[68Ga]Ga-Pentixafor PET/CT imaging for in vivo CXCR4 receptor mapping in different lung cancer histologic sub-types: correlation with quantitative receptors' density by immunochemistry techniques.

PURPOSE: In vivo CXCR4 receptor quantification in different lung cancer (LC) sub-types using [68Ga]Ga-Pentixafor PET/CT and to study correlation with quantitative CXCR4 receptors' tissue density by immunochemistry analyses. METHODS: [68Ga]Ga-Pentixafor PET/CT imaging was performed prospectively in 94 (77 M: 17F, mean age 60.1 ± 10.1 years) LC patients. CXCR4 receptors' expression on lung mass in all the patients was estimated by immunohistochemistry (IHC) and fluorescence-activated cell sorting (FACS) analyses. SUVmax on PET, intensity score on IHC, and mean fluorescence index (MFI) on FACS analyses were measured. RESULTS: A total of 75/94 (79.8%) cases had non-small cell lung cancer (NSCLC), 14 (14.9%) had small cell lung cancer (SCLC), and 5 (5.3%) had lung neuroendocrine neoplasm (NEN). All LC types showed increased CXCR4 expression on PET (SUVmax) and FACS (MFI). However, both these parameters (mean SUVmax = 10.3 ± 5.0; mean MFI = 349.0 ± 99.0) were significantly (p = 0.005) higher in SCLC as compared to those in NSCLC and lung NEN. The mean SUVmax in adenocarcinoma (n = 16) was 8.0 ± 1.9 which was significantly (p = 0.003) higher than in squamous cell carcinoma (n = 54; 6.2 ± 2.1) and in not-otherwise specified (NOS) sub-types (n = 5; 5.8 ± 1.5) of NSCLC. A significant correlation (r = 0.697; p = 001) was seen between SUVmax and MFI values in squamous cell NSCLC as well as in NSCLC adenocarcinoma (r = 0.538, p = 0.031) which supports the specific in vivo uptake of [68Ga]Ga-Pentixafor by CXCR4 receptors. However, this correlation was not significant in SCLC (r = 0.435, p = 0.121) and NEN (r = 0.747, p = 0.147) which may be due to the small sample size. [68Ga]Ga-Pentixafor PET/CT provided good sensitivity (85.7%) and specificity (78.1%) for differentiating SCLC from NSCLC (ROC cutoff SUVmax = 7.2). This technique presented similar sensitivity (87.5%) and specificity (71.4%) (ROC cutoff SUVmax = 6.7) for differentiating adenocarcinoma and squamous cell variants of NSCLC. CONCLUSION: The high sensitivity and specificity of [68Ga]Ga-Pentixafor PET/CT for in vivo targeting of CXCR4 receptors in lung cancer can thus be used effectively for the response assessment and development of CXCR4-based radioligand therapies in LC.

Indian patients with human immunodeficiency virus infection have high prevalence but mild severity of non-alcoholic fatty liver disease.

BACKGROUND AND AIMS: Antiretroviral therapy (ART) has substantially decreased AIDS-related mortality. Non-AIDS related diseases like chronic liver disease are becoming more frequent in people living with HIV-AIDS (PLHA). Non-alcoholic fatty live disease (NAFLD) is a common etiology of liver disease in the general population. Our aim was to analyse the prevalence and risk factors of NAFLD in Indian PLHA. METHODS: One hundred consecutive adults (age:36.89 ± 10.4 years, males:65%) with HIV infection were prospectively enrolled. Patients with significant alcohol intake, Hepatitis B or Cco-infection, other liver disease, malignancy or HIV stage IV were excluded. Hepatic steatosis was assessed using hepatobiliary ultrasoundand controlled attenuation parameter (CAP). Fibrosis was assessed non-invasively using FIB-4, NAFLD fibrosis score (NFS) and liver stiffness measurement (LSM). Metabolic and HIV-related risk factors were compared between PLHA with and without NAFLD. RESULTS: Prevalence of NAFLD using CAP was 60%. Among patients with NAFLD, 27 (45%) were lean. Majority had mild-moderate steatosis. Advanced fibrosis was present in 1 (1.67%) and 4 (6.67%) patients using NFS and LSM and none using FIB-4. PLHA with NAFLD were more likely to be overweight or obese (OR = 4.21,p = 0.002) with a higher proportion of abdominal obesity (OR:25.26,p = 0.001). Other metabolic comorbidities, duration of HIV infection, duration and type of ART, CD4-count or HIV-stagewere not significantly different among PLHA with or without NAFLD. CONCLUSION: Prevalence of NAFLD among Indian PLHA is high although most have mild disease. Almost half of these patients are lean. HIV-related factors do not impact the risk of NAFLD.

