Nodal Low-Grade B-Cell Lymphoma Co-Expressing CD5 and CD10 but Not CD23, IRTA1, or Cyclin D1: The Diagnostic Challenge of a Splenic Marginal Zone Lymphoma.

The diagnosis of lymphoma is based on histopathological and immunophenotypical features. CD5 and CD10 are traditionally considered a T-cell antigen and a germinal center B-cell antigen, respectively. It is very unusual for a low-grade B-cell lymphoma (BCL) to co-express CD5 and CD10. Although the biologic basis or clinical significance of such co-expression is unclear, this rare event may pose a significant diagnostic challenge. Here, we report a case of a 63-year-old male presenting with bilateral cervical lymphadenopathy and lymphocytosis. Histologically, the nodal tumor was largely diffuse with neoplastic small atypical lymphocytes co-expressing CD5, CD10, and CD20, but not CD23 or cyclin D1. The leukemic cells in the peripheral blood exhibited hairy projections. Taking together the marked splenomegaly, involvement of lymph nodes, bone marrow, and peripheral blood, a final diagnosis of splenic marginal zone lymphoma (SMZL) was reached. The patient was alive with partial response for 10 months after immunochemotherapy. The dual expression of CD5 and CD10 is extremely unusual for low-grade BCL and may lead to an erroneous diagnosis. Integrating the findings into peripheral blood smear tests, flow cytometry, histopathology, imaging, and clinical features is mandatory to exclude other lymphoma types and to reach a correct diagnosis, particularly for a case with nodal presentation.

Predicting lung cancer survival based on clinical data using machine learning: A review.

Machine learning has gained popularity in predicting survival time in the medical field. This review examines studies utilizing machine learning and data-mining techniques to predict lung cancer survival using clinical data. A systematic literature review searched MEDLINE, Scopus, and Google Scholar databases, following reporting guidelines and using the COVIDENCE system. Studies published from 2000 to 2023 employing machine learning for lung cancer survival prediction were included. Risk of bias assessment used the prediction model risk of bias assessment tool. Thirty studies were reviewed, with 13 (43.3%) using the surveillance, epidemiology, and end results database. Missing data handling was addressed in 12 (40%) studies, primarily through data transformation and conversion. Feature selection algorithms were used in 19 (63.3%) studies, with age, sex, and N stage being the most chosen features. Random forest was the predominant machine learning model, used in 17 (56.6%) studies. While the number of lung cancer survival prediction studies is limited, the use of machine learning models based on clinical data has grown since 2012. Consideration of diverse patient cohorts and data pre-processing are crucial. Notably, most studies did not account for missing data, normalization, scaling, or standardized data, potentially introducing bias. Therefore, a comprehensive study on lung cancer survival prediction using clinical data is needed, addressing these challenges.

Panfolliculoma: Report of the Youngest Case and Literature Review of Its Histopathologic Variants.

Background: Panfolliculoma (PF) is a relative rare, benign follicular tumor comprised of all elements of the hair follicle, with a limited number of cases reported in the literature. Articles on the demographic and pathological analysis of this tumor are also lacking. Case presentation: In this report, we presented an unusual case of cystic PF on the back of a 14-year-old male, and we performed a thorough literature review and analysis of all previously reported cases. Conclusions: PF is a rare benign follicular neoplasm with characteristic differentiation toward all components of the hair follicle. In our analysis, PF occurred most frequently on the head region and was usually diagnosed in middle- to old-aged persons, with cystic PF being the most common histologic subtype. Since this tumor is rare and easily misdiagnosed as other tumors both clinically and pathologically, a thorough understanding of the histopathological manifestations and differential diagnosis of this tumor is necessary for both dermatologists and pathologists.

The ethical, legal and social implications of using artificial intelligence systems in breast cancer care.

Breast cancer care is a leading area for development of artificial intelligence (AI), with applications including screening and diagnosis, risk calculation, prognostication and clinical decision-support, management planning, and precision medicine. We review the ethical, legal and social implications of these developments. We consider the values encoded in algorithms, the need to evaluate outcomes, and issues of bias and transferability, data ownership, confidentiality and consent, and legal, moral and professional responsibility. We consider potential effects for patients, including on trust in healthcare, and provide some social science explanations for the apparent rush to implement AI solutions. We conclude by anticipating future directions for AI in breast cancer care. Stakeholders in healthcare AI should acknowledge that their enterprise is an ethical, legal and social challenge, not just a technical challenge. Taking these challenges seriously will require broad engagement, imposition of conditions on implementation, and pre-emptive systems of oversight to ensure that development does not run ahead of evaluation and deliberation. Once artificial intelligence becomes institutionalised, it may be difficult to reverse: a proactive role for government, regulators and professional groups will help ensure introduction in robust research contexts, and the development of a sound evidence base regarding real-world effectiveness. Detailed public discussion is required to consider what kind of AI is acceptable rather than simply accepting what is offered, thus optimising outcomes for health systems, professionals, society and those receiving care.

