Search

BackgroundNon-small cell lung cancer (NSCLC) is the leading cause of cancer-related morbidity and mortality worldwide. Immune checkpoint inhibitors (ICIs) including anti-PD-1 and anti-PD-L1 antibodies, have significantly changed the treatment outcomes with better overall survival, but only 15-40% of the patients respond to ICIs therapy. The search for predictive biomarkers of responses is warranted for better clinical outcomes. We aim here to identify pre-treatment soluble immune molecules as surrogate biomarkers for tissue PD-L1 (TPD-L1) status and as predictors of response to anti-PD-1/PD-L1 therapy in NSCLC patients. Sera from 31 metastatic NSCLC patients, eligible for anti-PD-1/PD-L1 or combined chemoimmunotherapy, were collected prior to treatment. Analysis of soluble biomarkers with TPD-L1 status showed significant up/down regulation of the immune inhibitory checkpoint markers (sSiglec7, sSiglec9, sULBP4 and sPD-L2) in patients with higher TPD-L1 (TPD-L1 >50%) expression. Moreover, correlation analysis showed significant positive linear correlation of soluble PD-L1 (sPD-L1) with higher TPD-L1 expression. Interestingly, only responders in the TPD-L1 >50% group showed significant down regulation of the immune inhibitory markers (sPD-L2, sTIMD4, sNectin2 and CEA). When responders vs. non-responders were compared, significant down regulation of other immune inhibitory biomarkers (sCD80, sTIMD4 and CEA) was recorded only in responding patients. In this, the optimal cut-off values of CD80

Introduction: Acute anterior poliomyelitis (AAP) is an endemic human disease caused by a worldwide spreading enterovirus. The late consequences of AAP include a new picture of muscle weakness together with abnormal muscle fatigue, amyotrophy, and myoarticular pain, configuring a condition known as post-polio syndrome (PPS). This new condition comprises a specific set of health problems due to the polio virus, resulting in decreased functional capacity and/or the onset of new disabilities. Case Report: A 53-year-old female, human resources analyst, reported that she had been shaken by AAP at the age of 2. Currently she was presented with gait on the knees, osteo-myoarticular pain, inadequate synergies of movements. Imaging exams showed great disproportion in the pelvic region with marked amyotrophy and liposubstitution of the muscle, more evident in the left leg. Although there was some preservation of the plantar flexor muscles, interstitial edema was evident. In the thighs there was amyotrophy with liposubstitution of the muscle, more evident on the left. In the left knee joint there was a lesion of the cruciate ligaments with extensive deep chondral erosions in the load area of the femorotibial compartment, with exposure of the subchondral bone, without edema. Osteopenia also affected it. Conclusion: Through the data obtained in this study, it can be seen that there are many reasons why patients affected by post-polio syndrome develops bone deformities and joint interferences that cause the individual to suffer losses and aggravations in health and quality of life. Nevertheless, there is a lack of theoretical framework available in the literature, justifying the importance of further studies on this topic.

PDF file - 655K, Supplementary Figure 1. TNRC9 promoted cell proliferation in MDA-MB-231 breast cancer cells. Supplementary Figure 2. shRNA-mediated knockdown of TNRC9. Supplementary Figure 3. H&E staining of tumors (10�Magnification) from xenograft nude mice subcutaneously injected with control ZR-75-1cells (upper row I � V) were compared with those injected with TNRC9-depeltion ZR-75-1 cells (lower row VI � VIII, no palpable tumor in two mice). �-� represents 400μm. Supplementary Figure 4. Knocking-down TNRC9 sensitizes cancer cells to apoptosis signal. Supplementary Figure 5. BRCA1 and TNRC9 expression in TNRC9 abrogated and control cells. Supplementary Figure 6. The expression profile of TNRC9 knockdown MCF-7 cells. Supplementary Figure 7. In silico analysis of TNRC9 and BRCA1 gene expression among ovarian cancer patients. Supplementary Figure 8. The effects of TNRC9 on luciferase activity driven by BRCA1 promoter. Supplementary Table 1 The list of transcripts significantly altered in TNRC9 knockdown MCF-7 cells comparing to control MCF-7 cells

Immune checkpoint inhibitors (ICIs) including anti-PD-1 and anti-PD-L1 antibodies, have significantly changed the treatment outcomes of NSCLC patients with better overall survival. However, 15-40% of the patients still fail to respond to ICIs therapy. Identification of biomarkers associated with responses are mandated in order to increase the efficacy of such therapy. In this study we evaluated 27 serum-derived exosomal immuno-oncological proteins and 44 cytokines/chemokines before and after ICIs therapy in 17 NSCLC patients to identify surrogate biomarkers for treatment/monitoring patient stratification for maximum therapeutic benefit. We first confirmed the identity of the isolated exosomes to have their specific markers (CD63, CD81, HSP70 and CD91). We have demonstrated that baseline concentration of exosomal-PD-L1 (p

Background Immune checkpoint proteins, especially PD-L1 and PD-1, play a crucial role in controlling the intensity and duration of the immune response, thus preventing the development of autoimmunity. These proteins play a vital role in enabling cancer cells to escape immunity, proliferate and progress. Methods This brief review highlights essential points related to testing for immune checkpoint therapy that histopathologists need to know. Results In recent years, several inhibitors of these proteins have been used to reactivate the immune system to fight cancer. Selection of patients for such therapy requires demonstration of PD-L1 activation on the tumor cells, best done by immunohistochemical staining of the tumor and immune cells using various antibodies with predetermined thresholds. Conclusions Immune checkpoint therapy appears to be promising and is rapidly expanding to include a large variety of cancers.