68Ga-Pentixafor PET/CT Demonstrating In Vivo CXCR4 Receptor Overexpression in Rare Lung Malignancies: Correlation with Histologic and Histochemical Findings.

68Ga-pentixafor PET/CT imaging allows noninvasive assessment of C-X-C chemokine receptor type 4 (CXCR4) expression in various malignancies, but its use in rare lung cancer variants has not been reported. Methods: 68Ga-pentixafor PET/CT imaging was performed on 6 patients (3 men, 3 women; mean age, 57.0 ± 16.8 y) with suspected lung masses. Whole-body PET/CT images were acquired 1 h after intravenous injection of 148.0-185.0 MBq of the tracer. PET/CT images were reconstructed and analyzed. The image findings were correlated with histopathologic and quantitative (CXCR4) fluorescence-activated cell sorting analysis. Results: Histopathologic diagnosis of hemangioendothelioma, sarcomatoid carcinoma, and hemangiopericytoma was confirmed in 1 patient each. Lung metastasis was diagnosed in the remaining 3 of 6 patients with primary sarcoma (n = 1), renal cell carcinoma (n = 1), and unknown primary (n = 1). Increased uptake in the primary lung mass, with an SUVmax of 3.0, 6.34, and 13.0, was noted in the hemangiopericytoma, sarcomatoid carcinoma and hemangioendothelioma cases, respectively. The mean SUVmax, mean fluorescence intensity, and percentage of stained cells were highest in hemangioendothelioma. Among 3 patients with lung metastases, the highest SUVmax, 9.5, was in the primary sarcoma patient. Conclusion: 68Ga-pentixafor selectively targets the in vivo whole-body disease burden of CXCR4 receptors. This approach thus holds promise for developing suitable radiotheranostics for lung cancers expressing these targets.

Evaluation of breast cancer stem cells in human primary breast carcinoma and their role in aggressive behavior of the disease.

BACKGROUND AND AIM: To delineate the underlying molecular mechanisms responsible for the intratumoral enrichment of breast cancer stem cells (BCSCs) in aggressive breast tumors, we evaluated the frequency and characteristics of BCSCs within the tumor tissue in primary human breast carcinomas. We assessed the expression profiles of various genes in cancer cells (CC) and stromal cells (SC) from these tumors to delineate the role played by the cellular niche in de novo origin or expansion of intra-tumoral cancer stem cells (CSC). METHOD: The study included primary tumor and adjacent normal breast tissue specimens from chemotherapy-naïve breast carcinoma patients. The BCSCs, identified as Lin-CD44+CD24- and aldehyde dehydrogenase 1 A1 positive, were enumerated. The flow-cytometrically sorted stromal, and CC were processed for gene expression profiling using a custom-designed polymerase chain reaction array of genes known to facilitate disease progression. RESULTS: The frequency of BCSCs within the tumor mass correlated significantly with histopathological and molecular grades of tumors, indicating a direct relationship of BCSC with the aggressive behavior of breast cancer. Further, a significantly increased expression of the genes associated with growth factors, cytokines and matricellular proteins in tumors were found in high BCSCs compared to Lo-BCSC tumors, suggesting the possible contribution of stromal and CC in an intratumoral expansion of CSCs. Similarly, a significant upregulation of genes associated with hypoxia and angiogenesis in Hi-BCSCs tumors further supported the role of a hypoxic environment. CONCLUSION: Overall, the findings suggest the molecular crosstalk between SC and CC potentially (directly or indirectly) contributes to the expansion of CSC. RELEVANCE FOR PATIENTS: The current study highlights the importance of CSC as a potential future predictive/prognostic marker for aggressive breast cancer. The present study predicts the potential risk stratification based on the frequency of BCSCs in primary breast tumors and existing prognostic factors.

