Hodgkin’s Lymphoma or Disease (HD)

Pathology of lymph nodesA. 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)

Lacunar variant

Hodgkin Lymphoma Non-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 contiguity Noncontiguous spread

Mesenteric nodes and Waldeyer ring rarely involved

Mesenteric nodes and Waldeyer ring commonly involved

Extranodal involvement uncommon Extranodal 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 cells Differential diagnosis

Lymphocyte predominance

Monotonous, Small cells

Rare (LP cells)

Small lymphocyteHistiocytes

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

Type Clinical Features Frequency 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

Painless Lymphadenopathy

Nodular Sclerosing HD

Lymphocyte predominant HD

Lymphocyte depledet HD

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; cervical lymph node involvement

Hodgkin's Disease - StagingStage 1 Only a single lymph node site or extranodal site is

involved

Stage 2 Two or more lymph node sites on one side of the diaphragm are involved, or limited contiguous extranodal site involvement

Stage 3 Lymph node sites on both sides of the diaphragm are involved, with splenic or limited contiguous extradodal site involvement, or both

Stage 4 Lymph node sites on both sides of the diaphragm are involved, with splenic or limited contiguous extradodal site involvement, or both

Hodgkin’s Disease (Liver&Lymph node)

Complications of HDMostly 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.

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