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ORIGINAL ARTICLE
Polymorphous Low-Grade Adenocarcinoma
The University of Pittsburgh Experience
Raja R. Seethala, MD; Jonas T. Johnson, MD; E. Leon Barnes, MD; Eugene N. Myers, MD
Objective: To reappraise the clinical and histologic vari-
ables associated with a more aggressive outcome in polymorphous low-grade adenocarcinoma (PLGA).
Design: Retrospective cohort.
Setting: University hospital.
Patients: Twenty-four patients with PLGA treated from
January 1, 1973, through December 31, 2005.
Main Outcome Measure: Analysis of clinical and
pathologic variables in 30 biopsy or resection specimens from 24 patients.
Results: Only 4 PLGAs were not initially diagnosed as
such. However, 8 non-PLGAs (thus excluded) were incorrectly diagnosed as PLGA. Most carcinomas (14 of 24
[58%]) were palatal. Recurrent carcinomas had a significantly higher mitotic rate (2.7 mitoses per 10 highpower fields) compared with primary tumors (1.2 mito-
T
Author Affiliations:
Departments of Pathology
(Drs Seethala and Barnes) and
Otolaryngology (Drs Johnson
and Myers), University of
Pittsburgh School of Medicine,
UPMC Presbyterian University
Hospital, Pittsburgh,
Pennsylvania.
ses per high-power fields, P = .046), and 3 of 7 (43%)
recurrences showed progression to an intermediategrade histologic type. No patient died of disease. Median disease-free survival was 12.8 years. Four of 24 patients (17%) had regional lymph node metastases, 3 with
carcinomas of the base of the tongue. One PLGA metastasized to the subcutaneous tissue of the face, orbit, and
lungs at 19.6 years. An extrapalatal site was the only significant determinant of disease-free survival (P=.03).
Conclusions: Diagnosis of PLGA remains a challenge.
Extrapalatal carcinomas appear to behave in a more aggressive fashion than those of the palate, and cancer arising from the base of the tongue frequently metastasizes
to the cervical lymph nodes, suggesting a role for neck
dissection in these patients. Recurrent cancers show evidence of histologic progression, justifying an aggressive
approach to achieving initial complete excision.
Arch Otolaryngol Head Neck Surg. 2010;136(4):385-392
HE TERM POLYMORPHOUS
low-grade adenocarcinoma
(PLGA) was introduced by
Evans and Batsakis1 in 1984
to describe a cytologically
bland but architecturally diverse malignant neoplasm of minor salivary gland origin that had been previously recognized
as lobular carcinoma,2 terminal duct carcinoma,3 and low-grade papillary adenocarcinoma.4 Despite the fact that this term
has existed for nearly 25 years, PLGA remains a diagnostic challenge.5 Although
originally described as cancer of a minor
salivary gland origin in the oral cavity,
PLGA has also been described at several
sites outside the oral cavity, including major salivary glands.6-8 Polymorphous lowgrade adenocarcinoma should be thought
of as distinct from adenoid cystic carcinoma, a common differential diagnostic
consideration, because of the more relentless and aggressive behavior of the latter.9 However, with sufficient long-term
follow-up,10 the recurrence rate for PLGA
is high at almost 33%, and distant metas-
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385
tasis or even transformation to a highgrade adenocarcinoma11,12 has been noted.
The surprisingly aggressive behavior of
these adenocarcinomas in some of our patients despite the term low grade prompted
the present study.
Perhaps the oldest controversy is
whether to consider papillary predominant carcinomas as variants of PLGA or
as separate tumors altogether.10,13-15 Regardless of classification, predominantly
papillary cancers have been reported to
have a more aggressive biological behavior, although this has been validated in
only 1 series.10 Despite the reported frequent occurrence of these tumors,16,17 large
series in which patients were treated at a
single institution are rare.5,7,10 To reappraise and validate prior findings and concepts, we present the clinicopathologic
findings of our PLGA cohort.
METHODS
The Head and Neck Oncology Registry of the
University of Pittsburgh School of Medicine,
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lymph node status, locoregional recurrence, distant metastasis, and survival.
