Ubaldo Familiari

Azienda Ospedaliero Universitaria San Luigi Gonzaga, Orbassano, Piedmont, Italy

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Publications (18)55.87 Total impact

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    ABSTRACT: Background: The development of secondary malignancies is a potential long-term complication after haematopoietic stem cell transplantation (HSCT). In particular, a higher incidence of oral squamous cell carcinoma (OSCC) has been reported in patients experiencing chronic graft vs host disease (cGvHD) secondary to HSCT. The International Consensus Conference on clinical practice in cGVHD reported that Tacrolimus is the first-line treatment for oral cGVHD. Recently, however, the FDA reviewed the safety of topical tacrolimus, which resulted in a warning that the use of calcineurin inhibitors may be associated with an increased risk of cancer. Case summary: Multiple Myeloma (MM) was diagnosed in a 39-years-old woman in September 2006. Six months after diagnosis, the patient underwent autologous stem cell transplantation (ASCT) and 9 months later an allogenic stem cell transplantation was performed. Sixteen months later, she developed a multisystemic cGVHD with oral, ocular and genital involvement. Systemic ciclosporin and prednisone were alternatively administered. Oral topical treatment with tacrolimus 0.1% was performed for 22 months from November 2008. From September 2012 to April 2013 topical clobetasol was alternatively administered for 6 months. From April 2013 to March 2014 three microinvasive carcinomas were observed on the right dorsal tongue. They all were surgically excised with free surgical margins. Conclusions: This report describes the development of three synchronous SCC of the oral tongue in a patient with oral manifestations of cGVHD, topically treated with Tacrolimus ointment 0.1%, thus showing a clear field effect in carcinogenesis related to cGVHD and it highlights a potential adjunctive role for topical application of calcineurin inhibitors as previously reported. Therefore, the use of Tacrolimus as a first-line treatment in cGVHD and its duration should be carefully evaluated on a case-by-case approach and clinical follow- up is mandatory to early detect malignant transformation.
    12th Biennial Congress of the European Association of Oral Medicine, 11–14 September 2014, Gloria Hotels and Resort Antayla, Turkey, Issue Supplement s2, pages 24–35, September 2014; 09/2014
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    ABSTRACT: Chronic myeloid leukemia (CML) is a myeloproliferative disorder characterized by the t(9;22) translocation coding for the chimeric protein p210 BCR-ABL. The tumor suppressor PTEN has recently been shown to play a critical role in the pathogenesis of CML. Nuclear localization and proper nuclear-cytoplasmic shuttling is crucial for PTEN's tumor suppressive function. In this study, we show that BCR-ABL enhances HAUSP-induced de-ubiquitination of PTEN in turn favoring its nuclear exclusion. We further demonstrate that BCR-ABL physically interacts with and phosphorylates HAUSP on tyrosine residues to trigger its activity. Importantly, we also find that PTEN delocalization induced by BCR-ABL does not occur in the leukemic stem cell compartment due to high levels of PML, a potent inhibitor of HAUSP activity towards PTEN. We therefore identify a new proto-oncogenic mechanism whereby BCR-ABL antagonizes the nuclear function of the PTEN tumor suppressor, with important therapeutic implications for the eradication of CML minimal residual disease.Leukemia accepted article preview online, 9 December 2013. doi:10.1038/leu.2013.370.
    Leukemia: official journal of the Leukemia Society of America, Leukemia Research Fund, U.K 12/2013; · 10.16 Impact Factor
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    ABSTRACT: Oral dysontogenic cysts result from defective embryonic development. Among them teratoid cysts are the most unusual presentation and may be lined by gastric, intestinal, respiratory, squamous, ciliated epithelium or even pancreatic structures. Teratoid cysts containing respiratory and gastrointestinal epithelium have typically been called choristomas. This article describes a 15-year-old boy presenting a choristoma involving both the floor of the mouth and the anterior tongue and characterized by the presence of squamous epithelium with skin adnexa, gastric and respiratory epithelium.
