bluuebunny/crossref_metadata_2025_split huggingface dataset:
Squamous Cell Carcinoma of the Vulva: Clinicopathologic Features of Human Papillomavirus (HPV) Associated and Independent Lesions
Authors: Fernandez M , Kop M , Terada K , Shimizu D , Vierkoetter K R 
Published: November 2022

Abstract

Introduction/Objective
Vulvar squamous cell carcinoma (VSCC) develops via HPV-associated and HPV-independent pathways. Each subset is notable for distinct precursor lesions, morphology, epidemiology and prognoses. There is no consensus regarding the incidence of HPV-associated VSCC, although the literature estimates a range of 15–79%. The current investigation aims to determine the incidence and clinicopathologic features of HPV-associated and HPV- independent VSCC in a diverse, multi-ethnic population.

Methods/Case Report
Resections specimens of VSCC from 1991 to 2020 were retrospectively identified. Cases were reviewed for confirmation of diagnosis, followed by immunohistochemical staining for p16. Age at diagnosis, ethnicity, body mass index, smoking history, tumor size, depth of invasion, and stage were obtained. Statistical analyses included t and Fisher’s exact tests as appropriate, with p&lt;0.05 considered statistically significant.

Results (if a Case Study enter NA)
Sixty-seven VSCC cases were reviewed. By immunohistochemistry, 34 (51%) were HPV-associated. Age at diagnosis was statistically significant (p = 0.0008), with an average age of 63 years for HPV-associated and 75 years for HPV-independent VSCC.Tumor size approached statistical significance (p = 0.0577), with larger tumors occurring in the absence of HPV. Additionally, the incidence of HPV-independent VSCC nearly doubled every 10 years while the incidence of HPV-associated VSCC remained constant.

Conclusion
In this diverse, multi-ethnic cohort, the incidence of HPV-associated VSCC (51%) is at the higher end of the global range of 15-79%. Differences in age demonstrated statistical significance, supporting existing data describing HPV-associated VSCC diagnosed in relatively younger women. Tumor size approached statistical significance, signaling a correlation between HPV-independent VSCC and larger tumors; findings that may support reports of HPV-independent VSCC being associated with a worse prognosis. The increasing incidence of HPV- independent VSCC compared to a constant rate of HPV-associated VSCC suggests changing patterns of detection and pathogenesis.
Automated prognosis marker assessment in 2,004 breast cancers using an artificial intelligence-based framework for BLEACH&STAIN multiplex fluorescence immunohistochemistry
Authors: Mandelkow T , Bady E , Müller J , Debatin N F , Lurati M C , Lennartz M , Sauter G , Blessin N C 
Published: November 2022

Abstract

Introduction/Objective
Introduction: Prognostic markers in routine clinical practice of breast cancer are currently assessed using multi-gene panels. However, the fluctuating tumor purity can reduce the predictive value of such tests. Immunohistochemistry holds the potential for a better risk assessment.

Methods/Case Report
Methods: To enable automated prognosis marker detection (i.e. HER2, GATA3, progesterone-[PR], estrogen- [ER], and androgen receptor [AR], TOP2A, Ki-67, TROP2), we have developed and validated a framework for automated breast cancer identification, which comprises three different artificial intelligence analysis steps and an algorithm for cell-distance analysis of 11 + 1 marker BLEACH&STAIN multiplex fluorescence immunohistochemistry (mfIHC) staining in 2,004 breast cancers.

Results (if a Case Study enter NA)
Results: The optimal distance between Myosin+ basal cells and benign panCK+ cells was identified as 25 µm and used to exclude benign glands from the analysis combined with several deep learning-based algorithms. Our framework discriminated normal glands from malignant glands with an AUC of 0.96. The accuracy of the approach was also validated by well-characterized biological findings, such as the identification of 13% HER2+, 73% PR+/ER+, and 14 triple negative cases. Furthermore, the automated assessment of GATA3, PR, ER, TOP2A-LI, Ki-67-LI and TROP2 was significantly liked to the tumor grade (p&lt;0.001each). Furthermore, a high expression level of HER2, GATA3, PR, and ER was associated with a prolonged overall survival (p≥0.002 each).

