ABSTRACT
Sentinel lymph node biopsy (SLNB) is a standard procedure for regional lymph node staging and still has the most important prognostic value for the outcome of patients with thin melanoma. In addition to ulceration, SLNB had to be considered even for a single mitotic figure in thin (<1 mm) melanoma according to AJCC7th guideline, therefore, a retrospective review was conducted involving 403 pT1 melanoma patients. Among them, 152 patients suffered from pT1b ulcerated or mitotic rate ≥ 1/ mm2 melanomas according to the AJCC7th staging system. SLNB was performed in 78 cases, of which nine (11.5%) showed SLN positivity. From them, interestingly, we found a relatively high positive sentinel rate (6/78-8%) in the case of thin primary melanomas Ë0.8 mm. Moreover, the presence of regression increased the probability of sentinel positivity by 5.796 fold. After reassessing pT stage based on the new AJCC8th, 37 pT1b cases were reordered into pT1a category. There was no significant relation between other characteristics examined (age, gender, Breslow, Clark level, and mitosis index) and sentinel node positivity. Based on our data, we suggest that mitotic rate alone is not a sufficiently powerful predictor of SLN status in thin melanomas. If strict histopathological definition criteria are applied, regression might be an additional adverse feature that aids in identifying T1 patients most likely to be SLN-positive. After reassessing of pT1b cases according to AJCC8th regression proved to be independent prognostic factor on sentinel lymph node positivity. Our results propose that sentinel lymph node biopsy might also be considered at patients with regressive thin (Ë0.8 mm) melanomas.
Subject(s)
Melanoma/diagnosis , Melanoma/pathology , Sentinel Lymph Node Biopsy/methods , Skin Neoplasms/diagnosis , Skin Neoplasms/pathology , Adult , Aged , Female , Humans , Lymphatic Metastasis/diagnosis , Lymphatic Metastasis/pathology , Male , Middle Aged , Mitotic Index , Neoplasm Staging/methods , Retrospective Studies , Young Adult , Melanoma, Cutaneous MalignantABSTRACT
From a dermatological aspect, it posed a considerable challenge the skin-limited form of mastocytosis, urticaria pigmentosa and indolent systemic mastocytosis (ISM) with cutaneous lesions. Despite the favourable prognosis, lifelong dermatological control is needed, during which the average symptomatic therapy does not always seem adequate. We report here the case of a female ISM patient with recurrent cutaneous symptoms that impaired her quality of life, with a follow-up time of 27 years. During this long follow-up period, the cutaneous lesions could be controlled by antihistamines, leukotriene antagonists, glucocorticoids, local immunosuppressants or local UV radiation for only relatively short periods. Imatinib mesylate was, therefore, introduced in an attempt to control the cutaneous lesions. Tyrosine kinase inhibition is an unusual dermatological therapeutic option. This case illustrates that imatinib mesylate was a good choice with which to achieve a reduction of the skin lesions in this KIT D816V mutation-negative disease: it led to a temporary appreciable improvement of the patient's quality of life.
Subject(s)
Mastocytosis, Systemic/diagnosis , Urticaria Pigmentosa/diagnosis , Adult , Diagnosis, Differential , Female , Humans , Imatinib Mesylate/therapeutic use , Mastocytosis, Systemic/complications , Mastocytosis, Systemic/drug therapy , Protein Kinase Inhibitors/therapeutic use , Proto-Oncogene Proteins c-kit , Quality of Life , Urticaria Pigmentosa/complications , Urticaria Pigmentosa/drug therapyABSTRACT
BACKGROUND: Langerhans cell histiocytosis (LCH) is characterized by the proliferation of pathologic Langerhans cells. The disease can develop in any age and can affect almost any organ. Cutaneous involvement is frequent in LCH. The recent demonstration of the activating, oncogenic BRAFV600E gene mutation in LCH samples strongly supports the neoplastic origin of the disease. OBJECTIVES: Our aim was to analyse the clinical data of the patients and whether BRAFV600E mutation is present in skin lesions of patients with adult onset LCH, and to investigate whether the BRAFV600E mutation status has any effect on the clinical presentation and the outcome of the disease. METHODS: We diagnosed and treated 15 adult LCH patients in the period of 1987-2012 and collected their clinical data. Three of our patients suffered from skin involvement and 12 patients had multiorgan disease (five patients out of the multisystem group died). Eleven formalin-fixed paraffin-embedded skin samples from 10 patients were available for BRAFV600E mutation analysis. RESULTS: Among the 11 examined samples, 6 contained the BRAFV600E mutation (54.5%). Our results indicate that in the adult group of LCH patients the presence of BRAFV600E mutation is similar to what was previously suggested in case of the childhood forms, at least as far as skin lesions are concerned. The BRAF mutation status of our patients does not seem to correlate with the extent and/or the outcome of the disease. CONCLUSION: Our results support the neoplastic origin of LCH and suggest that skin lesions of LCH are sufficient for the diagnosis of the disease and for assessing its BRAF status. In addition, analysis of BRAF status of patients with LCH can lead to the administration of new targeted therapies which may provide better disease control and prognosis.
