Eyelid Kaposi Sarcoma in HIV-Negative Patient

Introduction: Kaposi sarcoma disease is a proliferative and multifocal disorder with dual components, vascular and fibroblastic cellular, cutaneous and visceral expression. Kaposi Sarcoma can affect the ocular surface and adnexa and can masquerade as other entities, delaying prompt diagnosis can lead to diagnostic wandering delaying treatment. Our aim is to describe a case of KS of the eyelid in an HIV seronegative patient. Case Presentation: A seventy-year-old man developed a bilateral growing tumoral reddish purple vascular mass on both the lower and upper eyelid involving rapidly for 6 months. Both feet and the two shanks show the presence of a brown-violet tumor-shaped formation. The patient was negative for HIV. Histology examination showed a nodular tumor-like mass with a fibro hemangioma-epitheliomatous. Polymerase chain reaction was positive for human herpes virus 8. Initial chemotherapy followed by surgery was proposed to the patient. Unfortunately, the patient rejected treatment and was lost to follow-up. Conclusion: This case reports the difficulty of managing KS in developing countries.

Can endoscopic atrophy predict histological atrophy? Historical study in United Kingdom and Japan

AIM: To assess the diagnostic concordance between endoscopic and histological atrophy in the United Kingdom and Japan.METHODS: Using published data,a total of 252 patients,126 in the United Kingdom and 126 in Japan,aged 20 to 80 years,were evaluated. The extent of endoscopic atrophy was classified into five subgroups according to a modified Kimura-Takemoto classification system and was compared with histological findings of atrophy at five biopsy sites according to the updated Sydney system.RESULTS: The strength of agreement of the extent of atrophy between histology and visual endoscopic inspection showed good reproducibili ty,wi th a weighted kappa value of 0.76(P < 0.001). Multivariate analysis showed that three factors were associated with decreased concordance: Japanese ethnicity [odds ratio(OR) 0.22,95% confidence interval(CI) 0.11-0.43],older age(OR = 0.32,95%CI: 0.16-0.66) and endoscopic atrophy(OR = 0.10,95%CI: 0.03-0.36). The strength of agreement between endoscopic and histological atrophy,assessed by cancer risk-oriented grading,was reproducible,with a kappa value of 0.81(95%CI: 0.75-0.87). Only nine patients(3.6%) were endoscopically underdiagnosed with antral predominant rather than extensive atrophy and were considered false negatives.CONCLUSION: Endoscopic grading can predict histological atrophy with few false negatives,indicating that precancerous conditions can be identified during screening endoscopy,particularly in patients in western countries.

Liver involvement in the course of thymoma-associated multiorgan autoimmunity:The first histological description

To the Editor:Thymoma-associated multiorgan autoimmunity(TAMA)is a rare paraneoplastic syndrome described in patients with thymoma and characterized by multiorgan failure and graft-versus-host dis-ease(GVHD)like pathology affecting the skin,the gastrointestinal tract,and the liver.To date,only 21 cases are reported in liter-ature[1],with some patients presenting gastrointestinal and hep-atic manifestations,mainly colitis,diarrhea,and abnormal liver en-zymes,but the hepatic involvement has not been histologically characterized yet.

Hypoxic pre-conditioned adipose-derived stem/progenitor cells embedded in fibrin conduits promote peripheral nerve regeneration in a sciatic nerve graft model

