Abstract
Objective:
To evaluate the safety and utility of core needle biopsy (CNB) for diagnosis of salivary gland lymphoma in Sjögren’s syndrome (SS).
Methods:
We analyzed data from consecutive SS patients who underwent ultrasound-guided major salivary gland CNB for lymphoma diagnosis and determined whether CNB yielded an actionable diagnosis without need for further intervention.
Results:
CNB were performed in 24 patients to evaluate discrete parotid (n=6) or submandibular (n=2) gland masses or diffuse enlargement (n=16; 15 parotid). One patient had 3 CNB of the same mass. Of the 26 CNB, 24 included flow cytometry using CNB and/or fine needle aspirate material and 14 targeted sonographically-identified focal lesions. No patient reported complications. In the 23 patients with one CNB, final diagnoses were marginal zone lymphoma of mucosa-associated lymphoid tissue (MALT; n=6), atypical lymphoid infiltration (n=3), benign lymphoepithelial sialadenitis (BLEL, n=9), normal gland tissue (n=4), and lymphoepithelial cyst (n=1). In the patient with serial CNB, the initial one without flow cytometry was benign but the next two showed atypical lymphoid infiltration. Monoclonal lymphoid infiltration was detected in 12 patients: six with MALT lymphoma, three benign and three atypical lymphoid infiltration. Of the latter three, one was treated with rituximab and two with expectant observation. The diagnosis changed from atypical lymphoid infiltration to MALT lymphoma in one patient following biopsy of inguinal adenopathy 6 months post-CNB. CNB provided actionable results and avoided open excisional biopsies in all cases.
Conclusion:
CNB is safe and useful in the evaluation of suspected salivary gland lymphoma in SS.
Ultrasound-guided core needle biopsy (CNB) is an important technique in the diagnosis of salivary gland masses (1). The procedure utilizes ultrasonography to guide the placement of a hand-held spring-loaded device to obtain core samples of a salivary gland lesion. In contrast to fine needle aspiration (FNA) cytology, it provides biopsies with preserved architecture that are amenable to immunohistochemical staining and can be used for staging and grading of neoplasms. This is particularly relevant to the diagnosis of lymphoma, where analysis of tissue histopathology is essential. In a meta-analysis, sensitivity and specificity for the diagnosis of malignant salivary gland lesions were estimated to be 96% and 100% respectively (1). A portion of the tissue can also be used for flow cytometry, thereby increasing the diagnostic yield in the evaluation of lymphoma (2). CNB has a superior diagnostic yield over FNA alone and is associated with few complications (1).
Patients with Sjögren’s syndrome (SS) have a 6 to 18-fold increased risk of non-Hodgkin lymphoma, particularly marginal zone lymphoma involving the parotid gland (3). The development of a salivary gland mass or persistent enlargement can be a sign of development of lymphoma. FNA can yield material for flow cytometry and the detection of a monoclonal B cell population, but this is not sufficient for the diagnosis of lymphoma. A larger sample is required for histopathology, including immunohistochemical staining. While excisional biopsies are preferred for lymphoma diagnosis, the trend has been to employ CNB whenever possible (4). Identification of salivary gland lymphoma with CNB avoids surgical resection, most often superficial parotidectomy, with its attendant risks.
We sought to evaluate the safety and utility of CNB in the diagnostic evaluation of salivary gland lymphoma in patients with SS.
PATIENTS AND METHODS:
Patients.
We identified all SS patients who underwent ultrasound-guided CNB of either the parotid or submandibular gland as part of a diagnostic evaluation for salivary gland lymphoma in the Johns Hopkins Sjögren’s Syndrome Center between 7/2009–8/2018. Clinical data on patients seen in the Center are maintained in a computer database, under a protocol approved by the Johns Hopkins Institutional Review Board. SS was defined by fulfillment of the ACR/EULAR classification criteria (5). None of the patients had a prior history of lymphoma.
Technique.
