Case report

A 51-year old male presented with progressive right facial fullness that had developed over four years with recent facial pain and serosanguinous drainage. Systems review was negative for fever, fatigue, weight loss, or facial weakness. There was no history of trauma or radiation. Physical examination was notable for a palpable 4 cm right parotid mass. Cranial nerve VII was intact bilaterally and there were no palpable lymph nodes.

Contrast-enhanced computed tomography of the neck demonstrated a 3.3 × 2.8 × 3.2 cm peripherally enhancing cystic and solid mass in the right superficial lobe of the parotid gland [Figure 1]. The patient received a right superficial parotidectomy and selective right neck dissection involving the level II and III lymph nodes.

Gross pathology demonstrated a unilocular cystic mass [Figure 2]. Histopathology demonstrated a large cyst lined by either papillary projections or a single layer of cuboidal cells with mild to moderate atypia and surrounding solid tumor nests with focal cribriform pattern [Figure 3a–c]. No mitosis or necrosis was identified. A focus of lymphovascular invasion [Figure 3d] and multiple foci of stromal invasion [Figure 3b] were noted. Perineural invasion was not identified. There were two foci of invasion into the subcutaneous fibroadipose tissue [Figure 3e]. One of 12 nodes was positive for metastatic carcinoma without extranodal extension [Figure 3f]. We rendered a diagnosis of intermediate-grade PCA in agreement with two additional pathologists.

Discussion

PCA was first included in the 1991 WHO classification scheme of salivary gland neoplasms4 and was lumped under the category of adenocarcinoma, NOS in the more recent 2017 WHO classification.6 Papillary was dropped from the name in the 2005 WHO classification, as the intracystic papillary projections were not always a prominent feature.5 The Armed Forces Institute of Pathology originally described PCA as demonstrating prominent cystic features and frequent papillary growth that otherwise lacked features of cystic variants of more common salivary gland malignancies.1 It is often considered the malignant counterpart to the non-Warthin benign cystadenoma, and given the former’s bland nuclear features and lack of atypia, histological differentiation from cystadenoma may often be challenging and largely depends on identifying stromal invasion.15

The rare incidence, terminological revisions, and challenging histological differentiation contribute to the often poorly characterized nature and limited understanding of PCA. The largest study of PCAs was published in a series of 57 cases.2 All tumors demonstrated cystic components and stromal invasion, and approximately 75% of cases demonstrated intraluminal cystic papillary projections. Most cases demonstrated minimal atypia and low mitotic rate (0-1/10 high power field (hpf)), consistent with low-grade features. Of the parotid gland cases, lymph node metastasis was rarely observed and only seen in one case. The tumor in our case demonstrated stromal invasion and predominantly mild with focal moderate nuclear pleomorphism cytologically. The presence of regional lymph node metastasis in our case may have been related to the higher-grade histological features, such as the extra-parenchymal subcutaneous tissue and lymphovascular invasion, which were similarly observed in another case.12

Moreover, while most cases have been considered low-grade, scattered reports of clinically aggressive and histologically high-grade features have been reported [Table 1].9–14 Although there is no universally advocated grading system, high-grade PCAs tend to demonstrate locally aggressive features, cytologic atypia, high mitotic rate, necrosis, and the absence of papillary features [Table 2]. For example, a high-grade PCA demonstrated a mitotic rate of
15–20/10 hpf and nuclear pleomorphism, which were associated with four large metastatic lymph nodes, extranodal extension, and postoperative recurrence (albeit in a setting of not receiving adjuvant radiation therapy).10 Accordingly, another study classified PCAs into well- and poorly-differentiated subtypes, and observed an association between differentiation and nodal metastases and recurrence.13 Lastly, in the previously mentioned case series, those with moderate atypia and higher mitotic rates comprised a larger proportion of those also with lymph node metastases and recurrence.2

While clinical features are neither specific nor reliable in differentiating between high- and low-grade PCAs, certain clinical findings may suggest a malignant entity, such as the presence of a painless mass, lack of tenderness and a degree of fixation to surrounding tissues on palpation, and cranial VII neuropathy.16 The radiological differential diagnosis of a solitary mixed cystic-solid parotid lesion is broad. Considerations include focal presentation of Sjogren syndrome, lymphoepithelial cysts, first branchial cleft cyst, Warthin’s tumor, acinic cell carcinoma, mucoepidermoid carcinoma, salivary duct carcinoma, and metastatic thyroid papillary carcinoma. In most cases, imaging findings of parotid tumors are nonspecific. Low-grade malignant parotid tumors may appear deceivingly nonaggressive and well-defined. Instead, the mainstay of imaging is delineating the extent of the disease preoperatively, which includes evaluating deep or superficial lobe involvement, extraglandular invasion of adjacent structures, perineural invasion, and cervical lymph node metastases. The magnetic resonance imaging findings of an intermediate-grade PCA revealed a well-marginated, heterogeneous mass and with predominantly T1 and T2 prolongation, consistent with mixed cystic-solid components.11 From a histological standpoint, the extent of papillary morphology in PCA is variable. Hence, the pathological differential diagnosis can be broad, and includes salivary duct carcinoma, metastatic thyroid papillary carcinoma, mucoepidermoid carcinoma, papillary cystic variant of acinic cell carcinoma, adenoid cystic carcinoma, intraductal carcinoma, and polymorphous adenocarcinoma.17

The treatment of PCA is complete surgical excision. In general, adequate surgical margins for major salivary gland tumors are recommended and are often > 2 cm when excising high-grade tumors.16 Higher stage and higher-grade parotid tumors, including the presence of an encased functional or impaired facial nerve, are strongly considered for complete parotidectomy. Moreover, neck dissection is recommended for high-grade tumors, those ≥ 4 cm in size, or in cases of clinicoradiological positive nodal disease.16 In many case reports of PCAs, additional postoperative radiation therapy was also considered,14 as in the current case. Considerations for adjuvant radiation therapy are driven by high histological grade, lymphovascular and perineural invasion, nodal metastases, and close surgical margins.16 While PCAs have been reported to foretell a good prognosis,1,2 the intermediate-grade features in the current case, reports of recurrence in prior high-grade PCAs,10,12 and the lack of data available associating clinical outcome with histological features prompted the option of performing adjuvant chemotherapy concurrently with radiation therapy. Ultimately, meaningful conclusions on optimal treatment of specifically PCA are limited by the relative rarity of this entity and few descriptions of this entity in the existing literature.

Conclusion

Although PCA is considered a low-grade carcinoma, both clinically and histologically high-grade features may be seen. No universally advocated grading system exists, but high-grade PCA tends to demonstrate locally aggressive features, cytologic atypia, high mitotic rate, necrosis, and absence of papillary features. An association between histologically high-grade features and lymph node metastases and recurrence may exist, but meaningful conclusions are limited by the low number of studies in the existing literature and the low level of evidence.

Disclosure

The authors declared no conflicts of interest.

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