APPROACH TO THE PATIENT WITH LYMPHADENOPATHY AND SPLENOMEGALY

1. APPROACH TO THE PATIENT WITH LYMPHADENOPATHY AND SPLENOMEGALY

2. NHL اهداف اختصاصي : 1-مشخصات كلي 2- DD 3- برخورد 4-تعريف و اتيولوژي 5-طبقه بندي 6-STAGING 7-تظاهرات 8-پيش آگهي 9-درمان HD 1- تعريف 2-اپيدميولوژي 3-پاتولوژي 4-تشخيص 5-تظاهر 6-پيش آگهي 7-درمان

3. APPROACH TO THE PATIENT WITH LYMPHADENOPATHY AND SPLENOMEGALY • PHYSIOLOGY AND ANATOMY • Lymph nodes are populated predominantly by • macrophages, • dendritic cells, • B lymphocytes, and • T lymphocytes. • B lymphocytes are located primarily in the follicles and perifollicular areas, • T lymphocytes are found primarily in the interfollicular or paracortical areas of the lymph node.

4. APPROACH TO THE PATIENT WITH LYMPHADENOPATHY AND SPLENOMEGALY • PHYSIOLOGY AND ANATOMY • In young childrenpalpable lymphadenopathy is the rule. • who are continuously undergoing exposure to new antigens, • In fact, the absence of palpable lymphadenopathy would be considered abnormal • In adults, lymph nodes larger than 1 to 2 cm in diameter are generally considered abnormal. • However, lymph nodes 1 to 2 cm in diameter in the groin are sufficiently frequent to often be considered "normal.“

5. APPROACH TO THE PATIENT WITH LYMPHADENOPATHY AND SPLENOMEGALY • Generalized immune proliferation and lymphadenopathy can occur with a • systemic disorder of the immune system, • disseminated infection, or • disseminated neoplasia. • Malignancies of the immune system might be manifested as: • localized or • disseminated lymphadenopathy.

6. APPROACH TO THE PATIENT WITH LYMPHADENOPATHY AND SPLENOMEGALY • more than two-thirds of patients with LAP have : • nonspecific causes or upper respiratory illnesses (viral or bacterial), • fewer than 1% have a malignancy • in another study :16% had a malignancy • (lymphoma or metastatic adenocarcinoma) • Thus, the vast majority of patients with lymphadenopathy will have a nonspecific etiology requiring few diagnostic tests.

7. APPROACH TO THE PATIENT WITH LYMPHADENOPATHY AND SPLENOMEGALY Differential diagnosis of lymphadenopathy TABLE 178–1. CAUSES OF LYMPHADENOPATHY Infection Bacterial (e.g., all pyogenic bacteria, cat-scratch disease, syphilis, tularemia) Mycobacterial (e.g., tuberculosis, leprosy) Fungal (e.g., histoplasmosis, coccidioidomycosis) Chlamydial (e.g., lymphogranuloma venereum) Parasitic (e.g., toxoplasmosis, trypanosomiasis, filariasis) Viral (e.g., Epstein-Barr virus, cytomegalovirus, rubella, hepatitis, HIV) Benign disorders of the immune system (e.g., rheumatoid arthritis, systemic

8. APPROACH TO THE PATIENT WITH LYMPHADENOPATHY AND SPLENOMEGALY TABLE 178–1. CAUSES OF LYMPHADENOPATHY lupus erythematosus, serum sickness, drug reactions such as to phenytoin, Castleman's disease, sinus histiocytosis with massive lymphadenopathy, Langerhans'cell histiocytosis, Kawasaki syndrome, Kimura's disease) Malignant disorders of the immune system (e.g., chronic and acute myeloid and lymphoid leukemia, non-Hodgkin's lymphoma, Hodgkin's disease, angioimmunoblastic-like T-cell lymphoma, Waldenström's macroglobulinemia, multiple myeloma with amyloidosis, malignant histiocytosis) Other malignancies (e.g., breast carcinoma, lung carcinoma, melanoma, head and neck cancer, gastrointestinal malignancies, germ cell tumors, Kaposi's sarcoma) Storage diseases (e.g., Gaucher's disease, Niemann-Pick disease) Endocrinopathies (e.g., hyperthyroidism, adrenal insufficiency, thyroiditis) Miscellaneous (e.g., sarcoidosis, amyloidosis, dermatopathic lymphadenitis)

