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Presents cases of multiple minute digitate hyperkeratosis, a chronic disorder of keratinization. Types of the disease; Familial variant of the disease with autosomal dominant inheritance; Sporadic variant of the disease; Clinical appearance and histopathology of the disease.

Background: Previous investigations pointed out a role for antigen stimulation in Sezary syndrome (SS). High-throughput sequencing of the T cell receptor (TR) offers several applications beyond diagnostic purposes, including the study of T cell pathogenesis., Methods: We performed high-throughput RNA sequencing of the TR alpha (TRA) and beta (TRB) genes focusing on the complementarity-determining region 3 (CDR3) in 11 SS and one erythrodermic mycosis fungoides (MF) patients. Five psoriasis patients were employed as controls. Peripheral blood CD4 + cells were isolated and RNA sequenced (HiSeq2500). High-resolution HLA typing was performed in neoplastic patients., Results: Highly expanded predominant TRA and TRB CDR3 were only found in SS patients (median frequency: 94.4% and 93.7%). No remarkable CDR3 expansions were observed in psoriasis patients (median frequency of predominant TRA and TRB CDR3: 0.87% and 0.69%, p < 0.001 compared to SS). CDR3 almost identical to the predominant were identified within each SS patient and were exponentially correlated with frequencies of the predominant CDR3 (R 2  = 0.918, p < 0.001). Forty-six different CDR3 were shared between SS patients displaying HLA similarities, including predominant TRA and TRB CDR3 in one patient that were found in other three patients. Additionally, 351 antigen matches were detected (Cytomegalovirus, Epstein-Barr, Influenza virus, and self-antigens), and the predominant CDR3 of two different SS patients matched CDR3 with specificity for Influenza and Epstein-Barr viruses., Conclusions: Besides detecting clonality, these findings shed light on the nature of SS-related antigens, pointing to RNA sequencing as a useful tool for simultaneous clonality and biological analysis in SS., (© 2023 The Authors. Journal of Clinical Laboratory Analysis published by Wiley Periodicals LLC.)

Background and Objective: Primary cutaneous lymphomas (PCL) are uncommon. Observations based on the first year of data from the Spanish Registry of Primary Cutaneous Lymphomas (RELCP, in its Spanish abbreviation) of the Spanish Academy of Dermatology and Venereology (AEDV) were published in February 2018. This report covers RELCP data for the first 5 years., Patients and Methods: RELCP data were collected prospectively and included diagnosis, treatments, tests, and the current status of patients. We compiled descriptive statistics of the data registered during the first 5 years., Results: Information on 2020 patients treated at 33 Spanish hospitals had been included in the RELCP by December 2021. Fifty-nine percent of the patients were men; the mean age was 62.2 years. The lymphomas were grouped into 4 large diagnostic categories: mycosis fungoides/Sézary syndrome, 1112 patients (55%); primary B-cell cutaneous lymphoma, 547 patients (27.1%); primary CD30+lymphoproliferative disorders, 222 patients (11%), and other T-cell lymphomas, 116 patients (5.8%). Nearly 75% of the tumors were registered in stage I. After treatment, 43.5% achieved complete remission and 27% were stable at the time of writing. Treatments prescribed were topical corticosteroids (1369 [67.8%]), phototherapy (890 patients [44.1%]), surgery (412 patients [20.4%]), and radiotherapy (384 patients [19%])., Conclusion: The characteristics of cutaneous lymphomas in Spain are similar to those reported for other series. The large size of the RELCP registry at 5 years has allowed us to give more precise descriptive statistics than in the first year. This registry facilitates the clinical research of the AEDV's lymphoma interest group, which has already published articles based on the RELCP data., (Copyright © 2022 AEDV. Publicado por Elsevier España, S.L.U. All rights reserved.)

