Rare Cells Research Articles

Clinical insights and management perspectives in sacrococcygeal teratoma: Beyond the scalpel.

Sacrococcygeal teratoma (SCT), a rare germ cell malignancy in newborns, necessitates prompt surgical intervention for complete resection. Long-term follow-up is crucial for monitoring recurrence and managing potential complications, regardless of histopathological findings, ensuring optimal outcomes and early intervention if needed.

Silicon heterojunction back contact solar cells by laser patterning.

Back contact silicon solar cells, valued for their aesthetic appeal by removing grid lines on the sunny side, find applications in buildings, vehicles and aircrafts, enabling self-power generation without compromising appearance1-3. Patterning techniques arrange contacts on the shaded side of the silicon wafer, offering benefits for light incidence as well. However, the patterning process complicates production and causes power loss. Here we employ lasers to streamline back contact solar cell fabrication and enhance power conversion efficiency. Our approach produces the first silicon solar cell to exceed 27% efficiency. Hydrogenated amorphous silicon layers are deposited on the wafer for surface passivation and collection of light-generated carriers. A dense passivating contact, diverging from conventional technology practice, is developed. Pulsed picosecond lasers at different wavelengths are used to create back contact patterns. The developed approach is a streamlined process for producing high-performance back contact silicon solar cells, with a total effective processing time of about one-third that of emerging mainstream technology. To meet terawatt demand, we develop rare indium-less cells at 26.5% efficiency and precious silver-free cells at 26.2% efficiency. The integration of solar solutions in buildings and transportation is poised to expand with these technological advancements.

One case of Rosai-Dorfman disease misdiagnosed as facial inflammation.

Rosai-Dorfman disease (RDD) is a rare non-Langerhans cell histiocytosis. The etiology and pathogenesis of RDD have not been fully explained, and its occurrence is even rarer in the maxillofacial region. This paper reported a patient who was first misdiagnosed as facial inflammation caused by oral disease and finally diagnosed as RDD. Clinical features, diagnosis, treatment, and prognosis were discussed based on the literature. This work provides reference for future diagnosis and differentiation of RDD in cheek.

Primary anaplastic extramedullary plasmacytoma in the lacrimal sac

We report the case of a 60-year-old man diagnosed with unilateral, solitary, extramedullary plasmacytoma located in the right lacrimal sac fossa, with no systemic involvement. This rare plasma cell dyscrasia is usually found in the respiratory tract. Clinical and radiological features of the mass and histopathological results are described. The patient was successfully treated with complete surgical excision. There were no clinical or radiological indications of disease recurrence at 10 months’ follow-up.

A Rapidly Growing Nodule on the Eyebrow of a Pediatric Patient

A 11-year-old Caucasian girl presented to our Dermatology Unit with a 2-month history of an erythematous nodule, localized to the medial portion of her left eyebrow, rapidly growing in the two weeks before presentation. The histopathological examination revealed a dermal multi-nodular epithelial neoplasm composed of clear cells, squamous cells, and glandular cells, characterized by cytologic atypia, high mitotic activity, and an infiltrative deep growth pattern. The immunohistochemical profile of the lesion was as follows: CKAE1/AE3+, EMA+, CK8/18+, CK7+, CK19+, AR negative, p63 focally +, Ki67 25%, rare cells GCDFP15+, p53+.

(Don't) take my breath away: Rare epithelial cells in our airways initiate reflexes to guard against harmful stimuli.

Rare epithelial cells in our airways initiate reflexes to guard against harmful stimuli.

