Changes

{{Under Construction}}

{{Under Construction}}

<blockquote class='blockedit'>{{Box-round|title=Content Update To WHO 5th Edition Classification Is In Process; Content Below is Based on WHO 4th Edition Classification|This page was converted to the new template on 2023-12-07. The original page can be found at [[HAEM4:ALK-Positive Large B-cell Lymphoma]].

<blockquote class="blockedit">{{Box-round|title=Content Update To WHO 5th Edition Classification Is In Process; Content Below is Based on WHO 4th Edition Classification|This page was converted to the new template on 2023-12-07. The original page can be found at [[HAEM4:ALK-Positive Large B-cell Lymphoma]].

}}</blockquote>

}}</blockquote>

<span style="color:#0070C0">(General Instructions – The main focus of these pages is the clinically significant genetic alterations in each disease type. Use [https://www.genenames.org/ <u>HUGO-approved gene names and symbols</u>] (italicized when appropriate), [https://varnomen.hgvs.org/ HGVS-based nomenclature for variants], as well as generic names of drugs and testing platforms or assays if applicable. Please complete tables whenever possible and do not delete them (add N/A if not applicable in the table and delete the examples); to add (or move) a row or column to a table, click within the table and select the > symbol that appears to be given options. Please do not delete or alter the section headings. The use of bullet points alongside short blocks of text rather than only large paragraphs is encouraged. Additional instructions below in italicized blue text should not be included in the final page content. Please also see </span><u>[[Author_Instructions]]</u><span style="color:#0070C0"> and [[Frequently Asked Questions (FAQs)|<u>FAQs</u>]] as well as contact your [[Leadership|<u>Associate Editor</u>]] or [mailto:CCGA@cancergenomics.org <u>Technical Support</u>])</span>

<span style="color:#0070C0">(General Instructions – The focus of these pages is the clinically significant genetic alterations in each disease type. This is based on up-to-date knowledge from multiple resources such as PubMed and the WHO classification books. The CCGA is meant to be a supplemental resource to the WHO classification books; the CCGA captures in a continually updated wiki-stye manner the current genetics/genomics knowledge of each disease, which evolves more rapidly than books can be revised and published. If the same disease is described in multiple WHO classification books, the genetics-related information for that disease will be consolidated into a single main page that has this template (other pages would only contain a link to this main page). Use [https://www.genenames.org/ <u>HUGO-approved gene names and symbols</u>] (italicized when appropriate), [https://varnomen.hgvs.org/ <u>HGVS-based nomenclature for variants</u>], as well as generic names of drugs and testing platforms or assays if applicable. Please complete tables whenever possible and do not delete them (add N/A if not applicable in the table and delete the examples); to add (or move) a row or column in a table, click nearby within the table and select the > symbol that appears. Please do not delete or alter the section headings. The use of bullet points alongside short blocks of text rather than only large paragraphs is encouraged. Additional instructions below in italicized blue text should not be included in the final page content. Please also see </span><u>[[Author_Instructions]]</u><span style="color:#0070C0"> and [[Frequently Asked Questions (FAQs)|<u>FAQs</u>]] as well as contact your [[Leadership|<u>Associate Editor</u>]] or [mailto:CCGA@cancergenomics.org <u>Technical Support</u>].)</span>

==Primary Author(s)*==

==Primary Author(s)*==

Fabiola Quintero-Rivera, MD, FACMG (University of California, Irvine)

Fabiola Quintero-Rivera, MD, FACMG (University of California, Irvine)

==WHO Classification of Disease==

==WHO Classification of Disease==

|}

|}

==Definition / Description of Disease==

==WHO Essential and Desirable Genetic Diagnostic Criteria==

 

<span style="color:#0070C0">(''Instructions: The table will have the diagnostic criteria from the WHO book <u>autocompleted</u>; remove any <u>non</u>-genetics related criteria. If applicable, add text about other classification'' ''systems that define this entity and specify how the genetics-related criteria differ.'')</span>

Diffuse, monomorphic neoplasm of large B-cells with a plasmablastic immunophenotype and ALK expression due to ''ALK'' rearrangement

{| class="wikitable"

