HAEM4:Mycosis Fungoides
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Primary Author(s)*
Jane Scribner, MD and Daynna J. Wolff, PhD
Cancer Category/Type
Cancer Sub-Classification / Subtype
- Mycosis Fungoides (MF)
Definition / Description of Disease
MF is a primary cutaneous T-cell lymphoma (CTCL) of epidermotropic small to medium-sized T lymphocytes presenting with skin patches that progress slowly to plaques and tumors. The disease is postulated to be caused by skin-homing mature T cells, the majority of which are CD4-positive. Sézary syndrome (SS) is often used to refer to the leukemic phase of mycosis fungoides. However, recently studies have suggested that there are major genomic and phenotypical differences between these two entities. [1]
Synonyms / Terminology
- Cutaneous T-cell lymphoma
- Alibert-Bazin syndrome
Epidemiology / Prevalence
Clinical Features
- Pruritic, erythematous or poikilodermatous and atrophic skin lesions with a fine scale
- Progresses over years to decades from patches to plaques and less commonly to nodules/tumors
- Rarely, MF can present with erythroderma without a diagnosis of Sézary syndrome[8]
- May have symptoms and/or diagnosis of other inflammatory skin diseases (e.g., eczema or psoriasis) for 3 - 4 years prior to the diagnosis of MF[9]
Sites of Involvement
- Skin
- Typically sun protected areas: trunk, buttock, upper thighs
- Some MF variants: head and neck, axillae and groin, or acral sites
- Advanced disease - lymph nodes, liver, spleen, lungs and blood
Morphologic Features
Pathologic features are variable and may be non-specific with overlap with benign reactive processes.
- Early patch stage: superficial band-like or lichenoid infiltrate of lymphocytes and histiocytes; atypical small to medium-sized lymphocytes with cerebriform nuclei confined to basilar epidermis, may have halo and "tag" the basilar layer keratinocytes
- Plaque stage: Epidermotropism (atypical lymphocytes in epidermis without associated spongiosis); intraepidermal collections of atypical cells (Pautrier microabscesses); papillary dermal fibrosis
- Tumor stage: Dermal infiltrate more diffuse; may lose epidermotropism
Histologic large cell transformation, defined by >25% of large lymphoid cells in the dermal infiltrate, may occur at any stage, but most commonly in tumor stage mycosis fungoides. They may be positive or negative for CD30[8]
Immunophenotype
The immunologic milieu of mycosis fungoides is predominantly that of mature memory Th2 gene expression and associated cytokine production. [10]
The aberrant loss of normal T-cell antigen expression by immunohistochemistry staining is a useful ancillary test in the diagnosis of mycosis fungoides. [11]
| Finding | Marker |
|---|---|
| Positive (T-cell lineage markers) | CD3, CD4, CD45RO |
| Variable expression | CD2, CD5, CD7 (often lost, significant only if 90% loss) |
| Markers with aberrant expression | CD8 (CD4:CD8 ratio of 10:1 suggestive of mycosis fungoides), CD30 (may indicate transformation) |
The majority of lymphocytes in mycosis fungoides express the αβ TCR, but rare cases have been reported that express γδ TCR.
Mycosis fungoides T-cells are T resident memory cells, exhibiting CCR4+/CLA+/L-selectin-/CCR7- expression. [12]
Chromosomal Rearrangements (Gene Fusions)
- No consistent gene fusions
- CD28-CTLA4 gene fusion identified, resulting in activation of TCR signaling [13]
Characteristic Chromosomal Aberrations / Patterns
Complex chromosomal abnormalities have been identified in mycosis fungoides, usually in tumor stage. Specific translocations have not been identified.
Genomic Gain/Loss/LOH[14]
Mycosis fungoides does not have a defining disease specific molecular abnormality. However, the molecular profile of mycosis fungoides and other CTCLs continues to be investigated.
