Publications by authors named "Shamayel Mohammed"

29 Publications

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Nodular lymphocyte-predominant Hodgkin lymphoma characteristics, management of primary and relapsed/refractory disease and outcome analysis: the first comprehensive report from the Middle East.

BMC Cancer 2021 Apr 1;21(1):351. Epub 2021 Apr 1.

Oncology Center, King Faisal Specialist Hospital and Research Center, Riyadh, Kingdom of Saudi Arabia.

Background: Nodular lymphocyte-predominant Hodgkin lymphoma (NLPHL) is an uncommon variant of Hodgkin lymphoma. There is limited data on treatment, management of refractory and relapsed disease, and long-term outcome. Many registries or country-wide data reports are unable to provide detailed primary and subsequent management. We are reporting our observation on patient's characteristics, management, and outcome.

Methods: This single-institution retrospective cohort analysis includes NLPHL patients seen from 1998 to July 2019. We used Fisher's exact test, chi-square, and Kaplan-Meier (KM) method for various analyses.

Results: Two hundred patients were identified, (6.34% of all the HL). Male:female was 3:1. The median age at diagnosis was 22 years (4-79 years). Stage I-II in 145 (72.5%) cases. One hundred patients (50%) received chemotherapy, 68 (34%) chemotherapy + radiation therapy (RT); 87% of all chemotherapy was ABVD (adriamycin, bleomycin, vinblastine, dacarbazine). Thirteen patients (6.5%) received RT alone and 16 (8%) had surgery alone. Complete response in 82%, partial response in 5.5% and progressive disease in 10.5%. The median follow is 60 months (5-246). Median 5 and 10 years overall survival (OS) is 94.8 and 92.4% (stages I-II, 97.7 and 97.7%, stage III-IV, 94.8 and 92.4%). Median event-free survival (EFS) is 62.3 and 54% respectively (stage I-II, 72 and 64%, stage III-IV, 36.4 and 18.2%). Stage I-II vs III-IV OS (p = < 0.001) and EFS (p = < 0.001) were significant. For stage I-II, 5 year EFS of chemotherapy + RT (83.3%) was superior to chemotherapy alone (60%, p = 0.008). Five year EFS for early favorable (80%), early unfavorable (60%), and advanced (36.4%) was significant (p = < 0.001). Eleven patients (5.5%) had high-grade transformation. Twenty-nine patients underwent HDC auto-SCT, all are alive (28 in remission). 25% of patients had pathologically proved nodal hyperplasia at some point in time.

Conclusion: OS of NLPHL is excellent and independent of treatment type. EFS is better for chemotherapy + RT than chemotherapy alone. Stem cell transplant in refractory / multiple relapses resulted in excellent disease control. There is a need to identify optimal treatment strategies accordingly to the risk stratification.
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http://dx.doi.org/10.1186/s12885-021-08074-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8017738PMC
April 2021

Intraocular T-cell lymphoma metastasizing from a primary adrenal T-cell lymphoma: Case report.

Ann Med Surg (Lond) 2020 Dec 27;60:646-650. Epub 2020 Nov 27.

Department of Ophthalmology, College of Medicine, King Saud University, Riyadh, Saudi Arabia.

Introduction: Most intraocular T-cell lymphomas arise from metastatic source. We are reporting a rare case of intraocular T-cell lymphoma masquerading as pseudo-hypopyon and vitritis. The eye involvement proved to represent a metastatic spread from a co-existing adrenal T-cell lymphoma, which was discovered after the initial ophthalmic presentation.

Presentation Of Case: Our patient was a 71-year-old Saudi man, who was admitted for workup of anemia and weight loss. He also noticed a gradual, painless decline in his vision of both eyes, for which he was referred to the ophthalmology unit. Ocular examination revealed left eye 3 mm pinkish hypopyon. A diagnosis of T-cell lymphoma was made based on careful microscopic examination of the left aqueous fluid, immunohistochemical (IHC) and Flow cytometry analysis. Computerized tomography showed a large invasive left adrenal mass, which has proven to be a primary adrenal lymphoma with multiple metastasis including the intraocular involvement.

Discussion: Primary intraocular lymphoma is the most common lymphoma in the eye. Intraocular T-cell lymphoma is rare and is mostly metastatic. On the other hand, primary adrenal lymphoma (especially T-cell lymphoma) is also rare. There are only 5 cases of primary adrenal lymphoma, two of which, resulted in eye metastasis similar to our case. Primary adrenal lymphoma is known to be aggressive. Our patient eventually passed away.

Conclusion: This report stresses the importance of referring patients with systemic lymphoma to an ophthalmologist to be evaluated for ocular involvement. Even though intraocular metastatic adrenal T cell lymphoma is rare, high clinical suspicion in patients who are presenting with pinkish hypopyon in the presence of other constitutional symptoms is essential.
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http://dx.doi.org/10.1016/j.amsu.2020.11.066DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7718212PMC
December 2020

CD3+T-lymphocyte infiltration is an independent prognostic factor for advanced nasopharyngeal carcinoma.

BMC Cancer 2020 Mar 21;20(1):240. Epub 2020 Mar 21.

Stem Cell & Tissue Re-engineering Program, Research Centre, King Faisal Specialist Hospital and Research Centre, PO, Box 3354; Riyadh 11211; (MBC 03), Riyadh, Kingdom of Saudi Arabia.

Background: Locally advanced nasopharyngeal carcinoma (LA-NPC) is a relatively rare disease in the west but more common in East Asia and areas of the Middle East like Saudi Arabia. Despite the advances in radiation therapy techniques, some patients relapse after treatment. In the coming era of cancer immunotherapy, prognostic factors for LA-NPC need to be further defined using immune-relevant markers. Several markers are available; however, the most robust and accessible/affordable marker is not well-defined.

