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Splenic marginal zone lymphoma

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Muhammad Affan M.D.[2], Sowminya Arikapudi, M.B,B.S. [3]

Synonyms and keywords: SMZL, SLVL, Splenic marginal zone B-cell lymphoma, Splenic B-cell marginal zone lymphoma Splenic lymphoma with circulating villous lymphocytes, splenic lymphoma with villous lymphocytes,

Overview

Overview

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Muhammad Affan M.D.[2], Sowminya Arikapudi, M.B,B.S. [3]

Overview

Splenic marginal zone lymphoma (SMZL) is rare, indolent B-cell lymphoma that may arise from either pre germinal or germinal/post germinal center replacing the normal architecture of the white pulp of the spleen. Chromosomal aberrations and gene mutations involved in the pathogenesis of splenic marginal zone lymphoma include 7q32 deletion, gain of function 3q, 4q and NOTCH2, TP53, KLF2 and immunoglobulin heavy chain gene. On microscopic histopathological analysis, micronodular lymphocytic infiltration of the white pulp along with biphasic distribution of neoplastic B-cells in the follicles of spleen, mixed pattern of lymphocytic infiltration of the bone marrow and villous lymphocytes in peripheral blood, are the characteristic findings of splenic marginal zone lymphoma (SMZL). Hepatitis C viral antigen is also assumed to be involved in its causation. Splenic marginal zone lymphoma (SMZL) must be differentiated from other B-cell lymphomas such as chronic lymphocytic leukemia, follicular lymphoma, and mantle cell lymphoma and unclassifiable splenic lymphomas including hairy cell leukemia variant (HCL-v) and splenic diffuse red pulp small B-cell lymphoma (SDRPL). The incidence of splenic marginal zone lymphoma (SMZL) increases with age; the median age at diagnosis is 65-70 years. Splenic marginal zone lymphoma (SMZL) affects men and women equally. There are no established risk factors. According to the the U.S. Preventive Service Task Force (USPSTF), there is insufficient evidence to recommend routine screening. Low Hemoglobin levels, high lactate dehydrogenase levels, low blood serum albumin levels, and genetic mutations in NOTCH2 TP53 genes are associated with poor prognosis. According to the Lugano classification, there are four stages of splenic marginal zone lymphoma (SMZL) based on the number of nodes and extranodal involvement. The most common symptoms of splenic marginal zone lymphoma include fever, weight loss, skin rash, night sweats, chest pain, abdominal pain, bone pain, and painless swelling in the neck, axilla, groin, thorax, and abdomen. Common physical examination findings of splenic marginal zone lymphoma (SMZL) include fever, rash, ulcer, splenomegaly, chest tenderness, abdomen tenderness, bone tenderness, peripheral lymphadenopathy, and central lymphadenopathy. Laboratory tests for splenic marginal zone lymphoma (SMZL) include complete blood count (CBC), blood chemistry studies, cytogenetic analysis, flow cytometry, immunohistochemistry, genetic testing, FISH, PCR, and immunophenotyping. Lymph node or extranodal tissue( spleen, bone marrow) biopsy is diagnostic of splenic marginal zone lymphoma.splenomegaly and lymphadenopathy and other organs involvement may be seen on abdominal ultrasound, CT scan, MRI and PET scan in patients with splenic marginal zone lymphoma (SMZL). Other diagnostic studies include laparoscopy, laparotomy. The optimal therapy for splenic marginal zone lymphoma (SMZL) depends on the clinical presentation of the patient. Asymptomatic patients may be observed closely without any treatment. Splenomegaly related symptoms such as abdominal distension, tenderness, early satiety, bloating and cytopenia due to hypersplenism may be managed with splenectomy but if bone marrow is involved it will persist even after surgery. Splenectomy was considered to be the first line treatment option but studies reported recently that rituximab alone or in combination with chemotherapy is equally effective if not better in terms of complete remission, progression free and overall survival and in addition there is no surgical risk. Studies have also shown that patients who relapsed while on treatment with rituximab, responded well with retreatment. Patients with hepatitis C who developed splenic marginal zone lymphoma (SMZL) have shown tumor regression with antiviral therapy.

Historical Perspective

The term splenic marginal zone lymphoma (SMZL) was used by C. Schmid in 1992 and is described as separate entity from marginal zone lymphoma in the World Health Organization classification of lymphoid neoplasms in 2001.

Pathophysiology

The exact pathogenesis of splenic marginal zone lymphoma (SMZL) is not clearly understood but according to some studies chronic immunologic stimulation and certain gene mutations are assumed to be involved. The common chromosomal aberrations and genetic mutations in splenic marginal zone lymphoma (SMZL) includes 7q32 deletion, gain of function mutation in 3q and NOTCH2, TP53, KLF2 gene mutations. These genes control certain cell regulation pathways that are involved in normal functioning of the cell. Hepatitis C viral antigen has also been assumed to be involved in its pathogenesis. Spleen, bone marrow, lymph nodes, liver and blood may be infiltrated with the tumor and have certain distintive features. On microscopic histopathological analysis, B-cells, villous lymphocytes, and sinus invasion are characteristic findings of splenic marginal zone lymphoma (SMZL).

Causes

Some studies suggest an association between Hepatitis C and splenic marginal zone lymphoma (SMZL) and assume that it may have some role in its causation.

Differential Diagnosis

Splenic marginal zone lymphoma (SMZL) must be differentiated from other B-cell lymphomas such as chronic lymphocytic leukemia, follicular lymphoma, mantle cell lymphoma and unclassifiable B-cell lymphomas including Hairy cell leukemia variant (HCL-v) and splenic diffuse red pulp small B-cell lymphoma (SDRPL) on the basis of cytogenetics, immunophenotyping and morphological as the treatment for these conditions varies.

Epidemiology and demographics

Splenic marginal zone lymphoma (SMZL) constitutes less than 1% of all non-Hodgkin’s lymphomas. Its incidence increases with age. It is found to be more common in caucasians. Splenic marginal zone lymphoma (SMZL) affects men and women equally.

Risk Factors

There are no established risk factors for splenic marginal zone lymphoma.

Screening

According to the the U.S. Preventive Service Task Force (USPSTF), there is insufficient evidence to recommend routine screening for splenic marginal zone lymphoma

Natural History, Complications and Prognosis

Splenic marginal zone lymphoma (SMZL) is a rare, slow growing B-cell lymphoma that is mostly asymptomatic at the time of diagnosis. It is commonly diagnosed at an old age. Patients typically have splenomegaly, lymphocytosis or cytopenias. Bone marrow is frequently involved but lymphadenopathy and liver involvement is rare.There are automimmune conditions that may develop in this conditions such autoimmune hemolytic anemia, idiopathic thrombocytopenic purpura, angioedema and von-willebrand disease. It may transform into diffuse large B-cell lymphoma. The prognosis is generally good. Several factors including lymphadenopathy, non-hematopoietic site involvement, histologic transformation affects the prognosis. Low Hemoglobin levels, high lactate dehydrogenase levels, low blood serum albumin levels, and genetic mutations such as mutations in NOTCH2, TP53, KLF2 are associated with poor prognosis among patients with splenic marginal zone lymphoma.

Diagnosis

Diagnostic Study of Choice

Histological examination of the spleen is considered as a gold standard for the diagnosis of splenic marginal zone lymphoma (SMZL). But as splenectomy is not as frequently performed as it was other diagnostic options are sought which includes histological analysis and immunohistochemistry of the bone marrow biopsy and peripheral blood. Cytogenetic analysis is also helpful in making the diagnosis.

Staging

According to the Lugano classification, there are four stages of splenic marginal zone lymphoma (SMZL) based on the number of nodes and extranodal involvement.

History and Symptoms

The most common symptoms of splenic marginal zone lymphoma (SMZL) include fever, weight loss, skin rash, night sweats, chest pain, abdominal pain, bone pain, and painless swelling in the neck, axilla, groin, thorax, and abdomen.

Physical Examination

Common physical examination findings of splenic marginal zone lymphoma (SMZL) include fever, rash, ulcer, splenomegaly, chest tenderness, abdomen tenderness, bone tenderness, peripheral lymphadenopathy, and central lymphadenopathy.