Statistical analyses were performed using SPSS statistical software, version 14.0 (SPSS Inc, Chicago, Illinois). For papillary
components, solid percentiles, and mitotic indices, the nonparametric Mann-Whitney test was used for comparison between the 2 groups. For comparison of frequencies of categorical variables between groups, a Fisher exact test was used with
a 2-tailed distribution. Overall survival was reported descriptively, and the arithmetic median survival was used. Diseasefree survival (DFS) was assessed using the Kaplan-Meier method
with groupwise comparisons made via a univariate Cox proportional hazards model. The Kaplan-Meier median (the time
at which 0.5 patient remained disease free) was reported. P⬍.05
was considered statistically significant.
Figure 1. A carcinoma commonly misclassified as polymorphous low-grade
adenocarcinoma (hematoxylin-eosin staining used in both parts of Figure).
This parotid epithelial-myoepithelial carcinoma shows a solid growth pattern
with scattered tubules and mostly shows elongated nuclei with open
chromatin and delicate nuclear membranes reminiscent of polymorphous
low-grade adenocarcinoma (original magnification ⫻200). However, even at
this magnification the tumor is biphasic, consisting of a clear cell population
surrounding compressed, lightly eosinophilic cuboidal epithelium-lined
tubules (arrows). Inset, This dual population is readily apparent on higher
magnification, and there are central nucleoli evident in the ductal component
but not the outer myoepithelial component (original magnification ⫻400).
Pittsburgh, Pennsylvania, was assessed retrospectively. This review was approved by the University of Pittsburgh institutional review board. All patients classified as having PLGA were
reevaluated by one of us (R.R.S.). Material from patients treated
in our institution from January 1, 1973, through December 31,
2005, was available. For patients who presented after the recognition of PLGA at our institution (in 1985), the search terms
used included the following: polymorphous low-grade adenocarcinoma; adenocarcinoma, not otherwise specified (NOS); papillary adenocarcinoma; and cribriform adenocarcinoma of tongue.
For patients who presented before the use of the term PLGA,
search terms included the following: adenocarcinoma, papillary adenocarcinoma, adenoid cystic carcinoma, terminal duct carcinoma, pleomorphic adenoma, and monomorphic adenoma.
The histologic definition of PLGA used for inclusion in this
study was a modification of the World Health Organization definition,16 with additional descriptors derived from the histologic variables gathered from previous series:1,10,15 “a monophasic malignant salivary gland adenocarcinoma with
polymorphous growth patterns (tubular, cribriform, papillary
and/or solid), but bland, monomorphic cytonuclear features including characteristic ovoid nuclei with open vesicular chromatin.” Carcinomas arising in the major salivary glands, pharynx, and base of the tongue that fulfilled this definition were
also included.
Gross and histologic variables were recorded. The solid
and papillary (because of its reported importance)10 components were evaluated as separate variables in all patients and
estimated to the nearest fifth percentile. Mitotic counts were
recorded as number per 10 high-power fields (HPF) (⫻40microscopic objective lens). Other oncologically relevant histologic variables, including the status of the margins of resection, perineural invasion (PNI), angiolymphatic invasion
(ALI), and bone invasion, were recorded as well. For patients
with PNI, the presence of intraneural invasion or large nerve
PNI was also recorded. A large nerve was defined arbitrarily as
a nerve with a cross-sectional diameter of 0.25 mm or larger
(roughly half of 1 HPF, ⫻40 microscopic objective lens).
