Histiocyte-rich pseudotumors (HRPT) developing postchemoradiation therapy are a florid response to treatment and reparative change. Although these are benign processes, clinically and radiologically, these may mimic recurrent/relapsed disease. We describe a case of an adult male with history of diffuse large B-cell lymphoma (DLBCL), status postchemoradiation therapy, who developed HRPT at the site of original involvement, mimicking relapse of disease on positron emission tomography/computed tomography (PET/CT) imaging. This is one of the few reported cases of posttreatment HRPT. This entity is important to point out the limitations of PET/CT imaging in patients with lymphomas and metastatic disease and stresses the importance of an excisional biopsy for determining relapse and the need for further treatment.
Chemoradiation therapy is a commonly prescribed regimen for malignant disease [
HRPT, also described as inflammatory pseudotumors [
Here, we describe such a case of an adult male with history of diffuse large B-cell lymphoma, status postchemoradiation therapy, who presented with a mass at the original site of diagnosis that clinically and radiologically mimicked residual disease. This case highlights the limitations of imaging studies and the importance of an excisional biopsy in reaching a definitive diagnosis to guide further treatment options.
The patient is a 34-year-old nonsmoker Caucasian male with a history of cutaneous DLBCL of the scalp, who was treated with external radiation therapy. The patient was in remission for about 5 years, when he presented with a right neck mass. PET/CT studies showed increased metabolic activity in the right cervical lymph nodes as well as in the spleen. An excisional biopsy of the lymph node confirmed involvement by DLBCL. A staging bone marrow biopsy was performed and was negative for lymphoma.
The patient received cyclophosphamide, doxorubicin, vincristine, and prednisone, plus rituximab (R-CHOP) for 4 months. Post-PET imaging revealed residual activity in the right neck node, and he underwent consolidative radiation therapy. The patient’s right cervical lymphadenopathy persisted, and a repeat PET/CT scan performed 6 months later revealed increasing standardized uptake value (SUV) from 3 to 5.4 and 18F-fluorodeoxyglucose (FDG) avidity (Figure
(a) PET scan shows increased uptake in the right cervical lymph node (white arrow). (b) Gross picture of the lymph node cross-section showing tan-yellow nodular areas with focal necrosis.
The patient was asymptomatic and denied weight loss, fevers, night sweats, dysphagia, odynophagia, otalgia, pain/tenderness, hoarseness, bleeding, hemoptysis, or cranial neuropathies. An excisional biopsy of the neck mass was performed to rule out residual disease.
Gross examination revealed a soft tan-yellow fibroadipose tissue measuring
Histologic sections revealed fibroadipose tissue with an intense foamy histiocytic infiltrate with numerous giant cells, cholesterol clefts, hyalinizing necrosis, dystrophic calcification, and scattered small lymphocytes (Figures
H&E staining (a) shows a diffuse cellular infiltrate with areas of necrosis (black arrow). Higher power at 200x (b) shows the infiltrate composed of numerous foamy macrophages with abundant pink cytoplasm, scattered lymphocytes, (c) multinucleated giant cells (red arrows), and (d) cholesterol clefts (dashed arrows).
Immunohistochemical stains reveal scattered CD3-positive T-cells (a), rare CD20-positive B-cells (b), and majority of the cells staining positive for CD68 (c). Pancytokeratin stain is negative (d).
Chemotherapy can induce tumor necrosis and inflammatory response to phagocytize the dead necrotic tissue. Chemokines released from the dying tissue recruit monocytes from the circulation. These monocytes differentiate into activated histiocytes (macrophages) that have phagocytic capabilities. These histiocytes ingest lipid-containing debris and persist as foam cells [
Postchemotherapy HRPT have been described in only rare case reports in the past several years [
Histologically, these lesions have a xanthogranulomatous appearance composed of numerous vacuolated macrophages, multinucleated giant cells, and a lymphocytic infiltrate in a background of necrosis. Occasionally, cholesterol clefts may be noted, but tumor cells are not present. The most important feature of this entity is an abundance of cytologically benign histiocytes without any nuclear atypia. The mitotic count in these entities is null to very low as this is a result of margination of macrophages and not due to proliferation. If any nuclear atypia or increased mitotic figures are identified, it is important to rule out other neoplasms that can mimic histological features of this entity, such as Follicular Dendritic Cell Sarcoma (FDCS), Langerhans Cell Histiocytosis (LCH), Gaucher’s disease, Inflammatory Myofibroblastic Tumor (IMT), and histiocytic sarcoma. Fortunately, these other more worrisome entities can be easily differentiated using appropriate immunohistochemical markers and a good clinical history.
FDCS, specifically the inflammatory pseudotumor-like variant, can mimic HRPT. However, this variant of FDCS has a marked female predominance and often presents with systemic symptoms [
LCH shows predilection for osseous, pulmonary, and integumentary systems, but a minority of patients can present with lymph node involvement [
Gaucher’s disease is more prevalent in Ashkenazi Jews and presents with hepatosplenomegaly, bone lesions, and cytopenias [
IMT is a proliferation of myofibroblasts with background of plasma cells, eosinophils, histiocytes, and lymphocytes. However, there are prominent/atypical mitotic figures present with atypical polygonal cells with oval nuclei. The cells are positive for smooth muscle actin. Chromosomal translocations leading to activation of the anaplastic lymphoma kinase (ALK) can be detected in approximately 50% of IMTs, particularly those arising in young patients [
Histiocytic sarcoma is an aggressive disease associated with B symptoms, lymphadenopathy, and hepatosplenomegaly. The tumor cells are histiocytic in nature, staining positive for CD68, CD163, CD11c, lysozyme, and variable S100 and negative for CD1a, CD13, and CD21. However, the cells are very atypical with variable pleomorphism, irregular nuclei with prominent nucleoli. There is necrosis, giant cells, and mitotic figures easily identified [
The cervical mass in our patient lacked the atypical morphological features noted on these more aggressive entities mentioned above. However, if there is any doubt, immunohistochemistry is indispensable to rule out more aggressive and malignant processes.
In conclusion, HRPT is a benign florid response to chemotherapy-induced cell necrosis leading to margination and accumulation of cytologically benign histiocytes in the tissue, which may appear metabolically active on PET-CT. An excisional biopsy should be performed in such cases for definitive diagnosis of residual disease and need for additional therapy.
The authors have no conflicts of interest.