ABSTRACT
Germline mutations leading to aneuploidy are rare, and their tumor-promoting properties are mostly unknown at the molecular level. We report here novel germline biallelic mutations in MAD1L1, encoding the spindle assembly checkpoint (SAC) protein MAD1, in a 36-year-old female with a dozen of neoplasias. Functional studies demonstrated lack of full-length protein and deficient SAC response, resulting in ~30 to 40% of aneuploid blood cells. Single-cell RNA analysis identified mitochondrial stress accompanied by systemic inflammation with enhanced interferon and NFκB signaling both in aneuploid and euploid cells, suggesting a non-cell autonomous response. MAD1L1 mutations resulted in specific clonal expansions of γδ T cells with chromosome 18 gains and enhanced cytotoxic profile as well as intermediate B cells with chromosome 12 gains and transcriptomic signatures characteristic of leukemia cells. These data point to MAD1L1 mutations as the cause of a new variant of mosaic variegated aneuploidy with systemic inflammation and unprecedented tumor susceptibility.
ABSTRACT
BACKGROUND: There is limited literature on efficacy in 5-aminolaevulinic acid (BF-200 ALA) and methyl-5-aminolaevulinate (MAL) for superficial basal cell carcinoma (sBCC). AIMS: To investigate the efficacy and safety of PDT in sBCC. METHODS: Analytical observational study between January 2014 and January 2017. Follow-up at 12, 24 and 52 weeks. Lesions were treated with one BF-200 ALA-PDT or MAL-PDT cycle of two sessions in one week. A second treatment cycle, with the same photosensitizer precursor, was performed in cases of clinical persistence at 12 weeks. RESULTS: A total of 22 patients (30 lesions) were enrolled in the study. By sex, 13 men and 9 women. Average age of 72,14 years. In the 12-month follow-up 15/16 lesions were resolved (93,75%) after one or two BF-200 ALA-PDT cycle and 7/14 lesions (50%) after one or two MAL-PDT cycles. In most patients, tolerance to the therapy was good or regular, with no differences between the two groups. No long-term adverse effects were reported. LIMITATIONS: The observational nature and the low number of patients. CONCLUSION: PDT is a safe and non-invasive treatment option in sBCC. Our results suggest a better response with BF-200 ALA-PDT over MAL-PDT, at 12 months of follow-up.
Subject(s)
Aminolevulinic Acid/therapeutic use , Carcinoma, Basal Cell/drug therapy , Photochemotherapy/methods , Photosensitizing Agents/therapeutic use , Skin Neoplasms/drug therapy , Aged , Aminolevulinic Acid/analogs & derivatives , Female , Humans , MaleSubject(s)
Folliculitis , Scalp Dermatoses , Adult , Age of Onset , Anti-Bacterial Agents/therapeutic use , Bacteria/isolation & purification , Biopsy , Chronic Disease , Dermatologic Agents/therapeutic use , Follow-Up Studies , Hair Follicle/microbiology , Hair Follicle/pathology , Humans , Male , Middle Aged , Retrospective Studies , Treatment Outcome , Young AdultABSTRACT
We report a 52-year old woman with a 28-year historyof disfiguring facial discoid lupus erythematosus(DLE), persistent despite both classical therapiesand rituximab. Ustekinumab 45 mg was started incombination with methotrexate and intralesionalcorticosteroids. Methotrexate and intralesionalcorticosteroids were withdrawn 30 months later andustekinumab maintained as monotherapy. Fortyeight months later stable improvement was achievedwithout side effects. Only nine patients with cutaneouslupus erythematosus (CLE) treated with ustekinumabhave been reported to date. Ustekinumab could be apromising alternative in severe and recalcitrant casesof CLE. Possibly, the Th17-inflammation pathway isplaying a role in these patients.
