Hematologic Malignancies Diagnosed in the Context of the mRNA COVID-19 Vaccination Campaign: A Report of Two Cases.

BACKGROUND: During the last two years, the COVID-19 pandemic led to millions of disease-related deaths worldwide. The efforts of the scientific community facing this global challenge resulted in outstanding achievements. Thus, within one year, new mRNA-based vaccines against SARS-CoV-2 viral infection were released, providing highly efficient protection and showing a very good safety profile in the general population. However, clinical data collection after vaccination is a continuous process for the long-term safety of any new medical product. The aim of our paper is to present two cases of hematological malignancies: diffuse large B-cell non-Hodgkin lymphoma and T/NK-cell lymphoma, diagnosed shortly after the administration of the mRNA COVID-19 vaccine. METHODS AND RESULTS: Case 1: A female patient was admitted with a suspicious cervical mass that emerged within one week after the administration of second dose of the BNT162b2 COVID-19 vaccine. Surgical removal followed by pathology assessment of the specimen confirmed the diagnosis of diffuse large B-cell non-Hodgkin lymphoma. Case 2: A male patient was admitted with multiple ulcerative oral lesions arising on the third day after the initial dose of the BNT162b2 COVID-19 vaccine. These lesions had a progressive character and during the following months were complicated with repetitive episodes of heavy oral bleeding, requiring blood transfusions. The incisional biopsy of the lesions and pathological assessment of the specimens confirmed the diagnosis of T/NK-cell lymphoma. CONCLUSIONS: The safety profile of the mRNA-based vaccines is an undeniable fact. In most cases, suspicions of potentially aggressive side effects were ruled out, proving to be transient post-vaccine reactions. Clinicians should remain alert to report any potentially aggressive manifestations emerging in the context of mRNA COVID-19 vaccination, such as these cases of hematological malignancies, in order to promote additional investigations on the particular mechanisms of action of COVID-19 vaccines and to provide the best medical care to the patients.

Assessment of Serum Urea, Creatinine and Uric Acid in Oral Cancer.

BACKGROUND: Oral squamous cell carcinoma (OSCC) is a common malignancy worldwide, leading to significant disease-associated social and financial burdens. The investigation of underlying mechanisms involved in carcinogenesis and tumor progression in OSCC might provide new therapeutic perspectives with an impact on disease control and patient survival. Our study aims to investigate the interrelation between metabolic processes, expressed through final catabolism products and clinicopathological characteristics in OSCC. MATERIALS AND METHODS: This is a single cancer comparative retrospective study investigating metabolic byproducts, namely serum urea, creatinine and uric acid, detected at the moment of diagnosis in patients with OSCC, in comparison to healthy controls. Clinical and paraclinical data regarding exposure to risk factors, disease staging and pathological characteristics were collected for all patients. Subjects with co-existing systemic or metabolic diseases, or with a history of malignancy, were excluded from the study. Subsequently, the metabolic byproducts revealing significant changes in OSCC patients were considered for a correlation analysis with the disease clinico-pathological characteristics. RESULTS: Blood levels for urea, creatinine and uric acid were determined in a total of 225 subjects: 145 patients diagnosed with OSCC and 80 healthy control subjects admitted to our hospital between 2016 and 2021. The comparative analysis between groups revealed that the serum urea level was significantly lower in OSCC patients (p = 0.0344). Serum creatinine and uric acid did not reveal significant differences between groups. Furthermore, in advanced stages of the disease (stages III and IV), the blood level of urea was significantly lower compared to incipient OSCC (stages I and II) (p = 0.003). We found a negative correlation of serum urea levels with smoking (p = 0.0004) and cervical lymph node metastasis (p = 0.0070), and a positive correlation with aging (p = 0.0000). We found no significant correlation of serum urea with primary tumor size (p = 0.5061) and patient survival (p = 0.2932). CONCLUSIONS: Decreased serum urea levels are detected in patients with advanced OSCC, in correlation with lymph node metastasis. The invasive features of tumor cells in OSCC might be promoted in association with dysregulation of protein catabolism processes, facilitating aggressive behavior in OSCC.