Immunohistochemical expression of bcl-2; an apoptosis regulatory protein in squamous cell carcinoma of oropharynx: A diagnostic cross-sectional study.

BACKGROUND: The Oropharyngeal squamous cell carcinoma is the second most common head and neck malignancy. Bcl-2 expression alterations have been reported invariably in different cancers. It plays a part in carcinogenesis by inhibiting programmed cell death and thus increasing cell survival. MATERIALS AND METHODS: The present study was conducted in Department of Pathology, S.G.T. Medical College and University, Gurugram over a period of one year (2019-20) on biopsy proven cases of squmaous cell carcinoma of oropharynx. Grading of the tumor was done using Anneroth's multifactorial grading system. The Bcl-2 scoring was done. RESULTS: In the present study, a total of 75 cases of oropharyngeal SCC constituted the study group, with the mean age at presentation of 56.63 years. The correlation between Anneroth's grading system and WHO grade was found to be statistically significant, while correlation between WHO grade with lymph node status was found to be statistically non significant. CONCLUSION: There was significant correlation between Anneroth's grading system and WHO grading system in SCC of oropharynx and it was found to be more relevant in predicting the stage of tumor. Bcl-2 expression did not correlate with the grading of tumor.

Diagnostic utility of endoscopic brush cytology in upper gastrointestinal malignancies.

INTRODUCTION: The advent of endoscopy and endoscopic biopsy has greatly facilitated the detection and diagnosis of gastrointestinal neoplasms. Brush cytology often complements and increases the sensitivity and specificity of detection of GIT lesions in many ways. MATERIALS AND METHODS: The present prospective study was conducted in the Department of Pathology in collaboration with Department of Gastroenterology at S.G.T. Medical College and University, Gurugram. A total of 50 patients suspected of having upper gastrointestinal malignancies formed the study group. After taking the detailed history, patients were subjected to endoscopy using flexible video endoscope. After brushing, biopsies were taken from the lesions and preserved in 10% formalin. The aim of the study was to evaluate the utility of endoscopic brush cytology in diagnosing upper gastrointestinal malignancies and its comparison with endoscopic biopsy. RESULTS: In the present study, a total of 50 cases constituted the study group, during the period of 2018-2019, with the age of patients ranging from 30 to 85 years. Mean age at presentation was 58 years. The most frequent age group affected was 41-60 (44%) and most of them were men (66%). The sensitivity and positive predictive value in our study is 84.4% and 97.4%, respectively, while the specificity and negative predictive value is 100% and 50%, respectively. CONCLUSION: To conclude, brush cytology is a reliable, simple, safe, rapid, noninvasive yet effective, and inexpensive method of detecting malignancy of upper gastrointestinal tract.

Plexiform neurofibroma with neurofibromatosis type I/ von Recklinghausen's disease: A rare case report.

