Biomedical subjects

Marco Santucci

Publications and source records attributed to Marco Santucci.

26 records · Page 2Linked to original sources

PubMed2003

Plasma cell granuloma--an enigmatic lesion: description of an extensive intracranial case and review of the literature.

We present an unusual case of intracranial plasma cell granuloma in a 70-year-old man with a 6-month history of progressive visual disturbance. The lesion extensively involved the cranial base, extended into the frontal region, and reached the floor of the third ventricle in the suprasellar area. Microscopic examination of multiple diagnostic transsphenoidal biopsies showed an inflammatory proliferation with a predominance of cells that were immunohistochemically determined to be polyclonal plasma cells. Ultrastructural analysis confirmed the presence of numerous mature plasma cells in a mixed inflammatory proliferation. In situ hybridization for Epstein-Barr viral RNA revealed no evidence of viral expression. The patient was treated with steroid therapy and radiotherapy, without any appreciable reduction of the lesion's size. He is alive with persistent severe visual disturbance 14 months after the diagnosis. We discuss the etiopathogenetic, diagnostic, and therapeutic issues related to this entity, and review the literature.

Aged↗

PubMed2002

Expression of matrix metalloproteinase 1, matrix metalloproteinase 2, and matrix metalloproteinase 9 in carcinoma of the head and neck.

BACKGROUND: Numerous reports have documented a direct involvement of matrix metalloproteinase (MMP) overexpression in the development and progression of head and neck squamous cell carcinoma (HNSCC). In this study, the authors examined whether the expression of MMPs in HNSCC is correlated with other steps involved in tumor growth and metastasis, like angiogenesis, activation the nitric oxide (NO) pathway, and alteration of the p53 tumor suppressor gene. METHODS: MMP-1, MMP-2, and MMP-9 expression levels were examined immunohistochemically in samples from 43 patients with HNSCC. Microvessel density (MVD) was determined by immunostaining of endothelial cells with anti-CD31 monoclonal antibody. Inducible nitric oxide synthase (iNOS) activity and cyclic guanosine monophosphatate (cGMP) levels were assessed in fresh tumor samples, whereas exons 5-9 of the p53 gene were analyzed by reverse transcriptase-polymerase chain reaction, single-strand conformation polymorphism analysis and were sequenced. RESULTS: MMP-1 overexpression (>10% of tumor cells) was identified in 32 tumors (74.5%), whereas elevated levels of MMP-2 and MMP-9 were detected in 17 tumors (39.5%) each. Tumors with MMP-9 overexpression were characterized by significantly higher MVD (P = 0.05) and significantly higher iNOS activity and cGMP levels (P = 0.005 and P = 0.02, respectively). Moreover, p53 mutation was associated strongly with MMP-9 overexpression (P = 0.004). Conversely, no correlation was found between MMP-1 and MMP-2 expression, angiogenesis, iNOS activity, cGMP levels, and p53 mutation in this series. CONCLUSIONS: This study documents the existence of a correlation between MMP-9 expression, activity of the iNOS pathway, p53 status, and angiogenesis in patients with HNSCC. This raises the possibility that p53 mutation, which frequently is present in HNSCC, may result in increased angiogenesis and invasiveness related to increased nitric oxide and MMP production by tumor cells, ultimately contributing to tumor progression.

Carcinoma, Squamous Cell↗

PubMed2002

Inducible nitric oxide synthase expression in laryngeal neoplasia: correlation with angiogenesis.

BACKGROUND: The nitric oxide (NO) pathway plays a relevant role in angiogenesis and tumor progression in squamous cell carcinoma (SCC) of the head and neck. The aim of this study was to assess whether the NO pathway may be correlated with angiogenesis in the transition from laryngeal dysplasia to invasive carcinoma. METHODS: We investigated the expression of the inducible NO synthase (iNOS) in 26 laryngeal precancerous lesions and 35 squamous cell carcinomas with respect to microvessel density. In addition, we determined iNOS activity and cGMP levels in specimens from SCCs. RESULTS: There was a significant increase of iNOS levels detected immunohistochemically passing from hyperplastic/mild dysplastic to moderate/severe dysplastic lesions to SCC (p =.04). Accordingly, Northern and Western analyses demonstrated higher iNOS mRNA and protein levels in SCCs than dysplastic mucosa. iNOS expression was significantly correlated with microvessel counts both in the group of preneoplastic lesions (p =.02) and in the group of SCCs (p =.01). In addition, iNOS activity was correlated with iNOS immunohistochemical expression (p =.1) and was significantly associated with increased vascularization (p =.03) in SCCs. Similarly, iNOS expression was significantly correlated with cGMP levels in SCC (p =.02) and increased tumor vascularization correlated with higher cGMP levels (rs =.4; p =.01). CONCLUSIONS: Our data indicate that the NO pathway may play a relevant role in the angiogenesis associated with the progression from laryngeal dysplasia to laryngeal SCC.

