Lymphoepithelioma-like Carcinoma Research Articles

Lymphoepithelioma-Like Carcinoma of the Uterine Cervix: A Pathologic Study of Eight Cases With Emphasis on the Association With Human Papillomavirus.

Lymphoepithelioma-like carcinoma (LELC) of the uterine cervix is a rare tumor. The goal of this study was to evaluate a series of cases of cervical LELC and to investigate possible association with human papillomavirus (HPV) and/or Epstein-Barr virus (EBV). Immunohistochemistry for p63, p16, human leukocyte antigen-D related (HLA-DR), and B-cell lymphoma 2 (BCL-2); in situ hybridization (ISH) for EBV and HPV; and polymerase chain reaction (PCR) genotyping were performed. Mismatch repair (MMR) studies and PD-L1 status were obtained. We found eight cases of LELC. Tumors demonstrated sheets of cells containing vesicular nuclei, amphiphilic cytoplasm, and dense peri- and intratumoral lymphocytic infiltrates. All tumors stained for p63, p16, and HLA-DR; two also stained for BCL-2. When combining ISH and PCR results, seven tumors were HPV positive; they were all Epstein-Barr encoding region negative. All cases were MMR intact, and most overexpressed PD-L1. This study shows that cervical LELCs are associated with HPV and not EBV.

P2.04-30 PD-1/PD-L1 Inhibition Might be an Option for the Treatment of Advanced Primary Pulmonary Lymphoepithelioma-Like Carcinoma

P2.04-30 PD-1/PD-L1 Inhibition Might be an Option for the Treatment of Advanced Primary Pulmonary Lymphoepithelioma-Like Carcinoma

1921P - Somatostatin receptor 2 expression and clinical significance in pulmonary lymphoepithelioma-like carcinoma

1921P - Somatostatin receptor 2 expression and clinical significance in pulmonary lymphoepithelioma-like carcinoma

P2.01-111 Clinical Features and Prognosis of Eighty-Five Patients with Primary Pulmonary Lymphoepithelioma-Like Carcinoma

P2.01-111 Clinical Features and Prognosis of Eighty-Five Patients with Primary Pulmonary Lymphoepithelioma-Like Carcinoma

1368P - Clinical features and prognosis of eighty-five patients with primary pulmonary lymphoepithelioma-like carcinoma

1368P - Clinical features and prognosis of eighty-five patients with primary pulmonary lymphoepithelioma-like carcinoma

An integrated automated multispectral imaging technique that simultaneously detects and quantitates viral RNA and immune cell protein markers in fixed sections from Epstein-Barr virus-related tumours

Background/aimEpstein-Barr virus (EBV) is an oncovirus that is commonly associated with the development of lymphomas and epithelial carcinomas. In the era of immunotherapy, histological evaluation of EBV-related cancers is currently a multi-sample, multi-technique process requiring separate time-consuming detection of EBV-encoded small RNAs by in situ hybridisation (ISH), and parallel labelling of sections for cancer-associated protein markers. MethodsUsing EBV-associated tumours as proof-of-concept for feasibility, here we developed an approach that allows simultaneous detection of EBV RNAs and multiple protein markers such as PD-L1, EBV-LMP, CD8, CD4, CD20, CD30 and CD15on a single tissue section based on our recently reported automated staining protocol. ResultsWe successfully combined multiplex immunofluorescence (mIF) to detect 3 abovementioned protein markers involved in cancer, with ISH, and applied the protocol to f tissue samples from patients diagnosed with EBV-associated pulmonary lymphoepithelioma-like carcinoma (LELC), gastric carcinoma and Hodgkin's Lymphoma. Empowered by the Vectra 3 Automated Quantitative Pathology Imaging System, we demonstrate the utility and potential of this integrated approach to concurrently detect and quantitate viral RNA and protein biomarkers of immune and tumour cells. ConclusionThis study represents an important step forward in the research and diagnosis of EBV-associated cancers, and could be readily modified to include other proteins and RNA markers to apply to other malignancies. More importantly, the novel automated ISH-mIF protocol that we detailly described here could also be readily reproduced by most of the diagnostic and research lab to future projects that aim to look at both RNA and protein markers.

