Morphological alterations in tongue epithelial cells infected by SARS-CoV-2: A case-control study.

OBJECTIVE: The aim of the present case-control study was to evaluate the morphological aspects of the epithelial cells from the dorsum of the tongue and the expression of the SARS-CoV-2 Spike protein in these cells, in patients with and without COVID-19 infection. METHODS: 24 individuals with at least one symptom of COVID-19 were recruited among inpatients from Hospital Universitário Pedro Ernesto (Rio de Janeiro, Brazil). 14 patients who tested positive for COVID-19 by RT-PCR were included in the case group, and 10 patients who tested negative were included in the control group. Cytological smears from the dorsum of the tongue were obtained from all patients and analyzed using immunohistochemistry directed against SARS-CoV-2-Spike protein. Morphological changes in epithelial cells were analyzed using light microscopy. RESULTS: Immunohistochemistry showed that 71% of the COVID-19 patients presented epithelial cells positive for the presence of the SARS-CoV-2 Spike protein, and all cells coming from patients in the control group were negative. Cytological analysis showed significant differences when comparing epithelial cells from COVID-19-positive and COVID-19-negative patients. CONCLUSION: COVID-19 may generate dimensional changes in tongue epithelial cells; however, further studies are necessary to understand how this happens.

Oral leukoplakia, leukoerythroplakia, erythroplakia and actinic cheilitis: Analysis of 953 patients focusing on oral epithelial dysplasia.

BACKGROUND: To analyse the clinical and histological characteristics from a series of oral leukoplakias, leukoerythroplakias, erythroplakias and actinic cheilitis diagnosed in a 14-year period. METHODS: The files were reviewed and all cases diagnosed as leukoplakia, leukoerythroplakia, erythroplakia and actinic cheilitis were selected. Clinical information was obtained from the biopsy submission forms, and histological review was performed in all cases. RESULTS: Final sample included 953 lesions, mostly affecting females (534, 56%), and 87.5% of the patients were 41 to 80 years old. The most commonly affected regions were the lower lip (20.1%), tongue (18.1%) and buccal mucosa (16.9%). Leukoplakias, actinic cheilitis, leukoerythroplakias and erythroplakias represented, respectively, 74.6%, 15.2%, 9.3% and 0.8% of the sample. Most cases presented no dysplasia (42.1%) or mild dysplasia (33.5%). Lesions in the tongue, floor of mouth and lower lip, as well as lesions that presented hyperparakeratosis, showed higher frequencies of moderate dysplasia and severe dysplasia/carcinoma in situ. The most common histological criteria were the increase in number and size of nucleoli, loss of polarity of the basal cells and variations in cellular size and shape. Classification by the binary system showed that 7% were high-risk lesions. CONCLUSION: All histological criteria for classification of oral epithelial dysplasia recommended by the World Health Organization showed increased frequency as grading increased. Additional criteria seem to be useful in grading oral epithelial dysplasia, such as the presence of normal and abnormal superficial mitotic figures and endophytic epithelial proliferation.

Oral and oropharyngeal lymphomas: A multi-institutional collaborative study.

BACKGROUND: Lymphomas in the oral and oropharyngeal regions are relatively uncommon, and their diagnosis is challenging and complex due to the myriad histopathological subtypes. Herein, we report a large series of oral and oropharyngeal lymphomas and compare our data with the currently available literature. METHODS: All cases diagnosed as lymphomas affecting the oral and oropharyngeal regions were retrospectively retrieved from seven Brazilian institutions. Clinicodemographic data and histopathological features were evaluated and described, while a comprehensive literature review was undertaken in order to compare our findings. RESULTS: A total of 304 cases of oral and oropharyngeal lymphomas were obtained, mostly affecting individuals aged 60-69 years (n = 68) with a mean age at diagnosis of 54.2 ± 20.1 years. Males and females were equally affected. Mature B-cell neoplasms (87.2%) were the most common group, followed by mature T- and NK-cell neoplasms (11.2%) and precursor lymphoid neoplasms (1.6%). The most frequent subtypes in each group were diffuse large B-cell lymphomas, not otherwise specified (n = 99), extranodal NK/T-cell lymphomas, nasal type (n = 12), and B-lymphoblastic leukaemia/lymphomas, not otherwise specified (n = 4). The most commonly involved sites were the palate (26.3%), mandible (13%), and maxilla (10.5%). CONCLUSION: Diffuse large B-cell lymphoma, not otherwise specified, remains the most common subtype of lymphomas in the oral and oropharyngeal region. Older patients are the most affected, with no gender predilection and the palate and jaw are usually affected.

