Difference between revisions of "Hodgkin lymphoma"

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{{ Infobox diagnosis
'''Hodgkin [[lymphoma]]''', abbreviated '''HL''', is a haematological [[malignancy]]. If not otherwise specified, Hodgkin lymphoma generally refers to classical Hodgkin lymphoma (CHL) rather than [[nodular lymphocyte-predominant Hodgkin lymphoma]] (NLPHL). The latter accounts for only about 5% of the loose label of Hodgkin lymphoma<ref name=Ref_WMSP567/> and shows a sufficiently different biology and immunophenotype that is essentially a different disease (see [[nodular lymphocyte-predominant Hodgkin lymphoma|main article on NLPHL]]). The common feature is large atypical cells: Hodgkin/Reed-Sternberg cells in the case of classical Hodgkin lymphoma and "popcorn"/lymphohistiocytic/L&H cells in NLPHL. However, at least in typical cases, there are morphological and immunophenotypic differences.
| Name      = Nodular lymphocyte-predominant Hodgkin lymphoma
 
| Image      = Popcorn_cell_in_nodular_lymphocyte_predominant_Hodgkin_lymphoma_-_very_high_mag_cropped.jpg
Classical Hodgkin lymphoma has a bi-modal distribution, afflicting young adults and with a further peak in incidence in middle-age. Fortunately, it usually has a good prognosis.
| Width      =
| Caption    = Popcorn cell in nodular lymphocyte-predominant Hodgkin lymphoma
| Micro      = Popcorn cells (relatively) small (compared to classic RSCs) - have lobulated nucleus (key feature), small nucleoli; subtle nodularity at low power
| Subtypes  = none
| LMDDx      = [[diffuse large B cell lymphoma]] (esp. ''T-cell/histiocytic-rich LBCL''), [[anaplastic large cell lymphoma]],
B-cell lymphoma, unclassifiable, with features intermediate between diffuse large B-cell lymphoma and classical Hodgkin lymphoma, classical Hodgkin lymphoma
| Stains    =
| IHC        = LCA (CD45) +ve, CD20 +ve, CD10 +ve, Bcl-6 +ve, EMA +ve, CD30 -ve, CD15 -ve
| EM        =
| Molecular  =
| IF        =
| Gross      =
| Grossing  =
| Site      = usu. [[lymph node]]
| Assdx      =
| Syndromes  =
| Clinicalhx =
| Signs      = lymphadenopathy
| Symptoms  =
| Prevalence = uncommon
| Bloodwork  =
| Rads      =
| Endoscopy  =
| Prognosis  = good
| Other      =
| ClinDDx    =
}}
'''Hodgkin [[lymphoma]]''', abbreviated '''HL''', is a [[malignancy]] that often afflicts people in the prime of their life. Fortunately, it usually has a good prognosis.


Pathologists say "... it is both the easiest and hardest diagnosis to make." The reason for this is: the diagnosis depends on finding Reed-Sternberg cells (or Popcorn cells); if they are obvious the diagnosis is easy... if you can't find 'em and an alternative diagnosis is not apparent -- you wonder whether you're missing them.
Pathologists say "... it is both the easiest and hardest diagnosis to make." The reason for this is: the diagnosis depends on finding Reed-Sternberg cells (or Popcorn cells); if they are obvious the diagnosis is easy... if you can't find 'em and an alternative diagnosis is not apparent -- you wonder whether you're missing them.
Line 75: Line 47:
*Usually good.
*Usually good.
*Unlike non-Hodgkin lymphomas, it spreads in a predictable pattern; thus, staging plays an important role in determining the therapy.<ref name=PCPBoD8_315>{{Ref PCPBoD8|315}}</ref>
*Unlike non-Hodgkin lymphomas, it spreads in a predictable pattern; thus, staging plays an important role in determining the therapy.<ref name=PCPBoD8_315>{{Ref PCPBoD8|315}}</ref>
*Clinically classified into early favourable, early unfavourable and late/advanced disease.


