Compendium of Cancer Genome Aberrations

HAEM5:Plasma cell neoplasms with associated paraneoplastic syndrome: Difference between revisions

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{{DISPLAYTITLE:Plasma cell neoplasms with associated paraneoplastic syndrome}}
{{DISPLAYTITLE:Plasma cell neoplasms with associated paraneoplastic syndrome}}
[[HAEM5:Table_of_Contents|Haematolymphoid Tumours (5th ed.)]]
[[HAEM5:Table_of_Contents|Haematolymphoid Tumours (WHO Classification, 5th ed.)]]


{{Under Construction}}
{{Under Construction}}


<blockquote class='blockedit'>{{Box-round|title=HAEM5 Conversion Notes|This page was converted to the new template on 2023-12-04. The original page can be found at [[HAEM4:POEMS Syndrome]].
<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:POEMS Syndrome]].
Other relevent pages include: [[TEMPI Syndrome]]
Other relevent pages include: [[HAEM4:TEMPI Syndrome]]


Note: author needs to include POEMS, TEMPI, and look for AESOP content
Note: author needs to include POEMS, TEMPI, and look for AESOP content
}}</blockquote>
}}</blockquote>
<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)*==


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Tharanga Niroshini Senaratne, PhD
Tharanga Niroshini Senaratne, PhD
==WHO Classification of Disease==


__TOC__
{| class="wikitable"
 
!Structure
==Cancer Category / Type==
!Disease
 
|-
[[HAEM4:Plasma Cell Neoplasms|Plasma Cell Neoplasm]]
|Book
 
|Haematolymphoid Tumours (5th ed.)
==Cancer Sub-Classification / Subtype==
|-
 
|Category
[[HAEM4:Plasma Cell Neoplasms with Associated Paraneoplastic Syndrome]]
|B-cell lymphoid proliferations and lymphomas
 
|-
==Definition / Description of Disease==
|Family
|Plasma cell neoplasms and other diseases with paraproteins
|-
|Type
|Plasma cell neoplasms
|-
|Subtype(s)
|Plasma cell neoplasms with associated paraneoplastic syndrome
|}


POEMS syndrome is a rare blood disorder which is considered to be a subtype of plasma cell neoplasm. It is a multisystem disorder and stands for '''<u>P</u>'''olyneuropathy, '''<u>O</u>'''rganomegaly, '''<u>E</u>'''ndocrinopathy/edema, '''<u>M</u>'''onoclonal-protein (increased levels in blood), and '''<u>S</u>'''kin changes. In this condition, abnormal monoclonal proteins are secreted by plasma cells leading to its clinical presentations which include nerve damage, enlargement of spleen and/or lymph nodes, endocrine involvement leading to diabetes, thyroid abnormalities and certain skin/ hair changes such as hyperpigmentation, thickening of skin, red spots and increased facial hair growth.
==Related Terminology==


==Synonyms / Terminology==
*<ref name=":0">https://rarediseases.org/rare-diseases/poems-syndrome/</ref>Crow-Fukase syndrome
*<ref name=":0" />Osteosclerotic myeloma
*<ref name=":0" />PEP syndrome (Polyneuropathy-endocrinopathy-plasma cell dyscrasia syndrome)
*<ref name=":0" />Shimpo syndrome
*<ref name=":0" />Takatsuki syndrome<ref name=":1">{{Cite journal|last=Suichi|first=Tomoki|last2=Misawa|first2=Sonoko|last3=Beppu|first3=Minako|last4=Takahashi|first4=Sho|last5=Sekiguchi|first5=Yukari|last6=Shibuya|first6=Kazumoto|last7=Amino|first7=Hiroshi|last8=Tsuneyama|first8=Atsuko|last9=Suzuki|first9=Yo-Ichi|date=2019-09-03|title=Prevalence, clinical profiles, and prognosis of POEMS syndrome in Japanese nationwide survey|url=https://pubmed.ncbi.nlm.nih.gov/31371568|journal=Neurology|volume=93|issue=10|pages=e975–e983|doi=10.1212/WNL.0000000000008062|issn=1526-632X|pmid=31371568}}</ref>
==Epidemiology / Prevalence==
Not much information can be derived regarding the incidence and prevalence of POEMS syndrome.<ref group="Epidemiology">https://www.orpha.net/consor/cgi-bin/OC_Exp.php?Lng=GB&Expert=2905</ref>. Some information can be derived from the study conducted in Japan in the year 2015. The result showed that the prevalence is 0.3 per 1,00,000 with a male: female ratio of 1.5:1.<ref name=":1" /> The median age of  occurrence is 54.<ref>{{Cite journal|last=Suichi|first=Tomoki|last2=Misawa|first2=Sonoko|last3=Beppu|first3=Minako|last4=Takahashi|first4=Sho|last5=Sekiguchi|first5=Yukari|last6=Shibuya|first6=Kazumoto|last7=Amino|first7=Hiroshi|last8=Tsuneyama|first8=Atsuko|last9=Suzuki|first9=Yo-Ichi|date=2019-09-03|title=Prevalence, clinical profiles, and prognosis of POEMS syndrome in Japanese nationwide survey|url=https://pubmed.ncbi.nlm.nih.gov/31371568|journal=Neurology|volume=93|issue=10|pages=e975–e983|doi=10.1212/WNL.0000000000008062|issn=1526-632X|pmid=31371568}}</ref> However, few cases have also been seen in patients in their twenties.<ref name=":0" /> Mean survival is 13.7 years.<ref>{{Cite journal|last=Marinho|first=Flauberto Sousa|last2=Pirmez|first2=Rodrigo|last3=Nogueira|first3=Renata|last4=Cuzzi|first4=Tullia|last5=Sodré|first5=Celso Tavares|last6=Silva|first6=Marcia|date=2015|title=Cutaneous Manifestations in POEMS Syndrome: Case Report and Review|url=https://www.karger.com/Article/FullText/381302|journal=Case Reports in Dermatology|language=english|volume=7|issue=1|pages=61–69|doi=10.1159/000381302|issn=1662-6567|pmc=PMC4448059|pmid=26034475}}</ref>
==Clinical Features==
Put your text here and fill in the table <span style="color:#0070C0">(''Instruction: Can include references in the table'') </span>
{| class="wikitable"
{| class="wikitable"
|'''Signs and Symptoms'''
|+
|EXAMPLE Asymptomatic (incidental finding on complete blood counts)
|Acceptable
 
