Search

Amyloidoma, otherwise known as tumoral amyloidosis, is a localized deposition of amyloid (AL-type or AA type) without systemic amyloidosis. It is the rarest form of tissue amyloid deposition, and up to 7% of amyloidomas develop systemic amyloidosis.Cutaneous AL-type amyloidoma is considered by many authors as an unusual variant of primary cutaneous marginal zone lymphoma. Although cutaneous amyloidoma can form calcifications, ossification is extremely unusual, with only 1 case previously published to date.We report the case of a 75-year-old woman with voluminous and strikingly ossifying AL-type amyloidoma in the left pretibial skin. Her medical history included excision of hepatic hydatidic cysts 25 years prior and diffuse large B-cell lymphoma of the left parotid gland 8 years prior treated with chemotherapy and radiotherapy with complete response. After the diagnosis of amyloidoma, an extension study with cervical, chest, abdominal, and pelvic TC was performed, with no additional lesions found. Serum and protein electrophoresis revealed elevations in kappa light chain and IgA immunoglobulin levels but did not reveal monoclonal bands. In situ hybridization for immunoglobulin light chains showed monotypic kappa expression in plasma cells infiltrating the amyloidoma.Extensive ossification in amyloidomas can make diagnosis difficult; therefore, we describe an interesting case of this histopathologically peculiar amyloidoma.

Relatively little is known about the true aggressive potential of pleomorphic dermal sarcoma (PDS) or optimal management strategies. To describe the outcomes of 16 cases of PDS treated at our hospital (14 with modified Mohs micrographic surgery [M-MMS] and two with conventional surgery) and establish an adequate plan for management. We reviewed 16 PDS cases treated at our hospital between October 2007 and June 2019 and compared our results with the available evidence. In total, 69% of cases had recurred after initial conventional surgery, M-MMS led to local disease control in 83% of cases, and 19% of patients developed metastasis. Combining all published PDS cases with ours, we calculated an overall metastasis rate of 12%, and an overall recurrence rate of 35% after conventional surgery and 17% after M-MMS. PDS is more aggressive than previously estimated, with an overall metastatic rate of 12%. Despite high recurrence rates with previous conventional surgery (69%), M-MMS achieved a good rate of local disease control (83%). Given the potential aggressivity of PDS and the importance of clear surgical margins, M-MMS appears to be more adequate than conventional excision. Staging studies and close monitoring are warranted in PDS patients, for which we propose a management algorithm.

Background: Merkel cell carcinoma (MCC) is a malignant skin cancer with a 5-year survival rate of approximately 50%. Knowledge of MCC has increased in recent years mostly due to improved diagnosis techniques. In Spain there is lack of information regarding the incidence and tumour characteristics, and the treatment approaches are not standardised. The objective of this study was to provide information of the clinical and epidemiological characteristics of MCC patients in Spain. Methods: Retrospective, observational study involving 192 patients from 25 Spanish hospitals. Evaluated variables included overall survival and incidence rate of Merkel cell polyomavirus, in patients diagnosed from 2012 to 2016. Results: The Spanish incidence rate was estimated 0.32/100,000 inhabitants/year, with variations according to geographical regions, being slightly higher in areas with greater sunlight exposure. In total, 61.5% of tumours showed expansive growth (progressive growth of the tumour), 78.6% showed localisation in UV-exposed skin. 97.4% of patients were diagnosed by excisional biopsy. Surgery was the first line treatment in 96.6% of patients, radiotherapy in 24.6%, and chemotherapy in 6.3%. These treatments were not mutually exclusive. Median overall survival was 38.3 months (78.4% at 12 months and 60% at 24 months). MCPyV was present in 33.8% of patients. Conclusion: The incidence of MCC in Spain is one of the highest in Europe, with a slight predominance in men. The sample has shown that a biopsy is available for diagnosis in most cases. Moreover, the treatment is surgical when the tumour is localized and is associated with lymphadenectomy, and/or it is radiotherapy if widespread, This study has been developed with GETHI group (Spanish group of orphan and infrequent tumours, from the Spanish Grupo Espanol ˜ de Tumores Hu´erfanos e Infrecuentes) as promotor. This research was financially supported by Merck KGaA, Darmstadt, Germany, as part of an alliance between Merck KGaA and Pfizer. Merck KGaA, Darmstadt, Germany and Pfizer reviewed the manuscript for medical accuracy only before journal submission. The authors are fully responsible for the content of this manuscript, and the views and opinions described in the publication reflect solely those of the authors

Background Dermatofibrosarcoma protuberans (DFSP) is an invasive skin tumor traditionally associated with very high recurrence rates when treated with conventional surgery (CS). Objective To calculate the minimum margin that would have been required to achieve complete tumor clearance with hypothetical CS. To analyze DFSP characteristics and Mohs micrographic surgery (MMS) effectiveness in treatment of this tumor. Materials and methods Minimum margin was calculated by measuring the largest distance from the visible edge of the tumor to the edge of the surgical defect. Tumor variables (age, sex, size, time since onset, and location) were correlated with surgical variables (number of stages and minimum margin). Results We studied 222 cases of DFSP treated with MMS. A mean of 1.47 MMS stages and a mean minimum margin of 1.23 cm were required to achieve tumor clearance. Tumors on the head and neck required significantly more stages and a significantly wider margin. Tumor size was positively correlated with time to diagnosis, age, and number of MMS stages. Conclusion Tumors located on the head and neck have greater subclinical extension. Tumor size was also a predictor of surgical difficulty, but time to diagnosis was not.

