Primary cutaneous acral CD8-positive T-cell lymphoproliferative disorder
Haematolymphoid Tumours (WHO Classification, 5th ed.)
Primary Author(s)*
Ahmed Eladely, MBBCh; Andrew Siref, MD
Creighton University, Omaha, NE
WHO Classification of Disease
| Structure | Disease |
|---|---|
| Book | 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(s) | Primary cutaneous acral CD8-positive T-cell lymphoproliferative disorder |
Related Terminology
| Acceptable | N/A |
| Not Recommended | Indolent CD8+ lymphoid proliferation of the ear; primary cutaneous acral CD8-positive T-cell lymphoma |
Gene Rearrangements
Chromosomal rearrangements contributing to tumor formation have not yet been described.
| Driver Gene | Fusion(s) and Common Partner Genes | Molecular Pathogenesis | Typical Chromosomal Alteration(s) | Prevalence -Common >20%, Recurrent 5-20% or Rare <5% (Disease) | Diagnostic, Prognostic, and Therapeutic Significance - D, P, T | Established Clinical Significance Per Guidelines - Yes or No (Source) | Clinical Relevance Details/Other Notes |
|---|---|---|---|---|---|---|---|
| N/A | N/A | N/A | N/A | N/A | N/A | N/A | N/A |
Individual Region Genomic Gain/Loss/LOH
Individual region genomic gain, loss, or LOH contributing to tumor formation have not yet been described.
| Chr # | Gain, Loss, Amp, LOH | Minimal Region Cytoband and/or Genomic Coordinates [Genome Build; Size] | Relevant Gene(s) | Diagnostic, Prognostic, and Therapeutic Significance - D, P, T | Established Clinical Significance Per Guidelines - Yes or No (Source) | Clinical Relevance Details/Other Notes |
|---|---|---|---|---|---|---|
| N/A | N/A | N/A | N/A | N/A | N/A |
Characteristic Chromosomal or Other Global Mutational Patterns
Characteristic chromosomal patterns contributing to tumor formation have not yet been described.
| Chromosomal Pattern | Molecular Pathogenesis | Prevalence -
Common >20%, Recurrent 5-20% or Rare <5% (Disease) |
Diagnostic, Prognostic, and Therapeutic Significance - D, P, T | Established Clinical Significance Per Guidelines - Yes or No (Source) | Clinical Relevance Details/Other Notes |
|---|---|---|---|---|---|
| N/A | N/A | N/A | N/A | N/A | N/A |
Gene Mutations (SNV/INDEL)
One study described recurrent mutations on analysis of 5 cases.[1]
| Gene | Genetic Alteration | Tumor Suppressor Gene, Oncogene, Other | Prevalence -
Common >20%, Recurrent 5-20% or Rare <5% (Disease) |
Diagnostic, Prognostic, and Therapeutic Significance - D, P, T | Established Clinical Significance Per Guidelines - Yes or No (Source) | Clinical Relevance Details/Other Notes |
|---|---|---|---|---|---|---|
| KIR3DL1 | Homozygous gene deletion (copy number loss) | Other (inhibitory immune receptor) | Common (2/5 cases) | D | No | Most prominent recurrent alteration. Loss of inhibitory signaling may lead to chronic T-cell activation. Loss of expression supports diagnosis but is not fully specific, as variable expression seen in other CD8+ cutaneous lymphomas. |
| PIK3R1 | Loss-of-function frameshift mutation | Tumor suppressor | Recurrent (1/5 cases) | Unknown | No | Encodes inhibitory regulatory subunit of PI3K. Mutation likely leads to constitutive PI3K–AKT activation. Supports oncogenic signaling despite indolent behavior |
| POLE | Frameshift mutation | Other (DNA replication/repair) | Recurrent (1/5 cases) | Unknown | No | Detected in one case; low tumor mutational burden argues against classic POLE-ultramutator phenotype. Clinical relevance unclear in acral CD8⁺ TLPD. |
| PRDM9 | Frameshift mutations (two truncating variants in same case) | Other | Recurrent (1/5 cases) | Unknown | No | |
| KMT2D | Frameshift mutation | Tumor suppressor | Recurrent (1/5 cases) | Unknown | No | |
