Undiagnosed tuberculosis associated with hemophagocytic lymphohistiocytosis due to improper use of corticosteroid.

INTRODUCTION: Hemophagocytic lymphohistiocytosis (HLH) is a rare and life-threatening hematologic disease segregated into familial (primary) and acquired (secondary) subtypes. Hyperinflammation and HLH occur when the immune system fails to clear activated macrophages and histiocytes. Infections, malignancies, and rheumatologic disorders are the major triggers leading to HLH. Miliary tuberculosis is a serious disease with a lymphohematogenous spread of Mycobacterium tuberculosis, which is known to be one of the causative agents of HLH. Miliary tuberculosis and HLH have atypical presentations which are similar to routine diseases. Hence, physicians may face challenges to diagnose and treat these complications. CASE REPORT: We report the case of a 60-year-old man with a history of prolonged fever, shortness of breath, jaundice, altered mental status, undiagnosed lower back pain, and overuse of parenteral betamethasone. Miliary tuberculosis was diagnosed by diffuse, vague random micronodules in both lungs and positive acid-fast bacilli in bronchoalveolar lavage and bone marrow aspiration and biopsy. Moreover, compatible presentation and pancytopenia, hypertriglyceridemia, high serum level of ferritin and fibrinogen-derived products, and evidence of hemophagocytosis on bone marrow aspirate led to the diagnosis of HLH. Unfortunately, despite nearly two months of an anti-tuberculosis regimen (standard and salvage) and eight doses of etoposide, he eventually passed away after clinical improvement. CONCLUSIONS: Irrational and indiscriminate use of glucocorticoids can be a devastating cause of the spread of tuberculosis and its rare complications, such as HLH.

Mucormycosis, New Causative Agents, and New Susceptible Populations: Review of Cases in a Tertiary Care Hospital in Iran (2007-2021).

Background: Mucormycosis is an aggressive opportunistic fungal infection that afflicts patients with severe underlying immunosuppression, uncontrolled hyperglycemia and/or ketoacidosis, iron overload, and occasionally healthy patients who are inoculated with fungal spores through traumatic injuries. The epidemiology of mucormycosis has changed after the COVID-19 pandemic, with mucormycosis becoming the most common and the fatal coinfection. Methods: In a retrospective, cross-sectional study, 82 hospitalized patients with a definite diagnosis of mucormycosis were reported from 2007 to 2021 in a referral, tertiary care center in Tehran, Iran. Results: The number of post-COVID cases increased 4.6 times per year, with 41.5% of patients admitted during the two years of the pandemic. Mucormycosis was more common in women (57.3%), and the most common underlying diseases were diabetes (43.7%), both COVID-19 and diabetes (23.2%), cancer (11%), rheumatic diseases (7.3%), COVID-19 without other underlying diseases (6.1%), and transplantation (4.9%). Rhino-orbito-cerebral Mucormycosis (54.9%) followed by Sino-orbital infection (23.2%) was the most common presentation. There was a significant relationship between the use of immunosuppressive agents and the development of Mucormycosis (P<0.005) The average mortality was 41.5%, but this ratio decreased to 35% during the pandemic era. Conclusion: The COVID-19 pandemic caused a 4.6-fold increase in the number of mucormycosis patients, and there was a significant relationship between hyperglycemia, corticosteroid use, and mucormycosis. The death rate during the COVID-19 pandemic has decreased by 6.5%, and during the COVID period, the interval between the arrival of a patient with mucormycosis and the start of the correct treatment was significantly decreased.

Cerebellopontine angle meningioma originating from choroid plexus of the foramen of Luschka: An extremely rare entity and overlook of literature.

