----.

In [year], [diagnostic test/therapy] was developed by [scientist] to treat/diagnose [disease name].

Classification

There is no established system of classification for lymphoplasmacytic lymphoma (LPL).
However, it may be classified according to the patterns of bone marrow infiltration by small lymphocytes as:^[18]
- Diffuse
- Interstitial
- Nodular
- Paratrabecular

OR

[Disease name] may be classified according to [classification method] into [number] subtypes/groups: [group1], [group2], [group3], and [group4].

OR

[Disease name] may be classified into [large number > 6] subtypes based on [classification method 1], [classification method 2], and [classification method 3]. [Disease name] may be classified into several subtypes based on [classification method 1], [classification method 2], and [classification method 3].

OR

Based on the duration of symptoms, [disease name] may be classified as either acute or chronic.

OR

If the staging system involves specific and characteristic findings and features: According to the [staging system + reference], there are [number] stages of [malignancy name] based on the [finding1], [finding2], and [finding3]. Each stage is assigned a [letter/number1] and a [letter/number2] that designate the [feature1] and [feature2].

OR

The staging of [malignancy name] is based on the [staging system].

OR

There is no established system for the staging of [malignancy name].

Pathophysiology

The exact oncogenesis of WM has not been defined yet. However, several factors that play a role in pathogenesis of WM are listed as follow:

History of B-cell disorders in first-degree relatives of patient with WM.^[13]^[19]^[20]
Previous history of IgM Monoclonal gammopathy of undetermined significance (MGUS) in patient of WM.^[21]^[22]^[22]^[23]
Age older than 60 years.^[24]
Personal history of autoimmune diseases with autoantibodies leads to 2-3 fold higher risk of developing WM, especially elevated risks are associated with following:
- Hepatitis C virus infection (overall 20-30% increased risk for non-Hodgkin lymohoma and 3-fold increased risk for WM).^[20]^[25]
- HIV.^[25]
- Rickettsiosis.^[25]
Being a male.^[24]^[26]
Being a Caucasian.^[24]

Genetics

There are many cytogenetic abnormalities & mutations associated with WM:

MYD88 L265P somatic mutation (90%).^[27]^[28]^[29]^[30]^[31]^[32]^[33]
Deletions in 6q21-22.1 gene (50%).^[34]
Somatic hypermutation in IGHV.^[24]
t(9;14)(p13;q32) (50%).^[24]
C-X-C chemokine receptor type 4 (CXCR4) mutations (30-35%).^[24]
Trisomy 4 (20%).^[24]

OR

It is thought that [disease name] is the result of / is mediated by / is produced by / is caused by either [hypothesis 1], [hypothesis 2], or [hypothesis 3].

OR

[Pathogen name] is usually transmitted via the [transmission route] route to the human host.

OR

Following transmission/ingestion, the [pathogen] uses the [entry site] to invade the [cell name] cell.

OR

[Disease or malignancy name] arises from [cell name]s, which are [cell type] cells that are normally involved in [function of cells].

OR

The progression to [disease name] usually involves the [molecular pathway].

OR

The pathophysiology of [disease/malignancy] depends on the histological subtype.

Causes

Disease name] may be caused by [cause1], [cause2], or [cause3].

OR

Common causes of [disease] include [cause1], [cause2], and [cause3].

OR

The most common cause of [disease name] is [cause 1]. Less common causes of [disease name] include [cause 2], [cause 3], and [cause 4].

OR

The cause of [disease name] has not been identified. To review risk factors for the development of [disease name], click here.

Differentiating ((Page name)) from Other Diseases

[Disease name] must be differentiated from other diseases that cause [clinical feature 1], [clinical feature 2], and [clinical feature 3], such as [differential dx1], [differential dx2], and [differential dx3].

OR

[Disease name] must be differentiated from [[differential dx1], [differential dx2], and [differential dx3].

Epidemiology and Demographics

The incidence/prevalence of [disease name] is approximately [number range] per 100,000 individuals worldwide.

OR

In [year], the incidence/prevalence of [disease name] was estimated to be [number range] cases per 100,000 individuals worldwide.

OR

In [year], the incidence of [disease name] is approximately [number range] per 100,000 individuals with a case-fatality rate of [number range]%.

