Presence Of Multinucleated Giant Cells Research Articles

Trem2-expressing multinucleated giant macrophages are a biomarker of good prognosis in head and neck squamous cell carcinoma.

Patients with head and neck squamous cell carcinomas (HNSCC) often have poor outcomes due to suboptimal risk-management and treatment strategies; yet integrating novel prognostic biomarkers into clinical practice is challenging. Here, we report the presence of multinucleated giant cells (MGC) - a type of macrophages - in tumors from patients with HNSCC, which are associated with a favorable prognosis in treatment-naive and preoperative-chemotherapy-treated patients. Importantly, MGC density increased in tumors following preoperative therapy, suggesting a role of these cells in the anti-tumoral response. To enable clinical translation of MGC density as a prognostic marker, we developed a deep-learning model to automate its quantification on routinely stained pathological whole slide images. Finally, we used spatial transcriptomic and proteomic approaches to describe the MGC-related tumor microenvironment and observed an increase in central memory CD4 T cells. We defined an MGC-specific signature resembling to TREM2-expressing mononuclear tumor associated macrophages, which co-localized in keratin tumor niches.

Optical frequency domain imaging (OFDI) represents a novel technique for the diagnosis of giant cell arteritis.

Giant cell arteritis (GCA) is an inflammatory vascular disease in which prompt and accurate diagnosis is critical. The efficacy of temporal artery biopsy (TAB) is limited by 'skip' lesions and a delay in histological analysis. This first-in-man ex-vivo study aims to assess the accuracy of optical frequency domain imaging (OFDI) in diagnosing GCA. 29 TAB samples of patients with suspected GCA were submerged in 0.9% sodium chloride and an OFDI catheter was passed through the lumen to create cross-sectional images prior to histological analysis. The specimens were then preserved in formalin for histological examination. Mean intimal thickness (MIT) on OFDI was measured, and the presence of both multinucleate giant cells (MNGCs) and fragmentation of the internal elastic lamina (FIEL) was assessed and compared with histology, used as the diagnostic gold standard. MIT in patients with/without histological evidence of GCA was 0.425 mm (±0.43) and 0.13 mm (±0.06) respectively compared with 0.215 mm (±0.09) and 0.135 mm (±0.07) on OFDI. MIT measured by OFDI was significantly higher in patients with histologically diagnosed arteritis compared to those without (p = 0.0195). For detecting FIEL and MNGCs, OFDI had a sensitivity of 75% and 28.6% and a specificity of 100% and 77.3% respectively. Applying diagnostic criteria of MIT > 0.20 mm, or the presence of MNGCs or FIEL, the sensitivity of detecting histological arteritis using OFDI was 91.4% and the specificity 94.1%. OFDI provided rapid imaging of TAB specimens achieving a diagnostic accuracy comparable to histological examination. In-vivo imaging may allow imaging of a longer arterial section.

Xanthogranulomatous mastitis: a rare entity presenting with breast lump and mimicking fibroadenoma in a young female

Introduction and importance: Xanthogranulomatous mastitis is a rare chronic granulomatous inflammation of breast tissue, characterized by the presence of multinucleated giant cells, lipid-laden foamy macrophages, and cholesterol crystals. The breast is an extremely rare location for xanthogranulomatous inflammation. Case presentation: The authors describe a case of xanthogranulomatous mastitis in a 26-year-old female patient who presented with a 4×5 cm lump in her right breast. After ultrasonography (revealed a well-circumscribed hypoechoic lesion, with increased vascularity), and surgical consultation, an excisional biopsy was done, and sent for histopathologic examination, which showed features suggestive of xanthogranulomatous mastitis. Clinical discussion: Xanthogranulomatous mastitis, clinically as well as radiologically mimics some other conditions of breast like breast cancer, or fibroadenoma. Ultrasonography usually reveals a well-circumscribed hypoechoic lesion, with increased vascularity, and mammography usually shows BIRADs 3 to 5. Diagnosis is usually based on histopathologic findings of multinucleated giant cells, lipid-laden foamy macrophages, and cholesterol crystals. Treatment is usually surgical excision. Conclusion: Though xanthogranulomatous inflammations are rare in the breast, they must be considered a differential diagnosis in patients presenting with various breast symptoms like lump, pain, or features of breast malignancy.

