Plaque-Like Myofibroblastic Tumor of Infancy: A New Case Report and Literature Review.

Plaque-like myofibroblastic tumor of infancy is a rare entity, with only a few reports described in the literature. Herein we present a new case of a nodular plaque-like lesion of the left lower back in an 18-month-old boy. The lesion might initially be thought to be a dermatofibroma, but the overall characteristics suggested the diagnosis of plaque-like myofibroblastic tumor of infancy. We also provide a summary of previous reports in the literature about this exceptional tumor.

Qualitative analysis of small (≤2 cm) regenerative nodules, dysplastic nodules and well-differentiated HCCs with gadoxetic acid MRI.

BACKGROUND: The characterization of small lesions in cirrhotic patients is extremely difficult due to the overlap of imaging features among different entities in the step-way of the hepatocarcinogenesis. The aim of our study was to evaluate the role of gadoxetic-acid MRI in the differentiation of small (≤2 cm) well-differentiated hepatocellular carcinomas from regenerative and dysplastic nodules. METHODS: Seventy-three cirrhotic patients, with 118 focal liver lesions (≤2 cm) were prospectively recruited. MRI examination was performed with a 3T magnet and the study protocol included T1 - and T2-weighted pre-contrast sequences and T1 -weighted gadoxetic-acid enhanced post-contrast sequences obtained during the arterial, venous, late dynamic and hepatobiliary phases. All lesions were pathologically confirmed. Two radiologists blinded to clinical and pathological information evaluated two imaging datasets; another radiologist analysed the signal intensity characteristics of each lesion. Sensitivity, specificity and diagnostic accuracy were considered for statistical analysis. RESULTS: Good agreement was reported between the two readers (κ 0.70). Both readers reported a significantly improved sensitivity (57.7 and 66.2 vs 74.6 and 83.1) and diagnostic accuracy (0.717 and 0.778 vs 0.843 and 0.901) with the adjunction of the hepatobiliary phase 57.7 vs 74.6 and 66.2 vs 83.1 (p ≤ 0.04). CONCLUSIONS: Gadoxetic-acid MRI is a reliable tool for the characterization of HCC and lesions at high risk to further develop.

Hepatocellular carcinoma (HCC) in non-cirrhotic liver: clinical, radiological and pathological findings.

OBJECTIVES: Our aim was to evaluate the clinical and pathological findings, mutidetector-row computed tomography (MDCT) and magnetic resonance imaging (MRI) appearances, treatment and 1-year survival of patients with HCC in non-cirrhotic liver. METHODS: Histopathological and laboratory findings of 30 non-cirrhotic patients with 32 HCCs were reviewed retrospectively. MDCT and gadobenate dimeglumine-enhanced MR images were evaluated in consensus by two radiologists in terms of HCC size, presence of tumour capsule, necrosis, haemorrhage, fat and calcification, and vascular involvement. Imaging patterns were compared directly with HCC findings in a matched group of cirrhotic patients. RESULTS: No differences between non-cirrhotic and cirrhotic patients were noted in terms of serum α-fetoprotein levels (elevated in 11 [36.7%] and 21 [35%] patients, respectively). The imaging appearance at CT and contrast-enhanced MRI was typical in 27 (84.3%) and 28 (87.5%) cases respectively. Most lesions presented as a well-differentiated large solitary mass, with well-defined margins, areas of necrosis and peripheral capsule. No significant differences in HCC pattern were observed between cirrhotic and non-cirrhotic liver. CONCLUSIONS: In non-cirrhotic patients, HCC is more likely to manifest as an asymptomatic mass with elevation of serum tumour markers similar to that seen in cirrhotic patients. HCC in cirrhotic and non-cirrhotic livers show similar enhancement patterns. KEY POINTS: HCC shows similar CT/MRI pattern in cirrhotic and non-cirrhotic livers. Non-invasive diagnostic criteria for HCC should also be extended to non-cirrhotic livers. No differences were found between α-fetoprotein levels in non-cirrhotic and cirrhotic patients.

Sinonasal Undifferentiated Carcinoma in a Patient Previously Treated for an Intestinal-Type Adenocarcinoma: Metachronous Neoplasms or Recurrence of a Different Tumor Type?

A case of a sinonasal undifferentiated carcinoma occurring 2 years after a successfully surgically treated intestinal-type adenocarcinoma has never been reported. Treatment modality of paranasal sinus cancer strictly depends on histology so it is important to recognize a different tumor type in the follow-up of these patients.

Alveolar Ridge Preservation with nc-HA and d-PTFE Membrane: A Clinical, Histologic, and Histomorphometric Study.