    Journal of oral and maxillofacial surgery: official journal of the American Association of Oral and Maxillofacial Surgeons 07/2013; · 1.58 Impact Factor
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    ABSTRACT: BACKGROUND: Thymic epithelial tumors include several entities with different biologic behavior. Chemotherapy is indicated in advanced disease, but limited data exist on gene expression correlation with the response to chemotherapeutic agents. PATIENTS AND METHODS: A series of 69 thymic neoplasms (7 A-, 6 AB-, 6 B1-, 10 B2-, 14 B3-thymomas, 22 carcinomas and 4 combined tumors) was collected to assess gene expression of thymidylate synthase (TS), excision repair cross complementing-1 (ERCC1), ribonucleotide reductase subunit 1 (RRM1), topoisomerase 2α (TOP2A) and mTOR. RESULTS: A strong linear correlation between TS gene and protein expression was observed (P<0.0001, R=0.40). TS expression was significantly lower in pure A-thymomas and thymic carcinomas (P<0.0001) and progressively decreasing from B1-type to thymic carcinomas (B1>B2>B3>C; P<0.0001). RRM1 and TOP2A mRNA expression levels were significantly correlated with TS levels (both P=0.03) with a similar trend of expression among histotypes. RRM1 and TOP2A high levels were significantly correlated with high TS (P=0.03) and low tumor stages (I-II) (P<0.0001 and P<0.01, respectively). No relevant changes of ERCC1 and mTOR were detected. CONCLUSIONS: Low TS and, to a minor extent, RRM1 and TOP2A expression were detected in aggressive thymic tumors. These findings should be prospectively considered in selecting the most appropriate chemotherapy.
    Lung cancer (Amsterdam, Netherlands) 12/2012; · 3.14 Impact Factor
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    Hematology - Science and Practice, 03/2012; , ISBN: 978-953-51-0174-1
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    ABSTRACT: Oral fields of visually normal and non-dysplastic mucosa (ODFs) may represent the precursors of oral potentially malignant lesions (OPMLs). Aim of the study was to provide new evidence for the concept of the "field carcinogenesis" model by comparing the ODF and OPML genomic aberration profiles obtained by high resolution DNA flow cytometry (hr DNA-FCM) and array-Comparative Genomic Hybridization (a-CGH). A second aim was to investigate if specific CGH aberrations were associated with DNA aneuploidy. Nineteen patients with single OPMLs were recruited for the study. In parallel with obtaining samples of OPML tissue from 11 leukoplakias without dysplasia (nd-OPMLs) and 8 with dysplasia (d-OPMLs), we also obtained samples from distant ODFs. DNA aneuploid nuclei detected by hr DNA-FCM were physically separated, based on DNA content, from the DNA diploid components with a DNA-FCM-Sorter. These relatively pure subpopulations of epithelial nuclei were then submitted to DNA extraction and a-CGH for a genome-wide analysis of DNA copy number aberrations (CNAs). The frequencies of DNA aneuploidy (DI ≠ 1) among ODFs and OPMLs were respectively 5.3% and 32%. The DI aneuploid values of ODFs and nd-OPMLs were all near-diploid (DI ≠ 1 and DI ≤ 1.4), while for d-OPMLs were high-aneuploid (DI > 1.4) in 40% of the cases. CNA averages were 1.9 in ODFs and 6.5 in OPMLs. The gain of the chromosomal region 20q13.33-qter was observed in 37% of both ODFs and corresponding OPMLs. Additional common regions included 7p22.2-pter, 11p15.5-pter and 16p13.3-pter where gains were observed. Furthermore, gains of 20q13.31-q13.33 and of 5p13.33-pter and loss of 9p21.3 were detected at high frequency (respectively, at 62.5%, 50% and 50%) only in d-OPMLs. In particular, loss at 9p21.3, gain at 5p13.33-pter and gain of 20q13.31-q13.33 were associated with DNA aneuploidy (p = 0.00004; p = 0.0005; p = 0.01). ODFs and OPMLs showed common CNAs in specific chromosomal regions suggesting that they may represent early events of the natural history of oral carcinogenesis according to the field effect cancerization and may contribute to the ODF-OPML transition. In addition, loss at 9p21.3 and gains at 5p13.33-pter and 20q13.31-q13.33 may contribute to DNA aneuploidization.
    Cellular oncology (Dordrecht). 12/2011; 35(1):43-52.
