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carcinome intraductal

Low Grade Salivary Duct Carcinoma
A Distinctive Variant with a Low Grade Histology and a Predominant Intraductal
Growth Pattern
Ruby Delgado, M.D.’
David Klimstra, M.D.’
Jorge Albores-Saavedra, M.D.’
Division of Anatomic Pathology, Department
of Pathology. University of Texas Southwestern
Medical Center, Dallas, Texas.
* Department
of Pathology, Memorial SloanKettering Cancer Center, New York, New York.
BACKGROUND. Salivary duct carcinoma (SDC) has been established as a morphologically distinct and highly aggressive (HG)malignancy of the major salivary
glands. However, a low grade (LG) or intermediate grade salivary duct neoplasm
has not been described.
METHODS. We report the clinicopathologic findings of 10 cases believed to represent the (1.G) counterpart of SDC. lrnmunoperoxidase stains were performed on
tive cases, and electron microscopy o i l three.
RESULTS. hll of the tumors occurred in adult patients with no sex predilection,
and presented as slow growing parotid gland lesions. Four cases involved the
superficial lobe, one the deep lobe, and one arose within an intraparotid lymph
node. The exact location of the tumor within the parotid gland was not stated in
four cases. The size of the tumors ranged from 0.7 to 4 cm in greatest dimension,
with most measuring between 1 and 2 cni. 1he gross appearance was focally to
predominantly cystic. Microscopically, the tumors were characterized by intraductal proliferative lesions exhibiting three main patterns: (1) cystic ducts with micropapillaq, tufted, and plaque-like intralurninal projections; (2) ducts distended by
a solid or pseudocribriform (fenestrated) cellular proliferation, with varied cystic
dilatation; and (3) ducts exhibiting architectural atypia. The three patterns coexisted arid merged in most tumors, in varying proportions. All tumors shared bland
to LG cytologic features, with the exception of one that had focal high-grade cytologic ductal atypia. Despite gross circumscription, there was microscopic multifocality, and in one case, stromal invasion. By immunohistochemistry the neoplastic
cells expressed the conventional ductal and glandular epithelial cell markers in
addition to strong positivity for S-100 with coexpression for CK-903. Electron microscopy contirmrd the ductal phenotype of the tumors and supported an in situ
process evidenced by the presence of native myoepitlielial cells. Nine patients
underwent total parotidectoniy and one superficial parotidectorny. One patient
received radiation therapy following total parotidecotmy. Follow-up for 6 cases
ranged from 2 to 12 years and revealed no evidence of disease.
CONCLUSIONS. LG-SDC represents the LG end of the spectrum of salivary duct
malignant neoplasms anti exhibits differentiation towards an intercalated ductlike cell phenotype. Its relationship to 1IG-SL)C should be Purther explored. Cancer
1996; 78:958-67. 0 I996 American Curicer Society.
The authors thank Mrs. R. Nelly Murillo for her
assistance in the preparation of this manuscript.
KEYWORDS salivary gland, duct carcinoma, low grade, high grade, immunohistochemistry, electron microscopy.
Address for reprints: Ruby Delgado, M.D., Department of Pathology, University of Texas
Southwestern Medical Ctr., 5323 Harry Hines
Blvd., Dallas. TX 75235-9072.
Received February 16, 1996; revision received
May 23, 1996; accepted June 3, 1996.
c) 1996 American Cancer Society
lthough the histomorphogenesis of some salivary gland neoplasms remains unclarified, the term salivary duct carcinoma
(SDC) has been restricted to tumors composed predominantly or exclusively of ductal cells with the formation of structures resembling
distended salivary ducts. In most instances SDC has been recognized
by its striking resemblance to mammary duct carcinoma. To date
Low Grade Salivary Duct Carcinoma/Delgado et al.
