-
Animals : An Open Access Journal From... Jun 2024Primary hyperthyroidism is a rarely diagnosed endocrinopathy in equids and there have been no previous reports of structural and functional cardiac changes associated...
Primary hyperthyroidism is a rarely diagnosed endocrinopathy in equids and there have been no previous reports of structural and functional cardiac changes associated with hyperthyroidism in these species. This case report investigates a 20-year-old mule gelding that presented for a three-month history of thin body condition despite polyphagia, with a heart murmur and elevated free and total thyroid hormone concentrations. On presentation, physical exam revealed a body condition score of two out of nine, persistent tachycardia, pansystolic heart murmur and firm bilateral ventral proximal cervical masses. Bloodwork confirmed markedly elevated free T4, total T4 and T3 concentrations. Echocardiogram demonstrated left ventricular concentric hypertrophy with increased ventricular and atrial systolic function. Bilateral thyroidectomy was performed under standing sedation without complications. Histopathology demonstrated adenocarcinoma of the left thyroid gland and multiple adenomas with osseous metaplasia within the right thyroid. The mule was supplemented with levothyroxine sodium two weeks post-op after a thyroid panel demonstrated undetectable concentrations. Polyphagia resolved following surgery and the mule began gaining weight. Echocardiographic changes improved but did not resolve at two years post-operative. Continued bi-annual follow up and monitoring of thyroid levels was recommended. This case represents the first documentation of hemodynamically relevant cardiac remodeling in an equid associated with primary hyperthyroidism.
PubMed: 38891707
DOI: 10.3390/ani14111660 -
Cells May 2024The dysregulation of gene expression is one of the key molecular features of colorectal cancer (CRC) development. This study aimed to investigate whether such...
BACKGROUND
The dysregulation of gene expression is one of the key molecular features of colorectal cancer (CRC) development. This study aimed to investigate whether such dysregulation is reflected in rectal swab specimens of CRC patients and to evaluate its potential as a non-invasive approach for screening.
METHODS
We compared the expression level of 14 CRC-associated genes in tumor and adjacent non-tumor tissue of CRC patients and examined the correlation of their levels in tissue with paired rectal swab specimens. The level of these 14 genes in rectal swab specimens was compared among patients with CRC or polyp and control subjects, and the diagnostic potential of each dysregulated gene and the gene panel were evaluated.
RESULTS
The expression of , , , , , , , , , and was significantly higher in CRC, and there was a significant correlation in the levels of most of them between the CRC and rectal swab specimens. In the training study, we showed that , , and levels were significantly higher in the rectal swab specimens of the CRC patients. Such result was confirmed in the validation study. A panel of these four genes was developed, and ROC analysis showed that this four-gene panel could identify CRC patients with an AUC value of 0.83 and identify overall polyp and precancerous adenoma patients with AUC values of 0.6522 and 0.7322, respectively. Finally, the predictive study showed that the four-gene panel demonstrated sensitivities of 63.6%, 76.9% and 88.9% in identifying overall polyp, precancerous adenoma and CRC patients, respectively, whereas the specificity for normal subjects was 72.2%.
CONCLUSION
The expression of CRC-associated genes in rectal swab specimens reflects the dysregulation status in colorectal tissue, and the four-gene panel is a potential non-invasive biomarker for early precancerous adenoma and CRC screening.
Topics: Humans; Early Detection of Cancer; Biomarkers, Tumor; Male; Colorectal Neoplasms; Female; Middle Aged; Rectum; Aged; Gene Expression Regulation, Neoplastic
PubMed: 38891062
DOI: 10.3390/cells13110930 -
Acta Neurochirurgica Jun 2024Invasion of the CS is one of the limiting factors for total resection for PitNet tumors with cure rates less than 30%. Extended approaches may be considered in selective...
BACKGROUND
Invasion of the CS is one of the limiting factors for total resection for PitNet tumors with cure rates less than 30%. Extended approaches may be considered in selective and well-studied cases of secreting adenomas.