|For POEMS syndrome: osteosclerotic myeloma
EXAMPLE B-symptoms (weight loss, fever, night sweats)
 
EXAMPLE Fatigue
 
EXAMPLE Lymphadenopathy (uncommon)
|-
|-
|'''Laboratory Findings'''
|Not Recommended
|EXAMPLE Cytopenias
|N/A
 
EXAMPLE Lymphocytosis (low level)
|}
|}


==Gene Rearrangements==


<blockquote class='blockedit'>{{Box-round|title=v4:Clinical Features|The content below was from the old template. Please incorporate above.}}
As mentioned earlier, POEMS syndrome is a rare disorder which comprises of constellation of clinical presentations with neuropathy present in almost 100% of the cases. Following are the clinical features:
*'''<u>Polyneuropathy</u>:''' One of the earliest presentations or may be the only presentation. The onset is usually sub-acute with mixed (sensory-motor) distal & symmetrical involvement. This is often associated with abnormal sensations like allodynia. Sensory involvement precedes motor loss. Most patients need assistance soon after developing polyneuropathy either because of  loss of function or pain.<ref name=":2">{{Cite journal|last=Brown|first=Rachel|last2=Ginsberg|first2=Lionel|date=2019|title=POEMS syndrome: clinical update|url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6342878/|journal=Journal of Neurology|volume=266|issue=1|pages=268–277|doi=10.1007/s00415-018-9110-6|issn=0340-5354|pmc=6342878|pmid=30498913}}</ref>
*'''<u>Organomegaly and Organ dysfunction:</u>'''  There are multiple organ involvement and damage leading to organ dysfunction. Most common involved organs are lymph nodes, liver, kidney and spleen. Other organs which can be affected are CNS, renal, lung which can lead to asymptomatic parenchymal thickening, decreased GFR and pulmonary HTN; respectively. <ref name=":2" /> Furthermore, arterial vascular involvement  has been noted which can lead to cerebro-vascular accidents and ischemic strokes. <ref name=":2" />
*'''<u>Endocrinopathy:</u>''' Multiple endocrinal organs can be involved. Most common presentation noted in males are erectile dysfunction because of hypogonadism which may be because of involvement of hypothalamus, pituitary or the primary organ itself(testes).<ref>{{Cite journal|last=Dispenzieri|first=Angela|last2=Kourelis|first2=Taxiarchis|last3=Buadi|first3=Francis|date=2018-02|title=POEMS Syndrome|url=http://dx.doi.org/10.1016/j.hoc.2017.09.010|journal=Hematology/Oncology Clinics of North America|volume=32|issue=1|pages=119–139|doi=10.1016/j.hoc.2017.09.010|issn=0889-8588}}</ref>  Other presentations can be diabetes, hypo/hyperthyroidism or adrenal gland abnormalities.
*'''<u>Monoclonal antibodies</u>''': POEMS syndrome is typically considered to be a plasma cell abnormality where plasma cells produce excessively high paraproteins particularly light chains (lambda proteins mainly of IgA type). The unique feature of POEMS which distinguish this condition from rest of the gammopathies is that- it is found that in approximately 50% of the pre-treatment specimens have reactive lymphoid aggregates which  contain a mixture of both B and T cells with a thin rim of plasma cells. Other consistent finding are atypically appearing megakaryocytes with hyperplasia. Increased platelets counts are seen in 54% of the cases.<ref name=":4">{{Cite journal|last=Dispenzieri|first=Angela|date=2019|title=POEMS Syndrome: 2019 Update on diagnosis, risk-stratification, and management|url=https://onlinelibrary.wiley.com/doi/abs/10.1002/ajh.25495|journal=American Journal of Hematology|language=en|volume=94|issue=7|pages=812–827|doi=10.1002/ajh.25495|issn=1096-8652}}</ref>  PBS is usually normal. <ref name=":2" />
*'''<u>Skin involvement:</u>''' About 68% patients diagnosed with POEMS syndrome present with skin involvement. Most common is diffuse hyperpigmentation(purplish hue), acrocyanosis, calciphylaxis, thickening of skin, papular lesions, excessive sweating; aka; hyperhidrosis. Areas most commonly involved are extensor surfaces, neck,  arm pit. Nail changes such as leukonychia. Hypertrichosis has also been reported. In few cases, hemangiomas such as cherry and capillary hemangiomas has been noted.
*'''<u>Other findings</u>'''- fluid accumulation in body cavities leading to peritoneal effusion, pleural effusion and ascites.
*'''<u>Papilledema</u>'''
*'''<u>Polycythemia</u>'''
*'''<u>Specific finding in males</u>'''- gynecomastia and  impotence noted in male patients.
*'''<u>Specific findings in Females</u>'''- amenorrhea and galactorrhea have been reported in female patients with POEMS syndrome
</blockquote>
==Sites of Involvement==
POEMS syndrome involves multiple systems of the body.
*'''<u>Peripheral nerves and spinal cord</u>''': Peripheral neuropathy is present in 100% of the cases. This is the most common manifestation of POEMS syndrome.
*'''<u>Reticuloendothelial system</u>'''- Lymph node, spleen and Liver are also most frequently involved. Lymph node simulates Castleman disease. Hepatosplenomegaly is present in almost 50% of the cases.
