A Comparison of Diagnostic and Immunohistochemical Workup and Literature Review Capabilities of Online Artificial Intelligence Assistance Models in Pathology.

Artificial intelligence (AI) is a suite of technologies that enables computers to learn and interpret information like human cognition. It has found applications across various fields, including healthcare, agriculture, astronomy, navigation, and robotics. Within healthcare, AI has the potential to enhance diagnostic accuracy, facilitate drug research, and automate patient experiences. This comparative study focuses on the proficiency of AI in generating accurate differential diagnoses in the field of pathology. Six medical vignettes were crafted, and each scenario was then input into three different AI platforms. The pathologist reviewed and determined the most accurate AI model.

Cor Adiposum as the Cause of Sudden Cardiac Death: A Case Report and Literature Review.

We present a case of sudden cardiac death in a 65-year-old patient who came to the emergency room with shortness of breath. The gross examination of the heart was significant for extensive left ventricular lipomatosis in association with myocardial fibrosis. Microscopic examination revealed extensive fatty replacement of the myocardial tissue throughout the entire thickness of the ventricular wall (transmural lipomatous myocardial remodeling). We suggest using the term "cor adiposum" to categorize this morphological condition when the transmural lipomatous transformation of the myocardium is present. The fatty replacement of the heart muscle would have led to impaired cardiac function, ultimately resulting in sudden cardiac death in this patient. We also hypothesize that the accumulation of fat in the myocardium might be a compensatory process to preserve ventricular wall compliance.

Diffuse Alveolar Hemorrhage Occurring Suddenly in a Diabetic Patient With Asthma Exacerbation.

Diffuse alveolar hemorrhage (DAH) is a rare but potentially life-threatening condition characterized by bleeding into the alveolar spaces of the lungs. DAH can occur due to a wide range of etiologies including autoimmune diseases, infections, drugs, and malignancies. The clinical presentation is variable and may include cough, dyspnea, fever, and hemoptysis. Diagnosis is often challenging due to the nonspecific symptoms and a lack of definitive diagnostic criteria. Treatment is primarily aimed at addressing the underlying cause and providing supportive care.

Massive Hemorrhage Following Spontaneous Mediastinal Inflammatory Myofibroblastic Tumor Rupture: A Case Report.

A 45-year-old male in a hypertensive emergency was admitted with complaints of frontal headache, progressive chest discomfort, shortness of breath, dysphagia, and right upper quadrant abdominal pain radiating across the epigastrium and to the back that increases in intensity with deep inspiration. He denied any history of abdominal pain, vomiting, dyspnea, nausea, and weight loss. A computed tomography (CT) scan of the chest showed a posterior mediastinal mass between the esophagus and descending aorta. A magnetic resonance imaging (MRI) scan revealed a non-enhancing posterior mediastinal mass possibly compressing both the esophagus and the airway. A 30-degree thoracoscope was inserted in the chest cavity revealing a large hemothorax from a possibly ruptured inflammatory myofibroblastic tumor (IMT) encompassing nearly the entire pleural space with both fresh and clotted blood. Two liters of fresh blood was removed via a right thoracotomy procedure. Once removed, a large fibrinous clot-filled mass was resected entirely and sent to pathology. Postoperative recovery was uneventful; dysphagia and shortness of breath resolved. The patient gradually resumed his regular diet.

Ectopic Cushing Syndrome in Adenocarcinoma of the Lung: Case Report and Literature Review.

Paraneoplastic syndromes are rare disorders that occur with many types of tumors. Ectopic cushing syndrome (ECS) is the second most common paraneoplastic syndrome that is only seen in 1-5% of all small cell lung cancers (SCLC), with limited papers reporting this syndrome since it was first described by Brown in 1928 or in carcinoid tumors. It is also found to be associated to a lesser extent with pheochromocytoma, thymic tumors, pancreatic carcinoma, and anaplastic thyroid carcinoma. While lung adenocarcinoma is the most common histological type of lung neoplasms, it is seldom associated with Cushing syndrome. In this article, we describe a patient who initially presented with Cushing syndrome and found to have adenocarcinoma of the lung.

