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Follicular lymphoma transformation into histiocytic sarcoma: indications for a common neoplastic progenitor

Leukemia volume 28, pages 1937–1940 (2014)Cite this article

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Histiocytic sarcomas are rare, poorly differentiated neoplasms with histiocytic phenotype.1 The 2001 World Health Organization (WHO) classification of hematopoietic and lymphoid tissues depended on the absence of clonal B- or T-cell receptor rearrangements to establish a diagnosis of histiocytic sarcoma.2 Nevertheless, some unequivocal cases of histiocytic sarcomas with immunoglobulin heavy chain (IGH) gene rearrangements have been described.3 Consequently, the current WHO classification of 2008 no longer excludes cases with IGH or T-cell receptor (TCR) gene rearrangements, but classifies them as examples of transdifferentiation from one hematopoietic cell lineage to another.1 However, the process of transformation remains to be delineated. Three models are currently being considered to explain it: (1) direct transdifferentiation; (2) dedifferentiation followed by re-differentiation; and (3) evolution from a common progenitor.4, 5, 6, 7 Here we provide evidence of a common neoplastic progenitor clone in a patient who had a longstanding history of follicular lymphoma (FL), which later on transformed into histiocytic sarcoma.

A 75-year-old female was diagnosed with FL grade II in March 2007. Computed tomographic evaluation revealed diffusely enlarged lymph nodes on both sides of the diaphragm and splenomegaly. A bone marrow biopsy showed 80% infiltration by the FL. According to the FL international prognostic index, the patient was classified into the high-risk group and received five cycles of R-CHOP (rituximab, cyclophosphamide, hydroxydaunorubicin, oncovin, prednisone) therapy with two additional cycles of rituximab. In January 2008, complete remission was confirmed by clinical, radiological and laboratory findings. In April 2009, the patient relapsed and treatment with rituximab and bendamustine was initiated. Again, complete remission was achieved as assessed by positron emission tomography/computed tomography scan and bone marrow histology. In March 2011 second recurrence occurred, documented by lymph node biopsy. There was no evidence of transformation, and the patient received prednisone and ofatumumab treatments followed by combined therapy with chlorambucil, prednisone, cladribine and rituximab. However, no response was observed. A treatment attempt with lenalidomide was terminated due to adverse effects. In September 2012, radiation therapy with a total of 4 Gy of the left axillary and inguinal region was performed due to symptomatic lymph node enlargement. A resected lymph node at this time showed infiltration of the known FL without evidence of transformation. In February 2013 the patient presented with rapidly enlarging cervical lymphadenopathy and deterioration of her general condition. Imaging studies revealed necrotic cervical lymph nodes, and a diagnostic lymph node excision resulted in the integrative diagnosis of histiocytic sarcoma. In April 2013, the patient died due to progressive disease and decreasing general condition.

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Acknowledgements

This work was supported by the Krebsliga beider Basel and Stiftung zur Krebsbekämpfung Zürich.

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  1. A Tzankov and D Juskevicius: These authors contributed equally to this work.

Authors and Affiliations

  1. Institute of Pathology, Kantonsspital Baselland, Liestal, Switzerland

    P Brunner, N Willi & G Cathomas

  2. Institute of Pathology, University Hospital of Basel, Basel, Switzerland

    A Rufle, S Dirnhofer, A Tzankov & D Juskevicius

  3. Oncology/Hematology, Medical University Clinic, Kantonsspital, Liestal, Switzerland

    A Lohri

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Brunner, P., Rufle, A., Dirnhofer, S. et al. Follicular lymphoma transformation into histiocytic sarcoma: indications for a common neoplastic progenitor. Leukemia 28, 1937–1940 (2014). https://doi.org/10.1038/leu.2014.167

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