 

|+

|WHO Essential Criteria (Genetics)*

 

|

Not recommended: ALK-positive plasmablastic B-cell lymphoma; ALK-positive diffuse large B-cell lymphoma

|-

 

|WHO Desirable Criteria (Genetics)*

==Epidemiology / Prevalence==

|

 

|-

|Other Classification

**~ 200 cases reported in literature to date<ref>{{Cite journal|last=Castillo|first=Jorge J.|last2=Beltran|first2=Brady E.|last3=Malpica|first3=Luis|last4=Marques-Piubelli|first4=Mario L.|last5=Miranda|first5=Roberto N.|date=2021-12|title=Anaplastic lymphoma kinase-positive large B-cell lymphoma (ALK + LBCL): a systematic review of clinicopathological features and management|url=https://pubmed.ncbi.nlm.nih.gov/34151703|journal=Leukemia & Lymphoma|volume=62|issue=12|pages=2845–2853|doi=10.1080/10428194.2021.1941929|issn=1029-2403|pmid=34151703}}</ref>

|

 

|}

*Range: 9-85 years; median: ~ 40 years<ref>{{Cite journal|last=Pan|first=Zenggang|last2=Hu|first2=Shimin|last3=Li|first3=Min|last4=Zhou|first4=Yi|last5=Kim|first5=Young S.|last6=Reddy|first6=Vishnu|last7=Sanmann|first7=Jennifer N.|last8=Smith|first8=Lynette M.|last9=Chen|first9=Mingyi|date=2017-01|title=ALK-positive Large B-cell Lymphoma: A Clinicopathologic Study of 26 Cases With Review of Additional 108 Cases in the Literature|url=https://pubmed.ncbi.nlm.nih.gov/27740969|journal=The American Journal of Surgical Pathology|volume=41|issue=1|pages=25–38|doi=10.1097/PAS.0000000000000753|issn=1532-0979|pmid=27740969}}</ref><ref>{{Cite journal|last=Castillo|first=Jorge J.|last2=Beltran|first2=Brady E.|last3=Malpica|first3=Luis|last4=Marques-Piubelli|first4=Mario L.|last5=Miranda|first5=Roberto N.|date=2021-12|title=Anaplastic lymphoma kinase-positive large B-cell lymphoma (ALK + LBCL): a systematic review of clinicopathological features and management|url=https://pubmed.ncbi.nlm.nih.gov/34151703|journal=Leukemia & Lymphoma|volume=62|issue=12|pages=2845–2853|doi=10.1080/10428194.2021.1941929|issn=1029-2403|pmid=34151703}}</ref>

<nowiki>*</nowiki>Note: These are only the genetic/genomic criteria. Additional diagnostic criteria can be found in the [https://tumourclassification.iarc.who.int/home <u>WHO Classification of Tumours</u>].

*Male to Female ratio: 3-4:1<ref>{{Cite journal|last=Sukswai|first=Narittee|last2=Lyapichev|first2=Kirill|last3=Khoury|first3=Joseph D.|last4=Medeiros|first4=L. Jeffrey|date=2020-01|title=Diffuse large B-cell lymphoma variants: an update|url=https://pubmed.ncbi.nlm.nih.gov/31735345|journal=Pathology|volume=52|issue=1|pages=53–67|doi=10.1016/j.pathol.2019.08.013|issn=1465-3931|pmid=31735345}}</ref><ref>{{Cite journal|last=Castillo|first=Jorge J.|last2=Beltran|first2=Brady E.|last3=Malpica|first3=Luis|last4=Marques-Piubelli|first4=Mario L.|last5=Miranda|first5=Roberto N.|date=2021-12|title=Anaplastic lymphoma kinase-positive large B-cell lymphoma (ALK + LBCL): a systematic review of clinicopathological features and management|url=https://pubmed.ncbi.nlm.nih.gov/34151703|journal=Leukemia & Lymphoma|volume=62|issue=12|pages=2845–2853|doi=10.1080/10428194.2021.1941929|issn=1029-2403|pmid=34151703}}</ref>

==Related Terminology==

 

<span style="color:#0070C0">(''Instructions: The table will have the related terminology from the WHO <u>autocompleted</u>.)''</span>

{| class="wikitable"

{| class="wikitable"

|'''Signs and Symptoms'''

|+

|Asymptomatic lymphadenopathy

|Acceptable

 

|-

|-

|'''Laboratory Findings'''

|Not Recommended

|Serum LDH elevation

|

|}

|}

==Sites of Involvement==

==Gene Rearrangements==

 

