Cytomorphological features of papillary cystadenocarcinoma of parotid gland: A case report with review of literature

Cytology

Fine needle aspiration was done with a 22 G needle. The aspiration yielded 8 ml of hemorrhagic fluid following which the swelling regressed but did not disappear completely. The fluid so obtained was cytocentrifuged and smears were prepared. The second aspiration was performed from the residual swelling. All the smears thus prepared were stained with May-Grunwald-Giemsa, hematoxylin and eosin, and Papanicolaou stain.

Microscopy showed cellular smears which were comprised of neoplastic cells arranged in groups, solid nests, and complex branching papillary fragments. Most of these cells were cuboidal to columnar with eccentrically placed bland appearing nuclei exhibiting mild pleomorphism with minimal mitotic activity. Some of these cells also revealed oncocytic changes. Amidst, these cells were the cyst macrophages. Most of the cells had dense cytoplasm with a fair number of them displaying small vacuolated, soap bubble-like appearance of the cytoplasm [Figure 1]. Occasional univacuolated signet ring cells and mucin vacuoles were also noted. These cells were positive for periodic acid–Schiff with acid digestion (PAS-AD) [Figure 2]. Features were suggestive of low-grade PCA (LGPCA). The patient underwent surgery with wide excision of the uninvolved tissue.

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Figure 1

(a and b) Complex papillary pattern along with singly scattered cells (a: Papanicolaou, ×40). Fibrovascular cores are also visible (b: May-Grunwald-Giemsa, ×100). (c) Dispersed cells displaying cuboidal to columnar cells with eccentrically placed nuclei exhibiting mild pleomorphism. An occasional mitotic figure is also seen at the top of the field (May-Grunwald-Giemsa, ×400). (d) Cells showing vacuolated cytoplasm with soap bubble appearance (May-Grunwald-Giemsa, ×400)

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Figure 2

(a) Some cells show eccentric nuclei with bright eosinophilic mucin vacuole (May-Grunwald-Giemsa, ×400). (b) Vacuolated cells showing periodic acid–Schiff with acid digestion positivity (PAS-AD, ×400). (c) A partially cystic and partially solid mass with friable papillary projections. (d) Sections showing cuboidal to columnar cells with mild cellular atypia displaying pseudostratification (H and E, ×100)

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Histopathology

Grossly, a partially cystic and partially solid mass was received measuring 3.5 cm × 3.0 cm × 2.0 cm with many friable papillary projections [Figure 2c].

Microscopy revealed multiple cystic spaces with intraluminal papillary projections, which were lined by cuboidal to columnar cells displaying mild cellular atypia. At places, pseudostratification with mitosis was also seen [Figure 2d]. There was invasion of the underlying muscle.

Differential diagnosis

As benign appearing cells are seen in PCA, benign neoplasms having prominent papillary architecture are included in the differential diagnosis. Large, complex, and branching papillary structures as compared to small and simple papillary groups along with occasional mitosis can be a helpful feature in differentiating this malignant neoplasm from benign neoplasms.

IDPs and SP affect minor salivary gland. They have simple papillary architecture with bland nuclear features. In addition, inverted ductal papillomas have squamous and basaloid appearing epithelium.[7]

Papillary cystadenoma has almost similar features to LGPCA, but the papillary architecture is somewhat simple rather than complex and there is lack of mitosis.[78] However, its differentiation from PCA is almost impossible based on cytomorphology alone.

Smears from WT show monolayered sheets of oncocytic cells, many lymphocytes in the background of amorphous granular debris, and rarely squamous metaplastic cells.[789]

ACC-PCV is the closest differential diagnosis of PCA after papillary cystadenoma as they have overlapping features. The specimens are cellular, arranged in tightly cohesive fragments as well as monolayered sheets, often with a prominent papillary architecture. The polymorphous population of the cells includes granular cells, vacuolated cells, nondescript small cuboidal cells, and ductal type epithelium displaying high nuclear, cytoplasmic ratio along with the presence of squamoid and metaplastic oncocytic epithelium, which can help in differentiating this entity from PCA.[410] Although tumor cells with small vacuoles having soap bubble-like appearance of cytoplasm, they are common findings of both PCA and ACC-PCV.[2] Special stains for mucin are negative in ACC-PCV.[1]

PLGA, a common salivary gland neoplasm of oral cavity, palate, and upper lips, occurs mostly in older females. Cytological smears can have a prominent papillary architecture, but the papillae are composed of both epithelial and connective tissue components. Its differentiation from PCA is based on the presence of eosinophilic magenta-colored stromal red cores that branches with the associated epithelial papillary structures.[8] Stromal fragments may also be seen in the form of hyaline globules.[1] Hyaline globules were absent in both the epithelial sheets and cores of the papillae in PCA.

SDC occurs predominantly in the parotid. Smears show tubules, glands with occasional presence of the papillary architecture. The individual cells display features of overt malignancy including nuclear enlargement, high nuclear, cytoplasmic ratio, and prominent nucleoli as compared to the bland nuclear morphology in PCA. The background contains some necrosis, apoptotic bodies, and macrophages.[7]

Smears from LGMEC rarely have papillary architecture, but the presence of all the three cellular components comprising of mucous cells, intermediate cells, and squamous cells is the most helpful feature in differentiating it from PCA.[78]

EMC is another salivary gland neoplasm rarely associated with a papillary architecture. A combination of three dimensional well-defined cell clusters surrounded by homogenous acellular material, clear cytoplasm in peripheral cells, and fragments of acellular nonfibrillar material are sufficient to confirm EMC.[11]

Thus, we suggest diagnostic cytomorphological features of this great imitator of salivary gland neoplasms having papillary architecture:

• Aspiration of cyst fluid

• A complex branching papillary pattern, single cells, and sheets of cells

• The cells lining the papillary structures are cuboidal to columnar with basally located nuclei

• Cells with dense to finely vacuolated cytoplasm (soap bubble appearance)

• Individual dispersed cells with eccentrically placed nuclei

• Nuclei are bland appearing with low nuclear cytoplasmic ratio

• Minimal anaplasia and occasional mitosis

• Mucin vacuoles positive for mucin stain

• Hyaline globules are absent

• Proteinaceous to mucoid background with cystic macrophages.