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Investigative Ophthalmology & Visual... Apr 2024The lacrimal gland (LG) is the main organ responsible for tear secretion and an important pathogenic site for dry eye disease (DED). This study aimed to comprehensively...
PURPOSE
The lacrimal gland (LG) is the main organ responsible for tear secretion and an important pathogenic site for dry eye disease (DED). This study aimed to comprehensively characterize LG cellular heterogeneity under normal and DED conditions using single-nucleus RNA sequencing (snRNA-seq).
METHODS
Single LG nuclei isolated from mice with or without DED induced by scopolamine (SCOP)/desiccating stress (DS) were subjected to snRNA-seq using the 10x Genomics platform. These cells were clustered and annotated using the t-distributed stochastic neighbor embedding (t-SNE) method and unbiased computational informatic analysis. Cluster identification and functional analysis were performed based on marker gene expression and bioinformatic data mining.
RESULTS
The snRNA-seq analysis of 30,351 nuclei identified eight major cell types, with acinar cells (∼72.6%) being the most abundant cell type in the LG. Subclustering analysis revealed that the LG mainly contained two acinar cell subtypes, two ductal cell subclusters, three myoepithelial cell (MECs) subtypes, and four immunocyte subclusters. In the SCOP-induced DED model, three major LG parenchymal cell types were significantly altered, characterized by a reduced proportion of acinar cells with a lowered secretion potential and an augmented proportion of ductal cells and MECs. LG immunocytes in DED scenarios showed an intensified inflammatory response and dysregulated intercellular communication with three major LG parenchymal cells.
CONCLUSIONS
Overall, this study offers a systemic single-nucleus transcriptomic profile of LGs in both normal and DED conditions and an atlas of the complicated interactions of immunocytes with major LG parenchymal cells. The findings also facilitate understanding the pathogenesis of DED.
Topics: Animals; Dry Eye Syndromes; Mice; Scopolamine; Lacrimal Apparatus; Disease Models, Animal; Mice, Inbred C57BL; Female; Cell Nucleus; Tears; Epithelial Cells
PubMed: 38687491
DOI: 10.1167/iovs.65.4.46 -
International Journal of Gynecological... Apr 2024Human papillomavirus (HPV)-associated multiphenotypic sinonasal carcinoma is a rare and recently described epithelial neoplasm exhibiting myoepithelial differentiation...
Human papillomavirus (HPV)-associated multiphenotypic sinonasal carcinoma is a rare and recently described epithelial neoplasm exhibiting myoepithelial differentiation and morphological overlap with salivary gland neoplasms, especially adenoid cystic carcinoma; it is commonly associated with HPV, especially type 33. It has mainly been reported in the nasal cavity and paranasal sinuses with a single case reported in the breast. Herein, we report the first vulval example in a 47-year-old patient who presented with a large craggy mass in the region of the Bartholin gland. The histologic features were of a high-grade carcinoma composed of basaloid cells arranged in sheets and nests, with occasional ductal formations, surrounded by densely hyalinised basement membrane-type material. There was diffuse block-type immunoreactivity with p16 and HPV genotyping revealed high-risk HPV type 16. In reporting this case, we highlight the propensity for "salivary gland-type" neoplasms to arise in the vulva, especially in the Bartholin gland, and stress that pathologists should consider salivary-type neoplasms when faced with a morphologically unusual vulval tumor.
PubMed: 38661560
DOI: 10.1097/PGP.0000000000001034 -
The Journal of Veterinary Medical... Jun 2024We describe here a case of canine mammary benign mixed tumor with sebaceous metaplasia in the right fifth mammary gland of an eight-year-old, intact female Poodle dog....
We describe here a case of canine mammary benign mixed tumor with sebaceous metaplasia in the right fifth mammary gland of an eight-year-old, intact female Poodle dog. Grossly, the mass was firm with off-white, poorly lobulated cut surfaces. Histologically, the luminal epithelial cells and myoepithelial cells proliferated with cartilage formation and focal squamous metaplasia. Moreover, a large number of nests of various sizes, which were filled with foamy cells in the center and associated with basaloid reserve-like cells in the periphery, showed sebaceous gland-like structures. Immunohistochemically, myoepithelial cells and reserve-like cells in the metaplastic sebaceous gland-like structures were CK14, α-smooth muscle actin (α-SMA) and p63 positive, suggesting a possibility that these two components may have a common cell of origin.
Topics: Animals; Dogs; Female; Dog Diseases; Mammary Neoplasms, Animal; Sebaceous Glands; Metaplasia
PubMed: 38644184
DOI: 10.1292/jvms.23-0506 -
Cureus Mar 2024Myoepithelioma is an uncommon benign tumor of the orofacial region arising from the salivary glands. These tumors are composed of specifically myoepithelial cells...
