Trends in AI-powered Classification of Thyroid Neoplasms Based on Histopathology Images - a Systematic Review.

Background: Assessment of thyroid nodules histopathology using AI is crucial for an accurate diagnosis. This systematic review analyzes recent works employing deep learning approaches for classifying thyroid nodules based on histopathology images, evaluating their performance, and identifying limitations. Methods: Eligibility criteria focused on peer-reviewed English papers published in the last 5 years, applying deep learning to categorize thyroid histopathology images. The PubMed database was searched using relevant keyword combinations. Results: Out of 103 articles, 11 studies met inclusion criteria. They used convolutional neural networks to classify thyroid neoplasm. Most studies aimed for basic tumor subtyping; however, 3 studies targeted the prediction of tumor-associated mutation. Accuracy ranged from 77% to 100%, with most over 90%. Discussion: The findings from our analysis reveal the effectiveness of deep learning in identifying discriminative morphological patterns from histopathology images, thus enhancing the accuracy of thyroid nodule histopathological classification. Key limitations were small sample sizes, subjective annotation, and limited dataset diversity. Further research with larger diverse datasets, model optimization, and real-world validation is essential to translate these tools into clinical practice.

Adenomyoepithelioma of the Breast: A Report of 3 Cases.

BACKGROUND Breast adenomyoepithelioma is a rare benign breast tumor characterized by a biphasic proliferation of epithelial and myoepithelial cells with variable clinical and diagnostic features. Establishing the diagnosis, determining optimal therapy, and predicting outcome are problematic because of the rarity of this entity. There have been only 2 large series of adenomyoepitheliomas of the breast, reported by Tavassoli and Rosen, which included 27 and 18 patients, respectively. In this report, we present 3 cases of breast adenomyoepithelioma. CASE REPORT Herein, we report 3 cases of breast adenomyoepithelioma. The first case is of a 64-year-old woman who was found to have right breast microcalcification on a screening mammogram. The second case is of a 74-year-old woman who had a right breast mass. These 2 patients were managed by wide local excision. Postoperative microscopic examination revealed adenomyoepithelioma. The third case is of a 49-year-old woman with bilateral saline breast implants who presented with a left breast mass. A core needle biopsy was done and revealed adenomyoepithelioma associated with usual ductal hyperplasia and ductal carcinoma in situ. CONCLUSIONS Breast adenomyoepithelioma is a rare condition that can pose diagnostic challenges due to variable imaging presentations, necessitating percutaneous core biopsy for initial diagnosis. Correct diagnosis is usually possible only on excisional biopsy and confirmed by demonstrating the biphasic nature of the tumor by IHC. Clinical suspicion coupled with utilizing both radiological and histopathological facilities can aid in the accurate diagnosis and management. For the most part, they are considered to be benign, but they can locally recur.

Correlation of prognostic and predictive indicators in breast cancer patients from the eastern province of Saudi Arabia.

OBJECTIVES: To highlight and correlate demographic and histopathological features of breast cancer along with prognostic and predictive biomarkers, in Saudi patients from the Eastern Province and compare it to a cohort of non-Saudi patients. METHODS: In a retrospective study between January 1998 and December 2017, data were collected from the medical records of breast cancer patients who were admitted at King Fahd University Hospital (KFHU), Dammam, Saudi Arabia. The information included demographic, histopathological, and immunohistochemical findings. RESULTS: Out of 482 breast cancer patients, 60% (n=286) were Saudis, and 40% (n=196) were non-Saudis. Data showed a wide age distribution; however, most cases (80%) were seen in the third through fifth decades, with a median age at diagnosis of 51 ±12 years. Over years, breast cancer in Saudi patients was increasingly seen at a younger age (p=0.003). While tumors were increasingly detected at earlier stages (p=0.003); however, stage III & IV tumors (p=0.033) and human epidermal growth factor receptor-2 overexpressed tumors (p=0.035) were more frequently seen at a younger age. Interestingly, these associations were not significant in non-Saudi patients. CONCLUSION: Although, the current findings might help future studies to identify variables that could lead to better management of breast cancer in this region; however, a wider investigation including other centers in the eastern province is needed.

Concomitant hepatic tuberculosis and hepatocellular carcinoma: a case report and review of the literature.

