Expression of P53 and isoforms in bening and malignant lesions of the head and neck.

BACKGROUND: P53, a crucial suppressor of tumor formation, generates multiple isoforms, whose role in disease is still being defined. METHODS: By immunohistochemistry, we studied the expression of P53 protein and relative isoforms in benign papillomas (PA, n=9), inverted papilloma (IPA, n=10) and squamous cell carcinomas (SCC, n=21). RESULTS: In all lesions, P53 isoforms were significantly more expressed than P53. Immunoexpression of P53 matched with P53 isoforms in IPA as well as in SCC. Simultaneous immunoexpression of P53 and related isoforms was double in SCC compared to IPA (10% vs 24%), while expression of P53 isoforms was strongly reduced (70% vs 43%). IPA showed the highest percentage of both reactive cases and immunostained cells expressing P53 isoforms. CONCLUSIONS: We found the higher expression of P53 isoforms in IPA and SCC compared to PA, suggesting their role in local aggressiveness and malignant proliferation in head-neck lesions.

Invasive macrodystrophia lipomatosa of the hand.

OBJECTIVE: The Authors point out the interest of differential diagnosis and conservative surgical treatment of a rare case of digital and ulnar side of the hand gigantism, with massive fatty infiltration of soft tissues and a neurovascular bundle, to be included into Macrodystrophia Lipomatosa with fibrolipomatous hamartomata. PATIENTS AND METHODS: Excision of the mass included 4th ray disarticulation (the fifth had been amputated several years ago) as well as microsurgical external and internal neurolysis of the ulnar nerve, the ulnar neurovascular bundle being exposed and covered with dermal substitute INTEGRATM, with a good result both from a cosmetic and functional point of view at three year follow up. RESULTS: This is the first report of INTEGRATM covering of a neurovascular bundle. Samples taken from the dermal substitute matrix interface at day 6 and day 25 were examined with transmission Electron Microscopy: a newly formed tissue, rich in precursor cells, was detected. CONCLUSIONS: Conservative surgery, requiring particular microsurgical skills and use of dermal templates, plays an outstanding role in treatment of these rare but aggressive soft tissues masses of the upper limb.

Cell proliferation parameters and apoptosis indices in pituitary macroadenomas.

BACKGROUND: Pituitary adenomas are usually well-differentiated tumors but may show locally aggressive behavior. AIM: To investigate the relationship between proliferation and apoptosis parameters and tumor recurrence in a series of 20 radically resected pituitary macroadenomas (11 functioning, 9 non-functioning). MATERIALS AND METHODS: Proliferative activity and DNA ploidy were analyzed by flow cytometry (FCM) on fresh surgical specimens. Immunohistochemistry for Ki-67/MIB-1 and for the anti-apoptotic protein Bcl-2 was performed on paraffin-embedded specimens from the same tumors. Tumor regrowth was evaluated by magnetic resonance imaging (MRI). RESULTS: Six adenomas recurred after surgery, regardless of hormonal hypersecretion. Pre-surgical tumor size was significantly higher in recurrent than in non-recurrent adenomas (p=0.003). Pre-surgical MRI demonstrated cavernous sinus (CS) invasiveness in all recurrent tumors, while none of the non-invasive adenomas recurred (p=0.042, by Fisher's exact test). The DNA content was aneuploid in 5/20 adenomas, one of which recurred. Cell percentages in the S (%SPF) and G2+M (%G2-M) phases and proliferative index (PI) (PI=%SPF+%G2-M) were significantly higher in aneuploid than in diploid adenomas (p<0.05), but no significant differences concerning all FCM parameters were observed between recurrent and non-recurrent adenomas. Similarly, MIB-1 did not show a significant difference of expression between recurrent and non-recurrent adenomas (p=0.33). Bcl-2 immunoreactivity was detected in 12/15 pituitary adenomas, involving 63±35% of tumor cells, regardless of tumor recurrence. CONCLUSIONS: In this group of radically resected pituitary macroadenomas, neuroradiological finding of CS invasiveness--but not FCM parameters nor MIB-1 and Bcl-2 expression--is useful for predicting tumor recurrence.

