Hard to face: cutaneous malignant melanoma.

An 88-year-old Caucasian man recently sought medical attention due to recrudescence of skin disease in the area of previously excised nodule (in 2002) on the nose dorsum. The original lesion was clinically considered as a pigmented basal cell carcinoma, after which histological examination revealed a superficial spreading melanoma in vertical growth face (Clark level IV; Breslow thickness 2.1 mm) arising from a pre-existing nevus. The adjacent skin also showed significant actinic damage both in the epidermis and in the dermis. A sentinel node was positive (micrometastases of melanoma) and radical lymph node dissection of the neck was performed. Other lymph nodes did not contain metastasis. Computed tomography scans of brain, chest, abdomen and pelvis performed at that time showed no evidence of systemic disease.

Effects of heavy metals on ultrastructure and Hsp70 induction in Lemna minor L. exposed to water along the Sarno River, Italy.

The effects of freshwater pollution in the highly contaminated river Sarno (Campania, Southern Italy) have been evaluated using bags containing the aquatic plant Lemna minor (Lemnacee, Arales), in order to determine morpho-physiological modifications as a response to pollutants. The exposition of Lemna bags for 7 days on three different sites along the river path showed alterations in chloroplasts and vacuoles shape and organization. Moreover, some specimens were exposed in vitro at the same heavy metal (HM) concentrations measured in the polluted sites of the river, and compared with data from the bag experiment; to verify the dose and time dependent effects, samples were exposed to HM in vitro at concentrations ranging from 10(-6) to 10(-4)M up to 7 days. Transmission electron microscopy (TEM) observations on in vitro plants confirmed that ultrastructural alterations affected most of plastids and the shape of different subcellular structures, namely vacuoles; in in vitro stressed specimens, Heat Shock Proteins 70 (Hsp70) levels changed, in dependence of changing levels of HM measured in different sites along the river path. Thus L. minor exhibited a possible correlation between the levels of HM pollution and Hsp70 occurrence; interestingly, the data presented showed that copper specifically increased Hsp70 levels at concentrations detected in polluted river waters, whereas cadmium and lead did not; on the other side, the latter represent highly toxic elements when specimens were exposed to higher levels in vitro. The effects of specific elements in vitro are compared to those observed in bags exposed along the river path; thus results are examined in order to propose L. minor as an organism able to be utilized to monitor heavy metals pollution; the possibility of using Hsp70s as specific markers of HM pollution is discussed.

Differential expression of transglutaminase genes in patients with chronic periodontitis.

OBJECTIVE: Gingival epithelium plays a key role in the protection of oral tissues from microbial challenge, especially during the periodontal disease. This study was aimed to evaluate levels of mRNA transcripts of different forms of transglutaminase in the human gingival tissues from patients with chronic periodontitis and relative controls. SUBJECTS AND METHODS: This study included 22 patients with chronic periodontitis (CP) and 22 healthy controls. For each patient, the values of probing depth (PD), clinical attachment level (CAL), and bleeding on probing (BOP) were recorded. Gene expression of transglutaminase 1, transglutaminase 2, transglutaminase 3, and metalloprotease 2 was evaluated by real-time PCR, while that of Factor XIIIA and metalloprotease 9 by RT-PCR. RESULTS: The values of all the clinical parameters were significantly higher in the CP group than in the healthy control group (P < 0.05). In the CP group, the mRNA expression of transglutaminase 1 and transglutaminase 3 was significantly decreased in comparison with healthy control group. A slight nonsignificant changes of transglutaminase 2 gene expression were observed in samples from CP patients in comparison with controls. CONCLUSIONS: These observations suggest that transglutaminase gene expression may be modified in response to chronic injury in the damaged gingival and emphasizes the key role of these enzymes in gingival remodelling/healing and adaptive processes.

Hearing Loss and Oxidative Stress: A Comprehensive Review.

