| Waldenström's macroglobulinemia |
| Classification and external resources |
| ICD-10 |
C88.0 |
| ICD-9 |
273.3 |
| ICD-O: |
M9761/3 |
| OMIM |
153600 |
| DiseasesDB |
14030 |
| MedlinePlus |
000588 |
| eMedicine |
med/2395 |
| MeSH |
D008258 |
Waldenström's macroglobulinemia (WM, also known as lymphoplasmacytic lymphoma) is cancer affecting B cells, a type of white blood cell. The main attributing antibody is immunoglobulin M (IgM). WM is an "indolent lymphoma," (i.e., one that tends to grow and spread slowly). It is a type of lymphoproliferative disease, which shares clinical characteristics with the indolent non-Hodgkin lymphomas.[1]
The disease, named after the Swedish oncologist Jan G. Waldenström, was first identified in 1944. As with other lymphomas, the disease is characterized by an uncontrolled increase of B-cells, i.e., white blood cells formed in the bone marrow and lymph nodes. The proliferation of B-cells interferes with the production of red blood cells, resulting in anemia. A unique characteristic of the disease is that the B-cells produce excess amounts of immunoglobulin protein (IgM), thickening the blood, and requiring additional treatment. WM is a rare disease, with only about 1,500 cases per year in the U.S. While the disease is incurable, it is treatable. Because of its indolent nature, many patients are able to lead active lives, and, when treatment is required, may experience years of symptom-free remission.[2]
Contents
- 1 History and classification
- 2 Causes
- 3 Biochemistry
- 4 Epidemiology
- 5 Symptoms
- 6 Pathophysiology
- 7 Diagnosis
- 8 Prognosis
- 9 Treatment
- 9.1 Watchful waiting
- 9.2 First-line
- 9.3 Salvage therapy
- 9.4 Drug pipeline
- 9.5 Patient stratification
- 10 See also
- 11 References
- 12 External links
History and classification[edit]
WM was first described by Jan G. Waldenström (1906–1996) in 1944 in two patients with bleeding from the nose and mouth, anemia, decreased levels of fibrinogen in the blood (hypofibrinogenemia), swollen lymph nodes, neoplastic plasma cells in bone marrow, and increased viscosity of the blood due to increased levels of a class of heavy proteins called macroglobulins.[3]
For a time, WM was considered to be related to multiple myeloma due to the presence of monoclonal gammopathy and infiltration of the bone marrow and other organs by plasmacytoid lymphocytes. The new World Health Organization (WHO) classification, however, places WM under the category of lymphoplasmacytic lymphomas, itself a subcategory of the indolent (low-grade) non-Hodgkin lymphomas.[4] In recent years, there have been significant advances in the understanding and treatment of WM.[5]
Causes[edit]
Waldenström's macroglobulinemia is characterized by an uncontrolled clonal proliferation of terminally differentiated B lymphocytes. Somatic mutations in MYD88 causing a change from leucine to proline at amino acid position 265 occur in over 90% of patients [6]. Recently, somatic mutations in the C-terminal domain of CXCR4 which are similar to those that appear in the germline of patients with WHIM syndrome were reported, along with small deletions effecting many genes involved in B-cell lymphoma genesis [7] There has been an association demonstrated with the locus 6p21.3 on chromosome 6.[8] There is a 2- to 3-fold risk increase of developing WM in people with a personal history of autoimmune diseases with autoantibodies and particularly elevated risks associated with hepatitis, human immunodeficiency virus, and rickettsiosis.[9]
There are genetic factors, with first-degree relatives shown to have a highly increased risk of also contracting Waldenström's.[10] There is also evidence to suggest that environmental factors including exposure to farming, pesticides, wood dust, and organic solvents may influence the development of Waldenström's.[11]
Biochemistry[edit]
Although believed to be a sporadic disease, studies have shown increased susceptibility within families, indicating a genetic component.[12][13] A mutation in gene MYD88 has been found to occur frequently in patients.[14] WM cells show only minimal changes in cytogenetic and gene expression studies. Their miRNA signature however differs from their normal counterpart. It is therefore believed that epigenetic modifications play a crucial role in the disease.[15]
Comparative genomic hybridization identified the following chromosomal abnormalities: deletions of 6q23 and 13q14, and gains of 3q13-q28, 6p and 18q.[16] FGFR3 is overexpressed.[17] The following signalling pathways have been implicated:
- CD154/CD40[18]
- Akt[19]
- ubiquitination, p53 activation, cytochrome c release[20]
- NF-κB[21][22]
- WNT/beta-catenin[23]
- mTOR[24]
- ERK[21]
- MAPK[25]
- Bcl-2[26]
The protein Src tyrosine kinase is overexpressed in Waldenström macroglobulinemia cells compared with control B cells.[27] Inhibition of Src arrests the cell cycle at phase G1 and has little effect on the survival of WM or normal cells.