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    ABSTRACT: 'Field cancerization' is an accepted model for oral carcinogenesis. So far, genetically altered fields have been just reported in the presence of carcinomas. This study assessed the distant mirror fields (MFs) of oral precancer by DNA high-resolution flow cytometry (hr DNA-FCM) and array-Comparative Genomic Hybridization (a-CGH). Five leukoplakias without dysplasia (OLs), seven dysplastic leukoplakias (DOLs), and 12 corresponding visually normal and non-dysplastic MFs were analyzed. DNA aneuploidy (DNA Index, DI ≠ 1) was detected by hr DNA-FCM on DAPI stained nuclei suspensions. The epithelial DNA aneuploid subclones were FCM-sorted to obtain genomic DNA for a-CGH. Mirror fields, OLs, and DOLs showed increasing prevalence of DNA aneuploidy of, respectively, 8%, 20%, and 57%. The average number of chromosome aberrations (Ch-Abs) was 2.8 in MFs, 3 in OLs, and 10.6 in DOLs. MFs relative to OLs and DOLs had average numbers of Ch-Abs, respectively, of 1.8 and 3.6. Ch-Abs were also observed in DNA diploid sublines, and often the same aberrations were observed in both MFs and corresponding OLs/DOLs. DNA aneuploidy and Ch-Abs in MFs, the last ones being mainly gains, indicate an early onset of field effect in oral carcinogenesis.
    Journal of Oral Pathology and Medicine 09/2011; 41(2):119-23. · 2.06 Impact Factor
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    ABSTRACT: Oral verrucous carcinomas (OVCs) are characterized by better prognosis than oral squamous cell carcinomas (OSCCs). Because chromosomal instability (CIN) in solid tumors is indicative of prognosis, this study investigated whether OVCs and OSCCs were characterized by differences in CIN biomarkers. Fresh or frozen multiple tissue samples were submitted to high-resolution DNA flow cytometry (hr DNA-FCM). DNA aneuploid sublines were detected in 6 of 9 OVCs (66.7%) and in 20 of 25 OSCCs (80.0%). Multiple DNA aneuploid sublines were observed, respectively, in 2 of 6 (33.3%) DNA aneuploid OVCs and in 14 of 20 (70%) DNA aneuploid OSCCs (P = .163). OVCs were mainly characterized by DNA Index (DI) values in the near-diploid region (DI≠1 and DI < 1.4), whereas aneuploid OSCCs carried most frequently multiple aneuploid sublines with high DI values (DI ≥ 1.4). DNA near-diploid and high aneuploid sublines were, respectively, 87.5% and 12.5% for the OVCs versus 30% and 70% for the OSCCs (P = .004). Present data suggest that OVCs are characterized by a lower degree of CIN and tumor heterogeneity than OSCCs, such that they appear as "frozen" in an early stage of DNA near-diploid aneuploidy, as previously observed for oral preneoplastic lesions. These DI characteristics, which can easily be obtained by hr DNA-FCM, appear to reflect the well-known differences in aggressiveness and prognosis of OVCs and OSCCs.
    Cancer 05/2011; 117(22):5052-7. · 5.20 Impact Factor
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    ABSTRACT: Multicentric Castleman's disease (MCD) is a rare lymphoproliferative disorder with systemic symptoms and poor prognosis and is characterized by an abnormal proliferation of polyclonal plasmablasts in the mantle zone of B-cell follicles. The disease is found primarily in chronic HIV carriers and is usually strictly associated with human herpes virus type 8 (HHV-8) coinfection, which is believed to play a key role in the pathogenesis of MCD. The disease is also diagnosed in HIV-negative patients, who are usually elderly or immunosuppressed; however, in about half of these cases, no evidence of HHV8 infection is found. The anti-CD20 monoclonal antibody rituximab is now the preferred treatment for HIV-positive MCD. However, it is not clear whether rituximab is effective in HIV-negative patients with MCD, particularly in the HHV8-positive subset. We report here the clinical and biologic courses of two HIV-negative, HHV8-positive patients with MCD who were treated with rituximab. In both cases, a significant clinical improvement was observed after the first two infusions, which was shortly followed by a drop in HHV8 viremia to undetectable levels. Both patients underwent complete clinical remission, which persisted without relapse at 30 and 9 months of follow-up, respectively. No reactivation of the Kaposi sarcoma found in a lymph node of one of the patients was observed. Our report, along with additional data present in the literature, suggests that rituximab may be an appropriate and safe first-line therapy for HIV-negative, HHV8-positive MCD.