Background Small series of ultrasound findings in dermatofibrosarcoma protuberans (DFSP) have been published, but the usefulness of this technique as a preoperative planning tool for tumor resection has not been studied. Materials and methods We retrospectively reviewed patients with DFSP at our hospital that underwent ultrasound examination. Depth of invasion was evaluated by ultrasound and histopathology. Accuracy of ultrasound for assessing depth of tumor invasion was estimated. Results Thirty histopathologically confirmed DFSPs were studied. Classic finger-like projections were observed in 73.3% of cases. A posterior hyperechoic area extending deep into the subcutaneous tissue correlated with the honeycomb DFSP pattern and was observed in 53.3% of patients. Concordance between ultrasound and histopathologic depth measurements was excellent. Lateral tumor extension and Doppler activity were not evaluated in our series. Conclusion Ultrasound showed excellent prediction of depth of invasion. Further studies are required to define the usefulness of ultrasound for determining lateral tumor extension.

Angiosarcomas (AS) represent a heterogenous group of tumors with variable clinical presentation. AS share an important morphologic and immunohistochemical overlap with other sarcomas, hence the differential diagnosis is challenging, especially in poorly-differentiated tumors. Although molecular studies provide significant clues, especially in the differential diagnosis with other vascular neoplasms, a thorough hematoxylin and eosin analysis remains an essential tool in AS diagnosis. In this review, we discuss pathological and molecular insights with emphasis on implications for differential diagnosis in cutaneous, breast, soft tissue and visceral AS.

There are 3 types of leiomyosarcoma of the skin: dermal, subcutaneous, and metastatic cutaneous. Dermal leiomyosarcoma arises from smooth muscle fibers in arrector pili muscles, genital dartos muscles, and the nipple-areola complex. It is an intermediate-grade tumor associated with a tendency for local recurrence (24%) and low metastatic potential (4%). Subcutaneous leiomyosarcoma originates from smooth muscle in blood vessel walls and has higher rates of local recurrence (37%) and metastasis (43%). Plemorphic dermal sarcoma typically affects elderly patients and arises in sun-exposed areas (e.g., the scalp). Its histologic and immunohistochemical characteristics are similar to those of atypical fibroxanthoma, but it is more aggressive (metastasis rate of 10-20%). Histologically, it can be distinguished from atypical fibroxanthoma by the observation of subcutaneous tissue invasion, perineural invasion, and foci of necrosis.

Cutaneous squamous cell carcinoma (cSCC) is the second most common skin cancer and its incidence is rising. The prognosis is mostly good but patients with high-risk cSCC have a greater risk of recurrence and death. The aim of the present study was to conduct a systematic review analyzing the prevalence, predictors and prognostic utility of sentinel lymph node (SLN) involvement in cSCC. We performed a published work search in Ovid MEDLINE and reviewed the reference lists of selected studies. Based on the 23 studies included in the systematic review, the proportion of patients with cSCC and positive SLN biopsy findings was 8% (95% confidence interval, 5.1-10.8%; I2 = 44.51%). We found no studies reporting on predictors of SLN involvement in cSCC or on the prognostic utility of this finding following adjustment for confounders. The rate of positive SLN in cSCC is less than previously reported. Criteria for recommending SLN biopsy as a staging tool for cSCC vary considerably from study to study, and none of the studies were large enough to reliably identify predictors of SLN positivity. No randomized controlled trials have yet analyzed whether SLN biopsy may improve the prognosis of cSCC. More studies are required on the prognostic value of SLN positivity and the associated risk factors in cSCC.

Basal cell carcinoma (BCC) represents the most commonly diagnosed human cancer among persons of European ancestry with etiology mainly attributed to sun-exposure. In this study we investigated mutations in coding and flanking regions of PTCH1 and TP53 and noncoding alterations in the TERT and DPH3 promoters in 191 BCC tumors. In addition, we measured CpG methylation within the TERT hypermethylated oncological region (THOR) and transcription levels of the reverse transcriptase subunit. We observed mutations in PTCH1 in 58.6% and TP53 in 31.4% of the tumors. Noncoding mutations in TERT and DPH3 promoters were detected in 59.2% and 38.2% of the tumors, respectively. We observed a statistically significant co-occurrence of mutations at the four investigated loci. While PTCH1 mutations tended to associate with decreased patient age at diagnosis; TP53 mutations were associated with light skin color and increased number of nevi; TERT and DPH3 promoter with history of cutaneous neoplasms in BCC patients. Increased reverse transcriptase subunit expression was observed in tumors with TERT promoter mutations and not with THOR methylation. Our study signifies, in addition to the protein altering mutations in the PTCH1 and TP53 genes, the importance of noncoding mutations in BCC, particularly functional alterations in the TERT promoter.

Background Recommendations on when to perform sentinel lymph node (SLN) biopsy in cutaneous squamous cell carcinoma (cSCC) are lacking despite the tumor's clear predilection for lymphatic spread. Objective To analyze the frequency of SLN metastasis in published series of cSCC in the context of the eighth edition of the American joint Committee on Cancer (AJCC-8) and the Brigham and Women's Hospital (BWH) staging criteria. Methods Systematic review of studies of patients with cSCC who underwent SLN biopsy that described biopsy results. Results In total, 153 patients with 24 positive SLN biopsies (15.7%) were included. Based on the AJCC-8 criteria positivity rates in the T2 and T3 categories were 8.3% (1/12 patients) and 25% (8/32), respectively. Using the BWH system there were, 2/33 in category T2a (6.5%), and 5/17 in category T2b (29.8%). On applying the same criteria to tumors of the trunk and extremities the results were similar. Conclusion It would seem reasonable to recommend SLN biopsy for patients with AJCC-8 Stage T3+ disease or BWH Stage T2b/T3 disease. Both the AJCC-8 and the BWH systems would appear to be useful for staging cSCC of the trunk and extremities.

