Papers by Salvatore Romeo
International Forum of Allergy & Rhinology, 2015
Our primary endpoint was to use nasal cytology to compare woodworkers with unexposed subjects to ... more Our primary endpoint was to use nasal cytology to compare woodworkers with unexposed subjects to see if wood dust exposure correlates with specific patterns of inflammatory or infectious rhinitis. A secondary endpoint was to identify any differences in the exposed group's nasal symptoms or nasal cytology by years of exposure or personal exposure levels. Ninety-two woodworkers and 90 controls were assessed using a questionnaire and nasal cytology (on nasal mucosa obtained by scraping). Wood dust exposure was investigated using personal sampling methods. Woodworkers reported significantly more nasal symptoms than controls (p < 0.00001). The woodworkers' nasal smears revealed more neutrophils (p = 0.001) and significantly higher mean neutrophil scores (p = 0.001) than control smears. Lymphocytes were also found more often in the woodworkers' rhinocytograms (statistical trend, p = 0.06). Neutrophilic rhinitis was diagnosed more frequently in the exposed workers than in controls (chi-square = 5.97, p < 0.05). Woodworkers with lymphocytes in their nasal smears had been exposed to wood dust for longer periods of time (statistical trend; p = 0.06). No differences in nasal symptoms or cell counts emerged when woodworkers were stratified by levels of personal exposure. Nasal cytology should be further investigated in woodworkers before considering it a screening method for identifying woodworkers with chronic inflammatory rhinitis.
Head and neck pathology, Jan 19, 2015
Interdigitating dendritic cell sarcoma (IDCS) is an exceedingly rare neoplasm originating from pr... more Interdigitating dendritic cell sarcoma (IDCS) is an exceedingly rare neoplasm originating from professional antigen presenting cells normally located in the T zone of the lymph node. The purpose of this report was to describe the first case of the IDCS of the submandibular gland and perform a review of the literature of head and neck IDCS. We present a case of an 81-year-old man with a 5 months history of slowly enlarging painless mass in right submandibular region. Fine needle aspiration cytology was suggestive of squamous cell carcinoma. The patient underwent surgical resection of the right submandibular gland and neck dissection. A malignant spindle cell proliferation involving the submandibular gland and colonizing one laterocervical lymph node was found. Morphology and immunophenotype prompted a differential diagnosis of a metastatic spindle cell melanoma versus an IDCS. Transmission electron microscopy was performed and supported a diagnosis of IDCS. The diagnosis of IDCS is a...
British journal of cancer, 2009
Osteosarcoma is the most prevalent primary malignant bone tumour in children and young adults, wi... more Osteosarcoma is the most prevalent primary malignant bone tumour in children and young adults, with poor survival in 40% of patients. To identify the signalling pathways involved in tumourigenesis, we compared gene expression in osteosarcoma with that in its presumed normal counterparts. Genome-wide expression profiles were generated from 25 high-grade central osteosarcoma prechemotherapy biopsies, 5 osteoblastomas, 5 mesenchymal stem cell (MSC) populations and these same MSCs differentiated into osteoblasts. Genes that were differentially expressed were analysed in the context of the pathways in which they function using the GenMAPP programme. MSCs, osteoblasts, osteoblastomas and osteosarcomas clustered separately and thousands of differentially expressed genes were identified. The most significantly altered pathways are involved in cell cycle regulation and DNA replication. Several upstream components of the Wnt signalling pathway are downregulated in osteosarcoma. Two genes invo...
The Journal of pathology, 2006
Chondromyxoid fibroma (CMF) is a rare benign cartilaginous bone tumour with a lobular architectur... more Chondromyxoid fibroma (CMF) is a rare benign cartilaginous bone tumour with a lobular architecture containing stellate and myofibroblast-like spindle cells. The aim of this study was to investigate the presence, spatial distribution, and extent of myoid differentiation in CMF and to evaluate a possible causative role for TGF-beta1 signalling, which is known to promote smooth muscle actin (SMA) expression. Twenty cases were studied for immunoreactivity for muscle-specific actin (MSA), SMA, desmin, h-caldesmon, calponin, TGF-beta1, and plasminogen activator inhibitor type 1 (PAI-1). The extent of myofibroblastic differentiation was further investigated ultrastructurally, including immuno-electron microscopy using antibodies against MSA and SMA, focusing upon the different cell types in CMF. The expression of potential genes driving this process was quantified by Q-RT-PCR (TGF-beta1, fibronectin, its EDA splice variant, and PAI-1). Tumour cells, especially those with a spindled morphol...
