bluuebunny/crossref_metadata_2025 huggingface dataset:
Histological anatomical levels of penile shaft. A histochemical evaluation of 15 cases
Authors: Canete Portillo S , Theriault A , Sanchez D F , Cubilla A L , Celias L , Fernandez-Nestosa M
Published: November 2023

Introduction/Objective

Penile carcinomas (PeCa) arising in the skin of the shaft are rare. Staging systems for PeCa are based on tumor invasion of anatomical levels designed for tumors arising in the glans and foreskin but not for those primary of the shaft. There is scant information about anatomical levels in the shaft. The objective of this study was to evaluate and describe anatomical levels of the shaft with emphasis of the fascias, using histochemical stains.

Methods/Case Report

Sections of penile mid shaft from 15 penectomies with PeCa from 2000-2015 were evaluated. H&E, trichromic and orcein stains were performed to evaluate and describe anatomical levels of the shaft.

Results (if a Case Study enter NA)

Skin: Epidermis: 7-15 cell thick, thin keratin, granulosis, basal pigmentation. Papillary dermis: Loose connective tissue, capillaries, nerve fibers pilo-sebaceous structures. Absence of elastic fibers. Reticular dermis. prominent elastic fibers layer parallel to epidermis merging with dartos. Dartos (superficial fascia): Poorly delineated, merging with reticular layer with no separating space, composed of thin smooth muscle bundles. Deep fascia (Busck's fascia): All tissues between dartos and tunica albuginea. Fibro-elastic, encases vessels, nerves and fibro adipose tissues. Closely attached to the albuginea.Tunica albuginea: Dense mostly fibrous tissue with few elastic fibers encasing corpora cavernosa. Corpus cavernosum: Thick-walled inter-anastomosed vessels. Smaller nutritional vessels, nerves and adipose tissue. No elastic fibers present.

Conclusion

There are 5 distinct anatomical layers in the shaft. Reticular dermis and dartos should be considered as one layer given the poor delineation between them. This knowledge is necessary for staging and prognosis of the rare PeCa arising in the shaft.
RARE PRIMARY CLEAR CELL CARCINOMA OF BLADDER OF MULLERIAN ORIGIN: MORPHO- IMMUNOHISTOCHEMICAL PROFILING
Authors: Jain D , Alazawi S , Ballouk C , Jaiman S
Published: November 2023

Introduction/Objective

Primary clear cell carcinoma of urinary bladder (PCCCUB) is a rare and aggressive cancer variant with uncertain and debatable histogenesis. The hypotheses include origins from the urothelium, pre-existing Müllerian precursors, or mesonephric remnants. Definitive diagnosis is achieved through histology and immunohistochemistry (IHC). We present an unusual case of PCCCUB in a sexagenarian woman.

Methods/Case Report

Patient with history of diabetes, hypertension, and smoking presented with gross hematuria. Computed tomography urogram revealed a 2.3 x 1.2 cm enhancing mass at the base of the urinary bladder. Patient underwent transurethral resection of the bladder tumor (TURBT). Histopathology revealed features of tubulo-papillary, solid, glandular structures with hyalinized stroma. Cytologic features varied from flat, hobnail, to polygonal with abundant clear to eosinophilic cytoplasm and prominent nucleoli. Immunohistochemistry revealed strong reactivity for PAX8, CK7, ER, and racemase; focal reactivity for vimentin, napsin A, p53, CA125; and non-reactivity for PAX2, WT1, PR, GATA3, pCEA, CK20, p63, p40, CD10, RCC, BRST-2, and mammaglobin. P53 showed a wild type staining pattern and Ki-67 was 10%. Combined morphologic and IHC features confirmed PCCCUB, and in the absence of muscularis mucosal invasion, tumor was staged pT1N0. PAX8 positivity and urothelial marker negativity excluded clear cell pattern of urothelial carcinoma. IHC also excluded nephrogenic adenoma, and metastasis. The female gender, and CK 7 (+)/CK 20 (−) profile supported Müllerian origin. Restaging TURBT showed consistent results.

Subsequently, anterior pelvic exenteration and bilateral pelvic lymph nodes dissection was performed revealing muscularis propria invasion upstaging to mpT2 N0.

Results (if a Case Study enter NA)

NA

Conclusion

Poor prognosis, aggressive behavior, and advanced stage at the time of diagnosis warrants accurate diagnose of PCCCUB. Ambiguous origin, limited literature, and lack of clear management guidelines merit reporting in order to enhance knowledge of this rare and intriguing entity.
Upregulation of TIM3 and reduced expression of PD-1 on immune cell subsets in advanced prostate cancers
Authors: Blessin N C , Huang Z , Debatin N F , Bady E , Mandelkow J Müller T , Simon R , Lennartz M , Sauter G , Clauditz T S , Burandt E , Graefen M , Gorbokon N
Published: November 2023

Introduction/Objective

Although most prostate cancers behave in an indolent manner, a small proportion is highly aggressive. Both primary and advanced prostate cancer is widely known as a non-inflamed cancer that is characterized by a paucity of immune infiltration.

Methods/Case Report

To assess the spatial interplay of more than 30 TIM3, CTLA-4, PD-1/-L1 expressing leukocyte subpopulations in 453 prostate cancers, tissue microarrays were stained with 21 antibodies using our BLEACH&STAIN multiplex fluorescence immunohistochemistry approach and analyzed using a deep learning-based image analysis framework.