Conclusion
Conclusion: A deep learning-based framework for automated breast cancer identification using BLEACH&STAIN multiplex fluorescence IHC facilitates automated prognosis marker quantification in breast cancer.
Malignant Dural Solitary Fibrous Tumor; An Exceedingly Rare Entity
Authors: Kaur N , Hussain F , Al Hmada Y 
Published: November 2022

Abstract

Introduction/Objective
A solitary fibrous tumor (SFT) is an extremely rare mesenchymal neoplasm, accounting for &lt;1% of all primary CNS tumors. Most SFT is dural-based and occurs predominantly in the fourth to sixth decade of life. Here, we present a case of a dural solitary fibrous tumor.

Methods/Case Report
A 28-year-old male presented with intermittent throbbing headache, nausea, and vomiting. Imaging revealed a large, well-circumscribed left parafalcine, dural-based multilobulated, solid, and cystic mass. The patient underwent craniotomy with mass resection. Preliminary intraoperative findings were of a spindle cell neoplasm. Histopathologic examination showed hypercellular neoplasm composed of the spindle to ovoid cells with a high nuclear to cytoplasmic ratio and limited intervening stroma arranged in a haphazard pattern with prominent branching staghorn vasculature. Focal areas of necrosis and mitotic counts of 8/10 high power field were also seen. The lesional cells showed focal cytoplasmic CD34 expression and strong STAT6 nuclear expression. Finally, a diagnosis of SFT, haemangiopericytoma phenotype classified as grade 3, was made.

Results (if a Case Study enter NA)
NA

Conclusion
Most SFTs are considered clinically benign (grade 1 tumors) with favorable outcomes after complete resection. However, haemangiopericytoma phenotype with hypercellularity, necrosis, and elevated mitotic count (&gt; 4/10 HPF) is known to have an increased risk of local recurrence and rare metastasis, requiring patients to receive adjuvant radiotherapy after resection for longer progression-free survival. Therefore, it is vital to be aware of this entity for optimal management and more active systemic surveillance in patients with high-grade SFT tumors. Our patient is currently doing well post-adjuvant radiotherapy and is under active annual surveillance.
Embryonal rhabdomyosarcoma of oropharynx in a 65-year-old male with indolent clinical presentation and unusual morphology
Authors: Surucu A , Hou T 
Published: November 2022

Abstract

Introduction/Objective
Embryonal rhabdomyosarcoma (ERMS) is a malignant primitive mesenchymal tumor which commonly affects children and adolescence. Although head and neck area is a common location for ERMS, oropharynx is rarely involved. ERMS in adults often present with stage IV disease and show a relatively poor prognosis. Loss of heterozygosity in 11p15.5 is one of the common genetic findings in sporadic ERMS.

Methods/Case Report
A 65-year-old male with no significant medical history, presented with pharyngodynia and was found to have a polypoid mass originating from the pharyngeal surface of the soft palate and extends into the vallecula. He reported having this mass for a decade and having intermittent episodes of similar oropharyngeal symptoms which were usually resolved with antibiotics.

Results (if a Case Study enter NA)
Excisional biopsy shows a 2.4 cm polypoid mass with atypical cellular proliferation in submucosa. Tumor cells demonstrate ovoid to round nuclei and eosinophilic cytoplasm. No mitotic figure was found and Ki67 proliferation index was extremely low (&lt;1%). Immunostains showed that the tumor cells are positive for Desmin and MyoD1. Scattered cells are positive for Myogenin. Due to the unusual clinical presentation and low proliferation activity, late onset of fetal rhabdomyoma was also considered in the differential diagnosis. The specimen was sent for chromosomal microarray which showed chromosomal gains and losses including loss of heterozygosity in chromosome 11. This finding together with cytologic atypia are mostly compatible with the diagnosis of ERMS. Post-biopsy MRI and PET-CT did not reveal any residual disease or distant metastasis. Patient has been followed up for 6 months after biopsy with no sign of recurrence.

Conclusion
Our case indicates that ERMS in adult can present with an indolent clinical process and low proliferating activity. Diagnosis can be challenging in this scenario. Chromosomal microarray is a useful tool to help confirm the diagnosis.
A Health Equity Study on Access by Ethnicity to Fecal Immunochemical Testing for Colorectal Cancer Screening at a Veteran Affairs Medical Center
Authors: Petersen J M , Jhala D 
Published: November 2022

Abstract

Introduction/Objective
It has been documented in the literature that significant ethnic and racial disparities in access to healthcare exist. Additionally, it has also been shown that these disparities can be corrected. Integrated health care systems such as the Veterans’ Administration health care system have previously been demonstrated to lead to more equitable care delivery and improved outcomes with lower racial and ethnic differences in access to care. Standard of care guidelines issued by the U.S. Preventive Services Task Force (USPSTF) exist recommending screening for colorectal cancer in adults, of which one of the screening methods involves the convenient fecal immunochemical test (FIT). FIT is a noninvasive simple screening test compared to alternatives such as colonoscopy. Given FIT’s benefits, the authors explored the accessibility by ethnicity for this important test at a Veteran Affairs Medical Center (VAMC).