Patients of all age groups may develop [disease name].

OR

The incidence of [disease name] increases with age; the median age at diagnosis is [#] years.

OR

[Disease name] commonly affects individuals younger than/older than [number of years] years of age.

OR

[Chronic disease name] is usually first diagnosed among [age group].

OR

[Acute disease name] commonly affects [age group].

There is no racial predilection to [disease name].

OR

[Disease name] usually affects individuals of the [race 1] race. [Race 2] individuals are less likely to develop [disease name].

[Disease name] affects men and women equally.

OR

[Gender 1] are more commonly affected by [disease name] than [gender 2]. The [gender 1] to [gender 2] ratio is approximately [number > 1] to 1.

The majority of [disease name] cases are reported in [geographical region].

OR

[Disease name] is a common/rare disease that tends to affect [patient population 1] and [patient population 2].

Risk Factors

There are no established risk factors for [disease name].

OR

The most potent risk factor in the development of [disease name] is [risk factor 1]. Other risk factors include [risk factor 2], [risk factor 3], and [risk factor 4].

OR

Common risk factors in the development of [disease name] include [risk factor 1], [risk factor 2], [risk factor 3], and [risk factor 4].

OR

Common risk factors in the development of [disease name] may be occupational, environmental, genetic, and viral.

Screening

There is insufficient evidence to recommend routine screening for [disease/malignancy].

OR

According to the [guideline name], screening for [disease name] is not recommended.

OR

According to the [guideline name], screening for [disease name] by [test 1] is recommended every [duration] among patients with [condition 1], [condition 2], and [condition 3].

Natural History, Complications, and Prognosis

If left untreated, [#]% of patients with [disease name] may progress to develop [manifestation 1], [manifestation 2], and [manifestation 3].

OR

Common complications of [disease name] include [complication 1], [complication 2], and [complication 3].

OR

Prognosis is generally excellent/good/poor, and the 1/5/10-year mortality/survival rate of patients with [disease name] is approximately [#]%.

Diagnosis

Diagnostic Study of Choice

The diagnosis of [disease name] is made when at least [number] of the following [number] diagnostic criteria are met: [criterion 1], [criterion 2], [criterion 3], and [criterion 4].

OR

The diagnosis of [disease name] is based on the [criteria name] criteria, which include [criterion 1], [criterion 2], and [criterion 3].

OR

The diagnosis of [disease name] is based on the [definition name] definition, which includes [criterion 1], [criterion 2], and [criterion 3].

OR

There are no established criteria for the diagnosis of [disease name].

History and Symptoms

The majority of patients with [disease name] are asymptomatic.

OR

The hallmark of [disease name] is [finding]. A positive history of [finding 1] and [finding 2] is suggestive of [disease name]. The most common symptoms of [disease name] include [symptom 1], [symptom 2], and [symptom 3]. Common symptoms of [disease] include [symptom 1], [symptom 2], and [symptom 3]. Less common symptoms of [disease name] include [symptom 1], [symptom 2], and [symptom 3].

Physical Examination

Patients with [disease name] usually appear [general appearance]. Physical examination of patients with [disease name] is usually remarkable for [finding 1], [finding 2], and [finding 3].

OR

Common physical examination findings of [disease name] include [finding 1], [finding 2], and [finding 3].

OR

The presence of [finding(s)] on physical examination is diagnostic of [disease name].

OR

The presence of [finding(s)] on physical examination is highly suggestive of [disease name].

Laboratory Findings

An elevated/reduced concentration of serum/blood/urinary/CSF/other [lab test] is diagnostic of [disease name].

OR

Laboratory findings consistent with the diagnosis of [disease name] include [abnormal test 1], [abnormal test 2], and [abnormal test 3].

OR

[Test] is usually normal among patients with [disease name].

OR

Some patients with [disease name] may have elevated/reduced concentration of [test], which is usually suggestive of [progression/complication].

OR

There are no diagnostic laboratory findings associated with [disease name].

Electrocardiogram

There are no ECG findings associated with [disease name].

OR

An ECG may be helpful in the diagnosis of [disease name]. Findings on an ECG suggestive of/diagnostic of [disease name] include [finding 1], [finding 2], and [finding 3].

