Departments of 1 Hematology, 2 Radiology, 3 Pathology and 4 Social Medicine, Hadassah Medical Center, Jerusalem, Israel
Received 11 March 2003; revised 4 May 2003; accepted 22 May 2003
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Abstract |
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Histological transformation is a common clinical event in patients with lymphoproliferative diseases, often requiring a modification in therapy. Minimally invasive biopsy techniques have been used for initial diagnosis of these disorders but their role has not been systematically evaluated in disease progression. The purpose of this study was to evaluate the yield of computed tomography (CT)-guided core needle biopsy in patients with lymphoproliferative disorders and suspected disease progression.
Patients and methods:
We performed a retrospective analysis of the records of patients with known lymphoproliferative disorders who underwent CT-guided core needle biopsy during the course of their disease, between 1990 and 2002.
Results:
A total of 130 patients with lymphoproliferative disorders (91 patients with non-Hodgkins lymphoma, 21 with Hodgkins disease, 10 with chronic lymphocytic leukemia, six with combined malignancies and two with Castlemans disease) underwent CT-guided core needle biopsy 4.7 ± 5.1 (standard deviation) (range 040) years after initial diagnosis. The procedure was diagnostic in 98 cases (75.4%). In 22 patients (17%) a subsequent open biopsy was performed, and in 10 (7.6%) the final diagnosis remained unconfirmed. Histological transformation was found in 20 cases (15.4%), of which 19 were suspected clinically. A new diagnosis (malignant and non-malignant) was apparent in 18 cases (13.9%) and relapsed or ongoing evidence of the original disease was found in 82 (63%).
Conclusions:
CT-guided core needle biopsy is a reliable procedure in patients with suspected histological transformation of lymphoproliferative disorders, and should be used as the initial tool for pathological re-evaluation.
Key words: core needle biopsy, diagnosis, image-guided, lymphoproliferative disorders, transformation
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Introduction |
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Patients and methods |
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Biopsy technique
The biopsy technique has been previously described in detail [3].
Histological preparations
Histological results were based on the interpretation of biopsy material prepared by the standard techniques used in the pathology department of our hospital. Immunoperoxidase staining was performed in all cases on 5-µm sections of formalin-fixed paraffin-embedded tissue of the biopsies. The histological appearance on the hematoxylin and eosin-stained slides dictated the choice of immunohistochemical stains. When lymphoma was suspected, an extended panel of immunohistochemical stains was used, which included leukocyte-common antigen (LCA), CD20 (L26), CD3, CD45RO, CD8, CD4, LN1 (CDw75), LN2 (CD74), CD30 (Ki-1, Ber-H2), CD15 (LeuM1) and Tdt. All antibodies were obtained from Dako (Glostrup, Denmark), except for cytokeratin K-18 (Sigma, St Louis, MO, USA) and LN1, LN2 and UCHL-1 (Zymed, San Francisco, CA, USA) [2].
Statistical analysis
We calculated the number and per cent of patient characteristics. Since there were no a priori hypotheses tested, we do not report P values. We calculated time from initial diagnosis to re-evaluation using the core biopsy procedure and time from reevaluation to death using the Lifetest procedure in SAS (Cary, NC, USA). In the latter analysis censoring occurred at date of last follow-up.
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Results |
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The final histological diagnoses after CT-guided core needle biopsy included relapse of original disease in 55 patients (42.3%), ongoing disease without change in histology in 27 (20.7%), histological transformation to a higher grade of disease in 20 (15.4%), new malignant disease in 12 (9.3%), new non-malignant disorder in six (4.6%) and insufficient tissue for diagnosis in 10 (7.7%) (Figure 1). New malignant diseases were mostly carcinomas. New non-malignant diseases were sarcoidosis, mediastinal fibrosis, bronchiolitis obliterans organizing pneumonia, progressive transformation of germinal center, cirrhosis and reactive lymph node. The biopsy in these cases was performed because of clinical suspicion of relapse in five cases and clinical progression in one case.
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There were no reported complications after the procedure.
At the time of this review, 71 of 130 patients (54.6%) have died, with median time to death from second biopsy of 32 months (range 1146). The time from second biopsy to death is shown in Figure 2. Of 20 patients who had a histological transformation of their lymphoma, six (30%) were alive 15 years after diagnosis. The remaining 14 patients have died, with a median survival of 6 months.
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Discussion |
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Fine-needle aspiration was the first minimally invasive tool used for biopsy [11]. This technique had the advantage of differentiating benign from malignant masses, although it usually could not provide the precise diagnosis or the exact subtype of lymphoma. Core needle biopsy is now commonly used for histological diagnosis in patients with suspected lymphoma, and several reports have confirmed the reliability and safety of this procedure [17]. CT guidance is the most commonly used modality in our institution as it has the advantage of permitting biopsies of deep and small masses. The core biopsy can be taken from peripheral nodes [5], but its major advantage is in cases of deep tissue or organ involvement, where general anesthesia can be avoided. Both safety and yield have been reported to be high in biopsies taken from the mediastinum [4, 5], the abdomen and the retroperitoneum [1, 5] and other organs [1, 2]. Previous series included mainly patients at presentation of their disease, or a combination of patients at diagnosis and follow-up. The largest previous study of CT-guided core needle biopsy performed for reevaluation of lymphoma included 92 patients with suspected recurrence or progression who underwent 109 procedures [1]. These procedures yielded precise diagnosis of lymphoma in 89% of cases.
In the present series, we describe the clinical characteristics and the yield of CT-guided core needle biopsy in a larger group of patients with a history of lymphoproliferative disease. The diagnostic yield of the procedure in this study was 75.4%, slightly less than that reported by De Kerviler and colleagues [1]. There are no data from which to evaluate the reasons for this difference.
The major indication for reevaluation was suspected recurrence, and the second most common reason for biopsy was suspected histological transformation (Table 2). Indeed, most cases had no change in the histological type of lymphoma, having either relapse (42.3%) or ongoing disease (21%). There was a tendency to over-suspect disease transformation (only 30.7% of patients in this group had histological progression), with the sensitivity of clinical suspicion being 94.1% and the positive predictive value 30%. Only one patient had evidence of histological transformation when it was not clinically suspected. A new diagnosis entity was found in a total of 16 patients (12.4%), either malignant or non-malignant, again emphasizing the need for accurate diagnosis for further therapeutic decisions.
The need for pathological evaluation may in itself be a poor prognostic sign, with a median survival of 32 months for all patients who underwent the procedure. An especially short survival was noted in patients with histological transformation.
We conclude that image-guided core biopsy should be considered as the initial tool for the pathological reevaluation of lymphoproliferative disorders during follow-up due to its high yield (75.4%) and lack of complications. This minimally invasive technique can serve as an important guide for clinical decision-making whenever there is a suspicion of clinical progression, since histological transformation may require a modification of the treatment regimen, and since new, previously unsuspected, diagnoses are not uncommon.
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Footnotes |
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References |
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