Methods/Case Report
A search of all FIT testing performed at a regional VAMC from 10/1/2018 to 6/4/2022 was performed to determine the patient demographics including age, gender, and ethnicity. The ethnic distribution of all tested patients was compared to the local census population demographics of the county (Philadelphia) in which the VAMC is located (updated July 1, 2021).

Results (if a Case Study enter NA)
There were a total of 10,110 FIT tests conducted during the study period. From these 10,110 FIT tests, the ethnic composition of the test population is as follows: 5,164 or 51% (5,164/10,110) were African American, 4,389 or 43% (4,389/10,110) were Caucasian American, 65 or 0.6% (65/10,110) were Asian American, 48 or 0.5% were American Indian or Alaska Native American, 111 or 1% (111/10,110) were Native Hawaiian or other Pacific Islander Americans, and 333 or 3.2% (333/10,110) were unknown or declined to state in the medical record. Per the local county census, 44.8% of the local population was Caucasian American and 43.6% were African American.

Conclusion
The VAMC, being an integrated health care system, provides equitable access to FIT to screen for colorectal cancer.
Top Accurate Cell Detection and Segmentation Using A Pen, Agile Digital Image Processing for Deep Learning Models
Authors: Elsafty A M , Ahmed Y M 
Published: November 2022

Abstract

Introduction/Objective
The Hematopathology labs suffer from insufficient productivity, profitability and increased liability. The predicted shortage in the Hematopathologists in the USA is 25% by 2040. Medical errors and results variability due to fatigue and stress could also increase. At least 99% specificity or 99% sensitivity is required in automated visual review of peripheral blood and bone marrow smears to be generalizable and work-fit. Fortunately, the growing digital Hematopathology scanners market besides the vastly developed artificial intelligence (AI) and machine deep learning (DL) technologies could make this realized soon. The AI/DL production cycle includes (1) images collection, (2) image processing/data science, (3) technology, (4) engineering, (5) testing and validation.

Methods/Case Report
Integration with a Hematopathology lab using digital scanners and/or integrated cameras on microscopes is the mean for whole slide images (WSI) collection. Image processing refers to AI/DL spoon-feeding with accurate, diverse and highly-dissimilar materials for learning. This requires providing hundreds of thousands examples of (a) WSI context correction for stain and resolution normalization, (b) cellular dimensions on the WSI patches for detection, (c) cellular segmentation/boundaries determination for counting (d) cellular labels for classification. Comparing with the confirmatory testing results including flow cytometry and immunohistochemistry is essential in both image processing and validation. Currently, image processing resembles 80-90% of the AI/DL cycle/pipeline which may take years of hectic work. Our proposed developed tool enables the Hematopathologists to use pens and draw on the boundaries of each cell in a field/patch. 3-15 seconds are needed for each cell. The required ground truth/masks for segmentation and dimensions for detection are generated in real-time with no need for data scientists.

Results (if a Case Study enter NA)
NA

Conclusion
Similar to the automated agile development-operation loop concept (DevOps), enabling the Hematopathologists to perform image processing directly will reduce the production cycles from years to weeks. No technology can perform qualitatively better than the human eyes, the proposed pen-based cell detection and segmentation tool results in 10-50 fold increase in quality and quantity. Promisingly, there is a trend among the AI/DL platforms companies to automate the AI/DL coding.
Concurrent JAK2 V617F Acute Myeloid Leukemia (AML) and Leukemic non-nodal Mantle Cell Lymphoma (LN-MCL): Case study
Authors: Ohan H , Inamdar K , Shen Y , liu W , Gomez-Gelvez J C , Ghosh S 
Published: November 2022

Abstract

Introduction/Objective
We report a unique case of concurrently occurring Acute Myeloid Leukemia (AML) and Leukemic non-nodal Mantle Cell Lymphoma (LN-MCL) in an 86-year-old male. To the best of our knowledge, this is the first report of AML occurring in the background of LN-MCL, with no known history of any malignancy or chemotherapy.