Methods: Retrospectively, tumor-infiltrating lymphocytes (TIL), their subsets as well as tumoral PD-L1 expression were analyzed in tumor tissues from 63 LA-NPC patients treated with platinum-based concurrent chemo-radiotherapy (CCRT) in addition to 20 cases with metastatic (MET) disease. Immunostaining was done using a validated and fully automated system. Scoring was done by two independent pathologists and results were compared.

Results: There was no statistical difference between LA-NPC and MET disease in terms of CD3+, CD8+ TIL infiltration, or tumoral PD-L1 expression. In LA-NPC, low CD3+ TIL infiltration highly correlated with shorter disease-free survival (DFS, HR = 8.5, p = < 0.001) and overall survival (OS, HR = 13, p = 0.015) with substantial agreement between scoring pathologists. A similar correlation was found between low CD8+ TIL and survival. Correlation of total TIL was significant with DFS (HR = 4.0, p = 0.008), borderline with OS and the correlation was dependent on the scoring pathologist. Having histological WHO type I&II correlated significantly with shorter DFS (HR 4.03, p = 0.008) and low CD3+ TIL (p = 0.009). Subgroup analysis of LA-NPC that included undifferentiated type (WHO type III) cases only (n = 58), showed a strong correlation between low CD3+ TIL and shorter DFS (HR = 7.2, p = < 0.001) and OS (HR = 17.3, p = 0.008). PD-L1 was expressed in 72% of type III LA-NPC cases while lacking PD-L1 expression correlated with shorter OS (HR = 6.1, p = 0.031). Patients with a combination of low CD3+ TIL and lack of PD-L1 expression had the worst OS (p < 0.001).

Conclusions: CD3+ TIL is promising as a robust and independent prognostic marker for DFS and OS of LA-NPC patients treated with platinum-based CCRT. We would suggest the use of CD3 + TIL as a stratifying factor for LA-NPC, which warrants further validation in prospective trials.
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http://dx.doi.org/10.1186/s12885-020-06757-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7227256PMC
March 2020

Telomerase reverse transcriptase promoter mutations in cancers derived from multiple organ sites among middle eastern population.

Genomics 2020 03 31;112(2):1746-1753. Epub 2019 Oct 31.

Human Cancer Genomic Research, King Faisal Specialist Hospital and Research Center, Riyadh 11211, Saudi Arabia. Electronic address:

Sanger Sequencing and immunohistochemistry was employed to investigate the TERT promoter mutations and TERT protein expression with their association to clinicopathological characteristics in over 2200 samples of Middle Eastern origin from 13 different types of cancers. The TERT promoter mutations were most frequently present in bladder cancer (68.6%), followed by central nervous system tumors (28.7%), thyroid cancer (15.4%), prostate cancer (9.3%), endometrial carcinoma (3.7%), rhabdomyosarcoma (1.4%), colorectal cancer (1%), epithelial ovarian carcinoma (0.7%) and breast cancer (0.7%). No mutations were observed in other types of cancers. In bladder cancer, we found significant inverse association with metastasis and a trend to good survival in patients with TERT mutations. In gliomas, TERT promoter mutations predicted poor prognosis. In thyroid cancer, high frequency of TERT mutation was observed in poorly differentiated carcinoma. In addition, TERT promoter mutations were associated with aggressive markers and poor outcome in follicular thyroid carcinomas.
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http://dx.doi.org/10.1016/j.ygeno.2019.09.017DOI Listing
March 2020

Organizing pneumonia secondary to cetuximab in a patient with colorectal cancer.

Monaldi Arch Chest Dis 2019 Sep 11;89(3). Epub 2019 Sep 11.

Department of Medicine, Qassim University; Department of Medicine, Section of Pulmonary, King Faisal Specialist Hospital and Research Center, Riyadh.

Organizing pneumonia (OP) may be idiopathic or secondary to a variety of causes including drugs. OP and other forms of pulmonary toxicity secondary to cetuximab, however, have been described rarely. It is paramount to recognize and differentiate OP from other common conditions that cancer patients are prone to such as infection and pulmonary embolism. A 69-year-old man with colorectal cancer received ten cycles of palliative chemotherapy [FOLFIRI (5-Fluorouracil, Leucovorin, Irinotecan) and cetuximab] with clinical and radiological response. He developed dyspnea following cycle 4, then 6 weeks later presented with cough, fever, tachypnea, hypoxia, bilateral crackles and diffuse pulmonary shadows. He was started on antibiotics but his condition deteriorated further. Cultures, including blood and bronchioalveolar lavage, grew no pathogens and molecular analysis and cytology for bacteria viruses were negative. Trans-bronchial biopsy was consistent with organizing pneumonia. Treatment with corticosteroids resulted in dramatic clinical and radiological resolution with normalization of gas exchange and pulmonary function. Corticosteroids were stopped and he was restarted on FOLFIRI and remained well with no relapse over a year of follow up. Although pulmonary toxicity secondary to cetuximab is uncommon, it is important to recognize, as it may be associated with poor prognosis. To the best of our knowledge, this is the first report of OP attributed to cetuximab with histopathological evidence.
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http://dx.doi.org/10.4081/monaldi.2019.1074DOI Listing
September 2019

An atypical pulmonary fibrosis is associated with co-inheritance of mutations in the calcium binding protein genes and .

Eur Respir J 2019 07 18;54(1). Epub 2019 Jul 18.