Laboratory tests

Laboratory tests for splenic marginal zone lymphoma (SMZL) include complete blood count (CBC), blood chemistry studies, immunohistochemistry, genetic testing, flow cytometry, FISH, PCR, and immunophenotyping.

Biopsy

Lymph node or extranodal tissue biopsy is diagnostic of splenic marginal zone lymphoma (SMZL).

CT

CT scan may be helpful in the diagnosis and estimating the extent of tumor spread in splenic marginal zone lymphoma (SMZL).

MRI

MRI may be helpful in the diagnosis of splenic marginal zone lymphoma (SMZL).

Ultrasound

Abdomen ultrasound may be helpful in the diagnosis of splenic marginal zone lymphoma (SMZL). Findings on ultrasound abdomen suggestive of splenic marginal zone lymphoma (SMZL) include splenomegaly and lymphadenopathy.

Other Imaging Studies

PET scan may be helpful in the diagnosis of splenic marginal zone lymphoma (SMZL).

Other Diagnostic Studies

Other diagnostic studies for splenic marginal zone lymphoma (SMZL) include laparoscopy and laparotomy.

Treatment

Medical Therapy

There is no standardized treatment of splenic marginal zone lymphoma (SMZL) The optimal therapy depends on the clinical presentation. Asymptomatic patients may only be observed routinely without any treatment as it is an indolent tumor. Symptomatic patients may treated with either surgery, immunotherapy, chemotherapy, immunochemotherapy or antiviral drugs. Both surgery and immunotherapy are equally effective but recently immunotherapy is considered as a better treatment option as there is no risk of complications that are associated with surgery.

Surgery

Splenectomy was considered to be the 1st line treatment option for splenic marginal zone lymphoma (SMZL) but recent studies have shown that rituximab is equally effective if not better treatment option in terms of overall survival. Splenectomy is still performed but mainly in patients with splenomegaly without lymphadenopathy having low surgical risk or in those who are refractory to rituximab therapy.

Historical Perspective

Historical Perspective

Overview

The term splenic marginal zone lymphoma (SMZL) was first used by C. Schmid in 1992 and described as separate entity from marginal zone lymphoma in the World Health Organization classification of lymphoid neoplasms in 2001.

Historical Perspective

References

  1. ↑ Schmid C, Kirkham N, Diss T, Isaacson PG (May 1992). “Splenic marginal zone cell lymphoma”. Am. J. Surg. Pathol. 16 (5): 455–66. PMID 1599024.
  2. ↑ Chan JK (December 2001). “The new World Health Organization classification of lymphomas: the past, the present and the future”. Hematol Oncol. 19 (4): 129–50. PMID 11754390.

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Classification

Classification

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Muhammad Affan M.D.[2], Sowminya Arikapudi, M.B,B.S. [3]

Overview

There is no established system for the classification of splenic marginal zone lymphoma (SMZL).

Classification

There is no established system for the classification of splenic marginal zone lymphoma (SMZL)

References

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Pathophysiology

Pathophysiology

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [3]; Associate Editor(s)-in-Chief: Muhammad Affan M.D.[4], Sowminya Arikapudi, M.B,B.S. [5]

Overview

The exact pathogenesis of splenic marginal zone lymphoma (SMZL) is not clearly understood but according to some studies chronic immunologic stimulation and certain gene mutations are assumed to be involved. The common chromosomal aberrations and genetic mutations in splenic marginal zone lymphoma (SMZL) includes 7q32 deletion, gain of function mutation in 3q and NOTCH2, TP53, KLF2 gene mutations. These genes control certain cell regulation pathways that are involved in normal functioning of the cell. Hepatitis C viral antigen has also been assumed to be involved in its pathogenesis. Spleen, bone marrow, lymph nodes, liver and blood may be infiltrated with the tumor and have certain distintive features. On microscopic histopathological analysis, B-cells, villous lymphocytes, and sinus invasion are characteristic findings of splenic marginal zone lymphoma (SMZL).

Pathophysiology

Pathogenesis

Genetics

  • There are several pathways involved in the normal functioning of the cells. Genetic dysregulation may affect these pathways resulting in abnormal function.
  • Common genetic abnormalities and their affected pathways in splenic marginal zone lymphoma are summarized under:
Pathways Gene mutations

NFkB[24][25][19]

Apoptosis[26][27]

Cell communication[28][29][30]

Cell cycle control[15][27][30]

Lymphocyte development and regulation[28][25][30]

Chromosomal and transcriptional regulation[25][31]

Associated conditions

Microscopic Pathology

Spleen

  • Micronodular pattern of lymphocytic infiltration of the white pulp involving both mantle and marginal zone component.[39]
  • Biphasic distribution of neoplastic B-cell in the follicles i.e small cells having dense chromatin and scant cytoplasm surrounded by intermediate size cells of marginal zone having variable nuclear contour and relatively abundant cytoplasm with interspersed large B-cells.
  • Red pulp may also be involved either sparingly or diffusely penetrating the sinuses and cords.[40]

Bone Marrow:

