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Immunohistopathology of Papillary Cystadenoma Lymphomatosum (Warthin’S Tumor) CHARLES K

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Immunohistopathology of Papillary Cystadenoma Lymphomatosum (Warthin’S Tumor) CHARLES K ANNALS OF CLINICAL AND LABORATORY SCIENCE, Vol. 14, No. 1 Copyright © 1984, Institute for Clinical Science, Inc. Immunohistopathology of Papillary Cystadenoma Lymphomatosum (Warthin’s Tumor) CHARLES K. FOULSHAM, II, M.D.,* GEORGE S. JOHNSON, M.D., Ph.D .,ft G. GORDON SNYDER, III, M.D.,*§ ROBERT J. CARPENTER, III, M.D.,* and NELOFAR Q. SHAFI, M.D.fi *Department of Otolaryngology and Facial Plastic Surgery, fDepartment of Laboratory Medicine, University of Connecticut Health Center, Farmington, CT 06032 and fDepartment of Laboratory Medicine, Veterans Administration Medical Center, Newington, CT 06111 ABSTRACT A retrospective study of various benign salivary gland neoplasms was designed to study the frequency distribution and density of immunoglob­ ulins (Igs) located within their various tissue compartments. Buffered- formalin fixed, paraffin embedded sections of Warthin’s tumor, cystade­ noma, oncocytoma, autoimmune thyroiditis, normal salivary gland, and reactive peripheral lymph node were obtained and processed via the per- oxidase-antiperoxidase method following trypsinization to re-expose anti­ genic sites. The subepithelial and parafollicular zones of Warthin’s tumor show an Ig density distribution (IgA IgG) >> IgM, but the relative densities in the germinal center are (IgG = IgM) >> IgA. In contrast, the normal salivary gland displays almost exclusively IgA positive cells with only an occasional IgG or IgM positive cell. In general, the three salivary gland neoplasms considered all display a relatively similar fre­ quency distribution with (IgA 5= IgG) >> IgM and much greater densities of all Igs than encountered in the normal salivary gland; however, the densities of IgA and IgG positive cells are greatest in Warthin’s tumor. A similar frequency distribution of immunocytes in the parafollicular zone of autoimmune thyroiditis and Warthin’s tumor is noted with an increased density of all Igs occurring in autoimmune thyroiditis. A significant in­ crease in the density of IgA immunocytes is noted in the germinal centers of autoimmune thyroiditis. A comparison of Warthin’s tumor with a reac­ tive peripheral lymph node shows a marked increase in the density and § Send reprint reQuests to G. Gordon Snyder, III, Surgery, University of Connecticut Health Center, M.D., Division of Otolaryngology and Facial Plastic Farmington, CT 06032. 47 0091-7370/84/0100-0047 $02.00 © Institute for Clinical Science, Inc. 48 FOULSHAM, JOHNSON, SNYDER, CARPENTER, AND SHAFI frequency of IgA in the parafollicular zone in the former lesion, and sig­ nificant elevations of IgG and IgM in the latter process both in the para­ follicular zone and in the germinal centers. No data generated by this study support an autoimmune etiology of Warthin’s tumor. Histopathologically, the oncocytoma appears to repre­ sent a pathologic entity distinctly different from papillary cystadenoma lymphomatosum. Our data tend to support the hypothesis that Warthin’s tumor arises within ectopic salivary gland elements trapped within para- parotid or intraparaotid lymph nodes during embryogenesis. The cystad­ enoma appears to represent a similar pathologic process arising in salivary gland elements independent of lymphoid tissue. Introduction arising in such ectopic locations as the tonsillar fossa, maxillary sinus, larynx, Papillary cystadenoma lymphoma­ neck, and lacrimal glands.4,7,17,19,24,28 This tosum (PCL), better known as Warthin’s is the only parotid tumor known to occur tumor, was first described in 1910 by Al­ bilaterally and is frequently multicen- brecht and Arzt1 and further character­ tric.6,18 ized by Warthin34 in 1929. Since then it Papillary cystadenoma lymphoma­ has appeared frequently in descriptions tosum has no distinguishing features of ectopic salivary gland tissue and in the which clinically differentiate this benign analysis of its histologic components. lesion from a malignant lesion. There is Warthin’s tumor is classified as an ad- no evidence of metastasis or local inva­ enolymphoma, a subtype of the salivary sion and the facial nerve is unaffected. gland monomorphic adenoma.32 Al­ Sialography may show displacement of though initially considered a rare lesion the ductal system by a mass lesion within it now accounts for about six percent of or outside of the parotid gland, but this, all parotid tumors and three or four too, is not diagnostic. Diagnosis may be percent of minor salivary gland tu­ made preoperatively via a Technetium- mors.20,28,32 99 scan which will show increased uptake Clinically there is a preponderance of in those lesions with a preponderance of Caucasian males (3:1) in the fifth to sev­ oncocytes — namely oncocytomas and enth decade. The tumor shows a definite Warthin’s tumor.7,24 predilection for the parotid gland, pre­ senting as an asymptomatic, slow grow­ ing, nontender mass which is round or P a t h o lo g y oval, firm to cystic in consistency and is On gross examination, Warthin’s tu­ usually present for six months to sev­ mor is well