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CAR T‑Cell therapy for the management of mantle cell lymphoma

Mantle cell lymphoma (MCL) is a subtype of Non-Hodgkin lymphoma (NHL) of mature B-cells characterized by translocation, which is typically due to excess expression of Cyclin D1. However, with the progress in our knowledge of the causes of MCL and available treatments for MCL, this cancer is still incurable. Age, male gender, rapid advancement, significant nodal involvement, elevated serum lactate dehydrogenase level, and prognostic indications including increased expression of Ki-67 and presence of TP53 mutation, are symbols of poor outcome. Advanced immunotherapy using chimeric antigen receptor (CAR)-T cells is advantageous for patients suffering from B-cell malignancies and MCL. Targeting B-cell antigens on the cell surface is a feasible approach in re-occurring (R/R) MCL because of significant responses obtained in other B-cell cancers. USFDA has approved brexucabtagene autoleucel (Tecartus, KTE-X19), a novel CAR T-cell therapy to be used in patients with MCL who have not responded to previous treatments or have relapsed. The FDA approved this new treatment depending on the outcomes of the ZUMA-2 clinical trial. Serious adverse reactions, moderate anti-tumor activity, allergen withdrawal, antigen escape, limited tumor infiltration, and trafficking are major barriers to successful CAR T-cell therapy. This review is a brief synopsis of the development of CAR T-cell therapy for MCL.

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ROLE OF NLRP3 INFLAMMASOME COLITIS-ASSOCIATED COLORECTAL CANCER

NLRP3 inflammasome remains controversial with both protective and harmful effects reported in experimental colitis and colitis associated colorectal cancer (CAC) murine models. To address this controversy, we designed the world first murine model deficient in NLRP3 in a spontaneous chronic colitis mouse model Winnie1. Our results of WinniexNlrp3−/− at 12 and 16 weeks, shows spontaneous multiple colonic tumours with significant colonic shortening, increased activity of myeloperoxidase, Nitric Oxide and serum C-reactive protein. Histopathology revealed high-grade dysplasia and adenocarcinoma regions with increased DNA damage, oxidative stress, Ki-67, VEGF and Survivin biomarkers. Colon tissue culture supernatants identified differential expression of cytokines and chemokines. Protein analysis of colonic tumours showed upregulation of Wnt/β-catenin and PI3K/ AKT pathways while qPCR identified upregulation of CAC biomarkers. Faecal microbiota analysis revealed significant increase in colitogenic members in the phylogenetic architecture in WinniexNlrp3−/− mice while metabolomics profiling revealed upregulation of key metabolites and short chain fatty acids. In addition, we looked at the therapeutic effect of specific small molecule NLRP3 inhibitor, MCC950 in Winnie mice. Oral administration of MCC950 significantly improved colonic length, disease activity index, histopathology and significantly reduced proinflammatory cytokines ameliorating colitis 2 .Our results show genetic ablation of NLRP3 gene in a chronic colitis model lead to CAC. However, chemical inhibition of an overactive NLRP3 inflammasome in chronic colitis attenuates severity of the disease. Altogether our results stresses the need for careful investigation of temporal therapeutic strategies for NLRP3 inhibitors in the gut at different disease phases in clinically relevant experimental models.

References

1. Heazlewood, C. K. et al. Aberrant mucin assembly in mice causes endoplasmic reticulum stress and spontaneous inflammation resembling ulcerative colitis. PLoS Med. 5, e54 (2008).

2. Perera, A. P. et al. MCC950, a specific small molecule inhibitor of NLRP3 inflammasome attenuates colonic inflammation in spontaneous colitis mice. Scientific Reports. 8, 8618 (2018).

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Desmoplastic fibroma of the mandible: case report
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Introduction :

Desmoplastic fibroma is an extremely rare and locally aggressive benign tumor. It can affect all bones of the body but most frequently the mandible, followed by long bones (the femur, radius, and tibia) and the bones of the pelvis.