 

 

{| class="wikitable sortable"

{| class="wikitable sortable"

|-

|-

!Finding!!Marker

!Driver Gene!!Fusion(s) and Common Partner Genes!!Molecular Pathogenesis!!Typical Chromosomal Alteration(s)

|-

|-

|Positive (universal)||ALK, CD138, VS38, IRF4/MUM1, BLIMP1, XBP1

|<span class="blue-text">EXAMPLE:</span> ''ABL1''||<span class="blue-text">EXAMPLE:</span> ''BCR::ABL1''||<span class="blue-text">EXAMPLE:</span> The pathogenic derivative is the der(22) resulting in fusion of 5’ BCR and 3’ABL1.||<span class="blue-text">EXAMPLE:</span> t(9;22)(q34;q11.2)

|<span class="blue-text">EXAMPLE:</span> Common (CML)

|<span class="blue-text">EXAMPLE:</span> D, P, T

|<span class="blue-text">EXAMPLE:</span> Yes (WHO, NCCN)

|<span class="blue-text">EXAMPLE:</span>

|-

|-

|Positive (subset)||EMA (90%), Cytoplasmic Ig (90%), IgA (80%), CD45 (90%), CD30 (15%), CD4 (50%), CD57 (10%), CD43, Cytokeratin (10%)

|<span class="blue-text">EXAMPLE:</span> ''CIC''

|<span class="blue-text">EXAMPLE:</span> ''CIC::DUX4''

|<span class="blue-text">EXAMPLE:</span> Typically, the last exon of ''CIC'' is fused to ''DUX4''. The fusion breakpoint in ''CIC'' is usually intra-exonic and removes an inhibitory sequence, upregulating ''PEA3'' genes downstream of ''CIC'' including ''ETV1'', ''ETV4'', and ''ETV5''.

|<span class="blue-text">EXAMPLE:</span> t(4;19)(q25;q13)

|<span class="blue-text">EXAMPLE:</span> Common (CIC-rearranged sarcoma)

 

''DUX4'' has many homologous genes; an alternate translocation in a minority of cases is t(10;19), but this is usually indistinguishable from t(4;19) by short-read sequencing (add references).

|-

|-

|Negative (universal)||Pan-T cell antigens, CD8, B-cell antigens, CD10, BCL-6, Cyclin-D1, HHV8

|<span class="blue-text">EXAMPLE:</span> ''ALK''

|}

|<span class="blue-text">EXAMPLE:</span> ''ELM4::ALK''

Put your text here and fill in the table

|<span class="blue-text">EXAMPLE:</span> Fusions result in constitutive activation of the ''ALK'' tyrosine kinase. The most common ''ALK'' fusion is ''EML4::ALK'', with breakpoints in intron 19 of ''ALK''. At the transcript level, a variable (5’) partner gene is fused to 3’ ''ALK'' at exon 20. Rarely, ''ALK'' fusions contain exon 19 due to breakpoints in intron 18.

|-

|-

!Chromosomal Rearrangement!!Genes in Fusion (5’ or 3’ Segments)!!Pathogenic Derivative!!Prevalence

!Diagnostic Significance (Yes, No or Unknown)

!Prognostic Significance (Yes, No or Unknown)

|<span class="blue-text">EXAMPLE:</span> Intragenic deletion of exons 2–7 in ''EGFR'' removes the ligand-binding domain, resulting in a constitutively active tyrosine kinase with downstream activation of multiple oncogenic pathways.

|<span class="blue-text">EXAMPLE:</span> Recurrent (IDH-wildtype Glioblastoma)

|<span class="blue-text">EXAMPLE:</span> D, P, T

|-

|-

|<span class="blue-text">EXAMPLE:</span> t(9;22)(q34;q11.2)||<span class="blue-text">EXAMPLE:</span> 3'ABL1 / 5'BCR||<span class="blue-text">EXAMPLE:</span> der(22)||<span class="blue-text">EXAMPLE:</span> 20% (COSMIC)

|

|

|Yes

|

|No

|

|Yes

|

|<span class="blue-text">EXAMPLE:</span>

|

 

|

|

|}

|}

<blockquote class='blockedit'>{{Box-round|title=v4:Chromosomal Rearrangements (Gene Fusions)|The content below was from the previous version of the page. Please incorporate above.}}</blockquote>