==Hodgkin lymphoma subtypes==
===Classic HL sub-types===
Types:<ref name=Ref_WMSP567/>
*Classical HL (CHL) - ~95% of HL.
*Nodular lymphocyte-predominant HL (NLPHL) - ~5% of HL.
 
===Classic HL===
*Four types of classic HL (see below).
 
===NLPHL===
*AKA ''lympho-histiocytic variant''.
*Abbreviated ''NLPHL''.
*Different IHC and morphologic appearance than classic HL.
*Significant risk for transformation into [[diffuse large B cell lymphoma]] (DLBCL); 10-year cumulative transformation rate (to DLBCL) in one study was 12%.<ref name=pmid20029973 >{{cite journal |author=Biasoli I, Stamatoullas A, Meignin V, ''et al.'' |title=Nodular, lymphocyte-predominant Hodgkin lymphoma: a long-term study and analysis of transformation to diffuse large B-cell lymphoma in a cohort of 164 patients from the Adult Lymphoma Study Group |journal=Cancer |volume=116 |issue=3 |pages=631–9 |year=2010 |month=February |pmid=20029973 |doi=10.1002/cncr.24819 |url=}}</ref>
 
==Gross==
Location:
*Almost always arises from a [[lymph node]] - classically in the neck.
**''Extranodal Hodgkin lymphoma'' is (case report) rare.<ref name=pmid11100066>{{Cite journal  | last1 = Vadmal | first1 = MS. | last2 = LaValle | first2 = GP. | last3 = DeYoung | first3 = BR. | last4 = Frankel | first4 = WL. | last5 = Marsh | first5 = WL. | title = Primary localized extranodal hodgkin disease of the transverse colon. | journal = Arch Pathol Lab Med | volume = 124 | issue = 12 | pages = 1824-7 | month = Dec | year = 2000 | doi = 10.1043/0003-9985(2000)1241824:PLEHDO2.0.CO;2 | PMID = 11100066 }}</ref>
 
==Microscopic==
By definition, HL has ''Reed-Sternberg cells'' (RSCs) or ''Popcorn cells''.
 
===Classical HL===
Features (classic HL):
*Reed-Sternberg cell.
**Large binucleated cell (>= 45 micrometres).<ref name=Ref_PCPBoD8_329>{{Ref PCPBoD8|329}}</ref>
***May be multinucleated.
***May have a horseshoe-like shape.
**[[Macronucleolus]] - approximately the size of a RBC (~8 micrometers).
**Well-defined cell border.
**Abundant cytoplasm.
 
Notes:
*Large mononuclear cells are common (so called "mononuclear RSCs") but not diagnostic.
 
====Images (classic HL)====
<gallery>
Image:Hodgkin_lymphoma_cytology_large.jpg | HL mixed cellularity - cytology. (WC)
Image:Hodgkin_lymphoma_cytology_small.jpg | HL mixed cellularity - cytology. (WC)
Image:Hodgkin_lymphoma_%281%29_mixed_cellulary_type.jpg | HL mixed cellularity. (WC)
</gallery>
====Subtypes of classic HL====
====Subtypes of classic HL====
There are four CHL subtypes:<ref name=Ref_WMSP567/>
There are four CHL subtypes:<ref name=Ref_WMSP567/>
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*The subtypes prevalence is in reverse alphabetical order.
*The subtypes prevalence is in reverse alphabetical order.


