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Year : 2016  |  Volume : 59  |  Issue : 3  |  Page : 368-371
Cytomorphological findings and histological correlation of papillary cystadenocarcinoma of the parotid: Not always a low-grade tumor

1 Department of Pathology, R. N. Cooper Hospital, Mumbai, Maharashtra, India
2 Department of Pathology, Tata Memorial Hospital, Mumbai, Maharashtra, India

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Date of Web Publication10-Aug-2016


Papillary cystadenocarcinoma (PCAC) is a rare salivary gland tumor characterized by a predominantly cystic growth that often exhibits intraluminal papillary growth without specific histologic features of other cystic salivary gland tumors. The preoperative cytological diagnosis can pose a diagnostic challenge as it has to be differentiated from other cystic papillary tumors such as mucoepidermoid carcinoma, papillary cystic variant of acinic cell carcinoma, and low-grade cribriform CAC. It is considered to be a low-grade malignant salivary gland tumor with an indolent biological behavior. We report a case of PCAC of the parotid in a 55-year-old male diagnosed on fine needle aspiration cytology. Although it showed mild atypia cytologically, on excision tumor showed vascular and perineural invasion with regional node metastasis indicating a wider morphologic spectrum than what is described. This prompted us to write a case report describing the cytological and histological features of this rare tumor and also discuss the diagnostic challenges.

Keywords: Cytology, histology, papillary cystadenocarcinoma, parotid

How to cite this article:
Khatib Y, Dande M, Patel RD, Kane SV. Cytomorphological findings and histological correlation of papillary cystadenocarcinoma of the parotid: Not always a low-grade tumor. Indian J Pathol Microbiol 2016;59:368-71

How to cite this URL:
Khatib Y, Dande M, Patel RD, Kane SV. Cytomorphological findings and histological correlation of papillary cystadenocarcinoma of the parotid: Not always a low-grade tumor. Indian J Pathol Microbiol [serial online] 2016 [cited 2020 Jul 9];59:368-71. Available from: http://www.ijpmonline.org/text.asp?2016/59/3/368/188114

   Introduction Top

Papillary cystadenocarcinoma (PCAC) of the salivary gland was first included as a separate entity in the WHO classification of salivary gland tumors in 1991.[1] However, in the 2005 WHO classification, it was renamed as CAC because though all are cystic tumors some may lack the papillary architecture.[1] Other synonyms used to describe this entity include malignant papillary cystadenoma, low-grade papillary adenocarcinoma, and mucus producing adenopapillary carcinoma. It usually involves the parotid and sublingual gland but is also seen in minor salivary glands of buccal mucosa, lip, and palate. Cytological diagnosis is important to distinguish it from other cystic lesions of salivary gland. Cellular smears with papillary fragments and clusters of cells against a mucinous or proteinaceous background with histiocytes are characteristic of PCAC. Cells show mild to moderate atypia with dense and vacuolated cytoplasm. There have been only a few reports describing the cytological features of this tumor on fine needle aspiration cytology (FNAC).[1],[2],[3],[4]

   Case Report Top

A 55-year-old male presented with a gradually increasing painless swelling in the right parotid region since 3 years. Clinical examination revealed a firm, parotid mass measuring 6 cm × 5 cm. FNAC smears were cellular with tumor cells arranged in papillary fragments, sheets, and singly [Figure 1]a. The lining cells were low to high cuboidal with dense cytoplasm. The nuclei were enlarged and appeared hyperchromatic, some showing eccentric location [Figure 1]b. Background showed mucus with few macrophages [Figure 2]a and [Figure 2]b. Cytologic interpretation of a low-grade papillary neoplasm was given. A superficial parotidectomy was performed. Gross examination revealed a 6 cm × 5.5 cm partially encapsulated mass with microcystic areas on cut section. Cysts were filled with mucoid fluid. Tumor was infiltrating into the parenchyma of the parotid gland and into the overlying dermis [Figure 3]a. Histologically, the neoplasm contained variably sized small multicystic spaces lined by papillary structures [Figure 3]b Focal extracellular mucin was noted. Occasional psammoma bodies were seen. Cyst wall showed infiltration with tumor islands with a cribriform pattern [Figure 4]a and [Figure 4]b. Lining cells were tall cuboidal with moderately enlarged vesicular nuclei and prominent nucleoli [Figure 5]. Perineural and lymphovascular invasion was seen. Squamous or acinar differentiation was not seen. Two regional nodes showed the presence of metastasis [Figure 6]a. On immunohistochemistry (IHC), the tumor cells were strongly and diffusely positive for cytokeratin 7 [Figure 6]b and were negative for CK 20, p63, and cerb2. MIB labeling index was 10%. Mucin stain showed focal intracytoplasmic positivity. Based on the histological and IHC findings, a diagnosis of PCAC was made.
Figure 1: (a) Microphotograph from parotid showing cellular aspirate composed of tumor cells in papillary fragments and clusters (PAP, ×10). (b) Higher magnification showing a papilla composed of cells with dense cytoplasm and enlarged hyperchromatic nuclei (Giemsa, ×40)

