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Core needle biopsy is a safe and accurate initial diagnostic procedure for suspected lymphoma
The American Journal of Surgery
Excisional biopsy is currently recommended for the analysis of lymphadenopathy suspicious for lymphoma. This study aims to evaluate the efficacy and safety of image-guided core needle biopsy (IGCNB) for the diagnosis of lymphoma using a standard protocol for tissue acquisition and analysis.
All IGCNBs from 2008 to 2014 performed under the study protocol were included in analysis. Demographics, pathology results, additional studies, and follow-up information were recorded.
Seventy-three IGCNBs were performed in 71 consecutive patients. Lymphoma was diagnosed in 37 patients (51%). All 37 patients (100%) were subtyped and treated based on IGCNB results. The remaining 36 IGCNBs in 34 patients did not have subsequent diagnosis of lymphoma in a mean follow-up of 15 months (range, 0 to 54 months). There were no complications.
IGCNB performed under a standard protocol is effective and safe and should be considered as an initial diagnostic tool for the evaluation of lymphadenopathy suspicious for lymphoma.
Keywords: Core biopsy, Core needle biopsy, Lymphoma, Diagnosis, Ultrasound, Ultrasound-guided biopsy.
Evaluation of lymphadenopathy requires tissue sampling for diagnosis. Excisional or incisional biopsies are currently recommended for the initial diagnosis of lymphoma, as these methods obtain sufficient tissue samples for pathologic evaluation of the lymph node. 1 Adequate assessment of the nodal architecture distinguishes lymphoma from benign reactive hyperplasia, metastatic carcinoma, infectious processes, and other lymphoproliferative disorders. 2 Prognosis and management of lymphoma is guided by the specific subtype. 3 Although open surgical biopsy readily provides sufficient tissue for pathologic assessment, disadvantages of this approach include the need for operating room time, possible need for general anesthesia, postoperative incisional pain, and procedural risks such as nerve and vascular injury, hematoma, seroma, and wound infection. 4
In recent years, image-guided core needle biopsy has been demonstrated to be effective in the diagnosis of lymphoma3, 5, 6, 7, 8, 9, 10, and 11and has been associated with fewer complications and procedural costs. 12 Despite emerging evidence supporting this approach, many pathologists and clinicians are reluctant to adopt image-guided core needle biopsy in the evaluation of lymphadenopathy, citing the need to assess lymph node architecture through excisional biopsy to reach an accurate diagnosis. 6
The aim of this study was to evaluate the efficacy and safety of image-guided core needle biopsy in the diagnostic workup of lymphadenopathy suspicious for lymphoma using a standard protocol for tissue acquisition and analysis.
Institutional review board approval was obtained before the initiation of this study. All patients that were referred to the outpatient general surgical service at Harbor-UCLA Medical Center between April 2008 and January 2014 for biopsy of cervical, axillary, or groin lymph nodes for suspected lymphoma were included in this study. Patients with mediastinal or intra-abdominal lymphadenopathy were excluded, as these areas were inaccessible to an ultrasound-guided core needle approach. Patients were also excluded if the lymphadenopathy was associated with a known primary malignancy other than lymphoma that accounted for the abnormal lymph nodes. Patients underwent a standard protocol of evaluation as detailed below.
Basic demographic information and pathology results were recorded for each patient, along with any history of other conditions (human immunodeficiency virus infection, rheumatoid arthritis, systemic lupus erythematosus) that could be associated with lymphadenopathy. The pathologic results of any subsequent excisional biopsies, when performed, were evaluated for discordance with image-guided core needle biopsy. The initiation of definitive therapy based on the results of the core needle biopsy was considered to be a successful image-guided core needle biopsy, whereas any alteration in therapy based on subsequent excisional biopsy was considered a failure. For patients whose core biopsies identified nonmalignant processes, clinic records were reviewed for evidence of further biopsies or other evidence of a subsequent lymphoma diagnosis. Procedural complications were also assessed for both image-guided core needle biopsy and excisional biopsies.