Pembrolizumab - emerging treatment of pulmonary sarcomatoid carcinoma: A case report.

BACKGROUND: Few studies have addressed the efficacy of pembrolizumab in pulmonary sarcomatoid carcinoma (PSC), a rare, previously rapidly fatal subtype of non-small-cell lung cancer. CASE SUMMARY: We report the case of a 69-year-old man presented with respiratory distress caused by a large left upper lung lobe mass diagnosed as PSC with programmed death-ligand 1 expressed on more than 50 percent of tumor cells. The patient was started on pembrolizumab and, after 5 cycles, there was a more than 80 percent decrease in the size of the tumor mass. Further decrease was seen at the end of 10 cycles. The patient has been tolerating pembrolizumab well, with no limiting side-effects. Fourteen months after first coming into the hospital, he remains asymptomatic. CONCLUSION: Pembrolizumab appears as a viable emerging treatment for PSC.

Unique presentation of occult breast cancer with uterine cervix metastasis.

We are reporting a case of occult breast cancer (OBC) diagnosed via biopsy of an asymptomatic cervical mass. While non-OBC has occasionally been reported as metastatic to the uterine cervix, OBC never has, to our knowledge. Awareness of this presentation can be beneficial for a more expedite diagnosis and treatment.

Significance of pigmented urothelial and non-urothelial cells in voided urine specimens: A case report and review.

We present a case of metastatic malignant melanoma to the urinary bladder diagnosed on a voided urinary cytology specimen in a patient who visited the emergency department complaining of right flank pain, and dark urine. The patient reported having previous episodes of kidney stones. Additionally, more detailed clinical history obtained after the cytological diagnosis, revealed a previous excision of malignant melanoma on the back 10 years ago. The diagnosis of metastatic malignant melanoma was based solely on voided urine cytology. While metastases of malignant melanoma to urinary bladder are well known, the significance of pigmented cells in voided urine specimens is not well documented. In this article we provide a discussion as well as a review of the literature about possible disease entities associated with pigment containing urothelial as well as non-urothelial cells.

Adult rhabdomyosarcoma of the maxillary sinus with orbital extension.

A 40-year-old male presented with 2 weeks of left facial pain, nasal congestion, dysphonia, and epistaxis along with left-sided epiphora. CT showed a large infiltrative mass centered in the left maxillary sinus with extension into the left orbit, bilateral paranasal sinuses, nasal cavity, and bilateral enlarged cervical lymph nodes. Biopsy results confirmed adult alveolar rhabdomyosarcoma (RMS). Systemic workup confirmed bilateral cervical lymph node metastasis. Currently the patient is undergoing chemotherapy. We describe a rare case of adult paranasal sinus RMS with orbital invasion.

Reduced virulence of an extensively drug-resistant outbreak strain of Mycobacterium tuberculosis in a murine model.

Bacterial drug resistance is often associated with a fitness cost. Large outbreaks of multidrug-resistant (MDR) and extensively drug-resistant (XDR) TB have been described that predominately affect persons with HIV infection. We obtained four closely-related Mycobacterium tuberculosis strains (genotype F15/LAM4/KZN) from an outbreak in KwaZulu-Natal (KZN), South Africa, including drug-sensitive, MDR, and XDR clinical isolates. We compared the virulence of these strains in a murine model of aerosol M. tuberculosis infection for four phenotypes: (1) competitive in vivo growth in lung and spleen, (2) non-competitive in vivo growth in lung and spleen, (3) murine survival time, and (4) lung pathology. When mixtures of sensitive, MDR, and XDR KZN strains were aerosolized (competitive model), lung CFUs were similar at 60 days after infection, and spleen CFUs were ordered as follows: sensitive > MDR > XDR. When individual strains were aerosolized (non-competitive model), modest differences in lung and spleen CFUs were observed with the same ordering. C57BL/6, C3H/FeJ, and SCID mice all survived longer after infection with MDR as compared to sensitive strains. SCID mice infected with an XDR strain survived longer than those infected with MDR or sensitive strains. Lung pathology was reduced after XDR TB infection compared to sensitive or MDR TB infection. In summary, increasing degrees of drug resistance were associated with decreasing murine virulence in this collection of KZN strains as measured by all four virulence phenotypes. The predominance of HIV-infected patients in MDR and XDR TB outbreaks may be explained by decreased virulence of these strains in humans.

