Invisible Mycosis Fungoides: Not to be Missed in Chronic Pruritus.
ABSTRACT: INTRODUCTION: Pruritus without visible dermatoses may be the first manifestation of hematological malignancies such as Hodgkin disease, chronic lymphocytic leukemia and mycosis fungoides (MF) and may precede the definitive diagnosis by weeks to years. CASE REPORT: We present a case of 'invisible' MF associated with chronic generalized pruritus in an elderly patient. CONCLUSION: Our case highlights the importance of performing skin biopsies in patients with chronic unexplained pruritus, especially in the absence of cutaneous lesions. This can prompt the clinician to consider possible underlying malignancy, such as 'invisible' MF.
Project description:Mycosis fungoides (MF) is the most common and best studied of cutaneous T-cell lymphoma (CTCL). Three clinical cutaneous stages have been described (patch, plaque and tumor) as the disease progress developing also the disease lymph node, peripheral blood or systemic involvement in late stages. Clinical and pathologic diagnosis of early MF stages (patch and plaque) is difficult as its morphologic similarity to inflammatory dermatoses and low proportion of tumoral cells. Overall design: 14 MF and 15 reactive skin lesions were hybridized on a 8 x 15K human miRNA one-color platform (Agilent) containing probes for 723 human miRNAs.
Project description:MicroRNAs (miRNAs) are small RNA species that regulate gene expression post-transcriptionally and are aberrantly expressed in many malignancies including lymphoma. However, the role of miRNAs in the pathogenesis of T-cell lymphoid malignancies is poorly understood. Previously we examined the miRNA profile of Sézary syndrome (Sz), a leukemia of skin-homing memory T cells. In this study we determined the complete miRNome of mycosis fungoides (MF), the most common type of cutaneous T cell lymphoma. The miRNA profile of skin biopsies from 19 patients with tumor stage MF and 12 patients with benign inflammatory dermatoses (eczema and lichen planus) were compared by microarray analysis. We identified 49 miRNAs that are differentially expressed in tumor stage MF compared to benign inflammatory dermatoses using ANOVA analysis (P < 0.05, Benjamini-Hochberg corrected). The majority of the differentially expressed miRNAs (30/49) were up-regulated in tumor stage MF. The most significant differentially expressed were miR-155 and miR-92a (both up-regulated in tumor stage MF), while miR-93 showed the highest up-regulation in tumor stage MF with a fold difference of 5.8. Differential expression of a selection of these miRNAs was validated by miRNA-Q-PCR on additional test groups (tumors and controls). None of the miRNAs up-regulated in tumor stage MF was previously shown to be up-regulated in Sz, and only 2 of the 19 miRNAs down-regulated in tumor stage MF were also down-regulated in Sz. Taken together this report is the first describing the miRNA signature of tumor stage MF.
Project description: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.
Project description:OBJECTIVES: The histopathological diagnosis of Mycosis Fungoides (MF) is challenging in its early stages and can easily be confused with inflammatory dermatoses. This study aims to; (i) assess the frequency and significance of different histopathological parameters in early MF, seen in Saudi patients, and (ii) to study the utility of these parameters in differentiating between early MF and inflammatory dermatoses. METHODS: This is a five years study of 66 skin biopsies generated from 58 patients with clinically suspicious MF lesions or early patch stage MF. These cases were retrieved from the archives of the Department of Pathology, King Khalid University Hospital, Riyadh from the year 2002 to 2006. Histological criteria were assessed and graded semi-quantitatively on a four-point scale by a dermatopathologist and two pathologists independently. RESULTS: The histological parameters suggesting the diagnosis in early stages MF include epidermotropism, dermal fibrosis, Pautrier's micro abscesses, Basal alignment of neoplastic lymphocytes, hyperconvoluted dermal and epidermal lymphocytes and grandiosity sign (size of lymphocytes becoming larger as they migrate towards granular layer of epidermis). These parameters on univariate analysis achieved statistical significance (p<0.05) in differentiating MF from non-MF cases. In addition, hyperconvoluted dermal and epidermal lymphocytes proved to be highly reliable with high specificity and sensitivity. CONCLUSION: The histopathological diagnosis of early MF lesions and their discrimination from inflammatory simulators can be achieved by carefully observing the hyperconvoluted dermal and epidermal lymphocytes along with the constellation of the other parameters.
Project description:RATIONALE:Mycosis fungoides (MF) is the most common cutaneous T-cell lymphoma. It appears as patches, plaques, and tumors depending on the stage of the disease, which presents a chronic progressive course. Compared to CD4/CD8 MF, CD4/CD8 dual-positive MF is an uncommon immune phenotype. PATIENT CONCERNS:A 36-year-old male patient presented with dryness and scales on his whole body. DIAGNOSIS:The patient was diagnosed with MF based on results of pathological examination, immunohistochemical staining, and T-cell receptor gene rearrangement test. INTERVENTIONS:The patient was advised to take an herbal medicine orally twice daily and apply a topical moisturizer after showering. OUTCOMES:After treatment and follow-up, the patient's symptoms of dryness and scales improved and his condition stabilized. CONCLUSIONS:While reviewing the literature, we found no previous reports on the treatment of dual-positive MF with Chinese medicine. In this report, we presented the first case of dual-positive MF successfully treated with Chinese medicine. The results suggest that oral ingestion of herbal medicine may be a feasible method for alleviating clinical symptoms of early stage MF. Therefore, the therapy should be explored for clinical use in the future.