Clinical genomic profiling of malignant giant cell tumor of bone: A retrospective analysis using a real‑world database.

Malignant giant cell tumor of bone (GCTB) is identified by the presence of multinucleated giant cells, with an aggressive behavior and a high risk of metastasis, which has not been genetically characterized in detail. H3 histone family member 3A (H3F3A) gene mutations are highly recurrent and specific in GCTB. The present study analyzed the clinical information and genomic sequencing data of eight cases of malignant GCTB (out of 384 bone sarcoma samples) using an anonymized genomic database. There were 5 males and 3 females among the cases, with a median age of 33 years at the time of the initial diagnosis. H3F3A G34W and G34L mutations were detected in 3 patients and 1 patient, respectively. In 75% of cases without H3F3A mutation, mitogen-activated protein kinase (MAPK) signaling pathway gene alterations were found (KRAS single nucleotide variant, KRAS amplification, nuclear respiratory factor 1-BRAF fusion). Moreover, the collagen type I alpha 2 chain-ALK fusion was detected in remaining one case. The most frequent gene alterations were related to cell cycle regulators, including TP53, RB1, cyclin-dependent kinase inhibitor 2A/B and cyclin E1 (75%, 6 of 8 cases). On the whole, the present study discovered recurrent MAPK signaling gene alterations or other gene alterations in cases of malignant GCTB. Of note, two fusion genes should be carefully validated following the pathology re-review by sarcoma pathologists. These two fusion genes may be detected in resembling tumors, which contain giant cells, apart from malignant GCTB. The real-world data used herein provide a unique perspective on genomic alterations in clinicopathologically diagnosed malignant GCTB.

Manifestações clínicas e imaginológicas do querubismo: Um relato de caso

Introduction: Kerubism is a rare hereditary disorder characterized by bilateral enlargement of the gnathic bones in children, with a tendency to spontaneous remission at puberty. In some cases, it can develop without a family history. Aim: This report presents a case of non-hereditary cherubism affecting the dentition in a 7-year-old patient. Case report: A 7-year-old male patient complained of a bilateral increase in volume on the face in the mandibular body and ramus, which had been developing for 3 years, asymptomatically and with slow growth, with no history of similar cases in the family. Intraorally, the increase in volume extended from the canine to the molar, bilaterally, with anomalies in the teeth involved. Hematological tests were within limits. Panoramic radiography and facial CT revealed multiple multiloculated lesions in the mandibular body and ramus bilaterally. An incisional biopsy was performed under local anesthesia, which revealed the presence of multinucleated giant cells. Based on the clinical, imaging and histopathological findings, the final diagnosis was kerubism. Due to the self-limiting behavior of the pathology, surgical interventions were not necessary and the case will be followed up. Discussion: Although the lesions tend to be symmetrical, here they were more prominent on the right side. The radiographic features were typical of the disease. The lesions can cause malocclusions due to ectopic eruptions, as seen in this case. Despite the hereditary characteristic, there was no family history of the disease. Histological and laboratory analyses are important to rule out other fibro-osseous lesions, but clinical and radiographic aspects are paramount in the diagnosis. Once the bone matures, the lesion tends to regress. However, cosmetic surgery may still be necessary afterwards. Conclusion: The diagnosis of the disease should be based mainly on clinical and imaging findings, since histological analysis is of limited value. Once confirmed, the case should be followed up and surgical interventions postponed if necessary at a later date.

