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1.
PLoS One ; 13(6): e0198477, 2018.
Article in English | MEDLINE | ID: mdl-29894486

ABSTRACT

Differentiating early mycosis fungoides (MF) from inflammatory dermatitis is a challenge. We compare the differential expression profile of early-stage MF samples and benign inflammatory dermatoses using microRNA (miRNA) arrays. 114 miRNAs were found to be dysregulated between these entities. The seven most differentially expressed miRNAs between these two conditions were further analyzed using RT-PCR in two series comprising 38 samples of early MFs and 18 samples of inflammatory dermatitis. A series of 51 paraffin-embedded samples belonging to paired stages of 16 MF patients was also analyzed. MiRNAs 26a, 222, 181a and 146a were differentially expressed between tumoral and inflammatory conditions. Two of these miRNAs (miRNA-181a and miRNA-146a) were significantly deregulated between early and advanced MF stages. Bioinformatic analysis showed FOXP3 expression to be regulated by these miRNAs. Immunohistochemistry revealed the level of FOXP3 expression to be lower in tumoral MFs than in plaque lesions in paraffin-embedded tissue. A functional study confirmed that both miRNAs diminished FOXP3 expression when overexpressed in CTCL cells. The data presented here suggest that the analysis of a restricted number of miRNAs (26a, 222, 181a and 146a) could be sufficient to differentiate tumoral from reactive conditions. Moreover, these miRNAs seem to be involved in MF progression.


Subject(s)
Forkhead Transcription Factors/genetics , MicroRNAs/genetics , Mycosis Fungoides/genetics , Skin Neoplasms/genetics , 3' Untranslated Regions , Biomarkers, Tumor/genetics , Cell Line, Tumor , Disease Progression , Female , Forkhead Transcription Factors/metabolism , Gene Expression Regulation, Neoplastic , Humans , Male , Mycosis Fungoides/metabolism , Skin Neoplasms/metabolism
3.
Pediatr Dermatol ; 31(6): e126-7, 2014.
Article in English | MEDLINE | ID: mdl-25243976

ABSTRACT

Tinea imbricata (TI) is a geographically restricted dermatophytosis with distinctive clinical and immunologic features. We present a case of TI occurring in a native Brazilian child with previously undiagnosed human immunodeficiency virus infection. Physicians should bear in mind that diagnosis of TI may be a clinical clue to potentially serious underlying immunodeficiency.


Subject(s)
HIV Infections/diagnosis , Tinea/diagnosis , Trichophyton/isolation & purification , Administration, Oral , Antifungal Agents/therapeutic use , Child, Preschool , Forehead , Griseofulvin/therapeutic use , HIV Infections/drug therapy , HIV Infections/microbiology , Humans , Male , Tinea/drug therapy , Tinea/microbiology
4.
Blood ; 123(13): 2034-43, 2014 Mar 27.
Article in English | MEDLINE | ID: mdl-24497536

ABSTRACT

Cutaneous T-cell lymphoma (CTCL) is a heterogeneous group of primary cutaneous T-cell lymphoproliferative processes, mainly composed of mycosis fungoides and Sézary syndrome, the aggressive forms of which lack an effective treatment. The molecular pathogenesis of CTCL is largely unknown, although neoplastic cells show increased signaling from T-cell receptors (TCRs). DNAs from 11 patients with CTCL, both normal and tumoral, were target-enriched and sequenced by massive parallel sequencing for a selection of 524 TCR-signaling-related genes. Identified variants were validated by capillary sequencing. Multiple mutations were found that affected several signaling pathways, such as TCRs, nuclear factor κB, or Janus kinase/signal transducer and activator of transcription, but PLCG1 was found to be mutated in 3 samples, 2 of which featured a redundant mutation (c.1034T>C, S345F) in exon 11 that affects the PLCx protein catalytic domain. This mutation was further analyzed by quantitative polymerase chain reaction genotyping in a new cohort of 42 patients with CTCL, where it was found in 19% of samples. Immunohistochemical analysis for nuclear factor of activated T cells (NFAT) showed that PLCG1-mutated cases exhibited strong NFAT nuclear immunostaining. Functional studies demonstrated that PLCG1 mutants elicited increased downstream signaling toward NFAT activation, and inhibition of this pathway resulted in reduced CTCL cell proliferation and cell viability. Thus, increased proliferative and survival mechanisms in CTCL may partially depend on the acquisition of somatic mutations in PLCG1 and other genes that are essential for normal T-cell differentiation.