Subject(s)
Histiocytosis, Langerhans-Cell/genetics , Histiocytosis, Langerhans-Cell/pathology , Proto-Oncogene Proteins B-raf/genetics , Skin Diseases/genetics , Skin Diseases/pathology , Adult , Age of Onset , Aged , Aged, 80 and over , Female , Humans , Male , Middle Aged , Mutation , Severity of Illness Index , Young AdultABSTRACT
Non-melanoma skin cancer is the most common malignancy that shows increasing incidence due to our cumulative exposure to ultraviolet irradiation. Its major subtypes, basal cell carcinoma (BCC) and squamous cell carcinoma (SCC) differ in pathobiology, phenotype and clinical behavior, which must be reflected at the molecular level. In this study, protein expression profiles of BCC and SCC were tested in tissue microarrays and correlated with that of actinic keratosis, Bowen's disease, seborrheic keratosis and normal epidermis by detecting 22 proteins involved in cell interactions, growth, cell cycle regulation or apoptosis. The significantly more reduced collagen XVII, CD44v6, pan-Desmoglein levels and more evident E-Cadherin delocalization in BCC compared to SCC correlated with the de novo dermal invasion of BCC against the progressive invasion from in situ lesions in SCC development. EGFR was also expressed at a significantly higher level in SCC than in BCC. The upregulated cell communication protein connexin43 in BCC could contribute to the protection of BCC from metastatic invasion. Elevated cell replication in BCC was underlined by the increased topoisomerase IIα and reduced p21(waf1) and p27(kip1) positive cells fractions compared to SCC. Compared to differentiated keratinocytes, caspase-8 and -9 were equally upregulated in skin carcinoma subtypes for either mediating apoptosis induction or immune escape of tumor cells. Hierarchical cluster analysis grouped SCC and actinic keratosis cases exclusively together in support of their common origin and malignant phenotype. BCC cases were also clustered fully together. Differentially expressed proteins reflect the distinct pathobiology of skin carcinoma subtypes and can serve as surrogate markers in doubtful cases.
