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29-9-2014 Oral Medicine lec #3 Lana Ajlouni Biopsy: removal of a small piece of tissue from the living body for the purpose of diagnostic microscopic examination. Indications : 1. Lesions that has neoplastic or premalignant features. (ex. White lesion of an unidentifiable aetiology such as leukoplakia/ erythroplakia). 2. Persistent lesion of uncertain etiology. (Unknown etiology such as leukoplakia). 3. Persistent lesion failing to respond to treatment. 4. Persistent focal lesion involving gingival, periodontium. 5. Conformation of clinical diagnosis. (the dr. mentioned a patient with enlarged tongue –macroglossia- the patient is old and it started a year ago, the clinical diagnosis is amyloidosis, to confirm our diagnosis we should take a biopsy, and we see amyloid deposits under the microscope). - The dr. asked what is the stain used in amyloidosis?? (imp.) 6. Lesions causing patients concern. 7. Aid the diagnosis of a systemic disease. (Suspected systemic syndrome). Such as Sjögren's syndrome, so we take biopsy from the labial mucosa to confirm the diagnosis, homocystinuria in children is difficult to diagnose in blood tests, so we take biopsy from the oral cavity, so we can see iron deposits in the submucosa. So oral biopsy is beneficial in many cases such as Sjögren's syndrome and sarcoidosis. Types of biopsy: 1) Excisional -> complete removal of the lesion (diagnostic and therapeutic). 1 29-9-2014 Oral Medicine lec #3 Lana Ajlouni 2) Incisional -> removal of part of the lesion. 3) Exofoliative cytology -> used for screening purposes (Pap smear, which is used for cervical cancer) using cotton pellet. 4) Brush biopsy-> screening purposes (Pap smear) using small brush. (it takes cells from the whole thickness of the epithelium, and nothing from the submucosa). 5) Needle biopsy (also called aspiration) -> used in radiolucent lesions and neck masses. If we have a radiolucent lesion first of all we do aspiration to know the type of fluid or even if there is fluid or not, sometimes the fluid is brown dentigerous cyst / white fluid keratocyst / no fluid solitary cyst (this negative result is important, as it may indicate a solid mass tumor). So aspiration is important as a first stage especially in bone lesions. - Sometimes no fluid is aspirated, but instead cells are aspirated, it's called Fine needle aspiration cytology (mainly used in neck lesions such as thyroid masses). When the mass is located deep in the neck, and is difficult to reach, we do what is called ultrasound guided aspiration biopsy. We can see the exact location of the needle to make sure we are aspirating from the right place. 1 + 2 are the main types. Any type of biopsy depends on: size, shape, type, and location. If the lesion is suspicious for malignancy we take incisional biopsy, which mean we remove part of the lesion not all. 3 + 4 are almost the same; they also have not that much use in clinics. It’s a simple technique. In biopsy, orientation is very important, it's upper, lower, anterior, or posterior border. Processing: i. Fixation in 10% buffered formalin ii. Dehydration 70% absolute alcohol iii. Immersion in xylen to remove alcohol 2 29-9-2014 Oral Medicine lec #3 iv. v. vi. vii. viii. ix. Lana Ajlouni Liquid paraffin (to obtain paraffin block) Microtome(5-6 microM) Water bath Blank slide Staining using H&E Removal of paraffin Soft tissue Vs. calcified tissue, calcified tissue need more time because we decalcify by staining, so it takes about 2 weeks. Immunoflurescence testing: Commonly used in oral medicine. Used in immune based diseases, such as pemphigus. We look for specific antigens in the biopsy, these antigens are attracted by specific antibody attached to flucescin, and then it's seen under the microscope using specific light. If there is an antigen, the antibody will bind to it, and a light will occur when examined under the microscope, so we conclude that this tissue contain the antigen of concern. It's either: (IMP) 1) Direct tissue (QUALITATIVE) 2) Indirect serum/plasma (QUALITATIVE + QUANTITATIVE) so it's related to severity. For ex. if IgG is very high very severe. So it helps in disease progress, and response to treatment. Toluidine blue It’s a type of vital staining. It’s a blue stain used for patients with oral lesion, so if the lesion has increase growth rate or dysplasia there will be an uptake of the stain and will appear as bluish lesion Beneficial specially in patients with multiple oral lesion like a patient with five white lesion all over the oral cavity so we don’t know from where we should take 3 29-9-2014 Oral Medicine lec #3 Lana Ajlouni the biopsy so we use toluidine blue to know where is the most suspicious area where there’s cytological Changes The idea is that the cells with increase growth rate or increase nuclei will take up the stain more than the others it appear bluish. It has special techniques and not used routinely except for the case where there're multiple white spread lesions the technique is : we make the patient rinse with diluted acetic acid water toluidine blue acetic acid so the area with dysplasia or atypia will appear rinse 20 sec with 1% acetic acid rinse 