X-ray

There are no x-ray findings associated with [disease name].

OR

An x-ray may be helpful in the diagnosis of [disease name]. Findings on an x-ray suggestive of/diagnostic of [disease name] include [finding 1], [finding 2], and [finding 3].

OR

There are no x-ray findings associated with [disease name]. However, an x-ray may be helpful in the diagnosis of complications of [disease name], which include [complication 1], [complication 2], and [complication 3].

Echocardiography or Ultrasound

There are no echocardiography/ultrasound findings associated with [disease name].

OR

Echocardiography/ultrasound may be helpful in the diagnosis of [disease name]. Findings on an echocardiography/ultrasound suggestive of/diagnostic of [disease name] include [finding 1], [finding 2], and [finding 3].

OR

There are no echocardiography/ultrasound findings associated with [disease name]. However, an echocardiography/ultrasound may be helpful in the diagnosis of complications of [disease name], which include [complication 1], [complication 2], and [complication 3].

CT scan

There are no CT scan findings associated with [disease name].

OR

[Location] CT scan may be helpful in the diagnosis of [disease name]. Findings on CT scan suggestive of/diagnostic of [disease name] include [finding 1], [finding 2], and [finding 3].

OR

There are no CT scan findings associated with [disease name]. However, a CT scan may be helpful in the diagnosis of complications of [disease name], which include [complication 1], [complication 2], and [complication 3].

MRI

There are no MRI findings associated with [disease name].

OR

[Location] MRI may be helpful in the diagnosis of [disease name]. Findings on MRI suggestive of/diagnostic of [disease name] include [finding 1], [finding 2], and [finding 3].

OR

There are no MRI findings associated with [disease name]. However, a MRI may be helpful in the diagnosis of complications of [disease name], which include [complication 1], [complication 2], and [complication 3].

Other Imaging Findings

There are no other imaging findings associated with [disease name].

OR

[Imaging modality] may be helpful in the diagnosis of [disease name]. Findings on an [imaging modality] suggestive of/diagnostic of [disease name] include [finding 1], [finding 2], and [finding 3].

Other Diagnostic Studies

There are no other diagnostic studies associated with [disease name].

OR

[Diagnostic study] may be helpful in the diagnosis of [disease name]. Findings suggestive of/diagnostic of [disease name] include [finding 1], [finding 2], and [finding 3].

OR

Other diagnostic studies for [disease name] include [diagnostic study 1], which demonstrates [finding 1], [finding 2], and [finding 3], and [diagnostic study 2], which demonstrates [finding 1], [finding 2], and [finding 3].

Treatment

Medical Therapy

There is no treatment for [disease name]; the mainstay of therapy is supportive care.

OR

Supportive therapy for [disease name] includes [therapy 1], [therapy 2], and [therapy 3].

OR

The majority of cases of [disease name] are self-limited and require only supportive care.

OR

[Disease name] is a medical emergency and requires prompt treatment.

OR

The mainstay of treatment for [disease name] is [therapy].

OR The optimal therapy for [malignancy name] depends on the stage at diagnosis.

OR

[Therapy] is recommended among all patients who develop [disease name].

OR

Pharmacologic medical therapy is recommended among patients with [disease subclass 1], [disease subclass 2], and [disease subclass 3].

OR

Pharmacologic medical therapies for [disease name] include (either) [therapy 1], [therapy 2], and/or [therapy 3].

OR

Empiric therapy for [disease name] depends on [disease factor 1] and [disease factor 2].

OR

Patients with [disease subclass 1] are treated with [therapy 1], whereas patients with [disease subclass 2] are treated with [therapy 2].

Surgery

Surgical intervention is not recommended for the management of [disease name].

OR

Surgery is not the first-line treatment option for patients with [disease name]. Surgery is usually reserved for patients with either [indication 1], [indication 2], and [indication 3]

OR

The mainstay of treatment for [disease name] is medical therapy. Surgery is usually reserved for patients with either [indication 1], [indication 2], and/or [indication 3].

OR

The feasibility of surgery depends on the stage of [malignancy] at diagnosis.

OR

Surgery is the mainstay of treatment for [disease or malignancy].