There are no large series describing cutaneous histologic changes during treatment with vismodegib in locally advanced basal cell carcinoma (BCC).To analyze histologic changes in skin biopsy specimens from patients with locally advanced BCC treated with vismodegib.A descriptive, retrospective study of patients with locally advanced BCC treated with vismodegib between June 2012 and December 2017 at the Instituto Valenciano de Oncología, Spain. Nineteen patients were biopsied before and during the treatment with vismodegib, and we compared histologic changes observed.Seven patients (37%) achieved complete response, which was characterized by replacement of tumor stroma with a hyaline scar, lymphocytic inflammatory infiltrate, keratin formation, and infundibular cysts. Twelve patients (63%) achieved partial response; 5 showed no phenotypic changes, whereas 7 showed histologic changes; 5 cases showed metatypical differentiation; and 2 cases presented squamous differentiation. We observed no cases of squamous cell carcinoma arising at vismodegib treatment sites and no association between initial histologic subtype and clinical response.Many biopsy specimens were obtained by punch biopsy and may not be representative of the full tumors. We studied histologic changes only in complete and partial responses.Vismodegib can induce histologic changes toward metatypical or squamous differentiation of BCC in patients with partial response. Keratinizing phenomena were frequent, both in partial and complete response groups.

Background: Treatment of oral erosive lichen planus is considered a therapeutic challenge. Various systemic and topical agents aimed at controlling the symptoms, rather than curing the lesions, have been used with varying results. Objective: To evaluate the response to treatment with antimalarial drugs in patients with oral erosive lichen planus. Methods: Eight patients diagnosed with oral erosive lichen planus were treated with antimalarial agents. The first clinical evaluation was made after a month of treatment and then every 2-3 months. Baseline ophthalmologic examinations were performed, and laboratory values were monitored before and during treatment. Results: All studied patients who had previously been resistant to other treatments responded favorably. Pain relief and reduced erythema and erosions were observed after of a mean of 2.4 months. Conclusion: Antimalarials may be useful for the treatment of oral erosive lichen planus. They are easily administered and affordable, with few adverse effects.

Summary Background Dermatofibrosarcoma protuberans (DFSP) is an uncommon skin tumour with aggressive local growth. Whether DFSP should be treated with conventional surgery (CS) or Mohs micrographic surgery (MMS) has long been a topic of debate. Objectives To calculate, in a large series of DFSP treated by MMS, the minimum margin that would have been needed to achieve complete clearance by CS. Secondly, to calculate the percentage of healthy tissue that was preserved by MMS rather than CS with 2- and 3-cm margins. Methods The minimum margin was calculated by measuring the largest distance from the visible edge of the tumour to the edge of the definitive surgical defect. Tumour and surgical defect areas for hypothetical CS with 2- and 3-cm margins were calculated using AutoCAD for Windows. Results A mean minimum margin of 1·34 cm was required to achieve complete clearance for the 74 tumours analysed. The mean percentages of skin spared using MMS rather than CS with 2- and 3-cm margins were 49·4% and 67·9%, respectively. Conclusions MMS can achieve tumour clearance with smaller margins and greater preservation of healthy tissue than CS.

Sarcomas comprise a broad group of tumors, many of whose biological behavior and aggressiveness differ from one type to another. The therapeutic approach is generally multidisciplinary and often complex. Developments in surgical and oncological dermatology during the last few decades have positioned dermatologists as specialists in the diagnosis and treatment of skin cancer. The aim of this article is to review the main soft tissue sarcomas that typically affect the skin. Dermatofibrosarcoma protuberans is a low-grade malignant sarcoma. It exhibits slow-growth, is locally invasive, and has low metastatic potential (

Cutaneous angiosarcoma (AS) is an uncommon, aggressive sarcoma whose incidence is rising because of the increasing use of radiation therapy, especially in breast cancer. The few studies on the relevance of prognostic factors, such as MYC status in cutaneous AS, have reported inconclusive findings, with some authors reporting MYC amplification only in postirradiation and lymphedema-associated AS and others reporting evidence of MYC amplification in idiopathic AS. We analyzed 17 cases of cutaneous AS (6 idiopathic AS, 10 postirradiation AS, and 1 lymphedema-associated AS) treated at our institute between 2000 and 2015. Follow-up data were available in all cases. We compared the presence/absence of MYC amplification by fluorescence in situ hybridization (FISH) and immunohistochemical (IHC) MYC overexpression in the different AS subtypes. We also investigated potential associations between MYC amplification and prognosis. MYC amplification was observed by FISH in 6 of 14 informative cases. The positive cases were all secondary AS (5 postirradiation AS and 1 lymphedema-associated AS). IHC detected MYC overexpression in 8 of 15 informative cases (7 secondary AS and 1 idiopathic AS). In conclusion, MYC amplification and MYC overexpression were detected almost exclusively in secondary AS. No associations were found between MYC amplification/overexpression and prognosis. We found MYC amplification or overexpression in a similar proportion of the patients who died and who were still alive at the end of the study. In the group of 9 patients who died, MYC was detected by FISH in 4 cases and by IHC in 5. The corresponding figures in the group of 6 patients still alive were 2 by FISH and 3 by IHC.

Introduction and objectives Imiquimod is an excellent option for patients with actinic keratosis, although its use may be limited by the long course of treatment required (4 weeks) and the likelihood of local skin reactions. The objectives of the present study were to demonstrate the effectiveness of a 12-day course of imiquimod 5% for the treatment of actinic keratosis and to examine the association between treatment effectiveness and severity of local reactions. Patients and methods We included patients with at least 8 actinic keratoses treated with imiquimod 5% cream for 12 consecutive days. Local reactions were classified as mild, moderate, or severe. The statistical analysis of the association between local reactions and clinical response was based on the Pearson χ2 test and the Spearman rank correlation test. Results Sixty-five patients completed the study. Complete response was recorded in 52.3% and partial response in 75.4%. We found a statistically significant association between severity of the local reaction and response to treatment in both the Pearson χ2 test and the Spearman rank correlation test. Conclusions A 12-day course of imiquimod 5% proved effective for the treatment of actinic keratosis. Severity of local reactions during treatment was correlated with clinical response.

Postirradiation morphea is an uncommon entity that has been mostly described in women with breast cancer. The increasing use of radiotherapy to treat breast cancer and the clinical similarities between morphea and other conditions, such as radiodermatitis, postirradiation fibrosis, and tumor recurrence, highlights the need for dermatologists to be familiar with this entity. We present a series of 6 women with a mean age of 64.2 years and a mean latency of 9.5 years between radiotherapy for breast cancer and onset of morphea. Four of the patients had a history of autoimmune disease: rheumatoid arthritis, Sjogren syndrome, vitiligo, and Crohn disease. No specific risk factors for postirradiation morphea have been identified to date, although it would appear that a history of autoimmune disease could be associated with an increased risk of morphea in patients treated with radiation therapy.