Lymph nodes

Blood

References

  1. ↑ Fonte E, Agathangelidis A, Reverberi D, Ntoufa S, Scarfò L, Ranghetti P, Cutrona G, Tedeschi A, Xochelli A, Caligaris-Cappio F, Ponzoni M, Belessi C, Davis Z, Piris MA, Oscier D, Ghia P, Stamatopoulos K, Muzio M (November 2015). “Toll-like receptor stimulation in splenic marginal zone lymphoma can modulate cell signaling, activation and proliferation”. Haematologica. 100 (11): 1460–8. doi:10.3324/haematol.2014.119933. PMC 4825289. PMID 26294727.
  2. ↑ Franco G, Guarnotta C, Frossi B, Piccaluga PP, Boveri E, Gulino A, Fuligni F, Rigoni A, Porcasi R, Buffa S, Betto E, Florena AM, Franco V, Iannitto E, Arcaini L, Pileri SA, Pucillo C, Colombo MP, Sangaletti S, Tripodo C (March 2014). “Bone marrow stroma CD40 expression correlates with inflammatory mast cell infiltration and disease progression in splenic marginal zone lymphoma”. Blood. 123 (12): 1836–49. doi:10.1182/blood-2013-04-497271. PMID 24452203.
  3. ↑ Dunn-Walters DK, Boursier L, Spencer J, Isaacson PG (June 1998). “Analysis of immunoglobulin genes in splenic marginal zone lymphoma suggests ongoing mutation”. Hum. Pathol. 29 (6): 585–93. PMID 9635678.
  4. ↑ Miranda RN, Cousar JB, Hammer RD, Collins RD, Vnencak-Jones CL (March 1999). “Somatic mutation analysis of IgH variable regions reveals that tumor cells of most parafollicular (monocytoid) B-cell lymphoma, splenic marginal zone B-cell lymphoma, and some hairy cell leukemia are composed of memory B lymphocytes”. Hum. Pathol. 30 (3): 306–12. PMID 10088550.
  5. ↑ Tierens A, Delabie J, Pittaluga S, Driessen A, DeWolf-Peeters C (April 1998). “Mutation analysis of the rearranged immunoglobulin heavy chain genes of marginal zone cell lymphomas indicates an origin from different marginal zone B lymphocyte subsets”. Blood. 91 (7): 2381–6. PMID 9516137.
  6. ↑ Camacho FI, Mollejo M, Mateo MS, Algara P, Navas C, Hernández JM, Santoja C, Solé F, Sánchez-Beato M, Piris MA (October 2001). “Progression to large B-cell lymphoma in splenic marginal zone lymphoma: a description of a series of 12 cases”. Am. J. Surg. Pathol. 25 (10): 1268–76. PMID 11688461.
  7. ↑ Stevenson F, Sahota S, Zhu D, Ottensmeier C, Chapman C, Oscier D, Hamblin T (April 1998). “Insight into the origin and clonal history of B-cell tumors as revealed by analysis of immunoglobulin variable region genes”. Immunol. Rev. 162: 247–59. PMID 9602369.
  8. ↑ Campo E, Swerdlow SH, Harris NL, Pileri S, Stein H, Jaffe ES (May 2011). “The 2008 WHO classification of lymphoid neoplasms and beyond: evolving concepts and practical applications”. Blood. 117 (19): 5019–32. doi:10.1182/blood-2011-01-293050. PMC 3109529. PMID 21300984.
  9. ↑ Spencer J, Perry ME, Dunn-Walters DK (September 1998). “Human marginal-zone B cells”. Immunol. Today. 19 (9): 421–6. PMID 9745206.
  10. ↑ Timens W, Poppema S (September 1985). “Lymphocyte compartments in human spleen. An immunohistologic study in normal spleens and uninvolved spleens in Hodgkin’s disease”. Am. J. Pathol. 120 (3): 443–54. PMC 1887979. PMID 3898859.
  11. ↑ [1] Dunn-Walters DK, Boursier L, Spencer J, Isaacson PG. “Analysis of immunoglobulin genes in splenic marginal zone lymphoma suggests ongoing mutation.” Hum Pathol. 1998 Jun;29(6):585-93. PMID: 9635678
  12. ↑ Boonstra R, Bosga-Bouwer A, van Imhoff GW, Krause V, Palmer M, Coupland RW, Dabbagh L, van den Berg E, van den Berg A, Poppema S (December 2003). “Splenic marginal zone lymphomas presenting with splenomegaly and typical immunophenotype are characterized by allelic loss in 7q31-32”. Mod. Pathol. 16 (12): 1210–7. doi:10.1097/01.MP.0000095895.19756.77. PMID 14681321.
  13. ↑ Hernández JM, García JL, Gutiérrez NC, Mollejo M, Martínez-Climent JA, Flores T, González MB, Piris MA, San Miguel JF (May 2001). “Novel genomic imbalances in B-cell splenic marginal zone lymphomas revealed by comparative genomic hybridization and cytogenetics”. Am. J. Pathol. 158 (5): 1843–50. doi:10.1016/S0002-9440(10)64140-5. PMC 1891967. PMID 11337382.
  14. ↑ Andersen CL, Gruszka-Westwood A, Atkinson S, Matutes E, Catovsky D, Pedersen RK, Pedersen BB, Pulczynski S, Hokland P, Jacobsen E, Koch J (January 2005). “Recurrent genomic imbalances in B-cell splenic marginal-zone lymphoma revealed by comparative genomic hybridization”. Cancer Genet. Cytogenet. 156 (2): 122–8. doi:10.1016/j.cancergencyto.2004.04.026. PMID 15642391.
  15. ↑ 15.0 15.1 Salido M, Baró C, Oscier D, Stamatopoulos K, Dierlamm J, Matutes E, Traverse-Glehen A, Berger F, Felman P, Thieblemont C, Gesk S, Athanasiadou A, Davis Z, Gardiner A, Milla F, Ferrer A, Mollejo M, Calasanz MJ, Florensa L, Espinet B, Luño E, Wlodarska I, Verhoef G, García-Granero M, Salar A, Papadaki T, Serrano S, Piris MA, Solé F (September 2010). “Cytogenetic aberrations and their prognostic value in a series of 330 splenic marginal zone B-cell lymphomas: a multicenter study of the Splenic B-Cell Lymphoma Group”. Blood. 116 (9): 1479–88. doi:10.1182/blood-2010-02-267476. PMID 20479288.
  16. ↑ Rossi D, Trifonov V, Fangazio M, Bruscaggin A, Rasi S, Spina V, Monti S, Vaisitti T, Arruga F, Famà R, Ciardullo C, Greco M, Cresta S, Piranda D, Holmes A, Fabbri G, Messina M, Rinaldi A, Wang J, Agostinelli C, Piccaluga PP, Lucioni M, Tabbò F, Serra R, Franceschetti S, Deambrogi C, Daniele G, Gattei V, Marasca R, Facchetti F, Arcaini L, Inghirami G, Bertoni F, Pileri SA, Deaglio S, Foà R, Dalla-Favera R, Pasqualucci L, Rabadan R, Gaidano G (August 2012). “The coding genome of splenic marginal zone lymphoma: activation of NOTCH2 and other pathways regulating marginal zone development”. J. Exp. Med. 209 (9): 1537–51. doi:10.1084/jem.20120904. PMID 22891273.
  17. ↑ Trøen G, Wlodarska I, Warsame A, Hernández Llodrà S, De Wolf-Peeters C, Delabie J (July 2008). “NOTCH2 mutations in marginal zone lymphoma”. Haematologica. 93 (7): 1107–9. doi:10.3324/haematol.11635. PMID 18508802.
  18. ↑ Piva R, Deaglio S, Famà R, Buonincontri R, Scarfò I, Bruscaggin A, Mereu E, Serra S, Spina V, Brusa D, Garaffo G, Monti S, Dal Bo M, Marasca R, Arcaini L, Neri A, Gattei V, Paulli M, Tiacci E, Bertoni F, Pileri SA, Foà R, Inghirami G, Gaidano G, Rossi D (February 2015). “The Krüppel-like factor 2 transcription factor gene is recurrently mutated in splenic marginal zone lymphoma”. Leukemia. 29 (2): 503–7. doi:10.1038/leu.2014.294. PMID 25283840.
  19. ↑ 19.0 19.1 Rossi D, Deaglio S, Dominguez-Sola D, Rasi S, Vaisitti T, Agostinelli C, Spina V, Bruscaggin A, Monti S, Cerri M, Cresta S, Fangazio M, Arcaini L, Lucioni M, Marasca R, Thieblemont C, Capello D, Facchetti F, Kwee I, Pileri SA, Foà R, Bertoni F, Dalla-Favera R, Pasqualucci L, Gaidano G (November 2011). “Alteration of BIRC3 and multiple other NF-κB pathway genes in splenic marginal zone lymphoma”. Blood. 118 (18): 4930–4. doi:10.1182/blood-2011-06-359166. PMID 21881048.
  20. ↑ Spina V, Rossi D (August 2016). “NF-κB deregulation in splenic marginal zone lymphoma”. Semin. Cancer Biol. 39: 61–7. doi:10.1016/j.semcancer.2016.08.002. PMID 27503810.
  21. ↑ Baldini L, Fracchiolla NS, Cro LM, Trecca D, Romitti L, Polli E, Maiolo AT, Neri A (July 1994). “Frequent p53 gene involvement in splenic B-cell leukemia/lymphomas of possible marginal zone origin”. Blood. 84 (1): 270–8. PMID 8018922.
  22. ↑ Gruszka-Westwood AM, Hamoudi RA, Matutes E, Tuset E, Catovsky D (June 2001). “p53 abnormalities in splenic lymphoma with villous lymphocytes”. Blood. 97 (11): 3552–8. PMID 11369650.
  23. ↑ [2] Corcoran MM, Mould SJ, Orchard JA, Ibbotson RE, Chapman RM, Boright AP, Platt C, Tsui LC, Scherer SW, Oscier DG. “Dysregulation of cyclin dependent kinase 6 expression in splenic marginal zone lymphoma through chromosome 7q translocations.” Oncogene. 1999 Nov 4;18(46):6271-7. PMID: 10597225