Objective and importance : A unique aspect of our studyis the rare focus on desmoplastic fibroma in children. Furthermore, reports of this pathology are exceedingly rare.

Presentation of the case:

We studied a 3-year-old patient, with no notable pathological history, who presented with swelling in the cheek area that has been developing since birth without pain or inflammatory signs.

The radiological examination showed a multilocular lesion breaking the bony cortex and reaching the jugal soft tissues.

A biopsy of the mass was performed intraorally.

Results :

Histologically, it is a tumoral proliferation made of bundles of regular and uniform myofibroblastic cells. The stroma is collagenous, the seat of a few congestive capillaries aligned parallel to the bundles. This proliferation is non-encapsulated and infiltrates the surrounding muscle and bone tissue.

The absence of cytonuclear atypia, atypical mitoses, and necrosis.

An immunohistochemical study was carried out showing:

- The positive marking of tumor cells using β-cathenin and AML.

By combining clinical, radiological, histological, and immunohistochemical data, the diagnosis of a desmoplastic fibroma was made.

Discussion :

Desmoplastic fibroma is an exceptional tumor that constitutes less than 0.1% of all primary bone tumors. It mainly affects adolescents and young people with a peak age between 20 and 30 years old and there is no gender predominance.

Clinically, desmoplastic fibroma is manifested by a painless swelling, difficulty in opening the mouth, and displacement of teeth. Sometimes, the tumor is asymptomatic and the discovery is incidental.

Radiologically, desmoplastic fibroma manifests as a well-defined, multilocular, and radiolucent lesion. Intralesional trabeculations are often present. Large lesions can destroy the bone cortex and infiltrate the surrounding soft tissue, which is clearly shown by MRI displaying a lesion with T1 and T2 hyposignal.

Histologically, it is a sparsely cellular-infiltrating tumor proliferation arranged in bundles of monomorphic spindle cells resting on the abundant collagenous stroma. It is characterized by the absence of necrosis and very rare mitoses. This proliferation may show positive cytoplasmic staining using β-cathenin and AML. The main differential diagnoses are fibrous dysplasia, low-grade central osteosarcoma, low-grade myofibrodysplasia, myoepithelial tumors, follicular dendritic tumors, and synovialosarcoma.

We selected surgical resection with wide resection margins as the treatment. Aggressive curettage may be used. Tumoral surgical margins were associated with higher recurrence rates.

Conclusion :

Desmoplastic fibroma is an extremely rare, benign, and locally aggressive tumor that most frequently affects the mandible. It generally occurs in children and young adults in the form of an osteolytic mass. The positive diagnosis of histological and molecular biology is recommended to eliminate differential diagnoses. Treatment is based on surgery and the prognosis is characterized by recurrences in the case of excision with tumoral margins.

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OPTIMIZATION AND DEVELOPMENT OF MAGNETICALLY TRIGGERED LETROZOLE NANOLIPOSOMES FOR BREAST CANCER TARGETING
Published: 27 March 2024 by MDPI in The 4th International Electronic Conference on Cancers session Cancer Therapy

ABSTRACT

BACKGROUND:

Breast cancer is one of the most frequently diagnosed cancers and is the leading cause of death among women worldwide. Breast cancers are most common among women and they represent the second most common cancer condition. Moreover, breast cancers account for14% of all cancers in women. The development of magnetic nanoliposomes as carrier-loaded drug delivery system promotes the active-site-targeted delivery of drug molecules with increased biocompatibility and reduced toxicity and side-effects.

AIM:

The research work aims to develop and characterize magnetically letrozole nanoliposomes used for breast cancer targeting.

METHODOLOGY:

The thin film hydration method is carried out in preparation of letrozole nanoliposomes. Citric-acid-coated magnetic nanoparticles are synthesized via the chemical co-precipitation method. The formulated nanosuspension is characterized through initial characterization studies.

