Generative Adversarial Networks in Digital Histopathology: Current Applications, Limitations, Ethical Considerations, and Future Directions.

Generative adversarial networks (GANs) have gained significant attention in the field of image synthesis, particularly in computer vision. GANs consist of a generative model and a discriminative model trained in an adversarial setting to generate realistic and novel data. In the context of image synthesis, the generator produces synthetic images, whereas the discriminator determines their authenticity by comparing them with real examples. Through iterative training, the generator allows the creation of images that are indistinguishable from real ones, leading to high-quality image generation. Considering their success in computer vision, GANs hold great potential for medical diagnostic applications. In the medical field, GANs can generate images of rare diseases, aid in learning, and be used as visualization tools. GANs can leverage unlabeled medical images, which are large in size, numerous in quantity, and challenging to annotate manually. GANs have demonstrated remarkable capabilities in image synthesis and have the potential to significantly impact digital histopathology. This review article focuses on the emerging use of GANs in digital histopathology, examining their applications and potential challenges. Histopathology plays a crucial role in disease diagnosis, and GANs can contribute by generating realistic microscopic images. However, ethical considerations arise because of the reliance on synthetic or pseudogenerated images. Therefore, the manuscript also explores the current limitations and highlights the ethical considerations associated with the use of this technology. In conclusion, digital histopathology has seen an emerging use of GANs for image enhancement, such as color (stain) normalization, virtual staining, and ink/marker removal. GANs offer significant potential in transforming digital pathology when applied to specific and narrow tasks (preprocessing enhancements). Evaluating data quality, addressing biases, protecting privacy, ensuring accountability and transparency, and developing regulation are imperative to ensure the ethical application of GANs.

New insights inside the interdigitating dendritic cell sarcoma-pooled analysis and review of literature.

Interdigitating dendritic cell sarcoma is a rare haematological neoplasm with high debatable management protocols. The data extracted from 127 case reports published between 1981 and 2018 were analysed. The median age at diagnosis was 58 years with a male to female ratio of 1.65:1. The median OS and PFS of IDCS were 12 and 6 months, respectively, with a disease-specific mortality rate of 36.4%. Two-thirds of patients had a localised disease, while 30% had a disseminated form with 1-year mortality rates of 21.1% and 78.9%, respectively. Twenty per cent of cases were associated with other malignancies. Histologically, the proliferation of large spindle-shaped cells with fascicular growth was described in 84.3% of cases. Based on Cox-regression model, surgical resection was the only treatment modality linked to survival improvement with no recorded survival benefits of radiotherapy and chemotherapy. The 1-year mortality rates in resected and non-resected disease were 17.8% and 63.2%, respectively (P < 0.0001).

Management of presumed trematode induced granulomatous uveitis in pediatric patients.

PURPOSE: To outline the management of newly identified trematode induced uveitis in pediatric patients STUDY DESIGN: Prospective interventional case series METHODS: Patients with distinctive uveitis were recruited to either receive steroid monotherapy or undergo surgical excision of the inflammatory lesions based on a scoring system. Outcome measures included best corrected visual acuity (BCVA), intraocular inflammatory activity, and incidence of ophthalmic complications RESULTS: 170 patients (174 eyes) were recruited. Mean age was 11.1 years. Mean initial decimal BCVA (± SD) was 0.58 (± 0.31). Of 116 eyes with disease scores <5, 109 were treated effectively with steroids (93.97%). Surgical excision was offered to 58 patients and proved curative in the treated eyes. Protracted inflammation with persistence of the granulomas was noted in 5 patients refusing surgery. Mean follow up period was 21.5 months. Mean final BCVA was 0.69 (±0.27). A significant change in BCVA was noted (p=0.002). There has not been a need for retreatment in any of the study patients, who were also given instructions on evading exposure to fresh water habitats. Larger lesions, mixed disease morphology, older age at presentation were associated with higher rates of ophthalmic complications and vision loss CONCLUSION: A novel waterborne trematode inducing uveitis has been identified in Egypt. A favorable response to steroid monotherapy is demonstrated in low grade disease, while surgical excision was found to be curative in patients with larger lesions or those showing suboptimal response to medical treatment.