Immunohistouhemical Findings in Five Cases of LG-SDC
No. of
Pattern of immunoreactivity
S-100 protein
membranous > cytoplasmic
diffusea; i
menibrdnous > cpoplasniic
diffusea: 4 t14+*
luniinal diffuse; 7 c
c p p l a s m i c focahpocrine
metaplastic cells; A +
nuclear & ryoplasmic diffiise"'';
cytoplasmic limited to
myoepithelial cells; - 4
In one case fresh tissue was fixed in glutaraldehyde and routinely processed for transmission electron microscopic examination. Selected tumoral tissue
was retrieved from paraffin embedded blocks in the
other two cases. The tissue was processed following
deparaffinization in xylene and rehydration through
graded ethanol solutions. All tumors were examined
in a JEOL 1200 electron microscope (JEOL Ltd., Tokyo,
A clinical summary of all cases is provided in Table 2.
I.G-SI)C: lowgradi s a l i g dutr carcinoma; pCE4: polyclonal carcinoenibryonic anrign; CCIEP gross
c!\rir d i w w lluij prorein; !N\:
smoorh muscle spPrific aciin
Inrludrr yacuol;i[rd c~lls.
liitl:itle(i some of [he n y q i ~ h e l i a (ells.
Snurtv & I)iluunrl: (:\iokeraun Cnm 5.2 (Hecron-[)ickinson. \,luun[ain View. CAiPrediluredi: Cvokeraiiii \lA(IOJ ; E m lhgnoslicr Inc. Srw York, NI':I:?Ol: pCE4 il)ako Corporalion. Carpinierta. CNI:40;;
HEY-?hignrt :abiiralorie, Inc, Dcdhani. S1hil:IOOi; S-I00 prolein :Dako Corporaiion, Carpinreria,
C4i1.300!, 5\19 6ignia Ihgnosrics, Sr. 1.ouir. MOil:100i.
only a high grade SIX has been recognized, showing
the characteristic in situ and invasive growth phases.'."
During our review of SDCs we encountered tumors characterized by the proliferation of salivary duct
structures and exhibiting ductal differentiation (by
light microscopy, immunohistochemistry, and electron microscopy), but lacking both the aggressive morphologic features and clinical behavior of the high
grade S I X W e believe these tumors represent the low
grade end of the spectrum of salivary duct malignancies.
Four cases were accrued in consultation. A fifth case
was retrieved from the surgical pathology files of Parkland Memorial Hospital in Dallas, Texas, and the remaining five from the surgical patholoby files of Memorial Hospital in New York, New York. Clinical information and follow-up data were provided by the
referring physicians in three cases and from the patients' charts in four cases; three patients were lost
to follow-up. Routine hematoxylin and eosin stained
sections were examined. Additional sections from all
cases were prepared for histochemical, periodic acidSchiff (PAS), and mucicarmine, and immunohistochemical analysis. Immunostains were performed using the standard avidin-biotin peroxidase method.
Commercially available antibodies were used with appropriate controls (Table 1).
Microscopically, the tumors were characterized by a
heterogeneous intraductal proliferative process with
three dominant patterns or components: (1) cystically
dilated ducts exhibiting partial to circumferential intracystic micropapillary and tufted formations focally
anastomosing and coalescing into solid plaque-like
epithelial stratification (Figs. IA-C). The micropapillae were composed of cuboidal to small columnar cells
exhibiting conspicuous intracytoplasmic microvacuoles which increased in number from base to lumen
and were accompanied by a fine granular yellowbrown pigment. In its fullest expression the cells were
filled and distended by sharply outlined minute vacuoles causing indentation of the nucleus and accentuation of the cytoplasmic rim, resulting in scallopshaped micropapillae (Figs. 2A, B). Better developed
papillae with fibrotic fibrovascular cores and psammoma bodies were also present. In the nonproliferative areas the cysts were lined by a simple apocrine
epithelium showing attenuation and squamous metaplasia. (2) Ducts distended by solid, pseudocribriform
(fenestrated) or solid-papillary ductal proliferation
(Fig. 3A). The cells comprising these neoplastic ducts
were ovoid to cuboidal with dense pale to bright eosinophilic cytoplasm, indistinct cell borders, and oval nuclei with finely dispersed chromatin and pinpoint
nucleoli. Foci of apocrine metaplasia were also seen
(Fig. 313, inset). The cells were arranged in a somewhat
loose to overlapping fashion forming solid sheets or
slit-like to irregular luminal spaces or fenestrae resulting in a pseudocribriform appearance (Fig. 38).