Several variants of dermatofibrosarcoma protuberans, a low-grade superficial sarcoma, are well recognized. The most prognostically important is the fibrosarcomatous variant. We report a case of biphasic dermatofibrosarcoma protuberans in which the high-grade component exhibited a previously undescribed plexiform pattern. A clinicopathological study complemented with immunohistochemical, ultrastructural, reverse transcription polymerase chain reaction and fluorescence in situ hybridization analyses of this unique case. Histopathologically, a conventional low-grade dermatofibrosarcoma protuberans was admixed with intratumoral high-grade areas showing a striking labyrinthine plexiform pattern characterized by a higher cellularity of larger and slightly atypical tumor cells. CD34 expression was present in both components, while Ki-67 immunostaining was significantly higher in the plexiform high-grade areas. Focal epithelial membrane antigen and claudin-1 immunostaining was present at the interphase between high- and low-grade areas. COL1A1-PDGFB fusion transcripts, with breakpoints at exon 25 of COL1A1 and exon 2 of PDGFB, were present in both components, being more numerous, as the extra copies of both genes, in the high-grade areas. A previously undescribed histopathologic pattern of high-grade sarcomatous transformation of dermatofibrosarcoma protuberans is reported: a biphasic tumor with a labyrinthine plexiform high-grade component.

Cutaneous apocrine adenocarcinoma (CAA) is a rare adnexal neoplasm that histologically can mimic breast carcinoma metastatic to the skin or apocrine carcinoma arising in ectopic breast tissue. It can present with a wide range of clinical modalities and can often simulate many benign processes, which delays its diagnosis and hinders its prognosis. We describe a case of a 33-year-old man who had a short-evolution small nodule in the right axilla with local lymph node metastases. The immunohistochemical characterization was closer to that of breast adenocarcinoma than to an adnexal neoplasm. This was established as the main differential diagnosis. Diagnosis of cutaneous apocrine adenocarcinoma may be difficult and immunomarkers are not specific. The anatomical criteria and systemic investigation are mandatory to establish the correct diagnosis.

Background Granulomatous reactions to silicone facial fillers are well described in the literature. Clinically, these reactions present as nodules or pseudotumors that are frequently described as silicone granulomas or siliconomas. Objective We want to report a peculiar form of granulomatous reaction to injected silicone characterized by recurrent episodes of facial edema. Methods We collected silicone infiltrated patients with a similar clinical picture consisting of asymptomatic episodes of unilateral facial edema that had been recurring for months or years. Results We found four women with recurrent episodes of facial edema. They had been infiltrated with silicone in the face. Histology showed silicone deposits and a granulomatous infiltrate in all 4 cases. Conclusion We describe and illustrate a new type of adverse reaction to injected silicone simulating orofacial granulomatosis. The reaction presents as recurrent, unilateral, asymmetric facial edema of the cheek in patients who have been injected with silicone in the face. Familiarity with this adverse reaction will help to prevent erroneous diagnoses such as idiopathic angioedema, Melkersson Rosenthal syndrome, and orofacial granulomatosis.

Superficial/cutaneous small round-cell tumors comprise a heterogeneous group of neoplasms including sarcoma, carcinoma, melanoma, and lymphomas. Among superficial sarcomas, the Ewing's sarcoma family of tumors (ESFT) represents a poorly understood rare variant, having a behavioral difference characterized by a relative favorable prognosis. Several problems are still to be resolved in superficial ESFT, including the differential diagnosis between ESFT of bone (intraosseous or periosteal) with superficial infiltration and superficial ESFT with bone infiltration, especially in the fingers. Our aim is to review the most common types of small round-cell tumors included in the differential diagnosis of superficial ESFT, analyzing the histopathology, phenotype, and molecular alterations of each entity.

Dermatofibrosarcoma protuberans (DFSP) is a rare superficial tumor characterized by high rates of local recurrence and low risk of metastasis. DFSP occurs most commonly on the trunk and proximal extremities, affects all races, and often develops between the second and fifth decade of life. The tumor grows slowly, typically over years. Histologically, several variants of DFSP have been described and should be well characterized to avoid misdiagnosis with other tumors. These include pigmented (Bednar tumor), myxoid, myoid, granular cell, sclerotic, atrophic DFSP, giant cell fibroblastoma, and DFSP with fibrosarcomatous areas. Of all these variants, only the DFSP with fibrosarcomatous areas is high grade, with a higher rate of local recurrence and distant metastasis. DFSP is genetically characterized by the t(17;22)(q22;q13), resulting in the fusion of alpha chain type 1 of collagen gene and platelet-derived growth factor beta gene. This translocation is present in 90% of DFSP and represents a very useful tool in the differential diagnosis of DFSP with other tumors with similar histology. The standard treatment is wide local excision with at least a 2-cm margin. However, local recurrence after apparently adequate surgical excision is well recognized. Mohs micrographic surgery would be the treatment of choice with a better cure rate and maximal conservation of tissue. When surgery is insufficient, clinical evidence has suggested that imatinib mesylate is a safe and effective treatment in DFSP, especially in cases of local advanced or metastatic disease. This article presents an overview of the state of the art in the clinicopathological management of this disease.

