Secretome of Stem Cells: Roles of Extracellular Vesicles in Diseases, Stemness, Differentiation, and Reprogramming

Increasing evidence suggests that stem cells or stem cell-derived cells may contribute to tissue repair, not only by replacing lost tissue but also by delivering complex sets of secretory molecules, called secretomes, into host injured tissues. In recent years, extracellular vesicles (EVs) have gained much attention for their diverse and important roles in a wide range of pathophysiological processes. EVs are released from most types of cells and mediates cell–cell communication by activating receptors on target cells or by being taken up by recipient cells. EVs, including microvesicles and exosomes, encapsulate and carry proteins, nucleic acids, and lipids in the lumen and on the cell surface. Thus, EV-mediated intercellular communication has been extensively studied across various biological processes. While a number of investigations has been conducted in different tissues and body fluids, the field lacks a systematic review on stem cell-derived EVs, especially regarding their roles in stemness and differentiation. Here, we provide an overview of the pathophysiological roles of EVs and summarize recent findings focusing on EVs released from various types of stem cells. We also highlight emerging evidence for the potential implication of EVs in self-renewal, differentiation, and reprograming and discuss the benefits and limitations in translational approaches.

Morule-like features in pulmonary adenocarcinoma associated with epidermal growth factor receptor mutations: two case reports with targeted next-generation sequencing analysis

Morules, or morule-like features, can be identified in benign and malignant lesions in various organs. Morular features are unusual in pulmonary adenocarcinoma cases with only 26 cases reported to date. Here, we describe two cases of pulmonary adenocarcinoma with morule-like features in Korean women. One patient had a non-mucinous-type adenocarcinoma in situ and the other had an acinarpredominant adenocarcinoma with a micropapillary component. Both patients showed multiple intra-alveolar, nodular, whorled proliferative foci composed of atypical spindle cells with eosinophilic cytoplasm. Targeted next-generation sequencing was performed on DNA extracted from formalin-fixed paraffin-embedded samples of the tumors. Results showed unusual epidermal growth factor receptor (EGFR) mutations, which are associated with drug resistance to EGFR tyrosine kinase inhibitors, revealing the importance of identifying morule-like features in pulmonary adenocarcinoma and the need for additional study, since there are few reported cases.

Human Papillomavirus–Related Multiphenotypic Sinonasal Carcinoma with Late Recurrence

No abstract available.

Adenocarcinoma Arising in an Ectopic Hamartomatous Thymoma with HER2 Overexpression

No abstract available.

Combined Adenosquamous and Large Cell Neuroendocrine Carcinoma of the Gallbladder

Large cell neuroendocrine carcinoma (LCNEC) of the gallbladder is extremely rare and usually combined with other type of malignancy, mostly adenocarcinoma. We report an unusual case of combined adenosquamous carcinoma and LCNEC of the gallbladder in a 54-year-old woman. A radical cholecystectomy specimen revealed a 4.3×4.0 cm polypoid mass in the fundus with infiltration of adjacent liver parenchyma. Microscopically, the tumor consisted of two distinct components. Adenosquamous carcinoma was predominant and abrupt transition from adenocarcinoma to squamous cell carcinoma was observed. LCNEC showed round cells with large, vesicular nuclei, abundant mitotic figures, and occasional pseudorosette formation. The patient received adjuvant chemotherapy. However, multiple liver metastases were identified at 3-month follow-up. Metastatic nodules were composed of LCNEC and squamous cell carcinoma components. Detecting LCNEC component is important in gallbladder cancer, because the tumor may require a different chemotherapy regimen and show early metastasis and poor prognosis.

Hyalinizing Cholecystitis and Associated Carcinoma: A Case Report

No abstract available.

