Anaplastic large cell lymphoma, ALK negative
Template:DiseaseDisorder infobox Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Alberto Plate [2]
Synonyms and keywords: ALCL-ALK(-); ALK-negative ALCL; ALK negative ALCL; ALK negative anaplastic large cell lymphoma
Overview
ALK negative anaplastic large cell lymphoma (ALCL) is a type of peripheral T-cell lymphoma (non-Hodgkin's lymphoma). ALK negative ALCL T-cells express CD30, but not the ALK (Anaplastic Lymphoma Kinase) chimeric protein,[1] which explains the difference in clinical outcome compared to that of ALK(+)-ALCL.[2] T-cells in ALK negative ALCL have a chromosomal rearrangement that involves DUSP22 and TP63 gene. ALK negative ALCL patients with DUSP22 mutation have a higher five-year overall survival rate in comparison with ALK positive ALCL.[3]
Historical Perspective
In 2008, the World Health Organization (WHO) added ALK negative ALCL as a provisional entity in the peripheral T-cell lymphoma classification.[4]
Causes
ALK negative ALCL is characterized by a translocation T(6;7)(p25.3;q32.3), which inactivates the DUSP22 gene and leads to a higher proliferation rate.[5] In healthy people, the product of the DUSP22 gene, the DUSP22 protein (also known as the JNK pathway-associated phosphatase or JKAP), inactivates the LCK tyrosine kinase protein during T-cell receptor signaling.[6]
DUSP22 mutations are also associated with breast cancer (the UDSMP22 protein can also block estrogen receptors)[7] and primary cutaneous ALCL.[2]
Differential Diagnosis
- Peripheral T-cell lymphoma-not otherwise specified (PTCL-NOS)[8][9]
- Classical Hodgkin's lymphoma[8]
- Primary cutaneous anaplastic large cell lymphoma[1]
- Anaplastic large cell lymphoma, ALK positive[9]
Epidemiology and Demographics
ALK negative ALCL represents 2%-3% of all non-Hodgkin's lymphomas (NHL) and 12% of all T-cell NHL.[4]
Age
ALK negative ALCL affects primarily adults between 40-60 years old.
Gender
There is a modest male predominance in the prevalence of the disease.[1]
Risk Factors
- Breast implants[8]
Natural History, Complications and Prognosis
Prognosis
The International Prognostic Index (IPI) is used to estimate the prognosis of patients.[10] The IPI takes into account 5 variables:
- Patient's age (>60 years)
- Elevated serum lactate dehydrogenase (LDH)
- Eastern Cooperative Oncology Group (ECOG) performance status
- Ann Arbor clinical stage III or IV
- Number of involved extra nodal sites > 1
If any of this criteria is met, one point is awarded for the IPI. The interpretation of the total score is as follows:
- 0 to 1: Low risk
- 2: Low-intermediate risk
- 3: High-intermediate risk
- 4 to 5: High risk
Diagnosis
History and Symptoms
Patients typically present B symptoms (fever, weight loss and lymphadenopathy). ALK negative ALCL patients have a higher incidence of cutaneous, hepatic and gastrointestinal involvement than ALK positive ALCL.[9] Other sites of involvement include the bronchus[11], central nervous system,[12] pancreas,[13] rectum,[14] breast peri-implant seromas,[15] skeletal muscle,[16] and bone.[17]
Cytology Findings
According to the World Health Organization (WHO), the most important factor to diagnose a ALK negative ALCL is morphology and immunophenotype:[18]
Morphologic criteria
- Absence of small-to-medium sized lymphocytes.
Immunophenotype criteria
- CD30 expression
- Nuclear negativity for the PAX5 transcription factor (usually expressed in Hodgkin’s lymphoma classic variant)
- Negativity for the EBV markers EBER and LMP1 (which may be expressed in Hodgkin’s lymphoma classic variant)
- Presence of clonal T-cell receptor rearrangements (usually absent in Hodgkin’s lymphoma classic variant).
Laboratory Findings[9]
- Anemia
- Thrombocytopenia
- Increased LDH
Treatment
Although the peripheral T-cell lymphomas are a heterogenous group of pathologies, the treatment is the same:[19]
CHOP Regimen
- This regimen includes:
Some evidence suggest that although CHOP regimen is effective in treating the ALK(-) ALCL, a short 2-year event-free survival requires extra management[20], reason why CHOP regimen must then be followed by an autologous stem cell transplant during remission.[19]
Alternative Therapy
A novel drug, Brentuximab, has effectively treated refractory, CD30 positive ALCL in the japanese population.[21] The most common side effects associated with brentuximab are peripheral sensory neuropathy and neutropenia.[22]
References
- ↑ 1.0 1.1 1.2 Swerdlow, Steven (2008). WHO classification of tumours of haematopoietic and lymphoid tissues. Lyon, France: International Agency for Research on Cancer. ISBN 9789283224310.
- ↑ 2.0 2.1 Xing X, Feldman AL (2015). "Anaplastic large cell lymphomas: ALK positive, ALK negative, and primary cutaneous". Adv Anat Pathol. 22 (1): 29–49. doi:10.1097/PAP.0000000000000047. PMID 25461779.