Subject(s)
Lymphoma, T-Cell/genetics , Mutation , Phospholipase C gamma/genetics , Skin Neoplasms/genetics , Animals , Cell Line, Tumor , Cell Survival/genetics , Cohort Studies , DNA Mutational Analysis , Female , High-Throughput Nucleotide Sequencing , Humans , Lymphoma, T-Cell/pathology , Male , Mice , NIH 3T3 Cells , Skin Neoplasms/pathology
5.
J Am Acad Dermatol ; 69(3): 357-65, 2013 Sep.
Article in English | MEDLINE | ID: mdl-23796549

ABSTRACT

BACKGROUND: Primary cutaneous marginal zone B-cell lymphomas are low-grade lymphomas running an indolent course. Skin relapses have been frequently reported but little information about disease-free survival (DFS) is available. OBJECTIVE: We sought to evaluate relapse rate and DFS in patients with primary cutaneous marginal zone B-cell lymphomas. METHODS: Clinical features, European Organization for Research and Treatment of Cancer/International Society for Cutaneous Lymphomas stage, light chain restriction, clonality, treatments, skin relapses, DFS, stage progression, extracutaneous disease, and outcome are analyzed in a series of 137 patients. RESULTS: Patients were classified as solitary lesion (T1) (n = 70; 51%), regional skin involvement (T2) (n = 40; 29%), and generalized skin lesions (T3) (n = 27; 20%). Surgical excision, local radiotherapy, or a combination were the initial treatment in 118 patients (86%). In 121 of 137 patients (88%) a complete remission was observed after initial treatment, including 99 of 106 patients (93%) with solitary or localized disease and 22 of 31 patients (71%) with multifocal lesions. Cutaneous relapses were observed in 53 patients (44%). Median DFS was 47 months. Patients with multifocal lesions or T3 disease showed higher relapse rate and shorter DFS. No significant differences were observed between surgery and radiotherapy, but surgery alone was associated with more recurrences at initial site. Overall survival at 5 and 10 years was 93%. Six patients (4%) developed extracutaneous disease during follow-up. LIMITATIONS: This was a case series retrospective study. CONCLUSION: Our results support long-term follow-up in patients with primary cutaneous marginal zone B-cell lymphomas. Disseminated skin lesions have higher relapse rate and shorter DFS suggesting further investigation on systemic therapies in such a group of patients.


Subject(s)
Lymphoma, B-Cell, Marginal Zone/pathology , Lymphoma, B-Cell, Marginal Zone/therapy , Neoplasm Recurrence, Local/pathology , Skin Neoplasms/pathology , Skin Neoplasms/therapy , Adult , Aged , Aged, 80 and over , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Combined Modality Therapy , Disease-Free Survival , Female , Follow-Up Studies , Humans , Kaplan-Meier Estimate , Male , Middle Aged , Neoplasm Staging , Radiotherapy , Remission Induction , Retrospective Studies , Survival Rate , Young Adult
7.
Am J Surg Pathol ; 37(3): 375-84, 2013 Mar.
Article in English | MEDLINE | ID: mdl-23348211

