bluuebunny/crossref_metadata_2025_split huggingface dataset:
Systemic Sweet Syndrome Recurrence in Lung Allograft: Autopsy Findings from First Reported Case
Authors: Lilley C M , Goldstein J D 
Published: October 2024

Abstract

Introduction/Objective
Sweet syndrome is a non-vasculitic neutrophilic dermatosis characterized by acute, neutrophilic inflammation, most classically in the skin. Sweet syndrome can, however, manifest with systemic organ involvement including the lungs. Pulmonary involvement by Sweet syndrome is exceedingly rare, and its recurrence in a pulmonary allograft is understudied.

Methods/Case Report
A 43-year-old female with a history of Sweet syndrome with pulmonary involvement developed chronic bronchiolitis obliterans requiring bilateral lung transplantation. Seven years after transplantation, the patient began exhibiting shortness of breath requiring hospitalization. During the patient’s hospital stay, cytomegalovirus viremia and SARS-CoV-2 positivity were detected, and new oral lesions were concerning for a Sweet syndrome flare. Her respiratory status continued to decline requiring escalating ventilatory support. An autopsy limited to the chest and abdomen was performed after she expired. The pleural cavities had extensive adhesions, and both lungs were heavy. Microscopically, the lungs showed extensive, intralumenal acute inflammation of the bronchi and bronchioles with marked chronic inflammation of the submucosa, histologically similar to the patient’s explanted lung specimen. There was also focal endogenous lipoid pneumonia due to bronchiolar obstruction. In addition to the inflammatory findings, multiple infectious agents were identified in the patient’s respiratory tract including SARS-CoV-2, cytomegalovirus, Epstein-Barr virus, Candida glabrata, Klebsiella pneumoniae, and Stenotrophomonas maltophilia. No underlying malignancy was identified. (This patient’s earlier course was reported previously: PMC8411443)

Results (if a Case Study enter NA)
NA

Conclusion
Pulmonary involvement in Sweet syndrome can cause significant morbidity, and prior to this case, allograft recurrence of Sweet syndrome had not previously been reported. For transplant patients with a history of pulmonary Sweet syndrome, recurrence should be considered in cases of allograft dysfunction. This case also highlights the importance of thorough microbiological studies in autopsies of patients with systemic inflammatory diseases being treated with extensive immunosuppressive therapies.
DICER1 Syndrome in a 25-Year-Old Female: Autopsy Case Report of Mixed Sex Cord-Stromal and Primitive Sarcoma Tumors with Diverse Differentiation Patterns
Authors: Al Hosri R , Prete A R , Smith S C 
Published: October 2024

Abstract

Introduction/Objective
DICER-1 syndrome is a rare disorder characterized by germline mutations in the DICER1 gene, known to confer a lifetime risk of developing a variety of benign and malignant pathologies. This syndrome typically affects young individuals, though it exhibits exceedingly variable and relatively low penetrance of the neoplastic manifestations.

Methods/Case Report
We report on a 25-year-old woman with a history of metastatic DICER-1 related mixed pattern sex-cord stromal tumor of the ovary and primitive sarcoma of the liver. Her treatment involved extensive surgeries, including oophorectomy, salpingectomy, and partial hepatectomy, and multiple cycles of chemotherapy. Antemortem surgical pathological analyses revealed a poorly differentiated, primitive sarcoma in the liver and a sex cord-stromal tumor with Sertoli-Leydig and juvenile granulosa cell tumor-like features. The liver tumor exhibited a primitive spindle cell sarcoma with anaplastic features as well as chondrosarcomatous and rhabdomyosarcomatous patterns, suggesting a primary DICER1-related sarcoma. Immunohistochemistry confirmed the tumor’s complex multilineage differentiation, showing variable positivity for CD99, vimentin, CD10, BCL2, and Glypican-3. Positivity for Desmin and MyoD1 was focal, while the tumor was negative for inhibin, calretinin, AE1/3, AFP, and beta-catenin, overall supporting a DICER1-associated sarcoma diagnosis. She eventually died from terminal cardiac arrest secondary to complications from her metastatic cancer. An autopsy revealed a significant abdominopelvic mass leading to hemoperitoneum and extensive organ involvement, highlighting the aggressive nature of DICER1-associated malignancies.

