The heterogeneous manifestations of granulomatosis with polyangiitis pose a challenge in diagnosis of this rare disease since virtually any organ can be affected, and radiologists should recognize ... Granulomatosis with polyangiitis (GPA) is an antineutrophil cytoplasmic antibody–associated vasculitis. It is an uncommon multisystem disease involving predominantly small vessels and is characteri...
Bone marrow mesenchymal stem/stromal cells (BM-MSCs) have immunoregulatory properties and have been used as immune regulators for the treatment of graft-versus-host disease (GVHD). Human dental tissue mesenchymal stem cells (DT-MSCs) constitute an attractive alternative to BM-MSCs for potential clinical applications because of their accessibility and easy preparation. The aim of this in vitro study was to compare MSCs from dental pulp (DP-MSCs), gingival tissue (G-MSCs), and periodontal ligament (PDL-MSCs) in terms of their immunosuppressive properties against lymphoid cell populations enriched for CD3+ T cells to determine which MSCs would be the most appropriate for in vivo immunoregulatory applications. BM-MSCs were included as the gold standard. Our results demonstrated, in vitro, that MSCs from DP, G, and PDL showed immunoregulatory properties similar to those from BM, in terms of the cellular proliferation inhibition of both CD4+- and CD8+-activated T-cells. This reduced proliferation in cell co-cultures correlated with the production of interferon-γ and tumor necrosis factor alpha (TNF-α) and the upregulation of programmed death ligand 1 (PD-L1) in MSCs and cytotoxic T-cell-associated Ag-4 (CTLA-4) in T-cells and increased interleukin-10 and prostaglandin E2 production. Interestingly, we observed differences in the production of cytokines and surface and secreted molecules that may participate in T-cell immunosuppression in co-cultures in the presence of DT-MSCs compared with BM-MSCs. Importantly, MSCs from four sources favored the generation of T-cell subsets displaying the regulatory phenotypes CD4+CD25+Foxp3+ and CD4+CD25+CTLA-4+. Our results in vitro indicate that, in addition to BM-MSCs, MSCs from all of the dental sources analyzed in this study might be candidates for future therapeutic applications.
12 January 2022 in European Journal of Histochemistry
Desmoplastic stroma (DS) and the epithelial-to-mesenchymal transition (EMT) play a key role in pancreatic ductal adenocarcinoma (PDAC) progression. To date, however, the combined expression of DS and EMT markers, and their association with variations in survival within each clinical stage and degree of tumor differentiation is unknown. The purpose of this study was to investigate the association between expression of DS and EMT markers and survival variability in patients diagnosed with PDAC. We examined the expression levels of DS markers alpha smooth muscle actin (α-SMA), fibronectin, and vimentin, and the EMT markers epithelial cell adhesion molecule (EPCAM), pan-cytokeratin, and vimentin, by immunohistochemistry using a tissue microarray of a retrospective cohort of 25 patients with PDAC. The results were examined for association with survival by clinical stage and by degree of tumor differentiation. High DS markers expression -α-SMA, fibronectin, and vimentin- was associated with decreased survival at intermediate and advanced clinical stages (p=0.006-0.03), as well as with both poorly and moderately differentiated tumor grades (p=0.01-0.02). Interestingly, the same pattern was observed for EMT markers, i.e., EPCAM, pan-cytokeratin, and vimentin (p=0.00008-0.03). High expression of DS and EMT markers within each clinical stage and degree of tumor differentiation was associated with lower PDAC survival. Evaluation of these markers may have a prognostic impact on survival time variation in patients with PDAC.