Myoepithelioma is an uncommon benign tumor of the orofacial region arising from the salivary glands. These tumors are composed of specifically myoepithelial cells lacking ductal differentiation and were initially considered as a type of pleomorphic adenoma. Though they commonly arise from the parotid gland, there are a few cases that emerge from the minor salivary glands of the palate and oral cavity. Myoepitheliomas resemble many other tumors arising from the palate including pleomorphic adenoma. This report depicts a case of myoepithelioma of the minor salivary gland of the palate in a 23-year-old patient and the successful management of the lesion.
PubMed: 38629005
DOI: 10.7759/cureus.56305 -
Iranian Journal of Medical Sciences Mar 2024Human papillomavirus (HPV)-related multi phenotypic sinonasal carcinoma (HMSC) is a recently described tumor subtype with an unknown prognosis, often misdiagnosed with...
BACKGROUND
Human papillomavirus (HPV)-related multi phenotypic sinonasal carcinoma (HMSC) is a recently described tumor subtype with an unknown prognosis, often misdiagnosed with other sinonasal carcinomas, and associated with high-risk HPV (HR-HPV). The present study aimed to evaluate the expression of vascular endothelial growth factor (VEGF), Bcl-2-associated X protein (BAX), epidermal growth factor receptors (EGFR), ProExC, and human telomerase reverse transcriptase (hTERT) and assess their association with survival and clinicopathological characteristics.
METHODS
Between 2017 and 2022, 40 HMSC patients underwent surgical resection at the School of Medicine, Zagazig University Hospitals (Zagazig, Egypt). Tissue samples were examined for the presence of HR-HPV; absence of myeloblastosis (MYB), MYB proto-oncogene like 1 (MYBL1), and nuclear factor I/B (NFIB) fusions and the presence of myoepithelial proteins (calponin, S100, SMA), squamous differentiation markers (p63, p40, calponin), VEGF, BAX, ProExC, and hTERT by immunohistochemistry. All patients were followed up for about 54 months until death or the last known survival data. Data were analyzed using the Chi square test and Kaplan-Meier method.
RESULTS
The expression of VEGF, hTERT, and ProExC was significantly associated with age, advanced tumor stages, lymph node metastasis, tumor size, mortality, relapse, poor disease-free survival (DFS), and overall survival (OS) (P<0.001). BAX expression was significantly associated with tumor size, age, poor DFS, and relapse (P=0.01, P<0.001, P=0.035, and P=0.002, respectively).
CONCLUSION
HMSC is strongly associated with HR-HPV. The expression of VEGF, EGFR, BAX, hTERT, and ProExC is associated with aggressive malignant behavior, poor survival, and poor prognosis, making them novel prognostic biomarkers for targeted therapeutics in HMSC.
Topics: Humans; Vascular Endothelial Growth Factor A; bcl-2-Associated X Protein; Human Papillomavirus Viruses; Prognosis; Papillomavirus Infections; Papillomaviridae; Neoplasm Recurrence, Local; Carcinoma; Paranasal Sinus Neoplasms; ErbB Receptors; Recurrence; Biomarkers
PubMed: 38584650
DOI: 10.30476/IJMS.2023.97341.2906 -
Journal of Cutaneous Pathology Jul 2024While the list of fusion-driven soft tissue neoplasms is expanding rapidly, their importance among cutaneous and superficial mesenchymal and adnexal neoplasms remains...
Fusion-driven cutaneous and superficial mesenchymal and adnexal tumors-A clinicopathologic and molecular study of 15 cases, including a novel case of ACTB::ZMIZ2-rearranged adnexal carcinoma.
BACKGROUND
While the list of fusion-driven soft tissue neoplasms is expanding rapidly, their importance among cutaneous and superficial mesenchymal and adnexal neoplasms remains poorly understood. This challenge is especially evident in cases with ambiguous histopathology that are difficult to classify based on morphology.
AIMS
Our goal was to investigate the benefits of next-generation sequencing in diagnosing complex cutaneous neoplasms.
MATERIALS & METHODS
Departmental archives were searched for fusion-driven cutaneous neoplasms. Slides were retrieved and clinical information including follow-up was obtained.
