Gastrointestinal basidiobolomycosis: a rare manifestation of Basidiobolus ranarum in a non-endemic region.

Gastrointestinal basidiobolomycosis (GIB) is a rare fungal infection caused by the Basidiobolus ranarum, and it possesses a significant challenge to diagnose it as it presents with non-specific symptoms that often mimic cancer. Herein, we report a case of GIB in a 51-year-old male from the central region of Saudi Arabia, a non-endemic region of GIB, which was initially misdiagnosed as colon cancer. A 51-year-old man presented with abdominal pain for two-months, non-bloody diarrhea, loss of appetite, and weight loss. Abdominal examination revealed a large mass measuring ~10x15cm. Radiological findings prompted the diagnosis of a colon mass, and the patient was surgically treated under that impression. Hemicolectomy and end colostomy with mucous fistula from distal sigmoid stump were done. Histopathology was consistent with GIB. The diagnosis of GIB presents a serious challenge and requires a high index of clinical suspicion.

Macular amyloidosis diagnostic outcomes of skin biopsy: A systematic review.

Macular amyloidosis (MA) is a primary localized cutaneous amyloidosis, characterized by amyloid deposition in the papillary dermis. The clinical presentation includes pruritic hyperpigmented macules and patches with a reticulated or rippled pattern, primarily found on the upper back and extremities. Biopsy is an essential diagnostic tool for confirming MA. This systematic review focused on the biopsy outcomes in patients diagnosed with MA.

The effect of p53 on the activity of NRF2 and NDRG2 genes through apoptotic pathway in IDH-wildtype glioblastoma.

BACKGROUND: Tumor suppressor (p53) acts to integrate multiple stress signals into diverse antiproliferative responses. Its potential to transactivate or downregulate genes through apoptotic pathway in IDH-wildtype glioblastoma has never been explored. METHODS: A group of twenty patients diagnosed with IDH-wildtype glioblastoma, were tested for p53 expression and NDRG2/NRF2 genes activity through protein and gene profiling assays. The connotation between these elements has been explored. RESULTS: The mean patients' age was 64-years. All tumors were IDH-wildtype. p53 was expressed in 12 tumors and absent in 8 tumors. The activity of NDRG2 gene was downregulated in all cases. The activity of NRF2 gene was upregulated in 17 tumors and downregulated in 3 tumors. There was a significant statistical difference in PFS among tumors exhibiting different levels of p53 expression and NDRG2 gene activity [p-value= 0.025], in which 12 tumors with downregulated NDRG2 expression and positive p53 expression had earlier tumor recurrence. This statistical difference in PFS was insignificant when we compared p53 expression with NRF2 gene activity [p-value= 0.079]. CONCLUSIONS: During cell cycle arrest at G2 phase, p53 expression in IDH-wildtype glioblastoma in elderly individuals, coupled with the downregulation of NDRG2 gene activity, led to an aberrant increase in tumor cell proliferation and accelerated tumor recurrence. However, the influence of p53 on NRF2 gene activity was found to be insignificant.

Extracranial metastasis of brain glioblastoma outside CNS: Pathogenesis revisited.

BACKGROUND: The most prevalent malignant tumor of the CNS in adults is glioblastoma. Despite undergoing surgery and chemoradiotherapy, the prognosis remains unfavorable, with a median survival period ranging between 15 and 20 months. The incidence of glioblastoma metastasis outside CNS is uncommon with only 0.4%-2% reported rate, compared to other tumors that exhibit a 10% incidence rate of metastasis to the brain. On average, it takes about 11 months from the time of initial diagnosis for the tumor to spread beyond CNS. Consequently, the prognosis for metastatic glioblastoma is grim, with a 6-month survival rate following diagnosis. FINDINGS: The rarity of extracranial metastasis is attributed to the blood-brain barrier and lack of a lymphatic drainage system, although rare cases of hematogenous spread and direct implantation have been reported. The possible mechanisms remain unclear and require further investigation. Risk factors have been widely described, including previous craniotomy or biopsies, ventricular shunting, young age, radiation therapy, prolonged survival time, and tumor recurrence. Due to the lack of understanding about extracranial metastasis of glioblastoma pathogenesis, no effective treatment exists to date. Aggressive chemotherapies are not recommended for metastatic glioblastoma as their side effects may worsen the patient prognosis. CONCLUSION: The optimal treatment for extracranial metastasis of glioblastoma requires further investigation with a wide inclusion of patients. This review discusses the possible causes, factors, and underlying mechanisms of glioblastoma metastasis to different organs.