Plasmacytoma and plasma cell myeloma affecting the jaws: A multi-institutional collaborative study.

BACKGROUND: Plasma cell neoplasms are characterized by the proliferation of a single clone of plasma cells with production of a monoclonal immunoglobulin. They can manifest as a single lesion (plasmacytoma) or as multiple lesions (multiple myeloma). METHODS: Paraffin-embedded tissue blocks of patients microscopically diagnosed with plasma cell neoplasms in the jaws were retrieved from five pathology files. Data including clinical, radiographic, microscopic and immunohistochemical findings, treatment employed and follow-up status were retrieved from the pathology reports. RESULTS: Fifty-two cases were retrieved (mean age: 59.4 years) without sex predilection. The mandible was the most affected site (67.3%), usually associated with pain and/or paresthesia (53.8%). Lesions in other bones besides the jaws were reported for 24 patients (46.2%). Radiographically, tumours usually presented as poorly defined osteolytic lesions with unilocular or multilocular images, while microscopy revealed diffuse proliferation of neoplastic plasma cells with nuclear displacement and abundant eosinophilic cytoplasm. Two cases were classified as anaplastic, and amyloid deposits were found in two other cases. Immunohistochemistry was positive for plasma cell markers and negative for CD20 and CD3, and monoclonality for kappa light chain predominated. The overall survival rate after 5 years of follow-up was 26.6%. CONCLUSION: Plasma cell neoplasms are aggressive tumours with a poor prognosis and involvement of the jaws may be the first complaint of the patient. Thus, oral pathologists, head and neck surgeons and dentists should be aware of their clinical, radiographic and microscopic manifestations.

Peripheral giant cell granuloma associated with a dental implant.

BACKGROUND: Peripheral giant cell granuloma (PGCG) is an uncommon pathology that affects gingival or alveolar mucosa. Although PGCG can be associated with dental implants, little is known about this lesion and implant osseointegration as well as its etiopathogenesis and the treatments available. This study sought to report a rare case of PGCG associated with dental implant, emphasizing its clinical and histopathological aspects. CASE PRESENTATION: A 53-year-old man had an exophytic, reddish lesion, around a crown attached to a dental implant located in the left mandible. Radiographically, there was bone loss around the implant. After excisional biopsy, histological examination revealed a submucosal proliferation of multinucleated giant cells rendering the diagnosis of peripheral giant cell granuloma. Patient has been under follow-up for 6 months with no recurrence. CONCLUSIONS: Peri-implant lesions must be completely removed to prevent recurrence of PGCG and implant failure, even in cases suspected to be reactive. Besides, histological examination must be performed on all peri-implant reactions to achieve the appropriate diagnosis and, consequently, the best treatment and follow up.

Pathogenesis of primordial odontogenic tumour based on tumourigenesis and odontogenesis.