HER2 expression is a strong independent predictor of nodal metastasis in breast cancer.

Identification of metastatic potential of breast cancer cells is necessary for proper management of this disease. This work aimed to estimate likelihood of axillary lymph node (ALN) involvement in breast cancer patients based on human epidermal growth factor receptor 2 (HER2) expression. Primary tumors of 317 breast cancer patients were evaluated for estrogen receptor (ER), progesterone receptor (PR) and HER2 expression by immunohistochemistry. The validity of these molecules to predict ALN metastasis was measured statistically and compared to predictive effect of other clinicopathological parameters. ER, PR and HER2 expression was detected in 75.7%, 73.2% and 19.9% of tumors, respectively. Although increased tumor size and grade, ER and PR negativity and HER2 positivity were strong indicators of ALN metastasis on univariate analyses, only tumor size and HER2 expression were independent predictors of ALN involvement on multivariate analysis. ROC curve showed a strong validity of the model using these two parameters to predict ALN status (AUC 0.86; p<0001). HER2-rich, luminal B and triple negative tumors had 6.87, 6.32 and 3.58 times increased risk of metastasis compared to luminal A tumors; respectively. HER2 expression in pT1 and pT2 tumors raised the risk of ALN metastasis by 7.7 and 7.6 times, respectively and grade 1 and 2 tumors that expressed HER2 were 16.0 and 7.8 times more likely to have ALN metastasis, respectively. To conclude, HER2 expression is associated with a significant rise of metastatic potential of breast cancer cells and could be a strong indicator of regional and distant metastasis of breast cancer.

Ocular Surface Disorders in a Group of Egyptian Children with End Stage Renal Failure on Dialysis: A Cross-Sectional Study.

Purpose. To investigate tear function, ocular manifestations, and squamous metaplasia of the conjunctival epithelium (SMCE) in children with end stage renal failure (ESRF) on dialysis. Methods. Thirty children with ESRF and 20 age and sex matched controls during the period from January 2014 to May 2015 underwent full ophthalmologic examination and the tear function was investigated by the Schirmer and tear film break-up time (TBUT) tests. SMCE was evaluated by impression cytology and immunocytochemistry. The correlations of tear function status with ESRF-related clinical and biochemical variables were measured statistically. Results. Dry eye symptoms were detected in 26% of children with ESRF, compared with none of the controls (P = 0.05) and SMCE was almost absent. Values of the Schirmer and TBUT tests were significantly lower in children with ESRF for right eye (t = 24.63, P = 0.01, and t = 11.9, P = 0.002, resp.) and left eye (t = 24.7, P = 0.02, and t = 11.4, P = 0.0004, resp.). TBUT and the Schirmer test values were correlated inversely with the duration of ESRF (R = -0.45, P = 0.01, and R = -0.46, P = 0.01, resp.) and with the duration of dialysis (R = -0.39, P = 0.03, and R = -0.45, P = 0.01, resp.). None of the following parameters was associated with distorted tear function including serum creatinine, electrolytes, parathyroid hormone, total protein, albumin, CBC parameters, and systolic or diastolic blood pressure. Conclusion. The basal tear secretion and tear film stability were lower while the dry eye symptoms such as itching and redness were more common among children with ESRF. The duration of ESRF and dialysis duration seem to be related to the disturbances in tear secretion and tear film stability. However, SMCE is very rare.

Rhinoscleroma: a detailed histopathological diagnostic insight.