20 sec with plain water rinse 60 sec with 1% toluidine blue rinse 20 sec with 1% acetic acid Punch biopsy: Same as incisional or excisional biopsy but without using a blade we use something called punch ( looks like a pen and we put it on the tissue that we want to take the biopsy from and we’ll have a small piece . Characteristic : The specimen is always adequate The incision is controlled The patient is not disturbed by the sight of the blade and suture because suturing is not always needed in this technique Easier; you only put and it takes a biopsy from the tissue by itself . Before taking any biopsy we should take comprehense medical history, if the patient has bleeding tendency or any systematic disease that might affect the procedure, we take that into consideration Then we gice him a brief description if the procedure, why and how we’re taking a biopsy and what to expect after the procedure is done (pain, swelling , any complications) The patient must sign a consent form before any biopsy 4 29-9-2014 Oral Medicine lec #3 Lana Ajlouni Pre-Op consideration : comprehensive med patient education (brief description) consent techniques of biopsy: aim: to take adequate sample (we should have tissue from the lesions as well as normal tissue to compare between them) LA We take from the normal and lesional tissue and we try nto to be aggressive with the lesion in order for it not to be distorted under the microscope Tech (LA, representive, normal + lesion tissue, gentle handling) After taking the biopsy we fill the request form of the sample and we give the patients the post-op instruction ( which is= same instruction after extraction) We should write the patient name and file number in the form and where did we take the biopsy and the site from which the biopsy was taken and size of the biopsy and the differential diagnosis as the clinical diagnosis and if the patient has undergone a previous biopsy Sometimes we take more than one biopsy because the first one was not representative or there were findings not related to the clinical features Now we’ll take about the rest of the investigation methods other than biopsy. We’ll take about some disease that we might need extra investigation to diagnose or treat. Oral dysaesthesia (burning mouth syndrome): A common disease specially in females after 40 (older women) It’s the experience of a burning sensation in the absence of identifiable organic pathology The patient usually suffer from pain and burning sensation and discomfort in the oral tissue but when examined there’s nothing to explain these presentations 5 29-9-2014 Oral Medicine lec #3 Lana Ajlouni Considered as medical unexplained syndrome (MUS) This disease has psychogenic/ neurophathic basis Most frequent affect the tongue thus called sometimes (burning tongue syndrome) Difficult to treat and need psychoactive medications ”psychatric therapy” Some of its causes: (allergies, bioxism, or parafunctional habits, candidiosis, drugs such as ACE (angiotensin converting enzyme) That’s why it's important to take medical history from the patient with oral symptoms. Erythma migrans and fissured tongue might cause burning sensation. Hematinic deficiency and magnesium deficiency cause that also Diabetes Hypothyroidtism Hyposalivation We’ll take these disease later in details So any patient with burning tongue syndrome we make a complete blood picture which is 1. 2. 3. 4. 5. 6. 7. 8. 9. CBC hematinic (which are ferritin, B12, folic acid) ESR 8 Sialometry (measurement of the salivary how much the patient produce saliva in 1 minute for example Thyroid function test Blood glucose in some cases we also make culture and sensitivity when suspecting a microbial cause psychological assessment allergy testing if all these test were normal and no reason to explain the disease we diagnose it as a “burning mouth syndrome” but if the patient has low hematinic (low ferritin and low folic acid) it’s diagnosed as “burning mouth syndrome secondary to hematinic deficiency” so these tests helps in the diagnosis and treatment 6 29-9-2014 Oral Medicine lec #3 Lana Ajlouni so if the patient has hematinic deficiency and we gave him/her B,E + iron the symptoms will disappear but if all test were normal and we gave the patient those the symptoms won't disappear. DRY MOUTH: same patient complain from dryness in the mouth / Xerostomia Xerostomia; it’s a subjective sense of dryness due to reduced salivary flow or changes in the salivary composition There’re a lot of causes of dry mouth: psychogenic / stress like in exams increase stimulation of sympathetic nervous system dry mouth so the patient with chronic stress and anxiety suffer from dry mouth some medication cause dry mouth specially antinhypertensive, also antimalarial drugs antidepressants cancer chemo and radio therapy salivary gland disease Sjogren’s syndrome dehydration (like in fasting) complications of chronic xerostomia: increase carries increase candidiosis salivary gland infection halitosis the dr showed us an example :a patient who works as a college doctor came complaining from dryness in mouth he had diabetes. Sometimes the first presentation of a systemic disease can be dry mouth. Other patient with the same complain the cause was hypothyroidism. 