Publications by authors named "Virginia Mancini"

24 Publications

  • Page 1 of 1

Burkitt lymphoma with granulomatous reaction: A M1/TH1-polarized microenvironment associates with controlled growth and spontaneous regression.

Histopathology 2021 May 5. Epub 2021 May 5.

Department of Medical Biotechnologies, University of Siena, Siena, Italy.

Aims: Burkitt lymphoma (BL) is an aggressive B-cell lymphoma, which in some instances, may show a granulomatous reaction associated with a favourable prognosis and occasional spontaneous regression. In the present study, we aimed to define the tumour microenvironment (TME) in four of such cases, two of which regressed spontaneously.

Methods And Results: All cases showed aggregates of tumour cells with the typical morphology, molecular cytogenetics and immunophenotype of BL surrounded by a florid epithelioid granulomatous reaction. All four cases were Epstein-Barr virus (EBV) positive with type I latency. The investigation of the tumour microenvironment (TME) showed similar features in all four cases. The analysis revealed a pro-inflammatory response triggered by Th1 lymphocytes and M1 polarized macrophages encircling the neoplastic cells with a peculiar topographic distribution.

Conclusions: Our data provide an in vivo picture of the role that specific immune cell subsets might play during the early phase of BL, which may be capable of maintaining the tumour in a self-limited state or inducing its regression. These novel results may provide insights to explore new potential therapeutic avenues in EBV-positive BL patients in the era of cellular immunotherapy.
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http://dx.doi.org/10.1111/his.14391DOI Listing
May 2021

Extrapalmoplantar pustolosis in Sonozaki Syndrome.

Ital J Dermatol Venerol 2021 Apr 9;156(2):264-265. Epub 2020 Oct 9.

Section of Dermatology, Department of Medical, Surgical and Neurological Science, S. Maria alle Scotte Hospital, University of Siena, Siena, Italy.

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http://dx.doi.org/10.23736/S0392-0488.20.06635-3DOI Listing
April 2021

Anetoderma observed with reflectance confocal microscopy.

G Ital Dermatol Venereol 2020 Oct 9. Epub 2020 Oct 9.

Dermatology Section, Department of Medical, Surgical and Neurological Science, S. Maria alle Scotte Hospital, University of Siena, Siena, Italy.

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http://dx.doi.org/10.23736/S0392-0488.20.06627-4DOI Listing
October 2020

Prognostic impact of tumor-associated macrophages, lymphocyte-to-monocyte and neutrophil-to-lymphocyte ratio in diffuse large B-cell lymphoma.

Am J Blood Res 2020 25;10(4):97-108. Epub 2020 Aug 25.

Unit of Pathology, Department of Medical Biotechnologies, University of Siena Siena, Italy.

Introduction: Microenvironment has a prognostic influence in diffuse large B-cell lymphoma (DLBCL); among its components, tumor-associated macrophages (TAM) play a leading role. TAM can be classified into M1 (anti-tumor) and M2 (pro-tumor). Another prognostic factor could be represented by lymphocyte-to-monocyte and neutrophil-to-lymphocyte ratio (LMR and NLR).

Objective: The aim of the study is to evaluate the prognostic impact of M1 and M2 TAM subtypes, LMR and NLR in DLBCL.

Methods: We analyzed 37 consecutive patients between 2009 and 2013. Out of 37 patients, 28/37 (75.6%) received R-CHOP/CHOP-like regimens, 9/37 (24.4%) less intensive therapies. Immunohistochemistry was performed with antibodies against CD68 and CD163. We divided our cohort into 2 categories according to the Steidl score. TAM who coexpressed CD68 and CD163 were considered as M2. For LMR and NLR we used previously published cut-offs of 2.71 and 2.81.

Results: CR rate was 70.3%; we did not record a significant correlation between CD68+ TAM, CD163+ TAM, CD68+/CD163+ TAM, LMR, NLR and CR. We observed a reduced PFS in patients with IPI ≥ 2 and high M2 TAM expression and a trend between higher expression of CD68+ TAM and improved PFS.