These histologic variables were linked with clinical and
demographic data, including age at diagnosis, sex, treatment,
RESULTS
INITIAL DIAGNOSIS
Twenty-eight patients were initially diagnosed as having PLGA. Eight of 28 patients diagnosed as having PLGA
(29%) were excluded from this study. Their tumors did
not fulfill our definition of PLGA and were compatible
with other specific salivary gland malignant neoplasms
in 5 patients. Diagnoses for these patients included 3 epithelial-myoepithelial carcinomas (Figure 1); 3 lowgrade to intermediate-grade adenocarcinomas, NOS; 1 adenoid cystic carcinoma; and 1 low-grade salivary duct
carcinoma (also known as low-grade cribriform cystadenocarcinoma). The low-grade salivary duct carcinoma
was seen at our institution before the description of this
entity in 1996.18
Four additional patients treated at our institution were
not initially diagnosed as having PLGA but, on review,
fulfilled the criteria for PLGA. Three of these 4 patients
(75%) had their conditions diagnosed before 1984, the
year the term PLGA was first used.1 The original diagnoses for these patients included 1 adenocarcinoma, NOS;
1 pleomorphic adenoma; 1 monomorphic adenoma; and
1 mucoepidermoid carcinoma. Thus, in total, 24 patients were satisfactorily diagnosed as having PLGA.
Fourteen of these 24 patients were initially diagnosed as having PLGA at outside institutions. Of these,
6 (43%) were diagnosed as having PLGA, whereas other
diagnoses were 4 adenocarcinomas, NOS; 2 adenoid cystic carcinomas; 1 mucoepidermoid carcinoma; and 1 pleomorphic adenoma.
CLINICAL AND DEMOGRAPHIC FEATURES
The mean age at diagnosis was 59.4 years (range, 26-85
years). There was a female predilection with a female to
male ratio of 2.4:1.0. The site distribution was as follows: palate, 14 (hard palate, 9; and soft palate, 5); base
of the tongue, 3; nasopharynx, 3; upper lip, 2; tonsil, 1;
and parotid, 1.
PATHOLOGIC FEATURES: PRIMARY TUMORS
The slides and reports from the primary cancers, including cancers originally diagnosed at an outside hospital,
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Figure 2. Forms of invasion seen in polymorphous low-grade adenocarcinoma (PLGA) (hematoxylin-eosin staining used in all parts of Figure). A, Nasopharyngeal
PLGA demonstrating bone invasion (original magnification ⫻40). B, This PLGA arising in the parotid gland demonstrates invasion around this large nerve (original
magnification ⫻200). C, This carcinoma of the lip shows a large tumor embolus (original magnification ⫻200).
were available in 23 of 24 patients; 1 patient had only
the recurrences available for review. A gross measurement of tumor size was available in 16 patients. The mean
size of the tumor was 2.4 cm (range, 1.1-6.8 cm). The
mean size of extrapalatal tumors (3.6 cm; range, 2.2-6.8
cm) was significantly greater than that of palatal tumors
(1.4 cm; range, 1.1-1.8 cm) (P = .01).
Margin status was available in 20 patients. Final margins (even after reexcision of initially positive margins)
were positive in 9 patients (45%) (palate, 5; nasopharynx, 2; base of the tongue, 1; and parotid, 1). Gross and/or
microscopic bone invasion was present in 6 of 23
primary tumors (26%) overall. All 3 nasopharyngeal
PLGAs invaded bone (Figure 2A), whereas 3 of 13 primary palatal tumors (23%) invaded bone.
Overall, PNI was identified in 12 of 23 tumors (52%)
(Figure 2B). Relative frequencies based on site are as follows: palate, 8 of 14 (57%); upper lip, 1 of 2 (50%); base
of the tongue, 1 of 3 (33%); nasopharynx, 1 of 3 (33%);
and parotid, 1 of 1 (100%). Seven of 12 PLGAs with PNI
(58%) showed large nerve involvement: palate, 3; base
of the tongue, 1; nasopharynx, 1; upper lip, 1; and parotid, 1. Three of 12 tumors with PNI (25%) also showed
intraneural invasion (palate, 2; and parotid, 1). Angiolymphatic invasion was identified in 7 of 23 patients (30%)
overall (Figure 2C). Site distribution was as follows: base
of the tongue, 3 of 3 (100%); upper lip, 2 of 2 (100%);
nasopharynx, 1 of 3 (33%); and palate, 1 of 13 (8%). The
1 parotid tumor in this study did not show angiolymphatic invasion.