Merkel cell carcinoma is a malignant skin tumor with a poor prognosis that primarily affects photoexposed areas of elderly patients. Tumor size is a very strong prognostic factor, with much better outcomes associated with small lesions, measuring less than 1 cm. However, such lesions are rarely seen in the clinic in view of the rapid growth of this tumor. We report 2 cases of incipient Merkel cell carcinoma. Both cases of incipient Merkel cell carcinoma measured approximately 5 mm in diameter. One tumor was confined to the epidermis and papillary dermis on the nose of a 79-year-old man and the other was located in the deep dermis, almost in the hypodermis, on the buttock of an 82-year-old woman. In both cases, the lesions had appeared weeks earlier. The first tumor seemed to originate in the dermoepidermal junction whereas the second originated almost in the hypodermis. Although the lesions were at a similar disease stage and had a similar size, their different locations within the dermis highlight once again the controversy about which cells give rise to Merkel cell carcinoma. The precursor cells could feasibly be Merkel cells in the first case but not in the second. © 2011 Elsevier Espana, S.L. and AEDV. All rights reserved.

A 53-year-old woman with a history of cervical cancer was treated with radical hysterectomy nine years ago and chemotherapy. Two months after stopping the chemotherapy for pancytopenia, she developed fever, neutrophilia, and multiple tender, indurated, erythematous-violaceous and oedematous plaques and nodules, ranging from 1 to 3 cm in diameter and involving bilateral upper and lower extremities (figures 1A, B). Punch biopsy specimen of the leg revealed predominantly lobular neutrophilic panniculitis [...]

Merkel cell carcinoma (MCC) is a rare, highly aggressive tumor, and local or regional disease recurrence is common, as is metastasis. MCC usually develops in sun-exposed skin in patients of advanced age. Its incidence has risen 4-fold in recent decades as the population has aged and immunohistochemical techniques have led to more diagnoses. The pathogenesis of MCC remains unclear but UV radiation, immunosuppression, and the presence of Merkel cell polyomavirus in the tumor genome seem to play key roles. This review seeks to update our understanding of the epidemiology, etiology, pathogenesis, and clinical features of MCC. We also review histologic and immunohistochemical features required for diagnosis. MCC staging is discussed, given its great importance in establishing a prognosis for these patients.

MdC González-Vela et al., Merkel cell carcinoma (MCC) is a highly malignant neuroendocrine tumor of the skin whose molecular pathogenesis is not completely understood, despite the role that Merkel cell polyomavirus can play in 55–90% of cases. To study potential mechanisms driving this disease in clinically characterized cases, we searched for somatic mutations using whole-exome sequencing, and extrapolated our findings to study functional biomarkers reporting on the activity of the mutated pathways. Confirming previous results, Merkel cell polyomavirus-negative tumors had higher mutational loads with UV signatures and more frequent mutations in TP53 and RB compared with their Merkel cell polyomavirus-positive counterparts. Despite important genetic differences, the two Merkel cell carcinoma etiologies both exhibited nuclear accumulation of oncogenic transcription factors such as NFAT or nuclear factor of activated T cells (NFAT), P-CREB, and P-STAT3, indicating commonly deregulated pathogenic mechanisms with the potential to serve as targets for therapy. A multivariable analysis identified phosphorylated CRE-binding protein as an independent survival factor with respect to clinical variables and Merkel cell polyomavirus status in our cohort of Merkel cell carcinoma patients., This work was supported by grants from Instituto de Salud-Carlos III (ISCIII); cofinanced by the European Union; (FEDER) (PI12/00357), and a Ramón and Cajal research program (MINECO; RYC-2013-14097) to JPV, Asociación Española Contra el Cáncer and ISCIII grants (RD06/0020/0107, RD012/0036/0060) to MAP, and Coordinated Project of Excellence inter-Institutos de investigación acreditados institutes (ISCIII; PIE15/00081) to MAP. The Ramón and Cajal research program also supports IV. SD was supported by the Torres Quevedo subprogram (MICINN; PTQ-12-05391).

Introduction: Surgical excision with margins of 0.5 cm is the standard treatment for lentigo maligna (LM). Excision, however, is often incomplete as many of these tumors have indistinct borders. Objective: To identify clinical predictors of subclinical extension in primary and recurrent LM of the head and thereby determine which lesions might require wider surgical margins. Material and methods: We reviewed the clinical records of patients with LM of the head treated definitively with conventional surgical excision or slow micrographic Mohs surgery (MMS) at the dermatology department of Instituto Valenciano de Oncologia between January 1993 and April 2011. Results: Surgical margins larger than 0.5 cm were required in 69.2% of recurrent LM and 26.5% of primary LM. Factors associated with the need for wider margins were prior treatment that might have interfered with the clinical delineation of the border, lesions in the center of the face, and skin phototypes III to V. Conclusions: Surgical margins of 0.5 cm are inadequate for the treatment of a considerable number of LM lesions located on the head, particularly if these are recurrent. Slow MMS using paraffin-embedded sections appears to be the treatment of choice in such cases, particularly for recurrent lesions or lesions with poorly defined borders or possible subclinical extension.

The different features of spitzoid melanoma are not well characterized in the literature, and the lesion often has to be described in comparison with Spitz nevus. We evaluated the histopathological appearance of spitzoid melanoma by reviewing all spitzoid melanomas treated at our hospital and all referrals from 1998 to 2010. The final study sample comprised 18 cases, 11 from our institution and 7 referrals from other centers. We recorded clinical parameters (eg, age, sex, site, time between onset and excision, recurrence, and death) and a series of histopathological parameters (eg, size, ulceration, symmetry, Clark level, Breslow thickness, cell density, atypia, mitosis). Clinical and histopathological criteria were not available for the 7 referrals. Mean age was 35.2 years (15-56), and 8 patients were women. Mean size of the lesions was 7.27 mm (Clark III/IV and Breslow 2.51 mm), and these were found on the limbs and trunk. Cell density was high in 10 cases and atypia present in 9 (marked in 1). Mitoses were observed in 8 cases (atypical in 4, clusters in 4). Maturation was absent in 9 cases and zonation in 8. Our analysis revealed 5 previously undefined subtypes of spitzoid melanoma (genuine (7 cases), uniform (5 cases), packed (5 cases), polypoid (3 cases) and pigmented (2 cases)]. Four cases showed 2 patterns at the same time. The most useful parameters for the differential diagnosis were cell density, mitosis, zonation, infiltration pattern, and consumption of the epidermis. Assignation of a spitzoid melanoma to 1 of more of our 5 subtypes can enable a more confident diagnosis to be made.