Large-scale genomic analysis using array comparative genomic hybridization and next generation sequencing including whole genome, transcriptome and exome sequencing, reveals significant genomic complexity in mycosis fungoides, [15] with an observation that there is an inverse correlation between genomic complexity and survival. [16]
| Chromosome Number | Gain/Loss/Amp/LOH | Percent of cases | Consequence |
|---|---|---|---|
| 1p | Loss | 38% | Minimal region of deletion at D1S228; other candidate genes in mycosis fungoides map to 1p12p26 |
| 17p | Loss | 21% | Disease progression by inactivation of genes on 17p, including p53 |
| 4/4q | Gain | 18% | Oncogenes on chromosome 4: hPTTG, TBC1D1, FGFR3, KIT, PDGFRA |
| 10q/10 | Loss | 15% | Minimal region of deletion at 10q26; cancer-related genes mapped to 10q: PTEN, LG11, DMBT1, FAS |
| 19 | Loss | 15% | |
| 18 | Gain | 15% | |
| 17q/17 | Gain | 12% |
Chromothripsis has been observed in up to 65% of CTCLs. Most events occur in chromosomes 10, 2, and 1. It is possible that these events may be the mechanism for simultaneous inactivation of multiple tumor suppressor genes see in mycosis fungoides. [17]
Gene Mutations (SNV/INDEL)
Although no disease specific molecular abnormalities exist in mycosis fungoides, but some changes are seen more frequently than others.[18] Single copy number variations (SCNV) are important mutational drivers for CTCLs and mycosis fungoides and are seen with greater frequency than somatic single nucleotide variations (SSNV) when compared to other cancers with significantly higher SCNV/SSNV ratios.[15] [17] Alterations in tumor suppressor genes are frequently implication the pathogenesis of mycosis fungoides, and more than 90% of variants arise from copy number alterations. [15]
| Gene | Mutation | Oncogene/Tumor Suppressor/Other | Presumed Mechanism (LOF/GOF/Other; Driver/Passenger) | Prevalence (COSMIC/TCGA/Other) |
|---|---|---|---|---|
| TNFRSF1B | Thr377Ile | Recurrent point mutation; constitutive activation of NFkB signaling pathway | 18%[19] | |
| HNRNPK | Tumor Suppressor | Inhibitor of JAK-STAT signaling[20] | ||
| SOCS1 | Tumor Suppressor | Inhibitor of JAK-STAT signaling [20] | ||
| ZEB1 | Tumor Suppressor | Zinc-finger transcription repressor | 56-65%[17] | |
| PDCD1 | Expressing PDL1, deleted | 36%[17] | ||
| TP53 | Tumor Suppressor | Deletion | 92.5% [17] | |
| TOX | Encodes member of homeobox family, upregulated in MF[21] |
Epigenomics (Methylation)
Epigenetic modifiers of DNA, including DNMT3A, are frequently mutated in mycosis fungoides. [22]
An epigenetic mediator, the writer KMT2C of the histone methyltransferases (KMT) family, is recurrently deleted in mycosis fungoides. [17]
Genes and Main Pathways Involved
Diagnostic Testing Methods
A definitive diagnosis of mycosis fungoides may be made on the basis of clinical, histopathologic and immunohistochemical features alone.
Assessment of aberrant loss of T-cell antigen expression by immunohistochemical staining for CD2, CD3, CD5, and CD7 are useful ancillary studies.
Demonstration of T-cell receptor clonality often facilitates diagnosis and serves as an adjunct to the diagnosis.[23] Presence of identical clones from two different biopsy sites is quit specific for mycosis fungoides[24] and may be useful in early or histologically equivocal cases. However early mycosis fungoides may commonly be negative for clonal TCR rearrangements [25] and T-cell clonality itself is not diagnostic of a T cell lymphoma as many dermatitis may have dominant T cells clones[18].
There are various methods to assess TCR clonality, with different techniques and sensitivities. PCR based assays have sensitivities ranging from 50-90% in various studies[26] [27]. The use of Next generation sequencing (NGS)/high throughput sequencing has improved the sensitivity of detection of TCR clonality, and may be as high as 85%[28][29].
In 2020, the American Society of Clinical Pathology, the College of American pathologists, and the American Society of Hematology released a statement from an expert panel convened to develop evidence-based guidelines for appropriate evaluation process for adult patients with suspected lymphomas[30]. In their summary, it is stated that clinical care providers should not routinely use up-front PCR-based clonality studies of antigen receptor genes (i.e., T-cell receptor) in the initial investigation of lymphoma. However, there may be a confirmatory role of these tests in certain settings. Providers should rely on immunophenotyping by flow cytometry and/or IHC in addition to morphology for the evaluation of specimens for the diagnosis and sub-classification of lymphoma[30]. A recent study demonstrated that positive TCR gene rearrangement studies are not predictive of lymphoproliferative disorders in patients which otherwise negative phenotyping[31].
