Difference between revisions of "HAEM5:Primary cutaneous CD8-positive aggressive epidermotropic cytotoxic T-cell lymphoma"

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==Chromosomal Rearrangements (Gene Fusions)==
 
==Chromosomal Rearrangements (Gene Fusions)==
  
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Put your text here and fill in the table
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Various Jak2 fusions are described. Upregulated JAK-2 signaling is observed in nearly all cases, a feature not detected in other cytotoxic cutaneous T-cell lymphomas.<ref name=":3">{{Cite journal|title=Deregulation of JAK2 signaling underlies primary cutaneous CD8+ aggressive epidermotropic cytotoxic T-cell lymphoma|url=https://pubmed.ncbi.nlm.nih.gov/33792220/|journal=Haematologica|date=2022-03-01|issn=1592-8721|pmc=8883537|pmid=33792220|pages=702–714|volume=107|issue=3|doi=10.3324/haematol.2020.274506|first=Armando N.|last=Bastidas Torres|first2=Davy|last2=Cats|first3=Jacoba J.|last3=Out-Luiting|first4=Daniele|last4=Fanoni|first5=Hailiang|last5=Mei|first6=Luigia|last6=Venegoni|first7=Rein|last7=Willemze|first8=Maarten H.|last8=Vermeer|first9=Emilio|last9=Berti}}</ref>
  
 
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!Notes
 
!Notes
 
|-
 
|-
−
|EXAMPLE t(9;22)(q34;q11.2)||EXAMPLE 3'ABL1 / 5'BCR||EXAMPLE der(22)||EXAMPLE 20% (COSMIC)
+
|JAK2 fusions||KHDRBS1-JAK2, PCM1-JAK2, TFG-JAK2||Self-oligo/dimerization of JAK2||Detected in 3 out of 12 patients
−
EXAMPLE 30% (add reference)
 
 
|Yes
 
|Yes
−
|No
+
|Unknown
 
|Yes
 
|Yes
−
|EXAMPLE
+
|Confer cytokine-independent survival ability, potential therapeutic target with JAK inhibitors.<ref name=":3" />
−
 
 
−
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).
 
 
|}
 
|}
 
 
 
==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>
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<br />
  
 
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!Notes
 
!Notes
 
|-
 
|-
−
|EXAMPLE
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|1p
−
 
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|Deletion
−
7
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|chr1:1-123,456 [hg38]
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|EXAMPLE Loss
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|1p
−
|EXAMPLE
 
−
 
 
−
chr7:1- 159,335,973 [hg38]
 
−
|EXAMPLE
 
−
 
 
−
chr7
 
−
|Yes
 
 
|Yes
 
|Yes
 +
|Unknown
 
|No
 
|No
−
|EXAMPLE
+
|Associated with chromatin remodeling and tumor suppression.
−
 
 
−
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).
 
 
|-
 
|-
−
|EXAMPLE
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|8p
−
 
+
|Deletion
−
8
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|chr8:1-234,567 [hg38]
−
|EXAMPLE Gain
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|8p
−
|EXAMPLE
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|Yes
−
 
+
|Unknown
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chr8:1-145,138,636 [hg38]
 
−
|EXAMPLE
 
−
 
 
−
chr8
 
−
|No
 
−
|No
 
 
|No
 
|No
−
|EXAMPLE
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|Common in fusion-negative cases.<ref name=":3" />
−
 
 
−
Common recurrent secondary finding for t(8;21) (add reference).
 
 
|}
 
|}
 
==Characteristic Chromosomal Patterns==
 
==Characteristic Chromosomal Patterns==
  
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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>
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<br />
  
 
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!Notes
 
!Notes
 
|-
 
|-
−
|EXAMPLE
+
|Deletions within 1p, 8p, 9q, 10p, 11q and 13q; gains within 7q, 8q, 17q and 21q
−
 
 
−
Co-deletion of 1p and 18q
 
 
|Yes
 
|Yes
−
|No
+
|Unknown
−
|No
+
|Unknown
−
|EXAMPLE:
+
|Identified in fusion-negative cases.<ref name=":3" />
−
 
 
−
See chromosomal rearrangements table as this pattern is due to an unbalanced derivative translocation associated with oligodendroglioma (add reference).
 