NON-CASEATING GRANULOMAS ARE ASSOCIATED WITH STRICTURING CROHN’S DISEASE AND THEIR NUMBER AND SIZE ARE INCREASED IN THE MUSCULARIS PROPRIA OF STRICTURED COMPARED TO NON-STRICTURED INTESTINGAL SEGMENTS

Abstract BACKGROUND Crohn’s disease (CD) is a chronic inflammatory disorder of the gastrointestinal tract that progressively leads to fibrosis-induced narrowing of the intestinal lumen, bowel obstruction, and need for surgery. CD exhibits transmural inflammation manifested by immune cell infiltrates composed of multiple immune cell types spanning the entire gut wall. Non-caseating granulomas are a typical hallmark of up to 60% of CD patients. Scarce evidence indicates an association of granulomas with post-operative recurrence suggesting a role of granulomas in disease pathogenesis. Strikingly, while evidence exists from other granulomatous diseases, granulomas have not been linked with stricturing CD. METHODS A total of 348 H&E stained sections from segments of small bowel CD surgical resection specimens were evaluated for non-caseating granulomas. Granulomas were defined by a trained inflammatory bowel disease pathologist as a cluster of ≥ 5 epithelioid histiocytes with or without the presence of multinucleated giant cells. CD segments were classified as non-involved (CDni), inflamed non-strictured (CDi), and strictured (CDs) to confirm whether histopathological presence of granulomas correlates with stricturing CD. Paired sets were available in 150 segments of 50 CD patients and analyzed further to determine whether granuloma number, location within the intestinal wall, or size of granulomas correlates with stricturing CD. RESULTS Granulomas were present in 20% of all CD tissue segments. 28% of CDs, 9% of CDi, and 5% of CDni segments were found to have granulomas and the fraction of segments containing granulomas was significantly higher in CDs compared to CDni and CDi (P<0.0001). The paired patient sections resembled the larger dataset with 16% of patients having granulomas in at least one of the three segments (16% of CDs, 8% of CDi, and 0% CDni). Further comparing the CDi and CDs sections in this subset of patients, we found that neither the total number nor the average size of granulomas were significantly different between CDs versus CDi tissue sections. Analysis of the layers of the intestinal wall revealed that the number (P<0.05) and average size (P<0.01) of granulomas were significantly increased in the muscularis propria of CDs versus CDi sections. There were no significant changes in number or average size in the mucosal or submucosal layers of the intestinal wall. CONCLUSION Together these data indicate that non-caseating granulomas are associated with stricturing CD and these granulomas are increased in number and size in the muscularis propria of strictured versus inflamed tissues from the same patient, but not other intestinal layers. This suggests a potential link between granulomas and the pathogenesis of stricturing CD.

Unusual Localization of Eczema Herpeticum to Tinea Corporis and Cruris

Abstract Eczema herpeticum (EH), known as Kaposi varicelliform eruption presents with multiple vesiculopustular lesions localized to areas of preexisting eczematous or erosive dermatoses. Most commonly seen in atopic dermatitis but colocalization with tinea cruris and corporis is atypical. In our case, multiple vesicles, pustules, and small crusted erosions associated with pain were seen confined to the areas of dermatophytosis. Tzanck smear from vesicles showed multiple multinucleated giant cells and acantholytic cells. In view of strong clinical suspicion and the presence of multinucleated giant cells, she was prescribed oral acyclovir 400 mg thrice a day for 7 days. She was reviewed after a week with complete clearance of the vesicles and crusting.

Giant cells: multiple cells unite to survive.

Multinucleated Giant Cells (MGCs) are specialized cells that develop from the fusion of multiple cells, and their presence is commonly observed in human cells during various infections. However, MGC formation is not restricted to infections alone but can also occur through different mechanisms, such as endoreplication and abortive cell cycle. These processes lead to the formation of polyploid cells, eventually resulting in the formation of MGCs. In Entamoeba, a protozoan parasite that causes amoebic dysentery and liver abscesses in humans, the formation of MGCs is a unique phenomenon and not been reported in any other protozoa. This organism is exposed to various hostile environmental conditions, including changes in temperature, pH, and nutrient availability, which can lead to stress and damage to its cells. The formation of MGCs in Entamoeba is thought to be a survival strategy to cope with these adverse conditions. This organism forms MGCs through cell aggregation and fusion in response to osmotic and heat stress. The MGCs in Entamoeba are thought to have increased resistance to various stresses and can survive longer than normal cells under adverse conditions. This increased survival could be due to the presence of multiple nuclei, which could provide redundancy in case of DNA damage or mutations. Additionally, MGCs may play a role in the virulence of Entamoeba as they are found in the inflammatory foci of amoebic liver abscesses and other infections caused by Entamoeba. The presence of MGCs in these infections suggests that they may contribute to the pathogenesis of the disease. Overall, this article offers valuable insights into the intriguing phenomenon of MGC formation in Entamoeba. By unraveling the mechanisms behind this process and examining its implications, researchers can gain a deeper understanding of the complex biology of Entamoeba and potentially identify new targets for therapeutic interventions. The study of MGCs in Entamoeba serves as a gateway to exploring the broader field of cell fusion in various organisms, providing a foundation for future investigations into related cellular processes and their significance in health and disease.

