FISH analyses for 1p and 19q status on gliomas: Reporting an 8 years' experience from a tertiary care center in the Middle East.

Diffuse gliomas are the most common primary malignancies of the central nervous system (CNS). The 2016 edition of the World Health Organization (WHO) classification of CNS tumors opted to integrate current molecular data with the traditional histologic diagnosis in the definition of the disease. This integrated diagnosis offers a greater level of objectivity and helps in establishing more definitive diagnoses for tumors that may have been controversial on histology alone. The classification of gliomas may require FISH technique to identify chromosomal abnormalities. FISH is commonly used to identify 1p/19q codeletion, but many challenges are encountered in the process. In this study, we review the FISH results for 1p/19q codeletion of n = 85 diffuse glioma samples examined at a tertiary care center in the Middle East over a period of 8 years. We also conduct a literature review to study the potential role of DNA-microarray in the identification of 1p/19q deletions. Glioblastoma (GBM), WHO grade IV is the most common glioma type identified (n = 24; 29%). All oligodendrogliomas show 1p/19q codeletion (26/26) while 12.5% of GBMs have 1p/19q codeletion (3/24). Isolated 1p deletions are only identified in one case of diffuse astrocytoma, WHO grade II. Isolated 19q deletions are identified in oligoastrocytoma, anaplastic astrocytoma, and glioblastoma. FISH is the most commonly used technique to diagnose oligodendroglioma because it is a simple, effective, and accessible technique in settings with limited resources. However, the optimization process remains highly variable between laboratories. Microarray is a more objective technique that can provide more information about the genetic alterations of the tumor for better diagnosis and sub-classification of diffuse glioma types.

Helicobacter pylori Prevalence in Laparoscopic Sleeve Gastrectomy Specimen.

INTRODUCTION: Laparoscopic sleeve gastrectomy (LSG) has become a common surgical procedure. The value of routine histopathologic examination of the LSG specimens remains, however, a controversial issue. Helicobacter pylori was the most prevalent finding in several previous studies, but the overall results were dissimilar. We aim to assess the prevalence of Helicobacter pylori and other histopathologic findings in LSG specimens and the effect of increasing the number of sections for histology, from LSG specimens, on the rates of abnormal findings. METHODS: We retrospectively reviewed the histopathologic data of all patients who had undergone LSG, in a tertiary care center, over a 4-year period (n = 481). Patient characteristics and histopathologic findings were recorded and analyzed. RESULTS: Inactive chronic gastritis was the most common histopathologic finding (62.16%) followed by Helicobacter pylori gastritis (35.34%). Intestinal metaplasia was identified in 1.66% of the cases. There was no diagnosis of malignancy. Increasing the number of sections submitted for histopathologic examination resulted in a significantly higher rate of H. pylori gastritis detection. CONCLUSION: Routine histopathologic examination of LSG specimens may detect H. pylori in a significant proportion of patients, and increasing the number of sections for histology from LSG specimens improves the rate of detection of this bacterium and identifies individuals who may benefit from treatment.

Pancreatic sarcoidosis mimicking neoplasia: Case report.

INTRODUCTION: Although sarcoidosis rarely involves the pancreas, such involvement may mimic pancreatic cancer. We herein report a case of pancreatic sarcoidosis giving rise to a cancer-mimicking retention cyst, concomitant with a neuroendocrine adenoma. PRESENTATION OF CASE: A 47-year-old Caucasian male presented to follow-up for a benign-appearing cyst of the tail of the pancreas, detected incidentally on CT scan done for a urinary stone in 2017. He had been asymptomatic since his last presentation. The lesion was found to have increased in size from 1 cm to 3 cm in greater diameter. Yet, a CT angiography showed no evidence of invasion of surrounding organs, vessels, or lymph nodes. The patient had previous medical history of treated sarcoidosis, hypertension, recurrent nephrolithiasis, and gout. Due to the size increment a neoplastic cystic lesion was considered and distal pancreatectomy was performed. Pathologic examination revealed a retention cyst associated with chronic pancreatitis and the presence of non-caseating granulomas consistent with sarcoidosis. In addition, a neuroendocrine adenoma, and an adjacent focus of pancreatic intraepithelial neoplasia-1 and 2 were noted. DISCUSSION: Such presentations may be asymptomatic, as in this case, and a multidisciplinary workup is often required. Care must be taken to rule out pancreatic cancer. A possible relationship between pancreatic sarcoidosis and pancreatic cancer merits further study. CONCLUSION: The diagnosis of pancreatic sarcoidosis is difficult, and conclusive diagnosis requires histopathologic assessment.