 
|}
 
|}
 
==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>
 
  
 
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!Notes
 
!Notes
 
|-
 
|-
−
|EXAMPLE: TP53; Variable LOF mutations
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|JAK2
  
−
EXAMPLE:
+
Fusion genes: KHDRBS1-JAK2, PCM1-JAK2, TFG-JAK2
−
 
+
|Self-oligo/dimerization
−
EGFR; Exon 20 mutations
+
|Detected in 3 out of 12 patients
−
 
+
|MYC fusions
−
EXAMPLE: BRAF; Activating mutations
+
|PTPRC, SH2B3
−
|EXAMPLE: TSG
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|Yes
−
|EXAMPLE: 20% (COSMIC)
+
|Unknown
−
 
+
|Yes
−
EXAMPLE: 30% (add Reference)
+
|Potential therapeutic target with JAK inhibitors.<ref name=":3" />
−
|EXAMPLE: IDH1 R123H
+
|}
−
|EXAMPLE: EGFR amplification
 
−
|
 
−
|
 
−
|
 
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|EXAMPLE:  Excludes hairy cell leukemia (HCL) (add reference).
 
 
<br />
 
<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.
 
  
 
==Epigenomic Alterations==
 
==Epigenomic Alterations==
  
−
Put your text here
+
Unknown
  
 
==Genes and Main Pathways Involved==
 
==Genes and Main Pathways Involved==
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−
Put your text here and fill in the table <span style="color:#0070C0">(''Instructions: Can include references in 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
+
|JAK2;Fusion with KHDRBS1, PCM1, TFG
−
|EXAMPLE: MAPK signaling
+
|JAK-STAT signaling
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|EXAMPLE: Increased cell growth and proliferation
+
|Upregulation leads to cytokine-independent activation.
 
|-
 
|-
−
|EXAMPLE: CDKN2A; Inactivating mutations
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|SH2B3;Deletion
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|EXAMPLE: Cell cycle regulation
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|JAK-STAT negative regulation
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|EXAMPLE: Unregulated cell division
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|Loss leads to hyperactivation of JAK2 signaling.<ref name=":3" />
−
|-
 
−
|EXAMPLE:  KMT2C and ARID1A; Inactivating mutations
 
−
|EXAMPLE:  Histone modification, chromatin remodeling
 
−
|EXAMPLE:  Abnormal gene expression program
 
 
|}
 
|}
 
==Genetic Diagnostic Testing Methods==
 
==Genetic Diagnostic Testing Methods==
  
−
Put your text here
+
JAK2 by Next-generation sequencing (NGS). SH2B3 by PCR or FISH.<ref name=":3" />
  
 
==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>
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Unknown
  
 
==Additional Information==
 
==Additional Information==
−
 
−
Put your text here
 
  
 
==Links==
 
==Links==

Revision as of 22:15, 13 July 2024


Haematolymphoid Tumours (5th ed.)

(General Instructions – The main focus of these pages is the clinically significant genetic alterations in each disease type. Use HUGO-approved gene names and symbols (italicized when appropriate), HGVS-based nomenclature for variants, 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). 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 Author_Instructions and FAQs as well as contact your Associate Editor or Technical Support)

Primary Author(s)*

Ahmed Eladely, MBBCh. Andrew Siref, MD.

Creighton University, Omaha, NE.

Cancer Category / Type

Book WHO Classification of Disease - Haematolymphoid Tumours (5th ed.)
Category T-cell and NK-cell lymphoid proliferations and lymphomas
Family Mature T-cell and NK-cell neoplasms
Type Primary cutaneous T-cell lymphoid proliferations and lymphomas
Subtype Primary cutaneous CD8-positive aggressive epidermotropic cytotoxic T-cell lymphoma

Cancer Sub-Classification / Subtype

None

Definition / Description of Disease

Primary cutaneous CD8-positive aggressive epidermotropic cytotoxic T-cell lymphoma (PCAETL) is a rare and poorly characterized neoplastic proliferation of T lymphocytes with CD8 expression and cytotoxic molecules. PACETL is marked by epidermal necrosis, a high proliferation index, and aggressive clinical behavior. It should be distinguished from other rare epidermotropic subtypes of cutaneous gamma-delta T-cell lymphomas (such as gamma-delta mycosis fungoides), CD8+ mycosis fungoides, localized pagetoid reticulosis, type D lymphomatoid papulosis and Woringer-Kolopp disease.[1][2][3]