Alveolar ridge preservation has become a very common procedure following tooth extraction. This study presents a clinical, histologic, and histomorphometric analysis of postextraction bone changes using nanocrystalline hydroxyapatite (nc-HA) and exposed high-density polytetrafluoroethylene (d-PTFE) membrane. A total of 10 extraction sockets were treated. Clinical measurements were taken after tooth extraction with a customized acrylic stent to ensure the same measurement points. At 6 months, clinical measurements were repeated and bone specimens taken. An overall bone reduction was observed. The histologic and histomorphometric analysis revealed newly formed bone (25.92% ± 18.78%), soft tissue (28.55% ± 9.73%), and residual graft particles (15.43% ± 11.08%). Further studies are necessary to evaluate the efficacy of this technique over the long term.

Neurotrophins and neurotransmitters in human palatine tonsils: an immunohistochemical and RT-PCR analysis.

Lymphoid organs are supplied by many nerve endings associated with different kinds of cells and macrophages. The role of these neuromediators on the release of locally active molecules is still unknown. Here we focused our attention on the expression of some neurotrophins (NTs), their high- and low-affinity receptors and several neurotransmitters in human palatine tonsils. Light and electron microscopy immunohistochemistry showed that human tonsillar samples were positive for all analyzed neurotrophins (NGF, BDNF and NT-3) and their high-affinity receptors (TrkA, TrkB and TrkC, respectively). All of these molecules were strongly expressed in macrophages whereas, in some patients, a weaker specific staining of lymphocytes and blood vessels was also found. The low-affinity receptor for NGF (p75) was always absent in the analysed samples. RT-PCR confirmed the occurrence of specific transcripts for NTs and their high-affinity receptors as well as the absence of mRNA for p75 protein. Also, specific immunoreactivity for neurotransmitters SP, VIP, CGRP, ChAT and nNOS was mainly expressed by macrophagic cells. These results suggest the presence of an extensive network of innervation in the human palatine tonsils which may play a role in the regulation of some immune functions as well as in the modulation of a possible functional scenario of interactions among different immune cellular subtypes.

Clinical and molecular evidence for c-kit receptor as a therapeutic target in neuroblastic tumors.

PURPOSE: Clinicobiological characteristics of neuroblastic tumor (NT) expressing c-kit tyrosine kinase receptor and/or its ligand, stem cell factor (SCF), are debated. This study aimed at investigating the clinicobiological features of primary NTs expressing c-kit and/or SCF in order to define the clinical relevance of selective therapeutic targeting. EXPERIMENTAL DESIGN: c-Kit and SCF expression was studied in 168 NTs using immunohistochemistry and in 106 of 168 using Northern blot. Quantitative determination of c-kit expression in 54 additional NTs was also done using real-time reverse transcription-PCR. Correlations between c-kit and SCF expression and clinicobiological features were analyzed using chi2 test, univariate, and multivariate regression analyses. RESULTS: c-Kit protein was detected in 21 of 168 NTs (13%) and its mRNA in 23 of 106 NTs (22%). SCF protein was shown in 30 of 106 NTs (28%) and its mRNA in 33 of 106 NTs (31%). No mutations in exon 11 of c-kit gene were identified. By univariate analysis, c-kit and SCF expression correlated with advanced stage, MYCN amplification, and 1p36 allelic loss. Cox simple regression analysis showed that overall survival probability was 17% in the c-kit-positive subset versus 68% in the negative (P < 0.001), 43% in the SCF-positive subset versus 78% in the negative (P < 0.001). When using real-time reverse transcription-PCR, significant levels of c-kit mRNA were found in 35 of 54 NTs (65%), but the correlations with clinicobiological features were no longer documented. CONCLUSIONS: c-Kit expression can be detected in the majority of primary NTs. High levels of expression are preferentially found in tumors with unfavorable clinicobiological variables. c-Kit may represent a useful therapeutic target in a subset of otherwise untreatable NTs.

Squamous cell carcinoma arising on a forearm free flap 21 years after hemiglossectomy.