Base Sequence↗

PubMed2002

Tumor angiogenesis as a prognostic factor in thick cutaneous malignant melanoma. A quantitative morphologic analysis.

The prognostic value of the extent of neovascularization in cutaneous melanoma is a highly controversial issue. The aim of the current study was to evaluate whether the morphometric analysis of tumor vascularity may be helpful in predicting the clinical outcome of patients with thick cutaneous melanomas. A series of 15 patients with melanoma (>3 mm in thickness) who did not experience disease progression after long-term follow-up (10 years) and 30 matched controls who underwent recurrence and/or metastases were selected for the study. Microvessels were immunohistochemically stained with anti-CD31 antibody. Several parameters, including vessel number, vascular density, vessel area, equivalent circle diameter, perimeter, shape factor, compactness, and the number of vascular ramifications per 100 vessel sections, were quantitatively assessed by a computer-aided semi-automatic image analysis system. Mean vessel area was 341.69 microm2 in cases without progression and 512.55 microm2 in the progressed melanomas (P=0.008, Mann-Whitney U test). The mean equivalent circle diameter was 18.95 microm in non-progressed melanomas and 22.57 microm in progressed melanomas (P=0.009). The mean number of ramifications was 0.8 in cases without progression and 1.9 in the controls (P=0.03). Microvessel count and vascular density were higher in progressed cases (17.37 vs. 11.73 and 28.94/mm2 vs. 19.55/mm2, respectively), but the difference did not reach statistical significance (P=0.06). Our results suggest that neovascularization is a critical event in the progression of thick melanoma. Its prognostic significance is better assessed by quantification of vessel area, equivalent circle diameter, and microvessel branching, whereas microvessel count and vascular density do not provide significant prognostic information.

Adult↗

PubMed2002

IL-4, IL-5, TGF-beta1 and IFN-gamma mRNAs detected by a new in situ amplification system in cicatricial pemphigoid.

The process that induces chronic progressive scarring in cicatricial pemphigoid (CP), a rare group of autoimmune mucocutaneous blistering diseases, is still under investigation. The tendency to heal with scar formation observed in CP could be due to the specific localization of the antigen in the basement membrane zone or could depend on the frequent recurrence of the disease in a localized area. The release of soluble fibrogenic factors by inflammatory infiltrating cells has also been considered as pathogenetically relevant. The aim of this study is to evaluate the expression of mRNA for IL-4, IL-5, TGF-beta1, IFN-gamma in patients with CP, and investigate the role of the cytokine profile as a possible cause of the clinical features and course of the disease. Fourteen patients (3 male, 11 female; age range 40-72 years) with oral (n = 10), preputial (n = 3) and cutaneous (n = 1) CP were studied. The formalin-fixed and paraffin-embedded biopsies were examined by in situ hybridization performing a new amplification system based on biotinyl-tyramide. As a control, 4 patients (2 male, 2 female; age range 58-73 years) affected by bullous pemphigoid (BP), the most common autoimmune subepidermal blistering disease, were also examined. In CP, IL-4 mRNA expression was present in 4 out of the 14 cases analysed. IL-5 was detected in 12 CP biopsies. TGF-beta1 and IFN-gamma mRNAs were identified in 9 and 11 CP cases, respectively. In BP, an IL-4 hybridization signal could not be observed in any of the cases. By contrast IL-5, TGF-beta1 and IFN-gamma mRNA analyses were positive in all four BP cases. Our results suggest the presence of a T-cell population with a mixed cytokine pattern in the cellular infiltrate of both blistering diseases, with a corresponding increase of Th2-like activity in fully developed lesions, irrespective of the different sites involved. In addition, on the basis of the constant presence of TGF-beta1 mRNA in the different lesional phases of CP, and its overlapping expression in BP, we hypothesize that the involvement of additional factors is responsible for the scarring course typical of CP.

Adult↗

PubMed2002

Sinonasal undifferentiated carcinoma, nasopharyngeal-type undifferentiated carcinoma, and keratinizing and nonkeratinizing squamous cell carcinoma express different cytokeratin patterns.

