A positive PET/CT after treatment for Hodgkin’s lymphoma

Issue: July 10, 2008

ByMunir Ghesani, MD, FACNM

ByCarrie Wasserman, MD

A 36-year-old man presented with several weeks of night sweats and enlarged left cervical lymph nodes. Imaging revealed extensive mediastinal lymphadenopathy with encroachment on the pericardium, enlarged supraclavicular lymph nodes. A staging bone marrow biopsy was negative. Lymph node biopsy revealed Hodgkin’s lymphoma, nodular sclerosis type and the patient’s clinical stage was IIB.

The patient began chemotherapy with doxorubicin, bleomycin, vinblastine and dacarbazine (ABVD) and completed four cycles, but was changed to cyclophosphamide, vincristine, procarbazine, prednisone (C-MOPP) for the last two cycles for fever, pulmonary toxicity and paresthesias of the hands and feet. Following chemotherapy, he received consolidative radiation to the mediastinum. Follow-up images were consistent with a complete response. The patient continued regular follow-up without evidence of recurrent disease.

Five years later, the patient developed abdominal pain that awoke him from sleep. A PET/CT revealed asymmetric bilateral metabolic activity of the tonsils, hypermetabolic cervical lymph nodes, and a large retrocaval paraspinal soft tissue mass. He also had a large hypermetabolic right sided celiac axis mass and enlarged gastrohepatic, peripancreatic, gastrosplenic, retrocrural, mesenteric and retroperitoneal lymphadenopathy. The spleen was mildly enlarged with numerous hypermetabolic hypodense lesions. His bone marrow biopsy was again negative, but celiac lymph node biopsy via endoscopic ultrasound revealed a non-Hodgkin’s lymphoma of follicular center origin. Flow cytometry confirmed these results.

In light of the patient’s bulky disease, he began treatment with R-CHOP shortly thereafter. A restaging PET/CT after cycle three confirmed a decrease in hypermetabolism of the tonsils and a decrease in size and hypermetabolism of the splenic lesions. The abdominal lymphadenopathy was also decreased in size and standardized uptake value activity. A PET/CT after six cycles and again four months later did not show evidence of residual hypermetabolism, and the patient has remained asymptomatic and continues to work full time.

Figure 1: A focused PET/CT image of the spleen demonstrates a hypodense lesion in the spleen which is no longer hypermetabolic. In the given clinical context this is consistent with treated lymphoma.

Figure 2: Selected axial CT image of the upper abdomen demonstrates retrocaval lymphadenopathy. On the axial PET image, degree of metabolic activity corresponding to the lymphadenopathy is no higher than adjacent background. The findings are again consistent with treated lymphoma. A follow-up PET/CT (not shown) after four months revealed no interval change.

Figure 3: Axial CT image at the level of mid abdomen demonstrates "misty" appearance to the mesentery which, when compared to the CT scan at the baseline (a staging study performed at the time of initial diagnosis of non-Hodgkin's lymphoma - not shown), revealed interval improvement.

Source: M Ghesani

CASE DISCUSSION

More than 80% of patients with Hodgkin’s disease can be cured with first-line treatment, depending on their risk factor profile. Long-term survivors are at risk for second malignancy, which are often fatal. Solid tumors, leukemia and non-Hodgkin’s lymphoma (NHL) have all been reported. In a British review of 5,519 Hodgkin’s disease patients treated over a 30-year period, 322 second malignancies occurred and 50 of those were NHL. The 20-year cumulative risk of NHL in those patients was 2.3% (95% CI, 1.6-3.1). Smaller series have also found the cumulative incidence for NHL after primary Hodgkin’s disease ranges between 1% and 6%. Some groups have reported that this risk remained constant during the follow-up period, while others noted that the greatest risk began 10 years after first-line treatment. The timing and relationship with previous therapy remains unclear. In a large series by the German Hodgkin’s Lymphoma Group from 2001, the incidence of secondary NHL remained constant from zero to eight years. These differences may be due to differences in observation time, infrequent use of rebiopsy at time of relapse, the lack of uniform pathologist review, or incorrect original diagnosis in the smaller series.