Background Photodynamic therapy (PDT) and imiquimod are the treatments of choice for actinic keratosis (AK). As they have different mechanisms of action, it seems reasonable to assume that applying both treatments sequentially would be efficacious. Objectives We sought to determine which of these therapeutic modalities provides a better clinical and histologic response in patients with AK and whether sequential use of both was more efficacious than each separately. Methods Patients were randomly assigned to one treatment group: group 1, PDT only; group 2, imiquimod only; or group 3, sequential use of PDT and imiquimod. The primary outcome measure was complete clinical response. Partial clinical response was defined as a reduction of more than 75% in the initial number of lesions. A complete clinicopathologic response was defined as lack of evidence of AK in the biopsy specimen. Results In all, 105 patients completed the study (group 1, 40 patients; group 2, 33 patients; group 3, 32 patients). Sequential application of PDT and imiquimod was more efficacious in all the outcome measures. More patients were satisfied with PDT than with the other two modalities ( P = .003). No significant differences were observed among the 3 modalities and tolerance to treatment. Limitations Only one cycle of imiquimod was administered. The follow-up period was brief. Conclusions Sequential application of PDT and imiquimod provides a significantly better clinical and histologic response in the treatment of AK than PDT or imiquimod monotherapy. It also produces less intense local reactions and better tolerance and satisfaction than imiquimod monotherapy.

Dermatofibrosarcoma protuberans (DFSP) is characterized by asymmetrical and poorly defined growth. Magnetic resonance imaging (MRI) has been proposed for the delimitation of this tumor.To study the utility of MRI in evaluating the depth of infiltration in DFSP and to compare the efficiency of clinical palpation with that of MRI in delimiting the invasiveness of DFSP.Observational, prospective study of DFSP cases. The MRI scans for all cases were compared with the exact histological infiltration plane obtained using modified Mohs micrographic surgery (MMS).Forty-three DFSPs were included: 22 primary, nine recurrent, and 12 extirpated with positive margins. Sensitivity for detecting deep invasion was 58% on examination using palpation and 67% using MRI.We present the largest series of DFSP cases studied using MRI published to date. In primary cases, MRI has greater sensitivity than palpation for detecting depth of infiltration (67% vs 58%). MRI seems to be useful in primary DFSP in locations other than the head, neck, and upper part of the thorax. MRI is not useful for confirming tumor persistence in extirpated DFSP with positive margins or for studying lateral extension in primary DFSP.

Background: Superficial/cutaneous Ewing’s sarcoma family of tumors (ESFT) are rare and have a relatively favorable prognosis compared with deep-seated tumors. The aim of the present study is to describe the clinicopathological characteristics of six genetically confirmed ESFT presenting a superficial location. Methods: Clinical data, radiology, histopathology, immunohistochemistry, molecular study [reverse transcriptase-polymerase chain reaction (RT-PCR)/fluorescence in situ hybridization], treatment and follow-up data were retrieved. Results: Locations included fingers (2), back (1), neck (1), thigh (1) and subcutaneous breast (1). Two tumors showed conventional morphology, one consisted of primitive neuroectodermal tumor and three tumors showed atypical vascular morphology with hemosiderin deposition and pigmentation. All cases showed CD99, FLI-1, HNK-1 and CAV-1 positivity. RT-PCR revealed the EWS/Fli1 gene fusion in all cases. Treatment was by wide excision in all cases; one received chemotherapy (CT) and one CT and radiotherapy. Available follow-up revealed the following: two patients with metastasis and death at 5 months and 2 years and one local recurrence at 18 years. Conclusions: Superficial ESFT appears to have a relatively favorable prognosis but further studies with additional series, a larger number of cases and more extensive follow-up are necessary to confirm this statement.

The growth rate (GR) of melanomas is not uniform. A fast-growing subtype has been identified and seems to have a role in the stabilization of the mortality rates because of melanoma. To examine features associated with fast-growing melanomas (FGMs) and to determine the relationship between the GR and well-recognized prognostic factors of melanoma, a series of 386 new invasive cutaneous melanomas seen during 2004-2009 were retrieved from our database. The GR was calculated according to earlier published studies. FGMs were defined as those whose GR was greater than 0.49 mm per month. Differences in clinical, epidemiological, and pathological features were evaluated. Correlations between the GR, tumor thickness, and mitotic rate were also analyzed. FGMs were significantly more prevalent among patients aged over 65 years and with a higher rate of past personal history of nonmelanoma skin cancer. This subtype was over-represented among melanomas located on both nonexposed and usually exposed skin and was less related to earlier sunburns. Patients with FGMs presented with more aggressive pathological features and had more advanced disease with sentinel node analysis affected in up to 35% of cases. There was a strong positive correlation between the GR and tumor thickness (r=0.762), and mitotic rate (r=0.542). This study was limited by being retrospective in nature. FGMs are a highly aggressive subtype of melanomas that seem to develop after at least two routes, one related to chronic sun exposure and another unrelated to the sun. Older patients have a higher predisposition to develop this kind of tumor. This variant warrants specific strategies to improve primary and secondary prevention.

Summary Background Photodynamic therapy (PDT) is an effective treatment for actinic keratoses, Bowen’s disease and basal cell carcinoma. The main drawback of PDT is pain during application. Objectives To compare the efficacy of supratrochlear and supraorbital nerve block with cold air analgesia to control the pain experienced during PDT. Methods A controlled open clinical trial was conducted in 34 patients having multiple actinic keratoses in the frontal region treated with PDT. On one side of the frontal region the supratrochlear and supraorbital nerves were blocked, while on the other side cold air was used as the method of analgesia. Pain was recorded on a visual analogue scale after treatment. Results Thirty-one of 34 patients reported less pain in the zone treated with nerve block. This difference was statistically significant. Conclusions Nerve block is superior to cold air and is an easy, safe, effective means of controlling the pain associated with PDT.