The Genomic Landscape of Colorectal Cancer in the Saudi Arabian Population Using a Comprehensive Genomic Panel.

PURPOSE: Next-generation sequencing (NGS) technology detects specific mutations that can provide treatment opportunities for colorectal cancer (CRC) patients. PATIENTS AND METHODS: We analyzed the mutation frequencies of common actionable genes and their association with clinicopathological characteristics and oncologic outcomes using targeted NGS in 107 Saudi Arabian patients without a family history of CRC. RESULTS: Approximately 98% of patients had genetic alterations. Frequent mutations were observed in BRCA2 (79%), CHEK1 (78%), ATM (76%), PMS2 (76%), ATR (74%), and MYCL (73%). The APC gene was not included in the panel. Statistical analysis using the Cox proportional hazards model revealed an unusual positive association between poorly differentiated tumors and survival rates (p = 0.025). Although no significant univariate associations between specific mutations or overall mutation rate and overall survival were found, our preliminary analysis of the molecular markers for CRC in a predominantly Arab population can provide insights into the molecular pathways that play a significant role in the underlying disease progression. CONCLUSIONS: These results may help optimize personalized therapy when drugs specific to a patient's mutation profile have already been developed.

Metastatic Crohn's Disease in External Genitalia With Good Outcome on Adalimumab: A Rare Case of a Saudi Female and a Short Review.

Crohn's disease (CD), an inflammatory bowel disease that involves the gastrointestinal tract, is observed in daily hospital practice. On the other hand, metastatic Crohn's disease (MCD) is a rare entity in which cutaneous lesions are found in regions apart from the digestive system. This article describes a rare case of cutaneous CD in a Saudi female, which manifested initially as vulvar and perianal skin lesions. The diagnosis was proven by skin biopsy, and adalimumab offered effective treatment. Although cutaneous MCD is rare, it is an important cutaneous manifestation, as early detection creates the possibility of accessing effective management.

The Role of Liquid Biopsy in the Diagnosis and Prognosis of WHO Grade 4 Astrocytoma.

Liquid biopsy, as a non-invasive diagnostic tool, has recently gained significant attention in the field of oncology. It involves the analysis of various biomarkers present in bodily fluids, such as blood or cerebrospinal fluid, to provide information about the underlying cancer. In the case of WHO grade 4 astrocytomas, liquid biopsy has the potential to significantly impact the diagnosis and prognosis of this aggressive malignant brain tumor. By detecting specific genetic mutations, such as IDH1 or EGFR, and monitoring levels of circulating tumor DNA, liquid biopsy can aid in the early detection and monitoring of disease progression. This innovative approach is gradually being acknowledged as a less invasive and cost-effective procedure for cancer diagnosis and management to improve patient outcomes and quality of life. Various kinds of biomarkers circulating in cerebrospinal fluid (CSF), such as circulating tumor cells (CTC) and different types of nucleic acids like cell-free DNA (cfDNA), cell-free RNA (ctRNA), and microRNAs (miRNA), have been identified. These biomarkers, which require dependable detection methods, are comparatively simple to obtain and allow for repeated measurements, making them significantly superior for disease monitoring. This review aims to compare the latest liquid biopsy analysis tools for both CSF and plasma in the central nervous system.

The synergistic effect of IDH mutation and NDRG-2 dysregulation in the progression of WHO-grade 4 astrocytomas.

