A case of proliferative nodule arising within blue nevus.

Abstract: Blue nevi are a heterogeneous group of lesions that can display a variety of different clinicopathological characteristics. Although attempts are made to classify each lesion into defined subtypes, there can be overlap between the subtypes. The clinical , dermoscopic and histolopathologic features of a case of proliferative nodule arising within blue nevus is discussed. Running title: Blue nevi are an heterogeneous group of melanocytic lesions blue tinctorial properties. Proliferative nodules are rare benign lesions often present at birth as a component of a large congenital melanocytic nevi, congenital or acquired nevi. We first report a case of proliferative nodule arising within blue nevus.

PET-guided Switch from Immunotherapy to Targeted Therapy in a Metastatic Melanoma Patient: a personalized approach.

An early identification of non-responders in oncology is of crucial importance to rapidly switch treatment regimens. Here we report a positron emission tomography, (PET)-guided switch from immunotherapy to targeted therapy in a patient affected by metastatic melanoma. We describe the case of a 78-years-old male patient diagnosed with nodular melanoma, submitted to baseline PET/CT with 18fluorodeoxyglucose (18F-FDG) that showed cutaneous and skeletal metastases (stage IV). The patients started immunotherapy with pembrolizumab. A PET/CT performed 3 months after the start of immunotherapy demonstrated progressive metabolic disease both at skeletal and cutaneous level, confirmed also by the biopsy. As patients resulted positive for BRAF V600k mutation, treatment regimen was rapidly switched to combined anti-BRAF/MEK targeted therapy. The PET/CT performed 3 months later, showed almost complete metabolic response. Ten months after the beginning of targeted therapy, the patient continues to present a durable metabolic response. PET/CT with 18F-FDG may help in monitoring the response to treatment in metastatic melanoma thus defining personalized therapeutic pathways.

A case of hidradenitis suppurativa linked to trisomy 1q.

Hidradenitis suppurativa (HS) is a chronic relapsing disorder of the apocrine gland affecting mainly areas subjected to friction (e.g. the axillae, groin, perineum and medial aspects of the thighs). This condition can be linked to different comorbidities: autoimmune and inflammatory disease, hormone-related disorders, obesity and the metabolic syndrome, as well as rare syndromes such as Bazex-Dupré-Christol, Down's, KID, PAPASH, PASS, PASH, and SAPHO syndromes, or Dowling-Degos disease. We report a case of severe HS in a patient with Trisomy 1q;13, a very rare cytogenetic anomaly characterized by severe anomalies including dysmorphisms, multiple congenital malformations, heart defects and intellectual disability.

Primary HPV test screening in cervical cancer: a two-year experience of a single screening center in Latina (Italy).

OBJECTIVE: The aim of this study was to evaluate the effect and performance of the new algorithm in cervical cancer screening program in two years' experience of Latina (Italy). MATERIALS AND MTHODS: The female population was divided into two groups, the first group was referred to PAP test and the second one to hr-HPV test according to national guidelines. RESULTS: In two years the participation mean rate increased among women aged 35-64 compared to women aged 25-34. The primary PAP test positive rate and hr-HPV test positive rate were 4.0% and 5.2%, respectively. The PAP test positive rate among hr-HPV+ women decreased from 2012 to 2013. Women with hr-HPV+/PAP+ were referred immediately to colposcopy and this rate was 1.2%. The predictive positive value for CIN2+ to colposcopy was 10.9% in 2012 and 9.1% in 2013, while the detection rate for CIN2+ was 1.6% in 2012 and 1.4% in 2013. CONCLUSION: The stratification of the female population leads to a decreased inappropriate therapeutic path while the combination of hr-HPV test with PAP test in woman aged 35-64 lets obtain high levels specificity and sensitivity results.

Serum and urine biomarkers for human renal cell carcinoma.

