Mansur ibn Ilyas Shirazi (1380-1422 AD), a pioneer of neuroanatomy.

History of anatomy is as long as the history of medicine itself. Development of this basic science was not possible without the dedicative effort of those physicians and scholars who were committed to discover the mysteries of human anatomy. In this regard, Iranian scholars played an important role in the development of the anatomical sciences despite the religious limitations in their societies. Mansur ibn Ilyas Shirazi is an Iranian physician of fourteenth century who wrote the first color illustrated anatomical book, Mansur's Anatomy. A considerable portion of the book has been dedicated to the central and peripheral nervous system so that he could be considered as one of the pioneers of neuroanatomy.

Delay in the Diagnosis of APECED: A Case Report and Review of Literature from Iran.

Autoimmune polyendocrinopathy candidiasis ectodermal dystrophy (APECED) syndrome is a rare monogenic autosomal recessive disorder caused by biallelic mutations in the AIRE (autoimmune regulator) gene. Patients with APECED present with heterogeneous endocrine and non-endocrine manifestations. In this study, we report an Iranian patient who presented with Addison disease, chronic mucocutaneous candidiasis, alopecia totalis, keratopathy and asplenia treated as an isolated endocrinopathy for 25 years. In the adulthood, the diagnosis of APECED was made by genetic analysis which demonstrated homozygous nonsense p.R257* (c.769C>T) mutation of AIRE. APECED has been shown to be frequent in some ethnicities including Iranian Jews. Therefore, we reviewed 39 Iranian APECED patients published in the literature. We found that most of the Iranian patients were of Jewish ethnic background and presented hypoparathyroidism, adrenal insufficiency, and candidiasis as the main clinical manifestation.

Susceptibility to mycobacterial disease due to mutations in IL-12Rß1 in three Iranian patients.

In the last decade, autosomal recessive interleukin-12 receptor ß1 (IL-12Rß1) deficiency, the most common cause of Mendelian susceptibility to mycobacterial disease (MSMD), has been diagnosed in a few children and adults with severe tuberculosis in Iran. Here, we report three cases referred to the Immunology, Asthma and Allergy ward at the National Research Institute of Tuberculosis and Lung Diseases (NRITLD) at Masih Daneshvari Hospital from 2012 to 2017 with Mycobacterium tuberculosis and non-tuberculous mycobacteria infections due to defects in IL-12Rß1 but with different clinical manifestations. All three were homozygous for either an IL-12Rß1 missense or nonsense mutation that caused the IL-12Rß1 protein not to be expressed on the cell membrane and completely abolished the cellular response to recombinant IL-12. Our findings suggest that the presence of IL-12Rß1 deficiency should be determined in children with mycobacterial infections at least in countries with a high prevalence of parental consanguinity and in areas endemic for TB like Iran.

Assessment of the EuroSCORE risk scoring system for patients undergoing coronary artery bypass graft surgery in a group of Iranian patients.

BACKGROUND AND AIMS: Previous studies around the world indicated validity and accuracy of European System for Cardiac Operative Risk Evaluation (EuroSCORE) risk scoring system we evaluated the EuroSCORE risk scoring system for patients undergoing coronary artery bypass graft (CABG) surgery in a group of Iranian patients. MATERIALS AND METHODS: In this cohort 2220 patients more than 18 years, who were performed CABG surgery in Massih Daneshvari Hospital, from January 2004 to March 2010 were recruited. Predicted mortality risk scores were calculated using logistic EuroSCORE and Acute Physiology and Chronic Health Evaluation II (APACHE II) and compared with observed mortality. Calibration was measured by the Hosmer-Lemeshow (HL) test and discrimination by using the receiver operating characteristic (ROC) curve area. RESULTS: Of the 2220 patients, in hospital deaths occurred in 270 patients (mortality rate of 12.2%). The accuracy of mortality prediction in the logistic EuroSCORE and APACHE II model was 89.1%; in the local EuroSCORE (logistic) was 91.89%; and in the local EuroSCORE support vector machines (SVM) was 98.6%. The area under curve for ROC curve, was 0.724 (95% confidence interval [CI]: 0.57-0.88) for logistic EuroSCORE; 0.836 (95% CI: 0.731-0.942) for local EuroSCORE (logistic); 0.978 (95% CI: 0.937-1) for Local EuroSCORE (SVM); and 0.832 (95% CI: 0.723-0.941) for APACHE II model. The HL test showed good calibration for the local EuroSCORE (SVM), APACHE II model and local EuroSCORE (logistic) (P = 0.823, P = 0.748 and P = 0.06 respectively); but there was a significant difference between expected and observed mortality according to EuroSCORE model (P = 0.033). CONCLUSION: We detected logistic EuroSCORE risk model is not applicable on Iranian patients undergoing CABG surgery.