MicroRNAs involved in Waldenström's:[28][29]
- increased expression of miRNAs-363*,[30] -206,[31] -494,[32] -155,[33] -184,[34] -542–3p.[35]
- decreased expression of miRNA-9*.[36]
MicroRNA-155 regulates the proliferation and growth of WM cells in vitro and in vivo, by inhibiting MAPK/ERK, PI3/AKT, and NF-κB pathways.
In WM-cells, histone deacetylases and histone-modifying genes are de-regulated.[37]
Bone marrow tumour cells express the following antigen targets CD20 (98.3%), CD22 (88.3%), CD40 (83.3%), CD52 (77.4%), IgM (83.3%), MUC1 core protein (57.8%), and 1D10 (50%).[38]
Epidemiology[edit]
Of all cancers involving the same class of blood cell, 1% of cases are WM.[39]
WM is a rare disorder, with fewer than 1,500 cases occurring in the United States annually.[1] The median age of onset of WM is between 60 and 65 years, with some cases occurring in late teens.[1][40]
Symptoms[edit]
Symptoms of WM include weakness, fatigue, weight loss and chronic oozing of blood from the nose and gums.[41] Peripheral neuropathy can occur in 10% of patients. Lymphadenopathy, splenomegaly, and/or hepatomegaly are present in 30-40% of cases.[40] Other possible symptoms include blurring or loss of vision, headache, and (rarely) stroke or coma.
Pathophysiology[edit]
Symptoms include blurring or loss of vision, headache, and (rarely) stroke or coma are due to the effects of the IgM paraprotein, which may cause autoimmune phenomenon or cryoglobulinemia. Other symptoms of WM are due to the hyperviscosity syndrome, which is present in 6-20% of patients.[42][43][44][45] This is attributed to the IgM monoclonal protein increasing the viscosity of the blood by forming aggregates to each other, binding water through their carbohydrate component and by their interaction with blood cells.[46]
Diagnosis[edit]
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A diagnosis of Waldenström's macroglobulinemia depends on a significant monoclonal IgM spike evident in blood tests and malignant cells consistent with the disease in bone marrow biopsy samples.[47] Blood tests show the level of IgM in the blood and the presence of proteins, or tumor markers, that are the key symptoms of WM. A bone marrow biopsy provides a sample of bone marrow, usually from the back of the pelvis bone. The sample is extracted through a needle and examined under a microscope. A pathologist identifies the particular lymphocytes that indicate WM. Flow cytometry may be used to examine markers on the cell surface or inside the lymphocytes.[48]
Additional tests such as computed tomography (CT or CAT) scan may be used to evaluate the chest, abdomen, and pelvis, particularly swelling of the lymph nodes, liver, and spleen. A skeletal survey can help distinguish between WM and multiple myeloma.[48] Anemia is typically found in 80% of patients with WM. Leukopenia, and thrombocytopenia may be observed. Neutropenia may also be found in some patients.[47]
Chemistry tests include lactate dehydrogenase (LDH) levels, uric acid levels, erythrocyte sedimentation rate (ESR), renal and hepatic function, total protein levels, and an albumin-to-globulin ratio. The ESR and uric acid level may be elevated. Creatinine is occasionally elevated and electrolytes are occasionally abnormal. Hypercalcemia is noted in approximately 4% of patients. The LDH level is frequently elevated, indicating the extent of Waldenström macroglobulinemia–related tissue involvement. Rheumatoid factor, cryoglobulins, direct antiglobulin test and cold agglutinin titre results can be positive. Beta-2-microglobulin and C-reactive protein test results are not specific for Waldenström macroglobulinemia. Beta-2-microglobulin is elevated in proportion to tumor mass. Coagulation abnormalities may be present. Prothrombin time, activated partial thromboplastin time, thrombin time, and fibrinogen tests should be performed. Platelet aggregation studies are optional. Serum protein electrophoresis results indicate evidence of a monoclonal spike but cannot establish the spike as IgM. An M component with beta-to-gamma mobility is highly suggestive of Waldenström macroglobulinemia. Immunoelectrophoresis and immunofixation studies help identify the type of immunoglobulin, the clonality of the light chain, and the monoclonality and quantitation of the paraprotein. High-resolution electrophoresis and serum and urine immunofixation are recommended to help identify and characterize the monoclonal IgM paraprotein.