Assessment of programmed cell death ligand-1 expression by 4 diagnostic assays and its clinicopathological correlation in a large cohort of surgical resected non-small cell lung carcinoma

Immune checkpoint blockade targeting the PD-1/PD-L1 axis has recently demonstrated efficacy and promise in cancer treatment. Appropriate biomarker selection is therefore essential for improving treatment efficacy. However, the establishment of PD-L1 assay in pathology laboratories is complicated by the presence of multiple testing platforms using different scoring systems. Here we assessed the PD-L1 expression in 713 consecutive non-small cell lung carcinomas by four commercially available PD-L1 immunohistochemical assays, namely, 22C3, 28-8, SP142 and SP263. The analytical performances of the four assays and diagnostic performances across clinically relevant cutoffs were evaluated. The prevalence of PD-L1 (22C3) expression was 21% with a ≥50% cutoff and 56% with a ≥1% cutoff. High PD-L1 expression (using a ≥50% cutoff) was significantly associated with male sex (P = 0.001), ever smoking history (P < 0.001), squamous cell carcinoma (P = 0.001), large cell carcinoma (P < 0.001), lymphoepithelioma-like carcinoma (P = 0.006), sarcomatoid carcinoma (P < 0.001), mutant KRAS (P = 0.005) and wild-type EGFR (P = 0.003). Elevated PD-L1 expression was also significantly associated with shorter survival in patients with adenocarcinoma (log-rank P = 0.026) and remained an independent prognostic factor by multivariable analysis. Among the four assays, 22C3, 28-8 and SP263 were highly concordant for tumor cell scoring. With a cutoff of ≥50% (i.e., the threshold for first-line patient selection), inter-rater agreement was high among the three assays with percentage agreement >97%. In conclusion, three PD-L1 assays showed good analytical performance and a high agreement with each other, but not all cases were correctly classified using the same clinical cutoff. Further studies comparing the predictive value of these assays are required to address the interchangeability of these assays for clinical use.

Poorly Differentiated Nonkeratinizing Squamous Cell Carcinoma of the Thymus

Thymic carcinoma represents a rare and poorly understood type of thymic epithelial neoplasm that has been the subject of much controversy. Poorly differentiated nonkeratinizing squamous cell carcinoma, also known as lymphoepithelioma-like thymic carcinoma, is a rare variant of thymic carcinoma that has not been adequately characterized in the literature. The clinicopathologic, immunohistochemical, ultrastructural, and molecular features of 25 cases are reported. The patients were 19 men and 6 women, ranging in age from 20 to 85 years (mean: 60 y). The tumors presented clinically as anterior mediastinal masses with chest pain and shortness of breath or were found incidentally on imaging studies. Tumor size ranged from 2.0 to 13.5 cm in greatest diameter. Most of the tumors were small, well-circumscribed and confined to the mediastinum. Five cases presented with large, bulky, and infiltrative masses. Histologically, the hallmark of these tumors was a neoplastic proliferation of large, round to oval cells with vesicular nuclei, prominent eosinophilic nucleoli, and scant cytoplasm. Two histologic growth patterns were identified: tumors with a heavy lymphoplasmacytic stroma (lymphoepithelioma-like pattern), and tumors showing abundant desmoplastic stroma (desmoplastic pattern). Immunohistochemical stains showed strong positivity of the tumor cells for cytokeratin AE1/AE3, CK5/6, CK18, MOC31, p16, p40, and p63. MIB-1 showed on average 35% nuclear positivity. CD117 was positive in 21/25 cases and CD5 in 20/25 cases. Epstein-Barr encoded RNA in situ hybridization was positive in only 1 case. Electron microscopy in 4 cases showed primitive round to oval cells with prominent nucleoli, scant cytoplasm and immature cell junctions. Molecular features were studied by next-generation sequencing using high quality sequence data obtained from 18 patients. Variants with allele frequency between 5% and 45% and quality scores >50 were classified as somatic. A total of 16/18 cases had one or more somatic variants of unknown significance. One case showed an IDH1 p. R132C mutation, also of unknown significance. No "actionable" genes amenable to currently available targeted therapies were identified in this cohort. Clinical follow-up was obtained in 20 patients; 14 patients were alive and well with no evidence of disease between 1.5 and 16 years after diagnosis (median survival: 4 y; mean: 5.5 y). Most survivors had relatively small tumors (<5 cm. diameter), were in stage I and II at diagnosis and showed clear surgical margins. Five patients died of their tumors with metastases to bone, brain, chest wall, lungs and lymph nodes; all were in advanced stages and showed positive margins. Prognosis for these tumors appears to be correlated with the staging and status of the margins at the time of initial surgery.