Background: Brentuximab vedotin (BV) has been approved for CD30-expressing cutaneous T-cell lymphoma (CTCL) after at least one previous systemic treatment. However, real clinical practice is still limited., Objectives: To evaluate the response and tolerance of BV in a cohort of patients with CTCL., Methods: We analysed CTCL patients treated with BV from the Spanish Primary Cutaneous Lymphoma Registry (RELCP)., Results: Sixty-seven patients were included. There were 26 females and the mean age at diagnosis was 59 years. Forty-eight were mycosis fungoides (MF), 7 Sézary syndrome (SS) and 12 CD30+ lymphoproliferative disorders (CD30 LPD). Mean follow-up was 18 months. Thirty patients (45%) showed at least 10% of CD30+ cells among the total lymphocytic infiltrate. The median number of BV infusions received was 7. The overall response rate (ORR) was 67% (63% in MF, 71% in SS and 84% in CD30 LPD). Ten of 14 patients with folliculotropic MF (FMF) achieved complete or partial response (ORR 71%). The median time to response was 2.8 months. During follow-up, 36 cases (54%) experienced cutaneous relapse or progression. The median progression free survival (PFS) was 10.3 months. The most frequent adverse event was peripheral neuropathy (PN) (57%), in most patients (85%), grades 1 or 2., Conclusions: These results confirm the efficacy and safety of BV in patients with advanced-stage MF, and CD30 LPD. In addition, patients with FMF and SS also showed a favourable response. Our data suggest that BV retreatment is effective in a proportion of cases., (© 2022 European Academy of Dermatology and Venereology.)

Background: Reliable prognostic factors for patients with primary cutaneous anaplastic large cell lymphoma (PCALCL) are lacking., Objective: To identify prognostic factors for specific survival in patients with PCALCL., Methods: Using the convenience sampling method, patients with PCALCL diagnosed from May 1986 to August 2017 in 16 University Departments were retrospectively reviewed., Results: One hundred eight patients were included (57 males). Median age at diagnosis was 58 years. All of them showed T1-3N0M0 stages. Seventy per cent of the cases presented with a solitary lesion, mostly at the limbs. Complete response rate after first-line treatment was 87%, and no advantage was observed for any of them (surgery, radiotherapy, chemotherapy or other approaches). Nodal and visceral progression rate was 11% and 2%, respectively. 5-year specific survival (SSV) reached 93%; 97% for T1 patients and 84% for T2/T3 patients (P = 0.031). Five-year SSV for patients developing early cutaneous relapse was 64%; for those with late or no relapse, 96% (P = 0.001). Estimated median SSV for patients showing nodal progression was 103 months (95% CI: 51-155 months); for patients without nodal progression, estimated SSV did not reach the median (P < 0.001). Nodal progression was an independent predictive parameter for shorter survival (P = 0.011)., Conclusion: Multiple cutaneous lesions at presentation, early skin relapse and nodal progression portrait worse prognosis in patients with PCALCL., (© 2019 European Academy of Dermatology and Venereology.)

Background: Data regarding response to treatment in lymphomatoid papulosis (LyP) are scarce., Aim: To assess the daily clinical practice approach to LyP and the response to first-line treatments., Methods: This was a retrospective study enrolling 252 patients with LyP., Results: Topical steroids, methotrexate and phototherapy were the most common first-line treatments, prescribed for 35%, 20% and 14% of the patients, respectively. Complete response (CR) was achieved in 48% of treated patients. Eczematous lesions significantly increased relative risk (RR) of not achieving CR (RR = 1.76; 95% CI 1.16-2.11). Overall median time to CR was 10 months (95% CI 6-13 months), and 78% of complete responders showed cutaneous relapse; both results were similar for all treatment groups (P > 0.05). Overall estimated median disease-free survival (DFS) was 11 months (95% CI 9-13 months) but DFS for patients treated with phototherapy was 23 months (95% CI 10-36 months; P < 0.03). Having the Type A LyP variant (RR = 2.04; 95% CI 0.96-4.30) and receiving a first-line treatment other than phototherapy (RR = 5.33; 95% CI 0.84-33.89) were significantly associated with cutaneous early relapse. Of the 252 patients, 31 (13%) had associated mycosis fungoides unrelated to therapeutic approach, type of LyP or T-cell receptor clonality., Conclusions: Current epidemiological, clinical and pathological data support previous results. Topical steroids, phototherapy and methotrexate are the most frequently prescribed first-line treatments. Although CR and cutaneous relapse rates do not differ between them, phototherapy achieves a longer DFS. Presence of Type A LyP and use of topical steroid or methotrexate were associated with an increased risk of early relapse., (© 2017 British Association of Dermatologists.)