CNB were performed by radiologists with extensive experience in ultrasonography. Biopsies were typically obtained with an 18 gauge INRAD core biopsy needle (INRAD Inc, Grand Rapids, MI). In order to accurately place the device either within the glandular parenchyma or within a focal intraglandular lesion, the CNB was performed under real-time ultrasound guidance, using an 18- or 12-mHz linear transducer (Figure 1). Typically two passes were made in the same or very nearly the same location using the same core biopsy device. One core was placed in formalin for standard surgical pathology and the other was placed in culture medium for flow cytometry. For parotid gland biopsy, the patient was placed in the decubitus position. Entry site was typically from the posterior glandular border slightly caudal to the level of attachment of the ear lobe. Local infiltration anesthesia was employed in the skin and subcutaneous fat up to the surface of the gland but not within the gland. A small skin incision was made with a scalpel. The biopsy needle was directed from posterior to anterior, with care taken to keep the needle path located superficially within the gland parenchyma and the entire trough of the needle within parenchyma. For submandibular gland biopsy, the procedure was similar but with the patient in an oblique position, head mildly extended and rotated away from the operator. The approach was also from posterior to anterior. In the case of focal lesions, care was taken to minimize traversal of normal parotid parenchyma and to proceed from a posterior to anterior approach.
Figure 1:
Parotid gland core needle biopsy with ultrasound guidance. A, The biopsy needle is directed from posterior to anterior, with care taken to keep the needle path located superficially within the gland parenchyma and the entire trough of the needle within parenchyma; B, Patient is in right side down decubitus position with head on the right side of the photograph as biopsy needle approaches left parotid gland from its posterior aspect. The biopsy is guided by real-time ultrasound, under aseptic conditions; C, Both the operator and the assisting sonographer monitor the path of the needle on the ultrasound screen.
FNA was routinely included in the same procedure as the CNB and targeted the same lesion or glandular location as the CNB. FNA and CNB material were routinely submitted together for flow cytometry.
Patients were contacted by telephone by radiology department nurses on the day following the biopsy to determine if any symptoms suggesting complications were present. They were queried as to whether swelling, pain, bleeding, or facial changes had taken place.
Pathologic interpretation:
All biopsies with suspicious lymphoid infiltrates were reviewed by hematopathologists, and a final diagnosis was achieved through integration of histopathology, immunohistochemistry, and flow cytometry and/or molecular studies.
Data analysis:
The utility of CNB was judged by whether it yielded an actionable diagnosis, allowing for either initiation of treatment or final determination of benignity requiring no further intervention (6).
RESULTS:
Twenty-four SS patients underwent ultrasound-guided CNB to evaluate for possible salivary gland lymphoma (Table). The cohort included 22 women and two men with a median age of 53 years (range, 18–74). Two patients had secondary SS. Additional phenotypic features are listed in the Supplemental Table. The salivary gland abnormalities were bilateral parotid (n=13), unilateral parotid (n=2) or submandibular (n=1) gland enlargement, and discrete masses in the parotid (n=6) or submandibular (n=2) glands. There were 26 procedures in total, with one patient (#16) undergoing three CNB of the same mass over a 17-month period. The parotid was biopsied in 23 and the submandibular gland in three. The 26 procedures involved CNB alone (n=5) or with FNA (n=21). Sampling was restricted to one gland only, except for two patients (#4, 19) who underwent CNB of both parotid glands. The average number of CNB per gland per procedure was 2.29 ± 0.66 (range 1–4). Cyst aspiration was performed during four procedures. Biopsy material was sent for flow cytometry in 24 procedures; this consisted of CNB specimens alone in five procedures or combined with FNA material in 21. None of the patients reported complications one day post-procedure or during longitudinal follow-up in our center [median (range) duration=595 days (1–1403)].
