Interactive Pathology Tutorial in Neoplastic Hematology Disorders for Medical Hematology-Oncology Fellows.

Hematology-oncology (HO) fellows receive limited instruction in the process of establishing a diagnosis for hematologic neoplasms, and learning neoplastic hematology often occurs in limited encounters. In the current study, we developed a web-based interactive pathology tutorial in neoplastic hematologic disorders for HO fellows to work up simulated cases and establish the diagnosis. An online system ("Pathology Playground") was utilized to load case materials including microscopic images and ancillary studies. Twelve high-yield simulated cases of common leukemias and lymphoma were included. At the beginning of each case, trainees review the clinical history and slide images, and then, they are given the option to request additional pathology work-up. Based on the results, they can enter their diagnostic impression. If the diagnosis is correct, the user is shown a short educational presentation. If the diagnosis is not correct, the user gets notified by the message "Incorrect." The tutorial was integrated in the educational curriculum of our HO fellowship program, and bimonthly teaching sessions were held to review two cases each time. During the sessions, trainees request ancillary studies to complete the diagnostic work-up using the software and interpret the findings. As the case is being worked up by the trainee, the hematopathologists and HO fellowship program director discuss the findings, the appropriate work-up tools, and the implications on management. All of our six HO fellows attended the sessions, and a survey from the trainees showed high ease of use of the system and they viewed it as a very useful educational tool. A pre-test and post-test were administered for one of the sessions, and the result showed improvement in the average from 62 to 73%. Expanding the use of this online interactive tutorial and incorporating additional cases would enhance its value as a learning resource.

Assessment of potential predictors affecting preoperative anxiety in Indian children- A prospective observational study.

Background and Aims: Preoperative anxiety is a common problem among children undergoing surgery. The aim of the study was to assess the incidence and identify various predictors of preoperative anxiety in Indian children. Material and Methods: A prospective, observational study was conducted on 60 children of the American Society of Anesthesiologists Physical status 1/2, aged 2-6 years and scheduled for elective surgery under general anesthesia in a tertiary care teaching hospital. Preoperative parental anxiety was assessed using the State-Trait Anxiety Inventory questionnaire. The children's anxiety was assessed in the preoperative room, at the time of parental separation, and at the induction of anesthesia using modified Yale Preoperative Anxiety Scale (mYPAS) scoring by an anesthesiologist and a psychologist. Sedative premedication was employed prior to parental separation. Logistic regression analysis was carried out to identify the possible predictors of anxiety. Results: The incidence of high preoperative anxiety among the studied children was 76% in the preoperative room, 93% during parental separation, and 96% during anesthetic induction. Among the nine possible predictors identified on univariate regression, the presence of siblings was found to be a significant independent predictor on multivariate regression analysis (P = 0.04). The inter-rater agreement was excellent for the assessment of preoperative anxiety using mYPAS by the anesthesiologist and psychologist (weighted Kappa, k = 0.79). Conclusion: The incidence of preoperative anxiety in Indian children in the age group of 2-6 years is very high. The preop anxiety escalates progressively at parental separation and induction of anesthesia despite sedative premedication. The presence of siblings is a significant predictor of preoperative anxiety.

Encapsulated Papillary Oncocytic Neoplasm: A Newly Recognized Hurthle Cell Neoplasm With Unique Morphology.

Diagnosis of oncocytic neoplasm of the thyroid gland can be challenging especially on fine needle aspiration biopsy (FNAB), given the wide differential diagnoses. In this report, we present the case of a 66-year-old male with an incidental thyroid nodule identified on imaging. In this case, identification of the distinctive cytologic features leads to the diagnosis of papillary oncocytic neoplasm on FNAB and helped to decide the appropriate surgical management. To date, the cytomorphologic features of this lesion are not well studied and established, with only a single case report in the literature. Herein, we describe the characteristic cytomorphologic and immunophenotypic features of this neoplasm. The recognition of the unique cytomorphologic features and awareness of the non-classic expression of the thyroid lineage markers will help in accurate diagnosis and management of this entity.

