bluuebunny/crossref_metadata_2025_split huggingface dataset:
Novel Approach for Detection of BRAF and KRAS Mutations Using ARMS (amplification refractory mutation system) Primers for Colon Cancer Therapeutic Response Prediction
Authors: Moon J J 
Published: October 2024

Abstract

Introduction/Objective
KRAS and BRAF V600E mutations are confirmed predictive biomarkers for anti-EGFR monoclonal antibody therapy response and prognosis for colorectal cancer and often considered mutually exclusive with few exceptions (0.05% of mCRC cases). We have developed a multiplex PCR assay utilizing ARMS (amplification refractory mutation system) Primers and Probes for screening and further testing of BRAF mutation status in a 2 step process.

Methods/Case Report
The Multiplex PCR Assay or BRAF/KRAS mutation was designed as a 5 color assay. Primers and Probes consisted of Wild Type Kras and wild and mutant (V600E/V600K) type BRAF primers and probes. For specimen, Positive and negative control standards made of engineered positive control plasmids for wild type KRAS & BRAF and mutant type V600E & V600K BRAF as well as internal control of bet actin and 2 Patient samples with known BRAF V600E mutant status were run. Mutant type V600E & V600K BRAF were mixed with wild type V600 controls in different ratios as well. Results were interpreted as BRAF wild KRAS wild/ BRAF wild KRAS mutant/ BRAF V600E KRAS wild/BRAF V600K KRAS wild type and NGS was recommended in cases of concurrent BRAF and KRAS mutations.

Results (if a Case Study enter NA)
Positive/negative/internal control standards for wild type KRAS & BRAF and mutant type V600E & V600K BRAF showed expected results in both CFX 96 and ABI 7500 runs in triplicates. Graphs were able to determine separate Ct values and sigmoidal amplification plots that readily differentiated KRAS wild/BRAF wild/ BRAF V600E types. Mutant type V600E & V600K BRAF that were mixed with wild type V600 controls in different ratios all showed expected results and were able to differentiate between wild and mutant types with accuracy. Also, the 2 patient samples with known (Sanger sequencing-diagnosed) V600E mutation status showed positive Ct values for KRAs wild and V600E probes and negative CT values for V600 wild/V600K probes. No invalid runs or unexpected control results were observed.

Conclusion
The ARMS BRAF/KRAS multiplex test is a efficient, accurate 2 step assay. In the patients and positive and negative controls prepared, it was able to reliably diagnose KRAS and BRAF mutation status in a matter of 4 hours running time. Given the fact that this is a cost effective assay that can utilize most commonly used Real time PCR machines this test may be clinically implemented if larger clinical trials utilizing tissue samples from a larger number of colon cancer patients are conducted.
Molecular Testing Prevents Overdiagnosis of Epithelioid Hemangioma
Authors: Gabutan E , Salahi N , Alejandro N , Gupta R , Mendoza R P , Li Z 
Published: October 2024

Abstract

Introduction/Objective
Epithelioid hemangiomas (EH) are mostly solitary benign vascular tumors commonly involving the dermal and subcutaneous areas of the head and neck. However, reports of multifocality are increasing, specially in same anatomic region. Some reported cases of EH show morphologic features that may mimic malignant vascular tumors such as hemangioendotheliomas or angiosarcomas. However, there are no reported overlaps in the molecular characteristics of these tumors. We describe a multifocal EH with atypical features, suspicious for angiosarcoma, which needed molecular testing to resolve the diagnosis.

Methods/Case Report
The patient is a previously healthy 42-year-old male with a 5-month history of multiple growing painless penile nodules. Biopsy of one of the nodules was done. Histologic examination showed multifocal dermal- based ill-circumscribed nodules with interspersed inflammatory infiltrates and focal areas of necrosis. Tumor periphery shows vasoformative growth with intraluminal and extravasated red blood cells. Neoplastic cells were large and ovoid with abundant eosinophilic cytoplasm, large vesicular pleomorphic nuclei and prominent nucleoli.
Immunohistochemical stains showed strong expression of ERG, FLI-1, and CD31 and negativity for AE1/AE3, CD34, HHV8 and EMA. The morphologic and immunohistochemical features of the specimen showed significant overlap of two primary differential diagnoses - epithelioid angiosarcoma and epithelioid hemangioma. Ultimately, molecular testing revealed ZFP36-FOSB fusion, confirming the diagnosis of EH.