Conclusion: M2 TAM could have a prognostic role for IPI ≥ 2 DLBCL patients receiving R-CHOP, which thus warrants further investigation.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7486489PMC
August 2020

Frequent traces of EBV infection in Hodgkin and non-Hodgkin lymphomas classified as EBV-negative by routine methods: expanding the landscape of EBV-related lymphomas.

Mod Pathol 2020 12 1;33(12):2407-2421. Epub 2020 Jun 1.

Section of Pathology, Department of Medical Biotechnology, University of Siena, Siena, Italy.

The Epstein-Barr virus (EBV) is linked to various B-cell lymphomas, including Burkitt lymphoma (BL), classical Hodgkin lymphoma (cHL) and diffuse large B-cell lymphoma (DLBCL) at frequencies ranging, by routine techniques, from 5 to 10% of cases in DLBCL to >95% in endemic BL. Using higher-sensitivity methods, we recently detected EBV traces in a few EBV-negative BL cases, possibly suggesting a "hit-and-run" mechanism. Here, we used routine and higher-sensitivity methods (qPCR and ddPCR for conserved EBV genomic regions and miRNAs on microdissected tumor cells; EBNA1 mRNA In situ detection by RNAscope) to assess EBV infection in a larger lymphoma cohort [19 BL, 34 DLBCL, 44 cHL, 50 follicular lymphomas (FL), 10 T-lymphoblastic lymphomas (T-LL), 20 hairy cell leukemias (HCL), 10 mantle cell lymphomas (MCL)], as well as in several lymphoma cell lines (9 cHL and 6 BL). qPCR, ddPCR, and RNAscope consistently documented the presence of multiple EBV nucleic acids in rare tumor cells of several cases EBV-negative by conventional methods that all belonged to lymphoma entities clearly related to EBV (BL, 6/9 cases; cHL, 16/32 cases; DLBCL, 11/30 cases), in contrast to fewer cases (3/47 cases) of FL (where the role of EBV is more elusive) and no cases (0/40) of control lymphomas unrelated to EBV (HCL, T-LL, MCL). Similarly, we revealed traces of EBV infection in 4/5 BL and 6/7 HL cell lines otherwise conventionally classified as EBV negative. Interestingly, additional EBV-positive cases (1 DLBCL, 2 cHL) relapsed as EBV-negative by routine methods while showing EBNA1 expression in rare tumor cells by RNAscope. The relapse specimens were clonally identical to their onset biopsies, indicating that the lymphoma clone can largely loose the EBV genome over time but traces of EBV infection are still detectable by high-sensitivity methods. We suggest EBV may contribute to lymphoma pathogenesis more widely than currently acknowledged.
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http://dx.doi.org/10.1038/s41379-020-0575-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7685982PMC
December 2020

Immune landscape in Burkitt lymphoma reveals M2-macrophage polarization and correlation between PD-L1 expression and non-canonical EBV latency program.

Infect Agent Cancer 2020 6;15:28. Epub 2020 May 6.

11Department of Cellular Pathology, University College Hospital, London, London UK.

Background: The Tumor Microenviroment (TME) is a complex milieu that is increasingly recognized as a key factor in multiple stages of disease progression and responses to therapy as well as escape from immune surveillance. However, the precise contribution of specific immune effector and immune suppressor components of the TME in Burkitt lymphoma (BL) remains poorly understood.

Methods: In this paper, we applied the computational algorithm CIBERSORT to Gene Expression Profiling (GEP) datasets of 40 BL samples to draw a map of immune and stromal components of TME. Furthermore, by multiple immunohistochemistry (IHC) and multispectral immunofluorescence (IF), we investigated the TME of additional series of 40 BL cases to evaluate the role of the Programmed Death-1 and Programmed Death Ligand-1 (PD-1/PD-L1) immune checkpoint axis.

Results: Our results indicate that M2 polarized macrophages are the most prominent TME component in BL. In addition, we investigated the correlation between PD-L1 and latent membrane protein-2A (LMP2A) expression on tumour cells, highlighting a subgroup of BL cases characterized by a non-canonical latency program of EBV with an activated PD-L1 pathway.

