Transformation of Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma to Histiocytic/Dendritic Cell Sarcoma

Abstract

Chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) transforming into a more aggressive lymphoma (i.e., Richter syndrome) is well documented in the literature. In recent years, transdifferentiation of CLL/SLL to histiocytic/dendritic/Langerhans cell sarcomas has also been reported. We hereby describe a case of a 55-year-old female who was incidentally diagnosed with CLL after presenting to the hospital for symptoms of undiagnosed rheumatoid arthritis. At the time of presentation, CLL was stage 1, and the patient was placed on observation. Eight years after being diagnosed with CLL, and after several treatment modalities for her rheumatoid arthritis, the patient re-presented with progression of adenopathy, intermittent fevers, 5-pound weight loss, and worsening respiratory status requiring airway management. Computed tomography (CT) imaging revealed a soft tissue mass in the nasopharynx, lingual tonsillar hypertrophy with airway compromise, and bulky cervical, supraclavicular, and axillary lymphadenopathy. A biopsy of an enlarged cervical lymph node yielded a diagnosis of histiocytic/dendritic cell sarcoma favoring interdigitating dendritic cell sarcoma, likely representing transdifferentiation from CLL/SLL, of which there are no standard of care treatment guidelines. The patient was treated with ifosfamide, carboplatin, and etoposide (ICE) for three cycles, followed by rituximab, etoposide, prednisone, vincristine, cyclophosphamide, and doxorubicin (R-EPOCH) in combination with zanubrutinib. She then underwent haploidentical hematopoietic stem cell transplantation. At the time of the making of this manuscript, the patient was 45 days post-transplant without any notable complications.

Keywords: Chronic lymphocytic leukemia; Histiocytic sarcoma; Histiocytic/dendritic cell sarcoma; Interdigitating dendritic cell sarcoma; Small lymphocytic leukemia; Transdifferentiation; Transformation.

Figure 1

Photomicrograph of the ultrasound-guided core biopsy of an enlarged lymph node in the posterior triangle of the right neck shows lymphoid tissue with many paler areas. (H&E stain, original magnification, × 100). H&E: hematoxylin and eosin.

Figure 2

Photomicrographs of the ultrasound-guided core biopsy of an enlarged lymph node in the posterior triangle of the right neck. The paler areas contain sheets of atypical histiocytic/dendritic cells with irregular nuclear contours and prominent/distinct nucleoli. There are occasional mitotic figures, including atypical ones (a, short arrow). Small mature lymphocytes and scattered eosinophils (b, long arrows) are admixed (H&E stain, original magnification, (a) × 200, (b) × 400). H&E: hematoxylin and eosin.

Figure 3

Immunohistochemical (IHC) characterization of the tumor. The histiocytic/dendritic cells are positive for CD4 (a), CD45 (not shown), CD68 (granular and Golgi pattern (b), CD163 (small subset, not shown), BCL6 (c), cyclin D1 (d), lysozyme (e), and S-100 (f), weakly positive for OCT-2 (g) and BCL2 (subset, not shown), and were negative for CD1a (not shown), CD3 (not shown), CD5 (not shown), CD10 (not shown), CD20 (not shown), CD21 (not shown), CD23 (not shown), CD30 (not shown), CD79a (not shown), ALK1 (not shown), BOB.1 (h), MUM1 (not shown), PAX-5 (not shown), and cytokeratin AE1/AE3 (not shown). (i) Ki67 IHC stain shows a high proliferation rate (immunoperoxidase staining; original magnification, × 200).

Figure 4

A small focus of chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) by immunohistochemistry. The CLL/SLL cells are negative for CD3 (a), but express CD5 (b), CD20 (c), and CD23 (d). The background T-lymphocytes are positive for both CD3 and CD5 (immunoperoxidase staining; original magnification, × 200). CLL/SLL: chronic lymphocytic leukemia/small lymphocytic lymphoma.