Results (if a Case Study enter NA)
NA

Conclusion
Differentiating benign and malignant epithelioid vascular neoplasms can sometimes be challenging. There can be overlap in terms of architectural variety, presence of necrosis, vasoformation, inflammatory cell components and cytologic features, especially in EH with atypical features and epithelioid angiosarcoma (EA). Both of these tumors show positive immunoreactivity for CD31, CD34, FLI1 and ERG, and negativity for most keratins.
Currently, the most reliable way to distinguish each tumor is molecular testing, with EH having FOS/FOSB rearrangements and EA with MYC or FLT4 amplification. Benign and malignant epithelioid vascular tumors can be indistinguishable morphologically and immunohistochemically. Molecular tests can help differentiate these neoplasms to better tailor patient management.
Thyroid Lesion with a Novel Concurrent ETV6-NTRK3 Translocation and DICER1 Mutation
Authors: Gabutan E , Salahi N , Cilento J , Gupta R , Mendoza R P 
Published: October 2024

Abstract

Introduction/Objective
Understanding of the behavior of thyroid tumors expand as the basis of their classification gradually move from morphologic to molecular/genetic. The use of molecular methods in detecting mutations in fine needle aspiration (FNA) specimens further helped in tailoring patient management. Here, we describe a case of a thyroid lesion which was diagnosed with atypia of undetermined significance (AUS) on FNA and discovered to have an unreported concurrent mutation pattern.

Methods/Case Report
The patient is a 26 year-old female with long standing history of prominent anterior neck mass. New onset of neck pain prompted sonographic analysis which revealed a 1.1 cm hypoechoic left thyroid nodule with microcalcification. FNA was done, and was signed out as AUS which initiated molecular genetic testing. The lesion was found to have both ETV6/NTRK3 translocation and DICER1 p.P375R mutation. Existing literature on NTRK3 rearrangements in thyroid tumors confer a &gt;95% risk of malignancy. It is commonly associated with BRAF-negative papillary thyroid carcinomas (PTC) with both in BRAF-like behavior in terms of nodal metastases and extrathyroidal extension. On the other hand, there are no existing literature specifying the malignancy risk of the exact DICER1 mutation identified since it has been linked to follicular neoplasms in general. Furthermore, isolated DICER1 mutations in the thyroid showed RAS-like behavior. Subsequent resection of the thyroid revealed that the tumor is morphologically a PTC, with lymphovascular invasion.

Results (if a Case Study enter NA)
NA

Conclusion
Molecular testing in thyroid lesions with morphologically indeterminable features on FNA significantly aided in prognostication of patients and prediction of malignancy risk. In this case with a previously unreported combination of mutations, existing literature helped in describing the probable behavior of the patient’s tumor. Thus, the researchers emphasize the importance of databases of identified mutations in tumors and their associated characteristics such as The Cancer Genomic Atlas (TCGA) and The Catalogue of Somatic Mutations in Cancer (COSMIC).
DICER1 Mutations Enable Rare Tumor Formation
Authors: Bhuiyan T A , Velasquez-Zarate L 
Published: October 2024

Abstract

Introduction/Objective
DICER1 is a tumor suppressor gene that imparts a slight increase in tumor formation when mutated. The protein plays a role in processing miRNA that silences transcription. Germline mutations of DICER1 predispose to tumors in a known set of organs and rarely in other locations. However the presence of additional genetic aberrations further increases the likelihood of tumor formation. Acting as a compounding factor, DICER1 mutations can present a constantly shifting cancer phenotype of affected patients. Of particular interest here is the development of both Pineoblastoma and Malignant spindle cell sarcoma in a young patient. Sarcomas are estimated to make up only 10% of pediatric cancers and Pineal masses only 3%.