===Nodular lymphocyte predominant Hodgkin lymphoma===
==Gross==
Features (nodular lymphocyte-predominant Hodgkin's lymphoma):
Location:
*''Popcorn cell'' (previously known as ''Lymphocytic & histiocytic'' cell (L&H cell)<ref name=pmid9499174>{{cite journal |author=Küppers R, Rajewsky K, Braeuninger A, Hansmann ML |title=L&H cells in lymphocyte-predominant Hodgkin's disease |journal=N. Engl. J. Med. |volume=338 |issue=11 |pages=763–4; author reply 764–5 |year=1998 |month=March |pmid=9499174 |doi=10.1056/NEJM199803123381113 |url=}}</ref>) - variant of RSC:
*Almost always arises from a [[lymph node]] - classically in the neck, but may be in the axilla and mediastinum
**Cells (relatively) small (compared to classic RSCs).
*Spleen may be involved
**Lobulated nucleus - '''key feature'''.
*Bone marrow involvement is unusual (~5% of cases, higher in HIV-associated cases), so bone marrow assessment is usually not performed
**Small nucleoli.  
*''Extranodal Hodgkin lymphoma'' is (case report) rare.<ref name=pmid11100066>{{Cite journal | last1 = Vadmal | first1 = MS. | last2 = LaValle | first2 = GP. | last3 = DeYoung | first3 = BR. | last4 = Frankel | first4 = WL. | last5 = Marsh | first5 = WL. | title = Primary localized extranodal hodgkin disease of the transverse colon. | journal = Arch Pathol Lab Med | volume = 124 | issue = 12 | pages = 1824-7 | month = Dec | year = 2000 | doi = 10.1043/0003-9985(2000)1241824:PLEHDO2.0.CO;2 | PMID = 11100066 }}</ref>
*Subtle nodularity at low power (2.5x or 5x objective).
 
==Microscopic==
Defined by ''Reed-Sternberg cells'' (RSCs). Morphologically similar mononuclear cells are known as Hodgkin cells. RSCs are:
*Large binucleated cell (>= 45 micrometres).<ref name=Ref_PCPBoD8_329>{{Ref PCPBoD8|329}}</ref>
**May be multinucleated.
**May have a horseshoe-like shape.
*[[Macronucleolus]] - approximately the size of a RBC (~8 micrometers).
*Well-defined cell border.
*Abundant cytoplasm.
 
RSC may show peri-cellular clearing, making the cells appear within a space. These are called lacunar cells (as they are in a "lake"). Apoptotic RSC may show pyknotic nuclei and scant eosinophilic cytoplasm and are sometimes known as "mummified" cells.


====Images (NLPHL)====
===Images (classic HL)===
www:
*[http://webpathology.com/image.asp?case=388&n=16 Popcorn cell (webpathology.com)].
<gallery>
<gallery>
Image:Popcorn_cell_in_nodular_lymphocyte_predominant_Hodgkin_lymphoma_-_very_high_mag_cropped.jpg | Popcorn cell. (WC)
Image:CHL mummified cell x40.jpg | "Mummified" RSC. (WC)
Image:CHL lacunar cell x40.jpg | "Lacunar cell". (WC)
Image:16S14098 cHL multinucleate HRS cell x40c.jpg | Multinucleate RSC. (WC)
Image:Hodgkin_lymphoma_cytology_large.jpg | HL mixed cellularity - cytology. (WC)
Image:Hodgkin_lymphoma_cytology_small.jpg | HL mixed cellularity - cytology. (WC)
Image:Hodgkin_lymphoma_%281%29_mixed_cellulary_type.jpg | HL mixed cellularity. (WC)
</gallery>
</gallery>
===DDx both CHL & NLPHL===
===DDx both CHL & NLPHL===
*CHL/NLPHL.
*CHL/NLPHL.
*[[Diffuse large B cell lymphoma]] (DLBCL), esp. ''T-cell/histiocytic-rich LBCL''.
*[[Diffuse large B cell lymphoma]] (DLBCL), esp. ''T-cell/histiocytic-rich LBCL''.
*[[Anaplastic large cell lymphoma]] (ALCL).
*[[Anaplastic large cell lymphoma]] (ALCL).
*B-cell lymphoma, unclassifiable, with features intermediate between diffuse large B-cell lymphoma and classical Hodgkin lymphoma.<ref name=pmid22222636>{{Cite journal  | last1 = Gualco | first1 = G. | last2 = Natkunam | first2 = Y. | last3 = Bacchi | first3 = CE. | title = The spectrum of B-cell lymphoma, unclassifiable, with features intermediate between diffuse large B-cell lymphoma and classical Hodgkin lymphoma: a description of 10 cases. | journal = Mod Pathol | volume =  | issue =  | pages =  | month = Jan | year = 2012 | doi = 10.1038/modpathol.2011.200 | PMID = 22222636 | URL = http://www.nature.com/modpathol/journal/vaop/ncurrent/full/modpathol2011200a.html }}</ref>
*B-cell lymphoma, unclassifiable, with features intermediate between diffuse large B-cell lymphoma and classical Hodgkin lymphoma.<ref name=pmid22222636>{{Cite journal  | last1 = Gualco | first1 = G. | last2 = Natkunam | first2 = Y. | last3 = Bacchi | first3 = CE. | title = The spectrum of B-cell lymphoma, unclassifiable, with features intermediate between diffuse large B-cell lymphoma and classical Hodgkin lymphoma: a description of 10 cases. | journal = Mod Pathol | volume =  | issue =  | pages =  | month = Jan | year = 2012 | doi = 10.1038/modpathol.2011.200 | PMID = 22222636 | URL = http://www.nature.com/modpathol/journal/vaop/ncurrent/full/modpathol2011200a.html }}</ref> (typically in cases of numerous large atypical cells where the morphology and immunophenotype do not neatly fit into either DLBCL or CHL).


