Tumors of Salivary Gland Lymph Nodes

PRIMARY LYMPH NODE TUMORS Lymphomas

Primary lymphoma of the salivary glands is rare. Eighty percent of lymphomas of the salivary glands are found in the parotid gland and 20% in the submandibular gland, with only case reports of sublingual and minor gland involvement (Eraso, Lorusso, and Palacios 2005) (Figure 11.10).

Other authors have found a higher incidence of submandibular involvement (39%) (Dunn, Kuo, and Shih et al. 2004). In 121 parotid tumors 8.3% were lymphomas (Shine, O'Leary, and Blake 2006), and in 51 submandibular tumors 14% were lymphomas (Preuss, Klussman, and Wittekindt et al. 2007).

Patients with Sjogren's syndrome, AIDS, and hepatitis C have an increased risk of developing salivary lymphomas. In a review of 463 cases of Sjogren's syndrome, 27 patients had a diagnosis of lymphoma (5.8%) (Tonami, Matoba, and Kuginuki et al. 2003). In this series 26 of the 27 patients had non-Hodgkin's lymphoma [including 6 mucosa-associated lymphoid tissue (MALT) lymphomas] and only 1 patient had Hodgkin's lymphoma. At the initial presentation 14 (52%) of patients had extra-nodal disease, with 9 of 27 (33%) in the salivary glands. However, 21 patients (78%) had nodal involvement, mostly in the cervical nodes. Masaki and Sugai (2004) also reported a figure of 5% of Stage III Sjogren's patients developing lymphomas that are thought to arise from lymphoepithelial lesions. The B cells in these lesions become activated by interactions between CD40L and CD40 with progression from polyclonal lymphoprolifera-tion, to monoclonal lymphoproliferation, to MALT lymphoma, and finally to high-grade lymphoma as a multistep process. Other authors have highlighted

Pathology Salivary Gland Adenoma

Figure 11.10a. Elderly lady with itchy facial and neck rash who complains of an intraoral swelling.

Elderly Swollen Parotid Gland
Figure 11.10b. A red fleshy swelling of the sublingual gland is appreciated with retraction of the commissure by the patient's finger and retraction of the tongue by the mirror. Biopsy showed a non-Hodgkin's lymphoma of the sublingual gland.

the difficulty in diagnosing true lymphoma from the other lymphoproliferative disorders occurring in Sjogren's syndrome, although there is a forty-fold increased risk in developing B-cell lymphomas (Prochorec-Sobieszek and Wagner 2005). Clinical features associated with lymphoma include persistent major salivary enlargement (>2 months), persistent lymphadenopathy or splenomegaly, monoclonal gammopathy, and type II mixed cryoglobulinemia.

Hepatitis C is also associated with MALT lymphomas of the salivary glands. In a series of 33 cases of primary salivary MALT lymphomas, 15 patients had a history of Sjogren's syndrome (45.5%), 2 (6%) other autoimmune disease, and 7 (21%) hepatitis C infection (Ambrossetti, Zanotti, and Passaro et al. 2004). There is an increase in lymphoma in AIDS, however, although in 51% of patients in a study of 100 patients who died with AIDS without salivary gland symptoms who

Figure 11.11. A 52-year-old man with a left parotid mass and a firm level II node who has a salivary lymphoma as a presenting sign of previously undiagnosed AIDS.

showed histologic signs of parotid disease, only 1 case of lymphoma was found (Vargas, Mauad, and Bohm et al. 2003) (Figure 11.11).

Not all primary salivary lymphomas fall into the MALT group, and follicular lymphomas comprise 30% and 22% of two recently published series (Kojima, Nakamura, and Ichimura et al. 2001; Nakamura, Ichimura, and Sato et al. 2006) (Figure 11.12). These lymphomas have a younger age of onset than MALT lymphomas, do not occur in patients with autoimmune disease, and appear relatively more common in the submandibular gland.

Most salivary lymphomas present as unilateral, painless masses, usually with a history of <4 months, and although CT scans show poorly

Submental Glands
Figure 11.12. Non-Hodgkin's lymphoma of the left parotid gland and submental nodes.

defined indistinct margins, there is no pathognomic sign for salivary lymphoma (Shine, O'Leary, and Blake 2006). The lesions may be multiple in the ipsilateral gland and associated lymphadenopathy can be noted. The use of FNAB in diagnosing salivary lymphoma has been questioned as inaccurate with high rates of false negative results.

Waldeyer Ring Pathology
Figure 11.13a. A 35-year-old lady with MALT lymphoma of Waldeyer's ring controlled by chemotherapy. Now has bilateral parotid involvement that is not responding to medical therapy and she is concerned regarding her appearance.
Over Frown Saliva Gland

Figure 11.13b. CT scan shows homogenous mass of MALT lymphoma in the anterior portion of the right parotid (arrow), which has slowly increased in size over a 3-year period.

