bluuebunny/crossref_metadata_2025_split huggingface dataset:
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

Abstract

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

Abstract

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&gt;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

Abstract

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

Abstract

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

Abstract

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

Abstract

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

Abstract

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

Abstract

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

Abstract

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.