BACKGROUND: NDRG2 is a tumour suppressor gene involved in tumor growth inhibition. Its effect on tumour recurrence remains controversial. The aim of this study is to explore the dual effect of IDH mutation and NDRG2 dysregulation in WHO-Grade 4 astrocytoma recurrence. METHODS: A group of 36 patients with WHO-Grade 4 astrocytoma were examined for NDRG2 expression using protein and gene expression assays. The relationship between IDH, NDRG2 protein and gene expressions, and recurrence-free interval [RFI] was explored. RESULTS: The mean patients age in this study was 45-years with 21 males and 15 females. IDH was mutant in 22 tumors. NDRG2 protein expression was low in 23 tumors, and high in 13 tumors. NDRG2 gene expression was upregulated in 4 tumors and 32 tumors showed NDRG2 gene downregulation. The consistency between two tasting methods of NDRG2 expression was 52.8%. There was a significant statistical difference in RFI among tumors with varying NDRG2 gene expression and IDH mutation [p-value= 0.021]. IDH-mutant tumours with downregulated NDRG2 expression showed late recurrence compared to IDH-wildtype glioblastoma. CONCLUSIONS: IDH-mutant WHO Grade-4 astrocytoma with downregulated NDRG2 gene are associated with late tumor recurrence. IDH mutations cause excessive accumulation of D-2-hydroxyglutarate, that may inhibit the activity of TET proteins, potentially leading to DNA hypermethylation and gene silencing.

Evaluation of the histopathological spectrum of skin biopsies in patients with chronic kidney disease: A single-center experience.

BACKGROUND AND AIM: Patients with chronic kidney disease (CKD), particularly those with end-stage renal disease (ESRD), frequently experience skin problems. Here, we present and discuss the histopathology results of skin biopsies performed on renal patients at our facility. MATERIALS AND METHODS: We retrospectively reviewed all histopathological reports and slides of skin biopsies taken from CKD patients for the last 5 years at the Pathology Department of King Saud University Medical City, King Saud University in Riyadh. DESIGN: This is a retrospective cross-sectional study. RESULTS: Patients were 19 (43.2%) males and 25 (56.8%) females, with a mean age of 53.4 19.8 years. Diabetic nephropathy, hypertensive nephropathy, and lupus nephritis were the three most common kidney pathologies (59.1%, 11.4%, and 11.4%, respectively). Seventeen patients (38.5%) were receiving hemodialysis. Acquired perforating collagenosis (APC), which was observed in 16 (36.4%) of our patients, was the most prevalent skin pathology, followed by bullous drug reactions in nine (20.5%), leukocytoclastic vasculitis (LCV) in eight (18.2%), calciphylaxis in six (13.6%), and prurigo nodularis in five (11.4%) patients. Erythematous plaques and papules were the most prevalent skin conditions at the time of presentation in 12 patients (27.3%), followed by pruritus in six (13.6%) and ulcerations in six (13.6%) patients. Collected data were analyzed using the Statistical Package for Social Sciences (SPSS) version 26.0. CONCLUSION: A spectrum of skin conditions may be seen in CKD patients. The quality of life of CKD patients will be significantly improved by identifying and managing these conditions. Pathologists' familiarity with this spectrum is important, as a correct histopathologic diagnosis will lead to a better outcome.

Intranasal administration of abatacept enhances IL-35+ and IL-10+ producing Bregs in lung tissues of ovalbumin-sensitized asthmatic mice model.

BACKGROUNDS: Treating asthmatic rheumatoid arthritis patients with abatacept has been shown to associate with better control of asthma symptoms. However, the mechanism behind that is not investigated. METHODS: Ovalbumin (OVA)- sensitized BALB/c female mice were treated intranasally (IN) or intraperitoneally (IP) with abatacept 4 hrs before the OVA challenge. The effects of abatacept IN or IP on the lungs and blood levels of Tregs and Bregs and their production of immunosuppressive cytokines, were determined using FACS analysis and ELISA assay. RESULTS: Treating OVA- sensitized asthmatic mice model with abatacept, IN or IP, reduced lung inflammation. IN treatment with abatacept increased the frequency of IL-35 and IL-10 producing Bregs in the lung tissues to a higher level compared to IP treatment. Moreover, the frequency of lungs LAG3+ Tregs was significantly increased following treatment. This was also associated with a reduction in lung tissue and serum IL-17 levels of treated mice. CONCLUSIONS: These results suggest that abatacept by enhancing IL-35+IL-10+ Bregs and LAG3+ Tregs might reverse IL-17 induced lung inflammation during asthma.