The light chain of the monoclonal protein is usually the kappa light chain. At times, patients with Waldenström macroglobulinemia may exhibit more than one M protein. Plasma viscosity must be measured. Results from characterization studies of urinary immunoglobulins indicate that light chains (Bence Jones protein), usually of the kappa type, are found in the urine. Urine collections should be concentrated.
Bence Jones proteinuria is observed in approximately 40% of patients and exceeds 1 g/d in approximately 3% of patients. Patients with findings of peripheral neuropathy should have nerve conduction studies and antimyelin associated glycoprotein serology.
Prognosis[edit]
Current medical treatments result in survival of some longer than 10 years; in part this is because better diagnostic testing means early diagnosis and treatments. Older diagnosis and treatments resulted in published reports of median survival of approximately 5 years from time of diagnosis.[1] Currently, median survival is 6.5 years.[49] In rare instances, WM progresses to multiple myeloma.[50]
The International Prognostic Scoring System for Waldenström’s Macroglobulinemia (IPSSWM) is a predictive model to characterise long-term outcome.[51][52] According to the model, factors predicting survival (n.b. the study quoted conversely refers to them as "5 adverse covariates") are:
- Age >65 years
- Haemoglobin ≤11.5 g/dL
- Platelet count ≤100×109/L
- B2-microglobulin >3 mg/L
- Serum monoclonal protein concentration >70 g/L
The risk categories are:
- Low: ≤1 adverse variable except age
- Intermediate: 2 adverse characteristics or age >65 years
- High: >2 adverse characteristics
Five-year survival rates for these categories are 87%, 68% and 36% respectively.[53]
The IPSSWM has been shown to be reliable.[54] It is also applicable to patients on a Rituximab-based treatment regimen.[53] An additional predictive factor is elevated serum lactate dehydrogenase (LDH).[55]
Treatment[edit]
There is no single accepted treatment for WM.[56] There is marked variation in clinical outcome due to gaps in knowledge of the disease's molecular basis. Objective response rates are high (>80%) but complete response rates are low (0-15%).[5]
There are different treatment flowcharts: Treon[57] and mSMART.[58]
WM patients are at higher risk of developing second cancers than the general population, however it is not yet clear whether treatments are contributory.[59]
Watchful waiting[edit]
In the absence of symptoms, many clinicians will recommend simply monitoring the patient.[60] But on occasion the disease can be fatal, as it was to its best known sufferer, the former French president Georges Pompidou, who died in 1974. Indeed, in 1991, Waldenström himself raised the question of the need for effective therapy.[61]
First-line[edit]
Should treatment be started it should address both the paraprotein level and the lymphocytic B-cells.[62]
In 2002, a panel at the International Workshop on Waldenström Macroglobulinemia agreed on criteria for the initiation of therapy. They recommended starting therapy in patients with constitutional symptoms such as recurrent fever, night sweats, fatigue due to anemia, weight loss, progressive symptomatic lymphadenopathy or splenomegaly, and anemia due to marrow infiltration. Complications such as hyperviscosity syndrome, symptomatic sensorimotor peripheral neuropathy, systemic amyloidosis, renal insufficiency, or symptomatic cryoglobulinemia were also suggested as indications for therapy.[63]