Primary pulmonary lymphoepithelioma-like carcinoma in a 12-year-old African child

Pulmonary lymphoepithelioma-like carcinoma is a rare malignant tumour predominantly occurring in Asian patients. It has identical histological features to nasopharyngeal carcinoma. To date, Epstein–Barr virus (EBV) in pulmonary lymphoepithelioma-like carcinoma has been limited to the Asian population. This manuscript presents an unusual case in a 12-year-old African boy in which the tumour tested positive for EBV.

Abstract 3051: Prognostic value of 18F-FDG PET/CT parameters in patients with primary pulmonary lymphoepithelioma-like carcinoma

Abstract Introduction Pretreatment tumor metabolic burden, which measured by fluorine-18 fluorodeoxyglucose positron emission tomography/computerized tomography (18F-FDG PET/CT) have been shown to predict outcomes in various malignancies. Epstein-Barr virus (EBV) serology titer in pulmonary LELC is correlated to stage. However, the prognostic value of 18F-FDG PET/CT in patients with pulmonary lymphoepithelioma-like carcinoma (LELC) and the relationship between EBV viral load remained unknown. The current study aims to investigate the prognostic value and association between functional parameters of 18F-FDG PET/CT and serum EBV DNA in patients with pulmonary LELC. Methods This retrospective study comprised 32 patients with pulmonary LELC who underwent pretreatment 18F-FDG PET/CT between January 2008 and December 2016. The EBV viral load and the functional parameters of 18F-FDG PET/CT were used for survival analysis. Results The value of pre-treatment serum EBV DNA had significantly positive correlation with whole MTV (r = 0.63, P = 0.0337) and whole TLG (r = 0.77, P = 0.0093). Advanced tumor stage (≥III) and high whole MTV (≥72.58) significantly predicted poor PFS. Multivariate survival analysis for PFS showed that there was a trend toward a lower risk of recurrence in patients with early tumor stage (≤II) (HR = 0.112, 95% CI =0.011-1.117, P = 0.062, Table 3), albeit not significantly so. Advanced tumor stage (≥III), high whole MTV (≥72.58) and high whole TLG (≥278.4) were predictors of poor OS. However, in multivariate survival analysis, none of them were independent predictors for OS. EBV viral load was not prognostic factor for both PFS and OS. Conclusion Greater whole MTV and whole TLG predicted poorer OS in patients with primary pulmonary LELC. Functional parameter of 18F-FDG PET/CT may provide useful prognostic information. Serum EBV DNA was closely related to whole MTV and TLG, but not a prognostic factor. Citation Format: Yueh-Fu Fang, Chun-Yu Lin. Prognostic value of 18F-FDG PET/CT parameters in patients with primary pulmonary lymphoepithelioma-like carcinoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 3051.

Thymoma and thymic carcinoma associated with multilocular thymic cyst: a clinicopathologic analysis of 18 cases

BackgroundMultilocular thymic cysts (MTCs) associated with thymomas or thymic carcinomas (TCs) are rare and may be misdiagnosed as other benign cystic lesions.MethodsWe retrospectively analysed 18 cases of thymomas or TCs associated with MTCs, which were retrieved from 309 consecutive patients with thymomas or TCs in the Chinese population, emphasizing clinicopathologic characteristics, immunophenotypes and the prognostic impact.ResultsA total of 14 tumours were described as cystic or solid-cystic masses, and the other 4 tumours were described as solid masses. Histologically, 2 atypical type A, 2 type AB, 1 type B1, 8 type B2, 1 type B3, 1 microscopic thymoma (type A), 2 squamous cell carcinomas (SCCs) and 1 lymphoepithelioma-like carcinoma (LELC) were classified. Prominent multilocular cystic areas with chronic inflammation were observed. The follow-up ranged from 2 to 79 months. Sixteen patients survived without any evidence of recurrence after complete resection.ConclusionsOur study suggests that thymomas or TCs associated with MTCs are rare in the Chinese population and have a better clinical behaviour than thymomas or TCs without MTCs. Our data also expand the histologic spectrum of thymomas or TCs accompanied by MTC. To our knowledge, this is the first report of atypical type A thymoma and LELC associated with MTCs.