  24. ↑ Clipson A, Wang M, de Leval L, Ashton-Key M, Wotherspoon A, Vassiliou G, Bolli N, Grove C, Moody S, Escudero-Ibarz L, Gundem G, Brugger K, Xue X, Mi E, Bench A, Scott M, Liu H, Follows G, Robles EF, Martinez-Climent JA, Oscier D, Watkins AJ, Du MQ (May 2015). “KLF2 mutation is the most frequent somatic change in splenic marginal zone lymphoma and identifies a subset with distinct genotype”. Leukemia. 29 (5): 1177–85. doi:10.1038/leu.2014.330. PMID 25428260.
  25. ↑ 25.0 25.1 25.2 Parry M, Rose-Zerilli MJ, Ljungström V, Gibson J, Wang J, Walewska R, Parker H, Parker A, Davis Z, Gardiner A, McIver-Brown N, Kalpadakis C, Xochelli A, Anagnostopoulos A, Fazi C, de Castro DG, Dearden C, Pratt G, Rosenquist R, Ashton-Key M, Forconi F, Collins A, Ghia P, Matutes E, Pangalis G, Stamatopoulos K, Oscier D, Strefford JC (September 2015). “Genetics and Prognostication in Splenic Marginal Zone Lymphoma: Revelations from Deep Sequencing”. Clin. Cancer Res. 21 (18): 4174–4183. doi:10.1158/1078-0432.CCR-14-2759. PMC 4490180. PMID 25779943.
  26. ↑ Ruiz-Ballesteros E, Mollejo M, Rodriguez A, Camacho FI, Algara P, Martinez N, Pollán M, Sanchez-Aguilera A, Menarguez J, Campo E, Martinez P, Mateo M, Piris MA (September 2005). “Splenic marginal zone lymphoma: proposal of new diagnostic and prognostic markers identified after tissue and cDNA microarray analysis”. Blood. 106 (5): 1831–8. doi:10.1182/blood-2004-10-3898. PMID 15914563.
  27. ↑ 27.0 27.1 Trøen G, Nygaard V, Jenssen TK, Ikonomou IM, Tierens A, Matutes E, Gruszka-Westwood A, Catovsky D, Myklebost O, Lauritzsen G, Hovig E, Delabie J (November 2004). “Constitutive expression of the AP-1 transcription factors c-jun, junD, junB, and c-fos and the marginal zone B-cell transcription factor Notch2 in splenic marginal zone lymphoma”. J Mol Diagn. 6 (4): 297–307. doi:10.1016/S1525-1578(10)60525-9. PMC 1867488. PMID 15507668.
  28. ↑ 28.0 28.1 Parry M, Rose-Zerilli MJ, Gibson J, Ennis S, Walewska R, Forster J, Parker H, Davis Z, Gardiner A, Collins A, Oscier DG, Strefford JC (2013). “Whole exome sequencing identifies novel recurrently mutated genes in patients with splenic marginal zone lymphoma”. PLoS ONE. 8 (12): e83244. doi:10.1371/journal.pone.0083244. PMC 3862727. PMID 24349473.
  29. ↑ Fresquet V, Robles EF, Parker A, Martinez-Useros J, Mena M, Malumbres R, Agirre X, Catarino S, Arteta D, Osaba L, Mollejo M, Hernandez-Rivas JM, Calasanz MJ, Daibata M, Dyer MJ, Prosper F, Vizcarra E, Piris MÁ, Oscier D, Martinez-Climent JA (September 2012). “High-throughput sequencing analysis of the chromosome 7q32 deletion reveals IRF5 as a potential tumour suppressor in splenic marginal-zone lymphoma”. Br. J. Haematol. 158 (6): 712–26. doi:10.1111/j.1365-2141.2012.09226.x. PMID 22816737.
  30. ↑ 30.0 30.1 30.2 Martínez N, Almaraz C, Vaqué JP, Varela I, Derdak S, Beltran S, Mollejo M, Campos-Martin Y, Agueda L, Rinaldi A, Kwee I, Gut M, Blanc J, Oscier D, Strefford JC, Martinez-Lopez J, Salar A, Sole F, Rodriguez-Peralto JL, Diez-Tascón C, García JF, Fraga M, Sebastián E, Alvés J, Menárguez J, González-Carreró J, Casado LF, Bayes M, Bertoni F, Gut I, Piris MA (June 2014). “Whole-exome sequencing in splenic marginal zone lymphoma reveals mutations in genes involved in marginal zone differentiation”. Leukemia. 28 (6): 1334–40. doi:10.1038/leu.2013.365. PMID 24296945.
  31. ↑ Rinaldi A, Forconi F, Arcaini L, Mian M, Sozzi E, Zibellini S, Baldini L, Franceschetti S, Gaidano G, Marasca R, Mollejo M, Piris MA, Tucci A, Facchetti F, Bhagat G, Favera RD, Rancoita PM, Zucca E, Kwee I, Bertoni F (December 2010). “Immunogenetics features and genomic lesions in splenic marginal zone lymphoma”. Br. J. Haematol. 151 (5): 435–9. PMID 21113978.
  32. ↑ Chuang SS, Liao YL, Chang ST, Hsieh YC, Kuo SY, Lu CL, Hwang WS, Lin IH, Tsao CJ, Huang WT (July 2010). “Hepatitis C virus infection is significantly associated with malignant lymphoma in Taiwan, particularly with nodal and splenic marginal zone lymphomas”. J. Clin. Pathol. 63 (7): 595–8. doi:10.1136/jcp.2010.076810. PMID 20530156.
  33. ↑ Gurvits GE, Mahtani R, Halperin I (November 2007). “Hepatitis C virus and splenic marginal zone lymphoma with villous lymphocytes: away from conventional therapy”. Scand. J. Gastroenterol. 42 (11): 1392–3. doi:10.1080/00365520701420800. PMID 17852855.
  34. ↑ Weng WK, Levy S (July 2003). “Hepatitis C virus (HCV) and lymphomagenesis”. Leuk. Lymphoma. 44 (7): 1113–20. doi:10.1080/1042819031000076972. PMID 12916862.
  35. ↑ Quinn ER, Chan CH, Hadlock KG, Foung SK, Flint M, Levy S (December 2001). “The B-cell receptor of a hepatitis C virus (HCV)-associated non-Hodgkin lymphoma binds the viral E2 envelope protein, implicating HCV in lymphomagenesis”. Blood. 98 (13): 3745–9. PMID 11739181.
  36. ↑ Hermine O, Lefrère F, Bronowicki JP, Mariette X, Jondeau K, Eclache-Saudreau V, Delmas B, Valensi F, Cacoub P, Brechot C, Varet B, Troussard X (July 2002). “Regression of splenic lymphoma with villous lymphocytes after treatment of hepatitis C virus infection”. N. Engl. J. Med. 347 (2): 89–94. doi:10.1056/NEJMoa013376. PMID 12110736.
  37. ↑ Zinzani PL (2012). “The many faces of marginal zone lymphoma”. Hematology Am Soc Hematol Educ Program. 2012: 426–32. doi:10.1182/asheducation-2012.1.426. PMID 23233614.
  38. ↑ Arcaini L, Rossi D, Paulli M (April 2016). “Splenic marginal zone lymphoma: from genetics to management”. Blood. 127 (17): 2072–81. doi:10.1182/blood-2015-11-624312. PMID 26989207.
  39. ↑ Papadaki T, Stamatopoulos K, Belessi C, Pouliou E, Parasi A, Douka V, Laoutaris N, Fassas A, Anagnostopoulos A, Anagnostou D (March 2007). “Splenic marginal-zone lymphoma: one or more entities? A histologic, immunohistochemical, and molecular study of 42 cases”. Am. J. Surg. Pathol. 31 (3): 438–46. doi:10.1097/01.pas.0000213419.08009.b0. PMID 17325486.
  40. ↑ Mollejo M, Algara P, Mateo MS, Sánchez-Beato M, Lloret E, Medina MT, Piris MA (January 2002). “Splenic small B-cell lymphoma with predominant red pulp involvement: a diffuse variant of splenic marginal zone lymphoma?”. Histopathology. 40 (1): 22–30. PMID 11903595.
  41. ↑ Mohanpuria A, Kumar V, Suteri P, Marwah S, Nigam AS (July 2017). “Important Diagnostic Clues for Diagnosing Splenic Marginal Zone Lymphoma in Absence of Splenic Histology”. J Clin Diagn Res. 11 (7): ED15–ED17. doi:10.7860/JCDR/2017/27149.10190. PMC 5583942. PMID 28892912.
  42. ↑ Iannitto E, Ambrosetti A, Ammatuna E, Colosio M, Florena AM, Tripodo C, Minardi V, Calvaruso G, Mitra ME, Pizzolo G, Menestrina F, Franco V (November 2004). “Splenic marginal zone lymphoma with or without villous lymphocytes. Hematologic findings and outcomes in a series of 57 patients”. Cancer. 101 (9): 2050–7. doi:10.1002/cncr.20596. PMID 15389479.
  43. ↑ Kent SA, Variakojis D, Peterson LC (May 2002). “Comparative study of marginal zone lymphoma involving bone marrow”. Am. J. Clin. Pathol. 117 (5): 698–708. doi:10.1309/MECJ-GLK1-WEBW-UEVE. PMID 12090417.
  44. ↑ Ponzoni M, Kanellis G, Pouliou E, Baliakas P, Scarfò L, Ferreri AJ, Doglioni C, Bikos V, Dagklis A, Anagnostopoulos A, Ghia P, Stamatopoulos K, Papadaki T (November 2012). “Bone marrow histopathology in the diagnostic evaluation of splenic marginal-zone and splenic diffuse red pulp small B-cell lymphoma: a reliable substitute for spleen histopathology?”. Am. J. Surg. Pathol. 36 (11): 1609–18. doi:10.1097/PAS.0b013e318271243d. PMID 23073320.
  45. ↑ Mollejo M, Lloret E, Menárguez J, Piris MA, Isaacson PG (July 1997). “Lymph node involvement by splenic marginal zone lymphoma: morphological and immunohistochemical features”. Am. J. Surg. Pathol. 21 (7): 772–80. PMID 9236833.
  46. ↑ Wolfe JM (1979). “The computer paper illusion”. Perception. 8 (3): 347–8. doi:10.1068/p080347. PMID 534161.