Primary Prevention

There are no established measures for the primary prevention of [disease name].

OR

There are no available vaccines against [disease name].

OR

Effective measures for the primary prevention of [disease name] include [measure1], [measure2], and [measure3].

OR

[Vaccine name] vaccine is recommended for [patient population] to prevent [disease name]. Other primary prevention strategies include [strategy 1], [strategy 2], and [strategy 3].

Secondary Prevention

There are no established measures for the secondary prevention of [disease name].

OR

Effective measures for the secondary prevention of [disease name] include [strategy 1], [strategy 2], and [strategy 3].

References

↑ Hatem Kaseb & Prerna Mewawalla (2018). "Cancer, Lymphoma, Lymphoplasmacytic (Waldenstrom Macroglobulinemia)". Unknown parameter |month= ignored (help); Text " pmi " ignored (help)
↑ ^2.0 ^2.1 ^2.2 Konoplev, Sergej; Medeiros, L. Jeffrey; Bueso-Ramos, Carlos E.; Jorgensen, Jeffrey L.; Lin, Pei (2005). "Immunophenotypic Profile of Lymphoplasmacytic Lymphoma/Waldenström Macroglobulinemia". American Journal of Clinical Pathology. 124 (3): 414–420. doi:10.1309/3G1XDX0DVHBNVKB4. ISSN 0002-9173.
↑ MASSARI R, FINE JM, METAIS R (1962). "Waldenstrom's macroglobulinaemia observed in two brothers". Nature. 196: 176–8. PMID 13933388.
↑ Altieri A, Bermejo JL, Hemminki K (2005). "Familial aggregation of lymphoplasmacytic lymphoma with non-Hodgkin lymphoma and other neoplasms". Leukemia. 19 (12): 2342–3. doi:10.1038/sj.leu.2403991. PMID 16224483.
↑ Blattner WA, Garber JE, Mann DL, McKeen EA, Henson R, McGuire DB; et al. (1980). "Waldenström's macroglobulinemia and autoimmune disease in a family". Ann Intern Med. 93 (6): 830–2. PMID 6778280.
↑ Fine JM, Lambin P, Massari M, Leroux P (1982). "Malignant evolution of asymptomatic monoclonal IgM after seven and fifteen years in two siblings of a patient with Waldenström's macroglobulinemia". Acta Med Scand. 211 (3): 237–9. PMID 6805257.
↑ Fine JM, Muller JY, Rochu D, Marneux M, Gorin NC, Fine A; et al. (1986). "Waldenström's macroglobulinemia in monozygotic twins". Acta Med Scand. 220 (4): 369–73. PMID 3099545.
↑ Gétaz EP, Staples WG (1977). "Familial Waldenström's macroglobulinaemia: a case report". S Afr Med J. 51 (24): 891–2. PMID 408931.
↑ Linet MS, Humphrey RL, Mehl ES, Brown LM, Pottern LM, Bias WB; et al. (1993). "A case-control and family study of Waldenstrom's macroglobulinemia". Leukemia. 7 (9): 1363–9. PMID 8371587.
↑ Ogmundsdóttir HM, Jóhannesson GM, Sveinsdóttir S, Einarsdóttir S, Hegeman A, Jensson O; et al. (1994). "Familial macroglobulinaemia: hyperactive B-cells but normal natural killer function". Scand J Immunol. 40 (2): 195–200. PMID 8047841.
↑ Seligmann M, Danon F, Mihaesco C, Fudenberg HH (1967). "Immunoglobulin abnormalities in families of patients with Waldenström's macroglobulinemia". Am J Med. 43 (1): 66–83. PMID 4143650.
↑ Taleb N, Tohme A, Abi Jirgiss D, Kattan J, Salloum E (1991). "Familial macroglobulinemia in a Lebanese family with two sisters presenting Waldenström's disease". Acta Oncol. 30 (6): 703–5. PMID 1958390.
