ABSTRACT
Psoriasis is a chronic immune-mediated disease that is linked to an increased risk of cancer. Although numerous studies have explored whether neoplasms are concurrent conditions or are induced by psoriasis, a definitive definition remains elusive. In this study, we conducted a comprehensive narrative literature review to offer practical guidance to oncologists and dermatologists regarding the initiation and discontinuation of biologics for psoriasis. The findings indicate that a customized approach is recommended for each patient, and that a history of malignancies does not constitute an absolute contraindication for biologics. Growing evidence supports the treatment of selected patients, emphasizing a nuanced assessment of benefits and risks. There is a lack of data specifying a safe timeframe to initiate biologics following a neoplasm diagnosis due to influences from cancer-related and patient-specific characteristics impacting prognosis. Some patients may continue anti-psoriasis therapy during cancer treatments. Enhanced comprehension of the biological mechanisms in cancer progression and the immune microenvironment of psoriasis holds promise for refining therapeutic strategies. In conclusion, a personalized treatment approach necessitates collaboration between oncologists and dermatologists, considering factors such as cancer prognosis, psoriasis clinical manifestations, patient characteristics, and preferences when making treatment decisions.
Subject(s)
Biological Products , Neoplasms , Psoriasis , Humans , Neoplasms/drug therapy , Psoriasis/drug therapy , Psoriasis/pathology , Biological Products/therapeutic use , Tumor MicroenvironmentABSTRACT
BACKGROUND: Fluorescence-advanced videodermatoscopy (FAV) is a new non-invasive high-resolution skin imaging technique to assess pigmented lesions in conjunction with the clinical examination and dermatoscopy. OBJECTIVES: This is the first prospective study to identify morphologic descriptors and standardized terminology to examine facial pigmented lesions using FAV. The objectives were to identify FAV indicators, which can assist physicians in diagnosing suspicious flat facial pigmented lesions. METHODS: Consecutive equivocal pigmented lesions were retrospective analysed. Histopathological examination was performed for all the lesions. The main cytomorphological and cytoarchitectural FAV features were described and correlated with histopathological characteristics. RESULTS: From January to October 2020, 21 consecutive clinically suspected pigmented lesions in 20 patients were analysed using dermatoscopy and FAV and then surgically excised. Histopathological examination identified lentigo maligna (LM), lentigo maligna melanoma (LMM), solar lentigo (SL), flat seborrheic keratosis (SK) and pigmented actinic keratosis (PAK). Thirteen malignant melanocytic lesions were removed (11 LM, 2 LMM), two were diagnosed as PAK, and the remaining six pigmented lesions were SL-SKs. With FAV, large ovoid pleomorphic and dendritic cells arranged in the intrafollicular disposition, are typical of most malignant melanocytic lesions (12/13, 92.3%). No benign lesions displayed these features. In dermatoscopy, this folliculotropism corresponded to the presence of an annular-granular pattern with slate grey dots that were aggregated asymmetrically around follicular openings. CONCLUSIONS: FAV features can provide an improved diagnostic approach in the differential diagnosis of flat pigmented facial lesions.
Subject(s)
Hutchinson's Melanotic Freckle , Keratosis, Actinic , Lentigo , Skin Neoplasms , Dermoscopy/methods , Diagnosis, Differential , Humans , Hutchinson's Melanotic Freckle/diagnosis , Keratosis, Actinic/pathology , Prospective Studies , Retrospective Studies , Skin Neoplasms/diagnosis , Skin Neoplasms/pathologyABSTRACT
BACKGROUND: Atypical Spitz tumours (ASTs) are regarded as an intermediate category distinguished from prototypical Spitz naevus by presenting one or more atypical features and often by an uncertain malignant potential. Clinical and dermoscopic features may play a relevant role in the diagnostic approach. AIM: To evaluate the clinical and dermoscopic features of ASTs, and their evolution over time. METHODS: This was a descriptive, multicentre study of the clinical and dermoscopic characteristics of ASTs. Data on clinical and dermoscopic characteristics, histopathology, local extension, therapy and follow-up, lymph node staging, complete lymph node dissection, and outcome were collected from the databases of four Italian Dermatology Units for the period 2004-2021. RESULTS: The study population consisted of 99 patients (62 female, 37 male) with a histologically confirmed diagnosis of AST, including age at presentation ranged from 2 to 70 years (mean 28.1 years, median 24 years). Of the 99 patients, 29 (29.3%) underwent sentinel lymph node biopsy, which showed evidence of micrometastases in three cases (10.3%); all three patients underwent complete lymph node dissection with no evidence of further metastasis. Considering the whole study population, the clinical outcome was excellent, as all of the patients have no evidence of recurrence or distant metastasis. The follow-up period ranged from 6 to 216 months (mean 81.6 months, median 78 months). In addition, we collected data on the clinical and dermoscopic features of 26 lesions. The most frequent dermoscopic pattern observed was the multicomponent pattern (34.6%), followed by homogeneous (26.9%) and nonspecific (23.2%). In 66.7% of amelanotic ASTs, we observed glomerular (coiled) vessels uniformly distributed within the entire lesion, without asymmetry. CONCLUSION: The results of our study with a long follow-up show no recurrence or distant metastases, confirming the good clinical outcome, even in the case of sentinel lymph node positivity. From a diagnostic point of view, our series identified a typical dermoscopic picture for amelanotic ASTs, with a glomerular vascular pattern throughout the lesion in the absence of other dermoscopic parameters, making the correct diagnosis possible.
