2Pathology of lymph nodes A. Infections1. Bacterial2. Fungal, mycobacterialB. Reactive hyperplasias1. Exaggerations of normal histology. Expansion of all regions or selective expansion of one. Some types characteristic of certain diseases, but most not2. Follicular hyperplasia increase in number and size of germinal centers, spread into paracortex, medullary areasa. Collagen vascular diseases,b. Systemic toxoplasmosis,c. Syphillis3. Interfollicular hyperplasia- paracortex-a. Skin diseasesb. Viral infectionsc. Drug reactions4. Sinus histiocytosis- expansion of the medullary sinus histiocytes-a. Adjacent cancerb. InfectionsC. SarcoidosisD. Metastatic tumorsE. Malignant lymphomas (Non-Hodgkins' lymphomas-NHLs) and Hodgkin's lymphoma
4Hodgkin’s Lymphoma (Hodgkin's disease) (Thomas Hodgkin ;1832) Less common than NHL;approximately 10,000 cases per yearIncidence with respect to age bimodal, with one peak in late adolescence, young adulthood, second peak in sixth decade A potentially curable malignant lymphoma with distinct histology, biologic behavior, and clinical characteristics.Young adults (male predominance)particularly evident in children, where 85% of the cases are males.
5Palpable, painless, firm lymphadenopathy (rubbery adenopathy): Clinical findingsPalpable, painless, firm lymphadenopathy (rubbery adenopathy):cervical area (60-80%),axilla (6-20%),inguinal area (6-20%).Waldeyer ring or occipital or epitrochlear areas is observed infrequently.Splenomegaly may be present.Patients may have hepatomegaly.
6Central nervous system (CNS) symptoms or signs may be due to paraneoplastic syndromes, including cerebellar degeneration,neuropathy,Guillain-Barré syndrome,multifocal leukoencephalopathy.
7Fever (classic Hodgkin's fever is the "Pel-Ebstein fever", or intermittent spiking fever) PruritusEosinophiliaA complication of AIDS.
8ETIOLOGYThe etiology of HD is unknown.Infectious agents, especially the Epstein-Barr virus (EBV)Previous history of Epstein-Barr Virus Infectious MononucleosisAlmost 100% of HIV-associated HD cases are EBV-positive.Patients with HIV infection have a higher incidenceHowever, HD is not considered an AIDS-defining neoplasm.Genetic predispositionApproximately 1% of patients with HD have a family history of the disease.HLA-DP alleles are more common.It is now agreed that Hodgkin lymphoma is a neoplasm arising from germinal center B cells.
9A malignant disease with four histologic subtypes; to make the diagnosis need to see an acceptable Reed-Sternberg cell (the malignant cell of Hodgkin's disease) in the proper reactive cellular background, consisting ofsmall lymphocytes,histiocytes,plasma cells,eosinophils.
11Reed-Sternberg cellThe Reed-Sternberg cells represent a clonal proliferation of B lymphocytes that derive from the germinal centers of lymph nodes and that have lost their ability to express their antibodies because of the introduction of multiple somatic mutations.Large binucleated cellwith large, red owl-eye nucleoli (same size as a small lymphocyte) with surrounding halomultilobed nucleus (often appears "binucleate"), with lobes appearing as mirror images of one anotherPink-to-lavender cytoplasm.
15Reed-Sternberg variants Mononuclear Reed-Sternberg-like cells ("Hodgkin cells") have single-lobed nuclei and one nucleolus. They may be seen in any variant of Hodgkin's disease.LP cells ("L&H cells") have scanty cytoplasm, big knobby nuclei, and small nucleoli. They are seen in lymphocyte predominance Hodgkin's disease.Lacunar Reed-Sternberg cells have abundant, pale cytoplasm, and single, hyperlobated nucleus with small nucleoli. They are seen in nodular sclerosis Hodgkin's disease.Polylobated Reed-Sternberg cells (popcorn cells) look like good Reed-Sternberg cells, except that the nucleoli aren't so impressive. They are typical of mixed cellularity Hodgkin's disease.Pleomorphic Reed-Sternberg cells are anaplastic versions of the familiar form. They make up the bulk of the tumor in lymphocyte depletion Hodgkin's disease.