Zurrida, Alasio, and Tradati et al. (1993) were only able to identify 2 of 7 lymphomas (28.6%), and Hughes, Volk, and Wilbur (2005) found a 57% false negative rate in salivary lymphomas in reviewing the data from the College of American Pathologists Interlaboratory Comparison Program in Nongynecologic Cytology. In the absence of Sjogren's syndrome or clinical suspicion of lymphoma, these lesions are frequently diagnosed following surgical removal.

Scan For Sjogren

Figure 11.13c. CT scan shows smaller mass of MALT lymphoma in the anterior left parotid gland.

Pathology Salivary Gland Adenoma

Figure 11.13d. Proposed parotidectomy and excision of MALT lymphoma.

Treatment is by chemotherapy, medical therapy, and radiation therapy depending on the histologic diagnosis and the clinical staging. MALT lymphomas of salivary glands appear to have a low-grade indolent course with 5-year overall survival, case-specific survival, and progression-free survival of 85% (±8%), 94% (±6%), and 65% (±10%), respectively (Ambrossetti, Zanotti, and Passaro et al. 2004). These results were noted despite 42% of their patients being Stage IV, and local therapy was often adequate (Figure 11.13). Dunn, Kuo, and Shih et al. (2004) in 23 primary salivary lymphomas, 19 MALT, 3 diffuse large cell, and 1 follicular found overall 5-year survival of 94.7% and relapse-free survival of 51.4%. Only 2 patients died; MALT lymphoma in 1 patient transformed into diffuse large cell lymphoma and the patient died. Kojima, Nakamura, and Ichimura et al. (2001) noted that follicular lymphomas arising from salivary glands appeared to share some of the characteristics of MALT lymphoma with an indolent prognosis.

SECONDARY LYMPH NODE TUMORS Regional Metastases

The lymph nodes associated with the major glands may all become involved by regional metastases. In the parotid gland, skin cancer, particularly squa-mous cell carcinoma (SCC) and malignant melanoma (MM) of the scalp, forehead, temple, upper lip, cheek, and ear is most common, although Merkel cell tumors, malignant syringomas, and other more unusual skin cancers can be seen (Figure 11.14).

The largest experience with these tumors is in Australia, where squamous cell carcinoma and melanoma of the facial skin is epidemic and meta-static cutaneous cancer is the commonest parotid malignancy (O'Brien, McNeil, and McMahon et al. 2002). Although less than 5% of patients with cutaneous SCC do metastasize to lymph nodes, certain features may give these tumors an increased risk of metastasizing. In a review of 266 patients, 61% having parotid lymph node involvement ± cervical involvement, tumor thickness >4-5 mm, and proximity to the parotid (temple/forehead, cheek, or ear) were high risks, and increasing tumor size and recurrence contributed to an increased risk (Veness, Palme, and Morgan 2006) (Figure 11.15). In 2002 O'Brien, McNeil, and

Lymph Node Tumor Forehead
Figure 11.14. Malignant syringoma of forehead metastatic to the left parotid gland and fungating through preauricular skin.

McMahon et al. suggested that the TNM system of designating all nodal metastases from cutaneous cancer N1 was limited and did not accurately delineate the extent of disease. They suggested separating disease in the parotid P1 <3 cm, P2 >3 cm and <6 cm, P3 >6 cm from neck disease: N0 no nodal disease, N1 a single node <3 cm, N2 multiple nodes or any node >3 cm for staging. In a multivariate analysis of 87 patients they found that increasing P stage, positive margins, and lack of adjuvant RT independently predicted for decreased local control in the parotid. Clinical and pathologic N stage both significantly impacted survival. They concluded that patients with positive nodes in both parotid and neck had the worst prognosis, and that prognosis was worse for nodal disease > N1 (Figure 11.16). A much smaller study from Israel showed a zero overall survival for patients with both parotid and cervical nodes positive for metastatic cutaneous SCC (Barzilai et al. 2005). Using the separate staging system for parotid disease (P) and neck disease (N) proposed by

Salivary Gland Infection
Figure 11.15a. PET scan of elderly woman with left preauricular mass post-resection of squamous cell carcinoma of the cheek. Scan shows a hot spot (SUV 6.7).
Lymph Incisions Neck

Figure 11.15c. Proposed surgery of superficial parotidec-tomy with extended Blair incision to allow for supraomohy-oid neck dissection.

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  • Charity
    Can follicular lymphoma cause enlarged lymph nodes in saliva glands?
    10 months ago

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