Rituximab is used as second-line therapy in patients with immune thrombocytopenic purpura (ITP) who do not respond to first-line management. The response rate for Rituximab is variable in different populations ranging from 30% to 90%. The adverse effects of rituximab in patients with ITP range from infusion site reactions to the reactivation of hepatitis B virus and progressive multifocal leukoencephalopathy and interpopulation variation.We conducted a single-center, retrospective study in Qatar's National Center for Cancer CareResearch. The study included patients with chronic refractory ITP who received rituximab as second-line therapy. Descriptive and summary statistics were used to describe the sociodemographic parameters of the study cohort.Of the 41 patients with chronic ITP, 26 were Arabs, 12 were Asians, and 3 were of other ethnicities. Rituximab was associated with an overall response rate of 80.4%. Arabic patients had the highest clinical response (84.6%) among the ethnicities with the lowest adverse effects (11.5%). Asians had a response rate of 66.6%, and adverse effects were seen in 16.7% of the patients.In chronic refractory ITP, rituximab appears to have a better clinical response in the Arabic population with minimal toxicity than in other ethnicities.

Background Spinal metastasis of cerebral glioblastoma (GBM) is rare, with some reports suggesting a prevalence of 1%−2%. Case Description Herein, we present 2 unique cases of spinal metastasis of cerebral GBM, 1 of which was histologically proven to be a drop spinal GBM metastasis. The first case was a 25-year-old female who presented with a spinal intradural intramedullary spinal lesion a few months after resection of a left temporal lobe GBM (isocitrate dehydrogenase wild type). The patient underwent surgical resection of the new lesion, and subsequent histopathologic examination proved that the intramedullary spinal lesion was GBM. The patient experienced full recovery postoperatively, and then a few months later, she presented again with widespread drop metastasis of the spinal cord. The second case is a middle-aged male with right temporal GBM who developed spinal metastasis 10 months after his diagnosis. Conclusions We are reporting these 2 cases due to the rarity of spinal metastasis in GBM. We reviewed the current literature and included genetic and molecular profiles in the discussion. Currently, there are no established treatment guidelines for GBM spinal metastasis. The Stupp protocol after initial brain surgery for GBM did not appear to have beneficial effects on prolonging survival in these patients with spinal metastasis. The goal of treatment was primarily to alleviate pain and neurologic deficits with no effect on overall outcome. Prognosis following the diagnosis of spinal metastasis is poor.

Testicular stromal tumors are uncommon, although mostly benign. The purpose of this study is to assess the role of multi-parametric MRI in differentiating benign testicular stromal tumors from malignant testicular neoplasms (non-stromal and stromal). A single-center retrospective study comparing benign stromal tumors (STs) to malignant testicular neoplasms (MTNs) was conducted. MR imaging assessment included tumor size, T2- and T1-weighted signal intensity, T2- and T1-weighted texture pattern, diffusion restriction, presence of hemorrhage and/or necrosis, and measurement of apparent diffusion coefficient and dynamic contrast enhancement (DCE). Inter-observer agreement was assessed using Cohen’s kappa and Bland–Altman and data were compared using independent t-tests or χ2. Receiver operating characteristic curve analysis was used to test models incorporating various imaging features. Radical orchiectomy and histopathology revealed 20 testicular neoplasms: seven STs (35%) and thirteen MTNs (65%). MTNs were significantly larger in size than STs (5.1 ± 2.36 cm vs. 1.27 ± 0.56 cm; p-value

Amyloidosis is related to the extracellular deposition of abnormal protein fibrils in various tissues. It can be either localized to an organ or generalized, affecting multiple systems. Amyloidosis of the urinary bladder is a rare histopathological finding. It is clinically interesting that such cases' clinical, radiological, and even endoscopic presentation mimic urothelial carcinoma to a great extent. Here, we discuss a case of a 49‐year‐old gentleman who presented with frank painless hematuria. The patient was diagnosed with a bladder mass suspicious of malignancy depending on the clinical presentation aided by the cystoscopic and radiological evaluation. Histopathologic samples of the transurethral resection of the mass proved to be primary bladder amyloidosis. This case is of unique clinical interest in that it is the first case reported of bladder amyloidosis that is complicated by extraperitoneal bladder rupture post‐operatively. However, no immediate intraoperative perforation to the bladder wall during resection was evidenced., Primary urinary bladder amyloidosis is a rare histopathological finding. Interestingly, it presents clinically and radiologically similar to urothelial carcinoma of the bladder. The only differentiation can be reached by histopathologic examination. Resection of such bladder lesions requires special care as such flat pathological lesions can be complicated by bladder perforation.

Intramedullary spinal cord arachnoid cysts are rare. So, we present an interesting case of adult male presented with myelopathic symptoms and signs. Further investigations revealed a finding of thoracic intramedullary cystic lesion, found postoperatively to be an arachnoid cyst. Patient improved remarkably postoperative and during follow up period.