Clinicopathological characteristics of extranodal Rosai-Dorfman disease: A retrospective case series of 25 patients

Rosai-Dorfman disease (RDD) is a rare non-Langerhans cell histiocytosis, classically affecting the lymph nodes. Even rarer extranodal disease is diagnostically challenging due to overlapping histologic features with other entities and lack of a universally agreed set of biomarkers. Cyclin D1 immunohistochemistry (IHC) may serve as a useful adjunct in diagnosing extranodal RDD. We present a retrospective case series of patients diagnosed with extranodal RDD between January 2013 and December 2023. IHC staining for cyclin D1 was performed on archived tissue samples. Baseline IHC results for biomarkers supporting the RDD diagnosis were recorded along with patient demographic characteristics, clinical features, and disease outcomes. A total of 25 patients with extranodal RDD were included: 21 women (84 %) and 4 men (16 %). The mean age at diagnosis was 42.6 years. Cutaneous and deep tissue involvement was seen in 5 (20 %) and 20 (80 %) patients, respectively. 11 patients (44 %) had disease localized to the trunk and extremities, and 13 had disease in the head and neck region (52 %), of which 5 occurred in the nose and paranasal tissues. Available follow-up data showed most patients fully recovered (n = 11; 78.6 %). However, 1 patient had disease recurrence, 1 developed blindness, and 1 developed deafness. Cyclin D1 IHC was positive in all samples (100 %), consistent with previous studies. The clinicopathologic findings in this study highlight the spectrum of potential disease sites, possible morbid outcomes related to disease site, and the diagnostic utility of cyclin D1 IHC.

Clinical cell-surface targets in metastatic and primary solid cancers.

Therapies against cell-surface targets (CSTs) represent an emerging treatment class in solid malignancies. However, high-throughput investigations of CST expression across cancer types have been reliant on data sets of mostly primary tumors, despite therapeutic use most commonly in metastatic disease. We identified a total of 818 clinical trials of CST therapies with 78 CSTs. We assembled a data set spanning RNA-seq and microarrays in 7,927 benign samples, 16,866 primary tumor samples, and 6,124 metastatic tumor samples. We also utilized single-cell RNA-seq data from 36 benign tissues and 558 primary and metastatic tumor samples, and matched RNA versus protein expression in 29 benign tissue samples, 1,075 tumor samples, and 942 cell lines. High RNA expression accurately predicted high protein expression across CST therapies in benign tissues, tumor samples, and cell lines. We compared metastatic versus primary tumor expression, identified potential opportunities for repositioning, and matched cell lines to tumor types based on CST and global RNA expression. We evaluated single-cell heterogeneity across tumors, and identified rare normal cell subpopulations that may contribute to toxicity. Finally, we identified combinations of CST therapies for which bispecific approaches could improve tumor specificity. This study helps better define the landscape of CST expression in metastatic and primary cancers.

Intracranial Solitary Fibrous Tumor in a 25-Year-Old Woman

<p><strong>Introduction:</strong> Intracranial solitary fibrous tumors (ISFTs) are extremely rare spindle cell tumors originating from dendritic mesenchymal cells expressing CD34 antigens that are usually benign, although malignant transformation had been reported. The knowledge of natural course and prognostic factors of ISFTs is still limited and the tumor is easily misdiagnosed.</p><p><strong>Case Presentation:</strong> An intra-cranial extra-axial tumor tissue resection from a 25-year-old woman was evaluated in the Surgical Pathology Laboratory. Histologic findings (cellular spindle cell tumor with ‘patternless’ pattern, staghorn blood vessels and <5 mitoses per 10 hpf) and immunophenotype (positive for CD34, weakly and focally positive for STAT6) suggested a diagnosis of intracranial solitary fibrous tumor WHO Grade II.</p><p><strong>Discussion:</strong> ISFTs have very low incidence in the CNS and are difficult to distinguish radiologically from meningiomas, thus post operative pathological examination and immunohistochemistry markers evaluations are the mainstay for diagnosis. ISFT is associated with NAB2-STAT6 gene fusion and may exhibits a wide spectrum of histological features. STAT6 immunohistochemistry is considered as one of the most sensitive diagnostic methods, while the evaluation of CD34 expression can be used as alternative diagnostic method despite having lower sensitivity.</p>