Background: Extranodal natural killer/T-cell lymphoma, nasal type (ENKTL) is an aggressive lymphoma with a very low incidence in western populations., Objective: To review the clinicopathological features and outcome of a multicentre series of ENKTL in Spain., Materials & Methods: A multicentre retrospective study was performed based on cases of ENKTL, collected from 1995 to 2004, from 12 dermatology departments included in the Spanish Lymphoma Study Group. The clinical, histopathological, and evolutive features of all these cases were reviewed., Results: Eighteen patients (three male, 15 female) with median age of 67 years were included in the study. The onset of lesions occurred in the nasal region in 11 patients and on the skin outside this region in the remaining cases. The observed lesions were clinically heterogeneous, corresponding to papules, plaques, and nodules, with or without ulceration. All patients except four received different polychemotherapy regimens, either alone (n = 11) or in combination with radiotherapy (n = 4). After a variable follow-up period (1-36 months), only two patients remained alive. One patient was recently diagnosed (four months ago) with ENKTL in the nasal region and the other presented with skin-limited disease. The median overall survival was 9.5 months., Conclusions: The results of this retrospective survey confirm that ENKTL is a rare subtype of lymphoma in the Spanish population. All patients showed an aggressive clinical course and poor prognosis, regardless of the initial clinical presentation. Prospective data on larger series of patients treated homogenously are needed to establish the best treatment modality.

Afatinib is an irreversible ErbB family blocker tyrosine kinase inhibitor (TKI), which has recently been approved for the treatment of patients with EGFR M+ non-small cell lung cancer. As observed with reversible EGFR TKIs, it can induce class-effect adverse events. Appropriate management of afatinib-related adverse events improves quality of life and clinical outcomes in these patients. Here we provide practical recommendations for the prophylaxis and treatment of the most common of these (e.g., diarrhea, rash, mucositis and others).

Chromosomal aberrations involving T-cell receptor (TCR) gene loci have been described in several T-cell malignancies. In primary cutaneous T-cell lymphomas (CTCL), the frequency of these aberrations has not yet been well established. We analyzed TCR gene loci (TCRAD, TCRB, and TCRG) status in CTCLs by fluorescence in situ hybridization (FISH). Twenty-five patients with CTCLs were included in the study: 13 Sézary syndromes (SS), six tumoral stage mycosis fungoides (MFt), and six primary cutaneous anaplastic large cell lymphomas CD30(+) (cALCL-CD30(+)). FISH was performed with three break-apart probes flanking TCRAD (14q11), TCRB (7q34), and TCRG (7p14) loci in each case. TCR gene chromosomal rearrangements were not detected in any of the analyzed cases. Gains of TCRB and TCRG genes were observed in 23% (3 of 13) of SS and 50% (3 of 6) of MFt, reflecting the presence of trisomy and/or tetrasomy of chromosome 7 already detected by conventional cytogenetics and array comparative genetic hybridization techniques. TCR loci rearrangements are not frequent in CTCLs; however, we cannot exclude a pathogenic role in these malignancies., (Copyright © 2011 Elsevier Inc. All rights reserved.)

