Herein, we report a rare case of pleural epithelioid malignant mesothelioma with a prominent myxoid stroma. To date, detailed morphological or molecular pathological findings have not been reported for this type of tumor. Hence, we aimed to describe the cytological, histological, immuno-cytohistological, electron-microscopic, and molecular pathological findings using fluorescence in situ hybridization (FISH) in such a case. The patient was a male in his mid-sixties with a history of asbestos exposure and had originally visited the hospital with a persistent cough and fever. Chest radiography revealed left pleural effusion, and laboratory examination revealed a high titer for hyaluronic acid in the effusion. Additionally, computed tomography revealed diffuse multinodular or cystic lesions in the left parietal pleura, and pleural effusion cytology revealed large epithelioid cells with mild nuclear atypia, which were considered reactive mesothelial cells. Cytologically, Giemsa staining revealed that these cells harbored variously sized intracytoplasmic vacuoles that were Alcian-blue-positive, suggesting hyaluronan production. Biopsy revealed large epithelioid cells that loosely proliferated against a prominent myxoid background. These cells were immuno-positive for calretinin, Wilms\' tumor 1, D2-40, vimentin, and cytokeratin AE1/AE3 but not for carcinoembryonic antigen, Ber-EP4, or desmin. BRCA 1 associated protein 1 immunostaining showed nuclear loss, and FISH showed homozygous deletion of cyclin-dependent kinase inhibitor 2A (p16) on chromosome 9p21. Based on these findings, the lesion was diagnosed as an epithelioid mesothelioma with a prominent myxoid stroma. Electron-microscopy demonstrated a dense microvillus pattern on the surface of the tumor cells, indicating a mesothelial cell origin, and variously sized vacuoles in the cytoplasm, confirming the presence of intracytoplasmic vacuoles demonstrated on cytology. The tumor tissues obtained during surgery harbored prominent myxoid stroma, which proved that the present tumor was consistent with this type of mesothelioma. After informed consent was obtained, the patient and family wished for total resection of the tumor and postoperative chemotherapy, and the patient eventually died eight months after surgery.

Basal cell carcinoma (BCC) is the most common skin cancer. Skin cancers may present either as a non-invasive tumor or an invasive malignancy. The terminology of carcinoma in situ is used when the tumor is either just limited to epidermis or not present as single cells or nests in the dermis. However, currently the terminology superficial BCC is inappropriately used instead of BCC in situ when the skin cancer is limited to epidermis. In this study we compare the pathologic changes of superficial, nodular, and infiltrative BCCs using electron microscopy to identify the ultrastructural characteristics and validate the previously proposed terminology. Three cases of BCC (superficial BCC, nodular BCC, and infiltrative BCC) diagnosed by dermatopathologists at our institute were selected for review. Paraffin block tissues from these cases were sent for electron microscopy studies which demonstrated disruption of basal lamina in both nodular and infiltrative type of BCC, while it remains intact in BCC superficial type after extensive examination. Therefore, similar to other in situ skin cancers, there is no invasion of the neoplasm in superficial BCC into the dermis. Hence, the older term superficial BCC should be appropriately replaced with the newer terminology BCC in situ.

UNASSIGNED: Klinefelter Syndrome (KS) is a sex chromosomal syndrome usually with an extra X chromosome (47, XXY) in males, which has various phenotype (mosaicism 47, XXY/46, XY, or more chromosomes 48, XXXY, 49, XXXXY) and clinical features, including eunuchoid body proportions, abnormally long legs and arm span, gynecomastia, ynecomastia, absent or decreased facial and pubic hair, small hyalinized testes, small penis, below-normal verbal intelligence quotient, and learning difficulties. At present, there are no studies on the correlation between the clinical characteristics of patients with KS and the ultrastructural changes of intracellular organelles in testicular tissue in China.
UNASSIGNED: Here we report the ultrastructure manifestation of the testis tissues in a KS patient with hypogonadism and androgen deficiency, to find a relationship between ultrastructural changes of organelles and spermatogenic dysfunction, clinical features, timing of surgery and metabolic abnormalities. It has been shown that the spermatocytes are absent and the ultrastructure of Sertoli cells and Leydig cells is obviously abnormal, which may lead to spermatogenic dysfunction, androgen deficiency, impaired glucose tolerance (IGT), and abdominal fat accumulation.
UNASSIGNED: Based on the European Academy of Andrology (EAA) Gudilines on Klinefelter Syndrome, this study conducted a retrospective study on the diagnosis and treatment of one adult patient with KS, aiming to provide a standardized diagnosis and treatment for patients with KS. This study is also highly concerned with the correlation between the ultrastructural changes of target organs and clinical symptoms.