METHOD
We describe the key steps of the endoscopic transcavernous approach for functional pituitary adenomas with a video illustration. The surgical anatomy is described along with the advantages and limitations of this approach.
CONCLUSION
A detailed knowledge of CS anatomy and familiarity with this surgical approach acquired in the laboratory is essential. Proper instrumentation is critical to decrease the risks of vascular injury.
Topics: Humans; Pituitary Neoplasms; Adenoma; Neuroendoscopy; Cavernous Sinus; Endoscopy; Neurosurgical Procedures
PubMed: 38890156
DOI: 10.1007/s00701-024-06168-x -
Clinical and Translational Medicine Jun 2024Sporadic parathyroid adenoma (PA) is the most common cause of hyperparathyroidism, yet the mechanisms involved in its pathogenesis remain incompletely understood.
BACKGROUND
Sporadic parathyroid adenoma (PA) is the most common cause of hyperparathyroidism, yet the mechanisms involved in its pathogenesis remain incompletely understood.
METHODS
Surgically removed PA samples, along with normal parathyroid gland (PG) tissues that were incidentally dissected during total thyroidectomy, were analysed using single-cell RNA-sequencing with the 10× Genomics Chromium Droplet platform and Cell Ranger software. Gene set variation analysis was conducted to characterise hallmark pathway gene signatures, and single-cell regulatory network inference and clustering were utilised to analyse transcription factor regulons. Immunohistochemistry and immunofluorescence were performed to validate cellular components of PA tissues. siRNA knockdown and gene overexpression, alongside quantitative polymerase chain reaction, Western blotting and cell proliferation assays, were conducted for functional investigations.
RESULTS
There was a pervasive increase in gene transcription in PA cells (PACs) compared with PG cells. This is associated with high expression of histone-lysine N-methyltransferase 2A (KMT2A). High KMT2A levels potentially contribute to promoting PAC proliferation through upregulation of the proto-oncogene CCND2, which is mediated by the transcription factors signal transducer and activator of transcription 3 (STAT3) and GATA binding protein 3 (GATA3). PA tissues are heavily infiltrated with myeloid cells, while fibroblasts, endothelial cells and macrophages in PA tissues are commonly enriched with proinflammatory gene signatures relative to their counterparts in PG tissues.
CONCLUSIONS
We revealed the previously underappreciated involvement of the KMT2A‒STAT3/GATA3‒CCND2 axis and chronic inflammation in the pathogenesis of PA. These findings underscore the therapeutic promise of KMT2A inhibition and anti-inflammatory strategies, highlighting the need for future investigations to translate these molecular insights into practical applications.
HIGHLIGHTS
Single-cell RNA-sequencing reveals a transcriptome catalogue comparing sporadic parathyroid adenomas (PAs) with normal parathyroid glands. PA cells show a pervasive increase in gene expression linked to KMT2A upregulation. KMT2A-mediated STAT3 and GATA3 upregulation is key to promoting PA cell proliferation via cyclin D2. PAs exhibit a proinflammatory microenvironment, suggesting a potential role of chronic inflammation in PA pathogenesis.
Topics: Humans; Parathyroid Neoplasms; Adenoma; Inflammation; Histone-Lysine N-Methyltransferase; Myeloid-Lymphoid Leukemia Protein; Proto-Oncogene Mas; Cell Proliferation
PubMed: 38888967
DOI: 10.1002/ctm2.1734 -
Frontiers in Oncology 2024Atypical Parathyroid Adenoma (APA) is a type of tumor that lies somewhere between parathyroid adenoma and parathyroid carcinoma. It often affects adults over the age of...
Atypical Parathyroid Adenoma (APA) is a type of tumor that lies somewhere between parathyroid adenoma and parathyroid carcinoma. It often affects adults over the age of 60, and the clinical symptoms are consistent with those of hyperparathyroidism. This condition has a low occurrence, and its ultrasonographic signs are strikingly similar to thyroid malignant tumors, making it easily misdiagnosed. As a result, a case of APA ultrasonography misdiagnosis admitted to our hospital was recorded in order to serve as a reference point for APA diagnosis.
