Innovation of the protocol for the application of cryolipolysis: Effects and mechanisms of action.

BACKGROUND: In recent years, aesthetic procedures aiming at body remodeling and have grown exponentially. Cryolipolysis (CLL) has stood out as a noninvasive resource that acts directly on the subcutaneous adipose tissue promoting a significant reduction of adipose tissue through of cooling that could lead to the crystallization cytoplasmic lipids, loss of cellular integrity, apoptosis/necrosis of adipocytes, and local inflammation, producing selective loss of adipose tissue. Thus, the objective of the present study was to evaluate the effects of a specific technique of CLL application on the inflammatory reactions of the target tissue in different post-application times. METHODS: This is a randomized, blind clinical study that evaluated the tissue sample of six patients after 45, 60, and 90 days of an innovative protocol for the application of CLL, with samples collected through abdominoplasty surgeries. The samples were evaluated by immunohistochemical analyses of several markers. RESULTS: A significantly greater increase in fibroblasts was observed at 45 days and greater phagocytic action at 60 days. Regarding the apoptosis process, the expression of caspase 3 and cleaved caspase 3 markers varied at different times, with cleaved caspase 3 being higher at 45 and 90 days after CLL application. CONCLUSION: The protocol of the CLL presented in this study was able to induce inflammatory responses in addition to confirming the selective apoptotic action at the different times studied.

Effects at cellular level of epilation with various laser wavelengths applied simultaneously on different skins: two case reports.

This study evaluated the effects of laser application of diverse wavelengths applied simultaneously and on different skins. The sample included two participants, a woman with light skin with abdominal hair and a woman with dark skin and hair on the inner part of the lower limbs, who received a laser therapy session. After 45 days from laser application, abdominoplasty and thigh dermolipectomy surgery were performed. In the control sample, the hair follicles were in the anagen phase, showing the presence of Bcl-2 expression. In the treated areas, follicles were observed in an advanced phase (telogen), with the presence of CK-18 and negativity of Bcl-2, highlighting the phase of hair loss at that moment and the complete apoptosis of the investigated follicle. Significant difference was observed in the comparison of the anagen phase (p = .00) and it similarly occurred in the comparison of the telogen phase (p = .00). The presence of a greater amount of follicles in the anagen phase in the control area and follicles in the telogen phase in the treated area demonstrates the efficiency of the laser at different wavelengths when reaching different skin phototypes and hair thickness, being reinforced by apoptosis and cell proliferation markers. Therefore, the hair-removal process has been optimized with various laser wavelengths.

The altered metabolic pathways of diffuse large B-cell lymphoma not otherwise specified.

Altered metabolic fingerprints of Diffuse large B-cell lymphoma, not otherwise specified (DLBCL NOS) may offer novel opportunities to identify new biomarkers and improve the understanding of its pathogenesis. This study aimed to investigate the modified metabolic pathways in extranodal, germinal center B-cell (GCB) and non-GCB DLBCL NOS from the head and neck. Formalin-fixed paraffin-embedded (FFPE) tissues from eleven DLBCL NOS classified according to Hans' algorithm using immunohistochemistry, and five normal lymphoid tissues (LT) were analyzed by high-performance liquid chromatography-mass spectrometry-based untargeted metabolomics. Partial Least Squares Discriminant Analysis showed that GCB and non-GCB DLBCL NOS have a distinct metabolomics profile, being the former more similar to normal lymphoid tissues. Metabolite pathway enrichment analysis indicated the following altered pathways: arachidonic acid, tyrosine, xenobiotics, vitamin E metabolism, and vitamin A. Our findings support that GCB and non-GCB DLBCL NOS has a distinct metabolomic profile, in which GCB possibly shares more metabolic similarities with LT than non-GCB DLBCL NOS.

Rhabdomyosarcoma with TFCP2 Rearrangement or Typical Co-expression of AE1/AE3 and ALK: Report of Three New Cases in the Head and Neck Region and Literature Review.