Subject(s)
Nevus, Epithelioid and Spindle Cell , Skin Neoplasms , Adolescent , Adult , Aged , Child , Child, Preschool , Female , Follow-Up Studies , Humans , Lymph Node Excision , Male , Middle Aged , Nevus, Epithelioid and Spindle Cell/diagnosis , Nevus, Epithelioid and Spindle Cell/epidemiology , Nevus, Epithelioid and Spindle Cell/surgery , Sentinel Lymph Node Biopsy , Skin Neoplasms/diagnostic imaging , Skin Neoplasms/epidemiology , Young AdultABSTRACT
Agminated Spitz nevi are an uncommon entity, and their management is challenging due not only the young age of the patients but also the tumor's uncertain malignant potential and the variability in the dermoscopic and clinical presentation. We report a case of a 6-year-old boy with multiple agminated Spitz nevi on a café au lait macule with different atypical clinical patterns and dermoscopic features.
Subject(s)
Nevus, Epithelioid and Spindle Cell , Skin Neoplasms , Cafe-au-Lait Spots , Child , Dermoscopy , Humans , Male , Nevus, Epithelioid and Spindle Cell/diagnosis , Nevus, Epithelioid and Spindle Cell/genetics , Skin Neoplasms/diagnosisABSTRACT
BACKGROUND: Lentigo maligna (LM) and lentigo maligna-melanoma (LMM) are histotypes of melanoma arising in skin with cumulative solar radiation damage. The extension of atypical melanocytes to the hair follicle (folliculotropism) is a histopathological feature of LM/LMM. Its role has not been totally clarified, but it may be correlated to treatment response in LM or to progression in LMM. OBJECTIVE: This retrospective, multicentric study aims to identify dermatoscopic features associated with folliculotropism in LMs/LMMs. PATIENTS AND METHODS: We analyzed cases of head and neck LMs/LMMs diagnosed between 2005-2014 at Melanoma Units, University of Bologna/Modena/Florence/Siena (Italy), Nice (France): 25 LMs and 73 LMMs were included. RESULTS: Grey circles (44 %) indicated an isthmic/bulb level of involvement, which were completely absent in the infundibular LM lesions (P = 0.041). In the group of LMMs, light/dark brown pseudonetwork and light brown structureless areas were an indicator of diffuse distribution of malignant melanocytes in the follicular units (P < 0.001 and P = 0.001, respectively), while grey circles indicated focal or diffuse distribution (P < 0.001). CONCLUSIONS: A better understanding of the extension of malignant melanocytes is helpful, aiding clinicians in their decision to perform a radical excision or obtaining a biopsy in the most invasive area of the lesion, which includes potential folliculotropism.