Evaluating the Managing Medicines for People With Dementia Website Version 2.

The Managing Medicines for People With Dementia version 2 website was developed in three languages, English, Italian, and Macedonian, to assist informal caregivers in the task of managing medications. Medication management is a complex task with potentially high stakes health outcomes, including hospitalization and death. A mixed-methods evaluation was carried out. A survey was available to site users and Web log data were collected over a 3-month period. Subsequently, the quality and suitability of the information and readability and usability of the Web site were evaluated. Focus groups and interviews were conducted with end users from all three language groups. Data collected from the evaluation surveys during the pilot test showed that users were generally satisfied with site usability (77%). The results of the readability testing indicate that future versions could be improved. Feedback from the focus groups and interviews was generally positive. The use of multiple methodologies provided comprehensive testing that is likely to have identified the majority of usability issues. Ways in which the site can be maintained with up-to-date information and be promoted to the target population, informal carers, need to be explored.

Breast cancer data analysis for survivability studies and prediction.

BACKGROUND: Breast cancer is the most common cancer affecting females worldwide. Breast cancer survivability prediction is challenging and a complex research task. Existing approaches engage statistical methods or supervised machine learning to assess/predict the survival prospects of patients. OBJECTIVE: The main objectives of this paper is to develop a robust data analytical model which can assist in (i) a better understanding of breast cancer survivability in presence of missing data, (ii) providing better insights into factors associated with patient survivability, and (iii) establishing cohorts of patients that share similar properties. METHODS: Unsupervised data mining methods viz. the self-organising map (SOM) and density-based spatial clustering of applications with noise (DBSCAN) is used to create patient cohort clusters. These clusters, with associated patterns, were used to train multilayer perceptron (MLP) model for improved patient survivability analysis. A large dataset available from SEER program is used in this study to identify patterns associated with the survivability of breast cancer patients. Information gain was computed for the purpose of variable selection. All of these methods are data-driven and require little (if any) input from users or experts. RESULTS: SOM consolidated patients into cohorts of patients with similar properties. From this, DBSCAN identified and extracted nine cohorts (clusters). It is found that patients in each of the nine clusters have different survivability time. The separation of patients into clusters improved the overall survival prediction accuracy based on MLP and revealed intricate conditions that affect the accuracy of a prediction. CONCLUSIONS: A new, entirely data driven approach based on unsupervised learning methods improves understanding and helps identify patterns associated with the survivability of patient. The results of the analysis can be used to segment the historical patient data into clusters or subsets, which share common variable values and survivability. The survivability prediction accuracy of a MLP is improved by using identified patient cohorts as opposed to using raw historical data. Analysis of variable values in each cohort provide better insights into survivability of a particular subgroup of breast cancer patients.

Prevalence and characteristics of hereditary non-polyposis colorectal cancer (HNPCC) syndrome in immigrant Asian colorectal cancer patients.

BACKGROUND: The prevalence of Hereditary Non-Polyposis Colorectal Cancer (HNPCC) is 2 to 5% in the Caucasian population. HNPCC is caused by genomic mutations in DNA mismatch repair genes (MMR), namely MLH1, MSH2, MSH6, PMS2, and EPCAM. A non-hereditary, acquired process of hypermethylation of the MLH1 promoter can also lead to silencing of MLH1 protein expression. Diagnosis of HNPCC in patients with colorectal and other related cancers is important in the clinical treatment and surveillance of related cancers. The prevalence and clinical characteristics of HNPCC in Asian colorectal cancer patients has been reported in small studies and unique features have been suggested. METHODS: We retrospectively reviewed the clinical characteristics of Asian patients who were diagnosed of colon cancer between 1/2002 and 6/2015, and performed IHC for four MMR protein expressions on tumor specimens as a screening test for HNPCC, followed by confirmatory tests of genomic sequencing and hypermethylation analysis. RESULTS: One hundred forty-three patients were identified. Thirty-one patients were diagnosed younger than 50 years old, while 112 patients were diagnosed older than 50 years old. Six cases of HNPCC were found with a prevalence of 4.19%. The prevalence in the group of patients diagnosed younger than 50 years old is 16.1%, and that in patients diagnosed older than 50 years old is 0.89%. All patients with HNPCC had family histories of colon or gastric cancer. Tumor locations in the HNPCC patients were predominantly in the descending or sigmoid colon (67%). Half of the HNPCC patients had MSH6 mutations. Hypermethylation of the MLH1 gene was only present in 2.80% of the patients. CONCLUSION: The prevalence of HNPCC is high in patients younger than 50 years old and extremely low in those older than 50 years old. These results may be useful in the future development of guidelines for HNPCC laboratory screening among Asian patients. The pathological and clinical features of HNPCC in this group of Asian immigrant patients are more similar to those reported on Asian patients in their home countries than to Caucasian patients in Western countries, and will warrant further large-scale evaluation.