Leveraging gene correlations in single cell transcriptomic data

BackgroundMany approaches have been developed to overcome technical noise in single cell RNA-sequencing (scRNAseq). As researchers dig deeper into data—looking for rare cell types, subtleties of cell states, and details of gene regulatory networks—there is a growing need for algorithms with controllable accuracy and fewer ad hoc parameters and thresholds. Impeding this goal is the fact that an appropriate null distribution for scRNAseq cannot simply be extracted from data in which ground truth about biological variation is unknown (i.e., usually).ResultsWe approach this problem analytically, assuming that scRNAseq data reflect only cell heterogeneity (what we seek to characterize), transcriptional noise (temporal fluctuations randomly distributed across cells), and sampling error (i.e., Poisson noise). We analyze scRNAseq data without normalization—a step that skews distributions, particularly for sparse data—and calculate p values associated with key statistics. We develop an improved method for selecting features for cell clustering and identifying gene–gene correlations, both positive and negative. Using simulated data, we show that this method, which we call BigSur (Basic Informatics and Gene Statistics from Unnormalized Reads), captures even weak yet significant correlation structures in scRNAseq data. Applying BigSur to data from a clonal human melanoma cell line, we identify thousands of correlations that, when clustered without supervision into gene communities, align with known cellular components and biological processes, and highlight potentially novel cell biological relationships.ConclusionsNew insights into functionally relevant gene regulatory networks can be obtained using a statistically grounded approach to the identification of gene–gene correlations.

DEPICT-seq: Single-Cell Transcriptomic Analysis of Rare Cell Subsets Isolated via Nucleic Acid Cytometry.

The ability to dive deep into specific rare cell populations is critical for understanding tissue physiology and pathology across various biological domains. As single-cell RNA-seq flourishes, many newly discovered cell subtypes are defined by their transcriptomic markers. However, our ability to retrieve and analyze cells based on their nucleic acid markers remains underdeveloped. Here, we present Double Emulsion PCR-Initiated Cell sorting and Transcriptomic Sequencing (DEPICT-seq), a high-throughput droplet nucleic acid cytometry method that integrates batch cell fixation for cellular information preservation, double emulsion digital PCR-based cell sorting to target nucleic acid markers of interest, and in-depth full-length transcriptomic analyses at single-cell resolution. We utilize DEPICT-seq to isolate and characterize T cell receptor (TCR)-engineered T cells within a mixed population and also demonstrate a variation of the workflow by incorporating an RNase H-dependent PCR step to enrich full-length TCR sequences for paired single-cell TCR sequencing and transcriptomic profiling.

Abstract C069: A conserved reepithelialization program driven by FOSL1 underlies malignancy in pancreatic ductal adenocarcinoma

Abstract Benign lesions named pancreatic intraepithelial neoplasia (PanIN) are frequent in the healthy population but are precursors to deadly pancreatic ductal adenocarcinoma (PDAC). Conversion of PanINs to PDAC is poorly understood. Here we harness high resolution spatial transcriptomics to identify a core transcriptional program associated with invasive growth across human PDAC and required for PanIN-to-PDAC progression in mice. The malignancy program is lineage restricted, and predominantly comprised of transcripts activated to drive reepithelialization during skin wound healing. This wound-like program appears in rare PanIN cells that also activate tumor suppressor genes (TSGs), which keep the incipient malignant cells in check. TSG KO in PanINs leads to rapid outgrowth of the wound-like population, unleashing invasive growth, driven by the wound-induced TF FOSL1. Bidirectional interactions between malignant epithelial cells and wound-like CTHRC1-expressing CAFs enforce the malignant state. Our results suggest that wound recapitulation drives the highly invasive properties of PDAC. Citation Format: Charles David, Melian Zhuo, Yong Li, Yifeng Zhang, Chenlu Yang, Ziqing Deng, Yupei Zhao, Wennming Wu, Junya Peng, Mo Chen. A conserved reepithelialization program driven by FOSL1 underlies malignancy in pancreatic ductal adenocarcinoma [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Advances in Pancreatic Cancer Research; 2024 Sep 15-18; Boston, MA. Philadelphia (PA): AACR; Cancer Res 2024;84(17 Suppl_2):Abstract nr C069.