BACKGROUND: Rhabdomyosarcoma (RMS) harboring EWSR1/FUS-TFCP2 fusions has been recently described as a distinct form of RMS with an aggressive course and predilection for the craniofacial bones, especially the jaws. METHODS: We report three new cases of this rare entity, two from Brazil and one from Guatemala, with detailed clinicopathologic, immunohistochemical, and molecular descriptions. Additionally, we explored the English-language literature searching RMS with TFCP2 rearrangement or typical immunophenotype with co-expression of AE1/AE3 and ALK in the head and neck region. RESULTS: Case 1 is a 58-year-old male with a 3-month history of painful swelling in the anterior maxilla. Case 2 is a 22-year-old male presenting with right facial swelling and proptosis. Case 3 is a 43-year-old female with a rapidly growing tumor located in the zygomatic region. Imaging examinations revealed highly destructive intraosseous masses in the first two cases, and a soft tissue tumor with bone invasion in case 3. Microscopically, all cases showed a hybrid spindle and epithelioid phenotype of tumor cells which expressed desmin, myogenin and/or Myo-D1, AE1/AE3, and ALK. FISH confirmed molecular alterations related to TFCP2 rearrangement in Cases 1-2. In case 3, there was no available material for molecular analysis. The patients were subsequently referred to oncologic treatment. Additionally, we summarized the clinicopathologic, immunohistochemical, and molecular features of 27 cases of this rare RMS variant in the head and neck region reported in the English-language literature. CONCLUSION: RMS with TFCP2 rearrangement is a rare and aggressive tumor with a particular predilection for craniofacial bones, especially the jaws. Knowing its clinicopathologic and immunohistochemical profile can avoid misdiagnosis.

Mantle cell lymphoma involving the oral and maxillofacial region: a study of 20 cases.

OBJECTIVE: To investigate the clinicopathologic features of mantle cell lymphoma (MCL) involving the oral and maxillofacial region. METHODS: The MCL cases were retrieved from the pathosis database of 6 pathology laboratories. Original hematoxylin and eosin slides and immunohistochemical reactions were reviewed for confirmation of the initial diagnosis. Clinical data of the cases were obtained from the patients' pathosis and/or medical charts. RESULTS: Twenty cases were included in the study, showing a male predominance and a mean age of 66 years. The oral cavity (12 cases) and the oropharynx (5 cases) were the most commonly involved subsites. Most cases presented as asymptomatic swellings, with 2 cases showing bilateral involvement of the palate. The classic histologic variant predominated (12/20 cases). All cases expressed CD20 with nuclear cyclin D1 positivity. SOX11 was seen in 9/13 cases, CD5 in 6/16 cases, Bcl2 in 16/19 cases, CD10 in 2/20 cases, and Bcl6 in 4/16 cases. Ki67 showed a mean proliferation index of 40.6%. The Epstein-Barr virus (EBV) was negative in all cases investigated. Follow-up data was available for 7 patients, with 5 currently alive and 2 deceased. CONCLUSION: Mantle cell lymphoma, albeit rare, may manifest in the oral and maxillofacial region. Its histologic heterogeneity demands a high degree of diagnostic skill from pathologists.

Lymphomas Affecting the Sublingual Glands: A Clinicopathological Study.

BACKGROUND: Lymphomas affecting the sublingual glands are extremely rare and very few case reports are currently available. Therefore, the aim of the current study is to describe the clinicopathological features of a series of lymphomas involving the sublingual glands. METHODS: Cases diagnosed in four pathology services were assessed and the formalin-fixed paraffin-embedded tissue blocks were retrieved for diagnosis confirmation. Clinical data were obtained from patients' medical files. RESULTS: We obtained seven cases of lymphomas in the sublingual glands, representing two follicular lymphomas, two diffuse large B cell lymphomas not otherwise specified (DLBCL NOS), two extranodal marginal zone B cell lymphoma of mucosa-associated lymphoid tissue (MALT lymphomas) and one mantle cell lymphoma (MCL). In all cases the tumor cells infiltrated the glandular parenchyma, although in two of them the neoplastic cells were located more superficially and permeated the glandular acini and ducts. Clinically, the tumors presented as asymptomatic nodules and two patients (affected by DLBCL NOS and MCL) died, while the other five patients remained alive at last follow-up. CONCLUSION: Lymphomas affecting the sublingual glands are usually of the mature B cell lineage, often represent low-grade subtypes and may clinically resemble other more common lesions in the floor of the mouth like salivary gland tumors.

Oral follicular lymphoma: a clinicopathologic and molecular study.