HOXC6 Overexpression Is Associated With Ki-67 Expression and Poor Survival in NPC Patients.

BACKGROUND: Homeobox (HOX) genes are expressed in adult cells and regulate expression of genes involved in cell proliferation as well as cell-cell and cell-extracellular matrix interactions. Dysregulation of HOX gene expression plays important roles in carcinogenesis in a variety of organs. Through data mining on a published transcriptome dataset, this study first identified Homeobox protein Hox-C6 (HOXC6) gene as one of the differentially upregulated genes in nasopharyngeal carcinoma (NPC). We aimed to evaluate HOXC6 expression and its prognostic effect in a large cohort of NPC patients. METHODS: We retrospectively examined the HOXC6 expression and Ki-67 index by immunohistochemistry in biopsy specimens from 124 patients with non-metastasized NPC. The results were correlated with the clinicopathological variables including disease-specific survival (DSS), metastasis-free survival (MeFS), and local recurrence-free survival (LRFS). RESULTS: HOXC6 high expression was positively correlated with increased Ki-67 labeling index, and significantly associated with increment of tumor stage (p=0.024), advanced nodal status (p<0.001) and American Joint Committee on Cancer (AJCC) stage (p=0.002). Its expression also correlated with worse prognosis in terms of DSS (p=0.008), MeFS (p=0.0047) univariately. In multivariate analyses, HOXC6 expression still remained prognostically independent to portend worse DSS (p=0.015, hazard ratio=1.988) and MeFS (p=0.036, hazard ratio=1.899), together with stage III-IV (p=0.024, DSS; p=0.043, MeFS). CONCLUSION: In summary, our results suggest HOXC6 may play a critical role in NPC progression and may serve as a potential prognostic biomarker in NPC patients.

Lymphoepithelioma-like carcinoma of the upper urinary tract.

In this report, we summarized the clinicopathologic features of ten cases of lymphoepithelioma-like carcinoma (LELC) of the upper urinary tract (ureter n = 6; renal pelvis n = 4), a rare variant of urothelial cancer characterized by a malignant epithelial component densely infiltrated by lymphoid cells. The initial diagnosis was made on radical nephrectomy in five cases, nephroureterectomy in three cases, and ureterectomy in two others. Four patients had pathologic stage T1 (n = 2) or T2 (n = 2) tumors, and six patients had stage pT3 disease. Microscopically, all tumors contained pure (n = 3) or predominant (n = 7) LELC, which composed 60 to 80% of the entire tumor. Non-LELC tumor component was adenocarcinoma (n = 2), spindle cell carcinoma (n = 1), or high-grade conventional urothelial carcinoma (n = 4). The LELC component was characterized by indistinct cytoplasmic borders and a syncytial growth pattern. Immunohistochemical staining showed LELC to be positive for cytokeratin AE1/AE3, CK7, CK34ßE12 (rare cells), CK5/6 (rare cells), and CK20 (rare cells); rare cells were p40 positive. GATA 3 was positive in all cases in a variable proportion of cells (20-80%). Lymphoid markers showed a polyclonal proliferation of predominant T cells admixed with B cells. In situ hybridization for the HPV genome was negative in all ten cases. Survival analysis showed no differences between LELC and conventional upper urinary tract urothelial carcinoma, pT classification being the only significant prognostic parameter. Morphologic recognition and distinction from other (non-)neoplastic lesions with prominent lymphoid stroma are critical for its clinical management.

