High DeltaN p63 isoform expression favours recurrences in odontogenic keratocyst--odontogenic keratocystic tumour.
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Biomedical subjects
Publications and source records attributed to M P Foschini.
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The study aimed to assess the proliferative activity and karyotype in Oral Lichen Planus (OLP) lesions. G-banding chromosomal analysis of short-term primary cultures, and immunohistochemical expression of Ki67 and p53 were applied in 30 consecutive OLP patients divided into two groups according to clinical presentation of the lesions, and in nine subjects as negative controls. Mean values of Ki67 and p53 expression differed significantly (P<.01) between controls and patients groups with reticular or atrophic-erosive forms of OLP, whereas there was no significant difference between the two groups of patients with reticular or atrophic-erosive lesions. Six OLP patients showed clonal chromosome alterations, four of them associated with p53 overexpression. In conclusion, OLP is characterized by a high cellular turnover in most patients irrespective of clinical disease presentation. The genetic instability found in some patients should be interpreted as a consequence of the enhanced epithelial turnover, although we cannot rule out the possibility that some of the cytogenetic non-random anomalies observed represent early steps in cancer development.
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AIMS: The presence of ground glass hepatocytes in a liver biopsy may be related to different conditions, including fibrinogen storage disease. Three types of fibrinogen storage disease have been described, namely types I, II and III. Type I is an hereditary hypofibrinogenaemia genetically characterized by a mutant variant of the fibrinogen molecule designated as fibrinogen Brescia, consistent with a gamma284 Gly-->Arg mutation. Only rare cases of types II and III fibrinogen storage disease have been described. The purpose of the present paper is to describe two cases of fibrinogen storage disease without associated hypofibrinogenaemia, which appeared during acute infectious diseases. METHODS AND RESULTS: Both patients were female, aged 77 and 73 years, who developed high transaminases during an infectious disease. In each case blood coagulation tests were within the normal range, and despite clinical and laboratory investigations no possible cause for liver disease could be found. Liver biopsies were performed; in both cases weakly eosinophilic cytoplasmic inclusions were observed. Using immunohistochemistry the inclusions were found to be due to fibrinogen accumulation. At ultrastructural level features corresponding to type II inclusions were observed. Molecular studies, performed in case 2, excluded the mutation typical of type I fibrinogen storage disease. Both patients also presented features of chronic hepatitis. In case 1, giant cell granulomas were additionally present. No close relatives of the patients presented any clinical or laboratory features of liver disease. In both patients altered liver function test values gradually, spontaneously, returned to within normal ranges after infectious disease was resolved. CONCLUSIONS: These cases suggest that, on rare occasions, hepatocytes may accumulate fibrinogen during an infectious disease.
Genome heterogeneity may be related to the wide variability of clinical and pathological features in hepatitis C virus (HCV)-related chronic liver disease. This paper addresses the possible association between HCV subtypes and clinical and histological features of chronically infected patients. Sixty-eight consecutive liver biopsies of chronic hepatitis constituted the basis of the study. HCV genotyping was performed on frozen tissue. Grading of necroinflammatory activity and staging of fibrosis were histologically assessed. Serologic HCV-RNA and liver function were assessed at the same time. All information was compared with clinical data including age, sex, HCV serology, and probable data and route of infection. Two cases were excluded as inadequate tissue was available. Five cases were negative to HCV-RNA in both serum and tissue. In 61 cases HCV RNA was present at the same time in serum and liver tissue. Forty-four patients were men (72%) and 17 (28%) were women. Two peaks of age were observed: 1 in the 4th decade of life, the 2nd in the 7th. The 2 groups had different HCV genotypes. Patients with genotypes 1b (mean age 50.7 years), 2c (mean age 61.3 years), and a subgroup of coinfections (mean age 60 years) were older than patients with genotypes 1a (mean age 35.5 years), 3 (mean age 36 years), and a subgroup of coinfections (mean age 33 years). Patients with genotypes 1b, 2, or 2c and a subgroup of coinfections more frequently had a history of blood transfusion and or surgical intervention dating up to 49 years previously. Patients with HCV 1a, 3, and a subgroup of coinfections frequently admitted a period of intravenous drug abuse. Patients with advanced liver disease, i.e., severe fibrosis and cirrhosis, showed the same 2 peaks of incidence: in the 4th and 7th decades of life, the first group mainly comprising patients with HCV types 1a and 3, the second, patients with HCV types 1b and 2c. Both these groups shared a clinical history of a long-standing infection. Two profiles of patients emerged. The largest group was composed of elderly patients, infected by HCV genotypes 1b or 2c, with a history of blood transfusion and/or surgery, presenting an advanced stage of liver disease (namely, severe fibrosis or cirrhosis). The second group was composed of younger patients, mainly in the 4th decade of life, infected by HCV types 3 or 1a, often presenting with chronic hepatitis in the stage of severe fibrosis or cirrhosis. The latter could be the profile of HCV infection in the near future.