Follicular lymphoma is a hematolymphoid neoplasm that originates from germinal center B cells. It is made up of a combination of small cleaved centrocytes and a varying quantity of larger non-cleaved centroblasts to describe the clinical, microscopic, immunohistochemical, and molecular features of oral follicular lymphomas. Follicular lymphomas affecting the oral cavity were retrieved from pathology files. Immunohistochemistry was performed to confirm the diagnosis, and fluorescence in situ hybridization (FISH) was employed to detect rearrangements in BCL2, BCL6, and MYC genes. Clinical and follow-up data were obtained from the patient's medical and pathology files. Twenty cases were obtained. There was an equal sex distribution (10 males: 10 females) and a mean age of 60.9 years (range: 10-83 years-old). Lesions presented as asymptomatic swellings, usually in the palate (10 cases) and the buccal mucosa (7 cases). Five patients presented with concomitant nodal involvement. Microscopic evaluation depicted the follicular growth pattern with diffuse areas in six cases. Grades 1 and 2 follicular lymphomas represented 12 cases, while grade 3A neoplasms accounted for other 8 cases. Two cases showed rearrangements in MYC, BCL2, and BCL6 genes, while single BCL2 translocation was found in eight cases. Two cases had no translocation. Three patients deceased and the 2-year overall survival achieved 88%. Follicular lymphoma affecting the oral cavity is uncommon, usually affects the palate as a non-ulcerated swelling and the presence of a systemic disease most always be ruled out.

Effect of Extracorporeal Shock Waves on Induced Neocollagenesis of Integumentary Tissue.

Background: Obesity became a worldwide public health problem and its treatment presents a strict relationship with skin flaccidity, for which the development of non-invasive therapies is an emerging field. Objective: This study aims to evaluate the physiological response of the skin tissue of individuals with obesity with flaccidity to the physiological stimulus of shockwave therapy (ESWT). Methods: This is a comparative intervention study based on histological and immunohistochemical analyses of a set of samples of skin tissue of women with Grade II obesity who achieved a 10 percent preoperative weight loss before bariatric surgery and complaints of skin flaccidity, subjected to the ESWT treatment. A total of seven sessions were carried out in the abdominal region on the left side, and the collateral side was used as control; the biological material was collected at the moment of the bariatric surgery. Hematoxylin and Eosin, Masson's trichrome, Picrosirius Red and the markers for immunohistochemical were used for the morphological evaluation. Results: Fourteen women were included in the research. The results demonstrated that the tissue which underwent the ESWT intervention presented significant increases of fibroblast cells (p<0.0001) and collagen fibers Type I and II (p<0.0002). In the significant expressions of the markers FGF1, FGF2, FGFR1 were identified in the exposed side (p<0.0002, 0.0017, <0.0001, respectively) as well as a significantly higher expression of Ki67 marker of cell proliferation (p<0.0002). Conclusion: ESWT was associated with a significant increase of cell proliferation and collagen expression in flaccid skin of individuals who achieved weight loss before bariatric surgery.

Effects of LED photobiomodulation therapy on the subcutaneous fatty tissue of obese individuals - histological and immunohistochemical analysis.

Photobiomodulation therapy (PBMT) has become an adjuvant therapeutic possibility in body remodeling procedures. Given this scenario, this study was proposed with the aim of evaluating the effects of PBMT to Light Emitting Diode (LED) associating the red (630 nm) and infrared (850 nm) wavelengths in the subcutaneous fatty tissue. This controlled study of comparative intervention that evaluated a sample of subcutaneous fatty tissue from women with grade II obesity. The participants received the LED PBMT treatment with associated red and infrared wavelengths sequentially on the left side of the abdomen and the right side was considered as control, with the collection of biological material performed at the time of bariatric surgery. For histological and immunohistochemical evaluation, Caspase 3, Cleaved Caspase 3, CD68+, HSL and adipophilin markers were used. The participants showed positivity in the expression of Caspase 3 and Cleaved Caspase (p < .0001), CD68+ macrophages (p < .0001), HSL (p < .0001) and adipophilin (p < .0013) in the intervention sample when compared to the control. PBMT and LED associating red and infrared wavelengths were able to promote autophagic lipolysis induced by adipocyte cell apoptosis in the subcutaneous tissue of obese individuals.

Expression of mitochondrial dynamic markers in adenoid cystic carcinoma.