Sinonasal undifferentiated carcinoma (SNUC) is a highly aggressive malignant neoplasm that is often difficult to distinguish from other poorly differentiated carcinomas arising in the sinonasal tract. To search for a differential cytokeratin (CK) expression that could be useful for diagnostic purposes, we compared the expression of a large panel of CKs in a series of 6 SNUCs, 10 poorly differentiated squamous cell carcinomas (SCCs), 10 nonkeratinizing squamous cell carcinomas (NKSCCs), and 5 nasopharyngeal-type undifferentiated carcinomas (NPTCs). SCC, NKSCC, and NPTC frequently showed immunoreactivity for CK5/CK6, CK8, CK13, and CK19. In addition, SCC and NKSCC expressed CK14, which was not detected in NPTC, and SCC expressed CK7 (60% of cases) and CK4 (30% of cases), which were absent in NKSCC and NPTC. Three NKSCCs were associated with a Schneiderian papilloma, and the results of the immunostaining were similar in the two components, with the exception of CK4 and CK7, which were expressed by the papilloma and not by the carcinoma. In contrast to other carcinomas, SNUC was characterized by the exclusive expression of CKs of simple epithelia, such as CK8 (100% of cases), CK7 (50% of cases), and CK19 (50% of cases). Thus, there are significant differences in the pattern of CK expression between SNUC, SCC, NKSCC, and NPTC, which could be of diagnostic aid. Moreover, these findings support the hypothesis that SNUC is a separate entity from SCC and NPTC of the sinonasal tract.

Adult↗

PubMedDate not supplied

The comparative role of immunohistochemistry and electron microscopy in the identification of myogenic differentiation in soft tissue pleomorphic sarcomas.

There is increasing evidence that histological classification of pleomorphic soft tissue sarcomas is prognostically useful, since a number of studies have provided evidence that myogenic differentiation is associated with a more aggressive clinical behavior. The aim of the current study was to analyze the role of electron microscopy in comparison with immunohistochemistry in the classification of soft tissue pleomorphic sarcomas. Thirty-nine pleomorphic sarcomas of the somatic soft tissues for which material for immunohistochemical and ultrastructural analysis was available were selected for this study. Cases were classified according to the criteria of the WHO classification of soft tissue tumors on the basis of the histologic appearance and of the results of immunohistochemical analysis, and then diagnoses were reconsidered at the light of the results of the ultrastructural analysis. The group of myogenic sarcomas included 13 leiomyosarcomas, 8 myofibrosarcomas, and 1 rhabdomyosarcoma, while the group of nonmyogenic sarcomas included 11 undifferentiated pleomorphic sarcomas/malignant fibrous histiocytomas (MFH), 4 myxofibrosarcomas, and 2 liposarcomas. Overall, there was a good concordance between immunohistochemistry and electron microscopy in recognizing myogenic differentiation in soft tissue pleomorphic sarcomas. Discrepancies included 1 case showing no immunoreactivity for muscle markers, which displayed ultrastructural features allowing reclassification as leiomyosarcoma, and 2 cases initially classified as undifferentiated pleomorphic sarcoma/MFH, which were reclassified as myofibrosarcomas after ultrastructural analysis. Ultrastructural analysis allowed the identification of pleomorphic sarcomas with myofibroblastic phenotype, a category that is not identifiable based on histologic and immunohistochemical profile. Notably, fibronexus junction was identified in tumor cells of 4 pleomorphic myofibrosarcomas, while 2 other lesions showed putative fibronexus junction structures, consisting of electron-dense straight fibrils adjacent to the cell surface, not clearly in continuity with cytoplasmic actin filaments. In conclusion, the results indicate that immunohistochemistry and electron microscopy can usefully complement each other in the classification of soft tissue pleomorphic sarcomas.

Actins↗

PubMedDate not supplied

Hyalinizing spindle cell tumor with giant rosettes and low-grade fibromyxoid sarcoma: an immunohistochemical and ultrastructural comparative investigation.

Hyalinizing spindle cell tumor with giant rosettes (HSCTGR) and low-grade fibromyxoid sarcoma (LGFMS) are 2 variants of fibrosarcoma, which share several clinicopathologic features. This study compares the light microscopic, immunohistochemical, and ultrastructural features of 2 examples of HSCTGR and 3 of LG FMS to determine the degree of overlap of these 2 tumors. HSCTGR were composed of bland spindle cells within hyalinized to myxoid stroma. Scattered throughout the lesions were characteristic rosette-like structures, formed by a central collagenous core surrounded by spindled neoplastic cells. LGFMS consisted of a mixture of fibrous and myxoid areas, composed of fibroblast-like cells arranged in a swirling, whorled growth pattern. Immunohistochemical analysis showed diffuse positivity for vimentin in all cases, while few scattered tumor cells stained for CD57, CD34, factor XIIIA, and actin. The extracellular matrix showed intense positivity for type IV collagen, laminin, and fibronectin, with the exception of myxoid areas of LGFMS and the central core of the giant rosettes in HSCTGR. Ultrastructurally, both tumor types were composed of cells with the features of fibroblasts, embedded in a collagenous stroma with irregular deposits of amorphous basal lamina-like substance. In conclusion, HSCTGR and LGFMS share similar immunophenotypic and ultrastructural features, and together with other fibrosing fibrosarcomas, like sclerosing epithelioid fibrosarcoma, may constitute a subset of fibrosarcomas formed by fibroblasts capable of producing large amounts of basal lamina-like material.

Adult↗