The cutaneous epithelioid angiomatous nodule is an uncommon benign vascular proliferation that has only recently been described. Clinically, it usually presents as a solitary, fast-growing, small reddish papulous or nodular lesion on the trunk or limbs of adults. Histopathologic study reveals a proliferation of epithelioid cells and predominantly solid, well delimited, unilobular growth in the superficial dermis. Well defined vessels are often found permeating the lesion, which also shows a certain degree of inflammatory infiltration. The cells contain abundant pink cytoplasm, often with vacuoles, and vesicular nuclei with prominent nucleoli. The morphology of these cells is relatively uniform, without atypia or pleomorphism, although mitoses are not uncommon. We report 2 new cases of cutaneous epithelioid angiomatous nodules, the first in a 28-year-old pregnant woman and the second in a 27-year-old man. In both cases, the usual characteristics of this entity were present, but with the peculiarity of a high mitotic index. We discuss the differential diagnosis of cutaneous epithelioid angiomatous nodules with other vascular proliferations that exhibit epithelioid cytology.

Cutaneous epithelioid angiomatous nodule is a peculiar and recently recognized vascular proliferation. Clinically, these lesions affect different areas of the body and histologically are characterized by a well-circumscribed, mainly unilobular, solid proliferation of endothelial cells with prominent epithelioid features. The cytoplasm is abundant and eosinophilic, and many of the neoplastic cells contain prominent vacuoles. Inflammatory infiltrates are variable. All the cases reported thus far have followed a benign course. We report 10 additional cases of this curious entity, including 2 which presented in an eruptive fashion and 5 that were located on the head and neck. We also discuss the histological differential diagnoses with other epithelioid proliferations and propose categorization within the spectrum of epithelioid hemangioma.

Introduction. Acral erythema, also known as palmoplantar erythrodysesthesia or hand-foot syndrome, is a relatively common cutaneous reaction caused by a variety of chemotherapeutic agents. It presents during cancer treatment as painful erythema and paresthesia affecting the palms and soles. It seems to be dose dependent and its appearance is determined by both the peak plasma concentration and the cumulative dose of the chemotherapeutic agent. The symptoms and histopathology findings are suggestive of direct cytotoxicity affecting the epidermis of the extremities caused by high concentrations of chemotherapeutic agents. The most commonly implicated agents are doxorubicin, 5-fluoracil and its derivatives, cytarabine, and docetaxel. Material and methods. We present the clinical and histologic characteristics of a series of patients diagnosed with chemotherapy-induced acral erythema. The study included all patients who developed acral erythema lesions following chemotherapy between January 2000 and December 2003. Results and conclusions. Out of 2186 patients who underwent chemotherapy, 44 cases of acral erythema were identified, representing an incidence of 2.01% during the study period and 16.75% of all cutaneous lesions attributed to chemotherapy. The most commonly implicated drug was 5-fluoracil administered by continuous infusion and the highest incidence was observed in patients treated with liposomal doxorubicin. Acral erythema was a dose-limiting toxic effect in 29.5% of cases. The histologic findings varied according to the clinical severity of the lesions and included interface dermatitis with variable keratinocyte necrosis, dilation of the superficial vascular plexus, and limited inflammatory infiltrate. The most commonly used treatment was pyridoxine, along with topical treatments such as cold compresses, emollients, and topical corticosteroids.

Dermatofibroma is a very frequent lesion that usually appears as a slowly growing nodule in the dermis, and preferentially involves the lower extremities of women. Several clinical variants have been described. Giant dermatofibroma has been defined as a rare variant of dermatofibroma measuring more than 5 cm that presents typical histological features and a benign biological behavior. We report the case of a 52-year-old man that presented a giant dermatofibroma with a diameter of 6 cm in the right shoulder and we review the few cases of this variant that have been described in the literature.

Recent reports suggested frequent occurrence of cancer associated somatic mutations within regulatory elements of the genome. Based on initial exome sequencing of 21 melanomas, we report frequent somatic mutations in skin cancers in a bidirectional promoter of diphthamide biosynthesis 3 (DPH3) and oxidoreductase NAD-binding domain containing 1 (OXNAD1) genes. The UV-signature mutations occurred at sites adjacent and within a binding motif for E-twenty six/ternary complex factors (Ets/TCF), at -8 and -9 bp from DPH3 transcription start site. Follow up screening of 586 different skin lesions showed that the DPH3 promoter mutations were present in melanocytic nevi (2/114; 2%), melanoma (30/304; 10%), basal cell carcinoma of skin (BCC; 57/137; 42%) and squamous cell carcinoma of skin (SCC; 12/31; 39%). Reporter assays carried out in one melanoma cell line for DPH3 and OXNAD1 orientations showed statistically significant increased promoter activity due to -8/-9CC > TT tandem mutations; although, no effect of the mutations on DPH3 and OXNAD1 transcription in tumors was observed. The results from this study show occurrence of frequent somatic non-coding mutations adjacent to a pre-existing binding site for Ets transcription factors within the directional promoter of DPH3 and OXNAD1 genes in three major skin cancers. The detected mutations displayed typical UV signature; however, the functionality of the mutations remains to be determined.

Dermatofibrosarcoma protuberans (DFSP) typically affects the dermis and subcutaneous tissue. The subcutaneous variant is rare.We sought to characterize the subcutaneous DFSP (SC-DFSP) variant and compare it with cutaneous DFSP (C-DFSP).This work was a retrospective study of DFSP treated in our institution.Of 124 cases of DFSP, 18 were SC-DFSP (14.5%). Except for the deep location, the pathologic and genetic features were indistinguishable from the C-DFSP variant. Histologically, of 18 SC-DFSP cases, 13 were classic DFSP, 3 fibrosarcomatous DFSP (FS-DFSP), 1 Bednar tumor, and 1 giant-cell fibroblastoma. All tumors expressed CD34 and the COL1A1-PDGFB fusion transcripts. In our series, higher proportions of SC-DFSP tumors (61%) than C-DFSP tumors (8.5%) were located on the head (P .001). Of the 20 DFSP tumors on the head (16.1%), 11 were SC-DFSP and 9 were C-DFSP. In addition, half the SC-DFSP tumors affected muscle or periosteum, compared with a quarter of the C-DFSP tumors (P = .009). SC-DFSP needed a higher number of Mohs stages than did C-DFSP (P = .009). Median follow-up time was 63 months, and 2 FS-DFSP tumors recurred (1 SC-DFSP, 1 C-DFSP).Limitations include the retrospective aspect of the study.Most DFSP tumors involving the head were subcutaneous and required more complex surgery. Dermatologists should be aware of this atypical presentation, especially in lesions involving the head.