*'''<u>Bone</u>'''- Bone is involved in 95% of the POEMS patient. Bone lesions are mostly sclerotic, but occasionally can be lytic lesions surrounded by thin rim of sclerosis. "Soap bubble" appearances have also been reported.<ref>{{Cite journal|title=POEMS Syndrome - an overview {{!}} ScienceDirect Topics|url=https://www.sciencedirect.com/topics/medicine-and-dentistry/poems-syndrome}}</ref>
*'''<u>Skin</u>'''- About 90% of the POEMS patients develop skin changes. Most commonly being skin pigmentations.
*'''<u>Kidney-</u>''' Kidney damage has been reported which can alter GFR and can lead to CKD.
*<u>'''Pancreas-'''</u>  Diabetes type2 has been noted.<ref name=":3">{{Cite journal|title=POEMS Syndrome - Hormonal and Metabolic Disorders|url=https://www.merckmanuals.com/home/hormonal-and-metabolic-disorders/polyglandular-deficiency-syndromes/poems-syndrome|language=en-US}}</ref>
*'''<u>Adrenal gland-</u>''' Involvement of adrenal glands cause malfunctioning leading to Addison's disease.<ref name=":3" />
*'''<u>Gonads</u>'''- decreased level of testosterone can lead to hypo functioning of male gonads eventually leading to hypogonadism.<ref name=":3" />
*'''<u>Thyroids</u>'''
*'''<u>Eye</u>'''
==Morphologic Features==
*'''<u>Bone marrow Findings</u>'''- Increased monoclonal plasma cells interspersed between polyclonal plasma cells with majority of monoclonal cells resembling λ chains. Plasma cell rimming around lymphoid aggregates. Also, Platelet precursors or megakaryocytes hyperplasia have been reported. <ref>{{Cite journal|last=Dao|first=Linda N.|last2=Hanson|first2=Curtis A.|last3=Dispenzieri|first3=Angela|last4=Morice|first4=William G.|last5=Kurtin|first5=Paul J.|last6=Hoyer|first6=James D.|date=2011-06-16|title=Bone marrow histopathology in POEMS syndrome: a distinctive combination of plasma cell, lymphoid, and myeloid findings in 87 patients|url=https://pubmed.ncbi.nlm.nih.gov/21385854|journal=Blood|volume=117|issue=24|pages=6438–6444|doi=10.1182/blood-2010-11-316935|issn=1528-0020|pmc=3123015|pmid=21385854}}</ref>
*'''<u>Nerve fiber biopsies</u>'''- POEMS syndrome has predilection for peripheral nerves compared to autonomic nerve fibers. The manifestation is severe and progressive. Biopsy specimens have shown 2 specific findings including axonal degeneration and epineural blood vessels formation which can be helpful in differentiating from C IDP(Chronic Inflammatory Demyelinating Polyradiculoneuropathy). CIDP presents as endoneurial inflammation and characteristic "onion bulb appearance".<ref>{{Cite journal|last=Piccione|first=Ezequiel A.|last2=Engelstad|first2=Janean|last3=Dyck|first3=Peter J.|last4=Mauermann|first4=Michelle L.|last5=Dispenzieri|first5=Angela|last6=Dyck|first6=P. James B.|date=2016-10-31|title=Nerve pathologic features differentiate POEMS syndrome from CIDP|url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5088652/|journal=Acta Neuropathologica Communications|volume=4|doi=10.1186/s40478-016-0389-1|issn=2051-5960|pmc=5088652|pmid=27799073}}</ref>
*'''<u>Skin Biopsies</u>'''-  Cases who developed hemangioma, biopsy showed "glomeruloid pattern"; accumulation of blood vessels containing RBCs in dilated vascular space resembling renal glomeruli. Patients who presented with skin thickening showed sclerosis with dilation of blood vessels on biopsy. Livedo reticularis biopsies showed thrombosis with necrosis in arterioles.<ref>{{Cite journal|last=Barete|first=Stéphane|last2=Mouawad|first2=Roger|last3=Choquet|first3=Sylvain|last4=Viala|first4=Karine|last5=Leblond|first5=Véronique|last6=Musset|first6=Lucile|last7=Amoura|first7=Zahir|last8=Khayat|first8=David|last9=Francès|first9=Camille|date=2010-06-01|title=Skin Manifestations and Vascular Endothelial Growth Factor Levels in POEMS Syndrome: Impact of Autologous Hematopoietic Stem Cell Transplantation|url=http://archderm.jamanetwork.com/article.aspx?doi=10.1001/archdermatol.2010.100|journal=Archives of Dermatology|language=en|volume=146|issue=6|doi=10.1001/archdermatol.2010.100|issn=0003-987X}}</ref>
*'''<u>Bone lesions biopsy</u>''':    Osteosclerotic bone lesions biopsy shows proliferation of plasma cells which stain positive for CD138.<ref>{{Cite journal|last=Hara|first=Daisuke|last2=Akiyama|first2=Hisanao|last3=Nukui|first3=Saki|last4=Shimizu|first4=Takahiro|last5=Hoshikawa|first5=Masahiro|last6=Hasegawa|first6=Yasuhiro|date=2017-10|title=Utility of osteosclerotic lesion biopsy in diagnosis of POEMS syndrome: A case report|url=https://pubmed.ncbi.nlm.nih.gov/29019884|journal=Medicine|volume=96|issue=41|pages=e8188|doi=10.1097/MD.0000000000008188|issn=1536-5964|pmc=5662307|pmid=29019884}}</ref>
==Immunophenotype==
Put your text here and fill in the table <span style="color:#0070C0">(''Instruction: Can include references in the table'') </span>


