MINISTRY OF EDUCATION AND TRAINING MINISTRY OF HEALTH HANOI MEDICAL UNIVERSITY HA THI THU HA RESEARCH ON CLINICAL, SUBCLINICAL CHARACTERISTICS AND TREATMENT RESULTS OF LACRIMAL GLAND TUMOURS Specialis[.]
MINISTRY OF EDUCATION MINISTRY OF HEALTH AND TRAINING HANOI MEDICAL UNIVERSITY HA THI THU HA RESEARCH ON CLINICAL, SUBCLINICAL CHARACTERISTICS AND TREATMENT RESULTS OF LACRIMAL GLAND TUMOURS Specialism: Ophthalmology Code: 62720157 ABSTRACT OF THESIS HÀ NỘI - 2022 The thesis has been completed at HANOI MEDICAL UNIVERSITY Supervisors: Supervisor1: A.Prof Pham Trong Van Supervisor 2: PhD Nguyen Quoc Anh Reviewer 1: Reviewer 2: Reviewer 3: The thesis will be present in front of board of university examiner and reviewer lever at on 2022 The thesis can be found at: National Library National Medical Informatics Library Library of Hanoi Medical University THE LIST OF WORKS HAS PUBLISHED AND RELATED TO THE THESIS Ha Thi Thu Ha, Nguyen Thi Thanh Huong, Nguyen Quoc Anh, Pham Trong Van (2020) “Clinical features and computed tomography of lacrimal gland tumors” Journal of Vietnamese Medicine, issues 1&2 in 2020, pp 173 - 176 Ha Thi Thu Ha, Nguyen Quoc Anh, Nguyen Ngoc Mai, Tran Hong Nhung, Pham Trong Van (2020) “Correlation between clinical features, computed tomography images and histology of lacrimal gland tumors” Journal of Practical Medicine, 2nd issue, 2020, pp 12 - 15 Ha Thi Thu Ha, Nguyen Thi Thanh Huong, Nguyen Quoc Anh, Pham Trong Van (2021) “Results of treatment of lacrimal gland tumors” Journal of Vietnamese Medicine, No 1, 2021, pages 149 - 154 INTRODUCTION A lacrimal gland tumor is a polymorphic lesion with characteristic clinical features, pathology and therapeutic results Classification of lacrimal adenomas is based on the World Health Organization (WHO) 1991 classification of salivary gland tumors Lacrimal adenomas account for 3% to 18% of orbital tumors Tumors are divided into two groups: epithelial (2045%) and non-epithelial (55-80%) The lacrimal adenocarcinoma consists of 55% of the benign (the most common mixed lacrimal gland tumor) and 45% of malignant (the most common and the most adenoid cystic carcinoma, accounting for 66% of the malignancies) Lacrimal gland cancer is the one with high malignancy, especially adenoid cystic carcinoma with high local recurrence and distant metastases, usually poor therapeutic result, with a mortality rate of about 50% The lacrimal non-epithelial neoplasms are mainly lymphoid lesions including benign lymphoid hyperplasia, atypical lymphoid hyperplasia, and malignant lymphoma In Vietnam, there are no report on the incidence of lacrimal gland tumors Early detection and diagnosis of malignant lacrimal adenomas are relevant for the monitoring, management, prognosis and survival rates of patients Diagnosis is based on clinical features, computed tomography images and pathology And, clinical features and oriented computed tomography diagnosis and pathology have definite diagnostic value In recent years, the understanding of the pathogenesis of lacrimal gland tumors has been improved, treatment method brings about better results Treatment of benign epithelial tumors is surgical resection of the entire tumor In contrast, the treatment of lacrimal adenocarcinoma remains controversial Eye-sparing and radiation therapy combined with chemotherapy are the main trends in the treatment of lacrimal carcinoma Targeted therapy studies aimed at oncogenes will have been used in the treatment of adenoid cystic carcinoma, particularly of value in recurrent or metastatic cancer Treatment of lymphoma includes monitoring, systemic corticosteroids, local radiation therapy, or chemotherapy In Vietnam, the actual rate of cancer, including orbital cancer in general and lacrimal gland cancer in particular, is increasingly reported At the National Institute of Ophthalmology, many patients with lacrimal gland cancer come for examination and treatment at a metastatic stage Therefore, the treatment results are very poor, even death within a short time since the disease is detected Lacrimal gland tumors are very diverse in clinical morphology, the