Promyelocytic Sarcoma of the Spine: A Case Report and Review of the Literature

Myeloid sarcoma (MS, previously named granulocytic sarcoma or chloroma) is a rare extramedullary tumour of immature myeloid cells. It can be present before, concurrently with, or after the diagnosis of acute myeloid leukemia. MS is extremely uncommon in acute promyelocytic leukemia (APL). In the case described here, MS was the sole site of APL relapse and the cause of spinal cord compression. The patient presented with neurologic symptoms due to a paravertebral mass of MS after 7 years of complete remission. He was treated with excision of the mass followed by local radiotherapy. Systemic treatment was also given with combined arsenic trioxide and all-trans retinoic acid and the patient was able to achieve a second prolonged clinical and molecular remission

Subcutaneous panniculitis-like T-cell lymphoma presenting with diffuse cutaneous edema in a 2-year-old child

N/

Skin homing of Sézary cells involves SDF-1-CXCR4 signaling and down-regulation of CD26/dipeptidylpeptidase IV

AbstractSézary syndrome (SS) is a rare form of cutaneous T-cell lymphoma (CTCL) characterized by a distinct metastatic pattern mainly involving blood and skin. Chemokines and their receptors play a critical role in cellular recruitment and homing to tissues and in the metastatic process of several tumors including non-Hodgkin T-cell lymphomas (NHLs). Here we report that SS cells express a functionally active CXCR4 and that its ligand SDF-1 is abundantly produced in the skin, which represents the main destination of SS cell spreading. SDF-1 is normally inactivated by proteolytic cleavage by the CD26/dipeptidylpeptidase IV (DPPIV). The lack of CD26 from the cell surface is a hallmark of circulating SS cells. We also show that the CD26- phenotype is maintained also in skin-infiltrating neoplastic T lymphocytes and that SS-affected individuals exhibit a reduced activity of plasma soluble CD26. Finally, we observe that the addition of soluble CD26 reduces the migratory response of SS cells to SDF-1 whereas the inhibition of the CD26 peptidase activity in Hut78, a CD26+ CTCL cell line, enhances the SDF-1-induced migration of these cells. Our findings suggest that the SDF-1-CXCR4 axis could play an important role in skin homing of SS through the regulatory activity of CD26

Prophylactic Dermatologic Treatment of Afatinib-Induced Skin Toxicities in Patients with Metastatic Lung Cancer: A Pilot Study

Background. Severe skin rash is listed among important side effects of EGFR tyrosine kinase inhibitors. Polydatin (PD), a glycosylated polyphenol, is endowed with anti-inflammatory activity in human epidermal keratinocytes. Objective. This study evaluated the effect of topical application of a moisturizer containing PD to prevent skin rash in patients with mutated non-small cell lung cancer (NSCLC) treated with afatinib. Materials and Methods. Eligible NSCLC patients with metastatic disease were treated with first-line afatinib 40 mg/die. One day before starting systemic therapy, all patients received topical administration of a 1.5% PD-based cream b.i.d. every day until the end of afatinib treatment. Results. Out of 34 treated patients, the incidence of skin rash (all grades) was 41.2% and grade 2 rash was 20.6%, and grade 3 rash was not observed in any of the patients. None of the patients discontinued therapy for toxicity. The mean duration of treatment was 6.4 months, calculated from the time treatment was started to the date treatment was stopped. Conclusion. The results showed that a PD-based cream can reduce the incidence of grade ≥2 skin toxicities in patients treated with afatinib. Clinical study registration number: Prot. No. 130/CE Lazio 1 Italy