BACKGROUND: Hepatocellular carcinoma (HCC) is the most common primary liver malignancy that is strongly associated with chronic liver disease. Isolated hepatic tuberculosis is an uncommon type of tuberculosis. Concomitant occurrence of both conditions is extremely rare. CASE PRESENTATION: We report the case of a 47-year-old man who presented with fever and abdominal pain for 3 months prior to presentation. He reported a history of anorexia and significant weight loss. Abdominal examination revealed a tender, enlarged liver. Abdominal computed tomography (CT) demonstrated a solid heterogeneous hepatic mass with peripheral arterial enhancement, but no venous washout, conferring a radiological impression of suspected cholangiocarcinoma. However, a CT-guided biopsy of the lesion resulted in the diagnosis of concomitant HCC and isolated hepatic tuberculosis. CONCLUSION: A rapid increase in tumor size should draw attention to the possibility of a concomitant infectious process. Clinicians must have a high index of suspicion for tuberculosis, especially in patients from endemic areas, in order to initiate early and proper treatment.

Polymorphic Variants in 5'-UTR Regions of the RAD51 Gene are Associated With RAD51 Expression and Triple-Negative Breast Cancer (TNBC): A Case-Control Study.

Breast cancer is a heterogeneous disease at morphologic and molecular levels, which is considered the most commonly occurring cancer in women. RAD51, a DNA-repairing protein, involves homologous recombination and has a vital role in genome stability. Polymorphism of the RAD51 gene, and its overexpression, has been proposed to be associated with the development of breast cancer. Overexpression of RAD51 in many types of human cancer including metastatic breast cancer may signify its potential use as a biomarker. Considering the numerous reports on the role of the 5'-UTR-RAD51 polymorphism in breast cancer, this study aimed to investigate the utility of RAD51 gene expression and its variants G135C and G172T as a possible foretelling factor of breast cancer development. DNA sequencing and immunohistochemistry of RAD51 were conducted on 103 samples from patients diagnosed with sporadic breast cancer and 80 samples from a control group. The results demonstrated that the RAD51 variants, G135C and G172T, were significantly presented in the breast cancer tissue compared with the control group. RAD51 expression was mainly shown in the cytoplasm of malignant cells (56% of cases) and significantly correlated with p53 and G135C, C135C variants. Moreover, the occurrence of the G172T variant was significantly associated with the expression of estrogen receptor. Interestingly, 21/26 (81%) of the triple-negative breast cancer showed G135C and C135C genotypes that were significantly associated with the expression of RAD51 (73%). In conclusion, the G135C and C135C variants together with the cytoplasmic expression of RAD51 may have clinical potential as a prognostic predictor for breast cancer development and aggressiveness.

The accuracy of nipple discharge cytology in detecting breast cancer.

OBJECTIVES: This study aimed to disclose the importance of nipple discharge (ND) and the accuracy of its economic and fast cytological interpretation. METHODS: All ND cytology cases for Saudi patients done between 2004 and 2013 were retrieved from the Pathology e-system. Only cases that have subsequent tissue diagnoses were included in this study (n = 228). Age and bloody nature of the ND were both tested for association with a higher chance of carcinoma. Diagnostic accuracy of ND cytology was calculated twice, including and excluding the "atypical" cases. RESULTS: Specificity and positive predictive value were 100% for ND cytology in both cases. Sensitivity (34.6%; 52.9%), negative predictive value (93.15 %; 96.1%), false-negative rate (65.4%; 47.1%), accuracy rate (93.4%; 96.2%), when atypical cases were included and excluded; respectively. Only 10.5% of the patients complaining from nipple discharge had breast cancer. For those who had cancer, nipple discharge cytology was positive and showed the cancer cells in only 37.5%, while the rest were false negative. Bloody ND disclosed a significant association with malignancy (p < 0.001), but the association was statistically not significant for old age (p = 0.062). CONCLUSIONS: The prospect of having breast cancer with the presentation of ND is low, and it can be missed by studying the ND cytology alone in a high proportion of cases. Excluding the atypical category did not make a significant improvement in the test's accuracy.

