Bailey.Glen at 21:34, 4 December 2023

2023-12-04T21:34:17Z

← Older revision		Revision as of 16:34, 4 December 2023
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	==Cancer Category/Type==		==Cancer Category/Type==

	*[[Mature B-Cell Neoplasms]]		*[[HAEM4:Mature B-Cell Neoplasms]]

	==Cancer Sub-Classification / Subtype==		==Cancer Sub-Classification / Subtype==
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	Some cases of gamma-HCD (γ-HCD) are concurrent with other lymphoid neoplasm have been reported in the literature and are listed below; treatment option varies with concurrent neoplasm		Some cases of gamma-HCD (γ-HCD) are concurrent with other lymphoid neoplasm have been reported in the literature and are listed below; treatment option varies with concurrent neoplasm

	*[[Chronic ~~Lymphocytic Leukemia~~/~~Small Lymphocytic Lymphoma~~\|Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma (CLL)]]		*[[HAEM5:Chronic lymphocytic leukaemia/small lymphocytic lymphoma\|Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma (CLL)]]
	*DLBCL-diffuse large B cell Lymphoma		*DLBCL-diffuse large B cell Lymphoma
	*LCPD-lymphoplasma cell proliferative disorder		*LCPD-lymphoplasma cell proliferative disorder
	*[[Lymphoplasmacytic ~~Lymphoma~~\|Lymphoplasmacytic Lymphoma (LPL]])		*[[HAEM5:Lymphoplasmacytic lymphoma\|Lymphoplasmacytic Lymphoma (LPL]])
	*MALT -mucosa-associated lymphoid tissue		*MALT -mucosa-associated lymphoid tissue
	*MDS-myelodysplastic syndrome		*MDS-myelodysplastic syndrome

Bailey.Glen at 18:51, 3 November 2023

2023-11-03T18:51:05Z

@@ Line 1: / Line 1: @@
 ==Primary Author(s)*==
 Manisha Brahmbhatt-Sutariya
@@ Line 177: / Line 182: @@
 ==Notes==
 <nowiki>*</nowiki>Primary authors will typically be those that initially create and complete the content of a page.  If a subsequent user modifies the content and feels the effort put forth is of high enough significance to warrant listing in the authorship section, please contact the CCGA coordinators (contact information provided on the homepage).  Additional global feedback or concerns are also welcome.

Bailey.Glen: Created page with "==Primary Author(s)*== Manisha Brahmbhatt-Sutariya Asst. Professor, Dept. of Pathology and Human Anatomy Technical Supervisor, Clinical Genetics Laboratory Loma Linda Unive..."

2023-11-03T18:12:27Z

Created page with "==Primary Author(s)*== Manisha Brahmbhatt-Sutariya Asst. Professor, Dept. of Pathology and Human Anatomy Technical Supervisor, Clinical Genetics Laboratory Loma Linda Unive..."

New page

==Primary Author(s)*==
Manisha Brahmbhatt-Sutariya

Asst. Professor, Dept. of Pathology and Human Anatomy

Technical Supervisor, Clinical Genetics Laboratory

Loma Linda University, Medical Center, CA

__TOC__

==Cancer Category/Type==

*[[Mature B-Cell Neoplasms]]

==Cancer Sub-Classification / Subtype==

*Gamma Heavy Chain Disease (gHCD)