OBJECTIVE: Primordial odontogenic tumour (POT) is a rare benign mixed epithelial and mesenchymal odontogenic tumour. POT is composed of dental papilla-like tissue covered with cuboidal to columnar epithelium that resembles to inner and outer enamel epithelium of the enamel organ without dental hard tissue formation. The aim of this study was to examine pathogenesis of POT based on tumourigenesis and odontogenesis. SUBJECTS AND METHODS: Six cases of POT were submitted for study. DNA analysis and transcriptome analysis were performed by next-generation sequencing. Expression of amelogenin, ameloblastin and dentin sialophosphoprotein (DSPP) was examined by immunohistochemistry. RESULTS: There were no gene mutations detected in any of analysed 151 cancer- and 42 odontogenesis-associated genes. Enamel protein-coding genes of Amelx, Ambn and Enam, and dentin protein-coding genes of Col1a1, Dspp, Nes and Dmp1 were expressed, whereas expression of dentinogenesis-associated genes of Bglap, Ibsp and Nfic was negative or very weak suggesting inhibition of dentin formation in POT after odontoblast differentiation. Immunoreactivity of amelogenin, ameloblastin and DSPP was detected in POT. CONCLUSIONS: Pathogenesis of POT is considered to be genetically different from other odontogenic tumours. It is suggested that inhibition of enamel and dentin formation in POT is due to defects in dentin formation process.

Anterior lingual mandibular bone depression: differential diagnosis of periapical inflammatory disorders.

Lingual mandibular bone depressions mainly affect the posterior region of the mandible. Depressions in the anterior region are rare, frequently posing difficulties in diagnosis. The aim of this article is to present a case of an anterior lingual mandibular bone depression (ALMBD) that was radiographically superimposed on the roots of anterior teeth. A 43-year-old man was referred for evaluation of a slight depression on the lingual surface of the anterior mandible. The depression was associated with a well-defined radiolucent area superimposed on the roots of the right canine and incisors. All teeth in the area proved to be vital, and cone beam computed tomography (CBCT) revealed a lingual depression in the area. The final diagnosis was an ALMBD, and the patient underwent clinical and radiographic follow-up examinations for 22 months that revealed no alterations in the area. When anterior mandibular radiolucencies are superimposed on the roots of the adjacent teeth, ALMBDs should be considered in the differential diagnosis along with periapical cysts and granulomas. Radiographic and CBCT analyses are useful to avoid unnecessary endodontic and surgical approaches.

Primordial odontogenic tumour: clinicopathological analysis of six cases of a previously undescribed entity.

AIM: To describe the clinicopathological and immuno-histochemical features of six tumours that do not fulfil the criteria of any of the currently classified odontogenic tumours. METHODS AND RESULTS: The patients were three males and three females, whose ages ranged from 3 years to 18 years (mean, 11.05 years). In all cases there were well-defined radiolucencies associated with unerupted teeth apparently showing a pericoronal relationship. Microscopically, all tumours were composed of variably cellular loose fibrous tissue with areas similar to dental papilla, entirely surrounded by cuboidal to columnar epithelium resembling the internal epithelium of the enamel organ. Mesenchymal tissue was positive only for vimentin, and Ki67 expression was very low (<2%). The epithelium was positive for CK AE1/AE3, CK5, CK14, and CK19, but negative for CK18 and CK20. All cases showed clear demarcation from the surrounding bone, and were surgically removed, with no recurrences after follow-up ranging from 6 months to 20 years. CONCLUSIONS: These findings differ from those observed in other odontogenic lesions, such as ameloblastic fibroma, odontogenic myxoma, odontogenic fibroma, and hyperplastic dental follicles. The term primordial odontogenic tumour is proposed to describe this novel lesion.

Ameloblastomas: clinicopathological features from 70 cases diagnosed in a single oral pathology service in an 8-year period.

