Cystic Lesion of the Parotid Gland with Squamous Metaplasia Mistaken for Squamous Cell Carcinoma DO NOT DUPLICATE
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1 Cystic Lesion of the Parotid Gland with Squamous Metaplasia Mistaken for Squamous Cell Carcinoma A Case Report Gita Jayaram, M.D.Path., M.I.A.C., M.R.C.Path., Rajadurai Pathmanathan, M.Path., M.R.C.Path., M.I.A.C., F.R.C.P.A., and Vijay Khanijow, F.R.C.S. BACKGROUND: The diverse range of diseases that affect the salivary glands may lead to problems and pitfalls in cyto-diagnosis. While false negative diagnosis of cystic salivary gland tumors is well known, false positive cytodiagnosis in nonneoplastic salivary cysts is less well documented. CASE: An 85-year-old female presented with a painless left parotid gland swelling of three months duration. Fine needle aspiration cytology yielded fluid, smears of which showed keratinizing squamous cells with nuclear atypia leading to a cytologic diagnosis of cystic squamous cell carcinoma. A total radical parotidectomy followed. Histopathologic study showed cystic dilatation of many of the salivary ducts, which were lined with metaplastic squamous epithelium that showed atypia. There was no evidence of squamous cell carcinoma. CONCLUSION: Squamous metaplasia is known to Interpretation of FNA cytologic preparations from salivary glands is...a difficult exercise, and problems and pitfalls have been encountered even in experienced hands. occur in benign salivary gland lesions, such as pleomorphic adenoma and Warthin s tumors, as well as in salivary duct cysts and necrotizing sialometaplasia. However, atypical squamous metaplasia of salivary duct cysts mimicking squamous cell carcinoma on cytology is unusual. (Acta Cytol 1998; 42: ) squamous cell. Keywords: parotid neoplasms; parotid diseases; metaplasia; carcinoma, The scope and value of fine needle aspiration (FNA) cytology in the diagnosis of salivary gland lesions is well known. 1,9,14,15 Problems and pitfalls in cytodiagnosis, however, are not surprising in view of the diverse range of neoplastic and nonneoplastic disease that affect the salivary gland. 21 Diagnostic problems arising from cystic tumors of salivary From the Departments of Pathology and Otorhinolaryngology, Faculty of Medicine, University Malaya, Kuala Lumpur, Malaysia. Dr. Jayaram is Associate Professor, Department of Pathology. Dr. Pathmanathan is Professor, Department of Pathology. Dr. Khanijow is Associate Professor, Department of Otorhinolaryngology. Address reprint requests to: Gita Jayaram, M.D.Path., M.I.A.C., M.R.C.Path., Department of Pathology, Faculty of Medicine, University Malaya, Kuala Lumpur, Malaysia (jjgj@pc.jaring.my). Financial Disclosure: The authors have no connection to any of the companies or products mentioned in this article. Received for publication October 7, Accepted for publication March 9, /98/ /$19.00/0 The International Academy of Cytology
2 Volume 42, Number 6/November December 1998 Cystic Lesion of Parotid 1469 Figure 1 Cells with pleomorphic, deeply staining nuclei in cytologic smears of cyst fluid (MGG stain, 400). glands are usually due to dilution of diagnostic tumor cells by the cyst fluid, leading to false negative cytodiagnosis. 21 False positive cytologic diagnosis in nonneoplastic cysts of the salivary gland are relatively less common and may be due to metaplastic changes associated with chronic obstructive sialadenopathy. 21 Squamous metaplasia in benign tumors, such as pleomorphic adenoma and Warthin s tumor, 21 on occasion leads to false positive diagnosis of squamous cell carcinoma (SCC), 10,12 even on histology. 17 Below we describe cytologic and histologic features in a parotid cyst in which squamous metaplasia produced cytologic features worrisome enough to lead to a false positive diagnosis of SCC. Case Report An 85-year-old, Chinese female presented with a three-month history of a painless, progressively enlarging, 5 5-cm swelling over the left parotid region. It was firm, mobile, nonfluctuant and nontender. The overlying skin was normal, and there was no facial nerve palsy or regional lymphadenopathy. The parotid duct opening was normal. There was no other sialomegaly. The patient was referred for FNA cytology, which was done in the outpatient department by the cytopathologist (G.J.) using a 22-gauge needle attached to a 20-mL, plastic syringe that was mounted on a handle for single-hand grip. Ten milliters of turbid fluid resembling pus was aspirated. The smears were air dried, fixed in methanol and stained with May- Grünwald-Giemsa (MGG) stain. A cytologic diagnosis of cystic squamous cell carcinoma was made, and the patient underwent a left total radical parotidectomy with right sural nerve graft. At surgery the parotid gland was gritty, especially near the tail. The skin was free, and the facial nerve was described as enmeshed by the tumor. Postoperative recovery was uneventful, and the patient was well one year following surgery. Cytologic Features MGG-stained smears showed a necrotic background with many degenerating, naked nuclei. A few isolated cells and small groups of cells showed deeply basophilic cytoplasm and a high-nuclear cytoplasmic ratio with opaque, deeply staining nuclei (Figures 1 and 2). These cells were of varying shapes round, polygonal, fiber and tadpole shaped and all showed opaque, deeply staining nuclei (Figures 1 4). A cytologic diagnosis of cystic squamous cell carcinoma was made. Gross Pathology Two of the three specimens were labelled lymph nodes and the third was the total parotidectomy specimen. Both lymph nodes measured 1.5 cm in diameter, and the cut section was homogeneous and pink. The parotidectomy specimen was greyish brown, weighed 66 g and measured cm. On cut section a cystic cavity measuring 2.5 cm in diameter was seen. The cyst wall was lined with yellowish grey material. The salivary glandular tis- Figure 2 Isolated and clustered cells with a high nuclear/cytoplasmic ratio and opaque, deeply staining nuclei in a necrotic background (MGG stain, 400).