16Lymphocytic and Hystiocytic (LH) cell variant Reed Sternberg cells in HD(pop-corn cells)
18Clinical Differences Between Hodgkin and Non-Hodgkin Lymphomas More often localized to a single axial group of nodes (cervical, mediastinal, para-aortic)More frequent involvement of multiple peripheral nodesOrderly spread by contiguityNoncontiguous spreadMesenteric nodes and Waldeyer ring rarely involvedMesenteric nodes and Waldeyer ring commonly involvedExtranodal involvement uncommonExtranodal involvement common
19WHO Classification of HD Microscopical types :Lymphocyte predominant (at low stage)Lymphocyte richNodular Sclerosis (often a mediastinal mass).Mixed cellularity (at low or high stage).Lymphocyte depleted (at high stage).Until the late stages of the disease, the tumor masses are composed primarily of inflammatory cells responding to the cancer.
20Lymphocyte (B)Reed-Sternberg cellsOther cellsDifferential diagnosisLymphocyte predominanceMonotonous, Small cellsRare (LP cells)Small lymphocyteHistiocytesSmall lymphocytic lymphomaMixed cellularityMixture of cellsMany (polylobated)Lymphocytes, plasma cells, eosinophils, histiocytesInfectious mononucleosisLymphocyte depletionLess lymphocytePresent (pleomorphic)Anaplastic B-cells, lots of fibers, few lymphocyteNodular sclerosisLess cell more fiber (collagen extending into the node)Present (lacunar)cellular islands containing lymphocytes, histiocytes, eosinophils, and plasma cells
21Clinical Features Frequency Prognosis Hodgkin's DiseaseTypeClinical FeaturesFrequencyPrognosisNodular sclerosisPainless Lymphadenopathy,more common in womenMost frequent type (68%)Good, most are stage I or IIMixed cellularityMost frequent in older persons, second most frequent overall (23%)Fair, most are stage IIILympho-cyte predomi-nanceYoung males, cervical nodesdiffuse or vaguely nodularUncommon (7%)Lympho-cyte depletionUncommon (2%)Poor, most are stage III or IVPainless LymphadenopathyPainless Lymphadenopathy
26Immunhistochemistry RS cells are expressing CD-15
27Positive staining for CD15 (Leu-M1) and CD30 (Ki-1) Negative staining for CD45
28Staging Stage I one node group or organ Stage II one side of the diaphragmStage III both sides of the diaphragmStage IV marrow, or two extra-lymphatic organs.Hodgkin's disease spreads predictably along contiguous groups of lymph nodes.As it spreads, there may be transformation:Lymphocyte predominance turns into mixed cellularity or lymphocyte depletion.Mixed cellularity turns into lymphocyte depletion.Nodular sclerosis generally keeps its type.
30Hodgkin's Disease - Staging Stage 1Only a single lymph node site or extranodal site is involvedStage 2Two or more lymph node sites on one side of the diaphragm are involved, or limited contiguous extranodal site involvementStage 3Lymph node sites on both sides of the diaphragm are involved, with splenic or limited contiguous extradodal site involvement, or bothStage 4
35Complications of HD Mostly during or after treatment. Irradiation-related complications:Cardiac complications (coronary artery disease, chronic pericarditis, pancarditis, valvular heart disease, and defects in the conduction system)Pulmonary complications (dyspnea)Breast cancerHypothyroidismImmunodeficiencyChemotherapy-reladed complications:Cardiac complications (congestive heart failure)Pulmonary complications (interstitial pneumonitis)Bone marrow complications (Myelodysplasia, acute myeloid leukemia)InfertilityNon-Hodgkin lymphoma.
36Infectious complications Sepsis: Patients who have undergone splenectomy are predisposed to bacterial sepsis secondary to encapsulated microorganisms (especially pneumococcal organisms)Herpes zoster.Other complications:Lung cancerMalignant melanomaOther cancers.