Methods/Case Report
This case involves an 8 year old male with a history of Pineoblastoma who originally presented with slowly worsening ataxia. A screening ultrasound on following visits identified an abdominal mass that was confirmed with computed tomography. Subsequent biopsies showed malignant spindle cells arranged in a herringbone pattern. Additionally these cells displayed high mitotic activity and hyperchromatic nuclei. Surprisingly, they also demonstrated extramedullary hematopoiesis. Multiple stains were performed however no significant conclusion could be made. The appearance of this tumor and its rarity prompted a request for a Complete Comprehensive Sarcoma Panel via Next Generation Sequencing. This confirmed the presence of pathologic BRAF and DICER1 genes. From that the diagnosis of DICER1 associated Malignant Spindle Cell Sarcoma was made. BRAF V600E is the most common genetic variant and is seen in multiple cancers but only seen in 1-3% of sarcomas.
Pathologic variants of the DICER1 gene exist on exons 13 and 25. The presence of these exon mutations in some way affect DICER1 protein function and compound the effects of the mutated BRAF gene. This situation is unique as such neoplasms are rarely found in the anterior abdominal wall and showcases the effects of DICER1 on rare tumor phenotypes.

Results (if a Case Study enter NA)
NA

Conclusion
Continuing research into both DICER1 protein pathways is essential for isolating a diagnosis and guiding treatment. It would seem screening images and genetic testing would benefit pediatric or even adult patients with common and rare cancers. Extra effort made toward this would not be outside the norm as personalized medicine is gradually becoming the standard for cancer treatment.
A Curious Case of Pancreatoblastoma in an Older Age Woman
Authors: Talreja S , Laury R , Kumar S 
Published: October 2024

Abstract

Introduction/Objective
Pancreatoblastoma is a malignant epithelial neoplasm of the pancreas and displays multiple lines of differentiation with acinar differentiation as the predominant pattern. The squamoid nests are considered a defining component of pancreatoblastoma. Pancreatoblastoma is seen most often in children, however, rare cases in adults have been described in the literature. In children, most pancreatoblastomas are indolent and curable, however, the prognosis is worse in adults due to the presence of frequent metastasis.

Methods/Case Report
We report an interesting case of pancreatoblastoma in a 65-year-old woman with no pertinent medical history who presented with abdominal discomfort. MRI abdomen showed an 11.3 cm mass with central necrosis within the head of the pancreas. Fine-needle aspiration (FNA) of the mass showed monotonous cells with neuroendocrine differentiation and FNA was signed out as a low-grade neuroendocrine tumor (NET). The patient underwent a Whipple resection for a presumed NET.
On gross examination, a 14 cm large solid, fleshy, lobulated, partially encapsulated mass was noted in the head of the pancreas. H&E slides on low power showed the tumor composed of highly cellular lobules separated by fibrous bands. Within the lobules, the neoplastic cells predominantly had an acinar differentiation with focal trabecular or solid areas. Dispersed within the tumor were squamoid nests composed of plump to spindle-shaped cells with abundant eosinophilic cytoplasm arranged in whorls. Immunohistochemical stains demonstrated squamoid nests being positive for CK5/6 and had a nuclear-staining pattern with beta-catenin. The remaining tumor was positive for trypsin, chymotrypsin, BCL-10, synaptophysin (focal), chromogranin (focal), and INSM-1 (patchy). On MSK-Impact (next- generation sequencing), a mutation in CTNNB1 was detected.

Results (if a Case Study enter NA)
NA

Conclusion
In adults, it is important to consider pancreatoblastoma in the differential diagnoses of solid pancreatic tumors while being cautious not to confuse it with neuroendocrine tumor or acinar cell carcinoma. The presence of squamoid nests is critical for its diagnosis. Making a diagnosis of pancreatoblastoma through FNA or pancreatic biopsy can be exceptionally challenging in cases lacking squamoid nests.
A fetus with a mass in the oral cavity: a rare case of large oral immature teratoma
Authors: Siddiqui H F , Anjum S 
Published: October 2024

Abstract

Introduction/Objective
Oral teratoma is a rare congenital neoplastic lesion composed of variable amounts of all three germ cell layers, comprising 2-9% of all teratomas. Teratomas are classified into subtypes depending upon the presence of immature components. Sacrococcygeal and head and neck regions are the most common sites, with slight female predominance. Mortality increases if diagnosed in the fetal or neonatal period.

