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Biomedical subjects

L Lo Muzio

Publications and source records attributed to L Lo Muzio.

At least 55 records · Page 3Linked to original sources

Early clinical diagnosis of solitary plasmacytoma of the jaws: a case report with a six year follow-up.

The authors reported a case of a solitary mandibular plasmacytoma in a 53-year-old male Caucasian patient. The histological examination of the specimen was positive for a plasmacytoma with anaplastic appearance. Since the patient refused a demolitive surgical treatment, he was treated with a local radiation therapy of 4000 rads over a 20-day period and polychemotherapy with cyclophosphamide, prednisone and melphalan. Six years after starting radiation treatment the patient is free of recurrent primary disease and not affected by multiple localization. In conclusion, the solitary bone plasmacytoma represents an initial stage of the multiple myeloma rather than a distinct clinical pathology. Unfortunately, the diagnosis of the plasmacytoma is only rarely carried out in the early phases of the disease. The importance of the identification of the initial stage without a clear M component, as in the reported case, is self-evident, since the prognosis is related to the mass of plasmacytoma cells that are present at the time of the diagnosis. The purpose of this study is to report an extremely rare case of solitary bone plasmacytoma with a mandibular localization treated with radio- and polychemotherapy.

Antineoplastic Agents, Alkylating↗

A possible role for the WNT-1 pathway in oral carcinogenesis.

Reductions in cell-cell adhesion and stromal and vascular invasion are essential steps in the progression from localized malignancy to metastatic disease for all cancers. Proteins involved in intercellular adhesion, such as E-cadherin and catenin, probably play an important role in metastatic processes and cellular differentiation. While E-cadherin and beta-catenin expression has been extensively studied in many forms of human cancers, less is known about the role of the Wingless-Type-1 (WNT-1) pathway in human tumors. A large body of genetic and biochemical evidence has identified beta-catenin as a key downstream component of the WNT signaling pathway, and recent studies of colorectal tumors have shown a functional link among beta-catenin, adenomatous polyposis coli gene product (APC), and other components of the WNT-1 pathway. WNT-1 pathway signaling is thought to be mediated via interactions between beta-catenin and members of the LEF-1/TCF family of transcription factors. The WNT signal stabilizes beta-catenin protein and promotes its accumulation in the cytoplasm and nucleus. In the nucleus, beta-catenin associates with TCF to form a functional transcription factor which mediates the transactivation of target genes involved in the promotion of tumor progression, invasion, and metastasis, such as C-Myc, cyclin D1, c-jun, fra-1, and u-PAR. There is a strong correlation between the ability of the WNT-1 gene to induce beta-catenin accumulation and its transforming potential in vivo, suggesting that the WNT-1 gene activates an intracellular signaling pathway that can induce the morphological transformation of cells. For these reasons, data obtained from the study of the WNT-1 pathway could be important in our understanding of the mechanisms of epithelial tumors, in general, and probably also of oral squamous cell carcinoma, in particular.

Animals↗

DNA ploidy and cyclin D1 expression in basal cell carcinoma of the head and neck.

Basal cell carcinomas (BCCs) may be subdivided into primary with a favorable biologic course (BCC1) and recurrent and/or metastatic (BCC2). No clear association between primary tumor location, histologic subtype, or other clinicopathologic variables and predisposition for BCC2 has been found. Histopathologic criteria are limited for prognostication. To identify prognostic factors useful for planning therapy, we studied cyclin D1 immunohistochemical expression, DNA ploidy, and epiluminescence light microscopic (ELM) patterns in 60 cases of BCC (30 BCC1 and 30 BCC2) in the head and neck region, half of which were hyperpigmented. Cyclin D1 was absent in 27 cases, expressed at low level in 4 cases, and overexpressed in 30 cases. Seven BCCs were euploid, 28 exhibited a mixed cellular population, and 25 were aneuploid. Among aneuploid tumors, hypodiploidy was found in 12. Among the 30 pigmented carcinomas, only 15 showed a typical ELM pattern. No association between pigmentation and more aggressive biologic behavior of BCC was found. These results and follow-up data seem to indicate that an unfavorable outcome can be predicted by hyperexpression of cyclin D1, aneuploidy, and an atypical ELM pattern for pigmented cases. A definite hypodiploid peak was associated with worse prognosis. The analysis of cyclin D1 expression and DNA ploidy may help identify BCC with an aggressive phenotype and a poor clinical outcome.

