An unusual case of dermatofibrosarcoma protuberans misdiagnosed as vascular malformation for over 30 years: A case report.

INTRODUCTION: Dermatofibrosarcoma protuberans (DFSP) is a rare and slowly growing soft tissue tumor and it is frequently misdiagnosed and mismanaged like more common masses. Therefore diagnostic delays are common and may result in challenging reconstructions. CASE PRESENTATION: We report the peculiar case of a 36-year-old patient with dermatofibrosarcoma protuberans of the right iliac fossa misdiagnosed as vascular malformation for over 30 years. Due to the delayed diagnosis resulting in a large tumor to be resected, surgical reconstruction was performed with a miniabdominoplasty approach with an excellent cosmetic and functional result. DISCUSSION: The review of the literature showed that mismanagements and delayed diagnosis of this sarcoma are frequent. Large skin and soft-tissue defects are frequently encountered in the surgical treatment of this tumor, and adequate knowledge of the reconstructive options is mandatory to provide the best possible outcome. CONCLUSIONS: Superficial skin masses could be easily misdiagnosed. These diagnostic delays may lead to increased patient morbidity and more challenging reconstructive procedures. In this scenario, preoperative biopsies of suspicious lesions may be useful to avoid mismanagement of rare malignant neoplasms such as DFSP. In some challenging cases, the use of a surgical approach typical of cosmetic procedures may be useful to obtain satisfactory aesthetic and functional results.

Primary Dermal Melanoma: A Rare Clinicopathological Variant Mimicking Metastatic Melanoma.

Primary dermal melanoma (PDM) is a rare distinct variant of cutaneous melanoma, predominantly occurring on the extremities of young or middle-aged adults. In comparison to conventional melanoma, PDM is characterized by unexpectedly prolonged survival and long-term survival. Thus, correct identification of this variant is crucial to avoid potential misdiagnosis and establish correct treatment and follow-up. In addition, no consensus and specific guidelines exist on the management of this peculiar subtype of cutaneous melanoma.

A case report of metastatic giant sarcomatoid melanoma with BRAF V600E mutation: a complete response to targeted therapy.

Sarcomatoid melanoma is an extremely rare pattern of malignant melanoma, and only few cases have been described throughout the literature. We herein report a case of a patient with newly diagnosed, metastatic giant sarcomatoid melanoma of the arm. The patient underwent surgical removal of the huge mass, and NGS sequencing demonstrated BRAF V600E mutation. In view of histological, immunohistochemical and molecular findings, a combined BRAF/MEK inhibitor (BRAF/MEK-i) therapy was prescribed as first line treatment. A complete response (over one year) to targeted therapy was obtained, and no adverse events have been reported. The patient maintained a full range of shoulder and elbow movements, and she is able to live independently and resume her daily activities. We therefore recommend that all patients with undifferentiated melanomas, sarcomatoid cutaneous malignancies or other mesenchymal tumours, should undergo BRAFV600E mutation testing.

Diffuse (Generalized) Plane Xanthoma Misdiagnosed as Carotenoderma: Usefulness of Reflectance Confocal Microscopy.

Diffuse (generalized) plane xanthoma is a rare normolipemic xanthomatosis, frequently associated with multiple myeloma and monoclonal gammopathy. Its clinical presentation is well described, and in most cases, clinical suspicion is immediate. Rarely, it can clinically present with a diffuse and uniform yellowish discoloration, and in this context, several investigations are required to identify the correct diagnosis. We describe a case characterized by progressive diffuse yellow-orange discoloration lasting about 3 years and classified as carotenoderma in which reflectance confocal microscopy addressed the diagnosis and drove the correct selection of the biopsy site. Definitive diagnosis of diffuse (generalized) plane xanthoma was confirmed later by histological examination.

Buschke-Ollendorff syndrome in a 6-year-old patient: clinical and histopathological aspects of a rare disease.