9. APPROACH TO THE PATIENT WITH LYMPHADENOPATHY AND SPLENOMEGALY • TABLE 178–2. MOST FREQUENT CAUSES OF LYMPHADENOPATHY IN ADULTS IN AMERICA • Unexplained • Infection • In drainage area of infection (e.g., cervical adenopathy with pharyngitis) • Disseminated (e.g., mononucleosis, HIV infection) • Immune disorders (e.g., rheumatoid arthritis) • Neoplasms • Immune system malignancies (e.g., leukemia and lymphomas) • Metastatic carcinoma or sarcoma

10. APPROACH TO THE PATIENT WITH LYMPHADENOPATHY AND SPLENOMEGALY • FACTORS TO CONSIDER IN THE DIAGNOSIS OF LYMPHADENOPATHY • Associated systemic symptoms • Patient age • History of infection, trauma, medications, travel experience, previousmalignancy, etc. • Location: cervical, supraclavicular, epitrochlear, axillary, intrathoracic(hilar versus mediastinal), intra-abdominal (retroperitoneal versus mesentericversus other), iliac, inguinal, femoral • Localized versus disseminated • Tenderness/inflammationSizeConsistency

11. APPROACH TO THE PATIENT WITH LYMPHADENOPATHY AND SPLENOMEGALY • LYMPH NODE EVALUATION. • a careful history • a thorough physical examination • laboratory tests • imaging studies to determine the extent and character of the • lymphadenopathy • age of the patient • The occurrence of fever, sweats, or weight loss • of a site of infection, a particular medication, atravel history, or a previous malignancy.

12. APPROACH TO THE PATIENT WITH LYMPHADENOPATHY AND SPLENOMEGALY • physical examination • localized or generalized • size of nodes • Texture • presence or absence of nodal tenderness • signs of inflammation over the node • skin lesions • splenomegaly.

13. APPROACH TO THE PATIENT WITH LYMPHADENOPATHY AND SPLENOMEGALY • Generalized adenopathy has been defined as • involvement of three or more noncontiguous lymph node areas. • generalized lymphadenopathy is frequently associated with nonmalignant disorders

14. APPROACH TO THE PATIENT WITH LYMPHADENOPATHY AND SPLENOMEGALY physical examination (localized or generalized), size of nodes, texture, presence or absence of nodal tenderness, signs of inflammation over the node, skin lesions, and splenomegaly. Generalized adenopathy has been defined as involvement of three or more noncontiguous lymph node areas. generalized lymphadenopathy is frequently associated with nonmalignant disorders The site of localized or regional adenopathy Nodes <1.0 cm2 in area (1.0 ´ 1.0 cm or less) are almost always secondary to benign, nonspecific reactive causes. Patients with node(s) <1.0 cm2 should be observed after excluding infectious mononucleosis and/or toxoplasmosis unless there are symptoms and signs of an underlying systemic illness.

15. APPROACH TO THE PATIENT WITH LYMPHADENOPATHY AND SPLENOMEGALY • METHODS OF LYMPH NODE EVALUATION • Physical examination • Imaging • Chest radiography • Lymphangiography • Ultrasonography • Computed tomography • Magnetic resonance imaging • Gallium scanning • Positron emission tomography • Sampling • Needle aspiration • Cutting needle biopsy • Excisional biopsy

16. APPROACH TO THE PATIENT WITH LYMPHADENOPATHY AND SPLENOMEGALY • lymph nodes that are tender are more likely to be due to an infectious process, • whereas painless adenopathy raises the concern of malignancy. • Lymph node consistency • lymph nodes containing metastatic carcinoma are rock hard, • lymph nodes containing lymphoma are firm and rubbery, • lymph nodes enlarged in response to an infectious process are soft. • The larger the lymph node, the more likely a serious underlying cause exists, and lymph nodes greater than 3 to 4 cm in diameter in an adult are very concerning