Comparison of two durations of triple-drug therapy in patients with uncomplicated brucellosis: A randomized controlled trial.

BACKGROUND: Brucellosis remains the most common zoonotic disease throughout the world and especially in Iran. Several clinical trials have tested different therapeutic regimens for brucellosis, but few have assessed the optimal duration of treatment. METHODS: We performed a randomized controlled trial to compare a triple-drug regimen of doxycycline plus rifampicin for 6 weeks and streptomycin for the first 7 days with doxycycline plus rifampicin for 8 weeks and streptomycin for 7 days in patients with uncomplicated brucellosis in Arak, Iran. The primary outcome measure for the treatment groups was the relapse rate measured at 1, 3, 6, 12, and 24 months after cessation of therapy. RESULTS: Eligible patients were randomized to one of the 2 groups with 72 per arm. We found no significant difference in the relapse rate for the 8-week treatment group compared to the 6-week group (9.7% vs 13.9%). There were no significant differences between the 6-week and 8-week groups regarding the relapse rate, period between clinical presentation and beginning of treatment, and time of relapse. Symptom resolution was achieved in all cases at a median 9.5 days and no cases experienced continuing symptoms after treatment. CONCLUSIONS: Our trial found no significant difference between 6-week and 8-week regimens of doxycycline and rifampicin plus streptomycin for the first 7 days. Further comparative studies with a large sample size should be implemented to achieve a consistent therapeutic regimen for uncomplicated brucellosis, to help identify those who may benefit from longer treatment, and to minimize adverse effects and unnecessary continuation of treatment.

Adverse effects of multidrug-resistant tuberculosis treatment with a standardized regimen: a report from Iran.

Compared with the treatment of drug-sensitive tuberculosis, the treatment of multidrug-resistant tuberculosis (MDR-TB) is more difficult. This study was conducted at the national referral center of tuberculosis in Tehran, Iran, to evaluate adverse drug reactions of treatment of MDR-TB. From 2006 to 2009, all patients admitted into Masih Daneshvari Hospital in Tehran, Iran, for MDR-TB were considered for this study. The standard treatment for MDR-TB consisted of amikacin, prothionamide, ofloxacin, and cycloserine. Ethambutol and pyrazinamide were added to treatment if mycobacterium was sensitive to them. All adverse effects observed in patients were recorded in our registry. Eighty patients were considered in the study; of this cohort, 44 were male and 36 were female. The mean age of patients was 40.64 ± 17.53 years (range, 14-81 years). All patients received standardized therapy for MDR-TB. The major adverse effects included neurologic side effects (depression, convulsions, consciousness, psychosis, suicide; 7.5%), hepatitis (5%), rash (1.3%), renal toxicity (3.8%), and auditory toxicity (14.5%). Those with neurologic side effects had less favorable outcome (P value = 0.038) and risk of death was increased among them (odds ratio, 13.8; 95% confidence interval, 2.2-86.77). Other adverse effects did not show statistical significance in our analysis. A major adverse effect such as neurologic side effects (depression, convulsions, consciousness, and psychosis) can result in an increased chance of death among patients with MDR-TB.

Inflammatory myofibroblastic tumor of the trachea.

This report described a 2-year-old boy who was presented with severe respiratory distress and stridor. Bronchoscopy and CT revealed a mass in the left anterolateral tracheal wall and histopathology showed a tracheal inflammatory myofibroblastic tumor. Initial removal by rigid bronchoscopy resulted in prompt recurrence of the tumor. Therefore, he underwent tracheal surgical resection. A bronchoscopy at 12 months after surgery did not show any recurrence sign.

Update on Immunology of COVID-19 Disease and Potential Strategy for Controlling.

Coronavirus disease 2019 (COVID-19) is caused by a novel form of the coronavirus that caused severe acute respiratory syndrome (SARS). SARS-CoV-2 raised in China and has broadcast to 261 countries globally. SARS-CoV-2 a member of ß-coronavirus family and has an almost matching genome sequence to a bat coronavirus, pointing to the bat as the natural host before it was transmitted to humans. SARS-CoV-2 uses the same receptor, angiotensin-converting enzyme 2 (ACE2) as that used by SARS-CoV and principally infects the respiratory tract. The clinical symptoms of COVID-19 patients include fever, cough and fatigue whilst small populations of patients have gastrointestinal symptoms. The old people and people with underlying metabolic and cardiovascular diseases are more affected to infection and have worse outcomes. These may be associated with acute respiratory distress syndrome (ARDS) and a cytokine storm. In this review, we discuss the pathogenesis and clinical characteristics of disease and the pharmacologic approaches that may control COVID-19.

