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The surface mucosa. Right. And it's. It arises from the stratified squamous epithelium of the surface mucosa. So today we will discuss about oral malignancies that are not derived from the surface stratified squamous epithelium. So usually I show a review case from the last lecture right from the pr...

The surface mucosa. Right. And it's. It arises from the stratified squamous epithelium of the surface mucosa. So today we will discuss about oral malignancies that are not derived from the surface stratified squamous epithelium. So usually I show a review case from the last lecture right from the previous lecture. But today I have included a salivary gland tumor towards the end of the lecture. So we will just discuss about salivary gland tumor. Okay. So a brief review of squamous cell carcinoma. So we know that it's the most common world cancer. More than 90% of the oral malignancies or oral squamous cell carcinoma. And as we age we are at increased risk for developing squamous cell carcinoma. Apart from genetic factors we know that alcohol and tobacco use tobacco and alcohol use increases is considered to be risk factors for development of oral squamous cell carcinoma, more common in men. But but that is because of tobacco use. So if women use tobacco they are they are also at increased risk for developing oral squamous cell carcinoma. What are the high risk sites? Intra orally. What are the high risk sites for oral squamous cell carcinoma? The lateral surface of the tongue. The ventral surface of the tongue. Floor of the mouth. Soft palate. Those are considered to be high risk sites. But you have to remember that squamous cell carcinoma can arise at other oral mucosal sites, too. So gingiva. Hard palate. Buccal mucosa, labial mucosa. Gingival carcinomas are especially tricky because in the initial stages they may mimic inflammatory lesions even when they are producing a mass they may mimic like a reactive gingival lesions. So you have to be careful. So these are, you know, lateral tongue ventral tongue float of mouth soft palate. Those are considered to be high risk sites. But that doesn't mean that you ignore other oral mucosal sites. Anything that looks suspicious needs to be biopsied. And metastatic. Metastatic spread is often through the lymphatics, and prognosis is related to the stage of the diagnosis, the TNM staging. So this figure shows the high risk sites for oral squamous cell carcinoma lateral tongue, ventral tongue, floor of the mouth, soft palate and some you know, authors. They include retro mula trigon the retro mula pad area also as high risk site. How does squamous cell carcinoma present intravenously? Is that a specific presentation it can present as a white lesion locally. It can present as a radiation therapy. It can present as a mixed red and white change a retro look, or it can present as an accelerated mass growing outwards, or it can present as an infiltrating mass growing inwards, or it can present as a persistent ulceration. So look at this example. So maybe this is an adult patient right. You can assume that this is an adult patient. Where is the lesion located. It's the posterior lateral tongue on the right side. Right posterior lateral tongue. How will you describe this lesion. So it's slightly raised. Very good. Yeah. You can see that there is a slight swelling right around this red and white change. And there's probably ulcerated surface. So ulcerated surface is a mix of red and white change slightly raised. And if it is a squamous cell carcinoma if you palpate this lesion it will feel integrated. It will feel like it's fixed to the underlying tissues. So how will you make the final diagnosis? Biopsy. Anything else in your differential diagnosis? Whenever you see red and white, change red and white lesion, especially in a high risk site. In an adult patient with risk factors, squamous cell carcinoma should be the number one in your differential. Okay. Leukemia. So leukemia represents malignancy of hematopoietic stem cell derivation. So malignant transformation of one of the stem cells hematopoietic stem cells. And initially this malignant stem cell it starts proliferating in the bone marrow. It fills up the bone marrow and normal precursor cells in the hematopoietic bone marrow like the normal precursor white blood cells, platelets, red blood cells, all those are crowded out, so it fills up the bone marrow. Then eventually it spreads or it spills out into the peripheral blood as well as it starts infiltrating other organs, other tissues and organs. See these leukemic cells, they crowd out the normal precursor white blood cells, red blood cells and platelets. What causes leukemia apart from genetic factors. So there are some leukemia, some types of leukemia leukemias. They show chromosomal translocations chromosomal abnormalities. And there could be environmental factors that can also cause leukemia. So exposure to ionizing radiation pesticides. Benzene harvest leukemia. Classified leukemia is classified based on the clinical course or the clinical behavior as acute and chronic leukemia, and based on history genesis. They are classified into myeloid and lymphocytic leukemia. So based on the clinical course or behavior acute leukemia, acute leukemia, it runs a very aggressive course. Sometimes in some kinds of acute leukemia, the patient may be dead within a few months. Chronic leukemia. It runs a more indolent course. And based on the history of genesis, it can be myeloid leukemia or lymphocytic leukemia, myeloid leukemia, the tumor cells, the leukemic cells. They resemble granulocytes. They resemble neutrophils, sniffles, basophils. Very rarely, they can resemble monocytes, erythrocytes, or even mega carrier sites, precursor cells of erythrocytes or mega mega carrier sites. Precursor cells for platelets. Whereas in lymphocytic leukemia, the leukemic cells, they resemble lymphocytes. So what are the signs and symptoms of leukemia? The signs and symptoms are because of the normal precursor cells, especially in the hematopoietic bone marrow, the normal precursor of white blood cells, the red blood cells and the platelets. They are wiped out right. So there's decreased red blood cell count. There's decreased white blood cell count. There's decreased platelets. So decreased white blood cell count. It results in patients are susceptible to infection. So patients can present with fever. And that could be the first sign that the patient has leukemia. Because of the decreased red blood cell count, patients can develop anemia. They can present with fatigue easily easy tiring Disney on exertion. They can present with thrombocytopenia. So that's decreased platelets right. That leads to thrombocytopenia. So patients can present with easy bleeding and bruising. They can present with spontaneous hemorrhages internally. They can present with spontaneous hemorrhages in the heart and soft palate gingival hemorrhages. Apart from that these leukemic cells. They start filling up the bone marrow, but they will ultimately, they will start infiltrating other organs also so they can infiltrate the lymph node. They can cause enlargement of the lymph nodes, resulting in lymphadenopathy. They can infiltrate the spleen and liver, causing enlargement of these organs so patients can present with a spleen. Omegalul hematoma. Ugly. Hepatol. Sorry. What are the oral manifestations of leukemia? The first thing that I think of whenever I think of