OBJECTIVE: To determine the effect on kidney oxalate-salt deposition of a prolonged diet which induced vitamin B6 deficiency in adult rats, as there are reports of the pathogenic involvement of vitamin B6 deficiency in the formation of renal calcium oxalate calculi. MATERIALS AND METHODS: The study comprised 24 6-month-old male albino Wistar rats; 12 were fed with a purified vitamin B6-deficient diet and the others provided with the same diet but supplemented with 6 mg/kg of vitamin B6. After 12 weeks, all rats were killed, and their kidneys fixed in formalin and routinely processed to paraffin for morphological examination; some fragments were fixed in glutaraldehyde and prepared for ultrastructural examination. From each rat consecutive sections of both kidneys were cut and stained with haematoxylin and eosin, periodic-acid Schiff, Sirius red and the Von Kossa method for calcium. Sections were examined in polarized light and by electron microscopy. RESULTS: The histopathological and ultrastructural features of the kidney of vitamin B6-deficient rats were those of tubular-interstitial nephritis, characterized by tubular atrophy, interstitial fibrosis and chronic inflammatory infiltration. Oxalate and phosphate crystals were present in the papillary and parenchymal connective tissue. Ultrastructural features confirmed severe tubular epithelial lesions and the presence of an interstitial and intraepithelial inflammatory infiltrate; there was mild interstitial fibrosis. None of these features were apparent in the kidney of control rats. CONCLUSIONS: Histopathological and ultrastructural data indicate that a prolonged vitamin B6-deficient diet may contribute to the formation and deposition of calcium phosphate and oxalate crystals, which lead to severe damage of the renal parenchyma. This phenomenon may occur not only in growing rats, which have more active protein metabolism and consequently higher vitamin B6 requirements, but also in adult rats.
TT virus is a recently discovered virus, of which the pathogenetic potential is still uncertain. The present paper describes the histopathological features of a case of TT virus-related acute recurrent hepatitis. The patient is a 28-year-old woman with no history of drug or alcohol abuse, presenting with repeated episodes of hypertransaminasemia evidenced during the last 4 years. No other markers of viral or autoimmune disease were found. On histological analysis, the liver parenchyma showed a preserved architecture. The histological features were those of a mild acute hepatitis. The clinicopathological findings suggest th
INTRODUCTION: TT virus has been recently isolated in Japan in patients with acute and chronic non-A/non-G hepatitis. Its possible etiopathogenetic role in causing hepatitis has been initially taken in consideration. On the contrary, more recent studies deny the importance of TT virus in causing liver damage. Most of the studies are based on serological data or on viral detection from frozen liver tissue. AIM OF THE STUDY: In the present paper we describe a method to detect viral genome from formalin-fixed and paraffin-embedded liver tissue. MATERIALS AND METHODS: Twelve needle biopsies from liver were studied. Six cases were selected on the basis of serological negativity for HBV and HCV markers. Five cases of HCV-related chronic hepatitis and one HCV- and HIV-positive intravenous drug abuser were also included. All patients underwent liver biopsy, performed with a 14-G needle. Liver specimens were formalin-fixed and paraffin-embedded as routine. From each block, sections were cut and stained for histopathologic examination. Additional 5 microns sections were employed to extract DNA for nested PCR. RESULTS: In 2 of 12 cases studied, TT virus genome was found. In both cases the presence of viral DNA was confirmed by sequencing. Both patients were male. The first patient was a 39-year-old HIV- and HCV-positive intravenous drug abuser. The second patient was a 60-year-old heavy alcohol drinker. In both cases the presence of TT virus apparently did not affect the histological picture. CONCLUSION: It is possible to detect TT virus genome from formalin-fixed and paraffin-embedded tissue. This method offers the possibility to perform retrospective studies.