Synonyms / Terminology

Ketron–Goodman, disseminated pagetoid reticulosis, Berti lymphoma (Historical)

Epidemiology / Prevalence

PCAETL is rare, comprising less than 1% of all cutaneous T-cell lymphomas. It typically occurs in adults and shows a predilection for males.[1][3]

Clinical Features

Signs and Symptoms Localized papules (less common)

Diffusely distributed papules (common)

Ulcerated nodules, tumors, and plaques

Erosion or central necrosis

Preceded by chronic, poorly defined patches (subset)

Disseminate to visceral sites (lungs, testes, CNS)

Lymph nodes spared

No association with immunosuppression[1][2][3]

Laboratory Findings None

Sites of Involvement

PACETL can present with either localized or generalized skin lesions and may affect oral mucosa.[4]

Morphologic Features

Put your text here

Immunophenotype

Put your text here and fill in the table (Instruction: Can include references in the table)

Finding Marker
Positive (universal) EXAMPLE CD1
Positive (subset) EXAMPLE CD2
Negative (universal) EXAMPLE CD3
Negative (subset) EXAMPLE CD4

Chromosomal Rearrangements (Gene Fusions)

Various Jak2 fusions are described. Upregulated JAK-2 signaling is observed in nearly all cases, a feature not detected in other cytotoxic cutaneous T-cell lymphomas.[5]

Chromosomal Rearrangement Genes in Fusion (5’ or 3’ Segments) Pathogenic Derivative Prevalence Diagnostic Significance (Yes, No or Unknown) Prognostic Significance (Yes, No or Unknown) Therapeutic Significance (Yes, No or Unknown) Notes
JAK2 fusions KHDRBS1-JAK2, PCM1-JAK2, TFG-JAK2 Self-oligo/dimerization of JAK2 Detected in 3 out of 12 patients Yes Unknown Yes Confer cytokine-independent survival ability, potential therapeutic target with JAK inhibitors.[5]

Individual Region Genomic Gain / Loss / LOH


Chr # Gain / Loss / Amp / LOH Minimal Region Genomic Coordinates [Genome Build] Minimal Region Cytoband Diagnostic Significance (Yes, No or Unknown) Prognostic Significance (Yes, No or Unknown) Therapeutic Significance (Yes, No or Unknown) Notes
1p Deletion chr1:1-123,456 [hg38] 1p Yes Unknown No Associated with chromatin remodeling and tumor suppression.
8p Deletion chr8:1-234,567 [hg38] 8p Yes Unknown No Common in fusion-negative cases.[5]

Characteristic Chromosomal Patterns


Chromosomal Pattern Diagnostic Significance (Yes, No or Unknown) Prognostic Significance (Yes, No or Unknown) Therapeutic Significance (Yes, No or Unknown) Notes
Deletions within 1p, 8p, 9q, 10p, 11q and 13q; gains within 7q, 8q, 17q and 21q Yes Unknown Unknown Identified in fusion-negative cases.[5]

Gene Mutations (SNV / INDEL)

Gene; Genetic Alteration Presumed Mechanism (Tumor Suppressor Gene [TSG] / Oncogene / Other) Prevalence (COSMIC / TCGA / Other) Concomitant Mutations Mutually Exclusive Mutations Diagnostic Significance (Yes, No or Unknown) Prognostic Significance (Yes, No or Unknown) Therapeutic Significance (Yes, No or Unknown) Notes
JAK2

Fusion genes: KHDRBS1-JAK2, PCM1-JAK2, TFG-JAK2

Self-oligo/dimerization Detected in 3 out of 12 patients MYC fusions PTPRC, SH2B3 Yes Unknown Yes Potential therapeutic target with JAK inhibitors.[5]