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Figure 2: (a) Microphotograph showing clusters of cells with macrophages in the background. (b) Microphotograph showing clusters of cell some showing vacuoles and some showing eccentric nuclei with mucin in the background

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Figure 3: (a) Gross photo showing partially encapsulated tumor mass with microcystic areas imparting a more solid than cystic appearance with tumor extending beneath skin. (b) Microphotograph showing cyst with papillary structures (H and E, ×4)

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Figure 4: (a) Microphotograph showing cribriform areas with mucin (H and E, ×40). (b) Microphotograph showing cribriform areas with mucin along with normal parotid seen at periphery (H and E, ×10)

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Figure 5: Microphotograph showing papilla lined by cells with vesicular nuclei and abundant cytoplasm. Core of the papilla shows lymphocytes (H and E, ×40)

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Figure 6: (a) Microphotograph of lymph node showing tumor metastasis (H and E, ×10) (b) Microphotograph of immunohistochemistry showing CK7 positive tumor infiltrating the skin (×10)

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   Discussion Top

PCAC is a rare malignant tumor, with an estimated incidence of 2% of malignant salivary gland tumors.[4] Foss et al.[5] described the histopathologic spectrum of CAC in a series of 57 cases. There was no gender preference and the average age was 57 years. The size ranged from 0.4 to 6 cm. Microscopically, all tumors showed multiple small or varied cysts and demonstrated an infiltrative growth which was the criterion used to distinguish it from cystadenoma. About 75% cases showed extensive papillary proliferation in the cystic areas and extracellular mucin. In 35% cases, cribriform areas were seen in the cyst wall. Only 5 cases showed perineural invasion and 1 case showed vascular invasion. Lymph node metastasis was seen in 1 case of parotid and 3 cases of minor salivary gland tumors. About 35 cases with low cuboidal cells showed minimal cytological atypia, mitosis of 0–1/hpf and were low grade. None developed metastasis and only one recurred. Nearly 9 cases with large cuboidal cells and 7 cases with columnar cells showed moderate atypia and higher mitotic rate. About 4 cases had metastasis and 3 recurred from this group. Although this tumor is considered to be low grade, there are reports of CAC with higher grade lesions and low-grade lesions with aggressive behavior as seen in the present case. Pollett et al.[6] have described a case of CAC with high-grade features and Mustafa et al.[7] have reported a case with intermediate grade features. Chen [8] in a study of 22 cases subdivided PCAC into well and poorly differentiated types and described a correlation between tumor differentiation recurrence and nodal metastasis.

There are only a few case reports on the cytological features of CAC on FNAC [Table 1]. Kapila and Verma [2] have described 4 cases of CAC on FNAC but raised difficulties in differentiating it from other cystic tumors such as mucoepidermoid carcinoma and acinic cell carcinoma-papillary cystic variant (ACC-PCV). The presence of cellular smears of low-grade papillary fragments, ball of cells, and single cells with a mucinous or proteinaceous background with histiocytes and lymphoid tissue has been described. Cells showed mild atypia were cuboidal or columnar with dense and vacuolated cytoplasm with bland and sometimes eccentric nuclei [Table 1]. Layfield and Gopez [9] and Kawahara et al.[10] have reported cells with larger nuclei and nucleoli in their cases.
Table 1: Cytological features of cystadenocarcinoma of parotid gland on fine needle aspiration cytology

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CAC has a range of differential diagnosis on FNAC which includes all the cystic lesions of the salivary gland.[6] Benign cystic lesions are paucicellular, and rarely cases of CAC with low cellularity have been mistaken for them.[9] Mucoepidermoid carcinoma shows a dirty and mucinous background along with intermediate and squamous cells.[2] In ACC-PCV cells show basophilic granular and vacuolated cytoplasm with the absence of mucin.[11] Cribriform CAC on cytology shows tumor cells with tight intercellular junctions forming a vague cribriform, solid or pseudopapillary arrangement with no mucin.[12] Tumor cells are bland looking ductal epithelial cells with scanty cytoplasm low nucleocytoplasmic ratio and small or absent nucleoli. PLGAC shows in addition to papillary fragments presence of stromal fragments and hyaline globules.[3] Cells have oval or polyhedral shape with mild nuclear pleomorphism. Cystadenoma shows a mucinous background with occasional epithelial cells with scanty cytoplasm and regular round nuclei. It is not always possible to distinguish cystadenoma from CAC on cytology as final diagnosis is based on stromal invasion.