Context-aware single-cell multiomics approach identifies cell-type-specific lung cancer susceptibility genes

Genome-wide association studies (GWAS) identified over fifty loci associated with lung cancer risk. However, underlying mechanisms and target genes are largely unknown, as most risk-associated variants might regulate gene expression in a context-specific manner. Here, we generate a barcode-shared transcriptome and chromatin accessibility map of 117,911 human lung cells from age/sex-matched ever- and never-smokers to profile context-specific gene regulation. Identified candidate cis-regulatory elements (cCREs) are largely cell type-specific, with 37% detected in one cell type. Colocalization of lung cancer candidate causal variants (CCVs) with these cCREs combined with transcription factor footprinting prioritize the variants for 68% of the GWAS loci. CCV-colocalization and trait relevance score indicate that epithelial and immune cell categories, including rare cell types, contribute to lung cancer susceptibility the most. A multi-level cCRE-gene linking system identifies candidate susceptibility genes from 57% of the loci, where most loci display cell-category-specific target genes, suggesting context-specific susceptibility gene function.

The role of the haematopoietic stem cell niche in development and ageing.

Blood production depends on rare haematopoietic stem cells (HSCs) and haematopoietic stem and progenitor cells (HSPCs) that ultimately take up residence in the bone marrow during development. HSPCs and HSCs are subject to extrinsic regulation by the bone marrow microenvironment, or niche. Studying the interactions between HSCs and their niche is critical for improving ex vivo culturing conditions and genetic manipulation of HSCs, which is pivotal for improving autologous HSC therapies and transplantations. Additionally, understanding how the complex molecular network in the bone marrow is altered during ageing is paramount for developing novel therapeutics for ageing-related haematopoietic disorders. HSCs are unique amongst stem and progenitor cell pools in that they engage with multiple physically distinct niches during their ontogeny. HSCs are specified from haemogenic endothelium in the aorta, migrate to the fetal liver and, ultimately, colonize their final niche in the bone marrow. Recent studies employing single-cell transcriptomics and microscopy have identified novel cellular interactions thatgovern HSC specification and engagement with their niches throughout ontogeny. New lineage-tracing models and microscopy tools have raised questions about the numbers of HSCs specified, as well as the functional consequences of HSCs interacting with each developmental niche. Advances have also been made in understanding how these niches are modified and perturbed during ageing, and the role of these altered interactions in haematopoietic diseases. In this Review, we discuss these new findings and highlight the questions that remain to be explored.

IL-13 induces loss of CFTR in ionocytes and reduces airway epithelial fluid absorption.

The airway surface liquid (ASL) plays a crucial role in lung defense mechanisms, and its composition and volume are regulated by the airway epithelium. The cystic fibrosis transmembrane conductance regulator (CFTR) is abundantly expressed in a rare airway epithelial cell type called an ionocyte. Recently, we demonstrated that ionocytes can increase liquid absorption through apical CFTR and basolateral barttin/chloride channels, while airway secretory cells mediate liquid secretion through apical CFTR channels and basolateral NKCC1 transporters. Th2-driven (IL-4/IL-13) airway diseases, such as asthma, cause goblet cell metaplasia, accompanied by increased mucus production and airway secretions. In this study, we investigate the effect of IL-13 on chloride and liquid transport performed by ionocytes. IL-13 treatment of human airway epithelia was associated with reduced epithelial liquid absorption rates and increased ASL volume. Additionally, IL-13 treatment reduced the abundance of CFTR-positive ionocytes and increased the abundance of CFTR-positive secretory cells. Increasing ionocyte abundance attenuated liquid secretion caused by IL-13. Finally, CFTR-positive ionocytes were less common in asthma and chronic obstructive pulmonary disease and were associated with airflow obstruction. Our findings suggest that loss of CFTR in ionocytes contributes to the liquid secretion observed in IL-13-mediated airway diseases.