Subject(s)
Carcinoma, Basal Cell/metabolism , Carcinoma, Squamous Cell/metabolism , Gene Expression Profiling , Gene Expression Regulation, Neoplastic , Skin Neoplasms/metabolism , Adult , Aged , Aged, 80 and over , Apoptosis , Biopsy , Caspase 8/metabolism , Caspase 9/metabolism , Cluster Analysis , Collagen/metabolism , Connexin 43/metabolism , ErbB Receptors/metabolism , Female , Humans , Male , Middle Aged , Oligonucleotide Array Sequence Analysis , Phenotype , Skin/metabolismABSTRACT
The 180 kDa transmembrane collagen XVII is known to anchor undifferentiated keratinocytes to the basement membrane in hemidesmosomes while constitutively shedding a 120 kDa ectodomain. Inherited mutations or auto-antibodies targeting collagen XVII cause blistering skin disease. Collagen XVII is down-regulated in mature keratinocytes but re-expressed in skin cancer. By recently detecting collagen XVII in melanocyte hyperplasia, here we tested its expression in benign and malignant melanocytic tumors using endodomain and ectodomain selective antibodies. We found the full-length collagen XVII protein in proliferating tissue melanocytes, basal keratinocytes and squamous cell carcinoma whereas resting melanocytes were negative. Furthermore, the cell-residual 60 kDa endodomain was exclusively detected in 62/79 primary and 15/18 metastatic melanomas, 8/9 melanoma cell lines, HT199 metastatic melanoma xenografts and atypical nests in 8/63 dysplastic nevi. The rest of 19 nevi including common, blue and Spitz subtypes were also negative. In line with the defective ectodomain, sequencing of COL17A1 gene revealed aberrations in the ectodomain coding region including point mutations. Collagen XVII immunoreaction-stained spindle cell melanomas, showed partly overlapping profiles with those of S100B, Melan A and HMB45. It was concentrated at vertical melanoma fronts and statistically associated with invasive phenotype. Antibody targeting the extracellular aa507-529 terminus of collagen XVII endodomain promoted apoptosis and cell adhesion, while inhibiting proliferation in HT199 cells. These results suggest that the accumulation of collagen XVII endodomain in melanocytic tumors is associated with malignant transformation to be a potential marker of malignancy and a target for antibody-induced melanoma apoptosis.
Subject(s)
Apoptosis/physiology , Autoantigens/genetics , Autoantigens/metabolism , Gene Expression Regulation, Neoplastic , Keratinocytes/pathology , Melanocytes/metabolism , Melanoma/metabolism , Non-Fibrillar Collagens/genetics , Non-Fibrillar Collagens/metabolism , Adolescent , Adult , Aged , Aged, 80 and over , Antibodies/metabolism , Blotting, Western , Cell Line, Tumor , Female , Humans , Hyperplasia/metabolism , Immunohistochemistry , Male , Melanocytes/cytology , Melanocytes/pathology , Melanoma/pathology , Middle Aged , Polymerase Chain Reaction , Collagen Type XVIIABSTRACT
Skin cancer incidence has increased exponentially over the last three decades. In 2008 skin cancer caused 2280 deaths in the UK, with 2067 due to malignant melanoma. Early diagnosis can prevent mortality, however, conventional treatment requires multiple procedures and increasing treatment times. Second harmonic generation (SHG) imaging could offer diagnosis and demarcation of melanoma borders non-invasively at presentation thereby short-cutting the excision biopsy stage. To test the efficacy and accuracy of SHG imaging of collagen in skin and to delineate the borders of skin cancers, unstained human melanoma biopsy sections were imaged using SHG microscopy. Comparisons with sister sections, stained with H&E or Melan-A were made for correlation of invasion borders. Fresh ex vivo normal human and rat skin was imaged through its whole thickness using SHG to demonstrate this technique is transferable to in vivo tissues. SHG imaging demonstrated detailed collagen distribution in normal skin, with total absence of SHG signal (fibrillar collagen) within the melanoma-invaded tissue. The presence or absence of signal changes dramatically at the borders of the melanoma, accurately demarcating the edges that strongly correlated with H&E and Melan-A defined borders (p<0.002). SHG imaging of ex vivo human and rat skin demonstrated collagen architecture could be imaged through the full thickness of the skin. We propose that SHG imaging could be used for diagnosis and accurate demarcation of melanoma borders on presentation and therefore potentially reduce mortality rates.
Subject(s)
Calcitriol/analogs & derivatives , Calcitriol/adverse effects , Dermatologic Agents/adverse effects , Hyperpigmentation/chemically induced , Psoriasis/drug therapy , Humans , Male , Melanoma/complications , Melanoma/therapy , Middle Aged , Psoriasis/complications , Skin Neoplasms/complications , Skin Neoplasms/therapyABSTRACT
Primary lymphoedema associated with chylous reflux is a very rare clinical entity. We report a 3-year-old girl with unilateral lymphoedema, xanthomatosis and vaginal lymphorrhoea. Biopsy also revealed intestinal lymphangiectasia. This paper also presents a brief review of the literature and draws attention to the significance of the xanthomatous eruption in the diagnosis of a chylous reflux.