A case of poorly cohesive NOS gastric carcinoma, characterised by high-grade tumour-associated tissue eosinophilia (TATE), is studied by transmission electron microscopy. Eosinophil clustering around single tumour cells constituted a recurrent ultrastructural hallmark. Some eosinophils were in intimate contact with tumour cells and exhibited extracellular trap cell death (ETosis): a non-apoptotic cell death process, recently described in non-neoplastic, eosinophil-associated diseases. Discharge of chromatin material and specific granules, due to eosinophil ETosis, was polarised towards single tumour cells that showed various degrees of cytopathogenic changes. Our data suggest that eosinophil ETosis may exert an antitumoural activity in gastric cancer.
CONCLUSIONS: A recent meta-analysis reported that TATE is a histopathological marker of favourable prognosis, particularly in patients with gastrointestinal cancer.Experimental studies have shown that eosinophils may exert antitumour activity through discharge of their highly cytotoxic granular proteins.Our ultrastructural findings add novel mechanism insights for eosinophil antitumoural activity, providing morphologic evidence of eosinophil ETosis in association with single tumour cell injury.

BACKGROUND: Hashimoto\'s thyroiditis (HT) is an autoimmune disease exhibiting stromal fibrosis and follicular cell destruction due to lymphoplasmacytic infiltration. Besides deprecated analyses, histopathological approaches have not employed the use of electron microscopy adequately toward delineating subcellular-level interactions.
METHODS: Biopsies for ultrastructural investigations were obtained from the thyroids of five patients with HT after a thyroidectomy. Transmission electron microscopy (TEM) was utilized to study representative tissue specimens.
RESULTS: Examination indicated interstitial extravasated blood cells and a plethora of plasma cells, based on their subcellular identity landmarks. These antibody-secreting cells were profoundly spotted near follicular cells, fibroblasts, and cell debris entrenched in collagenous areas. Pathological changes persistently affected subcellular components of the thyrocytes, including the nucleus, endoplasmic reticulum (ER), Golgi apparatus, mitochondria, lysosomes, and other intracellular vesicles. Interestingly, significant endothelial destruction was observed, specifically in the larger blood vessels, while the smaller vessels appeared comparatively unaffected.
CONCLUSIONS: Our TEM findings highlight the immune-related alterations occurring within the thyroid stroma. The impaired vasculature component and remodeling have not been described ultrastructurally before; thus, further exploration is needed with regards to angiogenesis in HT in order to achieve successful prognostic, diagnostic, and treatment-monitoring strategies.

A biopsy of gastrocnemius muscle from a patient with mitochondrial encephalomyopathy with lactic acidosis and stroke-like episodes (MELAS) syndrome was studied histologically in semithin sections stained by hematoxylin-and-eosin (H&E) and toluidine blue, and ultrathin sections by transmission electron microscopy (TEM). H&E stain demonstrated typical ragged-red fibers (RRFs) and affected fibers in fascicles. Toluidine-blue stain showed an irregular meshwork in the center of RRFs. TEM demonstrated damaged myofibrils and variations in mitochondrial structure in RRFs and affected fibers. Dense mitochondria were compacted with cristae and pleomorphic electron-dense inclusions. Lucent mitochondria included paracrystalline inclusions with a parking lot appearance. At high magnification, the paracrystalline inclusions were composed of plates that paralleled and connected with mitochondrial cristae. These observations indicated that electron-dense granular and paracrystalline inclusions resulted from cristal degeneration and overlapping in mitochondria in MELAS syndrome.

Amelogenesis imperfecta (AI) is a heterogeneous group of genetic disorders of dental enamel. X-linked AI results from disease-causing variants in the AMELX gene. In this paper, we characterise the genetic aetiology and enamel histology of female AI patients from two unrelated families with similar clinical and radiographic findings. All three probands were carefully selected from 40 patients with AI. In probands from both families, scanning electron microscopy confirmed hypoplastic and hypomineralised enamel. A neonatal line separated prenatally and postnatally formed enamel of distinctly different mineralisation qualities. In both families, whole exome analysis revealed the intron variant NM_182680.1: c.103-3T>C, located three nucleotides before exon 4 of the AMELX gene. In family I, an additional variant, c.2363G>A, was found in exon 5 of the FAM83H gene. This report illustrates a variant in the AMELX gene that was not previously reported to be causative for AI as well as an additional variant in the FAM83H gene with probably limited clinical significance.

