Oral Pathology Lecture Notes - Hematologic Neoplasms PDF

 Hematologic Neoplasms I (1) Lymphoid Hyperplasia ❖ The lymphoid tissue of the body plays an important role in the recognition and processing of foreign antigens, such as viruses, fungi, and bacteria. ❖ In addition, the lymphoid tissue has a protective functio...

 Hematologic Neoplasms I (1) Lymphoid Hyperplasia ❖ The lymphoid tissue of the body plays an important role in the recognition and processing of foreign antigens, such as viruses, fungi, and bacteria. ❖ In addition, the lymphoid tissue has a protective function through a variety of direct and indirect mechanisms. ❖ In responding to antigenic challenges, lymphoid cells proliferate, thus increasing their numbers, to combat the offending agent more effectively. ❖ This proliferation results in enlargement of the lymphoid tissue, which is seen clinically as lymphoid hyperplasia. Clinical Features ▪ Affect the lymph nodes, the lymphoid tissue of Waldeyer’s ring, or the aggregates of lymphoid tissue that are normally scattered throughout the oral cavity, particularly in the oropharynx, the soft palate, the lateral tongue, and the floor of the mouth. ▪ The site that the lymph node drains can be usually identified as a source of active or recent infection. ▪ In the head and neck region, the anterior cervical chain of lymph nodes is most commonly involved, although any lymph node in the area may be affected ▪ Appears as discrete, nontender, submucosal swellings, usually less than 1 cm in diameter, which may appear normal or dark pink in color if the aggregate is deeper; or creamy yellow- orange to amber hue if the collection of lymphocytes is closer to the surface.  ▪ Tonsillar size is variable, but lymphoid tissue is normally more prominent in younger individuals, usually reaching its peak early during the second decade of life and gradually diminishing thereafter. ▪ Some patients have such large tonsils that it seems as if they would occlude the airway (so-called kissing tonsils). ▪ As long as the large tonsils are symmetrical and asymptomatic, it is likely that they are normal for that particular patient. ▪ Tonsillar asymmetry is a potentially serious sign that should be evaluated further. ▪ With acute infections, the lymphadenopathy appears as enlarged, tender, relatively soft, freely movable nodules. ▪ Chronic inflammatory conditions produce enlarged, rubbery firm, nontender, freely movable nodes. ▪ Chronic hyperplastic lymph nodes may be difficult to distinguish clinically from lymphoma. ▪ In multiple persistently enlarged nontender lymph nodes, human immunodeficiency virus (HIV) infection should be considered in the differential diagnosis. Normal Tonsillar Histology  Histopathologic Features: ▪ Sheets of small, well-differentiated lymphocytes with numerous interspersed, sharply demarcated collections of reactive lymphoblasts called germinal centers (closer to each other). Treatment and Prognosis: ▪ Once the diagnosis of lymphoid hyperplasia is confirmed, no treatment is usually required because it is a completely benign process. (2) Langerhans Cell Histiocytosis (LCH) ❖ A spectrum of rare clinicopathologic disorders characterized by proliferation of Langerhans cells that are accompanied by varying numbers of eosinophils, lymphocytes, plasma cells, and multinucleated giant cells. ❖ Langerhans cells are dendritic mononuclear cells normally found in the epidermis, mucosa, lymph nodes, and bone marrow. ❖ These cells process and present antigens to T lymphocytes. ❖ Studies have shown this to be a monoclonal proliferation, a finding consistent with a neoplastic process. ❖ BRAF oncogene mutations have been identified in 40% to 60 of Langerhans cell histiocytosis lesions. Clinical and Radiographic Features ▪ LCH is particularly a disease of childhood (in adults it is less common). ▪ Can arise in virtually any organ system but has a particular affinity for bone. ▪ Bone lesions present as an incidental lytic lesion. ▪ Bone lesions present as either solitary or multiple (Unifocal or multifocal). ▪ The skull, ribs, vertebrae, and mandible are among the most frequent sites. ▪ The jaws are affected in 10% to 20% of all cases. ▪ Dull pain and tenderness often accompany bone lesions. ▪ Radiographically, the lesions often appear as sharply punched-out radiolucencies without a corticated rim, but occasionally an ill-defined radiolucency is seen. ▪ Lesions also can occur within the body of the mandible or maxilla, where they may simulate a periapical inflammatory condition. ▪ Bone involvement in the mandible usually occurs