17. APPROACH TO THE PATIENT WITH LYMPHADENOPATHY AND SPLENOMEGALY Chest radiographs provide the most economical and easiest method to assess mediastinal and hilar lymphadenopathy but are not as accurate as CT of the chest. lymphangiography provides an extremely accurate assessment of the lower abdominal lymph nodes and, because of retained contrast material, allows repeat examinations and assessment of the response to therapy. CT and ultrasound provide the most useful ways to assess abdominal and retroperitoneal lymphadenopathy ultrasound has the advantage of being less expensive and not requiring radiation exposure. MRI and gallium scanning are not first-line studies for the assessment of lymphadenopathy

18. APPROACH TO THE PATIENT WITH LYMPHADENOPATHY AND SPLENOMEGALY • Gallium scans • presence of active lymphoma in patients with lymphadenopathy and a proven diagnosis • Fine-needle aspiration • currently popular and is often an accurate way to diagnose infection or carcinoma • it is inappropriate as an initial diagnostic maneuver for lymphoma. • Cutting needle biopsies • will occasionally provide sufficient material for an unequivocal diagnosis and subtyping of the lymphom • excisional biopsy, • which is most likely to provide the pathologist with adequate material to perform histologic, immunologic, and genetic studies, is the most appropriate approach.

19. APPROACH TO THE PATIENT WITH LYMPHADENOPATHY AND SPLENOMEGALY AN APPROACH TO THE PATIENT WITH LYMPHADENOPATHY • AN APPROACH TO THE PATIENT WITH LYMPHADENOPATHY • Does the patient have a known illness that causes lymphadenopathy?Treat and monitor for resolution. • 2. Is there an obvious infection to explain the lymphadenopathy (e.g., infectious mononucleosis)?Treat and monitor for resolution. • 3. Are the nodes very large and/or very firm and thus suggestive of malignancy?Perform a biopsy. • 4. Is the patient very concerned about malignancy and unable to be reassured thatmalignancy is unlikely? Perform a biopsy. • 5. If none of the preceding are true, perform a complete blood count and if it isunrevealing, monitor for a pre-determined period (usually 2 to 6 weeks).If the nodes do not regress or if they increase in size, perform a biopsy.

20. APPROACH TO THE PATIENT WITH LYMPHADENOPATHY AND SPLENOMEGALY AN APPROACH TO THE PATIENT WITH LYMPHADENOPATHY • come to medical attention in several ways • felt a lymph node in the neck, axilla, or groin • an unexpected finding on routine physical examination or as part of the evaluation of another complaint. • Finally, patients might be found to have unexpected lymphadenopathy on imaging studies of the chest or abdomen. • The approach to a patient complaining of newly discovered lymphadenopathy in the neck, axilla, or groin will depend on the size, consistency, and number of enlarged lymph nodes and the patient's general health • a biopsy might be done more quickly in a patient who is very anxious about malignancy or who needs a definitive diagnosis expeditiously.

21. APPROACH TO THE PATIENT WITH LYMPHADENOPATHY AND SPLENOMEGALY AN APPROACH TO THE PATIENT WITH LYMPHADENOPATHY • Biopsymight be done more quickly in a patient who is very anxious about malignancy or who needs a definitive diagnosis expeditiously.

22. GENERAL ASPECTS OF LYMPHOID MALIGNANCIES ETIOLOGY AND EPIDEMIOLOGY • Hodgkin's disease • The cell of origin of • suggests that most are of B cell origin. • Hodgkin's disease is more common in whites than in blacks • more common in males than in females • A bimodal distribution of age at diagnosis has been observed, • with one peak incidence occurring in patients in their 20s • and the other in those in their 80s • younger age groups diagnosed in the United States largely have the nodular sclerosing subtype • Elderly patients, patients infected with HIV, and patients in third world countries more commonly have mixed-cellularity Hodgkin's disease or lymphocyte-depleted Hodgkin's disease • Infection by HIV is a risk factor for developing Hodgkin's disease. In addition, an association between infection by EBV and Hodgkin's disease has been demonstrated Dr.Mokarian

23. GENERAL ASPECTS OF LYMPHOID MALIGNANCIES ETIOLOGY AND EPIDEMIOLOGY • non-Hodgkin's lymphomas • have increased in frequency in the United States at the rate of 4% per year since 1950. • more frequent in the elderly and more frequent in men • Patients with both primary and secondary immunodeficiency states are predisposed to developing non-Hodgkin's lymphomas. • HIV infection; • patients who have undergone organ transplantation • patients with inherited immune deficiencies, • the sicca syndrome • rheumatoid arthritis Dr.Mokarian