Ectopic parotid: case report.

A recent case led the authors to re-examine the clinical characteristics of the cervical ectopia of the major salivary glands. These glands develop in the embryo between the sixth and seventh week, starting with the formation of endodermal invaginations of the branchial section of the floor of the primitive mouth. These cell cords, initially solid, proliferate in the underlying mesenchyme, starting from the opening of the future excretory duct, and subsequently branch and canalize. During embryogenesis, the endodermal invaginations become closely interconnected with the adjacent lymphatic tissue. It is thus possible for lymphoid tissue to migrate into the parotid or the other major salivary glands, or conversely, for salivary tissue to become included in the cervical lymph nodes. Very rarely, ectopic salivary gland tissue can also be found in other unusual locations, including the neck region, as a result of a developmental abnormality of the branchial apparatus. The base of the neck is the most common location, while ectopia of the mid third of the neck is quite rare. The authors discuss the clinical details and diagnostic procedure leading to preoperative diagnosis. This congenital anomaly can, albeit rarely, degenerate into cancer, and surgical excision is thus imperative.

An intriguing case of Prurigo pigmentosa in a Sicilian young patient.

Prurito pigmentosa is an inflammatory disease mainly reported by Japanese dermatologists. We report a case of Prurigo pigmentosa observed in a Sicilian young patient affected by intellectual disability. In the past, we had already observed and reported some cases of Prurigo pigmentosa in patients living in Sicily. The differential diagnosis, the treatment of the disease, the role of chronic intake of psychodrugs and the possible relation to G6PD deficiency of this patient are pointed out.

Human galectin-3 immunoexpression in thyroid follicular adenomas with cell atypia.

Human galectin-3 (hgal-3) is a beta-galactoside binding protein involved in a number of physiological and pathological processes. Increasing hgal-3 immunoexpression has been reported in several human tumors, including thyroid carcinomas, but not in benign thyroid lesions. We analyzed the immunolocalization of hgal-3 in cell compartments of benign and malignant thyroid lesions. Hgal-3 immunoperoxidase reaction was carried out on 133 thyroid tissue samples obtained from 113 patients; 20 of these were normal (NT), 85 were benign thyroid lesions [20 colloid nodules (CN), 21 nodular hyperplasias (NH), 7 focal lymphocytic thyroiditis (FLT), 15 Hashimoto's thyroiditis (HT), 22 follicular adenomas (FA)], 25 differentiated carcinomas [15 papillary carcinomas (PC), 6 follicular carcinomas (FC) and 4 Hürthle cell carcinomas (HC)] and 3 anaplastic carcinomas (AC). Among the malignant thyroid lesions, hgal-3 was detected in 12/15 (80%) PC, 3/4 (75%) HC and in 4/6 (66.6%) FC, but in none of the 3 AC. Conversely, hgal-3 immunoexpression was absent in NT and in all benign thyroid lesions, but 1/15 HT and 10/22 (45.4%) FA. In the latter, hgal-3 was mostly expressed in microfollicular areas and in five of the six atypical FA. Hgal-3 cytoplasmic-perinuclear immunolocalization was observed in the majority of thyroid carcinomas and in more than half of the FA, theoretically suggesting an involvement of this protein in thyroid tumorigenesis throughout an antiapoptotic activity. Moreover, hgal-3 expression in FA might anticipate the likelihood of evolution of these benign lesions towards malignancy.

Eruptive syringomas with calcium deposits in a young woman with Down's syndrome.

Eruptive syringomas are uncommon in the general population. We describe here an 18-year-old female, affected by Down's syndrome, who presented with an abrupt eruption of small skin-colored or reddish papules on the face, neck and limbs. Light microscopy allowed us to diagnose syringomas, whereas the study of the ultrastructural features revealed calcium deposits in many lumina and also in the mitochondria. This observation confirms the hypothesis that the syringeal structure plays a role in the pathogenesis of calcinosis cutis.