| FANCA | Frameshift mutation | Tumor suppressor | Recurrent (1/5 cases) | Unknown | No | |
| ZFHX3 | Missense variant (VUS) | Tumor suppressor | Recurrent (1/5 cases) | Unknown | No | |
| CDH10 | Missense variant (VUS) | Tumor suppressor | Recurrent (1/5 cases) | Unknown | No | |
| OR5D18 | Missense variant (VUS) | Other | Recurrent (1/5 cases) | Unknown | No |
Note: A more extensive list of mutations can be found in cBioportal,
Epigenomic Alterations
Epigenomic alterations contributing to tumor formation have not yet been described
Genes and Main Pathways Involved
Gene mutations contributing to tumor formation have not yet been described
Genetic Diagnostic Testing Methods
Molecular testing to detect detect clonal T-cell receptor (TCR) beta and/or gamma gene rearrangements.[2]
Familial Forms
None
Additional Information
- The tumor generally has an excellent prognosis, with no reported fatal outcomes. Complete remission following surgical excision or local radiation therapy is common. Recurrence after treatment is possible, more frequently seen in younger patients, and can occasionally occur at other cutaneous sites. Dissemination to extracutaneous sites has been reported in only one case.[2][3]
This disease is defined/characterized as detailed below:
- Primary cutaneous acral CD8-positive T-cell lymphoproliferative disorder is a rare type of lymphoproliferative disorder characterized by slow-growing papules and nodules primarily affecting acral sites, such as the ears, with a benign clinical course. [4]
The epidemiology/prevalence of this disease is detailed below:
- Rare disease accounting for < 1% of all primary cutaneous lymphomas. The disease predominates in males, with an M:F ratio of 2:1. The median age is 56 years. [5]
The clinical features of this disease are detailed below:
Signs and symptoms - Cutaneous, slowly progressive papule or nodule. Solitary or multiple (rare).[4] [6] [7]
Laboratory findings - None
The sites of involvement of this disease are detailed below:
- Ears (most common), retroauricular area, nose, and feet.
- Rare sites: leg, trunk, genitals, and eyelid.[4][7] [8]
The morphologic features of this disease are detailed below:
- On H&E, the tumor shows a dense, monotonous dermal proliferation of atypical medium-sized lymphocytes. The lymphocytes have irregular and frequently folded nuclei with fine chromatin and moderate nuclear pleomorphism.[9]A perivascular pattern may be seen, although it is less common.
- Usually, the epidermis is spared, but focal minimal epidermotropism and focal folliculotropism may be seen. A Grenz zone separates the epidermis from the dermal infiltrate in approximately one-third of cases. The proliferation may extend into the subcutis.
- Mitotic activity is absent or low. Plasma cells, histiocytes, neutrophils, and eosinophils are either absent or infrequent.[4][10]
The immunophenotype of this disease is detailed below:
- Positive - CD3, TIA1, CD45RA, CD68 (Golgi pattern)
- CD4/CD8 - CD4(-), CD8(+)
- CD2/CD5/CD7 - Loss of ≥ 1: CD2, CD5, and/or CD7
- TCR - TCR-βF1(+), TCRγδ(-)
- Ki-67/MIB1 - <15%
- Negative - CD56, CD57, CD30, CD45RO, Perforin, Granzyme B, ICOS, PD-1, EBER (always negative)
- There is one reported case with a CD4+/CD8+ phenotype. [11] Few reported cases have shown a high Ki67 proliferation index.[12] The Golgi dot-like staining pattern of CD68 in tumor cells is unique to this entity.[13]
Links
N/A
References
- ↑ Wobser, Marion; et al. (2024-10-17). "Oncogenic alterations in KIR3DL1 in cutaneous acral CD8+ lymphoproliferative disorder". British Journal of Dermatology. 191 (5): 816–822. doi:10.1093/bjd/ljae256. ISSN 0007-0963.