Mycosis fungoide (MF) patients who develop tumors or extracutaneous involvement usually have a poor prognosis with no curative therapy available so far. In the present European Organization for Research and Treatment of Cancer (EORTC) multicenter study, the genomic profile of 41 skin biopsies from tumor stage MF (MFt) was analyzed using a high-resolution oligo-array comparative genomic hybridization platform. Seventy-six percent of cases showed genomic aberrations. The most common imbalances were gains of 7q33.3q35 followed by 17q21.1, 8q24.21, 9q34qter, and 10p14 and losses of 9p21.3 followed by 9q31.2, 17p13.1, 13q14.11, 6q21.3, 10p11.22, 16q23.2, and 16q24.3. Three specific chromosomal regions, 9p21.3, 8q24.21, and 10q26qter, were defined as prognostic markers showing a significant correlation with overall survival (OS) (P=0.042, 0.017, and 0.022, respectively). Moreover, we have established two MFt genomic subgroups distinguishing a stable group (0-5 DNA aberrations) and an unstable group (>5 DNA aberrations), showing that the genomic unstable group had a shorter OS (P=0.05). We therefore conclude that specific chromosomal abnormalities, such as gains of 8q24.21 (MYC) and losses of 9p21.3 (CDKN2A, CDKN2B, and MTAP) and 10q26qter (MGMT and EBF3) may have an important role in prognosis. In addition, we describe the MFt genomic instability profile, which, to our knowledge, has not been reported earlier.

Introduction: The percentage of presentations at congresses that are later published is a measure of the scientific impact of these meetings. Our objective was to investigate how many studies presented in four Spanish national conferences (2000-2003) had been published in Spanish and international biomedical and dermatology journals, with or without an impact factor., Material and Methods: A search for publications in international indexed journals (using PubMed) or publications in unindexed Spanish journals (using Dermabase/Indice Médico Español) was undertaken by the name of first author, the first and last author, and the key words of the article., Results: Of a total of 1,471 scientific presentations, only 200 (13.5 %) were published (118 in Spanish journals and 82 in international ones); that is, 1,271 studies (86.5 %) were not published either in a Spanish or an international journal., Conclusions: We found a low impact in terms of the publication rate for abstracts presented in 4 consecutive Spanish National Dermatology and Venereology Congresses compared to the rate of publication for other dermatology meetings such as the British Association of Dermatologists Annual Meeting.

We report two patients with longstanding multiple sclerosis (MS) who developed vesicles and bullae consistent with the diagnosis of bullous pemphigoid (BP). Both patients showed linear IgG at the dermal-epidermal junction, located on the epidermal side of patients' skin previously treated with 1M NaCl. In the two cases, the ELISA test was positive for the extracellular fragment of BP 180. However, the indirect immunofluorescence test (IIF) was repeatedly negative. Therapy either with prednisone plus dapsone or prednisone alone was initiated and the disease was controlled after 23 and 15 months of therapy, in patients 1 and 2, respectively. However, the first patient had a flare-up 2 months after treatment was stopped. The association of MS and BP has been described previously in 35 cases. We compare our two cases with the 25 patients previously reported in detail in the literature. We emphasize the role of the ELISA test in establishing the diagnosis of BP.

Background: Drugs such as cetuximab or erlotinib, which inhibit the epidermal growth factor receptor, are increasingly being used in treatment of solid tumors. This has led to the appearance of new secondary effects., Objective: We sought to describe the cutaneous side effects and their management in patients with cancer treated with cetuximab or erlotinib., Methods: We clinically examined 30 patients determining type, frequency, treatment, and evolution of side effects., Results: Most patients presented with a cutaneous reaction consisting of a follicular eruption, typically appearing in seborrheic areas within the first 15 days of treatment. Painful fissures in palms and soles and paronychia were the second most common cutaneous toxicities. We also noticed an alteration in hair growth at several months' follow-up. As these secondary effects responded well to treatment, few patients discontinued the antineoplastic therapy because of cutaneous toxicity., Limitations: This was a prospective but uncontrolled study., Conclusion: Although these new targeted therapies have low systemic toxicity because of their high specificity, cutaneous side effects are common and may be serious.