AIM: Free and pedicled flap are methods of choice for reconstruction of post-surgical defects consequent to oral squamous cell carcinomas (SCCs), and missing intraoral mucosa is commonly reconstructed by the cutaneous component of the flap to guarantee an epithelial lining. Even if rare, cases of second tumors arising in the skin flap have been described. We present our experience reporting a clinical case. CASE REPORT: A squamous cell carcinoma arose on a forearm free flap 21 years after hemiglossectomy in a 72 years old woman. No smoking or alcohol habits were referred, and it was decided to perform surgical resection of the flap. RESULTS: Resection in free margins of a moderate differentiated (G2) SCC staged as pT2 was achieved and reconstruction with anterolateral thigh free flap was performed. DISCUSSION: Even if rare, secondary tumors arising in the skin flap in case of oral cavity defects reconstruction are described. It is important to recognize them early in order to perform surgical resection. CONCLUSION: We think that it is fundamental to perform a prolonged follow-up of skin flap if a white patch or erythema raising clinical suspicion are present. Incisional biopsy has to be performed in order to identify those lesions potentially inclined to a malignant transformation, such as p53 expression and Ki67 index. KEY WORDS: Free flap, Oral cancer, Squamous cell carcinoma.

Socket Preservation with d-PTFE Membrane: Histologic Analysis of the Newly Formed Matrix at Membrane Removal.

This study aimed to evaluate the efficacy of an exposed high-density polytetrafluoroethylene (d-PTFE) membrane in preventing epithelial migration in postextraction sockets. For this purpose, a histologic description of the newly formed soft tissue underlying the membrane is presented. The periodontal status of the adjacent teeth was also evaluated to assess the gingival response. Ten premolar extraction sockets were treated. After tooth extraction, the sockets were filled with nanocrystalline hydroxyapatite and covered with d-PTFE membranes. Subperiosteal pockets were created to ensure the stability of the membranes. Membranes were left intentionally exposed and were atraumatically removed after 28 days. At that time, a bioptic specimen of the newly formed soft tissue under the membranes was taken. All the histologic samples showed a dense connective tissue without epithelial cells and no signs of foreign body reaction. No significant variation of the periodontal indices was observed on the teeth adjacent to the extraction sites. The study results indicate that exposed d-PTFE membranes can prevent epithelial migration in healing sockets without consequences on the periodontal health.

MDCT classification of steatotic liver: a multicentric analysis.

PURPOSE: Fatty liver disease is the most common cause of chronic liver disease in the western world. The aim of this study was to analyze steatotic liver characteristics using multidetector row computed tomography (CT) to identify reliable criteria to identify the steatosis and quantify its severity. PATIENTS AND METHODS: Multiphasic CT scans of 51 consecutive adults (36 men, mean age 57.1±9.9 years), who underwent ultrasound-guided liver biopsy, were analyzed. In all patients, the Hounsfield units (HU) value was determined for each hepatic segment and for each contrast phase. Also, the splenic attenuation was quantified and the differences in the liver-spleen (DLS). Steatosis was graded according its severity into four grades. Receiver operating characteristic (ROC) curve analysis was carried out to calculate the sensitivity and specificity for the specific HU threshold. Pearson's ρ correlation was also calculated. A P value of 0.05 was considered statistically significant. RESULTS: We found that 14 individuals (10 men, mean age 56±9.8 years) did not have hepatic steatosis. Only the nonenhanced CT scans showed a statistically significant association with liver steatosis (with the only exception of region-of-interest selected in the Couinaud segment VII, where a P value of 0.0513 was obtained). For grades 1, 2, 3, and 4, we identified 50, 45, 35, and 20 HU as thresholds. A statistically significant association was found between steatosis and DLS in the nonenhanced and the arterial phase (P=0.0192 and 0.001, respectively). CONCLUSION: The result of our study indicates that the nonenhanced value of the liver can be used to identify steatosis of the liver and to grade its severity. Moreover, the DLS in the arterial phase represents another reliable parameter.

Peribronchial innervation of the rat lung.

Mammalian peribronchial tissue is supplied by several peptide-containing nerve fibers. Although it is well established that different neuropeptides exert significant effects on bronchial and vascular tone in the lungs, the role played by some neuromediators on the general regulation, differentiation and release of locally active substances is still controversial. We studied the innervation of rat peribronchial tissue by immunohistochemical techniques. The immunoperoxidase method with nickel amplification was applied to detect the distribution of nerve fibers using antibodies against the general neuronal marker PGP 9.5 (neuron-specific cytoplasmic protein), while the cholinacetyltransferase immunoreactivity was studied by immunohistochemistry. A slight immunoreactivity for NT receptors is observed in lung bronchial epithelium. There is increasing evidence that NTs may act with a paracrine mechanism regulating functional activity of neuronal and non-neuronal structures. A specific immunoreactivity for NTs and NT receptors was also demonstrated within different layers of large, medium and small sized intrapulmonary arteries and veins, according to a recent study of our group. Moreover our data describe the expression of NTs and NT receptors in lymphoid aggregates of the lung (BALT) in which both lymphocytes and macrophages express TrkA receptor and synthesize NTs. Our results show the presence of an extensive network of innervation in the rat peribronchial tissue, confirming a morphological basis for a possible neural modulation of the respiratory mucosa and the physiological/pathophysiological mechanisms of the lung.