- ↑ 2.0 2.1 Kempf, Werner; et al. (2022-05). "Clinical, histopathological and prognostic features of primary cutaneous acral CD8+ T-cell lymphoma and other dermal CD8+ cutaneous lymphoproliferations: results of an EORTC Cutaneous Lymphoma Group workshop". The British Journal of Dermatology. 186 (5): 887–897. doi:10.1111/bjd.20973. ISSN 1365-2133. PMID 34988968 Check
|pmid=value (help). Check date values in:|date=(help) - ↑ Alberti-Violetti, Silvia; et al. (2017-11). "Primary cutaneous acral CD8 positive T-cell lymphoma with extra-cutaneous involvement: A long-standing case with an unexpected progression". Journal of Cutaneous Pathology. 44 (11): 964–968. doi:10.1111/cup.13020. ISSN 1600-0560. PMID 28796362. Check date values in:
|date=(help) - ↑ 4.0 4.1 4.2 4.3 Greenblatt, Danielle; et al. (2013-02). "Indolent CD8(+) lymphoid proliferation of acral sites: a clinicopathologic study of six patients with some atypical features". Journal of Cutaneous Pathology. 40 (2): 248–258. doi:10.1111/cup.12045. ISSN 1600-0560. PMID 23189944. Check date values in:
|date=(help) - ↑ Tjahjono, Leonardo A.; et al. (2019-09). "Primary Cutaneous Acral CD8+ T-Cell Lymphoma-A Single Center Review of 3 Cases and Recent Literature Review". The American Journal of Dermatopathology. 41 (9): 644–648. doi:10.1097/DAD.0000000000001366. ISSN 1533-0311. PMID 31433793. Check date values in:
|date=(help) - ↑ Beltraminelli, Helmut; et al. (2010-01). "Indolent CD8+ lymphoid proliferation of the ear: a phenotypic variant of the small-medium pleomorphic cutaneous T-cell lymphoma?". Journal of Cutaneous Pathology. 37 (1): 81–84. doi:10.1111/j.1600-0560.2009.01278.x. ISSN 1600-0560. PMID 19602068. Check date values in:
|date=(help) - ↑ 7.0 7.1 Kempf, Werner; et al. (2013-04). "Primary cutaneous CD8(+) small- to medium-sized lymphoproliferative disorder in extrafacial sites: clinicopathologic features and concept on their classification". The American Journal of Dermatopathology. 35 (2): 159–166. doi:10.1097/DAD.0b013e31825c3a33. ISSN 1533-0311. PMID 22885550. Check date values in:
|date=(help) - ↑ Hagen, Joshua W.; et al. (2014-02). "Indolent CD8+ lymphoid proliferation of the face with eyelid involvement". The American Journal of Dermatopathology. 36 (2): 137–141. doi:10.1097/DAD.0b013e318297f7fd. ISSN 1533-0311. PMID 24556898. Check date values in:
|date=(help) - ↑ Petrella, Tony; et al. (2007-12). "Indolent CD8-positive lymphoid proliferation of the ear: a distinct primary cutaneous T-cell lymphoma?". The American Journal of Surgical Pathology. 31 (12): 1887–1892. doi:10.1097/PAS.0b013e318068b527. ISSN 0147-5185. PMID 18043044. Check date values in:
|date=(help) - ↑ Butsch, Florian; et al. (2012-03). "Bilateral indolent epidermotropic CD8-positive lymphoid proliferations of the ear". Journal der Deutschen Dermatologischen Gesellschaft = Journal of the German Society of Dermatology: JDDG. 10 (3): 195–196. doi:10.1111/j.1610-0387.2011.07859.x. ISSN 1610-0387. PMID 22142195. Check date values in:
|date=(help) - ↑ Toberer, Ferdinand; et al. (2019-03). "Double-positive CD8/CD4 primary cutaneous acral T-cell lymphoma". Journal of Cutaneous Pathology. 46 (3): 231–233. doi:10.1111/cup.13403. ISSN 1600-0560. PMID 30552698. Check date values in:
|date=(help) - ↑ Swick, Brian L.; et al. (2011-02). "Indolent CD8+ lymphoid proliferation of the ear: report of two cases and review of the literature". Journal of Cutaneous Pathology. 38 (2): 209–215. doi:10.1111/j.1600-0560.2010.01647.x. ISSN 1600-0560. PMID 21083681. Check date values in:
|date=(help) - ↑ Wobser, M.; et al. (2015-06). "CD68 expression is a discriminative feature of indolent cutaneous CD8-positive lymphoid proliferation and distinguishes this lymphoma subtype from other CD8-positive cutaneous lymphomas". The British Journal of Dermatology. 172 (6): 1573–1580. doi:10.1111/bjd.13628. ISSN 1365-2133. PMID 25524664. Check date values in:
|date=(help)
Notes
*Citation of this Page: Eladely A, Siref A. "Primary cutaneous acral CD8-positive T-cell lymphoproliferative disorder”. Compendium of Cancer Genome Aberrations (CCGA), Cancer Genomics Consortium (CGC), updated 01/6/2026, https://ccga.io/index.php/HAEM5:Primary_cutaneous_acral_CD8-positive_T-cell_lymphoproliferative_disorder.
*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 Associate Editor or other CCGA representative. When pages have a major update, the new author will be acknowledged at the beginning of the page, and those who contributed previously will be acknowledged below as a prior author.
Prior Author(s): N/A