Blood Purification Techniques, Inflammatory Mediators and Mortality in COVID-19 Patients.

BACKGROUND: Inflammatory mediators are an important component in the pathophysiology of the coronavirus disease 2019 (COVID-19). This study aimed to assess the effects of reducing inflammatory mediators using hemoperfusion (HP) and continuous renal replacement therapy (CRRT) on the mortality of patients with COVID-19. MATERIALS AND METHODS: Twelve patients with confirmed diagnosis of COVID-19 were included. All patients had acute respiratory distress syndrome (ARDS). Patients were divided into three groups, namely, HP, CRRT and HP+CRRT. The primary outcome was mortality and the secondary outcomes were oxygenation and reduction in inflammatory mediators at the end of the study. RESULTS: Patients were not different at baseline in demographics, inflammatory cytokine levels, and the level of acute phase reactants. Half of the patients (3 out of 6) in the HP+CRRT group survived along with the survival of one patient (1 out of 2) in the HP group. All four patients in the CRRT group died. Serum creatinine (SCr), Interleukin-1 (IL1), Interleukin-6 (IL6), Interleukin-8 (IL8), partial pressure of oxygen (PaO2), O2 saturation (O2 sat), and hemodynamic parameters improved over time in HP+CRRT and CRRT groups, but no significant difference was observed in the HP group (All Ps > 0.05). CONCLUSION: Combined HP and CRRT demonstrated the best result in terms of mortality, reduction of inflammatory mediators and oxygenation. Further investigations are needed to explore the role of HP+CRRT in COVID-19 patients.

Three Markers in Cancerous and Healthy Cells of Patients with Non-Small-Cell Lung Carcinoma (NSCLC).

Introduction: Lung cancer is the most common cause of cancer-related death among males and females. The diagnosis of lung cancer is of great importance for clinical considerations and follow-up treatment. This study aimed to examine the expression of CEA, LUNX, and CK19 biomarkers in the cancerous and healthy tissues of patients suffering from NSCLC. Methods: In this study, 30 patients with NSCLCs referring to Masih Daneshvari Hospital in Tehran were voluntarily selected prior to taking any treatment. A tissue sample from the center and a sample of healthy tissues close to the cancerous masses were prepared by a specialist in the bronchoscopy sector and tested using real-time RT-PCR. Results: Positive CEA mRNA was observed in cancerous tissues in the center of tumors of 25 out of 30 cases. In the healthy tissue group, the same was found in 10 out of 30 cases (P<0.001). The markers CK19 and LUNX mRNAs showed to be positive in cancerous samples in the center of tumors of 15 and 22 out of 30 cases, and in the healthy tissue group, the expression was observed in 5 and 4 out of 30 cases, respectively(P<0.001). Conclusion: This study confirms that the aformentioed markers are the ones with a relatively appropriate sensitivity and specificity for the diagnosis of lung cancer.

Immunologic Role of Extracellular Vesicles and Exosomes in the Pathogenesis of Cystic Fibrosis.

Cystic Fibrosis (CF) is the most common lethal autosomal recessive disease that affects many organs including, lung, pancreas and liver. Cystic fibrosis is a monogenic disease and occurs in the white Caucasians. Massive neutrophil granulocyte influx in the airways is one of the characteristics of CF. Extracellular Vesicles (EVs), microvesicles, and exosomes are vesicles released from cells into extracellular space of the body and are able to influence other cells by different methods. They have an important role in the intracellular communication by transferring information between donor and recipients cells. Granulocytes are known as the main source of microparticles in the CF patients. Microparticles derived from neutrophils are associated with the extensive neutrophil influx into airways and aggregation at the epithelial surface of the CF patient's respiratory tract. Exosomes are found in almost all body fluids, such as urine, sputum, Bronchoalveolar Lavage (BAL), milk, Cerebrospinal Fluid (CSF), plasma and sputum. Examination of exosomes derived from CF patients may be helpful in the characterization of pathogenesis of disease in detail. In this mini review, we have summarized the role of microparticles and exosomes in pathogenesis of CF and finally discussed the feasibility of this particle in treatment approaches.