Comparison of the Mismatch Repair System between Primary and Metastatic Colorectal Cancers Using Immunohistochemistry

BACKGROUND: Colorectal cancer (CRC) is one of the most common malignancies worldwide. Approximately 10%–15% of the CRC cases have defective DNA mismatch repair (MMR) genes. Although the high level of microsatellite instability status is a predictor of favorable outcome in primary CRC, little is known about its frequency and importance in secondary CRC. Immunohistochemical staining (IHC) for MMR proteins (e.g., MLH1, MSH2, MSH6, and PMS2) has emerged as a useful technique to complement polymerase chain reaction (PCR) analyses. METHODS: In this study, comparison between the MMR system of primary CRCs and paired liver and lung metastatic lesions was done using IHC and the correlation with clinical outcomes was also examined. RESULTS: Based on IHC, 7/61 primary tumors (11.4%) showed deficient MMR systems, while 13/61 secondary tumors (21.3%) showed deficiencies. In total, 44 cases showed proficient expression in both the primary and metastatic lesions. Three cases showed deficiencies in both the primary and paired metastatic lesions. In 10 cases, proficient expression was found only in the primary lesions, and not in the corresponding metastatic lesions. In four cases, proficient expression was detected in the secondary tumor, but not in the primary tumor. CONCLUSIONS: Although each IHC result and the likely defective genes were not exactly matched between the primary and the metastatic tumors, identical results for primary and metastatic lesions were obtained in 77% of the cases (47/61). These data are in agreement with the previous microsatellite detection studies that used PCR and IHC.

Extensive silicone lymphadenopathy after breast implant insertion mimicking malignant lymphadenopathy

Silicone implants are widely used in aesthetic and reconstructive breast surgery. Silicone lymphadenopathy is a well-known rare complication of implant insertion. Silicone leakage from a rupture or silicone bleeding can accumulate in lymph nodes. Foreign body reactions in the affected lymph nodes may be misdiagnosed as metastasis or malignant lymphadeno pathy upon initial presentation if silicone lymphadenopathy is not considered in the initial diagnosis. We report a case of siliconoma with extensive involvement of multiple lymph nodes mimicking malignant features to emphasize that clinicians should carefully evaluate each patient's medical history and disease status during differential diagnosis.

Extensive silicone lymphadenopathy after breast implant insertion mimicking malignant lymphadenopathy

Silicone implants are widely used in aesthetic and reconstructive breast surgery. Silicone lymphadenopathy is a well-known rare complication of implant insertion. Silicone leakage from a rupture or silicone bleeding can accumulate in lymph nodes. Foreign body reactions in the affected lymph nodes may be misdiagnosed as metastasis or malignant lymphadeno pathy upon initial presentation if silicone lymphadenopathy is not considered in the initial diagnosis. We report a case of siliconoma with extensive involvement of multiple lymph nodes mimicking malignant features to emphasize that clinicians should carefully evaluate each patient's medical history and disease status during differential diagnosis.

Does Polymerase Chain Reaction of Tissue Specimens Aid in the Diagnosis of Tuberculosis?

BACKGROUND: Mycobacterial culture is the gold standard test for diagnosing tuberculosis (TB), but it is time-consuming. Polymerase chain reaction (PCR) is a highly sensitive and specific method that can reduce the time required for diagnosis. The diagnostic efficacy of PCR differs, so this study determined the actual sensitivity of TB-PCR in tissue specimens. METHODS: We retrospectively reviewed 574 cases. The results of the nested PCR of the IS6110 gene, mycobacterial culture, TB-specific antigen-induced interferon-γ release assay (IGRA), acid-fast bacilli (AFB) staining, and histological findings were evaluated. RESULTS: The positivity rates were 17.6% for PCR, 3.3% for the AFB stain, 22.2% for mycobacterial culture, and 55.4% for IGRA. PCR had a low sensitivity (51.1%) and a high specificity (86.3%) based on the culture results of other studies. The sensitivity was higher (65.5%) in cases with necrotizing granuloma but showed the highest sensitivity (66.7%) in those with necrosis only. The concordance rate between the methods indicated that PCR was the best method compared to mycobacterial culture, and the concordance rate increased for the methods using positive result for PCR or histologic features. CONCLUSIONS: PCR of tissue specimens is a good alternative to detect tuberculosis, but it may not be as sensitive as previously suggested. Its reliability may also be influenced by some histological features. Our data showed a higher sensitivity when specimens contained necrosis, which indicated that only specimens with necrosis should be used for PCR to detect tuberculosis.

