Search

The literature on paediatric mycosis fungoides (MF) and especially its folliculotropic variant (FMF) is sparse.To describe the clinical manifestations, treatments, outcomes and long-term course of paediatric MF, including FMF.A retrospective analysis was conducted of all consecutive MF patients diagnosed at ≤18 years attending two medical centres in 1995-2015.The cohort included 71 patients, all but two of whom had early-stage disease: hypopigmented (55%), folliculotropic (42%) and classical MF (39%), alone or in combination. The head and neck area were involved in 43% of patients with early-stage FMF compared to 12% of the non-FMF group (P = 0.004). There was no difference in the involvement of other body areas between the groups. Pruritus, although mild, was more often recorded among patients with early-stage FMF compared to non-FMF (58% vs. 29%, respectively, P = 0.02). Complete response (CR) was achieved in 60 of the 69 patients with early-stage MF (87%) after an average of 1.8 treatment modalities. NBUVB was the most administered treatment to non-FMF patients with CR rates of 63% vs. 29% of FMF patients (P = 0.04). Systemic/bath PUVA and UVA+NBUVB were the most administered treatments to FMF patients with CR rates of 60% vs. 81% for non-FMF patients (P = 0.17). During a mean follow-up of 9.2 years (range 1-24), stage progression was observed in four (6%) of the patients with early-stage disease, two of whom (all FMF) to advanced stage.Paediatric MF presents as an early-stage disease with over-representation of hypopigmented and FMF variants. NBUVB and UVA-based therapies yield good response rates in non-FMF and FMF patients, respectively. Disease course is indolent, and even on relatively long follow-up, it has a very low progression rate from early to advanced-stage disease, occurring in patients with FMF. We propose a treatment algorithm for paediatric MF.

BACKGROUND Literature regarding exosomes as mediators in intercellular communication to promote progression in mycosis fungoides (MF) is lacking. OBJECTIVES To characterize MF-derived exosomes and their involvement in the disease. METHODS Exosomes were isolated by ultracentrifugation from cutaneous T-cell lymphoma (CTCL) cell lines, and from plasma of patients with MF and controls (healthy individuals). Exosomes were confirmed by electron microscopy, NanoSight and CD81 staining. Cell-line exosomes were profiled for microRNA array. Exosomal microRNA (exomiRNA) expression and uptake, and plasma-cell-free microRNA (cfmiRNA) were analysed by reverse-transcriptase quantitative polymerase chain reaction. Exosome uptake was monitored by fluorescent labelling and CD81 immunostaining. Migration was analysed by transwell migration assay. RESULTS MyLa- and MJ-derived exosomes had a distinctive microRNA signature with abundant microRNA (miR)-155 and miR-1246. Both microRNAs were delivered into target cells, but only exomiR-155 was tested, demonstrating a migratory effect on target cells. Plasma levels of cfmiR-1246 were significantly highest in combined plaque/tumour MF, followed by patch MF, and were lowest in controls (plaque/tumour > patch > healthy), while cfmiR-155 was upregulated only in plaque/tumour MF vs. controls. Specifically, exomiR-1246 (and not exomiR-155) was higher in plasma of plaque/tumour MF than in healthy controls. Plasma exosomes from MF but not from controls increased cell migration. CONCLUSIONS Our findings show that MF-derived exosomes promote cell motility and are enriched with miR-155, a well-known microRNA in MF, and miR-1246, not previously reported in MF. Based on their plasma expression we suggest that they may serve as potential biomarkers for tumour burden.