Project description:To report a case of corneal infiltration and xanthoma formation in mycosis fungoides (cutaneous T-cell lymphoma).A middle aged Japanese man with mycosis fungoides (MF) involving the face was referred to Ophthalmology for evaluation of unilateral, painless conjunctival injection. Biopsy of the conjunctiva revealed a malignant T cell population consistent with MF tumor invasion. Years later, he returned following several episodes of infectious keratitis with a painless, yellow, rapidly forming mass in the left eye over two weeks. Corneal biopsy showed foamy histiocytes and positive staining for CD68, and a diagnosis of corneal xanthoma was made.Severe ocular surface disease can rarely occur in MF by direct invasion of tumor cells. Corneal infiltration and xanthoma development may be avoidable by careful monitoring for infectious keratitis in patients with conjunctival involvement, as in our case.
Project description:Mycosis fungoides (MF) is the most frequently found cutaneous T-cell lymphoma with an unknown aetiology. Several aetiopathogenetic mechanisms have been postulated, including persistent viral or bacterial infections. We looked for evidence of Borrelia burgdorferi (Bb), the aetiologic agent of Lyme disease (LD), in a case study of MF patients from Northeastern Italy, an area with endemic LD. Polymerase chain reaction for the flagellin gene of Bb was used to study formalin-fixed paraffin-embedded lesional skin biopsies from 83 patients with MF and 83 sex- and age-matched healthy controls with homolocalised cutaneous nevi. Borrelia burgdorferi-specific sequence was detected in 15 out of 83 skin samples of patients with MF (18.1%), but in none out of 83 matched healthy controls (P<0.0001). The Bb positivity rates detected in this study support a possible role for Bb in the aetiopathogenesis of MF in a population endemic for LD.
Project description:Introduction. Mycosis fungoides (MF) is a form of primary cutaneous T-cell lymphomas, and radiotherapy (RT) has been used to treat localized/limited lesions of MF. In this case report, the results of low-dose RT applied for palliative purpose are shared. Case Report. A 70-year-old male patient was admitted to the outpatient clinic 7 months ago with a generalized itchy rash. The result of the biopsy was reported as mycosis fungoides. Systemic treatment was not performed due to comorbid diseases. The hemibody RT was applied. 2?Gy was given per fraction, with a total dose of 6?Gy. The significant clinical relief was observed with 6?Gy RT. The patient died due to multiorgan failure 2 months later, and no recurrence was observed. Conclusion. The palliation was achieved in the advanced MF patient with fractionated 6?Gy hemibody RT for the remaining 2 months of life.
Project description:<h4>Background</h4>Mycosis fungoides (MF) is the most common cutaneous T-cell lymphoma, for which there is no cure. Immune checkpoint inhibitors have been tried in MF but the results have been inconsistent. To gain insight into the immunogenicity of MF we characterized the neoantigen landscape of this lymphoma, focusing on the known predictors of responses to immunotherapy: the quantity, HLA-binding strength and subclonality of neoantigens.<h4>Methods</h4>Whole exome and whole transcriptome sequences were obtained from 24 MF samples (16 plaques, 8 tumors) from 13 patients. Bioinformatic pipelines (Mutect2, OptiType, MuPeXi) were used for mutation calling, HLA typing, and neoantigen prediction. PhyloWGS was used to subdivide malignant cells into stem and clades, to which neoantigens were matched to determine their clonality.<h4>Results</h4>MF has a high mutational load (median 3,217 non synonymous mutations), resulting in a significant number of total neoantigens (median 1,309 per sample) and high-affinity neoantigens (median 328). In stage I disease most neoantigens were clonal but with stage progression, 75% of lesions had >50% subclonal antigens and 53% lesions had CSiN scores <1. There was very little overlap in neoantigens across patients or between different lesions on the same patient, indicating a high degree of heterogeneity.<h4>Conclusions</h4>The neoantigen landscape of MF is characterized by high neoantigen load and significant subclonality which could indicate potential challenges for immunotherapy in patients with advanced-stage disease.
Project description:The distinction between mycosis fungoides (MF) and inflammatory dermatoses (ID) by clinicopathologic criteria can be challenging. There is limited information regarding the performance characteristics and utility of TCRG and TCRB clonality assays in diagnosis of MF and ID from paraffin-embedded tissue sections. In this study, PCR tests were performed with both TCRG and TCRB BIOMED-2 clonality methods followed by capillary electrophoresis and Genescan analysis using DNA samples from 35 MF and 96 ID patients with 69 and 133 paraffin-embedded specimens, respectively. Performance characteristics were determined for each test individually and in combination. TCRG and TCRB tests demonstrated identical sensitivity (64%) and specificity (84%) when analyzed as individual assays. The positive predictive value, negative predictive value, and change of posttest MF probability over a range of MF pretest probabilities were obtained. These data were used to construct an algorithm for sequential use of TCRG and TCRB. As single tests, commercially available BIOMED-2 PCR-based TCRG and TCRB clonality tests on paraffin-embedded tissue have no significant difference in terms of sensitivity and specificity. Combined use of the two tests in patients with intermediate pretest probabilities as proposed in the algorithm could improve test utility.