INTRODUCTION AND IMPORTANCE: Meningiomas without dural attachments are quite a novelty, with such meningiomas in the posterior fossa being even more far and few between. The authors describe an extremely rare cerebellopontine angle (CPA) meningioma lacking a dural attachment arising from the choroid plexus of the foramen of Luschka (CPFOL). CASE PRESENTATION: A 35-year-old male presented to our center complaining of a generalized and progressive headache for 10 months. A 3 cm × 4 cm well-defined lesion in the left CPA, hypointense in T1 and hyperintense in T2-weighted magnetic resonance imaging (MRI), was noted with no evident dural base or dural attachment. CPFOL was appreciated right at the point where the tumoral base was detected, which implied that the tumor originated from CPFOL. A gross total resection (GTR) was achieved, with the postoperative period remaining uneventful. The histopathologic investigation confirmed a transitional meningioma World Health Organization (WHO) grade I with no atypical features. CLINICAL DISCUSSION: Meningioma without dural attachment remains a rare phenomenon, with few available in English literature, and such pathology in the posterior fossa is even more unusual. Discriminating between CPFOL and another kind of CPA meningioma is mandatory when dealing with intracranial meningioma surgeries. CONCLUSION: While managing a space-occupying lesion around CPA, although extremely rare, a meningioma originating from CPFOL is suggested to be included in the differentials with necessary imaging analysis and advised to be imperatively pursued before proceeding for surgical intervention.

Concurrent omphalomesenteric duct cyst and ileal diverticulum causing small bowel obstruction; a case report.

INTRODUCTION AND IMPORTANCE: The omphalomesenteric duct (OMD) usually involutes by the ninth gestational week. If this obliteration fails, OMD remnant will result in different pathologies mostly in the pediatrics and infrequently in adults. The most well-known OMD remnant disease is Meckel's diverticulum. Omphalomesenteric cyst is rather rare, and their combination is even more exceptional with few cases in literature. CASE PRESENTATION: We present an adolescent patient with nausea and vomiting and occasional periumbilical abdominal pain who was diagnosed with concurrent omphalomesenteric cyst and ileal diverticulum, causing internal hernia and bowel obstruction that underwent surgery. CLINICAL DISCUSSION: OMD remnants mostly present in childhood with symptoms of intestinal obstruction, and rarely internal hernias for which conservative management is usually not curative, warranting surgery. Imaging presence of cystic lesion in mid abdomen in young patient with bowel obstruction should raise the suspicion for OMD remnants. Presence of OMD cyst together with Meckel's diverticulum necessitates more extensive resection, rare concurrence which is better to be prepared for in advance. CONCLUSION: Preoperative radiologic workup is helpful to diagnose the obstruction and its probable cause. Presence of periumbilical cyst should raise the suspicion of OMD remnant specially in young adults with previous episodes of crampy abdominal pain and obstruction without history of abdominal surgery. Being familiar with possible concurrence of OMD cyst and Meckel's diverticulum will increase preparedness at the time of surgery.

Association between serum inflammatory parameters and the disease severity in COVID-19 patients.

OBJECTIVE: Most patients infected with the novel coronavirus (SARS-CoV-2), as the causative agent of COVID-19 disease, show mild symptoms, but some of them develop severe illness. The purpose of this study was to analyze the blood markers of COVID-19 patients and to investigate the correlation between serum inflammatory cytokines and the disease severity. METHODS: In this prospective cross-sectional study, 50 patients with COVID-19 and 20 patients without COVID-19 were enrolled. According to ICU admission criteria, patients were divided into two groups of non-severe and severe. Differences in the serum levels of C-reactive protein (CRP), IL-6, and TNF-α, as well as erythrocyte sedimentation rate (ESR), lymphocytes (LYM) count, and neutrophils (NEU) count between the two groups were determined and analyzed. RESULTS: Out of the 50 patients with COVID-19, 14 were diagnosed as severe cases. There was no significant difference between the two groups of COVID-19 patients in terms of gender and age. Blood tests of COVID-19 patients showed a significant decrease and increase in NEU and LYM counts, respectively. There were significant differences in the serum levels of IL-6, TNF-α, and CRP between the severe and non-severe groups, which were higher in the severe group. Also, there was a significant correlation between the disease severity and CRP with ESR (r = 0.79), CRP with IL-6 (r = 0.74), LYM with NEU (r = -0.97), and ESR with TNF-α (r = 0.7). CONCLUSION: The findings of this study, as the first study in Iran, suggest that the levels of IL-6, TNF-α, ESR, and CRP could be used to predict the severity of COVID-19 disease.