Renal cell carcinoma (RCC) diagnosis is mostly achieved incidentally by imaging provided for unrelated clinical reasons. The surgical management of localized tumors has reported excellent results. The therapy of advanced RCC has evolved considerably over recent years with the widespread use of the so-called "targeted therapies." The identification of molecular markers in body fluids (e.g., sera and urine), which can be used for screening, diagnosis, follow-up, and monitoring of drug-based therapy in RCC patients, is one of the most ambitious challenges in oncologic research. Although there are some promising reports about potential biomarkers in sera, there is limited available data regarding urine markers for RCC. The following review reports some of the most promising biomarkers identified in the biological fluids of RCC patients.

The 16, 18, and 45 HPV infection in high grade squamous cervical lesions in primary hr-HPV test screening program.

Infection with high-risk human papillomavirus (hr-HPV) 16, 18, and 45 causes 94% of cervical carcinoma. In the present screening center the authors perform the hr-HPV test followed by Pap test to women aged 35-64 years if they result hr-HPV+. The authors' aimed to provide data regarding the genotyping test and eventually to propose this test as alternative to triage cytology. They used a genotyping test to identify HPV 16, 18, and 45 in 22 women with histological diagnosis of CIN2+, 22 women with histological diagnosis of CIN1 and 22 women hr-HPV+/Pap-. The group of CIN2+ showed the higher positivity to the test and the higher positivity to HPV 16 than other groups. Analyzing the clinical performance of the genotyping test the authors observed that the specificity was 64%. From these data they concluded that the identification of HPV 16 is predictive for high-grade lesions but this test could not be used alternatively to triage cytology.

A prospective study to evaluate the efficacy of Cistiquer in improving lower urinary tract symptoms in females with urethral syndrome.

AIM: The aim of the study was to compare Cistiquer, a new phytotherapeutic product developed for chronic bladder inflammatory diseases, and intra-vesical administration of gentamicin plus betametasone, in females with urethral syndrome. METHODS: Between september 2013 and may 2014, 60 women with urethral syndrome and trigonitis were incuded in this study. Patients were randomly assigned to treatment with intra-vesical administration of betametasone 8 mg plus gentamicin 80 mg (group A), and oral administration of Cistiquer (group B) for 7 weeks. Before and after the therapeutic protocol, symptoms were assessed by three days voiding diary, the overactive bladder questionnaire short form and a ten points visual analogic scale adopted to assess the micturition discomfort. Histologic findings were assessed by the examination of specimens obtained by cold bladder biopsies of the bladder trigone at baseline in all the subjects. RESULTS: The two groups had significant and comparable symptoms improvement. However, the score obtained from the visual analogic scale decreased significantly only in the group submitted to oral therapy. Furthermore, in the group treated with endovesical approach, higher drop out rate and higher incidence of urinary infection were observed. CONCLUSION: Patients with urethral syndrome and trigonitis improved symptoms either with oral therapy with Cistiquer and with intra-vesical administration of gentamicin plus betametasone. However, treatment adherence resulted higher for patients treated by oral therapy and rate of adverse events resulted higher for those submitted to endovesical treatment.

Growth factors, their receptor expression and markers for proliferation of endothelial and neoplastic cells in human osteosarcoma.

Osteosarcoma is the most common primary malignant tumour of the bone. Although new therapies continue to be reported, osteosarcoma-related morbidity and mortality remain high. Modern medicine has greatly increased knowledge of the physiopathology of this neoplasm. Novel targets for drug development may be identified through an understanding of the normal molecular processes that are deeply modified in pathological conditions. The aim of the present study is to investigate, by immunohistochemistry, the localisation of different growth factors and of the proliferative marker Ki-67 in order to determine whether these factors are involved in the transformation of osteogenic cells and in the development of human osteosarcoma. We observed a general positivity for NGF - TrKA - NT3 - TrKC - VEGF in the cytoplasm of neoplastic cells and a strong expression for NT4 in the nuclear compartment. TGF-beta was strongly expressed in the extracellular matrix and vascular endothelium. BDNF and TrKB showed a strong immunolabeling in the extracellular matrix. Ki-67/MIB-1 was moderately expressed in the nucleus of neoplastic cells. We believe that these growth factors may be considered potential therapeutic targets in the treatment of osteosarcoma, although proof of this hypothesis requires further investigation.

Rotator cuff re-tear or non-healing: histopathological aspects and predictive factors.