Correlation of High-Risk HPV Genotypes with Pap Test Findings: A Retrospective Study in Eastern Province, Saudi Arabia.

INTRODUCTION: High-risk human papillomavirus (HR HPV) is found to be responsible for 4.5% of cancer in general, primarily cervical cancer. We aim here to highlight the prevalence and genotypes of HR HPV and correlate its association with Pap tests' results, which are still not well known in the Eastern Province of Saudi Arabia. METHODS: Over 7 years (2013-2019), the results of 164 Saudi women coinvestigated for HR HPV along with Pap tests were collected from the archive of King Fahd University Hospital. Only women who had atypical squamous cells of undetermined significance (ASCUS) on the Pap test and those at elevated risk of infection were cotested for HR HPV; otherwise, the Pap test was the only screening modality for cervical cancer. Data were organized and statistically analyzed using IBM SPSS v26. RESULTS: Out of 164 Saudi women, 14.5% (n = 24/164) showed positive results for HR HPV (8 patients had HPV16 and 2 had both HPV16 and HPV18/45, while the remaining 14 had other HR HPV); among them, 41.5% (n = 10/24) had an abnormal Pap test (5 ASCUS and 5 LSIL), while 58.5% (n = 14/24) had a negative Pap test. On the other hand, 21% (n = 35/164) of patients, in the study, had an abnormal Pap test (24 ASCUS, 8 low-grade squamous intraepithelial lesion [LSIL], and 3 atypical glandular cell [AGC]). In 80% (n = 19/24) of ASCUS cases, HR HPV was not detected; however, 20% (n = 5/24) were positive for other HR HPV. Concerning LSIL cases, 62.5% (n = 5/8) were positive for HR HPV (1 case showed HPV16 and HPV18/45, 2 cases showed HPV16, and 2 cases showed other HR HPV), while in the remaining 37.5% (n = 3/8) LSIL cases, HR HPV was negative; similarly, all AGC cases were negative for HR HPV. Statistical analysis showed a significant correlation between HPV status and Pap test findings (p value <0.001). DISCUSSION/CONCLUSION: HR HPV frequency and genotype distribution, in this study, might reflect a different regional infection pattern. The high association of HR HPV with negative cytology emphasizes the need to add the HR HPV test to screening modalities of cervix cancer.

Investigations of a Possible Role of SNPs in KAI1 Gene on Its Down-Regulation in Breast Cancer.

OBJECTIVE: KAI1 (CD82) is a metastasis suppressor gene known to be down-regulated in carcinomas of breast, prostate and many other organs. The mechanism of KAI1 down-regulation is complex and not well understood. Here, we investigate the role of 8 SNPs (not previously studied) in KAI1 gene that could influence its expression in tumor tissue samples of breast cancer patients from the Eastern province of Saudi Arabia. METHODS: Single nucleotide polymorphisms (SNPs) in KAI1 gene were selected from the NCBI website (dbSNP) and were then filtered for those SNPs causing stop codon mutations (rs139889503 and rs150533529) or nonsynonymous mutation in the 5'-UTR (rs11541048, rs77359459, rs115500759, rs182579675, rs200238062, and rs372733853). SNPs genotyping was performed using TaqMan SNP Genotyping Assay and the results were correlated with KAI1 protein expression profile by immunohistochemistry (IHC) on formalin-fixed paraffin-embedded (FFPE) samples of breast cancer and control none-neoplastic tissues. RESULTS: KAI1 expression by IHC was observed in all none-neoplastic breast tissue samples and only in 35% out of the 59 breast cancer tissue samples. None of the samples was homozygous for the stop codon allele A in the SNP rs139889503 or allele T in the SNP rs150533529. The SNPs in the 5-UTR, rs11541048, rs115500759, and rs182579675, were only present in the homozygous state for the G and C alleles respectively in both cancer and control samples. The other SNPs in the 5'-UTR (rs77359459, rs200238062, and rs372733853) had no significant difference in the allele distribution between KAI1 expressing or none-expressing tissue samples. CONCLUSION: Our findings showed no significant effect of the studied SNPs on down-regulation of KAI1 expression.
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Pathway-Affecting Single Nucleotide Polymorphisms (SNPs) in RPS6KA1 and MBIP Genes are Associated with Breast Cancer Risk.