↑ ^13.0 ^13.1 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.
↑ Youinou P, le Goff P, Saleun JP, Rivat L, Morin JF, Fauchier C; et al. (1978). "Familial occurrence of monoclonal gammapathies". Biomedicine. 28 (4): 226–32. PMID 104746.
↑ Renier G, Ifrah N, Chevailler A, Saint-Andre JP, Boasson M, Hurez D (1989). "Four brothers with Waldenstrom's macroglobulinemia". Cancer. 64 (7): 1554–9. PMID 2505923.
↑ Harris NL, Jaffe ES, Diebold J, Flandrin G, Muller-Hermelink HK, Vardiman J; et al. (1999). "World Health Organization classification of neoplastic diseases of the hematopoietic and lymphoid tissues: report of the Clinical Advisory Committee meeting-Airlie House, Virginia, November 1997". J Clin Oncol. 17 (12): 3835–49. doi:10.1200/JCO.1999.17.12.3835. PMID 10577857.
↑ Harris NL, Jaffe ES, Stein H, Banks PM, Chan JK, Cleary ML; et al. (1994). "A revised European-American classification of lymphoid neoplasms: a proposal from the International Lymphoma Study Group". Blood. 84 (5): 1361–92. PMID 8068936.
↑ 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.
↑ McMaster ML, Csako G, Giambarresi TR, Vasquez L, Berg M, Saddlemire S; et al. (2007). "Long-term evaluation of three multiple-case Waldenstrom macroglobulinemia families". Clin Cancer Res. 13 (17): 5063–9. doi:10.1158/1078-0432.CCR-07-0299. PMID 17785558.
↑ ^20.0 ^20.1 Kristinsson SY, Björkholm M, Goldin LR, McMaster ML, Turesson I, Landgren O (2008). "Risk of lymphoproliferative disorders among first-degree relatives of lymphoplasmacytic lymphoma/Waldenstrom macroglobulinemia patients: a population-based study in Sweden". Blood. 112 (8): 3052–6. doi:10.1182/blood-2008-06-162768. PMC 2569164. PMID 18703425.
↑ 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.
↑ ^22.0 ^22.1 Kyle RA, Therneau TM, Rajkumar SV, Remstein ED, Offord JR, Larson DR; et al. (2003). "Long-term follow-up of IgM monoclonal gammopathy of undetermined significance". Blood. 102 (10): 3759–64. doi:10.1182/blood-2003-03-0801. PMID 12881316.
↑ Baldini L, Goldaniga M, Guffanti A, Broglia C, Cortelazzo S, Rossi A; et al. (2005). "Immunoglobulin M monoclonal gammopathies of undetermined significance and indolent Waldenstrom's macroglobulinemia recognize the same determinants of evolution into symptomatic lymphoid disorders: proposal for a common prognostic scoring system". J Clin Oncol. 23 (21): 4662–8. doi:10.1200/JCO.2005.06.147. PMID 16034042.
↑ ^24.0 ^24.1 ^24.2 ^24.3 ^24.4 ^24.5 ^24.6 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.
↑ ^25.0 ^25.1 ^25.2 Koshiol J, Gridley G, Engels EA, McMaster ML, Landgren O (2008). "Chronic immune stimulation and subsequent Waldenström macroglobulinemia". Arch Intern Med. 168 (17): 1903–9. doi:10.1001/archinternmed.2008.4. PMC 2670401. PMID 18809818.
↑ Giordano TP, Henderson L, Landgren O, Chiao EY, Kramer JR, El-Serag H; et al. (2007). "Risk of non-Hodgkin lymphoma and lymphoproliferative precursor diseases in US veterans with hepatitis C virus". JAMA. 297 (18): 2010–7. doi:10.1001/jama.297.18.2010. PMID 17488966.
↑ 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.
↑ 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.