Post-mortem Histopathologic Findings of Vital Organs in Critically Ill Patients with COVID-19.

BACKGROUND: The scientific evidence concerning pathogenesis and immunopathology of the coronavirus disease 2019 (COVID-19) is rapidly evolving in the literature. To evaluate the different tissues obtained by biopsy and autopsy from five patients who expired from severe COVID-19 in our medical center. METHODS: This retrospective study reviewed five patients with severe COVID-19, confirmed by reverse transcription-polymerase chain reaction (RT-PCR) and imaging, to determine the potential correlations between histologic findings with patient outcome. RESULTS: Diffuse alveolar damage (DAD) and micro-thrombosis were the most common histologic finding in the lung tissues (4 of 5 cases), and immunohistochemical (IHC) findings (3 of 4 cases) suggested perivascular aggregation and diffuse infiltration of alveolar walls by CD4+ and CD8+ T lymphocytes. Two of five cases had mild predominantly perivascular lymphocytic infiltration, single cell myocardial necrosis and variable interstitial edema in myocardial samples. Hypertrophic cardiac myocytes, representing hypertensive cardiomyopathy was seen in one patient and CD4+ and CD8+ T lymphocytes were detected on IHC in two cases. In renal samples, acute tubular necrosis was observed in 3 of 5 cases, while chronic tubulointerstitial nephritis, crescent formation and small vessel fibrin thrombi were observed in 1 of 5 samples. Sinusoidal dilation, mild to moderate chronic portal inflammation and mild mixed macro- and micro-vesicular steatosis were detected in all liver samples. CONCLUSION: Our observations suggest that clinical pathology findings on autopsy tissue samples could shed more light on the pathogenesis, and consequently the management, of patients with severe COVID-19.

MIR196A2 rs11614913 contributes to susceptibility to colorectal cancer in Iranian population: A multi-center case-control study and meta-analysis.

Maturation of MIR196A2 as a gene regulator with a high potential for targeted cancer therapy can be modulated by the rs11614913 polymorphism. Several studies evaluating the association between this variant and pathogenesis of colorectal cancer (CRC) found significant results in various ethnic groups. This study aimed at investigating this relationship in a large sample size of Iranians as well as in a systematic review and meta-analysis of the pooled data of the current study with previous reports from Iran and other populations. After extraction of genomic DNA from the formalin-fixed paraffin-embedded tissues and whole blood of 2150 subjects (42% CRC patients), the rs11614913 was genotyped in both cases and controls. Furthermore, we conducted a meta-analysis of the present case-control study together with a previous report from Iranian population. The results of case-control study identified significant association between the rs11614913 and susceptibility to CRC [TT vs. CC: 1.58 (1.26-1.98), p < 0.01; TT vs. CT: 3.94 (3.07-5.05), p < 0.01; TT vs. CC + CT: 0.70 (0.59-0.83), p < 0.01; and CT + TT vs. CC: 1.43 (1.21-1.70), p < 0.01]. After correction of the meta-analysis results by using Bonferroni protocol, no significant association was observed in overall and in Asians [T vs. C: 1.19 (1.00-1.43), p = 0.05 and 1.14 (0.83-1.56), p = 0.43, respectively], whereas association was significant in Caucasians [T vs. C: 1.14 (1.04-1.25), p = 0.004] influenced by the data from Iran [T vs. C: 1.15 (1.03-1.29), p = 0.02 and TT vs. CC + CT: 0.73 (0.60-0.87), p = 0.003]. In conclusion, MIR196A2 rs11614913 might play a potential role in the pathogenesis of CRC in Iranian population.