Case report of undifferentiated endometrial sarcoma in association with osteoclast-like giant cells.

We describe the clinical, gross and microscopic features of undifferentiated uterine stromal sarcoma associated with osteoclast-like giant cells. A case of low-grade endometrial stromal sarcoma is already described in association with osteoclast-like giant cells; however, the current case differs in that the tumor was a high grade and did not show any evidence of smooth muscle or epithelioid differentiation and was shown to be strongly positive for CD10 and focally for WT-1 and Inhibin supporting an endometrial stromal origin. The associated osteoclast-like giant cells were abundant, evenly distributed within the tumor and showed strong positivity for CD68. Interestingly, rare (less than 2%) giant cells also showed weak cytoplasmic positivity for b-hCG. The tumor infiltrated deep into the myometrium and had marked lymphovascular invasion. Although the regional lymph nodes and peritoneal washings were negative, the lesion showed a highly aggressive clinical course. Despite treatment, the tumor disseminated within the abdominal cavity and lungs and ultimately led to the patient's demise within 9 months of the diagnosis.

Computer-assisted image analysis of amyloid deposits in abdominal fat pad aspiration biopsies.

Amyloidosis is a heterogeneous group of diseases with a common outcome: deposition of insoluble protein in the visceral organs and tissues. Primary amyloidosis is a consequence of different plasma cell disorders, and it is the most common form of amyloidosis in the United States with an estimated 2,000 new cases annually. Other forms of amyloidosis include chronic inflammatory processes, familial type of amyloidosis, and localized forms like Alzheimer's disease.The diagnosis of amyloidosis is based on the clinical picture and demonstration of amyloid deposit in tissues with Congo-red stain. In our article, we describe a simple methodology for image analysis of fat pad biopsies for amyloidosis using a commercially available software Adobe Photoshop CS3(c) Extended Edition. The principle is based on calculation of the mean gray value of each blue and green channel and comparison of their ratios. As a negative control, we have used samples from heart, scar tissue, and skin with their representative control. Fibrous tissue often gives a white:blue to blue:green birefringence, which often is confused with the apple: green birefringence of the amyloid stain; however, we were successful in discriminating these colors using the methodology described in this article. We also analyzed 22 patients with at least 2 years follow-up in our institution. The specificity and the sensitivity of the computer-assisted image analysis were calculated to be 75% and 100%, respectively. These results are in agreement with the published papers (references here); however, caution should be exercised before drawing firm conclusions because of the small sample size presented here.

Fine-needle aspiration biopsy of metastatic malignant melanoma resembling a malignant peripheral nerve sheath tumor.

We report a case of metastatic malignant melanoma resembling a malignant peripheral sheath tumor, which posed a significant diagnostic challenge. The patient is a 76-year-old male, who presented in the emergency room with bilateral chest pain exacerbated by inspiration. The pain was present for 3 week and was not exacerbated by physical exercise. The diagnostic workup revealed bilateral parenchymal pulmonary infiltrates. The CT-scan guided fine-needle aspiration and the core biopsies of the largest pulmonary lesion revealed high-grade spindle cell neoplasm with individual cell apoptosis and necrosis. The immunohistochemical profile on the cell block showed that the cells are positive for Vimentin. The S-100 stain showed only focal positivity. The immunohistochemical stains for HMB45, Melan A, pancytokeratin, and smooth muscle actin were negative. Five years ago the patient was diagnosed with melanoma on the back with Clark level of IV. The melanoma was excised with clear margins and sentinel lymph nodes were negative. Careful examination of patient's previous slides revealed an area of spindle cell melanoma adjacent to a nodular type melanoma. Based on the patient's previous history, current clinico-pathologic presentation and immunohistochemical profile, the diagnosis of metastatic malignant melanoma resembling peripheral nerve sheath tumor was favored over the diagnosis of metastatic malignant spindle cell neoplasm of unknown primary site, which by itself is very rare clinical scenario.