==IHC==
==IHC==
Abbreviated panel:<ref name=Ref_WMSP568>{{Ref_WMSP|568}}</ref>
Abbreviated panel:<ref name=Ref_WMSP568>{{Ref_WMSP|568}}</ref>
*CD30 Reed-Sternberg cells (RSCs) +ve ~98%  
*CD30 Reed-Sternberg cells (RSCs) +ve ~98% (beware of mis-interpreting CD30+ activated lymphoid cells)
*CD15 Reed-Sternberg cells +ve ~80%, stains neutrophils.
*CD15 Reed-Sternberg cells +ve ~80%, stains neutrophils.
*Both CD30 and CD15 are classically positive in a membranous and Golgi pattern
*MUM1 +ve
*CD45 '''often negative''' in RSCs.
*CD45 '''often negative''' in RSCs.
*CD20 may stain RSCs.
*CD20 may stain RSCs (usually negative, but can be weak).
*PAX5 +ve.<ref name=Ref_APBR683>{{Ref APBR|683}}</ref>
*PAX5 +ve, though said to be weaker than background normal B-cells<ref name=Ref_APBR683>{{Ref APBR|683}}</ref>


Additional - for completeness:
Additional - for completeness:
*CD3 (T lymphocytes)
*CD3 (T lymphocytes) - negative in RSCs
*OCT2/BOB1 negative (co-transcription factors for immunoglobulin production, one or the other is usually negative)
*40% are EBV positive.