INTRODUCTION: Plexiform neurofibroma with neurofibromatosis type 1 (NF1) or Von Recklinghausen's disease is a rare entity and occurs in approximately 5-15% patients. These are slow growing, painless and locally infiltrating tumors. The pattern of inheritance is autosomal dominant and its penetrance is almost complete by 5 years of age. PRESENTATION OF CASE: We hereby report a case of 13 years old boy visited presenting with swelling of right eyelid and forehead. After surgical removal, the tissue was sent for histopathological evaluation. Microscopy revealed an unencapsulated tumor mass comprising of well organized mixture of multiple nerve bundles with interlacing neural tissue in background of spindle shaped cells along with myxoid areas and numerous blood vessels. DISCUSSION: The NF1 gene responsible for the disease is located on chromosome 17 at locus 17q11.2 that codes for the protein neurofibromin. The frequency of neomutations is particularly high and almost half of the cases are sporadic. NF1 is characterized by a wide variability of clinical expressions, even within a given family. Majority of patients can be diagnosed only after thorough physical examination. CONCLUSION: The wide variation of the clinical expression, the tumor risk and the totally unpredictable evolution of the disease impose regular monitoring of NF1 patients. This surveillance is mainly clinical and has to be adapted to the patient's age in order to assure early management of complications.

Prognostic role of immune cells in hepatocellular carcinoma.

Hepatocellular carcinoma (HCC), with rising incidence rates, is the most commonly occurring malignancy of the liver that exerts a heavy disease burden particularly in developing countries. A dynamic cross-talk between immune cells and malignant cells in tumor microenvironment governs the hepatocarcinogenesis. Monitoring immune contexture as prognostic markers is quite relevant and essential to evaluate clinical outcomes and to envisage response to therapy. In this review, we present an overview of the prognostic value of various tumor infiltrating immune cells and the continually evolving immune checkpoints as novel biomarkers during HCC. Tumor infiltration by immune cells such as T cells, NK cells and dendritic cells is linked with improved prognosis and favorable outcome, while the intra-tumoral presence of regulatory T cells (Tregs) or myeloid derived suppressor cells (MDSCs) on the other hand is associated with poor clinical outcome. In addition to these, the overexpression of negative regulatory molecules on tumor cells also provides inhibitory signals to T cells and is associated with poor prognosis. The limitation of a single marker can be overcome by advanced prognostication models and algorithms that evaluate multiple prognostic factors and ultimately aid the clinician in improving the disease free and overall survival of HCC patients.

Natural history and profile of selective cytokines in patients of acute pancreatitis with acute kidney injury.

OBJECTIVES: To study the natural course of patients with acute pancreatitis (AP) with acute kidney injury (AKI) and their cytokine profile. METHODS: Natural course of patients with AP and AKI was studied in 97 individuals. Levels of TNFα, IL-6, IL-10, IL-8 and IL-1ß were measured at presentation and at 72 h in patients who developed AKI. RESULTS: Amongst the entire cohort, 16.4% patients developed AKI (persistent AKI - 11 patients, transient AKI - 5 patients). Mortality rate was 25% amongst patients with AKI. Levels of IL-6 (p = 0.035) and IL-8 (p = 0.002) were found to be significantly higher in the AKI group. On multivariate analysis, IL-8 levels at baseline were found to be an independent predictor of AKI. AKI group had significant rise of TNF-α (P < 0.001), IL-6 (P < 0.001) and IL- 1ß (P < 0.001) on day 3 whereas persistent-AKI group had significant rise of TNF-α (p = 0.031), IL-6 (p = 0.001) and IL-1ß on day 3 and significant decline of IL-10 (p = 0.015). Using a cut-off of 105 pg/ml, IL-8 levels at baseline could predict AKI with a sensitivity of 87.5% and specificity of 59.2%, with area under the curve being 0.744 (p = 0.002). CONCLUSION: AP patients developing AKI have poor prognosis. IL-8 levels can predict AKI in patients with AP.

A juggernaut of innate & adaptive immune cells in chronic hepatitis C.