Salivary gland tumors frequently present myoepithelial cell differentiation that is not always easily identified on routinely stained sections. Recently novel markers of myoepithelium have been studied, such as calponin (CALP), caldesmon (CALD), and smooth muscle myosin heavy chain. These markers, together with smooth muscle actin may be useful tools for identifying myoepithelial cells. We immunohistochemically studied a series of 23 benign and malignant salivary gland tumors using antibodies to these four markers. The tumors were classified as follows: pleomorphic adenoma (n = 8), basal cell adenoma (n = 3), myoepithelioma with plasmacytoid cells (n = 2), epithelial-myoepithelial cell carcinoma (n = 6) and adenoid cystic carcinoma (n = 4). All tumors were positive for at least one of the four markers. CALP and smooth muscle actin were the markers more frequently expressed. Positivity was mostly located in the myoepithelial cells that constitute the external layer of the glandular or tubular neoplastic structures. In poorly differentiated epithelial myoepithelial carcinomas, composed of solid sheets of neoplastic cells and sometimes of clear cells, immunohistochemical staining for myoepithelial markers evidenced rudimentary glandular structures. CALP and smooth muscle actin were positive in the two cases of myoepithelioma with plasmacytoid cells. In conclusion, the combined staining with four markers helps to disclose myoepithelial cell differentiation and can be a useful tool for the correct histopathological diagnosis of salivary gland tumors. Among the four markers studied, CALP and smooth muscle actin were the most useful to identify myoepithelial cell differentiation.
Orbital cavernous hemangiomas (OCH) have thick and highly cellular vascular walls. Ultrastructural studies have demonstrated the smooth muscle nature of these cells. Vascular neoplasms can modify their morphological and clinical features under hormonal stimulation. The purpose of the present study was to investigate the presence of smooth muscle markers and sex steroid receptors in 12 cases of OCH. Orbital cases were compared with cutaneous hemangiomas and subcutaneous angioleiomyomas. Smooth muscle actin (SMA) and desmin were localized in spindle cells of the vascular walls of all 12 cases studied. OCH showed immunohistochemical positivity with progesterone receptor (PR) antibody both in smooth muscular and in endothelial cells. For comparison, sex steroid receptors were studied in 10 cases of cutaneous cavernous hemangioma and in 10 cases of subcutaneous angioleiomyoma. PR was found in smooth muscle and endothelial cells of 6 out of 10 cases of subcutaneous angioleiomyoma and in none of the cases of cutaneous cavernous hemangioma. No positivity was obtained with estrogen receptor (ER) antibody in any of the cases tested. The present data suggest that OCH share morphological and immunohistochemical features with subcutaneous angioleiomyomas. Furthermore, immunohistochemical positivity with PR antibody indicates that OCH have to be added to the list of mesenchymal lesions that express sex steroid receptors.