Epigenomic Alterations

Unknown

Genes and Main Pathways Involved

Gene; Genetic Alteration Pathway Pathophysiologic Outcome
JAK2;Fusion with KHDRBS1, PCM1, TFG JAK-STAT signaling Upregulation leads to cytokine-independent activation.
SH2B3;Deletion JAK-STAT negative regulation Loss leads to hyperactivation of JAK2 signaling.[5]

Genetic Diagnostic Testing Methods

JAK2 by Next-generation sequencing (NGS). SH2B3 by PCR or FISH.[5]

Familial Forms

Unknown

Additional Information

Links

Put your text placeholder here (or anywhere appropriate on the page) and use the "Link" icon at the top of the page (Instructions: Once you have a text placeholder entered to which you want to add a link, highlight that text, select the "Link" icon at the top of the page, and search the name of the internal page to which you want to link this text, or enter an external internet address including the "http://www." portion.)

References

(use the "Cite" icon at the top of the page) (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. 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.)

  1. ↑ 1.0 1.1 1.2 Berti, E.; et al. (1999-08). "Primary cutaneous CD8-positive epidermotropic cytotoxic T cell lymphomas. A distinct clinicopathological entity with an aggressive clinical behavior". The American Journal of Pathology. 155 (2): 483–492. doi:10.1016/S0002-9440(10)65144-9. ISSN 0002-9440. PMC 1866866. PMID 10433941. Check date values in: |date= (help)
  2. ↑ 2.0 2.1 Guitart, Joan; et al. (2017-05). "Primary cutaneous aggressive epidermotropic cytotoxic T-cell lymphomas: reappraisal of a provisional entity in the 2016 WHO classification of cutaneous lymphomas". Modern Pathology: An Official Journal of the United States and Canadian Academy of Pathology, Inc. 30 (5): 761–772. doi:10.1038/modpathol.2016.240. ISSN 1530-0285. PMC 5413429. PMID 28128277. Check date values in: |date= (help)
  3. ↑ 3.0 3.1 3.2 Robson, Alistair; et al. (2015-10). "Aggressive epidermotropic cutaneous CD8+ lymphoma: a cutaneous lymphoma with distinct clinical and pathological features. Report of an EORTC Cutaneous Lymphoma Task Force Workshop". Histopathology. 67 (4): 425–441. doi:10.1111/his.12371. ISSN 1365-2559. PMID 24438036. Check date values in: |date= (help)
  4. ↑ Travassos, Daphine Caxias; et al. (2022-06). "Primary cutaneous CD8+ cytotoxic T-cell lymphoma of the face with intraoral involvement, resulting in facial nerve palsy after chemotherapy". Journal of Cutaneous Pathology. 49 (6): 560–564. doi:10.1111/cup.14199. ISSN 1600-0560. PMID 35001425 Check |pmid= value (help). Check date values in: |date= (help)
  5. ↑ 5.0 5.1 5.2 5.3 5.4 5.5 5.6 Bastidas Torres, Armando N.; et al. (2022-03-01). "Deregulation of JAK2 signaling underlies primary cutaneous CD8+ aggressive epidermotropic cytotoxic T-cell lymphoma". Haematologica. 107 (3): 702–714. doi:10.3324/haematol.2020.274506. ISSN 1592-8721. PMC 8883537 Check |pmc= value (help). PMID 33792220 Check |pmid= value (help).

EXAMPLE Book

  1. Arber DA, et al., (2017). Acute myeloid leukaemia with recurrent genetic abnormalities, in World Health Organization Classification of Tumours of Haematopoietic and Lymphoid Tissues, Revised 4th edition. Swerdlow SH, Campo E, Harris NL, Jaffe ES, Pileri SA, Stein H, Thiele J, Arber DA, Hasserjian RP, Le Beau MM, Orazi A, and Siebert R, Editors. IARC Press: Lyon, France, p129-171.

Notes

*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. *Citation of this Page: “Primary cutaneous CD8-positive aggressive epidermotropic cytotoxic T-cell lymphoma”. Compendium of Cancer Genome Aberrations (CCGA), Cancer Genomics Consortium (CGC), updated 07/13/2024, https://ccga.io/index.php/HAEM5:Primary_cutaneous_CD8-positive_aggressive_epidermotropic_cytotoxic_T-cell_lymphoma.

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