<blockquote class="blockedit">{{Box-round|title=v4:Chromosomal Rearrangements (Gene Fusions)|The content below was from the previous version of the page. Please incorporate above.}}</blockquote>

{| class="wikitable sortable"

{| class="wikitable sortable"

----

----

</blockquote>

</blockquote>

==Individual Region Genomic Gain / Loss / LOH==

==Individual Region Genomic Gain/Loss/LOH==

{| class="wikitable sortable"

{| class="wikitable sortable"

|-

|-

!Chr #!!Gain / Loss / Amp / LOH!!Minimal Region Genomic Coordinates [Genome Build]!!Minimal Region Cytoband

!Chr #!!'''Gain, Loss, Amp, LOH'''!!'''Minimal Region Cytoband and/or Genomic Coordinates [Genome Build; Size]'''!!'''Relevant Gene(s)'''

!Diagnostic Significance (Yes, No or Unknown)

!'''Diagnostic, Prognostic, and Therapeutic Significance - D, P, T'''

!Prognostic Significance (Yes, No or Unknown)

!'''Established Clinical Significance Per Guidelines - Yes or No (Source)'''

!Therapeutic Significance (Yes, No or Unknown)

!'''Clinical Relevance Details/Other Notes'''

!Notes

|-

|-

|<span class="blue-text">EXAMPLE:</span>

|<span class="blue-text">EXAMPLE:</span>

7

7

|<span class="blue-text">EXAMPLE:</span> Loss

|<span class="blue-text">EXAMPLE:</span> Loss

|<span class="blue-text">EXAMPLE:</span>

|<span class="blue-text">EXAMPLE:</span>

 

chr7

chr7:1- 159,335,973 [hg38]

|<span class="blue-text">EXAMPLE:</span>

|<span class="blue-text">EXAMPLE:</span>

 

|<span class="blue-text">EXAMPLE:</span> D, P

|<span class="blue-text">EXAMPLE:</span> No

|Yes

|No

|<span class="blue-text">EXAMPLE:</span>

|<span class="blue-text">EXAMPLE:</span>

 

Presence of monosomy 7 (or 7q deletion) is sufficient for a diagnosis of AML with MDS-related changes when there is ≥20% blasts and no prior therapy (add reference).  Monosomy 7/7q deletion is associated with a poor prognosis in AML (add references).

Presence of monosomy 7 (or 7q deletion) is sufficient for a diagnosis of AML with MDS-related changes when there is ≥20% blasts and no prior therapy (add reference).  Monosomy 7/7q deletion is associated with a poor prognosis in AML (add reference).

|-

|-

|<span class="blue-text">EXAMPLE:</span>

|<span class="blue-text">EXAMPLE:</span>

8

8

|<span class="blue-text">EXAMPLE:</span> Gain

|<span class="blue-text">EXAMPLE:</span> Gain

|<span class="blue-text">EXAMPLE:</span>

|<span class="blue-text">EXAMPLE:</span>

 

chr8:1-145,138,636 [hg38]

17q12; chr17:39,700,064-39,728,658 [hg38; 28.6 kb]

|<span class="blue-text">EXAMPLE:</span>

|<span class="blue-text">EXAMPLE:</span>

 

|<span class="blue-text">EXAMPLE:</span> D, P, T

|

|No

|No

|<span class="blue-text">EXAMPLE:</span>

|<span class="blue-text">EXAMPLE:</span>

 

Amplification of ''ERBB2'' is associated with HER2 overexpression in HER2 positive breast cancer (add references). Add criteria for how amplification is defined.

Common recurrent secondary finding for t(8;21) (add reference).

|}

|}

<blockquote class='blockedit'>{{Box-round|title=v4:Individual Region Genomic Gain / Loss / LOH|The content below was from the previous version of the page. Please incorporate above.}}</blockquote>

<blockquote class="blockedit">{{Box-round|title=v4:Individual Region Genomic Gain/Loss/LOH|The content below was from the previous version of the page. Please incorporate above.}}</blockquote>