Subject(s)
Diseases in Twins , Lymphangiectasis, Intestinal/complications , Lymphedema/complications , Vaginal Discharge/complications , Xanthomatosis/complications , Child, Preschool , Female , Humans , Lymphangiectasis, Intestinal/diagnosis , Lymphedema/diagnosis , Lymphocytes , Toes , Vaginal Discharge/diagnosis , Xanthomatosis/diagnosisABSTRACT
Scleromyxedema is a sclerotic variant of papular mucinosis, in which lichenoid papules and scleroderma-like features are present. We describe a patient with scleromyxedema with IgG type lambda chain paraprotein, a systemic sclerosis-like illness, and myositis. The patient's serum contained Scl 70 antibodies, characteristic of scleroderma. Electromyography showed signs of acute myositis and the creatine phosphokinase (CPK) level was elevated. Multiply passaged fibroblasts from the patient's skin lesions showed altered growth response in vitro. The patient was treated with cyclosporin (4 mg/kg/day) with improvement.
Subject(s)
Mucinoses , Cyclosporine/therapeutic use , Fibroblasts/pathology , Humans , Immunoglobulin G/analysis , Male , Middle Aged , Mucinoses/drug therapy , Mucinoses/immunology , Mucinoses/pathology , Myositis/complications , Paraproteins/analysis , Scleroderma, Systemic/pathology , Skin/pathologySubject(s)
Dermatomyositis/complications , Panniculitis/etiology , Female , Humans , Middle Aged , PrognosisABSTRACT
A 7-year-old girl with generalized erythematous, scaling plaques and vesiculobullous lesions on the extremities was diagnosed as having pemphigus foliaceus. Lesional direct immunofluorescence revealed intercellular IgG, IgA and C3 deposition. The patient's serum gave positive reactions against one epitope of desmoglein 3 and the epitope of desmoglein 1 in enzyme-linked immunosorbent assays, but the blood sample for indirect immunofluorescence did not display any circulating antibodies. The patient was successfully treated systemically with prednisolone and dapsone. Currently, she is taking dapsone, 12.5 mg daily. She has been free of lesions for the last 3 years.
Subject(s)
Autoimmune Diseases/pathology , Pemphigus/pathology , Anti-Inflammatory Agents, Non-Steroidal/therapeutic use , Autoimmune Diseases/drug therapy , Autoimmune Diseases/immunology , Child , Dapsone/therapeutic use , Female , Fluorescent Antibody Technique, Direct , Glucocorticoids/therapeutic use , Humans , Pemphigus/drug therapy , Pemphigus/immunology , Prednisolone/therapeutic useABSTRACT
A 43-year-old woman developed annular and pustular cutaneous lesions preceded by tiny yellow pustules coating the surface of the oral mucosa. The clinical, histological and immunopathological evidence clearly showed that the patient had pyodermatitis-pyostomatitis vegetans. It is suggested that this disease is a distinct entity which should be differentiated from pemphigus vegetans.
Subject(s)
Pyoderma/pathology , Stomatitis/pathology , Diagnosis, Differential , Female , Humans , Middle Aged , Pemphigus/diagnosis , Pyoderma/diagnosis , Stomatitis/diagnosisABSTRACT
During the last 10 years (1981-1990) 14,178 skin tumors were histologically examined in the Department of Dermatology of the University Medical School of Szeged. Of these lesions 520 were diagnosed clinically and histologically as malignant melanoma (true-positive). 104 lesions were clinically diagnosed as malignant melanoma but were found histologically to be other tumors (false-positive). An additional 78 cases diagnosed clinically as other than malignant melanomas, were found histologically to be malignant melanoma (false-negative). The clinical diagnostic accuracy was 74.07%. The index of suspicion was 104.34%, thus demonstrating a slight degree of "overdiagnosis". The sensitivity, specificity and predictive values were consonant with those of the literature.