Results (if a Case Study enter NA)

The immune cell density of CD8+ cytotoxic T-cells, CD4+ T-helper cells, FOXP3+ regulatory T-cells, M1/ M2 macrophages, as well as CD11c+ dendritic cells increased consistently along with the Gleason grade in primary prostate cancer (p≤ 0.034 each). In recurrent prostate cancers under therapy, the density of FOXP3+regulatory T-cells and M1 macrophages further increased, while the density of CD8+ cytotoxic T-cells, CD4+ T-helper cells, as well as CD11c+ dendritic cells decreased (p≤0.017 each). Although the immune checkpoint expression of TIM3 on T-cell subsets, macrophages and dendritic cells was upregulated in advanced/ recurrent tumors, the expression level of PD-1 was downregulated in all analyzed T-cell subsets.

Conclusion

Although prostate cancer is a generally considered a low inflamed tumor, the degree of tumor infiltration by various immune cell subtypes increases markedly along with tumor progression and in recurrent tumors under therapy. Taken together, these data suggest that the evaluation of the spatial distribution of immune cell types along with their immune checkpoint expression can provide relevant clinical information in prostate cancer.
Microcystic Stromal Tumor of ovary; Report of a rare entity
Authors: Bajaj U , Lockart K J , Mehta V
Published: November 2023

Introduction/Objective

Microcystic stromal tumor (MCST) of the ovary is an extremely rare subtype of sex cord- stromal neoplasm first described by Irving and Young in 2009. MSCT is characterized by morphology with microcyst structure, solid cellular areas, and hyalinized fibrous stroma. The most reported tumors were stage I with good prognosis.

Methods/Case Report

We report a rare case of a microcystic stromal tumor of right ovary in a postmenopausal woman, measuring 25 cm in greatest dimension. The present patient underwent right ovarian tumor resection. Gross examination showed that the tumor was solid and cystic. Immunohistochemically, the tumor expressed CD10, WT1, cyclin D1 and vimentin, and nuclear immunoreactivity for β-catenin but negative for α-inhibin, calretinin, CK AE1/AE3, PLAP, SALL-4, CK7, P53, EMA, CD99, AFP, desmin, CgA, E-cadherin, and melanA. Next Generation Sequencing (NGS) showed rare, pathogenic, gain of function mutation CTNNB1 pT41I. The patient is free of disease at 1-year follow up.

Results (if a Case Study enter NA)

NA

Conclusion

MCST is a rare stromal tumor of the ovary. These tumors are considered benign neoplasms because almost all cases display unilateral, localized lesions and have benign outcomes, except for one recurrent case with familial adenomatous polyposis and another initial metastatic case with a CTNNB1 mutation (Zhang Y et al. Hum Pathol 2018, 78:171). MCST is histologically characterized by a microcystic growth pattern, solid cellular areas, and intervening hyalinized stroma, accompanied by immunohistochemical evidence of sex cord-stromal differentiation. Accumulation of nuclear -catenin was reported to be relevant to the pathogenesis of MCST (Maeda D et al. Am J Surg Pathol 2011, 35:1429). More specifically, Maeda et al. observed two cases of ovarian MCST that exhibited a CTNNB1 point mutation in exon 3 and strong nuclear immunoreactivity for -catenin. Other cases exhibited alterations of APC, which is associated with familial adenomatous polyposis (Lee SH et al. Genes Chromosomes Cancer 2015, 54: 353). MCST pathogenesis is linked to -catenin stabilization involving -catenin/Wnt signaling. In our case we found a rare pathogenic, gain of function CTNNB1 T41I c.122C>T mutation which maps within a Gsk3b phosphorylation site of the Ctnnb1 protein (UniProt.org). T41I is predicted to confer a gain of function to Ctnnb1 as demonstrated by nuclear accumulation of Ctnnb1 (Garcia-Rostan G et al. Cancer Res 1999, 59:1811). Our case further expands the histopathologic and molecular spectrum of this rare entity.
Two Cases of Mixed Mullerian Adenosarcoma and Endometrioid Adenocarcinoma of the Uterus
Authors: Kocas Z N , Cortes P , Ibrahim S , Cao J
Published: November 2023

Introduction/Objective

Endometrioid adenocarcinoma (EA) arising in close spatial association with Mullerian adenosarcoma (MA) is a recently described entity that should be distinguished from carcinosarcoma.

Methods/Case Report

We describe two cases of mixed MA and EA of the uterus that presented in our institution in the last 10 years. Both patients were in their 8th decade, showed low grade EA, low stage uterine tumor (pT1bN0),

with MA with sarcomatous overgrowth. Clinically, they presented with post-menopausal bleeding and both with history of a first degree relative with colon cancer at the age of 41 and 25, respectively. In case 1, the MA measured 13 cm with rhabdomyosarcoma. Case 2 had a 6 cm polypoid mass protruding from the cervical os. In case 1, the patient had laparoscopic total abdominal hysterectomy with bilateral salpingoophorectomy (TAH-BSO) and bilateral sentinel node biopsies. The patient was disease-free for 6 months, after which she presented with abdominal recurrence by CT scan. She was treated with chemotherapy (Adriamycin and Doxorubicin) but passed away 15 months after surgery.

Case 2 presented recently and has been asymptomatic and disease free 2 months after laparoscopic TAH-BSO and bilateral sentinel node biopsies. Both cases showed preservation of DNA mismatch repair protein expression.