All needle biopsies were performed by a single surgeon (C.D.) under ultrasound guidance with a spring-loaded 14-ga Achieve core biopsy needle with coaxial introducer (CareFusion Corporation, San Diego, CA). Ultrasonography was used to select the largest and most superficial abnormal appearing node, and color Doppler was used to confirm the absence of large blood vessels in the planned biopsy trajectory. In the axilla, the needle was inserted at the anterior axillary line and fired posteriorly while the arm was positioned in a relaxed pose with the hand lying beside the patient's ear. In the cervical region, stab incisions were made medial to the lymph node and the needle fired laterally with the face positioned away and sternocleidomastoid muscles relaxed. In the groin, the needle was inserted lateral to the lymph node and fired medially.
The biopsy site was sterilized using a chlorhexidine and alcohol formulation and the skin, subcutaneous fat, and tissues surrounding the lymph node were anesthetized with 10 to 20 mL of .5% lidocaine with epinephrine. A stab incision was made with an 11 blade through the skin at the site of the biopsy to facilitate entry of the core needle. Under ultrasound guidance, 8 to 10 core specimens were obtained from the suspicious lymph node. If a pass was unsuccessful, it was not counted. Half of the samples were then placed on a nonadhesive gauze pad soaked in saline, and the remaining half were placed in 10% buffered formalin solution with zinc. Small Steri-Strips (3M Steri-Strips, St. Paul, MN) and a gauze pad were used as dressing. Pressure was held over the biopsy site by the patient for 5 minutes. All patients were instructed to resume normal activities the following day, avoiding submersion of the wound in a bathtub, pool, or Jacuzzi for 1 week.
Excisional biopsies were subsequently performed if requested by the hematology service.
Tissue specimens were sent immediately to the pathology department for processing. The cores sent in formalin were set aside for later use, whereas the 4 to 5 cores placed on a saline-soaked gauze were processed on receipt. Touch imprints were made and then stained with Diff-Quick and/or hematoxylin and eosin, and a portion was left unstained. Based on the initial evaluation of the adequacy of the specimen and assessment of cytologic morphology, flow cytometry would be performed if non-Hodgkin lymphoma remained in the differential diagnosis. Otherwise, standard processing by formalin fixation and paraffin embedding of tissue with an initial hematoxylin and eosin stain and subsequent directed immunohistochemical staining with or without ancillary molecular studies were performed. The initially submitted formalin-fixed cores were available, and in cases in which initial cytomorphologic analysis by touch imprints obviated the need or adequacy for workup by flow cytometry, additional formalin-fixed and paraffin-embedded tissue was available for histologic analysis.
A total of 73 ultrasound-guided core needle biopsies were performed in 71 consecutive patients after the standardized protocol. The mean age of the group was 43.1 years (range, 18 to 71 years) and 40 (56%) were female. The number of biopsies per site were as follows: 46 in the axilla, 19 in the groin, and 8 in the supraclavicular or cervical region. Two additional patients evaluated with ultrasound were determined to be unsuitable candidates for image-guided core needle biopsy because of the depth of the pathologic lymph nodes and/or proximity to large intervening vessels; these patients underwent excisional biopsies and were not included further in our analyses.
The diagnosis of lymphoma was made by image-guided core needle biopsy in 37 patients (51%; Table 1 ); lymphoma subtypes were determined for all 37 of these biopsies. Four of these patients were human immunodeficiency virus (HIV)-positive. Six biopsies occurred in patients with a history of lymphoma, with core needle biopsy confirming disease recurrence. All 37 patients diagnosed with lymphoma were definitively treated based on core needle biopsy results alone. None of these patients required further excisional biopsy for additional analysis before definitive treatment of lymphoma.
|Non-Hodgkin lymphoma||25 (68%)|
|Precursor B-cell subtypes||0|
|Mature B-cell subtypes||25 (68%)|
|Diffuse Large B-cell||6|
|T-cell rich large B-cell||2|
|Nodal marginal zone||2|
|Small B-cell (Waldenstrom)||1|
|Other B-cell ∗||1|
|Precursor T-cell subtypes||0|
|Mature T-cell subtypes||0|
|Hodgkin lymphoma||12 (32%)|
|Classic—not otherwise specified||3|
∗ Large B-cell lymphoma with differential including diffuse large B-cell, grade III follicular, and large B-cell lymphoma transformed from small B-cell lymphoma with plasmacytic differentiation.