Friction melanosis, friction amyloidosis, macular amyloidosis, towel melanosis: many names for the same clinical entity.

Macular or friction amyloidosis is a cutaneous entity characterized by a brownish pigmentation distributed on the skin over bony regions of the trunk and limbs after the use, for many years, of a nylon towel or scrub brush to clean the skin. Electron microscopy is necessary for the diagnosis of this dermatosis and reveals deposits of amyloid in the papillary dermis. This condition is relatively unknown in Western countries. In this report, we describe 24 Italian patients affected by friction amyloidosis which was caused by the use of cotton towels, horse-hair gloves or artificial and rough sponges to clean their skin.

Primary adenocarcinoma of the arytenoid: an ultrastructural study.

Primary adenocarcinoma of the larynx is a rare neoplasm that tends to spread to both regional lymph nodes and distant sites. A case of primary adenocarcinoma of the arytenoid in a 74-year-old man is presented. The tumor was evaluated by light and electron microscopy. A high percentage of intranuclear pseudoinclusions (more than 20% of the neoplastic cells) was a peculiar characteristic of the tumor. To the best of our knowledge, such a feature has not been reported previously and should be considered a hallmark of more aggressive behavior.

Chronic heat-induced skin lesions (erythema ab Igne): ultrastructural studies.

Erythema ab igne (EI) is an uncommon skin lesion caused by mild and repeated exposure to infrared sources. The aim of this study was to investigate the ultrastructural alterations in this condition. The ultrastructural study was carried out on 5-outpatients who presented typical EI of their exposed sites. Skin punch biopsies were processed for standard electron microscopy. The epidermis was hyperpigmented, with focal regressive changes of basal keratinocytes. An apparent functional activation of melanocytes with numerical increase of dendritic processes was also observed. The dermis showed abundant melanophages and occasional elastic fiber alterations similar to actinic elastosis. No alterations consistent with preneoplastic skin conditions were observed. The ultrastructural findings associated with EI seem to be nonspecific and consistent with moderate regressive changes of keratinocytes as well as a consensual melanocytic activation and elastic fiber modifications. Similar alterations can be observed in chronic actinic skin damage. This condition is presumably more benign than the ultraviolet exposure. The association of EI and premalignant skin lesions, though occasionally described, seems relatively infrequent.

Raxofelast, a hydrophilic vitamin E-like antioxidant, stimulates wound healing in genetically diabetic mice.

BACKGROUND: Impaired wound healing is a well-documented phenomenon in experimental and clinical diabetes. Emerging evidence favors the involvement of free radicals in the pathogenesis of diabetes-related healing deficit. This study assessed the effect of systemic administration of raxofelast, a protective membrane antioxidant agent, on wound healing by using healing-impaired (db/db) mice. METHODS: The wound healing effect of raxofelast was investigated by using an incisional skin-wound model produced on the back of female diabetic C57BL/KsJ db+/db+ mice and their healthy littermates (db+/+m). Animals were then randomized to the following treatment: raxofelast (15 mg/kg/d intraperitoneally) or its vehicle (dimethyl sulfoxide/sodium chloride 0.9%, 1:1, vol/vol). The animals were killed on different days, and the wounded skin tissues were used for histologic evaluation and for analysis of malondialdehyde (MDA) level and myeloperoxidase (MPO) activity, wound breaking strength, and collagen content. RESULTS: Diabetic mice showed delayed wound healing together with low collagen content, breaking strength, and increased MDA levels and MPO activity when compared with their healthy littermates. The administration of raxofelast did not modify the process of wound repair in healthy (db/+) mice, but significantly improved impaired wound healing in diabetic mice through the stimulation of angiogenesis, reepithelialization, synthesis, and maturation of extracellular matrix. Furthermore, raxofelast treatment significantly reduced MDA levels, MPO activity, and increased the breaking strength and collagen content of the wound. CONCLUSIONS: The current study provides evidence that raxofelast restores wound healing to nearly normal levels in experimental diabetes-impaired wounds and suggests that an increased lipid peroxidation in diabetic mice may have a role in determining a defect of wound repair.