Hearing loss is a prevalent condition affecting millions of people worldwide. Hearing loss has been linked to oxidative stress as a major factor in its onset and progression. The goal of this thorough analysis is to investigate the connection between oxidative stress and hearing loss, with an emphasis on the underlying mechanisms and possible treatments. The review addressed the many forms of hearing loss, the role of reactive oxygen species (ROS) in causing damage to the cochlea, and the auditory system's antioxidant defensive mechanisms. The review also goes over the available data that support the use of antioxidants and other methods to lessen hearing loss brought on by oxidative stress. We found that oxidative stress is implicated in multiple types of hearing loss, including age-related, noise-induced, and ototoxic hearing impairment. The cochlea's unique anatomical and physiological characteristics, such as high metabolic activity and limited blood supply, make it particularly susceptible to oxidative damage. Antioxidant therapies have shown promising results in both animal models and clinical studies for preventing and mitigating hearing loss. Emerging therapeutic approaches, including targeted drug delivery systems and gene therapy, offer new possibilities for addressing oxidative stress in the auditory system. The significance of this review lies in its comprehensive analysis of the intricate relationship between oxidative stress and hearing loss. By synthesizing current knowledge and identifying gaps in understanding, this review provides valuable insights for both researchers and clinicians. It highlights the potential of antioxidant-based interventions and emphasizes the need for further research into personalized treatment strategies. Our findings on oxidative stress mechanisms may also affect clinical practice and future research directions. This review serves as a foundation for developing novel therapeutic approaches and may inform evidence-based strategies for the prevention and treatment of hearing loss, ultimately contributing to improved quality of life for millions affected by this condition worldwide.

Unilateral synchronous breast tumors. Rare association of myofibroblastoma and osteosarcoma.

The authors describe the case of a patient with two particularly rare contiguous tumors, myofibroblastoma and osteosarcoma, in the same breast. Rare does not mean untreatable, and the chance of recovery is no less than with more common tumors. However, rare tumors do present a significant problem for pathologists due to diagnostic difficulties, and so an exact prognosis is not always possible.

Mucocele of the appendix. Two case reports.

The authors present two cases of mucocele of the appendix and discuss them in relation to the literature and the clinical features of this disease. They clarify the definition of mucocele as an intraluminal accumulation of mucus in the appendix, and concentrate on the observable pathological processes, agreeing on the higher frequency of mucinous cystadenoma and the possibility that mucocele can develop into peritoneal pseudomyxoma or degenerate into cystadenocarcinoma. They also note that most diagnoses are made intra-operatively during appendectomy, and that, in cases suspected preoperatively, thorough investigation with imaging techniques is very important in order to plan the best treatment.

Investigation into FOXE1 genetic variations in cutaneous squamous cell carcinoma.

BACKGROUND: FOXE1 is a candidate tumour suppressor gene at human chromosome locus 9q22. This is a region frequently lost in squamous cell cancer. OBJECTIVES: To assess the influence of FOXE1 variations on genetic susceptibility to cutaneous squamous cell carcinoma (SCC). METHODS: We performed mutational analysis of FOXE1 in 320 DNA samples isolated from 60 SCC specimens, 60 adjacent histologically normal skin samples and 200 blood samples. RESULTS: No somatic mutations were evident. Instead the polyalanine tract showed marked variation in its length between samples from patients with SCC and normal controls. CONCLUSIONS: These results imply that another tumour suppressor gene at this locus may be more important than FOXE1 in skin carcinogenesis and suggest that variation in the FOXE1 polyalanine tract length predisposes to cutaneous SCC.

[Etiopathogenetic and clinical considerations of corpus luteum cysts]. / Considerazioni etiopatogenetiche e cliniche sulle cisti luteiniche del corpo luteo.