RESULTS:

The characterization studies show that various physical, chemical, and morphological integrity of nanoliposomal suspension. In vitro characterization studies reported that the average hydrodynamic size of LET-MNLs was 89.23 nm with a charge of -24mV and apolydispersity index of 0.395. The drug loading and encapsulation efficiency of the prepared formulation were studied at various stages to confirm the conjugation of letrozole with the magnetic nanoliposomal system, and the highest encapsulation efficiency was found to be 76.83%.

CONCLUSION:

Liposomal nanocarriers promote targeted responses and iron oxide nanoparticles create an onsite action and lower the toxicity associated with unwanted biodistribution. Based on the results from pharmaceutical characterizations, the developed formulation is fit for targeted drug delivery applications. Further in vitro and in vivo studies will be carried out to assess the anticancer efficacy of developed formulation.

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Two novel miRNAs encoded by oncogene MSI1
, , , , , , ,

Introduction: The RNA-binding protein Musashi1 (MSI1), well known for its increased expression level in several malignancies, has been reported as a prognostic biomarker. Since miRNAs are among the very stable non-coding RNAs in body fluids and are considered to be more efficient biomarkers in several biological processes, we were interested to find out if any novel miRNAs are encoded by MSI1 genes, which could be considered as novel biomarkers in future studies. Both experimental and computation-based methods were used to find the most reliable structures.

Methods: Several types of bioinformatics software were used to predict novel miRNA precursors based on RNA secondary structure criteria and evaluate the probability of producing mature miRNAs using Drosha/Dicer processing. For experimental confirmation, candidate miRNA precursors were transfected into HEK293T cells and their ability to produce mature miRNAs was assessed via RT-qPCR and sequencing. Additionally, we analyzed the endogenous expression of miRNAs in cancer cell lines and breast cancer samples.

Results: Two structures within the intron 4 of the MSI1 gene, named MSM2 and MSM3, which possessed the most characteristics of miRNA precursors, were selected for further studies. In HEK293T cells, the MSM3 precursor generated two mature miRNAs, MSM3-3p and MSM3-5p, while MSM2 generated only one mature miRNA, MSM2-5p. The significant endogenous expression of MSM2-5p and MSM3-3p was detected in MCF-7 and SH-SY5Y cell lines, but not the MSM3-5p. Interestingly, the expression of novel miRNAs was only detected in breast clinical samples with increased expression levels of MSI1.

Conclusion: Our RT-qPCR and sequencing results confirmed the presence of two novel miRNAs within the intronic region of the MSI1 gene. The expression of these novel miRNAs was confirmed in cancer cell lines and breast cancer samples. However, additional studies are necessary to fully understand the precise roles of these novel miRNAs in various cancers and assess their potential as biomarkers.

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Role of Oxidative/Nitrosative Stress in the Development and Progression of Clear Cell Renal Cell Carcinoma

It is believed that oxidative stress plays a role in the development and progression of renal cell carcinoma (RCC). Identifying oxidative and nitrosative modifications in proteins and defining their roles in clear cell RCC (ccRCC) may be helpful in the elaboration of targeted therapeutic approaches to mitigate protein damage. The study aimed to investigate the status of oxidative/nitrosative stress and to explore its role in development and progression. The studied group consisted of 48 newly diagnosed ccRCC and 30 healthy controls. Serum levels of oxidative stress markers, such as advanced oxidation protein products (AOPPs), thiol groups, Amadori products, 3-nitrotyrosine, nitrate/nitrite, malondialdehyde (MDA), 4-hydroxy-2-nonenal, and total antioxidant capacity (TAC), were determined. Additionally, associations between tumor stage assessed according to TNM classification, histological grade, and the effect of the presence of angioinvasion on the level of stress markers were evaluated. The levels of Amadori products, 3-nitrotyrosine, and nitrate/nitrite were elevated, while the levels of thiol groups and TAC decreased in the ccRCC group. The levels of AOPP, Amadori, and 3-nitrotyrosine increased, and thiol group and TAC levels decreased with the increasing clinical stage of the tumour. In the case of the advanced histological assessment of the tumour, we found decreasing levels of thiol groups and increasing levels of MDA. In patients with angioinvasion, nitrate/nitrite and MDA levels were significantly elevated in those without angioinvasion. Moreover, we found weak significant positive correlations of AOPP and MDA with age. Furthermore, the concentration of thiol groups and the TAC were inversely correlated with age. Surprisingly, there was not any correlation between markers of oxidative stress and sex of patients and their body mass index. Oxidative stress increased with the progression of the disease assessed according to the TNM and histological grade. These results demonstrate systemic oxidative stress in ccRCC, suggesting the therapeutic application of antioxidants.