Evidence for M2 macrophages in granulomas from pulmonary sarcoidosis: A new aspect of macrophage heterogeneity.

BACKGROUND: Sarcoidosis is a granulomatous disease of unknown etiology. Macrophages play a key role in granuloma formation with the T cells, having a significant impact on macrophage polarization (M1 and M2) and the cellular composition of the granuloma. This study evaluates macrophage polarization in granulomas in pulmonary sarcoidosis. MATERIALS AND METHODS: Tissue specimens from the Department of Pathology biobank at the Masih Daneshvari Hospital were obtained. Paraffin sections from 10 sarcoidosis patients were compared with those from 12 cases of tuberculosis using immunohistochemical staining. These sections consisted of mediastinal lymph nodes and transbronchial lung biopsy (TBLB) for sarcoidosis patients versus pleural tissue, neck, axillary lymph nodes and TBLB for tuberculosis patients. The sections were stained for T-cells (CD4+, CD8+) and mature B lymphocytes (CD22+). CD14+ and CD68+ staining was used as a marker of M1 macrophages and CD163+ as a marker for M2 macrophages. RESULTS: Immunohistochemical staining revealed a 4/1 ratio of CD4+/CD8+ T-cells in sarcoidosis granuloma sections and a 3/1 ratio in tuberculosis sections. There was no significance difference in single CD4+, CD8+, CD22+, CD14+ and CD68+ staining between sarcoidosis and tuberculosis sections. CD163 expression was significantly increased in sarcoidosis sections compared with those from tuberculosis subjects. CONCLUSION: Enhanced CD163+ staining indicates a shift towards M2 macrophage subsets in granulomas from sarcoidosis patients. Further research is required to determine the functional role of M2 macrophages in the immunopathogenesis of sarcoidosis.

Religious and cultural traits in HIV/AIDS epidemics in sub-Saharan Africa.

BACKGROUND: The pandemic of HIV/AIDS in sub-Saharan Africa and the rise of epidemics in Asia to the previously unforeseen level are likely to have global social, economic, and political impacts. In this emergency, it is vital to reappraise the weight of powerful religious and cultural factors in spreading the disease. The role of Islam in shaping values, norms, and public policies in North African states is to be appreciated for the lowest HIV prevalence in their populations. Yet, the place of religion in prevention of the disease diffusion is not fully understood nor worldwide acknowledged by the primary decision makers. Another topic, which has received little attention to date, despite the abundance of literature concerning the unfortunate Africa's anti-AIDS campaign, is an issue of colonial past. METHODS: To better comprehend the share of both traits in diverse spread of HIV in sub-Saharan Africa, we studied the correlation between Muslim and Christian proportions in the state's population and HIV rate. RESULTS: By this method, Muslim percentage came out as a potential predictor of HIV prevalence in a given state. In another approach, most subcontinental countries were clustered by colocalization and similarity in their leading religion, colonial past, and HIV seroprevalence starting from barely noticeable (0.6 - 1.2%, for Mauritania, Senegal, Somalia, and Niger) and low levels (1.9 - 4.8%, for Mali, Eritrea, Djibouti, Guinea, Guinea-Bissau, Burkina-Faso, and Chad) for Muslim populated past possessions of France and Italy, in the northern part of the subcontinent. Former territories of France, Belgium, Portugal, and the UK formed two other groups of the countries nearing the equator with Catholic prevailing (Democratic Republic of Congo, Republic of Congo, Rwanda, Gabon, and Burundi) or mixed populations comprising Christian, Muslim, and indigenous believers (Benin, Ghana, Uganda, Togo, Angola, Nigeria, Liberia, Kenya, Cameroon, Côte d'Ivoire, and Sierra-Leone), which covered the HIV prevalence range from 1.9% to 7%. Albeit being traced by origin to the central part of the continent, HIV has reached the highest rates in the South, particularly Malawi (14.2%), Zambia (16.5%), South Africa (21.5%), Zimbabwe (24.6%), Lesotho (28.9%), Botswana (37.3%), and Swaziland (38.8%)-all former British colonies with dominating Christian population. CONCLUSION: In the group ranking list, a distinct North to South oriented incline in HIV rates related to prevailing religion and previous colonial history of the country was found, endorsing the preventive role of the Islam against rising HIV and the increased vulnerability to menace in states with particular colonial record.

A long delay from the first symptom to definite diagnosis of pulmonary tuberculosis.