The present case fits into the WHO and AFIP definition of CAC with a predominant papillary and focal cribriform proliferation, extracellular mucin, intermediate grade cytological features but presence of perineural and vascular invasion, dermal infiltration lymph node metastasis indicate an aggressive lesion. Histological grading is a significant predictor of outcome in salivary gland tumors and is required for both prognosis and treatment. The present case and some of the earlier reports suggest a need to have a grading system even for PCAC so that all tumors are not considered low grade and under treated as in the present case.

The management of CAC is complete surgical excision with clear margins. Higher grade tumors may need a wider excision and additional radiotherapy. The prognosis of this tumor is good though it can show recurrence and lymph node metastasis in a few cases.

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Conflicts of interest

There are no conflicts of interest.

   References Top

Aloudah NM, Raddaoui E, Aldhahri S, Al-Abbadi MA. Low-grade papillary cystadenocarcinoma of the parotid gland: Presentation of a case with cytological, histopathological, and immunohistochemical features and pertinent literature review. Diagn Cytopathol 2009;37:128-31.  Back to cited text no. 1
Kapila K, Verma K. Cytomorphologic features of papillary cystadenocarcinoma of the parotid. Diagn Cytopathol 2002;26:392-7.  Back to cited text no. 2
Klijanienko J, Vielh P. Salivary carcinomas with papillae: Cytology and histology analysis of polymorphous low-grade adenocarcinoma and papillary cystadenocarcinoma. Diagn Cytopathol 1998;19:244-9.  Back to cited text no. 3
Mardi K, Sharma S, Gupta N. Papillary cystadenocarcinoma of submandibular salivary gland: A rare case report. J Cancer Res Ther 2010;6:330-2.  Back to cited text no. 4
Foss RD, Ellis GL, Auclair PL. Salivary gland cystadenocarcinomas. A clinicopathologic study of 57 cases. Am J Surg Pathol 1996;20:1440-7.  Back to cited text no. 5
Pollett A, Perez-Ordonez B, Jordan RC, Davidson MJ. High-grade papillary cystadenocarcinoma of the tongue. Histopathology 1997;31:185-8.  Back to cited text no. 6
Koç M, Yanilmaz M, Yildirim H, Gök U, Cobanoglu B. MRI findings of papillary cystadenocarcinoma of the submandibular gland. Diagn Interv Radiol 2010;16:20-3.  Back to cited text no. 7
Chen XM. Papillary cystadenocarcinoma of the salivary glands: Clinicopathologic analysis of 22 cases. Zhonghua Kou Qiang Yi Xue Za Zhi 1990;25:102-4.  Back to cited text no. 8
Layfield LJ, Gopez EV. Cystic lesions of the salivary glands: Cytologic features in fine-needle aspiration biopsies. Diagn Cytopathol 2002;27:197-204.  Back to cited text no. 9
Kawahara A, Harada H, Mihashi H, Akiba J, Kage M. Cytological features of cystadenocarcinoma in cyst fluid of the parotid gland: Diagnostic pitfalls and literature review. Diagn Cytopathol 2010;38:377-81.  Back to cited text no. 10
Shet T, Ghodke R, Kane S, Chinoy RN. Cytomorphologic patterns in papillary cystic variant of acinic cell carcinoma of the salivary gland. Acta Cytol 2006;50:388-92.  Back to cited text no. 11
Ko YS, Koo JS. Cytomorphological findings and histological correlation of low-grade cribriform cystadenocarcinoma of salivary gland in fine-needle aspiration: A case study. Korean J Pathol 2013;47:592-5.  Back to cited text no. 12

Correspondence Address:
Dr. Richa D Patel
Department of Pathology, R. N. Cooper Hospital, Mumbai - 400 012, Maharashtra
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/0377-4929.188114

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  [Figure 1], [Figure 2], [Figure 3], [Figure 4], [Figure 5], [Figure 6]

  [Table 1]

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[Pubmed] | [DOI]


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