EBV-associated lymphoepithelioma-like thyroid carcinoma with favorable outcome: case report with cytopathologic and histopathologic study

BackgroundLymphoepithelioma-like carcinoma (LELC) is a rare entity among thyroid tumors. Based on the limited number of case reports that exist, the association of Epstein–Barr virus (EBV) with primary thyroid LELCs seems inconsistent.Case presentationWe present a confusing cytological case of lymphoepithelioma-like thyroid carcinoma with expression of EBV. The patient presented with a central neck mass and bilateral lymphadenopathy. Fine-needle aspiration cytology revealed three-dimensional and syncytial fragments of epithelioid cells accompanied by small lymphocytes. The surgical specimen of resected thyroid tumor disclosed typical histopathological features of LELC. Metastatic papillary carcinoma was also discovered in the metastatic lymph nodes. In situ hybridization for EBV-encoded RNA (EBER-ISH) was positive in the tumor cells. Negative immunoreactivity for TTF-1, Pax-8, and CD5 was observed. The patient is currently undergoing regular follow-up and is 1 year and 10 months postresection with no evidence of recurrence.ConclusionsLong-term survival is discussed in relation to this variant of thyroid carcinoma, which might differ in behavior from anaplastic carcinoma. Further investigation is required to elucidate the clinical significance of EBV expression and progression of this unique variant of thyroid carcinoma.

Circulating PD-L1+ exosomes as potential prognostic and predictive biomarkers in pulmonary lymphoepithelioma-like carcinoma.

e24081Background: Primary pulmonary lymphoepithelioma-like carcinoma (LELC) is a histologically distinctive subtype of NSCLC. Exosomes isolated from plasma of cancer patients play a role in the reg...

Phase I/II trial of pembrolizumab(P) and vorinostat(V) in recurrent metastatic head and neck squamous cell carcinomas (HN) and salivary gland cancer (SGC).

6025 Background: Epigenetic modification is increasingly recognized as a mechanism for tumor immune evasion. This clinical trial explored the activity of P with the HDAC inhibitor V in HN and SGC. Methods: Patients(pts) with progressing incurable HN and SGC with ECOG ≤1, no prior immunotherapy, RECIST 1.1 measurable disease, and normal organ function were eligible. Controlled brain metastases were permitted. PDL1 expression was not an eligibility criterion. P 200mg was given IV q21 days (d) , with V 400mg QD PO, 5d on and 2d off, both started on d1 of each cycle. The primary endpoint was safety according to CTCAE v. 4.03. Secondary endpoints were RECIST 1.1 objective response rates and biomarker collection. Results: From 11/2015 to 8/2017, 25 HN and 25 SGC pts were enrolled. Among all 50 pts, median age was 61 (range 33-86) yrs, 39 (78%) were male, 21(62%) were never smokers, 27 (54%) had ECOG 0. In HN, primary sites were oropharynx 17 (68%), nasopharynx 4 (16%), oral cavity 1(4%), skin 2 (8%) and unknown 1 (4%). Thirteen(52%) were p16+ oropharynx HN. SGC histologies were adenoid cystic (ACC) 12(48%), acinic cell (AciC) 3(12%), mucoepidermoid 3(12%), ca ex. pl. adenoma 2(8%). There was 1(4%) pt each with adenocarcinoma, salivary duct, epithelial-myoepithelial, clear cell, parotid lymphoepithelioma-like(LEL-C) carcinoma. The median (range) treatment cycles received in HN was 6 (1-33), and SGC 9 (1-34). Adverse events regardless of cause (AEs) in all pts were: 27 (54%) Grade ≥1, 18(36%) Grade≥ 3. Nine(18%) pts required V dose reductions. The most common AEs in all pts were renal insufficiency in 7(14%), fatigue 6 (12%) and nausea 3 (6%). There were 3 (12%) deaths on study, 1 aspiration pneumonia, 1 myocardial infarction, and 1 presumed pneumonitis from P. Responses in HN were: complete response (CR) 0, partial response(PR) 8 (36%), stable disease(SD) 5 (20%). Efficacy in SGC:CR 0, PR 4 (16%) in 1 LEL-C, 2 AciC and 1 ACC, SD 14(56%). With a median follow up of 8.7 mos for all pts, in HN median PFS was 4.5 mos, median OS, 12.6 mos; in SGC median PFS was 7 mos, and median OS 13 mos. Conclusions: P+V demonstrated activity in HN, with fewer responses in SGC. Serum and tissue biomarker analyses are ongoing. Clinical trial information: NCT02538510.