Methods/Case Report
We report a case of male fetus diagnosed radiologically as ultrasound at 20 weeks of gestation revealed abnormal facial characteristics. A huge lump protruding from face measuring 10.8 x 6.7 cm was observed. Grossly a grey-white, multilobulated lesion was seen with cystic spaces originating from midline soft palate. Histologically an immature teratoma comprising bone, skin adnexae, glandular tissue and immature neuroepithelial tissue was identified. The case was distinguished as immature teratoma of the oropharynx.

Results (if a Case Study enter NA)
NA

Conclusion
Prenatal diagnosis with modalities including ultrasound, MRI, alpha fetoprotein concentrations, fetoscopy and fetal karyotyping is possible in early pregnancy which can aid in risk stratification and planning therapeutic interventions. Delayed diagnosis and treatment increase the likelihood of malignant transformation. Intrapartum intubation and resection of the tumor at the time of the cesarean section has shown better outcomes. However, despite all efforts, survival rates are low.
Calretinin Staining Pattern is Variable in Hirschsprung Disease Occurring in Patients with Down Syndrome
Authors: Prasad V , Conces M , Zinnen A 
Published: October 2024

Abstract

Introduction/Objective
Hirschsprung disease (HD), a congenital absence of enteric ganglion cells, affects 2-10% of patients with Down syndrome (DS). Submucosal nerve hypertrophy (SNH) and abnormal calretinin immunohistochemistry (IHC) support a diagnosis of HD, but the concordance of these findings can be variable in DS. Recognizing differences in HD occuring in DS can provide insight into the disease and help to improve outcomes and reduce delays in diagnosis for these patients. We sought to describe the histologic and calretinin staining patterns in HD occurring in patients with DS.

Methods/Case Report
From 2017-2023, 22 rectal biopsies from 20 patients with DS were retrospectively collected and reviewed. Subsequent pull-through (PT) resections were evaluated from 8 patients. Biopsies were evaluated for ganglion cells and SNH. Calretinin IHC was qualitatively evaluated for intensity (strong, weak) and density (many, partial, rare). Quantitative analysis used a calculation of the percent area above threshold (%AAT) function of the NIH ImageJ software version 2.1.0. Representative areas of the PT resections were also evaluated by ImageJ %AAT analysis.

Results (if a Case Study enter NA)
HD biopsies (12/22, 54.5%) were from male patients (age 3 days-6 weeks) and showed SNH in 11/12 (91.7%) with a mean nerve diameter of 57.3 microns (range 25-89 microns). Ganglionated biopsies (10/22, 45.5%) were collected from patients 3 days to 12 years old (M:F ratio 1:1.5) and showed SNH in 6/10 (60%) with a mean nerve diameter of 44.4 microns (range 10-70 microns). Strong normal calretinin staining was only seen in ganglionated biopsies (7/10 non-HD versus 0/12 HD). Negative calretinin staining was only seen in HD (0/10 non-HD vs 7/12 HD). Abnormal staining was seen in both non-HD (3/10, 30%) and HD (5/12, 41.7%) as partial strong positivity and rare weak positivity, respectively. ImageJ %AAT quantitative analysis revealed an average of 1.71 in biopsies with strong calretinin expression, 0.130 with weak staining, and 0.033 with negative staining. Evaluation of 8 PT resections (mean length of aganglionosis 7.1 cm) showed a mean nerve diameter in the aganglionic segment of 88.3 microns, 49.6 microns in the TZ, and 32.7 microns in the ganglionated segment. ImageJ %AAT quantitative analysis of calretinin revealed a mean of 0.044 in the aganglionic area, 0.66 in the TZ, and 1.56 in the ganglionated segment.

Conclusion
Recognition of the variable calretinin patterns seen in rectal biopsies from patients with DS can assist in accurate and timely diagnosis of HD.
Tumefactive Pulmonary amyloidosis in an elderly male: A Diagnostic Dilemma
Authors: siddiqui F , Alam A , Muzaffar S , Qureshi P M 
Published: October 2024

Abstract

Introduction/Objective
Tumefactive pulmonary amyloidosis is a rare variant of pulmonary amyloidosis characterized by the extracellular deposition of abnormal protein fibrils in the lung parenchyma, forming tumor-like masses called amyloidomas. Although most cases are clinically silent, it may present with findings that mimic a wide range of respiratory conditions (eg. primary or metastatic malignant nodules, granulomatous disease, multiple pulmonary hamartomas etc), thereby necessitating a comprehensive and broad-based approach to differential diagnosis.