leukemia presenting in the oral cavity, patients will present with diffuse gingival enlargement. There could be multiple reasons for diffuse gingival enlargement, right? It could be medication related gingival enlargement. It can be due to vitamin C. It can be just gingivitis. But in leukemia the the leukemic cells they infiltrate the gingival soft tissues and cause diffuse enlargement of the gingiva. And because there's decreased platelet count, patients can also present with hemorrhagic changes involving this enlarged gingiva. So hemorrhagic gingival enlargement is a classic presentation for leukemia. Apart from that, the patients can present with pedicle hemorrhages involving the heart and soft palate, buccal mucosa, tongue, so other areas can also show pedicle hemorrhages. And leukemic cells can infiltrate the Jawbones, and it will present as a radial loss and change if it presents in the periodical area. It can mimic a periodical inflammatory lesion like a pickle or granuloma, because of the decreased white blood cell count. These patients are at increased risk for developing infections so intravenously patients can present with candidiasis so either pseudo membranous candidiasis or erythematosus candidiasis. They are also susceptible to recurrent herpes infections. Remember her lesions recurrent lesions. How do they develop they intravenously. How to help indications develop recurrent hepatic lesions. Recurrent HSV one infection. Usually. There. They present us ulcers. Right. Involving the. Attached mucosa. So the primary hepatic lesions, they involve both the movable as well as the attached mucosa. But when they come back recurrent or secondary HSV one infection it typically affects the attached mucosa. But in patients who are immunocompromised, like patients with leukemia, the recurrent lesions they tend to involve both the attached as well as the movable mucosa. So how was the diagnosis of leukemia made? Peripheral blood analysis. Bone. Bone marrow biopsy. Histopathology examination. Microscopic examination. Along with immunohistochemical studies, cytogenetics, and molecular studies. All these are done to classify the type of leukemia, and the treatment depends. So various types of chemotherapeutic agents are used to treat leukemia, and the type of chemotherapeutic regimen depends on the type of leukemia. The prognosis also depends on the type of leukemia, the age at diagnosis, and whether there are any chromosomal abnormalities. So he's. The classic presentation for leukemia or interval presentation diffuse gingival enlargement. So you can see that both the maxillary and mandibular facial gingiva it shows diffuse enlargement. Usually it's very soft. On palpation. And this is the same patient. You can see that even the posterior buccal and lingual gingiva they are showing diffuse enlargement. So this is a different example. Diffuse gingival enlargement also showing hemorrhage right. This is hemorrhagic gingival enlargement in a patient with leukemia. This is like a pronounced case a dramatic hemorrhagic gingival enlargement in a patient with leukemia. So what is? Obviously if you biopsy the this tissue this affected gingiva it shows. Loss of normal tissue architecture, and it shows monotonous proliferation of poorly differentiated cells with Milo monocyte lymphoid features. All of the lesions or conditions that we are going to discuss today. The micro looks the same. The micro shows just C. We call that as small round blue cell tumors small meaning the cells are small in size round. They are round and shape blue cell tumors. Because these cells they have very hyper chromatic nuclei with very minimal cytoplasm. And the cells are all back packed together. So we use the description small round blue cell tumors. So all of the lesions that we are going to discuss today, the micro looks the same small round blue cell tumors. But we need additional studies either immunohistochemical studies in leukemia. We need not just immunohistochemical studies. They have to do additional cytogenetics studies to make the diagnosis as well as to classify the type of leukemia. So this this probably is a biopsy from the affected gingiva. Remember diffuse gingival enlargement. If you biopsy the affected gingiva you can see that the surface stratified squamous epithelium the reti ridges they are tapered. They are narrow. The epithelium is within normal limits. Look at the connective tissue. Is it normal. Is it pink fibrous connective tissue. No you don't see normal fibrous connective tissue. It's overrun by this by these small round blue cells. These are atypical cells. Leukemic cells. And this is the peripheral blood smear. You can see these are the atypical leukemic cells in a peripheral blood smear analysis. Hodgkin's lymphoma. So malignant lymphoma, proliferative disease. We'll discuss about Hodgkin's lymphoma and non-Hodgkin's lymphoma. Hodgkin's lymphoma. So this is a malignant proliferative disease that almost always begins in the lymph node. So when you think of lymphoma, it almost always, always it's the it's the it originates in the lymph node. And the affected lymph node will start to enlarge. And patients will present with persistent non tender enlargement of the affected lymph node. Remember in reactive lymph node enlargement the affected lymph node. If we have an infection the lymph nodes can show reactive enlargement. In those cases it's tender. And once the infection is resolved the lymph node goes back to its original size. Whereas in lymphoma, Hodgkin's lymphoma the affected lymph node, it shows persistent enlargement. And it's not tender. It's non tender persistent enlargement of the affected lymph node. Initially it's just the one lymph node is affected. And initially the affected lymph node is movable. But with time as the disease progresses the lymph node is attached to the underlying tissues. And then it starts affecting the adjacent normal tissues. And then it spreads to other lymph node groups. And ultimately it starts involving other tissues and organs. So if you biopsy this affected lymph node the lymph normal lymph node architecture is gone. And it's filled with inflammatory cells a mix of inflammatory cells. Scattered among these inflammatory cells are these atypical neoplastic cells. And they make up only 0.1 to 2% of the cells in the enlarged lymph node. So in the classic form of Hodgkin's lymphoma, there are several different patterns in the classic pattern of Hodgkin's lymphoma. These atypical lymphoid cells are called reed Sternberg cells. The causes are known, but it may be. Hodgkin's lymphoma may have a strong association with Epstein-Barr virus infection. It can affect any lymph node group, but 70 to 75% of the cases they affect the cervical and clavicle lymph nodes 5 to 10% of the cases. They affect the axillary and mediastinal lymph nodes and less than 5% of the cases. The Hodgkin's lymphoma can involve the inguinal or abdominal lymph nodes. So what is the age at diagnosis? It shows bimodal peak with regards to the age at diagnosis. So one group is a young group. So patients are between the ages of 15 to 35. So teenagers and young adults, another group the patients are older than 50. So it shows bimodal peak with regards to the age at diagnosis. And that is a male predominance. So. Signs and symptoms of Hodgkin's lymphoma Hodgkin's lymphoma almost almost always develops in a lymph node. So they are affected. So patients will present with enlargement of the affected lymph node. Apart