Background The molecular basis of unilesional mycosis fungoides (MF), characterized by a solitary lesion that is clinicopathologically indistinguishable from multifocal patch or plaque MF (early MF), is unknown. Objectives To investigate the microRNA profile in unilesional MF distinguishing it from early MF. Methods Biopsy samples of unilesional MF and early MF were evaluated with the Affymetrix microRNA array, with further comparison with inflammatory dermatosis, using quantitative polymerase chain reaction. NanoString technology was applied to analyse the gene expression of T helper (Th)1 immune markers, and immunohistochemistry was used to evaluate CXCR3 and GATA-binding protein 3 (GATA3) markers for Th1 and Th2 cells, respectively. Results Unilesional MF had a significantly higher level of expression of all members of the microRNA miR-17~92 cluster than early MF. Specifically, unilesional MF had a higher miR-17 level than early MF and inflammatory dermatoses. There was downregulation of the expression of phosphatase and tensin homolog (PTEN) and CREB1, known targets of miR-17~92 members; higher gene expression of interleukin-2 and interferon-γ; and a statistically lower average percentage of GATA3+ dermal cells (6·7% vs. 42·3%), were detected in unilesional MF compared with early MF. High immunoreactivity of CXCR3 was noted in both unilesional and early MF. Conclusions Unilesional MF exhibits a microRNA profile distinct from that of conventional early MF, with a higher level of miR-17~92 members along with Th1 skewing. These findings suggest a robust reactive T-cell immune response in unilesional MF and might account for the localized nature of this disease.

Background MicroRNA (miR)-155 contributes to the proliferation of mycosis fungoides (MF) in vitro and is upregulated in tumours of MF compared with early MF lesions. Objectives To investigate the contribution of miR-155 to the cancerous phenotype and drug resistance of MF/Sezary cell lines. Methods miR-155 was inhibited in MF cell lines (MyLa and MJ) by transduction of miRZip anti-miR-155, and overexpressed in Hut78 cells by transduction of miRVec-miR-155; empty plasmids served as controls. Cells were analysed for response to inducers of apoptosis and cell-cycle arrest, using fluorescence-activated cell sorting. Transduced MyLa cells were subcutaneously injected into severe combined immunodeficient mice, and tumours were analysed immunohistochemically and for final size. Result MyLa and MJ cells expressed a high level of miR-155; Hut78 cells expressed a low level. MF cell lines stably expressing miR-155 inhibitor showed increased G2/M arrest in response to N-p-tolyl-2-(3,4,5-trimethoxyphenyl quinazolin-4-amine) (SL111), an inducer of cell-cycle arrest, followed by increased apoptosis. Additionally, they showed increased apoptosis in response to suberoylanilide hydroxamic acid (SAHA). Tumours formed in mice from injected anti-miR-155-expressing MyLa cells had a significantly lower volume and higher occurrence of apoptosis than controls. Stable overexpression of miR-155 in Hut78 cells had no effect. Conclusions Oncogenic miR-155 appears to contribute to the cancerous phenotype of MyLa and MJ cells, but not of Hut78 cells, by interrupting activation of the G2/M checkpoint in response to SL111, and decreasing apoptosis in response to SL111 and SAHA, thereby facilitating tumour growth. These findings have implications for the potential development of novel therapeutic modalities for MF incorporating miR-155 inhibitors.

Background Survival in mycosis fungoides (MF) is varied and may be poor. The PROCLIPI (PROspective Cutaneous Lymphoma International Prognostic Index) study is a web‐based data collection system for early‐stage MF with legal data‐sharing agreements permitting international collaboration in a rare cancer with complex pathology. Clinicopathological data must be 100% complete and in‐built intelligence in the database system ensures accurate staging. Objectives To develop a prognostic index for MF. Methods Predefined datasets for clinical, haematological, radiological, immunohistochemical, genotypic, treatment and quality of life are collected at first diagnosis of MF and annually to test against survival. Biobanked tissue samples are recorded within a Federated Biobank for translational studies. Results In total, 430 patients were enrolled from 29 centres in 15 countries spanning five continents. Altogether, 348 were confirmed as having early‐stage MF at central review. The majority had classical MF (81·6%) with a CD4 phenotype (88·2%). Folliculotropic MF was diagnosed in 17·8%. Most presented with stage I (IA: 49·4%; IB: 42·8%), but 7·8% presented with enlarged lymph nodes (stage IIA). A diagnostic delay between first symptom development and initial diagnosis was frequent [85·6%; median delay 36 months (interquartile range 1290)]. This highlights the difficulties in accurate diagnosis, which includes lack of a singular diagnostic test for MF. Conclusions This confirmed early‐stage MF cohort is being followed‐up to identify prognostic factors, which may allow better management and improve survival by identifying patients at risk of disease progression. This study design is a useful model for collaboration in other rare diseases, especially where pathological diagnosis can be complex.