NLPHL IHC '''differs''' from the classical HL:<ref name=Ref_APBR683>{{Ref APBR|683}}</ref>
NLPHL IHC '''differs''' from the classical HL:<ref name=Ref_APBR683>{{Ref APBR|683}}</ref>
Line 169: Line 120:
*CD10 +ve.
*CD10 +ve.
*Bcl-6 +ve.
*Bcl-6 +ve.
*[[EMA]] +ve.
*[[EMA]] +ve (40-50%)
*CD30 -ve
*CD30 -ve
*CD15 -ve.
*CD15 -ve.
Line 181: Line 132:
|CD20 || +ve || -ve
|CD20 || +ve || -ve
|-
|-
|BCL6 || ||
|BCL6 || +ve || -ve
|-
|-
|MUM1<ref>URL: [http://www.ncbi.nlm.nih.gov/omim/601900 http://www.ncbi.nlm.nih.gov/omim/601900]. Accessed on: 10 August 2010.</ref> || -ve ||
|MUM1<ref>URL: [http://www.ncbi.nlm.nih.gov/omim/601900 http://www.ncbi.nlm.nih.gov/omim/601900]. Accessed on: 10 August 2010.</ref> || -ve || +ve
|-
|-
|CD30 || -ve || +ve (most sensitive).
|CD30 || -ve || +ve (most sensitive).
Line 207: Line 158:
|4 unstained || ||
|4 unstained || ||
|}
|}
==Sign out==
===Suggestive FNA===
<pre>
Lymph Node, Right Neck, FNA:
- Large binucleated and multinucleated cells with macronucleoli in
  a background of abundant lymphocytes, histiocytes, rare eosinophils.
Comment:
A cell block is not available for further work-up. The findings raise the possibility of Hodgkin's lymphoma.
A further biopsy is required for the diagnosis.
</pre>


==See also==
==See also==

Latest revision as of 22:01, 4 December 2018

Classical Hodgkin lymphoma
Diagnosis in short

HL mixed cellularity - cytology.
LM Reed-Sternberg cell (large binucleated cell (>= 45 micrometres), +/-multinucleated, +/-horseshoe-like shape, macronucleolus - approximately the size of a RBC (~8 micrometers)), well-defined cell border, abundant cytoplasm.
Subtypes nodular sclerosis CHL, mixed cellularity CHL, lymphocyte-rich CHL, lymphocyte-depleted CHL
LM DDx

diffuse large B cell lymphoma (esp. T-cell/histiocytic-rich LBCL), anaplastic large cell lymphoma,

B-cell lymphoma, unclassifiable, with features intermediate between diffuse large B-cell lymphoma and classical Hodgkin lymphoma, nodular lymphocyte-predominant Hodgkin lymphoma
IHC CD30 Reed-Sternberg cells (RSCs) +ve ~98%, CD15 Reed-Sternberg cells +ve ~80% (also stains neutrophils), CD45 often negative in RSCs, CD20 -ve/+ve, PAX5 +ve
Site usu. lymph node - classically in the neck
Clinical history young adults, older adults (bimodal distribution)
Signs lymphadenopathy - usu. neck, +/-B symptoms (fever, night sweats, weight loss)
Prevalence common
Prognosis usu. good, dependent on stage

Hodgkin lymphoma, abbreviated HL, is a haematological malignancy. If not otherwise specified, Hodgkin lymphoma generally refers to classical Hodgkin lymphoma (CHL) rather than nodular lymphocyte-predominant Hodgkin lymphoma (NLPHL). The latter accounts for only about 5% of the loose label of Hodgkin lymphoma[1] and shows a sufficiently different biology and immunophenotype that is essentially a different disease (see main article on NLPHL). The common feature is large atypical cells: Hodgkin/Reed-Sternberg cells in the case of classical Hodgkin lymphoma and "popcorn"/lymphohistiocytic/L&H cells in NLPHL. However, at least in typical cases, there are morphological and immunophenotypic differences.

Classical Hodgkin lymphoma has a bi-modal distribution, afflicting young adults and with a further peak in incidence in middle-age. Fortunately, it usually has a good prognosis.

Pathologists say "... it is both the easiest and hardest diagnosis to make." The reason for this is: the diagnosis depends on finding Reed-Sternberg cells (or Popcorn cells); if they are obvious the diagnosis is easy... if you can't find 'em and an alternative diagnosis is not apparent -- you wonder whether you're missing them.

General

Clinical

Symptoms:[1]

  • "B symptoms" - all required:[2] weight loss, night sweats and fever.
  • Infections due to immune dysfunction.

