Hodgkin lymphoma Pathological changes
HL most commonly involves cervical lymph nodes and supraclavicular lymph nodes, followed by axillary lymph nodes, mediastinal lymph nodes, retroperitoneal and para-aortic lymph nodes. Painless, progressive enlargement of local lymph nodes is often the first symptom. The spleen, liver, bone marrow and other places may be involved in the late stage, and the spleen is relatively common.
The general changes, the diseased lymph nodes are swollen and can be moved early. As the course of the disease progresses, adjacent swollen lymph nodes adhere to each other and fuse into large masses, sometimes with a diameter of more than 10 cm, which is not easy to push. If it occurs in the lymph nodes of the neck, it can even form a huge lump around the neck. As fibrosis increases, the lumps change from soft to hard. The lumps are often nodular, and the cut surface is gray-white and fish-like, with focal necrosis.
Under the microscope, the histological feature of HL is that there are unequal amounts of R-S cells and their variant cells scattered on the background of mixed infiltration of a variety of inflammatory cells, mainly lymphocytes. A typical R-S cell (diagnostic R-S cell) is a dinuclear or multinucleated tumor giant cell with a diameter of 20-50mm or larger. The tumor cells are round or elliptical, with rich cytoplasm, slightly eosinophilic or basophilic, with round or elliptical nuclei, and dual or multinucleated nuclei. The chromatin is rough, clumped along the nuclear membrane, and the nuclear membrane is thick and clear. Inside the nucleus is a large, eye-catching, eosinophilic median nucleolus with a diameter equivalent to that of a red blood cell. The dual nuclei of typical R-S cells are arranged face-to-face, symmetrical to each other, forming a so-called mirror image cell. In addition to the classic R-S cells, the mononuclear giant cells with the above-mentioned morphology are called Hodgkin cells, which may indicate HL, but they are not enough to confirm the diagnosis. It is generally believed that Hodgkin cells are the precursor cells of classical R-S cells.
Other common variants of RS cells include: ① Lacunar RS cells, that is, lacunar cells: These cells are large in size, about 40-50mm in diameter, rich in cytoplasm and empty, and their nuclei are leafy and wrinkled. The nuclear membrane is thin, chromatin is sparse, and there are many nucleoli, which are smaller and basophilic than the typical RS. The empty cytoplasm is caused by the shrinkage of the cytoplasm near the nuclear membrane after formaldehyde fixation, which is seen in nodular sclerosis and mixed cell type HL; ②Pleomorphic RS cells, tumor cells are large in size and irregular in size and shape. It has a fusiform shape with obvious pleomorphism. The nucleus is large, the shape is irregular, the chromatin is thick, and there are obvious large nucleoli. Mitosis is more common, and multipolar mitosis is common. Seen in lymphopenia HL. Classical H/R-S cells and their variant cells are only found in classic HL but not in nodular lymphocyte-based HL. The tumor cells that appear in the nodular lymphocyte-based type are L&H type R-S cells, or "popcorn cells". L&H type R-S cells are similar in size to immunoblasts or larger, often mononuclear, with less cytoplasm, and wrinkled or lobed nuclei, so they are called "popcorn" cells. Chromatin is often bubble-like, nuclear membrane is thin, nucleoli are often multiple, basophilic, smaller than typical RS cells, but sometimes some L&H type RS cells have more obvious nucleoli, similar to typical RS cell.
Almost all classic HL H/R-S cells are CD30 positive, and most (75%-85%) are CD15 positive. But it does not express T cell and B cell markers. PCR analysis of DNA extracted from a single cell found that 98% of classic HL had monoclonal rearrangements of the Ig gene. It suggests that the classic HL is still derived from B cells. The typical HL can be further divided into: nodular sclerosis, mixed cell type, lymphopenia and classic HL rich in lymphocytes.
Nodular lymphocytes predominantly HL L&H type R-S cells express B cell marker CD20. There may also be immunoglobulin single light chain positivity. But it does not express the classic R-S cell markers CD30 and CD15. Genetic analysis found that L&H type R-S cells have monoclonal Ig gene rearrangement, suggesting that this type of HL also originates from B cells.
There is a “background” composed of varying amounts of inflammatory or reactive components in HL tumor tissue, mainly lymphocytes, as well as plasma cells, neutrophils, eosinophils, and histiocytes. To a certain extent, it reflects the body's anti-tumor immune status, which is closely related to the histological classification and prognosis of HL. The number and proportion of reactive components gradually decrease with the progression of the disease, while the hyperplasia of fibrous tissue and hyaline change gradually increase.
