Pancreatic malignancies can be subdivided into endocrine and non-endocrine processes. Of the non-endocrine tumours, ductal carcinoma is the most common, and the ductal carcinomas can be further subdivided into adenocarcinomas and squamous cell carcinomas. The adenocarcinomas constitute most of the non-endocrine pancreatic malignancies, and the treatment options for these, although limited in efficacy, are relatively well established. The squamous cell carcinoma pathology is a rare entity, and few reports of it are found in the literature. As a result, treatment options for squamous cell carcinoma of the pancreas are poorly understood. Here, we report the presentation of a 48-year-old woman with metastatic squamous cell carcinoma of the pancreas. The subsequent investigations, treatment, and outcome are described.
Merkel cell carcinoma is an aggressive neuroendocrine tumor historically thought to arise from neural crest-derived cutaneous neuroendocrine cells. Recent evidence supports an epidermal origin. We present a case of Merkel cell carcinoma arising on the upper arm of a 94-year-old woman that had multiple morphologic patterns: small cells typical of Merkel cell carcinoma, malignant cells with squamous differentiation and malignant poorly differentiated spindle cells. Subsequent metastatic disease in regional lymph nodes showed only the small cells and the malignant spindle cells. To our knowledge, this is the first case of Merkel cell carcinoma showing these three patterns of differentiation at first presentation. This morphology raises the possibility that Merkel cell carcinomas may arise from epidermal stem cells that can differentiate along different lines.
Hematoxylin and eosin (H&E) staining is the gold standard for most histopathological diagnostics but requires lengthy processing times not suitable for point-of-care diagnosis. Here we demonstrate a 266-nm excitation ultraviolet photoacoustic remote sensing (UV-PARS) and 1310-nm microscopy system capable of virtual H&E 3D imaging of tissues. Virtual hematoxylin staining of nuclei is achieved with UV-PARS, while virtual eosin staining is achieved using the already implemented interrogation laser from UV-PARS for scattering contrast. We demonstrate the capabilities of this dual-contrast system for en-face planar and depth-resolved imaging of human tissue samples exhibiting high concordance with H&E staining procedures and confocal fluorescence microscopy. To our knowledge, this is the first microscopy approach capable of depth-resolved imaging of unstained thick tissues with virtual H&E contrast.
Realistic label-free virtual histopathology has been a long sought-after goal not yet achieved with current methods. Here, we introduce high-resolution hematoxylin and eosin (H&E)-like virtual histology of unstained human breast lumpectomy specimen sections using ultraviolet scattering-augmented photoacoustic remote sensing microscopy. Together with a colormap-matching algorithm based on blind stain separation from a reference true H&E image, we are able to produce virtual H&E images of unstained tissues with close concordance to true H&E-stained sections, with promising diagnostic utility.
The authors declare that there is no conflict of interest regarding the publication of this article.Character count: 52,408 (60,000 characters MAX including spaces and main figure legends but excluding STAR Methods text, supplemental item legends, and References section):
Summary (Currently 120 words): 120 words MAXWe comprehensively analyzed the genomic and transcriptional profiles of 97 laser capture microdissection (LCM) isolated cell clusters from a single patient with triple negative breast cancer (TNBC). By performing simultaneous genome and transcriptome amplification and sequencing (G&T-seq) on these clusters, we identified four RNA cancer cell clones that were directly linked to DNA clone counterparts. We also detected the presence of a lymphovascular invasive (LVI) clone characterized by chromosome instability (CIN), and a specific genomic and transcriptional pattern shared with several primary cancer cell clusters. Furthermore, combination phylogeny analysis pointed to three evolutionarily distinct metastatic pathways in this patient, and hub gene evaluation found the down regulation of ribosomal protein mRNA to be a potential prognostic marker for breast cancer.Keywords: Triple negative breast cancer (TNBC), lymphovascular invasion (LVI), metastasis, lymphatics, laser capture microdissection (LCM), G&T-seq (genome and transcriptome sequencing)
Significance (Currently 120 words): 120 words MAXThe lymphatic system is a unidirectional vascular network responsible for trafficking immune cells and lymphatic fluid. However, many cancer cell types use this system as a primary means of metastatic spread to regional lymph nodes. We describe the use of laser capture microdissection in the isolation of lymphovascular invasive (LVI) cancer cell clusters from within lymphatic vessels of a single breast cancer patient. Genomic and transcriptional profiling of LVI associated cancer cells, and cancer cell clusters derived from the primary tumor and lymph nodes of this patient, was performed using G&T-seq. Our findings improve our understanding of LVI metastatic mechanisms, and reveal that poor breast cancer survival outcomes may be related to the extensive down-regulation of transcripts encoding ribosomal proteins.
Highlights:1. LVI clone shares a specific genome and transcriptome pattern with a small proportion of primary cancer cell clusters.2. G&T sequencing revealed RNA cancer cell clones to be highly correlative to DNA clones.3. Three evolutionarily and transcriptionally distinct pathways of tumor clone development and metastasis were found in one TNBC patient using combination phylogeny analysis.
4.Extensive ribosomal protein down-regulation may be a potential marker of poor prognosis in breast cancer patients.
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