BACKGROUND: Genetic mutations and polymorphisms play an important role in the transformation of primary cells to malignant cells as it may lead to disturbance of vital pathways regulating cell cycle, DNA damage repair, and apoptosis. In this study, we genotyped single nucleotide polymorphisms (SNPs) which were predicted to affect certain pathways and to increase the risk of breast cancer. METHODS: The study included 81 Saudi breast cancer patients and 100 matching healthy controls from the Eastern Province in Saudi Arabia. The following SNPs (rs3168891, rs2899849, rs2230394, rs2229714) were then genotyped by TaqMan genotyping assay and the allele and genotype distribution was compared. RESULTS: The minor allele frequency of the following SNPs (rs3168891, rs2899849, rs2230394, rs2229714) was T=0.17, A=0.28, A=0.22, and G=0.16 respectively. The G allele of the SNP rs3168891 was significantly associated with increased breast cancer risk (P = 0.00001) while the T allele of the same locus was associated with reduced risk of breast cancer in both heterozygous and homozygous states. The T allele of SNP rs2229714 which is located in the RPS6KA1 gene was also significantly associated with the increased risk of breast cancer. However, the rs2899849 SNP located in the Integrin beta-1 (ITGB1) gene was not associated with the increased risk of breast cancer in our study population. Haplotype analysis revealed the presence of three risk haplotypes that increases the risk of breast cancer (TGGT, TGTA, GATA). CONCLUSION: We showed that three, previously untested, SNPs are associated with increased risk of breast cancer in our population.  This may be added to the list of factors involved in breast cancer risk assessment studies. The benefit and the utility of the in-silico prediction of disease risk factors and their genetic association had been demonstrated in this study, yet the predicted risk alleles have to be tested in clinical studies.
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Co-expression of CD34 and h-caldesmon in a benign meningioma-like dermal neoplasm, a case report.

Meningioma-like dermal tumor with diffuse coexpression of CD34 and hcaldesmon is rarely reported. Herein, we report a case of a 58-years-old woman who complained of a solitary dome-shaped papule on the left hand. An ellipse of skin measuring 1 x 0.5 x 0.5 cm was excised and sent for histopathological evaluation. Upon sectioning, the specimen showed a whitish firm dermal nodule measuring 3 mm in its greatest dimension. Microscopic examination revealed a well-circumscribed barely encapsulated dermal lesion showing compact round whorled sheets formed of round to ovoid uniform cells with abundant pink cytoplasm. Occasional intranuclear vacuoles were seen. A minor capillary-sized vascular component was seen in the background. Immunohistochemical (IHC) study revealed a diffuse positivity of tumor cells to CD34 and h-caldesmon along with faint reaction to Smooth Muscle Actin (SMA) and ER. However, Desmin, S100, HMB45, EMA, Pan Cytokeratin, and Chromogranin were all negative. Ki67 was very low (1%). The main differential diagnoses of the current lesion are meningioma and glomus family tumors. While the current lesion is morphologically reminiscent of cutaneous meningioma; neither the location nor the IHC stains support that diagnosis. The glomus family is highly suggestive. However, the location, the compact nature of the proliferation, and the positivity of CD34, all are unusual in such entities.

Transurethral Resection for the Treatment of an Inflammatory Myofibroblastic Tumor of the Urinary Bladder: A Case Report.

Inflammatory myofibroblastic tumors (IMT) of the urinary bladder is a remarkably rare bladder tumor. To this day, no standardized treatment protocol has been recognized. Here we report a case of bladder IMT in a 14-year-old girl presenting with urgency, frequency, and gross painless hematuria for a week. Complete excision of the bladder IMT was amenable with transurethral resection of bladder tumor (TURBT). Follow-up cystoscopy did not detect any recurrence. Minimally invasive bladder-sparing treatments are a valid option for treating IMT of the bladder.

Total Spondylectomy for Upper Thoracic Spine Giant Cell Tumor: A Case Report.