Results (if a Case Study enter NA)

NA

Conclusion

Twenty two out of 23 cases of this entity were described in the largest series by Hallani et al in the literature. It was suggested that the prognosis of these “mixed” tumors appears to be driven by the sarcomatous component, with only 2 deaths in the series due to MA with rhabdomyosarcoma or sarcomatous overgrowth. When MA with sarcomatous overgrowth was compared with carcinosarcoma by Krivak et al., MA with sarcomatous overgrowth had worse prognosis than carcinosarcoma. More cases of mixed MA and EA are needed for us to determine whether MA with sarcomatous overgrowth in this entity should be treated differently.
Pleomorphic Adenoma With Cystic Change, Extensive Squamous Metaplasia and Positive Block-Like p16 Staining Pattern: A Sheep In Wolf’s Clothing
Authors: Bikhet M , Mesa H , Saeed O A , Hou T
Published: November 2023

Introduction/Objective

Pleomorphic adenoma, the most common benign salivary gland neoplasm may show squamous metaplasia in up to 25% of cases, and less frequent cystic change. We report an unusual case of pleomorphic adenoma with cystic change, extensive squamous metaplasia and block-like p16 staining that was misdiagnosed as metastatic p16-positive squamous cell carcinoma in a limited core biopsy.

Methods/Case Report

A 78-year-old female with no history of malignancy presented with a right neck painless mass. PET-CT demonstrated a hypermetabolic ovoid mass adjacent to the right submandibular gland measuring 1.7 cm concerning for metastatic disease within a lymph node. Fine needle aspiration of lesion was hypocellular and showed cystic contents and rare atypical squamoid cells. Core biopsy of the lesion demonstrated sheets of squamoid cells with mild to moderate cytologic atypia in a hyalinized fibrotic stroma. Immunostain for p16 showed cytoplasmic and nuclear block-staining pattern. The biopsy was diagnosed as metastatic p16-positive squamous cell carcinoma.

Subsequent human papilloma virus (HPV) in situ hybridization for low- and high-risk types was negative. The patient underwent right level 1B neck dissection revealing a pleomorphic adenoma arising at the periphery of the submandibular gland with cystic change and extensive central squamous metaplasia. Repeated p16 staining showed diffuse positivity in the area with squamous metaplasia and heterogenous staining in the non-metaplastic areas.

Cobas HPV-PCR test covering 14 high-risk HPV subtypes was also negative.

Results (if a Case Study enter NA)

NA

Conclusion

We describe the unusual coexistence of extensive squamous metaplasia, cystic change and aberrant p16 staining pattern in an exophytic pleomorphic adenoma to raise awareness of how these changes individually, and more so in combination can mimic squamous cell carcinoma. The mechanism of p16 overexpression in metaplastic PAs appears to be independent of HPV infection.
DEK::AFF2 fusion-associated sinonasal carcinoma: A challenging entity mimicking sinonasal papilloma
Authors: Bishop J , Amin S E , Naik U , Ahmed A A , Saluja K , Bridge J
Published: November 2023

Introduction/Objective

DEK::AFF2 fusion-associated sinonasal carcinoma (DEK::AFF2 SC) also reported in the literature as low-grade papillary sinonasal carcinoma (LGPSC) is a rare, bland-appearing, but locally aggressive neoplasm. Morphologically, these tumors can closely resemble sinonasal papilloma (SP), leading to misdiagnosis. DEK::AFF2 SC is devoid of the underlying EGFR or KRAS driver mutations of SP, suggesting it represents a distinct unique entity. Herein, we present a case of DEK::AFF2 SC in a 65-year-old female who was repeatedly diagnosed as recurrent/atypical SP over ten years.

Methods/Case Report

We first encountered our patient in 2015 when she presented for endoscopic removal of recurrent SP, her fifth recurrence since 2011. From 2015-2021, she experienced four additional recurrences which were repeatedly diagnosed as atypical SP until 2021, when a diagnosis of LGPSC was favored. Imaging (in 2015) also revealed a concurrent mastoid sinus mass with extra-cranial extension to the sigmoid sinus with bone erosion. With each recurrence, imaging showed bone erosion and pushing growth, concerning for malignancy. The current (2023) imaging showed mass extending through mastoid process into the posterior cranial fossa. Over the years, all specimens from the nasal cavity, maxillary sinus, mastoid process, and middle ear revealed confluent, bland- appearing, papillary exophytic and inverted growth of squamous epithelium forming cords, trabeculae, and nests.

Neutrophilic infiltrate was more prominent interstitially than within the surface epithelium. No brisk mitoses, pleomorphism, or frank stromal invasion was identified. The tumor cells were CK5/6 and p63 immunoreactive. Ki-67 labeling index was low (~10%). Despite receiving chemo-radiotherapy, LGSPC recurred in 2023, and DEK::AFF2 fusion was identified by fluorescence in-situ hybridization.

Results (if a Case Study enter NA)

NA

Conclusion

This case highlights the challenges in diagnosing DEK::AFF2 SC. DEK::AFF2 SC should be considered in cases of recurrent/atypical SP, especially those exhibiting destructive growth patterns. The identification and association of DEK::AFF2 fusion in sinonasal carcinomas suggests the potential for targeted therapies, emphasizing the importance of early recognition. Future research is needed to explore the utility of targeted therapy in DEK::AFF2 SC management.
Opportunities for Promoting ASCPi Credentials in Current & Emerging International Markets
Authors: Baker J , Spiczka A , Fong K , Gebhart C , Altenburger D , Famitangco R , Francis E
Published: November 2023

Introduction/Objective

The objective of this study is to identify the positive viewpoints while clarifying and mitigating misconceptions applicants have about the BOC’s credentials for internationally educated laboratory professionals (ASCPi) and the Credential Maintenance Program (CMP).

With over 21,000 ASCPi credential holders worldwide since 2006, and an average yearly growth rate in the number of individuals seeking ASCPi credentials of 29 percent, it is clear ASCPi credentials are growing in recognition and popularity. However, despite the positive growth in the number of individuals seeking ASCPi credentials, the BOC credentials a fraction of ASCPi eligible laboratory professional graduates each year.

