Postgrad Med J (1992) 68, 643 - 647 © The Fellowship of Postgraduate Medicine, 1992

Magnetic resonance imaging for the assessment of residualmasses after treatment ofnon-Hodgkin's lymphomas

Carlos Montalb'an, Jose Luis Rodriguez-Garcia, Luis Mazairas',Inmaculada Ayala' and Jose Marcos-Robles'

Departments ofInternal Medicine and 'Radiology, Hospital Ramon y Cajal, Madrid, Spain

Summary: Eight patients with non-Hodgkin's lymphoma who were in clinical remission but showedresidual masses after therapy were examined with magnetic resonance imaging at 1.5 T at the end oftherapy, with the sequences TR/TE: 500/35, 500/70, 2000/35 and 2000/70. Residual masses were found inlymphoid areas (7), spleen (3) and kidney (1). In three patients, T2 showed high signal intensity. Diseaseprogressed in the following 1-3 months and active lymphoma was histologically identified. In the other fivepatients, T2 showed a very low signal intensity. One ofthem had a distant relapse in lymphoid areas but theremaining four patients are asymptomatic after a mean follow-up time of 13 months, suggesting that thelymphoma is cured and the mass inactive.We conclude that magnetic resonance imaging seems to distinguish active from non-active residual

masses after treatment of non-Hodgkin's lymphoma patients otherwise in clinical remission.

Introduction

Residual masses can occasionally be found aftercompletion of the initially planned treatment inHodgkin's disease (HD) and non-Hodgkin's lymph-oma (NHL), and their management is controver-sial. 1'2 Surgical resection and subsequent histologicalexamination is the most reliable method ofevaluating the viability of tumour in these residualmasses, but this procedure is not devoid of mor-bidity. As these masses may harbour no viabletumour cells, supplemental chemotherapy orradiotherapy should clearly not be given to theresidual mass without pathological confirmation.The usefulness of gallium scanning in treated

patients for distinguishing active tumour fromresidual, presumed fibrotic masses is limited.3Computed tomography (CT) and ultrasonographygive valuable information of tumour size anddistribution, but do not adequately reflect thenature of the mass (fibrosis, necrosis and inflam-matory components). Thus, conventional radio-logy and CT are not able to determine whether themass consists of active tumour or not.4'5 Fine-needle aspiration cytology of the mass providesdiagnosis in some patients, but there are falsenegative results.6

Previous reports have shown promising resultswith magnetic resonance imaging (MRI) in differ-entiating these conditions.7'8 The present studyanalysed the experience in treated patients withaggressive lymphoma who presented a radiologic-ally detectable residual mass while otherwiseappearing in a clinical complete remission (CR).We sought to correlate the residual masses and theclinical course with the findings in MRI in order todetermine better whether MRI can be used todifferentiate active from non-active disease.

Patients and methods

We studied eight patients with NHL who aftertreatment achieved a clinical remission, but inwhom a residual mass ofunknown significance wasfound on image studies. Patients were three menand five women (aged 22-67 years) (seven withhigh grade and the other with an intermediategrade NHL). Seven patients received only chemo-therapy (MACOP-B: methotrexate with leucovorinrescue, doxorubicin, cyclophosphamide, vincris-tine, prednisone and bleomycin), and the involvednodes of another patients were treated only withradiation therapy. All patients in this study com-pleted planned treatment and showed no evidenceof persisting disease at restaging but the residualmasses had been re-evaluated at the end of therapyboth clinically by imaging with X-ray, ultrasoundand CT scan. Persistent residual mass was defined

Correspondence: Carlos Montalban, M.D., Servicio deMedicina Interna, Hospital Ram6n y Cajal, Carretera deColmenar Km.9,100, 28034-Madrid, Spain.Accepted: 14 January 1992