Summary of additional diagnostic and prognostic testing methods:
- TCR gene rearrangement studies may be utilized for monitoring of residual disease[32]
- Tumor clone frequency as determined by high throughput sequencing of TCRβ gene has been investigated as a marker for progression and overall survival in mycosis fungoides[33]
- In cases with suspected large cell transformation, staining for CD30 positivity may provide additional therapeutic options[34]
- Recent diagnostic panels of gene expression profiling of MF/SS have been developed. A 17 gene signature panel including IL2RA, CCR4, STAT5A and TOX has been described to identify patients at risk for progression of disease[35]
- microRNA profiling may have a role in diagnosis and management of mycosis fungoides, with potential 95% sensitivity and specificity in differentiating early mycosis fungoides from benign lesions[36]
Clinical Significance (Diagnosis, Prognosis and Therapeutic Implications)
The staging system for mycosis fungoides, which also includes Sézary syndrome, was updated in 2007 by the International Society for Cutaneous Lymphomas (ISCL) and the European Organization of Research and Treatment of Cancer (EORTC) [37]. The revised TNMB staging of MF/SS determines management and treatment, and has been demonstrated to have prognostic significance. [4] The TNMB staging forms the basis for a risk-adapted approach to treatment of mycosis fungoides.
| Skin | |
| T1 | Limited patches, papules, and/or plaques covering <10% of the skin surface. May futher stratify to T1a (patch only) vs T1b (plaque +/- patch) |
| T1a | Patches only < 10% of skin surface |
| T1b | Plaques +/- patches < 10% of skin surface |
| T2 | Patches, papules or plaques covering > 10% of skin surface. May further stratify to T2a (patch only) vs T2b (plaque +/- patch) |
| T2a | Patches only > 10% of skin surface |
| T2b | Plaques +/- patches > 10% of skin surface |
| T3 | One or more tumors (> 1-cm diameter) |
| T4 | Confluence of erythema covering > 80% body surface area |
| Node | |
| N0 | No clinically abnormal peripheral lymph nodes (firm, irregular, clustered, fixed, or 1.5 cm or larger), biopsy not required |
| N1 | Clinically abnormal peripheral lymph nodes; histopathology Dutch grade 1 or NCI LN0-2 |
| N1a | Clone negative (defined by PCR or Souther blod analysis of T-cell receptor gene) |
| N1b | Clone positive defined by PCR or Souther blod analysis of T-cell receptor gene) |
| N2 | Clinically abnormal peripheral lymph nodes; histopathology Dutch grade 2 or NCI LN3 |
| N2a | Clone negative |
| N2b | Clone positive |
| N3 | Clinically abnormal peripheral lymph nodes; histopathology Dutch grades 3 - 4 or NVI LN4 (clone positive or negative) |
| Nx | Clinically abnormal peripheral lymph nodes; no histologic confirmation |
| Visceral | |
| M0 | No visceral organ invovlement |
| M1 | Visceral invovlement (must have pathology confirmation, for spleen and liver may be diagnosed by imaging criteria; specify organ involved) |
| Blood | |
| B0 | Absence of significant blood invovlement: , 5% of peripheral blood lymphocytes are atypical (Sezary) cells |
| B0a | Clone negative |
| B0b | Clone positive |
| B1 | Low blood tumor burdern: > 5% of peripheral blood lymphocytes are atypical (Sezary) cells but does not meet the criteria of B2 |
| B1a | Clone negative |
| B1b | Clone positive |
| B2 | High blood tumor burdern: > 1000/µL Sezary cells with positive clone |
The above listed chromosome rearrangement and several gene mutations provide the rational for the use of targeted therapy in mycosis fungoides. These are summarized in the table below.
| Molecular marker/mutation | Targeted therapy |
|---|---|
| CD30 | Brentuximab |
| CTLA4 | Ipilimumab |
| CD28-CTLA4 fusion | Ipilimumab |
| CCR4 | Mogamulizumab |
| NFkB | Bortezomib |
| TNFRSF1B | Bortezomib |
| CD158k/KIR3DL2 | IPH4102 |
| JAK/STAT pathway | Ruxolitinib (JAK 1/3), Tofacitinib (JAK 1/2) |
| PDCD1 | Pembrolizumab |
Familial Forms
- There are rare reports of familial MF, suggesting that a host genetic factor may contribute to the development of the disease[38]
Other Information
- N/A
Links
- N/A
References
(use "Cite" icon at top of page)
- ↑ Campbell, James J.; et al. (2010-08-05). "Sézary syndrome and mycosis fungoides arise from distinct T-cell subsets: a biologic rationale for their distinct clinical behaviors". Blood. 116 (5): 767–771. doi:10.1182/blood-2009-11-251926. ISSN 0006-4971. PMC 2918332. PMID 20484084.