Basal Cell Carcinoma↗

Metastases in small thickness oral squamous-cell carcinoma arising in oral lichen planus.

Oral lichen planus (OLP) is classified among precancerous conditions, as it is considered a generalized state associated with a significantly increased risk of cancer. The objective of this study was to discuss ultra-structural aspects of OLP that could play a role in enhancing metastatic potential, thus worsening the prognosis in oral squamous-cell carcinoma (OSCC). We report four cases of microinvasive OSCC which have occurred in OLP patients. All of them were stage I tumors, with a mean thickness of 1.75 mm. Recent studies indicate a tumor thickness over 4 mm as predictive of nodal metastases, but within 6 mo, our four patients with OSCC arising from OLP developed lymphnodal metastases. Our findings suggest that OLP-related OSCC may have a worse prognosis because of increased metastatic potential; obviously, further investigation is required, but this preliminary evidence emphasizes that extremely careful management of OLP patients is mandatory, and in cases of OSCC arising from OLP, a more radical treatment is probably required.

Aged↗

P53 and hMSH2 expression in basal cell carcinomas and malignant melanomas from photoexposed areas of head and neck region.

Ultraviolet (UV) radiation plays a pivotal role in skin damage and photocarcinogenesis. The basic mechanism of phototoxicity lies in DNA damage, and involves mutation of tumor suppressor genes, oncogenes and genes directly involved in the control of the stability of genome, such as the mismatch repair (MR) genes. The goal of this study was to evaluate the role of p53 and hMSH2 in the UV-related carcinogenetic process. An immunohistochemical study for p53 and hMSH2 was performed in a series of 43 basal cell carcinomas (BCC) and 60 melanomas (MM) from photoexposed areas of head and neck region, comparing the findings with follow-up. A deregulated p53 expression characterized less differentiated, more aggressive BCC (BCC2) but not the well-differentiated ones (BCC1). The hMSH2 protein was present, though expressed at varying levels, in 18 out of 21 BCC1 cases and in 4 out of 22 BCC2. In the remaining 3 cases of BCC1 and 18 cases of BCC2, a complete absence of hMSH2 expression was found, correlating directly with the presence of recurrence and/or death of the disease in case of melanoma (p<0.05). Overall, the expression of hMSH2 correlated inversely with the p53 overexpression (p<0.01). In MM, p53 was found overexpressed in 81.6% of the cases, and this correlated positively with the level of infiltration and with the presence of relapses (p<0.01) or metastasis (p<0.01) and inversely with the disease-free interval (p<0.05). These results are in agreement with the reported association between p53 deregulation and a more aggressive cancer phenotype. The evaluation of the expression of p53 and hMSH2 could improve the management of patients with BCC and MM, and could have a role also in the evaluation of the early cutaneous photo-inducted damage, contributing to the identification of presymptomatic patients predisposed to the development of UV-related new skin tumors, who could become candidates for chemoprevention trials.

Adult↗

Primary non-Hodgkin's lymphoma of the jaws: immunohistochemical and genetic review of 10 cases.

PURPOSE: Non-Hodgkin's lymphoma (NHL) comprises a group of malignant lymphoproliferative diseases characterized by clonal expansion of lymphocytes at various levels of ontogenetic development. The aim of this study was to review the immunohistochemical and cytogenetic features of 10 cases of NLH of the jaws to determine their respective derivation. PATIENTS AND METHODS: Histopathologic and immunohistochemical review of 10 cases of large-cell lymphomas of the jaws, together with Southern blot analysis of 2 of the cases, was performed and results compared with the findings in the literature. RESULTS: In the 10 cases studied, the average age of onset of the NHL was 51 years, with a male-to-female ratio of 3:2. Tumefaction was the first clinical sign of disease. Eight of 10 cases were high-grade, large-cell NHLs, centroblastic type. Two cases were high-grade, large-cell NHL, immunoblastic type. CONCLUSION: The immunohistochemical and Southern blot data remain the principal laboratory aids in the diagnosis and characterization of NHL, and they provide critical information for guiding clinicians to the appropriate treatment protocol for these malignancies.