UNLABELLED: Ameloblastomas are odontogenic tumors that can present some distinct clinicopathological profiles when comparing different populations and studies. OBJECTIVES: The aim of the present study was to analyze the clinicopathological features from a series of ameloblastomas diagnosed in a single Oral Pathology service in Brazil in an 8-year period. STUDY DESIGN: The files were revised and all cases diagnosed as ameloblastomas in the period were retrieved. All hematoxylin and eosin stained histological slides were reviewed and all clinical and radiological information were obtained through a review of the laboratory forms. Data were descriptively analyzed and a comparison was performed with the different ameloblastomas subtypes. RESULTS: Seventy ameloblastomas composed the final sample, including 57 (81%) solid/multicystic, 9 (13%) unicystic, 2 (3%) desmoplastic and 2 (3%) peripheral ameloblastomas. Mean age of the affected patients was in the forth decade of life and there was a slight male predominance. Most tumors presented as multilocular radiolucencies, were located in the posterior mandible and showed the follicular and plexiform histological patterns. There was no difference on the mean age of the patients affected by solid and unicystic ameloblastomas. CONCLUSIONS: The present results showed that the clinicopathological features of the ameloblastomas included in this Brazilian sample were similar to the features described in most other worldwide populations.

Clinical and laboratorial profile and histological features on minor salivary glands from patients under investigation for Sjögren's syndrome.

UNLABELLED: Diagnosis of Sjögren's syndrome (SS) is complex and the usefulness of labial minor salivary glands biopsy in this process remains controversial. OBJECTIVE: to evaluate the clinical and laboratorial profile and histological features on labial minor salivary glands from patients under investigation of SS. STUDY DESIGN: clinical charts from 38 patients under suspicion of SS and submitted to labial minor salivary glands biopsies were reviewed. Clinical and laboratorial data were retrieved from the clinical files and the HE-stained histological slides were reviewed under light microscopy. RESULTS: mean age of the patients was 56.5 years and 97% were females; histological analysis showed that 42% of the cases showed ductal dilatation, lymphocytic foci were found in 52.6% and, from this group, 80% of the cases presented a foci/lobules ratio above 0.8. Acinar/ductal ratio was considered diminished in 39.5% of the samples. Thirty six (95%) and 32 (84%) patients, respectively, complained about xerostomia and xerophthalmia. A study of the time interval of the symptoms that led to SS investigation showed a mean of 116 months. Moreover, sixty-six percent of the patients had already been submitted to immunosuppressive therapy prior to the labial minor salivary gland biopsy. Age of the patients, scintigraphic alterations on salivary function, antinuclear factor (ANF), anti-Ro and anti-La did not show statistical significant association with the histological features. Lobules/foci ratio above 0.8 was the only histological parameter statistically associated with Sjögren's syndrome diagnosis (p<0.0001). CONCLUSIONS: in the studied sample, lymphocytic foci on salivary glands were the only histological parameter associated to the diagnosis of SS. Early indication of labial minor salivary gland biopsy to patients under investigation of SS could limit the effects of immunosuppressive therapy on the histological features associated with the evolution of salivary gland involvement in SS.

Hard palate hyperpigmentation secondary to chronic chloroquine therapy: report of five cases.

Antimalarials are commonly prescribed in medical practice for conditions such as rheumatoid arthritis, lupus erythematosus, as well as malaria. They are generally well-tolerated, but side effects, although infrequent, are well known. The antimalarial chloroquine diphosphate may be associated with a bluish-gray to black hyperpigmentation of the oral mucosa, mainly on the hard palate. In this report we described five additional cases of palate hyperpigmentation related to the chronic use of chloroquine diphosphate. Professionals must be aware of the adverse effects of antimalarials as chloroquine diphosphate in order to make the correct diagnosis and appropriate management of the patient. Early diagnosis of oral pigmentation by antimalarials may be of great relevance, because it might be an early sign of ocular involvement, and therefore it may be helpful to prevent further complications of antimalarial therapy for the patient.

Oral Lesions as the Primary Manifestations of Behçet's Disease: The Importance of Interdisciplinary Diagnostics-A Case Report.