Lack of association of CASC8 rs1447295 with colorectal cancer in Iranian population: A multicenter case-control study.

Several studies reported the potential role of the rs1447295 polymorphism in susceptibility to cancer. This variant located in the cancer susceptibility candidate 8 (CASC8) is a long noncoding RNA (lnRNA) gene and does not code protein. LnRNA transcripts play a potential regulatory role in the expression of key genes involved in multiple cellular pathways, including cell cycle, pluripotency, and immune response. The aim of this study is to evaluate this association with colorectal cancer (CRC) in a large case-control study of the Iranian population. After extraction of genomic DNA by the standard protocols, the rs1447295 was genotyped in 2416 subjects (46% patients). Results of this case-control demonstrated no significant association between the rs1447295 polymorphism and risk of CRC or its characteristics under allele or alternative genotype models. In conclusion, it is unlikely that the rs1447295 polymorphism is a risk variant for the development of CRC in Iranian population.

MTRR rs1801394 and its interaction with MTHFR rs1801133 in colorectal cancer: a case-control study and meta-analysis.

AIM: This study aims to evaluate the association between the MTRR rs1801394 alone or in interaction with the MTHFR rs1801133 and susceptibility to colorectal cancer (CRC) and its characteristics in Iranian population. Additionally, both a systematic review and meta-analysis were performed to derive a more precise assessment of this association. MATERIALS & METHODS: Genomic DNA of 2332 subjects was genotyped for rs1801394. These data were pooled with 17 eligible studies for meta-analysis. RESULTS: No significant association was found between the rs1801394 or rs1801394-rs1801133 and CRC risk. Meta-analysis results also demonstrated no significant relationship between the rs1801394 and CRC risk. CONCLUSION: Results of this study showed that the rs1801394 alone or together with the rs1801133 is not a risk factor for CRC in Iranian population.

Eccrine Nevus Presenting with Umbilical Discharge: A Case Report and Review of the Literature.

Eccrine nevus is a rare skin lesion with protean manifestations like hyperhidrosis, discolored nodules, papules, and so forth, which has been reported in various anatomic parts of the body including the forearm, leg, thigh, back, and coccyx. Our patient was a 26-year-old male, who presented with increasing colorless and odorless episodic umbilical discharge. First impression for the patient was an umbilical sinus and the patient underwent surgery. Histopathological study revealed the lesion to be an eccrine nevus of the umbilicus. This is the first case of eccrine nevus presenting with umbilical discharge. We recommend that eccrine nevus should be considered as a differential diagnosis for umbilical discharge.

Comparison of P53 Intensity, Frequency and Size in Normal Skin Periphery of Squamous Cell Carcinoma, Basal Cell Carcinoma And Melanocytic Nevus in Persian Skin Type.

BACKGROUND: Non-Melanoma Skin Cancer (NMSC), the most prevalent types being Squamous Cell Carcinoma (SCC) and Basal Cell Carcinoma (BCC), is the most common type of malignancy in human beings. These neoplasms are more frequent in the elderly and fair skinned people and mainly occur on sun-exposed sites of the body. Ultraviolet B (UVB) has a well-known effect in induction and promotion of growth of these cancers. The p53 tumor suppressor gene is believed to be an early target in UV-induced skin carcinogenesis. Aggregates of keratinocytes with p53 protein overexpression are frequently identified in normal human skin and are more prevalent in chronically sun-exposed skin, and have been proposed to play a role in skin cancer pathogenesis. The aim of this study was to clarify the potential role of P53 in the development of NMSC. METHODS: Immunohistochemical evaluation of p53 expression in peri-lesional skin of 90 cases of SCC, BCC and melanocytic nevi was performed. RESULTS: The well-delineated compact type of p53 clone, but not the strong dispersed type, was significantly more predominant in SCCs in comparison with BCCs and melanocytic nevi (P value=0.001). The size of p53 clones was also significantly greater in SCCs compared to the BCCs (P=0.003) and melanocytic nevi (P=0.001). There was no significant difference between these neoplasms regarding the frequency of P53 clones (P=0.86). CONCLUSION: This study suggests the possible relationship of epidermal p53 clones with the pathogenesis of SCC.