Table:
Clinical abnormality, biopsy site, biopsy interpretation, and action taken based on biopsy results
| Case # | Age, Sex | Clinical concern | Site of biopsy | Random sampling or targeted focal lesion | Type of biopsy | Histology | Monoclonal population on flow cytometry | Final clinical impression/action taken |
|---|---|---|---|---|---|---|---|---|
| 1 | 56 M | Enlarged PG (R&L) | PG (R) | Random | Core only | No lymphoid infiltrate | Benign; no intervention | |
| 2 | 43 F | Enlarged PG (R&L) | PG (L) | Random | Core only | No lymphoid infiltrate | Mostly debris | Benign; no intervention |
| 3 | 56 F | Enlarged PG (R&L) | PG (L) | Random | Core & FNA | No lymphoid infiltrate | None | Benign; no intervention |
| 4 | 58 F | Enlarged PG (R&L) | PG (R&L) | Random | Core & FNA | LE cyst (right); FLS (left) | None | Benign; no intervention |
| 5 | 58 F | Enlarged PG (R&L) | PG (L) | Random | Core & FNA | Benign LES | B cell (2%) | Benign; no f/u available |
| 6 | 33 F | Enlarged PG (R&L) | PG (R) | Random | Core & FNA | Benign LES | B cell (12%) | Benign; no intervention |
| 7 | 39 F | PG mass (R) | PG (R) | 2 solid/cystic masses | Core & FNA | No lymphoid infiltrate | Mostly debris | Benign; no intervention |
| 8 | 36 F | Enlarged PG (R&L) | PG (R) | Random | Core & FNA | FLS | None | Benign; rituximab |
| 9 | 53 F | Enlarged PG (R) | PG (R) | Random | Core only | FLS | Benign; no intervention | |
| 10 | 74 F | Enlarged SMG on US (L) | SMG (L) | Random | Core & FNA | FLS | None | Benign; no intervention |
| 11 | 59 F | SMG mass (R) | SMG (R) | Hypo-echoic mass | Core & FNA | FLS | None | Benign; no intervention |
| 12 | 59 F | Enlarged PG (R) | PG (right) | Abnormal intra-PG LN | Core & FNA | FLS | None | Benign; no intervention |
| 13 | 50 F | PG mass (R) | PG (right) | Grouped hypo-echoic lesions | Core & FNA | FLS | None | Benign; no intervention |
| 14 | 18 F | Enlarged PG (R&L) | PG (left) | Random | Core only | FLS | None | Benign; RTX |
| 15 | 62 F | PG mass (R) | PG (right) | Two cystic masses | Core & FNA | FLS (mostly T-cell) | Atypical B cell (4%), lacking surface light chains | Benign; RTX |
| 16a | 53 M | PG mass (R) | PG (right) | Solid/cystic mass | Core & FNA | FLS | LPD; repeat biopsy‡ | |
| 16b | 53 M | PG mass (R) | PG (right) | Solid/ cystic mass | Core only | Atypical lymphoid infiltrate | B cell | LPD; expectant observation |
| 16c | 54 M | PG mass (R) | PG (right) | Abnormal intra-PG LN | Core & FNA | FLS | B cell (11%) | LPD; expectant observation |
| 17 | 66 F | PG mass (R) | PG (right) | Grouped hypo-echoic lesions | Core & FNA | Atypical lymphoid infiltrate | None* | LPD; RTX |
| 18 | 50 F | Enlarged PG (R&L) | PG (left) | Abnormal intra-PG LN | Core & FNA | Atypical lymphoid infiltrate | B cell (17%)* | LPD; expectant observation† |
| 19 | 59 F | Enlarged PG (R&L) | PG (bilateral) | Random | Core & FNA | MALT lymphoma | Suspicious B cell | Lymphoma; RTX |
| 20 | 47 F | Enlarged PG (R&L) | PG (right) | Random | Core & FNA | MALT lymphoma/ plasmacytic differen-tiation | Plasma-cytic (26%) | Lymphoma; RTX |
| 21 | 52 F | PG mass (L) | PG (left) | Grouped hypo-echoic lesions | Core & FNA | MALT lymphoma | B cell (20%) | Lymphoma; RTX |
| 22 | 31 F | Enlarged PG (R&L) | PG (left) | Solid/cystic mass | Core & FNA | MALT lymphoma | B cell | Lymphoma; RTX |
| 23 | 58 F | SMG mass (R) | SMG (right) | Multi-lobulated solid mass | Core & FNA | MALT lymphoma | B cell (10%) | Lymphoma; RTX |
| 24 | 46 F | Enlarged PG (R&L) | PG (right) | Grouped hypo-echoic lesions | Core & FNA | MALT lymphoma | B cell (41%) | Lymphoma; RTX |
Abbreviations: FLS: focal lymphocytic sialadenitis; FNA: fine needle aspirate; L: left; LE: lymphoepithelial; LES: lymphoepithelial sialadenitis; LPD: lymphoproliferative disorder, but insufficient evidence to classify as lymphoma; LN: lymph node; MALT: mucosa-associated lymphoid tissue; PG: parotid gland; R: right; RTX: rituximab; SMG: submandibular gland
IgH gene rearrangement studies documented a B-cell clonal population
Diagnosis of MALT lymphoma established 6 months later, via biopsy of new inguinal lymphadenopathy
Flow cytometry had shown a monoclonal B cell population on an FNA of the mass one month earlier, prompting continued concern for a possible lymphoproliferative disorder
Small hypoechoic ovoid lesions, a characteristic ultrasonographic abnormality of SS, were present in the parotid gland parenchyma of 18 of the patients (7). In 16 of these 18 patients, the hypoechoic lesions in composite occupied more than 50% of the glandular volume, corresponding to at least grade 2 severity on the OMERACT scoring system (7).