Palatal PLGA had a slightly higher prevalence of PNI
(58%) than extrapalatal PLGA (40%). Extrapalatal carcinomas had a significantly higher prevalence of ALI
(60%) than those of the palate (8%) (P= .02). The mean
mitotic count for primary PLGA was 1.3 per 10 HPF
(range, 0-3.0 per 10 HPF). Mean mitotic counts for pala-
tal PLGA (1.2 per 10 HPF) were similar to those for extrapalatal PLGA (1.3 per 10 HPF).
All carcinomas showed a mixture of tubular, cribriform, and papillary growth patterns (Figure 3A-C). The
mean solid component (Figure 3D) overall was 47%
(range, 0%-90%). Extrapalatal PLGA had only a slightly
higher mean solid component (49%) than palatal PLGA
(45%). The mean papillary component overall was 11%,
although the range was wide (0%-90%). Extrapalatal
PLGA had a slightly higher mean papillary component
(18%; range, 0%-90%) than palatal PLGA (6%; range, 0%40%). These differences were not statistically significant. However, more specific subsite stratification was
not attempted because of the small sample size. Nevertheless, descriptively, all PLGAs of the base of the tongue
were predominantly solid and papillary and showed by
far the highest mean papillary composition (47%; range,
20%-90%) of all sites. All nasopharyngeal PLGAs were
predominantly solid to cribriform with only focal papillary areas (mean, 13%; range, 10%-20%).
Carcinomas with ALI had a significantly higher percentageofpapillaryareas(mean,30%;range,0%-90%)thanthose
without (mean, 3%; range, 0%-20%) (P=.003). All carcinomas with more than 20% papillary areas showed ALI. No
significant correlations were noted between solid and papillary percentage and PNI of any type or bone invasion.
PATHOLOGIC FEATURES: RECURRENCES
Seven of 24 patients (29%) had a local recurrence.
Three patients had regional recurrences in cervical
lymph nodes (13%), 2 of whom had local recurrences as
well, yielding a total locoregional recurrence rate of
33% (8 patients). Slides of these recurrences were available in 7 of 8 patients, from whom 6 paired primary tumors were also available. The mean percentage of solid
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Figure 3. Common patterns in polymorphous low-grade adenocarcinoma (hematoxylin-eosin staining used in all parts of Figure). A, Tubular growth in this
carcinoma of the palate (original magnification ⫻200). B, Cribriform growth in this tumor of the upper lip with adenoid cysticlike cylindrical hyaline matrix
deposition (original magnification ⫻200). C, Papillary growth in this tumor of the palate (original magnification ⫻200). D, Tumor of the base of the tongue with
solid areas (original magnification ⫻200).
areas in recurrent disease was similar to primary disease
(46%; range, 20%-80%). The mean percentage of the
papillary component was, however, increased (26%;
range, 0%-70%) in recurrence disease, although this
difference was not significant. Mean mitotic counts
were, however, significantly higher in recurrent disease
(2.7 per 10 HPF; range, 1-5 per 10 HPF) (P = .046). In
addition, 3 of 7 recurrent cancers showed evidence of
histologic progression to an intermediate-grade morphologic type (Figure 4). These 3 patients constituted
the higher end of the mitotic range in recurrent cancers
(mean, 3.7 per 10 HPF; range, 3-5 per 10 HPF), with 1
patient even showing atypical mitoses. No recurrent
disease had high-grade transformation based on criteria
reported previously.12
TREATMENT, OUTCOME,
AND CLINICOPATHOLOGIC CORRELATIONS
Nineteen patients received primary treatment within our
health care system. The other 5 were initially treated elsewhere. Initial treatment included surgery in 19 patients,
surgery and adjuvant radion therapy in 4 patients, and
radion therapy alone in 1 patient.
One patient was lost to follow-up. Seven of 22 patients (32%) died (median time, 13.7 years; range, 1.216.3 years), but no deaths were attributed to PLGA. Median follow-up on surviving patients was 6.6 years (range,
2.7-35.1 years). As noted herein, the locoregional recurrence rate was 33% (8/24), with a median DFS of 12.8
years. Four of 24 patients (17%) had lymph node metastases, 1 on presentation and 3 as regional recurrences
as mentioned herein. One patient with the palate as the
primary site had a recurrence on the soft palate 7 years
later and metastases to the subcutaneous tissues of the
face, orbit, and lungs at 19.6 years (Figure 5).