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Causes

Causes

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Muhammad Affan M.D.[2], Sowminya Arikapudi, M.B,B.S. [3]

Overview

Some studies suggest an association between Hepatitis C and splenic marginal zone lymphoma (SMZL) and assume that it may have some role in its causation.

Causes

References

  1. ↑ Peveling-Oberhag J, Crisman G, Schmidt A, Döring C, Lucioni M, Arcaini L, Rattotti S, Hartmann S, Piiper A, Hofmann WP, Paulli M, Küppers R, Zeuzem S, Hansmann ML (July 2012). “Dysregulation of global microRNA expression in splenic marginal zone lymphoma and influence of chronic hepatitis C virus infection”. Leukemia. 26 (7): 1654–62. doi:10.1038/leu.2012.29. PMID 22307176.

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Differentiating Splenic marginal zone lymphoma from other Diseases

Differentiating Splenic marginal zone lymphoma from other Diseases

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Muhammad Affan M.D.[2], Sowminya Arikapudi, M.B,B.S. [3]

Overview

Splenic marginal zone lymphoma (SMZL) must be differentiated from other B-cell lymphomas such as chronic lymphocytic leukemia, follicular lymphoma, mantle cell lymphoma and unclassifiable B-cell lymphomas including Hairy cell leukemia variant (HCL-v) and splenic diffuse red pulp small B-cell lymphoma (SDRPL) on the basis of cytogenetics, immunophenotyping and morphological as the treatment for these conditions varies.

Differential Diagnosis

Splenic marginal zone lymphoma(SMZL) must be differentiated from other splenic B-cell lymphomas with the help of clincal, morphological, immunophenotypic and genetic data as the treatment of all these conditions are different from each other.[1][2][3][4][5][6][7][8][9][10][11][12][13][14][15][16][17][18][19][20][21][22][23][24][25][26][22][27][28]

Differential Diagnosis Cytogenetics Morphological Features Immunophenotype

Splenic marginal zone lymphoma

Splenic diffuse red pulp lymphoma

  • Uncommon: 7q deletion, trisomy 18, 17p deletion ( TP53)

Hairy cell leukemia variant

  • Common: Deletion 17p ( TP53),
  • Uncommon: 5q gain, deletion 7q
  • Gene mutation: MAP2K1

Hairy cell leukemia

  • Uncommon: 5q gain, 7q deletion
  • gene mutation: BRAF V600E

Lymphoplasmacytic lymphoma

  • Common: 6q deletion,
  • Uncommon: 13q deletion, 7q deletion
  • Gene mutation: MYD88 L265P