Adult↗

Primary intraosseous carcinoma of the mandible: a case report.

A case of primary intraosseous carcinoma of the mandible in a 75-year-old man is reported. This tumor is an uncommon lesion arising from odontogenic rests. This tumor affects men more than women and is more frequent in the sixth and seventh decades of age. Most tumors occur in the posterior mandible as painful, non-ulcerated lesions, even if several cases have shown complete absence of subjective symptoms in early phases; often they are detected first on routine radiographs. Radiographically the lesion usually shows a fully enclosed, irregular pattern of bone destruction, even if sometimes the margins are well defined. The accepted treatment is radical surgery; but metastases could occur in lymph nodes.

Aged↗

Oral pemphigus: long term behaviour and clinical response to treatment with deflazacort in sixteen cases.

Systemic corticosteroids remain the mainstay of therapy for pemphigus. Their use has transformed what was almost invariably a fatal illness into one whose mortality is now below 10%. Unfortunately, the high doses and prolonged administration of corticosteroids that are often needed to control the disease result in numerous side effects, many of which are serious or even life-threatening. Sixteen patients affected by oral pemphigus vulgaris were retrospectively examined to illustrate the natural course of the disease and to describe the efficacy of the treatment we utilised. Deflazacort, used with azathioprine, is the steroid of first choice in our therapeutic protocols, while cyclophosphamide and methylprednisolone "pulse therapy" are reserved for cases unresponsive to high doses of oral corticosteroids. In addition, the literature on oral pemphigus vulgaris was reviewed with respect to clinical history, signs and symptoms, management, and treatment outcome.

Administration, Oral↗

Oral lichen planus: different clinical features in HCV-positive and HCV-negative patients.

BACKGROUND: Hepatitis C virus (HCV) infection induces variable dermatologic manifestations. OBJECTIVE: To determine whether differences exist in the clinical features and behavior of oral lichen planus (OLP) between HCV-positive (HCV+ve) and HCV-negative (HCV-ve) patients. METHODS: Two hundred and sixty three patients (156 women and 107 men), with a mean age of 55.5 years, with OLP (76 HCV+ve and 187 HCV-ve) were clinically evaluated. Previously, all local factors that could modify the clinical characteristics were removed and were monitored carefully following morphology. RESULTS: In both groups, the prevalent clinical form of OLP was the mixed form (33.1% in HCV-ve and 35.5% in HCV+ve patients), in which reticular-plaque lesions coexist with atrophic-erosive ones. The reticular form was more frequent in HCV+ve (25%) than in HCV-ve (18. 7%) patients, whereas plaque lesions were more prevalent in HCV-ve (15.5%) than in HCV+ve (5.2%) patients (P < 0.01, chi-squared test). There were no significant differences in the frequency of erosive (27.2% in HCV-ve and 27.6% in HCV+ve) and atrophic (5.3% in HCV-ve and 5.2% in HCV+ve) forms between the two groups. CONCLUSIONS: Our findings show that there were statistically significant differences between OLP-HCV-ve and OLP-HCV+ve groups for reticular and plaque clinical forms. These findings underline the importance of liver examination in all OLP patients, including cases with mild, asymptomatic keratotic forms of the disease.

Adult↗

Prognostic value of apoptotic index in cutaneous basal cell carcinomas of head and neck.