BACKGROUND: Mitochondrial fission and fusion processes are known as mitochondrial dynamics and the occurrence of imbalances in the mitochondrial activity is related to the pathogenesis of many human cancers. However, the importance of mitochondrial dynamics in malignant salivary gland tumours remains unknown. Therefore, we aimed to investigate its prognostic significance in adenoid cystic carcinoma. METHODS: Fifty-seven formalin-fixed paraffin-embedded cases were retrieved and disposed in tissue microarray. Histological sections were submitted to immunohistochemical reactions against AMT, DRP1, FIS1, MFN1, MFN2 and OPA1 proteins. Clinical data were retrieved from the patients' medical files, including specific and disease-free survival data. RESULTS: It was observed that 50.9% of the cases were strongly positive for AMT and DRP1, and 49.1%, 21.1%, 22.8% and 24.6% strongly positive for FIS1, MFN1, MFN2 and OPA1, respectively. Reactions were observed in both epithelial and myoepithelial components of the tumour. The higher expression of MFN2 was associated with solid microscopic pattern (p = 0.016). DRP1 overexpression showed a trend towards a shorter overall survival (p = 0.054), while negative/weak OPA1 showed a trend towards a lower disease-free survival (p = 0.051) in the univariate analysis, but no mitochondrial marker represented an independent prognostic determinant under multivariate analysis. CONCLUSION: In conclusion, mitochondrial dynamics markers do not seem to carry a prognostic significance for adenoid cystic carcinoma patients, but these proteins may play an important role in its pathogenesis.

Langerhans cell histiocytosis mimicking a residual cyst.

Langerhans cell histiocytosis (LCH) is an uncommon myeloid neoplasm characterized by clonal neoplastic proliferation of Langerhans-type dendritic cells associated with a reactive inflammatory infiltrate composed predominantly of lymphocytes and eosinophils. Only three cases of LCH mimicking periapical lesions have been reported in the English-language literature to date. Herein, we report a rare case of LCH involving the mandible of a 45-years-old woman mimicking microscopically and radiographically a residual cyst. The patient underwent enucleation and curettage of the lesion. Microscopically, the lesion showed fibrous tissue with an intense inflammatory infiltrate and histiocytes with irregular to elongated nuclei with prominent nuclear grooves. The tumor cells were positive for S-100 protein, CD1a, and CD207. After careful evaluation through imaging tests to rule out lesions in other anatomical locations, the diagnosis was solitary LCH of the mandible. After four years of follow-up, the patient remained with no evidence of recurrence. This case emphasizes the importance of a carefully clinical, radiographic, and microscopical evaluation of bone lesions, including periapical or residual cysts, since some neoplasms can mimic common benign lesions of the jaws. Although conservative approaches to treating solitary mandibular bone lesions of LCH can be employed, long-term follow-up is strongly recommended.

Oral and maxillofacial manifestations of IgG4-related disease: A clinicopathological study.

BACKGROUND: IgG4-related disease is a fibroinflammatory and immune-mediated condition, which has extremely variable clinical manifestations. In this study, we aim to investigate the clinicopathological features of IgG4-related disease involving the oral and maxillofacial region. METHODS: Cases of IgG4-related disease manifesting in the oral and maxillofacial region were retrieved from three Brazilian institutions. Clinical and serological data were obtained from the patients' medical charts, while microscopic and immunohistochemical findings were revised by oral pathologists. Diagnosis followed the American College of Rheumatology/European League against Rheumatism criteria. RESULTS: Seven patients diagnosed with IgG4-related disease were included in this study. Women were affected in all analysed cases, with a mean age of 55.4 years. Two patients presented with the clinical involvement of more than one oral and maxillofacial anatomic site. Therefore, our sample comprised nine oral and maxillofacial anatomic sites affected by IgG4-related disease. The submandibular gland was affected in four cases, the tongue and the parotid gland in two cases each, and the palate in one case. In a few cases, exploratory lower lip biopsy was used as a diagnostic approach. A moderate-to-severe lymphoid infiltrate containing plasma cells and lymphocytes, with an increased IgG4/IgG ratio, was common. Treatment varied and steroids were the most frequently used (57.4%). Six patients remained alive, while one died from unknown causes. CONCLUSION: Although major salivary glands are commonly affected by IgG4-related disease, the oral cavity can also be involved, and lower lip biopsy may be an auxiliary diagnostic tool.