Primary Cutaneous Extranodal Natural Killer/T-Cell Lymphoma Misdiagnosed as Peripheral T-Cell Lymphoma: The Importance of Consultation/Referral and Inclusion of EBV In Situ Hybridization for Diagnosis.

BACKGROUND: Primary cutaneous T-cell lymphomas (CTCL) are heterogenous extranodal non-Hodgkin lymphomas including a few distinct and provisional entities. Compared with the West, Asian populations have a relatively higher frequency of nonmycosis fungoides CTCL. Primary cutaneous extranodal natural killer/T-cell lymphoma (PC-ENKTL) is distinct from other CTCL by the presence of EBV association. METHOD: In our recent retrospective Asian study of PC-ENKTL, we identified 5 cases initially misdiagnosed as various CTCL. We fully characterized these cases with immunohistochemistry, EBV in situ hybridization, and clonality study for T-cell receptor (TCR) γ-chain gene (TRG). RESULTS: The 5 patients included 3 males and 2 females with a median age of 45. All tumors were positive for EBER. Two cases were clonal for TRG gene rearrangement but without expression of ßF1 or TCR-γ (TCR-silent T-cell origin), 1 tumor expressed TCR-γ (γδ T-cell origin), and the remaining 2 were polyclonal for TRG and negative for TCR expression (NK-cell origin). On the basis of the initial diagnoses (2 as peripheral T-cell lymphoma, unspecified, 2 as primary cutaneous anaplastic large-cell lymphoma, and 1 as subcutaneous panniculitis-like T-cell lymphoma), all patients received CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisolone) chemotherapy with additional radiotherapy in 3. All patients experienced persistent disease or relapse despite treatment in a mean duration of 8.8 months (range, 1 to 12 mo). CONCLUSIONS: PC-ENKTL is rare and aggressive. These cases strongly demonstrate the importance of consultation/referral to experienced hematopathologists and the inclusion of EBER in the initial diagnostic work-up for patients with nonmycosis fungoides CTCL to avoid erroneous diagnosis and subsequent inadequate treatment of the patients.

Nasopharyngeal alveolar rhabdomyosarcoma expressing CD56: a mimicker of extranodal natural killer/T-cell lymphoma.

Alveolar rhabdomyosarcoma (ARMS) is remarkably rare in adults older than 45 years. Histologically, the tumor is composed of blue round cells with frequent expression of CD56 in addition to myogenic markers. Recent studies of ARMS have shown two specific recurrent translocations: PAX3-FKHR [t(2;13)(q35;q14)] or PAX7-FKHR [t(1;13)(p36;q14)]. Extranodal natural killer (NK)/T-cell lymphoma (ENKTL) occurs most frequently in the upper aerodigestive tract with a male preference in East Asia and Central and South Americas with neoplastic cells frequently expressing CD56. We report a 53-year-old Taiwanese man presenting with a nasopharyngeal mass, cervical lymphadenopathy, and multiple bone metastases. Histologically, the nasopharyngeal biopsy revealed diffuse sheets of small blue round tumor cells without obvious alveolar pattern, angioinvasion or tumor necrosis. An initial erroneous diagnosis of ENKTL was made due to CD56 expression using fresh tumor tissue with flow cytometric analysis and the patient was treated accordingly. Retrospective study showed that the tumor cells expressed CD56, desmin, and myogenin. Fluorescence in situ hybridization revealed that the tumor cells were positive for FKHR gene rearrangement, confirming the diagnosis of ARMS. Our case illustrates that a diagnosis of ENKTL based solely on CD56 expression can be misleading for a nasopharyngeal small blue round cell tumor. ARMS should be included as a differential diagnosis, and a correct diagnosis can be reached only after a high index of suspicion and a thorough histological examination with the aid of ancillary studies.

Rapidly fatal leukemia comprising pleomorphic large granular lymphocytes: a report of 2 cases.

BACKGROUND: Large granular lymphocytes (LGLs) are either cytotoxic T or natural killer (NK) cells exhibiting round nuclei and azurophilic cytoplasmic granules. Morphologically, neoplastic LGLs of T cell lineage (T-LGLLs) are usually indistinguishable from normal LGLs, while there is a wide morphological range of aggressive NK cell leukemia (ANKL). CASES: We present 2 consecutive cases of leukemia comprising pleomorphic LGLs. One patient presented with drowsy consciousness and unstable hemodynamics. Her peripheral blood smear disclosed a significant number of LGLs with pleomorphic nuclei expressing CD2, CD56 and HLA-DR but not surface or cytoplasmic CD3 (cCD3). The second patient, previously healthy, presented with a sudden death. Her peripheral blood revealed LGLs ranging from round to pleomorphic nuclei with a CD2+ cCD3+ surface CD3- CD56+ phenotype and clonally rearranged T cell receptor gene. The findings of the first patient were consistent with ANKL and the second, T-LGLL. Both patients passed away shortly before treatment. CONCLUSION: The 2 cases highlight the importance of a multidisciplinary approach in addition to cytological examination to reach accurate diagnoses of such rare leukemia cases.