Dermatofibrosarcoma Protuberans; Case Report in a Pediatric Patient

Dermatofibrosarcoma protuberans (DFSP) is a rare and locally aggressive mesenchymal neoplasm arising from the dermal and subcutaneous tissues. It typically manifests as a slow-growing, firm, protuberant or plaque-like lesion on the skin. DFSP predominantly affects young to middle-aged adults, with a slight predilection for females. This tumor exhibits a distinctive infiltrative growth pattern, characterized by tumor cells invading the surrounding tissues, including the deep subcutaneous layers and the underlying fascia. Histopathologically, DFSP presents characteristic features, such as the presence of spindle-shaped tumor cells arranged in a "storiform" pattern, as well as the presence of a prominent "honeycomb" appearance due to the presence of multinucleated giant cells. Immunohistochemical staining is essential to confirm the diagnosis, with positivity for CD34 being a hallmark of DFSP. Although DFSP rarely metastasizes, its extensive local invasion and high recurrence rate necessitate a wide surgical excision with clear margins as the mainstay of treatment. The use of Mohs micrographic surgery or adjuvant radiation therapy has demonstrated favorable outcomes in cases with challenging anatomical locations or microscopically positive margins. Imatinib mesylate, a tyrosine kinase inhibitor, has also emerged as a promising systemic therapy for advanced or unresectable DFSP, particularly cases with the COL1A1-PDGFB gene fusion, which represents the molecular hallmark of DFSP. Early diagnosis and appropriate management are crucial to achieving optimal outcomes in DFSP. This article provides a comprehensive review of the clinical, histopathological, and molecular aspects of DFSP, highlighting the significance of a multidisciplinary approach to ensure accurate diagnosis and tailored therapeutic strategies for patients affected by this rare dermatological neoplasm.

Morphological Study of Hashimoto Thyroiditis in Fine Needle Aspiration Cytology Specimens.

Hashimoto thyroiditis is an autoimmune disease which is diagnosed based on well-defined clinical and cytological criteria. The objective of this research is to study cytomorphological features in patients of Hashimoto thyroiditis and compare the findings with other studies. Literature on morphology of multinucleated giant cells was found to be lacking, and this study has focused on the number and morphology of these cells in this study. FNAC was done in patients who met the clinical diagnostic criteria of Hashimoto thyroiditis formulated by "Japan Thyroid Association" and smears were analyzed by light microscopy. Data analysis was done by XLSTAT in Microsoft Excel 2010. The Wilcoxon Signed Rank Testwas done to analyze the data on multinucleated giant cells. The null hypothesis was thatthe median of the population of differences between the paired data of small and large giant cells is zero. A total of 26 patients were included in a period of one year. Contrary to observations in other studies, multinucleated giant cells were found in most participants. The Wilcoxon Signed Rank Test proved that small multinucleated giant cells were significantly more common than large multinucleated giant cells in Hashimoto thyroiditis; P value (two-tailed) being <0.0001 at significance alpha of 0.05. This study has also revealed that a few patients with Hashimoto thyroiditis can have large and very large multinucleated giant cells in a small number. Data on other cytomorphological features were no different than in other studies. The presence of multinucleated giant cells in 92.3% of patients in this study is far higher than in other studies which can have important diagnostic implications. Few large multinucleated giant cells can be present in a small number in a few patients as in Hashimoto thyroiditis.

