Low-grade Cribriform Cystadenocarcinoma: A Review of the Literature and Case Report.

Low-grade cribriform cystadenocarcinoma (LGCCC) is a rare tumor of the salivary gland that most often arises from the parotid gland. A 51-year-old man developed a small mass on the right parotid gland 5 years ago. A preoperative magnetic resonance image showed abnormal intensity, an atypical characteristic for such a tumor; therefore, the diagnosis was difficult. Thus, a superficial parotidectomy was performed as a total excisional biopsy to remove the tumor. Histopathological analyses revealed that the tumor was composed of a single cyst comprising cells containing mucosal fluid, with proliferation of large cells. Also, proliferation of the tumor epithelium showed a papillary cribriform pattern of proliferation with a partial ring form, and the tissue inside the tumor was replaced by a hematoma. Mild cellular atypia was observed. Immunostaining for S-100 was positive, and the Ki-67 ratio was <5%. These histopathological findings led to a diagnosis of LGCCC of the parotid gland. At 54 months after surgery, the patient has had no recurrence or facial palsy. LGCCC is a rare neoplasm of the salivary gland and is listed in the current World Health Organization classification (2005) as a variant of cystadenocarcinoma. This case suggests that a thorough preoperative examination can lead to better diagnosis of rare tumors, including LGCCC. Thus, if a plastic surgeon is to correctly diagnose and treat parotid grand tumors, including LGCCC, then a detailed preoperative examination, including imaging, a disease course review, a physical examination, and differential diagnosis, should be considered carefully.

Low-grade cribriform cystadenocarcinoma (LGCCC) is a rare tumor of the salivary gland, which is not life-threatening; however, differential diagnosis is difficult because of a lack of characteristic symptoms and/or findings upon examination. In this case (see description below), we performed a superficial parotidectomy of the tumor. During surgery, we found that our initial worries about the risks associated with treating the tumor were unfounded. From our experience, attention should be paid to atypical magnetic resonance image (MRI) findings and “elastic hard” masses, and fine needle aspiration should be employed to consider any doubts concerning the malignancy of a tumor. A literature search suggested that the addition of FNA to other preoperative findings is useful for differential diagnosis, even though FNA alone cannot diagnose carcinoma with 100% certainty.[1-3] The results of this and previous studies suggest that more accurate diagnoses of rare tumors, including LGCCC, would be achieved if a patient is subjected to a thorough preoperative examination.

CASE REPORT

A 51-year-old man visited our department with a 4.5-cm right malar tumor. He first noticed the lump about 5 years ago when it measured approximately 1 cm. The tumor was slightly hard, and he felt an unpleasant sensation when it was touched, but there was no facial nerve palsy or pain.

An MRI revealed hyperintensity on T1-weighted imaging and hypointensity on T2-weighted imaging (Fig. 1A). The outer layer of the tumor, but not the core, showed slight enhancement. No metastasis to regional lymph nodes was observed. This MRI result is atypical of common tumors. The tumor was likely benign because of the low level of tenderness and pain and because 2 FNAs performed at another hospital were benign; however, we could not completely exclude the possibility of a malignant growth. Therefore, we performed a superficial parotidectomy to remove the tumor (Fig. 1B).

Fig. 1.

A, A T2WI shows a low-intensity area in the right parotid gland. B, The tumor did not adhere strongly to the parotid gland and measured 45 × 33 × 28 mm.

Histopathological analysis revealed a papillary cribriform pattern of tumor epithelial proliferation with a partial ring form and that the inside of the tumor was replaced by a hematoma. The tumor cells showed few hemosiderin deposits and contained intracytoplasmic mucin and proliferating large cells (Fig. 2). Additional immunostaining for S-100 was positive. Although mild cellular atypia was observed, the N/C ratios were low and Ki-67 was 3%; thus, this tumor was considered a noninvasive cystic lesion with a ductal or cribriform pattern of proliferation. On the basis of mild cellular atypia, we diagnosed the lesion as a noninvasive LGCCC arising from the parotid gland. At 54 months after surgery, the patient has no symptoms or recurrence.