BACKGROUND: Behçet's disease (BD) is a rare chronic auto-inflammatory systemic disease with non-specific oral manifestations, categorised as generalised variable vessel vasculitis that requires an interdisciplinary approach to diagnose due to its phenotypic heterogeneity. Whilst the oral lesions that reoccur in BD underpin the complex diagnostic process, the crucial role of dental professionals is highlighted in a case report summarised herein. We present a case of a 47-year-old male referred to the Oral Medicine Department by a rheumatologist after previous hospitalization for thrombosis of the iliac vein and inferior vena cava. He had elevated inflammatory C-reactive protein biomarker and an increased erythrocyte sedimentation rate. Recurrent episodes of folliculitis, oral and genital ulcers were reported. Clinical examination revealed multiple ulcerations in the oral mucosa. The complementary, histopathological analysis performed to rule out other disorders, based on excisional biopsy, showed non-keratinised stratified squamous epithelium with areas of exocytosis and ulceration. The connective tissue presented an intense mixed inflammatory infiltrate, congested blood vessels, haemorrhage, vasculitis, and HLA-B genotyping identified the expression of HLA-B15, further supporting the BD diagnosis. Treatment was initiated with colchicine, prednisolone, and weekly subcutaneous administration of methotrexate and resulted in the complete remission of oral lesions and no recurrence of other manifestations. CONCLUSIONS: This BD case report emphasizes the importance of a multidisciplinary approach in diagnosing BD, including the use of histopathological assessment and genetic profiling. It highlights the significance of thorough intraoral assessment and referral to a multidisciplinary team for diagnosis. The oral manifestations of BD as the primary symptoms often indicate underlying major systemic pathologies. The authors stress the need for a structured diagnostic algorithm to facilitate timely and effective management of BD.

Evaluation of Receptor Activator of Nuclear Factor Kappa B Ligand, Osteoprotegerin, Osteopontin, and Tumor Necrosis Factor Alpha on Chronic Apical Periodontitis in Smokers.

INTRODUCTION: Smoking can be considered a risk factor for chronic apical periodontitis (CAP). This study compared the immunoexpression of biomarkers receptor activator of nuclear factor kappa B ligand (RANKL), osteoprotegerin (OPG), osteopontin (OPN), and tumor necrosis factor alpha (TNF-α) in CAP in smokers and nonsmokers. METHODS: Twelve smokers and 12 nonsmokers diagnosed with CAP and indicated for tooth extraction were selected. Exclusion factors were teeth with a diagnosis of root fracture, previous endodontic treatment, or endoperiodontal injury, in addition to individuals with systemic diseases, under 18 years of age, users of anti-inflammatory and/or antibiotics in the last 3 months, and drug users. Specimens were processed for histopathologic and immunohistochemical analysis. RESULTS: Qualitative analysis of RANKL expression showed 66.66% weak/moderate and 33.33% strong in smokers and 100% weak/moderate in nonsmokers. OPG and OPN expressions were 100% negative to focal in the smoker group and 50% negative to focal and 50% weak/moderate in the nonsmoker group. TNF-α was 25% negative to focal and 75% weak/moderate in the smoker group and 33.33% negative to focal and 66.66% weak/moderate in the nonsmoker group. Quantitative analysis of the data using the Mann-Whitney U test showed that there was a significant difference in the immunoexpression of RANKL (P < .05), OPG (P < .05), and OPN (P < .05), but there was no statistical difference in the immunoexpression of TNF-α (P > .05) between the 2 groups. CONCLUSIONS: These findings suggest that smoking is capable of altering the inflammatory response, influencing the evolution of CAP.

Interleukin 17 expression in periapical lesions from elderly patients.