PURPOSE: The aim of the study was to evaluate the histopathological changes that occur in the tendon and subacromial bursal tissue in patients with rotator cuff tear trying to correlate these changes to their healing capability. METHODS: Eighty-four patients were clinically evaluated with the Constant Scale. Radiographs and MRI were performed preoperatively and ultrasound were performed postoperatively. For each patient, a biopsy of the supraspinatus tendon and subacromial bursa was performed, and the specimens were histopathologically analyzed. RESULTS: Tendons histopathological features consisted of loss of structural organization, poor or absent neoangiogenesis, chondral metaplasia, and fibrosis. Bursal features consisted of neoangiogenesis, absence of chondral metaplasia, hyperplasia/hypertrophy, and absence of necrosis. Direct correlation was seen between tendon and bursal hyperplasia and time of the onset of symptoms; between tendon chondral metaplasia, fibrosis, bursal neoangiogenesis, inflammation, and patient age; between tendon neoangiogenesis, hyperplasia, necrosis, fibrosis, bursal necrosis, inflammation, and lesion size; on the contrary, tendon fibrosis, necrosis, and bursal tissue inflammation decrease as time passes from the onset of symptoms. Tendon fibers disarray, neoangiogenesis, and inflammation decreases as the patient's age increases. Bursal tissue fibrosis decreases as lesion size increases. CONCLUSIONS: Simple histopathological techniques should be employed routinely to assess the tissue quality, with the aim to predict future clinical evolution (repair or non-repair). Comparing the histopathological data with the demographical information and the descriptive statistics, it is possible to define the RCT repair at risk and identify which RCT will be able to heal.

Skin iron deposition characterises lipodermatosclerosis and leg ulcer.

BACKGROUND: It is commonly reported that chronic venous disease (CVD) increases the skin iron content in which the excess is stored as haemosiderin. Despite increasing interest in the role of haemosiderin in venous ulceration, no study has systematically evaluated the occurrence of iron overload in the limbs of patients with CVD. PURPOSE: To evaluate skin haemosiderin deposition in relation to the presence and severity of skin changes in CVD legs designated according to the clinical, etiologic, anatomic and pathophysiologic (CEAP) classification. METHODS: A total of 85 skin biopsies were taken from the medial aspect of 49 limbs with CVD of CEAP clinical stages C2, C3, C4 and C6. The content of ferric ions was assessed by Perl's Prussian Blue (PPB) stain. RESULTS: No haemosiderin deposition was found in normal skin of C2, C3 and C4A legs, in less severe regions of pigmentation and in some parts of more severely affected limbs. Haemosiderin was always present in lipodermatosclerotic skin and ulcers. Occasionally, haemosiderin was found in the apparently normal perilesional skin of C4b and C6 legs. The regenerating dermis at the base of healing ulcers showed none or light haemosiderin deposition. CONCLUSION: Iron overload is not present in the less severe stages of skin damage due to CVD but lipodermatosclerosis and leg ulcers are always accompanied by haemosiderin deposition. In fact, no severe skin changes occur in CVD legs until iron overload occurs. Our results are in agreement with previous reports suggesting that a genetic inability to counteract skin iron overload is present in these patients. A more detailed analysis of disordered iron metabolism should be undertaken in CVD patients.

[Gallbladder polypoid lesions. Three clinical cases with difficult diagnosis and literature review]. / Lesioni polipoidi della colecisti. Presentazione di tre casi clinici di "difficile" diagnosi e revisione della letteratura.