Gender and age-specific seroprevalence of human papillomavirus 16 and 18 in general population in Tehran, Iran.

The assessment of the gender and age-specific seroprevalence of human papillomavirus (HPV) is essential for planning of HPV vaccine implementation into the preventive programs. In this study, we aimed to determine the age-specific seroprevalence of HPV-16 and 18 in both males and females in Tehran, Iran. Three hundred and seventy-eight women (10-35 years) and 162 men (10-25 years) from Tehran, Iran, were enrolled. Anti-HPV IgG antibodies against HPV-16 and HPV-18 were detected by ELISA using papillomavirus type 16 and 18 L1-capsids as antigen. HPV-16 antibody was detected in 15.6 and 13.6% of women and men, respectively. Antibody against HPV-18 was found positive in 12.7 and 8% of women and men, respectively. The highest seroprevalence of HPV-16 and 18 were seen in women aged 26-30 years (22.2 and 19.4%, respectively), and the lowest HPV-16 and 18 seropositivity rates were seen in males and females aged 10-15 years (9.3 and 1.9%, respectively). In our cohort of study, in males, both anti-HPV-16 and 18 increased after age 15 years, peaking in men aged 21-25 years. In women, both HPV-16 and 18 seropositivity increased after 15 years, declined at 21-25 years, peaked in women aged 26-30 years and again decreased after 30 years. Our data showed increasing exposure rate to high-risk HPV vaccine types in our studied population over 15 years of age. In order to prevent the HPV-related cancers, implementation of HPV vaccine into the national immunization program in Iran and vaccination of females and males less than 15 years of age are suggested.

MTHFR rs1801133 polymorphism and susceptibility to colorectal cancer in Iranian population: evidence of a case-control study and meta-analysis.

Several studies have investigated whether MTHFR rs1801133 polymorphism contributes to risk of colorectal cancer (CRC), however the results are inconclusive. AIM: The purpose of this study was to investigate this hypothesis in a case-control study and meta-analysis in Iranian population. MATERIALS & METHODS: This polymorphism was genotyped in the 2421 subjects (46% CRC patients) from Tehran. Meta-analysis was performed for determining the risk effect size of this polymorphism on CRC. RESULTS: Both case-control study and meta-analysis showed no association between rs1801133 and CRC risk or its features. CONCLUSION: This study failed to identify an association between the rs1801133 and susceptibility to CRC in Iranian population.

Mycobacterium haemophilum: A report of cutaneous Infection in a Patient with end-stage renal disease.

INTRODUCTION: Mycobacterium haemophilum is a slow-growing nontuberculous mycobacterium (NTM) that can cause ulcerating cutaneous or subcutaneous nodular skin lesions in immunocompromised and immunocompetent patients. Acid-fast staining cannot distinguish NTM from M. tuberculosis; culturing at two temperatures with iron-supplemented media and polymerase chain reaction (PCR) are needed for optimal detection of M. haemophilum. CASE PRESENTATION: A 32-year-old man with end-stage renal disease, undergoing hemodialysis twice a week, presented with multiple, painless, nonpruritic nodular lesions. A formalin-fixed paraffin-embedded tissue block from his finger lesion was sent to the Department of Pathology, Masih Daneshvari Hospital for consultation. The lesions were primarily diagnosed to be dermatofibroma by another pathologist. On microscopic examination, vague granuloma with areas of necrosis was observed. The diagnosis was established by positive acid-fast staining, negative PCR results for M. tuberculosis complex, and positive nested PCR results for M. haemophilum. CONCLUSION: Cutaneous lesions in immunocompromised patients with positive results in acid-fast staining and negative results for M. tuberculosis should be further assessed using skin culture and molecular techniques to identify rare, atypical mycobacterial species like M. haemophilum.