OBJECTIVE: To compare the expression of IL-17 in periapical lesions (cysts and granulomas) among elderly individuals and adults. We selected 20 periapical lesions of the elderly (12 granulomas and eight cysts) and 20 periapical lesions of adults (12 granulomas and eight cysts). MATERIALS AND METHODS: Immunohistochemistry was performed using a specific antibody for IL-17. The slides were subdivided into five high magnification fields and then the images were observed through an optical microscope. According to the number of positive markings for the antibody, grades were given, ranging from 0 to 2. RESULTS: The results demonstrate that there was no statistical difference when comparing the expression of IL-17 between cysts and granulomas of both groups (study group: cysts 0.7 ± 0.21 × granulomas 0.96 ± 0.58, p = .61; control group: cysts 0.37 ± 0.16 × granulomas 0.31 ± 0.23, p = .27). The comparison between adult (control group) and elderly patients (study group) showed a statistical difference both in cysts (study group: 0.7 ± 0.21 × control group: 0.37 ± 0.16, p = .007) and in granulomas (study group: 0.96 ± 0.58 × control group: 0.31 ± 0.23, p = .0009), in which elderly patients had a higher expression of interleukin 17, in relation to adult patients. CONCLUSION: We concluded that elderly patients have a higher expression of IL-17 in both cysts and granulomas, when compared to adult patients.

Squamous Odontogenic Tumor in the Posterior Region of Maxilla.

Squamous odontogenic tumor (SOT) is a rare benign but locally infiltrative tumor often misdiagnosed as other entities, such as ameloblastoma and squamous cell carcinoma, due to overlapping morphological findings. We document here the clinicopathological and imaging findings of an aggressive intraosseous SOT in the posterior left region of the maxilla in a 25-year-old male patient. On intraoral examination, the tumor extended from the region of the left lateral incisor to the upper left premolar and was covered by reddish mucosa, with discrete areas of ulceration. Imaging exams revealed an osteolytic lesion causing thinning, erosion, and buccal and lingual cortical plate perforation associated with an impacted canine. Microscopically, the tumor showed a proliferation of islands of well-differentiated squamous epithelium in a variably collagenized background. The peripheral cells of the islands were flat or slightly cuboidal and did not exhibit nuclei with peripheral palisade and reverse polarization. The diagnosis of SOT was rendered. The patient underwent surgical resection and has been under clinical follow-up for approximately 12 months with no signs of recurrence. A careful morphological evaluation is essential to avoid misdiagnosis and ensure a satisfactory treatment approach.

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.

Clinicopathologic analysis of oral dermoid and epidermoid cysts: a Brazilian multicenter study.

Dermoid cysts (DCs) and epidermoid cysts (ECs) are uncommon developmental cysts affecting the oral cavity. This study aims to evaluate patients with oral DCs and ECs and their demographic and clinicopathologic features. A retrospective descriptive cross-sectional study was performed. A total of 105,077 biopsy records of oral and maxillofacial lesions from seven Brazilian oral pathology centers were analyzed. All cases diagnosed as oral DCs and ECs were reviewed, and clinical, demographic, and histopathological data were collected. The series comprised 32 DCs (31.4%) and 70 ECs (68.6%). Most of the DCs occurred on the floor of the mouth (n = 14; 45.2%) of women (n = 17; 53.1%) with a mean age of 34.6 ± 21.6 years. All DCs were lined partially or entirely by stratified squamous epithelium (100%). Chronic inflammatory cells, melanin pigmentation, multinucleated giant cell reaction, and cholesterol clefts were observed in the fibrous capsule . Most of the ECs affected the labial mucosa (n = 20; 31.7%) of men (n = 39; 56.5%) with a mean age of 48.0±19.8 years. Microscopically, most ECs (n = 68; 97.1%) were lined entirely by stratified squamous epithelium. Two cysts (2.9%) showed areas of respiratory metaplasia. Chronic inflammatory cells, melanin pigmentation, multinucleated giant cell reaction, and cholesterol clefts were also observed in the fibrous capsule. Conservative surgical excision was the treatment of choice in all cases. Oral DCs and ECs are uncommon and often clinically misdiagnosed lesions. Clinicians should consider DCs and ECs in the differential diagnosis of soft tissue lesions in the oral cavity, mainly located on the floor of the mouth and labial mucosa.

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.