Univariate correlations with DFS are summarized in
the Table. Site was the only significant determinant of
DFS in this small series (P=.03). Although patients with
positive margins, large nerve PNI, bone invasion, and a
high percentage of papillary component showed a shorter
DFS, differences were not statistically significant.
COMMENT
Polymorphous low-grade adenocarcinoma remains a challenge in diagnosis and management almost a quarter-
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Figure 4. Two paired cancers with histologic progression (hematoxylin-eosin staining used in all parts of Figure). A, A primary polymorphous low-grade
adenocarcinoma (PLGA) in the parotid gland showing typical nuclear features (original magnification ⫻400). B, The recurrence of this carcinoma shows more
pronounced nuclear enlargement, coarser chromatin, and central nucleoli (original magnification ⫻400). C, A primary PLGA in the palate with papillary growth but
monomorphic nuclei (original magnification ⫻400). D, The recurrence shows a transition from a more typical morphologic type to scattered solid areas with
enlarged nuclei, enhanced clearing, and increased mitotic activity (original magnification ⫻400). A tripolar mitosis is highlighted by the arrow.
century after its initial description.1 However, our series
demonstrates an improved awareness of PLGA as a diagnostic entity. Only 4 PLGAs were initially diagnosed
as another entity by us, and 3 of these were diagnosed
before the description of this entity in 1984.1 This increased awareness is also reflected in the original diagnoses from outside institutions in which almost half were
correctly identified as PLGAs, which is an improvement
compared with the 22% reported by Pogodzinski et al.5
In contrast, however, another challenge has emerged:
more than one-fourth of the patients originally diagnosed as having PLGA actually had other salivary gland
malignant neoplasms. Thus, we report for the first time,
to our knowledge, a more frequent overdiagnosis of this
entity rather than the underdiagnosis that is traditionally reported.5,15 Our analysis of this series demonstrates 2 fundamental patterns of error. The first is the
failure to differentiate truly biphasic tumors (namely, adenoid cystic carcinoma and epithelial-myoepithelial carcinomas) from PLGAs. Although the PLGA has a multitude of patterns, it is a monophasic tumor. Although
myoepithelial differentiation in PLGA is described, transition to these areas is subtle and gradual, typically only
discernible focally on immunohistochemical stains.19 In
contrast, a luminal ductal and abluminal myoepithelial
configuration is integral to adenoid cystic carcinoma and
epithelial-myoepithelial carcinoma and is typically evident on routine histologic examination. The second pattern of error is the failure to recognize the characteristic
nuclear features of PLGA. All cancers reclassified as adenocarcinoma, NOS did not have the monomorphic ovoid
and open nuclei with delicate nuclear membranes that
essentially define PLGA. To prevent these errors, we suggest that the monophasic nature and classic nuclear features of PLGA be emphasized in the working definition
for this entity. The remaining patient misdiagnosed as
having a PLGA had a low-grade salivary duct carcinoma, which was not recognized as a distinct entity until the description by Delgado et al18 in 1996. Of note,
three-quarters of these tumors erroneously diagnosed as
PLGA were of parotid gland origin, suggesting that true
parotid PLGAs are indeed rare.
For the remaining cancers in the PLGA category, findings were generally in keeping with prior series.7,10,15 Despite the innocuous name, PLGA is indeed a malignant
neoplasm of salivary gland origin that, in our series,
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Figure 5. One patient with the palate as the primary site had a recurrence on the soft palate 7 years later and metastases to the subcutaneous tissues of the face,
orbit, and lungs at 19.6 years. A, Computed tomogram demonstrating multiple pulmonary nodules (arrows point to right and left lung nodules). B, Fine needle
aspiration biopsy specimen demonstrated metastatic polymorphous low-grade adenocarcinoma to the lung (Papanicolaou, original magnification ⫻400). This
cluster of cells shows the characteristic ovoid nuclei with delicate chromatin.