European Journal of Plastic Surgery, 2010
In this paper, we report a rare case of a solitary osteochondromatous tumour on the volar tip of ... more In this paper, we report a rare case of a solitary osteochondromatous tumour on the volar tip of the thumb of a 47-year-old woman. An X-ray examination showed a heavily calcific mass close to the bone and an alteration of the bone, next to the lesion. A wide-margin biopsy was performed on this tumour and a histological examination was conducted, which showed the characteristics of a bizarre parosteal osteochondromatous proliferation of the bone (Nora's lesion). The lesion was 0.8×0.9 cm. This neoplasm has a high tendency for local recurrence, although metastatic behaviour has not yet been reported. Due to its possible recurrence, this lesion requires radical surgery and, at times, amputation is necessary. In this case, wound healing was uncomplicated and there was no deficit after surgery. No recurrences were observed after 2 years from the surgery. At the end, we describe six differential diagnoses for the Nora's lesion. We explain some important characteristics of every one of the six lesions.
Virchows Archiv, 2012
Malignant fibrous histiocytoma (MFH) and fibrosarcoma (FS) of bone are rare malignant tumours and... more Malignant fibrous histiocytoma (MFH) and fibrosarcoma (FS) of bone are rare malignant tumours and contentious entities. Sixty seven cases labelled as bone MFH and bone FS (10) were retrieved from five bone tumour referral centres and reviewed to determine whether recent advances allowed for reclassification and identification of histological subgroups with distinct clinical behaviour. A panel of immunostains was applied: smooth muscle actin, desmin, h-caldesmon, cytokeratin AE1-AE3, CD31, CD34, CD68, CD163, CD45, S100 and epithelial membrane antigen. Additional fluorescence in situ hybridisation and immunohistochemistry were performed whenever appropriate. All cases were reviewed by six bone and soft tissue pathologists and a consensus was reached. Follow-up for 43 patients (median 42 months, range 6-223 months) was available. Initial histological diagnosis was reformulated in 18 cases (26.8 %). Seven cases were reclassified as leiomyosarcoma, six as osteosarcoma, three as myxofibrosarcoma and one each as Electronic supplementary material The online version of this article (
Nuclear Medicine and Biology, 2006
Drug resistance remains a significant impediment to successful chemotherapy and constitutes a maj... more Drug resistance remains a significant impediment to successful chemotherapy and constitutes a major prognostic factor in osteosarcoma (OS) patients. This study was designed to identify the role and prognostic significance of multidrug-resistance (MDR)-related transporters, such as multidrug resistance protein 1 (MDR1), multidrug-resistance-associated protein (MRP1) and breast-cancer-related protein (BCRP), in OS using cationic lipophilic radiotracers. We evaluated the chemosensitivity of four OS cell lines (Saos-2, 143B, MNNG/HOS and U-2OS) to doxorubicin (DOX), cisplatin (CIS) and methotrexate. The expression of MDR-related transporters was analyzed at mRNA level by quantitative polymerase chain reaction and at functional level by 99m Tc sestamibi and 99m Tc tetrofosmin. The effectiveness of MDR modulators [cyclosporin A (CsA) and imatinib] on transporter inhibition and on the reversal of resistance was also assessed.