Put your text here and fill in the table <span style="color:#0070C0">(''Instructions: Details on clinical significance such as prognosis and other important information can be provided in the notes section. Please include references throughout the table. Do not delete the table.'')</span>
{| class="wikitable sortable"
{| class="wikitable sortable"
|-
|-
!Finding!!Marker
!Driver Gene!!Fusion(s) and Common Partner Genes!!Molecular Pathogenesis!!Typical Chromosomal Alteration(s)
!Prevalence -Common >20%, Recurrent 5-20% or Rare <5% (Disease)
!Diagnostic, Prognostic, and Therapeutic Significance - D, P, T
!Established Clinical Significance Per Guidelines - Yes or No (Source)
!Clinical Relevance Details/Other Notes
|-
|-
|Positive (universal)||EXAMPLE CD1
|<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>
The t(9;22) is diagnostic of CML in the appropriate morphology and clinical context (add reference). This fusion is responsive to targeted therapy such as Imatinib (Gleevec) (add reference). BCR::ABL1 is generally favorable in CML (add reference).
|-
|-
|Positive (subset)||EXAMPLE CD2
|<span class="blue-text">EXAMPLE:</span> ''CIC''
|-
|<span class="blue-text">EXAMPLE:</span> ''CIC::DUX4''
|Negative (universal)||EXAMPLE CD3
|<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)
|<span class="blue-text">EXAMPLE:</span> D
|
|<span class="blue-text">EXAMPLE:</span>
 
''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 (subset)||EXAMPLE CD4
|<span class="blue-text">EXAMPLE:</span> ''ALK''
|}
|<span class="blue-text">EXAMPLE:</span> ''ELM4::ALK''




<blockquote class='blockedit'>{{Box-round|title=v4:Immunophenotype|The content below was from the old template. Please incorporate above.}}
Other fusion partners include ''KIF5B, NPM1, STRN, TFG, TPM3, CLTC, KLC1''
 
|<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.
Plasma cells in BM biopsy ranges from<5% to 60%. 95% of the cases have value <5%.<ref name=":6">{{Cite journal|last=Dispenzieri|first=Angela|date=2012-06-14|title=How I treat POEMS syndrome|url=https://doi.org/10.1182/blood-2012-03-378992|journal=Blood|volume=119|issue=24|pages=5650–5658|doi=10.1182/blood-2012-03-378992|issn=0006-4971|pmc=PMC3425020|pmid=22547581}}</ref> Usually there are a combination of normal polyclonal plasma cells and monoclonal plasma cells. The monoclonal plasma cells stains positive for λ chains (IgA and IgG). <ref>{{Cite journal|last=Dao|first=Linda N.|last2=Hanson|first2=Curtis A.|last3=Dispenzieri|first3=Angela|last4=Morice|first4=William G.|last5=Kurtin|first5=Paul J.|last6=Hoyer|first6=James D.|date=2011-06-16|title=Bone marrow histopathology in POEMS syndrome: a distinctive combination of plasma cell, lymphoid, and myeloid findings in 87 patients|url=https://doi.org/10.1182/blood-2010-11-316935|journal=Blood|volume=117|issue=24|pages=6438–6444|doi=10.1182/blood-2010-11-316935|issn=0006-4971|pmc=PMC3123015|pmid=21385854}}</ref>
|<span class="blue-text">EXAMPLE:</span> N/A
 
|<span class="blue-text">EXAMPLE:</span> Rare (Lung adenocarcinoma)
'''<u>POSITIVE</u>'''
|<span class="blue-text">EXAMPLE:</span> T
 
|
*CD138+ forms plasma cell rim around lymphoid aggregates
|<span class="blue-text">EXAMPLE:</span>
*CD38+ rim around lymphoid aggregates
*monoclonal Plasma cells stains positive for cytoplasmic λ chain immunoglobulins.
*Bright expression of CD45 and normal expression of CD19 in polytypic CD19 (Normal finding).
*Lymphoid aggregates were staining positive for CD20+ B cells and CD3+ T cells.
 
 
'''<u>NEGATIVE</u>'''
 
*Diminished expression of CD45 and loss of CD19 in monotypic plasma cells. (findings in POEMS).
 
*κ chain immunoglobulin stain absent.
*''JAK2<sup>V617F</sup>''  mutation absent
*HHV8 staining absent
 
<br />
</blockquote>
==Chromosomal Rearrangements (Gene Fusions)==
 
Put your text here and fill in the table


{| class="wikitable sortable"
Both balanced and unbalanced forms are observed by FISH (add references).
|-
|-
!Chromosomal Rearrangement!!Genes in Fusion (5’ or 3’ Segments)!!Pathogenic Derivative!!Prevalence
|<span class="blue-text">EXAMPLE:</span> ''ABL1''
!Diagnostic Significance (Yes, No or Unknown)
|<span class="blue-text">EXAMPLE:</span> N/A
!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.
!Therapeutic Significance (Yes, No or Unknown)
|<span class="blue-text">EXAMPLE:</span> N/A
!Notes
|<span class="blue-text">EXAMPLE:</span> Recurrent (IDH-wildtype Glioblastoma)
|<span class="blue-text">EXAMPLE:</span> D, P, T
|
|
|-
|-
|EXAMPLE t(9;22)(q34;q11.2)||EXAMPLE 3'ABL1 / 5'BCR||EXAMPLE der(22)||EXAMPLE 20% (COSMIC)
|
EXAMPLE 30% (add reference)
|
|Yes
|
|No
|
|Yes
|
|EXAMPLE
|
 
|
The t(9;22) is diagnostic of CML in the appropriate morphology and clinical context (add reference). This fusion is responsive to targeted therapy such as Imatinib (Gleevec) (add reference).
|
|}
|}