Dept of Cell Biology, King Faisal Specialist Hospital and Research Centre, Riyadh, Saudi Arabia

Background: Pulmonary fibrosis is one of the leading indications for lung transplantation. The disease, which is of unknown aetiology, can be progressive, resulting in distortion of the extracellular matrix (ECM), inflammation, fibrosis and eventual death.

Methods: 13 patients born to consanguineous parents from two unrelated families presenting with interstitial lung disease were clinically investigated. Nine patients developed respiratory failure and subsequently died. Molecular genetic investigations were performed on patients' whole blood or archived tissues, and cell biological investigations were performed on patient-derived fibroblasts.

Results: The combination of a unique pattern of early-onset lung fibrosis (at 12-15 years old) with distinctive radiological findings, including 1) traction bronchiectasis, 2) intralobular septal thickening, 3) shrinkage of the secondary pulmonary lobules mainly around the bronchovascular bundles and 4) early type 2 respiratory failure (elevated blood carbon dioxide levels), represents a novel clinical subtype of familial pulmonary fibrosis. Molecular genetic investigation of families revealed a hypomorphic variant in and a novel truncating mutation in , both segregating with the disease in an autosomal recessive manner. Family members that were either heterozygous carriers or wild-type normal for both variants were unaffected. Analysis of patient-derived fibroblasts demonstrated significantly reduced S100A3 and S100A13 expression. Further analysis demonstrated aberrant intracellular calcium homeostasis, mitochondrial dysregulation and differential expression of ECM components.

Conclusion: Our data demonstrate that digenic inheritance of mutations in and underlie the pathophysiology of pulmonary fibrosis associated with a significant reduction of both proteins, which suggests a calcium-dependent therapeutic approach for management of the disease.
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http://dx.doi.org/10.1183/13993003.02041-2018DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6637284PMC
July 2019

Pneumonia in HIV-Positive and HIV-Negative Patients: A Single-Center Retrospective Study.

Tanaffos 2019 Mar;18(3):238-243

Department of Medicine, King Faisal Specialist Hospital and Research Centre, Riyadh, Saudi Arabia.

Background: To describe the clinical presentations, treatment regimen, and outcomes of pneumonia (PJP) among immunocompromised patients at King Faisal Specialist Hospital and Research Center in Saudi Arabia.

Materials And Methods: In this retrospective cohort study, patients with a laboratory-confirmed diagnosis of PJP were included.

Results: During the study, 42 patients with confirmed PJP were identified. Twenty (48%) patients were HIV-infected, while 22 (52%) were HIV negative. The median T-cell count (CD ) was below 50 cells/mL in HIV patients with PJP at the time of HIV and PJP diagnoses. Graft rejection, cytomegalovirus (CMV) reactivation, and lymphopenia were associated with the development of PJP in transplant recipients; and high-dose steroids for non-transplant patients. The all-cause mortality at 90 days was lower in individuals with HIV-related PJP, compared to those with other predisposing conditions (10% and 32%, respectively; P=0.085). No specific risk factors were independently associated with the increased risk of mortality.

Conclusion: PJP remains an important cause of morbidity and mortality in immunocompromised patients, with a higher mortality rate reported in non-HIV patients.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7210573PMC
March 2019

Idiopathic pleuroparenchymal fibroelastosis: The first case to be managed with a successful lung transplant at King Faisal Specialist Hospital and Research Center, Riyadh.

Ann Thorac Med 2019 Jan-Mar;14(1):94-98

Section of Pulmonary Medicine, King Faisal Specialist Hospital and Research Center, Riyadh, Saudi Arabia.

Idiopathic Pleuro-Parenchymal Fibroelsatosis (PPFE) is a rare, progressive and recently recognized subtype of idiopathic interstitial lung disease with no recorded successful treatment other than lung transplant. We report a case of idiopathic pleuroparenchymal fibroelastosis from the Middle East, managed successfully by bilateral lung transplant performed on a 26 year old Saudi male.
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http://dx.doi.org/10.4103/atm.ATM_106_18DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6341862PMC
February 2019

Huge primary mediastinal synovial sarcoma fully occupying the right hemithorax.

J Cancer Res Ther 2018 Apr-Jun;14(3):682-686

Department of Surgery, College of Medicine, Alfaisal University; Department of Surgery, King Faisal Specialist Hospital and Research Center, Riyadh, Saudi Arabia.

Primary mediastinal synovial sarcomas are exceedingly uncommon tumors. Herein, we present the case of primary mediastinal synovial sarcoma (monophasic spindle cell-shaped variant) fully occupying the right hemithorax in a 37-year-old woman who presented to clinic with a 2-month history of right-sided chest pain and shortness of breath. Although extremely rare, however, synovial sarcoma should be considered in the differential diagnosis of all monophasic and biphasic spindle cell neoplasms of the mediastinum. Despite molecular testing for (t[x; 18] [p11.2; q11.2]) is characteristically positive in 90% of synovial sarcoma cases, it is not routinely done. Histopathological and immunohistochemical analyses can greatly confirm the diagnosis. Optimal surgical resection is the standard of care. Adjuvant therapy (radiotherapy and/or chemotherapy) is indicated in inoperable advanced disease or unachieved surgical tumor-free surgical margins. Prognosis is poor with a 5-year overall survival (OS) rate of 35.7%. Early diagnosis and prompt appropriate management yield better disease-free and OS rates.
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http://dx.doi.org/10.4103/0973-1482.172137DOI Listing
November 2018

Aspergillus flavus native valve endocarditis following combined liver and renal transplantation: Case report and review of the literature.