Morphometric Analysis of Thyroid Follicular Cells with Atypia of Undetermined Significance

BACKGROUND: Atypia of undetermined significance (AUS) is a category that encompasses a heterogeneous group of thyroid aspiration cytology. It has been reclassified into two subgroups based on the cytomorphologic features: AUS with cytologic atypia and AUS with architectural atypia. The nuclear characteristics of AUS with cytologic atypia need to be clarified by comparing to those observed in Hashimoto thyroiditis and benign follicular lesions. METHODS: We selected 84 cases of AUS with histologic follow-up, 24 cases of Hashimoto thyroiditis, and 26 cases of benign follicular lesions. We also subcategorized the AUS group according to the follow-up biopsy results into a papillary carcinoma group and a nodular hyperplasia group. The differences in morphometric parameters, including the nuclear areas and perimeters, were compared between these groups. RESULTS: The AUS group had significantly smaller nuclear areas than the Hashimoto thyroiditis group, but the nuclear perimeters were not statistically different. The AUS group also had significantly smaller nuclear areas than the benign follicular lesion group; however, the AUS group had significantly longer nuclear perimeters. The nuclear areas in the papillary carcinoma group were significantly smaller than those in the nodular hyperplasia group; however, the nuclear perimeters were not statistically different. CONCLUSIONS: We found the AUS group to be a heterogeneous entity, including histologic follow-up diagnoses of papillary carcinoma and nodular hyperplasia. The AUS group showed significantly greater nuclear irregularities than the other two groups. Utilizing these features, nuclear morphometry could lead to improvements in the accuracy of the subjective diagnoses made with thyroid aspiration cytology.

Taste Sensation in Drosophila melanoganster / 한양의대학술지

Animals find nutritious foods to survive, while avoiding aversive and toxic chemicals through the chemosensory faculties of olfaction and taste. The olfaction is comparatively well characterized, but the studies of taste are only recently developing since after 2000. Genetic, immunohistochemistry, and electrophysiological studies with knock-out transgenic mice opened up the taste field in mammals. Taste in insects has been only recently been studied after mammalian taste receptors were identified. Flies also discriminate the differences of sweet, salty and sour food, while being able to detect and reject potential foods contaminated with toxins or detrimental chemicals. These discriminatory abilities indicate that flies house basic taste receptors in their taste organs like humans. For the last decade, the sweet and bitter gustatory receptors in Drosophila have been characterized. In this review, we compare the taste anatomy between humans and insects. We also introduce five canonical taste sensations in Drosophila. In addition, we introduce new taste repertoires, that fruit flies can sense water and fatty acids as well as the carbonation buffer in beverage. These studies on simple model organisms will open up a new potential for scientists to further investigate these characteristics in vertebrates.

Phosphorylated Akt and Phosphorylated mTOR Expression in Breast Invasive Carcinomas: Analysis of 530 Cases / 한국유방암학회지

PURPOSE: The phosphatidylinositol 3-kinase (PI3K)/Akt/mammalian target of rapamycin (mTOR) pathway has a central role in regulation of cell proliferation, differentiation, motility and survival. This pathway has recently generated great interest because its elements are, potentially, novel targets for the treatment of various malignancies, including breast cancer. METHODS: Using tissue microarray sections of breast carcinoma, we performed immunohistochemical studies using antibodies against the phosphorylated forms of Akt (p-Akt) and mTOR (p-mTOR) in 530 invasive breast carcinomas and 30 ductal carcinomas in situ (DCIS). We investigated possible associations between expression of these proteins and clinicopathologic characteristics and disease outcomes. RESULTS: In 530 invasive carcinomas, weak and strong expression of p-Akt was observed in 180 (34.0%) and 288 (54.3%) cases, respectively. The expression of p-Akt was associated with expression of estrogen receptors (ER) (p=0.045), progesterone receptors (PR) (p=0.003), lymph node metastasis (p<0.001) and cancer stage (p=0.027). Weak and strong expression of p-mTOR was found in 136 (25.7%) and 207 (39.1%) cases, respectively. The mTOR pathway was more frequently activated in DCIS than in invasive breast carcinoma (p=0.001). p-mTOR expression was associated with expression of ER (p=0.040), PR (p=0.009), tumor size (p<0.001), and stage (p=0.002). In a univariate analysis, strong expression of p-Akt was associated with longer disease-free survival (DFS). In a multivariate analysis, neither p-Akt nor p-mTOR was associated with DFS. CONCLUSION: The PI3K/Akt/mTOR pathway is active in DCIS as well as in invasive carcinoma of the breast. Our study also suggests that the PI3K/Akt/mTOR pathway is influenced by ER rather than erbB-2, and that this pathway may contribute more to cancer pathogenesis in ER-positive tumors.

