Pathology of lymph nodes A. Infections 1. Bacterial 2. Fungal, mycobacterial B. Reactive hyperplasias 1. Exaggerations of normal histology. Expansion of all regions or selective expansion of one. Some types characteristic of certain diseases, but most not 2. Follicular hyperplasia increase in number and size of germinal centers, spread into paracortex, medullary areas a. Collagen vascular diseases, b. Systemic toxoplasmosis, c. Syphillis 3. Interfollicular hyperplasia- paracortex- a. Skin diseases b. Viral infections c. Drug reactions 4. Sinus histiocytosis- expansion of the medullary sinus histiocytes- a. Adjacent cancer b. Infections C. Sarcoidosis D. Metastatic tumors E. Malignant lymphomas (Non-Hodgkins' lymphomas-NHLs) and Hodgkin's lymphoma
Classification Non-Hodgkin’s Lymphoma T cell NHL B cell NHL Miscellaneous NHL Hodgkin’s Lymphoma Nodular sclerosis Hodgkin lymphoma Mixed cellularity Hodgkin lymphoma Lymhocyte predominant Hodgkin Lymphoma Lymphocyte-rich classical Hodgkin lymphoma Lymphocyte depleted Hodgkin lymphoma
Hodgkin’s Lymphoma (Hodgkin's disease) (Thomas Hodgkin ;1832) Less common than NHL; approximately 10,000 cases per year Incidence 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.
Palpable, 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. Clinical findings
Central nervous system (CNS) symptoms or signs may be due to paraneoplastic syndromes, including cerebellar degeneration, neuropathy, Guillain-Barré syndrome, multifocal leukoencephalopathy.
Fever (classic Hodgkin's fever is the "Pel- Ebstein fever", or intermittent spiking fever) Pruritus Eosinophilia A complication of AIDS.
ETIOLOGY The etiology of HD is unknown. Infectious agents, especially the Epstein-Barr virus (EBV) Previous history of Epstein-Barr Virus Infectious Mononucleosis Almost 100% of HIV-associated HD cases are EBV- positive. Patients with HIV infection have a higher incidence However, HD is not considered an AIDS-defining neoplasm. Genetic predisposition Approximately 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.
A 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 of small lymphocytes, histiocytes, plasma cells, eosinophils.
Reed-Sternberg cell The 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 cell with large, red owl-eye nucleoli (same size as a small lymphocyte) with surrounding halo multilobed nucleus (often appears "binucleate"), with lobes appearing as mirror images of one another Pink-to-lavender cytoplasm.
Reed-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.
Lymphocytic and Hystiocytic (LH) cell variant Reed Sternberg cells in HD(pop-corn cells)
Hodgkin LymphomaNon-Hodgkin Lymphoma More often localized to a single axial group of nodes (cervical, mediastinal, para-aortic) More frequent involvement of multiple peripheral nodes Orderly spread by contiguityNoncontiguous spread Mesenteric nodes and Waldeyer ring rarely involved Mesenteric nodes and Waldeyer ring commonly involved Extranodal involvement uncommonExtranodal involvement common Clinical Differences Between Hodgkin and Non-Hodgkin Lymphomas
WHO Classification of HD Microscopical types : Lymphocyte predominant (at low stage) Lymphocyte rich Nodular 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.
Lymphocyte (B) Reed- Sternberg cells Other cellsDifferential diagnosis Lymphocyte predominance Monotonous, Small cells Rare (LP cells) Small lymphocyte Histiocytes Small lymphocytic lymphoma Mixed cellularity Mixture of cells Many (polylobated) Lymphocytes, plasma cells, eosinophils, histiocytes Infectious mononucleosis Lymphocyte depletion Less lymphocyte Present (pleomorphic) Anaplastic B- cells, lots of fibers, few lymphocyte Nodular sclerosis Less cell more fiber (collagen extending into the node) Present (lacunar) cellular islands containing lymphocytes, histiocytes, eosinophils, and plasma cells
Hodgkin's Disease TypeClinical FeaturesFrequency Prognosis Nodular sclerosis Painless Lymphadenopathy, more common in women Most frequent type (68%) Good, most are stage I or II Mixed cellularity Most frequent in older persons, second most frequent overall (23%) Fair, most are stage III Lympho- cyte predomi- nance Young males, cervical nodes diffuse or vaguely nodular Uncommon (7%) Good, most are stage I or II Lympho- cyte depletion Uncommon (2%) Poor, most are stage III or IV Painless Lymphadenopathy
Immunhistochemistry RS cells are expressing CD-15
Positive staining for CD15 (Leu-M1) and CD30 (Ki-1) Negative staining for CD45
Staging Stage I one node group or organ Stage II one side of the diaphragm Stage III both sides of the diaphragm Stage 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.
Hodgkin's Disease - Staging Stage 1Only a single lymph node site or extranodal site is involved Stage 2Two or more lymph node sites on one side of the diaphragm are involved, or limited contiguous extranodal site involvement Stage 3Lymph node sites on both sides of the diaphragm are involved, with splenic or limited contiguous extradodal site involvement, or both Stage 4Lymph node sites on both sides of the diaphragm are involved, with splenic or limited contiguous extradodal site involvement, or both
Complications 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 cancer Hypothyroidism Immunodeficiency Chemotherapy-reladed complications: Cardiac complications (congestive heart failure) Pulmonary complications (interstitial pneumonitis) Bone marrow complications (Myelodysplasia, acute myeloid leukemia) Infertility Breast cancer Immunodeficiency Non-Hodgkin lymphoma.
Infectious complications Sepsis: Patients who have undergone splenectomy are predisposed to bacterial sepsis secondary to encapsulated microorganisms (especially pneumococcal organisms) Herpes zoster. Other complications: Lung cancer Malignant melanoma Other cancers.