Transpl Infect Dis 2018 Aug 26;20(4):e12891. Epub 2018 Apr 26.

Section of Infectious Diseases, Department of Medicine, King Faisal Specialist Hospital and Research Centre, Riyadh, Saudi Arabia.

Aspergillus endocarditis is a rare infection that occurs most commonly in patients with prior cardiac surgery but cases in post-transplant recipients without prior cardiac surgery have been reported. Diagnosis is often delayed and requires high index of suspicion. We here report a case of Aspergillus endocarditis in solid organ transplant recipient.
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http://dx.doi.org/10.1111/tid.12891DOI Listing
August 2018

Benign Pericardial Schwannoma: Case Report and Summary of Previously Reported Cases.

Am J Case Rep 2018 Jan 24;19:90-94. Epub 2018 Jan 24.

College of Medicine, Alfaisal University, Riyadh, Saudi Arabia.

BACKGROUND Primary pericardial tumors have a prevalence of between 6.7% and 12.8% of all tumors arising in the cardiac region. Pericardial schwannoma is a rare entity. It arises from the cardiac plexus and vagus nerve innervating the heart. Most of the reported cases, have presented with benign behavior, however, in rare situations, they can undergo transformation to malignant behavior When comparing the prevalence of cardiac tumors to that of pericardial tumors, the latter is much lower in occurrence. A review of English literature identified six pericardial schwannoma cases. CASE REPORT We present a case of a 30-year-old male patient who presented to our center with the chief complaint of six months of gradually progressive left chest pain. His past medical history (PMH) was positive for panic attacks (for which he was taking beta-blockers), paroxysmal tachycardia, sweating, and irritability. A computed tomography chest scan was done; a differential diagnosis of paraganglioma was suggested. However, histopathological examination confirmed the pericardial mass was a schwannoma. The patient was surgically treated by thoracotomy to resect the lesion. CONCLUSIONS This case adds to the existing limited literature on pericardial schwannoma as the seventh reported case. Neurogenic cardiac tumors; our case marks the second case reported to occur in the subcarinal area near the left atrium.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5789752PMC
http://dx.doi.org/10.12659/ajcr.907408DOI Listing
January 2018

Bilateral Mesenchymal Hamartoma of the Chest Wall in a 3-Month-Old Boy: A Case Report and Review of the Literature.

Case Rep Pathol 2017 16;2017:2876342. Epub 2017 Aug 16.

Department of Pathology and Laboratory Medicine (MBC-10), King Faisal Specialist Hospital and Research Center (KFSH&RC), P.O. Box 3354, Riyadh 11211, Saudi Arabia.

Mesenchymal hamartoma of the chest wall is a well-recognized but extremely rare entity. This entity is believed to be benign with no propensity for invasion or metastasis. Although the lesion manifests with alarming aggressive clinical, radiological, and histological features, it is considered benign and carries an excellent outcome. Therefore it is important to recognize this benign entity to avoid the possible misdiagnosis of malignancy and the unnecessary use of chemotherapy. We present a case of bilateral multifocal mesenchymal hamartomas of the chest wall in a male infant and a literature review of this entity. Our aim is to improve the awareness of this condition and highlight its benign behavior and satisfactory outcome following complete surgical resection.
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http://dx.doi.org/10.1155/2017/2876342DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5576409PMC
August 2017

Immature mediastinal teratoma with unusual histopathology: A case report of multi-lineage, somatic-type malignant transformation and a review of the literature.

Medicine (Baltimore) 2016 Jun;95(26):e3378

aCollege of Medicine, Alfaisal University bDepartment of Pathology and Laboratory Medicine cDepartment of Medical Oncology, Oncology Center dDivision of Thoracic Surgery, Department of Surgery, King Faisal Specialist Hospital and Research Center (KFSH&RC), Riyadh, Saudi Arabia.

Germ cell tumors (GCTs) represent a well-recognized group of heterogeneous neoplasms with diverse clinical, histopathological, diagnostic, and prognostic characteristics. We present a rare case of a locally aggressive, chemotherapy-resistant immature mediastinal teratoma with a peculiar histological finding of a multilineage somatic-type malignant degeneration. A 21-year-old male patient presented with a 3-week history of persistent, blood-tinged productive cough and shortness of breath. A contrast-enhanced computed tomography (CT) scan of the chest showed a heterogeneous mass occupying the right hemithorax and abutting on adjacent structures. CT-guided biopsy was consistent with immature teratoma. Combination chemotherapy with bleomycin, etoposide, and cisplatin was initiated, albeit without success; the mass showed interval progression in size, and surgical resection through clamshell incision was performed. Histological assessment of the resected mass confirmed the diagnosis of immature teratoma and revealed an extensive multilineage malignant differentiation into sarcomatous, carcinomatous, and melanomatous components. The patient underwent an uneventful recovery but presented 2 months later with extensive liver and bone melanomatous metastases. In this report, relevant findings from the literature are also highlighted. Despite being exceptionally rare, such tumors carry poor prognosis. Understanding the clinicopathological characteristics and biological behavior of such tumors may provide an insight into interventions tailored to improve the otherwise dismal disease outlook.
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http://dx.doi.org/10.1097/MD.0000000000003378DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4937890PMC
June 2016

Cancer Vaccines: Past, Present, and Future.

Adv Anat Pathol 2016 May;23(3):180-91

*Department of Pathology and Laboratory Medicine †Oncology Center, King Faisal Specialist Hospital and Research Centre ‡Department of Pathology and Laboratory Medicine, King Abdulaziz Medical City, Riyadh, Kingdom of Saudi Arabia.