Protection elicited by two glutamine auxotrophs of Mycobacterium tuberculosis and in vivo growth phenotypes of the four unique glutamine synthetase mutants in a murine model.

We generated four individual glutamine synthetase (GS) mutants (DeltaglnA1, DeltaglnA2, DeltaglnA3, and DeltaglnA4) and one triple mutant (DeltaglnA1EA2) of Mycobacterium tuberculosis to investigate the roles of GS enzymes. Subcutaneous immunization with the DeltaglnA1EA2 and DeltaglnA1 glutamine auxotrophic mutants conferred protection on C57BL/6 mice against an aerosol challenge with virulent M. tuberculosis, which was comparable to that provided by Mycobacterium bovis BCG vaccination.

Molecular aspects of diagnostic nucleolar and nuclear envelope changes in prostate cancer.

Prostate cancer is still diagnosed by pathologists based on subjective assessment of altered cell and tissue structure. The cellular-level structural changes diagnostic of some forms of cancer are known to be induced by cancer genes, but the relation between specific cellular-level structural features and cancer genes has not been explored in the prostate. Two important cell structural changes in prostate cancer-nucleolar enlargement and nuclear envelope (NE) irregularity-are discussed from the perspective that they should also relate to the function of the genes active in prostate cancer. Enlargement of the nucleolus is the key diagnostic feature of high-grade prostatic intraepithelial neoplasia (PIN), an early stage that appears to be the precursor to the majority of invasive prostate cancers. Nucleolar enlargement classically is associated with increased ribosome production, and production of new ribosomes appears essential for cell-cycle progression. Several cancer genes implicated in PIN are known (in other cell types) to augment ribosome production, including c-Myc, p27, retinoblastoma, p53, and growth factors that impact on ERK signaling. However, critical review of the available information suggests that increased ribosome production per se may be insufficient to explain nucleolar enlargement in PIN, and other newer functions of nucleoli may therefore need to be invoked. NE irregularity develops later in the clonal evolution of some prostate cancers, and it has adverse prognostic significance. Nuclear irregularity has recently been shown to develop dynamically during interphase following oncogene expression, without a requirement for post-mitotic NE reassembly. NE irregularity characteristic of some aggressive prostate cancers could reflect cytoskeletal forces exerted on the NE during active cell locomotion. NE irregularity could also promote chromosomal instability because it leads to chromosomal asymmetry in metaphase. Finally, NE irregularity could impact replication competence, transcriptional programming and nuclear pore function.

Rapid identification and susceptibility testing of Mycobacterium tuberculosis from MGIT cultures with luciferase reporter mycobacteriophages.