RESULTS
Fifteen cases occurred in eight female and seven male patients, with a median age of 26 years (range: 1-83) at diagnosis. Tumors involved the extremities (9), scalp (5), and head and neck (1). Predominant features included myoepithelial (5), nested spindled with clear cytoplasm (2), atypical adnexal/squamoid (2), small round blue cell (2), cellular spindled (3), and fibrohistiocytic morphology (1). Most frequently encountered fusions involved EWSR1 (6) fused to ERG (1), FLI1 (1), CREB1 (2), CREM (1), PBX3 (1), followed by PLAG1 (4) with LIFR (2), TRPS1 (1) and CHCHD7. Additional fusions encountered were YAP1::NUTM1, EML4::ALK, SS18::SSX1 (2), and a novel fusion: ACTB::ZMIZ2. Integration of histologic features and molecular findings led to final diagnoses of primary cutaneous Ewing sarcoma (2), soft tissue myoepithelioma (4), cutaneous syncytial myoepithelioma (1), cutaneous adnexal carcinoma (1), porocarcinoma (1), inflammatory myofibroblastic tumor (1), synovial sarcoma (2), clear cell sarcoma (2), and angiomatoid fibrous histiocytoma (1).
DISCUSSION AND CONCLUSION
Our results show that fusion testing can be a helpful diagnostic tool, especially in cases with unusual or uncommon morphology in superficial sites. Furthermore, it can allow for the identification of potential therapeutic targets in some instances.
Topics: Humans; Female; Male; Adult; Skin Neoplasms; Middle Aged; Aged; Child; Adolescent; Aged, 80 and over; Child, Preschool; Infant; Oncogene Proteins, Fusion; High-Throughput Nucleotide Sequencing; Transcription Factors; Neoplasms, Adnexal and Skin Appendage; Young Adult; Gene Rearrangement
PubMed: 38556256
DOI: 10.1111/cup.14610 -
Scientific Reports Mar 2024Biophysical cues from the cell microenvironment are detected by mechanosensitive components at the cell surface. Such machineries convert physical information into...
Biophysical cues from the cell microenvironment are detected by mechanosensitive components at the cell surface. Such machineries convert physical information into biochemical signaling cascades within cells, subsequently leading to various cellular responses in a stimulus-dependent manner. At the surface of extracellular environment and cell cytoplasm exist several ion channel families that are activated by mechanical signals to direct intracellular events. One of such channel is formed by transient receptor potential cation channel subfamily V member, TRPV4 that is known to act as a mechanosensor in wide variaty of tissues and control ion-influx in a spatio-temporal way. Here we report that TRPV4 is prominently expressed in the stem/progenitor cell populations of the mammary epithelium and seems important for the lineage-specific differentiation, consequently affecting mechanical features of the mature mammary epithelium. This was evident by the lack of several markers for mature myoepithelial and luminal epithelial cells in TRPV4-depleted cell lines. Interestingly, TRPV4 expression is controlled in a tension-dependent manner and it also impacts differentation process dependently on the stiffness of the microenvironment. Furthermore, such cells in a 3D compartment were disabled to maintain normal mammosphere structures and displayed abnormal lumen formation, size of the structures and disrupted cellular junctions. Mechanosensitive TRPV4 channel therefore act as critical player in the homeostasis of normal mammary epithelium through sensing the physical environment and guiding accordingly differentiation and structural organization of the bilayered mammary epithelium.
Topics: Humans; TRPV Cation Channels; Epithelium; Signal Transduction; Epithelial Cells; Cytoplasm
PubMed: 38514727
DOI: 10.1038/s41598-024-57346-x -
Head and Neck Pathology Mar 2024Oncocytoid salivary tumors include several entities such as oncocytoma, Warthin tumor, secretory carcinoma (SC), salivary duct carcinoma (SDC), acinic cell carcinoma... (Review)
Review
BACKGROUND
Oncocytoid salivary tumors include several entities such as oncocytoma, Warthin tumor, secretory carcinoma (SC), salivary duct carcinoma (SDC), acinic cell carcinoma (AciCC), oncocytic mucoepidermoid carcinoma (OMEC), intraductal carcinoma, and epithelial myoepithelial carcinoma (EMC). This review investigates the differential diagnosis of oncocytoid salivary tumors and explore the role of newly described immunostains as valuable tools for their diagnosing and potentially guiding treatment options.
METHODS
We assess the utility of incorporating new immunohistochemical markers in routine practice to aid in diagnosing oncocytoid salivary tumors and potentially provide treatment options.
RESULTS
In SDC, AR and Her2 immunostains are utilized as diagnostic tools and biomarkers for selecting patients who might benefit from Androgen-deprivation therapy (ADT) and HER2-targeted therapy. Furthermore, nuclear Pan-Trk immunostaining can aid in diagnosing SC. Additionally, NR4A3 immunostaining has been shown high sensitivity and specificity in identifying AciCC in both surgical and cytologic specimens. Similarly, RAS Q61R mutant-specific immunostaining, detected in EMC, may offer a cost-effective diagnostic marker for this tumor. Although further studies are required to evaluate the role of BSND, this marker has been reported to be positive in Warthin tumor and oncocytoma, aiding in differentiating them from other oncocytoid tumors, particularly OMEC. In addition, BRAFV600E mutant-specific immunostaining can serve as a diagnostic and potentially therapeutic marker for oncocytic intraductal carcinoma in mutation positive cases.
