Cytomorphological Findings and Histological Correlation of Low-Grade Cribriform Cystadenocarcinoma of Salivary Gland in Fine-Needle Aspiration: A Case Study

Abstract

Low-grade cribriform cystadenocarcinoma (LGCCC) of the salivary gland is a rare tumor. We report the cytologic features and histologic correlation of a patient with LGCCC. A 57-year-old man had a hardly palpable, nontender mass in the right cheek area followed over nine months. Radiologic analysis revealed a 1.2 cm multiseptated, cystic, solid nodule in an anterior superficial lobe of the right parotid gland. Fine-needle aspiration cytology revealed many irregular overlapping sheets or clusters of ductal epithelial cells forming solid, pseudopapillary, and cribriform architectures. Nuclei of the tumor cells revealed inconspicuous atypia with minimal size variation. On the basis of these findings, we confirmed a diagnosis of ductal epithelial proliferative lesion, favoring neoplasm, with uncertain malignant potential. Tumor excision was performed, revealing a tiny multicystic nodule (0.7 cm). Histopathologically, this tumor showed the characteristic morphology of LGCCC. This is the first report of cytomorphological findings of LGCCC in Korea. [PUBLICATION ABSTRACT]

Headnote

Low-grade cribriform cystadenocarcinoma (LGCCC) of the salivary gland is a rare tumor. We report the cytologic features and histologic correlation of a patient with LGCCC. A 57-year-old man had a hardly palpable, nontender mass in the right cheek area followed over nine months. Radiologic analysis revealed a 1.2 cm multiseptated, cystic, solid nodule in an anterior superficial lobe of the right parotid gland. Fine-needle aspiration cytology revealed many irregular overlapping sheets or clusters of ductal epithelial cells forming solid, pseudopapillary, and cribriform architectures. Nuclei of the tumor cells revealed inconspicuous atypia with minimal size variation. On the basis of these findings, we confirmed a diagnosis of ductal epithelial proliferative lesion, favoring neoplasm, with uncertain malignant potential. Tumor excision was performed, revealing a tiny multicystic nodule (0.7 cm). Histopathologically, this tumor showed the characteristic morphology of LGCCC. This is the first report of cytomorphological findings of LGCCC in Korea.

Keywords: Biopsy, fine-needle; Low-grade cribriform cystadenocarcinoma; Salivary glands

Low-grade cribriform cystadenocarcinoma (LGCCC) is a rare tumor defined as "a primary salivary duct tumor with clinically indolent behavior" in the 2005 World Health Organization (WHO) classification.1 This tumor was initially described as a "low grade salivary duct carcinoma" by Delgado et air The characteristic histologic findings of this tumor were detailed in previously reported cases by several authors, and these findings included the absence of encapsulation, but a well-circum- scribed, cystic, and cribriform pattem, resembling "low grade ductal carcinoma in situ or atypical ductal hyperplasia (ADH) pattem of breast".1'8 Clinically, salivary gland tumors are pri- marily aspirated, not excised. Although pathologists find fine- needle aspiration (FNA) cytology of salivary gland tumors diffi- cult to diagnose, there is one previous report by Nakazawa et al? that describes the cytologic features of LGCCC. Here, we share our experience regarding the cytologic features and histo- logic correlation obtained by FNA of one case of LGCCC.

CASE REPORT

Brief patient history

A 57-year-old man had a barely palpable, nontender mass in the right cheek area, followed up over a nine-month period. Contrast-enhanced computed tomography revealed a mildly enhancing mass in an anterior superficial lobe of the right pa- rotid gland (Fig. 1A). On ultrasonography, the lesion appeared as an approximately 1.2 cm large, multiseptated, cystic, solid nodule (Fig. IB). ENA was performed and the cytologic exami- nation led to a diagnosis of ductal epithelial proliferative lesion, favoring neoplasm, of uncertain malignant potential. Histologic confirmation was required.

Pathologic diagnosis

Excision of the lesion from the right parotid gland was per- formed. The surgical specimen revealed a tiny multicystic nod- ule (0.7 cm), which appeared to be surrounded by normal sali- vary gland tissue. The cut surface of the tumor was partly solid and partly cystic (Fig. 2A). Microscopically, it was a salivary ductal epithelial neoplasm showing multiple cysts lined by rel- atively bland ductal cells and a partly solid proliferation of duc- tal cells (Fig. 2B). Many of the superficial lining cells contained cytoplasmic apocrine-type microvacuoles that were periodic ac- id-Schiff-positive/diastase-resistant (Fig. 2C) and mucicarmine- positive (Fig. 2D). The tumor cells were strongly and diffusely S-100 protein positive (Fig. 2E). Myoepithelial markers (in- cluding actin and p63) highlighted the presence of cells sur- rounding the cystic spaces, confirming the intraductal nature of the lesion (Fig. 2F). No invasive foci were noted. On the basis of these findings, we diagnosed the mass as a low grade cribri- form cystadenocarcinoma, marginally excised.