encapsulated and sharply cir­ eral years prior to medical evalua­ cumscribed. Its cut surface is grayish tan tion 6>16.20.28.32 to pink in color and studded with whitish Although this lesion is frequently con­ areas representing germinal centers. tained within the superficial lobe of the Multiple cystic spaces formed by mul­ parotid gland, it has also been found to tiple papillary epithelial projections are lie outside the main substance of the usually present. These cystic spaces con­ gland. Warthin’s tumor is also known to tain a clear brownish mucoid mate­ arise in the submaxillary gland and minor rial 7,16,20,24,28 salivary glands of the palate. Scattered On histologic examination multiple ep­ reports have also documented this lesion ithelial infoldings are seen composed of WARTHIN’S TUMOR 49 two oxyphilic layers of cells, an outer The parotids, however, are encapuslated layer of tall columnar cells, and a basal later allowing an admixture of both epi­ layer of small irregular cells. The co­ thelial and mesenchymal tissues. In fre­ lumnar cells have hyperchromatic nuclei quent fetal and adult specimens, salivary and granular cytoplasm containing a ducts and acinar tissue can be found large number of mitochondria. The basal within both intraparotid and paraparotid cells have a vesicular oval nucleus and lymph nodes.3,4’5’6’71719 Salivary gland dense cytoplasm similar to oncocytes. tissue can occasionally be found in cer­ The cysts contain an eosinophilic pro- vical lymph nodes, sometimes at a dis­ teinaceous material with inclusions of tance from the parotid.4 cellular debris.2,7,18,20,24,25 The subepithe- Neoplastic proliferation of the epithe­ lial stroma is composed of lymphoid lial elements within the lymph node and tissue with numerous lymphoid follicles a resulting hyperplasia of the lymphatic which exhibit unremarkable germinal elements ultimately leads to clinical ev­ centers and ill-defined mantle regions. idence of a mass lesion.6,24 Dietert16 re­ Associated inflammatory response may ported a six percent incidence of War­ lead to infiltration by neutrophils and thin’s tumors found incidentally as part eosinophils. The stroma is dotted with of radical neck dissection specimens and large lymphoid cells consistent with stem Azyopardi and Hou3 reported a case of cells or large lymphocytes;17,24’29 plasma multiple Warthin’s tumors, one of which cells and histiocytes are abundant. The occurred within a lymph node and dem­ heterogenous nature of this cellular infil­ onstrated a transition from parotid ductal trate is similar to that found in Hashi- inclusions to an adenolymphoma. It is moto’s thyroiditis and other hypersensi­ felt by many authors that this embryo- tivity diseases. Occasionally lymphocytes logical rest theory adequately explains and histiocytes can be seen infiltrating the multicentricity and bilaterality of the epithelial lining as well as within the Warthin’s tumor. However, the quantity lumina of the cystic spaces.2 of lymphoid stroma frequently encoun­ tered is greatly in excess of that in a small O r ig in lymph node from which it presumably arises. The distribution, i.e., the lym­ The origin of Warthin’s tumor has long phoid follicles located at the tips of the been disputed. Currently two theories of papillary projections, an unlikely location origin have gained support: (1) hetero­ for preexisting follicles, also suggests that topic salivary gland tissue entrapped the stromal proliferation is in response to within lymph nodes; and (2) autoimmune the neoplastic process.32 response. Albrecht and Arzt suggested In 1971, Allegra2 proposed another or­ that proliferation of heterotrophic nests igin after his study of the immunoflu- of pharyngeal endoderm, the anlage of orescent characteristics of this neoplasm. salivary gland tissue, within parotid He noted that the morphologic charac­ lymph nodes was a likely source.1 Since teristics of the lymphoid stroma and the their original description, many authors distribution of immunoglobulin (IgG) as have agreed with this hypothesis. During demonstrated by immunofluorescence embryogenesis the anlage of the major resembled that found in delayed hyper­ salivary glands is surrounded by a lym­ sensitivity disease instead of normal or phoid stroma. The sublingual and sub- reactive lymph nodes. It was proposed maxillary glands are encapsulated from that oncocytomas, papillary cystade- this anlage early in embryogenesis and nomas and papillary cystadenoma lym- are thus devoid of lymphoid elements. phomatosum occupy a continuum of a 50 FOULSHAM, JOHNSON, SNYDER, CARPENTER, AND SHAFI specific pathologic process.17 Oxyphilic has many disadvantages.31 It requires metaplasia of the ductal epithelium oc­ fresh or specially processed tissue, pro­ curs with an associated increase in mi­ vides poor morphologic detail, and ex­ tochondria. Increasing cell volume and hibits interference with nonspecific proliferation of the epithelium leads to tissue autofluorescence. In addition, the characteristic papillary infolding and specialized microscopy is required and cyst formation followed by an accumula­ the resulting slide preparations are not tion of intraductal and intracystic secre­ permanent. The immunoperoxidase tions.
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