Profiling of microRNAs by next-generation sequencing: Potential biomarkers for diffuse large B-cell lymphoma.

Background: Lymphoma ranks fifth in prevalence among common cancer types worldwide. This lymphatic system cancer arises from T or B cells. Diffuse large B cell lymphomas (DLBCLs) are associated with most non-Hodgkin lymphomas. Non-coding microRNAs (miRNAs) greatly affect gene expression. A single miRNA can target numerous genes, thus largely influencing gene expression networks. MiRNAs can act as oncogenes or tumor suppressors in controlling DLBCL progression. This study investigated the roles of miRNAs in patients with DLBCL through next-generation sequencing, which was found to be sensitive, accurate, and robust. Methods: The study involved seven patients with DLBCLs and three controls at a hematology-oncology clinic. MiRNA was extracted from existing formalin-fixed, paraffin-embedded (FFPE) tissue specimens. Illumina next-generation sequencing was used to sequence samples for miRNA profiling. Results: Samples from patients showed expression of various hsa-mir miRNAs (1248, 3607, 21, 142, 1244, 182, 6516, 766, 1291, 4449, and 181a), whereas those from healthy individuals showed expression of hsa-mir 1248, 3607, 21, 142, and 877. Hsa-mir-877-3p is known to target multiple genes, and miRNAs such as hsa-mir-877-3p, hsa-mir-1291, and hsa-mir-181a-5p interact primarily with target genes. Conclusions: MiRNA profiling in FFPE tissues from patients with DLBCL suggested that miRNA levels can distinguish patients with DLBCL from controls, and therefore may provide prognostic or diagnostic biomarkers for DLBCL. Altered genes and miRNAs may also be potential therapeutic targets.

Oral squamous cell carcinoma with synchronous follicular lymphoma: A rare case report.

The occurrence of oral squamous cell carcinoma synchronously with lymphoma arising primarily in cervical lymph nodes is rare. Here, we report a case representing an infrequent finding. A 66-year-old male who was diagnosed with right mandibular squamous cell carcinoma and was subsequently found to have a nodal follicular lymphoma as a second malignancy. The patient underwent surgical resection for the oral squamous cell carcinoma with right selective neck dissection. The multidisciplinary team's postoperative treatment strategy involved adjuvant radiotherapy for the oral squamous cell carcinoma, while adopting a close follow-up approach for the follicular lymphoma. After an 18-month follow-up, there were no evidence of disease progression. This case report highlights the diagnostic challenges of synchronous primary malignancies occurring in the head and neck region. It also underscores the importance to conduct a comprehensive clinical and histopathological examination to rule out the possibility of synchronous neoplasms.

Application of Newly Customized Myeloid NGS Panel in the Diagnosis of Myeloid Malignancies.

Purpose: Genetic mutations are major factors in the diagnosis and prognosis of leukemia, and it is difficult to assess these variants using single-gene analysis. Therefore, this study aimed to develop a fast and cost-effective method for genetic screening of myeloid malignancies using a customized next-generation sequencing (NGS) panel. Patients and Methods: A customized myeloid panel was designed and investigated in 15 acute myeloid leukemia patients. The panel included 11 genes that were most commonly mutated in myeloid malignancies. This panel was designed to sequence the complete genome of CALR, IDH1, IDH2, JAK2, FLT3, NPM1, MPL, TET2, SF3B1, TP53, and MLL. Results: Among the 15 patients, 14 actual pathogenic variants were identified in nine samples, and negative results were found in six samples. Positive findings were observed for JAK2, FLT3, SF3B1, and TET2. Interestingly, non-classical FLT3 mutations (c.1715A>C, c.2513delG, and c.2507dupT) were detected in patients who were negative for FLT3-ITD and TKD by routine molecular results. All identified variants were pathogenic, and the high coverage of the assay allowed us to predict variants at a low frequency (1%) with 1000x coverage. Conclusion: Utilizing a custom panel allowed us to identify variants that were not detected by routine tests or those that were not routinely investigated. Using the costuming panel will enable us to sequence all genes and discover new potential pathogenic variants that are not possible with other commercially available panels that focus only on hotspot regions. This study's strength in utilizing NGS and implanting a customized panel to identify new pathogenic variants that might be common in our population and important in routine diagnosis for providing optimal healthcare for personalized medicine.

Unusual Presentation of Leukemic-Phase Mantle Cell Lymphoma: A Case Report.

Mantle cell lymphoma (MCL) is a rare subtype of B-cell lymphoma that can present in a variety of ways, including the leukemic phase, where it can occasionally be mistaken for acute leukemia due to the unusually high or rapidly growing number of leukocytes and the presence of circulating cancer cells that are morphologically similar to leukemic blasts in myeloid or acute lymphoblastic leukemia. We present the case of an 83-year-old Yemeni woman with multiple comorbidities who presented with abdominal pain and constitutional symptoms. She was found to have diffuse lymphadenopathy on clinical and radiological assessments. Her white blood cell count at presentation was 221 × 109/L with marked monocytosis (72.8%). Lymph node biopsy and bone marrow studies, including CCND1/IGH molecular studies, confirmed MCL, the pleomorphic subtype. The patient was deemed unfit for standard-of-care chemotherapy and was started on single-agent rituximab with a slow introduction to ibrutinib but succumbed to death after two weeks of ibrutinib 280 mg daily. This case serves as a reminder to keep an open mind and take into account atypical disease presentations when formulating differential diagnoses to prevent late diagnosis and any unnecessary intervention that can postpone appropriate therapy.