The spaces contained basophilic mucin alternating
with hyaline colloid-like material. Many of the ducts
showed cystic dilatation in varying degrees and were
filled by basophilic mucin. This cystic change was accompanied occasionally by the intracytoplasmic microvacuolar change previously described. Other ducts
had a solid-papillary appearance consisting of solid
sheets traversed by delicate fibrovascular cores. (3)
Ducts displaying conventional architectural atypia,
spanning the entire range of mild to severe (Fig. 4). All
CANCER September 1,1996 I Volume 78 I Number 5
Clinicopathologic Findings in Ten Patients with Low Grade Salivary Duct Carcinoma
Case #
Age (yrs)/sex
Original diagnosis
Parotid [superficial lobe;
I cni
0.7 rni
1.1 ciii
1.3 ciii
1.8 ciii
I cni
1.2 ciii
4 cni
0.9 cm
0.8 cm
Lowgrade papillocystic adeiiocarriiioma
Papillocystic carcinoma
Acinic cell carcinoma; positive margins
Aciiiic cell carcinoma
Aciiiic ceil carcinoma
Acinic cell carcinoma
69 / M
Right parotid (superfiria! lobe)
Right parotid (superficial lobel
Left parotid
Right parotid
Left parorid (superficial lobe)
Right parotid (intraparotid lymph node1
I.eR parotid
Right parotid (deep lobe)
LG-SDC with focal invasion; positive margins
NED at 12 yrs
NED at I 1 yrs
NED at 6 17s
NED at 2 yrs
NED at 2 ITS
NED a1 2 )rs
NED at 9 mos
NED: no evidence of disease; LG-SDC: low gade salivary duct carcinoma,
FIGURE 1. Papillocystic pattern of low grade salivary duct carcinoma. (A)
Delicate filigreed intracystic micropapillae with psamrnoma body rnicrocalcification (arrow). (8) Anastornosing micropapillae. (C) Mural tufting.
three patterns coexisted and merged in most tumors
in varying proportions and combinations. (The first
pattern was observed in 100% of the cases, the second
in 90%, and the third in 60%). In the cases where a
large cyst dominated the histologic picture, the other
two components were found in a pericystic arrangement and focally communicating with the major cyst.
All tumors were nonencapsulated but somewhat circumscribed by a dense sclerotic stroma exhibiting secondary changes such as remote hemorrhage, choles-
Low Grade Salivary Duct CarcinomalDelgado et al.
FIGURE 2. Intracytoplasrnic vacuolar change in papillocystic low grade salivary duct carcinoma. (A) Transition from apocrine-like cells to vacuolated
cells, with progressive accumulation of intracytoplasmic microvacuoles. (B) Vacuolated ductal cells are filled and distended by nonmernbrane bound
lipid droplets, anG show surface microvilli.
terol granulomas, and dystrophic calcification. Also
bordering the tumors was a marked lymphoid infiltrate (Fig. I , bottom).
Despite the apparent circumscription of the tumors, detached tumor foci were seen in the surrounding glandular parenchyma (Fig. 5), best interpreted as niultifocality, and in one case, stromal microinvasion (Fig. CiB) was noted disclosing its malignant
potent ial.
Onc tumor was remarkable for having originated
in an intraparotid lymph node, extending beyond it
into the immediate parotid parenchyma and surrounding but not invading peripheral nerve branches.
Mitotic activity was negligible in most cases, nonatypical mitotic figures being identified in two cases.
Mucicarrnine and PAS stains highlighted the matctrial in intercellular spaces, with no intracytoplasmic
niiicin positivity observed. No PAS-positive diastase
resistant material suggestive of zymogen granules
could be identified. Large PAS-diastase positive granules were present but confined to foci of apocrine
me t a pl asia.
Immunoperoxidase studies revealed the expected
reactivity to conventional epithelial markers (Table 1).