from that so persistent painless enlargement of the affected lymph node. Apart from that patients can also show other signs and symptoms like weight loss, fever, night sweats, and generalized pruritus generalized itching. So when these other signs and symptoms are present. The prognosis is considered to be poor. So staging of lymphoma is very important. So the staging of lymphoma is important for treatment planning purposes and also for estimating the prognosis. So when other these other signs and symptoms are present they are put in to category B. And when these other signs and symptoms are absent then it's it's category A. So category A has a better prognosis compared to category B. So when these other signs and symptoms are present the prognosis is considered to be poor. So diagnosis of Hodgkin's lymphoma first history. Physical examination microscopic examination biopsy of the affected lymph node. Immunohistochemical studies. Apart from that, in order to know how much. Whether the lymphoma has spread. Additional imaging studies have to be done like chest radiograph, CT scan, Pet scan, MRI studies, hematologic studies, treatment. It depends on the stage of involvement. It can be radiation therapy or it can be a combination of radiation and chemotherapy. So here's a patient presenting with enlargement of the cervical lymph node. So remember these patients they if it is left untreated it starts. It shows persistent persistent enlargement. Then it starts involving other lymph node chains also lymph node groups also. So if you biopsy non Hodgkin's I mean the affected lymph node you won't see the normal nodal architecture. So that is replaced by a mix of inflammatory cells. Neutrophils plasma cells lymphocytes and scattered among these inflammatory cells or these neoplastic large lymphoid cells. And in the classic form of Hodgkin's lymphoma these large lymphoid cells are called read Sternberg cells. And these cells are being nucleated. We described that as all I. Nucleus. And there are several histopathology subtypes are recognized. But the treatment planning or the prognosis they are not influenced by the histopathology subtypes. The staging of the lymphoma is very important and that determines the treatment planning as well as the prognosis. So here's a biopsy of the affected lymph node in Hodgkin's lymphoma. You can see it's you don't see a normal nodal architecture. It's full of inflammatory cells. Scattered among these inflammatory cells are these large atypical lymphoid cells. And these cells in classic form of Hodgkin's lymphoma. It's called reed Sternberg cells. And they have they are bi nucleated, kind of resembles all nucleus. They are described as outline nucleus. non-Hodgkin's lymphoma. It's also a malignant lymphoma. Proliferative disease Hodgkin's lymphoma almost always develops in a lymph node. non-Hodgkin's. So very rarely Hodgkin's lymphoma can originate in an extra nodal site. Even it can originate in a present as a soft tissue mass in the oral cavity. But those are very rare with regards to non-Hodgkin's lymphoma, almost 60 to 80% of the cases they originate in the lymph node. About 20 to 40% of the cases can present as extra nodal lymphoma. Some. And so when they involve the lymph nodes, it's similar to Hodgkin's lymphoma. The infected lymph node will show persistent non tender enlargement. Initially the lymph nodes are mobile but with with time as the disease progresses they become. They become fuzed attached to the underlying tissues. And then they start spreading to involve other lymph node groups and other tissues and organs. And initially these non-Hodgkin's lymphoma, they use the working formulation. So they classified non-Hodgkin's lymphoma as low grade, intermediate grade and high grade. But because that was not useful in treatment planning purposes currently in the US, they use the modified Real Revised European American Lymphoma Classification, revised European American Lymphoma Classification, or the W.H.O. classification. Because this classification, it takes into consideration in. The microscopic presentation, the immunohistochemical analysis, as well as whether there's cytogenetics alteration. So based on that they classify non-Hodgkin's lymphoma. It's it can affect any age group. But it's more common in the adult patient when it presents in the when it affects the lymph node. Patients will present with slowly enlarging non tender mass of the affected lymph node. Any lymph node group can be affected. Most common ones or cervical, axillary or inguinal lymph node. And then slowly adjoining. You know it starts involving the adjoining normal tissues and then spreads to other lymph node groups. Extra nodal presentation. Only 20 to 40% of the cases are extra nodal lymphoma. So they originate not in the lymph node but at another site and oral cavity can also be involved and oral lesions. Most common that type of non-Hodgkin's lymphoma is diffuse large Bcell lymphoma. So when we diagnosed lymphoma in the world cavity, it's mostly diffuse large basal lymphoma. So all manifestations. So lymphoma can present in the old soft tissues or it can present in the jawbone. This can be the primary tumor. It can originate in the world soft tissues, or it can originate in the jawbone or the oral. It can be part of a widely disseminated disease. So the oral involvement can be part of a widely disseminated disease. So when it present presents in the oral soft tissue, unlike leukemia, leukemia presents as diffuse gingival enlargement, whereas lymphoma it will present like a tumor like mass. Very rarely, leukemia can also present apart from the gingival enlargement. They can also present as tumor like mass. But with lymphoma it usually presents like a non tender swelling diffuse non tender soft fluctuation swelling, boggy consistency, boggy consistency meaning soft and fluctuate. It will feel as though it's filled with fluid many times because it tends to involve the hard palate, buccal mucosa, buccal vestibule. Many times the clinicians will assume that this is an abscess and they will try and do incision and drainage, but it's not an abscess. They are not able to drain any pus. There's no pus. Instead this mass, the soft and fluctuating mass is not filled with fluid, but it's filled with solid tissue. So they take a piece of tissue submitted to pathology. And that's how we make the diagnosis. If we suspect it's a lymphoma, then we will send it to pathologists and they do additional work and they make the diagnosis. And if the patient is wears a denture because it presents as a swelling in the vestibule, the patient will complain of inability to wear the denture that the denture doesn't fit. If it presents within the bone. Patients can complain of vague pain that mimics toothache. It will cause. Obviously it'll present as a radial lucent lesion. It's a malignant lesion. So it will present as an ill defined or ragged radial. And see when it involves the mandible. Patients can complain of paresthesia whenever patients present with num chien syndrome, which means num num chin. You have to consider malignancy in the differential abscess can also cause pain, so an inflammatory process like abscess infection can also cause prosthesis. But in the absence of an infection, in the absence of an inflammatory process or no abscess. And if patients complain of paresthesia, then you should consider malignancy in the differential. So if it is left untreated or non-Hodgkin's lymphoma, if it presents in