Objectives: Customer satisfaction surveys are a routine device used to assess performance. Surveys are used in hospitals to check physician and patient satisfaction. Hamad Medical corporation’s (HMC) histopathology laboratory is College of American pathologists (CAP) accredited with highly trained pathologists and technical staff that routinely undertake various educational courses and are involved in research related activities. The lab has state of the art staining and immunohistochemistry service as well. However, it was felt that not all clinicians are very comfortable approaching pathologists and some many times experience problems either contacting lab staff or updating histopathology orders. Hence to narrow down the problems encountered by the clinicians and improve the specimen flow through the lab along with the communication between clinician and pathologist, that we deem vital, we designed this pilot survey. Methods: The survey questionnaire was made online with 15 questions in total and the link was electronically mailed to all Consultant and Specialist physicians in Hamad medical corporation (HMC). Around 3500 emails were sent out but only 105 surveys were filled in two months’ time. The survey included questions pertaining to multiple facets of quality of histopathology services and information regarding the participant. Results: The overall satisfaction was highest for Multidisciplinary presentations (96%) and lowest (77%) for timeliness of reporting. The satisfaction was above 90% for clarity and format, Diagnostic accuracy and pathologists’ responsiveness to problems. Thirty six percent of the people rated MDT presentations as excellent while 46% of the people thought overall quality of professional interaction was good. The areas of improvement, as per this survey, was timeliness of reporting and notifications of significant abnormal results (overall satisfaction 79%). Majority of the people who took the survey (36%) were from internal medicine and half were members of multidisciplinary meetings (49%). Seventy-one of percent of the participants were from Hamad General hospital (HGH), while rest were from the other hospitals under HMC. Conclusion: The response rate for the survey was low, hence another survey with a wider reach, preferably by paper, is required to get more representative data. In general, the clinicians at HGH are satisfied with the services provided by the histopathology laboratory. Areas of improvement include Turnaround time (TAT), avoidance of descriptive reports and better communication with the ordering clinician. Keywords: Quality control, quality improvement, survey, histopathology, Laboratory

While evaluating the cause of Cushing's syndrome, biochemical confirmation should be sought first as imaging studies might misdirect the diagnosis toward the wrong problem. One of the rare secondary causes that should be kept in mind while evaluating Cushing's syndrome is the thymic neuroendocrine tumor.

Metastatic disease from solid extrapulmonary tumours affects the lungs frequently. Endobronchial metastases (EM) however are very rare. Most commonly breast, colorectal and renal carcinomas can result in endobronchial metastases. EM secondary to a prostate primary are even more uncommon. We present an unusual case of a synchronous diagnosis of EM and primary prostate cancer. The diagnosis was confirmed on bronchoscopic endobronchial biopsies and immunohistochemical examination. Just 3 such cases have been reported to the best of our knowledge in the last 15 years. We discuss frequencies, similarities with previously reported cases, possible developmental modes and the diagnosis of EM. We conclude that patients with a current or previous diagnosis of an extrapulmonary malignancy with apparently trivial respiratory symptoms and/or unexplained weight loss should be considered for a bronchoscopy. Bronchoscopy and immunohistochemical profiling is the gold standard for diagnosing EM, as they may not be visible on cross sectional imaging.

Background Although autophagy plays a dual role in suppressing or promoting certain cancers, the nature of its involvement in breast cancers remains unclear. Here, we investigated the function of STXBP6, a protein regulating the autophagy‐associated SNARE complex, in triple negative breast cancer (TNBC). Results We report that STXBP6 is profoundly downregulated in TNBC specimens in association with reduced overall patient survival. Notably, we found that STXBP6 promoter was specifically hyper‐methylated in TNBC specimens. Ectopic expression of STXBP6 inhibited TNBC cell proliferation in cellular and mouse models. Mass spectrometric analysis revealed physical interactions of STXBP6 with a number of autophagy‐related proteins including SNX27, a molecule involved in endocytosis of plasma membrane receptors and protein trafficking. Overexpression of STXBP6 elicited autophagy through inhibition of mTORC1 signaling. Reciprocally, induction of autophagy rescued STXBP6 expression by inhibiting EZH2 and altering STXBP6 methylation. The mutual regulation between STXBP6 and autophagy was replicated in luminal breast cancer cells only when estrogen receptor (ER) activation was abrogated. Ectopic expression of STXBP6 significantly reduced TNBC cells’ migratory ability in vitro and tumor metastasis in vivo. Conclusions Our results unveil a role of STXBP6 in TNBC that highlights a new paradigm in autophagy regulation. Our results significantly enhance the understanding of the mechanisms of TNBC aggressiveness, which might help in designing novel therapies targeting TNBC.

First described in 1995 by Meis-Kindbloom et al. as a variant of fibrosarcoma simulating carcinoma, sclerosing epithelioid fibrosarcoma (SEF) is a malignant soft tissue sarcoma characterized by epithelioid cells in dense sclerotic stroma, frequent immunoreactivity for MUC4 and heterogeneous genetic profile with recurrent EWSR1 gene rearrangement. It typically affects middle-age adults with a predilection for the lower extremity. It is believed that SEF is closely related to low-grade fibromyxoid sarcoma (LGFMS), both tumors show overlapping features in morphology, immunophenotype, and molecular profile. In this review, we discuss the clinical, morphologic, and immunohistochemical features of SEF with particular emphasis on its molecular diversity and relation to LGFMS.