Representative (i.e. random) sampling of glandular tissue was performed in 12 patients, opting for the salivary gland that was most enlarged. Targeted sampling of discrete sonographic lesions was performed in 12 patients. The targets included clinically palpable masses with a corresponding sonographic hypoechoic solid or cystic mass lesion(s) (n=6; patients #11, 13, 15, 17, 21, 23) or partly solid/partly cystic masses (n=2; #7, 16) and non-palpable sonographically-defined lesions, including a mass-like grouping of hypoechoic lesions (n=1, #24) and a partly solid/partly cystic mass (n=1; #22) and intraparotid lymph nodes that appeared sonographically abnormal (n=2, #12, 18) (Figure 2). CNB was performed three times on the same mass lesion in patient 16, following an initial FNA alone with flow cytometry that showed 9% clonal B cells. The first CNB did not include repeat FNA/flow cytometry while the second one did. A third CNB was performed 16 months after the second because of progressive enlargement of the mass lesion.
Figure 2:
Ultrasound images of lymphomatous lesions of the parotid gland. A, An abnormal intraparotid lymph node is evident in this longitudinal view (patient #18). The node was considered abnormal because of its enlargement and rounded shape; B, A blood vessel is seen on color Doppler imaging penetrating the hilum of the intraparotid node seen in panel A; C, A heterogeneously hypoechoic, mixed solid and cystic mass is evident in this longitudinal view (patient #22).
A final pathologic diagnosis was established through the integration of CNB histopathology with immunohistochemistry (n=12 procedures), cytology (n=21), flow cytometry (n=24), and molecular studies (n=2). In two procedures (patients #2, 7), flow cytometry samples were largely comprised of debris and were thus without diagnostic utility (one was material from CNB only and the other from combined CNB and FNA) (Supplemental Figures 1 and 2). Final pathologic diagnoses for the 23 patients with only one CNB were marginal zone lymphoma of mucosa-associated lymphoid tissue (MALT; n=6), atypical lymphoid infiltration suspicious for MALT lymphoma (n=2), benign focal lymphoid infiltration (n=8), benign lymphoepithelial sialadenitis (n=2), salivary gland tissue without inflammatory infiltrate (n=4), and lymphoepithelial cyst/focal lymphoid infiltration (n=1 with biopsies of right and left parotid glands). The diagnosis of MALT lymphoma was established a median of 6.1 years (range 1.3–8.0 years) after that of SS in the six affected patients. In the patient with serial CNB, the first was interpreted as benign focal lymphoid infiltration whereas the second (which included flow cytometry) confirmed an atypical lymphoid infiltrate seen on an earlier FNA. In the third CNB, a monoclonal B cell population was demonstrated again by flow cytometry but the lymphoid infiltrate in the CNB was too small for further characterization.
A clonally restricted cell population was detected by flow cytometry in 12 biopsy samples (B cell in 11, plasma cell in 1) performed on 11 patients and by molecular studies in one additional procedure (patient #17). Among these 12 patients with monoclonal lymphoid infiltrates, six were diagnosed with MALT lymphoma based on histopathology and immunohistochemistry. Among the other six, three were interpreted as showing atypical lymphoid infiltration, but insufficient morphologic findings to diagnose lymphoma. In one of these three patients (#18) with an atypical lymphoid infiltrate, biopsy of an enlarged inguinal node six months after the parotid biopsy showed MALT lymphoma. The other three (#5, 6, 15) were diagnosed with benign lymphoepithelial sialadenitis (#5, 6) or a benign T-cell predominant focal lymphocytic infiltrate (#15). The two patients described above with inadequate samples for flow cytometry (#2, 7) had no lymphoid infiltrate on CNB. Hypoechoic sonographic lesions were present in all patients with lymphoma, atypical lymphoid infiltration, and/or monoclonal B-cell population detected in the CNB.