Methods/Case Report
An 86-year old Caucasian male with unremarkable past medical history presented with pancytopenia, fatigue and generalized weakness. Abdominal CT scan was negative for lymphadenopathy or hepatosplenomegaly. Peripheral blood showed 2% blasts with atypical lymphocytes 89%. Bone marrow aspirate showed 30% myeloblasts expressing CD34, CD117, CD13, CD33, HLA-DR and CD56 (dim) by flow cytometry (FC). Lymphocytes accounted for 40% of bone marrow cellularity. FC identified a population of CD5+ kappa restricted clonal B cells 2%, consistent with a concurrent CD5+ B-lymphoproliferative disorder/lymphoma. The bone marrow biopsy was inadequate for further evaluation of the B- cell lymphoma. Chromosomal analysis revealed a normal male karyotype. FISH analysis was positive for t(11:14) CCND1::IGH rearrangement (in 3.5% of interphase cells) supporting involvement by MCL. Myeloid panel next generation sequencing (51 genes) was positive for JAK2 V617F (VAF, 38%) and ASXL1 P920Tfs*4 (VAF, 22%) variants

Results (if a Case Study enter NA)
NA

Conclusion
Concurrent presence of LN-MCL and AML as seen in our patient in the absence of prior history of malignancy or chemotherapy is rare. Presence of JAK2V617F mutation in de-novo AML is extremely rare (&lt;5%). There is no prior history of myeloproliferative neoplasm (MPN) or CBC data to suggest that this may have progressed from an MPN. While the absence of lymphadenopathy suggests that the CD5+ B-LPD likely represents LN-MCL, it is also likely that the CD5+, IgH/CCND1 rearranged B-cells may represent prior undetected circulating cells without overt LN-MCL development, similar to those reported in otherwise healthy individuals. It is unclear but tempting to speculate that the two co-occurring hematologic malignancies may have a common cell of origin
The Bone Marrow Clinic – The Concept of “Interventional Pathologist”
Authors: ASIF M , Ehsan A , Herschap B , Villa C , Sanchez-Salazar A 
Published: November 2022

Abstract

Introduction/Objective
Bone marrow biopsy (BMBx) is routinely performed and plays an integral role in diagnosing hematologic malignancies. BMBx are performed by mid-level practitioners/hematologists/oncologists (ON), interventional radiologists (IR), and uncommonly by hematopathologists (HP) in hospitals (HO), surgery centers (SC), physician offices (PO). We evaluated: a) cost savings, b) time period of biopsy, and c) impact on diagnosis when HP performed BMBx compared to other providers.

Methods/Case Report
A cross-sectional study was performed. A total of 4640 BMBx at different facilities by various providers were selected. Consent was obtained from patients. 50% (2320) performed by ON; 20% (928) by IR; 30% (1392) by HP. BMBx were performed at following facilities: 30% (1392) - HO; 20% (928) - SC; 50% (2320) - PO.

Results (if a Case Study enter NA)
Patients were divided into two sets based on BMBx performed by providers (Set A - ON, IR, HP) and at facilities (Set B - HO, SC, PO). The average cost for BMBx performed by ON and HP in the PO setting was $175; IR in SC was $1200; and performed at HO irrespective of providers was $3000. In outpatient settings, where the majority of BMBx were performed, the average time to perform BMBx by ON and IR was 10 days vs HP was two days. No difference was noted in HO settings among providers. Lastly, diagnostic samples obtained were superior by HP when compared to ON and IR (degeneration/crushing of cells, hemodilution, and lack of touch imprints).

Conclusion
The pathology curriculum should include evaluation and training for BMBx and other invasive techniques; as this study demonstrates cost savings, improved time to obtain BMBx, and superior quality for analysis when performed by HP. Thus, we emphasized the term “Interventional Pathologists” to describe pathologists directly impacting patient care in the field.
Acute Leukemias of Ambiguous Lineage presenting in Extramedullary Location – Unusual and Challenging Diagnoses: A Report of Two Cases
Authors: Pandiri M , Sallagonda A , Johari V , Freeman J 
Published: November 2022

Abstract

Introduction/Objective
Acute leukemias of ambiguous lineage are uncommon, accounting for &lt;1% of all leukemias, and extramedullary presentations of these leukemias are rare.