Results (if a Case Study enter NA)
NA

Conclusion
This case underscores the importance of recognizing the broad manifestations of DICER-1 syndrome for accurate diagnosis, genetic counseling, and tailored management. Highlighting tumor morphology and immunohistochemical features enriches our understanding of DICER-1 pathology, advancing diagnosis and treatment prospects for affected individuals.
Deaths from asthma: a series of cases and their presentations, and the impact on local and global health
Authors: Padasak C L , Boring S , Engleson A , Hammers J 
Published: October 2024

Abstract

Introduction/Objective
Asthma is a lung disease usually characterized by chronic inflammation that affects at least 300 million people globally at all life stages. Asthma is defined by respiratory symptoms such as coughing, wheezing, shortness of breath, and chest tightness with expiratory airflow limitation.The prevalence of asthma is increasing worldwide. Asthma is often under-diagnosed and under-treated, particularly in low- and middle-income countries.
Severe disease can result in reduced quality of life or even premature death. Epidemiologic studies are being utilized to compare international incidences of asthma between populations so that etiologic mechanisms involved in the development of asthma can be discovered through research. Asthma prevalence studies require large numbers and high response rates amongst a random population to establish prevalence and severity with reasonable precision.
Despite advances in treatments, guidelines, and preventable factors, deaths from asthma account for 250,000 premature deaths each year.
Pathology has a key role in asthma identification through examination endobronchial biopsies and whole lung postmortem examination

Methods/Case Report
We present a series of asthma deaths with variable clinical presentations and histopathologic findings. The postmortem gross and histologic findings highlight the varying severities that asthma can have on the lungs. Knowledge of the clinical symptom presentations, identification of gross findings, appropriate sampling of lung tissue, identification of microscopic acute and chronic features help identify asthma related changes. Understanding common lifestyle, environmental, genetic, and medical care factors that serve as asthma triggers and their role in the onset or continuation of an acute exacerbation will allow for accurate determination of cause, contributing cause, and manner of death. This information, listed on the death certificate, is what helps correlate asthma prevalence with mortality allowing for appropriate allocation of funds for research, prevention and treatment.

Results (if a Case Study enter NA)
EP abstract

Conclusion
Outlined are the impacts that asthma can have on individuals, communities, and health systems globally but also ways to identify when death may be or is likely the result of asthma. While asthma cannot be cured, measuring the prevalence of disease and accurately determining asthma as the cause or contributing cause of death can help raise awareness and mitigate the consequences of severe disease.
Retroperitoneal Myoepithelial Carcinoma with Heterologous Bone Formation and EWSR1::ZNF444
Authors: Choi J , Sahoo S , Hwang H 
Published: October 2024

Abstract

Introduction/Objective
Soft tissue myoepithelial tumors are rare tumors that affect a wide age range and diverse tissue sites. Fewer than five cases have been reported in the retroperitoneum. Most tumors are benign with the only histologic criterion for malignancy being cytologic atypia. The morphology is broad ranging from spindled to epithelioid cells of varying cellularity in sclerotic to myxoid stroma. Heterologous differentiation may be present. These tumors usually express cytokeratin, EMA, S100, and GFAP and show EWSR1 and FUS rearrangements. Here we present an unusual case of retroperitoneal myoepithelial carcinoma.

Methods/Case Report
A 29-year-old female presented with rash and painless jaundice. CT and MRCP revealed a relatively circumscribed 3.7 cm mass in the porta hepatis. On fine needle aspiration, a possible gastrointestinal stromal tumor was considered due to DOG1 expression. The patient underwent a Whipple procedure with negative margins showing tumor in soft tissue adjacent to the common bile duct. The tumor was multinodular and consisted predominantly of mild to moderately pleomorphic epithelioid cells in fibromyxoid stroma with interspersed woven bone. Mitoses were not appreciated, and necrosis not seen. The tumor was focally positive for CK AE1/AE3, GFAP, and DOG1 and negative for S100, SOX10, p63, and CD117. INI1 was retained. NGS identified EWSR1::ZNF44 and a diagnosis of myoepithelial carcinoma was rendered. The patient received no adjuvant therapy and has not shown any evidence of metastasis or recurrence for 17 months.