Nonspecific interstitial pneumonia pattern is a frequent finding in patients with post-acute COVID-19 syndrome treated with bilateral orthotopic lung transplantation: current best evidence

Patients withpost-acute COVID-19 (PA-COVID) syndrome or long COVID-19 syndrome develop persistent symptoms and complications that last beyond 4 weeks of the initial infection. There is limited information regarding the pulmonary pathology in PA-COVID patients who require bilateral orthotopic lung transplantation (BOLT). Our experience with 40 lung explants from 20 PA-COVID patients who underwent BOLT is described. Clinicopathologic findings are correlated with best evidence from literature. The lung parenchyma showed bronchiectasis (n=20) and severe interstitial fibrosis with areas resembling the nonspecific interstitial pneumonia (NSIP) pattern of fibrosis (n=20), interstitial fibrosis not otherwise specified (n=20), and fibrotic cysts (n=9). None of the explants exhibited a usual interstitial pneumoniapattern of fibrosis. Other parenchymal changes included multinucleated giant cells (n=17), hemosiderosis (n=16), peribronchiolar metaplasia (n=19), obliterative bronchiolitis (n=6), and microscopic honeycombing (n=5). Vascular abnormalities included thrombosis of a lobar artery (n=1) and microscopic thrombi in small vessels (n=7). Systematic literature review identified 7 articles reporting the presence in 12 patients of interstitial fibrosis showing the NSIP pattern (n=3), organizing pneumonia/diffuse alveolar damage(n=4) and not otherwise specified (n=3) patterns. All but one of these studies also reported the presence of multinucleated giant cells and none of the studies reported the presence of severe vascular abnormalities. PA-COVID patients undergoing BOLT show a pattern of fibrosis that resembles a mixed cellular-fibrotic NSIP pattern and generally lack severe vascular complications. As the NSIP pattern of fibrosis is often associated with autoimmune diseases, additional studies are needed to understand the mechanism of disease and learn whether this information can be used for therapeutic purposes.

The Contribution of the Sheep and the Goat Model to the Study of Ovarian Ageing.

Ovarian ageing stands as the major contributor towards fertility loss. As such, there is an urge for studies addressing the mechanisms that promote ovarian ageing and new strategies aiming to delay it. Recently, the presence of a unique population of multinucleated giant cells has been identified in the ovaries of reproductively aged mice. These cells have been considered hallmarks of ovarian ageing. However, up to date multinucleated giant cells have only been described in the ovaries of the mice. Therefore, the aim of the present work was to evaluate and characterize the presence of such hallmarks of ovarian ageing in the sheep and the goat. In this study, ovaries from juvenile (6 months) and mature animals (18-24 months) were used. The hematoxylin and eosin technique was performed to describe the ovarian morphology and evaluate the ovarian follicle reserve pool. Sudan black B staining and the detection of autofluorescence emission were used to identify and characterize the presence of multinucleated giant cells. Statistical analyses were performed with GraphPad Prism 9.0.0. A decrease in the follicle reserve pool and the presence of multinucleated giant cells, with lipofuscin accumulation and the emission of autofluorescence, were observed in the ovaries of the mature animals of both species. Our results support the interest in the use of the ovine and the caprine model, that share physiological and pathophysiological characteristics with humans, in future studies addressing ovarian ageing.

Central giant cell granuloma mimicking a malignant lesion of mandible: A case report

Central giant cell granuloma (CGCG) is a relatively uncommon benign osseous lesion with sometimes aggressive nature. The nature of this lesion is unknown and although the exact cause is unclear, the three theories about possibility of its nature are: developmental anomaly, reactive lesion or benign neoplasm. Histologically by presence of multinucleated giant cells within a stroma of spindle-shaped mesenchymal and fibro vascular connective tissue along with containing of hemorrhagic areas is characterized. This case report presents the diagnosis and management of a CGCG in a 50 years-old man with biopsy and surgical treatments. The lesion involve the left side of mandibular. Diagnosis plan was designed based on the combination of pathology and imaging. Finally after en bloc resection of involved regions of mandible, a titanium plate prosthesis was used for the jaw reconstruction. Since some of CGCG lesions can be highly invasive and inclinically and radiographic features can mimic as malignancy lesions.

