Large-Cell-Transformation

Large cell transformation (LCT) refers to the transformation of an existing low-grade (indolent) lymphatic disease into a more aggressive, high-grade lymphoma with large cell characteristics. This process is primarily known in connection with indolent B-cell lymphomas, such as follicular lymphoma or chronic lymphocytic leukemia (CLL). The occurrence of large cell transformation is also a sign of malignancy in cutaneous T-cell lymphomas (CTCL) (example - mycosis fungoides)

Characteristics of large cell transformation

• Morphology: The lymphoma cells change into large, atypical cells with prominent nuclei and nucleoli.
• Clinical course: The course of the disease becomes more aggressive, with faster growth of the lymph nodes, B-symptoms (fever, night sweats, weight loss) and possible involvement of extranodal organs.
• Prognosis: The prognosis usually worsens considerably and there is an increased need for therapy.

Examples of large cell transformation

• Richter transformation: This is a special form of large-cell transformation in which a CLL or small B-cell lymphoma transforms into an aggressive DLBCL.
• Transformation of a follicular lymphoma: In this case, the indolent follicular lymphoma develops into a DLBCL.
• Transformation of a CTCL: In the example of mycosis fungoides (transition from patch stage to tumor stage), a deep diffuse infiltrate of lymphocytic cells in the epidermis, a loss of epidermotropism, high mitotic activity and transformation of medium-sized lymphocytes into blastic tumor cells (>25% of the infiltrate) are characteristic. The LCT can be ^CD30+ or ^CD30-.

The diagnosis is made by:

• Biopsy: examination of skin infiltrates, lymph nodes or other affected tissues.
• Immunohistochemistry and molecular genetics: detection of changes such as mutations or clonal B- or T-cell expansions.
• Imaging: sonography, whole-body CT and, if necessary, PET-CT to assess the spread of the disease.

Treatment is usually based on the standards for aggressive lymphomas, e.g. with R-CHOP chemotherapy (rituximab, cyclophosphamide, doxorubicin, vincristine and prednisone).

In the case of cutaneous T-cell lymphomas of the mycosis fungoides type, chemotherapy, radiotherapy and alemtuzumab can be used.

In some cases, CAR T-cell therapy or stem cell transplants may also be considered.

1. Jonak C et al. (2021) Mycosis fungoides and Sézary syndrome. J Dtsch Dermatol Ges 19:1307-1335.
2. Trautinger F et al. (2017) European Eur J Cancer 77: 949-954 European Organization for Research and Treatment of Cancer consensus recommendations for the treatment of mycosis fungoides/Sézary syndrome - Update 2017. Eur J Cancer77:57-74.