Gains or amplifications of ''MYC'' (~50% of cases)<ref>{{Cite journal|last=Valera|first=Alexandra|last2=Colomo|first2=Lluis|last3=Martínez|first3=Antonio|last4=de Jong|first4=Daphne|last5=Balagué|first5=Olga|last6=Matheu|first6=Gabriel|last7=Martínez|first7=Mónica|last8=Taddesse-Heath|first8=Lekidelu|last9=Jaffe|first9=Elaine S.|date=2013-10|title=ALK-positive large B-cell lymphomas express a terminal B-cell differentiation program and activated STAT3 but lack MYC rearrangements|url=https://pubmed.ncbi.nlm.nih.gov/23599149|journal=Modern Pathology: An Official Journal of the United States and Canadian Academy of Pathology, Inc|volume=26|issue=10|pages=1329–1337|doi=10.1038/modpathol.2013.73|issn=1530-0285|pmc=6368829|pmid=23599149}}</ref>

Gains or amplifications of ''MYC'' (~50% of cases)<ref>{{Cite journal|last=Valera|first=Alexandra|last2=Colomo|first2=Lluis|last3=Martínez|first3=Antonio|last4=de Jong|first4=Daphne|last5=Balagué|first5=Olga|last6=Matheu|first6=Gabriel|last7=Martínez|first7=Mónica|last8=Taddesse-Heath|first8=Lekidelu|last9=Jaffe|first9=Elaine S.|date=2013-10|title=ALK-positive large B-cell lymphomas express a terminal B-cell differentiation program and activated STAT3 but lack MYC rearrangements|url=https://pubmed.ncbi.nlm.nih.gov/23599149|journal=Modern Pathology: An Official Journal of the United States and Canadian Academy of Pathology, Inc|volume=26|issue=10|pages=1329–1337|doi=10.1038/modpathol.2013.73|issn=1530-0285|pmc=6368829|pmid=23599149}}</ref>

----

----

</blockquote>

</blockquote>

==Characteristic Chromosomal Patterns==

==Characteristic Chromosomal or Other Global Mutational Patterns==

{| class="wikitable sortable"

{| class="wikitable sortable"

|-

|-

!Chromosomal Pattern

!Chromosomal Pattern

!Diagnostic Significance (Yes, No or Unknown)

!Molecular Pathogenesis

!Prognostic Significance (Yes, No or Unknown)

!Therapeutic Significance (Yes, No or Unknown)

'''Common >20%, Recurrent 5-20% or Rare <5% (Disease)'''

!Notes

!'''Diagnostic, Prognostic, and Therapeutic Significance - D, P, T'''

!'''Established Clinical Significance Per Guidelines - Yes or No (Source)'''

!'''Clinical Relevance Details/Other Notes'''

|-

|-

|<span class="blue-text">EXAMPLE:</span>

|<span class="blue-text">EXAMPLE:</span>

Co-deletion of 1p and 18q

Co-deletion of 1p and 18q

|Yes

|<span class="blue-text">EXAMPLE:</span> See chromosomal rearrangements table as this pattern is due to an unbalanced derivative translocation associated with oligodendroglioma (add reference).

|No

|<span class="blue-text">EXAMPLE:</span> Common (Oligodendroglioma)

|No

|<span class="blue-text">EXAMPLE:</span> D, P

|<span class="blue-text">EXAMPLE:</span>

|<span class="blue-text">EXAMPLE:</span>

 

See chromosomal rearrangements table as this pattern is due to an unbalanced derivative translocation associated with oligodendroglioma (add reference).

|<span class="blue-text">EXAMPLE:</span> Common (Endometrial carcinoma)

|}

|}

<blockquote class='blockedit'>{{Box-round|title=v4:Characteristic Chromosomal Patterns|The content below was from the previous version of the page. Please incorporate above.}}</blockquote>

<blockquote class="blockedit">{{Box-round|title=v4:Characteristic Chromosomal Patterns|The content below was from the previous version of the page. Please incorporate above.}}</blockquote>

N/A

N/A

----

----

</blockquote>

</blockquote>

==Gene Mutations (SNV / INDEL)==

==Gene Mutations (SNV/INDEL)==

{| class="wikitable sortable"

{| class="wikitable sortable"

|-

|-

!Gene; Genetic Alteration!!'''Presumed Mechanism (Tumor Suppressor Gene [TSG] / Oncogene / Other)'''!!'''Prevalence (COSMIC /  TCGA / Other)'''!!'''Concomitant Mutations'''!!'''Mutually Exclusive Mutations'''