Subject(s)
Dermatologic Agents/therapeutic use , Facial Dermatoses/drug therapy , Lupus Erythematosus, Discoid/drug therapy , Ustekinumab/therapeutic use , Adrenal Cortex Hormones/therapeutic use , Facial Dermatoses/pathology , Female , Humans , Immunologic Factors/therapeutic use , Immunosuppressive Agents/therapeutic use , Injections, Intralesional , Lupus Erythematosus, Discoid/pathology , Methotrexate/therapeutic use , Middle Aged , Rituximab/therapeutic use , Treatment FailureSubject(s)
Foot Deformities, Congenital/pathology , Lipomatosis/pathology , Toes/abnormalities , Class I Phosphatidylinositol 3-Kinases , Foot Deformities, Congenital/diagnostic imaging , Foot Deformities, Congenital/genetics , Humans , Infant, Newborn , Lipomatosis/diagnostic imaging , Lipomatosis/genetics , Male , Phosphatidylinositol 3-Kinases/genetics , Radiography , Toes/diagnostic imagingABSTRACT
OBJECTIVE: To validate dermoscopy as a real-time noninvasive diagnostic imaging technique for actinic keratosis (AK). DESIGN: Prospective study to validate a diagnostic test. SETTING: Dermatology department of a tertiary university hospital in Fuenlabrada, Madrid, Spain. PATIENTS: A total of 178 patients with a clinical diagnosis of AK participated in the study. MAIN OUTCOME MEASURES: An independent blinded comparison was performed between dermoscopy results and histopathological findings, the gold standard for the diagnosis of AK. All the patients underwent both diagnostic tests. RESULTS: One hundred seventy-eight lesions were evaluated. The concordance between dermoscopy results and histopathological findings was 0.917. The sensitivity of dermoscopy for the diagnosis of AK was 98.7%, with a specificity of 95.0%, a positive likelihood ratio of 19.74, and a negative likelihood ratio of 0.01. A diagnostic algorithm that combined follicular openings and erythematous pseudonetwork demonstrated a sensitivity of 95.6% and a specificity of 95.0% for the diagnosis of AK. CONCLUSIONS: The sensitivity and specificity of dermoscopy for the diagnosis of AK were high, as was the concordance between dermoscopy results and histopathological findings. As a real-time noninvasive diagnostic imaging technique for AK, dermoscopy may be incorporated in the management of patients with these lesions.
Subject(s)
Dermoscopy , Keratosis, Actinic/pathology , Adult , Aged , Aged, 80 and over , Algorithms , Chi-Square Distribution , Double-Blind Method , Female , Humans , Keratosis, Actinic/diagnosis , Likelihood Functions , Male , Middle Aged , Prospective Studies , Sensitivity and SpecificityABSTRACT
Dermatomyofibroma represents a rare benign fibroblastic/ myofibroblastic cutaneous tumor that mostly occurs in young adult women. It has been seldom reported in pediatric patients. In this analysis, the clinical, histopathological and immunohistochemical findings of 12 dermatomyofibromas occurring in patients up to 16 years of age are compared with those reported in adults. Six patients were male and six were female. Nine lesions were located on the neck, two on the back and one involved the chest. The usual presentation was as an asymptomatic plaque composed of bland spindled cells arranged in dermal fascicles that were oriented parallel to the epidermis. Immunohistochemically, the lesional cells expressed calponin in 11 cases, smooth muscle actin in six and muscle-specific actin in three. In contrast to prior reports from adults, dermatomyofibromas in pediatric patients do not show a female predilection. In addition, they are mostly located on the neck (56%), while in adults the most frequent location is the shoulder (35%). Dermatomyofibromas seem to stabilize after an initial period of enlargement. Punch biopsy and clinical follow up could be an alternative approach to the surgical excision in some cases of dermatomyofibroma, particularly in instances in which surgery might inflict cosmetic defects.
Subject(s)
Head and Neck Neoplasms/pathology , Histiocytoma, Benign Fibrous/pathology , Myofibroma/pathology , Skin Neoplasms/pathology , Actins/biosynthesis , Adolescent , Adult , Calcium-Binding Proteins/biosynthesis , Child , Child, Preschool , Diagnosis, Differential , Female , Follow-Up Studies , Gene Expression Regulation, Neoplastic , Head and Neck Neoplasms/metabolism , Head and Neck Neoplasms/surgery , Histiocytoma, Benign Fibrous/metabolism , Histiocytoma, Benign Fibrous/surgery , Humans , Immunohistochemistry/methods , Male , Microfilament Proteins/biosynthesis , Myofibroma/metabolism , Myofibroma/surgery , Neoplasm Proteins/biosynthesis , Retrospective Studies , Skin Neoplasms/metabolism , Skin Neoplasms/surgery , CalponinsSubject(s)
Hair/pathology , Nevus, Sebaceous of Jadassohn/pathology , Scalp/pathology , Biopsy , Female , Humans , Infant, NewbornABSTRACT
Erythrodermic psoriasis is a chronic condition that is difficult to treat. Biological agents offer a new alternative, but there are no controlled trials to support their use; there are a few reports of patients treated with these agents, but often only with short term results. We report a 68-year-old man with erythrodermic psoriasis and ankylosing spondylitis, treated with infliximab for 48 weeks and then low-dose etanercept monotherapy for 34 additional months. Excellent results were obtained for both conditions without significant side effects. We think etanercept can be a good therapeutic option for long-term control of erythrodermic psoriasis.