The mechanism of the pathogenesis of NHL in patients with Hodgkin’s disease remains elusive. Historically, some cases of NHL may have been misdiagnosed as HL. The mutagenic effects of radiation and chemotherapy may play a role. NHL might represent histologic conversion of Hodgkin’s disease, especially for the lymphocyte predominant subtype. The risk might also be related to the immunocommpromised status of a patient with Hodgkin’s disease, similar to the increased risk of NHL in a transplant patient. Other factors that may contribute to the development of secondary malignancy are older age, splenectomy, and splenic irradiation.

The majority of secondary NHL are intermediate or aggressive B-cell lymphomas. In the large series by the GHLG, a large proportion of secondary NHL in patients with Hodgkin’s disease were of the B-cell type, and the majority of those were diffuse large B-cell lymphoma (DLBCL). In accord with prior reports, a larger proportion than primary DLBCL presented with extranodal sites. Patients with DLBCL had a two-year freedom from treatment failure of 28% and overall survival of 35%. Patients with secondary T-cell lymphoma had a poor outcome with six of seven patients dying between three and 28 months after diagnosis. Thus, the prognosis of secondary DLBCL is worse than for primary disease, and the prognosis of secondary T-cell lymphoma is dismal.

The outcome was significantly influenced by the time of occurrence after Hodgkin’s disease and variables of the age-adjusted International Prognostic Factor Index (IPFI). Although the age adjusted IPFI was validated for primary NHL, patients in the high/high-intermediate risk group or low/ low-intermediate risk group had a two-year freedom from treatment failure of <10 % and 40% respectively. These high IPFI, poor-risk patients are generally not candidates for dose-intensified treatment as primary patients are, due to their prior therapy and compromised performance status. Therefore, they may be better candidates for palliative treatment.

Patients developing a secondary NHL within three months of finishing treatment for Hodgkin’s disease had an overall survival of 20% vs. 42% for those who developed the disease after 12 months. In terms of prognosis, patients with an early NHL recurrence are similar to patients with primary progressive Hodgkin’s disease. This poor prognosis could be due to an aggressive primary composite lymphoma that was not detected originally or treatment for Hodgkin’s disease may compromise further treatments. In this series, patients with DLBCL who were able to receive standard doxorubicin containing therapy, and were not limited by performance status or prior treatment, had a better prognosis.

The prognosis for secondary NHL patients who are younger and healthier with a low IPFI, like the one presented, is potentially good. On the other hand, patients with unfavorable histologies or high IPFI is quite poor. These patients might benefit from palliative treatment. The importance of adequate re-biopsy at the time of recurrence should not be underestimated, to avoid misdiagnosis and to allow accurate assessment of the incidence secondary lymphomas in the future. PET/CT may be helpful in selection of the optimal site for biopsy, with CT imaging generally useful in selecting the sites ideally suited for image-guided histologic sampling. Among the selected sites for biopsy based on CT findings, PET imaging can then help determine the site with higher standardized uptake values to increase the diagnostic yield and provide the highest histologic grade.

Munir Ghesani, MD, is Associate Clinical Professor of Radiology at Columbia University College of Physicians and Surgeons and Attending Radiologist at St. Luke’s-Roosevelt Hospital Center.

Carrie Wasserman, MD, is second year Hematology Oncology Fellow at St. Luke’s Roosevelt Hospital Center.

For more information:

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Enrici RM, et al: The risk of non-hodgkins lymphoma after Hodgkins disease, with special refernce to splenic treatment. Haematologica. 1998;83:636-644.

Rosenberg SA: The management of Hodgkin’s disease: Half a century of change. Annals of Oncology. 1996;7:555-560.

Rueffer U, et al. Non-hodgkins lymphoma after primary hodgkins disease in the German Hodgkins Lymphoma Study Group: incidence, treatment and prognosis. J Clin Oncol. 2001;19:2026-2032.

Swerdlow AJ et al. Risk of Second Malignancy after Hodgkins Disease in a Collaborative British Cohort: The Relation to Age at Treatment. J Clin Oncol. 2000;18:498 -509.

Tura S, et al: Splenectomy and the increasing risk of secondary acute leukemia in Hodgkins’s disease. J Clin Oncol. 1993;11:925-930.