Objective The current WHO classification categorises high grade neuroendocrine (NE) carcinomas of the prostate into small cell and large cell types. A distinct form of carcinoma demonstrating synchronous dual exocrine and NE differentiation, termed amphicrine carcinoma, has been described at various other sites, primarily within the gastrointestinal tract. In this study, we describe the clinicopathologic features of a series of metastatic prostatic carcinomas with amphicrine features. Methods Five cases of high grade prostatic carcinoma (PCa) demonstrating an amphicrine immunohistochemical phenotype were prospectively collected. Results Serum prostate specific antigen (PSA) level at diagnosis ranged from 38-992ng/ml (median 200ng/ml). All 5 patients had metastatic disease; 4 at initial presentation. Microscopically, the tumours demonstrated a solid/nested growth pattern composed of cells with amphophilic cytoplasm, vesicular nuclei and macronucleoli. Morphologic features of small cell or large cell NE carcinoma were absent. Compared with conventional high grade PCa, the tumour cells displayed greater nuclear pleomorphism, brisk mitotic activity and a high Ki67 proliferation index (median 50%). All cases demonstrated immunohistochemical positivity for PSA, androgen receptor (AR) and prostatic specific acid phosphatase (PSAP) combined with diffuse or confluent/non-focal positivity for chromogranin-A and synaptophysin. Two hormone-naive cases showed a clinical response to androgen deprivation therapy. Conclusion This series highlights a previously undefined, clinically aggressive variant of PCa exhibiting dual exocrine and NE differentiation, for which we are proposing the term PCa with amphicrine features. Increased recognition of these tumours may lead to a better understanding of their biology and ultimately improve their clinical management. This article is protected by copyright. All rights reserved.

Background Appendicular neuroendocrine tumors (NET, Carcinoid tumors) of the appendix are rare and mostly diagnosed incidentally on the post-operative histopathological examination. NET are usually associated with good 5-year survival rates. We aimed to assess our experience for the diagnosis and management of NET over 11 years. Method It is a retrospective chart review of all clinically suspected patients with acute appendicitis who underwent emergent appendectomy with intention to treat between January 2004–December 2014, and were clinically followed up until 2016. Results During the study period, a total of 13641 patients underwent emergency appendectomy, of which 32 were histologically confirmed NET. The mean age of the NET cases was 25.3 ± 7.9 years; 78% were males and all were clinically presented with acute appendicitis. The mean leucocyte was 15 ± 14 × 109 per Liter, and mean tumor size was 4.86 ± 3.18 (ranged 1.5–13) mm. The median length of hospital stay was 4 (2–15) days. One patient had right hemicolectomy; diagnosed with right colonic cancer with NET being an incidental finding as part of histopathological assessment. Another patient required a second stage procedure; he was diagnosed as goblet cell carcinoid with positive margin. None of the patients died 30-day postoperatively and all of them survived on clinical follow-up that ranged between 2 and 13 years. Conclusion Carcinoid tumors of the appendix are rare and typically diagnosed incidentally. Detailed examination of routine appendectomy specimens is the key for diagnosis. Simple appendectomy suffices for tumors

Patient: Female, 45 Final Diagnosis: Primary pituitary tuberculosis Symptoms: Headache • vomiting • vomiting Medication: — Clinical Procedure: Pituitary biospy Specialty: Endocrinology and Metabolic Objective: Rare disease Background: Primary pituitary tuberculosis (in absence of other organ involvement and constitutional symptoms) is an extremely rare disease with total reported cases in the literature fewer than a hundred. Misdiagnosis as pituitary adenoma is common and late diagnosis can result in a permanent endocrine dysfunction and/or long-term neurologic sequelae. Case Report: We report on the case of a middle-aged woman who presented with severe headache and left third cranial nerve palsy. Magnetic resonance imaging (MRI) revealed a large pituitary tumor invading the left cavernous sinus. The case was initially misdiagnosed as pituitary adenoma. A pituitary biopsy was performed and was suggestive of pituitary tuberculosis. Extensive radiologic investigations did not reveal any evidence of other organ involvement by tuberculosis. She was successfully treated with anti-tuberculous medications. Conclusions: In areas with a high pre-test probability of tuberculosis, pituitary tuberculosis should be included in the differential diagnosis of pituitary tumors in order to avoid unnecessary surgical interventions. Besides being the first histologically-proven primary pituitary tuberculosis case reported from Qatar, the current case is unique in that extensive radiologic investigations did not reveal any evidence of other systemic or pulmonary tuberculosis.

Cytokeratins belong to the family of intermediate filaments. They are expressed in a highly specific manner in epithelial cells where they play a crucial role in the integrity and mechanical stability of the cells. Several types of cytokeratins have been described in normal as well as neoplastic urothelium. In the case of urothelial neoplasms expression of CK20 and CK5/6 has been shown in several studies to have diagnostic and prognostic implications. Thus, low-grade urothelial carcinoma manifests CK expression limited to the umbrella cells, while high-grade tumors usually have an expression in the entire thickness of the urothelium except for the basal layer. CK5/6 expression on the other hand is expressed in the basal cells in all low-grade and some high-grade urothelial carcinomas. Diffuse CK20 staining accompanied by loss of CK5/6-positive basal layer is usually associated with aggressive clinical behavior. Double staining of the slides for these cytokeratins may facilitate proper interpretation and correlation.