    International journal of hematology 09/2009; 90(3):392-6. · 1.17 Impact Factor
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    ABSTRACT: Malignant fibrous histiocytoma (MFH) is a pleomorphic sarcoma, occurring most frequently in the deep soft tissues of the extremities, and it is most frequently seen in elderly patients. A primary MFH of the diaphragm is very rare, and to the best of our knowledge, a multi-phased spiral CT appearance of this tumour has not been previously reported. In this report, we describe the clinical and multi-phase CT features of a primary MFH of the diaphragm.
    European Radiology 09/2009; 19(9):2315-9. · 4.34 Impact Factor
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    ABSTRACT: First described by Klemperer and Rabin in 1931, solitary fibrous tumour of the pleura (SFTP) is a mesenchymal tumour that tends to involve the pleura, although it has also been described in other thoracic areas (mediastinum, pericardium and pulmonary parenchyma) and in extrathoracic sites (meninges, epiglottis, salivary glands, thyroid, kidneys and breast). SFTP usually presents as a peripheral mass abutting the pleural surface, to which it is attached by a broad base or, more frequently, by a pedicle that allows it to be mobile within the pleural cavity. A precise preoperative diagnosis can be arrived at with a cutting-needle biopsy, although most cases are diagnosed with postoperative histology and immunohistochemical analysis of the dissected sample. SFTP, owing to its large size or unusual locations (paraspinal, para-mediastinal, intra-fissural and intraparenchymal), can pose interpretation problems or, indeed, point towards a diagnosis of diseases of a totally different nature. We present some unusual radiographic and computed tomography (CT) images of large SFTP or SFTP located in atypical thoracic locations in patients who underwent surgical resection.
    La radiologia medica 09/2009; 114(2):204-15. · 1.46 Impact Factor
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    ABSTRACT: Thymic carcinoma (primary carcinoma of the thymic epithelium; type C thymoma) is a rare malignancy. It usually presents in middle-aged to elderly patients and can exhibit a wide variety of morphologic appearances. Thymic basaloid carcinoma (thymic BC) is a particularly rare subtype, with less than 20 cases published in the English literature, mostly in the form of individual case reports. In this study, we present the clinicopathologic and immunohistochemical features of 12 new cases of thymic BC. There were 10 (83%) men and 2 (17%) women. Ages at the time of initial diagnosis ranged from 34 to 77 years (mean 55 y). The 2 most common manners of presentation were dyspnea on exertion (3 patients) and as an incidental finding on radiographic imaging (2 patients). Tumors ranged in size from 4.4 to 17 cm (mean 10.1 cm). One of 12 cases (8.3%) was associated with a multilocular thymic cyst. Immunohistochemistry was performed in 8 cases. Pan-cytokeratin was positive in all cases. CD117 (c-kit) was positive in 6 of 8 cases (75%), p63 was positive in 7 of 8 cases (88%), p53 was positive in 7 of 8 cases (88%), ranging from <10% to 90%, CD5 was focally positive in 3 of 8 cases (38%), collagen type IV was positive in 4 of 8 cases (50%), and proliferative index, as estimated by Ki67, ranged from <1% to approximately 15%. In 1 of 2 cases with sarcomatoid differentiation, Ki67 was greater than 80% in the sarcomatoid area. Cases were negative for thyroid transcription factor-1 (0 of 8), S-100 (0 of 7), and synaptophysin (0 of 7). Long-term data was available in 8 patients with an average follow-up of 30 months. Five patients died of their disease at an average of 34 months from the time of diagnosis. Of the remaining 3 patients, 1 had a stable recurrence and died at 4 years from unrelated causes, and 2 were alive without the evidence of disease at 12 and 7 months, respectively. Thymic BC, although previously regarded as a low-grade neoplasm, has shown that it is capable of aggressive behavior and significant mortality. In this paper, we review the pertinent literature and discuss the possible relationship of thymic BC with thymic adenoid cystic carcinoma, as well as BCs and adenoid cystic carcinomas at other sites.
    The American journal of surgical pathology 05/2009; 33(8):1113-24. · 4.06 Impact Factor
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    ABSTRACT: Solitary fibrous tumor (SFT) of the pleura usually presents as a peripheral mass, in contact with the surface of the pleura. However, on occasion, it can occur separately from the pleura, in the lung parenchyma. We describe the radiological and imaging features of three SFTs of the lung, diagnosed in our department, with relevant clinical data. The diagnosis of SFT of the lung, although rare, should be considered in a slow-growing solitary lung parenchymal nodule.