[1] Hatem Kaseb & Prerna Mewawalla (2018). "Cancer, Lymphoma, Lymphoplasmacytic (Waldenstrom Macroglobulinemia)". Unknown parameter |month= ignored (help); Text " pmi " ignored (help)

[KonoplevMedeiros2005-2] 2.0 ^2.1 ^2.2 Konoplev, Sergej; Medeiros, L. Jeffrey; Bueso-Ramos, Carlos E.; Jorgensen, Jeffrey L.; Lin, Pei (2005). "Immunophenotypic Profile of Lymphoplasmacytic Lymphoma/Waldenström Macroglobulinemia". American Journal of Clinical Pathology. 124 (3): 414–420. doi:10.1309/3G1XDX0DVHBNVKB4. ISSN 0002-9173.

[pmid13933388-3] MASSARI R, FINE JM, METAIS R (1962). "Waldenstrom's macroglobulinaemia observed in two brothers". Nature. 196: 176–8. PMID 13933388.

[pmid16224483-4] Altieri A, Bermejo JL, Hemminki K (2005). "Familial aggregation of lymphoplasmacytic lymphoma with non-Hodgkin lymphoma and other neoplasms". Leukemia. 19 (12): 2342–3. doi:10.1038/sj.leu.2403991. PMID 16224483.

[pmid6778280-5] Blattner WA, Garber JE, Mann DL, McKeen EA, Henson R, McGuire DB; et al. (1980). "Waldenström's macroglobulinemia and autoimmune disease in a family". Ann Intern Med. 93 (6): 830–2. PMID 6778280.

[pmid6805257-6] Fine JM, Lambin P, Massari M, Leroux P (1982). "Malignant evolution of asymptomatic monoclonal IgM after seven and fifteen years in two siblings of a patient with Waldenström's macroglobulinemia". Acta Med Scand. 211 (3): 237–9. PMID 6805257.

[pmid3099545-7] Fine JM, Muller JY, Rochu D, Marneux M, Gorin NC, Fine A; et al. (1986). "Waldenström's macroglobulinemia in monozygotic twins". Acta Med Scand. 220 (4): 369–73. PMID 3099545.

[pmid408931-8] Gétaz EP, Staples WG (1977). "Familial Waldenström's macroglobulinaemia: a case report". S Afr Med J. 51 (24): 891–2. PMID 408931.

[pmid8371587-9] Linet MS, Humphrey RL, Mehl ES, Brown LM, Pottern LM, Bias WB; et al. (1993). "A case-control and family study of Waldenstrom's macroglobulinemia". Leukemia. 7 (9): 1363–9. PMID 8371587.

[pmid8047841-10] Ogmundsdóttir HM, Jóhannesson GM, Sveinsdóttir S, Einarsdóttir S, Hegeman A, Jensson O; et al. (1994). "Familial macroglobulinaemia: hyperactive B-cells but normal natural killer function". Scand J Immunol. 40 (2): 195–200. PMID 8047841.

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[pmid1958390-12] Taleb N, Tohme A, Abi Jirgiss D, Kattan J, Salloum E (1991). "Familial macroglobulinemia in a Lebanese family with two sisters presenting Waldenström's disease". Acta Oncol. 30 (6): 703–5. PMID 1958390.

[pmid16357024-13] 13.0 ^13.1 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.

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[pmid11554171-18] 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.

[pmid17785558-19] McMaster ML, Csako G, Giambarresi TR, Vasquez L, Berg M, Saddlemire S; et al. (2007). "Long-term evaluation of three multiple-case Waldenstrom macroglobulinemia families". Clin Cancer Res. 13 (17): 5063–9. doi:10.1158/1078-0432.CCR-07-0299. PMID 17785558.

[pmid18703425-20] 20.0 ^20.1 Kristinsson SY, Björkholm M, Goldin LR, McMaster ML, Turesson I, Landgren O (2008). "Risk of lymphoproliferative disorders among first-degree relatives of lymphoplasmacytic lymphoma/Waldenstrom macroglobulinemia patients: a population-based study in Sweden". Blood. 112 (8): 3052–6. doi:10.1182/blood-2008-06-162768. PMC 2569164. PMID 18703425.

[pmid12720118-21] 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.

[pmid12881316-22] 22.0 ^22.1 Kyle RA, Therneau TM, Rajkumar SV, Remstein ED, Offord JR, Larson DR; et al. (2003). "Long-term follow-up of IgM monoclonal gammopathy of undetermined significance". Blood. 102 (10): 3759–64. doi:10.1182/blood-2003-03-0801. PMID 12881316.

[pmid16034042-23] Baldini L, Goldaniga M, Guffanti A, Broglia C, Cortelazzo S, Rossi A; et al. (2005). "Immunoglobulin M monoclonal gammopathies of undetermined significance and indolent Waldenstrom's macroglobulinemia recognize the same determinants of evolution into symptomatic lymphoid disorders: proposal for a common prognostic scoring system". J Clin Oncol. 23 (21): 4662–8. doi:10.1200/JCO.2005.06.147. PMID 16034042.

