Williams Syndrome With Rare Ureteric Abnormality

Williams syndrome (WS), also known as Williams-Beuren syndrome, is a rare genetic disorder characterized by infantile hypercalcemia, short stature, a varying degree of mental retardation, elfin-like facial features, and cardiovascular abnormalities, including systemic hypertension, aortic hypoplasia, coarctation of the aorta, and valvular heart disease (aortic and pulmonic stenosis, mitral valve prolapsed or bicuspid aortic valve). It is also characterized by friendly and outgoing personality. The majority of WS cases are sporadic, while few are familial. Both sporadic and familial cases are due to deletion of chromosome 7 (7q11.23). Herein, we present an autopsy case of a 16-day-old male infant born to a 25-year-old mother with a history of William syndrome. Prenatal echocardiogram showed supravalvular aortic stenosis and pulmonary stenosis. The postnatal course was complicated by feeding difficulties and desaturation. Gross autopsy findings included generalized edema, macrocephaly with short neck, and multiple facial anomalies (mandibular hypoplasia, depressed nasal bridge, long philtrum, ear malformation, and wide mouth). The heart was hypertrophied with obstructed ventricles and rudimentary, hypoplastic aortic root. An enlarged, dilated, and tortuous left ureter was a unique finding to this case, in addition to variation in the renal arteries' size and an small bowel outpouching located 33 cm from the ileocecal valve. Cytogenetic analysis revealed deletion of chromosome 7 (7q11.23). In conclusion, majority of WS cases are sporadic, and few are familial and are inherited as autosomal dominant

The Mediating Role of Operations Management Practices on the Relationship Between the Dimensions of Manufacturing Flexibility and Competitiveness

Purpose: The aim of this study is to examine knowing the real role and impact of manufacturing flexibility on competitiveness through operations management practices, which is to determine the role and impact of manufacturing flexibility on competitiveness directly in the General Company for the Battery Industry. On the other hand, identifying the indirect role of flexible manufacturing systems in enhancing competitiveness.   Theoretical framework: The main purpose of the theoretical framework is to identify all the dimensions and variables included in the current study, and thus form a deep scientific view of the study and its variables.   Design/methodology/approach: field coexistence, personal interviews, and classification of data and information obtained in the questionnaire were adopted as the main tool used in the research and for a sample of 74 observations. Structural equations modelling was used to analyze the data using the programs (SPSS24, AMOS23).   Findings: the research reached important results that represent The most prominent of these is the significant impact of manufacturing flexibility in enhancing the competitiveness of the battery manufacturing company, and this effect is reinforced by improving operations management practices by the company.   Research, Practical & Social implications: The research was conducted in this company because it requires scientific research capable of solving many of its problems as a result of increased competition in the market, as well as the continuation of this company in production despite the cessation of many other companies as a result of.   Value: It stems from a vital issue related to aimed at a better future in terms of Operations Management Practices, Flexibility of Manufacturing, Operations Management Practices, and Competitiveness, especially after the crisis that led to a significant decline in the level of performance of organizations

Artificial intelligence-based multi-class histopathologic classification of kidney neoplasms

Artificial intelligence (AI)-based techniques are increasingly being explored as an emerging ancillary technique for improving accuracy and reproducibility of histopathological diagnosis. Renal cell carcinoma (RCC) is a malignancy responsible for 2% of cancer deaths worldwide. Given that RCC is a heterogenous disease, accurate histopathological classification is essential to separate aggressive subtypes from indolent ones and benign mimickers. There are early promising results using AI for RCC classification to distinguish between 2 and 3 subtypes of RCC. However, it is not clear how an AI-based model designed for multiple subtypes of RCCs, and benign mimickers would perform which is a scenario closer to the real practice of pathology. A computational model was created using 252 whole slide images (WSI) (clear cell RCC: 56, papillary RCC: 81, chromophobe RCC: 51, clear cell papillary RCC: 39, and, metanephric adenoma: 6). 298,071 patches were used to develop the AI-based image classifier. 298,071 patches (350 × 350-pixel) were used to develop the AI-based image classifier. The model was applied to a secondary dataset and demonstrated that 47/55 (85%) WSIs were correctly classified. This computational model showed excellent results except to distinguish clear cell RCC from clear cell papillary RCC. Further validation using multi-institutional large datasets and prospective studies are needed to determine the potential to translation to clinical practice