Table. Univariate Correlation of Clinicopathologic Variables
With Disease-Free Survival
Variable
Site (palatal vs extrapalatal)
ALI
Margin status
Large nerve PNI
Bone invasion
Papillary component
Hazard Ratio (95% CI)
P Value
10.68 (1.28-88.72)
5.22 (0.98-27.89)
4.48 (0.46-43.43)
1.93 (0.42-8.87)
1.71 (0.38-7.67)
1.01 (0.99-1.03)
.03
.05
.20
.40
.48
.41
Abbreviations: ALI, angiolymphatic invasion; CI, confidence interval;
PNI, perineural invasion.
showed a locoregional recurrence rate of more than 30%.
Lymph node metastases were uncommon, and distant metastases were rare. Primary treatment was surgical. Because few patients received initial radiotherapy, the impact of this treatment modality is unclear. However, our
limited findings of recurrence despite radiotherapy suggest it is likely of little benefit, as noted in prior series.15
Similar to what has been reported previously, PLGA in
our series most commonly occurred in the palate. However, the site distribution was slightly skewed toward unusual locations, such as the base of the tongue and the
nasopharynx, probably because ours is a tertiary care center. These extrapalatal PLGAs appeared to display more
aggressive features, clinically and pathologically.
Our subset of 3 patients with PLGA of the nasopharynx represents the largest series to date. Skeptics may suggest that our patients have nasopharyngeal papillary adenocarcinomas, which are distinct carcinomas not
included in the PLGA family.20 However, all our patients had disease that fulfilled the morphologic criteria
we delineated herein and, in addition, did not have pap-
illary-predominant disease. These cancers characteristically invaded bone and invariably recurred locally. Clear
margins could not be obtained in any patients in which
the original margin status was known, which likely contributed to this high recurrence rate. Two patients received radiotherapy but nevertheless experienced disease recurrence. Although any conclusions about
nasopharyngeal PLGAs are limited based on these few
patients and those described previously,8 PLGAs arising
in the nasopharynx are still intrinsically low grade with
low metastatic capacity. Because of the propensity of these
tumors for bone involvement and the limited surgical exposure and anatomic limitations, these tumors remain a
challenge in surgical management. Radiotherapy is currently of unproven benefit.
The PLGAs that arise in the base of the tongue also
represented an interesting subset. Michal et al21 suggested that cribriform adenocarcinoma of the tongue was
a more appropriate designation for their series of 8 carcinomas of the base of the tongue that were initially diagnosed as PLGA. The authors’ justification was that the
solid and microcystic cribriform pattern was sufficiently unique to recognize even without site designation and that these tumors, unlike PLGAs, invariably metastasized to lymph nodes. In our 3 patients, a solid and
papillary architecture was the norm. In addition, we found
no histologic novelty in the patterns seen in tumors in
the base of the tongue compared with other sites. Similar to cribriform adenocarcinomas of the tongue, however, all patients showed lymph node metastases on presentation or as regional recurrences. Because none of our
patients’ conditions fit the description of cribriform adenocarcinoma of the tongue, we cannot confirm or refute the validity of this entity. However, we contend that
it is the site of origin of the base of the tongue that im-
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parts the propensity for lymph node metastasis rather than
the tumor morphologic type. This is not a unique concept because squamous cell carcinoma of the base of the
tongue with its rich lymphatic network has a relatively
high propensity for lymph node metastases.22,23 Other salivary gland carcinomas involving the base of the tongue
may also have an aggressive course.24 From a practical
standpoint, current evidence suggests that a cancer of the
base of the tongue in the PLGA family, regardless of its
name, will metastasize to cervical lymph nodes. The fact
that most of the lymph node metastases in our series were
found as recurrence suggests that they were occult. An
elective neck dissection should be performed even in a
clinically node-negative patient with a PLGA of the base
of the tongue.
