Hodgkin's lymphoma pathophysiology: Difference between revisions

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==Overview==
==Overview==
On gross pathology, white-grey, uniform, and enlarged lymphnodes are characteristic findings of Hodgkin's lymphoma. On microscopic histopathological analysis, [[Reed-Sternberg cells]], reactive cell infiltrate, and complete or partial effacement of the lymph node architecture are characteristic findings of Hodgkin's lymphoma.
On gross pathology, white-grey, uniform, and enlarged [[lymph nodes]] are characteristic findings of Hodgkin's lymphoma. On microscopic histopathological analysis, [[Reed-Sternberg cells]], reactive cell infiltrate, and complete or partial effacement of the lymph node architecture are characteristic findings of Hodgkin's lymphoma.
==Pathophysiology==
==Pathophysiology==
'''Hodgkin's lymphoma''',<ref>{{cite book|title=Scientific Style and Format: The CBE Manual for Authors, Editors, and Publishers|url=https://books.google.com/books?id=PoFJ-OhE63UC&pg=PA97|year=1994|publisher=Cambridge University Press|isbn=978-0-521-47154-1|pages=97–}}</ref> also known as '''Hodgkin lymphoma''' or '''Hodgkin's disease''',<ref name=Lozano_2012>{{cite journal  |vauthors=Lozano R, Naghavi M, Foreman K, Lim S, Shibuya K, Aboyans V, etal | title = Global and regional mortality from 235 causes of death for 20 age groups in 1990 and 2010: a systematic analysis for the Global Burden of Disease Study 2010. | journal = Lancet | volume = 380 | issue = 9859 | pages = 2095–128 | date = Dec 15, 2012 | oclc = 23245604 | doi = 10.1016/S0140-6736(12)61728-0 }}</ref> is a type of [[lymphoma]], in which [[cancer]] originates from a specific type of [[white blood cell]]s called [[lymphocyte]]s.
Hodgkin's lymphoma, is a type of [[lymphoma]], in which [[cancer]] originates from a specific type of [[white blood cell]]s called [[lymphocyte]]s.<ref>{{cite book|title=Scientific Style and Format: The CBE Manual for Authors, Editors, and Publishers|url=https://books.google.com/books?id=PoFJ-OhE63UC&pg=PA97|year=1994|publisher=Cambridge University Press|isbn=978-0-521-47154-1|pages=97–}}</ref><ref name=Lozano_2012>{{cite journal  |vauthors=Lozano R, Naghavi M, Foreman K, Lim S, Shibuya K, Aboyans V, etal | title = Global and regional mortality from 235 causes of death for 20 age groups in 1990 and 2010: a systematic analysis for the Global Burden of Disease Study 2010. | journal = Lancet | volume = 380 | issue = 9859 | pages = 2095–128 | date = Dec 15, 2012 | oclc = 23245604 | doi = 10.1016/S0140-6736(12)61728-0 }}</ref>
==Associated Conditions==
==Associated Conditions==
Reports from countries like Honduras,<ref name="pmid8380725">{{cite journal| author=Ambinder RF, Browning PJ, Lorenzana I, Leventhal BG, Cosenza H, Mann RB et al.| title=Epstein-Barr virus and childhood Hodgkin's disease in Honduras and the United States. | journal=Blood | year= 1993 | volume= 81 | issue= 2 | pages= 462-7 | pmid=8380725 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=8380725  }} </ref> China,<ref name="pmid8397160">{{cite journal| author=Zhou XG, Hamilton-Dutoit SJ, Yan QH, Pallesen G| title=The association between Epstein-Barr virus and Chinese Hodgkin's disease. | journal=Int J Cancer | year= 1993 | volume= 55 | issue= 3 | pages= 359-63 | pmid=8397160 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=8397160  }} </ref> Mexico,<ref name="pmid7882287">{{cite journal| author=Zarate-Osorno A, Roman LN, Kingma DW, Meneses-Garcia A, Jaffe ES| title=Hodgkin's disease in Mexico. Prevalence of Epstein-Barr virus sequences and correlations with histologic subtype. | journal=Cancer | year= 1995 | volume= 75 | issue= 6 | pages= 1360-6 | pmid=7882287 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=7882287  }} </ref> Peru,<ref name="pmid8380728">{{cite journal| author=Chang KL, Albújar PF, Chen YY, Johnson RM, Weiss LM| title=High prevalence of Epstein-Barr virus in the Reed-Sternberg cells of Hodgkin's disease occurring in Peru. | journal=Blood | year= 1993 | volume= 81 | issue= 2 | pages= 496-501 | pmid=8380728 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=8380728  }} </ref> and Malaysia<ref name="pmid9088951">{{cite journal| author=Peh SC, Looi LM, Pallesen G| title=Epstein-Barr virus (EBV) and Hodgkin's disease in a multi-ethnic population in Malaysia. | journal=Histopathology | year= 1997 | volume= 30 | issue= 3 | pages= 227-33 | pmid=9088951 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=9088951  }} </ref> suggest an association between [[EBV infection]] and Hodgkin's lymphoma, an association that is more evident in the pediatric population<ref name="pmid8389527">{{cite journal| author=Armstrong AA, Alexander FE, Paes RP, Morad NA, Gallagher A, Krajewski AS et al.