Carcinoma indiferenciado linfoepitelioma-like de nasofaringe: tumor raro iniciado quadro com otite média secretora

A região nasofaríngea apresenta diferentes tipos de tecido e epitélios, podendo apresentar uma significativa diversidade de neoplasias. O tumor maligno originado a partir de células epiteliais denomina-se carcinoma. O carcinoma indiferenciado linfoepitelioma-like é raro, mas com boa resposta ao tratamento radioterápico. O objetivo deste relato é alertar para o diagnóstico de tumores de nasofaringe iniciando quadro com Otite Média Secretora. Neste caso, trata-se de um tumor raro cujo diagnóstico precoce foi crucial para a cura da doença antes de acometer estruturas vitais pelo seu crescimento.

The Role of Epstein-Barr Virus in Cervical Cancer: A Brief Update.

Epstein–Barr virus (EBV) belongs to the group of gamma-herpes viruses and was the first recognized human oncovirus. EBV is responsible for infectious mononucleosis and multiple lymphoid and epithelial malignancies including B-cell lymphomas (Burkitt lymphoma, Hodgkin lymphoma, and post-transplant lymphoproliferative disorder), various T-cell/NK lymphoproliferative disorders, nasopharyngeal carcinoma, and gastric carcinoma, respectively. In addition, the presence of EBV has been documented in other cancers including breast, prostate, oral, and salivary gland carcinomas. The presence and role of EBV in cervical cancer and its precursor lesions (CIN) have also been described, but the results from the literature are inconsistent, and the causal role of EBV in cervical cancer pathogenesis has not been established yet. In the present review, we briefly surveyed and critically appraised the current literature on EBV in cervical cancer and its variants (lymphoepithelioma-like carcinoma) as well as its precursor lesions (CIN). In addition, we discussed the possible interactions between EBV and human papilloma virus as well as between EBV and immune checkpoint regulators (PD-L1). Though further studies are needed, the available data suggest a possible causal relationship between EBV and cervical cancer pathogenesis.

Metastases of squamous cell carcinoma in the lymph nodes of the neck without the revealed primary focus

Objective is to identify regularity of metastases distribution of the squamous cell carcinoma (SCC) in the lymph nodes of the neck without revealed primary focus, as well as to evaluate the effectiveness of various methods of treatment. Materials and methods . Performed the retrospective 45 patients data analysis with metastases of SCC in cervical lymph nodes without the revealed primary focus treated in different departments of N.N. Blokhin National Medical Research Center of Oncology from 2005 to 2012. The source of information were outpatient studies and medical histories, histological preparations and paraffin blocks. Results. Metastases of SCC without revealed primary focus are most typical for nodes of a neck and upper part of the body, there are among the patients mostly males aged 50–59 years. To establish the localization of the primary focus, traditional diagnostic procedures are not always effective: in morphological analysis, the primary focus can be hidden behind inflammatory changes, in addition, the tumor lesion can be of a primary focus. Tumors, similar to lymphoepithelioma-like carcinoma, could also simulate metastasis in the lymph node. Tonsil cancer is very often not detected even with repeated biopsies, therefore diagnostic tonsillectomy is justified. Survival depends slightly on the identification of the source of metastasis. The range of treatment methods for SCC is limited, combined and complex methods demonstrate greater efficiency, chemotherapy is less reasonable. The leading prognostic factor is the degree of distribution of metastatic lesion. Virologic analysis allows only to assume localization of the tumor process in the nasopharynx in patients with human papillomavirus and predict their greater survival, and the number of patients with Epstein–Barr virus is too small for reasonable hypotheses. Conclusion . With metastases of SCC in the lymph nodes of the neck without the revealed primary focus, the hidden distributing tumor is most often appears in the pharyngeal tonsils and in the root region of the tongue. In some cases, the metastatic node can be the primary focus. The most effective complex therapy is surgical intervention with followed radiation therapy in combination with chemotherapy. The spectrum (range) of diagnostic procedures can include bilateral tonsillectomy and mucosectomy of the root region of the tongue.

