A 69-year-old man presented with enlarged left iliac lymph node which on PET-CT showed FDG-avidity with a standardized uptake value (SUV) max of 14.8. Needle core biopsy showed involvement by a diffuse large B-cell lymphoma. By immunohistochemistry, the neoplasm showed a germinal center B-cell phenotype with expression of CD10, CD20, BCL2, BCL6, and PAX5. Fluorescence in situ hybridization studies were negative for MYC, BCL2, and BCL6 gene rearrangements. He underwent 6 cycles of chemotherapy with R-CHOP (Rituximab, Cyclophosphamide, Hydroxydaunomycin (doxorubicin), Oncovin (Vincristine), Prednisolone).

Towards the completion of chemotherapy (5 months since diagnosis), imaging studies revealed residual PET-avidity of the left iliac lymph node with a SUV max of 10.2, highly suspicious for residual lymphoma. An excisional biopsy was subsequently performed which showed diffuse involvement by a histiocytic infiltrate with bland nuclei, inconspicuous nucleoli, and abundant foamy cytoplasm (Fig. 1A, Hematoxylin and eosin stain). Immunohistochemistry revealed positive staining for CD163 (Fig. 1B) and absence of B-cell markers including CD20 and PAX5 (Fig. 1C). Flow cytometry immunophenotyping did not demonstrate an abnormal B-cell or an aberrant T-cell population. There was no morphologic or immunophenotypic evidence of lymphoma. Possible differential diagnosis included histiocytic neoplasms arising in the setting of transdifferentiation. Evaluation for ALK-positive histiocytosis, Erdheim-Chester disease (ECD), and Rosai-Dorfman disease were ruled out by the absence of immunostaining for ALK, S100, Factor 13a (Fig. 1D), Cyclin D1 and BRAF V600E, respectively[1]. Furthermore, clinical and radiologic findings were not compatible with ECD[1]. The overall findings in the setting of post-chemotherapy were in keeping with the diagnosis of histiocyte-rich pseudotumor.

Fig. 1
figure 1

Histologic sections of the PET-avid post-chemotherapy lymph node biopsy. A) Hematoxlyin and eosin, B) immunohistochemistry for CD163, C) immunohistochemistry for PAX5 and D) immunohistochemistry for Factor 13a

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Histiocyte-rich pseudotumor, although a rare benign entity, often mimics residual lymphoma as demonstrated by increased FDG-avidity on imaging studies post-chemotherapy [2, 3]. It is essential to keep this entity as a potential differential diagnosis while evaluating residual PET-avid lesions in post-chemotherapy lymphoma patients to avoid unnecessary treatment. Follow-up imaging studies usually show a gradual decrease in FDG-avidity in such cases further attesting that they represent a benign/reactive process[2]. In this patient, follow-up imaging studies at 3 months from diagnosis of histiocytic-rich pseudotumor showed complete resolution of FDG-avidity.