We report a unique case of a 66-year-old man who was incidentally identified to have a mass in the thymus region by computerized tomography scan. CT revealed a well-defined 1.6 × 1 × 0.9 cm thymus mass with moderate uniform enhancement. Thoracoscopic thymectomy was performed, and the pathological diagnosis was primary glomus tumor of the thymus. There were no atypia or malignant histological features, and no primary tumors in other sites. To our knowledge, this is the first case of primary thymic glomus tumor reported in the literature.

OBJECTIVE: Angioleiomyoma, predominantly arising from the extremities, is a benign soft tissue tumor. Reports on its intracranial location are rare. We assessed clinical, radiological, and pathological features of intracranial angioleiomyoma (iALM) treated at our neurosurgical institution.
METHODS: We consecutively enrolled all patients with neuropathologically confirmed iALM treated at a single neurosurgical institution between 2013 and 2021. Clinical and imaging data were collected, and histological tissue sections were analyzed. A review of the literature on iALM was conducted.
RESULTS: Seven patients with iALM (four female) with a median age of 45 years (range: 32-76 years) were identified. In three cases, the lesion was found incidentally. In magnetic resonance imaging (MRI), all tumors were hypo- to isointense on T1-weighted, hyperintense on T2-weighted sequences, and gadolinium-enhancing. A strong FLAIR signal was seen in six patients. Surgery consisted of gross total resection in all cases without perioperative complications. Neuropathological staining was positive for smooth muscle actin (SMA) in all lesions. Mature smooth muscle cells arranged around blood vessels were typically observed. The Ki-67 index was ≤ 3%. The patients were discharged after a median of 6 days (range: 4-9 days). During a median follow-up time of 14 months (range: 4-41 months), no tumor recurrence occurred. In the current literature, 42 additional cases of iALM were identified.
CONCLUSIONS: Intracranial angioleiomyoma is a benign soft tissue tumor treated by gross total resection. Tumor morphology and positive staining for SMA lead to the neuropathological diagnosis.

BACKGROUND: Sex cord gonadal stromal tumors compose less than 10% of all testicular neoplasms and consist of a variety of histological subtypes. In 2016, the World Health Organization introduced a novel subtype, the myoid gonadal stromal tumor, that consists of spindle-shaped cells with immunohistologic features of muscle cells. Only few cases have been reported to date. Due to its rarity and owing to its only recent introduction, the current knowledge about myoid gonadal stromal tumor is limited, and particularly, appropriate clinical management is still ill-defined.
METHODS: A 47-year-old man of Caucasian descent presented with nonspecific scrotal discomfort. A roundish and well demarcated hypoechoic mass of 8.5 mm in diameter was detected in the cranial region of the left testis. Serum tumor marker levels were within normal ranges. Testis-sparing surgery revealed a 9-mm whitish, hard mass with sharp surgical margin. Histologically, the neoplasm consisted of microfibrillar tissue with spindle-shaped cells harboring elongated nuclei. Immunohistochemical work-up disclosed expression of desmin, small muscle actin, and S100 protein giving evidence for the myogenic nature of the neoplastic cells. There was no indication of malignancy, neither histologically nor clinically. Follow-up of 1 year was uneventful.
CONCLUSIONS: A literature survey revealed 22 previous cases of myoid gonadal stromal tumor. The median age was 37 years, the median size of the neoplasm was 20 mm, and there was no side-preponderance. Myoid gonadal stromal tumor is not much different from other subtypes of gonadal stromal tumors nor from testicular gem cell tumors regarding age and laterality; however, tumor size is smaller in myoid gonadal stromal tumors than in germ cell tumors. Although rarely performed so far, testis-sparing surgery probably constitutes an appropriate treatment of this neoplasm. Myoid gonadal stromal tumor represents an emerging novel entity of benign testicular new growths that caregivers of patients with testicular tumors should be aware of.

