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 Table of Contents  
CASE REPORT
Year : 2013  |  Volume : 2  |  Issue : 2  |  Page : 166-169

Extensive squamous metaplasia with cystic change in pleomorphic adenoma: A potential diagnostic pitfall in fine needle aspiration cytology


Department of Pathology, Pandit Deendayal Upadhyay Government Medical College and Hospital, Rajkot, Gujarat, India

Date of Web Publication19-Jun-2013

Correspondence Address:
Jitendra G Nasit
C/4, Suryadeep Society, Near Nutan School, Behiend Chankyapuri Society, New Sama Road, Vadodara - 390 024. Gujarat
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/2278-0513.113644

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  Abstract 

Pleomorphic adenoma (PA) is the most common salivary gland tumor, frequently affects the parotid gland. Histological diversities are common as PA may show mucous, sebaceous, oncocytic cells, and squamous metaplastic cells. Squamous metaplasia rarely results in formation of extensive keratin-filled cyst lined by squamous epithelium. This can be mistaken for malignancy, like squamous cell carcinoma and mucoepidermoid carcinoma on cytological interpretation, due to limited and selective sampling. Here, we report a case of slowly enlarging parotid mass in a 70-year-old male. Cytological smears revealed moderately atypical squamous cells, clumps of keratin material, necrosis, inflammatory cells and macrophages along with bland epithelial and myoepithelial cell in fibromyxoid stroma. Cytological diagnosis of squamous cell carcinoma ex-pleomorphic adenoma was suspected. Subsequent resection showed pleomorphic adenoma, with extensive squamous metaplasia and cystic change on histology. There was no evidence of squamous cell carcinoma. The cytopathology findings are probably related to ischemic infarction, which mimic malignancy. This case emphasizes the need for a cautious and systematic approach in the cytological interpretation of cystic pleomorphic adenoma with metaplastic epithelial changes. We discuss the pitfall in the cytological diagnosis including differential diagnosis of this uncommon presentation.

Keywords: Cystic change, fine needle aspiration cytology, pleomorphic adenoma, squamous metaplasia, squamous cell carcinoma


How to cite this article:
Nasit JG, Dhruva G. Extensive squamous metaplasia with cystic change in pleomorphic adenoma: A potential diagnostic pitfall in fine needle aspiration cytology. Clin Cancer Investig J 2013;2:166-9

How to cite this URL:
Nasit JG, Dhruva G. Extensive squamous metaplasia with cystic change in pleomorphic adenoma: A potential diagnostic pitfall in fine needle aspiration cytology. Clin Cancer Investig J [serial online] 2013 [cited 2019 Jun 25];2:166-9. Available from: http://www.ccij-online.org/text.asp?2013/2/2/166/113644


  Introduction Top


Pleomorphic adenoma (PA) is the most common benign tumor of major or minor salivary glands. [1],[2],[3] Fine needle aspiration cytology (FNAC) is an accurate tool for the diagnosis of PA, with a reported reliability of 80-95%. [4],[5] PA is characterized by biphasic pattern of epithelial/myoepithelial cells and fibromyxochondroid stroma. [1],[4] However, morphological variations cause difficulty in the cytodiagnosis. [1],[5] PA rarely presents with extensive keratin-filed cyst lined by squamous epithelium. Such microscopic findings may represent a diagnostic dilemma for pathologists and misinterpreted as squamous cell carcinoma or mucoepidermoid carcinoma on cytology. [1],[2],[3],[4],[5],[6],[7],[8],[9] We report a case of PA with extensive squamous metaplasia and cystic changes in a 70-year-old male. The cytopathological picture showed a puzzling mixture of necrosis, keratin, inflammation, and moderately atypical squamous cells with bland epithelial and myoepithelial cells in fibromyxochondroid stroma, simulating squamous cell carcinoma in preexisting PA. On subsequent parotidectomy squamous cell carcinoma was not found on extensive histological sampling. Infarction-induced striking atypia of metaplastic cells closely stimulate malignancy. This case highlights the difficulty of making a correct cytological diagnosis and discusses various differential diagnoses of such unusual entity.


  Case Report Top


A 70-year-old male presented with complaint of slow growing painless mass over the right parotid region since 5 years. Physical examination showed 5 × 4-cm sized, firm, mobile swelling with normal overlying skin. Radiological findings revealed solid-cystic lesion with high vascularity in the superficial lobe of the right parotid gland. Clinical and radiological findings suggest benign salivary gland neoplasm.