Follistatin-related protein 1 interacting partner of Syndecan-1 promotes an aggressive phenotype on Oral Squamous cell carcinoma (OSCC) models.

Syndecans belong to the family of transmembrane heparan sulfate proteoglycans and are associated with many physiopathological processes, including oral cancer. As previously shown soluble syndecan-1 (SDC1) fragments and synthetic SDC1 peptide were able to induce cell migration in oral cancer cell lines. In order to explore the role of SDC1 in oral cancer, we have investigated SDC1 interacting partners and its functional role in oral cancer models. Here we have shown that SDC1 interacts with follistatin-related protein 1 (FSTL1) by its ectodomain (ectoSDC1) and extracellular juxtamembrane peptide (pepSDC1) and that their transcript levels can affect tumor events. Using orthotopic mouse model we identified that the knock-down for FSTL1 (shFSTL1) or for both FSTL1 and SDC1 (sh2KD) produced less aggressive and infiltrative tumors, with lower keratinization deposition, but with increased levels of epithelial-mesenchymal transition and proliferation compared to control and SDC1 knock-down. Based on cell culture assays, we suggest that the shFSTL1 effect on tumor tissues might be from significant increase of mRNA levels of Activin A (ActA) and its resceptors. This study shows for the first time two different complexes, SDC1 and FSTL1; pepSDC1 and FSTL1, exhibiting a close relationship in cell signaling events, as FSTL1 promotes a more aggressive phenotype. SIGNIFICANCE: This work contributes to the understanding of new SDC1 functions, based on the investigation of protein-protein complex formation in Oral Squamous cell carcinoma (OSCC) models. The FSTL1 identification, as an interacting partner of SDC1 ectodomain and of its derived peptide promotes molecular events that favors cancer development and progression, as highlighted by Activin A (ActA) and Epithelial-mesenchymal transition (EMT) gene expression and by changes in the phenotype of orthotopic OSCC mouse tumor tissues when SDC1-FSTL1 expression is modulated.

CD30 Expression in Oral and Oropharyngeal Diffuse Large B Cell Lymphoma, not Otherwise Specified.

Diffuse large B cell lymphoma, not otherwise specified (DLBCL, NOS) is the most frequent non-Hodgkin lymphoma subtype. This aggressive neoplasm may variably express the CD30 protein, which may be used as a therapeutic target for this tumor. However, CD30 expression in DLBCL NOS arising from the oral cavity and the oropharynx has not been investigated. Therefore, this study aims to determine the frequency of CD30 expression and its prognostic significance for patients affected by oral/oropharyngeal DLBCL NOS. Fifty cases were retrieved from pathology files and submitted to immunohistochemistry against CD30. Reactivity was accessed by two oral pathologists using two cut-off values (> 0% and > 20% of tumor cells) to determine positivity in each case. Clinical data were obtained from the patients' medical files to investigate the prognostic potential of the protein. Seven high-grade B cell lymphomas and two EBV-positive DLBCL NOS were identified. We found one CD30-positive case in each of these two groups of lymphomas. Among the remaining 41 DLBCL NOS, other four cases (three in the oral cavity and one in the oropharynx) were positive for CD30, but only two expressed the protein in > 20% of tumor cells, both in the oral cavity. Survival analysis demonstrated that CD30-positive cases had a higher five-year overall survival rate (75%) than CD30-negative cases (32.3%), although a statistically significant result was not achieved (p = 0.19). Only a minor subset of oral and oropharyngeal DLBCL NOS express CD30 and these patients seems to have a higher survival rate.

Effect of extracorporeal shock waves on inflammation and angiogenesis of integumentary tissue in obese individuals: stimulating repair and regeneration.