Modern Pathology, 2012
The distinction between benign and malignant cartilaginous tumors located peripherally in the bon... more The distinction between benign and malignant cartilaginous tumors located peripherally in the bone may be a challenging task in surgical pathology. The aim of this study was to investigate interobserver reliability in histological diagnosis of cartilaginous tumors in the setting of multiple osteochondromas and to evaluate possible histological parameters that could differentiate among osteochondroma, low-and high-grade secondary peripheral chondrosarcoma. Interobserver reliability was assessed by 12 specialized bone-tumor pathologists in a set of 38 cases. Substantial agreement on diagnosis among all the reviewers was observed (intraclass correlation coefficient ¼ 0.78). Our study confirmed that mitotic figures and nuclear pleomorphism are hallmarks of high-grade secondary peripheral chondrosarcoma. However, despite the substantial agreement, we demonstrated that histology alone cannot distinguish osteochondroma from low-grade secondary peripheral chondrosarcoma in the setting of multiple osteochondromas, as nodularity, the presence of binucleated cells, irregular calcification, cystic/mucoid changes and necrosis were not helpful to indicate malignant transformation of an osteochondroma. On the other hand, among the concordant cases, the cartilage cap in osteochondroma was significantly less thicker than in low-and high-grade secondary peripheral chondrosarcoma. Therefore, our study showed that a multidisciplinary approach integrating clinical and radiographical features and the size of the cartilaginous cap in combination with a histological assessment are crucial to the diagnosis of cartilaginous tumors.
Laboratory Investigation, 2010
Primary cilia are specialized cell surface projections found on most cell types. Involved in seve... more Primary cilia are specialized cell surface projections found on most cell types. Involved in several signaling pathways, primary cilia have been reported to modulate cell and tissue organization. Although they have been implicated in regulating cartilage and bone growth, little is known about the organization of primary cilia in the growth plate cartilage and osteochondroma. Osteochondromas are bone tumors formed along the growth plate, and they are caused by mutations in EXT1 or EXT2 genes. In this study, we show the organization of primary cilia within and between the zones of the growth plate and osteochondroma. Using confocal and electron microscopy, we found that in both tissues, primary cilia have a similar formation but a distinct organization. The shortest ciliary length is associated with the proliferative state of the cells, as confirmed by Ki-67 immunostaining. Primary cilia organization in the growth plate showed that nonpolarized chondrocytes (resting zone) are becoming polarized (proliferating and hypertrophic zones), orienting the primary cilia parallel to the longitudinal axis of the bone. The alignment of primary cilia forms one virtual axis that crosses the center of the columns of chondrocytes reflecting the polarity axis of the growth plate. We also show that primary cilia in osteochondromas are found randomly located on the cell surface. Strikingly, the growth plate-like polarity was retained in sub-populations of osteochondroma cells that were organized into small columns. Based on this, we propose the existence of a mixture ('mosaic') of normal lining (EXT þ /À or EXT wt/wt ) and EXT À/À cells in the cartilaginous cap of osteochondromas.
The Journal of Pathology, 2009
High-grade osteosarcoma is characterized by extensive genetic instability, thereby hampering the ... more High-grade osteosarcoma is characterized by extensive genetic instability, thereby hampering the identification of causative gene mutations and understanding of the underlying pathological processes. It lacks a benign precursor lesion and reports on associations with hereditary predisposition or germline mutations are uncommon, despite the early age of onset. Here we demonstrate a novel comprehensive approach for the study of premalignant stages of osteosarcoma development in a murine mesenchymal stem cell (MSC) system that formed osteosarcomas upon grafting. By parallel functional and phenotypic analysis of normal MSCs, transformed MSCs and derived osteosarcoma cells, we provide substantial evidence for a MSC origin of osteosarcoma. In a stepwise approach, using COBRA-FISH karyotyping and array CGH in different passages of MSCs, we identified aneuploidization, translocations and homozygous loss of the cdkn2 region as the key mediators of MSC malignant transformation. We then identified CDKN2A/p16 protein expression in 88 osteosarcoma patients as a sensitive prognostic marker, thereby bridging the murine MSCs model to human osteosarcoma. Moreover, occasional reports in patients mention osteosarcoma formation following bone marrow transplantation for an unrelated malignancy. Our findings suggest a possible hazard for the clinical use of MSCs; however, they also offer new opportunities to study early genetic events in osteosarcoma genesis and, more importantly, to modulate these events and record the effect on tumour progression. This could be instrumental for the identification of novel therapeutic strategies, since the success of the current therapies has reached a plateau phase. . Long-term in vitro passaged cells and tumour cells acquire genetic aberrations; an overview of genomic aberrations observed in all cell lines used
