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__NOTOC__
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{{Anaplastic large cell lymphoma}}
{{Anaplastic large cell lymphoma}}
{{CMG}}; {{AE}} {{AS}}
{{CMG}}; {{AE}} {{AS}}, {{kakbar}}; {{GRR}} {{Nat}}
==Overview==
==Overview==
Anaplastic large cell lymphoma may be classified into 2 subtypes: [[anaplastic large cell lymphoma, ALK positive]] and [[anaplastic large cell lymphoma, ALK negative]]. Based on clinical presentations, anaplastic large cell lymphoma may be classified into either primary cutaneous anaplastic large cell lymphoma and primary systemic anaplastic large cell lymphoma.
 
Anaplastic large cell lymphoma may be classified into several subtypes based on immunophenotype, clinical presentation, and histology.
 
==Classification==
==Classification==
* Anaplastic large cell lymphoma (peripheral T-cell lymphoma [[Non-Hodgkin Lymphoma]]) may be classified into 2 subtypes:  
* Anaplastic large cell lymphoma (peripheral T-cell lymphoma [[Non-Hodgkin Lymphoma]]) may be classified into 2 sub-types: <ref name="pmid29617304">{{cite journal| author=Montes-Mojarro IA, Steinhilber J, Bonzheim I, Quintanilla-Martinez L, Fend F| title=The Pathological Spectrum of Systemic Anaplastic Large Cell Lymphoma (ALCL). | journal=Cancers (Basel) | year= 2018 | volume= 10 | issue= 4 | pages=  | pmid=29617304 | doi=10.3390/cancers10040107 | pmc=5923362 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=29617304  }} </ref>
:*[[Anaplastic large cell lymphoma, ALK positive]]
:*[[Anaplastic large cell lymphoma, ALK positive]]
:*[[Anaplastic large cell lymphoma, ALK negative]]
:*[[Anaplastic large cell lymphoma, ALK negative]]
* Based on clinical presentations, anaplastic large cell lymphoma may be classified into either<ref name= canadian.cancer>Anaplastic large cell lymphoma. Canadian Cancer Society. http://www.cancer.ca/en/cancer-information/cancer-type/non-hodgkin-lymphoma/non-hodgkin-lymphoma/types-of-nhl/anaplastic-large-cell-lymphoma/?region=on Accessed on October 7, 2015</ref>
* Based on clinical presentations, anaplastic large cell lymphoma may be classified into 3 sub-types:
:* Primary cutaneous anaplastic large cell lymphoma
:* Primary cutaneous anaplastic large cell lymphoma
:* Primary systemic anaplastic large cell lymphoma
:* Primary systemic anaplastic large cell lymphoma
* Based on morphology, anaplastic large cell lymphoma may be classified into 3 subtypes:
::* Nodal anaplastic large cell lymphoma
::* Extra nodal anaplastic large cell lymphoma
:* Implant associated anaplastic large cell lymphoma
* Based on histology, anaplastic large cell lymphoma may be classified into 3 sub-types:<ref name="pmid26104084">{{cite journal| author=Zeng Y, Feldman AL| title=Genetics of anaplastic large cell lymphoma. | journal=Leuk Lymphoma | year= 2016 | volume= 57 | issue= 1 | pages= 21-7 | pmid=26104084 | doi=10.3109/10428194.2015.1064530 | pmc=4732699 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=26104084  }} </ref>
:* Classical Variants
:* Classical Variants
:* Atypical Variants
:* Atypical Variants
:* Rare Variants
:* Rare Variants