A Rare Case of Pancreatic Adenocarcinoma With Incidental Synchronous Hepatic and Sigmoid Colonic Metastasis: A Case Report and Literature Review.

Metastasis of pancreatic adenocarcinoma to the colon is a very rare condition that might be underdiagnosed and underreported in the literature. We report a very rare case of incidental findings of sigmoid metastasis secondary to pancreatic adenocarcinoma in a 60-year-old Saudi male, who is a non-smoker with a normal medical and surgical history. The patient presented to a primary care clinic with abdominal bloating and vague on/off abdominal pain for almost 1 year as well as unintentional weight loss without lower gastrointestinal (GI) symptoms. After the case was discussed in the multidisciplinary tumor board, the patient was started on systematic palliative chemotherapy. However, after receiving the first cycle, he started to deteriorate rapidly and succumbed to secondary cardiopulmonary arrest. Cases of synchronous metastasis of pancreatic adenocarcinoma to the colon might not be well known or common. However, a high index of suspicion and individualizing the workup tools may need to be used.

A 66-Year-Old Man Presenting with Port-Site Metastatic Gastric Adenocarcinoma 4 Years After Laparoscopic Resection of a Rectal Adenocarcinoma.

BACKGROUND There is a recognized association between synchronous and metachronous colorectal and gastric adenocarcinoma. This report describes a 66-year-old man presenting with port-site metastatic gastric adenocarcinoma 4 years after laparoscopic resection of a rectal adenocarcinoma. CASE REPORT A 66-year-old male rectal cancer survivor presented to the clinic with a painless mass at the previous laparoscopic anterior resection port site. Physical examination revealed a soft port-site mass measuring 5×4 cm. Abdominal CT revealed enlargement of the right rectus abdominis muscle and thickening of the gastric fundus. A biopsy of the right abdominal wall mass revealed metastatic adenocarcinoma. Immunohistochemistry (IHC) testing was positive for cytokeratin 7 (CK7) and CDx2 and negative for cytokeratin 20 (CK20). The possible primary malignancy was upper gastrointestinal, and it was less likely to be colorectal in origin. Subsequently, the upper endoscopy revealed a friable, erythematous gastric mucosa. Biopsy revealed an invasive moderately differentiated gastric adenocarcinoma with positive IHC for CK7 and CDx2 and negative for CK20. The rectal adenocarcinoma pathology slides were reviewed, and IHC testing showed negative CK7 and positive CK20. Patient was known to have multiple comorbidities with poor functional status. The tumor board decision was made to manage him palliatively with best supportive care for the diagnosis of metastatic gastric cancer. CONCLUSIONS This report has presented a case of possible metachronous gastric adenocarcinoma with port-site metastasis following resection of a rectal adenocarcinoma. Clinicians should be aware of the association between synchronous and metachronous colorectal and gastric adenocarcinoma and the challenges associated with the diagnosis.

Ectopic ocular tissue in testicular teratoma: A case report and review of the literature.

INTRODUCTION AND IMPORTANCE: Teratoma is a common neoplasm in prepubertal and post-pubertal periods. It consists of various types of tissues arising from different germinal layers, endoderm, mesoderm, and ectoderm. Ectopic ocular tissue is a rare phenomenon, with only few reported cases in other locations. CASE PRESENTATION: This is a 10-month-old boy who presented with a painless scrotal mass. Following orchidectomy, the excised mass confirmed the presence of uveal and retinal tissues originating in a benign testicular teratoma by histopathological examination. DISCUSSION: Choroidal and retinal tissue are the most frequently encountered ectopic ocular tissue, while the least observed tissue is the lens. Most of the reported cases of ectopic ocular tissue present in ovarian teratomas. The only 2 previously reported cases of ocular-like tissue in testicular teratoma lack well-defined medullary epithelium, uveal, and retinal tissue as in our case. CONCLUSION: To our knowledge, developing ocular tissue in a testicular teratoma is extremely rare. Herein we report a unique case with mature defined ocular tissue within a testicular teratoma in an infant, which should not be overlooked.