24. GENERAL ASPECTS OF LYMPHOID MALIGNANCIES ETIOLOGY AND EPIDEMIOLOGY • non-Hodgkin's lymphomas • various subtypes differ geographically • T cell lymphomas are more common in Asia • follicular lymphoma are more common in western countries. • angiocentric nasal T/natural killer (NK) cell lymphoma has a striking geographic occurrence, being most frequent in Southern Asia and parts of Latin America. • human T cell lymphotropic virus (HTLV) I is seen particularly in southern Japan and the Caribbean. Dr.Mokarian

25. GENERAL ASPECTS OF LYMPHOID MALIGNANCIES ETIOLOGY AND EPIDEMIOLOGY • non-Hodgkin's lymphomas • environmental factors • infectious agents, • chemical exposures • medical treatments • Patients treated for Hodgkin's disease can develop non-Hodgkin's lymphoma • agricultural chemicals Dr.Mokarian

26. GENERAL ASPECTS OF LYMPHOID MALIGNANCIES ETIOLOGY AND EPIDEMIOLOGY • non-Hodgkin's lymphomas • HTLV-I infects T cells • directly to the development of adult T cell lymphoma (ATL) in a small percentage of infected patients. • cumulative lifetime risk of developing lymphoma in an infected patient is 2.5%. • transmitted by infected lymphocytes ingested by nursing babies of infected mothers, blood-borne transmission, or sexually • The median age of patients with ATL is about 56 years, emphasizing the long latency. Dr.Mokarian

27. GENERAL ASPECTS OF LYMPHOID MALIGNANCIES ETIOLOGY AND EPIDEMIOLOGY • non-Hodgkin's lymphomas • EBV • Burkitt's lymphoma in Central Africa and the occurrence of aggressive non-Hodgkin's lymphomas in immunosuppressed patients in western countries • EBV infection is strongly associated with the occurrence of extranodal nasal T/NK cell lymphomas in Asia and South America. Dr.Mokarian

28. GENERAL ASPECTS OF LYMPHOID MALIGNANCIES ETIOLOGY AND EPIDEMIOLOGY • non-Hodgkin's lymphomas • HIV • predisposes to the development of aggressive, B cell non-Hodgkin's lymphoma • overexpression of interleukin 6 by infected macrophages • Helicobacter pylori • Infection of the stomach by the bacterium • induces the development of gastric MALT (mucosa-associated lymphoid tissue) lymphomas. • The bacterium does not transform lymphocytes to produce the lymphoma; instead, a vigorous immune response is made to the bacterium and the chronic antigenic stimulation leads to the neoplasia. Dr.Mokarian

29. GENERAL ASPECTS OF LYMPHOID MALIGNANCIES ETIOLOGY AND EPIDEMIOLOGY • non-Hodgkin's lymphomas • Chronic hepatitis C virus • lymphoplasmacytic lymphoma • Human herpesvirus 8 is associated with primary effusion lymphoma • in HIV-infected persons and multicentric Castleman's disease, a diffuse lymphadenopathy associated with systemic symptoms of fever, malaise, and weight loss. Dr.Mokarian

33. HODGKIN'S DISEASE • Nodular Lymphocyte-Predominant Hodgkin's Disease • CLASSIC HD • LP • NST • MCT • LD

34. APPROACH TO THE PATIENT SPLENOMEGALY PHYSIOLOGY AND ANATOMY. • the largest lymphatic organ • function • the primary immune response • filter for the blood • removing from the circulation senescent red cells, • Removing blood cells and other cells coated with immunoglobulins • Red pulp • occupies more than half the volume of the spleen • is the site where senescent red cells are identified and destroyed and red cell inclusions are removed by a process known as pitting • In the absence of splenic function, inclusions known as Howell-Jolly bodies are seen in circulating red blood cells • White pulp • of the spleen contains macrophages, B lymphocytes, and T lymphocytes, participates in the recognition of microorganisms and foreign proteins, and is involved in the primary immune response