diagnosis of lacrimal gland tumor type, benign and malignant nature of the tumor and treatment prognosis are still challenging for clinicians Up to date, the studies on lacrimal gland tumors in Vietnam are still incomplete and the systematic and limited treatment methods have not caught up with the world trend We conducted the thesis "Research on clinical, subclinical characteristics and treatment results of lacrimal gland tumors" with three objectives: Description of clinical and subclinical characteristics of lacrimal gland tumors at the National Institute of Ophthalmology Evaluation of treatment results of lacrimal gland tumors of the study group of patients Analysis of some factors related to the results of treatment of lacrimal gland tumors THE SCIENTIFIC AND PRACTICAL CONTRIBUTION OF THESIS For the first time in Vietnam, there is a summary study on a large number of patients with lacrimal gland tumors Describe the clinical and paraclinical features of two types of lacrimal gland tumors, namely epithelial and non-epithelial neoplasms (mainly lymphoid lesions), showing the relationship between clinical and subclinical signs Evaluate the results of treatment methods for each different type of lacrimal gland tumor and analyze the factors affecting the treatment outcome of each method Based on research, ophthalmologists have more knowledge in the diagnosis, treatment indications and prognosis with different types of lacrimal gland tumors STRUCTURE OF THE THESIS The thesis is presented 156 pages: Introduction pages, Overview 33 pages, Meth odology 20 pages, Results 49 pages, Discussion 46 pages, Conclusion pages, Contribution of Thesis page, The direction of further research of the thesis page, Recommendation page with 175 Vietnamese and English references CHAPTER 1: OVERVIEW 1.1 Clinical and paraclinical features of lacrimal gland tumors 1.1.1 Outline of lacrima gland 1.1.2 Classification of lacrimal gland tumors based on histopathology The four most common types of lacrimal adenomas are benign lacrimal gland mixed tumor, lacrimal gland carcinoma, lymphoid hyperplasia and malignant lymphoma 1.1.3 Clinical and subclinical characteristics of some common lacrimal gland tumors * Benign lacrimal gland mixed tumor Mixed lacrimal gland tumor is the most common epithelial tumor of the lacrimal gland, accounting for 10-20% of lacrimal gland lesions and 1% of orbital tumors, usually originating from the orbital lobe, sometimes from the eyelid lobe (10%) The tumor usually grows slowly, without pain, the first sign is facial disproportion, ocular deviation, with limited ocular movement or diplopia On computed tomography, the tumor usually presents as a round or oval mass, smooth, well-demarcated, smooth shell, ocular displacement or deformity, mild to moderate attenuation Histopathology is often cortical, clearly demarcated, characterized by epithelial and parenchymal proliferation that varies according to tumor morphologies * Lacrimal gland carcinoma Lacrimal gland carcinoma includes adenoid cystic carcinoma, carcinoma ex pleomorphic adenom, adenocarcinoma Adenoid cystic carcinoma is the second most common form of epithelial lacrimal gland tumour and is the most common malignant carcinoma of the lacrimal gland, accounting for about 1.6% of orbital tumors and 3.8% of primary orbital tumors The disease occurs in both sexes The average age of patients is about 40 (6.5 - 79 years old) Clinical features include pain, eyeball displacement, eyelid swelling, and eyelid numbness Computed tomography showed a spherical, round, or elongated tumor, running along the outer orbital wall, dilated lacrimal fossa with bony infiltrates, serrated margins, and irregular density On the bony window there may be tumor infiltrates into the dura mater and intracranially In terms of histopathology, the gross tumor size can be small or large, the density is firm, often multi-size, the limit is unknown, the face is rough and invasive.The tumour-section is gray-white Necrosis and bleeding are rare, usually present only in cancers with high histology Microscopically, adenoid cystic