Thirty-six of the image-guided core needle biopsies (49%) performed in 34 patients did not show evidence of lymphoma ( Table 2 ). Two patients were diagnosed with metastatic carcinoma (breast and lung, respectively) with occult primary malignancies. Two patients with HIV infection were diagnosed with Kaposi sarcoma. Four patients underwent subsequent excisional biopsy, and an absence of lymphoma was pathologically confirmed in all 4 cases. The remaining 26 patients had no subsequent diagnosis of lymphoma over a mean of 15.0 months (range, 0 to 54 months) of follow-up. Two patients who re-presented with persistent lymphadenopathy suspicious for lymphoma underwent repeat image-guided core needle biopsy at 4 and 6 months later, respectively, and both again revealed benign results. In one patient who died of complications relating to Castleman disease, image-guided core needle biopsy results were confirmed on autopsy. Of 30 patients with benign disease, 2 had active rheumatoid arthritis, 6 had systemic lupus erythematosus, and 8 had HIV infection. Among 2 patients in remission from lymphoma, core biopsies revealed no evidence of recurrence.
|Diagnosis||n (%)||Associated comorbidities|
|Benign reactive||16 (44)||4 SLE; 2 RA/SLE; 2 HIV; 1 Crohn|
|Castleman||4 (11)||2 HIV|
|Granulomatous lymphadenitis||2 (6)|
|Metastatic CA||4 (11)|
|Atypical lymphoid hyperplasia||9 (25)||2 HIV; 1 RA; 1 SLE|
HIV = human immunodeficiency virus; SLE = systemic lupus erythematosus; RA = rheumatoid arthritis.
No procedural complications were noted in the image-guided core needle biopsy and excisional biopsy groups.
The results of this study further confirm that image-guided core needle biopsy provides sufficient tissue for the diagnostic evaluation of lymphadenopathy suspicious for lymphoma when a standard protocol is used. All diagnoses of lymphoma were made on the initial core biopsy specimens, and definitive therapy was initiated based on these results. Further excisional biopsy was requested by the primary provider and/or consulting hematologist in 4 patients whose needle biopsy results were not consistent with lymphoma, and the final pathologic diagnosis was concordant to that of the initial image-guided core needle biopsy. The remaining patients with a negative core needle biopsy were found to be free of lymphoma more than 1 year after initial biopsy, suggesting that those core needle biopsy results were accurate in ruling out lymphoma.
Previous studies have shown a diagnostic accuracy of 76% to 92% for core needle biopsies and that 84% to 92% of patients were treated on the basis of core needle biopsy alone ( Table 3 ).13, 14, and 15We achieved higher rates in our series and attribute this to the use of a standardized protocol that required at least eight 14-ga cores of tissue to be sent for evaluation. We believe that sending this amount of tissue for analysis sufficiently decreased sampling errors and provided adequate tissue to evaluate lymph node architecture, achieving an accuracy approaching that of excisional biopsy.
|Study||Number of cases||Imaging modality||Accuracy (%)|
|Agid et al (2003) 3||267||CT||83|
|de Kerviler et al (2000) 5||212||Ultrasound/CT||88|
|Hu et al (2013) 6||60||Ultrasound/CT||92|
|de Larrinoa et al (2007) 7||102||Ultrasound||88|
|Li et al (2005) 8||80||CT||76|
|Balestreri et al (2005) 9||137||CT||87|
|Burke et al (2011) 10||83||Ultrasound||81|
|Vandervelde et al (2008) 11||103||Ultrasound/CT||78|
CT = computed tomography.