INTRODUCTION: Gallbladder polypoid lesions occur in 1.3%-6.9% of cases. The preoperative diagnosis between benign, malignant and potentially malignant lesions is difficult. Therefore it is not possible any. PATIENTS AND METHODS: The Authors describe three cases. The case 1 was a gallbladder diffuse adenomyomatosis; the ultrasound and the CT were of little help in defining preoperatively the nature and the gravity of the thickening. Case 2 was an adenomyomatosis of the fundus: the ultrasound examinations were not able to establish preoperatively lesion's nature, site and dimensions. In the case 3, ultrasounds showed polypoid lesions and calculi concrections not found in colecistectomy. DISCUSSION: The ultrasound is the most widely used diagnostic tool in the evaluation of gallbladder polypoid lesions; its accuracy is only 66%. CT, which has an accuracy level of 75%, must be carried out there is any possibility of malignant degeneration of the polyp. If doubts persist, a MR, 93% accuracy, is indicated. In selected cases, PET can be of further help. CONCLUSIONS: The preoperative diagnosis of the nature of gallbladder polypoid lesions is "difficult" and this justifies the lack of consensus on treatment. However, the adenoma-carcinoma sequence, widely discussed in literature, can justifies to the use of CT, MR, PET and surgical treatment after an ultrasound examination.

Cannabinoid agonist WIN55,212 in vitro inhibits interleukin-6 (IL-6) and monocyte chemo-attractant protein-1 (MCP-1) release by rat pancreatic acini and in vivo induces dual effects on the course of acute pancreatitis.

BACKGROUND: Cannabinoids (CBs) evoke their effects by activating the cannabinoid receptor subtypes CB1-r and CB2-r and exert anti-inflammatory effects altering chemokine and cytokine expression. Various cytokines and chemokines are produced and released by rodent pancreatic acini in acute pancreatitis. Although CB1-r and CB2-r expressed in rat exocrine pancreatic acinar cells do not modulate digestive enzyme release, whether they modulate inflammatory mediators remains unclear. We investigated the CB-r system role on exocrine pancreas in unstimulated conditions and during acute pancreatitis. METHODS: We evaluated in vitro and in vivo changes induced by WIN55,212 on the inflammatory variables amylasemia, pancreatic edema and morphology, and on acinar release and content of the cytokine interleukin-6 (IL-6) and chemokine monocyte chemo-attractant protein-1 (MCP-1) in untreated rats and rats with caerulein (CK)-induced pancreatitis. KEY RESULTS: In the in vitro experiments, WIN55,212 (10(-6) mol L(-1)) inhibited IL-6 and MCP-1 release from acinar cells of unstimulated rats and after CK-induced pancreatitis. In vivo, when rats were pretreated with WIN55,212 (2 mg kg(-1), intraperitoneally) before experimentally-induced pancreatitis, serum amylase, pancreatic edema and IL-6 and MCP-1 acinar content diminished and pancreatic morphology improved. Conversely, when rats with experimentally-induced pancreatitis were post-treated with WIN55,212, pancreatitis worsened. CONCLUSIONS & INFERENCES: These findings provide new evidence showing that the pancreatic CB1-r/CB2-r system modulates pro-inflammatory factor levels in rat exocrine pancreatic acinar cells. The dual, time-dependent WIN55,212-induced changes in the development and course of acute pancreatitis support the idea that the role of the endogenous CB receptor system differs according to the local inflammatory status.

Carcinosarcoma of the uterus: a case report and review of the literature.

Carcinosarcoma is a rare tumor of the uterus with a poor prognosis. We present a case of uterine carcinosarcoma in an 82-year-old woman who suffered from pervaginal bleeding for ten months duration with progressive anemia. Abdominopelvic nuclear magnetic resonance (NMR) imaging showed the presence of an intrauterine mass, infiltrating the myometrium and reaching the cervix. The patient was submitted to total abdominal hysterectomy with bilateral salpingo-oophorectomy. The carcinosarcoma, arising from the lumen of the uterus, infiltrated the inner one-third of the myometrial layer (pT1b, pNx, pMx; FIGO Stage 1B). A CT of the total body performed six months after surgery showed no signs of recurrent and/or metastatic tumor. The clinicopathological features, treatment options and prognosis of this aggressive neoplasm are reviewed.

[A case of uterine carcinosarcoma]. / Carcinosarcoma dell'utero: descrizione di un caso clinico.