A combination of two regional flaps for the complex reconstruction after head and neck cancer surgery as an alternative approach during the COVID-19 pandemic: A case report.

Since the COVID-19 pandemic outbreak, the medical systems were challenged by continuously increasing numbers of infections and faced critical issues when trying to find solutions for patients suffering from other diseases, including patients with head and neck cancers. Complex surgeries were delayed due to an acute deficit of specialized intensive care medical staff and equipment, which were redirected towards COVID-19 hospitalized cases, with irreversible consequences for the patients. In the present study, the case of locally advanced head and neck cancer was presented, which was treated radically during the heaviest wave of the COVID-19 pandemic in Romania using an alternative approach for immediate defect reconstruction. The case of locally advanced buccal carcinoma (staged T4aN0Mx) was reported, where radical tumor excision was followed by immediate reconstruction using a combination of two regional flaps, temporal and submental, in order to provide timely and optimal medical care. In the difficult context of the COVID-19 pandemic, the standard reconstructive technique, which is the free vascularized tissue transfer, could not be performed for this patient, due to the acute deficit of anesthetists and associated medical staff, as well as the lack of free beds in intensive care units. Combinations of local and regional flaps, such as temporal muscle flap and submental flap, are simple and accessible surgical techniques that require reduced surgical time, minimal equipment, and basic surgical training, advantages that become crucial in historically challenging times, such as a global pandemic. Individual cases, like elderly patients or patients with severe comorbidities, should be considered for these types of reconstructive techniques: simple solutions, single or in combination, which may be an improved therapeutic option for these patients.

Persistent Changes of Peripheral Blood Lymphocyte Subsets in Patients with Oral Squamous Cell Carcinoma.

BACKGROUND: Oral squamous cell carcinoma (OSCC) is a common cancer with high morbidity and mortality. Alterations of antitumor immune responses are involved in the development of this malignancy, and investigation of immune changes in the peripheral blood of OSCC patients has aroused the interest of researchers. METHODS: In our study, we assessed the proportions of CD3+ total T lymphocytes, CD3+CD4+ helper T lymphocytes, CD3+CD8+ suppressor/cytotoxic T lymphocytes, CD3-CD19+ total B lymphocytes, and CD3-CD16+CD56+ NK cells in the peripheral blood of OSCC patients. RESULTS: The data obtained both pre- and post-therapy showed a similar level of total CD3+ T lymphocytes in OSCC patients and control subjects, pinpointing the stability of this immune parameter. On the other hand, pre-therapeutic data showed a lower proportion of helper T lymphocytes (CD4+), a significantly higher level of cytotoxic/suppressive T lymphocytes (CD8+), and a much lower CD4+ T lymphocyte/CD8+ T lymphocyte ratio compared to control subjects. Conversely, evaluation of circulating NK (CD16+) cells showed a markedly higher pre-therapeutic level compared to the control group. CONCLUSIONS: Our results related to immune changes in the peripheral blood add new information to this complex universe of connections between immuno-inflammatory processes and carcinogenesis.

Minimally Invasive Two-Staged Surgery in the Treatment of Large Cystic Lesions of the Jaw.

BACKGROUND: Cystic lesions of the jaw are commonly found in clinical practice. Large, expansive cysts raise challenges for the clinician from both diagnostic and surgical perspectives. The aim of our work is to present a combined, two-staged surgical approach in histologically confirmed non-aggressive cystic lesions of the jaw. METHODS AND RESULTS: We report the case of an extensive mandibular cyst, associating a high risk of bone fracture, that is treated in the initial stage by cystic decompression through marsupialization with concomitant histological diagnostic confirmation, followed in the second stage by radical excision and mandibular reconstruction with titanium mesh, with the purpose of prevention for oro-cystic chronic fistula formation. CONCLUSIONS: Large odontogenic mandibular cysts imply a meticulously conducted assessment and treatment. Marsupialization should be taken into consideration for the treatment of large cystic lesions, followed by secondary enucleation, with minimal risks for the patient. The soft tissue healing process can be optimized with the use of titanium meshes, as an alternative for other reconstructive techniques, in the management of large cystic lesions.