Noradrenergic and cholinergic innervation of the bone marrow.

Bone marrow is supplied by sensory and autonomic innervation. Although it is well established that hematopoiesis is regulated by cytokines and cell-to-cell contacts, the role played by neuromediators on the proliferation, differentiation and release of hematopoietic cells is still controversial. We studied the innervation of rat femur bone marrow by means of fluorescence histochemistry and immunohistochemistry. Glyoxylic acid-induced fluorescence was used to demonstrate catecholaminergic nerve fibers. The immunoperoxidase method with nickel amplification was applied to detect the distribution of nerve fibers using antibodies against the general neuronal marker PGP 9.5 (neuron-specific cytoplasmic protein), while the cholinacetyltransferase immunoreactivity was studied by immunohistochemistry. Our results show the presence of an extensive network of innervation in the rat bone marrow, providing a morphological basis for the neural modulation of hemopoiesis.

Aberrant bcl-2 and bax protein expression related to chemotherapy response in neuroblastoma.

Neuroblastoma (NB) is a tumor of the sympathetic nervous system which develops in young children. It derives from cells of the embryonal neural crest that form many different tissues, including the adrenal medulla and the sympathetic ganglia. Survival rates for patients with neuroblastoma have remained unchanged despite intensive efforts to develop more effective treatment strategies. The intrinsic resistance of many tumor types to antineoplastic therapies and the appearance of resistant cell populations upon relapse of an originally responsive tumor represent major impediments to successful treatment. The possibility exists that these neoplasms, particularly those that have become refractory to chemotherapeutic drugs, may occur in part because of failed apoptosis. In this study we investigated the immunocytochemical expression, before and after a trial of chemotherapy of the bcl-2 and bax proteins in 15 cases of NB, including 8 stroma-poor and 7 stroma-rich NBs. Patients with strong expression of bcl-2 before the treatment had shorter survival than those with weak or moderate expression of the protein (p = 0.004). Moreover, bcl-2 protein expression was correlated to the stroma-poor histotype only after the treatment (p = 0.031). An association between bax protein expression before treatment and longer survival (p = 0.014) was also found. We conclude that bcl-2 and bax expression, before the treatment, could be of prognostic value in neuroblastomas.

Metastatic uterine leiomyosarcoma in the upper buccal gingiva misdiagnosed as an epulis.

Uterine leiomyosarcoma (LMS) is a rare tumor constituting 1% of all uterine malignancies. This sarcoma demonstrates an aggressive growth pattern with an high rate of recurrence with hematologic dissemination; the most common sites are lung, liver, and peritoneal cavity, head and neck district being rarely interested. Only other four cases of metastasis in the oral cavity have been previously described. The treatment of choice is surgery and the use of adjuvant chemotherapy and radiation has limited impact on clinical outcome. In case of metastases, surgical excision can be performed considering extent of disease, number and type of distant lesions, disease free interval from the initial diagnosis to the time of metastases, and expected life span. We illustrate a case of uterine LMS metastasis in the upper buccal gingiva that occurred during chemotherapy in a 63-year-old woman that underwent a total abdominal hysterectomy with bilateral salpingo-oophorectomy for a diagnosis of LMS staged as pT2bN0 and that developed lung metastases eight months after primary treatment. Surgical excision of the oral mass (previously misdiagnosed as epulis at a dental center) and contemporary reconstruction with pedicled temporalis muscle flap was performed in order to improve quality of life. Even if resection was achieved in free margins, "local" relapse was observed 5 months after surgery.

Magnetic resonance-guided focused ultrasound ablation in abdominal moving organs: a feasibility study in selected cases of pancreatic and liver cancer.