The prognostic significance of duodenal wall invasion in pancreatic adenocarcinoma.

OBJECTIVE: The most recent edition of the American Joint Committee on Cancer Staging Manual (AJCC, 8th edition) relies only on tumor size for staging resectable pancreatic adenocarcinoma, and the presence of duodenal wall invasion (DWI) no longer has an impact on staging. However, very few studies have evaluated its significance. In this study, we aim to evaluate the prognostic significance of DWI in pancreatic adenocarcinoma. METHODS: We reviewed 97 consecutive internal cases of resected pancreatic head ductal adenocarcinoma, and clinicopathologic parameters were recorded. All cases were staged according to the 8th edition of AJCC, and the patients were divided into two groups based on the presence or absence of DWI. RESULTS: Out of our 97 cases, 53 patients had DWI (55%). In univariate analysis, DWI was significantly associated with lymphovascular invasion and lymph node metastasis (AJCC 8th edition pN stage). In univariate analysis of overall survival, age > 60, absence of DWI, and African American race were associated with worse overall survival. In multivariate analysis, age > 60, absence of DWI, and African American race were associated with worse progression-free survival and overall survival. CONCLUSION: Although DWI is associated with lymph node metastasis, it is not associated with inferior disease-free/overall survival.

Investigation on Centrifugally Spun Fibrous PCL/3-Methyl Mannoside Mats for Wound Healing Application.

Fibrous structures, in general, have splendid advantages in different forms of micro- and nanomembranes in various fields, including tissue engineering, filtration, clothing, energy storage, etc. In the present work, we develop a fibrous mat by blending the bioactive extract of Cassia auriculata (CA) with polycaprolactone (PCL) using the centrifugal spinning (c-spinning) technique for tissue-engineered implantable material and wound dressing applications. The fibrous mats were developed at a centrifugal speed of 3500 rpm. The PCL concentration for centrifugal spinning with CA extract was optimized at 15% w/v of PCL to achieve better fiber formation. Increasing the extract concentration by more than 2% resulted in crimping of fibers with irregular morphology. The development of fibrous mats using a dual solvent combination resulted in fine pores on the fiber structure. Scanning electron microscope (SEM) images showed that the surface morphology of the fibers in the produced fiber mats (PCL and PCL-CA) was highly porous. Gas chromatography-mass spectrometry (GC-MS) analysis revealed that the CA extract contained 3-methyl mannoside as the predominant component. The in vitro cell line studies using NIH3T3 fibroblasts demonstrated that the CA-PCL nanofiber mat was highly biocompatible, supporting cell proliferation. Hence, we conclude that the c-spun, CA-incorporating nanofiber mat can be employed as a tissue-engineered construct for wound healing applications.

Pathology Playground: An Interactive Web-Based System for Pathology Unknowns With Immunohistochemistry and Molecular Studies.

CONTEXT.­: Anatomic pathology slide unknown conferences are usually limited to a microscopic slide, slide images, or a virtual slide that is previewed prior to a conference. The answer is provided at a conference along with the ancillary studies, such as immunohistochemical or molecular studies, that enabled the diagnosis. In this rigid system the learner never gains experience with an appropriate workup for cases that will enable the definitive diagnosis. OBJECTIVE.­: To develop an interactive system in which the user can work through a difficult case, ordering stains and other special studies, ideally leading to more involvement and retention. DESIGN.­: An online system was developed using HTML, PHP Hypertext Preprocessor, and JavaScript for ordering and result display. When the user selects a study, an image or text result is displayed. Studies include immunohistochemistry, cytogenetics, flow cytometry, molecular, and radiology. The user then selects the diagnosis and, if correct, is shown some additional didactics. RESULTS.­: Unknown conferences were held at 3 institutions using this novel teaching method that allowed residents to work up unknown cases. Conferences are available online (http://www.drdoubleb.com/unknowns/) and include general, soft tissue, and hematopathology cases. Evaluations were obtained that showed that residents enjoyed the system, considered it better than standard unknown sessions and lectures, and wanted more sessions. CONCLUSIONS.­: This system was very highly received by the residents in all programs, who enjoyed getting immediate results and being able to work through interesting cases. More widespread use of this system could make for an effective learning tool.