- ↑ Parrilla Castellar ER, Jaffe ES, Said JW, Swerdlow SH, Ketterling RP, Knudson RA; et al. (2014). "ALK-negative anaplastic large cell lymphoma is a genetically heterogeneous disease with widely disparate clinical outcomes". Blood. 124 (9): 1473–80. doi:10.1182/blood-2014-04-571091. PMC 4148769. PMID 24894770.
- ↑ 4.0 4.1 "Anaplastic large cell lymphoma, ALK-negative".
- ↑ Feldman AL, Dogan A, Smith DI, Law ME, Ansell SM, Johnson SH; et al. (2011). "Discovery of recurrent t(6;7)(p25.3;q32.3) translocations in ALK-negative anaplastic large cell lymphomas by massively parallel genomic sequencing". Blood. 117 (3): 915–9. doi:10.1182/blood-2010-08-303305. PMC 3035081. PMID 21030553.
- ↑ "The phosphatase JKAP/DUSP22 inhibits T-cell receptor signalling and autoimmunity by inactivating Lck".
- ↑ "Discovery of recurrent t(6;7)(p25.3;q32.3) translocations in ALK-negative anaplastic large cell lymphomas by massively parallel genomic sequencing".
- ↑ 8.0 8.1 8.2 Ferreri AJ, Govi S, Pileri SA, Savage KJ (2013). "Anaplastic large cell lymphoma, ALK-negative". Crit Rev Oncol Hematol. 85 (2): 206–15. doi:10.1016/j.critrevonc.2012.06.004. PMID 22789917.
- ↑ 9.0 9.1 9.2 9.3 "ALK- anaplastic large-cell lymphoma is clinically and immunophenotypically different from both ALK+ ALCL and peripheral T-cell lymphoma, not otherwise specified: report from the International Peripheral T-Cell Lymphoma Project".
- ↑ "International Prognostic Index for non-Hodgkin lymphoma".
- ↑ Xu X (2014). "ALK-negative anaplastic large cell lymphoma primarily involving the bronchus: a case report and literature review". Int J Clin Exp Pathol. 7 (1): 460–3. PMC 3885507. PMID 24427373.
- ↑ Nomura M, Narita Y, Miyakita Y, Ohno M, Fukushima S, Maruyama T; et al. (2013). "Clinical presentation of anaplastic large-cell lymphoma in the central nervous system". Mol Clin Oncol. 1 (4): 655–660. doi:10.3892/mco.2013.110. PMC 3915681. PMID 24649224.
- ↑ Savopoulos CG, Tsesmeli NE, Kaiafa GD, Zantidis AT, Bobos MT, Hatzitolios AI; et al. (2005). "Primary pancreatic anaplastic large cell lymphoma, ALK negative: a case report". World J Gastroenterol. 11 (39): 6221–4. PMID 16273656.
- ↑ Template:Citeweb
- ↑ Brody GS, Deapen D, Taylor CR, Pinter-Brown L, House-Lightner SR, Andersen J; et al. (2014). "Anaplastic Large Cell Lymphoma (ALCL) Occuring in Women with Breast Implants: Analysis of 173 Cases". Plast Reconstr Surg. doi:10.1097/PRS.0000000000001033. PMID 25490535.
- ↑ Kubo Y, Aoi J, Johno T, Makino T, Sakai K, Masuguchi S; et al. (2014). "A case of anaplastic large cell lymphoma of skeletal muscle". J Dermatol. 41 (11): 999–1002. doi:10.1111/1346-8138.12641. PMID 25292453.
- ↑ Yu G, Huang X, Li M, Ding Y, Wang X, Lai Y; et al. (2014). "[Clinicopathologic features and prognosis of primary bone anaplastic large cell lymphoma]". Zhonghua Bing Li Xue Za Zhi. 43 (8): 512–5. PMID 25346119.
- ↑ "Anaplastic large cell lymphoma: changes in the World Health Organization classification and perspectives for targeted therapy".
- ↑ 19.0 19.1 Moskowitz AJ, Lunning MA, Horwitz SM (2014). "How I treat the peripheral T-cell lymphomas". Blood. 123 (17): 2636–44. doi:10.1182/blood-2013-12-516245. PMID 24615779.
- ↑ Rattarittamrong E, Norasetthada L, Tantiworawit A, Chai-Adisaksopha C, Nawarawong W (2013). "CHOEP-21 chemotherapy for newly diagnosed nodal peripheral T-cell lymphomas (PTCLs) in Maharaj Nakorn Chiang Mai Hospital". J Med Assoc Thai. 96 (11): 1416–22. PMID 24428090.
- ↑ Ogura M, Tobinai K, Hatake K, Ishizawa K, Uike N, Uchida T; et al. (2014). "Phase I / II study of brentuximab vedotin in Japanese patients with relapsed or refractory CD30-positive Hodgkin's lymphoma or systemic anaplastic large-cell lymphoma". Cancer Sci. 105 (7): 840–6. doi:10.1111/cas.12435. PMID 24814862.
- ↑ Terriou L, Bonnet S, Debarri H, Demarquette H, Morschhauser F (2013). "[Brentuximab vedotin: new treatment for CD30+ lymphomas]". Bull Cancer. 100 (7–8): 775–9. doi:10.1684/bdc.2013.1778. PMID 23831822.