Elbow Cystic Lymphangioma in an 8-Month-Old Boy.

Cystic lymphangiomas are benign tumors originating mainly in the head and neck of the pediatric population. The authors report a rare case of cystic lymphangioma in the right elbow of an 8-month-old baby treated successfully by complete surgical resection.

A Case Report of Meningeal Hemangiopericytoma: A 9-Year Journey from the Brain to the Spine.

BACKGROUND: Hemangiopericytomas (HPCs) are rare and aggressive vascular mesenchymal tumors. Unlike meningiomas, which have a similar radiologic appearance, these tumors have a higher risk of local recurrence after resection, and distant metastasis can reach up to 23%. Metastases to the vertebral bones from an intracranial HPC are very rare, with so far only 9 cases reported in the literature. CASE DESCRIPTION: We present the case of a 46-year-old man who was surgically treated for a presumed left parieto-occipital falx meningioma in 2008. He presented 9 years later with a thoracic vertebral mass that was causing relentless pain. Reexamination of the cranial pathology allowed correction of the diagnosis performed in 2008 to a meningeal HPC, and the spinal lesion was confirmed after surgery to be a metastatic tumor. CONCLUSIONS: The literature lacks randomized controlled trials and large studies defining the natural history of HPC to draw clear recommendations for a precise management of the disease. However, en bloc resection followed by radiation therapy seems to provide the optimal treatment for a long disease-free survival.

Calcaneus Metastasis from Follicular Thyroid Carcinoma 12 Years after Total Thyroidectomy.

We report the case of a sixty-eight-year-old female patient who presented for left ankle pain; X-rays and MRI showed a benign calcaneal cyst, found to be delayed distant metastasis from primary papillary thyroid carcinoma. Patient required surgical excision of the cyst. Results of histological examination showed metastatic papillary thyroid carcinoma. The patient underwent total thyroidectomy 12 years prior to presentation, with the same pathology. Postoperatively, she was treated with radioactive iodine. At 10-year follow-up post calcaneal mass excision, she was found to have a right proximal tibial mass and found to be recurrent with the same pathology. This case reports a rare condition that will be taken into consideration in bone metastasis with thyroid cancer.

Intramasseteric Schwanoma mimicking an isolated cheek mass: Case report and review of literature.

INTRODUCTION: Schwannoma is a benign well circumscribed tumor of the nerve sheath and it is mostly localized in the head and neck. Intramasseteric schwannoma represents a very rare entity and a few cases have been described in the literature. PRESENTATION OF CASE: We present a case of an isolated, asymptomatic and slowly progressive right cheek tumor in a middle aged man. Although multiple investigations, including neck scanner and fine needle aspiration, were done, the diagnosis was obscure and difficult before definite surgical resection. Surgery showed an isolated and well-defined tumor inside the masseter muscle which was completely resected. Histopathologic finding confirmed the diagnosis of schwannoma with the characteristic Antoni A and Antoni B cells. DISCUSSION: Among benign tumors of the peripheral nerves, schwannoma is a specific type that originates from Schwann cells. It is typically slowly growing, neoplasm that is displacing neural structures without direct invasion. History, physical examination, fine needle aspiration, and magnetic resonance imaging are used as diagnostic modalities, however definitive diagnosis and identification of the affected nerve are often difficult up to the time of surgery. CONCLUSION: Herby we describe a very rare localization of schwannoma arising from masseter muscle in a 30 year old man who presents with painless neck mass. This rare entity should be considered in the differential diagnosis in any patient presented with cheek mass.

Metachronous, Single Metastasis to the Parotid, from Primary Breast Cancer: A Case Report and Review of the Literature.