Results (if a Case Study enter NA)
NA

Conclusion
Soft tissue myoepithelial carcinomas are aggressive tumors with approximately 40% recurrence and over 50% metastasis. Standard treatment is complete surgical resection. The efficacy of radiation and chemotherapy is not clear. EWSR1 fusions with various partners including POU5F1, PBX1/3, and ZNF44 have been identified. Due to their rarity and varying histology and immunohistochemical expression, identification of gene fusions can be invaluable in diagnosing soft tissue myoepithelial tumors, especially in unusual locations.
An Anaplastic Lymphoma Kinase (ALK) Immunohistochemical Pitfall: ALK-positive Histiocytosis versus Angiomatoid Fibrous Histiocytoma
Authors: Chang J , Diaz-Perez J , Smith S C 
Published: October 2024

Abstract

Introduction/Objective
The 5th Edition WHO classification expanded the histiocytic/dendritic cell neoplasms to include ALK-positive histiocytosis, which can present as multisystem or single-site disease, affecting various age groups. These tumors lack high-grade cytologic features but express ALK by immunohistochemistry, typically indicating ALK locus rearrangements. In this case study, a cutaneous mass initially suspected as ALK-positive histiocytosis was found to be angiomatoid fibrous histiocytoma (AFH) with ALK expression, highlighting the potential diagnostic pitfall due to overlapping histomorphology and ALK expression.

Methods/Case Report
A previously healthy twelve-year-old boy sought evaluation for a growing and ulcerating mass on his left arm, which developed gradually over a year post-injury. Laboratory tests showed elevated inflammatory markers and mild anemia. A biopsy of the ulcer revealed Staphylococcus aureus infection. Initial histological examination revealed mixed inflammatory infiltrates with focal necrosis, prominent histiocytes, and giant cells. Despite favoring an infectious cause, immunostains were performed. AE1/AE3, ERG, CD34, CD30, S100, SOX10, SMA, and MyoD1 were negative, while INI1 was retained. However, ALK was strongly positive in some histiocytoid cells, suggesting ALK-positive histiocytosis. Surgical resection was subsequently performed to manage the abscess and characterize the lesion. Histologic examination revealed a solid nodule containing spindled and epithelioid cells with a bland histiocytoid appearance, arranged in a compact syncytial growth pattern within the dermis and subcutis.
Surrounding the tumor, there was a distinct cuffing of fibrosis with organized lymphoplasmacytic cells. Break apart fluorescence in situ hybridization studies showed rearrangement of EWSR1 but not ALK. The diagnosis of angiomatoid fibrous histiocytoma was rendered.

Results (if a Case Study enter NA)
NA

Conclusion
This case highlights the importance of understanding immunohistochemical features, especially those that are unusual and unexpected in rare diseases. With the growing use of minimally invasive sampling techniques, this case study underscores the significance of integrating molecular diagnostics with clinical, histological, and immunophenotypic evaluations to achieve an accurate diagnosis in surgical pathology.
Unexpected Encounters: Ossifying Fibromyxoid Tumor Unveiled During Evaluation for Inguinal Hernia
Authors: Pham T , Vo T , Rao R 
Published: October 2024

Abstract

Introduction/Objective
Soft tissue pathology often presents diagnostic surprises, elucidating the intricate nature of disease processes. In this introduction, we discuss the unexpected discoveries that can arise during clinical evaluations and emphasize the importance of thorough evaluation in soft tissue pathology.

Methods/Case Report
We present the case of a 40-year-old male who underwent evaluation for a right inguinal hernia, during which an ossifying fibromyxoid tumor (OFMT) was incidentally discovered. Imaging modalities intended for hernia assessment revealed a 4.5 cm mass abutting the hernia site. Surgical exploration, initiated for hernia repair, unveiled the unsuspected coexistence of a direct inguinal hernia and an OFMT. Histopathological analysis of the excised mass revealed a complex OFMT architecture, characterized by a plexiform growth pattern, fibrous to fibromyxoid matrix, and distinct cellular features. The neoplastic cells exhibited bland round to ovoid nuclei, occasional multinucleation, and scattered mitotic figures. Immunohistochemistry demonstrated variable positivity for desmin and focal positivity for S-100 protein, while CD34, keratin AE1/AE3, smooth muscle actin, and p63 were consistently negative. Notably, the tumor exhibited areas of hypercellularity and easily identifiable mitotic figures, consistent with morphologic features of malignancy in OFMT.

Results (if a Case Study enter NA)
N/A

Conclusion
This case highlights the intricate interplay between primary clinical concerns and incidental pathological findings, underscoring the necessity for comprehensive evaluation in soft tissue pathology. Understanding the nuanced histological and immunohistochemical characteristics of OFMT is pivotal for accurate diagnosis and optimal patient management. The unexpected discovery of OFMT during evaluation for inguinal hernia emphasizes the importance of thorough assessment and consideration of incidental findings in clinical practice.
The diagnostic challenge of a Papillary lesion of the breast in a patient with Peutz-Jeghers syndrome
Authors: Khan B , Kaur N , Hassan M 
Published: October 2024

Abstract

Introduction/Objective
Peutz-Jeghers syndrome (PJS) is an autosomal dominant disorder with elevated risk of various neoplasms, including breast cancer. The incidence of cancer among PJS patients is estimated to be 15-fold higher than the general population. The spectrum of breast lesions in PJS varies from benign papillomas to invasive carcinomas, presenting significant diagnostic complexities. The case presented here revolves around a unique papillary lesion in a PJS patient.