| title=Association of Epstein-Barr virus with pediatric Hodgkin's disease. | journal=Am J Pathol | year= 1993 | volume= 142 | issue= 6 | pages= 1683-8 | pmid=8389527 | doi= | pmc=PMC1886981 | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=8389527  }} </ref> and in the subtype of mixed cellularity.<ref name="pmid9110300">{{cite journal| author=Andriko JA, Aguilera NS, Nandedkar MA, Abbondanzo SL| title=Childhood Hodgkin's disease in the United States: an analysis of histologic subtypes and association with Epstein-Barr virus. | journal=Mod Pathol | year= 1997 | volume= 10 | issue= 4 | pages= 366-71 | pmid=9110300 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=9110300  }} </ref>
Reports from countries like Honduras,<ref name="pmid8380725">{{cite journal| author=Ambinder RF, Browning PJ, Lorenzana I, Leventhal BG, Cosenza H, Mann RB et al.| title=Epstein-Barr virus and childhood Hodgkin's disease in Honduras and the United States. | journal=Blood | year= 1993 | volume= 81 | issue= 2 | pages= 462-7 | pmid=8380725 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=8380725  }} </ref> China,<ref name="pmid8397160">{{cite journal| author=Zhou XG, Hamilton-Dutoit SJ, Yan QH, Pallesen G| title=The association between Epstein-Barr virus and Chinese Hodgkin's disease. | journal=Int J Cancer | year= 1993 | volume= 55 | issue= 3 | pages= 359-63 | pmid=8397160 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=8397160  }} </ref> Mexico,<ref name="pmid7882287">{{cite journal| author=Zarate-Osorno A, Roman LN, Kingma DW, Meneses-Garcia A, Jaffe ES| title=Hodgkin's disease in Mexico. Prevalence of Epstein-Barr virus sequences and correlations with histologic subtype. | journal=Cancer | year= 1995 | volume= 75 | issue= 6 | pages= 1360-6 | pmid=7882287 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=7882287  }} </ref> Peru,<ref name="pmid8380728">{{cite journal| author=Chang KL, Albújar PF, Chen YY, Johnson RM, Weiss LM| title=High prevalence of Epstein-Barr virus in the Reed-Sternberg cells of Hodgkin's disease occurring in Peru. | journal=Blood | year= 1993 | volume= 81 | issue= 2 | pages= 496-501 | pmid=8380728 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=8380728  }} </ref> and Malaysia<ref name="pmid9088951">{{cite journal| author=Peh SC, Looi LM, Pallesen G| title=Epstein-Barr virus (EBV) and Hodgkin's disease in a multi-ethnic population in Malaysia. | journal=Histopathology | year= 1997 | volume= 30 | issue= 3 | pages= 227-33 | pmid=9088951 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=9088951  }} </ref> suggest an association between [[EBV infection]] and Hodgkin's lymphoma, an association that is more evident in the pediatric population<ref name="pmid8389527">{{cite journal| author=Armstrong AA, Alexander FE, Paes RP, Morad NA, Gallagher A, Krajewski AS et al.| title=Association of Epstein-Barr virus with pediatric Hodgkin's disease. | journal=Am J Pathol | year= 1993 | volume= 142 | issue= 6 | pages= 1683-8 | pmid=8389527 | doi= | pmc=PMC1886981 | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=8389527  }} </ref> and in the subtype of mixed cellularity.<ref name="pmid9110300">{{cite journal| author=Andriko JA, Aguilera NS, Nandedkar MA, Abbondanzo SL| title=Childhood Hodgkin's disease in the United States: an analysis of histologic subtypes and association with Epstein-Barr virus. | journal=Mod Pathol | year= 1997 | volume= 10 | issue= 4 | pages= 366-71 | pmid=9110300 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=9110300  }} </ref>
==Gross Pathology==
==Gross Pathology==
On gross pathology, affected [[lymph nodes]] (most often, laterocervical lymph nodes) are enlarged, but their shape is preserved because the capsule is not invaded. Usually, the cut surface is white-grey and uniform. In some histological subtypes (e.g. [[nodular sclerosis]]), the cut surface may have a nodular aspect.
On gross pathology, affected [[lymph nodes]] (most often, latero cervical lymph nodes) are enlarged, but their shape is preserved because the capsule is not invaded. Usually, the cut surface is white-grey and uniform. In some histological subtypes (e.g. [[nodular sclerosis]]), the cut surface may have a nodular aspect.