Rhinoscleroma (RS) is a chronic specific disease of nose and upper respiratory passages caused by Klebsiella rhinoscleromatis bacilli. It is endemic in Egypt and in sporadic areas worldwide. Diagnosis of RS depends on identification of the pathognomonic Mickulicz cells (MCs) which is most prominent during granulomatous phase but spares or absent during catarrhal or sclerotic phases of the disease. This study aimed to identify the potential diagnostic features of nasal RS when MCs are absent. Nasal biopsies from 125 patients complaining of chronic nasal symptoms were retrieved for this study; including 72 chronic non specific inflammatory lesions and 53 RS diagnosed by PAS and Geimsa stains. The detailed histological differences among the two groups were measured statistically. RS was frequently a bilateral disease (P < 0.05) of young age (P < 0.001) with a female predominance (P < 0.05) and usually associated with nasal crustations (P < 0.001). Five strong histological indicators of RS were specified by univariate binary logistic regression analyses including squamous metaplasia (OR 27.2, P < 0.0001), dominance of plasma cells (OR 12.75, P < 0.0001), Russell bodies (OR 8.83, P < 0.0001), neutrophiles (OR 3.7, P < 0.001) and absence of oesinophiles (OR 12.0, P < 0.0001). According to Multivariate analysis, the diagnostic features of RS in absence of MCs can be classified into major criteria including dominance of plasma cells infiltration and absence of oesinophiles and minor criteria including young age, female gender, bilateral nasal involvement, nasal crustation, squamous metaplasia, Russell bodies, and neutrophiles. The diagnostic model using the two major criteria confirmed or excluded RS in 84.3% of the investigated cases.

E-cadherin and CD10 expression in atypical hyperplastic and malignant endometrial lesions.

BACKGROUND: Loss of E-cadherin is a critical step for development and progression of malignant tumors. CD10; a marker of non-neoplastic and neoplastic endometrial stroma, is associated with aggressiveness of many epithelial malignancies. AIMS: To evaluate expression and correlation of E-cadherin and CD10 in endometrial lesions and their possible role in differentiating atypical endometrial hyperplasia from endometrial carcinoma. The association of E-cadherin and CD10 expression with clinico-pathological parameters of endometrial carcinoma was also investigated. MATERIALS AND METHODS: Fifty four cases including 28 endometrial carcinomas; 19 endometrial hyperplasia and 7 cases of normal endometrial changes were enrolled for this study. The expression of E-cadherin and CD10 was evaluated by immunohistochemistry using the streptavidin-biotin technique. RESULTS: There was a strong association between malignant change of endometrial glands and membrano-cytoplasmic localization of E-cadherin (p<0.001). Expression of E-cadherin but not CD10 was significantly higher in endometrial carcinomas compared to atypical endometrial hyperplasia (p<0.01). Expression of E-cadherin was not associated with CD10 expression in different endometrial lesions. High grade tumors expressed low levels of both E-cadherin (p<0.01) and CD10 (p<0.05) and serous endometrial carcinoma had low E-cadherin and CD10 expression compared to endometrioid carcinoma (p<0.01 and <0.05, respectively). Expression of both molecules showed no association with depth of tumor invasion or FIGO stage. Tumors with lower E-cadherin or CD10 expression had higher rates of vascular tumor emboli (p<0.01 and <0.07, respectively). CONCLUSIONS: Although expression of E-cadherin and CD10 in endometrial lesions was not correlated, reduced expression of both molecules could be critical for progression of endometrial carcinoma.

TFF3 is a normal breast epithelial protein and is associated with differentiated phenotype in early breast cancer but predisposes to invasion and metastasis in advanced disease.

The trefoil protein TFF3 stimulates invasion and angiogenesis in vitro. To determine whether it has a role in breast tumor metastasis and angiogenesis, its levels were measured by immunohistochemistry in breast tissue with a specific monoclonal antibody raised against human TFF3. TFF3 is expressed in normal breast lobules and ducts, at higher levels in areas of fibrocystic change and papillomas, in all benign breast disease lesions, and in 89% of in situ and in 83% of invasive carcinomas. In well-differentiated tumor cells, TFF3 is concentrated at the luminal edge, whereas in poorly differentiated cells polarity is inverted and expression is directed toward the stroma. Expression was high in well-differentiated tumors and was associated significantly with low histological grade and with estrogen and progesterone receptor expression, accordant with induction of TFF3 mRNA by estrogen in breast cancer cells. Paradoxically, TFF3 expression was associated with muscle, neural, and lymphovascular invasion and the presence and number of involved lymph nodes, and it was an independent predictive marker of lymphovascular invasion and lymph node involvement. Consistent with an angiogenic function, TFF3 expression correlated strongly with microvessel density evaluated with CD31 and CD34. In conclusion, TFF3 is expressed in both the normal and diseased breast. Although associated with features of good prognosis, its profile of expression in invasive cancer is consistent with a role in breast tumor progression and tumor cell dissemination.