Predictors of Outcome in the Phenotypic Spectrum of Polymorphous Low-grade Adenocarcinoma (PLGA) and Cribriform Adenocarcinoma of Salivary Gland (CASG)

Abstract

Polymorphous low grade adenocarcinoma (PLGA) shows histologic diversity with fascicular and targetoid features while cribriform adenocarcinoma (CASG) demonstrates predominant cribriform and solid patterns with glomeruloid appearance and optical clear nuclei. The current study is designed to identify pathological features that may predict clinical outcome in 69 PLGA/CASG. Seven patients had recurrences or distant metastasis, including three local recurrences, 2 nodal metastases, and 2 distant metastases. The following histological factors predicted disease free survival on univariate analysis: tumor size, bone invasion, lymphovascular invasion (LVI), tumor necrosis, ≥10% papillary pattern, and ≥30% cribriform pattern. On multivariate analysis, 10% of papillary pattern and 30% cribriform pattern were independent prognostic factors of disease free survival (DFS). Histologic classification of the 69 tumors (based on the prior reported definition of CASG) showed 21 CASGs (30%), 23 PLGAs (33%), and 22 (32%) with indeterminate features of PLGA and CASG. Additionally, 3 (4%) tumors demonstrated a predominant papillary pattern (≥50%). Interestingly, not all CASGs were located in the minor salivary gland and two tumors were identified in the parotid. One patient died from her disease and she harbored a CASG with >30% cribriform pattern. In conclusion, tumor size, bone invasion, and LVI are significant parameters that can predict adverse clinical behaviors in PLGA/CASG on univariate analysis. Using the prior reported definition, an overlapping histology between PLGA and CASG was noted in over a third of the cases. Regardless of tumor subclassification, the percentage of cribriform and papillary patterns seems to be prognostically relevant and should be documented.

Newly described salivary gland tumors

“…In several recent studies, the authors have argued that there is a significant proportion (about 35%) of the tumors on the PLGA spectrum exhibiting mixed morphology between PLGA and CAMSG. [97][98][99] Although CAMSG and PLGA may show morphologic overlap, and both tumor entities have molecular alterations affecting the same gene locus PRKD1/2/3, there are significant differences. Although mutations in PRKD genes 100 including novel PRDK1 hotspot somatic mutation encoding p.Glu710Asp were reported in classic PLGA, 101 most cases of CAMSGs harbor PRKD1/2/3 translocations.…”

Fine needle aspiration cytology of cribriform adenocarcinoma of minor salivary gland, a recently defined entity

“…Adjuvant radiation may be administered. Despite the high incidence of nodal metastases, the prognosis following appropriate therapy is good, with distant metastases or death being reported only occasionally . Size of the tumour, bone invasion, lymphovascular emboli and increased proportion of cribriform or papillary patterns have been reported to be predictive of worse outcome …”

“…Despite the high incidence of nodal metastases, the prognosis following appropriate therapy is good, with distant metastases or death being reported only occasionally. 2,4,10 Size of the tumour, bone invasion, lymphovascular emboli and increased proportion of cribriform or papillary patterns have been reported to be predictive of worse outcome. 10 Although infrequently encountered, the diagnosis of CAMSG on aspirates has significant clinical implications, necessitating awareness of its cytomorphological features.…”

“…2,4,10 Size of the tumour, bone invasion, lymphovascular emboli and increased proportion of cribriform or papillary patterns have been reported to be predictive of worse outcome. 10 Although infrequently encountered, the diagnosis of CAMSG on aspirates has significant clinical implications, necessitating awareness of its cytomorphological features. Our report corroborates documented findings and is the first to describe the presence of glomeruloid structures in aspirates from the primary tumour as well as lymph node metastases, which may be an additional feature to help to distinguish CAMSG from morphologically similar tumours, particularly at metastatic sites.…”

Advancing toward a molecular characterization of polymorphous low grade adenocarcinoma

“…Interestingly, the two cases that did not show mutations in our study were the only ones classified as CAMSG. There has been a lot of controversy regarding the subclassification of PLGA and CAMSG [8–10]. Additional molecular studies in independent series of tumors may help to start shedding a light on this issue.…”