Four patients presenting a peculiar clinical variant of erythema annulare centrifugum are reported. The lesions were clinically and histopathologically indistinguishable from classic superficial erythema annulare centrifugum but constant annual and seasonal recurrences for many years or decades were observed. No clear precipitating factor could be identified. No associated symptoms were present and the eruption regressed spontaneously after a variable period of days to months. Annually recurring erythema annulare centrifugum seems to represent a rare distinct clinical entity that has received little attention in literature. Clinicopathologic features of this peculiar clinical disorder and the differential diagnosis with other recurrent seasonal eruptions are reviewed.

Epithelioid granuloma formation has rarely been observed in specific cutaneous lesions from T-cell lymphomas other than those of mycosis fungoides/Sézary syndrome (MF/SS). Three patients diagnosed with nodal and/or extranodal (tonsillar) non-Hodgkin's peripheral T-cell lymphoma (PTCL) and one patient with angioimmunoblastic T-cell lymphoma (AILD), developed specific cutaneous involvement showing prominent epithelioid cell and/or granulomatous inflammation. The original diagnostic lesions had no granulomatous features. In addition to a specific lymphomatous infiltrate, prominent dermal and/or subcutaneous granulomatous infiltrates were observed. Sarcoid-like granulomas were observed in two patients (one of them presented a granuloma annulare-like pattern in early lesions), granulomatous panniculitis was noted in one patient and in one patient with AILD, masses of epithelioid cells were noted. The clinicopathological features of cutaneous involvement by PTCL showing a florid epithelioid and/or granulomatous cell reaction are reviewed. Various histopathological patterns can be observed. The diagnostic difficulties of these cases are stressed.

The association of mycosis fungoides and a primary cutaneous CD30+ lymphoproliferative disorder has been reported and probably represents different clinical aspects of a unique T-cell monoclonal expansion. In this study, 12 patients (6 men and 6 women) presented with lymphomatoid papulosis and mycosis fungoides. A TCRgamma gene rearrangement study was performed by an automated high-resolution PCR fragment analysis method on skin biopsy specimens taken from the different clinical lesions in each patient. An indolent clinical course was observed in the majority of patients. T-cell clonality was identified in 7 of 12 lymphomatoid papulosis lesions (58%) and in 6 skin biopsies of plaque stage mycosis fungoides (50%). In each individual case, where T-cell clonality was detected, both mycosis fungoides and lymphomatoid papulosis specimens exhibited an identical peak pattern by automated high-resolution PCR fragment analysis, confirming a common clonal origin. Only one case showed a clonal TCRgamma rearrangement from the lymphomatoid papulosis lesion, which could not be demonstrated in the mycosis fungoides specimen. The demonstration of an identical clone seems to confirm that both disorders are different clinical manifestations of a unique T-cell monoclonal proliferation. Our results also seem to confirm that the association of mycosis fungoides with a primary cutaneous CD30+ lymphoproliferative disorder usually carries a favourable prognosis.

The term hypomelanosis of Ito (HI) is applied to individuals with skin hypopigmentation following the lines of Blaschko (type 1a of patterns indicative of somatic mosaicism as defined by Happle). Even though originally described as a purely cutaneous disease, subsequent reports of HI have included a 30-94% association with multiple extracutaneous manifestations. The frequency of extracutaneous associations has led many authors to consider HI to be neurocutaneous disorder. We report a male infant with cutaneous hypomelanosis along the lines of Blaschko distributed on the left half of the body who developed status epilepticus. Neuroimaging studies disclosed an angiomatous enlargement of the right choroid plexus and a gyral pattern of cortical and subcortical calcification in the right occipital region. Thus a diagnosis could be made of HI and associated Sturge-Weber syndrome-like leptomeningeal angiomatosis. This previously unreported association lends further support to the consideration of hypomelanosis of Ito as a marker of somatic mosaicism with frequently associated neurologic abnormalities. A relationship between HI and Sturge-Weber syndrome, two neuroectodermal disorders with a genetic mosaicism basis, might be possible due to nonallelic twin-spotting which in the embryologic period would define an abnormal development of neural, vascular, and cutaneous structures.