==Microscopic Pathology==
==Microscopic Pathology==
Microscopic examination of the [[lymph node]] biopsy reveals complete or partial effacement of the lymph node architecture by scattered large malignant cells known as [[Reed-Sternberg cells]] (typical and variants) admixed within a reactive cell infiltrate composed of variable proportions of [[lymphocytes]], [[histiocytes]] [[eosinophils]]  and [[plasma cells]]. The Reed-Sternberg cells are identified as large often bi-nucleated cells with prominent nucleoli and an unusual [[CD45]]-, [[CD30]]+, and [[CD15]]+/- immunophenotype.  In approximately 50% of cases, the Reed-Sternberg cells are infected by the [[Epstein-Barr]] [[virus]].
Microscopic examination of the [[lymph node]] biopsy reveals complete or partial effacement of the lymph node architecture by scattered large malignant cells known as [[Reed-Sternberg cells]] (typical and variants) admixed within a reactive cell infiltrate composed of variable proportions of [[lymphocytes]], [[histiocytes]], [[eosinophils]], and [[plasma cells]]. The Reed-Sternberg cells are identified as large often bi-nucleated cells with prominent nucleoli and an unusual [[CD45]]-, [[CD30]]+, and [[CD15]]+/- immuno phenotype.  In approximately 50% of cases, the Reed-Sternberg cells are infected by the [[Epstein-Barr]] [[virus]].




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| style="padding: 5px 5px; background: #F5F5F5;" | Lacunar Reed-Sternberg cells  
| style="padding: 5px 5px; background: #F5F5F5;" | Lacunar Reed-Sternberg cells  
| style="padding: 5px 5px; background: #F5F5F5;" | Have a single hyper lobulated nucleus, multiple, small nucleoli and eosinophilic cytoplasm which is retracted around the nucleus, creating an empty space ("lacunae").
| style="padding: 5px 5px; background: #F5F5F5;" | Have a single hyper lobulated nucleus, multiple, small nucleoli and [[eosinophilic]] cytoplasm which is retracted around the nucleus, creating an empty space ("lacunae").
|-
|-
| style="padding: 5px 5px; background: #F5F5F5;" | Pleomorphic Reed-Sternberg cells
| style="padding: 5px 5px; background: #F5F5F5;" | Pleomorphic Reed-Sternberg cells
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|-
| style="padding: 5px 5px; background: #F5F5F5;" | "Mummy" Reed-Sternberg cells
| style="padding: 5px 5px; background: #F5F5F5;" | "Mummy" Reed-Sternberg cells
| style="padding: 5px 5px; background: #F5F5F5;" | Have a compact nucleus with no nucleolus and basophilic cytoplasm.
| style="padding: 5px 5px; background: #F5F5F5;" | Have a compact nucleus with no nucleolus and [[basophilic]] cytoplasm.
|}
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Revision as of 15:46, 23 September 2015

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Sowminya Arikapudi, M.B,B.S. [2]

Overview

On gross pathology, white-grey, uniform, and enlarged lymph nodes are characteristic findings of Hodgkin's lymphoma. On microscopic histopathological analysis, Reed-Sternberg cells, reactive cell infiltrate, and complete or partial effacement of the lymph node architecture are characteristic findings of Hodgkin's lymphoma.

Pathophysiology

Hodgkin's lymphoma, is a type of lymphoma, in which cancer originates from a specific type of white blood cells called lymphocytes.[1][2]

Associated Conditions

Reports from countries like Honduras,[3] China,[4] Mexico,[5] Peru,[6] and Malaysia[7] suggest an association between EBV infection and Hodgkin's lymphoma, an association that is more evident in the pediatric population[8] and in the subtype of mixed cellularity.[9]

Gross Pathology

On gross pathology, affected lymph nodes (most often, latero cervical lymph nodes) are enlarged, but their shape is preserved because the capsule is not invaded. Usually, the cut surface is white-grey and uniform. In some histological subtypes (e.g. nodular sclerosis), the cut surface may have a nodular aspect.

Microscopic Pathology

Microscopic examination of the lymph node biopsy reveals complete or partial effacement of the lymph node architecture by scattered large malignant cells known as Reed-Sternberg cells (typical and variants) admixed within a reactive cell infiltrate composed of variable proportions of lymphocytes, histiocytes, eosinophils, and plasma cells. The Reed-Sternberg cells are identified as large often bi-nucleated cells with prominent nucleoli and an unusual CD45-, CD30+, and CD15+/- immuno phenotype. In approximately 50% of cases, the Reed-Sternberg cells are infected by the Epstein-Barr virus.