in the posterior areas, and a characteristic “scooped out” appearance may be evident when the superficial alveolar bone is destroyed. ▪ The resulting bone destruction and loosening of the teeth clinically may resemble severe periodontitis. ▪ Extensive alveolar involvement causes the teeth to appear as if they are “floating in air”. ▪ Ulcerative or proliferative mucosal lesions or a proliferative gingival mass may develop if the disease breaks out of bone. ▪ Occasionally, this process may involve only the oral soft tissues. Histopathologic Features: ▪ Diffuse infiltration of large, pale-staining mononuclear cells that resemble histiocytes. ▪ Varying numbers of eosinophils, plasma cells, lymphocytes, and multinucleated giant cells are often seen, and areas of necrosis and hemorrhage may be present. ▪ Identification of lesional Langerhans cells by immunohistochemical markers is necessary to confirm the diagnosis.  Treatment and Prognosis: ▪ Most patients with oral involvement have single organ disease affecting the jaws, although other skeletal lesions may be present. o Accessible bone lesions are usually treated by curettage. o Less accessible bone lesions: radiation, or intralesional injection with corticosteroids. ▪ The prognosis for bone lesions in the absence of significant visceral involvement is generally good; however, progression or dissemination of the disease may occur. ▪ Chemotherapy when multiple organs are involved, regimen depends on severity. ▪ In general, prognosis is poorer for patients who develop the disease at a very young age and somewhat better for patients who are older at the time of onset. Leukemia & Lymphoma ❖ Both originate in lymphocytes. ❖ However, leukemia typically originates in bone marrow and spreads through the bloodstream, while lymphoma usually originates in lymph nodes or the spleen and spreads through the lymphatic system. ❖ Lymphomas ▪ Comprise a diverse group of malignant lymphoproliferative disorders, classified by WHO based on lymphocytic origin: o Hodgkin lymphomas arise from precursor B cells (Reed-Sternberg cells). o Non-Hodgkin lymphomas arise from monoclonal expansion of malignant B or T cells. (3) Leukemia ❖ Several types of malignancies of hematopoietic stem cell derivation. ❖ Malignant transformation of one stem cell; initial proliferation in bone marrow and eventual overflow into peripheral blood. ❖ Classified according to their histogenesis (myeloid or lymphoid) and clinical behavior (acute or chronic). ❖ Probably a result of a combination of environmental and genetic factors. ❖ Certain syndromes are associated with an increased risk, e.g., Down syndrome. ❖ Certain types of leukemia show specific chromosomal abnormalities, e.g., the Philadelphia chromosome in chronic myeloid leukemia. ❖ Some environmental agents are associated with an increased risk of leukemia, e. g. Pesticides. ❖ Ionizing radiation: increased frequency of chronic myeloid leukemia in survivors of atomic bomb blasts. ❖ Viruses, e.g., retrovirus human T-cell leukemia/lymphoma virus type 1 (HTLV-1), transmitted by contaminated blood cause a relatively rare form of malignancy of T lymphocytes, which may present as a leukemia or non-Hodgkin lymphoma. Clinical Features ▪ Crowding out of normal hematopoietic stem cells by the malignant proliferation; marked reduction in numbers of normal white and red blood cells and platelets (myelophthisic anemia). ▪ Malignant cells may infiltrate other organs: o Splenomegaly, hepatomegaly, and lymphadenopathy o May infiltrate oral tissues. ▪ Occasionally, the leukemic cells infiltrate the oral soft tissues (most frequently with the myeloid types): o Diffuse, nontender swelling, may or may not be ulcerated, or prominent tumor-like growth (myeloid sarcoma) ▪ Infiltration of the periapical tissues, simulating periapical inflammatory disease both clinically and radiographically. ▪ Reduced RBC counts: o Fatigue, easy tiring, and dyspnea on mild exertion. ▪ Reduced WBC counts: o Fever associated with infection may be the initial sign. o Perirectal infections, pneumonia, urinary tract infections, and septicemia are common.  