Methods/Case Report
A 40-year-old African American female, with PJS presented with a palpable abnormality in the right subareolar region with sanguineous nipple discharge. Multiple prior biopsies revealed intraductal papillomas with no atypia. Imaging showed a 7.0 cm complex solid and cystic subareolar mass, which had increased in size by 42% within a short period. Given the rapid increase in size, malignant transformation was clinically suspected. The patient underwent bilateral mastectomy. Macroscopic examination showed a 9.0 cm tan firm subareolar nodule with solid and cystic components. Histopathology revealed areas consistent with intraductal papilloma, however, additional complexities, including epithelial and myoepithelial proliferations with mild cytologic atypia, squamous, apocrine, and sebaceous metaplasia made the diagnosis challenging. No necrosis or increased mitotic activity was identified.
Immunostaining for CK5/6 and p63 highlighted the myoepithelial layer, while estrogen receptor demonstrated heterogeneous positive staining. This picture raised suspicion of adenomyoepithelioma, but there was a significant overlap with intraductal papilloma. A final diagnosis of intraductal papillary neoplasm with epithelial and focal myoepithelial atypia was rendered.

Results (if a Case Study enter NA)
NA

Conclusion
This case presented a complex diagnostic dilemma. The rapid growth of the lesion, coupled with cytological atypia, raised significant concern necessitating precise differentiation between adenomyoepithelioma and intraductal papilloma. Further research is imperative to explore the pathophysiology of breast lesions in PJS, their impact on surveillance, management, potential for malignancy, and prognosis. Investigating additional diagnostic modalities and molecular markers to aid in accurate differentiation between benign and malignant papillary neoplasms in PJS patients warrants consideration.
Risks of Tacrolimus and Paxlovid Therapy in SARS-CoV-2 Positive Transplant Recipients: A Case Discussion and Institutional Data Review
Authors: Olp M D , Higginson E , Gherasim C 
Published: October 2024

Abstract

Introduction/Objective
Transplant recipients maintained on immunosuppressants like tacrolimus continue to be at high risk for morbidity due to SARS-CoV-2 infection and are strong candidates for antiviral therapies. However, co- administration of the antiviral Paxlovid (nirmatrelvir/ritonavir) poses a significant risk to these patients due to ritonavir- mediated inhibition of CYP3A, an important mediator of tacrolimus metabolism. Consequently, Paxlovid therapy in post-organ transplant patients on tacrolimus requires careful consideration. Our investigation aims to assess the continuing risk posed by this drug-drug interaction and better understand clinical circumstances linked to critically high tacrolimus levels due to Paxlovid co-administration.

Methods/Case Report
We conducted a large-scale retrospective analysis of tacrolimus measurements at the University of Michigan Medicine beginning in January 2020. We also performed a detailed review of patients with critically high tacrolimus levels coinciding with Paxlovid administration.

Results (if a Case Study enter NA)
Of 39,752 tacrolimus measurements examined, 682 correspond to 329 patients with recent positive SARS-CoV-2 nucleic acid testing, and 37 correspond to 18 patients with documented Paxlovid co- administration. Patients receiving concurrent Paxlovid and tacrolimus demonstrate 1.6- and 1.8-fold higher mean tacrolimus levels (14.1 ng/mL, p = 3e-5) compared to other SARS-CoV-2 positive (8.7 ng/mL) and negative/untested (7.9 ng/mL) patients, respectively. Among SARS-CoV-2 patients, those prescribed Paxlovid are more likely to present with supratherapeutic tacrolimus levels (OR 4.1, 95% CI 1.6 – 10.7). A detailed case review of three organ transplant recipients presenting with tacrolimus levels &gt;60 ng/mL and creatinine levels increased by 0.45 ± 0.27 mg/dL from baseline shows Paxlovid was prescribed at outside facilities, and regular tacrolimus dose was continued. Three other patients exhibited supratherapeutic tacrolimus levels (20 – 30 ng/mL), and creatinine levels increased by 0.41 ± 0.23 mg/dL from baseline despite dose reduction or cessation before initiating Paxlovid.