the bone, it will can be discovered during routine radiographic examination as a defined radiologist and C, but it fit is left untreated. It can cause cortical expansion, cortical perforation. Mobility of teeth. So diagnosis. Just like a Hodgkin's lymphoma non-Hodgkin's lymphoma diagnosis based on history and physical examination. Biopsy of the affected tissue. Microscopic examination. Immunohistochemical studies, cytogenetics studies, molecular studies, and then additional imaging to look for other locations. Chest radiographs, CT scans, Pet scans, MRI scans, hematologic studies, and the treatment depends on the stage and the grade of lymphoma and treated with chemo and chemotherapy and radiation therapy. So patient presenting with enlarged cervical lymph node. Enlarged axillary lymph node. So if it is an extra nodal present, if it involves if lymphoma involves the oral cavity, it can be part of a disseminated disease or it can originate within the oral cavity. Oral soft tissues or within the bone could be the primary location and patients usually present. So palate gingiva vestibule. These are the common locations. Clinical presentation diffuse enlargement. So there's diffuse non tender enlargement. So look at this example. There's diffuse enlargement involving the palate. And it crosses the midline right. What will be in your differential for this one. It's a diffuse enlargement, like soft, soft tissue enlargement in the palate. Okay. So. Yeah. Abscess. Right. So many times the clinicians assume that this is an abscess because it feels soft and fluctuate. And when they try incision and drainage, that's when they realize that this is a soft tissue mass and not a not not an abscess. And this is an ulcerated mass in the palate. So for a swelling in the palate or on the gingiva or the buckle vestibule, you have to include lymphoma in the differential. Micro. Another a small round blue cell tumor. Right? Monotonous proliferation of lymphocytic appearing cells and the normal architecture is destroyed and the tumor cells show varying degrees of differentiation. Several patterns are recognized nodular, follicular, diffuse. So majority of the cases of oral lymphomas or diffuse large B-cell lymphoma. Majority of the cases are B-cell lymphoma. Diffuse large B cell lymphomas. So micro just C of blue cells right. These are atypical lymphocytic appearing cells. That are packed together. They they have minimal cytoplasm. They are hyper chromatic nuclei and they are all packed together. Burkitt lymphoma. So this is also a malignant lymphoma proliferative disease. It's a B lymphocyte origin and it's named after this condition is named after Doctor Burkett with who was missionary and unique geographic differences in clinical presentation. So there are two types of buckets lymphoma. One is the endemic or the African form of Burkitt lymphoma, and the endemic form, the African form of Burkitt lymphoma affects the jawbones and usually affects the children. And this endemic form the African form of buckets lymphoma. There's a strong association with Epstein-Barr virus. More than 90% of the tumor cells. They express EBV antigen and they have high antibody titers against Epstein-Barr virus. So the affected patients, patients diagnosed with lymphoma, the endemic form, they show high antibody titers against EBV. These patients also tend to show high antibody titers against malaria parasites. So there's some link between the malarial infection as well as development of Burkitt lymphoma. And it tends to occur in countries where there's where malarial infection is prevalent. And researchers have also identified specific cytogenetics chromosomal translocations with regards to the endemic buckets lymphoma, the American form, the sporadic variant or the American form. It does not affect the jawbones. Usually patients are adult patients and they present with abdominal mass. So two forms of Burkitt lymphoma, the endemic form or the African form, and then the American form. The African form usually seen in Central Africa, very rare in the US, the African form 50. So majority of the cases they they affect the jawbones they can affect the maxilla and the mandible. It affects the maxilla more commonly than the mandible. And the posterior area is affected more commonly than the anterior area. And it predominantly affects children till the median age at diagnosis is seven years, so it affects the jawbones mostly in children, and it's more common in the predominantly affects the maxilla compared to the mandible, and more common in male patients compared to females. So the male to female ratio is two is to one and 90% of the cases of the African form, it's associated with EBV infection. So these patients who are diagnosed with lymphoma, they show elevated antibody titers against EBV. And the tumor cells express EBV antigen. The American form. It can affect a wide age range, but most patients are adult patients. Rarely affects the jaws. Mostly, these patients will present with abdominal mass and only 15 to 30% of the American form, so only 15 to 30% are EBV associated. So oral. Burkitt lymphoma, the African variant of Burkitt lymphoma. We know that it affects the jawbones and the maxilla. Maxillary posterior is the most common location. Patients are children, right? They are predominantly children and they present with facial swelling, ptosis, bulging of the. I can occur if if the maxilla is involved because it's an aggressive tumor, it can cause destruction of the alveolar bone. And so patients can present with tooth mobility. Radiographic. It's a radial lucent change, ill defined or ragged radial. See. So here's a child presenting with a right facial swelling. Another example right facial swelling. And intravenously, you can see that the tumor has perforated the cortical bone and produced an like ulcerated mass intravenously. This is also a small, round blue cell tumor, but it has a characteristic appearance. So sheets of small hyper chromatic tumor cells with brown nuclei and minimal cytoplasm. But scattered among these small, round blue cells are these macrophages. Macrophages. They have large cytoplasm. The cytoplasm is pale or foamy cytoplasm. So it produces because it's a sea of small round blue cells hyper chromatic cells dark staining cells. And then you see scattered macrophages. It's described as starry sky appearance. Even in the low power, you will be able to appreciate that starry sky appearance. So buckets. Lymphoma. So the tumor cells are small, round, hyper chromatic cells, minimal cytoplasm. They are packed together. They are aggressive tumors. So high mitotic figures you see lots of mitotic figures. And then scattered among these blue cells or these macrophages you can see that these are the large cells. These are pale cells. These are macrophages. And that produces the study sky appearance like a night sky with stars. Multiple myeloma and other malignant lymphoma. Proliferative disease. This is a malignancy of plasma cell origin. So and multi centric origin within the bone. That's why it's called multiple myeloma. It can affect multiple locations within the bone. And the causes are known. And it represents 1% of all malignancies and 10 to 15% of all hematologic malignancies. So it's not that common. And it represents monoclonal proliferation of plasma cells. All of the tumor cells they came from the same precursor malignant plasma cell. So all of these tumor cells they produce the same protein. So that's why we say it's