Treatment includes the monoclonal antibody rituximab, sometimes in combination with chemotherapeutic drugs such as chlorambucil, cyclophosphamide, or vincristine or with thalidomide.[64] Corticosteroids, such as Prednisone, may also be used in combination. Plasmapheresis can be used to treat the hyperviscosity syndrome by removing the paraprotein from the blood, although it does not address the underlying disease.[65]
Recently, autologous bone marrow transplantation has been added to the available treatment options.[66][67][68][69]
Salvage therapy[edit]
When primary or secondary resistance invariably develops, salvage therapy is considered. Allogeneic stem cell transplantation can induce durable remissions for heavily pre-treated patients.[70]
Drug pipeline[edit]
As of October 2010, there have been a total of 44 clinical trials on Waldenstrom's macroglobulinemia, excluding transplantion treatments. Of these, 11 were performed on previously untreated patients, 14 in patients with relapsed or refractory Waldenstrom's.[71] A database of clinical trials investigating Waldenström's macroglobulinemia is maintained by the National Institutes of Health in the US.[72]
Patient stratification[edit]
Patients with polymorphic variants (alleles) FCGR3A-48 and -158 were associated with improved categorical responses to Rituximab-based treatments.[73]
See also[edit]
- Waldenström hyperglobulinemic purpura
- List of hematologic conditions
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- ^ Kastritis, E.; Kyrtsonis, M.; Hadjiharissi, E.; Symeonidis, A.; Michalis, E.; Repoussis, P.; Tsatalas, C.; Michael, M.; Sioni, A.; Kartasis, Z.; Stefanoudaki, E.; Voulgarelis, M.; Delimpasi, S.; Gavriatopoulou, M.; Koulieris, E.; Gika, D.; Zomas, A.; Roussou, P.; Anagnostopoulos, N.; Economopoulos, T.; Terpos, E.; Zervas, K.; Dimopoulos, M. A.; Greek Myeloma Study, G. (2010). "Validation of the International Prognostic Scoring System (IPSS) for Waldenstrom's macroglobulinemia (WM) and the importance of serum lactate dehydrogenase (LDH)". Leukemia research 34 (10): 1340–1343. doi:10.1016/j.leukres.2010.04.005. PMID 20447689. edit
- ^ a b Dimopoulos, M.; Kastritis, E.; Delimpassi, S.; Zomas, A.; Kyrtsonis, M.; Zervas, K. (2008). "The International Prognostic Scoring System for Waldenstrom's macroglobulinemia is applicable in patients treated with rituximab-based regimens". Haematologica 93 (9): 1420–1422. doi:10.3324/haematol.12846. PMID 18641029. edit
- ^ Hivert, B.; Tamburini, J.; Vekhoff, A.; Tournilhac, O.; Leblond, V.; Morel, P. (2011-03-10). "Prognostic value of the International Scoring System and response in patients with advanced Waldenström macroglobulinemia". Haematologica 96 (5): 785–788. doi:10.3324/haematol.2010.029140. PMC 3084930. PMID 21393333. edit
- ^ Dhodapkar, M.; Hoering, A.; Gertz, M.; Rivkin, S.; Szymonifka, J.; Crowley, J.; Barlogie, B. (2009). "Long-term survival in Waldenstrom macroglobulinemia: 10-year follow-up of Southwest Oncology Group-directed intergroup trial S9003". Blood 113 (4): 793–796. doi:10.1182/blood-2008-07-172080. PMC 2630265. PMID 18931340. edit