Basal cell carcinoma (BCC) is the most common type of human cancer, often locally invasive, and following a benign clinical course. However, a proportion of BCCs do recur after treatment, causing extensive local tissue destruction, seldom metastasizing. Morphological methods to unequivocally distinguish the aggressive forms of these tumors (BCC2) from the ordinary ones (BCC1) have so far been lacking. Apoptosis, or programmed cell death, is thought to be important for the death of tumor cells in various stages of carcinogenesis. We analyzed the extent of apoptosis in BCCs of head and neck in a morphological, morphometric, and electron-microscopic study, to estabilish on a retrospective basis, the relative frequency of recurrence of tumors showing different apoptotic rates. We found that BCC1 showed lower apoptotic index (AI) than BCC2 [BCC1: AI from 2.03 to 10.45% (mean value: 5.98%) BCC2: AI from 21. 91 up to 43.82% (mean value: 39.82%)]. The morphometric analysis of both BCC1 and BCC2 revealed significant differences between the values concerning nuclear area, length, perimeter, and roundness of the apoptotic cells with respect to the 'viable' neoplastic cells. Electron-microscopy confirmed that the features of morphological apoptotic cells were characteristic of programmed cell death. We hypothesized that low apoptotic rates in BCC1 could be indicative of a good prognosis. In fact, this corresponded to an 'expansive' but not still invasive neoplastic state. In this phase, however, the tumor cells may constitute the target for genetic changes triggered by enviromental physical or chemical mutagenic agents, such as UV rays. BCC2, then, could be the result of newly selected mutated neoplastic cellular clones, with more aggressive biological behavior. The high apoptotic level found in BCC2 could thus be used as an indirect alarm signal from pathologists. This hypothesis seems to be supported by most of the current data in the literature and by the clinical outcome of BCC2 of our series. In our opinion, routine evaluation of apoptosis in BCCs could be proposed to facilitate their sub-classification, contributing toward the evaluation of the prospective outcome of the individual patients.

Adult↗

Nevoid basal cell carcinoma syndrome. Clinical findings in 37 Italian affected individuals.

Nevoid basal cell carcinoma syndrome (NBCCS) is a hereditary condition transmitted as an autosomal dominant trait with complete penetrance and variable expressivity. The syndrome is characterised by numerous basal cell carcinomas (BCCs), odontogenic keratocysts of the jaws, palmar and/or plantar pits, skeletal abnormalities and intracranial calcifications. In this paper, the clinical features of 37 Italian patients are reviewed. Jaw cysts and calcification of falx cerebri were the most frequently observed anomalies, followed by BCCs and palmar/plantar pits. Similar to the case of African Americans, the relatively low frequency of BCCs in the Italian population is probably due to protective skin pigmentation. A future search based on mutation screening might establish a possible genotype phenotype correlation in Italian patients.

Adolescent↗

Potentially malignant and malignant lesions of the lip. Role of silver staining nucleolar organizer regions, proliferating cell nuclear antigen, p53, and c-myc in differentiation and prognosis.

The cellular changes leading to carcinoma of the lip are still not completely understood. This study was carried out on 44 malignant and potentially malignant lesions of the lower lip [30 squamous cell carcinomas (SCC), 7 actinic cheilitis, 3 leukoplakias, and 4 nodal metastases from lower lip SCC]. Silver-stained nucleolar organizer regions (AgNORs) and the immunohistochemical expression of proliferating cell nuclear antigen (PCNA), p53, and c-myc were evaluated on formalin-fixed, paraffin-embedded sections. The results indicate that the size and numbers of AgNORs and the percentage of PCNA-positive cells are sensitive parameters for discriminating between potentially malignant lesions and SCC, and for the prognostic sub-typing of lower lip SCC. Furthermore, while p53 positivity was found more frequently in high-grade carcinomas, p53-positive cellular clones were also found in some potentially malignant lesions, a finding probably related to ultraviolet-related cellular damage. These p53-positive lesions could be considered at higher risk of progression to malignancy than the p53-negative ones, although there is no evidence for this as yet. c-myc positivity was found only in some high-grade carcinomas and metastases, and appeared correlated with the later phases of lip carcinogenesis. The combined evaluation of the proliferation status, together with the changes in p53 and c-myc oncoproteins, might constitute useful markers for the prognostic evaluation of potentially malignant, as well as malignant, lesions of the lip.

Adolescent↗

Oral manifestations of idiopathic lenticular mucocutaneous pigmentation (Laugier-Hunziker syndrome): a clinical, histopathological and ultrastructural review of 12 cases.