Assessment of Immune Cell Populations in Tumor Tissue and Peripheral Blood Samples from Head and Neck Squamous Cell Carcinoma Patients.

Head and neck squamous cell carcinoma (HNSCC) is a common type of cancer worldwide. Strong connections have been revealed between immune cells and the pathogenesis of HNSCC. Important differences regarding the levels of immune cell subpopulations in both peripheral circulation and tumor microenvironment were emphasized, with some of them having prognostic significance. In our study, we performed an analysis of immune changes in the tumor tissue and the peripheral blood of untreated HNSCC patients, investigating the proportions of different immune cell populations in these two compartments. The local infiltrating lymphocytes were mainly cytotoxic T cells (CD8+). We have also revealed an increased level of B lymphocytes (CD19+) in the tumor microenvironment. In peripheral blood, the most important lymphocyte subtype was represented by the helper T lymphocytes (CD4+). We also found an increased proportion of circulating NK cells (CD56+). Our results showed significant differences between all investigated lymphocyte subtypes in the peripheral blood and the tumor tissue of untreated HNSCC patients, suggesting that the local and systemic expressions of antitumor immune responses are different and that investigation of immune cell proportions in peripheral circulation has different cues that do not reflect the immune infiltrate pattern within the tumor microenvironment. Further studies are necessary to unveil the complex interplay involving local and systemic events in the immune system's fight against cancer.

The Hidden Treasures of Preoperative Blood Assessment in Oral Cancer: A Potential Source of Biomarkers.

(1) Background: Oral squamous cell carcinoma (OSCC) is a common malignancy, and the impact of immune and inflammatory mechanisms in its development and progression are of major interest. The aim of our study is to assess the prognostic potential of circulating immune and inflammatory elements determined preoperatively in patients with OSCC, as well as the development of a new compound parameter with predictive value. (2) Methods: We assessed preoperative fibrinogen (Fib) and the platelet-to-lymphocyte ratio (PLR) in 111 OSCC patients. Using a mathematic algorithm, we determined a composite parameter with cumulative information from Fib and PLR, named Fibrinogen-PLR Algorithm (FiPLA). Survival analysis, followed by bivariate and multivariate analyses, was subsequently conducted. (3) Results: Increased preoperative Fib and PLR levels were associated with poor outcome in OSCC (p = 0.0001 and p = 0.0015, respectively). Preoperative FiPLA values were also associated with poor patient survival (p < 0.0001). Multivariate analysis confirmed the independent prognostic role for FiPLA only (CI95% 1.232-67.770, p = 0.03), showing the superior predictive value of FiPLA compared to its individual components. (4) Conclusions: Preoperative assessments of circulating immune and inflammatory elements can provide high-quality prognostic information, and they represent valuable tools in clinical practice, facilitating the early risk stratification of patients with OSCC.

Prognostic Potential of Tumor-Infiltrating Immune Cells in Resectable Oral Squamous Cell Carcinoma.

(1) Background: The immune microenvironment plays an important role in carcinogenesis and has prognostic potential in many types of cancer. In this study we assess the prognostic character of tumor-infiltrating immune cells CD4+, CD8+ and CD56+ in resectable oral squamous cell carcinoma (OSCC); (2) Methods: We have evaluated the densities of CD4+, CD8+ and CD56+ in two distinct compartments, intratumor and invasion front, in 90 patients with OSCC; (3) Results: Significant differences were found between the tumor compartments for the CD4+ and CD8+ lymphocytes. An improved outcome (OS) was seen in patients with high densities of intratumor CD8+ lymphocytes (p = 0.0086), CD8+ lymphocytes at the front of invasion (p = 0.0011) and for intratumor CD56+ cells (p = 0.0016). Multivariate analysis confirmed the independent prognostic role of CD8+ at the front of invasion (OR = 3.75, CI95% 1.17-12.35, p = 0.026) and for intratumor CD56+ cells (OR = 3.669, CI95% 1.09-15.37, p = 0.035); (4) Conclusions: Tumor-infiltrating CD8+ lymphocytes at the front of invasion and CD56+ in the intratumor compartment display predictive traits in OSCC. A reach immune infiltration with these types of cells is associated with an improved patient outcome.

