Medical Molecular Morphology最新文献

Progastrin-releasing peptide (ProGRP), a neuropeptide, is a stable tumor marker for small cell lung carcinoma (SCLC) and other neuroendocrine tumors, such as medullary thyroid carcinoma. It has recently been reported as highly expressed in Ewing sarcoma (ES) and as a useful marker for this type of tumor. However, the mechanisms underlying ProGRP production remain unclear. This study aimed to elucidate its subcellular localization in human ES cell lines. Three ES cell lines (A-673, SK-N-MC, and SK-NEP-1) and one SCLC line (DMS 53) were transplanted into athymic mice. After 3-4 weeks, the tumors were excised, and the expression and localization of ProGRP were examined using immunohistochemistry and immunoelectron microscopy. Immunohistochemistry revealed that all three ES cell lines expressed ProGRP in a dot-like pattern in their cytoplasm, whereas SCLC cells showed a diffuse granular pattern. Immunoelectron microscopy revealed that ProGRP localized in neurosecretory granules (NSGs) in SCLC cells and in autolysosome-like structures in ES cells, with no NSGs observed in the ES cell lines. ES cells secrete high levels of ProGRP, similar to SCLC cells. However, in ES cells, ProGRP is localized in autolysosome-like structures, unlike the NSGs in SCLC, suggesting that ProGRP in ES can be transported and secreted without following the typical pathway for neuropeptides.

Pancreatic cancer is a malignant tumor that metastasizes to distant organs, such as the liver and lungs from an early stage. Few animal models can reproduce early metastasis. In addition, no model has been reported that reproduces cancer-related hypercoagulability, which is characteristic of pancreatic ductal adenocarcinoma and other adenocarcinomas. We hypothesized that the reason why the commonly used orthotopic cell xenograft model cannot reproduce the disease is inadequate construction of the cancer microenvironment. We developed an orthotopic tissue fragment xenograft model in which tumor tissue was transplanted into the pancreas of mice while preserving the microenvironment. Briefly, we injected single cancer cells subcutaneously to form a tumor, which was then cut with a scalpel into tumor fragments. A fragment was then sutured and fixed to the surface of the pancreatic tail. In this study, we evaluated the superiority of this model over a conventional orthotopic cell xenograft model. As a result, the novel orthotopic tissue xenograft model reproduced early distant metastasis to the liver and lung, nerve invasion, and cancer-related hypercoagulability of human pancreatic cancer, and showed greater similarity to clinical cases than the control orthotopic cell xenograft model.

Primary cilia are hair-like projections that protrude on most of mammalian cells and mediate reception of extracellular signals. Numerous studies have demonstrated that a variety of cancer cells including pancreatic ductal adenocarcinoma (PDAC) fail to form primary cilia. The loss of primary cilia is thought to cause carcinogenesis and progressive cell proliferation. However, the relationship of the primary cilia loss with carcinogenesis and/or cancer malignancy remains arguable. We herein examined whether ciliogenesis was increased in a model of more progressive PDAC and investigated effects of ciliogenesis on growth of PDAC using a pancreatic cancer cell line, PANC-1. The majority of PANC-1 cells in a cell cluster grown from a solitary cell possessed primary cilia. The rate of ciliogenesis was higher in cells grown from low density than in cells grown from high density. Almost all clones passing limiting dilution culture had abilities to grow primary cilia. Compared to the parental PANC-1 cells, clones that proliferated from a solitary cell showed increase in the ciliogenesis rate. Blocking ciliogenesis suppressed cell cluster formation. Our results suggest that pancreatic cancer cells that are more resistant to a solitary condition have abilities of ciliogenesis and form tumor-like cell clusters in a primary cilia-dependent manner.

To date, pagetoid spread-the proliferation of pagetoid cells in intraepidermal lesions, as observed in secondary extramammary Paget's disease-has not been reported in squamous epithelium derived from the extension of head and neck carcinomas. Herein, we report a case of pagetoid squamous cell proliferation associated with a primary intraosseous carcinoma (PIOC) arising in the periapical lesion of the maxilla, a finding not reported previously. A 60-year-old man presented with prostate adenocarcinoma and bilateral pubic bone, ilium bone, and sacral bone metastases. Radiological examination revealed a cyst that enveloped the apices of the left maxillary first molar roots. Histopathological examination of the cyst specimen indicated squamous cell carcinoma; hence, PIOC was suspected and partial left maxillectomy was performed. Histopathology results showed distant epitheliotrophic spread of atypical clear cells regarding the tumor. The epitheliotrophic cells were positive for cytokeratin (CK)19 and CK7 as odontogenic markers. These phenotypes were similar to those of tumor cells, suggesting pagetoid squamous cell proliferation associated with a PIOC arising. Although diagnosis of this condition is challenging, early detection is vital to ensure prompt treatment and improve patient prognosis.

Oncocytic sinonasal papilloma (OSP) is an uncommon, benign neoplasm characterized by papillary growths arising from the Schneiderian mucosa of the nasal and paranasal sinuses. OSP accounts for about 3-6% of all sinonasal papillomas (SPs), and clinically is often confused with inverted sinonasal papilloma (incidence 73%). Although SP shares some of the clinical characteristics of OSP, the pathogenesis differs and it is very important to distinguish between them. Here we present a case of OSP in the nasal and paranasal sinuses of a 67-year-old Japanese male, who complained of persistent left-sided nasal obstruction. A benign nasal paranasal tumor was diagnosed, and endoscopic sinus surgery was performed. Histopathologically, the tumor cells exhibited an exophytic and endophytic growth pattern, composed of multilayered eosinophilic columnar epithelium with finely granular cytoplasm, and forming microcysts filled with mucin or microabscesses. The epithelium was PTAH-positive, and showed positivity for cytokeratin-7 with oncocytic features. A review of the literature revealed 166 cases of OSP in the nasal and paranasal sinuses, with an overall recurrence rate of about 15%. Here we report a case of OSP in the nasal and paranasal sinuses for which PTAH staining specific for oncocytes was useful, together with a review of the relevant literature.