A case of paraprotein-negative POEMS syndrome: Case report and literature review.

POEMS syndrome is a rare monoclonal plasma cell disease. The diagnosis of POEMS requires polyradiculoneuropathy and monoclonal plasma proliferating as 2 mandatory criteria, at least 1 of the major criteria (Castleman disease, elevated vascular endothelial growth factor level, and sclerotic bone lesion), and at least 1 of the minor criteria (organomegaly, extravascular volume overload, endocrinopathy, skin changes, papilledema, and thrombocytosis/polycythemia). This multisystem disorder is of high heterogeneity, and few variants of POEMS with no evidence of monoclonal gammopathy have been described, which further complicates the diagnosis in clinical practice. Now, we report a case of paraprotein-negative POEMS syndrome. A 45-year-old woman complained of lower extremity edema, shortness of breath, abdominal distension, and lymphadenopathy for few years. Finally, she was diagnosed with paraprotein-negative POEMS syndrome. With the lenalidomide-based regimen, the symptoms were all relieved. Paraprotein-negative POEMS syndrome. Lenalidomide-based regimen and some supportive therapy. All symptoms were relieved after 1 year of treatment. Physicians should pay more attention to the POEMS syndrome, especially the POEMS syndrome variants, which are absence of paraprotein; probably, these variants are just "on the way" to classic POEMS syndrome antiplasma cell therapy, which remains the treatment of choice.

A RARE CASE OF COEXISTING BLADDER SMALL CELL NEUROENDOCRINE CARCINOMA AND PROSTATE ADENOCARCINOMA: CASE REPORT AND LITERATURE REVIEW

Objective: We present a case of synchronous malignancies of rare bladder small cell neuroendocrine carcinoma (SCNC) and prostate adenocarcinoma and provide literature review of bladder SCNC. Case(s) presentation: A 72-year-old male smoker presented with 3 months history of gross hematuria. Ultrasonography showed a large hypoechoic mass in the right bladder. TURBT was performed and histopathology of the TURBT specimen showed a high-grade papillary urothelial carcinoma. Abdominal contrast-enhanced computed tomography (CECT) demonstrated an isodense heterogenous undefined mass, with irregular border at right anterolateral side of bladder wall. Radical cystoprostatectomy, bilateral radical lymph node dissection and bilateral ureterocutaneostomy was performed. Histopathology and immunohistochemical examination after radical cystoprostatectomy revealed bladder small cell neuroendocrine carcinoma coexisting with prostate adenocarcinoma (Gleason score 3+3=6, group 1). The patient eventually succumbed to disease after having symptomatic disease progression and metastatic disease five months after the surgery. Discussion: Bladder SCNC is a rare malignancy with an incidence of 1–9/1,000,000 reported. This tumor has an aggressive clinical course with high incidence of metastasis, and it tends to confer dismal prognosis. No specific clinical symptom exists. Histopathological recognition and immunohistochemistry is required to differentiate this rare entity. Conclusion: Clinicians and pathologists should be alert to the possibility of bladder SCNC despite extremely scarce incidence. Keywords: Bladder cancer, small cell neuroendocrine carcinoma, synchronous malignancy, case report.

Concurrent delayed recurrence of peripheral primitive neuroectodermal tumors in orbital and sellar/suprasellar regions in an older adult.