The terminology “Intradural Extramedullary” is often associated with Nerve sheath tumors (schwannoma, Neurofibroma) and Meningioma, while dermoid cyst, epidermoid, neurenteric cyst are other benign entities. Hemangioblastomas are rare, accounting for 1-5% of all spinal cord tumours.1 75% of the Spinal hemangiblastoma are Intramedullary, and another 10-15% have combined intramedullary and extramedullary-intradural component, while isolated extramedullary hemangioblastoma are rare1. Our case had an isolated intradural extramedullary hemangioblastoma without any associated manifestations of VHL syndrome. Surgery is a preferred option where total resection is possible, where as SRS is also an option in case of residual or incomplete resection.

We present a rare case of epithelioid hemangioendothelioma arising from the wall of ulnar artery in distal forearm. The presentation was interesting in a 34-year-old man, with progressively worsening symptoms of ulnar neuropathy. A mass was seen arising from the ulnar artery on imaging with ultrasound and magnetic resonance imaging. Soft tissue epithelioid hemangioendothelioma in extremities almost always arise from the veins. Existing literature do not have elaborated imaging findings of epithelioid hemangioendothelioma arising from the arterial wall. The aim of this paper is to briefly review the interesting presentation and imaging features of this rare entity. Knowledge of such vascular tumor would avoid the mishap during surgery. Our case will add an interesting presentation of such rare pathology to the existing literature.

Bladder cancer is a highly prevalent disease throughout the world usually encountered in older patients, and associated with substantial morbidity, mortality, and cost. The treatment of bladder cancer has remained unchanged for the last several decades. However, in recent years the availability of comprehensive genomic data from The Cancer Genome Atlas and other large projects have considerably improved our understanding of the pathogenesis of these tumors. These studies demonstrated that bladder cancers can be grouped into 2 broad categories namely basal and luminal molecular subtypes with recognizable subgroups in each of these categories. Clinical data suggest that invasive basal cancers are more sensitive to neoadjuvant chemotherapy (NAC), such that most patients with basal cancers who are aggressively managed with NAC have excellent outcomes. Patients with luminal cancers do not appear to derive much clinical benefit from NAC, but some may appear to be sensitive to anti-programmed death-ligand 1 (PDL1) antibodies and possibly other immune checkpoint inhibitors. It is hoped that future studies will also identify biomarkers such as immunohistochemical markers which may be used to predict therapeutic response of these tumors. This will contribute substantially toward efficient and cost-effective diagnosis and management of these neoplasms.

Urothelial carcinoma in situ (CIS) is a high-grade noninvasive malignancy with a high tendency of progression. Although it is typically grouped with other nonmuscle invasive bladder cancers, its higher grade and aggressiveness make it a unique clinical entity. Urothelial CIS is histologically characterized by replacement of the urothelium by cells which fulfill the morphologic criteria of malignancy including nuclear pleomorphism, hyperchromasia, prominent nucleoli, and increased numbers of normal and abnormal mitoses. Urothelial CIS may be categorized as primary when it is not associated with any past or present urothelial carcinoma. It is termed as secondary when there is concomitant or previous urothelial carcinoma in the patient. In recent years detailed molecular studies have provided valuable data for intrinsic molecular subclassification of urothelial carcinoma into 2 broad categories namely luminal and basal types with significant implications for prognosis and therapy. Similar studies on urothelial CIS are limited but have provided crucial insight into the molecular basis of CIS. These studies have revealed that urothelial CIS may also be divided into luminal and basal subtypes, but luminal subtype is much more common. It has also been shown that in many cases, luminal type of urothelial CIS may undergo a class switch to basal type during progression to an invasive carcinoma. Additional studies may be required to confirm and further elaborate these findings.

Schistosomiasis is the third most widespread devastating parasitic disease worldwide and has a high mortality burden. Neuroschistosomiasis is one of the rare and most severe clinical presentations of the disease. It is caused by granuloma formation around eggs that lodge in the central nervous system, with Schistosoma japonicum usually causing most reported cerebral disease. Three unusual presentations of schistosomiasis in Qatar are described herein. The three patients were young males who presented with seizures and tumor-like lesions on brain imaging. The diagnosis was confirmed by biopsy, which showed necrotizing granulomas containing Schistosoma eggs. These cases raise awareness of neuroschistosomiasis as a potential cause of tumor-like brain lesions in migrants and returning travelers from endemic areas. Keywords: Neuroschistosomiasis, Schistosoma, Seizure, Granuloma, Tumor-like brain lesion

Granulosa cell tumours (GCTs) can be either juvenile or adult type, and more commonly occur in the ovaries. Adult-type GCTs of the testis (AGCTT) are very rare and only 46 cases have previously been reported. We report here on a 48-year-old Filipino man with a left testicular AGCTT, which measured 1.2 × 1.2 × 1.0 cm. He underwent radical orchidectomy with postoperative surveillance for 1 year, which included computed tomography with oral intravenous contrast and clinical examinations, which have been unremarkable. The previously reported AGCTTs were briefly reviewed.