FNAC was done using a 23-G needle attached to a 10-cc syringe. FNAC yielded whitish cheesy aspirate mixed with blood. Smears were fixed in 95% ethanol and stained with Hematoxylin-Eosin (H and E) stain. Cellular smears revealed many clusters and dispersed keratinized squamous cells intermingled with bland epithelial and myoepithelial cells, fibrillary chondromyxoid matrix, and hyaline globules. Few clusters of overcrowded squamous cells showed moderate to marked pleomorphism, hyperchromatic nuclei, prominent nucleoli, and moderate cytoplasm. Many dispersed tadpole-like squamous cells showed hyperchromatic and irregular nuclei with keratinized cytoplasm. Keratin flakes, necrosis, inflammatory cells, macrophages, and histiocytes were evident in background [Figure 1]. A diagnosis of squamous cell carcinoma ex-pleomorphic adenoma was suspected.
Figure 1: H and E stain: (a) Clusters and dispersed squamous cells admix with keratin, necrosis and chondromyxoid matrix (×40) (Inset fi gure × 200); (b) Bland epithelial cells are embedded in eosinophilic hyaline globule, with adjacent cluster of keratinized squamous cells in infl ammatory and necrotic background (×100); (c) Markedly atypical tadpole-shaped keratinized squamous cells show hyperchromatic, irregular nuclei, and keratinized cytoplasm (×200) (Inset fi gure × 400); (d) Squamous cells show moderate to marked pleomorphism, vesicular nuclei, prominent nucleoli, and scant to moderate cytoplasm (×400)

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In view of suspected malignancy, a nerve-sparing parotidectomy was performed. The mass was not adhered to the surrounding tissues. Grossly tumor was well encapsulated, grayish-white, and measured 5 × 4 × 4 cm. The cut surface was predominantly cystic and filled with yellowish necrotic material. Adjacent whitish firm area was evident near capsule [Figure 2]. Histology showed an encapsulated tumor mass with approximately 70% of the tumor volume composed of necrosis and keratin filled multicystic spaces, lined by metaplastic squamous epithelium with papillary finger-like fronds of squamous cells. Few solid sheets and nests of squamous cells were intermingled with fibrous stroma and inflammatory cells. Occasional foci of residual chondromyxoid matrix with ductal structures lined by bland cuboidal cells were seen. The cystic spaces containing eosinophilic amorphous material were lined by metaplastic squamous cells and cuboidal cells with granular cytoplasm. The rest of the areas showed fibrosclerotic and inflammatory response. On extensive multiple sampling, mucoid or malignant cells were not found [Figure 3]. A diagnosis of pleomorphic adenoma with extensive squamous metaplasia and cystic changes was made.
Figure 2: (a) Grossly well-encapsulated grayish-white tumor measures 5 × 4 × 4 cm. (b) The cut surface shows predominant cystic area, fi lled with yellowish necrotic material. Whitish fi rm area is evident near capsular margin

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Figure 3: H and E stain: (a) Necrosis and keratin-fi lled multicystic spaces are lined by metaplastic squamous cells with papillary fi nger-like fronds (×100); (b) Sheets and nests of squamous cells show mild atypia and keratinization with moderate inflammatory cells (×200) (Inset fi gure ×400); (c) Foci of chondromyxoid matrix with bland cuboidal cell-lined ducts, along with few metaplastic squamous cells
lined cystic spaces (×40); (d) Necrotic and eosinophilic material-fi lled cystic space is lined by cuboidal cells with granular cytoplasm, with adjacent fi brosclerotic tissue (×100) (Inset fi gure ×400)


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The postoperative course was uneventful. Patient had been reviewed regularly, without evidence of recurrence after a period of 3 years of excision.


  Discussion Top


Pleomorphic adenoma (PA) is the most common salivary gland neoplasm. [1],[2],[3] PA usually appears as a solitary, slowly growing, painless rubbery mass. [2],[3] Histological diversities are the hallmark of PA as its name implies. [1],[2],[3],[4] The proportion between epithelial and chondromyxoid elements are variable. [3] In addition, PA is characterized by wide spectrum of morphological patterns, including squamous cells, mucous cells, oncocytes, sebaceous cells, bone, adipose tissue, and crystalline materials. [1],[2],[3]