Background. The parotid gland is an unusual site for metastatic disease and when metastasis occurs, it commonly originates from head and neck primaries. Spread from distant infraclavicular sites such as the breast, into the parotid, is even more unusual with very few cases reported in the literature. Case Report. We describe the case of a 65-year-old woman presenting for a rapidly enlarging right parotid mass. She had a history of an invasive ductal carcinoma of the right breast and was disease-free in the past 6 years prior to her presentation. She was thereafter diagnosed as having a solitary parotid metastasis from breast origin. A total parotidectomy was done and she was referred for adjuvant radiotherapy. Conclusion. Any parotid metastasis should be investigated, especially in patients with a prior history of cancer where the possibility of metastasis, even if improbable, should be kept in mind. Fine needle aspiration biopsy (FNAB) is the first diagnostic procedure to be done and immunocytochemistry can provide valuable information even if it is not always needed for diagnosis. Superficial parotidectomy when feasible with adjuvant radiotherapy is the preferred approach for solitary metastasis of the parotid. The prognosis, however, remains poor regardless of the treatment modality used.

Phospho-MEK1/2 and uPAR Expression Determine Sensitivity of AML Blasts to a Urokinase-Activated Anthrax Lethal Toxin (PrAgU2/LF).

In this study, we attempt to target both the urokinase plasminogen activator and the mitogen-activated protein kinase pathway in acute myeloid leukemia (AML) cell lines and primary AML blasts using PrAgU2/LF, a urokinase-activated anthrax lethal toxin. PrAgU2/LF was cytotoxic to five out of nine AML cell lines. Cytotoxicity of PrAgU2/LF appeared to be nonapoptotic and was associated with MAPK activation and urokinase activity because all the PrAgU2/LF-sensitive cell lines showed both uPAR expression and high levels of MEK1/2 phosphorylation. Inhibition of uPAR or desensitization of cells to MEK1/2 inhibition blocked toxicity of PrAgU2/LF, indicating requirement for both uPAR expression and MAPK activation for activity. PrAgU2/LF was also cytotoxic to primary blasts from AML patients, with blasts from four out of five patients showing a cytotoxic response to PrAgU2/LF. Cytotoxicity of primary AML blasts was also dependent on uPAR expression and phos-MEK1/2 levels. CD34(+) bone marrow blasts and peripheral blood mononuclear cells lacked uPAR expression and were resistant to PrAgU2/LF, demonstrating the lack of toxicity to normal hematological cells and, therefore, the tumor selectivity of this approach. Dose escalation in mice revealed that the maximal tolerated dose of PrAgU2/LF is at least 5.7-fold higher than that of the wild-type anthrax lethal toxin, PrAg/LF, further demonstrating the increased safety of this molecule. We have shown, in this study, that PrAgU2/LF is a novel, dual-specific molecule for the selective targeting of AML.

Influence of proton pump inhibitors on gastritis diagnosis and pathologic gastric changes.

AIM: To investigate the influence of proton pump inhibitors (PPIs) exposure on the diagnosis of Helicobacter pylori (H. pylori) gastritis and intestinal metaplasia. METHODS: Chronic PPI use is associated with masking of H. pylori infection. Patients with H. pylori infection are predisposed to gastric and duodenal ulcers, and long-term infection with this organism has been associated with gastric mucosal atrophy and serious long-term complications, such as gastric lymphoma and adenocarcinoma. Three hundred patients diagnosed with gastritis between January 2008 and April 2010 were included in our study. The computerized medical database of these patients was reviewed retrospectively in order to assess whether the type of gastritis diagnosed (H. pylori vs non-H. pylori gastritis) is influenced by PPI exposure. H. pylori density was graded as low, if corresponding to mild density following the Updated Sydney System, or high, if corresponding to moderate or severe densities in the Updated Sydney System. RESULTS: Patients were equally distributed between males and females with a median age at the time of diagnosis of 50 years old (range: 20-87). The histological types of gastritis were classified as H. pylori gastritis (n = 156, 52%) and non-H. pylori gastritis (n = 144, 48%). All patients with non-H. pylori gastritis had inactive chronic gastritis. Patients with no previous PPI exposure were more likely to be diagnosed with H. pylori gastritis than those with previous PPI exposure (71% vs 34.2%, P < 0.001). Intestinal metaplasia was more likely to be detected in the latter patients (1.4% vs 6.5%, P = 0.023). Multivariate analysis has also demonstrated that in the presence of previous PPI exposure (OR = 0.217, 95%CI: 0.123-0.385), GERD (OR = 0.317, 95%CI: 0.132-0.763, P = 0.01), alcohol intake (OR = 0.396, 95%CI: 0.195-0.804, P = 0.01), the detection of H. pylori was less likely. Chronic use of PPIs may mask H. pylori infections promoting the diagnosis of non-H. pylori gastritis and leads to a significant drop in H. pylori densities and to an increased risk of intestinal metaplasia. CONCLUSION: The use of PPIs masks H. pylori infection, promotes the diagnosis of non-H. pylori inactive chronic gastritis diagnosis, and increases the incidence of intestinal metaplasia.