Subject(s)
Dermatitis, Exfoliative/drug therapy , Dermatologic Agents/therapeutic use , Immunoglobulin G/therapeutic use , Psoriasis/drug therapy , Receptors, Tumor Necrosis Factor/therapeutic use , Spondylitis, Ankylosing/drug therapy , Tumor Necrosis Factor-alpha/antagonists & inhibitors , Aged , Antibodies, Monoclonal/therapeutic use , Etanercept , Humans , Infliximab , Male , Treatment OutcomeSubject(s)
Dermatitis, Contact/etiology , Drug Eruptions/etiology , Hemorrhoids/drug therapy , Spirostans/adverse effects , Vasoconstrictor Agents/adverse effects , Administration, Cutaneous , Adult , Dermatitis, Contact/diagnosis , Drug Eruptions/diagnosis , Humans , Male , Patch Tests , Spirostans/administration & dosage , Vasoconstrictor Agents/administration & dosageABSTRACT
A distinctive clinical entity of acute genital ulcers occurring in adolescents, with nonvenereal infectious etiology was described by Lipschütz in 1913. We describe four puberal virgin girls who developed fever and painful genital ulcers. The main causes infectious and noninfectious of ulceration were rejected. Although the etiology is unknown, recent cases related with Epstein-Barr virus acute infection have been reported.
Subject(s)
Ulcer/pathology , Vulva/pathology , Vulvar Diseases/pathology , Adolescent , Antibodies, Viral/analysis , Bacillus/isolation & purification , Child , Edema/etiology , Epstein-Barr Virus Infections/complications , Female , Fever/etiology , Herpesvirus 4, Human/isolation & purification , Humans , Staphylococcus epidermidis/isolation & purification , Ulcer/microbiology , Vulvar Diseases/microbiologyABSTRACT
The association between leukocytoclastic vasculitis and solid tumors like renal carcinoma has been infrequently described. We present the case of a 76-year-old woman who began with skin lesions on the legs that were clinically and histologically diagnosed as leukocytoclastic vasculitis. During analysis of the symptoms, she was diagnosed with renal carcinoma. After the tumor was excised, the vasculitis lesions disappeared, with no recurrence during the follow-up period.
Subject(s)
Carcinoma, Renal Cell/complications , Kidney Neoplasms/complications , Vasculitis, Leukocytoclastic, Cutaneous/etiology , Aged , Carcinoma, Renal Cell/diagnostic imaging , Female , Humans , Kidney Neoplasms/diagnostic imaging , Kidney Neoplasms/surgery , Nephrectomy , Radiography , Remission Induction , Vasculitis, Leukocytoclastic, Cutaneous/surgeryABSTRACT
La asociación entre vasculitis leucocitoclástica y tumores sólidos como el carcinoma renal se ha descrito con poca frecuencia. Presentamos el caso de una mujer de 76 años que empezó con lesiones cutáneas en piernas clínica e histológicamente diagnosticadas de vasculitis leucocitoclástica y a la que, en el transcurso del estudio del cuadro, se le diagnosticó un carcinoma renal. Tras la extirpación del tumor renal, las lesiones de vasculitis desaparecieron sin recidiva en el seguimiento
The association between leukocytoclastic vasculitis and solid tumors like renal carcinoma has been infrequently described. We present the case of a 76-year-old woman who began with skin lesions on the legs that were clinically and histologically diagnosed as leukocytoclastic vasculitis. During analysis of the symptoms, she was diagnosed with renal carcinoma. After the tumor was excised, the vasculitis lesions disappeared, with no recurrence during the follow-up period
Subject(s)
Female , Middle Aged , Humans , Carcinoma, Renal Cell/complications , Carcinoma, Renal Cell/diagnosis , Vasculitis, Leukocytoclastic, Cutaneous/complications , Vasculitis, Leukocytoclastic, Cutaneous/pathology , Biopsy/methods , Prednisone/administration & dosage , Prednisone/therapeutic use , Skin Diseases, Vesiculobullous/complications , Skin Diseases, Vesiculobullous/diagnosis , Radiography, Thoracic/methodsSubject(s)
Hand Dermatoses/diagnosis , Mycobacterium Infections, Nontuberculous/diagnosis , Mycobacterium marinum/isolation & purification , Adult , Animals , Animals, Domestic , Disease Reservoirs/microbiology , Erythema/etiology , Fishes/microbiology , Hand Dermatoses/microbiology , Humans , Male , Mycobacterium Infections, Nontuberculous/microbiology , Mycobacterium Infections, Nontuberculous/transmission , Mycobacterium chelonae/isolation & purification , Tuberculoma/etiology , Water MicrobiologyABSTRACT
No disponible