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SYNTHESIS AND PRELIMINARY INVESTIGATION OF METAL NANOPARTICLES FROM THE STEM EXTRACT OF BACOPA sp. FOR THE TREATMENT OF LUNG CANCER
Published: 27 March 2024 by MDPI in The 4th International Electronic Conference on Cancers session Cancer Therapy

Lung cancer is the third most common cancer in women and the most common cancer in males. Chemotherapy, allopathy, hormone therapy, radiation therapy, surgery, immune system, and targeted therapies are frequently used to treat lung cancer. These medications induce other diseases and have a variety of negative effects. Thus, we used a different strategy and sought to treat lung cancer with medicinal herbs. We selected the perennial creeping herb Bacopa monnieri, which belongs to the Scrophulariaceae family, among other medicinal herbs. It contains several active phytoconstituents, including sterols, alkaloids, flavanoids, terpenoids, and saponins. The primary component with anti-lung cancer efficacy is phytosterol, according to the components. According to the phytochemical investigation, this plant contained it. The literature review indicates that the problem is lessened by nanoparticle production. Thus, the novelty of our work is the manufacture of zinc oxide nanoparticles for the treatment of lung cancer using BM stem extracts. Researchers have been interested in ZnO material because of its huge band gap (3.37 eV) with n-type semi-conductivity and high excitonic binding energy (60 meV) with regards to the different semiconductor nanomaterials, such as TiO2, SnO2, GaN, CuO, GaAs, Si, and ZnO. Zinc oxide in bulk is economical and can be used for many different industrial processes, such as the creation of nanoparticles. Zinc acetate serves as the precursor and stem extract serves as the reducing agent in the synthesis. The absorbance peak between 300 and 400 nm in UV spectroscopy was used to characterize the ZnO nanoparticles that were produced from hydromethanolic BM stem extract. In later research, lung cancer treatment might be considered. Given that lung (A549) cell lines will be treated with phytosterol-containing hydromethanolic BM stem extract in the form of ZnO nanoparticles, which will cause cell death by reducing cell proliferation, DNA damage and apoptosis may occur.

INTRODUCTION

One of the main causes of illness and mortality worldwide is cancer. Among non-communicable diseases, cancer ranks second in terms of mortality, after cardiovascular disease. Globally, cancer is responsible for one in eight fatalities, which is more than the combined deaths from AIDS, TB, and malaria. Treatment options for this complex, multifactorial, heterogeneous disease include chemotherapy, hormone therapy, surgery, radiation, immune system, and targeted therapies. The disease's defining feature is the unchecked growth and spread of abnormal cells, which can be brought on by a variety of internal, external, genetic, and environmental factors.

Lung cancer is the second most common cancer in both men and women, and is a highly metastatic disease. When compared to other tumor types, lung carcinoma is the most common cause of cancer-related death and has the lowest economic impact. Lung cancer accounts for 1.6 million cancer deaths annually (roughly 20% of all cancer deaths) and an additional 1.8 million new cases worldwide each year, making it the leading cause of cancer mortality worldwide in both high-income and low- and middle-income countries.