Methods/Case Report
We present a case of an 88-year-old male with a history of smoking and multiple comorbidities. He presented with numerous bilateral pulmonary nodules identified on a CT scan, concerning for malignancy. A biopsy from a left upper lobe lesion revealed necrotic tissue and was non-diagnostic. A PET scan to assess for metastatic disease was unremarkable, and demonstrated mild hypermetabolic activity, confined to the lungs, with standardized uptake values (SUV) ranging from 4.3 to a maximum SUV of 8.9. A subsequent right lung biopsy was positive for amyloid, confirmed by Congo red staining. A Mass spectrometry analysis further identified the amyloid as AL type. Serum, and urine protein electrophoresis with immunofixation were negative for M protein and the serum free light chain assay was normal as well. Significantly, the bone marrow biopsy also yielded normal results, and the patient was diagnosed with a localized form of AL amyloidosis.

Results (if a Case Study enter NA)
NA

Conclusion
This case highlights how tumefactive pulmonary amyloidosis poses a diagnostic challenge due to its rarity and resemblance to malignancy on imaging. Careful histopathological examination, including immunohistochemical stains and amyloid typing, was pivotal in establishing the correct diagnosis and underscores the essential role of pathology and laboratory medicine in differentiating rare pulmonary conditions, along with the need for a multidisciplinary approach in complex diagnostic scenarios.
The Potential Health Risks of Catha edulis Forsk (Khat) Consumption on Some Vital Organs
Authors: Abdelmonem M , Abo-Zaid M A , Alfattah M A , Ismail A H , El-Agamy S A , El-Azab K , Amin A H , Wasim H , Abdelmageed M , Saleh Abdelfattah M 
Published: October 2024

Abstract

Introduction/Objective
Introduction: Catha edulis Forsk (Khat) leaves are widely chewed by adults in the Arabian Peninsula and the Horn of Africa for their mild stimulating properties.

Objectives
To investigate the impact of an aqueous extract of Catha edulis Forsk leaves on the proper functioning of vital organs.

Methods/Case Report
Methods: Materials and methods: Twenty-five female albino rats were divided into two groups: a control group and a treated group which received a daily gavage of 1 ml of aqueous Khat extract with a concentration of 700 mg/kg body weight for four weeks. The effects of this treatment on selected organs, including the brain, hippocampus, heart, and ovaries, were assessed using various measurements and analyses.

Results (if a Case Study enter NA)
Results: Results: The antioxidant evaluation showed a significant increase in MDA levels in the khat group and a significant decrease in GSH, SOD, and CAT levels compared to the control group. There was a significant decrease in IL-4 and a significant increase in TNF-α and TGF-β1 compared to the control group. In contrast, the cardiac enzymes; Troponin, CK, CPK, and GOT showed a significant increase compared to the control group. The results of the hormonal assay indicated a significant increase in LH, FSH, and testosterone levels, along with a significant decrease in estrogen in the khat group compared to the control group. Furthermore, the histological investigations revealed significant changes in tissue architecture in the studied organs. In the heart, the treated group exhibited an intact, thick pericardium, along with markedly apoptotic cardiac muscle fibers and others with pyknotic nuclei and mildly congested blood vessels and capillaries. The examination of brain tissues in the treated group showed thick meninges with mild inflammatory infiltrate, marked astrogliosis with degenerated neurons in the cerebral cortex, inflammatory infiltrate with abscess formation and mildly congested blood vessels and eosinophilic plaque-like area in the deep cortex, and scattered degenerated neurons and some neurons with nuclear vacuoles and average glial cells in the white matter. In the ovaries, sections showed primary, secondary, and antral follicles, scattered cystically dilated follicles with atrophied lining, and multiple corpora lutea in the edematous stroma with scattered apoptotic stromal cells.

Conclusion
Based on these findings, long-term use of khat as a chewing material may harm vital organs.