Syndromic true hermaphroditism due to an R-spondin1 (RSPO1) homozygous mutation

XX true hermaphroditism, also know as ovotesticular disorder of sexual development (DSD), is a disorder of gonadal development characterized by the presence of both ovarian and testicular tissue in a 46,XX individual. The genetic basis for XX true hermaphroditism and sex reversal syndromes unrelated to SRY translocation is still mostly unclear. We report mutational analysis of the RSPO1 gene in a 46,XX woman with true hermaphroditism, palmoplantar keratoderma, congenital bilateral corneal opacities, onychodystrophy, and hearing impairment. R-spondin1 is a member of the R-spondin protein family and its pivotal role in sex determination has been recently described. We identified a homozygous splice-donor-site mutation in the RSPO1 gene in our patient. We found that the c.286+1G>A mutation led to an aberrantly spliced mRNA (r.95_286del), which is presumably translated into a partially functional protein (p.Ile32_Ile95del). Our case demonstrates for the first time, to our knowledge, that XX true hermaphroditism can be caused by a single gene mutation. The reported findings represent a further step toward a complete understanding of the complex mechanisms leading to DSDs. © 2007 Wiley-Liss, Inc

Hepatitis C virus-related B cell subtypes in non Hodgkin's lymphoma

AIM: To evaluate if indolent B cell-non Hodgkin’s lymphoma (B-NHL) and diffuse large B-cell lymphoma (DLBCL) in hepatitis C virus (HCV) positive patients could have different biological and clinical characteristics requiring different management strategies

Thymic epithelial tumors express vascular endothelial growth factors and their receptors as potential targets of antiangiogenic therapy: A tissue micro array-based multicenter study

Objectives: Tumor angiogenesis is an essential and complex process necessary for the growth of all tumors which represents a potential therapeutic target. Angiogenesis inhibitors targeting vascular endothelial growth factor (VEGF) or their receptor tyrosine kinases have been approved by the FDA. In thymic epithelial tumors (TET), targeted therapies have been sporadically applied due to their rarity. To ascertain the presence of potential therapeutic targets, we analyzed by immunohistochemistry the expression of angiogenesis-related biomarkers in a large series of TET arranged in Tissue Micro Arrays (TMA). Materials and methods: We assessed by immunohistochemistry the expression of the possible molecular target of anti-angiogenic therapy, i.e. VEGFA, VEGFC, VEGFD, VEGFR1, VEGFR2, VEGFR3, and PDGFRβ, in a TMA series of 200 TET collected in the framework of a multi-institutional collaborative project for Rare Diseases. Results: When compared to the low-risk tumors, high-risk TET (B2, B3, carcinomas) contained higher proportion of cancer cells expressing VEGFA, VEGFC and VEGFD (P< 0.001, P< 0.001, and P< 0.001) growth factors, and their receptors VEGFR1 (P= 0.002), VEGFR2 (P= 0.013), and VEGFR3 (P= 0.041). No differences were observed in terms of PDGFRβ expression. Conclusions: According to our data, it is possible to hypothesize the existence of multiple paracrine and/or autocrine loops in TET, particularly in the high-risk ones, involved in TET growth and progression. Anti-angiogenic agents, directed to inhibit these loops, are therefore to be considered as potential tools in advanced TET therapy. © 2014 Elsevier Ireland Ltd.Abstract OBJECTIVES: Tumor angiogenesis is an essential and complex process necessary for the growth of all tumors which represents a potential therapeutic target. Angiogenesis inhibitors targeting vascular endothelial growth factor (VEGF) or their receptor tyrosine kinases have been approved by the FDA. In thymic epithelial tumors (TET), targeted therapies have been sporadically applied due to their rarity. To ascertain the presence of potential therapeutic targets, we analyzed by immunohistochemistry the expression of angiogenesis-related biomarkers in a large series of TET arranged in Tissue Micro Arrays (TMA). MATERIALS AND METHODS: We assessed by immunohistochemistry the expression of the possible molecular target of anti-angiogenic therapy, i.e. VEGFA, VEGFC, VEGFD, VEGFR1, VEGFR2, VEGFR3, and PDGFRβ, in a TMA series of 200 TET collected in the framework of a multi-institutional collaborative project for Rare Diseases. RESULTS: When compared to the low-risk tumors, high-risk