Conclusion: In conclusion, our study analysed the TME in BL and identified a tolerogenic immune signature highlighting new potential therapeutic targets.
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http://dx.doi.org/10.1186/s13027-020-00292-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7201729PMC
May 2020

Amenorrhea secondary to vismodegib: An adverse event to consider especially in female patients with Gorlin-Goltz syndrome.

Dermatol Ther 2020 07 26;33(4):e13527. Epub 2020 May 26.

Department of Medical, Surgical and Neurological Science, Dermatology Section, University of Siena, S. Maria alle Scotte Hospital, Siena, Italy.

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http://dx.doi.org/10.1111/dth.13527DOI Listing
July 2020

Correction to: IGHV mutational status of nodal marginal zone lymphoma by NGS reveals distinct pathogenic pathways with different prognostic implications.

Virchows Arch 2020 07;477(1):169

Department of Medical Biotechnologies, Anatomic Pathology Division, University of Siena, Via delle Scotte, 6, 53100, Siena, Italy.

This error was caused due to the author's oversight and this does not change the views or the results presented in the manuscript.
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http://dx.doi.org/10.1007/s00428-020-02794-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7645535PMC
July 2020

IGHV mutational status of nodal marginal zone lymphoma by NGS reveals distinct pathogenic pathways with different prognostic implications.

Virchows Arch 2020 Jul 4;477(1):143-150. Epub 2019 Dec 4.

Department of Medical Biotechnologies, Anatomic Pathology Division, University of Siena, Via delle Scotte, 6, 53100, Siena, Italy.

The precise B cell of origin and molecular pathogenesis of nodal marginal zone lymphoma (NMZL) remain poorly defined. To date, due to the rarity of NMZL, the vast majority of already-published studies have been conducted on a limited number of samples and the technical approach to analyze the immunoglobulin genes was of amplifying rearranged variable region genes with the classical direct sequencing of the PCR products followed by cloning. Here, we studied the B cell Ig heavy-chain repertoires by next-generation sequencing (NGS) in 30 NMZL cases. Most of the cases were mutated (20/28; 71.5%) with homologies to the respective germ line genes ranging from 85 to 97, 83%, whereas 8/28 (28.5%) were unmutated. In addition, our results show that NMZL cases have a biased usage of specific immunoglobulin heavy-chain variable (IGHV) region genes. Moreover, we documented intraclonal diversity in all (100%) of the mutated cases and ongoing somatic hypermutations (SHM) have been confirmed by hundreds of reads. We analyzed the mutational pattern to detect and quantify antigen selection pressure and we found a positive selection in 4 cases, whereas in the remaining cases there was an unspecific stimulation. Finally, the disease-specific survival and the progression-free survival were significantly different between cases with mutated and unmutated IGHV genes, pointing out mutational status as a possible new biomarker in NMZL.
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http://dx.doi.org/10.1007/s00428-019-02712-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7320062PMC
July 2020

Molecular switch from MYC to MYCN expression in MYC protein negative Burkitt lymphoma cases.

Blood Cancer J 2019 11 20;9(12):91. Epub 2019 Nov 20.

Department of Medical Biotechnology, University of Siena, Siena, Italy.

MYC is the most altered oncogene in human cancer, and belongs to a large family of genes, including MYCN and MYCL. Recently, while assessing the degree of correlation between MYC gene rearrangement and MYC protein expression in aggressive B-cell lymphomas, we observed few Burkitt lymphoma (BL) cases lacking MYC protein expression despite the translocation involving the MYC gene. Therefore, in the present study we aimed to better characterize such cases. Our results identified two sub-groups of MYC protein negative BL: one lacking detectable MYC protein expression but presenting MYCN mRNA and protein expression; the second characterized by the lack of both MYC and MYCN proteins but showing MYC mRNA. Interestingly, the two sub-groups presented a different pattern of SNVs affecting MYC gene family members that may induce the switch from MYC to MYCN. Particulary, MYCN-expressing cases show MYCN SNVs at interaction interface that stabilize the protein associated with loss-of-function of MYC. This finding highlights MYCN as a reliable diagnostic marker in such cases. Nevertheless, due to the overlapping clinic, morphology and immunohistochemistry (apart for MYC versus MYCN protein expression) of both sub-groups, the described cases represent bona fide BL according to the current criteria of the World Health Organization.
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http://dx.doi.org/10.1038/s41408-019-0252-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6868231PMC
November 2019