A role for substance P has been proposed in musculoskeletal fibrosis, with effects mediated through transforming growth factor beta (TGFβ). We examined the in vitro effects of substance P on proliferation, collagen secretion, and collagen deposition in rat primary dermal fibroblasts cultured in medium containing 10% fetal bovine serum, with or without TGFβ. In six-day cultures, substance P increased cell proliferation at concentrations from 0.0002 to 100 nM. TGFβ increased proliferation at concentrations from 0.0002 to 2 pg/mL, although higher concentrations inhibited proliferation. Substance P treatment alone at concentrations of 100, 0.2, and 0.00002 nM did not increase collagen deposition per cell, yet when combined with TGFβ (5 ng/mL), increased collagen deposition compared to TGFβ treatment alone. Substance P treatment (100 nM) also increased smooth muscle actin (SMA) expression at 72 h of culture at a level similar to 5 ng/mL of TGFβ; only TGFβ increased SMA at 48 h of culture. Thus, substance P may play a role in potentiating matrix deposition in vivo when combined with TGFβ, although this potentiation may be dependent on the concentration of each factor. Treatments targeting substance P may be a viable strategy for treating fibrosis where both substance P and TGFβ play roles.

OBJECTIVE: This study was carried out in the submandibular salivary glands (SSGs) of rats to demonstrate the effect of a ketogenic diet (KD) in comparison with dietary chitosan supplementation.
METHODS: Eighteen albino rats were randomly divided into three equal groups of six animals each. Rats in Group I were fed a balanced diet and considered controls. Meanwhile, those of Groups II and III were fed a KD, a balanced diet with high molecular weight chitosan, respectively. After 45 days, rats were euthanized, and the SSGs were dissected carefully for staining with hematoxylin and eosin (H&E), alpha-smooth muscle actin (α-SMA) immunohistochemical staining, and Congo red special stain. Quantitative data from α-SMA staining and Congo red staining were statistically analyzed using one-way ANOVA followed by Tukey\'s multiple comparisons post hoc test.
RESULTS: Regarding Congo red and α-SMA staining, one-way ANOVA revealed a significant difference between the three groups. For α-SMA staining and Congo red staining, Group II had the highest mean values of 91.41 ± 3.30 and 68.10 ± 5.04, respectively, while Group I had the lowest values of 56.13 ± 3.96 and 16.87 ± 2.19, respectively. Group III had mean values of 60.70 ± 3.55 for α-SMA and 19.50 ± 1.78 for Congo red. Tukey\'s multiple comparisons post hoc test revealed significant differences between groups I & II and between groups II & III (P < 0.05). Meanwhile, there was a nonsignificant difference between groups I and III (P > 0.05).
CONCLUSIONS: A KD has a deleterious effect on rats\' SSG whatever the test we used, and dietary chitosan supplementation ameliorates these damaging effects.

OBJECTIVE: Do different subtypes of superficial peritoneal endometriotic lesions exist, based on the presence and morphology of smooth muscle, collagen fibres and immune cell populations?
METHODS: A retrospective cohort study of 24 patients, from across the menstrual cycle, with surgically and histologically confirmed endometriosis. Immunofluorescence was used to delineate the CD10 stromal area of lesions (n = 271 lesions from 67 endometriotic biopsies), and then smooth muscle actin (SMA) positive tissue and immune cell populations (CD45+ and CD68+) were quantified within and adjacent to these lesions. Second harmonic generation microscopy was used to evaluate the presence and morphology of type-1 collagen fibres within and surrounding lesions.
RESULTS: Overall, immune cell numbers and the area of SMA and collagen within endometriotic lesions tended to be low, but a spectrum of presentations significantly varied, particularly in the adjacent tissue microenvironment, based on lesion locations, the morphology of endometriotic gland profiles, or both. Lesions in which collagen fibres formed well aligned capsules around the CD10+ stromal border were identified compared with lesions in which collagen fibre distribution was random. Considerable inter- and intra-patient variability in the morphology of SMA and collagen was observed within and surrounding lesions.
CONCLUSIONS: These data demonstrate considerable diversity in the presence of immune cells and morphology of SMA and collagen within, but even more so, surrounding endometriotic lesions, even within individual patients. This heterogeneity, especially within individual patients, presents a challenge to incorporating these cell and tissue types into any new endometriosis classification systems or prognostic approaches.