A case of poorly differentiated tubular gastric adenocarcinoma with tumor-associated tissue eosinophilia (TATE) is studied by light and electron microscopy, focusing on membrane interactions between eosinophils and tumor cells. 29.2% of the eosinophils in contact with tumor cells showed intact granules, 28.3% exhibited piecemeal degranulation (PMD), 40% were characterized by coexistence of PMD and compound exocytosis in the same granulocyte, whereas classical exocytosis was found in 2.5% of the eosinophils with PMD. Eosinophil Sombrero Vesicles (EoSVs), important tubulovesicular carriers for delivery of cytotoxic proteins from the specific granules during PMD, were also studied at the ultrastructural level. In activated eosinophils, EoSVs and specific granules with ultrastructural signs of degranulation were polarized toward tumor cells. Ultrastructural changes in paraptosis-like cell death, such as mitochondrial swelling, dilation of the nuclear envelope, cytoplasmic vacuoles, and nuclear chromatin condensation, but without margination of the chromatin, were observed in these tumor cells. Our data support the notion that eosinophils may exert an antitumoral role in gastric cancer. Finally, the case reported provides, for the first time, ultrastructural evidence of classical and compound exocytosis of eosinophils in the tumor stroma of human adenocarcinoma.

UNASSIGNED: What is the main observation in this case? The main observation of this case report is that blood flow-restricted exercise can cause myofibrils to have an aberrant wave-like appearance that is accompanied by irregular pockets of sarcoplasm in the intermyofibrillar space, while traditional forms of damage to the Z-discs and contractile elements are not as apparent. What insights does it reveal? Our findings indicate that blood flow restriction-mediated fluid pooling might cause alterations in skeletal muscle ultrastructure after exercise that might be directly related to myofibre swelling.
UNASSIGNED: The acute effects of blood flow-restricted (BFR) exercise training on skeletal muscle ultrastructure are poorly understood owing to inconsistent findings and the use of largely imprecise systemic markers for indications of muscle damage. The purpose of this study was to compare myofibrillar ultrastructure before and 30 min after normal and BFR resistance exercise using transmission electron microscopy in a single individual to evaluate the feasibility of this more nuanced approach. One apparently healthy male with 13 years of resistance exercise completed six sets of both BFR [30% of one-repetition maximum (1-RM)] and normal non-occluded (70% of 1-RM) unilateral angled leg press on the contralateral leg, as a control, after assessment of 1-RM 72 h before. Vastus lateralis muscle biopsies were collected before and 30 min after each exercise session. The lengths and widths of 250 sarcomeres and the sarcoplasmic area were assessed via 20 individual transmission electron photomicrographs. Analysis revealed that BFR training (1.769 ± 0.12 μm) increased sarcomere length when compared with normal exercise (1.64 ± 0.17 μm; P < 0.001), without differences in sarcomere width between conditions (BFR, 0.90 ± 0.26 μm; normal, 0.93 ± 0.27 μm; P = 0.172). Furthermore, there were no significant interaction (P = 0.168) or condition effects between BFR (25.98 ± 4.17%) and normal (27.3 ± 6.49%) resistance exercise for sarcoplasmic area (P = 0.229). Exercise also increased sarcoplasmic area within the myofibril (pre-exercise, 24.42 ± 5.13%; postexercise, 28.95 ± 5.92%) for both conditions (P = 0.001). This case study demonstrates a unique BFR training-induced alteration in myofibril ultrastructure that appeared wave like and was accompanied by intracellular abnormalities that appeared to be fluid pockets of sarcoplasm disrupting the surrounding myofibrils.

Spicules are mineral-based biocomposites skeletal structures that are widely distributed among phylogenetically distant groups of invertebrates (Porifera, Cnidaria, Mollusca, Echinodermata). Subepidermal spicules are formed under the ectodermal epithelium and are characterized for all groups except mollusks (Aplacophora, Polyplacophora, Bivalvia), their spicules are located on the surface of the body. However, one group of mollusks (Gastropoda: Heterobranchia) have unique subepidermal spicules that have never been detected above the ectodermal epithelium and similarly to those characterized for Porifera, Cnidaria and Echinodermata. Understanding subepidermal spicule formation in mollusks could help solve the question on the origin of spicules. Spicules in nudibranchs have been described for more than 150 years, yet ontogenetic dynamics of spicules have never been studied and the full mechanism of their formation remains unknown. Herein we investigate the spicule formation in different stages of postlarval development of the nudibranch Onchidoris muricata (O.F. Müller, 1776). For the first time, ontogenetic transformations of the spicule complex are described using experiments and different morphological methods. Our studies demonstrate that spicules of O. muricata form in the subepidermal space in early developmental stages immediately after veliger settlement. A single spicule forms inside a huge vacuole within a sclerocyte and remains there throughout the entire life of the specimen. Signs of spicule or sclerocyte migration under the epithelium in postlarval development was not found. Spicules only form during larval settlement, increasing only in size as development furthers. For the first time, spicule mineralization zones were detected at the tips of the spicules as well as the presence of collagen I in the overall composition of the spicules. Thus, our findings suggest that spicules form by an ectodermal cell that emerged under the ectodermal epithelium during the earliest stages of postlarval development.