{| style="border: 0px; font-size: 90%; margin: 3px;" align=center
{| style="border: 0px; font-size: 90%; margin: 3px;" align="center"
|+ '''Classification based on the clinical presentation'''<ref name= canadian.cancer>Anaplastic large cell lymphoma. Canadian Cancer Society. http://www.cancer.ca/en/cancer-information/cancer-type/non-hodgkin-lymphoma/non-hodgkin-lymphoma/types-of-nhl/anaplastic-large-cell-lymphoma/?region=on Accessed on October 7, 2015</ref>
|+ '''Classification based on the clinical presentation'''
! style="background: #4479BA;; color:#FFF;" | Name
! style="background: #4479BA;; color:#FFF;" | Name
! style="background: #4479BA;; color:#FFF;" | Description
! style="background: #4479BA;; color:#FFF;" | Description
|-
|-
| style="text-align: center; padding: 5px 5px; background: #F5F5F5;" |  Primary cutaneous anaplastic large cell lymphoma
| style="text-align: center; padding: 5px 5px; background: #F5F5F5;" |  '''Primary cutaneous anaplastic large cell lymphoma'''
| style="padding: 5px 5px; background: #F5F5F5;" |  
| style="padding: 5px 5px; background: #F5F5F5;" |  
* Confined to the skin
* Confined to the skin.
* Usually have a single lump or tumor in the skin
* Usually a single lump or tumor in the skin.
* May also spread to lymph nodes in the area
* May also spread to lymph nodes in the area.
* Associated with a rare skin condition called [[lymphomatoid papulosis]]
* Associated with a rare skin condition called [[lymphomatoid papulosis]].
* Less aggressive than primary systemic anaplastic large cell lymphoma
* Less aggressive than primary systemic anaplastic large cell lymphoma.
* Occasionally individuals have a spontaneous remission
* Occasionally individuals have a spontaneous remission.
* Have a fairly good prognosis  
* Fairly good prognosis  
|-
|-
| style="text-align: center; padding: 5px 5px; background: #F5F5F5;" |  Primary systemic anaplastic large cell lymphoma
| style="text-align: center; padding: 5px 5px; background: #F5F5F5;" |  '''Primary systemic anaplastic large cell lymphoma'''
| style="padding: 5px 5px; background: #F5F5F5;" |
* Usually involves the lymph nodes.
* Can also occur in organs or tissues other than the lymph nodes (extranodal sites) including: lungs, liver, bone marrow, bone, gastrointestinal tract, skin, and soft tissue.
* Most individuals have advanced stage (stage III or IV) disease when they are diagnosed.
* Usually a fast-growing (aggressive) lymphoma.
|-
| style="text-align: center; padding: 5px 5px; background: #F5F5F5;" | '''Implant associated anaplastic large cell lymphoma''' 
| style="padding: 5px 5px; background: #F5F5F5;" |  
| style="padding: 5px 5px; background: #F5F5F5;" |  
* Usually involves the lymph nodes
* The tumor initially manifests with swelling of the breast due to fluid accumulation around the implant.
* Can also occur in organs or tissues other than the lymph nodes (extranodal sites), including:
* May progress to invade the tissue surrounding the capsule, and if left untreated may progress to axillary lymph nodes. <ref>Miranda RN, Aladily TN, Prince HM, Kanagal-Shamanna R, de Jong D, Fayad LE,Amin MB, Haideri N, Bhagat G, Brooks GS, Shifrin DA, O'Malley DP, Cheah CY, Bacchi CE, Gualco G, Li S, Keech JA Jr, Hochberg EP, Carty MJ, Hanson SE, Mustafa E, Sanchez S, Manning JT Jr, Xu-Monette ZY, Miranda AR, Fox P, Bassett RL, Castillo JJ, Beltran BE, de Boer JP, Chakhachiro Z, Ye D, Clark D, Young KH, Medeiros LJ. Breast implant-associated anaplastic large-cell lymphoma: long-term follow-up of 60 patients. J Clin Oncol. 2014 Jan 10;32(2):114-20.</ref>
:* lungs, liver, bone marrow, bone, gastrointestinal tract, skin and soft tissue
* Most individuals have advanced stage (stage III or IV) disease when they are diagnosed
* Usually a fast-growing (aggressive) lymphoma
|}
|}