Buschke-Ollendorff syndrome (BOS) is a rare genetic hereditary genodermatosis characterized by benign skeletal and cutaneous lesions. Skeletal alterations known as osteopoikilosis (OPK) or "spotted bone disease" are asymptomatic areas of sclerosing dysplasia. Two skin lesion patterns have been described because they may be of either elastic tissue (juvenile elastoma) or collagenous composition (dermatofibrosis lenticularis disseminata). We present the case of a 6-year-old male patient with yellowish papules that coalesced to form plaques localized on both thighs and on the upper limbs consistent with a connective tissue nevus (CTN) diagnosis. X-ray examination of the skeletal system revealed the presence of multiple small areas (measuring between 1 and 7 mm) of increased bone density (OPK) bilaterally. A skin biopsy was performed and did not show striking alterations in the number or dimension of the extracellular matrix fibers, but it showed mucin deposition between them, which is compatible with a CTN. This study reports on the clinical presentation and histological examination of this unusual disease.

Treatment of Moderate-to-Severe Psoriasis in the Presence of Kaposi's Varicelliform Eruption.

Kaposi's varicelliform eruption (KVE) is a disseminated cutaneous infection usually induced by herpesvirus type 1 or 2, vaccinia virus or Coxsackie A16 virus in a patient with an underlying dermatosis. Risk factors for KVE reported in the literature include erythroderma, systemic sepsis, therapy with immunosuppressants such as methotrexate and systemic steroids, and therapy with systemic retinoids. The occurrence of KVE in psoriasis is rare and it predominantly appears in patients affected by erythrodermic psoriasis during immunosuppressive treatment. We report our experience of a remarkable case of a patient affected by severe erythrodermic psoriasis and KVE that healed after antiviral treatment and after having received secukinumab. After 1 year, psoriasis was cleared and no recurrence of KVE had occurred.

Inflammatory myofibroblastic tumor of the transverse colon with synchronous gastrointestinal stromal tumor in a patient with ulcerative colitis: a case report.

INTRODUCTION: Inflammatory myofibroblastic tumor (IMT) is a rare proliferative disease of uncertain etiology, characterized by the proliferation of fusate or epithelioid myofibroblasts admixed with predominantly mononuclear inflammatory cells. IMT is generally considered a benign lesion, although in some cases this neoplasm has shown an aggressive behavior in terms of local recurrence and metastasis. We report the case of a patient with a ten-year history of ulcerative colitis affected by IMT of the transverse colon and by synchronous gastrointestinal stromal tumor (GIST) of stomach. PRESENTATION OF CASE: A 59-year-old woman with a ten-year history of ulcerative colitis has been admitted to our hospital with signs and symptoms of acute recurrence of ulcerative colitis: abdominal pain, diarrhea, hematochezia and rectal tenesmus. Colonoscopy showed a left colon with diffuse hyperemia, mucosal erosions and a 2-cm, irregularly shaped, polypoid lesion at the level of the transverse colon. Histopathological examination of the specimen obtained via biopsy of the polypoid lesion has revealed a mesenchymal neoplasm with uncertain characters of malignancy. Due to the severity of the inflammatory bowel disease resistant to immunosuppressive and steroid drug treatment, surgical indication was given. DISCUSSION: Although the relationship between IMT and Crohn's disease has been widely reported in literature, the relationship between IMT and ulcerative colitis has never been previously described. CONCLUSION: To the best of our knowledge, this is the first case of IMT associated with ulcerative colitis reported in literature and the synchronous association with a gastric GIST represents another primacy.

Pyoderma gangrenosum successfully treated with golimumab: Case report and review of the literature.