the monoclonal proliferation of plasma cells. And the signs and symptoms of multiple myeloma occurs as a result of uncontrolled proliferation of these malignant cells, as well as due to the uncontrolled production of proteins by these tumor cells. Multiple myeloma tends to affect adult patients. Most patients are older patients. It's older than 50 years. It's rare to see multiple myeloma affecting someone below the age of 40. There's a male predilection, and for some unknown reason, there's a. It occurs more commonly in black patients compared to white patients. So what are the signs and symptoms of multiple myeloma? The signs and symptoms are directly related to because of the uncontrolled proliferation of the tumor cells, as well as the protein that these tumor cells produce. And it affects the bone, right? The affected bone. Some patients can complain of pain, so they will present with bone pain. If it affects the spine, then patients will complain of back pain. And if the tumor cell starts proliferating, it can destroy the bone. It can result in pathologic fracture. Even the jawbones can be involved, and because it involves the bone marrow, hematopoietic bone marrow can be involved. It can crowd out the normal precursor cells. So normal precursor erythrocytes are white blood cells and platelets. So patients can present with anemia. They can present with infection and fever. They can present with pedicle hemorrhages and radiographic. The skull bone shows the classic punched out radial senses so well-defined round radial senses. So that is a classic presentation for multiple myeloma. And when it involves the skull bone. But when it involves the jawbone, it usually presents as an ill defined radio. Lose and see these patients are at risk for developing renal failure because the tumor cells are producing this excess abnormal protein, and the kidney is unable to manage these excess proteins. And about these abnormal proteins can be present in urine. About 30 to 50% of the patients so can show bench Jones protein the name. So that's the name Bence Jones proteins in the urine in patients with multiple myeloma. About 15% of the patients can present with amyloidosis. What is amyloid? Amyloid is an abnormal extracellular protein substance, and that can get it's produced by the tumor cells. And this amyloid can get deposited in tissues and organs. And when it gets deposited in the oral soft tissues, tongue is the most common location. So patients can present with enlarged tongue diffuse enlargement of the tongue. The next common location in the head and neck area is the orbital skin, so patients can present with firm, waxy, plaque like lesion involving their orbital skin. So here's a 50 year old male with a history of multiple myeloma presenting with left mandibular swelling intravenously. You can see. So the tumor has perforated the bone cortical bone and it has produced produce this ulcerated soft tissue mass intravenously. This is the radio. The radiograph of that area you can see an ill defined and see. And this is the excised soft tissue. And this is post biopsy. And. Not the same patient. Most likely it's a different patient. And that classic punched out radio licensee welldefined circular radius. And see, you can see it in the skull bone. If the skull bone is affected by multiple myeloma, this punched out radio and see. Can be seen. Micro, small, round blue cell tumor. But because these are malignant, you know, these tumor cells are derived from a malignant plasma cell precursor. They show plasma site features. They resemble plasma cells. They are not normal plasma cells. These are malignant plasma cells. They show plasma feature which means the nuclei they have eccentric nucleus. The nucleus is pushed to one side of the cell and they show increased mitotic activity. Let's say this tissue was this tissue was biopsied. So the tumor originated in the bone, perforated the cortical bone, produced a soft tissue mass. And that was biopsied. And that's why you see the surface epithelium. And this is the connective tissue. And you can see that this these cells small round blue cells, they are infiltrating the connective tissue. Destroying the normal architecture. So this is the high power view of these plasma cells. You can see that these are eccentric nucleus eccentrically placed nucleus, which means the nucleus is pushed to one side of the cell. So they have they resemble plasma cells. That's why we say plasma site appearance and plasma cells are generally positive for this immuno stain. CD 138. So this is the kitchen. And you can see that the cells are positive for CD 138. And remember these are monoclonal proliferation of plasma cells. Right. So the plasma cells they produce immunoglobulin kappa and lambda immunoglobulin. And generally let's say you're looking at a granulation tissue. Granulation tissue contains mixed inflammatory cells right. It will contain neutrophils lymphocytes plasma cells. And if you do. The kappa and lambda. If you do the kappa and lambda immunohistochemical study in a normal inflammatory cell population, the half of the plasma cells will be positive for kappa, and half of the plasma cells will be positive for lambda. So it's a mix of plasma cells. Whereas because it's a neoplastic in multiple myeloma it's a neoplastic proliferation of plasma cells. All of these plasma cells, they came the neoplastic plasma cells. They came from the same precursor plasma cell. So all of the tumor cells will either have one. They will either produce only kappa immunoglobulin molecule or will produce only lambda immunoglobulin molecule. So in this particular example you can see majority of the tumor cells are positive for kappa. And only very few cells are positive for lambda. So it could be reversed. So the tumor cells could be positive for lambda. And very few cells could be positive for kappa. So that demonstrates the monoclonal nature of these cells. So when that remember amyloidosis these tumor cells can deposit amyloid which is abnormal extracellular protein substance. It can be deposited in any organs. And when it gets deposited in the world cavity tongue is the most common location. So when it gets deposited in the tongue, the patient will present with diffuse enlargement of the tongue. Sometimes there could be nodular enlargement of the tongue. The tongue. The affected tongue will feel firm on palpation. These patients will have difficulty swallowing. Imagine the tongue being very firm and it's enlarged. And you can see that in this particular example, the patient has prominent clinicians because because of the enlargement the tongue couldn't fit into the space. And biopsy will show amyloid deposition. The next three tumors. These are very rare. Ewing sarcoma. Rhabdomyosarcoma. Nasopharyngeal carcinoma. These are rare. Let's continue. Let's not take a break. We'll finish early. Okay? Ewing's sarcoma is a primary malignant tumor of the bone. And it's also composed of micro, small, round blue cells and only 1 to 2% of the cells. They originate within the jawbones. So it's a pediatric malignancy. It's a primary pediatric malignancy of the bone. It can affect the jawbones but rare cases. So it's not that common. 