{| style="border: 0px; font-size: 90%; margin: 3px;" align=center
{| style="border: 0px; font-size: 90%; margin: 3px;" align="center"
|+ '''Morphologic Classification''' <ref>The anaplastic lymphoma kinase in the pathogenesis of cancer. http://go.galegroup.com/ps/retrieve.dosgHitCountType=None&sort=RELEVANCE&inPS=true&prodId=HRCA&userGroupName=mlin_b_bethidmc&tabID=T002&searchId=R1&resultListType=RESULT_LIST&contentSegment=&searchType=AdvancedSearchForm&currentPosition=1&contentSet=GALE%7CA188154738&&docId=GALE Accessed on October 8, 2015</ref>  
 
|+ '''Histological Classification''' <ref name="Swerdlow">{{cite book | last = Swerdlow | first = Steven | title = WHO classification of tumours of haematopoietic and lymphoid tissues | publisher = International Agency for Research on Cancer | location = Lyon, France | year = 2008 | isbn = 9789283224310 }}</ref>  
! style="background: #4479BA;; color:#FFF;" | Name
! style="background: #4479BA;; color:#FFF;" | Name
! style="background: #4479BA;; color:#FFF;" | Description
! style="background: #4479BA;; color:#FFF;" | Description
|-
|-
| style="padding: 5px 5px; background: #DCDCDC;" colspan=2 | '''Classical Variants'''
| colspan="2" style="padding: 5px 5px; background: #DCDCDC;" | '''Classical Variants'''
|-
|-
| style="text-align: center; padding: 5px 5px; background: #F5F5F5;" |  Common pattern
| style="text-align: center; padding: 5px 5px; background: #F5F5F5;" |  '''Common pattern'''
| style="padding: 5px 5px; background: #F5F5F5;" |  
| style="padding: 5px 5px; background: #F5F5F5;" |  
* ALK positive anaplastic large cell lymphoma
* ALK positive anaplastic large cell lymphoma
* Most common morphological variant (75%) <ref name="pmid9736036">{{cite journal| author=Falini B, Bigerna B, Fizzotti M, Pulford K, Pileri SA, Delsol G et al.| title=ALK expression defines a distinct group of T/null lymphomas ("ALK lymphomas") with a wide morphological spectrum. | journal=Am J Pathol | year= 1998 | volume= 153 | issue= 3 | pages= 875-86 | pmid=9736036 | doi=10.1016/S0002-9440(10)65629-5 | pmc=PMC1853018 | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=9736036  }}</ref>
* In large cells, nucleoli tend to be more prominent.
* The cytoplasm may be either [[basophilic]] or [[eosinophilic]] and the cell may have many nuclei with dispersed or clumped [[chromatin]].
* Given that the lymphomatous cells grow in the lymph node's sinuses, this variant may resemble a metastatic tumor.
|-
|-
| style="padding: 5px 5px; background: #DCDCDC;" colspan=6 | '''Atypical Variants'''
| colspan="6" style="padding: 5px 5px; background: #DCDCDC;" | '''Atypical Variants'''
|-
|-
| style="text-align: center; padding: 5px 5px; background: #F5F5F5;" |  Small cell
| style="text-align: center; padding: 5px 5px; background: #F5F5F5;" |  '''Small cell'''
| style="padding: 5px 5px; background: #F5F5F5;" |  
| style="padding: 5px 5px; background: #F5F5F5;" |  
* ALK positive anaplastic large cell lymphoma
* ALK positive anaplastic large cell lymphoma.
* Cells have nuclear irregularity and perivascular/intravascular distribution.<ref name="pmid8394652">{{cite journal| author=Kinney MC, Collins RD, Greer JP, Whitlock JA, Sioutos N, Kadin ME| title=A small-cell-predominant variant of primary Ki-1 (CD30)+ T-cell lymphoma. | journal=Am J Surg Pathol | year= 1993 | volume= 17 | issue= 9 | pages= 859-68 | pmid=8394652 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=8394652  }}</ref>
* Occasionally, lymphomatous cells have a pale cytoplasm with a central nucleus, described as "fried egg cell".<ref name="Swerdlow">{{cite book | last = Swerdlow | first = Steven | title = WHO classification of tumours of haematopoietic and lymphoid tissues | publisher = International Agency for Research on Cancer | location = Lyon, France | year = 2008 | isbn = 9789283224310 }}</ref>
|-
|-
| style="text-align: center; padding: 5px 5px; background: #F5F5F5;" |  Lymphohistiocytic