<blockquote class='blockedit'>{{Box-round|title=v4:Chromosomal Rearrangements (Gene Fusions)|The content below was from the old template. Please incorporate above.}}
<blockquote class="blockedit">{{Box-round|title=v4:Chromosomal Rearrangements (Gene Fusions)|The content below was from the old template. Please incorporate above.}}</blockquote>
<br />
<br />
<blockquote class="blockedit">
<center><span style="color:Maroon">'''End of V4 Section'''</span>
----
</blockquote>
</blockquote>




<blockquote class='blockedit'>{{Box-round|title=v4:Clinical Significance (Diagnosis, Prognosis and Therapeutic Implications).|Please incorporate this section into the relevant tables found in:
<blockquote class="blockedit">{{Box-round|title=v4:Clinical Significance (Diagnosis, Prognosis and Therapeutic Implications).|Please incorporate this section into the relevant tables found in:
* Chromosomal Rearrangements (Gene Fusions)
* Chromosomal Rearrangements (Gene Fusions)
* Individual Region Genomic Gain/Loss/LOH
* Individual Region Genomic Gain/Loss/LOH
* Characteristic Chromosomal Patterns
* Characteristic Chromosomal Patterns
* Gene Mutations (SNV/INDEL)}}
* Gene Mutations (SNV/INDEL)}}</blockquote>


Diagnosis of POEMS syndrome requires meticulous search for clinical features and testing because of clinical simulation with other common conditions. Being one of the rare disease entities it can easily be missed by clinicians.  
Diagnosis of POEMS syndrome requires meticulous search for clinical features and testing because of clinical simulation with other common conditions. Being one of the rare disease entities it can easily be missed by clinicians.  


'''<u>MANAGEMENT</u>'''<ref name=":4" />
'''<u>MANAGEMENT</u>'''<ref name=":4">{{Cite journal|last=Dispenzieri|first=Angela|date=2019|title=POEMS Syndrome: 2019 Update on diagnosis, risk-stratification, and management|url=https://onlinelibrary.wiley.com/doi/abs/10.1002/ajh.25495|journal=American Journal of Hematology|language=en|volume=94|issue=7|pages=812–827|doi=10.1002/ajh.25495|issn=1096-8652}}</ref>


Management of POEMS syndrome requires multiple steps.
Management of POEMS syndrome requires multiple steps.
Line 216: Line 170:
*clinical improvement in effusions
*clinical improvement in effusions


<blockquote class="blockedit">
<center><span style="color:Maroon">'''End of V4 Section'''</span>
----
</blockquote>
</blockquote>
==Individual Region Genomic Gain / Loss / LOH==
==Individual Region Genomic Gain/Loss/LOH==


Put your text here and fill in the table <span style="color:#0070C0">(''Instructions: Includes aberrations not involving gene fusions. Can include references in the table. Can refer to CGC workgroup tables as linked on the homepage if applicable.'') </span>


Put your text here and fill in the table <span style="color:#0070C0">(''Instructions: Includes aberrations not involving gene rearrangements. Details on clinical significance such as prognosis and other important information can be provided in the notes section. Can refer to CGC workgroup tables as linked on the homepage if applicable. Please include references throughout the table. Do not delete the table.'') </span>
{| class="wikitable sortable"
{| class="wikitable sortable"
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!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
|-
|-
|EXAMPLE
|<span class="blue-text">EXAMPLE:</span>
 
7
7
|EXAMPLE Loss
|<span class="blue-text">EXAMPLE:</span> Loss
|EXAMPLE
|<span class="blue-text">EXAMPLE:</span>
 
chr7:1- 159,335,973 [hg38]
|EXAMPLE
 
chr7
chr7
|Yes
|<span class="blue-text">EXAMPLE:</span>
|Yes
Unknown
|No
|<span class="blue-text">EXAMPLE:</span> D, P
|EXAMPLE
|<span class="blue-text">EXAMPLE:</span> No
 
|<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 reference).
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).
|-
|-
|EXAMPLE
|<span class="blue-text">EXAMPLE:</span>
 
8
8
|EXAMPLE Gain
|<span class="blue-text">EXAMPLE:</span> Gain
|EXAMPLE
|<span class="blue-text">EXAMPLE:</span>
 
chr8:1-145,138,636 [hg38]
|EXAMPLE
 
chr8
chr8
|No
|<span class="blue-text">EXAMPLE:</span>
|No
Unknown
|No
|<span class="blue-text">EXAMPLE:</span> D, P
|EXAMPLE
|
 