Therefore, to encourage additional interest in achieving BOC credentials and advance understanding for CMP, the BOC International Credentialing Committee (ICC) created and deployed a survey. This survey was intended to reach ASCPi credential holders worldwide.

The resulting report (based on analysis of the survey results) identified several opportunities and issues affecting participation in the BOC’s ASCPi and CMP offerings.

Methods/Case Report

1,460 individuals from 74 countries of education participated in the ICC-developed survey. The survey was deployed on December 8, 2022, and closed on January 20, 2023.

Results (if a Case Study enter NA)

This study confirmed a number of assertions the BOC had about the international credential market. The most important of these assertions is ASCPi credentials are appealing to internationally educated laboratory professionals due to ASCPi’s portability (i.e., work eligibility, emigration, etc.). Other confirmed

assertions include a moderate CMP participation rate, and that Facebook remains a popular social media channel in

most countries.

Conclusion

The BOC should continue leaning into the portability of ASCPi credentials, but needs to better promote its advanced credential offerings internationally. This is because ASCPi advanced exams have low application rates when compared to the application rates for ASCP advanced credential exams.

The BOC should also place greater emphasis on educating ASCPi credential holders on the importance of CMP and on what can be used for CE towards CMP. For example, our research provided insights that the BOC needs to create a social media campaign that helps international credential holders understand how CE may be earned for their country’s national CE requirements. Additional CMP insights include the utilization of employer-based professional or skill-development courses.
NEUTROPHILIC HOWELL-JOLLY BODY-LIKE INCLUSIONS IN CONCURRENT HIV AND SARS COVID-19 VIRUS INFECTIONS
Authors: Asad M , Pathan N , Fiedler P
Published: November 2023

Introduction/Objective

Howell-Jolly bodies are nuclear remnants found in red blood cells in various conditions such as post-splenectomy, sepsis, sickle cell disease, alcoholism, autoimmune disorders (lupus), and post-bone marrow transplantation. Howell-jolly body-like inclusions have also been documented in neutrophils, rarely in monocytes, lymphocytes, and other myeloid cells. We report an interesting case of Howell-jolly body-like inclusions found in the neutrophils of a patient who is concurrently infected with HIV and the SARS-COVID-19 virus.

Methods/Case Report

A 59-year-old HIV-positive woman on darunavir, cobicistat, emtricitabine, and tenofovir alafenamide, is a current smoker and has a past medical history of COVID-19 pneumonia and persistent leukopenia. She presented with complaints of worsening cough, fever, and chills for 3 weeks. Her physical examination revealed

diminished breath sounds at the bases of bilateral lungs. Her complete blood count (CBC) revealed white blood cells of 3.1 x 109/L, red blood cells of 2.55 x 1012/L, hemoglobin of 7.6 g/dL, and platelets of 164 x 109/L. Her last CD4

count was unknown and the current was 11. A SARS-CoV-2 PCR test was positive. Nucleic acid amplification tests for other respiratory viruses, Anaplasma and Babesia were negative. A computerized tomography scan of the chest showed multifocal pneumonia with a moderate pericardial effusion. Her beta-d-glucan level was within normal limits.

The peripheral blood smear exhibited numerous neutrophils with basophilic, “Howell-Jolly body-like” inclusions within their cytoplasm. Dohle bodies were also present. Blood culture was positive for methicillin-sensitive Staphylococcus aureus. Her bone marrow biopsy showed normocellular marrow with maturing trilineage hematopoiesis and mild myeloid left shift. The patient was treated with vancomycin and piperacillin-tazobactam.

Results (if a Case Study enter NA)

NA

Conclusion

The presence of Howell-Jolly body-like inclusions in granulocytes is thought to be the result of stressed or dysplastic granulopoiesis secondary to immunosuppressive drugs, viral infections, chemotherapy, post- transplantation, or myelodysplastic syndrome. An association with HIV infection has been previously described.

However, to the best of our knowledge, this is the first case of Howell-Jolly body-like inclusions in a patient with concurrent COVID-19 and HIV infections. These inclusions must be distinguished from other similar intracytoplasmic inclusions including Barr bodies, Anaplasma, and those seen in Chediak-Higashi syndrome.
Application of WHO CNS Fifth Edition Criteria for Glioblastoma Multiforme Diagnosis: A single center study
Authors: Bendari A , Sham S , Hammoud H , Al-Refai R , Abdelhafez A , Harshan M
Published: November 2023

Introduction/Objective

The fifth edition of the WHO classification of the tumors of the central nervous system (WHO CNS 5) published in 2021 introduced major changes that incorporate molecular diagnostics in CNS tumor classification along with histology and immunohistochemistry. Glioblastomas (GBM) were diagnosed based on the histologic features of diffuse and astrocytic glioma in adults, if there is microvascular proliferation and /or necrosis. Isocitrate dehydrogenase 1 (IDH) R132 H immunohistochemical stain expression and /or mutation analysis results were used to further classify GBMs as IDH mutant or IDH wild type. In WHO CNS 5 all IDH mutant diffuse astrocytic tumors are considered a single type (Astrocytoma, IDH mutant) and graded 2, 3, or 4. Glioblastoma IDH wild type is diagnosed in the setting of an IDH wild type diffuse and astrocytic glioma with microvascular proliferation or necrosis or TERT promoter mutation or EGFR gene amplification or +7/-10 chromosome copy number changes. In this study, we analyze how the change in diagnostic criterion would affect the classification of GBMs diagnosed in our institution retrospectively.

Methods/Case Report

The pathology database was searched for all diffuse gliomas diagnosed as GBM between 01/2019 and 12/2021. Age

of the patient, gender, location of tumor, histologic features, IDH status and molecular alterations ( Onkosight Advanced solid tumor panel, 50 genes) were reviewed.