Recent results emphasize the supportive effects of adipose-derived multipotent stem/progenitor cells(ADSPCs)in peripheral nerve recovery.Cultivation under hypoxia is considered to enhance the release of the regenerative potential of ADSPCs.This study aimed to examine whether peripheral nerve regeneration in a rat model of autologous sciatic nerve graft benefits from an additional custom-made fibrin conduit seeded with hypoxic pre-conditioned(2%oxygen for 72 hours)autologous ADSPCs(n=9).This treatment mode was compared with three others:fibrin conduit seeded with ADSPCs cultivated under normoxic conditions(n=9);non-cell-carrying conduit(n=9);and nerve autograft only(n=9).A 16-week follow-up included functional testing(sciatic functional index and static sciatic index)as well as postmortem muscle mass analyses and morphometric nerve evaluations(histology,g-ratio,axon density,and diameter).At 8 weeks,the hypoxic pre-conditioned group achieved significantly higher sciatic functional index/static sciatic index scores than the other three groups,indicating faster functional regeneration.Furthermore,histologic evaluation showed significantly increased axon outgrowth/branching,axon density,remyelination,and a reduced relative connective tissue area.Hypoxic pre-conditioned ADSPCs seeded in fibrin conduits are a promising adjunct to current nerve autografts.Further studies are needed to understand the underlying cellular mechanism and to investigate a potential application in clinical practice.

羟基磷灰石陶瓷诱导成骨细胞的研究

通过定量检测在羟基磷灰石(HA)表面生长的成骨细胞骨涎蛋白和骨钙蛋白的表达,研究了羟基磷灰石陶瓷对成骨细胞的影响.研究结果表明,随着成骨细胞培养时间的延长,在羟基磷灰石表面生长的成骨细胞骨钙蛋白和骨涎蛋白的表达量相对于对照组有显著增加.由于骨钙蛋白和骨涎蛋白是成骨细胞分化晚期高度表达的两种标志性蛋白质,因此其表达量的显著提高意味着羟基磷灰石陶瓷可以诱导成骨细胞的成熟.这一结果可进一步为理解HA陶瓷的生物相容性和生物活性提供分子生物学依据.

Helicobacter pylori infection in bleeding peptic ulcer patients after non-steroidal antiinflammatory drug consumption

AIM： TO establish the prevalence of He/icobacterpy/on （H. pylori） infection in patients with a bleeding peptic ulcer after consumption of non-steroidal antiinflammatory drugs （NSAIDs）.METHODS： A very early upper endoscopy was performed to find the source of upper gastrointestinal bleeding and to take biopsy specimens for analysis of H. pylori infection by the rapid urease （CLO） test, his- tological examination, and bacterial culture. TgG anti- CagA were also sought. The gold standard for identifying H. pylori infection was positive culture of biopsy specimens or contemporary positivity of the CLO test and the presence of H. pylori on tissue sections.RESULTS： Eighty patients, 61 males （76.3%）, mean age 61.2 ~ 15.9 years, were consecutively enrolled. Forty-seven （58.8%） patients occasionally consumed NSAIDs, while 33 （41.3%） were on chronic treatment with low-dose aspirin （LD ASA）. Forty-four （55.0%） patients were considered infected by H. pylori. The infection rate was not different between patients who occasionally or chronically consumed NSAIDs. The culture of biopsy specimens had a sensitivity of 86.4% and a specificity of 100%; corresponding figures for histological analysis were 65.9% and 77.8%, for the CLO test were 68.2% and 75%, for the combined use of histology and the CLO test were 56.8% and 100%, and for IgG anti-CagA were 90% and 98%. The high- est accuracy （92.5%） was obtained with the culture of biopsy specimens.CONCLUSION： Patients with a bleeding peptic ulcer after NSAID/LD ASA consumption frequently have H. pylori infection. Biopsy specimen culture after an early upper gastrointestinal tract endoscopy seems the most efficient test to detect this infection.

Proteomic and metabolic prediction of response to therapy in gastric cancer

Several new treatment options for gastric cancer have been introduced but the prognosis of patients diagnosed with gastric cancer is still poor. Disease prognosis could be improved for high-risk individuals by implementing earlier screenings. Because many patients are asymptomatic during the early stages of gastric cancer,the diagnosis is often delayed and patients present with unresectable locally advanced or metastatic disease. Cytotoxic treatment has been shown to prolong survival in general,but not all patients are responders. The application of targeted therapies and multimodal treatment has improved prognosis for those with advanced disease.However,these new therapeutic strategies do not uniformly benefit all patients.Predicting whether patients will respond to specific therapies would be of particular value and would allow for stratifying patients for personalized treatment strategies.Metabolic imaging by positron emission tomography was the first technique with the potential to predict the response of esophagogastric cancer to neoadjuvant therapy.Exploring and validating tissue-based biomarkers are ongoing processes.In this review,we discuss the status of several targeted therapies for gastric cancer,as well as proteomic and metabolic methods for investigating biomarkers for therapy response prediction in gastric cancer.