|<span class="blue-text">EXAMPLE:</span>
Common recurrent secondary finding for t(8;21) (add reference).
Common recurrent secondary finding for t(8;21) (add references).
|-
|<span class="blue-text">EXAMPLE:</span>
17
|<span class="blue-text">EXAMPLE:</span> Amp
|<span class="blue-text">EXAMPLE:</span>
17q12; chr17:39,700,064-39,728,658 [hg38; 28.6 kb]
|<span class="blue-text">EXAMPLE:</span>
''ERBB2''
|<span class="blue-text">EXAMPLE:</span> D, P, T
|
|<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.
|-
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<blockquote class="blockedit">{{Box-round|title=v4:Genomic Gain/Loss/LOH|The content below was from the old template. Please incorporate above.}}</blockquote>
A study conducted at Peking Union Medical college Hospital from November 2011 to June 2012 showed the following chromosomal abnormalities associated with POEMS syndrome.<ref>{{Cite journal|last=Kang|first=Wen-Ying|last2=Shen|first2=Kai-Ni|last3=Duan|first3=Ming-Hui|last4=Zhang|first4=Wei|last5=Cao|first5=Xin-Xin|last6=Zhou|first6=Dao-Bin|last7=Li|first7=Jian|date=2013-12|title=14q32 translocations and 13q14 deletions are common cytogenetic abnormalities in POEMS syndrome|url=https://onlinelibrary.wiley.com/doi/10.1111/ejh.12189|journal=European Journal of Haematology|language=en|volume=91|issue=6|pages=490–496|doi=10.1111/ejh.12189}}</ref>. In this study, BM plasma cells CD138+ were collected using MACS system and then FISH technique was applied.   
A study conducted at Peking Union Medical college Hospital from November 2011 to June 2012 showed the following chromosomal abnormalities associated with POEMS syndrome.<ref>{{Cite journal|last=Kang|first=Wen-Ying|last2=Shen|first2=Kai-Ni|last3=Duan|first3=Ming-Hui|last4=Zhang|first4=Wei|last5=Cao|first5=Xin-Xin|last6=Zhou|first6=Dao-Bin|last7=Li|first7=Jian|date=2013-12|title=14q32 translocations and 13q14 deletions are common cytogenetic abnormalities in POEMS syndrome|url=https://onlinelibrary.wiley.com/doi/10.1111/ejh.12189|journal=European Journal of Haematology|language=en|volume=91|issue=6|pages=490–496|doi=10.1111/ejh.12189}}</ref>. In this study, BM plasma cells CD138+ were collected using MACS system and then FISH technique was applied.   
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<blockquote class="blockedit">
<center><span style="color:Maroon">'''End of V4 Section'''</span>
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</blockquote>
</blockquote>
==Characteristic Chromosomal Patterns==
==Characteristic Chromosomal or Other Global Mutational Patterns==


Put your text here <span style="color:#0070C0">(''EXAMPLE PATTERNS: hyperdiploid; gain of odd number chromosomes including typically chromosome 1, 3, 5, 7, 11, and 17; co-deletion of 1p and 19q; complex karyotypes without characteristic genetic findings; chromothripsis'')</span>


Put your text here and fill in the table <span style="color:#0070C0">(I''nstructions: Included in this category are alterations such as hyperdiploid; gain of odd number chromosomes including typically chromosome 1, 3, 5, 7, 11, and 17; co-deletion of 1p and 19q; complex karyotypes without characteristic genetic findings; chromothripsis; microsatellite instability; homologous recombination deficiency; mutational signature pattern; etc. Details on clinical significance such as prognosis and other important information can be provided in the notes section. Please include references throughout the table. Do not delete the table.'')</span>
{| class="wikitable sortable"
{| class="wikitable sortable"
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!Chromosomal Pattern
!Chromosomal Pattern
!Diagnostic Significance (Yes, No or Unknown)
!Molecular Pathogenesis
!Prognostic Significance (Yes, No or Unknown)
!Prevalence -
!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
|-
|-
|EXAMPLE
|<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
|EXAMPLE:
|
 
|
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>
Microsatellite instability - hypermutated
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|<span class="blue-text">EXAMPLE:</span> Common (Endometrial carcinoma)
|<span class="blue-text">EXAMPLE:</span> P, T
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<blockquote class="blockedit">{{Box-round|title=v4:Characteristic Chromosomal Aberrations / Patterns|The content below was from the old template. Please incorporate above.}}</blockquote>


<br />
<br />


<blockquote class="blockedit">
<center><span style="color:Maroon">'''End of V4 Section'''</span>
----
</blockquote>
</blockquote>
==Gene Mutations (SNV / INDEL)==
==Gene Mutations (SNV/INDEL)==


Put your text here and fill in the table <span style="color:#0070C0">(''Instructions: This table is not meant to be an exhaustive list; please include only genes/alterations that are recurrent and common as well either disease defining and/or clinically significant. Can include references in the table. For clinical significance, denote associations with FDA-approved therapy (not an extensive list of applicable drugs) and NCCN or other national guidelines if applicable; Can also refer to CGC workgroup tables as linked on the homepage if applicable as well as any high impact papers or reviews of gene mutations in this entity.'') </span>


Put your text here and fill in the table <span style="color:#0070C0">(''Instructions: This table is not meant to be an exhaustive list; please include only genes/alterations that are recurrent or common as well either disease defining and/or clinically significant. If a gene has multiple mechanisms depending on the type or site of the alteration, add multiple entries in the table. For clinical significance, denote associations with FDA-approved therapy (not an extensive list of applicable drugs) and NCCN or other national guidelines if applicable; Can also refer to CGC workgroup tables as linked on the homepage if applicable as well as any high impact papers or reviews of gene mutations in this entity. Details on clinical significance such as prognosis and other important information such as concomitant and mutually exclusive mutations can be provided in the notes section. Please include references throughout the table. Do not delete the table.'') </span>
{| class="wikitable sortable"
{| class="wikitable sortable"
|-
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!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  
!Therapeutic Significance (Yes, No or Unknown)
!Established Clinical Significance Per Guidelines - Yes or No (Source)
!Notes
!Clinical Relevance Details/Other Notes
|-
|-
|EXAMPLE: TP53; Variable LOF mutations
|<span class="blue-text">EXAMPLE:</span>''EGFR''