BACKGROUND: Despite the recent advances in medicine, still many people suffer from long-standing tuberculosis. Delay in the diagnosis may result in further mortality and morbidity. Because of the importance of delay in the diagnosis, we decided to study and evaluate the patient delay and physician delay. METHODS: A descriptive analytical study was done on 97 patients referred to the National Research Institute of Tuberculosis and Lung Disease in Tehran from September 2002 through March 2003. Those individuals who fulfilled the inclusion criteria underwent a face to face interview. The questionnaires were filled out. The interval between the first appearance of the clinical manifestation and the first visit to the physician was calculated (patient delay). Also, the period between the patient's first visit to the physician and the final diagnosis was worked out. RESULTS: The mean patient delay time was 15 +/- 13 days with a median of 13 days. The mean physician delay time was 93 +/- 72 days with a median of 75 days. The mean total delay time was 108 +/- 71 days with a median of 96 days. CONCLUSION: The patient delay in our country is at an acceptable level compared with other countries, but our physician delay time has not been shortened during the last eight years. Improving and upgrading the mycobacteriological courses for general physicians and specialists during their academic years should be accompanied by short-term teaching courses after the graduation.

A fuzzy rule-based expert system for diagnosing cystic fibrosis.

BACKGROUND: Finding a valid diagnosis is mostly a prolonged process. Current advances in the sector of artificial intelligence have led to the appearance of expert systems that enrich the experiences and capabilities of doctors for making decisions for their patients. OBJECTIVE: The objective of this research was developing a fuzzy expert system for diagnosing Cystic Fibrosis (CF). METHODS: Defining the risk factors and then, designing the fuzzy expert system for diagnosis of CF were carried out in this cross-sectional study. To evaluate the performance of the proposed system, a dataset that corresponded to 70 patients with respiratory disease who were serially admitted to the CF Clinic in the Pediatric Respiratory Diseases Center, Masih Daneshvari Hospital in Tehran, Iran during August 2016 to January 2017 was considered. Whole procedures of system construction were implemented in a MATLAB environment. RESULTS: Results showed that the suggested system can be used as a strong diagnostic tool with 93.02% precision, 89.29% specificity, 95.24% sensitivity and 92.86% accuracy for diagnosing CF. There was also a good relationship between the user and the system through the appealing user interface. CONCLUSION: The system is equipped with information, knowledge, and expertise from certified specialists; hence, as a training tool it can be useful for new physicians. It is worth mentioning that the accomplishment of this project depends on advocacy of decision making in CF diagnosis. Nevertheless, it is expected that the system will reduce the number of false positives and false negatives in unusual cases.

Pattern recognitions receptors in immunodeficiency disorders.

Pattern recognition receptors (PRRs) recognize common microbial or host-derived macromolecules and have important roles in early activation and response of the immune system. Initiation of the innate immune response starts with the recognition of microbial structures called pathogen associated molecular patterns (PAMPs). Recognition of PAMPs is performed by germline-encoded receptors expressed mainly on immune cells termed pattern recognition receptors (PRRs). Several classes of pattern recognition receptors (PRRs) are involved in the pathogenesis of diseases, including Toll-like receptors (TLRs), C-type lectin receptors (CLRs), and Nod-like receptors (NLRs). Patients with primary immune deficiencies (PIDs) affecting TLR signaling can elucidate the importance of these proteins in the human immune system. Defects in interleukin-1 receptor-associated kinase-4 and myeloid differentiation factor 88 (MyD88) lead to susceptibility to infections with bacteria, while mutations in nuclear factor-κB essential modulator (NEMO) and other downstream mediators generally induce broader susceptibility to bacteria, viruses, and fungi. In contrast, TLR3 signaling defects are associated with susceptibility to herpes simplex virus type 1 encephalitis. Other PIDs induce functional alterations of TLR signaling pathways, such as common variable immunodeficiency in which plasmacytoid dendritic cell defects enhance defective responses of B cells to shared TLR agonists. Altered TLR responses to TLR2 and 4 agonists are seen in chronic granulomatous disease (CGD) and X-linked agammaglobulinemia (XLA). Enhanced TLR responses, meanwhile, are seen for TLRs 5 and 9 in CGD, TLRs 4, 7/8, and 9 in XLA, TLRs 2 and 4 in hyper IgE syndrome (HIES), and for most TLRs in adenosine deaminase deficiency. In this review we provide the reader with an update on the role of TLRs and downstream signaling pathways in PID disorders.

Frequency of positive purified protein derivative test in those infected with human immunodeficiency virus.

