<unk>  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 (usually excisional biopsy with microscopic 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. PET scans are also useful in functional imaging (by using a radiolabeled glucose to image tissues of high metabolism). In some cases, a gallium scan may be used instead of a PET scan. Types There are two main types of<unk> : classic<unk>  and nodular lymphocyte predominant<unk> . The prevalence of classic<unk>  and nodular lymphocyte<unk>  are approximately 90% and 10%, respectively. The morphology, phenotype, molecular features, and, therefore, the clinical behaviour and presentation of the two types differ. Classic Classic<unk>  (excluding nodular lymphocyte predominant<unk>  can be subclassified into four pathologic subtypes based upon Reed–Sternberg cell morphology and the composition of the reactive cell infiltrate seen in the lymph node biopsy specimen (the cell composition around the Reed–Sternberg cell(s)). Name Description ICD-10 ICD-O Nodular sclerosing<unk>  Is the most common subtype and is composed of large tumor nodules showing scattered lacunar classic RS cells set in a background of reactive lymphocytes, eosinophils and plasma cells with varying degrees of collagen fibrosis/sclerosis. 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 without sclerosis. This type is most often associated with Epstein-Barr virus infection and may be confused with the early, so-called 'cellular' phase of the nodular sclerosing subtype. This type of<unk>  is most commonly seen in immunocompromised people. . Lymphocyte-rich Is a rare subtype, show many features which may cause diagnostic confusion with nodular lymphocyte predominant B-cell non-Hodgkin lymphoma (B-NHL). This form also has the most favorable prognosis. Lymphocyte depleted Is a rare subtype, composed of large numbers of often pleomorphic RS cells with only few reactive lymphocytes which may easily be confused with diffuse large cell lymphoma. Many cases previously classified within this category would now be reclassified under anaplastic large cell lymphoma. Unspecified Lymph node biopsy showing<unk> , mixed-cellularity type CT image of a 46-year-old person with<unk> , image at neck height. On the left side of the person's neck enlarged lymph nodes are visible (marked in red). For the other forms, although the traditional B-cell markers (such as CD20) are not expressed on all cells, Reed–Sternberg cells are usually of B cell origin. Although<unk> 's is now frequently grouped with other B-cell malignancies, some T-cell markers (such as CD2 and CD4) are occasionally expressed. However, this may be an artifact of the ambiguity inherent in the diagnosis.<unk>  cells produce interleukin-21 (IL-21), which was once thought to be exclusive to T-cells. This feature may explain the behavior of classic<unk> , including clusters of other immune cells gathered around<unk>  cells (infiltrate) in cultures. Nodular lymphocyte predominant Nodular lymphocyte predominant<unk>  (NLPHL) is another subtype of<unk>  distinct from classic<unk>  and is characterized by the presence of popcorn cells which express CD20. Due to these differences, among others, NLPHL is often treated differently from classic<unk> , including using rituximab in combination with AVBD chemotherapy, though individual cases vary and clinical trials are ongoing. Staging The staging is the same for both<unk>  and non-Hodgkin lymphomas. After<unk>  is diagnosed, a person will be staged: that is, they will undergo a series of tests and procedures that will determine what areas of the body are affected. These procedures may include documentation of their histology, a physical examination, blood tests, chest X-ray radiographs, computed tomography (CT)/positron emission tomography (PET)/magnetic resonance imaging (MRI) scans of the chest, abdomen and pelvis, and usually a bone marrow biopsy. PET scan is now used instead of the gallium scan for staging. On the PET scan, sites involved with lymphoma light up very brightly enabling accurate and reproducible imaging. In the past, a lymphangiogram or surgical laparotomy (which involves opening the abdominal cavity and visually inspecting for tumors) were performed. Lymphangiograms or laparotomies are very rarely performed, having been supplanted by improvements in imaging with the CT scan and PET scan. On the basis of this staging, the person will be classified according to a staging classification (the Ann Arbor staging classification scheme is a common one): * Stage I is involvement of a single lymph node region (I) (mostly the cervical region) or single extralymphatic site (Ie); * Stage II is involvement of two or more lymph node regions on the same side of the diaphragm (II) or of one lymph node region and a contiguous extralymphatic site (IIe); * Stage III is involvement of lymph node regions on both sides of the diaphragm, which may include the spleen (IIIs) or limited contiguous extralymphatic organ or site (IIIe, IIIes); * Stage IV is disseminated involvement of one or more extralymphatic organs. The absence of systemic symptoms is signified by adding "A" to the stage; the presence of systemic symptoms is signified by adding "B" to the stage. For localised extranodal extension from mass of nodes that does not advance the stage, subscript "E" is added. Splenic involvement is signified by adding "S" to the stage. The inclusion of "bulky disease" is signified by "X". File:Diagram showing stage 1<unk> 's lymphoma CRUK 191.Stage 1<unk>  File:Diagram showing stage 2<unk> 's lymphoma CRUK 208.Stage 2<unk>  File:Diagram showing stage 3<unk> 's lymphoma CRUK 221.Stage 3<unk>  File:Diagram showing stage 4<unk> 's lymphoma CRUK 230.Stage 4<unk>  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) a nodular aspect may appear. A fibrin ring granuloma may be seen. ;Microscopy Micrograph of a classic Reed–Sternberg cell Micrograph showing a "popcorn cell", the Reed–Sternberg cell variant seen in nodular lymphocyte predominant<unk> . H&E stain 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 (RSC) (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 close to the nuclear membrane). Almost all of these cells have an increased copy number of chromosome 9p/9p24.1. Variants: *<unk>  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 hyperlobulated 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 with no nucleolus and basophilic cytoplasm.<unk>  can be sub-classified by histological type. The cell histology in<unk>  is not as important as it is in non-Hodgkin lymphoma: the treatment and prognosis in classic<unk>  usually depends on the stage of disease rather than the histotype.
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