| style="text-align: center; padding: 5px 5px; background: #F5F5F5;" |  '''Lymphohistiocytic'''
| style="padding: 5px 5px; background: #F5F5F5;" |  
| style="padding: 5px 5px; background: #F5F5F5;" |  
* ALK positive anaplastic large cell lymphoma
* ALK positive anaplastic large cell lymphoma
* [[Histiocytes]] have an [[acidophilic]] cytoplasm and a perinuclear clear area, with an eccentric nuclei and condensed chromatin.<ref>{{cite web|url=http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1858171/pdf/amjpathol00028-0072.pdf|title=
Frequent Expression ofthe NPM-ALK Chimeric Fusion Protein inAnaplastic Large-Cell Lymphoma, Lympho-Histiocytic Type}}</ref> 
* Lymphomatous cells cluster around the perivascular area as demonstrated by immunostaining with [[CD30]] and ALK antibodies.<ref name="Swerdlow">{{cite book | last = Swerdlow | first = Steven | title = WHO classification of tumours of haematopoietic and lymphoid tissues | publisher = International Agency for Research on Cancer | location = Lyon, France | year = 2008 | isbn = 9789283224310 }}</ref>
|-
|-
| style="text-align: center; padding: 5px 5px; background: #F5F5F5;" |  Giant cell
| style="text-align: center; padding: 5px 5px; background: #F5F5F5;" |  '''Giant cell'''
| style="padding: 5px 5px; background: #F5F5F5;" |  
| style="padding: 5px 5px; background: #F5F5F5;" |  
* ALK positive anaplastic large cell lymphoma
* ALK positive anaplastic large cell lymphoma
|-
|-
| style="text-align: center; padding: 5px 5px; background: #F5F5F5;" |  Hodgkin's like
| style="text-align: center; padding: 5px 5px; background: #F5F5F5;" |  '''Hodgkin's like'''
| style="padding: 5px 5px; background: #F5F5F5;" |  
| style="padding: 5px 5px; background: #F5F5F5;" |  
* ALK positive anaplastic large cell lymphoma
* The morphological characteristics of this pattern are similar to the nodular sclerosis variant of [[Hodgkin's lymphoma]].<ref name="pmid16434897">{{cite journal| author=Vassallo J, Lamant L, Brugieres L, Gaillard F, Campo E, Brousset P et al.| title=ALK-positive anaplastic large cell lymphoma mimicking nodular sclerosis Hodgkin's lymphoma: report of 10 cases. | journal=Am J Surg Pathol | year= 2006 | volume= 30 | issue= 2 | pages= 223-9 | pmid=16434897 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=16434897  }}</ref>
* This pattern is predominately more common among females.
* There are two immunophenotypes:<ref name="pmid16434897">{{cite journal| author=Vassallo J, Lamant L, Brugieres L, Gaillard F, Campo E, Brousset P et al.| title=ALK-positive anaplastic large cell lymphoma mimicking nodular sclerosis Hodgkin's lymphoma: report of 10 cases. | journal=Am J Surg Pathol | year= 2006 | volume= 30 | issue= 2 | pages= 223-9 | pmid=16434897 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=16434897  }}</ref><ref name="pmid26104084">{{cite journal| author=Zeng Y, Feldman AL| title=Genetics of anaplastic large cell lymphoma. | journal=Leuk Lymphoma | year= 2016 | volume= 57 | issue= 1 | pages= 21-7 | pmid=26104084 | doi=10.3109/10428194.2015.1064530 | pmc=4732699 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=26104084  }} </ref>
**Positive: [[CD30]], ALK, epithelial membrane antigen (EMA), [[CD43]] (only 66% of the times), and [[perforin]]
**Negative: [[CD15]], [[CD20]], Pax5/BSAP, and [[EBV]]
|-
|-
| style="padding: 5px 5px; background: #DCDCDC;" colspan=6 | '''Rare Variants'''
| colspan="6" style="padding: 5px 5px; background: #DCDCDC;" | '''Rare Variants'''
|-
|-
| style="text-align: center; padding: 5px 5px; background: #F5F5F5;" |  Sarcomatoid
| style="text-align: center; padding: 5px 5px; background: #F5F5F5;" |  '''Sarcomatoid'''
| style="padding: 5px 5px; background: #F5F5F5;" |
| style="padding: 5px 5px; background: #F5F5F5;" |
* ALK positive anaplastic large cell lymphoma
* ALK positive anaplastic large cell lymphoma
|}
|}