Results (if a Case Study enter NA)

A total of 74 adult high grade glial neoplasms were identified out of which 25 were GBMs. The age of the patients

ranged from 40 to 87 years. 14 were men and 11 were females. All tumors had histologic features of GBM such as necrosis and microvascular proliferation. 24 (96%) tumors were IDH negative by immunohistochemistry and mutation analysis, and 1 (4%) was IDH strongly positive by immunohistochemistry. Molecular studies were not performed on this tumor.

Conclusion

96% of GBMS diagnosed during the time period conformed to the WHO CNS 5 diagnostic criteria. The one IDH

positive tumor would be reclassified as diffuse astrocytoma, IDH mutant, Grade 4. Like previous WHO classifications, WHO CNS 5 is a work in progress attempting to introduce new knowledge into the classification hoping to provide practical guidance to pathologists and neuro-oncologists and to benefit the patients with CNS tumors.
GATA2 Mutation with Bone Marrow Failure. A Review of Ordering Next Generation Sequencing Testing while Triaging Bone Marrows in Patients with Cytopenias – Pathologists Challenge
Authors: Harrison K , Herschap B , Sanchez-Salazar A , Ehsan A , Hapani S
Published: November 2023

Introduction/Objective

GATA2 (germline) mutations are a cause of bone marrow (BM) failure in younger patients characterized by pancytopenia and hypoplastic BM with minimal or no dysplasia. These cases may have negative cytogenetic (CG)/FISH (FH) results and are diagnosed by next-generation sequencing (NGS) testing. We present a case where GATA2 testing was performed on a repeat BM resulting in delayed diagnosis. Insurance companies challenge providers and pathologists with frequent claims denials, thus the need to revise pre-authorization (PA) policies for triaging BMs in real time. We also reviewed our data where NGS was performed in patients with cytopenias, negative morphology (MO), flow cytometry (FC) & CG/FH studies.

Methods/Case Report

We did a retrospective analysis and selected 455 BMs (2018 to 2022) where the clinical indication was cytopenias and had negative MO, FC, CG, and FH. We evaluated MO again with NGS results to ensure diagnostic features were not overlooked.

Results (if a Case Study enter NA)

The index case was a 22-year-old female failing to show abnormality by MO, FL, CG, or FH. The patient continued to have cytopenias; BM was performed a year later and NGS showed GATA2 mutation. This prompted a retrospective analysis of 455 BMs as described under methods. 101/455 (22%) cases revealed abnormal NGS results with pathogenic mutation resulting in amended reports. 42/455 (9%) cases revealed mutations consistent with clonal hematopoiesis of indeterminate potential (CHIP) or clonal cytopenia of undetermined significance (CCUS).

Conclusion

1) PA policy for BM triaging is not practical since a decision for NGS testing is made in real-time; 2) Claim denials lead to underutilization of NGS, thus resulting in delayed patient care; 3) NGS may show pathogenic mutation despite negative MO/FL/CG/FH results; and 4) Insurance companies need to consider reviewing local coverage determination (LCD) policy for hematopoietic disorders as these tests are medically necessary, thus not requiring PA.
Thoracic SMARCA4-deficient undifferentiated tumor: A rare entity and challenging diagnosis
Authors: Sami F I , Lack M , Hamza A
Published: November 2023

Introduction/Objective

Thoracic SMARCA4-deficient undifferentiated tumor is a high-grade malignant neoplasm that frequently shows undifferentiated morphology and deficiency of SMARCA4. There is limited data in literature for this entity. The purpose of this report is to describe a case of this entity and to emphasize the importance of keep this entity in mind when dealing with poorly differentiated thoracic / lung tumors.

Methods/Case Report

A 49-year-old female with 7.5 pack years smoking history presented with a right shoulder pain. A chest x-ray showed rounded density in the right lung apex. This was followed by a CT chest which revealed a 5.6 cm mass with local destruction of the adjacent right third rib suggestive of a chest wall invasion. Also, hilar and paratracheal lymphadenopathy were noted. Subsequently the patient underwent a right upper lobe biopsy which showed diffuse discohesive sheets of moderately pleomorphic large epithelioid cells with vesicular chromatin, focal rhabdoid morphology, frequent mitoses, and extensive necrosis. Immunochemical staining showed the tumor cells to be positive for Cam 5.2, pancytokeratin (focal, weak), synaptophysin, p53 and TTF-1 (focal, weak) and negative for Napsin, SOX-10, CD45, chromogranin, INSM1, p40, CK7, and CK20. Ki-67 proliferation index was 40-50%. Tumor cells had intact expression of RB and were negative BRG1 (SMARCA4). Therefore, diagnosis of thoracic SMARCA4- deficient undifferentiated tumor was rendered. Next generation sequencing showed pathogenic variants in TP53, CDKN2A, and APC genes and likely pathogenic variants in ATR, SMARCA4, and BCOR genes. The patient received carbotaxol and radiation therapy and is alive with metastatic disease 4 months after initial diagnosis.

Results (if a Case Study enter NA)

NA

Conclusion

SMARCA4-deficient undifferentiated tumor is an aggressive malignancy that shows undifferentiated histology with frequent synaptophysin positivity and negativity for other neuroendocrine markers. Pathologists need to keep this entity in their differential when dealing with poorly to undifferentiated thoracic / lung tumors and appropriate immunohistochemical staining can clinch the diagnosis.
Evaluation of the LifeScale system for rapid phenotypic antimicrobial susceptibility testing from positive blood cultures
Authors: Montelongo-Jauregui Daniel , Slechta E Susan , Fisher Mark
Published: November 2023

Objective

The spread of antimicrobial resistance is a growing threat to public health, thus there is a critical need for prompt and reliable antimicrobial susceptibility testing (AST). Rapid AST may improve patient outcomes by allowing for quicker start of optimal therapy and reducing hospital length of stay, therefore decreasing overall healthcare costs. However, rapid results may not improve patient care if they are not considered equivalent to standard AST. Several platforms are under development that can provide rapid AST results; the objective of this work is to assess the performance of the new LifeScale rapid AST platform (Affinity Biosensors) that uses resonant mass measurements for calculation of antimicrobial susceptibility results.