3 1470 Jayaram et al sue around the cyst wall was greyish yellow and partly fibrosed. Microscopic Pathology Sections of the parotidectomy specimen showed the cyst wall to be lined with squamous epithelium, which showed mild nuclear atypia with opaque, deeply staining nuclei and cells with fiber and tadpole shapes, reflecting the cytomorphologic appearance of the aspirate (Figure 5). The outer cyst lining was composed of thick, fibrous tissue with aggregates of chronic inflammatory cells. The salivary gland parenchyma showed foci of fibrosis and diffuse infiltration of the glands by mature adipocytes (lipomatosis). 11 Smaller cysts of varying sizes were formed by dilated salivary ducts, some of which contained secretory deposits or crystalloid material. The crystalloids were of varying shapes (rods and rectangular and polyhedral shapes) and sizes. Periductal deposits of crystalloids (Figure 6) were accompanied by a foreign body giant cell reaction. Occasional dilated ducts were lined with epithelium showing oncocytic metaplastic changes. The multiple sections of the parotidectomy specimen as well as lymph nodes showed no evidence of malignancy. Discussion Problems encountered in the cytologic diagnosis of cystic salivary gland lesions are twofold: false negative cytology in tumors containing cystic areas 6,13 Figure 4 Tadpolelike cell and cells with deeply basophilic cytoplasm and opaque nuclei (MGG stain, 1,000). and worrisome nuclear or metaplastic changes in benign cystic salivary gland tumors, 10 chronic obstructive sialadenopathy, 21 necrotizing sialometaplasia 3 or, rarely, cytomegalovirus sialadenitis, 20 leading to false positive cytology. The present case fits into the second category and showed several features of salivary glands seen in elderly individuals: glandular cysts, crystalloid deposition and oncocytic metaplasia. 18 Cystic change is well known in metastatic nodal SCC 1,2,16,19 and has also been noted in primary SCC of the parotid gland. 6 The aspirate, as in the present case, often resembles pus, is usually hypocellular and may show degenerative features (personal experience). The age of the patient, the cystic nature of the lesion and the squamous atypia seen in the cytologic Figure 3 Tadpolelike cell and cells with deeply basophilic cytoplasm and opaque nuclei (MGG stain, 1,000). Figure 5 Section of parotidectomy specimen showing cyst lining composed of atypical squamous epithelium with fiber cells (hematoxylin and eosin, 250).
4 Volume 42, Number 6/November December 1998 Cystic Lesion of Parotid 1471 Figure 6 Periductal crystalloid deposits (hematoxylin and eosin, 100). smears together led to a false positive diagnosis of cystic SCC in this case. At that time the hypocellularity was explained on the basis of dilution of cells by fluid. The atypical squamous cells in the present case resembled the fiber and tadpole cells illustrated by Kumar et al 10 in a case of Warthin s tumor with squamous metaplasia misdiagnosed as SCC. On review of the cytologic material, it was thought that the atypia was possibly degenerative, which can sometimes mimic malignancy. The hypocellularity of the aspirate, coupled with the lack of clinically unequivocal malignant features, should have led to a more guarded cytologic opinion. The other conditions that can be mistaken, even on histology, for squamous cell carcinoma are postirradiation sialadenitis and necrotizing sialometaplasia, which usually affect the minor salivary glands of palate, lips and, rarely, gingiva and submandibular glands. 3,18 The association of salivary cysts with crystalloids was observed in FNA cytologic material by one of us (G.J.) 5 and subsequently documented by others. 4,7 The association of salivary cysts with oncocytic and squamous metaplasia and crystalloids has also been observed in cytologic material (personal observation), and is not surprising in view of the fact that all those are lesions seen in elderly individuals. 