  • Reed-Sternberg Hodgkin's Lymphoma[10]

    Reed-Sternberg Hodgkin's Lymphoma[10]

  • Micrograph showing Hodgkin lymphoma (Field stain)

    Micrograph showing Hodgkin lymphoma (Field stain)

  • Micrograph showing a "popcorn cell", the Reed–Sternberg cell variant seen in nodular lymphocyte predominant Hodgkin lymphoma. H&E stain

    Micrograph showing a "popcorn cell", the Reed–Sternberg cell variant seen in nodular lymphocyte predominant Hodgkin lymphoma. H&E stain


Reed-Sternberg cells (RSC) (Classical and variants)
Type of cell Characteristics
Classic
Reed-Sternberg cells (RSC) Include large size (20–50 micro metres), abundant, amphophilic, finely granular/homogeneous cytoplasm; two mirror-image nuclei (owl eyes) each with an eosinophilic nucleolus and a thick nuclear membrane (chromatin is distributed close to the nuclear membrane).
Variants
Hodgkin cells (Atypical mononuclear Reed-Sternberg cell) Have the same characteristics as Reed-Sternberg cells (RSC), but is mono nucleated.
Lacunar Reed-Sternberg cells Have a single hyper lobulated nucleus, multiple, small nucleoli and eosinophilic cytoplasm which is retracted around the nucleus, creating an empty space ("lacunae").
Pleomorphic Reed-Sternberg cells Have multiple irregular nuclei.
"Popcorn" Reed-Sternberg cells (Lympho-histiocytic variant) Have a very lobulated nucleus and small nucleoli.
"Mummy" Reed-Sternberg cells Have a compact nucleus with no nucleolus and basophilic cytoplasm.

References

  1. ↑ Scientific Style and Format: The CBE Manual for Authors, Editors, and Publishers. Cambridge University Press. 1994. pp. 97–. ISBN 978-0-521-47154-1.
  2. ↑ Lozano R, Naghavi M, Foreman K, Lim S, Shibuya K, Aboyans V, et al. (Dec 15, 2012). "Global and regional mortality from 235 causes of death for 20 age groups in 1990 and 2010: a systematic analysis for the Global Burden of Disease Study 2010". Lancet. 380 (9859): 2095–128. doi:10.1016/S0140-6736(12)61728-0. OCLC 23245604.
  3. ↑ Ambinder RF, Browning PJ, Lorenzana I, Leventhal BG, Cosenza H, Mann RB; et al. (1993). "Epstein-Barr virus and childhood Hodgkin's disease in Honduras and the United States". Blood. 81 (2): 462–7. PMID 8380725.
  4. ↑ Zhou XG, Hamilton-Dutoit SJ, Yan QH, Pallesen G (1993). "The association between Epstein-Barr virus and Chinese Hodgkin's disease". Int J Cancer. 55 (3): 359–63. PMID 8397160.
  5. ↑ Zarate-Osorno A, Roman LN, Kingma DW, Meneses-Garcia A, Jaffe ES (1995). "Hodgkin's disease in Mexico. Prevalence of Epstein-Barr virus sequences and correlations with histologic subtype". Cancer. 75 (6): 1360–6. PMID 7882287.
  6. ↑ Chang KL, Albújar PF, Chen YY, Johnson RM, Weiss LM (1993). "High prevalence of Epstein-Barr virus in the Reed-Sternberg cells of Hodgkin's disease occurring in Peru". Blood. 81 (2): 496–501. PMID 8380728.
  7. ↑ Peh SC, Looi LM, Pallesen G (1997). "Epstein-Barr virus (EBV) and Hodgkin's disease in a multi-ethnic population in Malaysia". Histopathology. 30 (3): 227–33. PMID 9088951.
  8. ↑ Armstrong AA, Alexander FE, Paes RP, Morad NA, Gallagher A, Krajewski AS; et al. (1993). "Association of Epstein-Barr virus with pediatric Hodgkin's disease". Am J Pathol. 142 (6): 1683–8. PMC 1886981. PMID 8389527.
  9. ↑ Andriko JA, Aguilera NS, Nandedkar MA, Abbondanzo SL (1997). "Childhood Hodgkin's disease in the United States: an analysis of histologic subtypes and association with Epstein-Barr virus". Mod Pathol. 10 (4): 366–71. PMID 9110300.
  10. ↑ http://picasaweb.google.com/mcmumbi/USMLEIIImages


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