HPV Associated Squamous Cell Carcinoma in the Rectal Tonsil.

Mucosa-associated lymphoid tissue has been reported throughout the gastrointestinal tract including rectum. Rarely, a nodular proliferation of predominantly submucosal lymphoid tissue in the rectum has been documented as rectal tonsil. Here we report a patient with HPV-associated squamous cell carcinoma of the rectal tonsil, presenting as a polyp. Previously, rare reports of HPV-associated lymphoepithelial carcinoma have been reported in the literature. We are presenting an extremely rare occurrence and emphasizing the importance of appropriate nomenclature based on the pathogenesis of the neoplasm.

Merlin immunohistochemistry is useful in diagnosis of tumours within the spectrum of biphasic hyalinizing psammomatous renal cell carcinoma.

AIMS: Biphasic hyalinizing psammomatous (BHP) renal cell carcinoma (RCC) is a newly described emerging entity within the spectrum of papillary RCC in the WHO 2022 classification. Molecular analyses have discovered that BHP RCC consistently harbour somatic mutations in the neurofibromin 2 (NF2) gene. The NF2 gene product, merlin, is known to primarily function as a tumour suppressor. Merlin protein loss correlates closely with the presence of NF2 mutations in benign and malignant tumours arising in different sites. In the present study we explored the role of merlin immunohistochemistry (IHC) in tumours within the spectrum of BHP RCC to determine the diagnostic utility of this marker. MATERIALS AND METHODS: We performed merlin IHC in 13 BHP RCC, 18 papillary RCC, 10 TFE3-translocation RCC, 15 TFEB-altered RCC (including 13 TFEB-rearranged and 2 TFEB-amplified), and 10 mucinous tubular and spindle cell carcinomas of unknown mutational status. RESULTS: Unequivocal loss of merlin expression in >90% of the tumour cells was observed in 12/13 BHP-RCC (92%), with the remaining tumour demonstrating weak focal cytoplasmic expression in ~10% of the tumour. In contrast, merlin was diffusely or multifocally expressed in all papillary RCC, TFE3-translocation RCC, and TFEB-altered RCC, as well as in 70% of mucinous tubular and spindle carcinomas. CONCLUSIONS: In this study, merlin IHC was ~92% sensitive and ~94% specific for BHP RCC. These data suggest that merlin IHC is a reliable surrogate marker for the presence of underlying NF2 gene inactivation, being diagnostically useful to identify BHP RCC. CONCLUSIONS: In this study, merlin IHC was ~92% sensitive and ~94% specific for BHP RCC. These data suggest that merlin IHC is a reliable surrogate marker for the presence of underlying NF2 gene inactivation, being diagnostically useful to identify BHP RCC.

A cyclodextrin-based macrocyclic oligosaccharide cavitand with a dual functionality limits the collagen fibrillogenesis: A possible carbohydrate-based therapeutic molecule for fibrotic diseases.

ß-Cyclodextrin (ß-CD), a macrocyclic oligosaccharide cavitand, is a well-known candidate for drug delivery and formulation. In this study, we extended the application of ß-CD using a ß-cyclodextrin sulfate (ß-CDS) as a possible therapeutic for fibrotic diseases caused by excess deposition of collagen fibrils. We have strategically chosen ß-CDS, which mimics the natural existence of dermatan sulfate in the extracellular matrix, for limiting collagen fibrillation. The hydrophobic nature of the inner core ß-CDS is expected to form an inclusion complex with hydrophobic side chain amino acids with the simultaneous action of forming an ionic bond through a negative charge on sulfate group with positively charged amino acids side chain in collagen. Various results suggested that such dual action not only limited the collagen fibrillation but also reduced the fibril size formed in the presence of ß-CDS. The contemporary results thus indicate that ß-CDS can be explored as a therapeutic molecule in fibrotic diseases.