INTRODUCTION: Giant cell tumors (GCT) are benign lesions that are generally locally aggressive tumors with occasional malignant behavior. These tumors are most frequently encountered in long bones; however, they also occur rarely in the spine. GCT of the spine are rare pathological entities, and spinal involvement shows a sacral predilection, with only a few cases involving the supra-sacral segment (mobile spine). Only a few cases of thoracic spinal GCT are reported in the literature; these tumors are particularly uncommon in the thoracic segment. PRESENTATION OF CASE: A 29-year-old man presented with a complaint of neck pain over the previous six months that radiated to his left hand. GCT of the upper thoracic spine was diagnosed, which was surgically managed using a 2-stage approach involving total resection of the tumor followed by spondylectomy and multilevel spinal fixation. DISCUSSION: Accurate diagnosis of vertebral column lesions, and choosing an optimum management plan are crucial. In the majority of cases, En-bloc resection of GCTs is not feasible ought to the close contact of the lesion with the spinal cord. Larger studies are encouraged to ascertain the efficacy of variable management approaches, particularly compared with piecemeal resection techniques. CONCLUSION: Spinal GCT are a unique group of tumors with an uncommon and unexpected presentation. Although surgery is the mainstay of treatment for spinal GCT, the management of this tumor can be challenging. No clear management algorithm has been established, and the tumor displays an unpredictable course. Therefore, each case needs tailored treatment.

A Rare Presentation of Inflammatory Myofibroblastic Tumor in the Nasolabial Fold.

Inflammatory myofibroblastic tumor (IMT) is a benign lesion that occurs most frequently in the soft tissues and viscera. In the head and neck region, the tumor has been reported to occur in the orbit, tongue, nasopharynx, larynx, and paranasal sinuses and the central nervous system. Despite being a benign lesion, it exhibits infiltrative and destructive behaviours, making histopathological examination necessary to confirm the diagnosis. We report the case of a 38-year-old female presented with a right nasolabial fold mass, which was confirmed histologically to be an IMT. Surgical excision of the mass was achieved through a sublabial approach with an uneventful postoperative period. To the best of our knowledge, this is the first reported case of an IMT in the nasolabial fold.

Alternative splicing is an important mechanism behind KAI1 loss of function in breast cancer patients from Saudi Arabia.

PURPOSE: KAI1 (also called CD82) is a metastasis suppressor gene known to be downregulated in breast cancer and other solid tumors. The downregulation of KAI1 or loss of its function is usually associated with bad prognosis. The mechanism behind KAI1 loss of function is complex. In this study, we investigated "alternative splicing" as a possible mechanism that underlies KAI1 loss of function in breast cancer patients from a tertiary hospital in Saudi Arabia. METHODS: Expression of KAI1 was studied in FFPE breast cancer and control tissue sections by IHC using two different antibodies targeting different domains of the protein. The TS82B antibody targets the extracellular loop, which constitutes most of the protein, while the second EPR4112 antibody targets the C-terminal intracellular domain of the protein. RESULTS: Out of 90 breast cancer samples, 67% showed loss of KAI1 expression. The remaining 33% showed KAI1 expression with (TS82B) antibody; however, the protein was detected in only 11% of cancers when using the antibody (EPR4112) indicating a truncation of the protein at the C-terminus (truncated-KAI1) in 22% of the studied cancer samples. A significant correlation was found between truncated-KAI1 expression and advanced cancer stage (association with lymph node metastasis, P value 0.008). CONCLUSION: Alternative splicing is an important mechanism underlying KAI1 loss of function in breast cancer, and it is associated with bad prognosis (advanced cancer stage).

Prevalence of Mouse Mammary Tumor Virus (MMTV)-like sequences in human breast cancer tissues and adjacent normal breast tissues in Saudi Arabia.

