Extensive Extranodal Involvement of Rare Sites in Non Hodgkin’s Lymphoma Detected on ¹⁸F- FDG PET-CT: A Case Report

Abstract

We present a case of a 23 year-old male treated for Hodgkin’s lymphoma who developed diffuse large B-cell lymphoma (DLBCL) 8 years after achieving remission. ¹⁸F-fluorodeoxyglucose positron emission tomography computed tomography (¹⁸F-FDG PET-CT) was done, which revealed extensive extranodal involvement of bilateral atria, bilateral kidneys, ileo-caecal junction and left testis along with mesenteric and retroperitoneal lymph nodal involvement. Renal and cardiac lesions were not detected by contrast-enhanced CT. Simultaneous lymphomatous involvement of rare sites such as heart, kidneys and testis in a single patient has not been reported before.

Introduction

Lymphoma is composed of indolent as well as aggressive human malignancies which arise from cells of the immune system at different stages of differentiation. They can manifest in a wide range of morphologic, immunologic and clinical findings. Malignancies of lymphoid cells may present as leukemia (i.e., primary involvement of bone marrow and blood), or as lymphoma (i.e., solid tumors of the immune system) [1]. The role of ¹⁸F-fluorodeoxyglucose positron emission tomography (¹⁸F-FDG PET) and PET-CT (positron emission tomography-computed tomography) has been extensively evaluated in the management of Hodgkin’s disease (HD) and non Hodgkin’s lymphoma (NHL) [2–7]. PET-CT has shown significant improvement in staging and restaging when compared to conventional imaging modalities such as contrast-enhanced computed tomography (CECT) [4–7]. The role of ¹⁸F-FDG PET-CT in detection, staging and restaging of patients with extranodal involvement in NHL has also been reported in the literature [2, 3]. Multiple isolated cases with extranodal involvement of NHL, detected on PET-CT, have been previously reported [8–11]. Here, we report a rare case of extranodal NHL involving multiple organs namely heart, bilateral kidneys, bowel, and left testis, in addition to mesenteric and retroperitoneal lymph nodes which were detected on ¹⁸F-FDG PET-CT.

Case Report

We report a case of a 23 year-old male who was treated for Hodgkin’s lymphoma of cervical lymph nodes (Stage IA) in 2003. He was in remission until 2011, when he developed intermittent, mild epigastric abdominal pain. He was prescribed a 2-week course of proton pump inhibitors and the symptoms apparently improved but recurred. Two weeks later, the abdominal pain intensified and became more generalized, along with constitutional symptoms like fever and lethargy. There were no cardiac symptoms. Abdominal examination revealed slightly distended abdomen, decreased bowel sounds and diffuse tenderness, most prominent in the right lower quadrant. Cardiovascular examination was unremarkable. The pulse was 88/min, regular, blood pressure was 118/78 mm of Hg and jugular venous pressure was not elevated. The heart sounds were audible and normal and there was no murmur, heave or rub. CECT of the abdomen and thorax revealed asymmetric thickening of the terminal ileum, along with multiple mesenteric and retroperitoneal lymphadenopathy (Fig. 1). Colonoscopy revealed ileo-colic intussusception and biopsy results of the lesion were consistent with diffuse large B-cell lymphoma (DLBCL). Serum lactate dehydogenase levels were elevated (630 IU/L). The patient was thereafter referred to the nuclear medicine department for staging ¹⁸F-FDG PET-CT. PET-CT showed abnormally increased ¹⁸F-FDG uptake in right and left atria, bilateral renal cortices, left testis, terminal ileum, ileo-caecal junction, and in multiple mesenteric and retroperitoneal lymph nodes (Figs. 2 and 3). Renal and cardiac lesions were not detected on CECT. Maximum standardized uptake value (SUV_max) and size of various nodal and extranodal lesions are given in the Table 1. The patient underwent equilibrium radionuclide gated blood-pool angiography (ERNA) for ejection fraction estimation prior to chemotherapy. It showed an ejection fraction of 60 % (normal >50 %) and no ventricular wall motion abnormality. The patient underwent combination chemotherapy with cyclophosphamide, hydroxydaunorubicin, oncovin and prednisone along with rituximab (R-CHOP regimen). ¹⁸F-FDG PET-CT was repeated after four cycles of chemotherapy to assess treatment response. It showed progression of disease at all sites including heart, kidneys and testes (Fig. 4). Interestingly secondary to bilateral testicular involvement, the patient developed bilateral testicular vein thrombosis. The patient is now being planned for second line chemotherapy.

Fig. 1.

Transaxial thorax CECT image (a) didn’t reveal any focal cardiac lesion. Transaxial abdominal CECT images did not show any renal lesion (b). It revealed presence of enlarged left testis (c), circumferential soft tissue attenuation thickening of the terminal ileum (arrow) more pronounced along the medial wall with adjacent small ileo-caecal node (d) and well marginated soft tissue attenuation lesions in left para-aortic (arrow) (e) and precaval location (arrow) (f) consistent with lymphomatous ileal involvement and nodal deposits

Fig. 2.

Maximum intensity projection images of PET-CT scan shows multifocal increased ¹⁸F-FDG uptake in the mediastinum (arrow head), gastrointestinal tract (outline arrow and connected arrow), kidneys (thin black arrow) and scrotal region (thick black arrow)

Fig. 3.

Transaxial PET-CT images show focally increased ¹⁸F-FDG uptake in bilateral atria (a) and bilateral renal cortices (b). It also shows a left testicular mass with intense ¹⁸F-FDG uptake (c), ileo-cecal mass with intense ¹⁸F-FDG uptake (d), ¹⁸F-FDG avid retroperitoneal (e) and mesenteric (f) lymphadenopathy. Findings were suggestive of lymphomatous involvement of above mentioned sites

Table 1.