Although there seems to be a common stem cell for the two epithelial cell types in the breast, the vast majority of breast cancers exhibit a luminal phenotype. Pure myoepithelial carcinomas are rare. We report our findings of genetic alterations in these tumors. We have analyzed 10 cases of pure myoepithelial cell carcinomas using laser capture microdissection and comparative genomic hybridization. The mean number of changes was 2.1 (range 0-4), compared with a mean of 8.6 (range 3.6-13.8) in unselected ductal carcinomas. Common alterations included loss at 16q (3/10 cases), 17p (3/10), 11q (2/10), and 16p (2/10), regions also commonly deleted in ductal carcinomas. The single case in which both pure myoepithelial carcinoma and invasive ductal carcinoma was present showed 2 alterations in the myoepithelial tumor (losses at 17p and 17q), whereas the invasive ductal component showed 15 alterations (5 gains and 9 losses), including loss at 17p. The sharing of 17p loss in myoepithelial and ductal carcinoma is consistent with a common stem cell model in the breast. The relatively few genetic alterations in otherwise aggressive neoplasms suggests that myoepithelial tumors may be a good model for the delineation of genes important in breast tumorigenesis.
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In the skin, endocrine tumors showing areas with nonendocrine features and nonendocrine tumors showing endocrine differentiation are present. (1) Neuroendocrine carcinomas with nonendocrine differentiation: Merkel cell carcinoma (MCC) of the skin has been frequently described in association with squamous cells carcinoma (SCC) which can arise separately (as synchronous or metachronous lesions) from MCC as well as closely intermixed. In the first event the possibility that the lesions are sustained by same causative factors (among which sun exposure is the most probable) is suggested. In cases of lesions closely intermixed the possibility of an origin from a common precursor is suggested. Furthermore, cases of MCC have been described to contain glandular, melanocytic, striated muscle, and lymphoepithelioma-like features. These latter findings further support the hypothesis of tumors showing divergent differentiations. (2) Nonendocrine tumors showing endocrine differentiation: Basal cell carcinoma (BCC) was the first cutaneous nonendocrine tumor described to contain neuroendocrine granules. Presence of endocrine features were subsequently confirmed with immunohistochemical studies. Endocrine features were then described in sweat gland apocrine and eccrine carcinomas. Endocrine elements present in BCC and in sweat gland carcinomas do not show morphological and immunohistochemical features of Merkel cells. Thus the possibility that these tumors develop an immature Merkel cell or a new type of endocrine cell of the skin is suggested. Tumors with follicular differentiation such as trichoblastomas and trichofolliculomas contain a high number of Merkel cells. As Merkel cells are numerous in hair follicles of human fetal skin, the possibility that these tumors recapitulate the human skin embryogenesis is suggested.
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BACKGROUND: The present case is an example of hypertrophic inflammatory neuropathy (HIN). This entity is a rare tumor-like, chronic inflammatory, focal or multifocal, mainly demyelinating neuropathy of unknown origin, most frequently involving the brachial plexus. CASE DESCRIPTION: The authors describe a 67-year-old man presenting with a nodular mass in his right supraclavicular fossa. A nodular mass grossly resembling a schwannoma originating from a single nerve fascicle was surgically removed from the right C6 spinal nerve. Histologically, endoneurial edema, fibrosis, focal chronic inflammation, and extensive "onion bulb" formation were seen. Electron microscopy studies and immunohistochemistry proved that the onion bulb-forming cells were schwannian in nature and that the whorls of onion bulbs surrounded a generally demyelinated axon. Three months following surgery the patient developed acute painless paralysis of his right biceps brachii muscle that rapidly reversed; after that he remained neurologically asymptomatic. MRI revealed multiple fusiform mass lesions involving the brachial plexus bilaterally. Electrophysiologic studies demonstrated a bilateral, asymmetrical, mainly demyelinating neuropathy involving the brachial plexus; they failed to reveal any abnormality suggestive of generalized neuropathy. CONCLUSION: HIN is different from other focal tumor-like neuropathies and in particular from localized hypertrophic neuropathy (LHN).