Assessment of Histological Features in Squamous Cell Carcinoma Involving Head and Neck Skin and Mucosa.

BACKGROUND: squamous cell carcinoma (SCC) is the second most common type of malignancy worldwide. Skin and mucosa of the head and neck areas are the most frequently affected. An aggressive behavior in SCC is not easily detected, and despite all efforts, mortality in these types of cancer did not show major improvements during recent decades. In this study, we aim to determine the role of histological features available through standard pathology assessment in SCC and their relation with tumor behavior and patients' survival. METHOD: in a group of one hundred patients diagnosed with SCC involving the head and neck areas, we assessed the presence of four histological features (tumor/stroma ratio, immune infiltration at the front of invasion, tumor-budding activity, and tumor necrosis), their correlations with tumor type (mucosal or cutaneous), tumor clinicopathological characteristics, and their prognostic potential. RESULTS: the comparison between histological features in cutaneous versus mucosal SCC reveals no significant differences for any of the four parameters assessed. We found significant correlations between tumor/stroma ratio and lymphatic metastasis (p = 0.0275), perineural invasion (p = 0.0006), and clinical staging (p = 0.0116). Immune infiltration at the front of invasion revealed similar correlations with lymph node involvement (p = 0.002), perineural invasion (p = 0.0138), and clinical staging (p = 0.0043). Tumor budding and tumor necrosis correlated with the size of the tumor (p = 0.0077 and p = 0.0004) and the clinical staging (p = 0.0039 and p = 0.0143). In addition, tumor budding was significantly correlated with perineural invasion (p = 0.0454). In mucosal SCC, patients with improved outcome revealed high values for the tumor/stroma ratio (p = 0.0159) and immune infiltration at the front of invasion (p = 0.0274). However, the multivariate analysis did not confirm their independent prognostic roles. CONCLUSIONS: extended histological assessments that include features such as tumor/stroma ratio, immune infiltration at the front of invasion, tumor budding, and tumor necrosis can be an easy, accessible method to collect additional information on tumor aggressiveness in skin and mucosa SCC affecting the head and neck areas.

Accuracy, Labor-Time and Patient-Reported Outcomes with Partially versus Fully Digital Workflow for Flapless Guided Dental Implants Insertion-A Randomized Clinical Trial with One-Year Follow-Up.

(1) Background: Prosthetically-driven implant positioning is a prerequisite for long-term successful treatment. Transferring the planned implant position information to the clinical setting could be done using either static or dynamic guided techniques. The 3D model of the bone and surrounding structures is obtained via cone beam computed tomography (CBCT) and the patient's oral condition can be acquired conventionally and then digitalized using a desktop scanner, partially digital workflow (PDW) or digitally with the aid of an intraoral scanner (FDW). The aim of the present randomized clinical trial (RCT) was to compare the accuracy of flapless dental implants insertion in partially edentulous patients with a static surgical template obtained through PDW and FDW. Patient outcome and time spent from data collection to template manufacturing were also compared. (2) Methods: 66 partially edentulous sites (at 49 patients) were randomly assigned to a PDW or FDW for guided implant insertion. Planned and placed implants position were compared by assessing four deviation parameters: 3D error at the entry point, 3D error at the apex, angular deviation, and vertical deviation at entry point. (3) Results: A total of 111 implants were inserted. No implant loss during osseointegration or mechanical and technical complications occurred during the first-year post-implants loading. The mean error at the entry point was 0.44 mm (FDW) and 0.85 (PDW), p ≤ 0.00; at implant apex, 1.03 (FDW) and 1.48 (PDW), p ≤ 0.00; the mean angular deviation, 2.12° (FDW) and 2.48° (PDW), p = 0.03 and the mean depth deviation, 0.45 mm (FDW) and 0.68 mm (PDW), p ≤ 0.00; (4) Conclusions: Despite the statistically significant differences between the groups, and in the limits of the present study, full digital workflow as well as partially digital workflow are predictable methods for accurate prosthetically driven guided implants insertion.