Pyoderma gangrenosum (PG) is a rare neutrophilic dermatosis frequently related to chronic inflammatory bowel disease (IBD) often associated with exacerbation of intestinal disease and/or loss of treatment efficacy. However, in patients with comorbidities, such as diabetes, the diagnosis may be a challenge. Here, we report the case of a 68-year-old man with a history of ulcerative rectocolitis (URC), type II diabetes and arterial hypertension, who had been treated with infliximab and adalimumab in the past. In September 2017, patient developed an erythematous, infiltrated and painful lesion of the third distal part of his left leg, with ulcerative evolution, rapidly worsened despite a broad-spectrum antibiotic treatment had been introducted. A worsening of rectocolitis occurred simultaneously. In agreement with the gastroenterologists, patient started a new biological therapy with golimumab, and oral prednisone with slow tapering of steroid dosage following the improvement of both cutaneous and intestinal symptoms. Dermatologists should be aware about the risk of PG in patient suffering from IBDs, and consider this diagnosis in all patients affected by URC developing rapidly extending ulcerative skin lesion. Moreover, therapeutic choice should take into consideration the effectiveness of golimumab on the inflammatory background, which sustains both intestinal and skin disease in this type of patients.

Impact of phosphoinositide-3-kinase and vitamin D3 nuclear receptor single-nucleotide polymorphisms on the outcome of malignant melanoma patients.

BACKGROUND: Several studies associating single nucleotide polymorphisms (SNPs) frequencies with tumors outcome have been conducted, nevertheless malignant melanoma literature data are inconclusive.Therefore we evaluate the impact of different genotypes for phosphoinositide-3-kinase (PI3K) and vitamin D3 nuclear receptor (VDR) SNPs on melanoma patients' outcome. MATERIALS AND METHODS: Genomic DNA of 88 patients was extracted from blood and tumor samples. SNPs were determined by PCR using TaqMan assays. We selected polymorphisms of the regulatory and catalytic subunit of PI3K (PIK3R1 and PIK3CA genes, respectively), analyzing rs2699887C>T of PIK3CA and rs3730089G>A of PIK3R1 SNPs. Furthermore we considered the following VDR SNPs: rs2228570A>G (Fok1), rs731236A>G (Taq1) and rs1544410C>T (Bsm1).Progression free survival (PFS) and overall survival (OS) were estimated with the Kaplan-Meier method and with Mantel-Haenszel log-rank test. RESULTS: The statistical analysis for Fok1 of VDR showed a significant difference in PFS after the first line therapy (median PFS= 21.2 months in the homozygous recessive genotype group vs. 3.3 months of homozygous dominant and heterozygous ones, p= 0.03). In particular, in homozygous recessive patients for Fok1 SNPs of VDR a high rate of histological regression and BRAF (B- Rapidly Accelerated Fibrosarcoma gene) mutation were observed. Furthermore, more efficacy of BRAF +/- MEK (MAPK-ERK-Kinase) inhibitors therapies in homozygous recessive patients vs. homozygous dominant and heterozygous ones was shown. CONCLUSIONS: Our study showed a significant correlation between homozygous recessive genotype of Fok1 SNPs of VDR gene and an increased PFS in patients who underwent a first line therapy with BRAF inhibitors.

A peculiar case of large primary cutaneous Ewing's sarcoma of the foot: Case report and review of the literature.

INTRODUCTION: Primary cutaneous extraskeletal Ewing's sarcomas (ESs) are extremely rare tumors, limited to the skin and generally appear as a single small lesion, circumscribed mid-to-deep dermis or involving subcutis. Due to their rarity and morphological similarity to other cutaneous tumors, ESs are subject to being clinically and pathologically subdiagnosed. PRESENTATION OF CASE: A 37-year-old man presented a large rapidly growing mass of the first toe measuring 9.5×8cm with no radiological evidence of bone involvement. The patient underwent wide surgical tumor resection; histological, immunohistochemical and molecular evaluation confirmed the diagnosis of ESs. Postoperative examinations revealed no metastasis and after 11 months follow-up no recurrences were detected. DISCUSSION: Current literature reports only a few isolated cases or small series. ESs are generally described as small masses with a favorable clinical behavior. Despite lower extremity is a relatively frequent site, only rare and small ESs of the foot have been reported. To our knowledge the present case is the largest ES of the foot. Despite its large size, the patient did not report any metastases confirming the hypothesis of treating superficial ES with surgery alone, thus avoiding adjuvant radiotherapy and/or chemotherapy and their related side-effects. CONCLUSION: ESs still remain exceedingly rare tumors and they could not be taken in consideration into differential diagnosis. This case represents a peculiar example of large ES in an uncommon site as the foot successfully treated with surgery alone, and may serve as an alert for those physicians who approach such rapidly growing superficial lesions.