Focal squamous metaplasia is found in about 25% of PA. [1],[2],[3],[4] Rarely extensive squamous metaplasia with cystic changes are reported. [1],[2],[3],[4],[5],[6],[7],[8] Squamous metaplasia is commonly associated with ischemia, repair following infarction, and necrosis of the salivary gland. [1],[2],[9] Squamous metaplasia is also evident in non-neoplastic entities like chronic sialadenitis, necrotizing sialometaplasia, lymphoepithelial cysts, salivary duct cyst and in neoplastic lesion like Warthin tumor. [1],[2],[7],[10] The tumor may be misdiagnosed as a squamous cell carcinoma when squamous metaplasia is extensive and shows nuclear atypia. [2] Adenexal differentiation in the form of extensive keratin-filled cysts, reminiscent of trichoepitheliomatous differentiation is also reported in literature. [3],[4] Stromal changes, such as chondroid, osseous, myxoid or mucoid changes are variable in PA. However, scanty or absence of stroma is an unusual finding. [3] Extensive squamous metaplasia with cystic changes in PA, especially in scanty or absent stroma, can lead to a misdiagnosis of benign condition like keratocystoma or malignancy including mucoepidermoid carcinoma and squamous cell carcinoma, due to limited and selective sampling by FNAC and incisional biopsy. [1],[2],[3],[4],[5],[6],[7],[8],[9] Morphological diversities are often not a problem in histopathology, where the whole tumor is available for examination. [4] Cyst formation might originate from the squamous metaplasia of tumor cells, enlargement of duct-like structures by secretion from tumor cells or salivary gland tissue, hemorrhagic infraction and necrosis in the malignant tumor. [11] In our case, extensive necrosis-filled cystic spaces and moderately atypical metaplastic squamous cells are probably related to the ischemia, necrosis, and reparative process. These changes on cytology mislead for squamous cell carcinoma in preexisting PA.

Keratocystoma, dermoid cyst, squamous cell carcinoma, and mucoepidermoid carcinoma (MEC) are the important differential diagnosis of this common benign entity with unusual presentation. [1],[3],[5],[7],[10],[12],[13],[14] Keratocystoma, previously known as choristoma, is a benign salivary gland tumor resembling a trichoadenoma. It shows keratotic lamellae-filled multi-cystic spaces, lined by multilayered stratified squamous epithelium. It also exhibits solid squamous cell islands surrounded by basement membrane within the collagenous stroma, keratinized masses outside the cysts with multinucleated giant cells and focal calcification. The keratinized squamous cells without granular layers are the unique feature of keratocystoma. [3],[12] Goulart MC et al., believes that the PA and keratocystoma may constitute related lesions, representing different stages in the evolution of a specific type of salivary gland tumor. [3] Our case shows many features of keratocystoma. However, keratocystoma lacks the myxochondromatous, myoepithelial, or glandular components that are demonstrated in our case. Moreover, the cystic spaces are lined by squamous epithelium with a granular cell layer in our case, which is absent in keratocystoma. FNAC of dermoid cyst of the parotid gland show anucleated and nucleated squamous epithelium, keratin debris, and skin adnexal structures. Histopathology confirms the diagnosis, by revealing a cyst wall with keratinization of the squamous epithelium and the presence of skin annexes (hair follicles, sweat glands, sebaceous glands). [12],[13] Anucleated squamous cells and skin appendages are not seen in our case. The features favoring squamous cell carcinoma in our case are the presence of atypical keratinized squamous cells, necrosis, keratin, inflammation, and cystic changes. Cytologic atypia in metaplastic squamous cells are the main culprit for the misdiagnosis. However, presence of fibrous capsule and absence of invasion are against the squamous cell carcinoma on histology. [1],[3],[5],[7],[10] MEC show mucous, intermediate, and squamoid cells. Unlike our case, multi-cystic spaces of MEC are usually lined by mucous cells. Prominent keratinization and epidermoid cells are rare in MEC. Potential for misdiagnosis of PA as MEC on cytology include squamous and basaloid cells mimicking squamous and intermediate cells of MEC, presence of sebaceous/mucinous metaplastic cells, vacuolated histiocytic cells, mucoid material and absence of chondromyxoid matrix. [1],[3],[4] To avoid misinterpretation of PA with squamous metaplasia as squamous cell carcinoma or MEC on FNAC, a close scrutiny for chondromyxoid stroma, a characteristic feature of pleomorphic adenoma, is important. However, even if the stroma of PA is identified, the differential diagnosis may still include a squamous cell carcinoma or MEC arising in a preexisting PA. However, these are exceedingly rare. [1],[3],[4],[6]