Fig. 2.

The tumor epithelium showed a papillary cribriform pattern of proliferation with a partial ring form. The tissue inside the tumor was replaced by a hematoma. Mild cellular atypia was observed. Phagocytosis of hemosiderin was noted; hematoxylin and eosin stain (×200).

DISCUSSION

LGCCC is a rare neoplasm of the salivary gland and is listed in the current World Health Organization classification (2005) as a variant of cystadenocarcinoma. This tumor was classified as a low-grade variant of salivary duct carcinoma (SDC) in 1996[3-5]; however, previous clinic pathological reports suggest that it differs from typical SDC with respect to its growth pattern, a lack of remarkable nuclear atypia, invasiveness into surrounding tissue, and metastasis to regional lymph nodes.[6]

LGCCC usually occurs in elderly people, with a female predominance of 2:1.[7] The parotid gland is the most common site of involvement. The tumor may present in the palate, submandibular gland, intraparotid lymph nodes, or accessory parotid gland, although such cases are rare.[8]

To the best of our knowledge, only 17 cases of LGCCC were reported between 2005 and 2016, none of which were associated with recurrence, metastasis, or mortality. Our literature search suggests that between 2005 and 2016, LGCCC often occurred in middle-age patients (median age, 50.35 y), with the female:male ratio being almost equal (9:8); these epidemiological findings seem to differ from those described previously in the literature[9] (Table 1). Of these 17 cases, 14 tumors (82%) arose from the parotid gland, one each from the submandibular and buccal mucosa and one from the palate. Because of the clinical indolence, the majority of cases were treated by excision without radiotherapy.[10]

Table 1.

Characteristics of Reported Cases and the Present Case of LGCCC

Histologically, LGCCC comprises cystically dilated salivary ducts, with proliferation of intraductal tumor cells. LGCCC tumor cells show few atypia or mitotic figures, with no tumor necrosis. Tumor-stromal invasion has been reported in a few cases, but no vascular invasion or metastasis.[1] Immunohistochemically, the tumor cells are strongly and diffusely positive for S-100 protein in almost all cases.[1,2,10]

Here, we made great efforts to obtain a differential diagnosis before surgery because we were unsure of the tumor characteristics and symptoms[8] (Table 1). For example, the MRI findings were not typical of a benign tumor. MRI findings of hyperintensity in T1-weighted image (T1WI) and hypointensity in T2-weighted image (T2WI) are atypical of most benign tumors, such as pleomorphic adenoma and Warthin tumor, and of several malignant tumors. Most parotid gland tumors show hypointensity in T1WI and isointensity/hyperintensity in T2WI.[8] Even though these findings are by no means universal, we consider MRI to be one of the most important preoperative diagnostic tools in such cases. Additionally, previous studies suggest that FNA may provide some clues to a preoperative diagnosis. Previous studies report the following cytomorphological findings: (1) proliferation of ductal epithelial cells with tight junctions; (2) mild nuclear atypia and minimal size variation; and (3) cytoplasmic vacuoles and squamoid or metaplastic changes in tumor cells. Based on such cytomorphological features, differential diagnoses of LGCCC include SDC, a papillary cystic variant of acinic cell carcinoma, mucoepidermoid carcinoma, and adenoid cystic carcinoma.[6] As far as we know, 7 of the 9 cases examined herein may have been a malignant tumor based on the results of FNA (cases with no data regarding FNA were excluded from this analysis), even though the sensitivity for detecting malignant by FNA is controversial.[1-3] The number of cases with atypical MRI findings that indicated malignant potential was 3 out of 7 and the number of cases with atypical physical findings that indicated malignancy was 7 out of 14 (Table 1). These atypical findings may also be a crucial factor for differential diagnosis.

Plastic surgeons should be aware of rare parotid tumors such as LGCCC because parotid gland tumors are often seen in the department. An accurate diagnosis and appropriate treatment depend on a complete and thorough preoperative examination and other physical examinations.