Describing SUVmax and dimension of lesions detected in PET/CT

Site of involvement	SUVmax	Size (cms)
Ileum	24.5	8.7
Mesenteric lymph nodes	22.7	3.6
Retroperitoneal lymph nodes	17.1	2.8
Left and right renal cortices	4.2, 13.9	0.5, 1.7
Left and right atria	15.8, 12.6	2.2, 1.7
Left testis	21.9	6.4

Fig. 4.

Images of ¹⁸F-FDG PET-CT done after four cycles of chemotherapy. Maximum intensity projection images of PET-CT scan (a) shows multifocal increased ¹⁸F-FDG uptake in the mediastinum (arrow head), gastrointestinal tract (line arrow and connected arrow), kidneys (non solid black arrow) and bilateral testes (solid black arrow). As compared to baseline PET-CT there is progression of disease at all sites including heart (b), kidneys (c) and testes (d). Interestingly, there is linear increased ¹⁸F-FDG uptake in bilateral testicular veins due to thrombosis (a, broken arrows)

Discussion

Patients treated for HD are infrequently known to develop NHL; it is not clear whether it is due to the dedifferentiation of existing disease or due to secondary effects of its treatment [1]. The involvement of extranodal sites is a common feature in the course of NHL. Moreover, some NHLs are considered to originate at sites other than the lymph nodes or the spleen, and are referred to as primary extranodal NHL (PE-NHL) [12, 13]. When NHL has extranodal presence, the involved sites can be the gastrointestinal tract, bone, brain, testis, ovary, lung, nasopharynx, soft tissue, thyroid, kidney, liver, breast, skin, etc. [14, 15].

DLBCL is the most common type of NHL, constituting 33 % of all cases. The patient can present either with a primary disease of lymph nodes or that of extranodal sites. More than half of the patients have some site of extranodal involvement at the time of initial diagnosis. Any organ can be involved, with the most common sites being the gastrointestinal tract and bone marrow, each being involved in 15–20 % of the patients [1]. Extranodal involvement in DLBCL is associated with a decreased overall survival rate in Stage I DLBCL. Paradoxically, a better outcome is observed in DLBCL stage IV patients with concomitant extranodal disease [16].

Gastrointestinal tract is involved in 10–30 % of all patients with NHL. The stomach is the most commonly affected followed by small bowel, large bowel, and esophagus [2]. In the small bowel, NHL usually occurs due to the direct extension of disease from the involved mesenteric lymph nodes and the distal ileum is most frequently affected site [17]. In the present case, mesenteric lymph nodes along with the distal ileum were involved, which culminated in the ileo-colic intussesception.

Testicular lymphoma, whether primary or secondary to the extensive disease, is a rare entity. The most common histological type is DLBCL. Inguinal and retroperitoneal lymph nodal spread can also be seen in some patients [2]. In our case, there was abnormally increased asymmetric radiotracer uptake in the enlarged left testis. Also, multiple retroperitonal (para-aortic and pre-aortic) lymph nodes showed abnormal ¹⁸F-FDG accumulation, signifying likely lymphomatous spread from the involved testis. Yin et al. reported a case of a 55-year-old man with NHL of the left testis and of the bilateral adrenals detected by ¹⁸F-FDG PET-CT and demonstrated its role in the diagnosis and assessment of therapeutic response [8].

Renal involvement is quite uncommon in DLBCL. In most of the cases it is secondary and occurs by hematogenous spread or by direct extension of the disease from a retroperitoneal mass. Villa et al. concluded that there is a high incidence of central nervous system relapse in patients with DLBCL and kidney involvement at diagnosis [18–20]. As ¹⁸F-FDG is excreted by the kidneys, it can lead to false positive and false negative interpretations on PET-CT. Renal involvement in NHL is seen as multiple focal areas of increased ¹⁸F-FDG uptake mostly in renal cortices that may be unilateral or less commonly, bilateral. There may or may not be corresponding lesions in non diagnostic CT scans [2]. In the present case, multiple focal areas of increased radiotracer uptake were noted in bilateral renal cortices. These lesions were isodense and non-enhancing on CECT.

Heart and pericardium are rarely involved in NHL. The involvement is usually revealed by cardiac complications and is associated with a poor prognosis [21, 22]. Few cases of cardiac involvement in NHL have been reported, both primary and metastatic, detected by ¹⁸F-FDG PET-CT [9–11]. Julian et al. reported two cases of NHL with cardiac involvement (apical septum, right ventricle and right auricle) detected by ¹⁸F-FDG PET-CT that allowed an early diagnosis and chemotherapy, therefore, improving the survival [9]. Synchronous lesions were detected in bilateral atria in our case, which were isodense and non-enhancing on CECT and therefore missed on CT.

Therefore, whole body imaging with a sensitive modality such as ¹⁸F-FDG PET-CT is mandatory to assess the extent of disease by detecting unexpected extranodal sites of disease or exclusion of disease in the presence of nonspecific extranodal CT findings [3]. In patients with known disease, other goals can be accomplished, which are evaluation of response to therapy (progression was demonstrated in the present case), identification of new or recurrent disease, and monitoring the complications of therapy. In patients, where the disease has not been confirmed, imaging helps in reaching a provisional diagnosis [23].

In conclusion, the present case highlights the utility of ¹⁸F-FDG PET-CT in detection of extranodal NHL at unsuspected sites which may have an important bearing on the management and prognosis.