Midfacial granuloma syndrome or an inflammatory non-specific disease? A case report.

We report a case of idiopathic midline destructive disease in a 57-year-old man. The patient had a non-specific histological pattern in biopsies obtained from the nose and upper lip, characterized by a granulomatous reaction with progressive destruction of the tissues. The patient's general medical history was non-contributory. Clinical and laboratory data did not support any feasible etiology for this destructive process. The patient was treated with prednisone until the discovery of type II diabetes mellitus (never diagnosed before) and was then in turn treated only with oral antidiabetic therapy. Follow-up controls revealed progressive reduction of the symptoms and of the nasal and lip lesions and total remission of symptoms up to 2 years after the onset of the disease. We discuss the diagnostic and subsequent therapeutic problems in the management of the midline necrotizing lesions.

Inhibition of lipid peroxidation restores impaired vascular endothelial growth factor expression and stimulates wound healing and angiogenesis in the genetically diabetic mouse.

Impaired wound healing is a well-documented phenomenon in experimental and clinical diabetes. Experimental evidence suggests that a defect in vascular endothelial growth factor (VEGF) regulation might be associated with wound-healing disorders. We studied the involvement of lipid peroxidation in the pathogenesis of altered VEGF expression in diabetes-related healing deficit by using an incisional skin-wound model produced on the back of female diabetic C57BL/KsJ db+/ db+ mice and their normal (db+/+m) littermates. Animals were then randomized to the following treatment: raxofelast (15 mg.kg(-1).day(-1) i.p.), an inhibitor of lipid peroxidation, or its vehicle (DMSO/NaCl 0.9%, 1:1 vol: vol). The animals were killed on different days (3, 6, and 12 days after skin injury), and the wounded skin tissues were used for histological evaluation, for analysis of conjugated dienes (CDs), as an index of lipid peroxidation and wound breaking strength. Furthermore, we studied the time course of VEGF mRNA expression throughout the skin-repair process (3, 6, and 12 days after skin injury), by means of reverse transcriptase-polymerase chain reaction, as well as the mature protein in the wounds. Diabetic mice showed impaired wound healing with delayed angiogenesis, low breaking strength, and increased wound CD content when compared with their normal littermates. In healthy control mice, a strong induction of VEGF mRNA was found between day 3 and day 6 after injury, while no significant VEGF mRNA expression was observed at day 12 after injury. In contrast, VEGF mRNA levels, after an initial increase (day 3), were significantly lower in diabetic mice than in normal littermates, and light induction of VEGF mRNA expression was also present at day 12 after injury. Similarly, the wound content of the angiogenic factor was markedly changed in diabetic mice. Administration of raxofelast did not modify the process of wound repair in normal mice, but significantly improved the impaired wound healing in diabetic mice through the stimulation of angiogenesis, re-epithelization, and synthesis and maturation of extracellular matrix. Moreover, raxofelast treatment significantly reduced wound CD levels and increased the breaking strength of the wound. Lastly, the inhibition of lipid peroxidation restored the defect in VEGF expression during the process of skin repair in diabetic mice and normalized the VEGF wound content. The current study provides evidence that lipid peroxidation inhibition restores wound healing to nearly normal levels in experimental diabetes-impaired wounds and normalizes the defect in VEGF regulation associated with diabetes-induced skin-repair disorders.

[Description of a particular case of the so-called Schmincke lymphoepithelioma and study of the correlation with Epstein-Barr virus]. / Descrizione di un caso particolare del cosiddetto linfoepitelioma di schmincke e studio delle correlazioni con il virus di Epstein-Barr.

