Lymphomas affecting the submandibular glands / Linfomas que afectan las glándulas submandibulares

Background: Lymphomas affecting the submandibular glands are very uncommon and few reports are currentlyavailable in the literature. Therefore, the aim of the current study is to describe the clinical and microscopic fea-tures of an original series of lymphomas affecting the submandibular glands.Material and Methods: The pathology files of two institutions were searched for lymphoma cases affecting thesubmandibular glands. The original hematoxylin and eosin, and immunohistochemical slides were revised by apathologist for diagnosis confirmation following the revised 4th edition of the World Health Organization classification of tumours of haematopoietic and lymphoid tissues. Clinical data regarding age, sex, clinical manifestation,treatment, follow-up and status at last appointment were retrieved from the patients’ medical charts.Results: During the period investigated, 16 cases were included in the study. Females predominated (10:6) with amean age of 57.8 years-old. Tumors usually presented as asymptomatic swellings. MALT lymphoma representedthe most common subtype, followed by diffuse large B cell lymphoma and follicular lymphoma. Three patientsdied, one of them affected by plasmablastic lymphoma, one by DLBCL and one by MALT lymphoma.Conclusions: Low-grade B cell lymphomas predominate in the submandibular glands, but DLBCL and other sub-types may also be rarely diagnosed in this salivary gland.(AU)

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.

Symptomatic subgemmal neurogenous plaque in patients with COVID-19: Is there an association?

BACKGROUND: Subgemmal neurogenous plaques (SNP) are composed of neural structures found in the posterolateral portion of the tongue, rarely biopsied as most of them are asymptomatic or eventually only clinically managed. We aimed to investigate a case series of possible correlation of symptomatic subgemmal neurogenous plaque (SNP) with coronavirus disease 2019 (COVID-19). METHODS: Eleven formalin-fixed paraffin-embedded cases from patients with previous confirmed COVID-19 (by RT-PCR) were retrieved from two pathology files. Histological sections were morphologically studied, and then submitted to immunohistochemical reactions against S-100 and neurofilament proteins, neuron-specific enolase, Glial fibrillary acidic protein (GFAP), synaptophysin, CD56, Ki67, cytokeratins (7, 8-18, 19, 20), nucleocapsid and spike proteins (SARS-CoV-1; and -2) and epithelial membrane antigen (EMA) antibodies. Clinical data were retrieved from the patients' medical files, including the symptoms and the complete history of the progression of the disease. RESULTS: The patients who had COVID-19 included in this study experienced painful lesions in the tongue that corresponded to prominent or altered SNP. Microscopically, neural structures were positive for S-100, GFAP and neurofilament protein. And the cellular proliferative index (by Ki-67) was very low. CONCLUSION: Thus, based on the current results, we hypothesize that symptomatic SNP may be a late manifestation of COVID-19 infection.

A Case of Doxycycline-induced Melanin in the Gingiva Tissue: Case Report.

BACKGROUND: Gingival pigmentation is a discoloration of the gingiva due to a variety of lesions and conditions associated with several endogenous and exogenous etiologic features. OBJECTIVE: The purpose of this study is to describe a report of gingival pigmentation in a patient who used doxycycline. CASE REPORT: A 21-year-old Caucasian female was under dermatological treatment and antibiotic therapy with doxycycline 100 mg (one time a day) for 90 days. She presented brown pigmentation at the gingival margin on the facial surfaces of the upper and lower anterior incisors and premolars. The patient was evaluated by immunohistochemical (S-100, Melan-A, and HMB-45) and histopathologic analyses, and clinical history. Blood levels of malondialdehyde (MDA), glutathione (GSH), and superoxide dismutase (SOD) were analyzed by UV/Vis spectroscopy. The adrenaline, noradrenaline, and dopamine in blood were analyzed by high-performance liquid chromatography (HPLC); dehidroepiandrosterone (DHEA) in serum by radioimmunoassay; and luteinizing hormone (LH) and 25-Hydroxyvitamin D by chemiluminescence. Hematoxylin-eosin stained sections revealed keratinocytes with pigment compatible with melanin. The Fontana-Masson staining was positive in melanophages and in some basal keratinocytes. S-100, Melan A and HMB-45 were confirmed as positive markers of melanocytic differentiation in gingival tissue. We observed a significant increase in malondialdehyde (p˂0.05) and a decrease in superoxide dismutase levels (p˂0.05). The dopamine value was found to be 15 pg/ml (reference value ≤ 10 pg/ml). CONCLUSION: The use of doxycycline is associated with an increase in oxidative stress and of dopamine with melanin pigments in the gingival tissue. This case report showed a cause-effect relationship between exposure to doxycycline and pigmentation of the marginal gingiva.

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.

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.

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.

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.

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

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.

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.

Morphological and tissue-based molecular characterization of oral lesions in patients with COVID-19: A living systematic review.

OBJECTIVE: This living systematic review aims to integrate the morphological and tissue-based molecular characterization of oral lesions occurring in individuals infected by COVID-19 (OLICs). MATERIALS AND DESIGN: This study was performed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. PubMed, Web of Science, Scopus, Ovid, Embase, and LILACS were searched to identify reports on OLICs with morphological and/or tissue-based molecular data. RESULTS: Four studies reporting five cases were included. Three patients were male, and the mean age of the individuals was 47.6 years. The most reported anatomical location was the palate (n = 4), whereas ulcers were the most frequent clinical presentation (n = 3). Histopathologically, all cases revealed cell vacuolization and exocytosis in the epithelial layer. In the mesenchymal layer, inflammatory cell infiltrate and thrombi/microvascular thrombosis were observed in three cases. Immunohistochemical reactions were performed in two cases. Both cases were negative for HHV-1, HHV-2, and CMV. One case revealed positivity for SARS-CoV-2 spike protein. No other molecular tests were found for the characterization of OLIC. CONCLUSIONS: The pathological characteristics of OLICs are still unspecific. However, with the ongoing COVID-19 pandemic and well-documented new cases, whether OLICs are due to coinfections or has a primary origin can be determined.