BACOPA Species

A genus of 70–100 aquatic plants is called Bacopa. The term "water hyssop" is commonly used, although it is misleading because Bacopa is not closely related to hyssop despite having a very similar look. These have upright or decaying stems, and they can be annual or perennial. The leaves are sessile and twisted in the opposite direction. The leaf has a regular, round-to-linear blade with a palmate or pinnate vein. The stems might be smooth or hairy. Seeds and broken stems are dispersed throughout the area. The scent of crushed leaves strongly resembles lemon. Herbs have been shown in preliminary clinical work to improve memory. Some of these plants are commonly utilized in warmer climates in freshwater ponds and aquariums.

ZINC OXIDE NANOPARTICLES

In the industrial setting, bulk zinc oxide is inexpensive and useful for several processes, such as the creation of nanoparticles. As a result, it can withstand strong electrical fields, elevated temperatures, and high power usage. Wurtzite architecture is a predominant feature of ZnO nanocrystals, with lattice parameters of a = 0.3296 nm and c = 0.52065 nm. In its most basic form, ZnO exhibits tetrahedron geometry, where each ion is surrounded by four counterions that point in the direction of the tetrahedron's corners. Three main mechanisms have been identified by NPs to improve food and package consistency: the release of antimicrobial ions, the disruption of bacterial cell integrity, and the generation of reactive oxygen species (ROS) as a result of light exposure.

AIM

To prepare and investigate the ZnO nanoparticles with the stem extract of Bacopa monnieri for the treatment of Lung cancer.

OBJECTIVES

  • To extract the components from the dried and powdered stem.
  • To synthesize the ZnO nanoparticles.
  • To screen the phytochemical components of the BM stem extract.
  • To characterize the extracts and nanoparticles.
  • To analyse the components present in it.

RESULTS AND DISCUSSION

Cancer treatment has benefited greatly from the discovery of drugs derived from medicinal plants. Additionally, throughout the past 50 years, the majority of new therapeutic uses of plant derivatives and secondary metabolites have been developed to combat cancer. After that, the project research was conducted to examine the phytochemistry and anticancer potential of stem extract from Bacopa monnieri (L.).

PHYTOCHEMICAL SCREENING TEST

Using established procedures, the phytochemical screening test was performed to verify that the stem extract included flavonoids, alkaloids, proteins, phytosterols, and carbs.

CHARACTERISATION OF ZINC OXIDE NANOPARTICLES

The creation of zinc oxide nanoparticles is confirmed by the absorbance peak seen between 300 and 400 nm. The optical characteristics of the produced ZnO NPs have been examined using UV—visible spectroscopy. Moreover, the heavy absorption band seen between 300 and 400 nm can be attributed to the intrinsic band gap absorption of ZnO due to the electron transitions from the valence band to the conduction band.

CONCLUSIONS

According to the aforementioned study, ZnO nanoparticles containing Bacopa monnieri stem extract contain phytosterols, which are used to cure lung cancer.

Following a battery of phytochemical screening assays, the hydromethanolic BM stem extract revealed the absence of quinoids, saponins, and phenols but the presence of proteins, carbohydrates, phytosterols, and flavonoids.

The next step is to create zinc oxide nanoparticles using a magnetic stirrer and a NaOH solution to modify the pH. The solution for white precipitate was made. Following centrifugation and drying, 23.2 mg of zinc oxide nanoparticles was produced.

UV—visible spectroscopy was used to describe the optical characteristics of the zinc oxide nanoparticles. In this case, the presence of zinc oxide nanoparticles was confirmed by the absorbance peak seen between 300 and 400 nm. We were unable to conduct FTIR analysis and detect the in vitro anti-cancerous activities of the synthesized ZnO NPs because of the pandemic conditions.