Of significance, however, was the strong nuclear and
cytoplasmic positivity for S-100 protein (Fig. 7) and the
cytoplasmic positivity for the high molecular weight
cytokeratin (3413E12 or MA903). All three morphologic
components exhibited similar immunostaining patterns, and encompassed the vacuolated and nonvacuolated cells. In addition, smooth muscle actin outlined
the ductal proliferative lesions in a pattern indicative
of a myoepithelial layer of pre-existing ducts involved
by an intraductal neoplastic proliferation (Fig. 8A).
Similarly, collagen type IV antibodies circled the neoplastic ducts. Immunoreactivity for antibodies to
GCDFP-15, observed in two cases, correlated with foci
of apocrine metaplasia.
Ultrastructurally, the tumors were composed of
ductal cells with interdigitating cell membranes forming intercellular lumina and bound by a continuous
basal lamina. The ductal cells displayed apical microvilli and contained a modest number of organelles,
except for occasional cells showing an increased number of mitochondria. Also identified in a peripheral
or basal location were myoepithelial cells with long
attenuated cytoplasmic prolongations (Fig. 8B). The
vacuolated cells were characterized as plump ductal
cells distended by what appeared as coalescing empty
nonmembrane bound spaces in some cells and lipid
droplets in others. These caused significant indentation of the nuclei and displaced the cytoplasmic organelles to a subplasmalemmal location (Fig. 2 R ) .
We report ten cases of a tumor which conforms to the
cytoarchitectural definition of a salivary duct neoplasm (composed primarily of ductal luminal cells
with formation of distended salivary duct structures),
that, to our knowledge, has not been previously characterized as such. Because it exhibits a bland histomorphology and has thus far demonstrated a favorable
behavior, we propose the term “low grade salivary
duct carcinoma” (IG-SDC).
CANCER September 1,1996 / Volume 78 / Number 5
FIGURE 3. (A) Classic pseudocribriform pattern of low grade salivary duct carcinoma (B) Proliferating ductal cells show somewhat overlapping
oval nuclei and indistinct cytoplasmic cell borders. Irregular intercellular spaces are filled with hyaline material. Focus of apocrine rnetaplasia (inset).
In contrast to its aggressive counterpart, the high
grade salivary duct carcinoma (HG-SDC), better
known for its reiterated similarity to breast duct carcinoma (mainly comedo type),’-6LG-SDC spans an appearance reminiscent of florid to atypical ductal hyperplasia to low grade intraductal breast carcinoma
(Table 3). Based on the accumulated experience with
HG-SDC,’-6 salivary duct neoplastic proliferations
have demonstrated a more aggressive behavior than
their morphologic counterparts in the breast. This apparent organ-specificity may be related to underlying
structural differences (i.e., regional anatomy or glandular microanatomy), to biologic differences (i.e., hormonal regulation), andlor to inherent tumor proper-
Low Grade Salivary Duct CarcinomalDelgado et al.
FIGURE 4. Architectural (cribriform) atypia in low grade duct salivary
duct carcinoma. Spaces are filled with basophilic mucin.
FIGURE 5. Isolated focus of low grade salivary duct carcinoma in adjacent parotid parenchyma (arrow), suggestive of multifocality.
ties. The terminology applied to the ductal proliferations of the salivary glands should reflect these
differences. Therefore, we propose the term “lowgrade salivary duct carcinoma” for the range of distinctive lesions we are describing. We acknowledge
them as being pijrt of a morphologic continuum in
salivary duct neoplasia. Progression was evidenced by
the acquisition of a higher cytologic grade and focal
microinvasion, observed in one case (Fig. 6A, B).
The entities lo be considered in the differential
diagnosis of LG-SDC vary from those of the HG-SDC.