- ↑ Bradford, Porcia T.; et al. (2009-05-21). "Cutaneous lymphoma incidence patterns in the United States: a population-based study of 3884 cases". Blood. 113 (21): 5064–5073. doi:10.1182/blood-2008-10-184168. ISSN 1528-0020. PMC 2686177. PMID 19279331.
- ↑ Criscione, Vincent D.; et al. (2007-07-01). "Incidence of Cutaneous T-Cell Lymphoma in the United States, 1973-2002". Archives of Dermatology. 143 (7). doi:10.1001/archderm.143.7.854. ISSN 0003-987X.
- ↑ 4.0 4.1 Agar, Nita Sally; et al. (2010-11-01). "Survival outcomes and prognostic factors in mycosis fungoides/Sézary syndrome: validation of the revised International Society for Cutaneous Lymphomas/European Organisation for Research and Treatment of Cancer staging proposal". Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology. 28 (31): 4730–4739. doi:10.1200/JCO.2009.27.7665. ISSN 1527-7755. PMID 20855822.
- ↑ Hinds, Ginette A.; et al. (2009-03). "Cutaneous T-cell lymphoma in skin of color". Journal of the American Academy of Dermatology. 60 (3): 359–375, quiz 376–378. doi:10.1016/j.jaad.2008.10.031. ISSN 1097-6787. PMID 19231637. Check date values in:
|date=(help) - ↑ Boccara, Olivia; et al. (2012-02). "Cutaneous hematologic disorders in children". Pediatric Blood & Cancer. 58 (2): 226–232. doi:10.1002/pbc.23103. ISSN 1545-5017. PMID 21445946. Check date values in:
|date=(help) - ↑ Fink-Puches, Regina; et al. (2004-09). "The spectrum of cutaneous lymphomas in patients less than 20 years of age". Pediatric Dermatology. 21 (5): 525–533. doi:10.1111/j.0736-8046.2004.21500.x. ISSN 0736-8046. PMID 15461755. Check date values in:
|date=(help) - ↑ 8.0 8.1 Elder DE, Massi D, Scolyer RA, Willemze R. WHO Classification of Skin Tumours. 4th edn. Lyon, France: International Agency for Research on Cancer; 2018
- ↑ Kim, Youn H.; et al. (2003-07-01). "Long-term Outcome of 525 Patients With Mycosis Fungoides and Sézary Syndrome: Clinical Prognostic Factors and Risk for Disease Progression". Archives of Dermatology. 139 (7). doi:10.1001/archderm.139.7.857. ISSN 0003-987X.
- ↑ Wilcox, Ryan A. (2016-01). "Cutaneous T-cell lymphoma: 2016 update on diagnosis, risk-stratification, and management". American Journal of Hematology. 91 (1): 151–165. doi:10.1002/ajh.24233. ISSN 1096-8652. PMC 4715621. PMID 26607183. Check date values in:
|date=(help) - ↑ Hristov, Alexandra C.; et al. (2019-07-31). "Mycosis fungoides and Sézary syndrome: 2019 update on diagnosis, risk‐stratification, and management". American Journal of Hematology. 94 (9): 1027–1041. doi:10.1002/ajh.25577. ISSN 0361-8609.