Cancer is a common and potentially deadly disease. Some of the cancers may be difficult to treat by conventional means such as surgery, radiation, and chemotherapy, but may be controlled by the stimulation of the immune response of the body with the help of cancer vaccines. The use of vaccines for preventing infections by oncogenic viruses such as hepatitis B virus and human papilloma virus has been extremely successful in reducing the incidence of cancers resulting from these infections. The use of vaccines for treating cancers that are not due to viral infections and that are already established is currently the object of numerous clinical trials. Several types of cancer vaccines are being tried. These include antigen vaccines, tumor cell vaccines, dendritic vaccines, deoxyribonucleic acid vaccines, and viral vector vaccines. The development of these therapeutic vaccines is proving difficult with only 1 recent success. However, there is significant enthusiasm and optimism regarding the development of effective therapeutic vaccines stemming from the fact that our understanding regarding the cancer immunology is considerably enhanced in recent years. This expanded knowledge regarding the mechanisms that cancers use to escape the immune system is likely to open new avenues in modulating the immune response to cancer, thus enhancing the effectiveness of therapeutic cancer vaccines.
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http://dx.doi.org/10.1097/PAP.0000000000000116DOI Listing
May 2016

A substitution mutation in cardiac ubiquitin ligase, FBXO32, is associated with an autosomal recessive form of dilated cardiomyopathy.

BMC Med Genet 2016 Jan 14;17. Epub 2016 Jan 14.

Heart Center, King Faisal Specialist Hospital & Research Centre, Riyadh, Saudi Arabia.

Background: Familial dilated cardiomyopathy (DCM) is genetically heterogeneous. Mutations in more than 40 genes have been identified in familial cases, mostly inherited in an autosomal dominant pattern. DCM due to recessive mutations is rarely observed. In consanguineous families, homozygosity mapping and whole exome sequencing (WES) can be utilized to identify the genetic defects in recessively inherited DCM.

Methods: In a consanguineous family with four affected siblings with severe DCM, we combined homozygosity mapping, linkage analysis and WES, to uncover the genetic defect.

Results: A region of homozygosity (ROH) on chromosome 8q24.13-24.23 was found to be shared by all of the four affected siblings. WES detected ~47,000 variants that were filtered to a homozygous mutation (p.Gly243Arg) in the FBXO32 gene, located within the identified ROH. The mutation segregated with the phenotype, replaced a highly-conserved amino acid, and was not detected in 1986 ethnically-matched chromosomes. FBXO32, which encodes a muscle-specific ubiquitin ligase, has been implicated in the pathogenesis of cardiomyopathy through the ubiquitin proteasome system (UPS). In addition, FBXO32-knockout mice manifest with cardiomyopathy. Screening the index patient for all of the WES variants in 48 genes known to be implicated in hypertrophic and dilated cardiomyopathy was negative.

Conclusions: Our data suggest that FBXO32 is a candidate gene for recessive DCM. Acting as a cardiac ubiquitin ligase, mutated FBXO32 could perturb the degradation of target proteins in the UPS, the impairment of which has been observed in cardiomyopathy. Our work proposes that genes encoding other ubiquitin ligases could also be implicated in familial cardiomyopathy.
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http://dx.doi.org/10.1186/s12881-016-0267-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4714499PMC
January 2016

Duodenal Obstruction as First Presentation of Metastatic Breast Cancer.

Case Rep Surg 2015 21;2015:605719. Epub 2015 Jul 21.

Department of Surgical Oncology, King Faisal Specialist Hospital and Research Center (KFSH&RC), P.O. Box 3354, Riyadh 11211, Saudi Arabia.

The metastatic breast cancer to the duodenum is rare in spite of common breast cancer. In this paper, we are reporting a rare case of 50-year-old lady who presented with intestinal obstruction as result of metastatic breast cancer which completely responds to chemotherapy. The tumor presents again as brain metastasis after stop of Herceptin due to cardiac toxicity.
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http://dx.doi.org/10.1155/2015/605719DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4523720PMC
August 2015

Splenic metastasis arising from recurrent nasopharyngeal carcinoma: a rare case report.

Indian J Pathol Microbiol 2015 Apr-Jun;58(2):256-8

Department of Surgery, College of Medicine, Alfaisal University, Riyadh; Department of Surgical Oncology, Oncology Center, King Faisal Specialist Hospital and Research Center, Riyadh, Saudi Arabia.

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http://dx.doi.org/10.4103/0377-4929.155350DOI Listing
April 2016

Pulmonary epitheloid hemangioendothelioma PET CT findings and review of literature.

Ann Saudi Med 2014 Sep-Oct;34(5):447-9

Dr. Imran Yaqoob Nizami, Organ Transplant Center, MBC 96, King Faisal Specialist Hospital and Research Centre, PO Box 3354 Riyadh 11211, Saudi Arabia, T: 966-11-4647272 loc 76164, F: 966-11-4647272 loc 76167,

We describe a case of pulmonary epitheloid hemangioendothelioma (PEH) in a 13 years old girl, the aggressive nature of the tumor in this particular case and the PET CT findings. PEH are rare tumors of vascular origin, first described by Dial and Liebow in 1975. This is an uncommon pulmonary neoplasm, 4 times more common in young women. This tumor can affect multiple organs (lung, liver, bones and soft tissue, skin, heart, central nervous system). However lung and liver represent 2 main locations. Clinical manifestations are variable; typically patients are asymptomatic, and PEH is detected on routine chest radiographs as bilateral small (1 cm or less) nodules in the lungs Diagnosis usually requires a surgical lung biopsy. The prognosis is very unpredictable, with life expectancy ranging from 1 to 15 years. The tumor is usually considered as low to intermediate grade sarcoma. There is no single effective treatment however spontaneous remissions and aggressive behavior has been described.
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http://dx.doi.org/10.5144/0256-4947.2014.447DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6074559PMC
November 2015

Control of histone H3 phosphorylation by CaMKIIδ in response to haemodynamic cardiac stress.