Demographic study of pituitary adenomas undergone trans-sphenoidal surgery in Loghman Hakim Hospital, Tehran, Iran 2001-2013.

BACKGROUND: Pituitary adenomas (PAs) are abnormal benign tumors that develop in the pituitary gland. This study aimed to assess the prevalence of different types of PAs with an indication for trans-sphenoidal surgery in a well-defined population referred to Loghman Hakim Hospital during 2001-2013. SUBJECTS AND METHODS: In this retrospective study, the prevalence rate and symptoms associated with pituitary mass and hormone excess in operated patients were investigated. The diagnosis was verified after retrieval of clinical, hormonal, radiological, and pathological data. Demographic data were collected in all cases. Descriptive analysis, t-test, one-way analysis of variance and Fischer exacts test were used. RESULTS: A total of 278 patients with PAs who underwent surgical interventions were evaluated. Most of the patients were aged 40-50 years with an average of 41 ± 14. The most prominent complaint was pressure effect, which was detected in 153 cases (55.2%). At the second place, hormonal disorders were observed in 125 cases (44.8%). Type of pituitary tumors were: Prolactinomas (29.1%), growth hormone (GH)-producing tumors (25%), nonfunctioning PAs (28.4%), adrenocorticotropic hormone (ACTH)-producing tumors (2.1%), thyroid stimulating hormone (TSH)-producing tumors (0.7%), GH/prolactin (13.6%), GH/ACTH (0.3%), and TSH/ACTH (0.3%). Fifty-seven patients presented with recurrent adenomas. Pituitary apoplexy was found in 11 patients. One case of Sheehan syndrome was recorded among these. The correlations between clinical symptoms and patients, age and sex were not significant. CONCLUSION: The overview of demographic characteristics in Iranian patients with PAs with surgical indication has been discussed in the present investigation. The prevalence of different types of PAs and the most common clinical symptoms have been demonstrated.

Primary Meningeal Melanocytoma in the Left Temporal Lobe Associated with Nevus Ota: a Case Report and Review of the Literature.

BACKGROUND: Primary melanocytic neoplasms of the central nervous system are rare lesions arising from melanocytes of the leptomeninge that are found at highest density underneath the brain stem and along the upper cervical spinal cord. Thus most reported cases of meningeal melanocytomas are located in the posterior fossa and the spinal cord, and presentation of a supratentorial tumor is rare. METHODS: A 19-year-old man presented with a headache and seizure at our department. Neurological examinations were otherwise normal. On physical examination he had asymptomatic, bluish, speckled, and well-demarcated hyperpigmented macules on the left midface extraorally. A left temporal space-occupying lesion was seen on magnetic resonance imaging. The mass was hyperintense on T1-weighted images and isointense on T2-weighted images. Enhancement was shown on contrast-enhanced magnetic resonance imaging (MRI). The preoperative diagnosis was meningioma. RESULT: Gross complete resection was performed. Pathological studies led to the diagnosis of meningeal melanocytoma World Health Organization (WHO) grade I. The patient received oncologic consultation. Because total resection of the tumor was achieved and its histopathologic grade was benign (WHO grade I), radiotherapy was not advised for the patient and he followed up every 6 months. No tumor was seen on follow-up MRI one year after surgery. CONCLUSION: Presentation of meningeal melanocytoma in the supratentorial compartment is rare, and its combination with nevus Ota has been reported in very few cases. Although this lesion is benign, it might behave aggressively. Complete surgical resection of the lesion is the preferred therapeutic option.