Validation of a novel animal model for sciatic nerve repair with an adipose-derived stem cell loaded fibrin conduit

Despite the regenerative capabilities of peripheral nerves, severe injuries or neuronal trauma of critical size impose immense hurdles for proper restoration of neuro-muscular circuitry. Autologous nerve grafts improve re-establishment of connectivity, but also comprise substantial donor site morbidity. We developed a rat model which allows the testing of different cell applications, i.e., mesenchymal stem cells, to improve nerve regeneration in vivo. To mimic inaccurate alignment of autologous nerve grafts with the injured nerve, a 20 mm portion of the sciatic nerve was excised, and sutured back in place in reversed direction. To validate the feasibility of our novel model, a fibrin gel conduit containing autologous undifferentiated adipose-derived stem cells was applied around the coaptation sites and compared to autologous nerve grafts. After evaluating sciatic nerve function for 16 weeks postoperatively, animals were sacrificed, and gastrocnemius muscle weight was determined along with morphological parameters（g-ratio, axon density ＆ diameter） of regenerating axons. Interestingly, the addition of undifferentiated adipose-derived stem cells resulted in a significantly improved re-myelination, axon ingrowth and functional outcome, when compared to animals without a cell seeded conduit. The presented model thus displays several intriguing features： it imitates a certain mismatch in size, distribution and orientation of axons within the nerve coaptation site. The fibrin conduit itself allows for an easy application of cells and, as a true critical-size defect model, any observed improvement relates directly to the performed intervention. Since fibrin and adipose-derived stem cells have been approved for human applications, the technique can theoretically be performed on humans. Thus, we suggest that the model is a powerful tool to investigate cell mediated assistance of peripheral nerve regeneration.

T-lymphoblastic lymphoma with cutaneous involvement

To study dermatological manifestation of T-lymphoblastic lymphoma and to help clinicians in the diagnosis, we report here the case of a 75-year-old patient who presented with violaceous nodules acquired during the last 4 wk and affecting the scalp and right arm. The diagnosis of systemic lymphoma was suggested upon the appearance of cutaneous tumors, palpable lymph nodes and general symptoms including asthenia and weight-loss. The pathology features: positive immunostaining for CD3 and terminal deoxynucleotidyl transferase(Td T) and staging, led us to the final diagnosis of T-lymphoblastic lymphoma(T-LBL) with cutaneous involvement. He received a CHOP regimen as first-line treatment. Unfortunately, the patient relapsed and died 8 mo after the treatment initiation. T-LBL may be diagnosed by skin lesions. Additional immunostaining including Td T and experienced histopathologists are needed to correctly classify this aggressive disease and discuss the correct management including bone-marrow transplantation where appropriate.

Hepatocellular carcinoma metastatic to the kidney mimicking renal oncocytoma

BACKGROUND:Renal metastases of hepatocellular carcinoma(HCC) are very rare.To our knowledge only five cases have been reported to the present;all had a well-known primary HCC.METHODS:We describe the clinico-pathological features of a rare case of HCC metastatic to the kidney in which the renal mass was the clinical debut of disease.The patient was a 54-year-old woman previously submitted to orthotopic liver transplantation,who underwent left nephrectomy for a renal mass.RESULTS:Histologically,the tumor was composed mainly of epithelioid cells with homogeneous acidophilic cytoplasm resembling oncocytoma or primary renal carcinoma with oncocytic features.A correct diagnosis was made on the basis of positive immunostaining for hepatocyte paraffin 1.CONCLUSIONS:Metastasis to the kidney is a rare complication that should be considered whenever a renal mass is present in patients with HCC.Since HCC may histologically resemble primary renal tumors such as oncocytoma,pathologists must be aware of this possibility above all in patients referred for liver transplantation and treated with immunosuppressant drugs.Immunohistochemistry is particularly helpful to establish a precise diagnosis in cases of doubt.