In 15 patients, the clinician concluded that the salivary gland process was “benign” and opted to make no change in treatment in 12. In three, the clinician opted to treat with rituximab due to persistent parotid gland enlargement (#8, 14) or the presence of interstitial nephritis (#15). In three patients, the clinician concluded that the patient had a possible lymphoproliferative disorder; one received rituximab treatment (#17), and two were observed expectantly (#16, 18). One of these latter patients (#18) developed inguinal adenopathy six months later, with a biopsy showing MALT lymphoma. Of the six patients with MALT lymphoma, five were treated with rituximab monotherapy, while one was managed with expectant observation, but then started on rituximab after an interval of 12 months.
DISCUSSION:
We utilized ultrasound-guided CNB to evaluate salivary gland abnormalities suspicious for lymphoma in 24 patients with SS. The indications included persistent salivary gland enlargement or a discrete salivary gland mass or lesion identified clinically or by ultrasound. None of the patients had a rapidly enlarging mass, minimizing concern for a high-grade lymphoma (e.g diffuse large B-cell) which can involve the parotid gland (8). Importantly, flow cytometry of cellular material from the CNB and/or FNA was included to increase the diagnostic yield in 24 of the 26 procedures. None of our patients underwent open surgical resection of salivary gland tissue following CNB, so validation of the utility of this diagnostic protocol rests on whether the results were actionable, allowing a clinical decision to be made without the need for further testing. Our experience provides strong support for the safety and diagnostic utility of ultrasound-guided core needle biopsy in the evaluation of salivary gland enlargement or focal abnormalities in individuals with SS.
None of the patients reported complications from the procedure. Notably, CNB avoided an open surgical excision, with its attendant risk of facial nerve injury, fistula formation, sialocele formation, and unacceptable cosmetic deformity (9). A surgical excision of the major salivary gland is also time-consuming and often requires hospital admission and general anesthesia. It may also exacerbate xerostomia in SS patients. In contrast to epithelial salivary gland tumors, the primary treatment of salivary gland lymphoma is not surgical excision, so diagnosis with a minimally invasive procedure can avoid the need for surgery (10, 11).
Our CNB diagnostic protocol provided sufficient material to differentiate a range of salivary gland pathologic findings expected in a cohort of patients with SS, namely normal salivary gland tissue, fatty replacement, focal lymphocytic sialadenitis, and more diffuse lymphocytic infiltration, representing either benign lymphoepithelial sialadenitis (BLEL) or MALT lymphoma. This constituted an advantage of CNB (often with FNA) over FNA alone. None of the patients had alternative forms of benign salivary gland inflammation, such as IgG4-related or granulomatous sialadenitis. Ultrasonographic imaging during the biopsy procedure enabled targeting of lesions that were suspicious for lymphoma. These corresponded to palpable masses in nine patients, but also clinically-occult lesions in five. On ultrasound, lesions that proved to be lymphomatous included mass-like conglomerates of hypoechoic lesions and abnormal intra-parotid lymph nodes. Notably, the parenchyma of the parotid and submandibular gland showed numerous hypoechoic lesions in all patients with lymphoma or atypical lymphoid infiltrates. This observation suggests that clinical enlargement of salivary glands in the absence of sonographic abnormality is not suspicious for lymphoma. A larger sample size would be necessary to generalize our experience with this cohort. Similar concerns have been raised by Jousse-Joulin et al (12).
In three of our patients with diffuse glandular lymphoid infiltration, a definitive diagnosis of indolent low-grade lymphoma could not be established. In each, flow cytometry demonstrated a monoclonal B-cell population, but the histologic findings were not sufficient to allow a definitive diagnosis of lymphoma. Differentiation of BLEL from low-grade lymphoma, most often MALT, can be difficult (13, 14). Both are characterized by polymorphous lymphoid infiltrates with an admixture of B and T cells and lymphoepithelial lesions. A monoclonal cell population is characteristic of MALT lymphoma (15), but can also be found in BLEL from SS as well as reactive nodes. They may represent reactive follicular center cells (16). While BLEL is a histologic precursor of MALT lymphoma, evolution to MALT lymphoma is slow and infrequent.