The Authors report a case of hemoperitoneum after breaking of luteal cyst of corpus luteum and stress the main characteristics of this pathology. Ovarian cysts are frequently observed in the annexa; they are distinguished in folliculis cysts, luteal cysts, luteal cysts of corpus luteum. Their evolution, influenzed so both by endocrine factors so many from plogistic stimulation, pass through three essential moments: - obliteration for quick cicatrization of the stigma Graafian follicle; - hematic pouring and central softening; - increase of intracavitary fluid that stops with constitution of the fibrous tissue. In the second phase of the menstrual cycle, functional-anatomic changes occur that cause the formation of gravidic corpus luteum or menstrual corpus luteum. The luteal cysts of corpus luteum represent the result of the cystic evolution of the corpus luteum. These cysts are characterized by an intense endocrine activity and can frequently produce a surplus of steroids, particulary of progesterone. They can cause bleeding, often of slight entity but also severe that; these represent a frequent and dangerous complication, especially in women subjected to anticoagulant treatment with warfarin. This drug can determine a raise of intracystic pressure with consequent breaking of the capsule and hemoperitoneum for which is necessary emergency operation like in the case here described.

Histological features used in the diagnosis of melanoma are frequently found in benign melanocytic naevi.

AIMS: The histological features used in the diagnosis of melanoma may be present in benign naevi, but quantitative data are not available. The aim of this study was to establish the real prevalence of such features in naevi. METHODS: Ten dermatopathologists, from nine Italian institutions, studied a series of naevi. Eleven histological parameters currently used in melanoma diagnosis were analysed: asymmetry, poor circumscription, predominance of single melanocytes, irregular confluent nests, suprabasal melanocytes, hair follicle involvement, absence of maturation, cytological atypia, dermal lymphocytic infiltrate, mitoses, and necrosis. RESULTS: Ninety one naevi were examined: 22 junctional, 59 compound, and 10 intradermal. None of the studied parameters was seen in 22 of the benign naevi studied. One or more investigated features were found in 69 naevi. Poor circumscription was found in 49 cases, single melanocytic predominating in 42, asymmetry in 41, irregular confluent nests in 16, cytological atypia in 14, suprabasal melanocytes in seven, and hair follicle involvement in seven; absence of maturation, mitoses and necrosis were not found. CONCLUSIONS: The histological features used for the histological diagnosis of melanoma are often present in benign melanocytic naevi. This suggests a critical, non-mechanical use of them in melanoma diagnosis.

Interobserver reproducibility of histological features in cutaneous malignant melanoma.

AIMS: To assess the interobserver reproducibility of certain histological features proposed for the diagnosis of melanoma. METHODS: In a series of melanomas, 13 histological parameters were analysed: dimension > 6 mm, asymmetry, poor circumscription, irregular confluent nests, single melanocytes predominating, absence of maturation, suprabasal melanocytes, asymmetrical melanin, melanin in deep cells, cytological atypia, mitoses, dermal lymphocytic infiltrate, and necrosis. RESULTS: The agreement (reproducibility) between the nine observers was excellent (kappa > 0.75) for 10 of the 13 examined features (dimension > 6 mm, poor circumscription, irregular confluent nests, single melanocytes predominating, absence of maturation, suprabasal melanocytes, asymmetrical melanin, melanin in deep cells, mitoses, and necrosis). The agreement for asymmetry was very close to excellence (kappa = 0.74), and that for cytological atypia (kappa = 0.65) and dermal lymphocytic infiltrate (kappa = 0.47) was slightly lower, but in the fair to good agreement range. The kappa values obtained by comparison with the majority diagnosis were generally high (> or = 0.85); the mean value of kappa was lower (0.70) for only one parameter (dermal lymphocytic infiltrate). CONCLUSIONS: The parameters investigated showed an overall good reproducibility.

Uterine pathologies in patients undergoing tamoxifen therapy for breast cancer: ultrasonographic, hysteroscopic and histological findings.

