Medication-related osteonecrosis of the jaw (MRONJ) is a major complication of bisphosphonate treatment in cancer patients, and its etiology is not completely clarified. The study’s goal is to find connections between the clinical and histopathological characteristics of osteonecrosis and bisphosphonates in a cohort of cancer patients who had osteonecrosis treated surgically. The retrospective study includes 51 patients of both sexes, aged 46 to 85 years, who underwent surgical treatment for MRONJ in two oral and maxillofacial surgery clinics (Craiova and Constanța). Demographic, clinical, and imaging data from the records of patients with osteonecrosis were analyzed. The surgical treatment removed the necrotic bone, and the harvested fragments were analyzed from a histopathological perspective. The histopathological examination data were evaluated and statistically processed to look for viable bone, granulation tissue, bacterial colonies, and inflammatory infiltrate. In the study groups, MRONJ was found particularly in the posterior regions of the mandible. Tooth extraction, but also periapical or periodontal infections, represented the trigger factors in most of the cases. The surgical therapy consisted of sequestrectomy or bone resection, and the histopathological examination of the fragments revealed osteonecrosis-specific features, such as the lack of bone cells, the development of an inflammatory infiltrate, and the existence of bacterial colonies. MRONJ in cancer patients receiving zoledronic acid is a severe complication that significantly lowers quality of life. Since these patients are not usually monitored by the dentist, they are identified in advanced stages of MRONJ. For these patients, thorough dental monitoring could reduce the incidence of osteonecrosis and its related complications.

Background: Telocytes (TCs) are a peculiar morphological type of stromal cells. They project long and moniliform telopodes, visible on various bidimensional sections. Originally regarded as “interstitial Cajal-like cells”, gastrointestinal TCs were CD34+. Further double-labelling studies found that colon TCs are negative for the expressions of the PDGFR-α and α-SMA. However, the TCs in colon were not distinguished specifically from endothelial cells (ECs), vascular or lymphatic. A combinational approach is important for accurate TC identification. Hence, we designed an immunohistochemical study of human colon to check whether ECs and CD34+ TCs express different markers. Methods: Immunohistochemistry was performed on archived paraffin-embedded samples of human colon (nine cases) for the following markers: CD31, CD34, CD117/c-kit and D2-40 (podoplanin). Results: A distinctive population of CD34+ TCs was found coating the myenteric ganglia. However, also perivascular cells and vascular ECs were CD34+. c-kit expression was equally found in interstitial Cajal cells (ICCs) and perivascular cells. The CD34 TCs did not express c-kit. As they were equally CD31- and D2-40- they were assessed as different from ECs. Conclusions: Testing specific markers of ECs, vascular and lymphatic, in the same tissues in which CD34+ TCs are found, is much more relevant than to identify TCs by transmission electron microscopy alone.

Impairment of the immune response in MRONJ (medication-related osteonecrosis of the jaws) is one of the still unclear etiopathogenic mechanisms of this condition encountered in cancer patients treated with bisphosphonates, with negative effects on the patient’s quality of life. The aim of the present study was to correlate the immune response with etiopathogenic factors via immunohistochemical evaluation of the maxillary tissues in zoledronic acid osteonecrosis. The retrospective study included a group of 51 patients with various types of cancers, diagnosed with stage 2 or 3 MRONJ at zoledronic acid and treated surgically. Immunohistochemical expressions of αSMA, CD3, CD4, CD8, CD20, CD79α, CD68, CD204, and tryptase were evaluated. Immunohistochemical markers expressions were statistically analyzed according to the duration of the treatment, the trigger factor, the location of the MRONJ, and the healing status. Analysis of the immune response included T lymphocytes, B lymphocytes, plasma cells, macrophages, and mast cells. The duration of treatment significantly influenced the immunohistochemical expression of most markers (p < 0.05). For an increasing trend in treatment duration, a decreasing trend in marker score was observed, suggesting an inverse correlation. The expression of the markers was different depending on the trigger factor, on MRONJ localization (maxilla/mandible), and the healing status, being more intense in patients cured per primam compared to those who had relapses. The patient’s immune response was negatively influenced by the duration of the treatment, the trigger factor, the location of the lesion in the mandible, and the recurrence of MRONJ.