With the understanding that the distinction between a benign and malignant lymphoproliferative process of the salivary gland may not be definitive in patients with SS, the decision about whether to treat is based on a number of factors, including systemic disease activity, symptoms or cosmetic concerns related to the salivary gland enlargement or mass, and overall health (10, 11). Treatment can be effective in reducing salivary gland enlargement and controlling systemic disease activity, but is not known to impact the recurrence rate of MALT lymphoma. Similarly, whether treatment of BLEL prevents or delays the development of frank lymphoma is not known.
The information provided by US-guided CNB, inclusive of flow cytometry, was “actionable” in all cases, allowing the practitioner to differentiate a benign salivary gland process from the presence of MALT lymphoma or a possible lymphoproliferative disorder. With respect to the latter two diagnoses, the treatment decision is between expectant observation and the institution of B-cell depleting therapy, either alone or with another agent. This decision is made on the basis of the clinical context, and in our patients could be made in conjunction with CNB without the need for excisional biopsy. Note is made of two patients who underwent additional biopsies, one due to enlarging inguinal nodes (showing MALT lymphoma) six months after the parotid gland biopsy, and a second who underwent repeat core biopsies of the same parotid gland mass over the ensuing 17 months, each time showing an atypical lymphoid infiltrate but no frank lymphoma.
We advocate for CNB only in certain clinical situations, namely persistent salivary gland enlargement, a palpable mass, or a sonographic abnormality such as an abnormal intraparotid lymph node or masslike conglomeration of the hypoechoic lesions characteristic of SS. Given the low grade and indolent behavior of salivary gland lymphoid neoplasms in SS, there must be circumspection in the use of CNB for routine disease monitoring. Early detection of lymphoma through repeated biopsies is unlikely to affect outcome and may engender undue anxiety.
The limitations of our study include our relatively small cohort which might not have been fully representative of the range of salivary gland lesions that may be encountered in this population. On the other hand, it is the largest experience as yet reported for CNB in suspected lymphoma in SS and is concordant with what has been reported by others.
In summary, CNB of the salivary glands in patients with SS is a safe and useful technique for evaluation of suspected salivary gland lymphoma, providing sufficient pathologic material to allow for definitive pathologic evaluation and appropriate clinical decision-making while avoiding the risks of an excisional biopsy.
Supplementary Material
SIGNIFICANCE AND INNOVATIONS.
Salivary gland lymphoma has a cumulative lifetime prevalence of 5–10% in patients with Sjögren’s syndrome (SS).
Biopsy procedures that utilize an ultrasound-guided core needle have gained increasing use for the diagnosis of lymphoma and have the advantage of avoiding a surgical excision with its attendant risks.
In the current study, ultrasound-guided core needle biopsy and pathologic analysis with both histopathology and flow cytometry in 24 SS patients was safe and avoided the need for excisional biopsy in all.
This study supports the routine use of the biopsy procedure in the evaluation of suspected salivary gland lymphoma in SS.
Acknowledgments
This study was supported by the Jerome L. Greene Foundation. Dr. Baer was supported by NIH RO1 DE12354–15A1 and NIH contract 75N92019P00427.
Footnotes
None of the authors report financial support or other benefits from commercial sources for the work reported on in the manuscript, or any other financial interests, which could create a potential conflict of interest or the appearance of a conflict of interest with regard to the work.