Hepatitis C virus (HCV) is a small positive-sense, single-stranded RNA virus, the causal organism for chronic hepatitis. Chronic hepatitis leads to inflammation of liver, causing cirrhosis, fibrosis and steatosis, which may ultimately lead to liver cancer in a few cases. Innate and adaptive immune responses play an important role in the pathogenesis of HCV infection, thus acting as an important component in deciding the fate of the disease. Numerous studies have indicated that the derangement of these immune responses results in the persistence of infection leading to chronic state of the disease. Interactions between virus and host immune system generally result in the elimination of virus, but as the virus evolves with different evading mechanisms, it makes environment favourable for its survival and replication. It has been reported that HCV impairs the immune system by functional modulation of the cells of innate as well as adaptive immune responses, resulting in chronic state of the disease, influencing the response to antiviral therapy in these patients. These defects in the immune system lead to suboptimal immune responses and therefore, impaired effector functions. This review highlights the involvement or association of different immune cells such as natural killer cells, B cells, dendritic cells and T cells in HCV infection and how the virus plays a role in manipulating certain regulatory mechanisms to make these cells dysfunctional for its own persistence and survival.

Human umbilical cord-derived mesenchymal stem cells induce tissue repair and regeneration in collagen-induced arthritis in rats.

The immunosuppressive and anti-inflammatory properties of mesenchymal stem/stromal cells (MSCs) have prompted their therapeutic application in several autoimmune diseases, including rheumatoid arthritis (RA). MSCs derived from bone marrow and adipose tissue has earlier been tried with limited success. However, Wharton's jelly present in human umbilical cord is discarded after delivery which makes a rich source of MSCs with least ethical issues. The immunomodulatory properties of human umbilical cord-derived MSCs (UC-MSCs) were evaluated in-vitro on the mononuclear cells from synovial fluid (SF) and peripheral blood of RA patients. The therapeutic potential of UC-MSCs was checked by transplanting the cells in rats with collagen-induced arthritis (CIA). MSCs isolated from Wharton's Jelly significantly suppressed the proliferation and activation of lymphocytes from both peripheral blood as well as SF of RA patients, down-modulated the functions of activated CD4+, CD8+ T-cells, suppressed the secretion of pro-inflammatory cytokines, and induced the expansion of T-regulatory cells. Xenotransplantation of UC-MSCs in CIA rats clearly indicated a sustained impact in terms of slowing down the progression of disease activity and reversal of arthritic processes along with triggering of joint tissue repair mechanisms, which could be observed till 6 weeks post-transplantation. The results from the current study suggest that human umbilical cord is a rich source of MSCs for allotransplantation. The UC-MSCs may be used successfully as a cell-based therapeutic option either in isolation or in conjunction with existing therapeutic drugs not only to relieve the joint inflammation but also regenerate the damaged bone and cartilage tissues in arthritis. RELEVANCE TO PATIENTS: The current study highlights the potential use of MSCs as a cell-based therapeutic option for the treatment of inflammatory RA.

High Selectivity Gas Sensing and Charge Transfer of SnSe2.

SnSe2 is an anisotropic binary-layered material with rich physics, which could see it used for a variety of potential applications. Here, we investigate the gas-sensing properties of SnSe2 using first-principles calculations and verify predictions using a gas sensor made of few-layer SnSe2 grown by chemical vapor deposition. Theoretical simulations indicate that electrons transfer from SnSe2 to NO2, whereas the direction of charge transfer is the opposite for NH3. Notably, a flat molecular band appears around the Fermi energy after NO2 adsorption and the induced molecular band is close to the conduction band minimum. Moreover, compared with NH3, NO2 molecules adsorbed on SnSe2 have a lower adsorption energy and a higher charge transfer value. The dynamic-sensing responses of SnSe2 sensors confirm the theoretical predictions. The good match between the theoretical prediction and experimental demonstration suggests that the underlying sensing mechanism is related to the charge transfer and induced flat band. Our results provide a guideline for designing high-performance gas sensors based on SnSe2.

Change in serum levels of inflammatory markers reflects response of percutaneous catheter drainage in symptomatic fluid collections in patients with acute pancreatitis.

