Hodgkin's lymphoma

Hodgkin's lymphoma, also known as Hodgkin's disease, is a type of lymphoma first described by Thomas Hodgkin in 1832. Hodgkin's lymphoma is characterized clinically by the orderly spread of disease from one lymph node group to another and by the development of systemic symptoms with advanced disease. Pathologically, the disease is characterized by the presence of Reed-Sternberg cells. Hodgkin's lymphoma was one of the first cancers to be cured by radiation. Later it was one of the first to be cured by combination chemotherapy. The cure rate is about 93%, making it one of the most curable.

 Epidemiology 

Unlike some other lymphomas, whose incidence increases with age, Hodgkin's lymphoma has a bimodal incidence curve; that is, it occurs most frequently in two separate age groups, the first being young adulthood (age 15–35) and the second being in those over 55 years old although these peaks may vary slightly with nationality. Overall, it is more common in men, except for the nodular sclerosis variant (see below), which is more common in women.

 The annual incidence of Hodgkin's lymphoma is about 1/25,000 people, and the disease accounts for slightly less than 1% of all cancers worldwide.

 The incidence of Hodgkin's lymphoma is increased in patients with HIV infection. In contrast to many other lymphomas associated with HIV infection it occurs most commonly in patients with higher CD4 T cell counts.

 Symptoms

 Swollen but painless lymph nodes are the most common sign of Hodgkin's lymphoma, often occurring in the neck. The lymph nodes of the chest are often affected and these may be noticed on a chest X-ray.

 Splenomegaly, or enlargement of the spleen, occurs in about 30% of people with Hodgkin's lymphoma. The enlargement, however, is seldom massive. The liver may also be enlarged due to liver involvement in the disease in about 5% of cases.

 About one-third of people with Hodgkin's disease may also notice some systemic symptoms, such as low-grade fever, night sweats, weight loss, itchy skin (pruritus), or fatigue. Classically, involved nodes are painful after alcohol consumption, though this phenomenon is rare. Patients may also present with a cyclic high-grade fever known as Pel-Ebstein fever, although there is debate as to whether or not this truly exists.  Systemic symptoms such as fever and weight loss are known as B symptoms.

Diagnosis

 Hodgkin's lymphoma must be distinguished from non-cancerous causes of lymph node swelling (such as various infections) and from other types of cancer. Definitive diagnosis is by lymph node biopsy (removal of a piece of lymph node tissue for pathological examination). Blood tests are also performed to assess function of major organs and to assess safety for chemotherapy. Positron emission tomography (PET) is used to detect small deposits that do not show on CT scanning. In some cases a Gallium Scan may be used instead of a PET scan.

Pathology

 Macroscopy

 Affected lymph nodes (most often, laterocervical lymph nodes) are enlarged, but their shape is preserved because the capsule is not invaded. Usually, the cut surface is white-grey and uniform; in some histological subtypes (e.g. nodular sclerosis) may appear a nodular aspect

Microscopy

 Microscopic examination of the lymph node biopsy reveals complete or partial effacement of the lymph node architecture by scattered large malignant cells known as Reed-Sternberg cells (typical and variants) admixed within a reactive cell infiltrate composed of variable proportions of lymphocytes, histiocytes, eosinophils, and plasma cells. The Reed-Sternberg cells are identified as large often bi-nucleated cells with prominent nucleoli and an unusual CD45-, CD30+, CD15+/- immunophenotype. In approximately 50% of cases, the Reed-Sternberg cells are infected by the Epstein-Barr virus.

 Characteristics of classic Reed-Sternberg cells include large size (20–50 micrometres), abundant, amphophilic, finely granular/homogeneous cytoplasm; two mirror-image nuclei (owl eyes) each with an eosinophilic nucleolus and a thick nuclear membrane (chromatin is distributed at the cell periphery).

Variants:

     * Hodgkin's cell (atypical mononuclear RSC) is a variant of RS cell, which has the same characteristics, but is mononucleated.

    * Lacunar RSC is large, with a single hyperlobated nucleus, multiple, small nucleoli and eosinophilic cytoplasm which is retracted around the nucleus, creating an empty space ("lacunae").

    * Pleomorphic RSC has multiple irregular nuclei.

    * "Popcorn" RSC (lympho-histiocytic variant) is a small cell, with a very lobulated nucleus, small nucleoli.

    * "Mummy" RSC has a compact nucleus, no nucleolus and basophilic cytoplasm.  

 Hodgkin's lymphoma can be sub-classified by histological type. The cell histology in Hodgkin's lymphoma is not as important as it is in non-Hodgkin's lymphoma: the treatment and prognosis in Hodgkin's lymphoma depend on the stage of disease rather than the histotype.

  Types

   Classical

 Classical Hodgkin's lymphoma (excluding nodular lymphocyte predominant Hodgkin's) can be subclassified into 4 pathologic subtypes based upon Reed-Sternberg cell morphology and the composition of the reactive cell infiltrate seen in the lymph node biopsy specimen.  

 Classic Hodgkin's Lymphoma (CHL) subtypes:

    1. Nodular sclerosing CHL is the most common subtype and is composed of large tumor nodules with lacunar RS cells subtype composed of numerous classic often pleomorphic RS cells with only few reactive lymphocytes which may easily be confused with diffuse large cell lymphoma.  

   2. Mixed-cellularity subtype is a common subtype and is composed of numerous classic RS cells admixed with numerous inflammatory cells including lymphocytes, histiocytes, eosinophils, and plasma cells

 Other

 Nodular lymphocyte predominant Hodgkin's lymphoma (NLPHL) is no longer classified as a form of classic Hodgkin's lymphoma. This is due to the fact that the RSC variants (popcorn cells) that characterize this form of the disease invariably express B lymphocyte markers such as CD20 (thus making NLPHL an unusual form of B cell lymphoma), and that (unlike classic HL) NLPHL may progress to diffuse large B cell lymphoma. There are small but clear differences in prognosis between the various forms.

 Lymphocyte predominant HL is an uncommon subtype composed of vague nodules of numerous reactive lymphocytes admixed with large popcorn-shaped RSC. Unlike classic RSC, the non-classic popcorn-shaped RS cells of NLPHL are CD15 and CD30 negative while positive for the B cell marker CD20.  

 Staging