Methods/Case Report
We report two cases of acute leukemia of ambiguous lineage presenting in extramedullary sites. Case 1 is a 41-year-old female who presented with right cervical lymphadenopathy and fatigue. Laboratory and imaging studies showed leukopenia, anemia, and abnormal cervical, supraclavicular, axillary, mediastinal, and abdominal pelvic lymphadenopathy. Biopsy of the axillary lymph node revealed sheets of morphologic blasts. Flow cytometry showed the blasts were of mixed phenotype, with T-cell differentiation supported by CD3 and TdT, and myeloid subpopulation supported by myeloperoxidase and lysozyme. Both these populations were negative for CD10, CD20, CD4, CD8, CD34, CD138, CD1a, CD79a. The morphology and immunophenote establish the diagnosis of T/myeloid mixed-phenotype acute leukemia, not otherwise specified. Case 2 is a 65-year-old female who presented with bilateral lower extremity weakness. Multiple lytic lesions involving the thoracic and cervical spine were detected by imaging. Biopsy of a T12 vertebral lesion revealed sheets of large malignant cells. Extensive immunohistochemical workup revealed positivity for CD45 (weak), CD4, and CD43, supporting a diagnosis of hematopoietic neoplasm of likely hematopoietic origin. Subsequent evaluation eventually led to discovery of chronic myeloid leukemia in blast phase with undifferentiated blasts, BCR-ABL1 positive, originally presenting as extramedullary acute leukemia with undifferentiated blasts.

Results (if a Case Study enter NA)
NA.

Conclusion
These cases highlight the challenges of diagnosing peripheral solid tumors of unknown origin. Extramedullary presentation of acute leukemia of ambiguous lineage are particularly challenging and, although rare, include phenotypes ranging from mixed phenotype to undifferentiated types.
A Unusual Case of Classic Hodgkin Lymphoma (cHL) with Aberrant T-Antigens Expression
Authors: Gaddam S , Oyedeji O , liu W , Gomez-Gelvez J C , Inamdar K , Carey J , Shen Y 
Published: November 2022

Abstract

Introduction/Objective
T-cell-associated antigens (TCA) are rarely expressed by Hodgkin/Reed-Sternberg (HRS) cells of classical Hodgkin lymphoma (cHL) and is associated with uncertain clinical significance.

Methods/Case Report
We present a very recent case of a 68 year-old female with no significant past medical history presented with a large right groin mass for 1 month. She denied any fever, night sweats, fatigue or weight loss. CT abdomen/pelvis showed inguinal/pelvic lymphadenopathy. Resection showed effaced nodal architecture with a vague nodular appearance and with large, atypical nucleolated cells in a background of small, mature lymphocytes and histiocytes. Eosinophils are conspicuously absent in the background. The large cells were polylobated lymphocyte and histiocyte rich (L & H) like, classic HRS cells as well as multinucleated in appearance. The morphologic features overlapped between Classic Hodgkin Lymphoma, and Nodular Lymphocyte Predominant Hodgkin Lymphoma. Given the immunohistochemical (IHC) features of the neoplastic cells [CD45 negative, PAX5+ (weak), CD30+ (strong), CD15+ (majority) and MUM1 +] the diagnosis was most compatible with CHL. Interestingly, a subset of the Hodgkin cells (10-20%) aberrantly expressed a number of T-cell markers (CD2, CD3, CD4, and CD8). However, the background smaller T-cells did not show cytologic atypia or aberrancies of T-cell antigen markers. The large cells were negative for CD43 and ALK1. TCR gamma gene rearrangement was also negative for clonal T-lymphocytes, thus excluding the possibility of peripheral T-cell lymphoma with Hodgkin-like cells. Based on the morphology and IHC profile, this case proves to be CHL with multiple TCA expression including CD2, CD3, CD4 and CD8. She was planned for chemotherapy. Four months after the initial diagnosis and after completion of 2 cycles of chemotherapy, her PET CT scan showed improvement with right inguinal adenopathy being smaller in size and decreased avidity, indicating a response to treatment. She is due for 2 more cycles. Till todate she is doing well with no further symptoms.

Results (if a Case Study enter NA)
NA.

Conclusion
So far reported cases of classic Hodgkin lymphoma (CHL) with aberrant T-cell antigen (TCA) expression were associated with decreased event-free survival and overall survival when compared with TCA-negative CHLs. Our finding contributes to the literature and improves our knowledge of the disease.