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Thyroid-sparing volume-modulated arc therapy (TS VMAT)in patients with non-distant metastatic nasopharyngeal carcinoma: a feasibility study
Published: 27 March 2024 by MDPI in The 4th International Electronic Conference on Cancers session Cancer Therapy

Introduction

Radiotherapy is an important treatment for nasopharyngeal carcinoma (NPC), but it can cause damage to other normal organs while improving the survival rate of patients. The most common of these is an imbalance of thyroid hormones caused by radiation damage to the thyroid gland, which affects many important functions of the body, such as regulating body temperature, metabolism, cholesterol levels, and growth. Moreover, there is no further research exploring whether we can minimize the radiation dose to the thyroid using volumetric-modulated arc therapy (VMAT) as the treatment for non-distant metastatic NPC. This study aimed to assess the feasibility of thyroid-sparing volumetric-modulated arc therapy (TS VMAT) in patients with non-distant metastatic NPC.

Methods

This dosimetric feasibility study included 30 patients with non-distant metastatic NPC who were treated with radiotherapy at the Affiliated Cancer Hospital of Shantou University Medical College between 2020 and 2023. Computed tomography datasets of 30 patients and inverse-planning VMAT with Eclipse version 15.6 treatment planning systems were used to generate thyroid-sparing volume-modulated arc therapy (TS VMAT) plans and non-thyroid-sparing volume-modulated arc therapy (NTS VMAT) plans. These patients were divided into 3 groups, including the bilateral upper neck irradiation group (bilateral UNI group), the one-side lower neck irradiation group (one-side LNI group), and the bilateral lower neck iradiation group (bilateral LNl group) with 10 patients in each group. All target volumes and organs at risk (OARs) were delineated by the radiation oncologists, according to Guidelines of Chinese Society of Clinical Oncology (CSCO, version 2023) and the Chinese Guidelines for Radiation Therapy of Nasopharyngeal Carcinoma (version 2022). The two radiotherapy plans were evaluated using dose volume histograms, homogeneity index (HI) and conformity index (CI) of all PTVs, and irradiation doses to the thyroid and other OARs.

Results

There were no statistically significant differences in HI and CI between two plans in all groups. In comparison to the NTS VMAT plans, there was a significant reduction in radiation dose to thyroid in TS VMAT plans of all groups, both in terms of the mean dose (Dmean), the minimum dose (Dmin), and the volume irradiated with 40 Gy or more (V40). For the protection of OARs, TS VMAT plans in the bilateral UNI group showed lower radiation dosages to left parotids (30.63±3.07 vs 30.41±3.08, p=0.025*) and left eyeballs (23.63±9.66 vs 21.78±9.05, p=0.006*), and the irradiation doses to other OARs had no significant differences between the two plans in all groups, such as brainstem PRV, brainstem, spinal cord PRV, lens, optic nerves, pituitary, oral cavity, and larynx.

Conclusions

The use of TS VMAT plans appears to be a viable approach in radiotherapy planning for patients with non-distant metastatic NPC. TS VMAT plans effectively reduce radiation dose to the thyroid gland compared with NTS VMAT plans, thus mitigating patients’ risks of developing hypothyroidism without exacerbating the homogeneity index (HI), conformity index (CI), and the irradiation doses to OARs. The encouraging results of our study need to be further validated by clinical trials with larger sample sizes to establish a clear advantage in the protection of thyroid function in NPC patients treated with TS VMAT plans.

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Comparative Study of Long-Term Efficacy and Safety of neoadjuvant chemotherapy before radical surgery versus concurrent chemoradiotherapy for FIGO 2018 stage IB3/IIA2 cervical squamous cell carcinoma: a propensity score-matched analysis
, , , , , , ,
Published: 27 March 2024 by MDPI in The 4th International Electronic Conference on Cancers session Cancer Therapy

Introduction: Cervical cancer remains a significant public health problem affecting middle-aged women, particularly in less resourced countries. Three-dimensional conformal radiotherapy (3DCRT) is still a commonly used radiotherapy technique in countries with fewer resources. This study was conducted to compare the long-term efficacy and safety of neoadjuvant chemotherapy before radical surgery (NCRS) and concurrent chemoradiotherapy (CCRT) for FIGO 2018 stage IB3/IIA2 cervical squamous cell carcinoma in a resource-limited setting where only a 3DCRT radiotherapy technique was accessible.