In a prospective study conducted in a diagnostic laboratory in Mexico City, luciferase reporter mycobacteriophages (LRPs) were evaluated for their utility and performance in identification and antibiotic-susceptibility testing of Mycobacterium tuberculosis complex (MTC) isolates from MGIT-960 cultures. Eighty-four consecutive MGIT cultures recovered from 54 patients were included in this study. The LRPs confirmed mycobacterial growth in 79 (94 %) of 84 MGIT cultures. Failure to confirm growth was due to low inoculum (n = 1) or growth with non-tuberculous mycobacteria (n = 4). The median time to confirmation of MGIT cultures was 1 day (range 1-55). Confirmed cultures were identified with p-nitro-alpha-acetylamino-beta-hydroxypropiophenone (NAP), a selective inhibitor of MTC species, and results obtained with LRPs were compared with those obtained by BACTEC-460. The sensitivity and specificity of the LRP NAP test were respectively 97 and 100 %, and the median turnaround time for identification was 3 days with both methods. The accuracy and speed of the LRPs for susceptibility testing with rifampicin, streptomycin, isoniazid and ethambutol were compared with BACTEC-460 and discrepant results were tested by the conventional agar proportion method. In total, 72 MTC cultures were tested. The overall agreement between the LRPs and BACTEC-460 was 98.6 %. Four isolates (5.6 %) were falsely identified as ethambutol-resistant. The median turnaround time for susceptibility testing was 3 days (range 3-57) with the LRPs and 9 days (range 7-29) with BACTEC-460. LRPs offer an accurate and rapid approach for identification and susceptibility testing of M. tuberculosis from MGIT-960 cultures.

Detection and drug-susceptibility testing of M. tuberculosis from sputum samples using luciferase reporter phage: comparison with the Mycobacteria Growth Indicator Tube (MGIT) system.

Rapid diagnosis of drug-resistant M.tuberculosis (Mtb) is desirable worldwide. We (i) describe a new luciferase reporter phage (LRP), phAE142 for this purpose; (ii) compare it to the automated MGIT 960 for time-to-detection of Mtb in clinical specimens; and (iii) evaluate its use for species confirmation and antibiotic susceptibility testing(AST) of Mtb. Twenty sputum samples were inoculated for testing by LRP, or by MGIT 960. After "positives" were identified by either method, the LRP was used for confirmation of Mtb complex (TBC) and for AST. The LRP method proved comparably efficient to MGIT 960 at detecting Mtb. Using an antibiotic uniquely inhibiting TBC with LRP provided species assignment, concurrently with AST, in a median of 3 days, with a sensitivity of 97%. Overall agreement in susceptibility results was 96%. Reliable susceptibility results and identification of TBC can be completed in a median of 12 days (range 8 to 16d) with LRP applied to sputum samples.

Specialized transduction: an efficient method for generating marked and unmarked targeted gene disruptions in Mycobacterium tuberculosis, M. bovis BCG and M. smegmatis.

The authors have developed a simple and highly efficient system for generating allelic exchanges in both fast- and slow-growing mycobacteria. In this procedure a gene of interest, disrupted by a selectable marker, is cloned into a conditionally replicating (temperature-sensitive) shuttle phasmid to generate a specialized transducing mycobacteriophage. The temperature-sensitive mutations in the mycobacteriophage genome permit replication at the permissive temperature of 30 degrees C but prevent replication at the non-permissive temperature of 37 degrees C. Transduction at a non-permissive temperature results in highly efficient delivery of the recombination substrate to virtually all cells in the recipient population. The deletion mutations in the targeted genes are marked with antibiotic-resistance genes that are flanked by gammadelta-res (resolvase recognition target) sites. The transductants which have undergone a homologous recombination event can be conveniently selected on antibiotic-containing media. To demonstrate the utility of this genetic system seven different targeted gene disruptions were generated in three substrains of Mycobacterium bovis BCG, three strains of Mycobacterium tuberculosis, and Mycobacterium smegmatis. Mutants in the lysA, nadBC, panC, panCD, leuCD, Rv3291c and Rv0867c genes or operons were isolated as antibiotic-resistant (and in some cases auxotrophic) transductants. Using a plasmid encoding the gammadelta-resolvase (tnpR), the resistance genes could be removed, generating unmarked deletion mutations. It is concluded from the high frequency of allelic exchange events observed in this study that specialized transduction is a very efficient technique for genetic manipulation of mycobacteria and is a method of choice for constructing isogenic strains of M. tuberculosis, BCG or M. smegmatis which differ by defined mutations.