Conclusion
Our findings highlight the importance of communication between primary and tertiary care providers and caution when prescribing Paxlovid in populations managed with tacrolimus therapy.
Evaluation of an Alternate Diluent for Tests to Ensure Timely Patient Management
Authors: Hettwer S , Gallegos A , Kumar V 
Published: October 2024

Abstract

Introduction/Objective
Recently, backorder of Multi-diluent (MD) for various assays on ADVIA Centaur analyzer (Siemens Healthineers) led to delay in reporting numeric values to the clients when results above the analytical measurement range (AMR) had to be reported as “&gt; value”. The samples were stored frozen (-20 degrees Celsius or - 80 degrees Celsius) for over 2 weeks until the diluent became available, then thawed and re-analyzed upon appropriate dilution. Delay in reporting results beyond AMR may impact patient management; therefore, this study evaluated saline as an alternative diluent for serum folate, carbohydrate antigen 19-9 (CA 19-9), and carbohydrate antigen 27-29 (CA 27.29).

Methods/Case Report
For each test, samples from 5 patients were tested in duplicate, and average of the results was considered the target value (results within undiluted AMR). Subsequently, the samples were diluted 20-fold with either MD or saline, tested in duplicate and average of the results was compared to the target value. The diluent was considered acceptable for use if the difference or % difference between diluted vs target value was less than the Total Allowable Error (TEA).

Results (if a Case Study enter NA)
For serum folate and CA 19-9, the bias between diluted and target value for each diluent (saline and Multi-diluent) was &lt; TEA, and the average bias was also &lt; TEA. For CA 19-9, the average difference from target for saline was smaller than that for Multi-diluent, suggesting it performs better (p-value of 0.0035). However, saline was not an acceptable diluent for CA 27.29 as the bias exceeded TEA.

Conclusion
Saline was an acceptable alternative diluent for serum folate and CA 19-9 but not for CA27.29.
Berberine and Berberine Nanoparticles Mitigate Scopolamine-Induced Amnesia in Rats
Authors: Abdelmonem M , Hemdan A , Ghareeb D , El demellawy M , El sayed M , Wasim H 
Published: October 2024

Abstract

Introduction/Objective
Berberine (BER) has garnered attention in research for its multifaceted biochemical and pharmacological properties, positioning it as a promising natural remedy. Conversely, scopolamine (SCO) functions as a non-selective muscarinic receptor antagonist, disrupting central cholinergic neurotransmission and impairing learning and short-term memory.

Methods/Case Report
Forty-two male Wistar rats were procured from the National Research Center in Cairo, Egypt, and allocated randomly into seven groups, each comprising six rats. The groups were as follows: Sham Control (no treatment), BSA Control (received oral administration of 1 ml Bovine Serum Albumin-NP solution daily for 28 days), BRB-NP Control (received oral administration of BRB-NP nanoparticles at 5 mg/kg/day for 28 days), Induced Group (intraperitoneal injection of SCO at 2 mg/kg dissolved in saline once daily for 28 days), BER Treated Group (received BER at 50 mg/kg suspended in saline followed by intraperitoneal injection of SCO at 2 mg/kg after 40 minutes daily for 28 days), BSA Treated Group (received oral administration of 1 ml BSA-NP solution followed by intraperitoneal injection of SCO at 2 mg/kg after 40 minutes daily for 28 days), and BER-NP Treated Group (received oral administration of BER-NP at 5 mg/kg followed by intraperitoneal injection of SCO at 2 mg/kg after 40 minutes daily for 28 days). Whole blood was collected via heart puncture, and brain tissue was promptly extracted for brain homogenate preparation. Routine biochemical assays were conducted on serum and brain samples.

Results (if a Case Study enter NA)
Statistically significant differences were observed among the seven experimental rat groups concerning plasma AST, albumin, total protein, and triglyceride levels, while differences in ALT and total cholesterol were non-significant.
Regarding brain parameters, significant differences were noted among groups in total protein, cholesterol, phospholipids, and uric acid levels.

Conclusion
Treatment with BRB NPs or free berberine led to a progressive increase in brain protein levels and a decrease in cholesterol content (p&lt;0.05). Additionally, SCO administration resulted in a gradual reduction in brain phospholipid content, while treatment with BER NPs, regardless of the rat’s condition, exhibited the highest phospholipid levels (p&lt;0.05). Furthermore, administration of BSA or free BRB improved brain uric acid levels (p&lt;0.05).