1 to 2% of the cases can affect the jawbones and certain histo genesis. It can be neuro ectoderm origin neuro. It can be derived from neural crest cells and 80% of the cases. So majority of the patients are young patients. They are children or teenagers below the age of 20. And it tends to affect white males. So there's a male predominance more common in Caucasians. And it affects the mandible more than the maxilla. And there's a specific chromosomal translocation. Signs and symptoms of Ewing circum up. And it affects the jawbone usually children or teenagers. Right. Patients are below the age of 20. It affects maxilla or mandible, more common in the mandible. Patients can present with pain, swelling, radiographic. It's an ill defined or ragged resolution. See. And microscopically, it's a small, round blue cell tumor. So you see this is a ragged, ill defined radial licensee affecting the posterior mandible. Micro, small round blue cell tumor. In this case, we use the special stain CD 99. And it's positive the tumor cells are positive for this immunohistochemical stain CD 99. So in the examination if we decide to ask Ewing sarcoma, let's say we found a very interesting or a classic example. And we decided to show that in the exam. Then we have to provide you with all these additional information. We have to show you where radiograph you typically affects young patient. And then we have to show you histopathology as well as either in the history or as part of the case. We have to provide this information that the tumor cells are positive for 99. Rhabdomyosarcoma. It's a malignant neoplasm of skeletal muscle origin. This also tends to affect children, and in the head and neck is the most common location. Several microscopic patterns embryonic rhabdomyosarcoma, alveolar pattern, play or morphic pattern. The embryonic and alveolar pattern they tend to present in the head and neck area. Patients will present with slow, painless infiltrate a rapidly growing mass, so it tends to affect head and neck area. Its phase and orbits are the most common location. Intravenously, it can present in the palate or it can affect the buckle mucosa. Treatment is local surgical excision followed by chemotherapy. The survival rate is about 55 to 75%. So here's a patient presenting with right facial swelling in early. You can see the soft tissue mass that fills the right maxillary vestibule. So. And if you biopsy the solution, it's a small round blue cell tumor. So sea of blue cells. And then we use special stains. In this case we have used Desman. And the tumor cells are positive for Desman. So remember this is a malignant tumor of skeletal muscle origin. So the tumor cells in this case shows positivity with desman nasopharyngeal carcinoma. Nasal pharyngeal carcinoma is very rare. And it arises from the lining of lining epithelium of the nasopharynx. And in this particular location the tissue is rich in lymphoid tissue. It's rare in the US, more common in southern China, Southeast Asia, Alaska, Greenland. And what are the contributing factors? EBV infection diets deficient in vitamin C, consumption of saltfish containing carcinogenic and nitrosamine tobacco HPV. All these are considered to be contributing factors. Most patients are middle aged between 40 and 60. There's a male predominance. Male to female ratio 3 to 1 arises the primary tumor. It arises in the lateral nasopharyngeal wall. Usually the primary tumor is very small. Initially, even clinicians can mist the tumor with endoscopic examination, and this tumor it tends to show yearly metastasis and cervical metastasis, so the patients can present with enlarged cervical lymph node, and that could be the first sign that the patient has nasopharyngeal carcinoma. So the patient can present with metastatic tumor to the cervical lymph node. And and then the the clinicians will look for the primary lesion. And it's very difficult because initially it's very small and difficult to detect even with the endoscopic examination. As the tumor enlarges then patients can have symptoms of epistaxis, nasal obstruction, pharyngeal pain, the treatment for nasopharyngeal carcinoma, radiation therapy, and chemotherapy. So patient presenting with cervical lymph node enlargement. So with nasopharyngeal carcinoma that could be the first sign that the patient has this carcinoma. Nasal pharyngeal carcinoma. The tumor tends to show yearly metastasis to the cervical lymph nodes. So patients can present with an enlarged cervical lymph node. And then when they start looking for the primary tumor, that's when they discover the tumor in the lateral nasopharyngeal wall. And there is a strong link to EBV infection EBV virus. This map shows the countries affected by EBV associated Burkitt lymphoma and nasopharyngeal carcinoma. This is a endoscopic exam that shows this ulcerated mass involving the lateral nasopharyngeal wall. And micro. It shows sheets of epithelial. Cells right. This is a carcinoma. So these are the tumor cells in the background of lymphoid tissue. Osteosarcoma and control sarcoma. Osteosarcoma. It's malignancy of the Mason cells. So these malignant Mason camel cells they produce osteo or immature bone or steered means and calcified bone matrix. So osteosarcoma. It's caused by these malignant mesenchymal cells that produce austenite, which is an calcified bone matrix or immature bone. So these tumor cells will produce bone. Immature bone or the etiology is unknown when osteosarcoma affects the long bones. When it involves the long bones in adolescence, it's believed that it could be because of hormonal factors and rapid bone growth. So we don't know what causes osteosarcoma in the jawbones when it involves the jaw bones. About 66% of all osteosarcoma they occur in the jawbones and patients are on the younger side, young adults 20 to 40 years control sarcoma. It tends to affect older patients. Patients are older than 50. Osteosarcoma. It tends to affect younger patients. There's a male predominance. It can affect both maxilla and mandible. Patients with osteosarcoma. When it affects the jaw bones, patients will present with pain and swelling. So pain is a feature. That's so patients with osteosarcoma, they will present with swelling and pain, whereas in contra sarcoma patients will present with painless swelling. And this is an aggressive tumor. It can cause destruction of the alveolar bone resulting in loosening of the teeth. If it involves the mandible, patients can present with prosthesis to remember numb chin syndrome whenever patients present with paresthesia. If it is not an abscess or an infection. Inflammatory process. Malignancy should be in the differential when it affects the maxillary bone, patients can present with nasal obstruction some osteosarcoma. They can exhibit slow growth. Radio graphically. So remember these tumor cells, they can produce acid which is an calcified bone matrix. So how will it appear radiographic if it is unclassified. Radio loosened, right. So radiographic osteosarcoma can be completely radial lucent, or it can be mixed lucent opaque. So if the tumor cells are producing as well as immature bone, then it can appear radiographic as mixed lucent opaque, or it can be completely radio opaque if the tumor cells are producing immature bone and it's composed of immature bone, the majority of the tumor is composed of immature bone, then radiographic. It can appear radio opaque. The tumor can cause cortical expansion. Cortical destruction, perforation, and parietal reaction can be seen, so the classic sunburst or sunray appearance is because of the parietal reaction, because the tumor is growing very rapidly. The periosteum reacts to the presence of this neoplasm by producing immature bone. It produces open bone and the. The open bone