Ramus to Ramus Mandibular Defect Reconstruction with Osteocutaneous Fibula Free Flap - Case Presentation.

Introduction: Head and neck defects after tumor resection can be difficult to reconstruct using autogenous tissue without utilizing a free flap. Osteocutaneous fibula free flap is now considered the gold standard used for mandibular reconstruction after resections due to malignancy. Case presentation: We present the case of a 49-year old female known with an ectopic mucoepidermoid carcinoma involving the mandibula from one ramus to another. After tumor resection, we have reconstructed the mandible by using the only method available for reconstruction in this case - an osteocutaneous fibula free flap. We were able to reconstruct the mandible using 3D printed custom-made surgical guides. Discussion: Postoperative imaging showed that the height and symmetry of the mandible were satisfactory. There were no microvascular failures and the intraoral healing time was about 10 days. The donor site skin defect from the left leg was grafted with an autograft harvested from the ipsilateral thigh. The donor site healed uneventfully. Conclusion: Osteocutaneous fibula free flap is a highly effective method and sometimes the only one available for reconstruction of mandibular defects after resection of intraoral malignancies. Modern technologies, such as surgical planning using computer-aided design, play a critical part in extensive reconstructions, lowering the total intervention time.

Non-invasive imaging techniques for early diagnosis of radiation-induced squamous cell carcinoma of the lip.

Ionizing radiation was used in the past for treatment of several benign cutaneous conditions, and particularly hemangiomas. Even though radiotherapy was generally effective, it significantly augmented the risk for malignancies, resulting in a consequent heavy decline of its use for benign conditions. However, radiation-induced neoplasia is still encountered in adult patients irradiated during childhood or adolescence. We report a case of well-differentiated squamous cell carcinoma developing on the lower lip of a 59-year-old woman who had previously undergone local radiotherapy for a hemangioma, in which the use of non-invasive imaging techniques such as in vivo reflectance confocal microscopy (RCM) and dermoscopy allowed an early diagnosis and a prompt, effective treatment. Owing to its capability of assessing microscopic features of dysplasia and neoplastic changes, RCM in combination with dermoscopy may provide an invaluable tool for early detection of malignant changes in previously irradiated cutaneous and mucosal areas.

Non-invasive imaging of actinic cheilitis and squamous cell carcinoma of the lip.

An early diagnosis is of overwhelming importance for the management and prognosis of mucocutaneous cancer. Actinic cheilitis (AC), defined by the clonal expansion of genomically unstable keratinocytes, is the most common potentially malignant lesion affecting the lips. Squamous cell carcinoma (SCC) is the most frequent oral malignancy, and there is strong evidence that the majority of the SCCs of the lip originate from AC. There is considerable difficulty in discerning between dysplasia and invasive carcinomas solely on a clinical basis. Although dermoscopy has become an essential tool for skin tumor evaluation, reflectance confocal microscopy (RCM) is a non-invasive imaging technology that has proved itself extremely useful in the diagnosis and monitoring of several skin diseases, including AC and SCC. The present study aimed to re-emphasize the usefulness of RCM in the early detection of malignant transformation, using AC and SCC of the lips as working examples. Due to the apparent innocuousness of AC for numerous patients, it is not possible to overstress the importance of a correct and early diagnosis, proper treatment and long-term patient follow-up as being essential for preventing the progression to lip SCC, or for its timely diagnosis.

From Normal Skin to Squamous Cell Carcinoma: A Quest for Novel Biomarkers.