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RESIDUAL MASSES AFTER NON-HODGKIN'S LYMPHOMA 645

as any mass that being present before therapy, hadinitially responded to combination chemotherapyand/or radiation therapy and then remained stablein size after completed treatment. Masses wereconsidered as bulky if they measured more than10 cm in at least one diameter.MRI was performed with a superconductive

equipment (Siemens Magnetom, 1.5 T, softwareNumaris, version B1). Double echo, multi-slice,spin-echo techniques were used with repetitiontimes (TR) of 500 and 2000 milliseconds and echotimes (TE) of35 and 70 milliseconds. In all patients,T, and T2-weighted images were obtained in thetransverse, axial and/or coronal planes. Contig-uous, 10 mm sections were obtained in the 8patients. A 256 x 256 matrix and a field of view of450 were used in all cases. Photography, window-ing and levelling of the images were automaticallyselected so that signal intensity could not bealtered.MRI analysis was made by two independent

radiologists without knowledge of the final patho-logical and/or clinical diagnosis. Signal intensity ofthe lesion at the region of interest was evaluatedand compared with striated muscle and adiposetissue signals.'

Figure 1 Patient 7. Transverse slices of the thorax. (A)Enlarged lymph nodes in the mediastinum (arrows) of apatient with non-Hodgkin's lymphoma having a lowimage intensity in T, (SE 500/35). (B) SE 2,000/70. Thesame mediastinal mass with high image intensity on T2suggesting active disease.

Results

Table I shows clinical characteristics, treatmentresults and outcome of the patients. The totalfollow-up period of patients varied between oneand 11 months (average, 7 months) after MRI.

In three patients in whom large masses persisted,T2-weighted images showed higher signal intensitythan on T1: mediastinum in one case (case 8),mediastinum (Figure 1), spleen and retroperi-toneum in another case (case 7) and pelvis andabdomen (Figure 2) in the remainder (case 6).Signal intensity was similar to that of fat. Diseaseprogressed in the following 1-3 months and activelymphoma was pathologically documented onperipheral lymph nodes (two patients, Cases 7 and8) and at laparotomy (one patient, Case 6, aftergenital bleeding). In the other five patients, on T,-and T2-weighted images, the lesions had a lowsignal intensity, similar to that ofmuscle (Figures 3and 4, Cases 1 and 4). One of them (Case 5) had adistant relapse in lymphoid areas (cervical andsupraclavicular areas) while residual mass withinthe kidney remained stable. The remaining fourpatients are asymptomatic for a mean of 13 months(range 9-15) after diagnosis. On follow-up, CT

Figure 2 Patient I. MRI of a patient with NHL thatshows a low image intensity T1-weighted image at thelymph nodes of the spleen hilium (arrows) in both T1 (A)and T2 (B) image intensities (non-active disease).

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646 C. MONTALBAN et al.

Figure 3 Patient 6. (A) A large retroperitoneal mass(arrows) in a patient with NHL (T,). (B) The mass showsa high-signal intensity on T2 (arrow) suggesting activedisease.

showed decrease in the size of the masses in twoexplored patients.

Discussion

A careful review of radiographs and CT scans ofthe chest and abdomen of patients with Hodgkin'sdisease show a high rate of residual abnormalities.The incidence is higher in those who present bulkymasses, varying between 64% up to 88%.9 In NHL,there are few references to residual masses provedto be non-malignant after surgery. However, whenaggressive NHL is treated with third-generationchemotherapy regimens, the high incidence ofpersistent residual masses in patients in otherwisegood clinical remission is an emerging problem.They have been found in 14-40% of the cases,appearing mainly in lymphoid areas with initialbulky disease.'0'3 A few reports describe thehistopathology of residual masses in the mediasti-num and abdomen as a mixture of fibrosis, necrosisand inflammatory lesions. The proportion of differ-ent components in the masses are variable with agradual increase of fibrosis after therapy.7 Fibrotictissue has similar MRI characteristics as muscle