BACKGROUND: Percutaneous catheter drainage (PCD) is used as the first step in the management of symptomatic fluid collections in patients with acute pancreatitis (AP). There are limited data on the effect of PCD on inflammatory markers. AIM: To study the effects of PCD on serum levels of C-reactive protein (CRP), IL-6, and IL-10 and its correlation with the outcome. METHODS: Consecutive patients of AP with symptomatic fluid collections undergoing PCD were evaluated for serum levels of CRP, IL-6, and IL-10 before PCD and at 3 and 7 days after PCD. Resolution of organ failure (OF), sepsis, and pressure symptoms was considered to demonstrate the success of PCD. Changes in levels following PCD were correlated with outcome. RESULTS: Indications of PCD in 59 patients (age 38.9 ± 13.17 years, 49 male) were suspected/documented infected pancreatic necrosis (n = 45), persistent OF (n = 40), and pressure symptoms (n = 7). A total of 49 (83.1%) patients improved with PCD, five patients required surgery, and six died. A significant difference was noted between baseline levels of CRP (P = 0.026) and IL-6 (P = 0.013) among patients who improved compared to those who worsened following PCD. Significant decrease (P < 0.01) of all three markers on day 3 of PCD insertion, with further decrease (P < 0.01) on day 7, was noted. The percentage of the decrease of IL-6 levels on day 3 and of CRP on day 7 correlated with the outcome. CONCLUSION: PCD is associated with a significant decrease in CRP, IL-6, and IL-10 levels. Percentage decrease in IL-6 on day 3 and CRP on day 7 correlated with the outcome of patients managed with PCD.

Cytokine profile in prediction of acute lung injury in patients with acute pancreatitis.

OBJECTIVES: To study the role of cytokines in prediction of acute lung injury (ALI) in acute pancreatitis. METHODS: Levels of TNFα, IL-6, IL-10, IL-8 and IL-1ß were measured in 107 patients at presentation and at 72 h in patients who developed acute lung injury. A model was devised to predict development of ALI using cytokine levels and SIRS score. RESULTS: The levels of TNF α (p < 0.0001), IL-6 (p < 0.0001), IL-8 (p < 0.0001) and IL-1ß (p < 0.0001) were significantly higher in the ALI group. IL-10 levels were significantly lower in persistent ALI (p-ALI) than in transient ALI (t-ALI) patients (p < 0.038). p-ALI group had significant rise of TNFα (p = 0.019) and IL-1ß (p = 0.001) while t-ALI group had significant rise of only IL-1ß (p = 0.044) on day 3 vs day 1. Combined values of IL-6 and IL-8 above 251 pg/ml had sensitivity of 90.9% and a specificity of 100% to predict future development of ALI. Composite marker-I (IL6 ≥ 80 pg/ml + SIRS) yielded sensitivity and specificity of 73% and 98% whereas composite marker-II (IL8 ≥ 100 pg/ml + SIRS) yielded sensitivity and specificity of 73% and 95% to predict future ALI. CONCLUSIONS: IL-6 and IL-8 can predict future development of ALI. When they are combined with SIRS, they can be used as comprehensive composite markers.

Spectrum of renal disease in HIV-infected children: report of five cases.

There is a paucity of literature on renal diseases associated with HIV infection in Asian countries. Renal disease in HIV-infected children can involve the glomerulus, interstitium, tubules or blood vessels of the kidney. In this case series, five HIV-infected children with various forms of renal disease are reported. The renal pathology included HIV-associated nephropathy, collapsing focal segmental glomerulosclerosis without tubular changes, tubule-interstitial nephritis and minimal change disease (MCD). Case five fulfilled the classification criteria for childhood polyarteritis nodosa (PAN). It is important to screen all HIV-infected children for renal disease to enable detection at an early stage.

Leishmania recombinant antigen modulates macrophage effector function facilitating early clearance of intracellular parasites.