Furthermore, continued progression toward classification of hematopoietic and lymphoid tumors by immunophenotypic and molecular studies increasingly improves the accuracy of diagnosis, the ability to predict prognosis, and the direction of treatment with biologic chemotherapeutic agents. 16 These techniques shift the balance between diagnosis by traditional morphologic evaluation (which is optimally performed with an excised intact lymph node) and immunologic, and/or molecular evaluation (which can be performed with core biopsies or even fine needle aspirations) away from the need to perform excisional biopsies of whole lymph nodes. 12
Over time, there has been a progressive level of acceptance of the lymph node biopsy protocol used in this study by the hematopathologists at our institution. The hematopathologists acknowledge that the amount and size of the core samples obtained according to the protocol used in this study are typically of sufficient size to detect the transformation to diffuse large B-cell lymphoma from low-grade follicular lymphoma in most cases. However, they would still advise interpreting benign results with caution defaulting to excisional biopsy when the clinical picture is discordant. Furthermore, our hematopathologists would not consider submission of fewer or smaller (16- or 18-ga) cores adequate for definitive analysis.
An additional interesting observation is the lack of T-cell lymphoma diagnoses in this cohort, despite the fact T-cell lymphomas constitute up to 15% of all non-Hodgkin lymphoma diagnoses in the United States. One potential explanation for this may be that patients with T-cell lymphomas often present with extranodal disease and the disease process can be quite aggressive. Because this study involved patients with palpable peripheral lymph nodes in an outpatient setting, that subgroup of patients may have been missed.
Vacuum-assisted core needle devices have been touted as providing larger tissue cores without having to remove and re-insert the needle device for each throw. Conceptually, this may provide better diagnostic accuracy with even fewer procedural risks. However, our experience with the vacuum-assisted devices was that the vacuum disrupted the architecture of the spongy nodal tissue, providing suboptimal samples for the pathologist.
Image-guided core needle biopsy has several advantages over excisional biopsy. The incision is reduced to only a puncture site, and patients experience minimal postprocedure discomfort. Wound infections, seromas, hematomas, and nerve injuries are more frequently reported after excisional biopsy, and when they occur, may delay the initiation of chemotherapy in patients with malignancy. Image-guided core needle biopsy can be performed in the office or radiology suite, forgoing the need to schedule operating room time, particularly at hospitals whose operating room schedules are full and often interrupted by trauma and acute surgery services. General anesthesia and sedation may be avoided, as acetaminophen or ibuprofen are often sufficient to manage postprocedural discomfort. image-guided core needle biopsy takes no more than 15 minutes and can be billed at approximately $822. 12 Open excisional biopsy requires up to 1 hour of operating room time, with additional preoperative assessments and postoperative recovery room stays, resulting in bills by an anesthetist, hospital, and surgeon averaging around $3,529. 12
Excisional biopsy may still be indicated preferentially over image-guided core needle biopsy in certain situations. Two patients in our series were evaluated with ultrasound and deemed unsuitable for image-guided core needle biopsy because of the depth of the involved lymph nodes and the presence of large intervening vessels. Also, if pathology from image-guided core needle biopsy is nondiagnostic for lymphoma but significant clinical suspicion persists, excisional biopsy may be indicated. Also, core needle biopsies guided by computed tomography often cannot safely obtain as much histologic material as is called for in our protocol owing to intrathoracic or intra-abdominal nodal locations and smaller needle gauge sizes. The experience of our pathologists with such samples (often 18 g or smaller, with sometimes few cores) was that often performing flow cytometry was not possible without sacrificing the ability to perform usual workup on formalin-fixed and paraffin-embedded tissue, and the tissue was often suboptimal for the evaluation of lymph node architecture. Therefore, excisional biopsy of these nodes is probably still preferable.
Image-guided core needle biopsy, when performed in accordance with a well-developed protocol, has the potential to reduce operative expenses and patient morbidity without compromising diagnostic yield. Our experience supports the use of image-guided core needle biopsy as an initial diagnostic tool for the histologic evaluation of lymphadenopathy suspicious for lymphoma.
Dr. Richard J. Gray(Phoenix, AZ): In the era of less invasive diagnostic and therapeutic techniques, many of us as surgeons have been dismayed to have the diagnosis of suspected lymphoma not become less invasive, or in some cases become more invasive. You are kind of preaching to the choir here today. But at my institution, our hematopathologists continue to favor excisional biopsy, whereas previously we were even using fine needle aspiration because of their continued value of architectural morphology.
So I have 3 questions.
First, you detailed that 8- to 10-core biopsies were obtained for each patient, which is quite a few. So how do the patients tolerate the procedures themselves?