Von Brunn’s Nests in the Ureter of Two Cats

The aim of this work is to emphasize the importance of a differential diagnosis of von Brunn’s nests in cats from other urothelial neoplastic disorders, as transitional cell carcinoma, for a subsequent optimal care. Von Brunn’s nests and cysts are submucosal benign urothelial processes, related to irritative stimuli (calculi and urinary infections), characterized by an invagination with buds and clusters of normal urothelium in the lamina propria. They are common findings in the urinary bladder of human beings, but few cases have been described in dogs and cats. We report macroscopic, histopathological and, in one case, immunohistochemical features of these rare forms in the left ureters of two cats. Macroscopic evidence during surgery of ureteral nodules in two cats was accompanied by histopathological diagnosis and, in one case, by immunohistochemical assessment. Histopathology was coherent with a rare condition characterized by nests and islands of normal urothelium in the lamina propria and submucosa, with formation of cysts and moderate focal subacute inflammation. In one case epithelial cells of the nests showed well differentiated urothelial cells with an intense immunoreactivity to pan-cytokeratin (CK AE1/AE3), CK19 in the first outer layers, a slight immunoreactivity to CK20 and a low proliferative activity using MIB-1 (Ki67).

Inflammation in irritable bowel syndrome:Myth or newtreatment target?

Low-grade intestinal inflammation plays a key role in the pathophysiology of irritable bowel syndrome(IBS), and this role is likely to be multifactorial. The aim of this review was to summarize the evidence on the spectrum of mucosal inflammation in IBS, highlighting the relationship of this inflammation to the pathophysiology of IBS and its connection to clinical practice. We carried out a bibliographic search in Medline and the Cochrane Library for the period of January 1966 to December 2014, focusing on publications describing an interaction between inflammation and IBS. Several evidences demonstrate microscopic and molecular abnormalities in IBS patients. Understanding the mechanisms underlying low-grade inflammation in IBS may help to design clinical trials to test the efficacy and safety of drugs that target this pathophysiologic mechanism.

Circulating tumor and cancer stem cells in hepatitis C virusassociated liver disease

AIM: To assess the role of circulating tumor cells (CTCs) and cancer stem cells (CSCs) in hepatitis C virus (HCV)-associated liver disease.

Finding the seed of recurrence:Hepatocellular carcinoma circulating tumor cells and their potential to drive the surgical treatment

The treatment for hepatocellular carcinoma(HCC)relies on liver resection,which is,however,burdened by a high rate of recurrence after surgery,up to 60%at 5 years.No pre-operative tools are currently available to assess the recurrence risk tailored to every single patient.Recently liquid biopsy has shown interesting results in diagnosis,prognosis and treatment allocation strategies in other types of cancers,since its ability to identify circulating tumor cells(CTCs)derived from the primary tumor.Those cells were advocated to be responsible for the majority of cases of recurrence and cancer-related deaths for HCC.In fact,after being modified by the epithelial-mesenchymal transition,CTCs circulate as“seeds”in peripheral blood,then reach the target organ as dormant cells which could be subsequently“awakened”and activated,and then initiate metastasis.Their presence may justify the disagreement registered in terms of efficacy of anatomic vs non-anatomic resections,particularly in the case of microvascular invasion,which has been recently pointed as a histological sign of the spread of those cells.Thus,their presence,also in the early stages,may justify the recurrence event also in the contest of liver transplant.Understanding the mechanism behind the tumor progression may allow improving the treatment selection according to the biological patient-based characteristics.Moreover,it may drive the development of novel biological tailored tests which could address a specific patient to neoadjuvant or adjuvant strategies,and in perspective,it could also become a new method to allocate organs for transplantation,according to the risk of relapse after liver transplant.The present paper will describe the most recent evidence on the role of CTCs in determining the relapse of HCC,highlighting their potential clinical implication as novel tumor behavior biomarkers able to influence the surgical choice.