Squamous cells carcinoma (SCC) is the second most frequent of the keratinocyte-derived malignancies after basal cell carcinoma and is associated with a significant psychosocial and economic burden for both the patient himself and society. Reported risk factors for the malignant transformation of keratinocytes and development of SCC include ultraviolet light exposure, followed by chronic scarring and inflammation, exposure to chemical compounds (arsenic, insecticides, and pesticides), and immune-suppression. Despite various available treatment methods and recent advances in noninvasive or minimal invasive diagnostic techniques, the risk recurrence and metastasis are far from being negligible, even in patients with negative histological margins and lymph nodes. Analyzing normal, dysplastic, and malignant keratinocyte proteome holds special promise for novel biomarker discovery in SCC that could be used in the future for early detection, risk assessment, tumor monitoring, and development of targeted therapeutic strategies.

Gene Expression and Proteome Analysis as Sources of Biomarkers in Basal Cell Carcinoma.

Basal cell carcinoma (BCC) is the world's leading skin cancer in terms of frequency at the moment and its incidence continues to rise each year, leading to profound negative psychosocial and economic consequences. UV exposure is the most important environmental factor in the development of BCC in genetically predisposed individuals, this being reflected by the anatomical distribution of lesions mainly on sun-exposed skin areas. Early diagnosis and prompt management are of crucial importance in order to prevent local tissue destruction and subsequent disfigurement. Although various noninvasive or minimal invasive techniques have demonstrated their utility in increasing diagnostic accuracy of BCC and progress has been made in its treatment options, recurrent, aggressive, and metastatic variants of BCC still pose significant challenge for the healthcare system. Analysis of gene expression and proteomic profiling of tumor cells and of tumoral microenvironment in various tissues strongly suggests that certain molecules involved in skin cancer pathogenic pathways might represent novel predictive and prognostic biomarkers in BCC.

Reflectance confocal microscopy and dermoscopy for in vivo, non-invasive skin imaging of superficial basal cell carcinoma.

Superficial basal cell carcinoma (sBCC) is the second most frequent histological type of basal cell carcinoma (BCC), usually requiring a skin biopsy to confirm the diagnosis. It usually appears on the upper trunk and shoulders as erythematous and squamous lesions. Although it has a slow growth and seldom metastasizes, early diagnosis and management are of crucial importance in preventing local invasion and subsequent disfigurement. Dermoscopy is nowadays an indispensable tool for the dermatologist when evaluating skin tumors. Reflectance confocal microscopy (RCM) is a novel imaging technique that allows the non-invasive, in vivo quasi-microscopic morphological and dynamic assessment of superficial skin tumors. Moreover, it offers the advantage of performing infinite repeatable determinations to monitor disease progression and non-surgical treatment for sBCC. Herein, we present three lesions of sBCC evaluated using in vivo and non-invasive imaging techniques, emphasizing the usefulness of combining RCM with dermoscopy for increasing the diagnostic accuracy of sBCC.

Comparison of Two Techniques for Lateral Ridge Augmentation in Mandible With Ramus Block Graft.

UNLABELLED: The purpose of this manuscript was to assess mandibular ramus block grafts used for augmentation of mandibular posterior segments, followed by subsequent implant placement. Twenty-four human subjects in need of lateral ridge mandibular augmentation were included in the current patient series. INCLUSION CRITERIA: recipient site had at least 10-mm residual height, but less than 4.3-mm bucco-lingual dimension. Autogenous bone blocks were harvested from the mandibular ramus. In the first group ramus block was used in association with platelet-rich fibrin and in the second in association with pericardium membrane. Implant surgery was performed 4 months after bone graft surgery when a total number of 44 implants were placed. Abutments were placed 4 months after implant surgery followed by final restoration. Ramus bone graft was successful in 100% patients for the first group and in 91.67% patients for the second group. Measurement on cone beam computed tomography revealed an average of 5.35 mm of lateral ridge augmentation for group 1 and 5.099 mm for group 2, achieved 4 months after surgery. All implants placed received fixed prosthetic restorations and are in use. Ramus block grafts can be used to allow optimal implant placement, with favor long-term success. Lateral ridge augmentation using mandibular ramus bone graft in association with platelet-rich fibrin is a more predictable and successful technique.