Background Unilesional folliculotropic mycosis fungoides (UFMF) has been rarely reported. Objective The aim of this study was to describe our experience with UFMF. Methods Data were collected on all patients with clinicopathological UFMF who attended the Department of Dermatology of a tertiary university-affiliated medical centre in 1996–2013 and were followed prospectively. Results The sample included seven patients (five male, two female) of mean age 38 years at diagnosis; two were aged

Summary Background Cutaneous lymphomas rarely occur in children and adolescents, and are mostly of the T-cell lineage. Low-grade primary cutaneous B-cell lymphoma (CBCL) is extremely rare in individuals under 18 years old. Only 11 patients under 20 years old have been reported in the literature. Objectives To evaluate the number of patients younger than 18 years with primary CBCL diagnosed at our centre and to investigate its clinicopathological features, treatment and course in this age group. Methods We reviewed the files of all 90 patients with primary CBCL who attended the Department of Dermatology of our tertiary care university-affiliated centre from 1992 to 2007. Results Four patients who met study criteria were identified: three girls and one boy. Mean age at diagnosis was 16·6 years (range 16–17). Three patients had cutaneous marginal zone lymphoma (CMZL), and one had a spindle-cell (sarcomatoid) lymphoma, most probably follicular centre cell type. All were treated with the standard regimen used in adults. The mean duration of follow up was 45 months. No extracutaneous progression was noted. At present two of the four patients are in complete clinical remission. Conclusions In Israel, primary CBCL apparently occurs more often in young patients than reported in the literature. CMZL is the most frequent type. Long follow up is mandatory to assess the biological behaviour of CBCL in the paediatric/adolescent age group.

The coexistence of mycosis fungoides, a peripheral T-cell lymphoma, and B-cell malignancies or Hodgkin's lymphoma in the same patient is unusual. Most descriptions are isolated case reports and case series are strikingly sparse.To detect cases of mycosis fungoides associated with B-cell malignancies or Hodgkin's lymphoma and to analyse the characteristics of and the interplay between the lymphoproliferative neoplasms.Patients with mycosis fungoides who had B-cell malignancies or Hodgkin's lymphoma were selected from among 398 patients either treated or followed up in two tertiary medical centres during a 7-year period.Eleven patients with mycosis fungoides and B-cell malignancy were detected (seven of non-Hodgkin's lymphoma, three of chronic lymphocytic leukaemia, one of multiple myeloma). No case of Hodgkin's lymphoma was found. In seven patients the mycosis fungoides preceded the B-cell malignancy whereas in four it was the B-cell malignancy which occurred first. The time elapsed between onset of the two malignancies ranged from 4 to 22 years (average: 12 years). Patients who had mycosis fungoides as the first neoplasm presented with earlier stages of mycosis fungoides (four of seven: IA, three of seven: IB) than those who had mycosis fungoides as their second neoplasm (of four, one: IB, one: folliculotropic, two: IIB). Among the four patients in whom the appearance of mycosis fungoides followed the B-cell malignancy, three had been treated with multiagent chemotherapy. Two patients who presented with early-stage mycosis fungoides (IA) as the first lymphoma developed mycosis fungoides tumours after becoming immunosuppressed. In two patients infiltrates composed of both malignant T- and B-cell populations were found in a single biopsy. One showed two distinct populations of the malignant cells in the skin tumour, thus constituting a classical composite lymphoma of mycosis fungoides and chronic lymphocytic leukaemia, while in the other patient the two malignant populations of marginal B-cell lymphoma and mycosis fungoides (as evidenced by both phenotypic and genotypic findings) were intermingled.This case series indicates that while the coexistence of Hodgkin's lymphoma and mycosis fungoides is extremely rare, the association of mycosis fungoides and B-cell malignancies is not as rare as reflected in the literature, with non-Hodgkin's lymphoma constituting the most common associated B-cell malignancy. In this series as well as in the cases reported in the literature mycosis fungoides usually preceded the development of B-cell malignancies, which may be in accordance with previous reports of an increased risk of developing a second haematological neoplasm. The importance of a competent immune system for patients with mycosis fungoides is well demonstrated in these cases. It is suggested that for greater precision the criteria for diagnosis of composite lymphoma of the skin should include both phenotypic and genotypic features.