Diffuse Large B-Cell Lymphoma with Anaplastic Clear Cells: A Rare Variant

Introduction: Diffuse Large B-Cell Lymphoma (DLBCL) is a heterogeneous group conformed by morphological and clinical varieties of neoplasms;it originates from peripheral B-cells and is distinguished into three groups: germinal center (GC), activated B lymphocyte (ABL), and the third type. The existence of DLBCL with anaplastic morphology and expression of CD30 without t (2;5) translocation is rare. The aim of the present article is to describe this morphologic variant in a 54-year-old woman and a 74-year-old man, respectively. Materials and Methods: Patients diagnosed with DLBCL with anaplastic variant were identified from the surgical pathology records. Results: Out of 357 biopsies with this diagnosis, 11 (3%) corresponded to the anaplastic variant, 2 presented morphological clear cells;they became visible because of an increase in volume in the cervical area of 4 months of evolution, usually associated to diaphoresis and weight loss with clinical fulminating progression. An autopsy study was performed to one patient and it showed infiltration in supraclavicular lymph nodes, thyroid, and lung. The neoplastic cells presented abundant clear cytoplasm and pleomorphic nuclei that expressed CD20, CD30 and CD45. Conclusion: This variation is rare. The clinical presentation and prognosis are controversial;we present the morphological and immunophenotype changes of this variant. The differential diagnosis from other clear cell neoplasms should be made.

How the COVID-19 pandemic has affected the colorectal cancer screening in Italy:A minireview

The coronavirus disease 2019(COVID-19)pandemic has caused detrimental effects on many aspects of healthcare practice.Screening programs for the commonest malignancies,namely colorectal cancer(CRC),breast cancer and cervical cancer have been discontinued or interrupted since the beginning of restriction measures aimed to limit transmission of the new coronavirus infection.Robust evidence exists in favour of the role of screening campaigns in reducing mortality from CRC.In fact,the majority of pre-malignant lesions of the colon and rectum can be diagnosed with colonoscopy and treated by endoscopic or surgical resection.Besides,colonoscopy screening allows the diagnosis of CRCs in their pre-clinical stage.Italy was one of the first European countries where a high level of COVID-19 infections and deaths was observed,and one of the first where lockdowns and strict measures were adopted to reduce the risk of COVID-19 diffusion among the population.A systematic review of the literature was performed,including the PubMed,Scopus,Web of Sciences,and Reference Citation Analysis databases,with the aim of critically evaluating the impact of the COVID-19 pandemic on CRC screening in Italy.We found that reduction of CRC screening activity surpassed 50%in most endoscopic units,with almost 600000 fewer CRC screening exams conducted in the first 5 mo of 2020 vs the same period of 2019.While the consequences of the discontinuation of endoscopy screening for the prognosis and mortality of CRC will be evident in the next few years,recent data confirm that CRC is currently treated at a more advanced stage than in the pre-COVID-19 era.Since delays in CRC prevention and early diagnosis may translate to increased CRC-specific mortality,world healthcare systems should adopt strategies to maintain the regularity of CRC screening during subsequent peaks of the COVID-19 pandemic,or future events that might hamper screening programs.

Diffuse Large B-Cell Lymphoma of the Central Nervous System. Immunophenotype, Clinicopathological Features and Differential Diagnosis