J Pathol 2015 Mar 17;235(4):606-18. Epub 2014 Dec 17.

Cardiovascular Research Programme, King Faisal Specialist Hospital and Research Centre, Riyadh, Kingdom of Saudi Arabia.

Heart failure is associated with the reactivation of a fetal cardiac gene programme that has become a hallmark of cardiac hypertrophy and maladaptive ventricular remodelling, yet the mechanisms that regulate this transcriptional reprogramming are not fully understood. Using mice with genetic ablation of calcium/calmodulin-dependent protein kinase II δ (CaMKIIδ), which are resistant to pathological cardiac stress, we show that CaMKIIδ regulates the phosphorylation of histone H3 at serine-10 during pressure overload hypertrophy. H3 S10 phosphorylation is strongly increased in the adult mouse heart in the early phase of cardiac hypertrophy and remains detectable during cardiac decompensation. This response correlates with up-regulation of CaMKIIδ and increased expression of transcriptional drivers of pathological cardiac hypertrophy and of fetal cardiac genes. Similar changes are detected in patients with end-stage heart failure, where CaMKIIδ specifically interacts with phospho-H3. Robust H3 phosphorylation is detected in both adult ventricular myocytes and in non-cardiac cells in the stressed myocardium, and these signals are abolished in CaMKIIδ-deficient mice after pressure overload. Mechanistically, fetal cardiac genes are activated by increased recruitment of CaMKIIδ and enhanced H3 phosphorylation at hypertrophic promoter regions, both in mice and in human failing hearts, and this response is blunted in CaMKIIδ-deficient mice under stress. We also document that the chaperone protein 14-3-3 binds phosphorylated H3 in response to stress, allowing proper elongation of fetal cardiac genes by RNA polymerase II (RNAPII), as well as elongation of transcription factors regulating cardiac hypertrophy. These processes are impaired in CaMKIIδ-KO mice after pathological stress. The findings reveal a novel in vivo function of CaMKIIδ in regulating H3 phosphorylation and suggest a novel epigenetic mechanism by which CaMKIIδ controls cardiac hypertrophy.
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http://dx.doi.org/10.1002/path.4489DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4383650PMC
March 2015

Primary pleural benign myxoid schwannoma in an 18-year-old female: a case report and literature review.

Case Rep Oncol Med 2014 4;2014:296961. Epub 2014 Mar 4.

Department of Pathology and Laboratory Medicine, King Faisal Specialist Hospital and Research Center, P.O. Box 3354, Riyadh 11211, Saudi Arabia.

Pleural schwannomas are exceedingly rare neoplasms of the thoracic cavity. To the best of our knowledge, less than 20 cases have been reported in the medical English literature. Herein, we report the case of primary pleural benign myxoid schwannoma in an 18-year-old female. The patient was originally referred to our tertiary care hospital for further management of right adrenal gland mass. Physical examination and all laboratory tests were normal. Contrast-enhanced computed tomography scan showed a 4.2 × 3.2 cm, heterogeneous noncalcified mass involving the right adrenal gland region. The right renal vein and inferior vena cava were intact. There was no pleural effusion, ascites, or lymphadenopathy. No pelvic masses were identified. Patient was scheduled for surgical resection. On laparotomy, the mass was not found in its radiologically expected location, and the right kidney and right adrenal gland were intact. The right-sided lower part of diaphragm was opened, and the mass was interestingly found inside the thorax attached to the pleura, and resected successfully. A final histopathological diagnosis of primary pleural benign myxoid schwannoma was established. At a postoperative 6-month followup, there was no radiological evidence of tumor recurrence. Furthermore, literature review on pleural schwannomas is also presented.
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http://dx.doi.org/10.1155/2014/296961DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3970368PMC
April 2014

Pancreatic tail schwannoma in a 44-year-old male: a case report and literature review.

Case Rep Oncol Med 2013 25;2013:416713. Epub 2013 Nov 25.

Department of Pathology and Laboratory Medicine, King Faisal Specialist Hospital and Research Center (KFSH&RC), P.O. Box 3354, Riyadh 11211, Saudi Arabia.

Pancreatic schwannomas are exceedingly uncommon neoplasms. According to a recent study in 2012, less than 50 cases of pancreatic schwannoma have been described in the English literature over the past thirty years. The vast majority of pancreatic schwannomas take place in the head and body of pancreas, respectively. Herein, we report the case of pancreatic tail ancient schwannoma in a 44-year-old man who presented with a 4-month history of epigastric pain. On physical examination, epigastric region was moderately tender to palpation without evidence of a palpable mass. All laboratory tests were normal. Contrast-enhanced computed tomography (CT) scan showed a 9.2 × 9.5 × 11.5 cm, huge, and well-defined left suprarenal mass arising either from adrenal gland, pancreas, or retroperitoneum. The mass demonstrated mild heterogeneous enhancement with central cystic/necrotic area. No evidence of distant metastasis was identified. At laparoscopy, the mass was noticed to originate from pancreatic tail. Patient underwent surgical resection of pancreatic tail. Microscopic and immunohistochemical examination of the pancreatic tail specimen showed ancient schwannoma. Patient received no adjuvant therapy. At a postoperative 6-month followup, patient was completely asymptomatic and CT scan imaging showed no evidence of tumor recurrence. Moreover, a literature review on pancreatic schwannomas is presented.
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http://dx.doi.org/10.1155/2013/416713DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3859158PMC
December 2013

Primary pleural angiosarcoma in a 63-year-old gentleman.

