Учебники / Textbook and Color Atlas of Salivary Gland Pathology - DIAGNOSIS AND MANAGEMENT Carlson 2008

266 Non-salivary Tumors of the Salivary Glands

be cystic in nature. They are common in the neck and seen more in the submandibular (37%) than parotid glands (31%) (Orvidas and Kasperbauer 2000). They may be prominent at birth as cystic hygromas and may pose a threat to the airway (Figure 11.4). In children they can increase considerably in size during upper respiratory tract infections. Some authors have documented the posterior triangle to be a more common site in the neck than the submandibular space, 54% versus 17%, respectively (Fageeh, Manoukian, and Tewfik et al. 1997). In a series of 324 pediatric patients with salivary gland masses, 89 (27.5%) were lymphangiomas compared to 192 (59.2%) being hemangiomas (Bentz et al. 2000). Many of these lesions are treated surgically, but persistence and recurrence are problematic (Orvidas and Kasperbauer 2000). Especially in the infiltrating lesions, complete excision may be impossible and debulking is performed. Surgery can be combined with sclerosing injections or these can be used as a

Figure 11.4. Lymphangioma involving both the parotid

single modality. Sclerosing agents are most effective in macrocystic lymphangiomas, and in 54 of these cases 49% had excellent results, 35% good, and 16% poor using sclerosant injection (Emran, Dubois, and Laberge et al. 2006).

Neural Tumors

In Siefert and Oehne’s (1986) review of 150 benign mesenchymal tumors of the salivary glands, 16% were neurogenic in origin distributed over the fourth to seventh decade. These were divided into neurilemmomas (neurinomas) in 12 of 27 cases, neurofibromas in 12 of 27 cases, and neurofibromatosis in 3 of 27 cases. There was a predominance of males, 75% for neurofibromas but 65% females for neurilemmomas. Both MR and CT scan may be useful in imaging. In the parotid gland extension of the tumor in the gland and in the petrous bone is well defined by MR imaging, while CT scan shows bone erosion and relationship to the inner ear. A combination of CT and MR is recommended when surgical resection is planned (Martin et al. 1992).

Complete removal of these lesions, especially the plexiform neurofibroma, can be extremely difficult due to their infiltrating nature and often increased vascularity (Figure 11.5). Although approximately one-third of neurilemmomas occur in the head and neck (Almeyda et al. 2004), they are comparatively rare in the salivary glands published as isolated case reports. However, as they may be mistaken for a malignant parotid tumor due to facial nerve dysfunction—for example, progressive weakness, sudden facial paralysis, hemifacial spasm and pain (Balle and Greisen 1984)—it is important to make the diagnosis to avoid inappropriate radical surgery. Regarding intra-parotid neurofibromas, a “conservative course of treatment with limited tumor excision and emphasis on retaining facial nerve function” is advocated (McGuirt, Johnson, and McGuirt 2003). Indeed, once the histologic diagnosis is made, because of the slow growth of the tumor and the unlikelihood of malignant change, conservative treatment of leaving the tumor in situ to preserve the nerve has been recommended (Fierke, Laskawi, and Kunze 2006).

Lipomas

and submandibular glands in an 8-month-old infant.

Approximately 15–20% of lipomas occur in the head and neck region (Weiss and Goldblum 2001),

and in reviewing 125 lipomas in the oral and maxillofacial region, 30 (24%) were parotid and 17 (13.6%) were submandibular in orgin (Furlong, Fanburg-Smith, and Childers 2004). In this series there was a 3 : 1 male to female gender ratio and a mean age of 51.9 years. Histologically almost half (62/125) were classic lipomas, while 59 were spindle cell/pleomorphic, 2 were fibrolipomas, and 2 chondroid lipomas. Spindle cell lipomas comprised the majority of parotid lipomas. In a review of 167 mesenchymal salivary gland tumors, Seifert and Oehne (1986) found lipomas comprised 22.5% of 150 benign tumors and 95% were in the parotid. Again 85% occurred in males. A report of 660 parotid neoplasms found only 8 patients had lipomatous tumors (1.3%), 5 with focal lipoma and 3 with diffuse lipomatosis (Ethunandan, Vura, and Umar et al. 2006). Only one tumor of 8 was in the deep lobe, but small series of parotid lipomas in the deep lobe have been reported (Gooskens and Mann 2006).

Lipomas are comparatively rare in the oral cavity, but in one paper with 46 cases, 2 patients were classified as having minor salivary gland lipomas (Fregnani, Pires, and Falzoni et al. 2003).

Salivary lipomas usually present as slowgrowing painless masses, and their appearance on CT or MR is diagnostic (Figure 11.6). Surgical excision is the treatment of choice, and although easy in classic lipoma, it can be challenging in the infiltrating variety (Figure 11.7).

Recently a designation of sialolipoma has been proposed for lipomas containing glandular elements, for example, ductal or acinar tissue (Nagao, Sugano, and Ishida et al. 2001). In their series of 2,051 salivary tumors, 7 sialolipomas, 5 in the parotid, and 2 palatal, were reported. Excision as for classic lipoma is curative. Since the initial report other cases both in major and minor glands have been published (Lin, Lin, and Chen et al. 2004; Michaelidis, Stefanopoulos, and Sambaziotis et al. 2006).