EXAMPLE:
<br />
 
|<span class="blue-text">EXAMPLE:</span> Exon 18-21 activating mutations
EGFR; Exon 20 mutations
|<span class="blue-text">EXAMPLE:</span> Oncogene
 
|<span class="blue-text">EXAMPLE:</span> Common (lung cancer)
EXAMPLE: BRAF; Activating mutations
|<span class="blue-text">EXAMPLE:</span> T
|EXAMPLE: TSG
|<span class="blue-text">EXAMPLE:</span> Yes (NCCN)
|EXAMPLE: 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).
 
|-
EXAMPLE: 30% (add Reference)
|<span class="blue-text">EXAMPLE:</span> ''TP53''; Variable LOF mutations
|EXAMPLE: IDH1 R123H
<br />
|EXAMPLE: 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> P
|
|<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
|<span class="blue-text">EXAMPLE:</span> Oncogene
|<span class="blue-text">EXAMPLE:</span> Common (melanoma)
|<span class="blue-text">EXAMPLE:</span> T
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|EXAMPLE:  Excludes hairy cell leukemia (HCL) (add reference).
|}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.
<br />
|}
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.
 


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


A study was conducted in 20 patients of POEMS syndrome. The study showed 7  gene shaving recurrent somatic gene mutations involved in POEMS syndrome.  It is important to know that none of the important gene mutations involved in MM such as NRAS, KRAS, BRAF, and TP53 were found in POEMS syndrome patients.<ref>{{Cite journal|last=Nagao|first=Yuhei|last2=Mimura|first2=Naoya|last3=Takeda|first3=June|last4=Yoshida|first4=Kenichi|last5=Shiozawa|first5=Yusuke|last6=Oshima|first6=Motohiko|last7=Aoyama|first7=Kazumasa|last8=Saraya|first8=Atsunori|last9=Koide|first9=Shuhei|date=2019-07|title=Genetic and transcriptional landscape of plasma cells in POEMS syndrome|url=https://www.nature.com/articles/s41375-018-0348-x|journal=Leukemia|language=en|volume=33|issue=7|pages=1723–1735|doi=10.1038/s41375-018-0348-x|issn=1476-5551}}</ref> [[HAEM4:Plasma Cell Neoplasms]]
A study was conducted in 20 patients of POEMS syndrome. The study showed 7  gene shaving recurrent somatic gene mutations involved in POEMS syndrome.  It is important to know that none of the important gene mutations involved in MM such as NRAS, KRAS, BRAF, and TP53 were found in POEMS syndrome patients.<ref>{{Cite journal|last=Nagao|first=Yuhei|last2=Mimura|first2=Naoya|last3=Takeda|first3=June|last4=Yoshida|first4=Kenichi|last5=Shiozawa|first5=Yusuke|last6=Oshima|first6=Motohiko|last7=Aoyama|first7=Kazumasa|last8=Saraya|first8=Atsunori|last9=Koide|first9=Shuhei|date=2019-07|title=Genetic and transcriptional landscape of plasma cells in POEMS syndrome|url=https://www.nature.com/articles/s41375-018-0348-x|journal=Leukemia|language=en|volume=33|issue=7|pages=1723–1735|doi=10.1038/s41375-018-0348-x|issn=1476-5551}}</ref> [[HAEM4:Plasma Cell Neoplasms]]
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<br />


<blockquote class="blockedit">
<center><span style="color:Maroon">'''End of V4 Section'''</span>
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</blockquote>
</blockquote>
==Epigenomic Alterations==
==Epigenomic Alterations==
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==Genes and Main Pathways Involved==
==Genes and Main Pathways Involved==


Put your text here and fill in the table <span style="color:#0070C0">(''Instructions: Can include references in the table.'')</span>
 
Put your text here and fill in the table <span style="color:#0070C0">(''Instructions: Please include references throughout the table. Do not delete the table.)''</span>
{| class="wikitable sortable"
{| class="wikitable sortable"
|-
|-
!Gene; Genetic Alteration!!Pathway!!Pathophysiologic Outcome
!Gene; Genetic Alteration!!Pathway!!Pathophysiologic Outcome
|-
|-
|EXAMPLE: BRAF and MAP2K1; Activating mutations
|<span class="blue-text">EXAMPLE:</span> ''BRAF'' and ''MAP2K1''; Activating mutations
|EXAMPLE: MAPK signaling
|<span class="blue-text">EXAMPLE:</span> MAPK signaling
|EXAMPLE: Increased cell growth and proliferation
|<span class="blue-text">EXAMPLE:</span> Increased cell growth and proliferation
|-
|-
|EXAMPLE: CDKN2A; Inactivating mutations
|<span class="blue-text">EXAMPLE:</span> ''CDKN2A''; Inactivating mutations
|EXAMPLE: Cell cycle regulation
|<span class="blue-text">EXAMPLE:</span> Cell cycle regulation
|EXAMPLE: Unregulated cell division
|<span class="blue-text">EXAMPLE:</span> Unregulated cell division
|-
|-
|EXAMPLE:  KMT2C and ARID1A; Inactivating mutations
|<span class="blue-text">EXAMPLE:</span> ''KMT2C'' and ''ARID1A''; Inactivating mutations
|EXAMPLE:  Histone modification, chromatin remodeling
|<span class="blue-text">EXAMPLE:</span> Histone modification, chromatin remodeling
|EXAMPLE:  Abnormal gene expression program
|<span class="blue-text">EXAMPLE:</span> Abnormal gene expression program
|-
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|}


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<blockquote class="blockedit">{{Box-round|title=v4:Genes and Main Pathways Involved|The content below was from the old template. Please incorporate above.}}</blockquote>