is laid perpendicular to the cortical bone. That's why it produces the sunray or sunburst appearance. Apart from the sunburst or sunray appearance, and patients radiate graphically. You can see symmetrical widening of the PDL space because the tumor cells are infiltrating the PDL space. Triangular elevation of the periosteum. Cardinal triangle is also considered to be a radiographic feature of osteosarcoma, and thus root resorption. Spiking root resorption. The roots will appear narrow and tapered. So. Osteosarcoma can cause cortical expansion. Cortical perforation. It can cause triangular elevation of the common triangle. It can cause symmetrical widening of the PDL space. Here's another example. Patient presenting with right mandibular swelling and radiograph shows the classic sunray or sunburst appearance. So this is the periosteum this vascular connective tissue that covers the cortical bone the periosteum. It reacts to this neoplastic process because the bone is getting destroyed the rapid growth of the neoplastic cells. So the periosteum reacts to the neoplasm by producing open bone. And these open bone are deposited perpendicular to the cortical bone and that produces the classic sunray appearance. Microscopically, these are malignant Mason cells that are producing osteo or immature bone. So you can see these malignant mesenchymal cells. They are hyper chromatic. They are pixels. You can see mitosis and they are deposit depositing or sty which is unclassified matrix. Or they are depositing immature bone. The treatment. Radical surgical excision. So surgical resection. Sometimes they use radiation and chemotherapy along with surgical excision. And the survival rate is about 60 to 70%. And metastasis is rare. So these are locally aggressive tumors rarely shows metastasis. But the metastatic sites could include lymph nodes lung. Brain. Control sarcoma. So this is also malignant neoplasm. These malignant mesenchymal cells instead of depositing osteo bone in control sarcoma these malignant Mason cells are depositing cartilaginous matrix. And the cartilaginous matrix can show calcification and. Average age. So remember osteosarcoma. Young adult age group. Right control sarcoma. Older patients. Patients average age at diagnosis is 51 years. There's a male predominance and controls can affect both maxilla and mandible and clinical presentation. Painless swelling osteosarcoma patients will present with pain and swelling, whereas condo sarcoma patients present with painless swelling. Destruction of the bone can result in mobility of teeth if it is the maxilla that is involved. Other symptoms like nasal obstruction epistaxis can also be present. Radiographic features. It's cartilage. The tumor cells are depositing cartilaginous matrix and if it is not calcified, then radiographic. The lesion can appear completely radial. Lucent. Rare cases. It can even appear as multi radial licensee. And if the cartilaginous matrix are calcified, then the radiographic contour circle will present as mixed lucent opaque change. So ill defined radial licensee with varying degrees of radial opacity, depending on whether the cartilaginous matrix is calcified or not. So it can cause cortical expansion, cortical perforation. It can also produce the sunburst or sunray appearance and root resorption and symmetric widening of the PDL space can also be seen. So radial lucent lesion with radial opaque foci involving the maxillary bone. Micro, these tumor cells these malignant mesenchymal cells, they are depositing this cartilage, these cartilaginous matrix that shows varying degrees of maturation. And the tumor cells can appear hyper chromatic. They can show player morphism and calcification of the cartilaginous matrix can also be seen. So this is the abnormal cartilage that is produced by the tumor cells. You can look at the control sites. They are very dark staining. They show different shapes. So play morphism hyper chromaticism. And look at this lacunae. You can see two nuclei within a single lacunae. So that's abnormal. So this is abnormal cartilaginous matrix that is produced by the tumor cells the malignant mesenchymal cells. Treatment. Surgical excision. Um and poorer prognosis compared to osteosarcoma. And they are considered to be locally aggressive, just like osteosarcoma. Low metastatic potential. They are locally aggressive tumors and very low metastatic potential. We have already covered melanoma in the pigmented lesions lecture. So we'll just briefly review the features. Melanoma is malignant neoplasm of melanocytes right. So cutaneous melanoma it's more common in fair skin patients. And cutaneous melanoma the risk factor is acute exposure to ultraviolet radiation and sunlight whereas. Oral melanoma. It's more common in dark skinned patients. So melanomas can occur anywhere. There's melanocytes so they can develop on the skin. They can involve any of the mucosal sites. Also wherever there's melanocytes you can develop melanoma. So oral melanomas obviously no connection to sun exposure. We don't know what causes oral melanomas. It's more common in dark skinned patients. And the most common location intravenously is the palate and the gingiva. But I have seen examples of oral melanomas on the tongue mandibular gingiva. So it's also possible that it can present in other locations. So any pigmented lesion that is recent onset exhibits rapid increase in size. It's evolving. It starts out as a small flat lesion than it has become a nodular. All those lesions should be biopsied to rule out melanoma mostly seen in older patients. So patients are above the age of 50 6070s and oral melanomas. They are more aggressive. They act more aggressively compared to the cutaneous melanomas. They show yearly metastasis, usually oral melanomas. They have poor prognosis because they are mostly diagnosed at an advanced stage. The prognosis. The five year survival rate is less than 20%. It's about 15 to 20%. So we use this ABCd system of evaluation. So the researchers have designed this ABCd system of evaluation to distinguish a benign melanoma lesion from melanoma. A represents asymmetry because these lesions they because they exhibit uncontrolled growth. It's a malignant lesion. So it's going to be asymmetrical. So the lesion will be flat in one area. It's slightly raised in another area. Or it can be nodular. And another area the borders are irregular within the same lesion different colors different shades of black brown blue red can be seen. The size of the lesion is greater than six millimeters size of a pencil eraser. And these lesions are evolving. Lesion. It started out as a small pigmented change but with time it's shown increase in size. It's shown the shape has changed. The the color of the lesion has changed. And it's an evolving lesion. So it's no longer flat. It's black like or nodular. And this is a skin melanoma. It fits all the criteria that we just discussed ABCd criteria criteria. So a for asymmetry so flat in one area slightly raised in another area block like in another area. Borders are irregular within the same lesion. You can notice different shades of brown light brown, dark brown almost black. The size of the lesion is greater than six millimeter size of a pencil eraser. So this is several centimeters in size. And this is an evolving lesion because it started out as a small lesion. Now it's such a large lesion an intra worldly gingiva maxilla gingiva palate considered to be the most common location. But any pigmented