Cytomorphological findings and histological correlation

The cellular smear showed many large sheets or clusters of ductal epithelial cells in an irregular overlapping arrangement (Fig. 3A). These cytologic components could be aspirated from the solid area of this tumor (Fig. 3B). Architecturally, the tu- mor cells had tight intercellular connections forming a vague cribriform (Fig. 3C), solid, or pseudopapillary (Fig. 3E) arrange- ment. These were matched with histologic findings. The solid areas revealed a cribriform pattem, resembling ADH and low- grade ductal carcinoma in situ of the breast (Fig. 3D). The pseu- dopapillary projections were found in the epithelial lining the cystic areas (Fig. 3F). Cytologically, almost all tumor cells were bland looking, ductal epithelial cells with low nuclear/cytoplas- mic (N/C) ratio. The nucleoli were found to be small, single, or entirely absent. Nuclear chromatin was fine or slightly coarse (Fig. 3G, H). Squamoid or metaplastic changes of the tumor cells, mentioned by Nakazawa et al.,9 were also identified in this case. Nuclear atypia was inconspicuous; however, one focus showed mild atypia with minimal nuclear size variation, prom- inent nucleoli, and vacuolated cytoplasm (Fig. 31, J). The back- ground was relatively clear in the cystic space. Scattered inflam- matory cells with hemosiderin-laden macrophages, neutrophils, and eosinophils were seen. No evidence of necrosis or mucin was found.

Postoperative outcome

Whole-body positron emission tomography-computed to- mography scanning was conducted after surgery. A residual, enhancing nodular lesion in the anteriosuperior aspect of the right parotid gland showed mild, increased fluorodeoxyglucose uptake. Overall, residual malignancy was suggested. Postopera- tive chemotherapy or radiation therapy was not recommended. A follow-up was conducted two months later. At that time, the patient was healthy, with no evidence of recurrence or distant metastasis.

DISCUSSION

This is the first report of the cytomorphological findings of LGCCC in Korea and the second report in the English literature. Compared with the first case, described by Nakazawa et al.,9 the two cases share common cytomorphology summarized as fol- lows: 1) irregular and overlapping sheets or clusters of ductal ep- ithelial proliferation with tight connections; 2) mild nuclear atypia with low N/C ratio, slightly coarse chromatin, inconspic- uous or one small nucleolus and minimal size variation; 3) cyto- plasmic vacuoles and squamoid or metaplastic changes of tumor cells; and 4) a cystic or inflammatory background with mixed inflammatory cells and hemosiderin-laden macrophages with no evidence of necrosis or mucin. Further, we report the following new findings that were not reported by Nakazawa et al.9: 1) tu- mor cells with solid, pseudopapillary, or cribriform architectural arrangement; 2) absence of "large yellow to brown pigments" in the cytoplasm of the tumor cells; 3) the smear in our case showed more benign-looking cytomorphology, with almost all tumor cells presenting inconspicuous cytologic atypia, resem- bling instead benign, ductal proliferating cells. Only a few clus- ters of tumor cells revealed minimal cytologic atypia.

Nakazawa et al: presented salivary duct carcinoma, papillary cystic variant of acinar cell carcinoma, and mucoepidermoid carcinoma as the results of differential diagnoses. However, in this case, we would consider benign salivary gland adenoma as the differential diagnosis since almost all tumor cells showed benign-looking cytomorphology. However, this diagnosis can be ruled out by the small clusters of mild cytologic atypia, as previously described. Adenoid cystic carcinoma (ACC) might be considered a differential diagnosis due to similar architecture at low magnification; however, the cribriform architecture of LGCCC is different from ACC. It can be described as "less de- fined" or "more vague" than ACC because basaloid cells were not identified in the cribriform area. Typical hyaline globules were also not seen in our case. Finally, the cytologic atypia ob- served in this case was too mild. High-grade tumors can also be ruled out as a diagnosis because the observed atypia was not se- vere or marked; rather, it was very minimal or mild.

In conclusion, when pathologists are presented with an aspi- ration cytology of salivary gland tumors, an effort must be made to discover any small foci showing minimal atypism; oth- erwise, there is potential to overlook the possibility of a low- grade malignancy such as LGCCC. We recommend more in- tensive investigation of FNA specimens.

This report is important as it is the second case report in the English literature on the cytologic features of LGCCC in FNA. Herein, we also described histologic correlations, which provide new observations, and the absence of previously reported fea- tures. Furthermore, we hope to encourage more authors to re- port cytomorphologic features of LGCCC in salivary gland in order to gather diagnostic criteria in FNA of this tumor. Until then, when LGCCC is suspected in ENA cytology, an improved descriptive diagnosis will facilitate the differential diagnosis and the recommendation of surgical excision, which would be preferred over a report limited only to a specific diagnosis.

Conflicts of Interest

No potential conflict of interest relevant to this article was reported.

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