- ↑ Campbell, James J.; et al. (2010-08-05). "Sézary syndrome and mycosis fungoides arise from distinct T-cell subsets: a biologic rationale for their distinct clinical behaviors". Blood. 116 (5): 767–771. doi:10.1182/blood-2009-11-251926. ISSN 0006-4971. PMC 2918332. PMID 20484084.CS1 maint: PMC format (link)
- ↑ Ungewickell, Alexander; et al. (2015-09). "Genomic analysis of mycosis fungoides and Sézary syndrome identifies recurrent alterations in TNFR2". Nature Genetics. 47 (9): 1056–1060. doi:10.1038/ng.3370. ISSN 1061-4036. PMC 6091217. PMID 26258847. Check date values in:
|date=(help)CS1 maint: PMC format (link) - ↑ Mao, X.; et al. (2002-09). "Molecular cytogenetic analysis of cutaneous T-cell lymphomas: identification of common genetic alterations in Sézary syndrome and mycosis fungoides". The British Journal of Dermatology. 147 (3): 464–475. doi:10.1046/j.1365-2133.2002.04966.x. ISSN 0007-0963. PMID 12207585. Check date values in:
|date=(help) - ↑ 15.0 15.1 15.2 Elenitoba-Johnson, Kojo S.J.; et al. (2017-01). "A new molecular paradigm in mycosis fungoides and Sézary syndrome". Seminars in Diagnostic Pathology. 34 (1): 15–21. doi:10.1053/j.semdp.2016.11.002. Check date values in:
|date=(help) - ↑ Wilcox, Ryan A. (2011-11). "Cutaneous T-cell lymphoma: 2011 update on diagnosis, risk-stratification, and management". American Journal of Hematology. 86 (11): 928–948. doi:10.1002/ajh.22139. ISSN 1096-8652. PMID 21990092. Check date values in:
|date=(help) - ↑ 17.0 17.1 17.2 17.3 17.4 17.5 Choi, Jaehyuk; et al. (2015-09). "Genomic landscape of cutaneous T cell lymphoma". Nature Genetics. 47 (9): 1011–1019. doi:10.1038/ng.3356. ISSN 1546-1718. PMC 4552614. PMID 26192916. Check date values in:
|date=(help) - ↑ 18.0 18.1 18.2 Walia, Ritika; et al. (2020-01-22). "An Update on Molecular Biology of Cutaneous T Cell Lymphoma". Frontiers in Oncology. 9: 1558. doi:10.3389/fonc.2019.01558. ISSN 2234-943X. PMC 6987372. PMID 32039026 Check
|pmid=value (help).CS1 maint: PMC format (link) - ↑ Izban, K (2000-12). "Constitutive expression of NF-κB is a characteristic feature of mycosis fungoides: Implications for apoptosis resistance and pathogenesis". Human Pathology. 31 (12): 1482–1490. doi:10.1053/hupa.2000.20370. Check date values in:
|date=(help) - ↑ 20.0 20.1 Bastidas Torres, Armando N.; et al. (2018-12). "Genomic analysis reveals recurrent deletion of JAK-STAT signaling inhibitors HNRNPK and SOCS1 in mycosis fungoides". Genes, Chromosomes and Cancer. 57 (12): 653–664. doi:10.1002/gcc.22679. PMC 6282857. PMID 30144205. Check date values in:
|date=(help)CS1 maint: PMC format (link) - ↑ Huang, Yuanshen; et al. (2014-06-30). "Thymocyte selection-associated high mobility group box gene (TOX) is aberrantly over-expressed in mycosis fungoides and correlates with poor prognosis". Oncotarget. 5 (12): 4418–4425. doi:10.18632/oncotarget.2031. ISSN 1949-2553. PMC 4147334. PMID 24947046.CS1 maint: PMC format (link)
- ↑ Kiel, Mark J.; et al. (2015-09-29). "Genomic analyses reveal recurrent mutations in epigenetic modifiers and the JAK–STAT pathway in Sézary syndrome". Nature Communications. 6 (1): 8470. doi:10.1038/ncomms9470. ISSN 2041-1723. PMC 4598843. PMID 26415585.CS1 maint: PMC format (link)
- ↑ Kirsch, Ilan R.; et al. (2015-10-07). "TCR sequencing facilitates diagnosis and identifies mature T cells as the cell of origin in CTCL". Science Translational Medicine. 7 (308): 308ra158. doi:10.1126/scitranslmed.aaa9122. ISSN 1946-6242. PMC 4765389. PMID 26446955.
- ↑ Thurber, Stacy E.; et al. (2007-11). "T-cell clonality analysis in biopsy specimens from two different skin sites shows high specificity in the diagnosis of patients with suggested mycosis fungoides". Journal of the American Academy of Dermatology. 57 (5): 782–790. doi:10.1016/j.jaad.2007.06.004. ISSN 1097-6787. PMID 17646032. Check date values in:
|date=(help) - ↑ Glusac, Earl J. (2003-06). "Criterion by criterion, mycosis fungoides". The American Journal of Dermatopathology. 25 (3): 264–269. doi:10.1097/00000372-200306000-00014. ISSN 0193-1091. PMID 12775992. Check date values in:
|date=(help) - ↑ Hsiao, Pa-Fan; et al. (2007-01-01). "Histopathologic-molecular Correlation in Early Mycosis Fungoides Using T-cell Receptor γ Gene Rearrangement by Polymerase Chain Reaction with Laser Capture Microdissection". Journal of the Formosan Medical Association. 106 (4): 265–272. doi:10.1016/S0929-6646(09)60251-5. ISSN 0929-6646.