Diagnosis:

  • HL cannot be diagnosed with standard flow cytometry (FC) - but has been diagnosed with specialized FC.[3]

Prognosis:

  • Usually good.
  • Unlike non-Hodgkin lymphomas, it spreads in a predictable pattern; thus, staging plays an important role in determining the therapy.[4]
  • Clinically classified into early favourable, early unfavourable and late/advanced disease.

Classic HL sub-types

Subtypes of classic HL

There are four CHL subtypes:[1]

  1. Nodular sclerosis CHL - ~70% of CHL.
    • Mixed cellular background - T cell, plasma cells, eosinophils, neutrophils and histiocytes.
    • Nodular sclerosing fibrosis - thick strands fibrosis.
  2. Mixed cellularity CHL - ~20-25% of CHL.
    • Like nodular sclerosis - but no fibrosis.
    • May be associated with HIV infection.[5]
  3. Lymphocyte-rich CHL - rare.
    • T lymphocytes only (no mix of cells).
  4. Lymphocyte-depleted CHL - rare.
    • May be associated with HIV infection.[5]

Memory device:

  • The subtypes prevalence is in reverse alphabetical order.

Gross

Location:

  • Almost always arises from a lymph node - classically in the neck, but may be in the axilla and mediastinum
  • Spleen may be involved
  • Bone marrow involvement is unusual (~5% of cases, higher in HIV-associated cases), so bone marrow assessment is usually not performed
  • Extranodal Hodgkin lymphoma is (case report) rare.[6]

Microscopic

Defined by Reed-Sternberg cells (RSCs). Morphologically similar mononuclear cells are known as Hodgkin cells. RSCs are:

  • Large binucleated cell (>= 45 micrometres).[7]
    • May be multinucleated.
    • May have a horseshoe-like shape.
  • Macronucleolus - approximately the size of a RBC (~8 micrometers).
  • Well-defined cell border.
  • Abundant cytoplasm.

RSC may show peri-cellular clearing, making the cells appear within a space. These are called lacunar cells (as they are in a "lake"). Apoptotic RSC may show pyknotic nuclei and scant eosinophilic cytoplasm and are sometimes known as "mummified" cells.

Images (classic HL)

  • "Mummified" RSC. (WC)

  • "Lacunar cell". (WC)

  • Multinucleate RSC. (WC)

  • HL mixed cellularity - cytology. (WC)

  • HL mixed cellularity - cytology. (WC)

  • HL mixed cellularity. (WC)

DDx both CHL & NLPHL

  • CHL/NLPHL.
  • Diffuse large B cell lymphoma (DLBCL), esp. T-cell/histiocytic-rich LBCL.
  • Anaplastic large cell lymphoma (ALCL).
  • B-cell lymphoma, unclassifiable, with features intermediate between diffuse large B-cell lymphoma and classical Hodgkin lymphoma.[8] (typically in cases of numerous large atypical cells where the morphology and immunophenotype do not neatly fit into either DLBCL or CHL).

IHC

Abbreviated panel:[9]

  • CD30 Reed-Sternberg cells (RSCs) +ve ~98% (beware of mis-interpreting CD30+ activated lymphoid cells)
  • CD15 Reed-Sternberg cells +ve ~80%, stains neutrophils.
  • Both CD30 and CD15 are classically positive in a membranous and Golgi pattern
  • MUM1 +ve
  • CD45 often negative in RSCs.
  • CD20 may stain RSCs (usually negative, but can be weak).
  • PAX5 +ve, though said to be weaker than background normal B-cells[10]

Additional - for completeness:

  • CD3 (T lymphocytes) - negative in RSCs
  • OCT2/BOB1 negative (co-transcription factors for immunoglobulin production, one or the other is usually negative)
  • 40% are EBV positive.

NLPHL IHC differs from the classical HL:[10]

  • LCA +ve.
  • CD20 +ve.
  • CD10 +ve.
  • Bcl-6 +ve.
  • EMA +ve (40-50%)
  • CD30 -ve
  • CD15 -ve.