carcinoma has many different morphologies: sieving, fibrous, basal (solid), cystic, and tubular It is most common to have a mixture of two or more of these morphologies in the same tumor, in different regions The staging of lacrimal gland cancer is based on the TNM classification system proposed by Denoix in 1943, which divides the cancer stage based on three factors: tumor (Tumor), lymph node (Node) and metastasis (Metastasis) * Lymphoid hyperplasia Lymphoid lesions include benign lymphoid hyperplasia, atypical lymphoid hyperplasia, and malignant lymphoma Lymphocytic hyperplasia is characterized by insidious onset, progressive swelling of the eyelids causing bulging or drooping of the eyelids, painless, common in the elderly, often bilateral, may have signs of inflammation, and a palpable mass in the upper outer corner of the eye socket On computed tomography, the lymphoid organization surrounds the lacrimal fossa, clearly demarcated, oblong, closes to the wall of the eyeball, clearly enhanced with contrast, rarely bone lesions Histopathology is characterized by dense infiltrate of small lymphocytes, the formation of reactive lymphoid follicles of different sizes reminiscent of a normal lymph node structure with multiple nuclei in the nucleus accumbens * Lymphoma Malignant lymphoma is a proliferative non-Hodgkin's low-grade B-lymphocyte, common in the elderly Tumor is most common in the 70-80 year old age group Manifestations of the disease in the lacrimal gland can be unilateral or bilateral, the rate of bilateral tumors accounts for 25% Duration of disease onset is usually less than year Malignant lymphoma often has chronic symptoms, slowly protruding eyes, drooping eyelids, palpable mass in the upper outer orbit, firm rubbery mass, painless On computed tomography, the tumor is ovoid or oblong, cast around the orbital structure, with moderate contrast enhancement, usually without bone lesions, rarely with calcification The histology of extranodal marginal zone lymphoma is characterized by a dense infiltrate of small cells with broad cytoplasm, slightly notched nuclei, and absence of nuclei like marginal cells 1.2 Management of lacrimal gland tumour Lacrimal adenomas are very variable in appearance and have many treatment options, depending on the specific case 1.2.1 Treatment of benign mixed lacrimal gland tumor Treatment of benign mixed lacrimal gland tumor is mainly complete resection of the tumor, removal of the entire tumor envelope, and no biopsy to avoid tumor recurrence 1.2.2 Treatment of lacrimal gland carcinoma Treatment includes surgery combined with radiotherapy and chemotherapy Prognosis is often poor The goals of treatment of lacrimal carcinoma are local control and prevention of distant metastases The issue of appropriate local treatment for lacrimal carcinoma is controversial The guideline of eye-sparing surgery combined with radiation therapy allows local control, preserves vision and less damage to the ocular surface Intra-arterial chemotherapy or adjuvant intravenous chemotherapy to reduce tumor size is very effective in combination with eye-sparing surgery, but the longevity benefit of adjuvant chemotherapy has not been demonstrated Preoperative adjuvant intra-arterial chemotherapy is only applicable to patients with intact lacrimal artery Targeted therapy is the cancer gene applied to cases of metastatic or recurrent cancer 1.2.3 Treatment of lymphoid hyperplasia Treatment of lymphoma is based on histopathological results, depending on each specific case Benign lymphoid hyperplasia is treated initially with high-dose steroids and/or external beam radiation therapy with approximately 20Gy Rituximab (monoclonal antibody) is also an optimal choice in cases that not respond to radiation therapy 1.2.4 Treatment of malignant lymphoma Treatment of malignant lymphoma in local radiation therapy, chemotherapy in patients with systemic lymphoma The immunological approach, using interferon-α for malignant lacrimal lymphoma, is not yet officially recognized The currently recognized monoclonal antibody used for malignant lymphomas, especially