Evaluations of prognostic markers in PLGA are difficult based on the numbers available in most series, including our own. In addition, many of these variables are
likely interdependent. For instance, we found that all
PLGAs with papillary components comprising greater than
20% of tumor showed ALI. As noted herein, the distinction between palatal and extrapalatal sites appears to affect
outcome the most. Positive margins and bone invasion
affected DFS, but the differences were too small to be significant in this series. Similarly, although ALI, papillarypredominant histologic type, and PNI predicted a shorter
DFS, none of these factors were statistically significant,
perhaps in a larger series similar to that of Evans and
Luna,10 statistical significance; for these variables may be
reached.
Similar to primary PLGA, recurrences are typically slow
growing and often amenable to reexcision with subsequent favorable outcomes. Only 1 patient in our series
had multiple recurrences and a distant metastasis. According to the literature, distant metastases are exceptionally rare, with the lung being the most common site
involved. Metastases usually occurred only after poor local control.5,10,15 Although biologically, recurrent tumors appear to retain their indolence, pathologic features of recurrent PLGA have not been well characterized.
Cases of transformation to a high-grade adenocarcinoma have been reported, suggesting the capacity for histologic transformation, but this appears to be a rare
event11,12; no carcinomas in our series fit this description. However, we noticed that almost half of the recurrences in our series progressed to an intermediate-grade
morphologic type with more nuclear size variation,
nucleolation, and an overall higher mean mitotic rate. Of
note, the 1 patient with lung metastases had been preceded by 2 local recurrences during a 19-year period with
intermediate-grade morphologic type. Thus, the potential for histologic progression is a legitimate concern in
disease recurrences. Because adjuvant therapy is unproven at best, adequate surgical excision even of recurrent disease may be the only useful safeguard against highgrade transformation.
In summary, familiarity with PLGA has increased during the past few decades, although now the current diagnostic challenge may be the prevention of this entity from
becoming a default diagnosis for all low-grade carcinomas of salivary gland origin. Although polymorphous in
pattern, this carcinoma is actually cytologically mono-
typic with pathognomonic delicate vesicular nuclei. Polymorphous low-grade adenocarcinoma may follow an indolent course with a favorable outcome, although with
adequate follow-up, recurrence may be encountered in almost one-third of patients. This finding suggests the need
for lifelong monitoring. Limited experience with radiotherapy fails to support its usefulness.
Extrapalatal PLGAs, particularly those of the base of
the tongue and nasopharynx, appear to be more aggressive, and carcinomas of the base of the tongue may present with cervical lymph node metastases. Our patients
demonstrate sufficient morphologic overlap to suggest
that site-specific differences in PLGA behavior may have
an anatomic basis (with regard to resectability and access to lymphatics) rather than a taxonomic one. Carcinomas with positive margins, bone invasion, papillarypredominant growth, and/or ALI may be more aggressive
as well, although the size of our series probably prevented these variables from achieving statistical significance. Almost half the recurrent PLGAs showed some degree of histologic progression, supporting the importance
of adequate excision of even recurrent disease to prevent the rare but catastrophic outcome of high-grade transformation.
Submitted for Publication: April 27, 2009; final revision received June 24, 2009; accepted November 6, 2009.
Correspondence: Raja R. Seethala, MD, Department of Pathology, University of Pittsburgh School of Medicine,
UPMC Presbyterian University Hospital, 200 Lothrop St,
Ste A614, Pittsburgh, PA 15213 ([email protected]).
Author Contributions: All authors had full access to all
the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis.
Study concept and design: Seethala, Johnson, Barnes, and
Myers. Acquisition of data: Seethala. Analysis and interpretation of data: Seethala and Johnson. Drafting of the
manuscript: Seethala. Critical revision of the manuscript
for important intellectual content: Seethala, Johnson,
Barnes, and Myers. Statistical analysis: Seethala. Administrative, technical, and material support: Johnson and
Myers. Study supervision: Johnson and Barnes.
Financial Disclosure: None reported.
Previous Presentation: This study was presented at the
American Head and Neck Society 2009 Annual Meeting; May 30, 2009; Phoenix, Arizona.
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