Chronic lymphocytic leukemia

Follicular lymphoma

Mantle cell lymphoma

References

  1. ↑ Matutes E, Oscier D, Montalban C, Berger F, Callet-Bauchu E, Dogan A, Felman P, Franco V, Iannitto E, Mollejo M, Papadaki T, Remstein ED, Salar A, Solé F, Stamatopoulos K, Thieblemont C, Traverse-Glehen A, Wotherspoon A, Coiffier B, Piris MA (March 2008). “Splenic marginal zone lymphoma proposals for a revision of diagnostic, staging and therapeutic criteria”. Leukemia. 22 (3): 487–95. doi:10.1038/sj.leu.2405068. PMID 18094718.
  2. ↑ Salido M, Baró C, Oscier D, Stamatopoulos K, Dierlamm J, Matutes E, Traverse-Glehen A, Berger F, Felman P, Thieblemont C, Gesk S, Athanasiadou A, Davis Z, Gardiner A, Milla F, Ferrer A, Mollejo M, Calasanz MJ, Florensa L, Espinet B, Luño E, Wlodarska I, Verhoef G, García-Granero M, Salar A, Papadaki T, Serrano S, Piris MA, Solé F (September 2010). “Cytogenetic aberrations and their prognostic value in a series of 330 splenic marginal zone B-cell lymphomas: a multicenter study of the Splenic B-Cell Lymphoma Group”. Blood. 116 (9): 1479–88. doi:10.1182/blood-2010-02-267476. PMID 20479288.
  3. ↑ Kiel MJ, Velusamy T, Betz BL, Zhao L, Weigelin HG, Chiang MY, Huebner-Chan DR, Bailey NG, Yang DT, Bhagat G, Miranda RN, Bahler DW, Medeiros LJ, Lim MS, Elenitoba-Johnson KS (August 2012). “Whole-genome sequencing identifies recurrent somatic NOTCH2 mutations in splenic marginal zone lymphoma”. J. Exp. Med. 209 (9): 1553–65. doi:10.1084/jem.20120910. PMC 3428949. PMID 22891276.
  4. ↑ Rossi D, Trifonov V, Fangazio M, Bruscaggin A, Rasi S, Spina V, Monti S, Vaisitti T, Arruga F, Famà R, Ciardullo C, Greco M, Cresta S, Piranda D, Holmes A, Fabbri G, Messina M, Rinaldi A, Wang J, Agostinelli C, Piccaluga PP, Lucioni M, Tabbò F, Serra R, Franceschetti S, Deambrogi C, Daniele G, Gattei V, Marasca R, Facchetti F, Arcaini L, Inghirami G, Bertoni F, Pileri SA, Deaglio S, Foà R, Dalla-Favera R, Pasqualucci L, Rabadan R, Gaidano G (August 2012). “The coding genome of splenic marginal zone lymphoma: activation of NOTCH2 and other pathways regulating marginal zone development”. J. Exp. Med. 209 (9): 1537–51. doi:10.1084/jem.20120904. PMC 3428941. PMID 22891273.
  5. ↑ Tiacci E, Trifonov V, Schiavoni G, Holmes A, Kern W, Martelli MP, Pucciarini A, Bigerna B, Pacini R, Wells VA, Sportoletti P, Pettirossi V, Mannucci R, Elliott O, Liso A, Ambrosetti A, Pulsoni A, Forconi F, Trentin L, Semenzato G, Inghirami G, Capponi M, Di Raimondo F, Patti C, Arcaini L, Musto P, Pileri S, Haferlach C, Schnittger S, Pizzolo G, Foà R, Farinelli L, Haferlach T, Pasqualucci L, Rabadan R, Falini B (June 2011). “BRAF mutations in hairy-cell leukemia”. N. Engl. J. Med. 364 (24): 2305–15. doi:10.1056/NEJMoa1014209. PMID 21663470.
  6. ↑ Waterfall JJ, Arons E, Walker RL, Pineda M, Roth L, Killian JK, Abaan OD, Davis SR, Kreitman RJ, Meltzer PS (January 2014). “High prevalence of MAP2K1 mutations in variant and IGHV4-34-expressing hairy-cell leukemias”. Nat. Genet. 46 (1): 8–10. doi:10.1038/ng.2828. PMC 3905739. PMID 24241536.
  7. ↑ Traverse-Glehen A, Baseggio L, Bauchu EC, Morel D, Gazzo S, Ffrench M, Verney A, Rolland D, Thieblemont C, Magaud JP, Salles G, Coiffier B, Berger F, Felman P (February 2008). “Splenic red pulp lymphoma with numerous basophilic villous lymphocytes: a distinct clinicopathologic and molecular entity?”. Blood. 111 (4): 2253–60. doi:10.1182/blood-2007-07-098848. PMID 18042795.
  8. ↑ Braggio E, Dogan A, Keats JJ, Chng WJ, Huang G, Matthews JM, Maurer MJ, Law ME, Bosler DS, Barrett M, Lossos IS, Witzig TE, Fonseca R (May 2012). “Genomic analysis of marginal zone and lymphoplasmacytic lymphomas identified common and disease-specific abnormalities”. Mod. Pathol. 25 (5): 651–60. doi:10.1038/modpathol.2011.213. PMC 3341516. PMID 22301699.
  9. ↑ Traverse-Glehen A, Bachy E, Baseggio L, Callet-Bauchu E, Gazzo S, Verney A, Hayette S, Jallades L, Ffrench M, Salles G, Coiffier B, Felman P, Berger F (May 2013). “Immunoarchitectural patterns in splenic marginal zone lymphoma: correlations with chromosomal aberrations, IGHV mutations, and survival. A study of 76 cases”. Histopathology. 62 (6): 876–93. doi:10.1111/his.12092. PMID 23611359.
  10. ↑ Xi L, Arons E, Navarro W, Calvo KR, Stetler-Stevenson M, Raffeld M, Kreitman RJ (April 2012). “Both variant and IGHV4-34-expressing hairy cell leukemia lack the BRAF V600E mutation”. Blood. 119 (14): 3330–2. doi:10.1182/blood-2011-09-379339. PMC 3321859. PMID 22210875.
  11. ↑ Matutes E, Morilla R, Owusu-Ankomah K, Houlihan A, Catovsky D (March 1994). “The immunophenotype of splenic lymphoma with villous lymphocytes and its relevance to the differential diagnosis with other B-cell disorders”. Blood. 83 (6): 1558–62. PMID 8123845.
  12. ↑ Venkataraman G, Aguhar C, Kreitman RJ, Yuan CM, Stetler-Stevenson M (October 2011). “Characteristic CD103 and CD123 expression pattern defines hairy cell leukemia: usefulness of CD123 and CD103 in the diagnosis of mature B-cell lymphoproliferative disorders”. Am. J. Clin. Pathol. 136 (4): 625–30. doi:10.1309/AJCPKUM9J4IXCWEU. PMID 21917686.
  13. ↑ Ponzoni M, Kanellis G, Pouliou E, Baliakas P, Scarfò L, Ferreri AJ, Doglioni C, Bikos V, Dagklis A, Anagnostopoulos A, Ghia P, Stamatopoulos K, Papadaki T (November 2012). “Bone marrow histopathology in the diagnostic evaluation of splenic marginal-zone and splenic diffuse red pulp small B-cell lymphoma: a reliable substitute for spleen histopathology?”. Am. J. Surg. Pathol. 36 (11): 1609–18. doi:10.1097/PAS.0b013e318271243d. PMID 23073320.
  14. ↑ Falini B, Tiacci E, Liso A, Basso K, Sabattini E, Pacini R, Foa R, Pulsoni A, Dalla Favera R, Pileri S (June 2004). “Simple diagnostic assay for hairy cell leukaemia by immunocytochemical detection of annexin A1 (ANXA1)”. Lancet. 363 (9424): 1869–70. doi:10.1016/S0140-6736(04)16356-3. PMID 15183626.
  15. ↑ Kanellis G, Mollejo M, Montes-Moreno S, Rodriguez-Pinilla SM, Cigudosa JC, Algara P, Montalban C, Matutes E, Wotherspoon A, Piris MA (July 2010). “Splenic diffuse red pulp small B-cell lymphoma: revision of a series of cases reveals characteristic clinico-pathological features”. Haematologica. 95 (7): 1122–9. doi:10.3324/haematol.2009.013714. PMID 20220064.
  16. ↑ Hunter ZR, Xu L, Yang G, Zhou Y, Liu X, Cao Y, Manning RJ, Tripsas C, Patterson CJ, Sheehy P, Treon SP (March 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): 1637–46. doi:10.1182/blood-2013-09-525808. PMID 24366360.
  17. ↑ Went PT, Zimpfer A, Pehrs AC, Sabattini E, Pileri SA, Maurer R, Terracciano L, Tzankov A, Sauter G, Dirnhofer S (April 2005). “High specificity of combined TRAP and DBA.44 expression for hairy cell leukemia”. Am. J. Surg. Pathol. 29 (4): 474–8. PMID 15767800.
  18. ↑ Morice WG, Chen D, Kurtin PJ, Hanson CA, McPhail ED (June 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.
  19. ↑ Behdad A, Bailey NG (October 2014). “Diagnosis of splenic B-cell lymphomas in the bone marrow: a review of histopathologic, immunophenotypic, and genetic findings”. Arch. Pathol. Lab. Med. 138 (10): 1295–301. doi:10.5858/arpa.2014-0291-CC. PMID 25268192.
  20. ↑ Shao H, Calvo KR, Grönborg M, Tembhare PR, Kreitman RJ, Stetler-Stevenson M, Yuan CM (April 2013). “Distinguishing hairy cell leukemia variant from hairy cell leukemia: development and validation of diagnostic criteria”. Leuk. Res. 37 (4): 401–409. doi:10.1016/j.leukres.2012.11.021. PMC 5575750. PMID 23347903.
  21. ↑ Konkay K, Uppin MS, Uppin SG, Raghunadha Rao D, Geetha C, Paul TR (September 2014). “Hairy cell leukemia: clinicopathological and immunophenotypic study”. Indian J Hematol Blood Transfus. 30 (3): 180–6. doi:10.1007/s12288-013-0231-x. PMC 4115087. PMID 25114404. Vancouver style error: initials (help)
  22. ↑ 22.0 22.1 Rudolf-Oliveira RC, Pirolli MM, de Souza FS, Michels J, Santos-Silva MC (2015). “Hairy cell leukemia variant: the importance of differential diagnosis”. Rev Bras Hematol Hemoter. 37 (2): 132–5. doi:10.1016/j.bjhh.2015.01.003. PMC 4382572. PMID 25818826.
  23. ↑ Pileri SA, Falini B (November 2009). “Mantle cell lymphoma”. Haematologica. 94 (11): 1488–92. doi:10.3324/haematol.2009.013359. PMC 2770958. PMID 19880776.
  24. ↑ Traverse-Glehen A, Baseggio L, Salles G, Coiffier B, Felman P, Berger F (April 2012). “Splenic diffuse red pulp small-B cell lymphoma: toward the emergence of a new lymphoma entity”. Discov Med. 13 (71): 253–65. PMID 22541613.
  25. ↑ Rahman K, Subramanian PG, Kadam PA, Gadage V, Galani K, Mittal N, Ghogale S, Badrinath Y, Ansari R, Kushte S, Nair R, Sengar M, Menon H, Gujral S (2012). “Morphological spectrum of leukemic mantle cell lymphoma”. Indian J Pathol Microbiol. 55 (1): 66–71. doi:10.4103/0377-4929.94860. PMID 22499304.
  26. ↑ Cessna MH, Hartung L, Tripp S, Perkins SL, Bahler DW (January 2005). “Hairy cell leukemia variant: fact or fiction”. Am. J. Clin. Pathol. 123 (1): 132–8. PMID 15762289.
  27. ↑ Kansal R, Singleton TP, Ross CW, Finn WG, Padmore RF, Schnitzer B (January 2002). “Follicular hodgkin lymphoma: a histopathologic study”. Am. J. Clin. Pathol. 117 (1): 29–35. doi:10.1309/M7YV-V8V2-A5VA-J1Y4. PMID 11789727.
  28. ↑ Autore F, Strati P, Laurenti L, Ferrajoli A (June 2018). “Morphological, immunophenotypic, and genetic features of chronic lymphocytic leukemia with trisomy 12: a comprehensive review”. Haematologica. 103 (6): 931–938. doi:10.3324/haematol.2017.186684. PMC 6058775. PMID 29748447.