Subject(s)
Melanoma/diagnosis , Skin Neoplasms/diagnosis , Carcinoma, Basal Cell/diagnosis , Carcinoma, Basal Cell/pathology , Diagnosis, Differential , False Positive Reactions , Humans , Melanoma/pathology , Nevus/diagnosis , Nevus/pathology , Predictive Value of Tests , Reproducibility of Results , Sarcoma, Kaposi/diagnosis , Sarcoma, Kaposi/pathology , Skin Neoplasms/pathologyABSTRACT
The authors present the case of a thirty-six-year-old woman with systemic lupus erythematosus with specific vesiculobullous symptoms. Degos dermal infarcts and Schönlein-Henoch-type purpura was observed in the course of her illness. Attention is drawn to the rarity of this symptom group, which has not been documented in previous publications. Degos lesions accompanying the systemic lupus erythematosus were benign. The effectiveness of sulfone in the treatment of vesiculobullous symptoms in this case is noted.
Subject(s)
IgA Vasculitis/complications , Lupus Erythematosus, Systemic/complications , Pigmentation Disorders/complications , Skin Diseases, Papulosquamous/complications , Skin Diseases, Vesiculobullous/complications , Adult , Female , Humans , IgA Vasculitis/pathology , Lupus Erythematosus, Systemic/pathology , Pigmentation Disorders/pathology , Skin Diseases, Papulosquamous/pathology , Skin Diseases, Vesiculobullous/pathologyABSTRACT
Ninety two patients suffering from porphyria cutanea tarda were examined ophthalmologically in a paired case-control study. The incidence of pinguecula and that of pterygium were 8 times and 2 times higher, respectively, in PCT patients that in the control group. The photodamage of the conjunctiva is presumed to be a result of the photoactivity of uroporphyrin in the tissues.
Subject(s)
Eye Diseases/etiology , Photosensitivity Disorders/etiology , Porphyria Cutanea Tarda/complications , Conjunctiva/pathology , Cornea/physiopathology , Eye/radiation effects , Female , Humans , Male , Porphyria Cutanea Tarda/urine , Porphyrins/urine , Sunlight , Ultraviolet Rays/adverse effectsABSTRACT
Ninety two patients with porphyria cutanea tarda (PCT) were examined ophthalmically in a paired case control study. The incidence of pinguecula and of pterygium was 8 and 2 times higher respectively, in PCT patients than in the control group. The photodamage to the conjunctiva is considered to be a result of the photoactivity of uroporphyrin in the tissues.
Subject(s)
Conjunctiva/radiation effects , Porphyria Cutanea Tarda/complications , Sunlight/adverse effects , Case-Control Studies , Conjunctiva/pathology , Conjunctivitis/etiology , Conjunctivitis/pathology , Female , Humans , Male , Middle Aged , Pterygium/etiologyABSTRACT
The case history of a patient is reported who was treated with a variety of antiarrhythmics over a period of years because of refractory ventricular "bigeminy". As the arrhythmia did not respond to any kind of therapy, amiodarone treatment was started, which the patient received in a maintenance dose of 600-400 mg/day for 4 years. More recently, a bluish-grey hyperpigmentation of the face and other areas of the skin exposed to sunlight developed. A cutaneous biopsy of the hand revealed pigment deposits and lamellated lysosomal inclusions characteristic for amiodarone dermatopathy. The interactive, computer-assisted analysis of the ventricular ectopic activity has clearly demonstrated its innocent, parasystolic nature. The differentiation between ventricular extrasystolic and parasystolic activity is essential, because the latter arrhythmia does not require specific antiarrhythmic pharmacotherapy.
Subject(s)
Amiodarone/adverse effects , Arrhythmias, Cardiac/diagnosis , Drug Eruptions/etiology , Arrhythmias, Cardiac/drug therapy , Cardiac Complexes, Premature/diagnosis , Cardiac Complexes, Premature/drug therapy , Cyanosis/chemically induced , Diagnostic Errors , Electrocardiography , Female , Humans , Middle Aged , Stroke VolumeABSTRACT
102 family members of 14 patients with primary melanoma and multiple atypical pigmented naevi were investigated. Additionally to 14 patients with melanoma, 31 family members were found to have multiple atypical pigmented naevi. Most of them had light complexion and poor pigmentation capacity. A relative high frequency of malignant tumors other than melanoma were observed among blood relatives without multiple naevi. Members of melanoma-prone families need regular medical surveillance.