Benign salivary gland tumors account for 73–86% of all parotid neoplasms, and WT is the second most common tumor (3–35%) after pleomorphic adenoma (73–80%) [12,13,14]. WT, also known as papillary cystadenoma lymphomatosum, is an oncocytic epithelial neoplasm originally reported by Hildebrand in 1895 and first reported in the English literature by Warthin in 1929 [15, 16]. Clinically, WT presents as a slowly growing mass of the parotid gland in patients mainly in their fifth to seventh decades of life. There is a slight male predilection, with a ratio of 1.6:1 [4, 17]; the gender ratio is less than initially reported (5:1 or 10:1) [18, 19]. The shift in WT incidence in females is likely due to the increase in smoking habits among females, since the majority (90%) of patients with WT have a history of cigarette smoking [4, 5]. WT most commonly occurs in the parotid. Extraparotid WT is infrequently seen in the submandibular gland (1–6.9%) and extremely rarely in the minor salivary glands (0.1–1.2%) [17, 20]. Bilateral or multifocal presentations are not unusual and occur in 10% and 12% of patients, respectively [5]. The exact pathogenesis has been debated, with multiple proposed theories, hence the different terminology used in the literature [21]. It was first thought to be a variant of lateral neck cyst when Hildebrand reported it [15]. However, the most plausible pathogenesis is that WT arises from salivary gland tissue entrapped within the intra-parotid lymph nodes during development. Recently, it was elegantly demonstrated with CAM5.2 reactivity of the extrafollicular reticulum cells within the lymphoid tissue of WTs, confirming that these tumors arise within the lymph nodes [3]. Histological features of WT are straightforward and readily recognizable. It consists of a variable degree of cystic spaces lined by oncocytic epithelium with papillary configuration within lymphoid tissue with occasional germinal centers. A closer examination of the oncocytic lining shows a double layer of luminal columnar cells and abluminal round to cuboidal cells; both cells have granular eosinophilic cytoplasm [1]. WT is treated by superficial or total parotidectomy, with a low recurrence rate of 0.8–4.2% [4].
Synchronous salivary gland neoplasms in the parotid gland are uncommon and account for only 3.6% of all parotid gland neoplasms [10, 22]. The very common WT is reported with almost every benign and malignant salivary gland neoplasm, including pleomorphic adenoma, basal cell adenoma, oncocytoma, mucoepidermoid carcinoma, adenoid cystic carcinoma, salivary duct carcinoma, and acinic cell carcinoma [10, 23,24,25]. Nonetheless, coexisting non-salivary gland neoplasms with WT are not reported in the literature within the same parotid gland except for one case of WT with LCH. Tan et al. [11] reported a synchronous WT and LCH in a 50-year-old man, which presented as painless right parotid swelling with a sudden increase in size and a recent inguinal lump. His blood count showed leukocytosis and eosinophilia. Typical histological features of WT were present. In addition, there were abundant eosinophils with scattered mononuclear cells with convoluted nuclei and distinct nuclear grooves within the intra-parotid lymph nodes; these cells were positive for CD1a and S100, confirming LCH diagnosis. Interestingly, the patient’s tumor also exhibited necrosis, eosinophilic abscesses, and granulomatous reaction within the intra-parotid lymph nodes, which raised KD as a differential diagnosis. However, there was no significant fibrosis, follicular hyperplasia, or other characteristic features of KD [11]. The patient underwent parotidectomy, with no evidence of recurrence after 4 months of follow-up [11].
KD is a rare immune-mediated, inflammatory disorder with unclear etiology. It was initially reported in the Chinese population in 1937 by Kimm et al. [26] and in a Japanese population in 1948 by Kimura et al. [27]. It presents as a subcutaneous nodule with head and neck predilection in young Asian males in their second to third decades of life [7]. Patients with KD usually have regional lymphadenopathy and/or salivary gland involvement. The majority of KD patients are of Asian descent with sporadic cases in Caucasians, Hispanics, Blacks, and Arabs with a very low incidence of salivary gland involvement [7]. Laboratory test shows peripheral eosinophilia and elevated serum IgE levels, which may have prognostic implications [28]. The main histological features of KD consist of sclerotic fibrosis, prominent eosinophilic microabscesses, follicular hyperplasia, foliculolysis, and postcapillary venule proliferation of the germinal centers. Other features seen in KD include germinal center necrosis, proteinaceous deposits or eosinophilic infiltrates in the germinal centers, polykaryocytes within the germinal center or interfollicular areas, reticular IgE deposition within the germinal center, and perivenular sclerosis [7]. Treatment of KD includes regional or systemic corticosteroids, cytotoxic drugs, or radiation; however, surgical removal is preferred [29].
LCH, Hodgkin lymphoma, and angiolymphoid hyperplasia with eosinophilia (ALHA) were considered in the differential diagnosis in the present case. Immunohistochemical staining of CD1a and S100 failed to detect Langerhans cells. The clinical presentation and the diffuse lymphocytic infiltrate histologically raised the possibility of Hodgkin lymphoma; however, no typical Reed–Sternberg cells were present in the sections examined. Lastly, ALHA was previously confused with KD and used interchangeably in the old literature. ALHA is currently considered a vascular neoplasm with known FOS and FOSB gene rearrangements [30]. Histologically, it shares many features with KD but shows prominent solid growth of endothelial proliferation, with epithelioid appearance and central dilated blood vessels. Additionally, patients with ALHA rarely show peripheral eosinophilia or high serum IgE [31]. The precise pathogenesis of this hybrid WT and KD is unknown. Many hypotheses can be proposed to explain their coexistence, including the possibility of collision tumors from the synchronous occurrence of WT and KD at the same location. Another possibility is that WT produced specific cytokines that induced the inflammatory or reactive processes mimicking KD or vice versa.