Figure 11.6a. Lipoma in the tail of the parotid.

Figure 11.6b. CT is diagnostic of lipoma.

Figure 11.6c. Intraoperative view of parotidectomy with parotid tail lipoma.

Figure 11.6d. Specimen with arrows showing lipoma.

Figure 11.6e. Histopathology confirms the presence of lipoma.

MALIGNANT MESENCHYMAL TUMORS

Sarcomas

Sarcomas of the salivary glands are very rare and case reports of virtually all histologic types have been reported. In Siefert and Oehne’s 1986 review of 167 mesenchymal tumors of the salivary glands, only 17 were sarcomas (10%). In this series, 5 cases were malignant fibrous histiocytomas, 5 cases were malignant schwannomas, 4 cases were embryonal rhabdomyosarcoma, and single cases of myxoid liposarcoma, leiomyosarcoma, and malignant hemangioendothelioma were reviewed. In reviewing salivary masses in children, rhabdomyosarcomas were the most common malignant mesenchymal tumor (7%) (Bentz et al. 2000), and in 137 children with rhabdomyosarcomas of the head and neck the parotid was the site for 6% of these tumors (Hicks and Flaitz 2002). Obviously treatment plans will be dictated by the individual sarcoma type, with initial chemotherapy for rhabdomyosarcoma in children followed by radiation therapy or surgery for residual disease. Rhabdomyosarcoma of the salivary glands appears locally aggressive with a poor prognosis (BenJelloun,

Jouhadi, and Maazouzi et al. 2005). In malignant fibrous histiocytoma, clear surgical margins appear to be the most important prognostic factor (Sachse, August, and Alberty 2006). Angiosarcoma may affect the parotid as a primary or metastatic tumor, and in a series of 29 angiosarcomas of the oral and salivary gland region there were 4 primary parotid and 3 primary submandibular gland angiosarcomas with a further 3 metastatic to the parotid (Fanburg-Smith, Furlong, and Childers 2003).

All of the metastatic patients died, but patients with primary salivary gland angiosarcoma appear to have a better prognosis than those with cutaneous or deep tissue angiosarcomas. Malignant neural sarcomas are treated with wide excision and facial nerve grafting or reanimation (McGuirt, Johnson, and McGuirt 2003). Other sarcomas of the salivary glands are rare; for example, Chadan et al. (2004) found only 11 reported cases of salivary gland liposarcoma in the literature.

Sarcomas can involve any of the major salivary glands although the parotid is most common, and due to its rarity, treatment is usually on an individual and empiric basis (Figure 11.8).

Figure 11.8a. Rapidly growing sublingual gland tumor diagnosed as synovial cell sarcoma on biopsy and immunohistochemistry.

Figure 11.8b. CT image reveals calcification in the mass leading to an initial clinical diagnosis of a high-grade malignant carcinoma ex-pleomorphic adenoma.

Figure 11.8c. CT bone window shows calcifications throughout the mass.

Figure 11.8d. Bilateral selective neck dissections in continuity with lip split to access the mandible.

Figure 11.8e. Midline mandibulotomy prior to excision of the floor of mouth and ventral tongue.

Figure 11.8f. Surgical specimen.

Figure 11.8h. Four weeks post-surgery.

Figure 11.8g. Post-resection—the reconstruction will be a microvascular forearm flap.

Figure 11.8i. Intraoral view showing the forearm flap reconstruction of the floor of the mouth.

Figure 11.9a. Elderly man with primary desmoid melanoma of the parotid gland. A 2 cm margin is marked; the light blue staining of the skin around the lesion is from dye injection for sentinel node biopsy (patient had lymphoscintigraphy immediately preoperatively).

Figure 11.9c. The neck dissection and parotidectomy with preservation of the facial nerve is complete. The submental flap is pedicled on its vascular supply prior to being rotated into the defect.

Figure 11.9b. Markings for the proposed surgery involving a total parotidectomy with left supraomohyoid neck dissection (unless sentinel nodes are found at levels IV or V). Reconstruction with a submental flap based on the submental vessels.

Figure 11.9d. Three months postoperatively.

EPITHELIAL NON-SALIVARY TUMORS

The major salivary glands may be infiltrated by squamous cell carcinoma from the overlying skin or be primarily involved by melanoma. Surgical resection with a margin of normal tissue preserving the facial nerve and utilizing neck dissection and adjuvant radiotherapy as indicated by the tumor stage is the appropriate treatment (Figure 11.9).

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 mucosaassociated lymphoid tissue (MALT) lymphomas] and only 1 patient had Hodgkin’s lymphoma. At the initial presentation 14 (52%) of patients had extranodal 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 lymphoproliferation, to monoclonal lymphoproliferation, to MALT lymphoma, and finally to high-grade lymphoma as a multistep process. Other authors have highlighted

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

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.

274 Non-salivary Tumors of the Salivary Glands

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

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

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.

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.

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.

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

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