Peripheral primitive neuroectodermal tumors (pPNETs) are rare and aggressive small round cell tumors, tending to occur in the thoracic and paravertebral soft tissues in children and young adults. This report describes an exceptionally rare case of concurrent delayed recurrence of pPNET in the orbital and sellar/suprasellar regions in an older adult, with a discussion supported by a literature review. We report an 82-year-old woman with a history of orbital pPNETs resection at age 62, followed by gamma knife radiosurgery for local recurrence at age 66. She presented left eye pain, left eye protrusion, decreased vision in the right eye, and right homonymous hemianopia. MRI revealed extensive lesions in the left orbital cavity and sellar/suprasellar region, contiguous through the optic canal. The recurrent tumor was treated through a two-stage resection via transcranial and transsphenoidal approaches, which resulted in symptom improvement and a pathologic diagnosis of pPNETs. This case highlights a highly rare instance of late-onset orbital pPNETs recurrence in an elderly patient, with evidence suggesting tumor progression into the sellar/suprasellar regions through the optic canal.

VICTOR: Validation and inspection of cell type annotation through optimal regression

Single-cell RNA sequencing provides unprecedent opportunities to explore the heterogeneity and dynamics inherent in cellular biology. An essential step in the data analysis involves the automatic annotation of cells. Despite development of numerous tools for automated cell annotation, assessing the reliability of predicted annotations remains challenging, particularly for rare and unknown cell types. Here, we introduce VICTOR: Validation and inspection of cell type annotation through optimal regression. VICTOR aims to gauge the confidence of cell annotations by an elastic-net regularized regression with optimal thresholds. We demonstrated that VICTOR performed well in identifying inaccurate annotations, surpassing existing methods in diagnostic ability across various single-cell datasets, including within-platform, cross-platform, cross-studies, and cross-omics settings.

Abstract P433: Impaired Renin Activity in a Bicistronic Ren1 c -T2A-tdTomato Reporter Mouse

The study of renin cell identity and function often requires the isolation of this rare cell type –0.01% of the kidney cells. Multicistronic constructs are commonly used to express reporter genes in mice. They consist of two or more genes linked by 2A peptide sequences, which produce separate proteins through a ribosomal skipping mechanism. Here, we report on the generation of a mouse model to label renin-expressing cells with a bright fluorescent reporter for the tracking and isolation of renin cells. Ren1 ctdTomato mice were generated by inserting a bicistronic T2A-tdTomato knock-in cassette upstream of the TGA stop codon of the Ren1 c gene. Kidneys from adult heterozygous (het) Ren1 ctdTomat o mice showed tdTomato signal confined to the JG area under basal conditions, and extending along the afferent arterioles and in the intraglomerular mesangium upon treatment with captopril + low-salt diet to induce the endocrine transformation of renin cells. Unexpectedly, homozygous (homo) mice exhibited increased tdTomato signal that extended in the afferent arterioles and the mesangium even under normal physiological conditions, and progressive thickening of the kidney arterioles with age. Despite reduced Renin immunostaining in the renal cortex, homo mice exhibited significantly higher kidney Ren1 mRNA (7.9 ± 1.2 vs 1.2 ± 0.6, p< 0.0001) and circulating Renin levels (121.7 ± 44.0 vs 66.7 ± 29.4 ng/ml, p< 0.003) when compared to het controls. Moreover, homo mice showed significantly lower blood pressure measured under anesthesia (62.3 ± 5.9 vs 90.0 ± 5.7 mmHg, p< 0.0001), and Ang I plasma levels (159.3 ± 34.8 vs 500.0 ± 184.1 pmol/L, p< 0.05), indicating compromised Renin activity. The concentric arteriolar hypertrophy phenotype observed in these mice is identical to that described when RAS is genetically or pharmacologically inhibited, including the presence of mutations in the renin gene. Unlike mice with global deletion of renin, these animals did not require neonatal saline injections to survive and did not develop other kidney abnormalities, indicating that the bicistronic approach rendered a renin hypomorphic mouse. Ren1 ctdTomato mice constitute an excellent model for the labeling of renin-expressing cells and for the study of the mechanisms involved in the development of concentric vascular hypertrophy under RAS inhibition. In addition, this model may provide a better understanding of factors controlling renin protein folding, stability, packaging, and release.