Figure 4 Patient 4. (A) T,-weighted image (500/35)showing a hypointense mass (arrow) in the spleen similarto that of muscle in a patient with non-Hodgkin'slymphoma. (B) T2 (2,000/70) showing the intrasplenicmass (arrow) with a very low signal intensity (non-activedisease).

and is displayed with low intensity in both T,- andT2-weighted images.5 We have previously reportedtwo patients who were treated with intensivechemotherapy and in whom large isolated intra-parenchymal masses (spleen and kidney) werefound on CT scan after clinical remission, withouttumoral infiltration.'4 In other series, viable lym-phoma in a residual mass has been found only in5% of patients.'5

Recent studies with MRI suggest that no signific-ant difference is discerned in the MRI parametersbetween lymph nodes with low- or high-gradeNHL'6-'8 and that residual masses after treatmentof non-Hodgkin's lymphomas might be distin-guished from active lymphoma by the lower signalintensity of fibrosis on T2-weighted images.'9Evaluation of these residual masses by MRI inNHL patients has been referred to previously.'9-21The data presented here show that two distinc-

tive patterns on MRI, differentiating active frominactive lesions, seem to emerge when residualmasses in patients with NHL in clinical remissionare studied. When residual masses show a lowsignal intensity similar to that of muscle with all

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RESIDUAL MASSES AFTER NON-HODGKIN'S LYMPHOMA 647

pulse sequences, the masses are probably com-posed of fibrotic material, as we have alreadyshown.'4 Residual masses from all patients whorelapsed showed a low signal intensity on T,-weighted images and high signal intensity onT2-weighted images similar to that of fat, suggest-

ing that the masses had been composed by activelymphoid tissue. MRI findings seem to be useful inthe evaluation and management of residual massesoccurring after remission in NHL, avoiding furtherunneccessary therapy in already cured patients.

References

1. Canellos, G.P. Residual mass in lymphoma may not beresidual disease. J Clin Oncol 1988, 6: 931-933.

2. Uematsu, M., Kondo, M., Tsutsu, T. et al. Residual masseson follow-up computed tomography in patients with media-stinal non-Hodgkin's lymphoma. Clin Radiol 1989, 40:244-247.

3. Peylan-Ramu, N., Haddy, T.B., Jones, E. et al. Highfrequency of benign mediastinal uptake of gallium-67 aftercompletion chemotherapy in children with high-grade non-Hodgkin's lymphoma. J Clin Oncol 1989, 7: 1800- 1806.

4. Wernecke, K., Vassallo, P., Hoffman, G. et al. Value ofsonography in monitoring the therapeutic response ofmedia-stinal lymphoma: comparison with chest radiography andCT. AJR 1991, 156: 265-272.

5. Nyman, R., Rehn, S., Glimelius, B. et al. Magnetic resonanceimaging for assessment of treatment effects in mediastinalHodgkin's disease. Acta Radiol 1987, 28: 145-151.

6. Zornoza, J., Cabanillas, F.F., Altoff, T.M. et al. Per-cutaneous needle biopsy in abdominal lymphoma. AJR 1981,136: 97-103.

7. Nyman, R., Rehn, S., Glimelius, B. et al. Residual media-stinal masses in Hodgkin's disease: prediction of size withMR imaging. Radiology 1989, 170: 435-440.

8. North, L.B., Fuller, L.M., Sullivan, J.A. & Hagemeister, F.B.Regression of mediastinal Hodgkin's disease after therapy:evaluation of the time interval. Radiology 1987, 164:599-602.

9. Radford, J.A., Cowan, R.A., Flanagan, M. et al. Thesignificance of residual mediastinal abnormality on the chestradiograph following treatment for Hodgkin's disease. J ClinOncol 1988, 6: 940-946.

10. Tredaniel, J., Lepage, E., Frija, J. et al. Les masses residuellesapres chimiotherapie des lymphomes non hodgkinienes.Nouv Rev Fr Hematol 1988, 30: 75-77.

11. Stewart, F.M., Williamson, B.R., Innes, D. & Hess, Ch.E.Residual tumor masses following treatment for advancedhistiocytic lymphoma. Cancer 1985, 55: 620-623.