==Definition / Description of Disease==

*gHCD is a B-cell neoplasm of lymphocytes, plasmacytoid lymphocytes and plasma cells<ref name=":0">{{Cite journal|last=Fermand|first=J. P.|last2=Brouet|first2=J. C.|last3=Danon|first3=F.|last4=Seligmann|first4=M.|date=1989-11|title=Gamma heavy chain "disease": heterogeneity of the clinicopathologic features. Report of 16 cases and review of the literature|url=https://pubmed.ncbi.nlm.nih.gov/2509855|journal=Medicine|volume=68|issue=6|pages=321–335|issn=0025-7974|pmid=2509855}}</ref><ref name=":1">{{Cite journal|last=Ramasamy|first=I.|last2=Rudzki|first2=Z.|date=2018|title=Two Cases of γ-Heavy Chain Disease and a Review of the Literature|url=https://pubmed.ncbi.nlm.nih.gov/30186642|journal=Case Reports in Hematology|volume=2018|pages=4832619|doi=10.1155/2018/4832619|issn=2090-6560|pmc=6109557|pmid=30186642}}</ref>
*Heterogenous clinical and pathological presentation<ref name=":0" />
*Disseminated lymphoproliferative disorder is present in most patients at diagnosis<ref name=":0" /><ref name=":1" /><ref name=":2">{{Cite journal|last=Wahner-Roedler|first=Dietlind L.|last2=Witzig|first2=Thomas E.|last3=Loehrer|first3=Laura L.|last4=Kyle|first4=Robert A.|date=2003-07|title=Gamma-heavy chain disease: review of 23 cases|url=https://pubmed.ncbi.nlm.nih.gov/12861101|journal=Medicine|volume=82|issue=4|pages=236–250|doi=10.1097/01.md.0000085058.63483.7f|issn=0025-7974|pmid=12861101}}</ref>
*It produces truncated monoclonal gamma (g) immunoglobulin (IgG) heavy chain that is incapable of associating with light chains<ref name=":1" />
*Have concomitant autoimmune disease (mostly rheumatoid arthritis)
*Three clusters of γ-HCD patients are identified:
*#In around 60% of cases, γ-HCD is associated to disseminated lymphoma and patients typically have poor condition.
*#In 25% of patients, γ-HCD is associated to localized lymphoma, affecting bone marrow, skin, thyroid, parotid, gastrointestinal or oropharynx tract (MALT lymphoma)
*#In 15% of patients, γ-HCD is associated with autoimmune disease, mainly RA<ref>{{Cite journal|last=Danic|first=Gwenvaël|last2=Dejoie|first2=Thomas|last3=Caillon|first3=Hélène|last4=Achille|first4=Aurélie|last5=Pottier|first5=Pierre|last6=Agard|first6=Christian|date=2021-03-17|title=Gamma heavy chain disease associated with rheumatoid arthritis: a case report|url=https://pubmed.ncbi.nlm.nih.gov/33726782|journal=Journal of Medical Case Reports|volume=15|issue=1|pages=121|doi=10.1186/s13256-021-02696-7|issn=1752-1947|pmc=7968189|pmid=33726782}}</ref>

==Synonyms / Terminology==

*Franklin disease<ref>{{Cite journal|last=Franklin|first=E. C.|last2=Lowenstein|first2=J.|last3=Bigelow|first3=B.|last4=Meltzer|first4=M.|date=1964-09|title=HEAVY CHAIN DISEASE- A NEW DISORDER OF SERUM GAMMA-GLOBULINS : REPORT OF THE FIRST CASE|url=https://pubmed.ncbi.nlm.nih.gov/14209281|journal=The American Journal of Medicine|volume=37|pages=332–350|doi=10.1016/0002-9343(64)90191-3|issn=0002-9343|pmid=14209281}}</ref>/ γHCD

==Epidemiology / Prevalence==

*Incidence: Very rare, till date, ~only 200 cases have been reported in the literature<ref name=":3">{{Cite journal|last=Munshi|first=Nikhil C.|last2=Digumarthy|first2=Subba|last3=Rahemtullah|first3=Aliyah|date=2008-04-24|title=Case records of the Massachusetts General Hospital. Case 13-2008. A 46-year-old man with rheumatoid arthritis and lymphadenopathy|url=https://pubmed.ncbi.nlm.nih.gov/18434654|journal=The New England Journal of Medicine|volume=358|issue=17|pages=1838–1848|doi=10.1056/NEJMcpc0800959|issn=1533-4406|pmid=18434654}}</ref>
*Median age: 68 years (range, 42–87 years)<ref>{{Cite journal|last=Zhou|first=Hebing|last2=Chen|first2=Wenming|last3=Zhang|first3=Juan|last4=Zeng|first4=Hui|last5=Jian|first5=Yuan|last6=Fu|first6=Chenxiao|date=2016-06|title=T cell receptor rearrangements in a patient with γ-heavy chain disease: A case report|url=https://pubmed.ncbi.nlm.nih.gov/27313757|journal=Oncology Letters|volume=11|issue=6|pages=4147–4151|doi=10.3892/ol.2016.4515|issn=1792-1074|pmc=4888291|pmid=27313757}}</ref>
*Slight female predominance<ref name=":2" />

==Clinical Features<ref name=":2" />==

'''Signs & Symptoms'''

*Anorexia
*Fever
*Weakness
*Weight loss
*Recurrent bacterial infections
*Concomitant autoimmune disorder
**Rheumatoid arthritis
**Myasthenia Gravis
**Autoimmune cytopenia
**Systemic Lupus Erythematosus
**Thyroiditis
**Vasculitis
**Wasting
**Sjögren syndrome
**Thrombocytopenia
**Autoimmune hemolytic anemia

'''Laboratory Findings'''

*Anemia
*Thrombocytopenia

'''Molecular Biology and Genetics'''