Angiomyolipoma is a hamartomatous process that most frequently occurs as a single lesion or multiple foci in the kidneys of patients affected by tuberous sclerosis. Angiomyolipoma can also arise in extrarenal sites, among which the liver is the most frequently recorded. Only rare cases of angiomyolipoma located in the head and neck region (ear and oral and nasal cavity) have been described. The purpose of the present article is to report a case of angiomyolipoma of the parotid gland. A 68-year-old woman appeared for treatment with a slow-growing nodule located in her right parotid gland. Ultrasound examination revealed a heterogeneous nodule with well-defined margins. The nodule was surgically removed by total parotidectomy and showed the characteristic appearance of angiomyolipoma, with an admixture of fat smooth muscle cells, and tortuous, thick-walled blood vessels. Careful physical examination of the patient failed to reveal features of tuberous sclerosis. Angiomyolipoma should be considered in the differential diagnosis of mesenchymal lesions involving the salivary gland.
INTRODUCTION: Helicobacter pylori is one of the most common causes of human gastritis. Recently, a new agent has been isolated, which also causes a gastritis. It has been initially named Gastrospirillum hominis and renamed Helicobacter heilmannii (Hh). Hh is extremely rare. In spite of the rarity it is important to recognize and diagnose it, as it requires a proper therapy, different from Hp therapy. Clinical presentation and serological results of Hh are superimposable to those of HP. Therefore differential diagnosis resides on histological grounds. PURPOSE of the present paper is to report 14 new cases of Hh gastritis, which constitutes the first italian series. RESULTS: Cases constituted 0.01% of all gastric biopsies seen in the period 1994-1998. Nine patients were male and five were female; age ranged from 32 to 76 years (50 years on average). All patients presented a mild to moderate gastritis. Hh is a spiral bacterium, being about 10 micra in length, localized in single or small groups in the glandular mucus. Two cases were associated with Hp. One case was associated with gastric adenocarcinoma. Two cases were diagnosed during the follow-up of duodenal ulcer. In CONCLUSION, the incidence of Hh gastritis in the present series seems consistent with that from other European countries. In all cases the presence of Hh was associated with features of gastritis. This confirms the pathogenetic role of Hh.
Extrahepatic neoplasms metastatic to the liver histologically are often indistinguishable from hepatocellular carcinoma (HCC). The differential diagnosis between HCC and metastatic liver tumours can be even more difficult in ultrasound guided fine-needle biopsies. Purpose of the present study was to investigate the utility of immunohistochemical staining with polyclonal anticarcinoembryonic antigen (pCEA) antibody and of in situ hybridization (ISH) revealing human albumin mRNA, with emphasis on tissues obtained via fine-needle procedure. Cases consisted of 52 primary HCC; 2 HCC metastatic to vertebral bones; 18 tumours metastatic to the liver; 24 non-hepatocellular tumours metastatic to the skin, lymph nodes and brain; 2 immature teratomas with areas of hepatoid differentiation. Forty-seven HCC (90%) and 7 liver metastases (38%) were obtained by ultrasound guided fine-needle biopsies (21 g needle was used). All the remaining cases were surgical specimens. All the cases were studied with immunohistochemistry for pCEA and ISH using a cRNA probe for human albumin mRNA. The immunohistochemical staining using pCEA showed a canalicular type of positivity in 37 cases of HCC (71%), in one HCC metastatic to vertebral bone and in the hepatoid areas of one immature teratoma. No canalicular type of positivity was obtained in non-hepatocellular neoplasms metastatic to the skin, brain, lymph-nodes and liver. Albumin mRNA was detected in 51 (98%) primary HCC, in both HCC bone metastases, and in the hepatoid areas of both immature teratomas. No positivity was obtained in non-hepatocellular tumours. The data here obtained indicate that immunostaining with pCEA and ISH revealing human albumin mRNA are markers of hepatocellular differentiation and confirm their diagnostic utility. Detection of albumin mRNA showed a higher sensitivity. In addition the cRNA probe here used seems more sensitive that the oligonucleotide probes employed in previous studies.