- ^ Leleu, X.; Gay, J.; Roccaro, A.; Moreau, A.; Poulain, S.; Dulery, R.; Champs, B.; Robu, D.; Ghobrial, I. (2009). "Update on therapeutic options in Waldenström macroglobulinemia". European journal of haematology 82 (1): 1–12. doi:10.1111/j.1600-0609.2008.01171.x. PMC 3133624. PMID 19087134. edit
- ^ Treon, S. P. (2009). "How I treat Waldenström macroglobulinemia". Blood 114 (12): 2375–2385. doi:10.1182/blood-2009-05-174359. PMID 19617573. edit
- ^ Ansell, S. M.; Kyle, R. A.; Reeder, C. B.; Fonseca, R.; Mikhael, J. R.; Morice, W. G.; Bergsagel, P. L.; Buadi, F. K.; Colgan, J. P.; Dingli, D.; Dispenzieri, A.; Greipp, P. R.; Habermann, T. M.; Hayman, S. R.; Inwards, D. J.; Johnston, P. B.; Kumar, S. K.; Lacy, M. Q.; Lust, J. A.; Markovic, S. N.; Micallef, I. N. M.; Nowakowski, G. S.; Porrata, L. F.; Roy, V.; Russell, S. J.; Short, K. E. D.; Stewart, A. K.; Thompson, C. A.; Witzig, T. E.; Zeldenrust, S. R. (2010). "Diagnosis and Management of Waldenström Macroglobulinemia: Mayo Stratification of Macroglobulinemia and Risk-Adapted Therapy (mSMART) Guidelines". Mayo Clinic proceedings. Mayo Clinic 85 (9): 824–833. doi:10.4065/mcp.2010.0304. PMC 2931618. PMID 20702770. edit
- ^ Varettoni, M.; Tedeschi, A.; Arcaini, L.; Pascutto, C.; Vismara, E.; Orlandi, E.; Ricci, F.; Corso, A.; Greco, A.; Mangiacavalli, S.; Lazzarino, M.; Morra, E. (2011). "Risk of second cancers in Waldenstrom macroglobulinemia". Annals of Oncology 23 (2): 411–415. doi:10.1093/annonc/mdr119. PMID 21525403. edit
- ^ http://emedicine.medscape.com/article/207097-treatment
- ^ Waldenström J (1991). "To treat or not to treat, this is the real question". Leuk Res 15 (6): 407–8. doi:10.1016/0145-2126(91)90049-Y. PMID 1907339.
- ^ Baehring, J.; Hochberg, E.; Raje, N.; Ulrickson, M.; Hochberg, F. (2008). "Neurological manifestations of Waldenström macroglobulinemia". Nature clinical practice. Neurology 4 (10): 547–556. doi:10.1038/ncpneuro0917. PMID 18813229. edit
- ^ Kyle RA, Treon SP, Alexanian R, Barlogie B, Bjorkholm M, Dhodapkar M, Lister TA, Merlini G, Morel P, Stone M, Branagan AR, Leblond V (2003). "Prognostic markers and criteria to initiate therapy in Waldenstrom's macroglobulinemia: consensus panel recommendations from the Second International Workshop on Waldenstrom's Macroglobulinemia". Semin Oncol 30 (2): 116–20. doi:10.1053/sonc.2003.50038. PMID 12720119.
- ^ Treon, S.; Soumerai, J.; Branagan, A.; Hunter, Z.; Patterson, C.; Ioakimidis, L.; Briccetti, F.; Pasmantier, M.; Zimbler, H.; Cooper, R. B.; Moore, M.; Hill j, J.; Rauch, A.; Garbo, L.; Chu, L.; Chua, C.; Nantel, S. H.; Lovett, D. R.; Boedeker, H.; Sonneborn, H.; Howard, J.; Musto, P.; Ciccarelli, B. T.; Hatjiharissi, E.; Anderson, K. C. (2008). "Thalidomide and rituximab in Waldenstrom macroglobulinemia". Blood 112 (12): 4452–4457. doi:10.1182/blood-2008-04-150854. PMC 2597120. PMID 18713945. edit
- ^ Gertz MA (2005). "Waldenstrom macroglobulinemia: a review of therapy". Am J Hematol 79 (2): 147–57. doi:10.1002/ajh.20363. PMID 15929102.
- ^ Yang L, Wen B, Li H, Yang M, Jin Y, Yang S, Tao J (1999). "Autologous peripheral blood stem cell transplantation for Waldenstrom's macroglobulinemia". Bone Marrow Transplant 24 (8): 929–30. doi:10.1038/sj.bmt.1701992. PMID 10516708.