Lymphoepithelioma-Like Gastric Carcinoma Misdiagnosed as a Submucosal Tumor

Lymphoepithelioma-Like Gastric Carcinoma Misdiagnosed as a Submucosal Tumor

Correlation and prognostic significance of PD-L1 and P53 expression in resected primary pulmonary lymphoepithelioma-like carcinoma.

Aberrant expression of programmed cell death-ligand 1 (PD-L1) and protein 53 (P53) has been observed in various malignancies, and recently, the mechanism of PD-L1 regulation by P53 has been elucidated. We aimed to explore possible correlations between PD-L1 and P53 expression and the prognosis of patients with resected pulmonary lymphoepithelioma-like carcinoma (LELC). A total of 67 consecutive patients with primary pulmonary LELC who underwent radical resection from January 2003 to December 2014 were enrolled in our study. Membranous PD-L1 and nuclear P53 expression were detected by immunohistochemical staining (IHC). Positive expression of PD-L1 in tumor cells (TCs), PD-L1 in tumor-infiltrating lymphocytes (TILs) and P53 was investigated in 44 patients (65.7%), 37 patients (55.2%), and 34 patients (50.7%), respectively. Using univariate and multivariable analysis, both PD-L1 (+) in TCs and P53 (+) were observed to be significantly independent prognostic factors associated with longer disease-free survival (DFS, P=0.037 and 0.039, respectively), along with early stage LELC (P=0.037), but had no association with overall survival (OS) (P>0.05). In the P53 (+) group, the rate of patients with PD-L1 (+) in TCs was significantly higher than in the P53 (-) group (85.3% vs. 45.5%, P=0.001). In addition, among the 45 patients who underwent adjuvant chemotherapy, DFS was significantly longer in patients with either PD-L1 (+) in TCs or P53 (+) (P=0.036 and 0.044, respectively). PD-L1 and P53 may be potential therapeutic targets for primary pulmonary LELC. PD-L1 (+) in TCs and P53 (+) were reliable predictors for longer DFS and benefits from adjuvant therapy in resected cases. Routine detection of these two indices in lung LELC may be warranted.

Research progress of the clinically uncommon gastric carcinoma

Gastric cancer is one of the most important diseases that endangers people's health. Beside gastric adenocarcinoma, gastric carcinoma also includes the following types: adenosquamous carcinoma, squamous carcinoma, gastric neuroendocrine tumor, gastric hepatoid adenocarcinoma, AFP-producing gastric cancer, EBV-associated gastric cancer, lymphoepithelioma-like carcinoma, undifferentiated-type gastric cancer, gastric carcinosarcoma and so on. The adenosquamous carcinoma, squamous carcinoma of stomach, gastric hepatoid adenocarcinoma, AFP-producing gastric cancer and gastric carcinosarcoma mainly occurred in old men, while the linitisplastica gastric cancer was common in young women. It refers to the gastric cancers that are clinically rare and have lower incidence, unique histological and pathological features, however, without obviously clinical manifestations. The clinically uncommon gastric cancers are easy to be misdiagnosed or missed, and further to miss the optimal opportunity for treatment due to the unclearly specific pathogenesis and disease progression. With the development of studies on the clinically uncommon gastric carcinoma, although people have a further knowledge of its pathologic features, methods of diagnosis and treatment, the diagnosis and treatment standards for the clinically uncommon gastric cancer has not yet been established and unified. The therapeutic principle of the clinically uncommon gastric cancers is also the radical surgery, radiotherapy and chemotherapy as the main comprehensive treatment supplemented by individualized treatment. With lucubrating the pathogenesis of them, specific diagnostic methods and treatment measures are new hope for improving the diagnosis and treatment of the clinically uncommon gastric cancers. So, the further researches on the clinically uncommon gastric cancers and exploring their etiology, pathogenesis, histological and pathological features have important significance to their diagnosis and treatment. This article makes a summary of the clinically uncommon gastric cancers with the aspects of epidemiology, histology, pathology, diagnosis, treatment, to provide reference to clinical diagnosis and scientific studies.