Methods: This retrospective study encompassed a cohort of 300 patients diagnosed with FIGO 2018 stage IB3/IIA2 cervical squamous carcinoma, who received treatment at Tianjin Central Hospital of Gynecology Obstetrics (Tianjin, China) from January 2011 to December 2016. The primary data utilized in this study can be accessed online without any restrictions. The clinical outcomes and incidence rates of adverse effects in 137 patients with stage IB3/IIA2 cervical squamous cell carcinoma who underwent neoadjuvant chemotherapy followed by radical surgery (NCRS) with those of 163 patients who underwent concurrent chemoradiotherapy (CCRT) were compared. None of these patients had received adjuvant chemotherapy or adjuvant radiotherapy after surgery or CCRT. Propensity score matching analysis was used to match the two groups, considering factors such as age, anemia, tumor diameter, degree of pathological differentiation, and clinical stage, to enable further statistical comparisons. Survival analysis was conducted using Kaplan—Meier curves, log-rank tests, and Cox proportional hazards regression analyses. Additionally, chi-squared tests were employed to compare the incidence rates of recurrence and adverse effects between the two groups.

Results: Propensity score matching identified 103 matched pairs of patients. The NCRS and CCRT groups displayed 5-year overall survival (OS) rates of 85.4% and 91.2%, respectively, with no statistically significant difference (p = 0.19). Additionally, the NCRS and CCRT groups exhibited 5-year disease-free survival (DFS) rates of 76.7% and 89.3% (p = 0.02), and the recurrence rates were 20.4% and 9.7% (P = 0.03), respectively. Notably, the CCRT group exhibited a higher incidence of early adverse events (including myelosuppression, gastrointestinal, and urinary complications) compared to the NCRS group. This difference was observed in both any-grade adverse events (79.6% vs 35.9%, p < 0.001) and grade-3 adverse events (15.5% vs 0.03%, p = 0.005). There was no statistically significant disparity observed between the two groups in relation to late adverse events. In the multivariate analysis of clinicopathologic characteristics for OS, stage IIA2 (HR 8.51; p = 0.037) emerged as an independent risk factor, while histologic grade 2–3 (HR 4.88; p = 0.03) and anemia (HR 2.76; p = 0.025) were identified as independent risk factors for DFS.

Conclusion: Although the incidence of early side effects was increased in patients treated with CCRT, patients had significantly higher DFS rates and lower recurrence rates compared to those treated with NCRS. In patients with FIGO 2018 stage IB3/IIA2 squamous cervical cancer, CCRT seems to be a better option compared to NCRS in a resource-limited setting where only a 3DCRT radiotherapy technique was available.

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Two cases of plunging goiter revealing primary thyroid lymphoma
, , ,

Introduction:

Thyroid lymphoma is a rare tumor that accounts for 5% of all thyroid neoplasms and 1 to 2% of extranodal lymphomas. The predominant histological type is diffuse large B-cell lymphoma. It mainly affects women in their sixth decade and it is manifested by a rapidly progressive cervical mass. The diagnosis is histological and treatment is essentially based on chemotherapy.

Case presentation:

Case 1: a 50-year-old female patient, with no notable pathological history, who presented with cervical swelling that has been present for 6 months and is associated with dysphagia, dyspnea, and respiratory difficulty.

The clinical examination found the patient conscious and stable on the hemodynamic and respiratory levels. Cervical examination reveals cervical swelling that is painful on palpation and mobile on swallowing.

The biological assessment found TSH at 8.71 mIU/l, free T4 at 8.64 mIU/l, and free T3 at 3.68 mIU/l, suggesting peripheral hypothyroidism. Anti-thyroperxydase antibodies were elevated at 177.88IU/ml.