!Gene!!'''Genetic Alteration'''!!'''Tumor Suppressor Gene, Oncogene, Other'''!!'''Prevalence -'''

!'''Diagnostic Significance (Yes, No or Unknown)'''

'''Common >20%, Recurrent 5-20% or Rare <5% (Disease)'''

!Prognostic Significance (Yes, No or Unknown)

!'''Diagnostic, Prognostic, and Therapeutic Significance - D, P, T  '''

!'''Established Clinical Significance Per Guidelines - Yes or No (Source)'''

!Notes

!'''Clinical Relevance Details/Other Notes'''

|-

|-

|<span class="blue-text">EXAMPLE:</span> TP53; Variable LOF mutations

|<span class="blue-text">EXAMPLE:</span>''EGFR''

<span class="blue-text">EXAMPLE:</span>

 

EGFR; Exon 20 mutations

 

<span class="blue-text">EXAMPLE:</span> BRAF; Activating mutations

|<span class="blue-text">EXAMPLE:</span> T

|<span class="blue-text">EXAMPLE:</span> TSG

|<span class="blue-text">EXAMPLE:</span> 20% (COSMIC)

|<span class="blue-text">EXAMPLE:</span> Exons 18, 19, and 21 mutations are targetable for therapy. Exon 20 T790M variants cause resistance to first generation TKI therapy and are targetable by second and third generation TKIs (add references).

 

<span class="blue-text">EXAMPLE:</span> 30% (add Reference)

|<span class="blue-text">EXAMPLE:</span> ''TP53''; Variable LOF mutations

|<span class="blue-text">EXAMPLE:</span> IDH1 R123H

|<span class="blue-text">EXAMPLE:</span> EGFR amplification

|<span class="blue-text">EXAMPLE:</span> Variable LOF mutations

|<span class="blue-text">EXAMPLE:</span> Tumor Supressor Gene

|<span class="blue-text">EXAMPLE:</span> Common (breast cancer)

|<span class="blue-text">EXAMPLE:</span> >90% are somatic; rare germline alterations associated with Li-Fraumeni syndrome (add reference). Denotes a poor prognosis in breast cancer.

|<span class="blue-text">EXAMPLE:</span> ''BRAF''; Activating mutations

|<span class="blue-text">EXAMPLE:</span> Activating mutations

|

|

|

|

|

|

|}Note: A more extensive list of mutations can be found in [https://www.cbioportal.org/ <u>cBioportal</u>], [https://cancer.sanger.ac.uk/cosmic <u>COSMIC</u>], and/or other databases. When applicable, gene-specific pages within the CCGA site directly link to pertinent external content.

|}

Note: A more extensive list of mutations can be found in cBioportal (https://www.cbioportal.org/), COSMIC (https://cancer.sanger.ac.uk/cosmic), ICGC (https://dcc.icgc.org/) and/or other databases. When applicable, gene-specific pages within the CCGA site directly link to pertinent external content.

 

<blockquote class='blockedit'>{{Box-round|title=v4:Gene Mutations (SNV / INDEL)|The content below was from the previous version of the page. Please incorporate above.}}</blockquote>

<blockquote class="blockedit">{{Box-round|title=v4:Gene Mutations (SNV/INDEL)|The content below was from the previous version of the page. Please incorporate above.}}</blockquote>

N/A

N/A

<nowiki>*</nowiki>''Citation of this Page'': “ALK-positive large B-cell lymphoma”. Compendium of Cancer Genome Aberrations (CCGA), Cancer Genomics Consortium (CGC), updated {{REVISIONMONTH}}/{{REVISIONDAY}}/{{REVISIONYEAR}}, <nowiki>https://ccga.io/index.php/HAEM5:ALK-positive_large_B-cell_lymphoma</nowiki>.

<nowiki>*</nowiki>''Citation of this Page'': “ALK-positive large B-cell lymphoma”. Compendium of Cancer Genome Aberrations (CCGA), Cancer Genomics Consortium (CGC), updated {{REVISIONMONTH}}/{{REVISIONDAY}}/{{REVISIONYEAR}}, <nowiki>https://ccga.io/index.php/HAEM5:ALK-positive_large_B-cell_lymphoma</nowiki>.

[[Category:HAEM5]][[Category:DISEASE]][[Category:Diseases A]]

[[Category:HAEM5]]

[[Category:DISEASE]]

[[Category:Diseases A]]