Nicotinamide N-methyltransferase overexpression is associated with Akt phosphorylation and indicates worse prognosis in patients with nasopharyngeal carcinoma.

Nicotinamide N-methyltransferase (NNMT) is overexpressed in many human cancers and is associated with poor prognosis. Akt (also known as protein kinase B) is an evolutionarily conserved serine/threonine kinase, serving as a downstream effector of the phosphatidylinositol 3-kinase signaling pathway. NNMT was first identified as a differentially upregulated gene in nasopharyngeal cancer tissues through data mining from published transcriptomic databases. Since no prior study has attempted to evaluate the clinical significance of NNMT or phosphorylated Akt (pAkt) expression in nasopharyngeal cancer, this study explores their expression in a large cohort of patients with nasopharyngeal cancer. The study included 124 nasopharyngeal cancer patients who were free of distant metastasis at initial diagnosis. Pathological slides were reviewed and clinical findings collected. We evaluated the expression of NNMT and pAkt immunohistochemically, stratified them into two groups (high and low expression) and examined the correlation with disease-specific survival (DSS), metastasis-free survival (MeFS), local recurrence-free survival (LRFS), and various clinicopathological factors. NNMT expression was significantly positively associated with pAkt expression. The high expression of both markers was significantly associated with an increment of tumor stage (p = 0.006 and p = 0.006, respectively). High expression of NNMT correlated significantly with a more aggressive clinical course and a significantly shorter DSS. Furthermore, NNMT expression and pAkt expression were strongly predictive of MeFS (p = 0.008; p = 0.0063) and LRFS (p = 0.005; p = 0.0125). In multivariate analysis, high expression of NNMT remained as a robust prognosticator for both end points evaluated. It independently portended inferior DSS (p = 0.02, HR = 1.976) and worse MeFS (p = 0.029, HR = 2.022) after tumor stage (p = 0.033, HR = 2.150; p = 0.028, HR = 2.942, for DSS and LRFS, respectively). We found NNMT positively correlated with pAkt expression and was independent adverse prognosticators of patient survival. NNMT therefore has potential utility as an indicator for prognosis, predicting treatment response to chemotherapy or radiation therapy, and even as a therapeutic target in the future.

Follicular lymphoma in Taiwan: a low frequency of t(14;18), with grade 3A tumours more closely related to grade 3B than to low-grade tumours.

AIMS: To investigate t(14;18)/IGH-BCL2 in follicular lymphoma (FL) cases from Taiwan. METHODS AND RESULTS: We retrospectively studied 93 consecutive cases, using immunohistochemistry and fluorescence in-situ hybridization (FISH). Fifty-nine (63%) tumours were low-grade (LG) and 34 (37%) were high-grade (HG; 24% FL3A and 13% FL3B). FISH showed IGH, BCL2 and BCL6 rearrangements in 59%, 47% and 11% of cases, respectively, and MYC rearrangement in 5% of FL3A tumours and 25% of FL3B tumours. The translocation partner of all BCL2 rearrangements was IGH, with IGH-BCL2 fusion in 63% of LG tumours and 18% of HG tumours. LG tumours were enriched with a CD10+/bcl-2+/MUM1- phenotype, and were frequently associated with BCL2 rearrangement but less commonly with BCL6 rearrangement. FL3A tumours were more closely related to FL3B tumours than to LG tumours in immunophenotype and genetic aberrations. There was no statistically significant difference between grade 1 and two tumours, between FL3A and FL3B tumours or between nodal and extranodal tumours in immunophenotypic or FISH findings. The cumulative survival rate was higher in LG FL patients with IGH-BCL2 translocation than in those without rearrangement. CONCLUSIONS: In Taiwan, FL3A tumours were more closely related to FL3B tumours than to LG tumours, and a literature review showed that the frequency of t(14;18)/IGH-BCL2 in FL in Taiwan is among the lowest in the world.