Subject(s)
Hutchinson's Melanotic Freckle , Melanoma , Skin Neoplasms , Humans , Italy , Retrospective StudiesABSTRACT
First reported in 2006, eccrine angiokeratomatous hamartoma is a very rare vascular malformation of the skin, with only few described cases. It has a peculiar histopathology with features deriving from the combination of two different vascular malformations of the skin: solitary angiokeratoma and eccrine angiomatous hamartoma. In the past, other authors described similar hamartomatous lesions with features deriving from verrucous venous malformation and eccrine angiomatous hamartoma. We believe that these lesions are clearly overlapping from clinical, histopathological, and immunohistochemical points of view and the term "eccrine angiokeratomatous hamartoma" should be used to indicate the whole spectrum of these lesions as suggested by Kanitakis et al. Herein we present two cases of this rare vascular hamartoma, with clinical, histopathological and immunohistochemical characterization. In addition, for the first time we report a complete and detailed review of the literature to clarify the clinical, epidemiological, and histopathological features of this unique entity.
Subject(s)
Angiokeratoma/pathology , Eccrine Glands/pathology , Hamartoma/pathology , Skin/blood supply , Adolescent , Adult , Angiokeratoma/metabolism , Angiokeratoma/ultrastructure , Child , Diagnosis, Differential , Female , Hamartoma/metabolism , Hamartoma/surgery , Hamartoma/ultrastructure , Humans , Infant , Male , Middle Aged , Platelet Endothelial Cell Adhesion Molecule-1/metabolism , Skin/pathology , Skin Neoplasms/pathology , Vascular Diseases/pathology , Vascular Malformations/pathologyABSTRACT
Electrochemotherapy (ECT) is a well-known nonconventional skin cancer ablative method that was shown to be safe and effective for treating both locoregional disease spreading and disseminated cutaneous and subcutaneous lesions from different types of cancer. The most common medications used are bleomycin and cisplatin. In the last years many studies were performed on ECT, lead it to be a valid therapeutic option in many international guidelines. Nevertheless, there are still no clear indications regarding timing of its use. The main aim of this study was first to assess the safety and effectiveness of intralesional cisplatin ECT for treating different types of nonmelanoma skin cancer in a group of eligible patients. The second endpoint was to assess patients' tolerability and symptoms improvement through the treatment. A single-center prospective study was performed. Patients with squamous cell carcinoma, basal cell carcinoma, or skin metastases were selected during 1 month. The ideal setting was the presence of two or three lesions with a maximum diameter of 2 cm. Both primary, recurrent, and metastatic lesions were included. Before and 8 weeks after treatment, all patients were evaluated to assess the number, measurement, and anatomical site of skin lesions using photography and metric notation. The medical device for membrane electroporation was the CLINIPORATOR EPS02 model. The cisplatin concentration was at least 1 mg/mL. The dose for each single lesion was calculated based on its volume, as is the standard procedure for ECT. Local or systemic adverse events and changes in symptoms were evaluated with a questionnaire based on a visual analog scale that was administrated before and after ECT. Eight patients with a total of 18 lesions underwent the procedure (six men and two women). Four out of eight (50%) patients had a complete response to the treatment. However, all eight patients had an overall tumor response (100%), experiencing an improvement in symptoms including less pain and bleeding from the tumor. Our study clearly show that ECT with intralesional cisplatin is a valuable and safety procedure for nonmelanoma skin cancer and cutaneous tumor metastasis. ECT with cisplatin was able to achieve a good local disease control leading to complete response in an half of cases. The results were stable after 1 year of follow-up. The outer ear area displayed a really good response, due to both ear's anatomical configuration and intralesional cisplatin pharmacological characteristics.
Subject(s)
Electrochemotherapy , Skin Neoplasms , Bleomycin/adverse effects , Cisplatin/adverse effects , Electrochemotherapy/adverse effects , Female , Humans , Male , Prospective Studies , Skin Neoplasms/drug therapy , Treatment OutcomeABSTRACT
Despite of the emerging new systemic and local oncologic treatments (immunotherapy and checkpoint inhibitors, oncolytic viral treatments and injected immunostimulants) the management of skin melanoma metastasis can be still challenging. The main aim of this review was to assess the efficacy and the role of imiquimod in local metastatic melanoma disease. An extensive literature review was performed from September 2000 to March 2020 using PubMed, MEDLINE, Embase, and Cochrane Library databases. Selected articles regarded topical imiquimod, its mode of action as an antitumoral agent and its applications in melanoma metastases treatment. We analyzed a total of 18 published article of clinical cases and small case series and five studies: two retrospective large case series, two Phase I and II clinical trials and one cohort non randomized study. Generally, the treatment is safe and well tolerated. Imiquimod lead to an unstable locoregional control. The use of topical imiquimod for the treatment of MM cutaneous metastases should be considered in selected cases and in palliative settings.