PURPOSE: This study was designed to evaluate preliminarily the feasibility and safety of magnetic resonance-guided focused ultrasound (MRgFUS) for treatment of solid tumors in the upper abdomen. METHODS: We enrolled one patient with hepatocellular carcinoma and two patients with pancreatic adenocarcinoma for MRgFUS ablation. Treatments were performed on a 3T scanner under controlled respiration. Treatment response was evaluated at 1, 3, and 6 months by assessing the nonperfused volume (NPV) of ablated tissue at MR and the degree of pain severity and pain interference. RESULTS: In the patient with HCC, NPV was 100% after treatment and 85% at 3 and 6 months follow-up. Histological analysis after liver transplantation showed fibrosis in the ablated area with minimal local tumor recurrence. In the two patients with pancreatic adenocarcinoma, NPV was 80 and 85% after treatment and 70 and 80% at 3 and 6 months follow-up. Pain severity and pain interference respectively decreased from a mean of 7 and 6.7 points, respectively, to a mean of 3 and 2 points after treatment. CONCLUSIONS: MRgFUS can be feasible and safe in selected patients with solid tumors in abdominal moving organs. However, this technique has several limitations due to the interposition of the rib cage or intestinal loops into the path of the ultrasonic beam, as well as to organ motion. Future technical developments are needed to implement advanced motion detection within the system to control organ and lesion position in real-time and keep the focus of the ultrasound beam on the targeted lesion.

Outpatient treatment for liposarcoma of the spermatic cord.

Liposarcoma of the spermatic cord is a very rare neoplastic disease. In effect little more than two hundred cases are described in literature. Natural history of this tumour is characterized by high local recurrence rate although hematogenic and lymphatic spread is usually a late event and involves high-grade tumours. The clinical diagnosis of spermatic cord liposarcoma can be difficult particularly for non expert surgeons, and is often mistaken for different diagnoses. Radical orchiectomy with high cord ligation is the treatment of choice to prevent local recurrence. Otherwise than commonly advised, the treatment is suitable to be performed under local anaesthesia and the patient easily and safely discharged few hours after surgery.

The use of Tachosil as hemostatic sealant in nephron sparing surgery for Wilms tumor: preliminary observations.

BACKGROUND: TachoSil, which is an absorbable collagen sponge coated with human fibrinogen and thrombin, has proven to enhance hemostasis and promote optimal wound healing in adults undergoing nephron sparing surgery (NSS). We report our preliminary experience using this hemostatic agent during NSS in children. METHODS: Prospective analysis of 3 patients with Wilms tumor (synchronous bilateral in one) undergoing NSS at our institution over an 18-month period. Primary outcome measures were intraoperative bleeding control and surgery-related postoperative sequelae. RESULTS: Overall, 4 kidneys underwent 5 NSS procedures, which included 3 partial nephrectomies and multiple tumor excisions performed on another kidney at initial and second-look surgery. After control of major bleeding and suturing of the collecting system, which was entered during 2 of the 5 NSS procedures, TachoSil was applied to the parenchymal surface of the kidney, achieving immediate hemostasis. All NSS procedures were performed without hilar clamping, drainage or stent placement. None of the patients required blood transfusion. Small perirenal fluid collections were documented postoperatively, and all spontaneously resolved within 4 weeks of surgery. CONCLUSION: In children undergoing NSS, TachoSil represents an effective and safe tool for control of mild to moderate bleeding, and also facilitates sealing and wound dressing.

Intrahepatic paratesticular cyst: unique presentation of vestigial remnants of Wolffian duct.

To report on a case of a progressively enlarging intrahepatic cyst in a 1-year-old boy who also presented with bilateral undescended testes. At surgery, the lesion emerged from the anterior surface of the liver but was unexpectedly found to arise from the epididymis of the right testis, which was located intra-abdominally. The histologic findings were consistent with a paratesticular cyst of vestigial remnants derived from the Wolffian duct. Such an unusual event has not been previously reported among the possible location of a paratesticular cyst, nor has it been described in the differential diagnosis of cystic lesions of the liver.

Protective role of parnaparin in reducing systemic inflammation and atherosclerotic plaque formation in ApoE-/- mice.

Atherosclerosis is a degenerative disease whose role in the onset and development of cardiovascular pathologies and complications is of importance. Due to its silent but progressive development, and considering the endothelial, immunological and inflammatory processes that are involved in its clinical course, this still relatively unknown pathological condition has been and continues to be a matter of investigation worldwide. Our experience with previous studies on atherosclerosis led us to investigate the possible influence of a low molecular weight heparin (LMWH) - Parnaparin® on the development and clinical course of atherosclerosis in double knock-out laboratory animals (ApoE-/- mice). Our experiments demonstrated a possible role of Parnaparin (PNP) in the control of atherogenic disease. In fact, in treated mice vs. untreated ones, PNP reduced the number and the size of atherosclerotic lesions in the aortic wall, as well as the development of liver steatosis, which was massive in untreated animals and moderate in treated ones. These preliminary observations require further clinical studies, but demonstrate a possible role of Parnaparin in the control of the development and clinical evolution of atherosclerosis and liver steatosis in laboratory animals.