Cervical ultrasound found a diffuse heterogeneous goiter associated with right supraclavicular lymphadenopathy, measuring 20 x 10 mm.

Cervicothoracic CT found a heterogeneous plunging goiter without suspicious lesions.

Case 2: a 75-year-old female patient, followed for hypertension under monotherapy, admitted for cervical swelling.

The clinical examination found the patient conscious and stable on the hemodynamic and respiratory levels. Cervical examination revealed a cervical swelling that was painful on palpation and mobile on swallowing.

The biological assessment showed a thyroid assessment without abnormalities.

Cervico-thoracic CT revealed a plunging and compressive nodular goiter starting from the left lobe associated with sub-centimeter laterocervical and mediastinal lymphadenopathy.

Both patients underwent surgical biopsy of the mass.

Results:

Histologically, the two biopsies corresponded to malignant tumor proliferation occurring mainly in diffuse layers. The tumor cells were dyscohesive, atypical, and large with hyperchromatic nuclei and clear-appearing cytoplasm. We also noted the presence of numerous mitotic figures.

The immunohistochemical study showed the following:

- Strong and diffuse positive marking of tumor cells by the anti-CD20 antibody.

- A tumor proliferation index estimated at 85% for the first case and 75% for the second case.

- Negative staining of tumor cells via anti-CK antibody and anti-CD3 antibody.

By combining clinical, radiological, histological, and immunohistochemical data, a diagnosis of diffuse large thyroid B-cell lymphoma was made for both cases.

Discussion:

Primary thyroid lymphoma (PLT) is defined as lymphoma developing from the thyroid gland and not from another area and arriving at the thyroid by contiguity or metastasis. It is generally a non-Hodgkin lymphoma, of which diffuse large B-cell lymphoma accounts for 70%, followed by B-cell non-Hodgkin lymphoma of mucosa-associated lymphoid tissue (MALT), follicular lymphoma, mantle cell lymphoma , Burkitt lymphoma, and finally angioblastic lymphoma.

A history of Hashimoto's thyroiditis is a well-recognized risk factor for developing PTL, with a relative risk of 67 compared with people without thyroiditis.

This pathology is generally manifested by rapidly progressive cervical swelling associated with signs of compression including dysphagia, dyspnea, and superior vena cava syndrome, with a deterioration in general condition and night sweats. The biological assessment found euthyroidism in patients followed for Hashimoto's thyroiditis treated with levothyroxine, and hypothyroidism in the other patients. Anti-thyroperoxidase antibodies were elevated in 60% of patients.

The use of ultrasound (US) scans can suggest a diagnosis, as the mass may be nodular, diffuse, or mixed. Common ultrasound findings include a hypoechoic solid lesion associated with hypervascularity and a diversity that characterizes its outline. Therefore, a thorough investigation is indicated in any patient with autoimmune thyroiditis who has suspicious findings on ultrasonography.

Fine needle aspiration (FNA) has become an essential tool in the management of thyroid diseases, but it has shown inconsistent results in the diagnosis of primary thyroid lymphomas; for this, core or surgical biopsies are necessary to establish a definitive diagnosis.

Histologically, LBDGC is characterized by a diffuse architecture with large B cells of variable appearance (centoblasts and immunoblasts). Tumor cells typically express CD20, PAX5, and CD79a. The tumor proliferation index (Ki67) is greater than 40%.

Primary thyroid lymphomas respond well to chemotherapy and radiotherapy. The chemotherapy regimen includes cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP). Radiation therapy is usually given after three to six cycles of chemotherapy. The prognosis depends on the stage of the disease at the time of presentation.

Conclusion:

Primary thyroid lymphoma is a rare cause of thyroid malignancy. It mainly affects women and is manifested by rapidly progressive cervical swelling. The diagnosis is histological and treatment is based on chemo-radiotherapy.

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