Case Rep Pulmonol 2013 13;2013:974567. Epub 2013 Jun 13.

College of Medicine, Alfaisal University, P.O. Box 50927, Riyadh 11533, Saudi Arabia.

Primary pleural angiosarcomas are extremely rare. As of 2010, only around 50 case reports have been documented in the literature. Herein, we report the case of a 63-year-old gentleman who presented with a 3-month history of right-sided chest pain, dyspnea, and hemoptysis. Chest X-ray showed bilateral pleural effusion with partial bibasilar atelectasis. Ultrasound-guided thoracocentesis showed bloody and exudative pleural fluid. Cytologic examination was negative for malignant cells. An abdominal contrast-enhanced computed tomography (CT) scan showed two right diaphragmatic pleural masses. Whole-body positron emission tomography/computed tomography (PET/CT) scan showed two hypermetabolic fluorodeoxyglucose- (FDG-) avid lesions involving the right diaphragmatic pleura. CT-guided needle-core biopsy was performed and histopathological examination showed neoplastic cells growing mainly in sheets with focal areas suggestive of vascular spaces lined by cytologically malignant epithelioid cells. Immunohistochemical analysis showed strong positivity for vimentin, CD31, CD68, and Fli-1 markers. The overall pathological and immunohistochemical features supported the diagnosis of epithelioid angiosarcoma. The patient was scheduled for surgery in three weeks. Unfortunately, the patient died after one week after discharge secondary to pulseless ventricular tachycardia arrest followed by asystole. Moreover, we also present a brief literature review on pleural angiosarcoma.
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http://dx.doi.org/10.1155/2013/974567DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3697234PMC
July 2013

Malignant glomus tumor (glomangiosarcoma) of intestinal ileum: a rare case report.

Case Rep Pathol 2013 8;2013:305321. Epub 2013 Apr 8.

College of Medicine, Alfaisal University, P.O. Box 50927, Riyadh 11533, Saudi Arabia.

Glomus tumors are rare mesenchymal neoplastic lesions arising from glomus bodies that are involved in skin thermoregulation. They are mostly benign tumors, and malignant variants have been rarely reported. The subungual zones of fingers and toes are the most frequent sites of observation. Glomus tumors arising in visceral organs of the gastrointestinal tract are exceedingly rare. Stomach antrum and intestinal duodenum are the most frequent organs involved. No single case of glomus tumor involving intestinal ileum has been previously reported in the English medical literature. To the best of our knowledge, we report the first case of malignant glomus tumor (glomangiosarcoma) of intestinal ileum in a 29-year-old female patient who presented with a 1-month history of a tender pelvi-abdominal mass, constipation, vomiting, and melena. The intestinal ileum glomus tumor was resected, and histopathological diagnosis was consistent with glomangiosarcoma. A postoperative 6-month followup failed to show any evidence of tumor recurrence.
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http://dx.doi.org/10.1155/2013/305321DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3638502PMC
May 2013

Recessively inherited severe aortic aneurysm caused by mutated EFEMP2.

Am J Cardiol 2012 Jun 20;109(11):1677-80. Epub 2012 Mar 20.

Cardiovascular Genetics Program, King Faisal Specialist Hospital and Research Centre, Riyadh, Saudi Arabia.

Familial aortic aneurysm (AA) is mostly inherited as an autosomal dominant disorder. However, recessively inherited AA has also been observed but in association with skin manifestations of cutis laxa, which is caused by a mutated EFEMP2 gene. In the present study, we recruited 9 patients, from 4 unrelated consanguineous families, with recessively inherited AA. The index cases, their parents, and siblings underwent clinical evaluation and cardiac imaging. In the affected subjects, the clinical presentation ranged from sweating and cyanosis at 3 months of age to incidental findings in an asymptomatic adult. The echocardiogram revealed a wide spectrum of severity of the AA, with a Z-score varying from 5 to 33. Intrafamilial variability was also evident; 2 unrelated subjects were detected at 17 and 20 years of age through family screening. The skin manifestations of cutis laxa were not found in any patient. In 1 family, genome-wide single-nucleotide polymorphism analysis detected a homozygous block, shared by 2 affected siblings, on chromosome 11 at q13. Sequence analysis of EFEMP2, located on chromosome 11 at q13, identified a novel homozygous mutation (p.E161K) in all 9 affected subjects. In this largest cohort of reported patients with a mutated EFEMP2 gene, we illustrate the phenotypic spectrum of inherited AA due to a novel EFEMP2 mutation. In conclusion, our work suggests that in families with apparently recessively inherited AA, molecular analysis of EFEMP2 gene might be warranted.
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http://dx.doi.org/10.1016/j.amjcard.2012.01.394DOI Listing
June 2012

Mitochondrial DNA related cardiomyopathies.

Front Biosci (Elite Ed) 2012 Jan 1;4:1706-16. Epub 2012 Jan 1.

Department of Lab. Medicine and Pathology, University of Alberta, Edmonton, Alberta, Canada.

