Salivary gland biopsy is a technique broadly applied for the diagnosis of Sjögren syndrome (SS), lymphoma in SS, and connective tissue disorders (sarcoidosis, amyloidosis). In SS characteristic histology findings are found, including lymphocytic infiltration surrounding the excretory ducts in combination with destruction of acinar tissue. In this article the main techniques are described for taking labial and parotid salivary gland biopsies with respect to their advantages, postoperative complications, and usefulness for diagnostic procedures, monitoring disease progression, and evaluation of treatment.
Key points
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In Sjögren diagnostics, parotid gland incision biopsies can overcome most disadvantages of minor salivary gland excision biopsies.
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Sensitivity and specificity of parotid and minor salivary gland biopsies for diagnosing Sjögren syndrome are comparable.
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Lymphoepithelial lesions and early stage lymphomas are easier to detect in parotid gland tissue of patients with Sjögren syndrome.
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In contrast to minor salivary glands, repeated biopsies of the same parotid gland are possible, which is an important asset in monitoring disease progression as well as in studying the efficacy of treatment at a glandular tissue level.
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Histopathologic results from the parotid gland can be compared with other diagnostic results derived from the same gland (sialometry sialochemistry, sialography, scintigraphy, ultrasound, computed tomography, MRI).
Introduction
Salivary gland biopsy is a technique broadly applied in the diagnostic work-up of Sjögren syndrome (SS) as well as lymphoma accompanying SS, sarcoidosis, amyloidosis, and other connective tissue disorders. A focus score of 1 or greater per 4 mm 2 labial salivary gland tissue is considered as one of the 4 objective European-American Consensus Group classification criteria (AECG) and one of the 3 objective American College of Rheumatology (ACR) provisional classification criteria for SS. The focus scores reflect the number of infiltrates of 50 or greater mononuclear inflammatory cells, predominantly lymphocytes, in a perivascular or periductal location, typically adjacent to normal acini, per 4 mm 2 salivary gland tissue. Also in the under-construction consensus classification criteria of the European League against Rheumatism (EULAR) and ACR, a labial focus score of 1 or greater will be maintained as a leading classification criterion.
Moreover, there are views that besides being of diagnostic value, labial salivary gland biopsies also may play a role in predicting lymphoma development as well as in monitoring disease and treatment efficacy. Recently, Fisher and colleagues reviewed the labial salivary gland pathologic changes that characterizes SS. They concluded that labial salivary gland biopsies offer a distinct potential as a biomarker in primary SS (pSS), particularly relevant to glandular involvement, and offer additional prognostic, stratification, and mechanistic insights. They also added that precise value of a labial salivary gland biopsy is yet hard to determine in the absence of proven immunomodulatory therapies in pSS and that further work on validation and understanding the natural history is needed.
In their review, Fisher and colleagues briefly mentioned parotid biopsies as an alternative to labial salivary gland biopsies but did not further state the advantages and disadvantages of parotid biopsies compared with labial salivary biopsies ( Table 1 ). In this contribution, the authors discuss the potential of parotid salivary gland biopsies as an alternative way to diagnose SS and also with emphasis of its added value in lymphoma diagnostics and rating disease progression and treatment efficacy.
| Technique | Advantages | Complications | |
|---|---|---|---|
| Labial gland | |||
| Chisholm & Mason, 1968 | Ellipse of oral mucous membrane down to the muscle layer; harvest of 6–8 glands; wound closure with 4-0 silk sutures, which must be removed after 4–5 d |
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| Greenspan et al, 1974 | 1.5–2.0 cm linear incision of mucosa, parallel to the vermillion border and lateral to the midline | ||
| Marx et al, 1988 | Mucosal incision of 3.0 × 0.75 cm | ||
| Delgado & Mosqueda, 1989 | Longitudinal incision of 1 cm in the labial mucosa in front of the mandibular cuspids | ||
| Guevara-Gutierrez et al, 2001 | Punch biopsy | ||
| Mahlstedt et al, 2002 | 1.0- to 1.5-cm wedge-shaped incision between the midline and commissure | ||
| Gorson & Ropper, 2003 | 1-cm vertical incision just behind the wet line through the mucosa and submucosa | ||
| Berquin et al, 2006 | Oblique incision, starting 1.5 cm from the midline and proceeding latero-inferiorly, avoiding the glandular free zone in the center of the lower lip | ||
| Caporali et al, 2007 | Small incision of 2–3 mm on the inner surface of the lower lip | ||
| Parotid gland | |||
| Kraaijenhagen, 1975 Marx et al, 1988 McGuirt et al, 2002 Baurmash, 2005 Pijpe et al, 2007 | 1- to 2-cm incision just below and behind the earlobe near the posterior angle of the mandible; skin is incised and the parotid capsule exposed by blunt dissection capsule of the gland opened and adequate amount of superficial parotid tissue removed, approximately 5 × 5 mm; procedure completed with a 2- to 3-layered closure |
|
|
| Adam et al, 1992 Berquin et al, 2006 | Mucosal incision 1 cm anterolaterally from the Wharton duct to 1 cm anteroposterior; blunt dissection and harvest of 0.5 cm 3 of glandular tissue; wound edges joined with 1–2 resorbable stiches | ||
Introduction
Salivary gland biopsy is a technique broadly applied in the diagnostic work-up of Sjögren syndrome (SS) as well as lymphoma accompanying SS, sarcoidosis, amyloidosis, and other connective tissue disorders. A focus score of 1 or greater per 4 mm 2 labial salivary gland tissue is considered as one of the 4 objective European-American Consensus Group classification criteria (AECG) and one of the 3 objective American College of Rheumatology (ACR) provisional classification criteria for SS. The focus scores reflect the number of infiltrates of 50 or greater mononuclear inflammatory cells, predominantly lymphocytes, in a perivascular or periductal location, typically adjacent to normal acini, per 4 mm 2 salivary gland tissue. Also in the under-construction consensus classification criteria of the European League against Rheumatism (EULAR) and ACR, a labial focus score of 1 or greater will be maintained as a leading classification criterion.