Immunohistochemical characteristics of Renomedullary interstitial cell tumor: a study of 41 tumors with emphasis on differential diagnosis of mesenchymal neoplasms

Renomedullary interstitial cell tumors (RMICT) are almost always incidentally identified either at autopsy or resection of the kidney for other reasons. However, rare cases have been reported which are large, resulting in a clinical mass. The immunohistochemical phenotype of usual, incidental RMICT using modern soft tissue tumor markers in is largely unknown, however, providing little information to aid in classification of larger or atypical tumors. We retrieved 41 RMICTs from 36 patients, and studied pathologic characteristics including morphology, immunohistochemistry (S100, keratin AE1/AE3, smooth muscle actin, desmin, estrogen and progesterone receptors, calponin, CD34, CD35), and histochemical staining. Data collected included age, gender, tumor size, laterality, and indication for kidney examination. RMICTs (n = 41) were identified in 23 men and 13 women, with mean age 57 years (range 24–83), tumor sizes ranged from <1 to 13 mm (median 4 mm). Kidneys were resected for 32 tumors, 1 chronic pyelonephritis, 1 trauma, and 2 autopsies. All (41, 100%) had entrapped renal tubules, 5 (12%) of which included cystic or dilated tubules. Most (35, 85%) had collagenous fibers, all of which were negative for Congo red. RMICT demonstrates a largely negative immunohistochemical phenotype with weak to moderate labeling for smooth muscle actin and calponin that is substantially less than myofibroblastic lesions. Positive staining for estrogen and progesterone receptor is common (61%), which could overlap with mixed epithelial and stromal tumor and other entities; however, staining is typically weak. CD34 is usually negative, with occasional weak labeling, in contrast to solitary fibrous tumor

DOG1 immunohistochemical staining of testicular biopsies is a reliable tool for objective assessment of infertility

Testicular biopsy may be a component of the work-up of male infertility. However, no reliable diagnostic tools are available for objective quantitative assessment of spermatogenic cells. It is well known that MAGE-A4 is selectively expressed in spermatogonia and our group has previously demonstrated that DOG1 differentially stains germ cells. Therefore, we performed DOG1 and a double stain cocktail (DOG1 and 57b murine monoclonal anti-MAGE-A4) immunohistochemical stains on 40 testicular infertility biopsies (10 each with active spermatogenesis, Sertoli cell-only, hypospermatogenesis, and maturation arrest), 25 benign seminiferous tubules from radical orchiectomies, and 5 spermatocytic tumors (ST). In biopsies/resections with active spermatogenesis, DOG1 stained spermatocytes and spermatids and was absent in spermatogonia, while MAGE-A4 stained spermatogonia and primary spermatocytes (weak). In hypospermatogenesis, DOG1 highlighted decreased spermatocytes/spermatids and MAGE-A4 highlighted decreased spermatogonia. DOG1 staining confirmed decreased to absent spermatocytes in maturation arrest and MAGE-A4 staining established the presence of preserved spermatogonia in all cases. All STs were negative for DOG1 and positive for MAGE-A4, while all Sertoli cell-only cases were negative for DOG1 and the double stain cocktail. In conclusion, we confirmed that DOG1 is expressed in spermatocytes and spermatids and MAGE-A4 highlights primarily spermatogonia. Usage of these stains facilitates confirmation of maturation arrest, assessment of the percentage of testis involvement in hypospermatogenesis and identification of mixed patterns. Finally, this study supports that the differentiation of STs is more closely related to spermatogonia than the more mature spermatocytes

Clear Cell Renal Cell Carcinoma With a Poorly-Differentiated Component: A Novel Variant Causing Potential Diagnostic Difficulty