Biphasic Hyalinizing Psammomatous Renal Cell Carcinoma: Another Provisional Entity Emerging From the Papillary Renal Cell Carcinoma Pandora's Box.

Papillary renal cell carcinoma (especially type 2) is a Pandora's box with many newly described renal cell carcinomas emerging from it as a result of enhanced molecular techniques. Biphasic hyalinizing psammomatous renal cell carcinoma (BHPRCC) is the latest addition, which was first described a few months ago. Here, we report a case of BHPRCC to supplement the very limited literature available about this entity, and to highlight the characteristic morphology as well as the recurring molecular alterations in the neurofibromatosis 2 gene.

Ferulic acid loaded microspheres reinforced in 3D hybrid scaffold for antimicrobial wound dressing.

Here we report the preparation of biomimetic fibrin/chitosan/keratin hybrid scaffolds with a synergistic combination of ferulic acid loaded silica microspheres for antimicrobial wound dressing applications. The infrared and X-ray powder diffraction studies confirm the homogenous nature of the prepared hybrid scaffolds without any major interactions between the constituents. The developed hybrid scaffolds show good thermal, porosity, compression and water uptake properties. Scanning electron microscopic analysis shows that the as-synthesized ferulic acid loaded silica microspheres exhibit an average size of 35 ± 10 µm and also exposes the smooth surface with interconnected porosity in the prepared hybrid scaffolds. The incorporated ferulic acid loaded silica microspheres hybrid scaffolds show effective antimicrobial activity against the common wound pathogens. In vitro NIH3T3 fibroblast cell culture and drug release studies reveal that the prepared hybrid scaffolds have enhanced cell proliferation and adhesion with a prolonged drug release for about 72 h. In vitro wound healing and actin cytoskeleton analysis reveal that the incorporated ferulic acid loaded silica microspheres in fibrin/chitosan/keratin hybrid scaffolds facilitates cell growth and migration to damaged area through cell-cell interactions. These results suggest that the prepared hybrid scaffolds with ferulic acid loaded silica microspheres have great potential for soft tissue engineering applications particularly for the treatment of chronic and infected wounds.

Pitfalls in Morphologic Diagnosis of Pathogens: Lessons Learned From the Pseudo-Cystoisospora Epidemic.

Multiple groups have recently reported involvement of the gallbladder mucosa of immunocompetent patients by cystoisospora organisms. However, this has recently been disproved with the support of molecular and ultrastructural studies. Here we present a summary of these events, recounting how this pseudo-Cystoisospora epidemic began and ended. This review also highlights the important role played by ancillary techniques in supplementing the morphologic diagnosis of pathogens.

Ferulic acid-loaded collagen hydrolysate and polycaprolactone nanofibres for tissue engineering applications.

There is a great need for the progress of composite biomaterials, which are effective for tissue engineering applications. In this work, the development of composite electrospun nanofibres based on polycaprolactone (PCL) and collagen hydrolysate (CH) loaded with ferulic acid (FA) for the treatment of chronic wounds. Response Surface Methodology (RSM) has been applied to nanofibres factor manufacturing assisted by electrospinning. For wound healing applications, the authors have created the efficacy of CH, and PCL membranes can act as a stable, protective cover for wound, enabling continuous FA release. The findings of the RSM showed a reasonably good fit with a polynomial equation of the second order which was statistically acceptable at P < 0.05. The optimised parameters include the quantity of hydrolysate collagen, the voltage applied and the distance from tip-to-collector. Based on the Box-Behnken design, the RSM was used to create a mathematical model and optimise nanofibres with minimum diameter production conditions. Using FTIR, TGA and SEM, optimised nanofibres were defined. In vitro, cytocompatibility trials showed that there was an important cytocompatibility of the optimised nanofibres, which was proved by cell proliferation and cell morphology. In this research, the mixed nanofibres of PCL and CH with ferulic could be a potential biomaterial for wound healing.