Uterine carcinosarcoma is a highly aggressive neoplasm with tendency to early recurrence and/or metastasis. The neoplasia has both epithelial and stromal malignant components. Clinically, it is characterized by a postmenopausal metrorrhagia, associated sometimes with abdominal pain. The Authors describe a case of carcinosarcoma in a 82-year old woman with a vaginal bleeding since 10 months and an ingravescent hypochromic anemia. The RMN of the abdomen and pelvis showed a mass occupying the whole uterine lumen, without signs of pelvic diffusion. A bilateral hystero-oophorectomy was performed; the patient's critical conditions and a high anaesthesiological risk advised us not to perform a bilateral pelvic lymphadenectomy with aortic sampling. Six months after operation, a clinical follow-up with a total-body CT didn't show any sign of local recurrence and/or distant metastasis. From the analysis of this case report and from the data of the literature some important considerations can be done: a) gynecologic check up in post-menopausal women with associated risk factors (obesity and hypertension) can allow an early diagnosis also in asymptomatic patients; b) sovrapubic and transvaginal US, abdomino-pelvic CT and MRI are essential for a correct clinical staging; c) surgical excision followed by the histological examination of the specimen is mandatory to establish a correct diagnosis.

Angiosarcoma of the heart: structural and ultrastructural study.

BACKGROUND: Primary cardiac tumours are rare. Nearly 70% of primary cardiac tumours are benign, the majority of which are represented by myxomas. The most frequent primary cardiac neoplasm is the angiosarcoma that represents 31% of primary cardiac malignant. We report a particular clinical case of cardiac angiosarcoma, its light and transmission electron microscopic aspects and a review of the recent literature. METHODS: A 52 years old man died for a severe right ventricle filling deficit caused by an intracavitary tumour originated from the right atrial anterolateral wall. The fragments obtained from autoptic tumoral cardiac tissue were processed for light and electron microscopy. The section were stained with haematoxilineosin, Masson trichromic and Gomori method. An immunohistochemical study for vimentin, Factor VIII related antigen and peroxidase-conjugated lectin from Ulex Europaeus was also performed using the unlabed peroxidase-antiperoxidase method. RESULTS: The hematoxylin-eosin staining showed that the tumoral mass was composed by a well-differentiated histotype characterized by numerous vascular areas in which neoplastic cells were loosely and irregularly arranged to form incomplete vessels or anastomized blood-filled vascular channels. On the other hand, some less-differentiated solid areas were present and irregularly surrounded the differentiated vascular areas. Results of Ulex Europeaeus Agglutinin I labelling were positive in both solid and vascular areas of the tumour although the positive reaction was less evident in the solid zones Factor VIII related antigen positive cells were less numerous and mainly found in vascular areas. The observation by electron microscopy showed the lack of evident pinocytotic vesicles, the presence of thin and delicate cytoplasmatic processes, Weibel-Palade bodies, and also the disarrangement of the extracellular fibrous matrix. CONCLUSION: The light microscopy observation and immunohistochemical study underscore that is not easy to obtain information about the level of differentiation of this tumour. The presence of blood-filled lumina and the identification of typical markers of endothelial cells seems to indicate a well-differentiated nature. However, the ultrastructural findings seem to indicate a less differentiated nature.

[Intraoperative limphonodal mapping in gastric, pulmonary and large bowel tumors. The sentinel limphonode technique]. / Mappatura linfonodale intraoperatoria in tumori gastrici, polmonari e del grosso intestino. La tecnica del linfonodo sentinella.

The concept of the sentinel lymphatic node was introduced by Cabanas in 1977, but it has proved to be successful for the treatment of the melanoma and breast cancer only since the 90s. Many studies have recently extended this technique to other neoplasias. This study deals with 36 patients who were to undergo surgery for 14 gastric adenocarcinomas, 11 of the colon and 11 pulmonary. Once the neoplastic mass was detected, 2 to 5 ml of a vital dye (Blu Patent) were injected in the serosa along the perimeter of the tumor by means of several 0.5 ml injections. A lymphatic node was diagnosed in 22 patients, respectively 10 gastric neoplasias, 6 pulmonary, 6 of the colon. In 14 cases the lymphatic node was found to be negative, in 8 cases positive. In the remaining 14 patients the lymphatic node was not detected. Although data do not always agree, the sentinel lymphatic node technique seems to have been successful for this kind of tumors. For this reason we have carried out this study and published our first data.