Background: Several variant histologic patterns of clear cell renal cell carcinoma (RCC) are well known, especially those with sarcomatoid and rhabdoid features. However, we have encountered rare cases in which a high-grade adenocarcinoma or urothelial carcinoma-like component would be difficult to appreciate as clear cell RCC. DesignWe retrieved 26 tumors with histologically typical clear cell RCC juxtaposed to a high-grade non-clear cell component.High grade non-clear cell component was defined as non-sarcomatoid, non-rhabdoid areas that would be difficult to assign as renal cell in origin if viewed in isolation. Tumors were studied with immunohistochemistry and fluorescence in situ hybridization (FISH) or sequencing.ResultsMedian percentage of poorly differentiated component: 50%(IQR20-70). All tumors showed abrupt transition from clear cell carcinoma to poorly-differentiated (non-sarcomatoid/non-rhabdoid) areas, which showed micropapillary (7/26; 27%), urothelial-like (10/26; 39%), and adenocarcinoma NOS features (9/26; 35%). 19 tumors had necrosis. Carbonic anhydrase IX (CA-IX) was uniformly positive in well-differentiated component (20/20); poorly differentiated component showed a median positivity of 82.5% (IQR 65-100). Poorly differentiated component was positive for CK7 (5/19; 26%), CK20 (3/12; 25%), AMACR (7/12; 58%), PAX8 (12/15; 80%), and showed intact FH (6/6; 100%). CDX2 was uniformly negative. Chromosome 3p loss or VHL mutation was present in 8/13 (62%), tested with either FISH (n = 9) or sequencing (n = 4). All tested cases were negative for TFE3 (0/11) and TFEB (0/9) rearrangements on FISH. 5/21 (24%) patients were alive with metastatic disease and 5/21 (24%) had died of disease on follow up. One metastasis was composed only of the poorly-differentiated component and was near-negative for CA-IX. Conclusion: Clear cell RCC with a poorly differentiated component resembling adenocarcinoma or urothelial carcinoma is a novel source of morphologic heterogeneity that has not been previously well characterized. Potential pitfalls include decreased or absent CA-IX staining the high-grade component and aberrant positivity for cytokeratin 7 or 20. With the increasing use of renal mass biopsy and biopsies of metastatic sites for targeted therapy, pathologists should be aware of this entity and consider the possibility of clear cell RCC even for morphologically unusual tumors.https://scholarlycommons.henryford.com/merf2019caserpt/1069/thumbnail.jp

Testicular Cancer: Contemporary Updates in Staging

Testicular tumors are the most common solid tumors in young men, the vast majority of which are of germ cell origin. The staging of human cancers is paramount to correct patient management. Staging systems have passed through several developments leading to the release of the most recent 8th edition of the American Joint Committee for Cancer (AJCC) staging manual, which is based on the current understanding of tumor behavior and spread. In this review, the authors summarize the current AJCC staging of the germ cell tumors, highlight essential concepts, and provide insight into the most important parameters of testicular tumors

Localized amyloidosis of the prostatic urethra mimicking urothelial carcinoma

Amyloidosis is a disease characterized by extracellular deposition of amyloid protein fibrils in tissues. It rarely involves the urethra with just over 50 cases reported in the English language literature. We report a case of urethral amyloidosis that mimicked urothelial carcinoma clinically. The patient is a 69-year-old male who presented to the emergency department with shortness of breath. An abdominal CT scan demonstrated a right hydronephrotic kidney and a large, predominantly hyperdense lesion, presumed to be hematoma largely occupying the urinary bladder. Pan-cystoscopy revealed a 6 cm bladder mass involving the prostatic urethra displacing the right ureteral orifice, which was biopsied. Histologic examination showed numerous osteoclast-type giant cells, with areas of extensive calcification and multifocal ossification interspaced by large deposits of amorphous eosinophilic material. Amyloid deposition was confirmed by Congo red and sulfated Alcian blue stains. Light chromatography tandem mass spectrometry was performed and detected multiple types of proteins including serum amyloid P component, apolipoprotein A4, and apolipoprotein E; however, a dominant amyloid type was not identified. The patient had no history of infection or localized inflammation. Further investigations for systemic amyloidosis were all negative. Amyloidosis of the urethra is extremely rare and may either be localized, idiopathic or a manifestation of systemic amyloidosis. Physicians among various specialties, including urologists, pathologists and radiologists should be aware of this rare entity, as this lesion may be easily mistaken for malignancy further emphasizing the importance of tissue diagnosis before definitive surgery. Long-term follow-up in the absence of symptoms may not be required

The Pathologic and Molecular Genetic Landscape of the Hereditary Renal Cancer Predisposition Syndromes

It is estimated that 5-8% of renal tumors are hereditary in nature with many inherited as autosomal dominant. These tumors carry a unique spectrum of pathologic and molecular alterations, the knowledge of which is expanding in the recent years. Indebted to this knowledge, many advances in treatment of these tumors have been achieved. In this review, we summarize the current understanding of the genetic renal neoplasia syndromes, the clinical and pathologic presentations, their molecular pathogenesis, the advances in therapeutic implications and targeted therapy