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Epidemiology and Demographics

Epidemiology and Demographics

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [2], Associate Editor(s)-in-Chief: Muhammad Affan M.D.[3], Sowminya Arikapudi, M.B,B.S. [4]

Overview

Splenic marginal zone lymphoma (SMZL) constitutes less than 1% of all non-Hodgkin’s lymphomas. Its incidence increases with age. It is found to be more common in caucasians. Splenic marginal zone lymphoma (SMZL) affects men and women equally.

Epidemiology and demographics

Incidence

  • Splenic marginal zone lymphoma represents less than 1% of all non-hodgkins lymphomas.[1][2]
  • It constitutes around 20% of all marginal zone lymphomas (MZL).[3]
  • The overall annual age adjusted incidence during 2001-2008 was 0.13/100,000 person per year that seems to gradually increasing with time.[4][5]

Age

  • The incidence of splenic marginal zone lymphoma increases with age
  • The median age at the time of diagnosis is 69 years.[6]

Race

  • Splenic marginal zone lymphoma is more common in the white patient population..[2]

Gender

Splenic marginal zone lymphoma affects men and women equally.[7]

=

References

  1. ↑ Armitage JO, Weisenburger DD (August 1998). “New approach to classifying non-Hodgkin’s lymphomas: clinical features of the major histologic subtypes. Non-Hodgkin’s Lymphoma Classification Project”. J. Clin. Oncol. 16 (8): 2780–95. doi:10.1200/JCO.1998.16.8.2780. PMID 9704731.
  2. ↑ 2.0 2.1 Liu L, Wang H, Chen Y, Rustveld L, Liu G, Du XL (July 2013). “Splenic marginal zone lymphoma: a population-based study on the 2001-2008 incidence and survival in the United States”. Leuk. Lymphoma. 54 (7): 1380–6. doi:10.3109/10428194.2012.743655. PMID 23101590.
  3. ↑ Swerdlow SH, Campo E, Pileri SA, Harris NL, Stein H, Siebert R, Advani R, Ghielmini M, Salles GA, Zelenetz AD, Jaffe ES (May 2016). “The 2016 revision of the World Health Organization classification of lymphoid neoplasms”. Blood. 127 (20): 2375–90. doi:10.1182/blood-2016-01-643569. PMC 4874220. PMID 26980727.
  4. ↑ Olszewski AJ, Castillo JJ (February 2013). “Survival of patients with marginal zone lymphoma: analysis of the Surveillance, Epidemiology, and End Results database”. Cancer. 119 (3): 629–38. doi:10.1002/cncr.27773. PMID 22893605.
  5. ↑ Al-Hamadani M, Habermann TM, Cerhan JR, Macon WR, Maurer MJ, Go RS (September 2015). “Non-Hodgkin lymphoma subtype distribution, geodemographic patterns, and survival in the US: A longitudinal analysis of the National Cancer Data Base from 1998 to 2011”. Am. J. Hematol. 90 (9): 790–5. doi:10.1002/ajh.24086. PMID 26096944.
  6. ↑ [1] Berger F, Felman P, Thieblemont C, Pradier T, Baseggio L, Bryon PA, Salles G, Callet-Bauchu E, Coiffier B. “Non-MALT marginal zone B-cell lymphomas: a description of clinical presentation and outcome in 124 patients.” Blood. 2000 Mar 15;95(6):1950-6. PMID: 10706860
  7. ↑ Traverse-Glehen A, Baseggio L, Salles G, Felman P, Berger F (September 2011). “Splenic marginal zone B-cell lymphoma: a distinct clinicopathological and molecular entity. Recent advances in ontogeny and classification”. Curr Opin Oncol. 23 (5): 441–8. doi:10.1097/CCO.0b013e328349ab8d. PMID 21760505.

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Risk Factors

Risk Factors

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1], Associate Editor(s)-in-Chief: Muhammad Affan M.D.[2], Sowminya Arikapudi, M.B,B.S. [3]

Overview

There are no established risk factors for splenic marginal zone lymphoma.

Risk Factors

There are no established risk factors for splenic marginal zone lymphoma.

References

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Screening

Screening

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Muhammad Affan M.D.[2], Sowminya Arikapudi, M.B,B.S. [3]

Overview

According to the the U.S. Preventive Service Task Force (USPSTF), there is insufficient evidence to recommend routine screening for splenic marginal zone lymphoma.

Screening

According to the the U.S. Preventive Service Task Force (USPSTF), there is insufficient evidence to recommend routine screening for splenic marginal zone lymphoma.[1]

References

  1. ↑ Recommendations. U.S Preventive Services Task Force. http://www.uspreventiveservicestaskforce.org/BrowseRec/Search?s=SPLENIC+MARGINAL+ZONE+LYMPHOMA Accessed on December 23, 2015

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Natural History, Complications and Prognosis

Natural History, Complications and Prognosis

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1], Associate Editor(s)-in-Chief: Muhammad Affan M.D.[2], Sowminya Arikapudi, M.B,B.S. [3]

Overview

Splenic marginal zone lymphoma (SMZL) is a rare, slow growing B-cell lymphoma that is mostly asymptomatic at the time of diagnosis. It is commonly diagnosed at an old age. Patients typically have splenomegaly, lymphocytosis or cytopenias. Bone marrow is frequently involved but lymphadenopathy and liver involvement is rare.There are automimmune conditions that may develop in this conditions such autoimmune hemolytic anemia, idiopathic thrombocytopenic purpura, angioedema and von-willebrand disease. It may transform into diffuse large B-cell lymphoma. The prognosis is generally good. Several factors including lymphadenopathy, non-hematopoietic site involvement, histologic transformation affects the prognosis. Low Hemoglobin levels, high lactate dehydrogenase levels, low blood serum albumin levels, and genetic mutations such as mutations in NOTCH2, TP53, KLF2 are associated with poor prognosis among patients with splenic marginal zone lymphoma.