Wide local excision is the treatment of choice. [3] PA has a low proliferative rate. Interestingly, the epithelial lining of the large keratin-filled cyst shows a higher proliferative index than the other areas. It may signify that the squamous metaplasia resulting in the large keratin-filled cyst in PA may be clinically significant, probably related to an important growth potential. [3]


  Conclusions Top


PA with extensive squamous metaplasia and cystic changes can pose significant diagnostic challenge on cytology. Careful cytological evaluation of such case is mandatory, as it would otherwise mislead to squamous cell carcinoma or MEC in pre-existing PA. Atypical metaplastic squamous cells should be evaluated with great caution. It is important to be aware of this rare benign entity, a mimicker of malignant lesion, to avoid unnecessary aggressive therapy.

 
  References Top

1.Abdul HA, Mandakini BT, Azhar F. Palatal pleomorphic adenoma with florid squamous metaplasia: A potential diagnostic pitfall. J Evol Med Dent Sci 2012;1:96-101.  Back to cited text no. 1
    
2.Aker H, Oztürk M, Ozeç I, Ozer H. An unusual buccal adenoma with extensive squamous metaplasia and cyst formation. J Chin Med Assoc 2003;66:184-8.  Back to cited text no. 2
    
3.Goulart MC, Freitas-Faria P, Goulart GR, Oliveira AM, Carlos-Bregni R, Soares CT, et al. Pleomorphic adenoma with extensive squamous metaplasia and keratin cyst formations in minor salivary gland: A case report. J Appl Oral Sci 2011;19:182-8.  Back to cited text no. 3
    
4.Batrani M, Kaushal M, Sen AK, Yadav R, Chaturvedi NK. Pleomorphic adenoma with squamous and appendageal metaplasia mimicking mucoepidermoid carcinoma on cytology. Cytojournal 2008;6:5.  Back to cited text no. 4
    
5.Su CC, Chou CW, Yiu CY. Neck mass with marked squamous metaplasia: A diagnostic pitfall in aspiration cytology. J Oral Pathol Med 2008;37:56-8.  Back to cited text no. 5
    
6.Siddaraju N, Murugan P, Basu D, Verma SK. Preoperative cytodiagnosis of cystic pleomorphic adenoma with squamous metaplasia and cholesterol crystals: A case report. Acta Cytol 2009;53:101-4.  Back to cited text no. 6
    
7.Jayaram G, Pathmanathan R, Khanijow V. Cystic lesion of the parotid gland with squamous metaplasia mistaken for squamous cell carcinoma. A case report. Acta Cytol 1998;42:1468-72.  Back to cited text no. 7
    
8.Lam KY, Ng IO, Chan GS. Palatal pleomorphic adenoma with florid squamous metaplasia: A potential diagnostic pitfall. J Oral Pathol Med 1998;27:407-10.  Back to cited text no. 8
    
9.Fulciniti F, Losito NS, Botti G, Manola M, Ionna F. Spontaneous infarction of pleomorphic adenoma: Report of a case simulating malignancy on fine-needle cytology sample. Diagn Cytopathol 2010;38:430-4.  Back to cited text no. 9
    
10.Seifert G, Donath K. Differential diagnosis of squamous epithelial carcinoma of the salivary glands. Pathologe 1998;19:201-8.  Back to cited text no. 10
    
11.Abiko Y, Kaku T, Shimono M, Noma H, Shigematsu T. Large cyst formation in pleomorphic adenoma. Bull Tokyo Dent Coll 1993;34:9-14.  Back to cited text no. 11
    
12.Nagao T, Serizawa H, Iwaya K, Shimizu T, Sugano I, Ishida Y, et al. Keratocystoma of the parotid gland: A report of two cases of an unusual pathologic entity. Mod Pathol 2002;15:1005-10.  Back to cited text no. 12
    
13.Baschinsky D, Hameed A, Keyhani-Rofagha S. Fine-needle aspiration cytological features of dermoid cyst of the parotid gland: A report of two cases. Diagn Cytopathol 1999;20:387-8.  Back to cited text no. 13
    
14.Trandafir V, Trandafir D, Ferariu D, Boiºteanu O, Haba D. Dermoid cyst of the parotid gland. Rev Med Chir Soc Med Nat Iasi 2011;115:572-8.  Back to cited text no. 14
    


    Figures

  [Figure 1], [Figure 2], [Figure 3]


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