Background: Smooth-muscle hamartoma is an uncommon, usually congenital cutaneous hyperplasia of the arrectores pilorum muscles. When it is acquired, it may be confused with Becker's nevus with a prominent smooth-muscle component. Both entities can be considered polar forms of a spectrum of dermal smooth muscle hyperplasia. We report three cases of acquired smooth-muscle hamartoma in adult patients., Case Reports: Three healthy women in their fifties presented with adult-onset asymptomatic, multiple small papules grouped on circumscribed areas of the trunk. Results of biopsy specimens showed an excess of haphazardly oriented smooth-muscle bundles in the mid to lower dermis with an unremarkable overlying epidermis. Immunohistochemical studies showed two components in this proliferation: a smooth muscle cell population expressing vimentin and smooth muscle actin, and another population of CD34 positive dendritic cells, interspersed among the former., Discussion: Proliferation of CD34+ dermal dendritic cells has been recently described as an additional component in the proliferation of smooth muscle cells, hair follicles and nerve fascicles that constitute congenital smooth muscle hamartomas. The results of immunohistochemical studies in our three cases extend this observation to the acquired variant of cutaneous smooth muscle hamartoma, which can be included in the expanding spectrum of diseases, recently characterized by the presence of a dermal proliferation of CD34 + cells.

Background: Multiple facial angiofibromas are considered a characteristic and pathognomonic feature of tuberous sclerosis. In contrast, the observation of localized multiple angiofibromas limited to one side of the face is a uncommon., Observations: We cared for two patients with multiple clustered unilateral angiofibromas (although one patient also presented a few angiofibromas on the other side) without other features associated with the sclerosis tuberous complex., Discussion: The possibility that these patients presented an independent disorder or a minor form of tuberous sclerosis is discussed.

Introduction: The classification of Langerhans' cell histiocytosis into 5 forms does not cover all types of clinical presentations. We observed a patient with inborn Langerhans' cell histiocytosis involving the skin and bone tissue. The clinical course was benign during the first two years of the patient's life., Case Report: Skin lesions noted at birth resolved spontaneously but recurred twice in a more benign form. Histology examination showed "band" infiltration of the papillary derma composed of Langerhans' cells in direct contact with the basal epidermal layer and a few eosinophils. Immunolabelling was intensely positive for protein S100 confirming the diagnosis of Langerhans' cell histiocytosis. Extension was limited to a lytic lesion in the lower part of the left tibia which was treated by curettage., Discussion: In our opinion, Langerhans' cell histiocytosis covers a wide range of clinical presentations. Our case was remarkable because of the benign course despite its congenital nature and dissemination to skin and bone. Prolonged surveillance of Langerhans' cell histiocytosis is required for patients without any apparent prognosis factors.

We report a 42-year-old white bisexual man with disseminated Kaposi's sarcoma limited to the skin and gastrointestinal tract. Results of several serum tests for human immunodeficiency virus (HIV) antibodies have been negative. The CD4/CD8 ratio has remained normal, and his Kaposi's sarcoma has had a benign clinical course during 30 months of follow-up. Similar reports of disseminated Kaposi's sarcoma with a benign clinical course in homosexual or bisexual men without demonstrable HIV infection are reviewed. Some cellular immune impairment that might be more prevalent in the homosexual population may be implicated in the pathogenesis of this type of Kaposi's sarcoma.

We report a large family with leiomyomatosis cutis et uteri. Sixty-four percent of the females were involved; 18% had only uterine myomas, 10% had only cutaneous piloleiomyomas, and 36% had both. Five patients (45%) had to have an hysterectomy before age 35. Management of female patients having leiomyomatosis cutis should include a periodical gynecological examination in order to rule out the presence of uterine myomas.