A panel

Antibody NLPHL CHL
CD45 +ve -ve
CD20 +ve -ve
BCL6 +ve -ve
MUM1[11] -ve +ve
CD30 -ve +ve (most sensitive).
CD15 -ve +ve
CD21 networks present no networks
CD23 networks present no networks
OCT-2 +ve -ve
PAX5 +ve +ve (proves B cell linage)
CD3 usu. < benign B cell usu. > benign B cell component
CD57 rosettes around malign. cells -
EBER -ve +ve/-ve
EMA +ve/-ve -ve
4 unstained

Sign out

Suggestive FNA

Lymph Node, Right Neck, FNA:
	- Large binucleated and multinucleated cells with macronucleoli in 
	  a background of abundant lymphocytes, histiocytes, rare eosinophils. 

Comment:
A cell block is not available for further work-up. The findings raise the possibility of Hodgkin's lymphoma. 

A further biopsy is required for the diagnosis.

See also

References

  1. ↑ 1.0 1.1 1.2 Humphrey, Peter A; Dehner, Louis P; Pfeifer, John D (2008). The Washington Manual of Surgical Pathology (1st ed.). Lippincott Williams & Wilkins. pp. 567. ISBN 978-0781765275.
  2. ↑ URL: http://lymphoma.about.com/od/symptoms/f/bsymptoms.htm. Accessed on: 11 August 2010.
  3. ↑ Fromm JR, Thomas A, Wood BL (March 2009). "Flow cytometry can diagnose classical hodgkin lymphoma in lymph nodes with high sensitivity and specificity". Am. J. Clin. Pathol. 131 (3): 322–32. doi:10.1309/AJCPW3UN9DYLDSPB. PMID 19228638.
  4. ↑ Mitchell, Richard; Kumar, Vinay; Fausto, Nelson; Abbas, Abul K.; Aster, Jon (2011). Pocket Companion to Robbins & Cotran Pathologic Basis of Disease (8th ed.). Elsevier Saunders. pp. 315. ISBN 978-1416054542.
  5. ↑ 5.0 5.1 Sissolak G, Sissolak D, Jacobs P (April 2010). "Human immunodeficiency and Hodgkin lymphoma". Transfus. Apher. Sci. 42 (2): 131–9. doi:10.1016/j.transci.2010.01.008. PMID 20138008.
  6. ↑ Vadmal, MS.; LaValle, GP.; DeYoung, BR.; Frankel, WL.; Marsh, WL. (Dec 2000). "Primary localized extranodal hodgkin disease of the transverse colon.". Arch Pathol Lab Med 124 (12): 1824-7. doi:10.1043/0003-9985(2000)1241824:PLEHDO2.0.CO;2. PMID 11100066.
  7. ↑ Mitchell, Richard; Kumar, Vinay; Fausto, Nelson; Abbas, Abul K.; Aster, Jon (2011). Pocket Companion to Robbins & Cotran Pathologic Basis of Disease (8th ed.). Elsevier Saunders. pp. 329. ISBN 978-1416054542.
  8. ↑ Gualco, G.; Natkunam, Y.; Bacchi, CE. (Jan 2012). "The spectrum of B-cell lymphoma, unclassifiable, with features intermediate between diffuse large B-cell lymphoma and classical Hodgkin lymphoma: a description of 10 cases.". Mod Pathol. doi:10.1038/modpathol.2011.200. PMID 22222636.
  9. ↑ Humphrey, Peter A; Dehner, Louis P; Pfeifer, John D (2008). The Washington Manual of Surgical Pathology (1st ed.). Lippincott Williams & Wilkins. pp. 568. ISBN 978-0781765275.
  10. ↑ 10.0 10.1 Lefkowitch, Jay H. (2006). Anatomic Pathology Board Review (1st ed.). Saunders. pp. 683. ISBN 978-1416025887.
  11. ↑ URL: http://www.ncbi.nlm.nih.gov/omim/601900. Accessed on: 10 August 2010.
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