Melanoma is potentially curable if diagnosed at its earliest stages and treated properly. The best approaches for reducing deaths due to melanoma are primary and secondary prevention. The objective of this study is to evaluate patient awareness of the risk factors for developing melanoma and attitudes toward its prevention. Also, this study aims to assess observance of recommended preventive measures and to identify possible factors associated with a low adoption of these measures. This cross-sectional study based on an online questionnaire included 185 consecutively enrolled subjects at risk of developing melanoma monitored in a pigmented lesion unit in Valencia (Spain). Level of knowledge, attitude, and observance of preventive measures were evaluated. Statistical analysis was carried out using contingency tables, chi-squared test, and Spearman correlation. Out of those who reported practicing skin self-examination, only 24.1 % performed it in the optimal way. A better attitude was observed in low-risk patients (r = −0.28, p

Lymphomatoid papulosis is a cutaneous lymphoma with an indolent clinical behaviour characterized by chronic development of recurrent, self-limited lesions appearing as necrotic papules and with a pathology compatible with T cell lymphoma. Mucosal involvement by lymphomatoid papulosis is very rare but has been reported in the literature. It usually appears as ulcers in patients previously diagnosed of lymphomatoid papulosis. From a histological perspective it is characterized by an infiltrate of CD 30 positive atypical lymphocytes together with a mixed inflammatory infiltrate of eosinophils, neutrophils, histiocytes and plasma cells. We report the case of a man previously diagnosed of lymphomatoid papulosis that developed two ulcerated lesions in the tongue whose biopsy confirmed the diagnosis of oral involvement by lymphomatoid papulosis.

Introduction and objectives Adult dermatomyositis presents as a paraneoplastic syndrome in up to 25% of cases, but no clinical, histologic, or laboratory markers completely specific for paraneoplastic disease in dermatomyositis have been identified to date. Furthermore, studies on adult dermatomyositis do not usually report the frequency of cutaneous features of dermatomyositis in patients with associated cancer. Our aim was to review the characteristics of paraneoplastic dermatomyositis in patients seen at our hospital. Material and methods We studied 12 cases of paraneoplastic dermatomyositis and recorded patient age and sex, associated cancer, time between onset of dermatomyositis and cancer, emergent cutaneous manifestations, muscle involvement, dysphagia, lung disease, and levels of creatine phosphokinase and circulating autoantibodies. Results The mean age of the patients was 61 years and the 2 most common malignancies were ovarian cancer and bladder cancer. The mean time between the diagnosis of cancer and dermatomyositis was 7 months and in most cases, the cancer was diagnosed first. Seven patients had amyopathic dermatomyositis. The most common cutaneous signs were a violaceous photodistributed rash sparing the interscapular area and a heliotrope rash, followed by Gottron papules and cuticle involvement. Superficial cutaneous necrosis was observed in 3 cases. Myositis-specific autoantibodies were not detected in any of the 6 patients who underwent this test. Conclusions Paraneoplastic dermatomyositis is often amyopathic. There are no specific cutaneous markers for malignancy in dermatomyositis. Myositis-specific antibodies are not associated with paraneoplastic dermatomyositis.

Background Dermatofibrosarcoma protuberans (DFSP) is characterized by unpredictable subclinical extension, meaning that positive margins are frequently detected following conventional surgical excision. Objective To study the presence or absence of residual tumour in DFSP with positive margins after conventional surgery and identify possible predictors of residual tumour or clear margins following a single Mohs micrographic surgery (MMS) stage. Methods A retrospective study of patients with DFSP and positive margins following conventional excision referred for MMS was performed. We studied gender, age, tumour site, time from presentation to diagnosis, and affected margins. Results We studied 58 cases, 35 (60.3%) of which had histological evidence of residual tumour. Tumours of the head and neck were significantly associated with the persistence of tumour. A single MMS stage was sufficient to achieve clearance in the majority of cases (n = 46). All tumours with lateral involvement only were resolved with a single Mohs stage. Conclusions DFSPs with positive margins after conventional surgical excision should undergo re-excision because the majority have histologic evidence of residual tumour. Re-excision with 1-cm margins beyond the scar could be an option in certain tumour sites, particularly when it is known which margins are involved.

Dermatofibrosarcoma protuberans (DFSP) was recently shown to express nestin, a marker that has been associated with poorer prognosis when present in high levels in certain tumors. The objective of this study is to explore the association between high nestin expression and deep invasion.We performed a retrospective, observational study in which we evaluated the degree of nestin expression in 71 DFSP. The odds of fascial involvement was calculated before and after adjusting for the following confounders: age, sex, tumor size, time to diagnosis, tumor site, the presence of fibrosarcomatous areas, pleomorphism, number of mitotic figures and predominant histopathologic pattern. We also calculated the Spearman Rho correlation coefficient between nestin staining intensity and depth of invasion.Nestin immunopositivity was found in 98.6% of the tumors, and high expression levels were significantly associated with invasion of the fascia. The odds of fascial involvement in tumors with strong nestin staining was 6.56 (p = 0.001) before adjustment for confounders and 14.86 after adjustment (p = 0.007). The Spearman rho correlation coefficient between nestin expression and deep invasion was 0.287 (p = 0.015).High inmunohistochemical nestin expression appears to be associated with deeper invasion in DFSP.