Fascin-1, an actin-bundling protein, plays a crucial role in cancer cell motility, invasion, and epithelial-mesenchymal transition (EMT). While its significance has been demonstrated in several malignancies, its clinical relevance in thymic carcinoma remains unclear. We retrospectively analyzed 10 surgically resected thymic carcinoma cases treated at Kochi University Hospital from 2008 to 2024. Immunohistochemical staining was performed to evaluate Fascin-1 expression using the Allred scoring system. Expression of EMT-related markers (TGF-β, pSmad3, Snail, and E-cadherin) was also assessed. Associations between Fascin-1 expression and postoperative recurrence were analyzed. Fascin-1 was highly expressed in tumor regions with low E-cadherin expression and co-localized with EMT-inducing markers such as TGF-β and Snail. Patients with postoperative recurrence showed significantly higher Fascin-1 scores than those without recurrence (P = 0.048). Double immunofluorescence confirmed an inverse relationship between Fascin-1 and E-cadherin expression. High Fascin-1 expression may serve as a potential marker for postoperative recurrence in thymic carcinoma and is closely associated with EMT. These findings suggest Fascin-1 as a promising prognostic biomarker and therapeutic target, although further studies with larger cohorts and functional analyses are warranted.

Cancer is one of the common diseases that affects people in the society, the prevalence of which has decreased somewhat in recent years. Various genetic and environmental factors play a role in the development and progression of cancer. NRF2 is a transcriptional regulator that controls the expression of antioxidant response element-related genes. It plays an important role in regulating the physiological and pathophysiological consequences of oxidant exposure. NRF2 is also responsible for regulating the expression of various cellular protective genes. NRF2 activity is regulated at multiple levels including protein stability, transcription, and post-transcription. The Keap1-Cul3-Rbx1 axis is the most prominent regulator of NRF2 activity. Apoptosis is a type of programmed cell death that is initiated by two intrinsic and extrinsic pathways. Caspases play a major role in this cell death pathway. Apoptosis pathway is related to many cells signaling pathways that are interconnected. Disruption in one pathway affects the other pathway. One of these signaling pathways is the NRF2 pathway, which is associated with apoptosis, which are interconnected and play an important role in disease prevention or progression. Therefore, in this study, we decided to investigate the relationship between NRF2 and apoptosis in cancer.

We used scanning electron microscopy to visualize the regeneration of goldfish scales on day 3 in vivo. Several vesicle-like structures of 100-700 nm diameter flowed onto the fibrous sheets in groups of spindle-shaped bodies arranged in the same direction. Transmission electron microscopy revealed that these structures were encircled by the lipid bilayer membrane. In addition, some had a small mass of high electron density. Scanning electron microscopic observations of specimens treated with bleach revealed particles of almost the same size as the observed electron-dense mass scattered between fibers, with a thickness of approximately 50 nm on day 3 of scale regeneration. The diameter of these particles increased by 5 times on day 14, sticking closely to the fibers. Furthermore, elemental analysis using electron probe microscopy showed that the particles were composed of calcium and phosphorous. These results confirmed that the spindle-shaped bodies and vesicle-like structures were osteoblasts and matrix vesicles, respectively.

This report presents the sixth case of chest wall epithelioid sarcoma (ES) in a 71-year-old Japanese man. The patient was incidentally diagnosed with a soft tissue tumor between the eighth and ninth ribs, presenting with an associated bone fracture and osteolytic change. Marginal resection followed by chest wall reconstruction was performed for a definitive diagnosis. Histopathological examination revealed multinodular growth associated with collagenous stroma, mimicking a necrotizing granulomatous process. Various tumor cells were observed, including epithelioid, spindle-shaped, and rhabdoid cells. Immunohistochemical analysis, conducted on trimmed tumor samples without decalcification, revealed positivity for cytokeratin AE1/AE3, vimentin, and CD34, as well as negativity for CK7, CK20, CD31, calretinin, and D2-40. INI expression was completely absent in tumor cells. The patient was diagnosed with ES. The chest wall is an unusual location for ES, and its diagnosis requires differentiation from other epithelioid neoplasms. This case highlights the importance of trimming tumor samples before decalcification to preserve antigenicity and ensure accurate immunohistochemistry analysis.

Anaplastic thyroid carcinoma (ATC) is a highly aggressive neoplasm with no effective treatment options. ATC with osteoclast-like giant cells (OGCs; ATC/OGC) is a rare variant of ATC, and no detailed pathological examination has been reported to date. A 59-year-old woman presented with sudden neck swelling. Computed tomography revealed a 5 cm tumor in the thyroid gland, which was surgically resected. Pathological examination revealed a diagnosis of ATC/OGC. The patient succumbed to progressive lung metastases within four months despite postoperative lenvatinib therapy. Immunohistochemical (IHC) examination indicated absence of PD-L1 expression in the OGCs, which comprised the majority of the tumor, with only sparse T cell infiltration in the area occupied by OGCs. Increased TGF-β expression was observed in the area containing OGCs, and both OGCs and infiltrating myeloid cells, including CD1a/CD11c-positive dendritic cells and CD68/CD163/CD204-positive macrophages, appeared to produce TGF-β. Pathological analysis of this case suggests that OGCs might be involved in immune suppression by secreting TGF-β, potentially serving as a critical cytokine in the immunosuppressive microenvironment of ATC/OGC. TGF-β-targeted therapy might be useful in the treatment of this very rare subtype of ATC.