*gHCD seems to be caused by deletions and/or insertions within the rearranged variable region genes (V), which could be a by-product of somatic hypermutation<ref name=":1" /><ref name=":5">{{Cite journal|last=Goossens|first=T.|last2=Klein|first2=U.|last3=Küppers|first3=R.|date=1998-03-03|title=Frequent occurrence of deletions and duplications during somatic hypermutation: implications for oncogene translocations and heavy chain disease|url=https://pubmed.ncbi.nlm.nih.gov/9482908|journal=Proceedings of the National Academy of Sciences of the United States of America|volume=95|issue=5|pages=2463–2468|doi=10.1073/pnas.95.5.2463|issn=0027-8424|pmc=PMC19376|pmid=9482908}}</ref>

==Sites of Involvement==

*Bone marrow
*Peripheral blood
*Spleen
*Liver
*Lymph nodes
*Waldeyer ring
*Gastrointestinal tract
*Extranodal sites

==Morphologic Features<ref name=":3" />==

*Mixed proliferation of various cell types:
**Lymphocytes
**Plasmacytoid lymphocytes
**Plasma cells
**Scattered immunoblasts
**Reed–Sternberg cells
**Eosinophils and histiocytes
*Vascular proliferation may give rise to the histologic differential diagnosis of Hodgkin’s lymphoma or certain forms of T-cell lymphoma

==Immunophenotype<ref name=":3" />==

{| class="wikitable sortable"
|-
!Finding!!Marker
|-
|Positive (B-cell lineage marker)||CD19, CD20, CD79a, IgG (cytoplasmic) without light chain
|-
|Positive-Plasmacytoid cells||MUM1/IRF4
|-
|Positive-Plasma cells
|CD38, CD138
|-
|Negative||CD5, CD10
|}

==Chromosomal Rearrangements (Gene Fusions)==

*No consistent gene fusions<ref>{{Cite journal|last=Witzig|first=Thomas E.|last2=Wahner-Roedler|first2=Dietlind L.|date=2002-06|title=Heavy chain disease|url=https://pubmed.ncbi.nlm.nih.gov/12057070|journal=Current Treatment Options in Oncology|volume=3|issue=3|pages=247–254|doi=10.1007/s11864-002-0014-3|issn=1527-2729|pmid=12057070}}</ref>

==Characteristic Chromosomal Aberrations / Patterns==

*No consistent pattern reported

==Genomic Gain/Loss/LOH<ref name=":1" /><ref name=":5" />==

*No consistent chromosomal gains or losses reported.
*A single case report of trisomy of chromosome 7<ref>{{Cite journal|last=O'Conor|first=G. T.|last2=Wyandt|first2=H. E.|last3=Innes|first3=D. J.|last4=Normansell|first4=D. E.|last5=Hess|first5=C. E.|date=1985-02-01|title=Gamma heavy chain disease: report of a case associated with trisomy of chromosome 7|url=https://pubmed.ncbi.nlm.nih.gov/3917846|journal=Cancer Genetics and Cytogenetics|volume=15|issue=1-2|pages=1–5|doi=10.1016/0165-4608(85)90125-6|issn=0165-4608|pmid=3917846}}</ref>

==Gene Mutations (SN V/INDEL)==

*g-HCD lacks ''MYD88'' L265p mutation associated with lymphoplasmacytic lymphoma, hence gHCD should no longer be considered a variant of LPL<ref>{{Cite journal|last=Hamadeh|first=Fatima|last2=MacNamara|first2=Stephen|last3=Bacon|first3=Chris M.|last4=Sohani|first4=Aliyah R.|last5=Swerdlow|first5=Steven H.|last6=Cook|first6=James R.|date=2014-09|title=Gamma heavy chain disease lacks the MYD88 L265p mutation associated with lymphoplasmacytic lymphoma|url=https://pubmed.ncbi.nlm.nih.gov/24859878|journal=Haematologica|volume=99|issue=9|pages=e154–155|doi=10.3324/haematol.2014.108688|issn=1592-8721|pmc=4562547|pmid=24859878}}</ref>
*Deletions and insertions account for approximately 6% of somatic point mutations introduced into rearranged VH region genes of germinal B cells<ref>{{Cite journal|last=Alexander|first=A.|last2=Anicito|first2=I.|last3=Buxbaum|first3=J.|date=1988-10-XX|title=Gamma heavy chain disease in man. Genomic sequence reveals two noncontiguous deletions in a single gene|url=https://pubmed.ncbi.nlm.nih.gov/3139711|journal=The Journal of Clinical Investigation|volume=82|issue=4|pages=1244–1252|doi=10.1172/JCI113722|issn=0021-9738|pmc=PMC442675|pmid=3139711}}</ref>.
*No sequencing data is available till date.

==Epigenomics (Methylation)==

*No recurrent epigenomic alterations have been reported.