Association between the severity of histopathological lesions and Mycobacterium avium subspecies paratuberculosis (MAP) molecular diversity in cattle in southern Chile.

The objective was to evaluate the association between the severity of histopathological lesions caused by Mycobacterium avium subspecies paratuberculosis (MAP) infection and the molecular diversity of this pathogen. Blood, ileum, and mesenteric lymph node samples were collected at slaughter, from 1,352 adult cattle [source population 1 (SP1)]. In addition, 42 dairy herds (n = 4,963 cows) were followed for 2 years, and samples from compatible paratuberculosis clinical cases [source population 2 (SP2)] were collected. MAP infection was confirmed using an ELISA test, liquid media culture, and PCR. Isolates were genotyped using five MIRU-VNTR markers. Tissues from confirmed samples were subjected to a histopathological examination. A histopathological severity score (HSS) system was developed and used to grade (0 to 5) the magnitude of lesions caused by MAP. In general, the HSS system assesses the number of foci and degree of macrophage infiltration, together with the presence of multinucleated giant cells (MGCs) and acid-fast bacilli (AFB), in addition to the fusion of the intestinal villi and hyperplasia of the crypts. Despite the large sampling effort, only 79 MAP isolates were successfully genotyped, where 19 different haplotypes were described. A mixed-effect Poisson regression model was used to assess the relationship between haplotypes and HSS values. The model was controlled by animal age, and the farm was used as a random effect. Haplotypes were grouped based on their relative frequency: the most frequent haplotype (group i, 49.4%), the second most frequent haplotype (group ii, 12.7%), and all other haplotypes (group iii, 37.9%). Model outputs indicated that group i had significantly higher HSS values than group iii. In addition, group i was also associated with higher optical density (OD) values of the ELISA test. These results support the existence of differences in pathogenicity between MAP haplotypes. However, results were based on a relatively small sample size; thus, these should be taken with caution. Despite this, study findings suggest that haplotypes would be associated with differences in disease progression, where the dominant haplotype tends to generate more severe lesions, which could be linked to a greater shed of MAP cells than non-dominant haplotypes, increasing their chances of transmission.

FNAC study of giant cell tumor of tendon sheath (localized tenosynovial giant cell tumor): Clinico-radiological correlation and cytopathological features.

Localized tenosynovial giant cell tumor (GCT) or giant cell tumor of tendon sheath (GCTTS), is a benign nodular lesion that arises from the synovium of the tendon sheath of the hands and foot. GCTTS is characterized by the presence of multinucleated giant cells and proliferation of synovial-like mononuclear cells. A clinical diagnosis of GCTTS is kept as a differential when a firm, nodular mass shows decreased signal intensity on both T1-and T2-weighted MR imaging. Treatment is usually marginal excision of the mass. It is a retrospective study, observed in the past 3 years at a tertiary care hospital. Those cases were included in the study in which histopathological confirmation was available or if clinico-radiological features were confirmatory of the diagnosis of GCTTS when correlated with cytological features. There was a total of 24 cases, out of which 16 were females and 8 males. The tumor was located in the upper limb in 21 cases and in 3 cases the tumor was present in the lower limb. In the upper limb, 18 cases were on the right side and three cases were on the left side. In the lower limb, 1 case was present on the left and 2 on the right side. The cytomorphology consisted of mononuclear stromal cells, multinucleated giant cells, and hemosiderin-laden macrophages in variable numbers. It is important to accurately diagnose and categorize giant cell-containing lesions because their prognosis depends on the exact categorization of the tumor.

Diagnosis of giant cell arteritis using clinical, laboratory, and histopathological findings in patients undergoing temporal artery biopsy