CONCLUSION
Oncocytoid salivary tumors may have overlapping morphologies, posing diagnostic challenges for pathologists. Recently described immunohistochemical markers may offer valuable tools for diagnosing and potentially guiding treatment options for these tumors.
Topics: Male; Humans; Adenoma, Oxyphilic; Adenolymphoma; Immunohistochemistry; Diagnosis, Differential; Carcinoma, Intraductal, Noninfiltrating; Androgen Antagonists; Biomarkers, Tumor; Prostatic Neoplasms; Salivary Gland Neoplasms; Carcinoma, Acinar Cell; Carcinoma, Ductal; Breast Neoplasms; Carcinoma
PubMed: 38502259
DOI: 10.1007/s12105-024-01622-9 -
International Journal of Surgical... Mar 2024Papillary carcinoma of the breast is a rare histologic subtype of invasive breast cancer. In contrast, ductal carcinoma in situ (DCIS) is a noninvasive, nonobligate...
Rare Presentation of Papillary Carcinoma Within a Sentinel Lymph Node in a Patient With Ductal Carcinoma in Situ of the Breast: A Challenging but Useful Case Report Discussion Regarding Displacement or True Metastasis?
Papillary carcinoma of the breast is a rare histologic subtype of invasive breast cancer. In contrast, ductal carcinoma in situ (DCIS) is a noninvasive, nonobligate precursor to invasive mammary carcinoma, confined within the terminal duct lobular unit of the breast and surrounded by an intact myoepithelial cell layer at the stromal/epithelial interface. We present an unusual case in which a patient with only DCIS of the breast exhibited papillary carcinoma within a sentinel lymph node, leading to questions about the origin of the lymph node lesion-whether it represents a true metastasis or iatrogenic displacement during diagnostic procedures. This case underscores the diagnostic challenges and clinical implications associated with such rare presentations.
PubMed: 38500348
DOI: 10.1177/10668969241235316 -
International Journal of Clinical... Jun 2024Salivary gland-type cancers (SGTCs) are histologically heterogeneous and can affect organs other than the salivary glands. Some tumors outside the salivary glands are...
BACKGROUND
Salivary gland-type cancers (SGTCs) are histologically heterogeneous and can affect organs other than the salivary glands. Some tumors outside the salivary glands are diagnosed on their unique histological characteristics. Comprehensive cross-organ studies on SGTCs are limited.
METHODS
We retrospectively analyzed the data of patients with salivary duct carcinoma (SDC), adenoid cystic carcinoma (AdCC), mucoepidermoid carcinoma (MEC), epithelial-myoepithelial carcinoma (EMC), acinic cell carcinoma (AcCC), and polymorphous adenocarcinoma (PAC) who visited our institution between 2009 and 2019. The primary tumor sites were classified into four categories; major salivary glands, head/neck (H/N) excluding (exc) major salivary glands (MSG) regions, broncho-pulmonary regions, and "others". H/N exc MSG was further divided into three subcategories, nasal/paranasal sinus, oral and pharynx/larynx.
RESULTS
We identified 173 patients with SGTCs, with SDC, AdCC, MEC, EMC, AcCC, and PAC accounting for 20%, 42%, 27%, 3%, 8%, and 1% of the cases, respectively. The most frequent primary site was the major salivary glands (64%), followed by H/N exc MSG regions (27%), broncho-pulmonary regions, and "others", thus non-salivary gland origins accounted for 9% of all cases. Patients with SDC, MEC, AcCC, or SGTC of the major salivary glands and broncho-pulmonary regions were more frequently treated by surgery. The overall survival time of the patients with MEC was significantly better than that of patients with SDC or EMC.
CONCLUSIONS
This cross-organ study highlights the clinical significance of SGTCs, underscoring the need for developing novel therapies for this rare disease entity.
Topics: Humans; Salivary Gland Neoplasms; Female; Male; Middle Aged; Retrospective Studies; Aged; Adult; Carcinoma, Mucoepidermoid; Carcinoma, Adenoid Cystic; Aged, 80 and over; Carcinoma, Acinar Cell; Young Adult; Adolescent; Adenocarcinoma; Salivary Glands
PubMed: 38492066
DOI: 10.1007/s10147-024-02505-3