- ^ Martino R, Shah A, Romero P, Brunet S, Sierra J, Domingo-Albos A, Fruchtman S, Isola L (1999). "Allogeneic bone marrow transplantation for advanced Waldenstrom's macroglobulinemia". Bone Marrow Transplant 23 (7): 747–9. doi:10.1038/sj.bmt.1701633. PMID 10218857.
- ^ Anagnostopoulos A, Dimopoulos MA, Aleman A, Weber D, Alexanian R, Champlin R, Giralt S (2001). "High-dose chemotherapy followed by stem cell transplantation in patients with resistant Waldenstrom's macroglobulinemia". Bone Marrow Transplant 27 (10): 1027–9. doi:10.1038/sj.bmt.1703041. PMID 11438816.
- ^ Tournilhac O, Leblond V, Tabrizi R, Gressin R, Senecal D, Milpied N, Cazin B, Divine M, Dreyfus B, Cahn JY, Pignon B, Desablens B, Perrier JF, Bay JO, Travade P (2003). "Transplantation in Waldenstrom's macroglobulinemia--the French experience". Semin Oncol 30 (2): 291–6. doi:10.1053/sonc.2003.50048. PMID 12720155.
- ^ Kyriakou, C.; Canals, C.; Cornelissen, J. J.; Socie, G.; Willemze, R.; Ifrah, N.; Greinix, H. T.; Blaise, D.; Deconinck, E.; Ferrant, A.; Schattenberg, A.; Harousseau, J. -L.; Sureda, A.; Schmitz, N. (2010). "Allogeneic Stem-Cell Transplantation in Patients with Waldenstrom Macroglobulinemia: Report from the Lymphoma Working Party of the European Group for Blood and Marrow Transplantation". Journal of clinical oncology : official journal of the American Society of Clinical Oncology 28 (33): 4926–4934. doi:10.1200/JCO.2009.27.3607. PMID 20956626. edit
- ^ Rourke, M.; Anderson, K. C.; Ghobrial, I. M. (2010). "Review of clinical trials conducted in Waldenstrom macroglobulinemia and recommendations for reporting clinical trial responses in these patients". Leukemia & Lymphoma 51 (10): 1779. doi:10.3109/10428194.2010.499977. edit
- ^ http://clinicaltrials.gov/ct2/results?term=Waldenstrom
- ^ Treon, S. P.; Yang, G.; Hanzis, C.; Ioakimidis, L.; Verselis, S. J.; Fox, E. A.; Xu, L.; Hunter, Z. R.; Tseng, H.; Manning, R. J.; Patterson, C. J.; Sheehy, P.; Turnbull, B. (2011). "Attainment of complete/very good partial response following rituximab-based therapy is an important determinant to progression-free survival, and is impacted by polymorphisms in FCGR3A in Waldenstrom macroglobulinaemia". British Journal of Haematology 154 (2): 223–228. doi:10.1111/j.1365-2141.2011.08726.x. PMID 21564078. edit
External links[edit]
- The Bing Center for Waldenström's Research
- The International Workshops on Waldenström's Macroglobulinemia
- The International Patient-Physician Summits on Waldenström's Macroglobulinemia
- The Waldenström's Macroglobulinemia Clinical Trials Group
- The International Waldenström's Macroglobulinemia Foundation site
- American Cancer Society Detailed Guide: Waldenström's Macroglobulinemia
- Lymphoma Association – Specialist UK charity providing free information and support to patients, their families, friends and carers
|
Hematological malignancy/leukemia histology (ICD-O 9590–9989, C81–C96, 200–208)
Lymphoid/Lymphoproliferative, Lymphomas/Lymphoid leukemias (9590–9739, 9800–9839)
|
|
B cell
(lymphoma,
leukemia)
(most CD19
|
|
By development/
marker
|
|
TdT+
|