10 The oncocytic metaplasia (which was focal) and presence of crystalloids were not detected in the FNA cytologic material in the present case. In the salivary glands, where trucut and incisional diagnostic biopsy have never found favor, FNA cytology can frequently provide a preoperative diagnosis to guide the surgeon in determining the de- gree of urgency necessary for hospital admission and permits an informed preoperative discussion with the patient. In a previous cytologic study of 247 salivary gland lesions, we found FNA to be of use not only in the diagnosis and typing of salivary gland tumors (with 87.8% sensitivity and 91% cytodiagnostic accuracy) but also in their segregation from nonneoplastic lesions, for which unnecessary surgery could be obviated. 10 Interpretation of FNA cytologic preparations from salivary glands is nevertheless a difficult exercise, and problems and pitfalls have been encountered 8 even in experienced hands. 15 In most centers, as in ours, FNA cytology has achieved an undisputed status, and cytologic diagnosis often forms the basis on which the therapeutic protocol is decided. Awareness of the limitations and pitfalls of FNA cytology is just as important as is knowledge of the scope of FNA in salivary gland and other lesions, and this can be achieved only by bringing to light problems and pitfalls encountered. References 1. Eneroth CM, Franzén S, Zajicek J: Cytologic diagnosis on aspirates from 1000 salivary gland tumours (suppl). Acta Otolaryngol 1967;224: Engzell V, Zajicek J: Aspiration biopsy of tumours of the neck: I. Aspiration biopsy and cytologic findings in 100 cases of congenital cysts. Acta Cytol 1970;14: Fechner RE: Necrotising sialometaplasia: A source of confusion with carcinoma of the palate. Am J Clin Pathol 1977;67: Gupa RK: Aspiration cytodiagnosis of crystalloids in a sudden swelling of parotid gland (lett). Diagn Cytopathol 1995; 12:83 5. Jayaram G, Khurana N, Basu S: Crystalloids in a cystic lesion of parotid salivary gland: Diagnosis by fine needle aspiration. Diagn Cytopathol 1993;9: Jayaram G, Verma AK, Sood N, Khurana N: Fine needle aspiration cytology of salivary gland lesions. J Oral Pathol Med 1994;23: Johnson FB, Oertel YC, Ammann K: Sialadenitis with crystalloid formation: A report of six cases diagnosed by fine needle aspiration. Diagn Cytopathol 1995;12: Kocjan G, Nayagam M, Harris M: Fine needle aspiration cytology of salivary gland lesions: Advantages and pitfalls. Cytopathology 1990;1: Koivuniemi A, Saksela E, Holopainen E: Cytologic aspiration biopsy in otorhinolaryngological practice: A preliminary report with special reference to method. Acta Otolaryngol 1970;263: Kumar N, Sharma S, Verma K: Atypical squamous cells in a fine needle aspirate from Warthin s tumor (lett). Acta Cytol 1996;40:
5 1472 Jayaram et al 11. Laucirica R, Farnum JB, Leopold SK, Kalin GB, Youngberg GA: False positive diagnosis in fine needle aspiration of an atypical Warthin s tumor: Histochemical differential stains for cytodiagnosis. Diagn Cytopathol 1989;5: Layfield LJ, Glasgow BJ, Goldstein N, Lufkin R: Lipomatous lesions of the parotid gland: Potential pitfalls in fine needle aspiration biopsy diagnosis. Acta Cytol 1991;35: Linsk JA, Franzén S: Clinical Aspiration Cytology. Philadelphia, JB Lippincott, 1983, pp 4-5, Mavec P, Eneroth CM, Franzén S, Morberger G, Zajicek J: Aspiration of salivary gland tumors: I. Correlation of cytologic reports from 652 aspiration biopsies with clinical and histological findings. Acta Otolaryngol 1964;58: Orell SR, Nettle WJS: Fine needle aspiration biopsy of salivary glands: Problems and pitfalls. Pathology 1988;20: Rosai J: Diseases of lymph node. In Ackerman s Surgical Pathology. Eighth edition, second volume. Edited by J Rosai. St Louis, CV Mosby, 1996, p Seifert G, Bull HG, Donath K: Histologic subclassification of the cystadenolymphoma of the parotid gland: Analysis of 275 cases. Virchows Arch 1980;388: Seifert G, Miehlke A, Haubrich J, Chille R: Diseases of the Salivary Gland. New York, George Thieme Verlag, 1986, pp , 253, Verma K, Mandal S, Kapila K: Cystic change in lymph nodes with metastatic squamous cell carcinoma. Acta Cytol 1995; 39: Wax TD, Layfield LJ, Zaleski S, Bhargara V, Cohen M, Leyerly HK, Fisher SR: Cytomegalovirus sialadenitis in patients with the acquired immunodeficiency syndrome: A potential diagnostic pitfall with fine needle aspiration cytology. Diagn Cytopathol 1994;10: Young JA: Diagnostic problems in fine needle aspiration cytopathology of the salivary glands. J Clin Pathol 1994;47:
Departments of Pathology and *Otorhinolaryngology, Faculty of Medicine, University of Malaya, Kuala Lumpur
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