Mycosis fungoides (MF) is a cutaneous T-cell lymphoma of unknown aetiology. A pathogenic role of human T-cell lymphotropic virus type 1 (HTLV-1) has been suggested but remains controversial. To determine whether MF is linked to HTLV-1.Blood samples were collected from 60 patients, 15 family relatives of patients with MF (MFRs), 20 healthy controls and 10 patients with HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP). The presence of HTLV-1 antibodies in serum was tested by the Western blot rp21e-enhanced test. DNA was extracted from the blood with the Qiagen blood kit. We used 500 ng of DNA either in conventional HTLV-1-specific polymerase chain reaction (PCR) or in real-time PCR using primers sk43 and sk44 together with a tax-specific fluorescent probe.In Western blot, antibodies against three to four HTLV-1 antigens were detected in 52% of patients with MF. All of the patients with HAM/TSP were positive, while only 7% of the MFRs and none of the 20 healthy controls reacted with HTLV-1 antigens in Western blot. One of 60 patients with MF and one of 15 MFRs were positive in HTLV-1 PCR. These two PCR-positive samples which were quantified in real-time PCR showed that fewer than five in 10(6) cells were HTLV-1 infected. We succeeded in amplifying and sequencing the 5' end of the provirus from the blood of the PCR-positive MFR by seminested PCR. A positive result was also obtained in this test. Phylogenetic tree analyses revealed a high homology of this sequence with other HTLV-1 sequences from the Middle East. The above PCR-positive MFR was the brother of a PCR-negative patient with MF.These findings demonstrate that HTLV-1 is probably not the aetiological agent of MF. However, it may play a role in immunosuppression and in the spreading of the disease.

We describe four patients with mycosis fungoides (MF) in whom depigmentation, and also leucotrichia in one, occurred following the resolution of the eruption during phototherapy (psoralen plus ultraviolet A treatment in three patients, climatotherapy in one). In all cases, the depigmentation was localized to the area of the pre-existing MF lesions. There was no clinically obvious phototoxicity. Biopsy study including S100 staining in all cases, and electron microscopy in one case, demonstrated the total absence of melanocytes, with no evidence of MF. It is suggested that the phototherapy may have activated a cell-mediated immunity leading to destruction of the melanocytes. We recommend that vitiligo-like leucoderma be added to the list of untoward effects of phototherapy in MF.

Unilesional mycosis fungoides (MF) is a rare variant of cutaneous T-cell lymphoma (CTCL), characterized by a solitary lesion clinically and by histopathological features indistinguishable from those of MF, and typically having a benign course.To describe the clinicopathological features of a series of patients with unilesional MF.The records of cases of unilesional MF identified during a 10-year period in two medical departments were reviewed.There were 7 patients: 6 males, 1 female; mean age at the time of diagnosis: 32 years; age range: 12-58 years; 3 were below the age of 18 years. The mean pretherapy follow-up period was 9 years (range: 2-20 years). In 5 patients, the eruption consisted of a characteristic patch or plaque of MF located on the trunk or upper extremity; in 2 it was atypical - in 1, a hypopigmented patch, and in 1, a plaque indistinguishable from MF-associated follicular mucinosis. Histopathologically all the lesions exhibited features characteristic of MF, with CD3+ lymphoid cells. In 6 cases (with available fresh frozen tissue) there was a predominance of CD3+ CD4+ cells; in 1 of 5 there was deletion of CD7, and in 3 of 5 there was an overexpression of IL-2 receptor. T-cell receptor gamma gene rearrangement was found in 1 of 4 cutaneous lesions tested; in 2 cases it was found in the blood but not in the skin. Treatment modalities included localized electron beam, excision, topical nitrogen mustard or topical steroids and sunbathing, resulting in all cases in a sustained complete clinical response. In 1 patient, however, there were 2 local recurrences and in yet another patient there was distant cutaneous spread 3.5 years after therapy.Unilesional MF is a rare variant of CTCL, has heterogeneous clinical manifestations and can affect any age group, including children. The histopathological and immunophenotypical features are in general indistinguishable from those observed in multilesional MF. Although it is a unifocal event, there may occasionally be cutaneous spread with the appearance of noncontiguous lesions, even a long time after therapy. Whether all cases represent minimal-stage IA MF or whether some are actually T-cell pseudolymphoma remains to be clarified.