Ultrastructural Characteristics of Gallbladder Epithelial Inclusions Mimicking Cystoisospora.

OBJECTIVES: There is recently reported increased prevalence of Isospora organisms in cholecystectomy specimens from immunocompetent patients, especially in acalculous cholecystectomies. We performed an ultrastructural and molecular evaluation of these specimens. METHODS: From 28 gallbladders with intraepithelial inclusions, two specimens with diffuse involvement of the gallbladder epithelium were analyzed by electron microscopy. Polymerase chain reaction was performed on five samples for the ITS2 region of C belli and eukaryotic 18S region. The 18S products were sequenced by next-generation sequencing. RESULTS: Electron microscopic analysis showed cytoplasmic condensations leading to vacuole formation. In contrast with true C belli, there were no identifiable organelles or organization. None of these cases showed amplified products other than human on molecular analysis. CONCLUSIONS: Electron microscopic analysis demonstrates that the inclusions are condensed cytoplasmic material and not true organisms.

Prognostic significance of venous invasion in node-negative head and neck squamous cell carcinoma.

BACKGROUND: Venous invasion (VI) is not frequently evaluated on routine histologic examination of head and neck squamous cell carcinoma (HNSCC), and the prognostic significance is largely unknown. Studies have shown that extramural venous invasion is an adverse prognostic factor in colorectal carcinoma. To our knowledge, this is the first study evaluating the prognostic significance of venous invasion in node-negative (without clinical or pathologic evidence of lymph node involvement) HNSCC, utilizing the elastic stain. METHODS: A total of 105 consecutive lymph node-negative (N0) HNSCC were evaluated for the presence of venous channel invasion by tumor utilizing the elastin stain. Clinical, demographic, and follow-up data were recorded. RESULTS: Of 37 patients with venous invasion, 19% had loco-regional recurrence, as opposed to 12% of those without. Univariate analysis revealed statistically significant decreased recurrence-free survival in the presence of venous invasion (log-rank [Mantel-Cox] test P-value .025). CONCLUSION: Identification of VI is greatly aided by elastic stain. In patients with node-negative HNSCC, presence of VI resulted in decreased recurrence-free survival on univariate analysis. The impact of VI as a prognostic marker should be further evaluated.

Candida Parapsilosis associated rice bodies in the extensor compartment of the wrist--an emerging finding.

Candida parapsilosis has been considered an emerging pathogen with increasing incidence reported in the literature. As a normal commensal of human skin, it is likely that Candida species could gain access to soft tissues of the hand and wrist by direct inoculation, resulting in an infectious tenosynovitis. With the increased prevalence of intravenous drug use (IVDU), users are at increasing risk for musculoskeletal infections including soft tissue abscesses, cellulitis, tenosynovitis, and septic arthritis. Chronic tenosynovitis, with rice body formation in particular, is a comparatively rare musculoskeletal infection. Knowledge of this entity, the related pathogens, imaging findings, and the treatment plan is important not only to the treating clinician, but also to radiologists as the physiological and anatomic consequences can be detrimental to patient recovery.

Langerhans Cell Histiocytosis Presenting as Progressively Worsening Neck Pain: A Case Report With a Review of Literature.