Background: Rosai-Dorfman disease (RDD) is an idiopathic nonneoplastic lymphadenopathy disorder which is characterized by lymph node enlargement, but it may also presents primarily involving a variety of extranodal sites, including central nerves system and craniospinal axis. This study reports five cases of craniospinal RDD, with review of epidemiology, clinical presentation, imaging, and histopathological features with current management strategies. Case Description: Five cases of RDD are diagnosed at Hamad General Hospital, Qatar, during 2013–2018. Two cases had dural-based cranial lesions with overlying cranial involvement while three cases were having extradural thoracic spine lesions. All cases underwent surgical intervention and confirmed by histopathology. Conclusion: Craniospinal RDD is a rare clinical presentation and poses significant diagnostic challenges preoperatively due to its similarity with other neoplastic or inflammatory diseases. Surgical option to remove compressive neural pathology provides a good clinical outcome with no recurrence in long-term follow-up.

Patient: Male, 43-year-old Final Diagnosis: Rifampicin-induced pneumonitis Symptoms: Dyspnea • fatigue • fever Medication: — Clinical Procedure: Bronchoalveolar lavage • bronchoscopy • CT scan • lung biopsy Specialty: Pulmonology Objective: Rare disease Background: Rifampicin-induced pneumonitis is an infrequent occurrence, with only a few cases reported in the literature. Furthermore, this condition constitutes a diagnostic challenge, particularly in the era of COVID-19 infection. Here, we report a case of rifampicin-induced pneumonitis with clinical, imaging, and histological features of acute respiratory distress syndrome (ARDS), which required severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) testing to exclude a diagnosis of coronavirus disease 2019 (COVID-19) pneumonia. Case Report: A 43-year-old man on anti-TB treatment for TB meningitis developed new-onset fever, fatigue, hypoxemic respiratory failure, and bilateral pulmonary opacities. His clinical, chest X-ray, and CT thorax findings of ARDS were similar to both rifampicin-induced pneumonitis and severe COVID-19 pneumonia. However, reverse transcription polymerase chain reaction (RT-PCR) testing from a nasopharyngeal swab and bronchoalveolar lavage (BAL) via the GeneXpert system was negative for SARS-CoV-2. A detailed workup, including lung biopsy, revealed drug-induced pneumonitis as the cause of his presentation. His pneumonitis improved after discontinuation of rifampicin and recurred following the rifampicin challenge. Conclusions: This case highlights the importance of early, rapid, and accurate testing for SARS-CoV-2 during the COVID-19 pandemic for patients presenting with acute respiratory symptoms, so that accurate diagnosis and early patient management are not delayed for patients with treatable causes of acute and severe lung diseases. Timely identification of rifampicin-induced pneumonitis via a high clinical suspicion, detailed workup, and histopathological analysis is required to avoid permanent damage to the lungs.

Introduction: Scleromyxedema (rare cutaneous mucinosis), is characterized by the formation of lichenoid papules and presence of Serum monoclonal IgG in most cases, or all; after repeated testing. Patient concerns : The patient is a 51-year-old male presented with thick, disfiguring elephant-like erythematous skin folds over the forehead, papular shiny eruptions over ears and trunk and waxy erythematous papules over arms and hands without dysphagia or respiratory or neurologic symptoms Diagnosis : Skin biopsy from right arm was consistent with scleromyxedema. Serum cryoglobulin was reported negative. Complete blood count and routine blood biochemistry were normal. Thyroid function tests were normal. Serum protein electrophoresis and immunofixation showed monoclonal band of 14.5 g/L typed as IgG lambda. Interventions : Our patient was refractory to lenalidomide however improved clinically on immunoglobulins infusions on monthly basis without change in the MGUS level. Outcomes : NGF analysis revealed approximately 0.25% Lambda monotypic plasma cells in the bone marrow expressing CD38, CD138, and CD27 with aberrant expression of CD56 and were negative for CD45, CD19, CD117, and CD81. We also detected 0.002% circulating plasma cells (PCs) in peripheral blood. Conclusion : The immunophenotype of circulating tumor cells (CTCs) remain close to the malignant PCs phenotype in the BM. Hence, we report NGF approach as a novel diagnostic tool for highly sensitive MRD detection in plasma cell dyscrasias including scleromyxedema.

Papillary renal cell carcinoma (PRCC) is the second most common type of renal carcinoma following clear cell renal cell carcinoma. Papillary renal cell carcinoma is usually divided histologically into 2 types namely, type 1 and type 2. This classification, however, is unsatisfactory as many of papillary carcinoma are unclassifiable by the existing criteria. In recent years there has been a remarkable progress in our understanding of the molecular basis of PRCC. These studies have revealed that type 2 PRCCs represent a heterogenous group which may be subdivided into additional subtypes based on the genetic and molecular make up of these tumors and reflecting different clinical course and prognosis. Some of the molecular features such a hypermethylation of CPG islands in the promotor regions of genes and over expression of the antioxidant pathways within tumor cells have been recognized as markers of poor prognosis. Targeted therapies for papillary carcinoma in the past have been unsuccessful because of lack of clear understanding of the molecular basis of these tumors. It is hoped that recent progress in our understanding of the pathogenesis of various subtypes of PRCC, effective targeted therapies will eventually emerge in due course.