Pyoderma gangrenosum secondary to total hip replacement.

G Ital Dermatol Venereol 2019 Apr 23. Epub 2019 Apr 23.

Dermatology Section, Department of Clinical Medicine and Immunological Science, University of Siena, Siena, Italy.

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http://dx.doi.org/10.23736/S0392-0488.19.06256-4DOI Listing
April 2019

Treatment of resistant granuloma annulare with Rifampin, Norfloxacin, and Minocycline combination therapy.

G Ital Dermatol Venereol 2019 Feb 4. Epub 2019 Feb 4.

Dermatology Section, Department of Medical, Surgical and Neurological Science, S. Maria alle Scotte Hospital, University of Siena, Siena, Italy.

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http://dx.doi.org/10.23736/S0392-0488.19.06270-9DOI Listing
February 2019

Tuscan consensus on the use of UVBnb phototherapy in the treatment of psoriasis.

G Ital Dermatol Venereol 2019 Apr 29;154(2):99-105. Epub 2018 Oct 29.

Section of Dermatology, Department of Clinical Medicine and Immunological Science, University of Siena, Siena, Italy.

Psoriasis (PSO) is traditionally defined as an immune-mediated, inflammatory dermatological disease characterized by a chronic-relapsing course and associated with multifactorial inheritance (genetic predisposition and influence of various environmental factors). Considered until recently a dermatological disease only, today PSO is correctly known as a systemic one because of the involvement of multiple organs with important impact on social life and relationships. PSO is found in the 0.3-4.6% of the world's population, while its prevalence in the Italian population is estimated at 2.8%. Therefore, if we consider that in Tuscany more than 100,000 people out of 3,672,202 suffer of psoriasis, it is of paramount importance to focus on a shared clinical and therapeutic protocol to manage the disease. With the aim of ensuring diagnostic-therapeutic suitability, high levels of care and standardization of treatment, a unique clinical-therapeutic management model has been developed and validated in Tuscany, involving all accredited regional dermatological centers. Among the possible alternatives to be implemented in the treatment of patients with mild, moderate-severe psoriasis, UVBnb phototherapy is widely used alone or in association with other systemic and non-systemic devices. Despite this, there is still no universally shared therapeutic protocol. In this context the CO.FO.TO working group (Consensus Fototerapia Toscana) is born with the aim of defining and validating the main guidelines in the use of phototherapy with UVBnb in psoriasis; the guidelines are based both on the real-life experience of the different centers of reference in the region and on the revision of the recent literature.
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http://dx.doi.org/10.23736/S0392-0488.18.06223-5DOI Listing
April 2019

New onset psoriasis in a patient with chronic inflammatory demyelinating polyneuropathy treated with Rituximab.

G Ital Dermatol Venereol 2020 Dec 22;155(6):802-803. Epub 2018 Oct 22.

Section of Dermatology, Department of Clinical Medicine and Immunological Science, University of Siena, Siena, Italy.

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http://dx.doi.org/10.23736/S0392-0488.18.06180-1DOI Listing
December 2020

The psychological burden in psoriatic patients beyond PASI.

J Psychosom Res 2018 08 31;111:118-119. Epub 2018 May 31.

Dermatology Section, Department of Clinical Medicine and Immunological Science, University of Siena, Siena, Italy.

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http://dx.doi.org/10.1016/j.jpsychores.2018.05.018DOI Listing
August 2018

Intravenous Immunoglobulins as a new opportunity to treat discoid lupus erythematosus: A case report and review of the literature.

