Nodal Recurrence of Salivary Polymorphous
Low-Grade Adenocarcinoma
Caitlin P. McMullen, MD1; Morris Edelman, MBCHB2; Douglas Frank, MD2
1Albert Einstein College of Medicine; 2North Shore-Long Island Jewish Health System
Outcome Objectives:
Polymorphous low-grade adenocarcinoma (PLGA) is an uncommon type of low-grade minor salivary cancer. Risk factors for aggressive phenotypes of PLGA are not
definitively known. PLGA with a predominantly papillary pattern may have a higher risk of nodal metastasis. The objective of this report is to examine two cases of late nodal
metastasis of polymorphous low-grade adenocarcinoma.
Methods
A retrospective chart review was performed at a tertiary, academic medical center. Patient demographic data, medical history, presentation, pathology, treatment modalities
and follow up information were collected.
Results
Two patients were identified with late recurrence of polymorphous low-grade adenocarcinoma, isolated to the cervical lymph nodes. After wide local excision, the first
patient recurred nine years later with a level II neck mass demonstrating PLGA. After resection and post-operative radiation, he has been doing well without evidence of
disease at 1 year. The second patient presented with a soft palate and tonsil lesion. He underwent an uncomplicated resection of the index tumor and free flap
reconstruction. Three years later, he recurred with a large level IB neck mass, with pathologic features consistent with his previous salivary malignancy.
Conclusion
Polymorphous low-grade adenocarcinoma is described in the literature as a rare tumor with low-grade metastatic potential. Recent evidence suggests not all PLGA tumors
behave the same. In order to counsel and manage patients with PLGA effectively, further study is needed to determine risk factors for the development of recurrence of this
low-grade malignancy.
Introduction
Polymorphous low-grade adenocarcinoma (PLGA) was first described
as a distinct clinicopathologic entity in 1984 by Evans and Batsakis.1
Typically, these neoplasms present on the palate and demonstrate indolent
behavior. The notable histologic traits of PLGA include uniformity on a
cellular level: lack of nuclear atypia, small-medium cell size, regular cell
shape, and rare mitotic figures.1,5 Histologically, PLGA is diverse, and a
number of growth patterns have been described including solid, tubular,
fascicular and papillary subtypes.1
The vast majority of patients have localized disease upon presentation,
and distant metastases are extremely rare. Cervical metastases are unusual
and may occur late- nearly a decade after initial presentation.1,3,7,8
Prognostic factors within PLAC are not well-defined. Perineural invasion
does not appear to be a high-risk feature or prognostic of recurrence.10
Tumors less than or equal to 2 cm at presentation and hard palate primary
site may be associated with better outcomes.2 Positive or unknown margin
status has been associated with an increased risk of local recurrence.3
Anecdotal evidence suggests that patients with papillary subtype are more
likely to develop cervical metastases.3 As with most cancers, recurrent
tumors display a more aggressive phenotype with histologic features
including more mitoses and, interestingly, increased papillary growth
patterns.9
Reports describing cervical metastases of PLAC in the existing
literature are limited. Furthermore, risk factors for a poorer prognosis are
not definitively known. There has been some suggestion in the literature
that the papillary subtype may display a more aggressive clinical course. In
this report, we present two cases of cervical metastases from PLGA, one of
which demonstrated papillary growth pattern.
Patient 1.
A 37-year-old male presented to an outside institution with a soft
palate mass. Wide local excision was performed for this primary lesion. Final
pathology revealed polymorphous low-grade adenocarcinoma with negative
margins. Histologic subtype was not available. He was followed regularly at
our institution without evidence of recurrence. After 9 years, he presented
with a small, palpable level II neck mass [Figure 1a]. An ultrasound-guided
fine-needle aspiration was performed, demonstrating malignant cells
consistent with his known history of PLGA. A neck dissection was
performed, and final pathology analysis demonstrated 4/43 lymph nodes
positive for adenocarcinoma with extracapsular spread [Figure 1b]. All
positive nodes were contained within level II. He also received adjuvant
post-operative radiotherapy. Fifteen months post-operatively, he was
without evidence of disease and doing well.
