Histopathology. (a) Histology of the primary CoM in 1990 demonstrated a mixed cell type with both spindle cells and epithelioid cells. (H&E stain, original magnification 40x). (b) Histology of the recurrence in 2011 demonstrated a similar mixed cell type, with mitoses, no ulceration and no vessel invasion. (H&E stain, original magnification 40x). (c) The subcutaneous nodule in 2015 demonstrated similarities to the lesion from 2011 in cell type, cell size and cellular configuration. (H&E stain, original magnification 40x). In 2011, 21 years after treatment for the primary lesion, the patient returned to our center with a nodular lesion in the superior fornix of the right eye, suspicious for recurrence of the CoM (Figure 2). Earlier, no abnormalities had been noticed by the patient. A CT scan showed a preseptal lesion and biopsy proved it to be a CoM. A total orbital exenteration (with removal of the globe, conjunctiva, and eyelids) was performed and histology of the specimen showed radical excision of the melanoma with widespread XXX (Figure 1).
Histopathology. We have evaluated 137 whole glomeruli. Of each glomerulus, three to five PAS-stained cross-sections were scored. A total of 2232 glomerular quadrants were each assigned to one of the four categories: normal, collaps- ing lesion, “typical” FSGS, and advanced sclerosis (Fig. 1). In 1541 quadrants, we saw a normal glomerular tuft (69%), 30 quadrants showed pure collapse with epithe- lial cell proliferation (hyperplasia) (1.5%), 588 quadrants showed “typical” FSGS lesions with segmental collapse, adhesions, foam cells, ECM accumulation, and variable epithelial cell swelling and hyperplasia (26%), and 73 quadrants were affected by advanced sclerosis (3.5%). Lesions of all categories could be located anywhere in the glomerulus (perihilar, at the tubular pole, or elsewhere). Within a single glomerulus, affected quadrants were sometimes assigned to different categories. In these cases, it often turned out that in such a glomerulus there was one confluent lesion with different morphology depending on the plane of sectioning. Glomeruli in the juxtamedullary half of the cortex were more frequently affected (38.4% of quadrants demonstrating FSGS lesions) than the more peripherally located glomerli (23.9% involved). Over- all, lesions showed a wide morphologic spectrum with at the one end collapse and prominent epithelial cell pro- liferation and at the other end sclerosis without promi- nent hypercelularity. Morphologic appearance of lesions was presumibly related to the age/developmental stage of the lesions. We focused on the lesions with prominent epithelial cell proliferation to study the relative role of podocytes and PECs. We studied the phenotype of epithelial cells in Bow- man’s space using consecutive sections and double stainings. We investigated the expression of markers specific for podocytes (synaptopodin, CD10, vimentin, and VEGF), PECs (CK8, Pan-cadherin, and PAX-2), macrophages (CD68), and myofibroblasts [a-smooth muscle actin (a-SMA)]. In both normal and affected glomeruli, we observed a uniform staining of the PECs lining Xxxxxx’x capsule for PAX-2 and Pan-cadherin. In glomeruli of normal control kidney tissue and in nonaffected glomeruli of our patient, CK8 staining was generally faint or absent (not shown). In our pa- tient, in all glomeruli with FSGS lesions, cells lining Xxxxxx’x capsule were segmentlly CK8-positive. No- tably, in our patient also in some glomeruli without FSGS lesions (serial sections were examined) we ob- served strong CK8 posi...
Histopathology. A similar procedure was followed for the histopathological diagnoses: previous diagnoses made by the Italian pathologists at Deparment of Human Pathology and Oncology, University of Siena, according to Vienna classification (Table 2), on at least 4 samples per case, were confirmed by the same pathologists on the same slides. These slides were then sent to Japanese pathologists at National Cancer Center in Tokyo, without any comments; the Japanese pathologists sent their diagnoses back to the pathologists in Siena. Reproducibility was checked and totally reached among histopathologists in Italy and in Japan respectively. Endoscopic diagnoses from Italy and Japan were evaluated for agreement-disagreement. Japanese endoscopic diagnoses were matched with Japanese histopathological diagnoses, and Italian endoscopic diagnoses were matched with Italian histopathological diagnoses. Finally, Japanese histopathological diagnoses were matched with Italian histopathological diagnoses. Data were submitted to statistical analysis.
Histopathology. In this deliverable, the results of the 12-months interim histopathological analyses of the chronic study obtained with cerium dioxide are described. Exposure-related microscopic changes were observed in the nasal cavity, larynx, lung, tracheobronchial and mediastinal lymph nodes. Nasal cavity The presence of (multi)focal intracytoplasmic eosinophilic globules within the olfactory epithelium was increased in incidence and grade in the 3 mg/m³ CeO2 exposure group (9/10; 5/10 very slight, 3/10 slight, 1/10 moderate) as compared to the clean air control (6/10; 5/10 very slight, 1/10 slight). A similar trend was observed for eosinophilic globules in the respiratory epithelium. The incidence in the clean air group 40 was 5/10 (all very slight) whereas 9/10 (7/10 very slight, 2/10 slight) females in the high dose group were affected (table 1). Although the difference between the control and CeO2 high-dose test group was statistically not significant, the increase in incidence and severity of this change in both types of epithelium is considered to be exposure-related. The same is true for (multi)focal very slight subepithelial (mixed) inflammatory cell infiltration which occurred in 3/10 and 7/10 females in the low and high dose groups, respectively. Table 1 Summary of histological changes in the nasal cavity and in the larynx Grading: 1, minimal; 2, slight; 3, moderate; 4, severe; 5, very severe Further exposure-related findings such as (multi)focal very slight accumulation of particle- laden macrophages within the NALT (nasal mucosa-associated lymphoid tissue) and multifocal very slight amounts of intraepithelial (intracytoplasmic) particles were diagnosed in all (10/10) animals of the high dose group. Occasional particles were seen not only in the respiratory and olfactory epithelium, but also in epithelial cells of the submucosal glands (Xxxxxx’x glands). Incidental findings in the nasal cavity which were considered to be unrelated to particle exposure included dilatation of submucosal glands, mucous cell hyperplasia, subepithelial mononuclear cell infiltration and subepithelial mineralization and were seen in up to 3/10 animals in both test groups. Larynx In 4/10 animals of the 3 mg/m³ CeO2 high exposure test group, (multi)focal subepithelial accumulation of particle-laden macrophages (3/10 very slight, 1/10 slight) was observed as exposure-related finding (table 1). Spontaneous findings included very slight to slight subepithelial mononuclear cell infiltra...