Journal of Pathology, 2006
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The Journal of Pathology, 2005
Chondromyxoid fibroma is a rare benign cartilaginous bone tumour characterized by morphological f... more Chondromyxoid fibroma is a rare benign cartilaginous bone tumour characterized by morphological features that resemble different steps of chondrogenesis in terms of both cellular morphology, ranging from spindled to rounded cells, and the extracellular matrix formed, which ranges from fibrous to cartilaginous. The presence in chondromyxoid fibroma of signalling molecules that regulate the spatial expression of proteins involved in normal cartilage proliferation and differentiation was investigated in samples from 20 patients and compared with articular chondrocytes from 11 normal donors cultivated in 3D pellet culture. Sections were stained with safranin-O and H&E, and immunohistochemistry was performed for p16, cyclin D1, FGFR3, BCL2, p21, PTHLH, PTHR1 and N-cadherin. Expression patterns were analysed using hierarchical clustering. In chondromyxoid fibroma, specific morphological features correlated with a distinct pattern of expression. Comparison with normal chondrocytes in pellet culture showed a striking morphological resemblance, but with an unmistakably different pattern of expression. N-cadherin, PTHLH, and PTHR1 were expressed to a significantly higher level (p < 0.01) in articular chondrocyte pellets but, conversely, there was significantly lower expression of cyclin D1, p16 and BCL2 (p < 0.05) in these cells. Morphological similarities reflect common steps in cartilage differentiation, albeit driven by different molecular mechanisms. The proteins we have found to be differentially expressed seem crucial for neoplastic chondrogenesis.
European Journal of Nuclear Medicine and Molecular Imaging, 2007
Purpose The purpose of this work was the development of an orthotopic model of osteosarcoma based... more Purpose The purpose of this work was the development of an orthotopic model of osteosarcoma based on luciferaseexpressing tumour cells for the in vivo imaging of multidrug resistance (MDR) with 99m Tc-sestamibi. Methods Doxorubicin-sensitive (143B-luc + ) and resistant (MNNG/HOS-luc + ) osteosarcoma cell lines expressing different levels of P-glycoprotein and carrying a luciferase reporter gene were inoculated into the tibia of nude mice. Local tumour growth was monitored weekly by bioluminescence imaging and X-ray. After tumour growth, a 99m Tcsestamibi dynamic study was performed. A subset of animals was pre-treated with an MDR inhibitor (PSC833). Images were analysed for calculation of 99m Tc-sestamibi washout half-life (t 1/2 ), percentage washout rate (%WR) and tumour/non-tumour (T/NT) ratio.
Developmental Brain Research, 2004
Metabotropic glutamate (mGlu) receptors have been implicated in the regulation of developmental p... more Metabotropic glutamate (mGlu) receptors have been implicated in the regulation of developmental plasticity. Here, we examined the expression of mGlu1a -b, -2, -3, -4a -b, and -5a receptor subtypes from embryonic day 12 (E12) to the early and late postnatal life. While all transcripts (with the exception of mGlu4 mRNA) were detected prenatally, only the mGlu5 receptor protein was found in detectable amounts in the embryonic brain. Immunohistochemical analysis showed that the mGlu5 receptor was mainly expressed by cells surrounding the ventricles at E15, whereas it was more diffusely expressed at E18. In the postnatal life, besides its classical expression sites, the mGlu5 receptor was found in zones of active neurogenesis such as the external granular layer (EGL) of the cerebellar cortex and the subventricular zone. In these regions, the presence of actively proliferating progenitor cells was detected by BrdU staining. No other subtype (among those we have examined) was found to be expressed in regions enriched of BrdU + cells. These data suggest a role for mGlu5 receptors in the early brain development and in basic cellular processes such as proliferation and/or differentiation. D
Connective Tissue Research, 2007
Clinical Cancer Research, 2007
Hodgkin's lymphoma (HL) is characterized by the presence of malignant so-called Hodgkin's͞Reed-St... more Hodgkin's lymphoma (HL) is characterized by the presence of malignant so-called Hodgkin's͞Reed-Sternberg (HRS) cells, which display resistance to certain apoptotic stimuli, including a lack of sensitivity to Fas-mediated cell death. However, the mechanisms responsible for their resistance to apoptosis inducers have not been elucidated.