Patient 2.
A 61-year-old male presented to our institution with dysphagia and
throat pain for 2.5 months. A large soft palate mass extending onto the tonsil
was visualized upon physical exam. There were no nodal or distant
metastases upon presentation. He underwent a tracheotomy, neck
dissection, mandibulotomy approach to the left soft palate, oropharyngeal
wall and lateral tongue base tumor. Reconstruction was performed with a
radial forearm free flap. This final pathology of the primary site was
reported as polymorphous low-grade adenocarcinoma well-to-moderately
differentiated with papillary features and few calcifications [Figure 2]. The
neck dissection was free of nodal disease. His post-operative course was
uncomplicated. He was decannulated and tolerated a regular diet. No
adjuvant therapy was administered. Three years later he developed a neck
mass [Figure 3]. The recurrent lesion was treated with revision neck
dissection and post-operative adjuvant radiotherapy. Final pathology
demonstrated PLGA with a papillary growth pattern, and there were no
other positive nodes. One year post-operatively from his recurrence, he was
without evidence of disease.
a.
b.
Figure 1a and 1b. Patient 1 recurrent disease imaging and
pathology.
Figure 2. Low and high power view of the pathology for
patient 2. The papillary growth pattern is evident.
Discussion
Cervical metastases of PLGA are considered to be a rare entity. Few
cases exist in the literature, and the reported rates of regional spread vary
greatly. The largest cohort of PLGA patients was recently described. Patel et
al. utilized the Surveillance, Epidemiology and End Results (SEER) database
to report 460 cases of PLGA and their clinical outcomes. Regional spread of
disease as defined by the SEER Local/Regional/Distant Staging system was
25.1% in their population, significantly higher than prior reports.3 Excluding
those with direct regional spread of the primary site, 5.0% of patients had
N1 or N2 disease at the time of database inclusion.2 Other authors report
approximately 5% of all PLGA patients have nodal disease at presentation,
with up to 17% eventually developing nodes.3,8,9
Few studies distinguish which growth pattern subtypes develop nodal
disease. Evans, et al. published a long-term follow-up study including 40
patients, 17 of whom had tumors with predominantly papillary patterns of
growth. 76% of papillary-type patients recurred locally and 35% had
cervical metastases. Nodal spread did not occur at all with other growth
pattern subtypes.3 Slootweg, et al. also found that cervical node metastases
were more likely with the papillary subtype.7 Seethala, et al. reported a
shorter disease-free survival with a high percentage of papillary component,
though not statistically significant.9 Patient 2 in this case series displayed the
papillary subtype. The tumor was more advanced at presentation and he
developed a nodal metastasis within a relatively short period of time. The
growth pattern subtype of Patient 1’s initial tumor was unknown.
For many head and neck cancers, elective management of the neck is
recommended if the risk of nodal metastases is greater than 15% - 25%. Due
to the rarity of nodal disease in PLGA, the clinically negative neck is not
electively treated. Excision of the primary site is usually sufficient therapy. It
is unclear whether the development of cervical nodes themselves
necessarily affect prognosis. Evans. et al, reported that nodal metastases did
not lead to uncontrolled disease, and neck dissection was adequate
treatment.3
In the Patel, et al. report, elective neck dissection was performed for
5.3% of patients2, higher than most other authors. Some authors advocate
for elective neck dissection only in the case of planned major
reconstruction.8 The reported incidence of cervical metastases for all PLGA
tumors is low, but the papillary subtype appears to be more aggressive and
may merit some additional initial consideration of the neck.
Conclusion
Cervical metastases of PLGA are rare, and there is limited literature on the
subject. Definitive risk factors for disease progression are unknown. Two
cases with cervical metastases are reported here. Accumulating evidence
suggests that the papillary subtype may display a distinct, and more
aggressive, clinical course.
Figure 3. Axial CT of the cervical metastasis for Patient 2.
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