Donor cell-specific tissue-engineered (TE) implants are a promising therapy for personalized treatment of cardiovascular diseases, but current development protocols lack a stable longitudinal assessment of tissue development at subcellular resolution. As a first step toward such an assessment approach, in this study we establish a generalized labeling and imaging protocol to obtain quantified maturation parameters of TE constructs in three dimensions (3D) without the need of histological slicing, thus leaving the tissue intact. Focusing on intracellular matrix (ICM) and extracellular matrix (ECM) networks, multiphoton laser scanning microscopy (MPLSM) was used to investigate TE patches of different conditioning durations of up to 21 days. We show here that with a straightforward labeling procedure of whole-mount samples (so without slicing into thin histological sections), followed by an easy-to-use multiphoton imaging process, we obtained high-quality images of the tissue in 3D at various time points during development. The stacks of images could then be further analyzed to visualize and quantify the volume of cell coverage as well as the volume fraction and network of structural proteins. We showed that collagen and alpha-smooth muscle actin (α-SMA) volume fractions increased as normalized to full tissue volume and proportional to the cell count, with a converging trend to the final density of (4.0% ± 0.6%) and (7.6% ± 0.7%), respectively. The image analysis of ICM and ECM revealed a developing and widely branched interconnected matrix. We are currently working on the second step, that is, to integrate MPLSM endoscopy into a dynamic bioreactor system to monitor the maturation of intact TE constructs over time, thus without the need to take them out.

Exposure to particulate matter ≤ 2.5 µm (PM2.5) is a risk factor for many lung diseases. Although the toxicologic effects of PM2.5 on airway epithelium are well-described, the effects of PM2.5 on fibroblasts in the lung are less studied. Here, we sought to examine the effects of PM2.5 on the differentiation of fibroblasts into myofibroblasts. Although a single treatment of fibroblasts did not result in a change in collagen or the myofibroblast marker α-SMA, exposing fibroblasts to sequential treatments with PM2.5 at low concentrations caused a robust increase in these proteins. Treatment of fibroblasts with IMD0354, an inhibitor to nuclear factor κB, but not with an antagonist to aryl hydrocarbon receptor, abolished the ability of PM2.5 to induce myofibroblast differentiation. These data demonstrate that potential impact of PM2.5 to fibroblast activation and fibrosis and support the importance of utilizing low concentrations and varying exposure protocols to toxicologic studies.

Normalization of secretory activity and differentiation status of mesenchymal cells, including fibroblasts, is an important biomedical problem. One of the possible solutions is modulation of unfolded protein response (UPR) activated during fibroblast differentiation. Here, we investigated the effect of phytohormones on the secretory activity and differentiation of cultured human skin fibroblasts. Based on the analysis of expression of genes encoding UPR markers, abscisic acid (ABA) upregulated expression of the GRP78 and ATF4 genes, while gibberellic acid (GA) upregulated expression of CHOP. Evaluation of the biosynthetic activity of fibroblasts showed that ABA promoted secretion and synthesis of procollagen I and synthesis of fibronectin, as well as the total production of collagen and non-collagen proteins of the extracellular matrix (ECM). ABA also stimulated the synthesis of smooth muscle actin α (α-SMA), which is the marker of myofibroblasts, and increased the number of myofibroblasts in the cell population. On the contrary, GA increased the level of fibronectin secretion, but reduced procollagen I synthesis and the total production of the ECM collagen proteins. GA downregulated the synthesis of α-SMA and decreased the number of myofibroblasts in the cell population. Our results suggest that phytohormones modulate the biosynthetic activity of fibroblasts and affect their differentiation status.

BACKGROUND: Multinucleated giant cells (MGCs) in bladder carcinomas are poorly studied.
OBJECTIVE: To describe the function, morphogenesis, and origin of mononuclear and MGCs in urothelial carcinoma (UC) of the bladder in Bulgarian and French patients.
METHODS: Urothelial bladder carcinomas (n = 104) from 2016-2020 were analyzed retrospectively using immunohistochemical (IHC) and histochemical stain examination. Giant cells in the bladder stroma were found in 35.6% of cases, more often in high-grades.
RESULTS: We confirm that MGCs in the mucosa in UC of the bladder were positive for both mesenchymal and myofibroblast markers (vimentin, smooth muscle actin, Desmin, and CD34) and the macrophage marker CD68. Furthermore, IHC studies revealed the following profile of these cells: Positive for p16; negative for epithelial (CK AE1/AE3 and GATA-3), vascular (CD31), neural (PS100 and C-KIT), cambial, blastic (CD34-blasts and C-KIT), and immune markers (IG G, immunoglobulin G4, and PD-L1); no proliferative activity, possess no specific immune function, and cannot be used to calculate the Combined Positive Score scale.
CONCLUSIONS: In conclusion, the giant stromal cells in non-tumor and tumor bladder can be used as a characteristic and relatively constant, although nonspecific, histological marker for chronic bladder damage, reflecting the chronic irritation or inflammation. Likewise, according to the morphological and IHC of the mono- and multinucleated giant cells in the bladder, they are most likely represent telocytes capable of adapting their morphology to the pathology of the organ.