    Acta Radiologica 04/2009; 50(4):379-82. · 1.33 Impact Factor
  • Radiologia Medica - RADIOL MED. 01/2009; 114(2):204-215.
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    ABSTRACT: We report the case of a 25-year-old woman with a chance detection at x-ray of a well-defined mass in the right upper lobe during a medical examination. The patient suffered from a modest flu syndrome, with cough and fever. She was a current smoker. CT scan showed a homogeneous well-defined perihilar mass without calcifications, located in the right upper lobe and fully surrounded by aerated parenchyma. A right upper lobectomy with mediastinal lymph node sampling was performed. A pathologic diagnosis of well-differentiated fetal adenocarcinoma of the lung was made and staged as T2N0. Few cases of this type of malignancy have been reported in literature.
    Journal of thoracic oncology: official publication of the International Association for the Study of Lung Cancer 05/2008; 3(4):441-3. · 4.55 Impact Factor
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    Leukemia 07/2007; 21(6):1305-6. · 10.16 Impact Factor
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    ABSTRACT: The purpose of this study was to identify the typical computed tomography (CT) features of solitary fibrous tumours of the pleura (SFTP) and determine which findings would allow confirmation of the pleural origin or benign behaviour of the tumour. Twenty-six preoperative CT studies of the chest (23 enhanced and 14 unenhanced) were retrospectively reviewed. Up to 50% of SFTP were larger than 10 cm. At unenhanced CT, they showed homogeneous attenuation in 5 cases (35.7%) and inhomogeneous attenuation in 9 (64.3%). At contrast-enhanced CT, they were inhomogeneous in 21 cases (91.3%), with geographic pattern (61.9% of cases), serpiginous linear areas of enhancement (intralesional vessels) (23.8%), rounded (52.4%) or linear (33.3%) areas of low attenuation (necrosis). Depending on location, size and histological features, SFTP may produce a large spectrum of findings. Typical CT features of small SFTP were well-defined margins and smooth contours, homogeneous attenuation and right or obtuse angles with the pleura. Larger lesions were characterised by well-defined margins and lobulated contours, geographic pattern in enhanced CT scans, acute angles or smooth tapering margins with the pleura.
    La radiologia medica 09/2006; 111(5):640-50. · 1.46 Impact Factor
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    ABSTRACT: The authors investigated the efficacy and safety of the histone deacetylase inhibitors valproic acid (VPA) and all-trans retinoic acid (ATRA) as differentiation agents in a cohort of older, poor-risk patients with acute myeloid leukemia (AML) or myelodysplastic syndrome (MDS). Twenty older patients with recurrent or refractory AML or MDS were treated in a Phase II protocol with sequential VPA and ATRA therapy. VPA was started at a dose of 10 mg/kg per day and then escalated to achieve the serum concentration of 45-100 microg/mL. ATRA was added at 45 mg/square meters (sm) per day when VPA reached the target serum concentration. Only patients treated continuously for > or = 2 months were considered evaluable. Hematologic improvement, according to World Health Organization criteria, was observed in 6 of 20 patients enrolled in the protocol but in 6 of 11 considered evaluable. In five patients, a major platelet response was observed, achieving platelet transfusion independence. Three of these five patients also exhibited a minor erythroid response. A sixth patient showed both a minor erythroid response and a platelet response. The median duration of response was 189 days (range, 63-550 days). No significant reduction in the blast count was observed. Grade 3 neurocortical toxicity was observed in four patients. Severe bone pain was experienced by 4 patients (2 Grade 4 and 2 Grade 3) and was associated with an increase in the peripheral blast cell count. Treatment with ATRA did not modify the response observed with VPA alone. Differentiation therapy with VPA was of clinical benefit in approximately 30% of elderly patients with AML and MDS of the refractory anemia with excess of blast type with unfavorable prognostic features. A striking platelet transfusion independence lasting several months may be obtained in some patients, reducing the burden of palliative care and improving the quality of life.
    Cancer 07/2005; 104(1):101-9. · 5.20 Impact Factor

Publication Stats

116 Citations
55.87 Total Impact Points

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Institutions

  • 2009
    • Azienda Ospedaliero Universitaria San Luigi Gonzaga
      Orbassano, Piedmont, Italy
  • 2005–2009
    • Università degli Studi di Torino
      • Dipartimento di Scienze Cliniche e Biologiche
      Torino, Piedmont, Italy