==References==
==References==
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[[Category:Pathology]]
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[[Category:Hematology]]
[[Category:Hematology]]
[[Category:Up-To-Date]]
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[[Category:Medicine]]
[[Category:Hematology]]
[[Category:Immunology]]

Latest revision as of 12:42, 11 April 2019

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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], Kamal Akbar, M.D.[3]; Grammar Reviewer: Natalie Harpenau, B.S.[4]

Overview

Anaplastic large cell lymphoma may be classified into several subtypes based on immunophenotype, clinical presentation, and histology.

Classification

  • Anaplastic large cell lymphoma (peripheral T-cell lymphoma Non-Hodgkin Lymphoma) may be classified into 2 sub-types: [1]
  • Based on clinical presentations, anaplastic large cell lymphoma may be classified into 3 sub-types:
  • Primary cutaneous anaplastic large cell lymphoma
  • Primary systemic anaplastic large cell lymphoma
  • Nodal anaplastic large cell lymphoma
  • Extra nodal anaplastic large cell lymphoma
  • Implant associated anaplastic large cell lymphoma
  • Based on histology, anaplastic large cell lymphoma may be classified into 3 sub-types:[2]
  • Classical Variants
  • Atypical Variants
  • Rare Variants
Classification based on the clinical presentation
Name Description
Primary cutaneous anaplastic large cell lymphoma
  • Confined to the skin.
  • Usually a single lump or tumor in the skin.
  • May also spread to lymph nodes in the area.
  • Associated with a rare skin condition called lymphomatoid papulosis.
  • Less aggressive than primary systemic anaplastic large cell lymphoma.
  • Occasionally individuals have a spontaneous remission.
  • Fairly good prognosis
Primary systemic anaplastic large cell lymphoma
  • Usually involves the lymph nodes.
  • Can also occur in organs or tissues other than the lymph nodes (extranodal sites) including: lungs, liver, bone marrow, bone, gastrointestinal tract, skin, and soft tissue.
  • Most individuals have advanced stage (stage III or IV) disease when they are diagnosed.
  • Usually a fast-growing (aggressive) lymphoma.
Implant associated anaplastic large cell lymphoma
  • The tumor initially manifests with swelling of the breast due to fluid accumulation around the implant.
  • May progress to invade the tissue surrounding the capsule, and if left untreated may progress to axillary lymph nodes. [3]
Histological Classification [4]
Name Description
Classical Variants
Common pattern
  • ALK positive anaplastic large cell lymphoma
  • Most common morphological variant (75%) [5]
  • In large cells, nucleoli tend to be more prominent.
  • The cytoplasm may be either basophilic or eosinophilic and the cell may have many nuclei with dispersed or clumped chromatin.
  • Given that the lymphomatous cells grow in the lymph node's sinuses, this variant may resemble a metastatic tumor.
Atypical Variants
Small cell
  • ALK positive anaplastic large cell lymphoma.
  • Cells have nuclear irregularity and perivascular/intravascular distribution.[6]
  • Occasionally, lymphomatous cells have a pale cytoplasm with a central nucleus, described as "fried egg cell".[4]
Lymphohistiocytic
  • ALK positive anaplastic large cell lymphoma
  • Histiocytes have an acidophilic cytoplasm and a perinuclear clear area, with an eccentric nuclei and condensed chromatin.[7]
  • Lymphomatous cells cluster around the perivascular area as demonstrated by immunostaining with CD30 and ALK antibodies.[4]
Giant cell
  • ALK positive anaplastic large cell lymphoma
Hodgkin's like
  • The morphological characteristics of this pattern are similar to the nodular sclerosis variant of Hodgkin's lymphoma.[8]
  • This pattern is predominately more common among females.
  • There are two immunophenotypes:[8][2]
    • Positive: CD30, ALK, epithelial membrane antigen (EMA), CD43 (only 66% of the times), and perforin
    • Negative: CD15, CD20, Pax5/BSAP, and EBV
Rare Variants
Sarcomatoid
  • ALK positive anaplastic large cell lymphoma