PubMed: 38884084
DOI: 10.3389/fonc.2024.1375373 -
Clinical Case Reports Jun 2024Acute chest pain can be the first manifestation of multiple endocrine neoplasia type 1(MEN1)-associated thymic neuroendocrine neoplasms (NEN). Comprehensive treatment...
KEY CLINICAL MESSAGE
Acute chest pain can be the first manifestation of multiple endocrine neoplasia type 1(MEN1)-associated thymic neuroendocrine neoplasms (NEN). Comprehensive treatment may be an effective strategy for MEN1-associated NEN.
ABSTRACT
Multiple endocrine neoplasia type 1(MEN1)-associated thymic neuroendocrine neoplasms (NEN) is caused by the mutation of tumor suppressor gene. Patients with MEN1-associated NEN initially presenting with acute chest pain are very rare. In the manuscript, we reported a case of a 45-year-old man who developed MEN1-associated NEN with acute chest pain as initial symptom. Thoracoscopic thymotomy was performed and thymic NEN was successfully removed. Genetic test showed a germline mutation of gene in this patient. Immunohistochemical staining exhibited Syn(+), CgA(+), INSM1(+), CD56(+) and Ki67-positive cells (2%) in MEN1-associated NEN. Further evaluation unveiled MEN1-associated benign tumors including digestive NEN and pituitary gland adenoma. The 99mTc-HYNIC-TOC scintigraphy showed that focally increased radioactivity in the mid-upper abdomen. This patient was administered with 50Gy/25F of radiation dose to treat the postoperative lesions. Subsequently, sandostatin LAR (30 mg per week) was used as systemic therapy. He had no recurrence or metastasis for 6-month follow-up. Thus, acute chest pain can be the first manifestation of MEN1-associated NEN, and comprehensive treatment including surgery, radiation and systemic treatment may be an effective strategy for MEN1-associated NEN.
PubMed: 38883224
DOI: 10.1002/ccr3.9031 -
Cureus May 2024Oncocytes are frequently encountered in routine thyroidectomies. The distinction between oncocytic hyperplastic nodules and oncocytic adenomas (OAs) may be challenging....
Oncocytes are frequently encountered in routine thyroidectomies. The distinction between oncocytic hyperplastic nodules and oncocytic adenomas (OAs) may be challenging. Although both entities are benign, a precise diagnosis is essential. We present two cases of solitary oncocytic lesions carrying pathogenic mutations in the p53 and NRAS genes, respectively, leading to a histological diagnosis of oncocytic hyperplastic nodules. Additionally, similar oncocytic nodules from two cases of autoimmune thyroiditis did not show any significant findings on molecular analysis (next-generation sequencing, NGS). Hence, this brief investigative series study is of particular diagnostic interest because it prompts pathologists to use the term adenoma when a solitary oncocytic nodule is encountered, regardless of the established criteria for the diagnosis of adenoma. This viewpoint leads to the possible need for the reevaluation of the histological criteria of adenomas when it comes to oncocytic lesions in order to gain a common diagnostic approach and nomenclature among pathologists and overcome any controversies in such cases.
PubMed: 38882980
DOI: 10.7759/cureus.60361 -
F1000Research 2023Apocrine carcinoma is an extremely rare malignant cutaneous neoplasm that usually arises in areas with a high density of apocrine glands. Diagnosis can be challenging as...
Apocrine carcinoma is an extremely rare malignant cutaneous neoplasm that usually arises in areas with a high density of apocrine glands. Diagnosis can be challenging as tumours share histological and immunophenotypic characteristics with them. At first evaluation, the disease is often assumed to be benign. There have been approximately 100 reports of apocrine neoplasms in the literature. A 48-year-old male presented with a right axillary mass which increased in size over a period of 2 years. The patient was reported to have had ayurvedic therapy, but his swelling remained unchanged. Axillary lymph nodes were palpable. USG axilla suggested a well-defined fungating solid isoechoic lesion. USG neck did not reveal any abnormality. The mass was surgically excised as a whole by removing the overlying skin with margins and lymph node excision. The patient was diagnosed with primary apocrine carcinoma after surgical excision. The differentials include adenocarcinoma of breast and prostate and apocrine adenoma. There are no established standards for the care of this form of carcinoma due to its rarity and the absence of clinical studies. A literature evaluation and further reporting will aid in developing diagnostic standards and the most efficient treatment options.