Objective: Mediastinal schwannomas are sometimes confused with other neoplasms during initial radiological studies, especially when there is a history of cancer in another area. In these cases, a more accurate analysis using computed tomography (CT) or even magnetic resonance (MRI) is required. Our study aimed to perform a retrospective analysis of the clinical and imaging features for a series of patients with mediastinal schwannomas that were confirmed by histology and immunohistochemistry. Results: We found eight patients, five men and three women, with an average age of 51 years for this study. The main signs and symptoms at diagnosis were chest pain, dyspnea, cough, and dysphagia. CT showed that the tumor was located in the posterior compartment of the chest in 7/8 cases. Tumors > 10 cm were more heterogeneous and showed cystic changes. All patients underwent posterolateral thoracotomy, and radiological follow-up showed no evidence of recurrence. Histological analysis was considered the gold standard to confirm diagnosis, along with at least one neurogenic IHC marker. In conclusion, mediastinal schwannomas are benign encapsulated tumors. According to CT, schwannomas > 10 cm show cystic degeneration more frequently. Posterolateral thoracotomy allows complete resection and is considered the surgical approach of choice.
Giant cell ependymoma of the filum terminale is a rare variant, generally manifested as a well-circunscribed intradural mass with an indolent biological behavior. We describe the case of a 48-year-old Mexican female who non-relevant past medical history, that developed a GCE of the filum terminale. Magnetic resonance imaging and computed tomography revealed the presence of an intra-axial tumor extending from L3 to L5 with extra-medullary invasion. Therefore the tumor was considered unresectable and only incisional biopsy was obtained, establishing the tentative diagnosis of a poorly differentiated neoplasia. A second evaluation of the case revealed the presence of numerous non-cohesive pleomorphic giant cells with intranuclear inclusions and broad eosinophilic cytoplasm, alternating with intermediate size cells with round, hyperchromatic nuclei and forming a perivascular pseudo-rosettes pattern. The ependymal phenotype was supported by light microscopy and corroborated by immunohistochemistry analysis. The patient was subsequently treated with radiotherapy 54Gy. She is alive after a 27-month follow-up, with residual disease, difficulty ambulating and pain. GCE of filum terminale may have an atypical clinical and radiological presentation, albeit with invasive characteristics and anaplasia on histologic analysis. However, its biological behavior is indolent and associated to longer survival. Due to the presence of giant cells, the differential diagnosis of other primary neoplasias at that site were considered, including paraganglioma, malignant peripheral nerve sheath tumors as well as metastatic malignant melanoma, adrenal carcinoma, thyroid gland carcinoma and urothelial carcinoma, that may all harbor giant cells.
Background: Macrofollicular variant of papillary thyroid carcinoma (MFV-PTC) is a rare subtype with histological features and an indolent clinical course that can be confused with nodular goiter or follicular adenoma. However, on rare occasions it may show more aggressive biological behavior. Only two cases of MFV-PTC with bone metastases have been reported previously. We describe the clinical-pathological characteristics of a man with MFV-PTC that developed femur metastasis. This the first case of MFV-PTC with femur metastases diagnosed histologically by means of an image-guided core needle biopsy in English literature. Case presentation: A 33-year-old man presented two years earlier with swelling in the right neck associated with weight loss and pain in the left knee. Neck ultrasonography showed hyperechogenic and hypogenic nodular images in the thyroid’s right lobe. A fine needle aspiration biopsy specimen was initially interpreted as nodular hyperplasia. A CT showed a large tumor involving right thyroid lobe with trachea and vascular structures displaced to the right, and a total thyroidectomy was performed. Subsequently, a MRI of the knee confirmed the presence of a destructive tumor in the femur. A guided core-needle biopsy of the knee tumor showed the presence of metastatic MFV-PTC. Re-assessment of the histology from thyroidectomy was also consistent with MFV-PTC. A whole-body 18F-FDG PET/CT showed presence of lesions in the left anterior costal arch, metaphysis of the left femur and in the sternum handle. Therefore, he received 200 mCi radioactive iodine, and 40 Gy of radiotherapy to left costal arches and knee, which decreased his symptoms. Currently, after 10 months of follow-up, the patient is alive with bone tumor activity. Conclusions: Our case supports the view that, on rare ocassions, MFV-PTC may show a more aggressive biological behavior than expected. The synchronous or asynchronous presence of one or more bone lesions, should raise the suspicion of metastasis. Given the suspicion, it is necessary to take a biopsy to confirm histologically. Only a careful analysis of the architectural and cytological characteristics of goiter or hyperplastic nodules will allow to recognize this rare variety of carcinoma.