**4. Differentiation of focus lymphocytic sialadenitis**

Focus lymphocytic sialadenitis should be differentiated with other microscopic findings:


Nonspecific chronic sialadenitis (NSCN) is characterized by scattered or focal infiltrates of lymphocytes, macrophages, and plasma cells that are not adjacent to normal-appearing acini and located in gland lobules that exhibit some combination of acinar atrophy, interstitial fibrosis, duct dilation, and luminal inspissated mucus.

Sclerosing chronic sialadenitis (SCS) is an advanced stage of NSCS in which interstitial fibrosis, various patterns of chronic inflammation, and acinar atrophy predominate.

Granulomatous inflammation is present when there are clusters of CD68 positive macrophages, with or without occasional multinucleated giant cells and absent necrosis.

Infiltrates within normal limits can be diagnosed in minor salivary glands with normal appearing architecture and scattered plasma cells, but without acinar atrophy and few if any lymphocytes.

**61**

*Laryngological and Dental Manifestations of Sjögren's Syndrome*

*Confirmation of SS in LSGB. Focus score 4 (staining H&E, magnitude 10×).*

Marginal zone (MALT) lymphoma is diagnosed in minor salivary glands exhibiting diffuse lymphocytic infiltration with loss of glandular architecture and composed of sheets of CD20 positive cells without follicular distribution, few scattered CD3 positive cells, and few if any follicular dendritic (CD21 or CD23 positive) cells. Germinal center presence is estimated in hematoxylin and eosin (H&E) stained sections by the presence of a cluster of relatively clear staining cells within a lymphocytic focus. More specific identification of germinal centers requires immunohistochemical staining for follicular dendritic cells with anti-CD21 or CD23 [4, 9]. There is no standardization of labial salivary gland biopsies in SS, but there are several points of importance in LSGB. The first issue refers to a sufficient amount of glandular tissue. A reasonable compromise is four glands, although a minimum sized

area to be sampled would give the best results, but a larger operative field increases the surgical risk. On the other hand, some glands may be atrophic or damaged, and the volume of the material obtained through the biopsy should be sufficient to overcome this artifact and achieve a valid result. It is more recommended to evaluate multiple different lobules than to concentrate on a single abnormal lobule, which may not be typical of the entire gland. In routine management, H&E staining is used in order to determine these structures. For clinical trials, additional staining with CD21 as well as CD20 and CD3 is required. CD21 is a marker of follicular dendritic cells. Germinal centers should be reported and pathologists are advised to use caution in order to avoid overestimating germinal centers by relying solely on CD21. Furthermore, the distribution of the inflammatory cells in the gland may be uneven. Considering this uneven distribution, a single tissue section may result in underdiagnosis. While increasing the number of sections has the potential to reduce this problem, the optimal number of sections has yet to be determined. Some research suggests taking labial salivary glands at different depths from the same incision. Focus score can change significantly at different tissue depths within the minor salivary glands. Multiple sections for LSGB increase the diagnostic

value and are more representative than a single section [7, 10] (**Figure 3**).

• Differentiation of FLS with nonspecific chronic sialadenitis and sclerosing

• Severe acinar atrophy, interstitial fibrosis, and increase in fat cells in biopsy

**5. Limitations of the assessment of focus score**

) may be achieved with 2–3 glands. The largest possible

*DOI: http://dx.doi.org/10.5772/intechopen.85687*

evaluable surface area (8 mm2

**Figure 3.**

chronic sialadenitis

specimens

*Laryngological and Dental Manifestations of Sjögren's Syndrome DOI: http://dx.doi.org/10.5772/intechopen.85687*

#### **Figure 3.**

*Chronic Autoimmune Epithelitis - Sjogren's Syndrome and Other Autoimmune Diseases...*

3 Diffuse infiltrate with partial destruction of acinar tissue with or without fibrosis 4 Diffuse infiltrate with or without fibrosis destroying the lobular architecture completely

**4. Differentiation of focus lymphocytic sialadenitis**

• Nonspecific chronic sialadenitis NSCS

2 Moderate infiltrate or less than one focus

*Grading systems for salivary gland biopsies of Tarpley.*

*Grading systems for salivary gland biopsies of Chisholm and Mason.*

• Sclerosing chronic sialadenitis SCS

• Granulomatous inflammation

• Infiltrates within normal limits

atrophy and few if any lymphocytes.

• Germinal center

**Grade Description** 0 Absent 1 Slight infiltrate

**Grade Description** 0 Normal

1 1 or 2 Aggregates 2 >3 Aggregates

3 One focus

4 More than one focus

predominate.

necrosis.

• Marginal zone (MALT) lymphoma

Focus lymphocytic sialadenitis should be differentiated with other microscopic

Nonspecific chronic sialadenitis (NSCN) is characterized by scattered or focal infiltrates of lymphocytes, macrophages, and plasma cells that are not adjacent to normal-appearing acini and located in gland lobules that exhibit some combination of acinar atrophy, interstitial fibrosis, duct dilation, and luminal inspissated mucus. Sclerosing chronic sialadenitis (SCS) is an advanced stage of NSCS in which interstitial fibrosis, various patterns of chronic inflammation, and acinar atrophy

Granulomatous inflammation is present when there are clusters of CD68 positive macrophages, with or without occasional multinucleated giant cells and absent

Infiltrates within normal limits can be diagnosed in minor salivary glands with

normal appearing architecture and scattered plasma cells, but without acinar

**60**

findings:

**Table 2.**

**Table 1.**

*Confirmation of SS in LSGB. Focus score 4 (staining H&E, magnitude 10×).*

Marginal zone (MALT) lymphoma is diagnosed in minor salivary glands exhibiting diffuse lymphocytic infiltration with loss of glandular architecture and composed of sheets of CD20 positive cells without follicular distribution, few scattered CD3 positive cells, and few if any follicular dendritic (CD21 or CD23 positive) cells.

Germinal center presence is estimated in hematoxylin and eosin (H&E) stained sections by the presence of a cluster of relatively clear staining cells within a lymphocytic focus. More specific identification of germinal centers requires immunohistochemical staining for follicular dendritic cells with anti-CD21 or CD23 [4, 9].

There is no standardization of labial salivary gland biopsies in SS, but there are several points of importance in LSGB. The first issue refers to a sufficient amount of glandular tissue. A reasonable compromise is four glands, although a minimum sized evaluable surface area (8 mm2 ) may be achieved with 2–3 glands. The largest possible area to be sampled would give the best results, but a larger operative field increases the surgical risk. On the other hand, some glands may be atrophic or damaged, and the volume of the material obtained through the biopsy should be sufficient to overcome this artifact and achieve a valid result. It is more recommended to evaluate multiple different lobules than to concentrate on a single abnormal lobule, which may not be typical of the entire gland. In routine management, H&E staining is used in order to determine these structures. For clinical trials, additional staining with CD21 as well as CD20 and CD3 is required. CD21 is a marker of follicular dendritic cells. Germinal centers should be reported and pathologists are advised to use caution in order to avoid overestimating germinal centers by relying solely on CD21. Furthermore, the distribution of the inflammatory cells in the gland may be uneven. Considering this uneven distribution, a single tissue section may result in underdiagnosis. While increasing the number of sections has the potential to reduce this problem, the optimal number of sections has yet to be determined. Some research suggests taking labial salivary glands at different depths from the same incision. Focus score can change significantly at different tissue depths within the minor salivary glands. Multiple sections for LSGB increase the diagnostic value and are more representative than a single section [7, 10] (**Figure 3**).

### **5. Limitations of the assessment of focus score**