Topics: Humans; Male; Middle Aged; Apocrine Glands; Sweat Gland Neoplasms; Skin Neoplasms; Diagnosis, Differential; Carcinoma
PubMed: 38882714
DOI: 10.12688/f1000research.135154.3 -
Ear, Nose, & Throat Journal Jun 2024Canalicular adenoma (CA) is a rare benign tumor of the salivary glands, predominantly affecting elderly females, with a strong predilection for the upper lip. While CA...
Canalicular adenoma (CA) is a rare benign tumor of the salivary glands, predominantly affecting elderly females, with a strong predilection for the upper lip. While CA commonly arises in the minor salivary glands, its occurrence in the parotid gland is exceptionally rare. In this report, we present a unique case of CA in the parotid gland, adding to the scant literature with only 8 documented instances. The patient, a 57-year-old Asian male, presented with a painless swelling in the left parotid gland that had been persisting for 8 years. Clinical examination and imaging studies identified a lobulated mass, prompting surgical intervention. The patient underwent a superficial parotidectomy, and pathological examination of the excised tissue confirmed the diagnosis of CA, with no signs of malignancy. This case illustrates the diagnostic and management challenges associated with CA, particularly given its rare presentation in the parotid gland. Accurate diagnosis is reliant on surgical biopsy, and careful surgical planning is imperative, especially considering the proximity of the facial nerve. Our case underscores the need for heightened awareness of CA's unique presentations, particularly within the Asian population. Given the potential for recurrence, long-term follow-up is essential. Further research is needed to elucidate the biological behavior of CA and to refine management strategies for optimal patient outcomes.
PubMed: 38881446
DOI: 10.1177/01455613241262652 -
Zhongguo Fei Ai Za Zhi = Chinese... May 2024Malignant pleural mesothelioma (MPM) is a rare cancer with high malignancy and aggressiveness on the pleural, caused by the following risk factors including asbestos... (Review)
Review
Malignant pleural mesothelioma (MPM) is a rare cancer with high malignancy and aggressiveness on the pleural, caused by the following risk factors including asbestos inhalation, genetic factors, and genetic mutation. The present chemotherapy, antiangiogenic therapy, and immunotherapy methods are ineffective and the survival time of patients is very short. There is an urgent need to find potential therapeutic targets for MPM. At present, it has been found the following types of targets: gene mutation targets such as BRCA associated protein 1 (BAP1) and cyclin-dependent kinase 2A (CDKN2A); epigenetic targets such as lysine (K)-specific demethylase 4A (KDM4A) and lysine-specific demethylase 1 (LSD1), and signal protein targets such as glucose-regulated protein 78 (GRP78) and signal transducer and activator of transcription 3 (STAT3). So far, available clinical trials include phase II clinical trials of histone methyltransferase inhibitor Tazemetostat, poly (ADP-ribose) polymerase (PARP) inhibitor Rucaparib and cyclin-dependent kinases 4 and 6 (CDK4/6) inhibitor Abemaciclib, as well as phase I clinical trials of mesothelin-targeting chimeric antigen receptor T-cell immunotherapy (CAR-T) cell injection in the thoracic cavity and TEA domain family member (TEAD) inhibitor VT3989 and IK-930, and the results of these trials have showed certain clinical efficacy. .
Topics: Humans; Mesothelioma, Malignant; Mesothelioma; Lung Neoplasms; Molecular Targeted Therapy; Pleural Neoplasms; Animals; Endoplasmic Reticulum Chaperone BiP
PubMed: 38880927
DOI: 10.3779/j.issn.1009-3419.2024.102.18