Second, a core biopsy works well to diagnose large B-cell lymphoma, as shown in this series. But at least with fewer cores than you obtained may not be enough to appreciate a mixed-pattern lymphoma, such as diffuse large B-cell lymphoma in a background of low-grade follicular lymphoma and vice versa, which may alter treatment. Were there any mixed-pattern patients detected and are your hematopathologists comfortable that this technique can do so?
Finally, there were no T-cell lymphomas in this cohort, which usually constitute about 10% of lymphomas. These tend to be a challenge without good architectural assessment because of the overlap with benign disorders and the lack of a simple way to show clonality by routine flow cytometry. So will this technique be adequate for these patients with T-cell lymphomas?
Dr. Brian Nguyen: The 8- to 10-core biopsies per patient were very well tolerated. We injected local anesthesia at the incision site and in the tract of the biopsy needle. A coaxial trocar was used for quick and easy reinsertion of the core needle. The biopsy procedure can be completed within 5 minutes and the patients rarely complained of pain during the procedure. In fact, these patients do not require narcotic pain medications for postprocedure pain control and are sent home on either acetaminophen or ibuprofen.
Regarding the second question, in speaking with the hematopathologists at our institution, the 14-ga cores that are obtained were adequately sized to see the transformation to diffuse large B-cell lymphoma for most cases. This is untrue for the smaller 18-ga cores. In any case, the hematopathologist would be able to quickly determine the adequacy and limitations of each specimen and ask for an excisional biopsy if necessary. Only 4 patients in our study required excisional biopsy, and in each case, a benign diagnosis was confirmed.
Finally, regarding the third question, I also noticed the paucity of T-cell diagnoses in our study. In speaking to the medical oncologists at our institution, one reason for this may be because many patients with T-cell lymphoma present with extranodal disease and the disease can be quite aggressive. Because our study involved patients with palpable peripheral lymph nodes seen in an outpatient setting, this might explain why patients with T-cell lymphoma were not included.
Dr. Charles Scoggins(Louisville, KY): I do not ever get these consults, the axillary or groin lymph nodes. I get these real Kentuckians that weigh about 300 pounds and have one big hot lymph node stuck behind the vena cava and the duodenum. None of my radiologists would do that for an anatomically challenging location for a lymph node. Do you have any experience with that approach? I would be very interested in using this type of technology for those really hard terribly complex-placed lymph nodes, but none of our guys would ever do it.
Dr. Brian Nguyen: I agree that these deep-seated lymph nodes present a challenge in obtaining tissue for diagnosis. Unfortunately, this study did not look at this patient population as we only biopsied patients that had superficially located lymph nodes that could be visualized using ultrasonography, namely the axillary, groin, and cervical regions. We feel that the reason our protocol was successful is because of the relatively large samples we obtained by using large 14-ga core needles and by making multiple passes. Therefore, our approach is likely not amenable to precariously located lymph nodes that are technically challenging to reach.
The point of this study was to illustrate that core needle biopsy can accurately diagnose lymphoma in many cases, but we recognize that there are still circumstances that would require more traditional approaches to diagnosis.
Dr. Martin McCarter(Aurora, CO): In the patients that did not have a cancer diagnosis, was the core biopsy able to provide any type of a benign diagnosis?
Dr. Brian Nguyen: Yes. I did not include that slide in my talk, but this was included in the manuscript. Table 2 illustrates the various benign diagnoses that were obtained in our study. They ranged from benign reactive disease, granulomatous lymphadenitis, and atypical lymphoid hyperplasia, to name a few.
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a Division of Surgical Oncology, Department of Surgery, Harbor-UCLA Medical Center, 1000 West Carson Box 25, Torrance, CA 90502, USA
b Department of Pathology, Harbor-UCLA Medical Center, Torrance, CA, USA
c Division of Hematology and Medical Oncology, Department of Medicine, Harbor-UCLA Medical Center, Torrance, CA, USA
∗ Corresponding author. Tel.: +1-310-222-6715; fax: +1-310-782-1562.
The authors declare no conflicts of interest.
This manuscript has been seen and approved by all the authors, and the material presented in this manuscript is previously unpublished.
© 2014 Elsevier Inc., All rights reserved.