ObjectiveTo identify the clinical, laboratory, and histopathological features that may predict the diagnosis of giant cell arteritis (GCA). MethodsA retrospective chart review was performed on patients who underwent temporal artery biopsy (TAB) between January 1, 2011 and March 31, 2019. Patient demographics, clinical characteristics, laboratory features, histopathological features, and biopsy results were collected. GCA status was determined by a neuro-ophthalmologist (OOA). Stepwise logistic regression analysis was performed to identify features that predict GCA status. ResultsOf 101 patients who underwent TAB, 31 (31%) were diagnosed with GCA. Age was found to be statistically significant for the diagnosis of GCA (P = 0.009), with an average age of 74.4 years ( ± 8.1) in those with GCA vs. 68.9 years ( ± 10.0) in those without. The incidence of transient vision loss was higher in GCA than non-GCA patients (P = 0.005). Anterior arteritic ischemic optic neuropathy (n = 3), ophthalmic artery occlusion (n = 2), and posterior ischemic optic neuropathy (n = 1) were seen only in the GCA group. Of the 31 GCA patients, 15 had active GCA (48%), 3 (10%) had healed temporal arteritis (HTA), 8 (26%) had suggested HTA, and 5 (16%) had false negative biopsies. Of the 70 non-GCA patients, 63 (90%) had negative biopsies, 2 (3%) had HTA, and 5 (7%) had suggested HTA. Histopathological analysis revealed that CD68 staining had a sensitivity of 69% and specificity of 86%. Both presence of multinucleated giant cells (MNGC) and transmural inflammation had 100% specificity; however, sensitivity was ≤ 50%. In patients with negative TABs and complete risk factor data available (n = 66), the odds of GCA increased 2.16-fold every 5 years of age, and 1.08-fold every mg/day of oral steroid use. A biopsy result of HTA had an odds ratio of 84.7 and suggested HTA of 49.2 against a negative TAB for diagnosis of GCA. ConclusionAge at time of biopsy, HTA, and suggested HTA are predictive for the diagnosis of GCA. Transient vision loss is more commonly seen in GCA, and anterior arteritic ischemic optic neuropathy, ophthalmic artery occlusion, and posterior ischemic optic neuropathy are important ophthalmic manifestations of GCA. CD68 staining is more sensitive but less specific for diagnosing GCA in comparison to other histopathologic findings such as presence of MNGC and transmural inflammation. Further work is recommended to investigate the importance of the specific histopathologic finding of CD68 staining in the diagnosis of GCA.

Multinucleated Giant Cells in Ameloblastoma: An Uncommon Finding

Ameloblastoma is a benign, slow growing and locally aggressive odontogenic tumor. Typical histopathological findings include islands, strands, sheets, cords of variable size with core of loosely arranged cells in reticular pattern and peripheral layer of palisading cuboidal to columnar cells. An uncommon event in this is presence of multinucleated giant cells. These cells are formed by the fusion of cells usually of monocyte or macrophage lineage and presence of these cells is indicative of the disease process. This case series affirms the presence of multinucleated giant cells in the different histopathological patterns of ameloblastoma. These cells may be related to the aggressive nature of the pathology. However, the origin and nature of the giant cells in the present case series could not be established. Further evaluation of more cases and investigations needs to be done to identify the nature and origin of these cells.

Evaluation of prime and prime-boost immunization strategies in BALB/c mice inoculated with Leishmania infantum transfected with toxic plasmids

The etiologic agents of visceral leishmaniasis are Leishmania infantum and Leishmania donovani. Despite the variety of drugs available to treat leishmaniasis, most lead to serious adverse effects, and resistance to these drugs has been reported. Currently, no leishmaniasis vaccine is available for humans. That is why the group developed transgenic L. infantum promastigote lines, which express toxic proteins after differentiation into amastigotes. That is why group developed the pFL-AMA plasmid and transfected it into L. Infantum promastigotes. This plasmid was expressed only in the amastigote form of the parasite. Sequences encoding toxic proteins (active bovine trypsin and egg avidin) were inserted in this plasmid, and the transfected parasites died after the differentiation process. In this study, two immunization protocols were performed in BALB/c mice: prime and prime-boost immunization prior to challenge with the wild-type L. infantum (WT). The parasite burdens in the spleen, liver, and bone marrow were evaluated to verify immunological protection. Histopathological analysis of the spleen and liver and the humoral immune response were also performed. The data showed that the parasite burden was reduced in prime-boosted mice in the spleen, liver, and bone marrow, indicating that mice immunized with two doses of the transfected parasites were satisfactorily protected. High levels of IgG, IgG1, and IgG2a antibodies were observed, as well as the presence of anti-inflammatory cytokine Interleukine-10 and pro-inflammatory cytokine Tumor Necrosis Factor-α (TNF-α) and Interferon-γ (IFN – γ) suggesting a Th1/Th2 mix response, in addition to the presence of multinucleated giant cells in the spleen and lymphocyte infiltration in the liver. Therefore, L. infantum transfected with a toxic plasmid is an excellent vaccine candidate against visceral leishmaniasis and the application of a boost before the challenge promotes greater protection against WT L. infantum infection.