Complete remission of peritonitis in a patient with luteinized thecomas of the type typically associated with sclerosing peritonitis using GnRH agonist and anti-estrogen.

•-We report a case of luteinized thecomas associated with sclerosing peritonitis (LTSP).•-Sclerosing peritonitis associated with LTSP is a main cause of mortality and morbidity.•-LTSP can be successfully treated with GnRH agonist and anti-estrogen.•-Early recognition of LTSP is necessary to avoid unnecessary surgery.

Atypical choroid plexus papilloma treated with single agent bevacizumab.

Choroid plexus papillomas (CPPs) are usually not malignant and occur in less than 1% of brain tumors in patients of all ages. They represent 3% of childhood intracranial neoplasms with a predilection in younger ages. Papillomas have an indolent course and carry a good long-term outcome if gross total surgical resection is achieved. However malignant evolution may occur, with a 10-30% incidence. Chemotherapy has been used with varied degrees of success. Most series are very small, some are only limited to case reports and cannot lead to guidelines or therapeutic recommendations. We are reporting the first case of recurrent CPP treated with 5 mg/kg of bevacizumab administered once every two weeks. Complete patient evaluations with follow-up contrast-enhanced magnetic resonance imaging (MRI) scans were obtained after the initial two treatments and every 8 weeks thereafter. Only after two treatments, the MRI scans showed radiological stabilization of the tumor, and the patient achieved an excellent clinical response with significant resolution of all skin lesions.

StarD13 is a tumor suppressor in breast cancer that regulates cell motility and invasion.

Breast cancer is one of the most commonly diagnosed cancers in women around the world. In general, the more aggressive the tumor, the more rapidly it grows and the more likely it metastasizes. Members of the Rho subfamily of small GTP-binding proteins (GTPases) play a central role in breast cancer cell motility and metastasis. The switch between active GTP-bound and inactive GDP-bound state is regulated by guanine nucleotide exchange factors (GEFs), GTPase-activating proteins (GAPs) and guanine-nucleotide dissociation inhibitors (GDIs). We studied the role of StarD13, a recently identified Rho-GAP that specifically inhibits the function of RhoA and Cdc42. We aimed to investigate its role in breast cancer proliferation and metastasis. The levels of expression of this Rho-GAP in tumor tissues of different grades were assayed using immunohistochemistry. We observed that, while the level of StarD13 expression decreases in cancer tissues compared to normal tissues, it increases as the grade of the tumor increased. This was consistent with the fact that although StarD13 was indeed a tumor suppressor in our breast cancer cells, as seen by its effect on cell proliferation, it was needed for cancer cell motility. In fact, StarD13 knockdown resulted in an inhibition of cell motility and cells were not able to detach their tail and move forward. Our study describes, for the first time, a tumor suppressor that plays a positive role in cancer motility.

Bifocal Presentation of Primary Testicular Extranasal NK/T-Cell Lymphoma: A Case Report and Review of the Literature.