Subject(s)
Antineoplastic Agents , Melanoma , Skin Neoplasms , Administration, Topical , Aminoquinolines/adverse effects , Antineoplastic Agents/adverse effects , Humans , Imiquimod/adverse effects , Melanoma/drug therapy , Retrospective Studies , Skin Neoplasms/drug therapyABSTRACT
BACKGROUND/OBJECTIVES: Primary cutaneous apocrine carcinoma is a rare malignant adnexal skin tumour that can recur locally, spread to regional lymph nodes and metastatize to visceral organs. Wide dissemination and death from disease are much less common. The axilla is the most common site of presentation. It is infrequently reported in the head and neck region. METHODS: All cases diagnosed as primary cutaneous apocrine carcinoma of the head and neck were retrospectively collected from the archives of the Division of Pathological Anatomy, University of Florence from 1996 to 2016. There was no history or clinical evidence of breast cancer. Clinical data and follow-up were collected by the clinicians. RESULTS: Nine cases were found, with a mean age of 76 years, ranging in size between 0.3 and 3.5 cm. Clinically, they were frequently mistaken for basal cell carcinomas. Histopathologically, all the tumours showed decapitation secretion, a tubular, solid or mixed (tubulo-papillary and solid-tubular) growth pattern and were predominantly classified as grade 2 tumours. GCDFP-15 and hormone receptors were variably expressed. HER2 and podoplanin were negative in all cases. In one case, spreading to regional lymph nodes was observed. No cases were associated with death due to the disease. CONCLUSION: As immunohistochemical analysis lacks specificity in distinguishing primary cutaneous apocrine carcinoma from a cutaneous metastasis of breast carcinoma, detailed clinical history, breast examination, adequate treatment and follow-up are necessary to confirm a diagnosis of primary cutaneous apocrine carcinoma.
Subject(s)
Adenocarcinoma/pathology , Apocrine Glands/pathology , Carcinoma, Skin Appendage/pathology , Head and Neck Neoplasms/pathology , Skin Neoplasms/pathology , Aged , Female , Humans , Immunohistochemistry , Retrospective StudiesABSTRACT
Basal cell carcinoma (BCC) is the most common type of carcinoma worldwide. BCC development is the result of a complex interaction between environmental, phenotypic and genetic factors. However, despite the progress in the field, BCC biology and mechanisms of resistance against systemic treatments have been poorly investigated. The aim of the present review is to provide a revision of BCC histological and molecular features, including microRNA (miRNA) dysregulation, with a specific focus on the molecular basis of BCC systemic therapies. Papers from the last ten years regarding BCC genetic and phenotypic alterations, as well as the mechanism of resistance against hedgehog pathway inhibitors vismodegib and sonidegib were included. The involvement of miRNAs in BCC resistance to systemic therapies is emerging as a new field of knowledge.
Subject(s)
Carcinoma, Basal Cell/drug therapy , Drug Resistance, Neoplasm/genetics , Hedgehog Proteins/genetics , MicroRNAs/genetics , Anilides/therapeutic use , Biphenyl Compounds/therapeutic use , Carcinoma, Basal Cell/genetics , Carcinoma, Basal Cell/pathology , Hedgehog Proteins/antagonists & inhibitors , Humans , Pyridines/therapeutic useABSTRACT
Metastatic skin lesions of gastric cancers usually appear as nonspecific, firm, and hyperpigmented nodules. However, they occasionally present as unusual skin manifestations that mimic other skin disorders. We describe a case of multiple cutaneous metastases from gastric cancer resembling sebaceous cysts with a synchronous melanoma, in a patient after fluoropyrimidine-based systemic chemotherapy. Melanoma occurring as a second cancer has been recognized in patients having undergone previous chemotherapy or radiation for another cancer. We can assume that the capecitabine-based chemotherapy may have played a role in the development of the melanocytic neoplasm. Our observation adds extra evidence to the link between fluoropyrimidine-based immunosuppression and the induction of melanocytes' proliferation and transformation. For these reasons, it is advisable to require dermatological checkups for patients undergoing chemotherapy treatments in order to identify suspicious melanocytic lesions as soon as possible.