7 29-9-2014 Oral Medicine lec #3 Lana Ajlouni Patients with sarcoidosis often complain form dry mouth. Upon examination the mirror will stick to the mucosa if there was dryness, or when the patient eats dry food remnants will stick to the surface of teeth. There are alot of tests for xerostomia depending on the case, but in most cases we use 1) SS-A SS-B ANA to diagnose sjogren's syndrome. 2) blood glucose to diagnose diabetes. 3) ESR to see if there's an inflammatory chronic disease. 4) ultrasound to check if there is a disease in the salivary glands. And alot more tests depending on the clinical presentation of each patient. A patient with Dry mouth, cough, chest pain and fatigue lately, we think of sarcoidosis, serum angiotensin converting enzyme will be elevated. Patient complaining of dry mouth with enlargement of salivary glands with dry eye and skin we think of sjogren's syndrome ( SS-A, SS-B, ANA). Cervical lymphadenopathy Lymph-node enlargement according to age, a child with with Lymph-node enlargement most probably it's viral infection as viral respiratory tract infection or kawasaki disease. Teenager between 10 to 20 years old might have respiratory tract infection, or bacterial infection or glandular fever due to EBV , or toxoplasmosis . Adults 20 to 40 might be: -lymphadenitis due to dental infection. -glandular fever. -malignancy like lymphoma. After 40 years : infection like periapical abcess, or malignancy , pr lymphadenitis. Older patient the percentage of malignancy cause increases. Younger patients infections are more probably the cause The main reasons for lymph-node enlargements are: 1) infections 8 29-9-2014 Oral Medicine lec #3 Lana Ajlouni 2) malignancy 3) inflammatory disease 1) Infections: could be: a) Viral: like cold. b) bacterial: like dental infections. c) systemic: fever. 2) Malignancy: - Primary: malignancy may look like lymph-node enlargement. - Secondary: metastasis to lymph nodes 3) Inflammatory diseases: like crohn's and sarcoidosis. Note: in rare cases drugs may cause lymph node enlargement. A patient came in last year for a complete denture, when examined they found a mass in s neck (submandibular gland), after biopsy it appeared to be Muco-epidermoid cancer. Lymph-node enlargement may also be from tuberculosis. Children with enlarged lymph-node the cause is mostly viral. People in the second decade of life with enlarged lymph-node are mostly bacterial infections. Facial pain Facial pain has many causes, maybe from dental procedures or even vascular diseases, psychogenic. A patient removed almost all his teeth from one side of his jaw complaining that his teeth were causing him pain. But it turned out he had Trigeminal Neuralgia. History of pain: 1) site 2) onset 3) character 4) radiation 5) association with other factors 6) aggravating factors 9 29-9-2014 Oral Medicine lec #3 Lana Ajlouni 7) force 8) severity We will talk later on about facial pain, but he have to take x-rays and teeth vitality tests to exclude dental causes. We sometimes take MRI ( brain tumor is the cause of facial pain), ASR, biopsy. Ulcers Oral ulcers are quite common but sometimes are hard to diagnose, sometimes a systemic disease is the cause of ulcers. ( like blood disorders, infections, GI diseases). Sometimes they are caused from malignancy or local factors like a trauma, or even from drugs. There is a book that we should get it has all the drugs and their side effects. Mostly blood tests are enough to diagnose or help to diagnose a case, but other times special blood tests like immunoglobulin tests for diagnosis of pemphigus vulgaris. Culture sensitivity if it is a bacterial infection. Chest x-ray if there is TB. A very important note is: If an ulcer persisted for more than 2 weeks we should take a biopsy and it should be considered malignant until proven otherwise. The doctor showed us a picture of a patient's tongue with an ulcer on the lateral border and asked what the diagnosis was? Because of its site and the persistence of the lesion it is most likely squamous cell carcinoma. An 80-year-old patient with an ulcer on the upper lip, the patient was leukemic and prone to infections , so this ulcer was from fungal infection (mucal mycosis) and is rapidly fatal! Aphthous ulcers can be stress related. A 40-year-old patient has recurrent aphthous ulcers in the same place, this is from low levels of folic acid. A 15-year-old girl came in with enlarged and ulcerated gingiva, what is the diagnosis? 10 29-9-2014 Oral Medicine lec #3 Lana Ajlouni The patient had pale skin and nails, so this is caused from he anemia she had. After blood tests they found that the patient had leukemia. An old denture wearing female came in with ulcerations on her alveolar ridge, at her age we should think this is caused from pemphigus vulgaris. Sometimes even if you go through all the investigations and the history, you may not find an answer. White lesions Sometimes we need biopsies if the lesion is found on the floor of the mouth. Other times it is obvious like candida infections where it can be rubbed off. Many thanks to Banan Zureikat, Farah Sweis, Yazan Abu Ghazzeh , George Allousi GOOD LUCK 11