Background Primary central nervous system lymphoma is a rare malignant tumor of the central nervous system. It is associated with poor prognosis and accounts for 0.7%–0.9% of all lymphomas and only 0.3%–1.5% of intracranial tumors. Typically, these lesions are in the cerebral white matter near the corpus callosum, the central gray matter, the basal ganglia-thalamus-hypothalamic region, the posterior fossa and the periventricular region. Only 2 cases with pure third ventricular lymphoma have been reported in the literature. Case Description A 72-year-old female patient known to have type II diabetes mellitus treated with insulin, hypertension, chronic kidney disease, dyslipidemia, and obesity presented with a history of acute confusion and urinary incontinence. No headache was reported on admission, but previously she had intermittent mild headaches and generalized body aches. She had no history of visual symptoms. Her family said she was mildly confused and had memory difficulties that started acutely 2 days before presentation to the hospital. The patient had urgent computed tomography of the brain, which showed a hyperdense lesion in the region of the foramen of Monro. Pre-operative images diagnosed the case as colloid cyst, but post-operative histopathology proved the lesion to be primary CNS lymphoma. Conclusions Eleven months after surgery, the patient is fully consciousness and oriented, with no memory issues or neurologic deficit. She is back to her baseline activities. We are reporting this case for the rarity of the disease and the unusual location of it.

Germ cell tumors can occur in the mediastinum. They account for about 20% of tumors at this location. The majority are located in the anterior mediastinum and usually occur in young adult males. Extension of mediastinal germ cell tumors into the neck with mass formation is a very rare and unusual event. Herein, we report a case of a 34 year old male who presented with a progressively enlarging neck mass. Fine Needle Aspiration (FNA) was performed as initial evaluation and showed cellular smears comprising atypical large cells with prominent irregular nucleoli and moderate amount of cytoplasm with lymphocytic infiltrate and some epithelioid granulomas in the background. The mass was misdiagnosed initially on the cytology smears as anaplastic thyroid carcinoma. The subsequent tissue core biopsy showed sheets and nests of atypical cells admixed with ill-defined granulomatous inflammation. By immunohistochemistry, the tumor cells were immunoreactive with SALL4, PLAP and OCT3/4, compatible with malignant germ cell tumor, seminomatous type. It is very rare for patients with primary mediastinal seminoma to present initially with a neck mass. Fine Needle Aspiration (FNA) of this "neck mass" can lead to misinterpretation of findings due to similarities in cytological features between malignant germ cell tumors and other undifferentiated malignant neoplasms and the diagnosis, therefore, can be very challenging.

Renal cell carcinoma (RCC) is a heterogenous group of tumors, >70% of which belong to the category of clear cell carcinoma. In recent years, crucial advances have been made in our understanding of the molecular and metabolic basis of clear cell carcinoma. This tumor manifests significant alterations in the cellular metabolism, so that the tumor cells preferentially induce the hypoxia response pathway using aerobic glycolysis, rather than the normal oxidative phosphorylation for energy. Most of the clear cell carcinomas (sporadic as well as familial) have mutations and deletions in the VHL gene located at 3p (p3.25). Normally, pVHL plays a crucial role in the proteasomal degradation of hypoxia-inducible factors (HIF)1 and HIF2. Lack of a functioning pVHL owing to genetic alterations results in stabilization and accumulation of these factors, which promotes cell growth, cell proliferation, and angiogenesis, contributing to a neoplastic phenotype. Several other genes normally located adjacent to VHL (BAP1, SETD2, PBRM1) may also be lost. These are tumor suppressor genes whose loss not only plays a role in carcinogenesis but may also influence the clinical course of these neoplasms. In addition, interaction among a variety of other genes located at several different chromosomes may also play a role in the genesis and progression of clear cell carcinoma.

Background Prostate cancer (PCa) is a complex disorder resulting from the combined effects of multiple environmental and genetic factors. Small non-coding RNAs (sRNAs), particularly microRNAs (miRNAs), regulate several cellular processes and have an important role in many human malignancies including PCa. We assessed the sRNA profiles associated with PCa in Arabs, a population that has rarely been studied. Methods We used next generation sequencing technology to obtain the entire sRNA transcriptome of primary prostate tumor formalin-fixed paraffin-embedded tissues, and their paired non-tumor tissues, collected from Bedouin patients (Qatari and Saudi). The miRNA and the target gene expression were evaluated by real-time quantitative PCR. miRNA KEGG pathway and miRNA target genes were subsequently analyzed by starBase and TargetScan software. Results Different expression patterns of several sRNA and miRNA editing were revealed between PCa tumor and their paired non-tumor tissues. Our study identified four miRNAs that are strongly associated with prostate cancer, which have not been reported previously. Differentially expressed miRNAs significantly affect various biological pathways, such as cell cycle, endocytosis, adherence junction and pathways involved in cancer. Prediction of potential targets for the identified miRNAs indicates the overexpression of KRAS, BCL2 and down-regulation of PTEN in PCa tumor tissues. Conclusion These miRNAs, newly associated with prostate cancer, may represent not only markers for the increased risk of PCa in Arabs, but may also reflect the clinical and pathological diversity as well as the ethno-specific heterogeneity of prostate cancer. Electronic supplementary material The online version of this article (10.1186/s12967-017-1362-x) contains supplementary material, which is available to authorized users.