Methods

Positive BACTEC blood-cultures collected from patients were included if the gram stain revealed only Gram-negative rods. Standard of care (SOC) AST results, as determined by a combination of BD Phoenix automated, Sensititre broth microdilution, and/or standard disk diffusion methods, were compared to results from direct positive blood culture testing on the LifeScale system. Minimum inhibitory concentrations (MICs) and categorical interpretations based on CLSI and/or FDA AST breakpoints were compared by microorganism and drug to calculate essential and categorical agreement for five species with pending claims on the LifeScale system: Escherichia coli (N=33), Klebsiella pneumoniae (N=10), K. oxytoca (N=5), Pseudomonas aeruginosa (N=11) and Acinetobacter sp. (N=1); tested against 13 relevant antibiotics: Amikacin, ampicillin, aztreonam, cefazolin, cefepime, ceftazidime, ceftazidime/avibactam ertapenem, gentamicin, levofloxacin, meropenem, piperacillin/tazobactam, and trimethoprim/sulfamethoxazole.

Results

LifeScale had 95.3% essential agreement with the SOC results, and a 93.1% categorical agreement based on CLSI M52 criteria. Of the 665 organism-drug combinations evaluated, agreement was high, with only 1 very major discrepancy, 8 major discrepancies and 37 minor discrepancies, of which 22 (47.8%) were within ±1 doubling dilution. Among these discrepancies, LifeScale MICs averaged 1 dilution higher than SOC MICs, which may reduce the risk of false-susceptible interpretations.

Conclusion

s: The accuracy and reliability of results from rapid AST is of utmost importance. The LifeScale technology is unique among AST platforms as it measures bacterial cell mass and counts to determine MICs for up to 14 antibiotics in ~4 h. These results suggest this platform is able to deliver rapid, actionable results to guide antimicrobial therapy for patients with bacteremia.
Wax on the surface of Phragmites australis leaves provides enemy-free space for the aphid Hyalopterus pruni
Authors: Yamawo Akira , Mukai Hiromi
Published: November 2023

The waxy layer on leaf surfaces may restrict the range of arthropod species that can grip the leaf, thus affecting biological interactions. Here, we report that the wax on the leaf surface of Phragmites australis leaves provides enemy-free space for the aphid Hyalopterus pruni. In our experiment, aphids had higher survival rates on Ph. australis leaves than on Prunus mume leaves in the presence of ladybirds. In addition, removal of wax from the surface of Ph. australis leaves enabled ladybugs to grip the surface of Ph. australis leaves and decreased the survival rate of aphids. These results indicate that the leaf wax of Ph. australis provides enemy-free space for H. pruni by inhibiting ladybird adhesion.
Itaconate as a key regulator of respiratory disease
Authors: Michalaki Christina , Albers Gesa J , Byrne Adam J
Published: November 2023

Macrophage activation results in the accumulation of endogenous metabolites capable of adopting immunomodulatory roles; one such bioactive metabolite is itaconate. After macrophage stimulation, the TCA-cycle intermediate cis-aconitate is converted to itaconate (by aconitate decarboxylase-1, ACOD1) in the mitochondrial matrix. Recent studies have highlighted the potential of targeting itaconate as a therapeutic strategy for lung diseases such as asthma, idiopathic pulmonary fibrosis (IPF), and respiratory infections. This review aims to bring together evidence which highlights a role for itaconate in chronic lung diseases (such as asthma and pulmonary fibrosis) and respiratory infections (such as SARS-CoV-2, influenza and Mycobacterium tuberculosis infection). A better understanding of the role of itaconate in lung disease could pave the way for novel therapeutic interventions and improve patient outcomes in respiratory disorders.
Emergent percutaneous closure of sub-annular aortic root pseudoaneurysm in the setting of composite graft dehiscence: a case report
Authors: Stephenson Samuel , Gambill Michael , Summers Matthew
Published: November 2023

Background

Aortic conduit pseudoaneurysms are rare complications of surgical aortic root replacements. These complications are typically treated with a redo-sternotomy, but these surgeries carry high mortality rates, and patients may not always be good surgical candidates. There have been a few reported cases where aortic pseudoaneurysms have been successfully treated percutaneously with both short- and long-term success. We describe a case were a sub-annular aortic root pseudoaneurysm was closed using an Amplatzer Vascular Plug 2 device.

Case summary

A 68-year-old man was admitted to the hospital 6 weeks after surgical aortic valve and aortic root replacement undergone for prosthetic valve endocarditis. On computed tomography, he was found to have a large fluid collection with extravasation into a false lumen located on the right side of the ascending aorta. Diagnostic catheterization confirmed flow into the pseudoaneurysm cavity from a sub-annular location. This defect was then closed using an Amplatzer Vascular Plug 2 device, with no residual flow or concern for re-opening at 8 months follow-up.