35. APPROACH TO THE PATIENT SPLENOMEGALY PHYSIOLOGY AND ANATOMY. • TABLE 178–6. CAUSES OF SPLENOMEGALY • Infection • Bacterial (e.g., endocarditis, brucellosis, syphilis, typhoid, pyogenic abscess) • Mycobacterial (e.g., tuberculosis) • Fungal (e.g., histoplasmosis, toxoplasmosis) • Parasitic (e.g., malaria, leishmaniasis) • Rickettsial (e.g., Rocky Mountain spotted fever) • Viral (e.g., Epstein-Barr virus, cytomegalovirus, HIV, hepatitis) • Benign disorders of the immune system (e.g., rheumatoid arthritis with • Felty's syndrome, systemic lupus erythematosus, drug reactions such as • to phenytoin, Langerhans' cell histiocytosis, serum sickness)

36. APPROACH TO THE PATIENT SPLENOMEGALY PHYSIOLOGY AND ANATOMY. • TABLE 178–6. CAUSES OF SPLENOMEGALY • Malignant disorders of the immune system (e.g., acute or chronic myeloid • or lymphoid leukemia, non-Hodgkin's lymphoma, Hodgkin's disease, • Waldenström's macroglobulinemia, angioimmunoblastic-like T-cell • lymphoma, malignant histiocytosis) • Other malignancies (e.g., melanoma, sarcoma) • Congestive splenomegaly (e.g., portal hypertension secondary to liver disease, • splenic or portal vein thrombosis) • Hematologic disorders (e.g., autoimmune hemolytic anemia, hereditary • spherocytosis, thalassemia major, hemoglobinopathies, elliptocytosis, • megaloblastic anemia, extramedullary hematopoiesis) • Storage diseases (e.g., Gaucher's disease) • Endocrinopathies (e.g., hyperthyroidism) • Miscellaneous (e.g., sarcoidosis, amyloidosis, tropical splenomegaly, cysts)

37. APPROACH TO THE PATIENT SPLENOMEGALY PHYSIOLOGY AND ANATOMY. • EVALUATION OF SPLENIC SIZE AND FUNCTION. • TABLE 178–7. METHODS FOR EVALUATION OF THE SPLEEN • Physical examination • Imaging • Ultrasonography • Computed tomography • Liver-spleen scanningGallium scanning • Positron emission tomography • BiopsyNeedle aspiration • Splenectomy • Laparotomy (total or partial splenectomy) • Laparoscopy

38. APPROACH TO THE PATIENT SPLENOMEGALY PHYSIOLOGY AND ANATOMY. an important skill, but it is not easily learned the existence of a splenic rub on inspiration can lead to the diagnosis of splenic infarct. In general, a splenic "biopsy" involves splenectomy, which can be performed at laparotomy or with laparoscopy a splenectomy done via laparoscopy leads to maceration of the organ and reduces the diagnostic information.

39. APPROACH TO THE PATIENT SPLENOMEGALY PHYSIOLOGY AND ANATOMY. • AN APPROACH TO THE PATIENT WITH SPLENOMEGALY • Does the patient have a known illness that causes splenomegaly(e.g., infectious mononucleosis)? Treat and monitor for resolution. • 2. Search for an occult infection (e.g., infectious endocarditis), hematologicdisorder (e.g., hereditary spherocytosis), occult liver disease (e.g., cryptogeniccirrhosis), autoimmune disease (e.g., systemic lupus erythematosus),or storage disease (e.g., Gaucher's disease). If found, manage appropriately. • 3. If systemic symptoms are present and suggest malignancy and/or focal replacementof the spleen is seen on imaging studies and no other site is available for biopsy,splenectomy is indicated. • 4. If none of the above are true, monitor closely and repeat studies until thesplenomegaly resolves or a diagnosis becomes apparent.

40. APPROACH TO THE PATIENT WITH LYMPHADENOPATHY AND SPLENOMEGALY • AN APPROACH TO THE PATIENT WITH SPLENOMEGALY • presentation • left upper quadrant pain or fullness or • of early satiety • catastrophic symptoms of splenic rupture • unexplained cytopenias • incidentally on physical examination • The presence of a palpable spleen on physical examination is almost always abnormal. • The one exception to this rule is a palpable spleen tip in a slender, young woman • In general, the presence of a palpable spleen should be considered a serious finding and an explanation should be sought.

41. APPROACH TO THE PATIENT WITH LYMPHADENOPATHY AND SPLENOMEGALY