A 29-year-old female with past medical history of chronic serous otitis media presented with worsening neck stiffness and pain over a period of 2 weeks. The patient described non-specific symptoms that were localized to the right side of her neck. She presented to the hospital only when the pain was so extreme that it limited her range of motion. The differential for acute neck pain without fever, chills or any inciting trauma is vast. They include medical emergencies such as meningitis, acute coronary syndromes and extend to rheumatologic diseases or simply musculoskeletal strain. On review of systems, she denied dizziness, headache, vision changes, dysphagia, or other facial pain. Based on the severity of her pain, she underwent a Computed Tomography scan of the neck, which was concerning for erosive calavarial lesions. Further imaging revealed multiple lytic foci and erosions from the right maxillary sinus to the right mandible to the C1 vertebra. Following requisite surgical intervention, she was found to have Langerhans cell histiocytosis, a rare disease of myeloid cells, usually affecting pediatric populations. Little is known about the adult manifestations of Langerhans Cell Histiocytosis. This review contributes to broadening the literature on this topic which can present with complaints as typical as neck pain.

5 Fluorouracil-loaded biosynthesised gold nanoparticles for the in vitro treatment of human pancreatic cancer cell.

In this study, green synthesis of gold nanoparticles (AuNPs) was performed by a sunlight irradiation method using the Borassus flabellifer fruit extract as a reducing agent. 5-Fluorouracil (5-FU)-loaded GG capped AuNPs (5FU-G-AuNPs) was prepared. The nanoparticles was further characterised by UV-visible spectra, particle size analysis, zeta potential, SAED, HRTEM, and XRD. The MTT assay results showed the suitability 5-FU-G-AuNPs. In this study, 5-FU-G-AuNPs exhibited potential cytotoxic and apoptotic effects on (MiaPaCa-2) cell line.

Collagen-silica bio-composite enriched with Cynodon dactylon extract for tissue repair and regeneration.

Development of biomaterials for tissue engineering applications is of great interest to meet the demand of different clinical requirements. The wound heal dressing biomaterials should necessarily contain well-defined therapeutic components and desirable physical, chemical and biological properties to support optimal delivery of therapeutics at the site of the wound. In this study, we developed collagen-silica wound heal scaffold incorporated with the extract of Cynodon dactylon, characterized and evaluated for its wound heal potential in vitro and in vivo against collagen (Col) and Collagen-silica (CS) scaffolds that served as controls. The prepared Collagen-Silica-Cynodon extract (CSCE) scaffold exhibits porous morphology with preferable biophysical, chemical, mechanical and mass transfer properties besides its controlled biodegradation at the wound site. Stability of CSCE was found to be better than that of native collagen due to intermolecular interactions between collagen and constituents of C. dactylon as confirmed by FTIR analysis. Notably, in vitro biocompatibility assay using DAPI and Rhodamine 123 staining demonstrated that the proliferation of NIH3T3 fibroblast cells was better for CSCE when compared to the Col and CS scaffolds. In vivo wound healing experiments with full-thickness excision wounds in wistar rat model demonstrated that the wounds treated with CSCE showed accelerated healing with enhanced collagen deposition when compared to wounds treated with Col and CS scaffolds, and these studies substantiated the efficacy of CSCE scaffold for treating wounds.

Lymphoma in autopsy cases.

Lymphoproliferative disorders cause significant morbidity and mortality, either related to the disease itself or therapy complications. Some cases of lymphoma may have vague clinical presentation, especially in the absence of lymphadenopathy, and a clinical work up may not be conclusive. Our study focuses on autopsy cases of lymphoma patients, emphasizing clinically unsuspected cases. Autopsy records from the last 20 years at our institution were searched, and the clinical parameters were recorded. Fifteen cases of lymphoma were identified, and 5 cases were diagnosed at the time of autopsy. Most B-cell lymphoma cases were mainly nodal disease, while T-cell lymphoma cases had widespread extra-nodal disease. Most deaths in B-cell lymphoma are due to infection/therapy induced immunosuppression, whereas T-cell lymphoma deaths are due to organ infiltration by lymphoma. Postmortem examination may reveal clinically unsuspected lymphoma, especially in rapidly deteriorating patients with vague presentation such as skin rash, bowel obstruction/bleeding or pacemaker malfunction.