'''<u>PATHOGENESIS OF POEMS SYNDROME</u>'''
'''<u>PATHOGENESIS OF POEMS SYNDROME</u>'''
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*'''<u>Pro-inflammatory markers</u>''' concentrations are increased leading to wide spread inflammation. Some of them are- TNF- α (Tumor Necrotic Factor), IFN-γ ( Interferon γ), IL-1β, IL-2, IL-6 (Interleukins). The cause of increased levels of cytokines are not known, but it has been hypothesized that cytokines are secreted because of stimulation by λ IGs secreted by plasma cells or by the tumor itself.
*'''<u>Pro-inflammatory markers</u>''' concentrations are increased leading to wide spread inflammation. Some of them are- TNF- α (Tumor Necrotic Factor), IFN-γ ( Interferon γ), IL-1β, IL-2, IL-6 (Interleukins). The cause of increased levels of cytokines are not known, but it has been hypothesized that cytokines are secreted because of stimulation by λ IGs secreted by plasma cells or by the tumor itself.
*'''<u>Decreased</u>''' level of '''<u>anti-inflammatory cytokines</u>-'''  A decreased level of TGF-β (Transforming Growth Factor β) may lead to imbalance between the pro and anti inflammatory factors resulting in disastrous clinical representation.
*'''<u>Decreased</u>''' level of '''<u>anti-inflammatory cytokines</u>-'''  A decreased level of TGF-β (Transforming Growth Factor β) may lead to imbalance between the pro and anti inflammatory factors resulting in disastrous clinical representation.
*Role of '''<u>VEGF</u>'''- Again, it is being hypothesized that VEGF (Vascular Endothelial Growth Factor) may lead to neovascularization leading to proliferation of small  blood vessels. It is important to note that disease activity correlates with VEGF levels even more than M proteins.<ref name=":6" />
*Role of '''<u>VEGF</u>'''- Again, it is being hypothesized that VEGF (Vascular Endothelial Growth Factor) may lead to neovascularization leading to proliferation of small  blood vessels. It is important to note that disease activity correlates with VEGF levels even more than M proteins.<ref name=":6">{{Cite journal|last=Dispenzieri|first=Angela|date=2012-06-14|title=How I treat POEMS syndrome|url=https://doi.org/10.1182/blood-2012-03-378992|journal=Blood|volume=119|issue=24|pages=5650–5658|doi=10.1182/blood-2012-03-378992|issn=0006-4971|pmc=PMC3425020|pmid=22547581}}</ref>
*'''<u>λ Immunoglobulins</u>'''
*'''<u>λ Immunoglobulins</u>'''


<blockquote class="blockedit">
<center><span style="color:Maroon">'''End of V4 Section'''</span>
----
</blockquote>
</blockquote>
==Genetic Diagnostic Testing Methods==
==Genetic Diagnostic Testing Methods==
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==Familial Forms==
==Familial Forms==


Put your text here <span style="color:#0070C0">(''Instructions: Include associated hereditary conditions/syndromes that cause this entity or are caused by this entity.'') </span>
Put your text here <span style="color:#0070C0">(''Instructions: Include associated hereditary conditions/syndromes that cause this entity or are caused by this entity.'') </span>
==Additional Information==
==Additional Information==


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==References==
==References==
(use the "Cite" icon at the top of the page) <span style="color:#0070C0">(''Instructions: Add each reference into the text above by clicking on where you want to insert the reference, selecting the “Cite” icon at the top of the page, and using the “Automatic” tab option to search such as by PMID to select the reference to insert. The reference list in this section will be automatically generated and sorted.''</span> <span style="color:#0070C0">''If a PMID is not available, such as for a book, please use the “Cite” icon, select “Manual” and then “Basic Form”, and include the entire reference''</span><span style="color:#0070C0">''.''</span><span style="color:#0070C0">) </span> <references />
(use the "Cite" icon at the top of the page) <span style="color:#0070C0">(''Instructions: Add each reference into the text above by clicking where you want to insert the reference, selecting the “Cite” icon at the top of the wiki page, and using the “Automatic” tab option to search by PMID to select the reference to insert. If a PMID is not available, such as for a book, please use the “Cite” icon, select “Manual” and then “Basic Form”, and include the entire reference. To insert the same reference again later in the page, select the “Cite” icon and “Re-use” to find the reference; DO NOT insert the same reference twice using the “Automatic” tab as it will be treated as two separate references. The reference list in this section will be automatically generated and sorted''</span><span style="color:#0070C0">''.''</span><span style="color:#0070C0">)</span> <references />


'''
<br />


==Notes==
==Notes==
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<nowiki>*</nowiki>''Citation of this Page'': “Plasma cell neoplasms with associated paraneoplastic syndrome”. Compendium of Cancer Genome Aberrations (CCGA), Cancer Genomics Consortium (CGC), updated {{REVISIONMONTH}}/{{REVISIONDAY}}/{{REVISIONYEAR}}, <nowiki>https://ccga.io/index.php/HAEM5:Plasma_cell_neoplasms_with_associated_paraneoplastic_syndrome</nowiki>.
<nowiki>*</nowiki>''Citation of this Page'': “Plasma cell neoplasms with associated paraneoplastic syndrome”. Compendium of Cancer Genome Aberrations (CCGA), Cancer Genomics Consortium (CGC), updated {{REVISIONMONTH}}/{{REVISIONDAY}}/{{REVISIONYEAR}}, <nowiki>https://ccga.io/index.php/HAEM5:Plasma_cell_neoplasms_with_associated_paraneoplastic_syndrome</nowiki>.
[[Category:HAEM5]][[Category:DISEASE]][[Category:Diseases P]]
[[Category:HAEM5]]
[[Category:DISEASE]]
[[Category:Diseases P]]
Retrieved from "https://test.ccga.io/index.php/HAEM5:Plasma_cell_neoplasms_with_associated_paraneoplastic_syndrome"