Intravascular large B-cell lymphoma (IVLBCL) is a subtype of extranodal B-cell lymphoma with growth limited to the lumina of small vessels. Intramural great vessel lymphoma (IMGVL), on the contrary, is extremely rare and there have been only two reported cases of primary B-cell lymphoma that occurred in the lumen of the superior vena cava and one case of primary B-cell lymphoma with intra-aortic growth, diagnosed at autopsy. We present the case of a 72-year-old man who presented with severe abdominal pain and was found to have thrombosed abdominal aortic aneurysm. The retrieved thrombus showed Epstein Barr virus-positive large B cell lymphoma (LBCL). Post-operative Echocardiography, Computerized tomography (CT) and Positron Emission Tomography (PET) scan did not show any residual tumor focus, abnormal mass or thickening, increased FDG uptake or hypermetabolism (Nodal or extranodal). This is the first case of large B cell lymphoma presenting as a thrombus within abdominal aortic aneurysm and third case of intramural great vessel lymphoma. Keywords: Lymphoma, Large B cell lymphoma, Aorta, Aneurysm, Intravascular large B cell lymphoma

Patient: Male, 48 Final Diagnosis: Pituitary apoplexy complicated by cerebral infarction Symptoms: Disturbed conscious level • loss of vision Medication: — Clinical Procedure: — Specialty: Radiology Objective: Unusual clinical course Background: Pituitary macroadenoma is a common benign tumor that usually presents with visual field defects or hormonal abnormalities. Cerebral infarction can be a complication of a large pituitary adenoma. We report a rare case of bilateral anterior cerebral arteries infarcts by a large pituitary macroadenoma with apoplexy. Case Report: A 48-year-old male patient presented with altered conscious level and sudden loss of vision for one-day duration. Magnetic resonance imaging of the brain showed a large seller and suprasellar hemorrhagic mass of pituitary origin, with associated bilateral areas of diffusion restriction in the frontal parasagittal regions, consistent with infarctions. Magnetic resonance angiography showed elevation and compression of A1 segment of both anterior cerebral arteries by the hemorrhagic pituitary macroadenoma. The patient underwent trans-sphenoidal resection of the pituitary adenoma, but unfortunately, ischemia was irreversible. Computed tomography (CT) done post-operatively showed hypodensity in the frontal and parietal parasagittal areas, which was also persistent in the follow up CT scans. The patient’s neurological function remained poor, with GCS of 8/15, in vegetative state. Conclusions: Vascular complications of the pituitary apoplexy, although uncommon, can be very severe and life threatening. Early detection of vascular compromise caused by hemorrhagic pituitary macroadenoma can prevent delay in intervention. Clinicians should also consider pituitary adenoma as a possible cause of stroke.

Pilomyxoid astrocytomas (PMAs) are low-grade (WHO Grade II) tumors for which the imaging features are similar to pilocytic astrocytomas (PAs), but for which histological features and the clinical course differ. They are classified as a variant of PA. They have only been recently recognized, and they behave more aggressively than PAs. Most cases occur in the hypothalamic-chiasmatic area, although they may be located in any part of the neuraxis. Posterior fossa PMAs are very rare. The authors report a case of a 2-year-old girl with cerebellar PMA.

The understanding of gastrointestinal stromal tumors (GIST) is complex because of their divergent differentiation and unpredictable behavior. However, our understanding is becoming clearer, despite some cases of tumors which are exceptions from the typical cases. Tumor size, mitotic rate and, to a lesser degree, location, are the most important predictive parameters for the behavior of GIST. In this study, expression of p53 protein was evaluated in 15 cases of GIST. Tumors were divided into three groups: (i) benign (mitotic index [MI] < 5/50 high-power fields [HPF] and size < 5 cm); (ii) borderline (MI < 5/50 HPF and size ≥ 5 cm); and (iii) malignant (MI ≥ 5/50 HPF, irrespective of size). The mean values of p53 expression in the three groups were significantly different (benign, 10.6%; borderline, 33.8%; and malignant, 71%). The conclusion of the present study is that p53 overexpression correlates well with the malignant potential of GIST.

Forty molar and non-molar placentas with hydropic changes (14 complete moles, 14 partial moles, and 12 hydropic non-molar placentas) were examined immunohistochemically for expression of oncoproteins p53 and Bcl-2. The data were evaluated to determine if p53 and Bcl-2 expression could aid in differentiating molar from non-molar pregnancies on the one hand and complete mole from partial mole on the other. Thirteen out of fourteen complete moles showed p53 expression (93%), 8 of the 14 partial moles expressed p53 (57%), and none of the non-molar pregnancies expressed p53 in the extravillous intermediate trophoblasts. Regarding Bcl-2, the syncytiotrophoblasts of most molar and non-molar placentas showed strong and diffuse positivity. These results suggest that p53 expression can be used as a distinguishing parameter between complete moles and placentas with hydropic changes on the one hand and to a lesser extent between partial moles and placentas with hydropic changes on the other hand. Bcl-2 cannot be used in the same way as p53.