Coexistence of Polyarteritis Nodosa of the Vulva and Retina in a Behçet's Disease Patient: A Case Report.

Polyarteritis nodosa (PAN) is a multisystem disease that may affect the vessels of multiple organ systems. It has clinical variants including single-organ disease and cutaneous-only PAN. To our knowledge, this is a unique case report describing the coexistence of PAN of the vulva and retina in a Behçet's disease (BD) patient.  We report a case of a 31-year-old Lebanese woman with painful genital ulcers and multiple oral aphthae associated with arthralgia, light flashes, blurry vision, and photosensitivity. There were well-defined, punched-out erosions over the buccal and gingival mucosa; specifically, multiple punched-out, deep ulcers with unremarkable borders and black eschar involving two-thirds of both labia majora and minora sparing the clitoris with bilateral inguinal lymphadenopathy. Dilated fundus examination showed a few cotton wool spots and intraretinal hemorrhage. Fundus fluorescein angiography showed multiple arteriolar infarctions involving the macula in both eyes, more so in the right eye. Vulvar biopsy was consistent with PAN due to the involvement of a medium-sized subcutaneous artery and showed neutrophilic infiltration of its wall. Stain for elastic lamina showed medium-sized subcutaneous artery involvement. After ruling out infectious aetiologies, she was managed by intravenous pulse methylprednisolone 1,000 mg for three days, followed by oral prednisolone 50 mg with a slow taper, oral colchicine 0.5 mg twice daily, and adalimumab 40 mg once every two weeks to stop the progression of the ocular insult and genital mutilation. There was significant improvement of the ulcer with no new cutaneous or systemic manifestations. This case report highlights the importance of considering PAN-like lesions in cases of Behçet's disease. We emphasized the addition of cutaneous PAN as one of the cutaneous manifestations of BD.

A Rare Occurrence of Sebaceous Carcinoma, Sebaceoma, Syringocystadenoma Papilliferum, and Trichoblastoma in a Single Nevus Sebaceous Lesion.

Nevus sebaceous (NS) is a benign tumor with the potential to develop secondary benign and malignant neoplasms. It is a rare phenomenon to develop 2 or more skin tumors in a single NS lesion. We report a case of multiple secondary tumors, such as sebaceoma, sebaceous carcinoma, syringocystadenoma papilliferum, and trichoblastoma, in a single NS lesion.

Cholesterol Granuloma of the Maxillary Sinus-A Case Report and Literature Review.

Cholesterol Granulomas of the Maxillary Sinus, considered an unusual presentation at this anatomical site. Over last 2 decades, only few cases are reported in the literature (English) and no available comprehensive reviews or studies on this entity. Herein in this article we present a comprehensive literature review of the available reports of 16 cases along with reporting a new case which we managed, aided with its histopathological pictures. This review article can be a reference for practitioners in the field of otorhinolaryngology who may encounter these cases. Also, it attracts the attention to consider this pathology among the differential diagnoses of nasal masses. Moreover, including a described pathological imaging may help young pathologist to identify this pathology.

A matrix-assisted laser desorption/ionization imaging mass spectrometric approach to study weight-related changes within thyroid tissue.