lesion in any other intramural mucosal sites. If you are suspicious, if you don't know what it is, it's okay to recommend a biopsy. We don't want to miss a melanoma so intravenously. This this lesion is presenting as an ulcerated pigmented mass involving the palatal gingiva. And. And the hot palate. Microscopically, melanomas can present as round cell tumors. They can present as spindle cell tumors, spindle meaning elongated nuclei and cytoplasm, so they can present as round cell tumors or spindle cell tumors. And these are malignant melanoma sites. So they can also produce melanin pigment. So in this example you can see that the tumor cells are producing this brown melanin pigment. And we use special stains the immunohistochemical stains I have not included those stains in this presentation. But I have shown some images of positive immunohistochemical stains in the pigmented lesions lecture. So these cells are positive for 100 stain mm 45 and March 1st. So those are the immuno stains that we use to confirm the diagnosis of melanoma. So in the examination if we have to show melanoma we will provide you with a brief history, a clinical picture of a pigmented lesion that fits that looks very suspicious. And then a micro histopathology along with either we will include the results of the immunohistochemical stain S100 positive for 45 positive and not one positive. Either it will be included in the history or we will provide you with images okay. Salivary gland malignancy. It's uncommon, but not rare. So what are the malignant salivary gland tumors that you guys are familiar with? So we talked about just five salivary gland tumors. Right. Whartons tumor. Those two are benign. What are the other three? Nuchal epidermal carcinoma. Adenoid cystic carcinoma. Polymorphous adenocarcinoma. We used to call that as plg a polymorphous low grade adenocarcinoma. We we no longer use the low grade in the terminology. Okay. What is the most intra world location, most common location for salivary gland tumors, whether benign or malignant? Palate because palate contains lots of mucous glands. So that is the number one the most common site for development of benign as well as malignant salivary gland lesions and other common locations. Or the next common location is actually the upper lip. So salivary gland tumors, they occur more commonly on the upper lip. They are very rare on the lower lip. Mucous seals. They are very common on the lower lip and rare on the upper lip. Apart from the upper lip palate, salivary gland tumors can involve anywhere the mucous glands are present like buccal mucosa. Floor of the mouth. Anterior ventral tongue. Posterior lateral tongue. Those are the areas where salivary glands are present, so salivary gland tumors can occur anywhere. The salivary glands of mucous glands there. So among epidermal carcinoma, adenoid cystic carcinoma, and polymorphous adenocarcinoma, adenoid cystic carcinoma, and polymorphous adenocarcinoma, they tend to occur in older patients, whereas epidermal carcinoma wide age group. So epidermal carcinoma can develop even in children and. So intravenously. These lesions, salivary gland tumors, they present as painless, slow growing swelling. So just based on the clinical presentation, you will never be able to tell whether it's a benign or a malignant salivary gland tumor. So they present as a soft tissue. Swelling and prognosis depends on the tumor type and the clinical stage at diagnosis. So here's a a swelling soft tissue swelling involving the left palate. And based on this clinical presentation, what are the lesions in your differential? Obviously a benign salivary gland tumor like polymorphic adenoma. Malignant salivary gland tumors like adenoid cystic carcinoma, micro epidermal carcinoma, polymorphous adenocarcinoma. You cannot tell just based on the clinical presentation. You need to biopsy the lesion in order to make the diagnosis. What else in the differential. Anything else? If this is your patient and this patient is presenting with this swelling. Period. Yeah. Abscess? Yeah. Abscess is in the differential. So remember abscess. That should be an intergenic infection. Right. There should be tooth pain. This is an acute presentation. So patient will be symptomatic. So abscess is in the differential okay. How? What is it? What kind of zest? This is a soft tissue swelling, right? I. Well, it's it's unilateral. This is not in the midline palate. And median palatal cyst is very very rare. Yes. non-Hodgkin's lymphoma. Lymphoma should be in the differential. Okay, so this one turned out to be a salivary gland tumor. And the biopsy shows duck like structures. Right. So these are biphasic tumors. So it's composed of ductal epithelium. And there's a cuff of cells around the duct like structures. And these are myo epithelial cells. The tumor cells are composed of ductal epithelial cells and myo epithelial cells. And the tumor cells are arranged in islands. And if you look at the islands, they show multiple cylindrical cyst like spaces. This is the form pattern. So the diagnosis is adenoid cystic carcinoma. That kind of looks like Swiss cheese. So multiple cylindrical Swiss like spaces. So each of these epithelial islands, they have ductal epithelium, they have myo epithelial cells. The cells are very small hyper chromatic cells. And this pattern this multiple cyst cylindrical cyst like spaces it's called the reform pattern. So the last topic is metastasis to the oral cavity. It's uncommon. Metastasis can occur. Metastatic tumor can involve the oral soft tissues or it can involve the jawbones. And management is usually palliative in nature because by the time the tumor, the metastatic tumor presents in the wall cavity or in the jawbone, it's part of a widely disseminated disease. So the prognosis is poor. So the management is usually palliative in nature. Metastatic tumors to the jawbones. So most common form of cancer involving. So it is one of the most common malignancy involving the bone. When there's metastasis to the jawbone the usual suspects are breast metastasis from breast carcinoma, lung carcinoma, thyroid, prostate, and renal carcinomas. These are the usual lesions or usual carcinomas that can show metastasis to the jawbones, and patients are usually older patients. That's predilection for the posterior mandible. Patients can present with pain, swelling, mobility of teeth, paresthesia. Remember numb chin syndrome whenever. Patients present with paresthesia. So when the lesion involves the mandible patients can present with prosthesis. So malignancy should be in the differential. Sometimes the patients can be asymptomatic and the jaw and discovered on routine radiographic examination. The jaw lesion could be the first sign of the malignant disease. The patient may not be aware that they have a primary malignancy, so the jaw could be the first sign that this patient has a primary malignancy somewhere. And radiographic. It's a malignant lesion. So it's going to present as an ill defined or ragged resolution like a moth eaten appearance. The micro if you biopsy this radiographic lesion then the micro will resemble the tumor of origin. So if it's a lung metastatic tumor then it will look like a lung carcinoma or a renal carcinoma. So wherever it came from metastatic tumors to the oral soft tissue gingiva is the most common sight. And when it presents on the gingiva tongue is the next common location. So when it involves the gingiva it can look like reactive gingiv