[pmid28366781-24] 24.0 ^24.1 ^24.2 ^24.3 ^24.4 ^24.5 ^24.6 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.

[pmid18809818-25] 25.0 ^25.1 ^25.2 Koshiol J, Gridley G, Engels EA, McMaster ML, Landgren O (2008). "Chronic immune stimulation and subsequent Waldenström macroglobulinemia". Arch Intern Med. 168 (17): 1903–9. doi:10.1001/archinternmed.2008.4. PMC 2670401. PMID 18809818.

[pmid17488966-26] Giordano TP, Henderson L, Landgren O, Chiao EY, Kramer JR, El-Serag H; et al. (2007). "Risk of non-Hodgkin lymphoma and lymphoproliferative precursor diseases in US veterans with hepatitis C virus". JAMA. 297 (18): 2010–7. doi:10.1001/jama.297.18.2010. PMID 17488966.

[TreonXu2012-27] 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.

[pmid23355535-28] 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.

[pmid26231802-29] 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.

[pmid23836557-30] 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.

[pmid21179087-31] 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.

[pmid24224040-32] 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.

[pmid29080258-33] 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.

[TreonHunter2006-34] 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.

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@@ Line 74: / Line 74: @@
 *Previous history of IgM Monoclonal gammopathy of undetermined significance (MGUS) in patient of WM.<ref name="pmid12720118">{{cite journal| author=Owen RG, Treon SP, Al-Katib A, Fonseca R, Greipp PR, McMaster ML et al.| title=Clinicopathological definition of Waldenstrom's macroglobulinemia: consensus panel recommendations from the Second International Workshop on Waldenstrom's Macroglobulinemia. | journal=Semin Oncol | year= 2003 | volume= 30 | issue= 2 | pages= 110-5 | pmid=12720118 | doi=10.1053/sonc.2003.50082 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=12720118  }} </ref><ref name="pmid12881316">{{cite journal| author=Kyle RA, Therneau TM, Rajkumar SV, Remstein ED, Offord JR, Larson DR et al.| title=Long-term follow-up of IgM monoclonal gammopathy of undetermined significance. | journal=Blood | year= 2003 | volume= 102 | issue= 10 | pages= 3759-64 | pmid=12881316 | doi=10.1182/blood-2003-03-0801 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=12881316  }} </ref><ref name="pmid12881316">{{cite journal| author=Kyle RA, Therneau TM, Rajkumar SV, Remstein ED, Offord JR, Larson DR et al.| title=Long-term follow-up of IgM monoclonal gammopathy of undetermined significance. | journal=Blood | year= 2003 | volume= 102 | issue= 10 | pages= 3759-64 | pmid=12881316 | doi=10.1182/blood-2003-03-0801 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=12881316  }} </ref><ref name="pmid16034042">{{cite journal| author=Baldini L, Goldaniga M, Guffanti A, Broglia C, Cortelazzo S, Rossi A et al.| title=Immunoglobulin M monoclonal gammopathies of undetermined significance and indolent Waldenstrom's macroglobulinemia recognize the same determinants of evolution into symptomatic lymphoid disorders: proposal for a common prognostic scoring system. | journal=J Clin Oncol | year= 2005 | volume= 23 | issue= 21 | pages= 4662-8 | pmid=16034042 | doi=10.1200/JCO.2005.06.147 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=16034042  }} </ref>
 *Age older than 60 years.<ref name="pmid28366781">{{cite journal| author=Yun S, Johnson AC, Okolo ON, Arnold SJ, McBride A, Zhang L et al.| title=Waldenström Macroglobulinemia: Review of Pathogenesis and Management. | journal=Clin Lymphoma Myeloma Leuk | year= 2017 | volume= 17 | issue= 5 | pages= 252-262 | pmid=28366781 | doi=10.1016/j.clml.2017.02.028 | pmc=5413391 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=28366781  }} </ref>
-*Having a Hepatitis C virus infection.