Introduction. Testicular lymphoma is an aggressive disease with a very poor prognosis. Nasal-type natural killer/T-cell lymphoma (NKTCL-N) in particular is very uncommon and has a rapidly progressive, fatal course. Case Report. We report a case of primary NKTCL-N of the testis in a 38-years-old Middle Eastern man. The patient had a history of primary right testicular tumor diagnosed at an outside institution as a seminoma and treated with orchiectomy followed by chemo/radiation. On admission, the patient had an enormous nasal granuloma with blood workup showing pancytopenia and elevated liver function tests due to active hepatitis B infection. CT scan of the sinuses showed a very large soft tissue mass, and PET scan showed splenomegaly with multiple lymph node masses in the pelvis and the chest areas. Bone marrow and nasal tumor biopsies as well as review of the slides from the initial orchiectomy were all in favor of NKTCL-N lymphoma. The patient was treated with CHOD based combination chemotherapy and responded dramatically to the first two cycles but passed away from fulminant hepatitis B infection. Conclusion. Despite all known treatments of NKTCL-N lymphoma of the testes, this disease has a very poor prognosis and invariably follows an aggressive clinical course.

Metastatic parotid myoepithelial carcinoma in a 7-year-old boy.

Myoepithelial carcinoma is a rare malignancy of the parotid gland that is usually seen in adults. We report the first case in children of myoepithelial carcinoma of the parotid gland with massive invasion of the facial nerve and metastasis to cervical lymph nodes. Due to its rarity, the treatment and the clinical course of this tumor are not well defined yet. We performed a total parotidectomy, a modified neck dissection, and a postoperative radiotherapy in 7-year-old boy. Sparing of the facial nerve was impossible; it was sacrificed and grafted with a sural nerve. Histopathology confirmed the diagnosis of a parotid gland carcinoma and immunohistochemical markers showed that the tumor cells express cytokeratin, epithelial membrane antigen, cytokeratin 7, smooth muscle actin, P63, CEA, and S100. This pattern of immunostaining is consistent with the diagnosis of myoepithelial carcinoma. On the postoperative tenth month he presented with a pulmonary and lumbar vertebra metastasis.

Pathology of the liver in obese and diabetic ob/ob and db/db mice fed a standard or high-calorie diet.

Non-alcoholic fatty liver disease (NAFLD) is one of the commonest liver diseases in Western countries. Although leptin deficient ob/ob and db/db mice are frequently used as murine models of NAFLD, an exhaustive characterization of their hepatic lesions has not been reported to date, particularly under calorie overconsumption. Thus, liver lesions were characterized in 78 ob/ob and db/db mice fed either a standard or high-calorie (HC) diet, for one or three months. Steatosis, necroinflammation, apoptosis and fibrosis were assessed and the NAFLD activity score (NAS) was calculated. Steatosis was milder in db/db mice compared to ob/ob mice and was more frequently microvesicular. Although necroinflammation was usually mild in both genotypes, it was aggravated in db/db mice after one month of calorie overconsumption. Apoptosis was observed in db/db mice whereas it was only detected in ob/ob mice after HC feeding. Increased apoptosis was frequently associated with microvesicular steatosis. In db/db mice fed the HC diet for three months, fibrosis was aggravated while steatosis, necroinflammation and apoptosis tended to alleviate. This was associated with increased plasma ß-hydroxybutyrate suggesting an adaptive stimulation of hepatic mitochondrial fatty acid oxidation (FAO). Nevertheless, one-third of these db/db mice had steatohepatitis (NAS ≥ 5), whereas none of the ob/ob mice developed non-alcoholic steatohepatitis under the same conditions. Steatosis, necroinflammation, apoptosis and fibrosis are modulated by calorie overconsumption in the context of leptin deficiency. Association between apoptosis and microvesicular steatosis in obese mice suggests common mitochondrial abnormalities. Enhanced hepatic FAO in db/db mice is associated with fibrosis aggravation.

Gene expression profiling in breast cancer.

Gene expression profiling has been increasingly used to determine new cancer markers. This technology holds major promises for improving the management of patients with breast cancer in which traditional clinicopathologic parameters do not account for all the heterogeneity of this disease and its distinct prognostic groups. Gene expression profiling has resulted in new classification of breast cancer and new assays are being developed and commercialized as prognostic and predictive tests. However, the use of these tests in a clinical setting presents many issues. The accuracy of this new technology is often overestimated and its limitations should be addressed. Although early results are promising, further validation and well designed clinical trials are required before incorporating these tests in routine clinical practice.