The technology of extracorporeal shock wave therapy (ESWT) has been studied around the world for its possible benefits in the treatment and rehabilitation of aesthetic disorders. To better elucidate its real physiological effect on the integumentary tissue, this study was proposed aimed at evaluating whether ESWT can act to stimulate the inflammatory process and angiogenesis in the dermis and epidermis of obese individuals. This is an immunohistological study that evaluated a set of samples of the integumentary tissue of women with grade II obesity with weight loss of 10% of the initial weight undergoing ESWT treatment; the collection of biological material was performed at the time of surgery of bariatric surgery. For immunohistochemical evaluation, the markers to assess the presence and distribution of inflammatory cells, anti-COX-2, CD3, CD20, CD163, and NK were used. For physiological stimulus pathways for blood vessel angiogenesis, markers CD 34, CD 105 and VEGF were used. Fourteen obese women were included in the study. Positivity was evidenced in the epidermal expression of markers of the inflammatory process COX-2, CD3, CD20, NK cells, CD68, and CD163 (p < 0.0001) in the intervention sample when compared to controls. There was a positive expression for the angiogenesis markers CD105 and VEGF (p < 0.0001) when comparing the intervention group with the control group. It was concluded that ESWT can stimulate a local inflammatory process, mediating and modulating important growth factors to act in the repair process and skin tissue regeneration, being considered a promising treatment for skin diseases related to weight gain or loss.

Oral Lymphoepithelial Cyst: A Collaborative Clinicopathologic Study of 132 Cases from Brazil.

The oral lymphoepithelial cyst (OLC) is an uncommon lesion whose pathogenesis remains poorly understood. The aim of this study was to report the clinicopathologic features of the OLCs and to verify a possible association between OLCs and subgemmal neurogenous plaque (SNP) in the posterior lateral region of the tongue. A retrospective descriptive cross-sectional study was carried out. A total of 106,282 biopsy records of oral and maxillofacial lesions from six oral pathology services in Brazil were analyzed. All cases of OLCs were reviewed, and clinical and histopathological data were collected. Immunohistochemical reactions for S-100 protein were performed to confirm the diagnosis of SNP. Among all lesions, there were 132 (0.11%) cases of OLCs. The series comprised 83 females (62.9%) and 49 males (37.1%), with a 1.7:1 female-to-male ratio and a mean age of 45.8 ± 17.7 years. Most cases involved the tongue (n = 80; 62.0%) and presented clinically as asymptomatic papules or nodules with a yellow or whitish color. Microscopically, most of the cysts were entirely lined by parakeratinized stratified epithelium (n = 89; 67.4%) and filled with desquamated cells, keratin debris, amorphous eosinophilic material, and inflammatory cells in varying amounts. Connection with the epithelium of oral mucosa was observed in 18 cases (13.6%). SNP was found in 9/80 (11.2%) cases involving the tongue. The clinical and demographic features of OLCs were similar to those described in previous studies. Overall, this lesion has a predilection for the posterior region of the tongue of female adults. Clinicians must include the OLC in the differential diagnosis of yellow/white papules and nodules of the oral cavity.

Comparative effects of fractional radiofrequency and microneedling on the genitalia of postmenopausal women: Histological and clinical changes

Abstract Objectives: The authors aimed to evaluate clinical and histological changes induced by Fractional Radiofrequency (FRF) and microneedling in vulvar tissue. Methods: Thirty postmenopausal women were randomly divided into G1 (FRF) and G2 (microneedling) groups. Sub-ablative FRF was executed using disposable fractionated electrodes with an intensity of 8 mJ. Microneedling was performed using a derma roller system. The authors evaluated before and after treatment using the Vaginal Laxity Questionnaire (VLQ), EuroQol Five-Dimensional (EQ-5D) questionnaire, and the Blatt and Kupperman Menopausal Index (BKMI). Additionally, the authors performed biopsies of the labia majora for histological analysis pre- and post-treatment. Data were expressed as mean (± standard deviation). A paired t-test was used for intra-group comparison (pre- and post-treatment), with an independent t-test used to compare intergroup data (both pre- and post-treatment). Results: In the G1 group, the VLQ values showed differences compared to the pre-treatment values with the data obtained 60 days after the beginning of the sessions (p = 0.01). Similarly, the data changes of the G2 group proved to be significant (p = 0.001) across the same time interval. In comparing the groups, VLQ values were not different (p > 0.05). Regarding histological analysis, FRF demonstrated improvement concerning the number of fibroblasts, blood vessels, and fatty degeneration (p < 0.05) compared to the control. Additionally, FRF and microneedling samples showed higher type III collagen and vimentin expression in the immunohistochemical analysis (p < 0.05). Conclusions: The therapies were found to be effective in treating the flaccidity of the female external genitalia. Additionally, histological changes were observed after interventions suggesting collagen remodeling.