Discussion

This case presents the first documented use of an Amplatzer Vascular Plug 2 to close an aortic root pseudoaneurysm in the sub-annular location. Heart team discussion is crucial in determining whether surgical or percutaneous treatment management should be performed. This case highlights a novel treatment method for sub-annular aortic root pseudoaneurysms which can be considered an alternative to surgery and potentially life-saving for high-risk patients.
Age-related variation in malignant cytology rates of thyroid nodules: insights from a retrospective observational study assessing the ACR TI-RADS
Authors: Walter Leonardo Barbi , Fernandes Paula Martins , Strieder Débora Lunkes , Scheinpflug Anita Lavarda , Zanella André Borsatto , Faccin Carlo Sasso , Farenzena Mauricio , Xavier Laura Fernandes , Zorzi Bianca Dalla Costa , Graudenz Marcia Silveira , Scheffel Rafael Selbach , Dora José Miguel , Goemann Iuri Martin , Maia Ana Luiza
Published: November 2023

Objective

The influence of age on the malignant cytology rate of thyroid nodules remains uncertain. The American College of Radiology Thyroid Imaging Reporting and Data System (ACR TI-RADS) is currently used to guide subsequent investigations of thyroid nodules, regardless of clinical variables. This study aimed to investigate the impact of age on the malignant cytology rates of thyroid nodules and the diagnostic performance of ACR TI-RADS across different age groups.

Design

A retrospective, single-center, observational study.

Methods

Patients aged ≥ 20 years with thyroid nodules, who underwent fine-needle aspiration biopsy between 2012 and 2019 were evaluated. Ultrasound images were used to obtain the TI-RADS data. Malignancy was determined based on suspicious for malignancy (Bethesda V) and malignant (Bethesda VI) cytology results or malignancy in cell block analysis.

Results

A total of 1023 nodules from 921 patients (88.2% female) were analyzed. The median age was 58.5 (interquartile range [IQR], 41.1-66.6) years, and the median nodule size was 2.4 (IQR, 1.7-3.6) cm. Stratification by age revealed a decreasing prevalence of malignant cytology across subgroups of 20-39, 40-59, and ≥60 years (10.7%, 8.5%, and 3.7%, respectively; P = .002). After adjusting for sex, multinodularity, nodule size, and ACR TI-RADS category, we observed that each year of age reduced the OR for malignant cytology by 3.0% (95% CI: 0.7%-5.3%; P = .011). When comparing the subgroups of 20-39 and ≥60 years, the malignant cytology rate decreased by half in TI-RADS 4 (from 21.4% to 10.4%) and two-thirds in TI-RADS 5 (from 64.7% to 22.6%).

Conclusions

Our study demonstrated that as patient age increased, the rate of malignant cytology in thyroid nodules decreased. Moreover, age significantly influences the malignancy rates of thyroid nodules classified according to the ACR TI-RADS.
A manifesto for communication studies
Authors: Coleman Stephen
Published: November 2023

In this article, a case is made for confident self-expression as a practice of democratic citizenship that is no less important than literacy. This article then considers what is entailed in ‘doing citizenship’ as opposed to ‘being a citizen’.
A study on the measurement of GSR with bloodstains by ICP-MS
Authors: Li Xiang , Yü Aoyang , Xia Xinxin , Zhu Yü , Song Hui
Published: November 2023

In forensic laboratories, analytical investigations of gunshot residues (GSRs) are usually conducted by scanning electron microscopy (SEM) in combination with energy dispersive X-ray microanalysis. If GSRs are covered with bloodstains, SEM cannot detect them. In this study, an inductively coupled plasma mass spectrometry method is proposed to solve this problem. Results show that bloodstains did not interfere with GSRs and low-level elements are detected. Qualitative and quantitative analyses of Sn, Sb, Ba, and Pb elements in GSRs are also carried out. Different pretreatment methods are adopted according to the characteristics of different samples. Our investigations suggest that the proposed method has the advantages of low detection limit and high sensitivity and it can be very important in expert testimony.

Key points
Finite source properties of large strike-slip earthquakes
Authors: Atterholt James , Ross Zachary E
Published: November 2023

Earthquake ruptures are complex physical processes that may vary with the structure and tectonics of the region in which they occur. Characterizing the factors controlling this variability would provide fundamental constraints on the physics of earthquakes and faults. We investigate this by determining finite source properties from second moments of the stress glut for a global data set of large strike-slip earthquakes. Our approach uses a Bayesian inverse formulation with teleseismic body and surface waves, which yields a low-dimensional probabilistic description of rupture properties including the spatial deviation, directivity and temporal deviation of the source. This technique is useful for comparing events because it makes only minor geometric constraints, avoids bias due to rupture velocity parametrization and yields a full ensemble of possible solutions given the uncertainties of the data. We apply this framework to all great strike-slip earthquakes of the past three decades, and we use the resultant second moments to compare source quantities like directivity ratio, rectilinearity, average moment density and vertical deviation. We find that most strike-slip earthquakes have a large component of unilateral directivity, and many of these earthquakes show a mixture of unilateral and bilateral behaviour. We notice that oceanic intraplate earthquakes usually rupture a much larger width of the seismogenic zone than other strike-slip earthquakes, suggesting these earthquakes may often breach the expected thermal boundary for oceanic ruptures. We also use these second moments to resolve nodal plane ambiguity for the large oceanic intraplate earthquakes and find that the rupture orientation is usually unaligned with encompassing fossil fracture zones.
Signalling mechanisms and agricultural applications of (Z)-3-hexenyl butyrate-mediated stomatal closure
Authors: Payá Celia , Belda-Palazón Borja , Vera-Sirera Francisco , Pérez-Pérez Julia , Jordá Lucía , Rodrigo Ismael , Bellés José María , López-Gresa María Pilar , Lisón Purificación
Published: November 2023