Despite the numerous advances in tumor molecular biology and chemotherapy options, gastric adenocarcinoma is still the most frequent form of gastric cancer. One of the core proteins that regulates inter-cellular adhesion, E-cadherin plays important roles in tumorigenesis as well as in tumor progression; however, the exact expression changes and modulation that occur in gastric cancer are not yet fully understood. In an attempt to estimate if the synthesis/degradation balance matches the final membrane expression of this adhesion molecule in cancer tissue, we assessed the proportion of E-cadherin that is found in the Golgi vesicles as well as in the lysosomal pathway We utilized archived tissue fragments from 18 patients with well and poorly differentiated intestinal types of gastric cancer and 5 samples of normal gastric mucosa, by using high-magnification multispectral microscopy and high-resolution fluorescence deconvolution microscopy. Our data showed that E-cadherin is not only expressed in the membrane, but also in the cytoplasm of normal and tumor gastric epithelia. E-cadherin colocalization with the Golgian vesicles seemed to be increasing with less differentiated tumors, while co-localization with the lysosomal system decreased in tumor tissue; however, the membrane expression of the adhesion molecule clearly dropped from well to poorly differentiated tumors. Thus E-cadherin seems to be more abundantly synthetized than eliminated via lysosomes/exosomes in less differentiated tumors, suggesting that post-translational modifications, such as cleavage, conformational inactivation, or exocytosis, are responsible for the net drop of E-cadherin at the level of the membrane in more anaplastic tumors. This behavior is in perfect accordance with the concept of partial epithelial-to-mesenchymal transition (P-EMT), when the E-cadherin expression of tumor cells is in fact not downregulated but redistributed away from the membrane in recycling vesicles. Moreover, our high-resolution deconvolution microscopy study showed for the first time, at the tissue level, the presence of Lysosome-associated membrane glycoprotein 1 (LAMP1)-positive exosomes/multivesicular bodies being trafficked across the membranes of tumor epithelial cells. Altogether, a myriad of putative modulatory pathways is available as a treatment turning point, even if we are to only consider the metabolism of membrane E-cadherin regulation. Future super-resolution microscopy studies are needed to clarify the extent of lysosome/exosome exchange between tumor cells and with the surrounding stroma, in histopathology samples or even in vivo.

Background/Objectives: Adenomyosis (A) is a benign but invasive uterine condition frequently associated with structural changes in the uterine wall that may contribute to infertility. Methods: This is a retrospective study involving 140 patients: 100 diagnosed with primary infertility (PI) or secondary infertility (SI) and 40 in the control group. All patients were assessed using transvaginal two-dimensional, three-dimensional, and hysterosalpingo-contrast sonography (HyCoSy), performed in the early proliferative phase. Evaluated parameters included uterine dimensions, endometrial thickness, and characteristics of the junctional zone (JZ). Criteria such as JZmax > 5 mm or JZmax − JZmin > 5 mm, alongside other findings, supported the diagnosis of adenomyosis. Results: Patients with PI showed larger uterine longitudinal diameters, while SI patients had thicker JZ measurements. PI patients were significantly younger. Histopathological examination confirmed the presence of endometrial glands and periglandular stroma disrupting myometrial architecture, forming chronic lesions potentially linked to infertility. Conclusions: HyCoSy revealed variable depths of myometrial invasion by A, with some cases extending near the serosa. The chronic lesions found in histopathological examination were potentially linked to infertility.

Background/Objectives: Ectopic pregnancy (EP) remains a major cause of maternal morbidity. This study aimed to describe the clinical, ultrasonographic and histopathological features of EP, including changes following methotrexate (MTX) therapy. Methods: A retrospective analysis was conducted on 60 patients diagnosed with EP between 2018 and 2024. Clinical characteristics, serum β-hCG (beta-human chorionic gonadotropin) dynamics, treatment type, site-specific ultrasonographic features, and histopathological aspects were evaluated. Results: Extrauterine EPs accounted for 63.3% of cases, predominantly tubal ectopic pregnancy (T-EP), while uterine ectopic pregnancy represented 33.3%, including cesarean scar pregnancy (CSP) in 20%. Heterotopic pregnancy was identified in 3.3%. T-EP most frequently required surgical management, whereas MTX was effective in selected T-EP and CSP cases, as demonstrated by a ≥ 15% decline in serum β-hCG levels at 7 days. Transvaginal ultrasonography (TVUS) enabled accurate site-specific localization of ectopic implantation. Histopathological evaluation confirmed ectopic implantation and MTX-related changes in treated cases. Conclusions: Integrating clinical findings, β-hCG dynamics, and targeted TVUS allows accurate diagnosis and individualized management of EP, with histopathology providing definitive confirmation and insight into treatment-related changes.