Subject(s)
Fluorouracil/therapeutic use , Melanoma/secondary , Skin Neoplasms/secondary , Stomach Neoplasms/drug therapy , Stomach Neoplasms/pathology , Subcutaneous Tissue/pathology , Administration, Oral , Antimetabolites, Antineoplastic/therapeutic use , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Fluorouracil/administration & dosage , Humans , Male , Melanoma/pathology , Middle Aged , Positron Emission Tomography Computed Tomography , Postoperative Complications/etiology , Prodrugs/administration & dosage , Skin Neoplasms/pathology , Stomach Neoplasms/surgery , Melanoma, Cutaneous MalignantABSTRACT
Antibodies directed against programmed death receptor 1 emerged as beneficial immune-checkpoint inhibitor therapy in many different types of cancer. However, programmed death receptor 1 is critical in promoting self-tolerance and the most common toxicities of checkpoint inhibitors are immune-related adverse events. We present a 48-year-old woman affected by metastatic uveal melanoma treated with nivolumab (3 mg/kg every 2 weeks). The patient had no previous history of autoimmune disease or dermatologic conditions. At the fourth month of treatment, on cutaneous examination, she presented multiple whitish vitiligo-like patches on the trunk, axillae, hands and face. Diagnosis of melanoma-associated leukoderma vitiliginous reaction was made. Over the following months, the melanoma-associated leukoderma lesions slowly progressed with cigarette paper-like appearance and indurated texture. A skin biopsy leaded the diagnosis of extragenital lichen sclerosus. To the best of our knowledge, this is the first reported case of extragenital lichen sclerosus on previous melanoma-associated leukoderma lesions related to nivolumab monotherapy. The increase in clinical experience with anti programmed death receptor 1 enhances the knowledge about adverse effects associated with these immunotherapies and allows to compare therapeutic strategies.
Subject(s)
Antineoplastic Agents, Immunological/adverse effects , Antineoplastic Agents, Immunological/therapeutic use , Lichen Sclerosus et Atrophicus/chemically induced , Melanoma/drug therapy , Nivolumab/adverse effects , Nivolumab/therapeutic use , Skin/drug effects , Uveal Neoplasms/drug therapy , Female , Humans , Middle AgedABSTRACT
Fluorescence advanced videodermatoscopy (FAV) has been proposed recently to be a new, noninvasive method for in vivo skin examination at high magnification. The working principle underlying FAV relates to the ability of endogenous molecules to absorb specific wavelengths and emit fluorescence. Herein we report our experience with FAV in the study of active, non-segmental vitiligo treated with narrowband UVB. Our findings indicate that FAV has the potential for application in the clinical follow-up, disease prognosis, and therapeutic monitoring of vitiligo.
Subject(s)
Dermoscopy/methods , Microscopy, Video/methods , Vitiligo/diagnosis , Dermoscopy/instrumentation , Humans , Microscopy, Fluorescence/methods , Prognosis , Ultraviolet Therapy/methods , Vitiligo/pathology , Vitiligo/radiotherapyABSTRACT
BACKGROUND/OBJECTIVES: Little is known about the dermoscopic features of atypical fibroxanthoma. METHODS: This was a case-control study. Atypical fibroxanthoma lesions were compared with a control group with non-melanoma skin cancer. RESULTS: Altogether 40 atypical fibroxanthoma were collected. Most developed in men (93%), appearing mainly as nodular (63%), amelanotic (93%) and ulcerated (78%) lesions. Most lesions were located on the scalp (55%) and the ears (13%). Dermoscopically, most atypical fibroxanthoma displayed red (83%) and white (70%) structureless areas and irregular linear vessels (43%). A series of features achieved statistical significance when comparing atypical fibroxanthoma with non-melanoma skin cancer. The presence of red and white structureless areas and white lines, and the absence of yellowish-white opaque scales, hairpin vessels and arborising vessels were predictive of atypical fibroxanthoma in univariate analysis. However, when squamous cell carcinoma was excluded from the analysis, none of the criteria achieved statistical significance. When basal cell carcinoma was excluded, three variables achieved statistical significance in predicting atypical fibroxanthoma: red, structureless areas, the absence of opaque yellowish-white scales and absence of white circles. CONCLUSIONS: Atypical fibroxanthomas seem to be barely distinguishable from basal cell carcinoma dermoscopically, but they are more easily distinguishable from a well to moderately differentiated squamous cell carcinoma. A histopathological examination is needed for the final diagnosis.