OBJECTIVE: To present a clinical, histopathological and ultrastructural study on a group of patients affected by idiopathic mucocutaneous pigmentation (Laugier-Hunziker syndrome: LHS). MATERIALS AND METHODS: Twelve patients were investigated: clinical examination, laboratory tests, and X-ray studies together with light microscopy and electron microscopy were performed in order to diagnose LHS. RESULTS: All cases showed acquired, benign, macular hyperpigmentation of buccal mucosa lips and nails. Histologically, pigmentations are due to an accumulation of melanin in the basal layer keratinocytes and an increase in the number of melanophages in the submucosa and/or papillary dermis. Ultrastructurally there were increased numbers of normal-appearing melanosomes in keratinocytes of the lower epithelium. No evidence of malignant changes were detected. CONCLUSIONS: The importance of this condition relates to it being included in the differential diagnoses of pigmentary disorders of the oral mucosa with associated nail involvement. It is important to recognize this acquired benign disorder to avoid unnecessary investigations and treatments.

Adult↗

Expression of cell cycle and apoptosis-related proteins in sporadic odontogenic keratocysts and odontogenic keratocysts associated with the nevoid basal cell carcinoma syndrome.

Odontogenic keratocysts are occasionally (4-5%) associated with the nevoid basal cell carcinoma syndrome, a pleiotropic, autosomal disorder presenting a spectrum of developmental abnormalities and a predisposition for the development of different neoplasms. The aim of this study was to establish whether keratocysts showing clinically aggressive behavior associated with nevoid basal cell carcinoma syndrome reflect differences in cellular proliferation rate and/or in the expression of oncoproteins and tumor suppressor genes. For this reason, formalin-fixed paraffin-embedded sections of odontogenic keratocysts associated with the nevoid basal cell carcinoma syndrome (16 cases) and sporadic odontogenic keratocysts (16 cases) were compared for expression of proliferating cell nuclear antigen (PCNA) and p53, bcl-2, and bcl-1 (cyclin D1) onco-proteins. Most of the epithelial lining of odontogenic keratocysts associated with the nevoid basal cell carcinoma syndrome showed nuclear immunopositivity for p53 protein and overexpression of cyclin D1 with various degrees of staining intensity. All sporadic odontogenic keratocysts were negative for p53 and cyclin D1. The expressions of bcl-2 oncoprotein were found to be substantially similar between the two groups of lesions, with a cytoplasmic immunopositivity localized only in the resting reserve basal layer of the epithelium. PCNA expression showed no statistically significant difference between the two groups of lesions. In conclusion, the finding of cyclin D1 and p53 overexpression in odontogenic keratocysts associated with the nevoid basal cell carcinoma syndrome could be considered a hallmark of a mutated cellular phenotype, thus leading to the hypothesis that their aggressive clinical behavior could be due to a dysregulation of the expression of cyclin D1 and p53 proteins, involved in a check-point control of cellular proliferation.

Analysis of Variance↗

Early diagnosis of nevoid basal cell carcinoma syndrome.

BACKGROUND: Nevoid basal cell carcinoma syndrome, or NBCCS, is a hereditary condition characterized by basal cell carcinomas, or BCCs; odontogenic keratocysts, or OKCs; and skeletal abnormalities. The authors conducted this study to determine the early signs of NBCCS. METHODS: The authors reviewed files from two Italian dental schools from January 1980 to January 1995 to determine the early signs of NBCCS and the age at which patients were first examined. They re-examined all of the patients, using the diagnostic criteria for NBCCS. RESULTS: The authors found 14 patients who fulfilled the criteria for diagnosis of NBCCS in five families. All of the patients were 16 years of age or younger. In 11 cases (78 percent), the first sign of NBCCS in the patients was an OKC. The OKCs diagnosed in patients older than 13 years of age were large and characterized by widespread bone resorption. One 11-year-old patient had six large OKCs. The authors also found a case of multiple OKCs in an 8-year-old patient. Only one patient showed BCCs. CONCLUSIONS: OKCs are often the first signs of NBCCS and can be detected in patients younger than 10 years of age. Our data suggest that OKCs arise earlier in patients who have NBCCS than in patients who do not have NBCCS. The patients' young ages explain the low incidence of BCCs in this study. CLINICAL IMPLICATIONS: The presence of multiple OKCs in a child or onset of BCC in a patient younger than 20 years of age should alert dentists to the possibility of the patient's having NBCCS.

Adolescent↗