Moreover, there are views that besides being of diagnostic value, labial salivary gland biopsies also may play a role in predicting lymphoma development as well as in monitoring disease and treatment efficacy. Recently, Fisher and colleagues reviewed the labial salivary gland pathologic changes that characterizes SS. They concluded that labial salivary gland biopsies offer a distinct potential as a biomarker in primary SS (pSS), particularly relevant to glandular involvement, and offer additional prognostic, stratification, and mechanistic insights. They also added that precise value of a labial salivary gland biopsy is yet hard to determine in the absence of proven immunomodulatory therapies in pSS and that further work on validation and understanding the natural history is needed.
In their review, Fisher and colleagues briefly mentioned parotid biopsies as an alternative to labial salivary gland biopsies but did not further state the advantages and disadvantages of parotid biopsies compared with labial salivary biopsies ( Table 1 ). In this contribution, the authors discuss the potential of parotid salivary gland biopsies as an alternative way to diagnose SS and also with emphasis of its added value in lymphoma diagnostics and rating disease progression and treatment efficacy.
| Technique | Advantages | Complications | |
|---|---|---|---|
| Labial gland | |||
| Chisholm & Mason, 1968 | Ellipse of oral mucous membrane down to the muscle layer; harvest of 6–8 glands; wound closure with 4-0 silk sutures, which must be removed after 4–5 d |
|
|
| Greenspan et al, 1974 | 1.5–2.0 cm linear incision of mucosa, parallel to the vermillion border and lateral to the midline | ||
| Marx et al, 1988 | Mucosal incision of 3.0 × 0.75 cm | ||
| Delgado & Mosqueda, 1989 | Longitudinal incision of 1 cm in the labial mucosa in front of the mandibular cuspids | ||
| Guevara-Gutierrez et al, 2001 | Punch biopsy | ||
| Mahlstedt et al, 2002 | 1.0- to 1.5-cm wedge-shaped incision between the midline and commissure | ||
| Gorson & Ropper, 2003 | 1-cm vertical incision just behind the wet line through the mucosa and submucosa | ||
| Berquin et al, 2006 | Oblique incision, starting 1.5 cm from the midline and proceeding latero-inferiorly, avoiding the glandular free zone in the center of the lower lip | ||
| Caporali et al, 2007 | Small incision of 2–3 mm on the inner surface of the lower lip | ||
| Parotid gland | |||
| Kraaijenhagen, 1975 Marx et al, 1988 McGuirt et al, 2002 Baurmash, 2005 Pijpe et al, 2007 | 1- to 2-cm incision just below and behind the earlobe near the posterior angle of the mandible; skin is incised and the parotid capsule exposed by blunt dissection capsule of the gland opened and adequate amount of superficial parotid tissue removed, approximately 5 × 5 mm; procedure completed with a 2- to 3-layered closure |
|
|
| Adam et al, 1992 Berquin et al, 2006 | Mucosal incision 1 cm anterolaterally from the Wharton duct to 1 cm anteroposterior; blunt dissection and harvest of 0.5 cm 3 of glandular tissue; wound edges joined with 1–2 resorbable stiches | ||
Minor salivary gland biopsy
Minor salivary glands are widely distributed in the labial, buccal, and palatal mucosa of the oral cavity. Because pathognomonic changes are seen in minor salivary glands, labial salivary gland biopsy is largely used for assisting the diagnosis of SS.
Surgical Considerations
Minor salivary glands, and labial salivary glands in particular, are easily accessible. The labial salivary glands lie above the muscle layer and branches of the mental nerve (labial sensory nerves) and are separated from the oral mucous membrane by a thin layer of fibrous connective tissue. Although the chance of excessive bleeding is minimal because the arterial supply to the lip lies deep, there is a serious hazard of sensory nerve injury, as the labial sensory nerves are closely associated to the minor salivary glands ( Fig. 1 ).
Chisholm and Mason introduced labial salivary gland biopsies in the diagnosis of SS. The biopsies involve oral preparation of patients with local anesthetic infiltration followed by excising an ellipse of oral mucous membrane down to the muscle layer. The wound was closed with 4-0–gauge silk sutures, which were removed after 4 to 5 days. Ideally 6 to 8 minor glands are harvested and sent for histopathologic examination.
Several clinicians have revised the Chisholm and Mason technique. Currently, the approach of Greenspan and colleagues and Daniels is mostly applied ( Fig. 2 ). This approach is described in detail on the Sjögren’s International Collaborative Clinical Alliance Web site. In short, the biopsy has to be performed through the mucosa of the lower lip that appears normal clinically. After applying local anesthetics, the lip is everted to expose the mucosa. Next, a 1.0- to 1.5-cm horizontal incision will be made to the right or left of the midline, approximately halfway between the vestibule and the vermilion border and halfway between the midline and the labial commissure. The lamina propria is bluntly dissected to release the minor salivary glands from the lamina propria beyond the incision and to bring them into the operating field. Approximately 7 minor salivary glands should be removed to provide a minimum gland section area of 8 to 12 mm 2 for microscopic focus scoring. Finally, the mucosal incision margins are repositioned and sutured with 5-0 rapid absorbable (polyglactin/ l -lactide acid) sutures (see Fig. 2 ).