12. Lewis, E., Bernardino, M.E., Salvador, P.G. et al. Post-therapy CT-detected mass in lymphoma patients. Is it viabletissue? J Comput Assist Tomogr 1982, 6: 792- 795.

13. Montalban, C., Rodriguez-Garcia, J.L., Marcos-Robles, J. etal. Tratamiento de linfomas no Hodgkin de celula grande conprotocolo MACOP-B. Med Clin (Barc) 1991, 97: 521-525.

14. Montalban, C., Arechaga, S., Calleja, J.L. et al. Masasresiduales no tumorales intraparenquimatosas despues deltratamiento de linfomas no hodgkinianos de celula grandecon quimioterapia intensiva. Med Clin (Barc) 1990, 94:461-464.

15. Surbone, A., Longo, D.L., DeVita, V.T. et al. Residualabdominal masses in aggressive non-Hodgkin's lymphomaafter combination chemotherapy. J Clin Oncol 1988, 6:1832-1837.

16. Nyman, R., Rhen, S., Glimelius, B. et al. An attempt tocharacterize malignant lymphoma in spleen, liver and lymphnodes with magnetic resonance imaging. Acta Radiol 1987,28: 527-533.

17. Rehn, S., Nyman, R., Glimelius, B. et al. Non-Hodgkinlymphoma: predicting prognostic grade with MR imaging.Radiology 1990, 176: 249-253.

18. Negendank, W.G., Al-Katib, A.M., Karanes, Ch. & Smith,M.R. Lymphomas: MR imaging contrast characteristics withclinical-pathologic correlations. Radiology 1990, 177: 209-216.

19. Zerhoumi, E.A., Fishman, E.K, Jones, R. et al. MR imagingof the "sterilized" lymphoma (abstract). Radiology 1986, 161:207.

20. Markisz, J.A., Kovosky, P.A., Knowles, J.R. et al. MRimaging evaluation of response to therapy in lymphomapatients (abstract). Radiology 1988, 169: 175.

21. Drace, J., Carlsen, S. & Chang, P. MR imaging strategies fordifferentiating benign residual versus active or recurrenttissue in lymphoma (abstract). Radiology 1989, 173: 273.

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Postgrad Med J (1993) 69, 251 - 252 i The Fellowship of Postgraduate Medicine, 1993

Erratum

Re: Magnetic resonance imaging for the assessmentofresidual masses after treatment ofnon-Hodgkin'slymphomas. C. Montalban, J.L. Rodriguez-Garcia,L. Mazairas, I. Ayala and J. Marcos-Robles.Postgraduate Medical Journal 1992 68: 643-647.

The Editorial Office and the authors apologisefor incorrectly labelling the illustrations to theabove article. We re-publish the illustrationsbelow, with the correct legends.

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Figure 1 Patient 7. Transverse slices of the thorax. (A)Enlarged lymph nodes in the mediastinum (arrows) of apatient with non-Hodgkin's lymphoma having a lowimage intensity in T1 (SE 500/35)X(B) SE 2,000/70. Thesame mediastinal mass with high image intensity on T'2suggesting active disease

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Figure 2 Patient 1. MRI of a patient with NHL thatshows a low image intensity T1-weighted image at thelymph nodes of the spleen hilium (arrows) in both T. (A)and T2 (B) image intensities (non-active disease).

252 ERRATUM

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Figure 3 Patient 6. (A) A large retroperitoneal mass(arrows) in a patient with NHL (T1). (B) The mass showsa high-signal intensity on T2 (arrow) suggesting activedisease.

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Figure 4 Patient 4. (A) T1-weighted image (500/35)showing a hypointense mass (arrow) in the spleen similarto that of muscle in a patient with non-Hodgkin'slymphoma. (B) T2 (2,000/70) showing the intrasplenicmass (arrow) with a very low signal intensity (non-activedisease).