Reed-Sternberg cells

Description

Hodgkin and Reed-Sternberg cells are the hallmark cells in Hodgkin’s disease. The cells are the tumor cells of Hodgkin’s lymphoma and are usually termed Hodgkin cells when mononucleated and Reed-Sternberg cells when multinucleated.

The cells are derived from (pre-apoptotic) germinal center B cells, but have have lost their B cell identity and show aberrant activation of multiple signalling pathways.

The cells are named after Thomas Hodgkin for his description of a lymphoid lesion in 1832; and Carl Sternberg (1898) and Dorothy Reed (1902) for their later histologic description of the cells. There is dispute of the eponymic recognition of Reed-Sternberg cells, and to whom credit for their recognition lies. Willis (1948) argued that Greenfield, Sutton and Coupland had “clearly depicted” the cells in 1878. However, it is accepted that none of the earlier descriptions of this particular cell are fully admissible, whereas Sternberg and Reed’s description come close.


History

1872Theodor Langhans (1839 – 1915) was one of the first to describe the histopathologic features of Hodgkin’s disease and to recognize the presence of multinucleated giant cells.

1878 – Symposium, chaired by Wilks, on the subject of lymphadenoma and leukaemia at the Pathological Society of London. This included several significant contributions referring to the large multinucleated tumour cells of Hodgkin’s disease. William Smith Greenfield (1846 – 1919) provided specimens illustrative of the pathology of lymphadenoma and leucocythemia. He described five cases, all with similar microscopic appearances:

…there was some general enlargement of the glands, the fibrous stroma appeared coarser, and there were a large number of multinucleated cells adherent to the trabeculae…These multinucleated cells, containing from four to eight or twelve nuclei, were often collected in dusters in parts of the gland especially where the fibrous change was progressing.

Greenfield 1878
Greenfield drawing Reed-Sternberg cells 1878
Histology of the lymph gland. Greenfield 1878: Plate XIII

1898Carl Sternberg (1872-1935) at the University of Vienna published 15 cases of Hodgkin’s disease with illustrations. He described the microscopic appearances of the lymph glands, the multinucleated giant cells; the mononuclear variant; mitotic figures; and distinguished the giant cells from the Langhans giant cells found in tuberculosis.

Sternberg drawing of Reed-sternberg cells 1898 Fig 3
Multinucleated cells, mononuclear variants and at least two mitoses. Sternberg 1898 Fig 3.

Sternberg essentially provided an accurate description of the microscopic pathology and illustrated the giant cells. However, as 8 of the 15 cases demonstrated tuberculosis in one or more organ, Sternberg concluded that Hodgkin’s disease was a chronic inflammatory process secondary to the tubercle bacillus, a belief he held until his death in 1935.

1901-1902 During her pathology fellowship at Johns Hopkins, Dorothy Reed (1874 – 1964) reviewed surgical specimens and autopsy material of cases that were considered to be Hodgkin’s disease. She found 8 cases which closely resembled each other clinically and histologically.

Reed firmly asserted the nature of Hodgkin’s disease:

We should limit the term Hodgkin’s disease to designate a clinical and pathological entity, the main features of which are painless progressive glandular enlargements, usually starting in the cervical region, without the blood changes of leukemia.

With respect to Hodgkin’s disease and tuberculosis:

The outcome of all this discussion seems to be that tubercle bacilli may be present in a malignant lymphomatous process, without any primary etiological connection between the two, and also that there may be advanced tuberculosis present in a case of malignant lymphoma without the presence of tubercle bacilli in the gland

Fig 4. The so-called endothelial cells with their branching protoplasmic processes in different stages of proliferation. Transition from uninuclear giant cells, originating from such endothelial cells, to large multinuclear giant cells are represented, showing the peculiar vesicular nuclei, prominent nucleoli, and protoplasmic processes

Reed accurately described and illustrated the cells characteristic of Hodgkin’s disease:

The nucleus is always large in proportion to the size of the cell. It may be single or multiple. If single, it is usually round. Bean-shaped and irregularly indented nuclei are common. If multiple, the nuclei may be arranged peripherally in the cell, or heaped in the center. Eight or ten nuclei have been seen in a single cell. The chromatin network is prominent in these nuclei, and one or more large nucleoli are always present. The nucleoli are usually oval, but they may be of any shape. The nucleoli always take a contrasting stain to the nucleus in the double stains, they have an affinity for acid dyes. No definite mitotic figures were ever seen in these cells. Direct division was frequently observed. The protoplasm is usually homogeneous, and stains well. It may appear granular, show vacuolization, or contain fat or pigment granules. Cells having bizarre and irregular nuclei are found in the oldest growths. These giant cells, so far as our observation reaches, are peculiar to this growth, and are of great assistance in diagnosis

Reed. 1902

1902 – Sir Frederick William Andrewes (1859-1932) independently published an illustrated description of the histopathology of Hodgkin’s disease having reviewed more than 20 cases over 3 years. He described the large multinucleated cells of Hodgkin’s disease (Reed-Sternberg cells) as well as nodular sclerosing Hodgkin’s disease. [Discussion on lymphadenoma in its relation to tuberculosis. Transactions of the Pathological Society of London]

FW Andrewes and Reed-Sternberg cells 1902
  • Fig 1. Section of an axillary lymphatic gland removed from a man aged 38. Emphasizes the pleocellularity of process, together with the giant cells
  • Fig 2. Section of a cervical lymphatic gland removed from a man aged 26 affected with lymphadenoma. Large numbers and great size of the ‘lymphadenoma cells’. These are for the most part multinucleate and deeply stained, but do not resemble the giant – cells of tubercle .
FW Andrewes and Reed-Sternberg cells 1902 2
  • Fig 3. Section of a cervical gland removed from a woman aged 32. Illustration of probable nodular sclerosing Hodgkin’s disease
  • Fig 4. Section of a lymphatic gland from the axilla of a boy aged 11. Characteristic multinucleate giant cells

1916 – Reed’s name was not initially linked to the giant multinucleated cell of Hodgkin’s disease. However William George MacCallum (1874-1944) mentions Dorothy Reed five times in a 6-page chapter on Hodgkin’s disease in his Text-book on Pathology. This irreversibly associated Reed’s name with the cell in various forms including Sternberg-Reed; Reed-Sternberg; and Dorothy Reed cell.


Associated Persons

Alternative names
  • Dorothy Reed cell
  • Reed-Sternberg cell
  • Sternberg-Reed Cell

References

eponymictionary CTA

eponymictionary

the names behind the name

Graduated from Cardiff Medical School in 2017 with MBBCh and BSc in Psychology and Medicine. Currently working as a doctor in the emergency department at Sir Charles Gairdner Hospital in Perth, Australia.

Emergency physician MA (Oxon) MBChB (Edin) FACEM FFSEM with a passion for rugby; medical history; medical education; and informatics. Asynchronous learning #FOAMed evangelist. Co-founder and CTO of Life in the Fast lane | Eponyms | Books | vocortex |

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