In those cases having a dominant cystic papillary component, LG-SDC has been often confused with papil-
lary-cystic acinic cell carcinoma (ACC).An additional
feature shared by both entities and a likely source of
confusion is the presence of vacuolated cells. Historically, vacuolated cells have been described as being
unique to ACC.“’,’ They are reported to be observed
in about one-third of the ACC and are the predominant cell type in a minority of the tumors. The nature
of the vacuolated cells has not been elucidated. Several
explanations have been postulated, including a retrogressive change in the zymogen granules and, the
presence of dilated and distended profiles of rough
endoplasmic reticulum (RER).’ Notwithstanding their
elusive nature, the vacuolated cells in ACC are characterized by large cells with wispy or reticulated cytoplasm containing a single vacuole having the appearance of an intracytoplasmic pseudolumen or several
macrovacuoles that coalesce into microcystic spaces
(Fig. 9B). Conversely, LG-SDC shows fine vacuolation
consisting of crowded punched-out microvacuoles
having a somewhat refractile quality (Fig. 2A). These
microvacuoles are associated with a pale yellowbrown pigment and are thus akin to the supravacuoles
that have been reported to characterize and identify
apocrine epithelium.” Another distinctive feature of
apocrine epithelium is the presence of apical glycolipid granules,9 which were also identified in LG-SDC
both by PAS-D and by electron microscopy. Conversely, in none of the tumors examined by light microscopy, histochemistry, or electron microscopy
could acinar differentiation be documented.
Failure to recognize LG-SDC as a distinct entity
may also stem from the cellular composition of the
ACC, alleged to be the result of a combination of five
individual cell
acinar, and its clear cell variant,12 nonspecific glandular, intercalated duct-like,
and vacuolated. Such heterogeneity has been explained by its origin in or differentiation towards the
terminal duct-acinar nit.^,'" Of the five cell types
mentioned, only the nonspecific glandular and intercalated duct-like cells are the likely constituents of the
LG-SDC. That is, LG-SDC appears to be the manifestation of a n entirely ductal proliferation/differentiation
without the concomitant acinar component, whereas
the latter by definition is expressed in the papillarycystic ACC. It is important to mention that tumors
composed exclusively of intercalated duct-like cells
have been documented; however, they have been reported as ACC on the basis of their papillary-cystic
morphologic pattern.” Whereas, conceivably, a morphologic continuum may exist between papillary-cystic ACC and LG-SDC, we believe that in the majority
of cases reproducible distinguishing criteria exist, including distinct vacuolated cell variants (Table 4, Figs.
9A, B).
The quality of the microvacuolar change and its
CANCER September 1, 1996 / Volume 78 / Number 5
FIGURE 6. (A) Neoplastic duct with a higher cytologic grade resembling high grade salivary duct carcinoma (right) arising in a low grade salivary
duct carcinoma (left) and associated with (B) a microscopic focus of stromal invasion.
FIGURE 7. Distinctive immunoreactive pattern of low grade salivary duct
carcinoma for S-100 protein antibody, with diffuse and intense nuclear
and cytoplasmic positivity.
prominence in some LG-SDC may raise the possibility
of a sebaceous neoplasm. However, no other features
of sebaceous differentiation such as the germinative
epithelium"" are present and the resemblance is
merely superficial.
Because of the low grade cytology the diagnosis
of a polymorphous low grade adenocarcinoma (PLGA)
may be entertained. However, LG-SDC lacks the tubular, ductular, trabecular, and single file patterns so often observed in PLGA, as well as, the characteristic
infiltrative appearance, mucohyaline stroma, and neurotropism.
Finally, two entities that must be discussed in defining LG-SDC are papillary cystadenocarcinoma and
papillary cystadenoma. According to the latest World
Health Organization (WHO) histologic classification of
salivary gland tumors,' papillary cystadenocarcinoma
is a malignant tumor characterized by cysts with papillary endocystic projections. Like LG-SDC they are considered low grade malignant neoplasms with potential
for infiltrative growth. Unlike LG-SDC they display well
developed papillae with narrow, fibrous, sometimes
hyalinized cores, covered with cuboidal or low columnar cells. Furthermore, they exhibit cytologic atypia,
nuclear pleomorphism, and significant mitotic activity. Although it is tempting to view papillary cystadenocarcinoma as the papillary variant of LG-SDC, we
believe its obvious more aggressive histologic features
warrant its separate designation. Conversely, and not
surprisingly, given their seemingly bland nature, cases
of LG-SDC have been illustrated as examples of cystadenomas.5While not denying the existence of benign
proliferative ductal lesions in the salivary gland, for the
reasons previously discussed, in particular the noted
progression to a higher cytologic grade lesion with invasion, we prefer to regard these tumors as potentially
malignant. Fortuitously, in the latest WHO classification of salivary gland tumors,' the term papillary cystadenoma is given to a tumor that closely resembles
Warthin tumor minus the lymphoid elements.