==Genes and Main Pathways Involved==

* N/A

==Diagnostic Testing Methods<ref>{{Cite journal|last=Mrosewski|first=Ingo|last2=Urbank|first2=Matthias|date=2020-01-01|title=Gamma Heavy Chain Disease - Diagnostic Challenges in an Unusual Case and a Brief Synopsis of the Current Literature|url=https://pubmed.ncbi.nlm.nih.gov/32013371|journal=Clinical Laboratory|volume=66|issue=1|doi=10.7754/Clin.Lab.2019.190623|issn=1433-6510|pmid=32013371}}</ref><ref>{{Cite journal|last=Thoren|first=Katie L.|last2=Eveillard|first2=Marion|last3=Chan|first3=Patrick|last4=Doddi|first4=Sital|last5=Cho|first5=Sun|last6=Murata|first6=Kazunori|date=2020-03|title=Identification of gamma heavy chain disease using MALDI-TOF mass spectrometry|url=https://pubmed.ncbi.nlm.nih.gov/31884198|journal=Clinical Biochemistry|volume=77|pages=57–61|doi=10.1016/j.clinbiochem.2019.12.010|issn=1873-2933|pmc=7046309|pmid=31884198}}</ref><ref>{{Cite journal|last=Ho|first=Y. H.|last2=Wang|first2=J. L.|last3=DeLelys|first3=M. E.|last4=Murali|first4=M. R.|last5=Pitman|first5=M. B.|last6=Sohani|first6=A. R.|date=2014-08|title=Gamma heavy chain disease: cytological diagnosis of a rare lymphoid malignancy facilitated by correlation with key laboratory findings|url=https://pubmed.ncbi.nlm.nih.gov/25180407|journal=Cytopathology: Official Journal of the British Society for Clinical Cytology|volume=25|issue=4|pages=270–273|doi=10.1111/cyt.12126|issn=1365-2303|pmid=25180407}}</ref>==

*Immunofixation (IF) is must and gold standard
*Serum Protein Electrophoresis (SPEP)
*Urine Electrophoresis
*Morphology and immunophenotyping
*

*MALDI-TOF MS could greatly improve the recognition of HCD because it directly detects the light chains and heavy chains and provides structural information about the proteins.

==Clinical Significance (Diagnosis, Prognosis and Therapeutic Implications)<ref name=":4">{{Cite journal|last=Singer|first=Sara|last2=Efebera|first2=Yvonne|last3=Bumma|first3=Naresh|last4=Khan|first4=Abdullah|last5=Devarakonda|first5=Srinivas|last6=Chaudhry|first6=Maria|last7=Benson|first7=Don|last8=Rosko|first8=Ashley E.|date=2020-08|title=Heavy Lifting: Nomenclature and Novel Therapy for Gamma Heavy Chain Disease and Other Heavy Chain Disorders|url=https://pubmed.ncbi.nlm.nih.gov/32245744|journal=Clinical Lymphoma, Myeloma & Leukemia|volume=20|issue=8|pages=493–498|doi=10.1016/j.clml.2020.02.020|issn=2152-2669|pmid=32245744}}</ref>==

* N/A

==Familial Forms==

*None reported

==Other Information<ref name=":4" />==

Some cases of gamma-HCD (γ-HCD) are concurrent with other lymphoid neoplasm have been reported in the literature and are listed below; treatment option varies with concurrent neoplasm

*[[Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma|Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma (CLL)]]
*DLBCL-diffuse large B cell Lymphoma
*LCPD-lymphoplasma cell proliferative disorder
*[[Lymphoplasmacytic Lymphoma|Lymphoplasmacytic Lymphoma (LPL]])
*MALT -mucosa-associated lymphoid tissue
*MDS-myelodysplastic syndrome
*MGUS-monoclonal gammopathy of undetermined Significance
*SDRPSBCL-splenic diffuse red pulp small B-cell lymphoma
*SMZL-splenic marginal zone lymphoma
*T-LGLL-T-cell large granular lymphocytic leukemia

==Links==

* None

==References==
<references />

==Notes==
<nowiki>*</nowiki>Primary authors will typically be those that initially create and complete the content of a page. If a subsequent user modifies the content and feels the effort put forth is of high enough significance to warrant listing in the authorship section, please contact the CCGA coordinators (contact information provided on the homepage). Additional global feedback or concerns are also welcome.

HAEM4:Gamma Heavy Chain Disease - Revision history

Bailey.Glen at 21:34, 4 December 2023

Bailey.Glen at 18:51, 3 November 2023

Bailey.Glen: Created page with "==Primary Author(s)*== Manisha Brahmbhatt-Sutariya Asst. Professor, Dept. of Pathology and Human Anatomy Technical Supervisor, Clinical Genetics Laboratory Loma Linda Unive..."