Obesity is associated with numerous comorbidities along with abnormalities of the endocrine system, more commonly manifesting as dysfunctions of the thyroid gland such as goiter. Changes in weight, especially an increase, could lead to an increase in the incidence of thyroid dysfunction; however, its pathophysiology remains to be elucidated. In the present study, we aimed to interrogate the changes in the protein distribution and abundance between the lean patients and patients with obesity thyroid tissue sections through utilizing this technique. The FFPE-fixed thyroid tissue blocks from the selected cases and controls were identified and targeted for matrix-assisted laser desorption/ionization (MALDI) imaging mass spectrometry (IMS) analysis. Patients in the 30 to 75 years age group and undergoing total thyroidectomy for benign thyroid disease were recruited. Patients with thyroid cancers, autoimmune disorders, and other inflammatory conditions were excluded from the study. The selected patients were divided into two groups according to their BMIs: lean (BMI < 25) and obese (BMI > 35). An initial trial set was used as a pilot study for the optimization of the MALDI IMS protocol that was next applied to the selected thyroid tissues. MALDI IMS data from all the samples were aligned and statistical analysis carried out by k-means and linear discriminant analysis (LDA) classification model using principle component analysis (PCA) results were evaluated between the two groups: controls (lean) and cases (obese). Receiver operator characteristic (ROC) curves were alternatively used to calculate the variability of the identified peptides. The discriminating peptides were also independently identified and related to their corresponding proteins by using liquid chromatography and tandem mass spectrometry (LC-MS/MS) analyses. Eight peptides mainly from thyroglobulin were found to be upregulated whereas 10 others were found to be downregulated in the lean compared to the obese group. Through this technique, we will be able to better understand the relationship between the disease entity and obesity.

Refractory Urticaria with Raised Antistreptolysin O (ASO) Titer: An Intriguing Case of Adult-Onset Still's Disease.

BACKGROUND Adult-onset Still's disease (AOSD) is a rare systemic autoinflammatory disease with a myriad of clinical presentations. The diagnosis is often challenging because there is no specific confirmatory test. Uncommon presentations can delay the proper diagnosis and management. CASE REPORT A 26-year-old woman presented with a history of urticaria for 2 years that had failed to respond to many types of treatment. Cutaneous biopsy showed neutrophilic urticaria. A diagnosis of AOSD was made after infectious, drug-related, neoplastic, and rheumatic etiologies had been excluded and based on the triad of fever, evanescent rash, and joint pain. Besides leukocytosis and increased levels of inflammatory markers, the patient's laboratory results showed an extremely high D-dimer concentration and an increased antistreptolysin O (ASO) titer. Treatment with prednisolone and methotrexate resulted in resolution of the woman's symptoms. Once clinical remission had been achieved, all laboratory markers returned to normal, yet the patient's ASO titer remained elevated during 18 months of follow-up. CONCLUSIONS Urticaria is a rare cutaneous manifestation of AOSD. Histopathology typically shows predominant neutrophilic infiltrates, which is a unique entity called neutrophilic urticarial dermatosis (NUD). Identifying diseases associated with NUD will facilitate prompt diagnosis and treatment of AOSD, as therapies for it largely differ depending on the underlying cause. Known etiologies of AOS include systemic lupus erythematosus (SLE), Schnitzler syndrome, hereditary autoinflammatory periodic syndromes, and serum sickness-like drug eruption. An elevated ASO titer is unusual, and in our case, it did not seem to follow the patient's clinical course. An elevated D-dimer concentration can be an indicator of disease activity and testing might be beneficial in a subset of patients with normal ferritin levels.

Acute subconjunctival pigmentation with an underlying ciliary body mass: An unusual case presentation.

Intraocular melanocytoma is a rare slowly growing benign tumor that may occur anywhere along the uveal tract including the ciliary body but is more commonly found near the optic disc. It is darkly pigmented and may exhibit fast growth and possibly malignant transformation. Ciliary body (CB) melanocytoma is rare and often misdiagnosed as a melanoma. We are reporting a case of CB melanocytoma in a 74-year old lady with unusual initial presentation of an acute onset of subconjunctival pigmentation and extra-scleral extension of the melanocytoma with coarse melanin granules. The diagnosis of melanocytoma was confirmed by histopathological examination of the prolapsed tissue and by ultrastructural studies. Literature review of similar cases is also summarized.