Autoimmun Rev 2018 Aug 6;17(8):791-795. Epub 2018 Jun 6.

Rheumatology Unit, Department of Medicine, Surgery and Neurosciences, University of Siena, Italy. Electronic address:

Discoid lupus erythematosus (DLE) is a chronic dermatological disease that can lead to scarring, alopecia and dyspigmentation, if not properly treated. Actually, no drugs are specifically approved for the treatment of CLE, although the first-line therapy usually consists of photoprotection associated to topical or oral steroids, topical calcineurin inhibitors and hydroxychloroquine (HCQ). In cases of DLE refractory to these medications, many other agents have been employed, such as dapsone, methotrexate, azathioprine, cyclophosphamide, biologic drugs and Intravenous Immunoglobulin (IVIG). We described the case of a DLE patient resistant to combination therapy with steroid and HCQ who was successfully treated with cyclical IVIG therapy. The treatment with IVIG resulted rapidly effective with persistent efficacy and low rates of relapses, although more cycles of IVIG are needed to achieve a stable clinical remission. We also discussed the beneficial and promising effects of IVIG in patients with Cutaneous Lupus reporting the previously published data.
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http://dx.doi.org/10.1016/j.autrev.2018.02.010DOI Listing
August 2018

BCC and vismodegib: can we treat and remold at the same time?

G Ital Dermatol Venereol 2020 Feb 16;155(1):119-120. Epub 2018 May 16.

Section of Dermatology, Department of Clinical Medicine and Immunological Science, University of Siena, Siena, Italy.

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http://dx.doi.org/10.23736/S0392-0488.18.06043-1DOI Listing
February 2020

Solitary vulvar neurofibroma in a patient without neurofibromatosis.

G Ital Dermatol Venereol 2018 Aug;153(4):591-593

Dermatology Section, Department of Clinical Medicine and Immunological Science, University of Siena, Siena, Italy.

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http://dx.doi.org/10.23736/S0392-0488.17.05706-6DOI Listing
August 2018

Neglected skin carcinomas and Vismodegib: our experience.

G Ital Dermatol Venereol 2019 Oct 7;154(5):597-599. Epub 2018 Feb 7.

Department of Dermatology, Misericordia Hospital, Grosseto, Italy.

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http://dx.doi.org/10.23736/S0392-0488.18.05873-XDOI Listing
October 2019

Clinical and histological evaluation in patients with mycosis fungoides treated with UVA1.

G Ital Dermatol Venereol 2020 Jun 24;155(3):306-311. Epub 2018 Jan 24.

Unit of Dermatology, Department of Medical, Surgical and Neurosciences, University of Siena, Siena, Italy.

Background: UVA1 phototherapy is a valid therapeutic alternative for skin lymphoproliferative disorders, although there are few studies concerning its role in mycosis fungoides (MF). Our aim was to evaluate and confirm the effectiveness of UVA1 phototherapy in patients in early stage MF.

Methods: We enrolled 12 patients, 9 males and 3 females (mean age 54.83±9.99, range 36-74) with a histological diagnosis of mycosis fungoides at early stage. All patients were treated with UVA1 for 22 sessions with two different protocols (3 times or 5 times per week) at the dose of 45 J/cm2. A punch biopsy was performed before and after the treatment, to evaluate the variation of histological features and of the proliferation index (Ki67/MIB1).

Results: At the end of the study, we found a marked clinical improvement in all patients, associated to a statistically significant reduction of the proliferation index Ki67/MIB1. Five patients achieved a complete clinical and histological response, while six a partial one and only one a minimal response.

Conclusions: Although in recent years the number of the therapeutic options available for all types of skin lymphoproliferative disorders, in particular mycosis fungoides, has increased considerably, there are few studies concerning UVA1 phototherapy. Our results represent a starting point for further studies, in order to investigate the role that these UV-rays can play either alone or in combination with other therapeutic regimens.
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http://dx.doi.org/10.23736/S0392-0488.18.05867-4DOI Listing
June 2020