Nine patients with follicular cutaneous T-cell lymphoma (CTCL), a recently described variant of lymphoma, are presented. On the basis of clinical manifestations and disease course, three groups of patients were distinguished: (i) two patients with follicular CTCL not associated with conventional lesions of mycosis fungoides (MF) and showing no evolution towards MF in follow-up periods of 3 and 6 years; (ii) one patient with follicular CTCL that evolved into conventional MF within 3 years; (iii) six patients showing conventional MF lesions either before or concurrently with the follicular lesions and thus representing follicular CTCL of the true MF type. The follicular lesions included hair-devoid patches or plaques with spiky hyperkeratotic papules (four patients), keratosis pilaris-like lesions (four), comedo-like lesions (four), follicular papules with alopecia (three) and milia-like lesions (three). Histopathological examination showed perifollicular and intrafollicular lymphocytes, without mucin deposition and with minimal or no involvement of the overlying epidermis. Significant syringotropism was also observed in three cases. Immunohistochemical analysis showed the predominance of CD4 + T cells, deletion of CD7 in some cases, Ki-67 + lymphocytes confined mainly to the follicular epithelium, and expression of keratinocyte intercellular adhesion molecule-1 exclusively in the hair follicle. T-cell receptor gamma gene rearrangement was positive in the one case studied from each group. Different treatment modalities were employed, the most commonly used as monotherapy being phototherapy: psoralen ultraviolet A in four patients, two of whom showed a complete clinical and histopathological remission, and ultraviolet B in one patient, who showed a complete remission (both clinical and histopathological). This study indicates that follicular CTCL is more common than reflected in the literature, has heterogeneous clinical manifestations, and is either an expression of or closely related to MF. The influence of the follicular involvement on the therapeutic response remains to be clarified. However, our therapeutic experience clearly suggests that some patients with follicular CTCL can benefit from phototherapy.

The aetiology of mycosis fungoides (MF) and Sézary syndrome (SS) is unknown. A pathogenic role for the human T-cell lymphotropic virus type 1 (HTLV-1) has been suggested but remains controversial. We used an animal model to test the possibility that peripheral blood mononuclear cells (PBMC) obtained from MF patients harbour the HTLV-1 virus which may be infective. The polymerase chain reaction (PCR) was used to detect HTLV-1 proviral DNA sequences in PBMC of 27 MF patients and one SS patient of non-Iranian origin. Positive results were found in six of the patients. Twelve of the 28 patients tested by Western blot showed HTLV-1 antibodies. Twenty-eight immunosuppressed inbred Fisher F344 rats were inoculated intravenously with cultures of PBMC obtained from the 28 patients. Eight of these 28 rats showed antibodies to HTLV-1 while the proviral genome was demonstrated in the blood of only two of the rats. PBMC from two MF patients, in spite of showing negative results for the proviral genome by PCR, still induced HTLV-1 antibody formation in the F344 rat model. None of 10 control rats inoculated with normal donor PBMC showed antibodies to HTLV-1, nor the proviral genome. The present study suggests that HTLV-1 plays a cofactor role in MF/SS patients.

A patient with epidermodysplasia verruciformis also had lesions of seborrheic keratosis, irritated seborrheic keratosis, and intraepidermal and invasive squamous cell carcinoma as well as infiltrating squamous cell carcinoma associated with eccrine poroma. Electron microscope studies revealed intranuclear virus particles. Immunoperoxidase studies using rabbit anti-bovine papilloma virus serum showed a positive reaction.