Cdc42 is involved in basal cell carcinoma carcinogenesis.

Basal cell carcinoma (BCC) is the most common type of skin cancer in older persons and is a rapidly rising incidence. E-cadherin-mediated cell-cell adhesion activates Cdc42, a Rho GTPase essential for cell polarity in numerous settings. No study has yet addressed a biological significance of Cdc42 alterations in BCC pathogenesis. Our aim was to investigate E-cadherin-dependent cell-cell contacts and Cdc42 activity in BCC formation. We evaluated E-cadherin and Cdc42 expression by immunohistochemistry and Western blot analysis in samples of 15 normal skin (NS) and 30 BCC (10 superficial, 9 nodular and 11 infiltrative subtypes). Low E-cadherin and high Cdc42 immunohistochemical expression were found in BCC samples compared with NS. E-cadherin staining was significantly reduced in infiltrative BCC compared with superficial and nodular. A significantly greater Cdc42 expression was observed in BCC compared with NS; moreover, superficial BCC had a significantly lower Cdc42 expression in respect to the other subtypes. Western blot analysis confirmed the significantly decreased E-cadherin expression in infiltrative BCC as well as Cdc42 reduction in superficial BCC in respect to the other subtypes. In BCC the increased Cdc42 in association with reduced E-cadherin might contribute to the disruption of adhesion mechanisms and to the loss of cell polarity, thus explaining a mechanism by which cancer cells can escape from the control of adjacent normal keratinocytes. Our study also showed that Cdc42 and E-cadherin expression differed according to aggressive behaviour of BCC subtypes and suggested important functions of these molecules in regulating tumour demarcation and progression.

Immunohistochemical expression of vascular endothelial growth factor, matrix metalloproteinase 2, and matrix metalloproteinase 9 in cutaneous melanocytic lesions.

BACKGROUND: Vascular endothelial growth factor (VEGF), an endothelial cell mitogen, plays a hierarchical role in regulating physiologic and pathologic angiogenesis. Moreover, the transformation from noninvasive to invasive carcinomas is accompanied by focal disruption and discontinuity of the basement membrane. Several groups of proteases have been implicated in tumor cell invasion, including the 72-kDa gelatinase A/Type IV collagenase (matrix metalloproteinase 2 [MMP-2]) and the 92-kDa gelatinase B/Type IV collagenase (MMP-9). METHODS: The authors assessed the immunohistochemical expression of VEGF and metalloproteinases MMP-2 and MMP-9 in paraffin embedded biopsy specimens of malignant melanomas (18 invasive melanomas and 10 in situ melanomas); dysplastic nevi with architectural disorder and cytologic atypia of melanocytes; Spitz nevi; and compound or predominantly intradermal, ordinary, benign melanocytic nevi. RESULTS: Strong cytoplasmic staining for VEGF was observed in melanoma cells in as many as 77% of primary invasive melanomas, whereas only 25% of the in situ melanomas exhibited a detectable immunoreactivity for VEGF. It is interesting to note that no immunoreactivity was shown by any nevi; Spitz nevi, in particular, showed negative immunoreactivity to VEGF. Invasive melanomas and in situ melanomas displayed coexpression of MMP-2 and MMP-9, although to a variable extent. In particular, high MMP-2 staining was observed in 14 of 18 invasive melanomas; moreover, strong MMP-2 expression also was observed in 60% of in situ melanomas, whereas the residual 40% of those melanomas showed a moderate level of positivity. CONCLUSIONS: On the basis of the current data showing that malignant melanocytic tumors displayed strong VEGF expression, whereas benign melanocytic proliferations showed no immunoreactivity for VEGF, VEGF also may be used as a discriminating factor to distinguish malignant melanoma from lesions of uncertain histology.