Subject(s)
Carcinoma, Basal Cell/diagnostic imaging , Carcinoma, Squamous Cell/diagnostic imaging , Dermoscopy , Fibroma/diagnostic imaging , Head and Neck Neoplasms/diagnostic imaging , Skin Neoplasms/diagnostic imaging , Xanthomatosis/diagnostic imaging , Aged , Aged, 80 and over , Case-Control Studies , Female , Fibroma/pathology , Head and Neck Neoplasms/pathology , Humans , Male , Societies, Medical , Xanthomatosis/pathologyABSTRACT
BACKGROUND: Lichenoid keratosis is a benign cutaneous lesion exhibiting many clinical faces and different dermoscopic features. OBJECTIVE: This study aims to determine the pattern of different clinical subtypes of lichenoid keratosis and to establish whether there is any correlation between the clinical variants of lichenoid keratosis and their dermoscopic appearance. METHODS: We retrospectively analyzed the medical records and clinical database of patients who had received a histological diagnosis of lichenoid keratosis. Based on the literature review and the clinical-dermoscopic features of lichenoid keratosis, we divided the lesions into 6 clinical subtypes to evaluate potential correlations between clinical and dermoscopic features in all subtypes. RESULTS: Fifty-one lesions were included in this clinical study. Preoperatively, only 1.9% of cases were clinically diagnosed as lichenoid keratosis, and the most common misdiagnosis was basal cell carcinoma (52.9%). We identified 6 subtypes of lichenoid keratosis and their corresponding dermoscopic features and clues. CONCLUSION: Since lichenoid keratosis has no pathognomonic dermoscopic clues and it is commonly misdiagnosed as malignant skin neoplasms, such as basal cell carcinoma and melanoma, improving the knowledge of both clinical and dermoscopic variability of lichenoid keratosis may help dermatologists to reduce unnecessary surgery and to reduce health care spending.
Subject(s)
Keratosis , Lichenoid Eruptions , Adult , Aged , Aged, 80 and over , Dermoscopy , Female , Humans , Keratosis/diagnosis , Keratosis/epidemiology , Keratosis/pathology , Lichenoid Eruptions/diagnosis , Lichenoid Eruptions/epidemiology , Lichenoid Eruptions/pathology , Male , Middle Aged , Retrospective Studies , Young AdultSubject(s)
Antineoplastic Agents , Carcinoma, Basal Cell , Hydroxymethylglutaryl-CoA Reductase Inhibitors , Skin Neoplasms , Anilides/therapeutic use , Antineoplastic Agents/therapeutic use , Carcinoma, Basal Cell/drug therapy , Hedgehog Proteins/metabolism , Hedgehog Proteins/therapeutic use , Humans , Hydroxymethylglutaryl-CoA Reductase Inhibitors/therapeutic use , Skin Neoplasms/drug therapy , Skin Neoplasms/metabolismABSTRACT
Systemic mastocytosis is a rare heterogeneous myeloproliferative neoplasm characterized by abnormal proliferation and activation of mast cells. We describe a large multicentre series of 460 adult patients with systemic mastocytosis, with a diagnosis based on WHO 2008 criteria, in a "real-life" setting of ten Italian centers with dedicated multidisciplinary programs. We included indolent forms with (n = 255) and without (n = 165) skin lesions, smouldering (n = 20), aggressive (n = 28), associated with other hematological diseases mastocytosis (n = 21) and mast cell leukemia (n = 1). This series was uniquely characterized by a substantial proportion of patients with low burden of neoplastic mast cells; notably, 38% of cases were diagnosed using only minor diagnostic criteria according to WHO 2008 classification, underlying the feasibility of early diagnosis where all diagnostic approaches are made available. This has particular clinical relevance for prevention of anaphylaxis manifestations, that were typically associated with indolent forms. In multivariate analysis, the most important features associated with shortened overall survival were disease subtype and age at diagnosis >60 years. Disease progression was correlated with mastocytosis subtype and thrombocytopenia. As many as 32% of patients with aggressive mastocytosis suffered from early evolution into acute leukemia. Overall, this study provides novel information about diagnostic approaches and current presentation of patients with SM and underlines the importance of networks and specialized centers to facilitate early diagnosis and prevent disease-associated manifestations. Am. J. Hematol. 91:692-699, 2016. © 2016 Wiley Periodicals, Inc.