o Oral infections: ✓ Oral ulceration, most severely affecting gingiva. ✓ Ulcers are deep and punched-out, with a gray-white necrotic base. ✓ Diffuse oral candidiasis. ✓ Herpetic infections involving any area, not confined to the keratinized mucosa as in immunocompetent patients. ▪ Reduced platelets count (Thrombocytopenia): o Easy bruising and bleeding. o Petechial hemorrhages of posterior hard palate and soft palate. o Spontaneous gingival hemorrhage. o Serious hemorrhagic complications may result from bleeding into the CNS or the lungs. ▪ Myeloid leukemias generally affect adults, but can affect children, especially acute myeloid leukemia. ▪ Lymphoblastic leukemias: o Acute lymphoblastic leukemia: predominantly in children; one of the more common childhood malignancies. o Chronic lymphocytic leukemia: the most common type, primarily affects older adults. Histopathologic Features: ▪ Microscopic examination of leukemia-affected tissue shows diffuse infiltration and destruction of the normal host tissue by sheets of poorly differentiated cells with either myelomonocytic characteristics or lymphoid features. Diagnosis: ▪ Usually established by confirming presence of poorly differentiated leukemic cells in peripheral blood and bone marrow. ▪ Bone marrow biopsy is performed because some patients may go through an aleukemic phase in which the atypical cells are absent from the circulation ▪ Classification: immunophenotyping by using immunohistochemical markers. ▪ Cytogenetic and molecular characterization of the lesional cells is typically necessary. ▪ In many cases, the results of these various studies will be significant because the patient’s prognosis is directly affected. Treatment and Prognosis: ▪ Chemotherapy depending on the type. ▪ Bone marrow transplant for suitable cases. ▪ Supportive care is often necessary for survival: o Platelet and RBC transfusions o Control of infections ▪ Oral care: o Many of these patients experience infections of the oral mucosa; optimal oral hygiene should be encouraged. o Investigation of any oral complaint as soon as possible to prevent serious oral infectious complications. ▪ Prognosis depends on: 1. Type of leukemia 2. Age o In children with acute lymphoblastic leukemia, nearly 90% are cured after appropriate treatment. o In an adult with the same diagnosis, the 5-year survival rate is generally much lower. 3. Cytogenetic alterations associated with the disease (4) Hodgkin Lymphoma ❖ A malignant lymphoproliferative disorder, current evidence points to a B-lymphocyte origin of Reed- Sternberg cell. ❖ Unlike most malignancies, the neoplastic cells (Reed-Sternberg cells) make up only about 0.1% to 2% of the cells in the enlarged lymph nodes that characterize this condition. ❖ Cause is unknown; Epstein-Barr virus (EBV) infection linked to a significant percentage. ❖ Hodgkin lymphoma is currently classified in the following manner: ▪ Nodular lymphocyte–predominant Hodgkin lymphoma, or ▪ Classical Hodgkin lymphoma; comprising five histopathologic subtypes Clinical Features ▪ Almost always begins in the lymph nodes, most commonly cervical and supraclavicular nodes. ▪ Overall male predilection ▪ Bimodal pattern is noted with respect to patient’s age at diagnosis o One peak between 15 and 35 years of age; another peak after the age of 50 ▪ Presenting sign: persistently enlarging, nontender, discrete mass or masses in one lymph node region. ▪ Involved lymph nodes movable in early stages. With progression, nodes become more matted and fixed to surrounding tissues ▪ If untreated, the condition spreads to other lymph node groups then spleen and other extralymphatic tissues, such as bone, liver, and lung. ▪ Oral involvement is rare ▪ Other systemic signs and symptoms in some cases: o weight loss, fever, night sweats, and generalized pruritus (itching) ▪ Absence of these systemic signs and symptoms is better in terms of prognosis. Histopathologic Features: ▪ Current immunohistochemical and molecular biologic techniques have allowed distinctions to be made among the various types. ▪ The common features include: o Effacement of the normal nodal architecture by a diffuse, often mixed, infiltrate of inflammatory cells. o Large, atypical neoplastic lymphoid cells: ✓ In classical Hodgkin lymphoma, this atypical cell is known as a “Reed-Sternberg cell” which is typically binucleated, although it may be multinucleated, with prominent nucleoli. ✓ The malignant cell in nodular lymphocyte–predominant Hodgkin lymphoma is the “popcorn cell”. Reed-Sternberg cell popcorn cell Treatment and Prognosis: ▪ The disease can cause death if appropriate therapy is not instituted. ▪ The treatment of this malignancy is one of the few major success stories in cancer therapy during the past 30 years. ▪ The treatment depends on the stage of involvement and includes radiotherapy and chemotherapy. ▪ The prognosis for this disease is good nowdays o Stage I and II disease: 80% to 90% 10-year survival rate o Stage III and IV disease: 55% to 75% 10-year survival rate DONE WITH LOVE ❤️