Biotic and abiotic stresses can severely limit crop productivity. In response to drought, plants close stomata to prevent water loss. Furthermore, stomata are the main entry point for several pathogens. Therefore, the development of natural products to control stomata closure can be considered a sustainable strategy to cope with stresses in agriculture. Plants respond to different stresses by releasing volatile organic compounds. Green leaf volatiles, which are commonly produced across different plant species after tissue damage, comprise an important group within volatile organic compounds. Among them, (Z)-3-hexenyl butyrate (HB) was described as a natural inducer of stomatal closure, playing an important role in stomatal immunity, although its mechanism of action is still unknown. Through different genetic, pharmacological, and biochemical approaches, we here uncover that HB perception initiates various defence signalling events, such as activation of Ca2+ permeable channels, mitogen-activated protein kinases, and production of Nicotinamide adenine dinucleotide phosphate (NADPH) oxidase-mediated reactive oxygen species. Furthermore, HB-mediated stomata closure was found to be independent of abscisic acid biosynthesis and signalling. Additionally, exogenous treatments with HB alleviate water stress and improve fruit productivity in tomato plants. The efficacy of HB was also tested under open field conditions, leading to enhanced resistance against Phytophthora spp. and Pseudomonas syringae infection in potato and tomato plants, respectively. Taken together, our results provide insights into the HB signalling transduction pathway, confirming its role in stomatal closure and plant immune system activation, and propose HB as a new phytoprotectant for the sustainable control of biotic and abiotic stresses in agriculture.
Clinical Impact of Serious Respiratory Disease in Children Under the Age of 2 Years During the 2021–2022 Bronchiolitis Season in England, Scotland, and Ireland
Authors: Williams Thomas C , Marlow Robin , Hardelid Pia , Lyttle Mark D , Lewis Kate M , Mpamhanga Chengetai D , Cunningham Steve , Roland Damian ,   PERUKI, Fraser Karena , Baker James , Bailie Helen , Tolhurst-Cleaver Meriel , Stellman Rob , Hartshorn Stuart , Watson Jessica , Begley Roisin , Hingley Sakura , Dutta Manali , Ramsden Gemma , Ryan Eleanor , Durnin Sheena , Koe Stanley , Halasz Gergely , Brearey Steve , Ranasinghe Darren , Gopi Mudiyur , Spalding Claudia , Gomes Sylvester , Woods Gracita , Aldridge Patrick , Owens Vicky , Balehithlu Hemantha , Richardson Simon , Hartin David , Mitchell Rachael , Downes Alice , Roland Damian , Sequeira Sabrina , Tillett Jo , Dowson Simon , Tomlinson Jo , Da Costa Adebayo , Sime Alfred , Kirby Claire , Lawton Adam , Wear Ruth , Gough Christopher , Gardner Sharryn , Haslam Zena , Rimmer Craig , Steensma Jiske , Rao Sahana , Deall Heather , Hall Sharon , Middleton Catriona , Walton Emily , Mackenzie Friyana Dastur , Thakker Manish , Robinson Gisela , Johnson Graham , Wong Shye , Diaba Cynthia , Foster Steve , Browning Jen , Rooney Lynsey , Challen Kirsty , Rosser Michael , Patel Pratiksha , Spicer Amy , Bagshaw Lorna , Gray Seb , Gibbs Sally , Mullen Niall , Fairley Louise , Bayreuther Jane , James David , Jarman Heather , O'Leary Clare , Clerihew Linda , Astin-Chamberlain Raine , Trippick Sarah , Armstrong Lawrence , Mulligan Joanne , Keers Sophie , Cahill Benjamin , Mohammad Misbah , Burridge Richard , Wilson Sarah , Anpananthar Amutha , Jamall Erum , Lacy David
Published: November 2023

Background

Interventions introduced to reduce the spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) led to a widespread reduction in childhood infections. However, from spring 2021 onwards the United Kingdom and Ireland experienced an unusual out-of-season epidemic of respiratory disease.

Methods

We conducted a prospective observational study (BronchStart), enrolling children 0–23 months of age presenting with bronchiolitis, lower respiratory tract infection, or first episode of wheeze to 59 emergency departments across England, Scotland, and Ireland from May 2021 to April 2022. We combined testing data with national admissions datasets to infer the impact of respiratory syncytial virus (RSV) disease.

Results

The BronchStart study collected data on 17 899 presentations for 17 164 children. Risk factors for admission and escalation of care included prematurity and congenital heart disease, but most admissions were for previously healthy term-born children. Of those aged 0–11 months who were admitted and tested for RSV, 1907 of 3912 (48.7%) tested positive. We estimate that every year in England and Scotland 28 561 (95% confidence interval, 27 637–29 486) infants are admitted with RSV infection.

Conclusions

RSV infection was the main cause of hospitalizations in this cohort, but 51.3% of admissions in infants were not associated with the virus. The majority of admissions were in previously healthy term-born infants.
Theorizing Infrastructures in Global Politics
Authors: Bueger Christian , Liebetrau Tobias , Stockbruegger Jan
Published: November 2023

A growing wave of studies in international relations is interested in “infrastructure.” Pipelines, ports, financial transaction arrangements, and other large technical systems increasingly occupy the minds of international theorists. This theory note provides direction to the debate by offering an important clarification of the concept of infrastructure and how it is theorized. Scholars have very different understandings of what infrastructures are, why they matter, and how to theorize and study them empirically. By outlining three distinct “styles of theorizing infrastructure,” we provide new directions for future research and how it can contribute to broader debates in international theory. The three styles allow to capture the disagreement over whether infrastructure is a theoretical concept at all, or if it solely refers to empirical phenomena. For some scholars, infrastructures are an object of politics, while others see them as developing political force or even agency on their own. Others see broader potential and note that “infrastructuralism” could provide a major new theoretical vocabulary. Each style provides major new avenues for international theory.