27.6Salivary Gland Biopsy

27.6.2Daniels’ Technique

The biopsy specimen is obtained through mucosa that appears normal and should contain at least five labial salivary glands. Following local anesthesia with 2% xylocaine, a horizontal incision (1.5–2 cm) is made on the inner surface of the lower lip between the midline and the commissure. Incisions in the midline of the lip should be avoided because there are fewer labial salivary glands in that zone. Blunt dissection is performed and salivary glands are removed. Closure of the incision is performed with suture material [32].

Variations on this technique have been described. For instance: (a) palpation of the lower lip to locate the lip salivary glands (submucosal nodules) instead of simply performing a blind incision in a conventional location [33]; (b) leaving the incision open and allowing spontaneous healing [33, 34]; and (c) holding an ice-pack on the lip for 20 min after the procedure to achieve better hemostasis.

27.6.3Punch Biopsy

This technique is also performed through normal-appearing mucosa of the lower lip. The lip is everted, anesthesia injected, and a 4-mm punch incision is made. The vermilion border of the lip should be avoided. The lip specimen is removed with an insulin needle. Patient is instructed to rinse her/his mouth. No suturing is required [35].

Short-term adverse events of the lip biopsy are local swelling (10%), local infection (4%), short-term local pain (25%), and long-term local numbness (1.7%). Among a cohort of 502 procedures, transient adverse events were reported in 13% of cases [36]. No permanent morbidity resulted from the procedure. Thus, minor salivary gland biopsy is simple, safe, reliable tool for the diagnosis of SS. However, under normal conditions, only two lower lip biopsies can be performed on an individual, therefore its use in clinical drug trials is limited [37].

27.6.4Major Salivary Gland Biopsy

Parotid gland tissue can be harvested easily and repeated biopsies may be performed [38]. In addition, some authors have reported a better yield from parotid biopsies compared to minor labial salivary gland biopsies. However, parotid biopsy is usually not recommended because it may be associated with fistula formation, injuries to the facial nerve, and scarring.

In contrast to labial salivary glands, lymphoepithelial islands and well-formed lymphoid follicles or germinal centers are found easily in the major salivary glands. One study reported that lip biopsy identified 58% of patients with SS, compared with 100% of such patients confirmed by parotid gland biopsy [39]. On the other hand, another study of 15 SS patients with SS indicated similar sensitivities and specificities. Many patients experienced transient (6 months) hypoanesthesia of the preauricular region after parotid biopsy, but no sialoceles or fistulas were reported [38].

27.6.5Lacrimal Gland Biopsy

The lacrimal glands are another major target organ of SS. However, complications of biopsies that might affect lacrimation or lead to hemorrhage or fistula formation have prevented the routine use of this biopsy. One study evaluated 32 subjects with SS with both labial and lacrimal gland biopsies. The authors found that epimyoepithelial islands and severe lymphocyte infiltration with germinal centers were observed only in lacrimal specimens. In addition, 19% of the cases failed to show early changes in labial salivary glands biopsies, indicating that lymphocytic infiltration in lacrimal glands may occur earlier and more extensively than in the labial gland [40].

27.6.6Focus Score

The characteristic histopathologic feature of the labial salivary gland in SS is the presence of focal lymphocytic sialadenitis (Fig. 27.6) at most of the glands in the specimen. Thus, once the lip biopsy is obtained, the specimen is evaluated with a semiquantitative technique to assess sialadenitis, originally described by Chisholm and Manson in 1968. These authors reviewed lip biopsy specimens from 40 patients with rheumatologic diseases as well as 60 postmortem controls. They observed that the presence of more than one focus of lymphocytes per 4 mm2 gland section was found only in patients with SS.

A focus is defined as a dense aggregate (round cell infiltrate) of 50 or more lymphocytes/plasma cells and macrophages in perivascular or periductal location [41]. In 1984, Daniels evaluating 362 lower lip biopsies concluded that a focus score >1 per 4 mm² tissue sample was indicative of SS [32]. The focus score correlates directly with the presence of keratoconjunctivitis sicca and inversely with the parotid flow rate [31].

For Daniels and colleagues, the finding of a focus score of exactly one may represent an early or mild form of the salivary component of SS [31]. Other grading systems (Table 27.5) besides the Chisholm–Manson scale (class I normal salivary gland with few lymphocytes to class IV [>1 lymphocyte foci]) [41] have been proposed. Greenspan et al. modified this system by recording the actual focus score. On the modified scale, which ranges from 0 (normal) to 12 (confluent infiltrates), a focus score of ³2 is indicative of SS [42]. In the grading system of Tarpley, biopsies are classified as normal (Grade 0), with 1–2 focus (Grade 1), >2 focus (Grade 2), diffuse infiltrate + partial acinar destruction (Grade 3), and diffuse infiltrate + total acinar destruction with or without fibrosis (Grade 4). On that scale, classes 2, 3, and 4 are considered to be diagnostic of SS [43].

In 1993, a group of investigators of the European Community proposed preliminary criteria set for the classification of SS, where a focus ³1 is considered a positive item [44]. They found a good balance between sensitivity (83.5%) and specificity (81.8%) when the presence of at least 1 focus was considered as indicative or SS. Conversely, when the cut-off value was raised to two or more foci, the sensitivity fell to 65% with only a slight increase of specificity (92.4%) [6].