Cardiomyopathies are a heterogeneous group of diseases characterized by impaired heart muscle function. Over the last few years, interest in mitochondrial cardiomyopathies has been galvanized by a number of significant molecular biology discoveries. There is overwhelming evidence that genetic factors play a pivotal role in the pathogenesis of primary cardiomyopathies. Mitochondrial cardiomyopathy is a cardiomyopathy in which the clinical and pathological phenotype result from mitochondrial diseases due to pathogenic mutation in both mitochondrial and/or nuclear genes causing defects in the oxidative phosphorylation system (OXPHOS) in cardiac muscle. We review and provide an update of the current concepts, molecular genetics, clinical features, pathology, diagnostic modalities, and latest therapeutic options in mitochondrial cardiomyopathies specifically caused by mutations in the mitochondrial DNA (mtDNA).
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http://dx.doi.org/10.2741/491DOI Listing
January 2012

Detection of c-KIT and PDGFRA gene mutations in gastrointestinal stromal tumors: comparison of DHPLC and DNA sequencing methods using a single population-based cohort.

Am J Clin Pathol 2010 Jan;133(1):149-55

Department of Laboratory Medicine, Cross Cancer Institute and University of Alberta, Edmonton, Canada.

Mutational analysis of c-KIT or PDGFRA has become an important laboratory assay for patients with gastrointestinal stromal tumors (GISTs) because the results are useful in predicting the responsiveness to imatinib. To assess the diagnostic usefulness of denaturing high-pressure liquid chromatography (DHPLC) in this setting, we performed DHPLC and DNA sequencing to study exons 9, 11, 13, and 17 of c-KIT and exons 12 and 18 of PDGFRA in 54 consecutive cases of GIST collected from a single population. Most (40/54 [74%]) carried c-KIT mutations, and 7 (13%) carried PDGFRA mutations. These results were similar to those described in the literature. It is important to note that DHPLC was found to be highly sensitive, detecting all of the mutations in these 6 exons that were identified by DNA sequencing. Our data suggest that DHPLC is a cost-effective, rapid, and sensitive test for screening for mutations of c-KIT and PDGFRA in GISTs.
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http://dx.doi.org/10.1309/AJCP1FNW7RGZFTYUDOI Listing
January 2010

Expression of B7-H1 in breast cancer patients is strongly associated with high proliferative Ki-67-expressing tumor cells.

Int J Cancer 2007 Aug;121(4):751-8

Tumor Immunology Unit, Department Biological and Medical Research, King Faisal Specialist Hospital and Research Center, MBC 03, P.O. Box 3354, Riyadh 11211, Saudi Arabia.

B7-H1, a co-inhibitory molecule, plays a role in immune escape of tumors. We have shown previously the expression of this molecule in breast cancer patients and demonstrated its association with high histological grade, progesterone and estrogen receptor negative status, all of which are known to have direct impact on cell proliferation. In the present work, we investigated the effect of proliferation, as measured by Ki-67 and mitotic count, on the induction of B7-H1. We used H&E stained sections to score for mitotic count in 69 breast cancer patients. Immunohistochemistry was used to investigate B7-H1 and Ki-67 expression. The relationship between B7-H1 induction and cell proliferation was further investigated in primary cultured cells. B7-H1 expression was recorded in patients with a high mitotic index (p = 0.007). There was a high significant correlation between B7-H1 expression and the presence of the proliferative marker Ki-67 (p < 0.001) indicating the association of proliferation with B7-H1 induction. Furthermore, B7-H1 was gradually induced in proliferating cells of 8/8 primary cell lines as measured by Ki-67 expression. Finally, B7-H1 was downregulated in quiescent cells and upregulated in cells stimulated with a mitogen confirming the association of proliferation with the induction of B7-H1. We have shown for the first time a direct association between proliferation and the expression of B7-H1 in breast cancer patients. The relationship between B7-H1 induction and cell proliferation was also thoroughly investigated in vitro, in which a strong link between B7-H1 expression and the presence of the proliferative Ki-67 marker was clearly demonstrated.
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http://dx.doi.org/10.1002/ijc.22703DOI Listing
August 2007

The B7-H1 (PD-L1) T lymphocyte-inhibitory molecule is expressed in breast cancer patients with infiltrating ductal carcinoma: correlation with important high-risk prognostic factors.

Neoplasia 2006 Mar;8(3):190-8

Tumor Immunology Unit, Department of Biological and Medical Research, King Faisal Specialist Hospital and Research Center, PO Box 3354, Riyadh 11211, Saudi Arabia.

B7-H1 molecule increases the apoptosis of tumor-reactive T lymphocytes and reduces their immunogenicity. Breast cancer is the second most common cause of mortality after lung cancer. Direct evidence linking B7-H1 with cancer has been shown in several malignancies; however, its expression in breast cancer has not been investigated. We used immunohistochemistry to investigate the expression of the B7-H1 molecule in 44 breast cancer specimens and to study its correlation with patients' clinicopathological parameters. The expression of B7-H1 was shown in 22 of 44 patients and was not restricted to the tumor epithelium (15 of 44, 34% in tumor cells), but was also expressed by tumor-infiltrating lymphocytes (TIL; 18 of 44, 41%). Interestingly, intratumor expression of B7-H1 was significantly associated with histologic grade III-negative (P = .012), estrogen receptor-negative (P = .036), and progesterone receptor-negative (P = .040) patients. In addition, the expression of B7-H1 in TIL was associated with large tumor size (P = .042), histologic grade III (P = .015), positivity of Her2/neu status (P = .019), and severe tumor lymphocyte infiltration (P = .001). Taken together, these data suggest that B7-H1 may be an important risk factor in breast cancer patients and may represent a potential immunotherapeutic target using monoclonal antibody against the B7-H1 molecule.
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http://dx.doi.org/10.1593/neo.05733DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1578520PMC
March 2006