PURPOSE OF INVESTIGATION: To evaluate endometrial abnormalities by ultrasonography, hysteroscopy and biopsy in postmenopausal patients treated with tamoxifen as adjuvant therapy for breast cancer. METHODS: The study was carried out on 113 patients who underwent vaginal ultrasonography, hysteroscopy and endometrial biopsy. RESULTS: There was a significative relation between ultrasonographic and hysteroscopic features (p < 0.001); 58 polyps were diagnosed at hysteroscopy, although 35 were not found at ultrasonography. A significant relation between ultrasonographic and histological findings was also documented (p < 0.005). A significant relation between histological findings and symptomatology was found (p < 0.05), although pathologies were also present in asymptomatic women. CONCLUSIONS: These results show that long-term tamoxifen therapy in breast cancer patients is associated with a higher incidence of uterine pathology. No significant relation has been documented between duration of treatment and grade of endometrial lesion (p > 0.05). Ultrasonography alone is useful in asymptomatic patients because it selects patients with increased endometrial thickness who should undergo hysteroscopy. Hysteroscopy is more accurate in detecting polyps, hyperplastic and neoplastic changes. Asymptomatic tamoxifen treated women should be evaluated as symptomatic patients.

Fibrohistiocytic tumors of soft tissues. An immunohistochemical study of 183 cases.

183 cases of soft tissue tumors were studied utilizing the immunoperoxidase technique to demonstrate alpha-1-antitrypsin, ferritin and lysozyme. The series comprises 50 malignant lesions, 34 intermediate malignancy lesions, 99 benign lesions of fibrohistiocytic origin, and 23 malignant tumors of non fibrohistiocytic origin. The actual results of the study are as follows: alpha-1-antitrypsin, ferritin and lysozyme were always absent in 10 fibrosarcomas, 2 liposarcomas, 2 Ewing sarcomas, 3 synovial sarcomas, 4 neurofibrosarcomas, and 2 rhabdomyosarcomas, but in 24 malignant fibrous histiocytomas, 34 cases of dermatofibrosarcoma protuberans and 102 benign fibrohistiocytic lesions, these activities were present in a percentage that ranged between 12% and 38% (average 25%). Differences in the frequency of positive reactions did not occur between benign and malignant fibrohistiocytic lesions. The immunohistological examinations carried out have, therefore, only a very limited value for the practical diagnostic evaluation, but, when positive, are important to clarify the histogenesis of the tumor.

Metastatic atypical fibroxanthoma of skin.

Metastases from an atypical fibroxanthoma of skin have been reported but are very few in the literature. We had a personal case which, originally localized on the nostril, gave metastases to the cervical regional lymph node with no local recurrence. We examined both the primary and metastatic tumor by conventional histological stains and by immunoperoxidase technique to localize lysozyme, alpha-1-antitrypsin, ferritin and factor VIII antigens. The results show a clear correspondence between the primary and metastatic tumor.

Effects of estrogens and progesterone on GABA system in ovariectomized rat retina.

In an attempt to characterize the effect of estrogens and progesterone on retinal GABA metabolism, female Wistar Nossan rats were ovariectomized and treated for three days with 17 beta-estradiol (1 microgram/day), estrone (2 micrograms/day), estriol (200 micrograms/day) and progesterone (500 micrograms/day) or vehicle. After 3 days of steroid hormones treatment, GAD, GABA-T activities and GABA content were measured in retina homogenate. Progesterone did not reduce GAD, GABA-T activities and GABA content from ovariectomized levels. 17 beta-estradiol, estrone and estriol decreased the GAD activity. Furthermore the decrease in GAD activity was maximal for 17 beta-estradiol whereas the estrogens treatment was ineffective on GABA-T. GABA content was significantly decreased only by 17 beta-estradiol. Estrogens reduced the Vmax of GAD for glutamate as a substrate without changing the Km.

Comparative non-blind trial of ceftriaxone and gentamicin in the treatment of complicated urinary tract infections.

Forty hospitalized patients with complicated urinary tract infections were treated with gentamicin 240 mg die i.m. or ceftriaxone, a new parenteral cephalosporin, 2 g die i.v. for 7 days. Ceftriaxone gave good clinical and bacteriological results which were better than those obtained with gentamicin, showing also an appreciable activity in cases of infection due to problematic organisms.

Autogenous vein and nerve grafts: a comparative study of nerve regeneration in the rat.