References

  1. ↑ Montes-Mojarro IA, Steinhilber J, Bonzheim I, Quintanilla-Martinez L, Fend F (2018). "The Pathological Spectrum of Systemic Anaplastic Large Cell Lymphoma (ALCL)". Cancers (Basel). 10 (4). doi:10.3390/cancers10040107. PMC 5923362. PMID 29617304.
  2. ↑ 2.0 2.1 Zeng Y, Feldman AL (2016). "Genetics of anaplastic large cell lymphoma". Leuk Lymphoma. 57 (1): 21–7. doi:10.3109/10428194.2015.1064530. PMC 4732699. PMID 26104084.
  3. ↑ Miranda RN, Aladily TN, Prince HM, Kanagal-Shamanna R, de Jong D, Fayad LE,Amin MB, Haideri N, Bhagat G, Brooks GS, Shifrin DA, O'Malley DP, Cheah CY, Bacchi CE, Gualco G, Li S, Keech JA Jr, Hochberg EP, Carty MJ, Hanson SE, Mustafa E, Sanchez S, Manning JT Jr, Xu-Monette ZY, Miranda AR, Fox P, Bassett RL, Castillo JJ, Beltran BE, de Boer JP, Chakhachiro Z, Ye D, Clark D, Young KH, Medeiros LJ. Breast implant-associated anaplastic large-cell lymphoma: long-term follow-up of 60 patients. J Clin Oncol. 2014 Jan 10;32(2):114-20.
  4. ↑ 4.0 4.1 4.2 Swerdlow, Steven (2008). WHO classification of tumours of haematopoietic and lymphoid tissues. Lyon, France: International Agency for Research on Cancer. ISBN 9789283224310.
  5. ↑ Falini B, Bigerna B, Fizzotti M, Pulford K, Pileri SA, Delsol G; et al. (1998). "ALK expression defines a distinct group of T/null lymphomas ("ALK lymphomas") with a wide morphological spectrum". Am J Pathol. 153 (3): 875–86. doi:10.1016/S0002-9440(10)65629-5. PMC 1853018. PMID 9736036.
  6. ↑ Kinney MC, Collins RD, Greer JP, Whitlock JA, Sioutos N, Kadin ME (1993). "A small-cell-predominant variant of primary Ki-1 (CD30)+ T-cell lymphoma". Am J Surg Pathol. 17 (9): 859–68. PMID 8394652.
  7. ↑ "Frequent Expression ofthe NPM-ALK Chimeric Fusion Protein inAnaplastic Large-Cell Lymphoma, Lympho-Histiocytic Type" (PDF).
  8. ↑ 8.0 8.1 Vassallo J, Lamant L, Brugieres L, Gaillard F, Campo E, Brousset P; et al. (2006). "ALK-positive anaplastic large cell lymphoma mimicking nodular sclerosis Hodgkin's lymphoma: report of 10 cases". Am J Surg Pathol. 30 (2): 223–9. PMID 16434897.

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