Natural history

Complications

Prognosis

References

  1. ↑ Arcaini L, Rossi D, Paulli M (April 2016). “Splenic marginal zone lymphoma: from genetics to management”. Blood. 127 (17): 2072–81. doi:10.1182/blood-2015-11-624312. PMID 26989207.
  2. ↑ Liu L, Wang H, Chen Y, Rustveld L, Liu G, Du XL (July 2013). “Splenic marginal zone lymphoma: a population-based study on the 2001-2008 incidence and survival in the United States”. Leuk. Lymphoma. 54 (7): 1380–6. doi:10.3109/10428194.2012.743655. PMID 23101590.
  3. ↑ Franco V, Florena AM, Iannitto E (April 2003). “Splenic marginal zone lymphoma”. Blood. 101 (7): 2464–72. doi:10.1182/blood-2002-07-2216. PMID 12446449.
  4. ↑ Melo JV, Hegde U, Parreira A, Thompson I, Lampert IA, Catovsky D (June 1987). “Splenic B cell lymphoma with circulating villous lymphocytes: differential diagnosis of B cell leukaemias with large spleens”. J. Clin. Pathol. 40 (6): 642–51. PMC 1141055. PMID 3497180.
  5. ↑ Olszewski AJ, Castillo JJ (February 2013). “Survival of patients with marginal zone lymphoma: analysis of the Surveillance, Epidemiology, and End Results database”. Cancer. 119 (3): 629–38. doi:10.1002/cncr.27773. PMID 22893605.
  6. ↑ 6.0 6.1 6.2 Chacón JI, Mollejo M, Muñoz E, Algara P, Mateo M, Lopez L, Andrade J, Carbonero IG, Martínez B, Piris MA, Cruz MA (September 2002). “Splenic marginal zone lymphoma: clinical characteristics and prognostic factors in a series of 60 patients”. Blood. 100 (5): 1648–54. PMID 12176884.
  7. ↑ Camacho FI, Mollejo M, Mateo MS, Algara P, Navas C, Hernández JM, Santoja C, Solé F, Sánchez-Beato M, Piris MA (October 2001). “Progression to large B-cell lymphoma in splenic marginal zone lymphoma: a description of a series of 12 cases”. Am. J. Surg. Pathol. 25 (10): 1268–76. PMID 11688461.
  8. ↑ Conconi A, Franceschetti S, Aprile von Hohenstaufen K, Margiotta-Casaluci G, Stathis A, Moccia AA, Bertoni F, Ramponi A, Mazzucchelli L, Cavalli F, Gaidano G, Zucca E (November 2015). “Histologic transformation in marginal zone lymphomas†”. Ann. Oncol. 26 (11): 2329–35. doi:10.1093/annonc/mdv368. PMID 26400898.
  9. ↑ Castelli R, Wu MA, Arquati M, Zanichelli A, Suffritti C, Rossi D, Cicardi M (March 2016). “High prevalence of splenic marginal zone lymphoma among patients with acquired C1 inhibitor deficiency”. Br. J. Haematol. 172 (6): 902–8. doi:10.1111/bjh.13908. PMID 26728240.
  10. ↑ Gebhart J, Lechner K, Skrabs C, Sliwa T, Müldür E, Ludwig H, Nösslinger T, Vanura K, Stamatopoulos K, Simonitsch-Klupp I, Chott A, Quehenberger P, Mitterbauer-Hohendanner G, Pabinger I, Jäger U, Geissler K (November 2014). “Lupus anticoagulant and thrombosis in splenic marginal zone lymphoma”. Thromb. Res. 134 (5): 980–4. doi:10.1016/j.thromres.2014.08.021. PMID 25201005.
  11. ↑ Salomon-Nguyen F, Valensi F, Troussard X, Flandrin G (1996). “The value of the monoclonal antibody, DBA44, in the diagnosis of B-lymphoid disorders”. Leuk. Res. 20 (11–12): 909–13. PMID 9009248.
  12. ↑ Perrone S, D’Elia GM, Annechini G, Ferretti A, Tosti ME, Foà R, Pulsoni A (May 2016). “Splenic marginal zone lymphoma: Prognostic factors, role of watch and wait policy, and other therapeutic approaches in the rituximab era”. Leuk. Res. 44: 53–60. PMID 270309618 Check |pmid= value (help).
  13. ↑ 13.0 13.1 Parry-Jones N, Matutes E, Gruszka-Westwood AM, Swansbury GJ, Wotherspoon AC, Catovsky D (March 2003). “Prognostic features of splenic lymphoma with villous lymphocytes: a report on 129 patients”. Br. J. Haematol. 120 (5): 759–64. PMID 12614206.
  14. ↑ Troussard X, Valensi F, Duchayne E, Garand R, Felman P, Tulliez M, Henry-Amar M, Bryon PA, Flandrin G (June 1996). “Splenic lymphoma with villous lymphocytes: clinical presentation, biology and prognostic factors in a series of 100 patients. Groupe Francais d’Hématologie Cellulaire (GFHC)”. Br. J. Haematol. 93 (3): 731–6. PMID 8652403.
  15. ↑ Thieblemont C, Felman P, Berger F, Dumontet C, Arnaud P, Hequet O, Arcache J, Callet-Bauchu E, Salles G, Coiffier B (June 2002). “Treatment of splenic marginal zone B-cell lymphoma: an analysis of 81 patients”. Clin Lymphoma. 3 (1): 41–7. PMID 12141954.
  16. ↑ Lenglet J, Traullé C, Mounier N, Benet C, Munoz-Bongrand N, Amorin S, Noguera ME, Traverse-Glehen A, Ffrench M, Baseggio L, Felman P, Callet-Bauchu E, Brice P, Berger F, Salles G, Brière J, Coiffier B, Thieblemont C (August 2014). “Long-term follow-up analysis of 100 patients with splenic marginal zone lymphoma treated with splenectomy as first-line treatment”. Leuk. Lymphoma. 55 (8): 1854–60. doi:10.3109/10428194.2013.861067. PMID 24206091.
  17. ↑ 17.0 17.1 Salido M, Baró C, Oscier D, Stamatopoulos K, Dierlamm J, Matutes E, Traverse-Glehen A, Berger F, Felman P, Thieblemont C, Gesk S, Athanasiadou A, Davis Z, Gardiner A, Milla F, Ferrer A, Mollejo M, Calasanz MJ, Florensa L, Espinet B, Luño E, Wlodarska I, Verhoef G, García-Granero M, Salar A, Papadaki T, Serrano S, Piris MA, Solé F (September 2010). “Cytogenetic aberrations and their prognostic value in a series of 330 splenic marginal zone B-cell lymphomas: a multicenter study of the Splenic B-Cell Lymphoma Group”. Blood. 116 (9): 1479–88. doi:10.1182/blood-2010-02-267476. PMID 20479288.
  18. ↑ Xing KH, Kahlon A, Skinnider BF, Connors JM, Gascoyne RD, Sehn LH, Savage KJ, Slack GW, Shenkier TN, Klasa R, Gerrie AS, Villa D (May 2015). “Outcomes in splenic marginal zone lymphoma: analysis of 107 patients treated in British Columbia”. Br. J. Haematol. 169 (4): 520–7. doi:10.1111/bjh.13320. PMID 25854936.
  19. ↑ Montalbán C, Abraira V, Arcaini L, Domingo-Domenech E, Guisado-Vasco P, Iannitto E, Iannito E, Mollejo M, Matutes E, Ferreri A, Salar A, Rattotti S, Carpaneto A, Pérez Fernández R, Bello JL, Hernández M, Caballero D, Carbonell F, Piris MA (October 2012). “Risk stratification for Splenic Marginal Zone Lymphoma based on haemoglobin concentration, platelet count, high lactate dehydrogenase level and extrahilar lymphadenopathy: development and validation on 593 cases”. Br. J. Haematol. 159 (2): 164–71. doi:10.1111/bjh.12011. PMID 22924582.
  20. ↑ Montalban C, Abraira V, Arcaini L, Domingo-Domenech E, Guisado-Vasco P, Iannitto E, Mollejo M, Matutes E, Ferreri AJ, Salar A, Rattotti S, Carpaneto A, Perez R, Bello JL, Hernandez M, Caballero D, Carbonell F, Piris MA (April 2014). “Simplification of risk stratification for splenic marginal zone lymphoma: a point-based score for practical use”. Leuk. Lymphoma. 55 (4): 929–31. doi:10.3109/10428194.2013.818143. PMID 23799931.
  21. ↑ Kiel MJ, Velusamy T, Betz BL, Zhao L, Weigelin HG, Chiang MY, Huebner-Chan DR, Bailey NG, Yang DT, Bhagat G, Miranda RN, Bahler DW, Medeiros LJ, Lim MS, Elenitoba-Johnson KS (August 2012). “Whole-genome sequencing identifies recurrent somatic NOTCH2 mutations in splenic marginal zone lymphoma”. J. Exp. Med. 209 (9): 1553–65. doi:10.1084/jem.20120910. PMC 3428949. PMID 22891276.
  22. ↑ Arribas AJ, Rinaldi A, Mensah AA, Kwee I, Cascione L, Robles EF, Martinez-Climent JA, Oscier D, Arcaini L, Baldini L, Marasca R, Thieblemont C, Briere J, Forconi F, Zamò A, Bonifacio M, Mollejo M, Facchetti F, Dirnhofer S, Ponzoni M, Bhagat G, Piris MA, Gaidano G, Zucca E, Rossi D, Bertoni F (March 2015). “DNA methylation profiling identifies two splenic marginal zone lymphoma subgroups with different clinical and genetic features”. Blood. 125 (12): 1922–31. doi:10.1182/blood-2014-08-596247. PMC 4416938. PMID 25612624.
  23. ↑ Gruszka-Westwood AM, Hamoudi RA, Matutes E, Tuset E, Catovsky D (June 2001). “p53 abnormalities in splenic lymphoma with villous lymphocytes”. Blood. 97 (11): 3552–8. PMID 11369650.
  24. ↑ Fodor A, Molnar MZ, Krenacs L, Bagdi E, Csomor J, Matolcsy A, Demeter J (December 2009). “Autoimmune hemolytic anemia as a risk factor of poor outcome in patients with splenic marginal zone lymphoma”. Pathol. Oncol. Res. 15 (4): 597–603. doi:10.1007/s12253-009-9159-8. PMID 19343544.

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