BACKGROUND: The objective of this study was to determine the frequency of positive purified protein derivative (PPD) skin test in those infected with human immunodeficiency virus (HIV) and to investigate its association with CD4-positive T cell count, demographic factors, and possible routes of transmission in Iran. METHODS: Fifty-one (36 males and 15 females) patients from an HIV clinic were selected and tested by a 5-tuberculin unit PPD. RESULTS: The mean +/- SD age of patients was 32.2 +/- 7.9 years. The probable route of HIV transmission was intravenous drug using in 21 (41%, CI95%: 28 - 54%) and sexual transmission in 17 (33%, CI95%: 20 - 46%) patients. Thirteen (26%, CI95%: 14 - 38%) patients had other risk factors. There were 13 (25%; 10 males and 3 females) PPD-positive patients among HIV-infected patients when a cut-off value of 5 mm was used; there were 15 (29%; 11 males and 4 females) when a cut-off point of 2 mm was employed. In addition, there was no significant correlation between the PPD test using both cut-off values of 5 and 2 mm, and none of the three probable routes of HIV transmission including intravenous drug using, sexual, and others. The mean +/- SD CD4+ T cell count was 674 +/- 487/mm3 in men and 573 +/- 327/mm3 in women (P > 0.05). No significant correlation could be demonstrated between the patient's PPD positivity rate and CD4+ T cell count. CONCLUSION: Considering the high rate of tuberculin reactivity, more attention should be paid to the importance of PPD test and isoniazid preventive therapy against tuberculosis in HIV-infected patients.

The effect of supplemental zinc on the height and weight percentiles of children.

BACKGROUND: Considering the high incidence of low weight and short stature among Iranian children as well as the high prevalence of both mild and moderate types of zinc deficiency, this study was conducted among patients who were referred to the Pediatric Clinic at Massih Daneshvari Hospital during 1997 - 1999. The aim of this study was to determine the effect of zinc supplementation on the children's height and weight percentiles. METHODS: Age, sex, and height and weight percentiles before and after administration of zinc were determined and recorded. The zinc supplement used in this project was in the form of a zinc sulfate solution in 0.1% and 0.5% concentrations. The dose was the upper limit of a tolerable dose, which was given in three divided doses per day. The serum zinc level was measured with the atomic absorption spectrophotometry method. The effect of age, sex, and initial serum zinc level on the percentile changes were determined. RESULTS: This study was conducted on 42 children with equal distribution of gender (21 male and 21 female patients). The mean age was 4.9 +/- 4.1 years. Means of height and weight were 101.8 +/- 23 cm and 16.5 +/- 8.1 kg, respectively. The initial serum zinc level was 85.1 +/- 31.6 microg/dL. The duration of zinc administration was 3.2 +/- 2.6 months. The subjects were followed for a minimum of one month to a maximum of 10 months. The percentage of children with weight and height percentiles below the 50th percentile was reduced from 69% to 54% (P < 0.05) and from 50% to 33% (P < 0.01), respectively. Also, it was noted that children with low serum zinc levels demonstrated greater percentile changes. CONCLUSION: It was concluded that supplemental zinc increases height and weight percentiles.

Cancers Related to Immunodeficiencies: Update and Perspectives.

The life span of patients with primary and secondary immunodeficiency is increasing due to recent improvements in therapeutic strategies. While the incidence of primary immunodeficiencies (PIDs) is 1:10,000 births, that of secondary immunodeficiencies are more common and are associated with posttransplantation immune dysfunction, with immunosuppressive medication for human immunodeficiency virus or with human T-cell lymphotropic virus infection. After infection, malignancy is the most prevalent cause of death in both children and adults with (PIDs). PIDs more often associated with cancer include common variable immunodeficiency (CVID), Wiskott-Aldrich syndrome, ataxia-telangiectasia, and severe combined immunodeficiency. This suggests that a protective immune response against both infectious non-self-(pathogens) and malignant self-challenges (cancer) exists. The increased incidence of cancer has been attributed to defective elimination of altered or "transformed" cells and/or defective immunity towards cancer cells. The concept of aberrant immune surveillance occurring in PIDs is supported by evidence in mice and from patients undergoing immunosuppression after transplantation. Here, we discuss the importance of PID defects in the development of malignancies and the current limitations associated with molecular pathogenesis of these diseases and emphasize the need for further knowledge of how specific mutations can modulate the immune system to alter immunosurveillance and thereby play a key role in the etiology of malignancies in PID patients.