- ALL (Precursor B acute lymphoblastic leukemia/lymphoma)
|
|
|
CD5+
|
mantle zone (Mantle cell)
|
|
|
CD22+
|
- Prolymphocytic
- CD11c+ (Hairy cell leukemia)
|
|
|
CD79a+
|
- germinal center/follicular B cell (Follicular
- Burkitt's
- GCB DLBCL
- Primary cutaneous follicular lymphoma)
marginal zone/marginal-zone B cell (Splenic marginal zone
- MALT
- Nodal marginal zone
- Primary cutaneous marginal zone lymphoma)
|
|
|
RS (CD15+, CD30+)
|
- Classic Hodgkin's lymphoma (Nodular sclerosis)
- CD20+ (Nodular lymphocyte predominant Hodgkin's lymphoma)
|
|
|
PCDs/PP
(CD38+/CD138+)
|
- see immunoproliferative immunoglobulin disorders
|
|
|
|
By infection
|
- KSHV (Primary effusion)
- EBV (Lymphomatoid granulomatosis
- Post-transplant lymphoproliferative disorder)
- HIV (AIDS-related lymphoma)
- Helicobacter pylori (MALT lymphoma)
|
|
|
Cutaneous
|
- Diffuse large B-cell lymphoma
- Intravascular large B-cell lymphoma
- Primary cutaneous marginal zone lymphoma
- Primary cutaneous immunocytoma
- Plasmacytoma
- Plasmacytosis
- Primary cutaneous follicular lymphoma
|
|
|
|
T/NK
|
T cell
(lymphoma,
leukemia)
(most CD3
|
|
By development/
marker
|
- TdT+: ALL (Precursor T acute lymphoblastic leukemia/lymphoma)
- prolymphocyte (Prolymphocytic)
- CD30+ (Anaplastic large-cell lymphoma
- Lymphomatoid papulosis type A)
|
|
|
Cutaneous
|
|
MF+variants
|
- indolent: Mycosis fungoides
- Pagetoid reticulosis
- Granulomatous slack skin
aggressive: Sézary's disease
- Adult T-cell leukemia/lymphoma
|
|
|
Non-MF
|
- CD30-: Non-mycosis fungoides CD30− cutaneous large T-cell lymphoma
- Pleomorphic T-cell lymphoma
- Lymphomatoid papulosis type B
CD30+: CD30+ cutaneous T-cell lymphoma
- Secondary cutaneous CD30+ large cell lymphoma
- Lymphomatoid papulosis type A
|
|
|
|
Other peripheral
|
- Hepatosplenic
- Angioimmunoblastic
- Enteropathy-associated T-cell lymphoma
- Peripheral T-cell lymphoma-Not-Otherwise-Specified (Lennert lymphoma)
- Subcutaneous T-cell lymphoma
|
|
|
By infection
|
- HTLV-1 (Adult T-cell leukemia/lymphoma)
|
|
|
|
NK cell/
(most CD56)
|
- Aggressive NK-cell leukemia
- Blastic NK cell lymphoma
|
|
|
T or NK
|
- EBV (Extranodal NK-T-cell lymphoma/Angiocentric lymphoma)
- Large granular lymphocytic leukemia
|
|
|
|
Lymphoid+myeloid
|
- Acute biphenotypic leukaemia
|
|
|
Lymphocytosis
|
- Lymphoproliferative disorders (X-linked lymphoproliferative disease
- Autoimmune lymphoproliferative syndrome)
- Leukemoid reaction
- Diffuse infiltrative lymphocytosis syndrome
|
|
|
| Cutaneous lymphoid hyperplasia |
- Cutaneous lymphoid hyperplasia
- with bandlike and perivascular patterns
- with nodular pattern
- Jessner lymphocytic infiltrate of the skin
|
|
|
|
cell/phys/auag/auab/comp, igrc
|
|
|
|
|
|
|
Immune disorders, Immunoproliferative immunoglobulin disorders (D89, 273)
|
|
| PCDs/PP |
- Plasmacytoma
- Multiple myeloma (Plasma cell leukemia)
- MGUS
- IgM (Macroglobulinemia/Waldenström's macroglobulinemia)
- heavy chain (Heavy chain disease)
- light chain (Primary amyloidosis)
|
|
| Other hypergammaglobulinemia |
|
|
|
|
cell/phys/auag/auab/comp, igrc
|
|
|
|
|
|