+*Personal history of autoimmune diseases with autoantibodies leads to 2-3 fold higher risk of developing WM, especially elevated risks are associated with following:
-*Being a male.<ref name="pmid28366781">{{cite journal| author=Yun S, Johnson AC, Okolo ON, Arnold SJ, McBride A, Zhang L et al.| title=Waldenström Macroglobulinemia: Review of Pathogenesis and Management. | journal=Clin Lymphoma Myeloma Leuk | year= 2017 | volume= 17 | issue= 5 | pages= 252-262 | pmid=28366781 | doi=10.1016/j.clml.2017.02.028 | pmc=5413391 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=28366781  }} </ref>
+**Hepatitis C virus infection (overall 20-30% increased risk for non-Hodgkin lymohoma and 3-fold increased risk for WM).<ref name="pmid18703425">{{cite journal| author=Kristinsson SY, Björkholm M, Goldin LR, McMaster ML, Turesson I, Landgren O| title=Risk of lymphoproliferative disorders among first-degree relatives of lymphoplasmacytic lymphoma/Waldenstrom macroglobulinemia patients: a population-based study in Sweden. | journal=Blood | year= 2008 | volume= 112 | issue= 8 | pages= 3052-6 | pmid=18703425 | doi=10.1182/blood-2008-06-162768 | pmc=2569164 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=18703425  }} </ref><ref name="pmid18809818">{{cite journal| author=Koshiol J, Gridley G, Engels EA, McMaster ML, Landgren O| title=Chronic immune stimulation and subsequent Waldenström macroglobulinemia. | journal=Arch Intern Med | year= 2008 | volume= 168 | issue= 17 | pages= 1903-9 | pmid=18809818 | doi=10.1001/archinternmed.2008.4 | pmc=2670401 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=18809818  }} </ref>
+**HIV.<ref name="pmid18809818">{{cite journal| author=Koshiol J, Gridley G, Engels EA, McMaster ML, Landgren O| title=Chronic immune stimulation and subsequent Waldenström macroglobulinemia. | journal=Arch Intern Med | year= 2008 | volume= 168 | issue= 17 | pages= 1903-9 | pmid=18809818 | doi=10.1001/archinternmed.2008.4 | pmc=2670401 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=18809818  }} </ref>
+**Rickettsiosis.<ref name="pmid18809818">{{cite journal| author=Koshiol J, Gridley G, Engels EA, McMaster ML, Landgren O| title=Chronic immune stimulation and subsequent Waldenström macroglobulinemia. | journal=Arch Intern Med | year= 2008 | volume= 168 | issue= 17 | pages= 1903-9 | pmid=18809818 | doi=10.1001/archinternmed.2008.4 | pmc=2670401 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=18809818  }} </ref>
+*Being a male.<ref name="pmid28366781">{{cite journal| author=Yun S, Johnson AC, Okolo ON, Arnold SJ, McBride A, Zhang L et al.| title=Waldenström Macroglobulinemia: Review of Pathogenesis and Management. | journal=Clin Lymphoma Myeloma Leuk | year= 2017 | volume= 17 | issue= 5 | pages= 252-262 | pmid=28366781 | doi=10.1016/j.clml.2017.02.028 | pmc=5413391 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=28366781  }} </ref><ref name="pmid17488966">{{cite journal| author=Giordano TP, Henderson L, Landgren O, Chiao EY, Kramer JR, El-Serag H et al.| title=Risk of non-Hodgkin lymphoma and lymphoproliferative precursor diseases in US veterans with hepatitis C virus. | journal=JAMA | year= 2007 | volume= 297 | issue= 18 | pages= 2010-7 | pmid=17488966 | doi=10.1001/jama.297.18.2010 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=17488966  }} </ref>
 *Being a Caucasian.<ref name="pmid28366781">{{cite journal| author=Yun S, Johnson AC, Okolo ON, Arnold SJ, McBride A, Zhang L et al.| title=Waldenström Macroglobulinemia: Review of Pathogenesis and Management. | journal=Clin Lymphoma Myeloma Leuk | year= 2017 | volume= 17 | issue= 5 | pages= 252-262 | pmid=28366781 | doi=10.1016/j.clml.2017.02.028 | pmc=5413391 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=28366781  }} </ref>
 ===Genetics===