For poorly differentiated rhinopharyngeal carcinomas, the clinical presentation (association with the Epstein-Barr virus, paraneoplastic syndromes, onset of lymphoma) and the histopathological features can be polymorphous and they can confound or delay diagnosis and preparation of an adequate treatment plan (radio-chemotherapy). Often these neoplasms arise as clinically primitive laterocervical metastases, masked by clinical findings and a history that can lead to the mistaken diagnosis of systemic lymphoproliferative processes such as Hodgkin's disease. Here an observation of this type is presented in a young patient (19 years old) who came under observation for a laterocervical tumefaction recurrent from a previous exeresis performed at another hospital and symptoms of serotine febricula, dysphagia and serology positive for the Epstein-Barr virus (EBV). The patient underwent surgery and then radiotherapy and has been under close post-operative follow-up for two years. To date the patient's condition--both local and general--is good. The particular histology of the neoformation lies in the abundant infiltration of plasma cell and lymphocyte eosinophils, at times in blastic form. Moreover, elements with a large clear nucleus and evident nucleolus (Hodgkin-like) and scattered multinucleate Langhans-type giant cells can be seen. Immunohistologically the tumor cells markedly express for cytokeratin and the latent membrane protein (LMP1) of the Epstein-Barr virus (EBV) and show a high growth fraction. Under the electron microscope, the plurinucleate giant cells present large nuclei with morphology similar to that of tumor cells. The clear cytokeratin-positivity of the tumor elements and the histological and ultrastructural features mentioned led to the diagnosis of a massive metastasis from lymphoepithelial carcinoma, the Schmincke variant, plus EBV infection of the neoplastic cells. The authors conclude assuming that the particular granulomatous reaction is due to the host's reaction to the tumor cells, but also to the reaction to the viral antigens. In the former case we find an attempt to limit the carcinomatous process; in the latter it is a response caused by the EBV and is not, apparently, aimed at protecting against the neoplasm rather it facilitates the neoplastic process.

[Biphasic hypopharyngeal synovial sarcoma: ultrastructural, cytofluorometric and immunohistochemical study and brief review of the literature]. / Sarcoma sinoviale bifasico a localizzazione ipofaringea: studio ultrastrutturale, citofluorometrico ed immunoistochimico e breve revisione della Letteratura.

Synovial sarcomas account for 7-10% of all soft tissue malignancies and the rare head and neck region location accounts for an average 5% of them. A brief review of the data in the Literature has shown that not more than one hundred cases of cervical-facial synovial sarcoma have been reported. In the head and neck locations this form of tumor is significantly less aggressive, with a higher survival rate and a recurrence rate much lower than the 60-70% shown for other locations in the limbs. After a brief review of the Literature, Authors present a rare clinical case of hypopharyngeal synovial sarcoma which recently came under observation. Despite the accurate diagnostic procedure, after surgical removal of the tumor by CO2 laser microlaryngoscopy, diagnosis required the use of histological and ultrastructural techniques. CT and NMR of the neck using contrast medium showed that the structure of the neoformation was similar to that of the soft tissues, it was 3-4 cm in diameter, located in the hypopharynx and had an extensive surface in contact with the left glossoepiglottic groove. The lesion appeared to involve the free edge of the aryepiglottic fold, coming into contact with the free edge of the epiglottis; it could not be dissociated form the epiglottis and obliterated both the homolateral glossoepiglottic vallecula and the pyriform sinus. Structural analysis after radiography with a contrast medium showed a marked impregnation of the lesion, indicative of high degree of vascolarization. Ultrastructural, cytofluormetric and immunohistochemical analyses were performed on the neoplasm in order to process all these data together with the clinical parameters; in other words a multi-parameter evaluation was performed, as suggested by other Authors, to determine the therapy and arrange more accurate monitoring of this patient, victim of a neoplasm with a high potential for metastases.