Background: Diffuse large B-cell lymphomas of the central nervous system (DLBCL CNS) represent less than 1% of all lymphomas and between 2% and 3% of all cerebral tumors. They occur in adults of 60 years of age or more. The objective of this work is to describe the clinical-pathological characteristics, the immunophenotype and the differential diagnosis. Clinical Case: From the files of the surgical pathology unit we found four cases of primary diffuse large B cell lymphoma of the central nervous system in a 6-year period. Three corresponded to women over 47 years of age and the other to a 42-year-old man. The time of evolution was between 2 and 4 months. The symptoms were headache, blurred vision, hemiparesis, and seizures. Localization was in the pineal region, the frontal, parietal regions, and the right thalamus. Morphologically, large lymphoid cells with a diffuse growth pattern and necrosis were observed. Immunohistochemical markers, such as CD 20 and bcl2 were positive, one was positive to CD3. Expression of bcl6 and CD 10 was positive in one case, and MUM-1 was positive in three cases. All the cases were negative for Epstein-Barr virus. Conclusions: The diffuse large-B cell lymphoma of the central nervous system is rare. Its average age of presentation is at 60 years or older. The localization is in the pineal, frontal, parietal and thalamic regions. Three cases were originated by activated B lymphocyte (MUM-1 expression) and other from the Germinal Center (GC) (CD 10 expression). The clinical course was bad. The four patients died shortly after the diagnosis.

Progressive nodular fibrosis of the skin:A pediatric case

The term fibromatosis describes fibrotic tumor-like lesions of the skin which are seen in all age groups. They may be congenital or acquired and occur as single or multiple lesions. Classification of fibromatosis includes several clinical and pathologic variants. Progressive nodular fibrosis of the skin is a rare condition which has been scarcely reported in the literature and never in pediatric age. The clinical presentation is not specific showing asymptomatic, reddish-brown nodules. Histology shows abundance of spindle-shaped dermal fibroblasts. Here we describe an unusual pediatric case and discuss the diagnosis, which is possible only with histopathology, and the importance of differential diagnosis.

Prognostic Role of miR-205 in Early-Stage (T1N0) Non-Small Cell Lung Cancer

Background: Published data have shown that microRNAs (miRNAs) could play a potential role as diagnostic and prognostic indicators in cancers. Data for the predictive value of miRNA let-7, miR-21, and miR-205 are inconclusive. The aim of the present analysis was therefore to evaluate the expression and the prognostic role of the above mentioned miRNAs?in early-stage?(T1N0) NSCLC patients. Methods: Quantification of let-7g, miR-21, and miR-205 expression was carried out into 105 early-stage NSCLC by quantitative Real Time-PCR (qRT-PCR).?Results: a significant association between the low miR-205 expression and ADC histotype (p??0.0001) compared to SCC?was found;moreover, survival analysis showed thattumors with a high?miR-205 expression had a significantly shorter mean PFS and OS compared to the patients with a low expression of this miRNA (p = 0.02 and p = 0.03, respectively). No other statistically significant correlations were observed between the analysed miRNAs and the main clinico-pathological characteristics of the NSCLC patients. Conclusion: The results indicated that miR-205 could represent a useful marker in the prognostic management of the early-stage (T1N0) NSCLC patients.

Could JC virus provoke metastasis in colon cancer?

AIM: To evaluate the prevalence of John Cunningham virus(JC virus) in a small cohort of patients with colon cancer and to assess its presence in hepatic metastasis.METHODS: Nineteen consecutive patients with histologically diagnosed colon cancer were included in our study, together with ten subjects affected by histologically and serologically diagnosed hepatitis C virus infection. In the patients included in the colon cancer group, JC virus was searched for in the surgical specimen; in the control group, JC virus was searched for in the hepatic biopsy. The difference in the prevalence of JC virus in the hepatic biopsy between the two groups was assessed through the χ2 test.RESULTS: Four out of 19 patients with colon cancer had a positive polymerase chain reaction(PCR) test for JC virus, and four had liver metastasis. Among the patients with liver metastasis, three out of four had a positive PCR test for JC virus in the surgical specimen and in the liver biopsy; the only patient with liver metastasis with a negative test for JC virus also presented a negative test for JC virus in the surgical specimen. In the control group of patients with hepatitis C infection, none of the ten patients presented JC virus infection in the hepatic biopsy. The difference between the two groups regarding JC virus infection was statistically significant(χ2 = 9.55, P = 0.002).CONCLUSION: JC virus may play a broader role than previously thought, and may be mechanistically involved in the late stages of these tumors.