low-grade B-cell lymphoma, is the anti-CD20 rituximab monoclonal antibody that destroys B cells 1.3 Factors associated with treatment outcome Factors that may affect treatment outcomes include: - Age: Tellado et al (1997) reported that younger patients with cystic adenocarcinoma had a better prognosis than older patients - Tumor size: Based on the tumor size, it is possible to choose the appropriate treatment method (surgery or medical treatment), choose the surgical method (partial or complete tumor removal) Tumor size is also related to tumor status after treatment, ocular deviation, ocular movement limitation, double vision, convexity, side effects of treatment (complications), tumor recurrence, and death - Tumor location: determine the appropriate approach to the tumor - Pathological properties of the tumor: including benign or malignant nature and AJCC grade affect treatment methods, tumor recurrence rate and mortality rate - Treatment methods: affect post-treatment complications, tumor recurrence, and death - The status of surrounding infiltrates: affects the choice of treatment method, tumor recurrence and mortality rate Ford et al (2021) showed a statistically significant association between nerve infiltration and high local recurrence rates in patients with lacrimal carcinoma 1.4 Research situation in Vietnam Hoang Cuong (2015) describes clinical and subclinical characteristics of ocular adnexal lymphoproliferative diseases and comments on treatment results of ocular adnexal lymphoproliferative diseases Tran Thi Thu Hang (2018) describes clinical and subclinical characteristics of eye protrusion due to orbital tumor at the National Institute of Opthalmology and learns some factors related to pathology - clinical and near-sightedness clinical manifestations of some types of orbital tumors Doan Minh Hoang (2018) specifically mentions conjunctival lymphoma, describes the clinical and subclinical characteristics of conjunctival lymphoid proliferation and evaluates the results of treatment for conjunctival lymphoma Mai Trong Khoa et al (2020) reported "Treatment of a rare case of lacrimal gland cancer at the Nuclear Medicine and Oncology Center, Bach Mai Hospital" is a clinical case of carcinoma Rare primary glandular tissue derived from lacrimal gland has been successfully treated However, to date, there have been no published studies on the clinical, laboratory and treatment results of general lacrimal adenomas and different types of lacrimal gland tumors CHAPTER PATIENTS AND METHODS 2.1 Patients The patient who came for examination and treatment of lacrimal gland tumor at the National Institute of ophthalmology from October 2016 to December 2019 Selection of patients with a confirmed diagnosis based on pathological results of the following groups of lacrimal gland tumors: benign mixed lacrimal gland tumor, lacrimal gland carcinoma, benign lymphoid hyperplasia, malignant lymphoma 2.2 Methods 2.2.1 Design Prospective descriptive study 2.2.2 Study sample size Apply the formula to calculate sample size: n: study sample size z: confidence limit value Choose reliability as 95% → = 1.96 α: Statistical significance level, α = 0.05 p: recurrence rate of lacrimal gland tumor (choose p = 0.22) : 0.36 (relative value from 0.1 → 0.4) Qua tính toán n = 105.09 Through calculation n = 105.09 How to choose a research sample: From October 2016 all eligible lacrimal adenomas patients were randomized, continuously until the sample size needed for the study was reached We collected 108 patients 2.2.3 Variables and how to evaluate variables according to research objectives *Clinical and subclinical characteristics - Age: mean age (quantitative), age group (qualitative) divided into age groups: 20, 21 - 40, 41 - 60, 61 - 80, 80+ - Gender (qualitative): Male / female - Reason for admission (qualitative) - Time from illness to medical examination: Mean time (qualitative) and time group (quantitative) divided into groups: ≤ months, - 12 months, > 12 months - How to assess visual acuity: Visual acuity according to WHO classification of visual acuity: ≥ 20/25 : Normal