BACKGROUND: Breast cancer is considered the most common cancer in women worldwide and is the leading cause of cancer mortality. Sequences similar to Mouse Mammary Tumor Virus (MMTV) were detected in human breast cancer in several studies from different geographical areas. However, the role played by this virus in breast cancer tumorigenesis is not completely understood. These MMTV-like sequences were found to be associated with breast cancer of more malignant types. The aim of this study is to determine the prevalence of MMTV-like envelope gene (env) positivity in breast cancer and non-cancerous breast tissue from Saudi Arabia. METHODS: Detection of MMTV-like env proviral sequences was done using newly designed primers for conventional polymerase chain reaction (PCR). One hundred nighty four samples were collected from 103 females with breast cancer in addition to 51 control breast tissue obtained from individuals without cancer. We additionally investigated the association of proviral positivity with age of the patients, grade of breast cancer and presence of lymph node metastasis. The results were confirmed by sequencing. RESULTS: The prevalence of MMTV-like env proviral positivity was 8.7% (9/103). MMTV env proviral sequences were detected in 5.9% (6/101) of breast cancer tissues and 9.7% (9/93) of non-cancerous adjacent tissues obtained from the same patients. None of the 51 control sample showed positive result for the MMTV env gene. No significant association was found between detection of the virus and the age of the patient, grade of the cancer or presence of metastasis. CONCLUSION: We document the presence of low frequency of MMTV env provirus sequence among breast cancer patients from Saudi Arabia. Further studies are needed to explore the role of the MMTV in breast cancer.

The updated grading system of prostate carcinoma: an inter-observer agreement study among general pathologists in an academic practice.

In 2016, the grading criteria for Gleason scoring (GS) have been updated in the WHO classification of tumors of the prostate, and a new set of grade groups (GG) was introduced. As the inter-observer discordance is a well-known concern in Gleason grading before the update and no reproducibility study testing the grade groups exists, we planned to evaluate the inter-observer agreement of the most updated grading system. Four pathologists assessed 126 cores of prostatic carcinoma, and Kappa (k) test was calculated. The agreements for both GS and GG were substantial (k = 0.753 and 0.752; respectively). Discerning GG 2 from 3 also attained reasonable outcome (k = 0.675). Based on our results, the updated grading system seems to be reproducible, with satisfactory inter-observer concordance rate.

HL7 CDA implementation guide for structured anatomic pathology reports methodology and tools.

UNLABELLED: Anatomic pathology reports (APR) provide diagnostic and prognostic information crucial to patient care, clinical research and epidemiology. Currently, it is difficult to collect and exchange APR data between different healthcare organizations at an international level. OBJECTIVE: IHE and HL7 anatomic pathology joint efforts aim at providing a methodology and tools to define an international HL7 "Clinical Document Architecture" (CDA) implementation guide for APRs and especially in the domain of cancer. METHODS: A four-step methodology is employed, consisting of comparing existing clinical model of APRs originating from different countries; deriving consensus-based clinical models (Delphi technique); providing the corresponding HL7 CDA implementation guide ("CDA templates") and validating these templates. RESULTS: International experts defined HL7 CDA implementation guides for breast and colon cancer APRs within an IHE content profile. CDA templates include required data elements, as well as optional ones, that can be further specified as required in national extensions. CONCLUSION: This study demonstrates that it is possible to define an international HL7 CDA implementation guide for cancer APRs. Further efforts are needed to provide CDA templates for approximately 60 other cancer APRs dedicated to different organs, diagnoses, and procedures as well as for APRs of non neoplastic pathologies. The methodology is not confined to APRs and could be applied to clinical documents of any type.

[A case of giant cell microscopic colitis?]. / Une colite microscopique à cellules géantes ?

Microscopic colitis is the most common cause of chronic watery diarrhea, with normal mucosal appearance during colonoscopy. The diagnosis is made by pathological examination of biopsy specimens showing colitis with normal architecture of the mucosa. The two most frequent forms of microscopic colitis are lymphocytic colitis and collagenous colitis, but other atypical variants have been described. We report a case of lymphocytic colitis with multinucleated large cells and we discuss a variant of giant cells microscopic colitis.

[On line digital microscopy in 2007: One technology, many uses]. / Lames virtuelles en ligne en 2007: une technologie au service de nombreuses applications en pathologie.

Digital microscopy enables several observers to look at any field of one microscopical section, at any magnification, through an Internet connexion. An overview of the systems used to digitize microscopy slides and to put them on line is presented. This technique is already used in many fields of pathology, for teaching, research and, to a lesser extent, diagnostic purposes. Several examples are given in this review, some of them with a true evaluation process, and strong points and weaker points are addressed. While conventional microscopy remains the keystone method in 2007 and for the coming years, it is also obvious that digital microscopy will be playing an increasing role. It is our task to make it evolve according to our needs.