ABSTRACT

Primary cutaneous γδ T-cell lymphomas (PCGD-TCLs) are considered a subgroup of aggressive cytotoxic T-cell lymphomas (CTCLs). We have taken advantage of a new, commercially available antibody that recognizes the T-cell receptor-γ (TCR-γ) subunit of the TCR in paraffin-embedded tissue. We have analyzed a series of 146 primary cutaneous T-cell lymphomas received for consultation or a second opinion in the CNIO Pathology Department. Cases were classified according to the World Health Organization 2008 classification as mycosis fungoides (MF; n=96), PCGD-TCLs (n=5), pagetoid reticulosis (n=6), CD30(+) primary cutaneous anaplastic large cell lymphomas (n=5), primary cutaneous CD8 aggressive epidermotropic CTCLs (n=3), primary cutaneous CTCL, not otherwise specified (n=4), and extranodal nasal-type NK/T-cell lymphomas primarily affecting the skin or subcutaneous tissue (n=11). Sixteen cases of the newly named lymphomatoid papulosis type D (LyP-D; n=16) were also included. In those cases positive for TCR-γ, a further panel of 13 antibodies was used for analysis, including TIA-1, granzyme B, and perforin. Clinical and follow-up data were recorded in all cases. Twelve cases (8.2%) were positive for TCR-γ, including 5 PCGD-TCLs, 2 MFs, and 5 LyP-Ds. All 5 PCGD-TCL patients and 1 MF patient died of the disease, whereas the other MF patient and all those with LyP-D were alive. All cases expressed cytotoxic markers, were frequently CD3(+)/CD8(+), and tended to lose CD5 and CD7 expressions. Eight of 12 and 5 of 11 cases were CD30(+) and CD56(+), respectively. Interestingly, 5/12 TCR-γ-positive cases also expressed TCR-BF1. All cases analyzed were negative for Epstein-Barr virus-encoded RNA. In conclusion, TCR-γ expression seems to be rare and is confined to cytotoxic primary cutaneous TCLs. Nevertheless, its expression is not exclusive to PCGD-TCLs, as TCR-γ protein can be found in other CTCLs. Moreover, its expression does not seem to be associated with bad prognosis by itself, as it can be found in cases with good and bad outcomes.


Subject(s)
Lymphoma, T-Cell, Cutaneous/immunology , Lymphoma, T-Cell, Cutaneous/pathology , Receptors, Antigen, T-Cell, gamma-delta/analysis , Skin Neoplasms/immunology , Skin Neoplasms/pathology , Adult , Aged , Aged, 80 and over , Female , Humans , Immunohistochemistry , Lymphoma, T-Cell, Cutaneous/metabolism , Male , Middle Aged , Polymerase Chain Reaction , Receptors, Antigen, T-Cell, gamma-delta/biosynthesis , Skin Neoplasms/metabolism , Tissue Array Analysis
8.
Mod Pathol ; 26(2): 171-81, 2013 Feb.
Article in English | MEDLINE | ID: mdl-22936066

ABSTRACT

Indolent primary cutaneous B-cell lymphoma is a group of malignant lymphomas comprising marginal zone B-cell lymphoma and centrofollicular B-cell lymphoma. Relapse rate of these tumors is close to 40%, and identifying those patients who are likely to progress remains a challenge. The aim of this study was to characterize the microRNA (miRNA) expression profile of a series of primary cutaneous B-cell lymphomas and correlate with histological and clinical findings. We studied a series of 68 patients with primary cutaneous B-cell lymphomas (30 cutaneous marginal-zone B-cell lymphomas and 38 primary cutaneous centrofollicular lymphomas). A set of 11 miRNAs associated with the differentiation stage of B cells was quantified by real-time PCR, using RNA extracted from formalin-fixed, paraffin-embedded tissue diagnostic samples. Relevant clinical variables were retrieved in a subset of 57 patients (28 cutaneous marginal zone B-cell lymphomas and 29 primary cutaneous centrofollicular lymphomas). miR-150 was upregulated in cutaneous marginal zone B-cell lymphomas relative to primary cutaneous centrofollicular lymphoma samples (false discovery rate <0.05). miR-155 and miR-150 expression levels were associated with progression-free survival in a univariate Cox regression analysis (P<0.1). After stratification by histological subtype, low-expression levels of miR-155 and miR-150 were both associated with shorter progression-free survival only in primary cutaneous marginal zone B-cell lymphomas cases (log-rank test, P<0.05). In summary, miRNA expression analysis can be used as a tool for diagnosis and outcome prognosis in indolent primary cutaneous B-cell lymphoma.


Subject(s)
Lymphoma, B-Cell/genetics , MicroRNAs , Skin Neoplasms/genetics , Adult , Aged , Aged, 80 and over , Disease-Free Survival , Female , Humans , Lymphoma, B-Cell/mortality , Lymphoma, B-Cell/pathology , Male , Middle Aged , Prognosis , Retrospective Studies , Skin Neoplasms/mortality , Skin Neoplasms/pathology , Survival Rate
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