Gliosarcoma with Components of Anaplastic Oligodendroglioma and Unclassifiable Spindle Cells: A Case Report

Gliosarcoma is a distinct disease entity that is characterized by a biphasic tissue pattern with alternating areas displaying glial and mesenchymal differentiation. The tumor in our case was a rare morphologic variant of gliosarcoma with components of anaplastic oligodendroglioma and unclassifiable spindle cells. Spindle cells showed CD34 and S-100 protein immunoreactivity, which was possibly related to peripheral nerve sheath differentiation. This unique feature has not been described previously and so this case expands the spectrum of possible divergent mesenchymal differentiation, and it lends support to pluripotential stem cells being the origin of this tumor.

Fine Needle Aspiration Cytology of Extranodal Marginal Zone B cell Lymphoma with Abundant Plasma Cells and Eosinophilic Histiocytes in Parotid Gland / 대한세포병리학회지

The authors present the fine needle aspiration cytology (FNAC) cytologic findings of a case of extranodal marginal zone B cell lymphoma (MZBCL), which featured abundant plasma cells and eosinophilic histiocytes arising in both parotid glands. A 49-year-old female presented with palpable masses in both parotid glands. She had been suffering from systemic lupus erythematosus and rheumatoid arthritis. The lesions were evaluated by FNAC and smears showed a small number of clusters of oncocytic cells with abundant eosinophilic granular cytoplasm and small nuclei, intermixed with small to medium-sized lymphoid cells containing round to lobulated nuclei, which suggested Warthin's tumor. Some of lymphoid cells had a plasmacytoid appearance, and some scattered large cells contained a large amount of eosinophilic cytoplasm. Bilateral superficial parotidectomy was performed and a histopathologic study indicated MZBCL with abundant plasma cells, intermixed with eosinophilic histiocytes. The presence of oncocytic cells and a mixture of lymphoid and plasma cells indicates Warthin's tumor, but the cytologic features of a relatively monotonous small to medium-sized lymphoid infiltrate suggest the possibility of MZBCL in the clinical setting of an FNAC study performed on a patient suffering from a connective tissue disease.

Metastatic Medullary Carcinoma of Thyroid to Breast; A Case Initially Diagnosed as Primary Invasive Lobular Carcinoma: A Case Report

Metastasis to the breast from medullary carcinoma of the thyroid is extremely rare. We report a case of metastatic medullary carcinoma of the thyroid which presented as multiple breast masses with ipsilateral axillary lymphadenopathy in a 48-year-old woman. Six years ago, she underwent total thyroidectomy and neck dissection because of palpable neck masses, with a diagnosis of medullary thyroid carcinoma. Histological features of breast masses showed single- file or linear-cord arrangements, with plasmacytoid appearance, and the initial diagnosis was invasive lobular carcinoma. She underwent modified radical mastectomy. The tumor cells were diffusely positive for E-cadherin, calcitonin and thyroid transcription factor-1 (TTF-1) and were metastatic medullary carcinoma of thyroid. In the patients with a history of medullary carcinoma of the thyroid, a careful examination is necessary for a breast mass composed of solid and cord-like clusters of small round to ovoid cells with plasmacytoid appearance. Immunohistochemical staining for E-cadherin, calcitonin and TTF-1 could be helpful for differential diagnosis.