BACKGROUND: Immunmodulation combined with chemotherapy has emerged as an alternative to treat infections. The study evaluates immunomodulatory properties of a Leishmania recombinant protein (rA6) in activating macrophages and clearing intracellular parasites. METHODS: The rA6 from a previously identified cDNA clone was analyzed for inducing the production of nitric oxide (NO) and reactive oxygen species (ROS) in macrophages, post and prior to infection with promastigotes by Griess method and flow cytometry. Phagocytosis and killing by treated macrophages was evaluated using Staphylococcus aureus as an index organism. Intracellular clearance of PKH67-labeled parasites from treated macrophages was assessed flowcytometrically. Combined effect of rA6 with miltefosine/AmBisome in reducing intracellular amastigotes was examined microscopically. RESULTS: Treatment with rA6 post infection caused increased production of NO with increased number of macrophages producing NO and ROS coupled with enhanced phagocytic and killing capacity. Antigen stimulated macrophages expressed high level of iNOS and TNF-α mRNA. It synergized with miltefosine and AmBisome and facilitated early clearance of intracellular amastigotes at sub-optimal drug doses. CONCLUSION: The study demonstrates immunomodulatory potential of rA6 and presents first evidence on synergism between rA6 and anti-leishmanial drugs, thus placing it as a promising candidate for adjunct therapy.

Reconstruction of a traumatically transected Stensen's duct using facial vein graft.

Traumatic injuries to the lower third of the face can result in damage to various vital structures. We report a case of traumatically avulsed Stenson's duct and facial vein wherein the vein was used as a free graft to lengthen the duct. The paper highlights the need on how best to utilise the locally available and viable tissues as free grafts.

Immunology of hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) is primarily a malignancy of the liver, advancing from a damaged, cirrhotic liver to HCC. Globally, HCC is the sixth most prevalent cancer and the third-most prevalent reason for neoplastic disease-related deaths. A diverse array of infiltrating immunocytes regulates the development and progression of HCC, as is the case in many other cancers. An understanding of the various immune components during HCC becomes necessary so that novel therapeutic strategies can be designed to combat the disease. A dysregulated immune system (including changes in the number and/or function of immune cells, cytokine levels, and the expression of inhibitory receptors or their ligands) plays a key role in the development of HCC. Alterations in either the innate or adaptive arm of the immune system and cross-talk between them make the immune system tolerant to tumors, leading to disease progression. In this review, we have discussed the status and roles of various immune effector cells (e.g., dendritic cells, natural killer cells, macrophages, and T cells), their cytokine profile, and the chemokine-receptor axis in promoting or impeding HCC.

Secondary jaw aneurysmal bone cyst (JABC)--a possible misnomer? A review of literature on secondary JABCs, their pathogenesis and oncogenesis.

CONTEXT: Aneurysmal bone cysts are rare pseudocysts, commonly seen in long bones and vertebral column. Although a well described and reported lesion, many misconceptions still prevail regarding their etiopathogenesis. Many of the reported cases of jaw aneurysmal bone cysts (JABC) present with another bone pathology. AIMS: The purpose of this review was to evaluate the incidence of neoplastic lesions occurring simultaneously with a JABC (in contrast to primary JABCs). Any pathogenetic and oncogenetic association between primary and secondary jaw ABCs has been reviewed and discussed. SETTINGS AND DESIGN: A methodical narrative review of literature was performed, given the incidence of mostly case reports on this topic. METHODS AND MATERIAL: A methodical electronic search of Pubmed, Pubmed Central, Medline and Cochrane databases was performed for reported cases of JABC. These articles were analysed and segregated into primary and secondary ABC and, if secondary, the lesion it concurrently occurred with. Another search was conducted to yield articles discussing the cytopathogenetic and oncogenetic origins of ABCs. RESULTS AND CONCLUSIONS: About 15% of the ABCs reported were of secondary nature. Amongst the associated lesions, cement-ossifying fibroma and ossifying fibroma were the most common, followed by fibrous dysplasia and central giant cell granuloma. No ABCs were associated with metastatic changes. The search for histopathogenesis pointed to a specific cytogenetic abnormality as the origin of primary ABCs, with USP6 as its main oncogene and spindle cell as the neoplastic cell, unlike with secondary ABCs, suggesting that they are distinct pathological processes.