Rare Presentation of FLT3-ITD-Positive Acute Myeloid Leukemia With Monocytic Differentiation: A Case Report.

Acute myeloid leukemia (AML) is a hematological malignancy that affects adults and has various presenting symptoms, the most common being shortness of breath, bleeding, and infection. Thrombosis is also believed to be a rare presenting symptom of AML; however, information about the association between AML and thrombosis is scarce. Here, we report the case of a 27-year-old female who presented with extensive coagulation disturbances leading to various thromboembolic complications (including multiple strokes and renal and splenic infarcts) and was eventually diagnosed with AML. Owing to the patient's functional status at diagnosis, chemotherapy induction was withheld, and close observation along with supportive treatment was initiated. The findings, in this case, provide useful information on the presentation of such unusual cases, so we aim to enrich and contribute to medical evolution.

Cytospin performance when using Paris system for reporting urinary cytology.

Objectives: The Paris System (TPS) for Reporting Urine Cytology has significantly improved the approach to evaluating urine cytology. TPS criteria were defined mainly according to ThinPrep and SurePath preparations, as they are widely utilized. The objective of this study is to validate urine cytology interpretation according to the TPS classification using cytospin technique in relation to the gold slandered histology. Material and Methods: This retrospective study examined and analyzed 316 urine specimens from King Abdulaziz University Hospital between 2015 and 2020. Cytospin technique is performed for all cases. Slides were recategorized using TPS criteria, then compared with the original histology diagnosis. Results: According to the TPS, 108 cases were classified as 101 AUC (32%), 95 NEG (30%), 59 HGUC (18.7%), 31 SHGUC (9.8%), and 30 (9.5%) others. The computed sensitivity of cytospin in urine cytology was 94.7%, with 73.9% specificity, a positive predictive value of 85.6%, a negative predictive value of 89.5%, and overall accuracy of 86.8%. Conclusion: Urine cytology testing is considered to be a non-invasive and sensitive method to screen for urothelial carcinoma. TPS defined standards are reliable on cytospin prepared slides for reporting urine cytology.

Primary Central Nervous System Burkitt Lymphoma, Presenting with Long-Term Fluctuating Level of Consciousness: A Case Report and Literature Review on Challenges in Diagnosis and Management.

BACKGROUND Burkitt lymphoma (BL) is an aggressive subtype of B-cell non-Hodgkin lymphoma (NHL) rarely affecting the central nervous system (CNS) as a primary disease. Over the past years, only a few cases of primary CNS Burkitt lymphoma were reported. There is a challenge in early recognition and diagnosis of this type of brain lymphoma. Furthermore, there is no specific treatment protocols for primary CNS Burkitt lymphoma, which adds to the difficulty in managing those patients. We introduce a case of a 65-year-old who presented with fluctuating memory disturbance diagnosed as cerebral Burkitt lymphoma. CASE REPORT A 65-year-old man developed a gradual decrease in his level of consciousness over a span of 4 days, associated with fluctuating memory disturbances. A CT scan showed a hyperdense mass in the region of the trigon of the left lateral ventricle and marked obstructive hydrocephalus involving the temporal, occipital horns, and the left lateral ventricle, with no evidence of other suspicious lesions. A brain biopsy of the lesion revealed features of encephalitis initially, but the patient presented later with worsening symptoms, and a repeated brain biopsy showed features of Burkett lymphoma, with normal pan-CT scan. CONCLUSIONS Primary CNS Burkitt lymphoma (PCNSBL) is a rare disease with no clear evidence in the literature of how to deal with it. Reporting such cases provides a better understanding of how to approach such unusual presentations. Treatment of PCNSBL is challenging and even with the currently adopted approaches, the disease still has a very poor outcome.

Challenges of Human Papillomavirus Infection and Associated Diseases in Low-Resource Countries.

CONTEXT: - The prevalence of human papillomavirus (HPV) infection varies worldwide. The high-risk viruses are usually associated with cancers of the cervix, vagina, and vulva in women, cancer of the penis in men, and cancers of the anus, tonsils, oropharynx, and base of the tongue in both sexes. OBJECTIVES: - To review literature about the challenges and burden associated with HPV infection in low-resource (ie, developing) countries, focusing on sub-Saharan Africa. To review the prevention, incidence, prevalence, morbidity, and mortality of HPV infections in sub-Saharan Africa. To review the therapy and management of HPV infections in low-resource countries in comparison to developed countries. DATA SOURCES: - Peer-reviewed literature and experience of some of the authors. CONCLUSIONS: - Sub-Saharan Africa has high HPV infection prevalence rates, with predominance of high-risk subtypes 16, 18, and 45. The difficulty of access to health care has led to higher morbidity and mortality related to HPV-related cancers. Improvement in screening programs will help in monitoring the spread of HPV infections. Survival studies can be more informative if reliable cancer registries are improved. HPV vaccination is not yet widely available and this may be the key to curtailing the spread of HPV infections in resource-poor countries.