Cancer, 2007
BACKGROUND. Chondroblastoma (CB) and chondromyxoid fibroma (CMF) are benign tumors of bone morpho... more BACKGROUND. Chondroblastoma (CB) and chondromyxoid fibroma (CMF) are benign tumors of bone morphologically recapitulating cartilage differentiation.
BMC Cancer, 2009
Background: Chondroblastoma is a benign cartilaginous tumour of bone that predominantly affects t... more Background: Chondroblastoma is a benign cartilaginous tumour of bone that predominantly affects the epiphysis of long bones in young males. No recurrent chromosomal re-arrangements have so far been observed. Methods: We identified an index case with a balanced translocation by Combined Binary Ratio-Fluorescent in situ Hybridisation (COBRA-FISH) karyotyping followed by breakpoint FISH mapping and array-Comparative Genomic Hybridisation (aCGH). Candidate region re-arrangement and candidate gene expression were subsequently investigated by interphase FISH and immunohistochemistry in another 14 cases.
Annals of Surgical Oncology, 2013
Background. The aim of the present study was to assess, in the setting of a single-institution pr... more Background. The aim of the present study was to assess, in the setting of a single-institution prospective clinical trial, the necessity of planned neck dissection (PND) in physically and radiologically complete responders with pretherapy advanced nodal disease. Methods. Between January 2000 and July 2007 a total of 139 patients were enrolled to receive a regimen of platinumbased multidrug induction-concurrent chemoradiotherapy (IC/CCRT). A total of 75 of the enrolled patients with advanced nodal disease were included in this retrospective study. Between 8 and 12 weeks from the end of treatment, the response to IC/CCRT was evaluated by fiber-optic endoscopy and head and neck contrast-enhanced computed tomography or magnetic resonance imaging. Results. The complete clinical response (cCR) rate was 68 %. Among the 51 patients who achieved locoregional cCR at the end of CCRT, 8 underwent PND according to the study recommendation. Of the 43 patients with cCR who did not undergo PND, 2 patients (4.7 %) experienced isolated regional recurrences with the 5-year regional control being 82 %. Patients with cCR did not have a significantly lower regional control compared with patients with cCR who underwent ND (P = .962). Pathological evidence of residual disease was found in 81 % of the patients with less than cCR who underwent ND.
The American Journal of Pathology, 2010
Chondromyxoid fibroma (CMF) is an uncommon benign cartilaginous tumor of bone usually occurring d... more Chondromyxoid fibroma (CMF) is an uncommon benign cartilaginous tumor of bone usually occurring during the second decade of life. CMF is associated with recurrent rearrangements of chromosome bands 6p23-25, 6q12-15, and 6q23-27. To delineate further the role and frequency of the involvement of three candidate regions (6q13, 6q23.3 and 6q24) in the pathogenesis of CMF, we studied a group of 43 cases using a molecular cytogenetic approach. Fluorescence in situ hybridization with probe sets bracketing the putative breakpoint regions was performed in 30 cases. The expression level of nearby candidate genes was studied by immunohistochemistry and quantitative RT-PCR in 24 and 23 cases, respectively. Whole-genome copy number screening was performed by array comparative genomic hybridization in 16 cases. Balanced and unbalanced rearrangements of 6q13 and 6q23.3 occurred in six and five cases, respectively, and a hemizygous deletion in 6q24 was found in five cases. Two known tumor suppressor genes map to the latter region: PLAGL1 and UTRN. However, neither of these two genes nor BCLAF1 and COL12A1, respectively located in 6q23.3 and 6q13, showed altered expression. Therefore, although rearrangements of chromosomal regions 6q13, 6q23.3, and 6q24 are common in CMF, the complexity of the changes precludes the use of a single fluorescence in situ hybridization probe set as an adjunct diagnostic tool. These data indicate that the genetic alterations in CMF are heterogeneous and are likely a result of a cryptic rearrangement beyond the resolution level of combined binary ratio fluorescence in situ hybridization or a point mutation.
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Papers by Salvatore Romeo