REFERENCES
- 1.Witt BL, Schmidt RL. Ultrasound-guided core needle biopsy of salivary gland lesions: a systematic review and meta-analysis. Laryngoscope 2014; March;124(3):695–700. [DOI] [PubMed] [Google Scholar]
- 2.Huang YC, Wu CT, Lin G, Chuang WY, Yeow KM, Wan YL. Comparison of ultrasonographically guided fine-needle aspiration and core needle biopsy in the diagnosis of parotid masses. J Clin Ultrasound 2012; May;40(4):189–94. [DOI] [PubMed] [Google Scholar]
- 3.Nocturne G, Mariette X. Sjogren Syndrome-associated lymphomas: an update on pathogenesis and management. Br J Haematol 2015; February;168(3):317–27. [DOI] [PubMed] [Google Scholar]
- 4.Cheson BD, Fisher RI, Barrington SF, Cavalli F, Schwartz LH, Zucca E, et al. Recommendations for initial evaluation, staging, and response assessment of Hodgkin and non-Hodgkin lymphoma: the Lugano classification. J Clin Oncol 2014; September 20;32(27):3059–68. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 5.Shiboski CH, Shiboski SC, Seror R, Criswell LA, Labetoulle M, Lietman TM, et al. 2016 American College of Rheumatology/European League Against Rheumatism classification criteria for primary Sjogren’s syndrome: A consensus and data-driven methodology involving three international patient cohorts. Ann Rheum Dis 2017; January;76(1):9–16. [DOI] [PubMed] [Google Scholar]
- 6.Drylewicz MR, Watkins MP, Shetty AS, Lin MF, Salter A, Bartlett NL, et al. Formulating a Treatment Plan in Suspected Lymphoma: Ultrasound-Guided Core Needle Biopsy Versus Core Needle Biopsy and Fine-Needle Aspiration of Peripheral Lymph Nodes. J Ultrasound Med 2019; March;38(3):581–6. [DOI] [PubMed] [Google Scholar]
- 7.Jousse-Joulin S, D’Agostino MA, Nicolas C, Naredo E, Ohrndorf S, Backhaus M, et al. Video clip assessment of a salivary gland ultrasound scoring system in Sjogren’s syndrome using consensual definitions: an OMERACT ultrasound working group reliability exercise. Ann Rheum Dis 2019; July;78(7):967–73. [DOI] [PubMed] [Google Scholar]
- 8.Zenone T Parotid gland non-Hodgkin lymphoma in primary Sjogren syndrome. Rheumatol Int 2012; May;32(5):1387–90. [DOI] [PubMed] [Google Scholar]
- 9.Wyss E, Mueller-Garamvolgyi E, Ghadjar P, Rauch D, Zbaren P, Arnold A. Diagnosis and treatment outcomes for patients with lymphoma of the parotid gland. Laryngoscope 2013; March;123(3):662–9. [DOI] [PubMed] [Google Scholar]
- 10.Voulgarelis M, Ziakas PD, Papageorgiou A, Baimpa E, Tzioufas AG, Moutsopoulos HM. Prognosis and outcome of non-Hodgkin lymphoma in primary Sjogren syndrome. Medicine (Baltimore) 2012; January;91(1):1–9. [DOI] [PubMed] [Google Scholar]
- 11.Pollard RP, Pijpe J, Bootsma H, Spijkervet FK, Kluin PM, Roodenburg JL, et al. Treatment of mucosa-associated lymphoid tissue lymphoma in Sjogren’s syndrome: a retrospective clinical study. J Rheumatol 2011; October;38(10):2198–208. [DOI] [PubMed] [Google Scholar]
- 12.Jousse-Joulin S, D’Agostino MA, Hocevar A, Naredo E, Terslev L, Ohrndorf S, et al. Could we use salivary gland ultrasonography as a prognostic marker in Sjogren’s syndrome? Response to: ‘Ultrasonographic damages of major salivary glands are associated with cryoglobulinemic vasculitis and lymphoma in primary Sjogren’s syndrome: are the ultrasonographic features of the salivary glands new prognostic markers in Sjogren’s syndrome?’ by Coiffier et al. Ann Rheum Dis 2019; October 10. [DOI] [PubMed]
- 13.Carbone A, Gloghini A, Ferlito A. Pathological features of lymphoid proliferations of the salivary glands: lymphoepithelial sialadenitis versus low-grade B-cell lymphoma of the malt type. Ann Otol Rhinol Laryngol 2000; December;109(12 Pt 1):1170–5. [DOI] [PubMed] [Google Scholar]
- 14.Hsi ED, Zukerberg LR, Schnitzer B, Harris NL. Development of extrasalivary gland lymphoma in myoepithelial sialadenitis. Mod Pathol 1995; October;8(8):817–24. [PubMed] [Google Scholar]
- 15.Stacchini A, Aliberti S, Pacchioni D, Demurtas A, Isolato G, Gazzera C, et al. Flow cytometry significantly improves the diagnostic value of fine needle aspiration cytology of lymphoproliferative lesions of salivary glands. Cytopathology 2014; August;25(4):231–40. [DOI] [PubMed] [Google Scholar]
- 16.Kussick SJ, Kalnoski M, Braziel RM, Wood BL. Prominent clonal B-cell populations identified by flow cytometry in histologically reactive lymphoid proliferations. Am J Clin Pathol 2004; April;121(4):464–72. [DOI] [PubMed] [Google Scholar]
Associated Data
This section collects any data citations, data availability statements, or supplementary materials included in this article.