A new experimental model using the rat sciatic nerve has been devised and used in ten rats to compare the results of using a vein and a nerve graft in different fascicles of the same sciatic nerve, a third fascicle being preserved intact as a control. The results, judged clinically, electrophysiologically and histologically, show persistence of the vein graft as a conduit even six months after the operation and a similar pattern of nerve regeneration in the two different grafts.

[Proposal of a new transurethral method for repeated prostatic biopsy]. / Proposta di una nuova metodica transuretrale nell'esecuzione di biopsie prostatiche iterative.

In many clinical situations a patient affected by pre-cancerous prostatic lesions, suspected cancer or true cancer (assessed through biopsies or incidentally) must undergo iterative bioptic examinations. Three groups can be sub-divided: A) Patients with no previous endoscopic resection. B) Patients with previous endoscopic resection for BPH. C) Patients with previous RP for cancer. A persistent clinical suspicion for high PSA, a bioptic assessment for Ca T1c or PIN belong to the first group. A suspected cancer in a patient who had already undergone TUR, or a T1a neoplasia assessed incidentally, or PIN found in the resected fragments constitute the second group. A suspected local relapse after a RP characterizes the third group. In 28 cases of these clinical diagnoses, we have applied a new method of bioptic trans-urethral sampling. We used an eco-reflectant, flexible needle and applied it under endoscopic vision to the transitional zone or to tissues of the already resected prostatic fossa. In the first case these biopsies were integrative of the usual randomized biopsies. If transrectal ultrasound had given evidence of altered structures, biopsy was carried out with selective ultrasound guided technique. This procedure has proved to be minimally invasive, easy to carry out and particularly adapted to bioptise zones that are easier to reach transurethrally or tissues with low thickness.

[Comparison of free/total PSA (F/T PSA) ratio and PSA density (PSAD) in the early diagnosis of cancer of the prostate]. / Confronto tra il rapporto PSA libero/totale (F/T PSA) e la densità di PSA (PSAD) nella diagnosi precoce del cancro della prostata.

The identification of the immuno reactive molecular forms of PSA has permitted the identification of a correlation between Free PSA and Total PSA as the most important factor in the early diagnosis of prostate cancer. Cut-off of 0.15 ng/ml seems to be the most appropriate. The Authors consider that the use of this limit is important in the decision to carry out a prostate biopsy on the patients with PSA in the range of 4-10 ng/ml who have neither any clinical symptoms nor an abnormal transrectal ultrasound. In particular the sensitivity and the specificity of F/T PSA and the density of PSA (PSAD) have been compared at his limit of 0.15. In our study of 60 patients (of whom 22 were affected by cancer and 38 by BPH) we have noticed that 27/60 patients had a value of PSA between 4 and 10 ng/ml and negative DRE and TRUS. On the whole the F/T PSA report showed a slightly higher specificity than PSAD; in contrast PSAD showed a slightly higher sensitivity. In conclusion, to identify the early detection of this cancer both tests are required as well as a biopsy.

[Urinary PSA (uPSA) in the monitoring of local recurrence following radical prostatectomy]. / I1 PSA urinario (PSAu) nel monitoraggio della recidiva locale dopo prostatectomia radicale.

The level of urinary PSA (PSAu) was measured for use as a marker in some clinical situations involving prostate cancer patients. Limits of physiological and pathological values, a quantity of which comes from the urethral glands and the umbilical median ligament (urachus), are still unknown. To establish the quantity of PSA secretion in the urethra, female PSAu was measured and found to be significantly low (< 0.1 ng/ml). The Authors report on 25 PR patients with negative margins and who had not received hormonal therapy for 30 months. The PSAu and the PSAs were measured on the 30th and the 60th day, and every 3 months thereafter in the first year and every 6 months in the second year. In 5 cases we observed an increase of PSAu between the 5th and 18th months. In 3 cases the PSAs increased 2 to 6 months later compared to the PSAu. In these 3 cases the biopsy indicated the presence of a localized relapse. Therefore the Authors recommend measuring the PSAu (cut-off 0.1 ng/ml) in the follow-up of the PR patients because the measurement may both identify a localized relapse earlier than the PSAs and indicate the localized response to hormonal or radiotherapy.