Pathological, Histological, and Molecular Based Investigations Confirm Novel Mycobacterium bovis Infection in Boselaphus tragocamelus.

Mycobacterium bovis (M. bovis) being the main cause of animal tuberculosis is a complex infectious agent and can be a cause of zoonotic tuberculosis zoonosis in public health. To date, the uncommon infection in public health due to M. bovis still is a great challenge to both veterinary and medical professions and requires a careful diagnosis and confirmation of the bacterium. Therefore, this study for the first time reports the clinical, gross, histopathological, and molecular based confirmation of M. bovis infection in wildlife animals (nilgai). Prior to death, the morbid animal showed severe pneumonic ailments like moist cough, thick nasal exudates, and dyspnoea. At necropsy, enlargement of mandibular cervical and mesenteric lymph nodes was observed. Different macroscopic lesions such as congestion and hyperaemia, creamy white and catarrhal exudates in trachea, consolidation, grey and red hepatisation of lungs, and micro- and macrogranulomatous tubercles containing caseous materials in lungs were observed. The heart of morbid animal showed congestions, myocarditis, and a copious amount of straw-colored fluid in the pericardial sac. At the microscopic level, lungs indicated granulomatous inflammatory response, presence of multinucleated giant cells, fibrosis, and punctuation of alveoli with chronic inflammatory cells. Histopathological examination of various sections of the heart of the infected animal showed chronic inflammatory response consisting of chronic inflammatory cells like monocyte, lymphocytes, and fibroblasts along with noncalcified eosinophilic materials. At the molecular level, M. bovis infection was confirmed in various tissues like the heart, lungs, cervical, and mesenteric lymph nodes in morbid animals. In conclusion, based on our results, it can be suggested that more molecular based epidemiological studies are crucial to know the exact cause of pulmonary and cervical tuberculosis in wild animals.

Unusual Histopathological Findings in Mechanically Removed Stroke Thrombi - A Multicenter Experience.

BackgroundSeveral studies have investigated the histopathology of mechanically retrieved thrombi from stroke patients. Thrombi with unusual components constitute about 1–2% of all stroke thrombi in clinical practice. Knowledge about these rare components is limited.ObjectivesTo characterize the histopathology of unusual stroke thrombi from a real-world setting with relation to clinical presentation, patient characteristics and procedural aspects of mechanical thrombectomy.MethodsOne-thousand and eight thrombi retrieved from stroke patients with mechanical thrombectomy at three different hospitals were retrospectively reviewed for unusual histological components. Fifteen thrombi were included in the study for further histopathological analysis. Clinical data and data on procedural aspects were collected.ResultsWe identified six cases with large amounts of extracellular DNA, of which three were calcified. All six cases except one received anticoagulant therapy. We describe two types of calcifications that differ with respect to general calcification morphology, von Kossa staining pattern, macrophage immunophenotype and presence of multinucleated giant cells. Cholesterol-rich (n = 3), adipocyte-like pattern-rich (n = 2), collagen-rich (n = 2) and myxomatous (n = 1) thrombi were also identified and are discussed with regard to pathogenesis and clinical and intervention characteristics. Finally, a thrombus with parts of a vascular wall is described. Suggestions for future studies are made and clinical and technical aspects of the management for these rare but important patients are discussed.ConclusionIn our retrospective multicenter study, we characterized stroke thrombi histopathologically and found subgroups of thrombi defined by presence of rarely seen components. These defined subgroups showed relation to underlying cardiovascular disease, patient characteristics, and mechanical thrombectomy technique. Knowledge about these components may increase our understanding of stroke pathophysiology and influence interventional procedures.