- ↑ Ponti, Renata; et al. (2008-04). "TCRγ-Chain Gene Rearrangement by PCR-Based GeneScan: Diagnostic Accuracy Improvement and Clonal Heterogeneity Analysis in Multiple Cutaneous T-Cell Lymphoma Samples". Journal of Investigative Dermatology. 128 (4): 1030–1038. doi:10.1038/sj.jid.5701109. ISSN 0022-202X. Check date values in:
|date=(help) - ↑ Sufficool, Kari E.; et al. (2015-08). "T-cell clonality assessment by next-generation sequencing improves detection sensitivity in mycosis fungoides". Journal of the American Academy of Dermatology. 73 (2): 228–236.e2. doi:10.1016/j.jaad.2015.04.030. ISSN 0190-9622. Check date values in:
|date=(help) - ↑ Rea, Bryan; et al. (2018-09). "Role of high-throughput sequencing in the diagnosis of cutaneous T-cell lymphoma". Journal of Clinical Pathology. 71 (9): 814–820. doi:10.1136/jclinpath-2018-205004. ISSN 0021-9746. Check date values in:
|date=(help) - ↑ 30.0 30.1 Kroft, Steven H.; et al. (2020-11-11). "Laboratory Workup of Lymphoma in Adults". Archives of Pathology & Laboratory Medicine. doi:10.5858/arpa.2020-0261-SA. ISSN 1543-2165.
- ↑ Mendoza, Hadrian; et al. (2021-02-01). "Evaluation of Positive B- and T-Cell Gene Rearrangement Studies in Patients With Negative Morphology, Flow Cytometry, and Immunohistochemistry". Archives of Pathology & Laboratory Medicine. 145 (2): 227–230. doi:10.5858/arpa.2019-0663-OA. ISSN 1543-2165.
- ↑ Weng, W.-K.; et al. (2013-12-04). "Minimal Residual Disease Monitoring with High-Throughput Sequencing of T Cell Receptors in Cutaneous T Cell Lymphoma". Science Translational Medicine. 5 (214): 214ra171–214ra171. doi:10.1126/scitranslmed.3007420. ISSN 1946-6234.
- ↑ de Masson, Adele; et al. (2018-05-09). "High-throughput sequencing of the T cell receptor β gene identifies aggressive early-stage mycosis fungoides". Science Translational Medicine. 10 (440): eaar5894. doi:10.1126/scitranslmed.aar5894. ISSN 1946-6234. PMC 6366329. PMID 29743350.CS1 maint: PMC format (link)
- ↑ Krathen, Michael; et al. (2012-11-16). "Brentuximab Vedotin Demonstrates Significant Clinical Activity in Relapsed or Refractory Mycosis Fungoides with Variable CD30 Expression". Blood. 120 (21): 797–797. doi:10.1182/blood.V120.21.797.797. ISSN 0006-4971.
- ↑ Litvinov, Ivan V.; et al. (2015-06-15). "The Use of Transcriptional Profiling to Improve Personalized Diagnosis and Management of Cutaneous T-cell Lymphoma (CTCL)". Clinical Cancer Research. 21 (12): 2820–2829. doi:10.1158/1078-0432.CCR-14-3322. ISSN 1078-0432. PMC 4470792. PMID 25779945.CS1 maint: PMC format (link)
- ↑ Ralfkiaer, Ulrik; et al. (2011-11-24). "Diagnostic microRNA profiling in cutaneous T-cell lymphoma (CTCL)". Blood. 118 (22): 5891–5900. doi:10.1182/blood-2011-06-358382. ISSN 0006-4971. PMC 3342856. PMID 21865341.CS1 maint: PMC format (link)
- ↑ Olsen, Elise; et al. (2007-09-15). "Revisions to the staging and classification of mycosis fungoides and Sezary syndrome: a proposal of the International Society for Cutaneous Lymphomas (ISCL) and the cutaneous lymphoma task force of the European Organization of Research and Treatment of Cancer (EORTC)". Blood. 110 (6): 1713–1722. doi:10.1182/blood-2007-03-055749. ISSN 0006-4971. PMID 17540844.
- ↑ Hodak, Emmilia; et al. (2005-03). "Familial mycosis fungoides: report of 6 kindreds and a study of the HLA system". Journal of the American Academy of Dermatology. 52 (3 Pt 1): 393–402. doi:10.1016/j.jaad.2003.12.052. ISSN 1097-6787. PMID 15761416. Check date values in:
|date=(help)
Notes
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