Regarding the so-called salivary gland cystadenocarcinoma, we believe it is a nonspecific descriptive
term that, like its counterpart, salivary gland adenocarcinoma, should only be used when a tumor eludes
any of the heretofore established entities.
Based on the histomorphogenetic classification
Low Grade Salivary Duct Carcinoma/Delgado et at.
FIGURE 8. (A) The neoplastic ducts are silhouetted by a continuous layer of myoepithelial cells (immunoperoxidase stain for smooth muscle actin).
as confirmed by electron microscopy, (6)cytoplasmic prolongations of a “native” myoepithelial cell circumscribe the neoplastic ductal cells
Distinguishing Histopathologic Features of Low Grade and High Grade Salivary Duct Carcinoma
Cornedo necrosis
Cell ;irrarigement
Cell shape
C!.toplasmic borders
Mitotic figures
Cellular composition
Myoepithelial component
low grade SDC
High grade SDC
Pseudocribriform with slit-like spaces, solid, and
cystically dilated: focal architectural atypia
Present (psainmoma bodies)
1.oose to overlapping
Predomiiiaiiily ovoid
Dense pale 10 bright eosinophilic
Oval, low grade
f leterogenous: ductal, apocrinc. vacuolared
Peripheral: rim
s-100 c 1vvlW-CK-903 *
Cribriforni with geometric spaces
scheme of salivary gland neoplasms proposed by
some, ’ I ’ ’ the salivary duct carcinoma is a tumor
composed predominantly of ductal luminal cells. In
I,G-SL)C, both by immunohistochemistry and electron microscopy, myoepithelial participation is limited to a peripheral localization and of a seemingly
non-neoplastic nature corresponding to an in situ
phase (intraductal carcinoma). Alternatively, LGSDC may represent a highly organized bicellular
ductal/myoepithelial growth. Of interest is the
strong inimunoreactivity of I.G-SDC for S-100 and
i t 5 coexpression with high-molecular weight cyto-
Only associated with comedo necrosis
I’redoniinaiitly polygonal
Powdery eosinophilic
Round to oval, moderate to high-grade
Moriomorphous: ductal
Peripheral: scattered
S-100 I~SlW-(X903T /
keratin (CK-903). Based on immunohistochemical
studies of the normal salivary gland, the former is
more often associated with intercalated duct cells
whereas the latter has been correlated with the basal
cells found mainly in the interlextralobular ducts.
However, such coexpression has been previously
noted to identify the intercalated duct cell component in ACC, the acinar cells being negative for both
anti bodies .‘I) Thus, this i mm u n o h is t o che m i cal find ing seems to characterize a neoplastic ductal phenotype morphologically akin to the intercalated duct
cells, supporting our interpretation of these cases
CANCER September 1,1996 I Volume 78 I Number 5
FIGURE 9. Papillocystic variant of acinar cell carcinoma, included for comparison. (A) lntracystic papillary tumor masses exhibiting secondary
follicular pattern. (B) Reticulated acinar and clear cells with macrovacuoles coalescing into microcystic spaces.
Distinguishing Histomorphologic Features of Low Grade Salivary Duct Carcinoma and Papillarv-CvsticAcinic Cell Carcinoma
Low Grade SDC
Papillary-Cystic ACC
GroiLzh pattern
Micropapillary to plaque-like
(:ellular composition
Partial intraluminal groulh
~pocritieivacuolated,intercalated duct-like, nonspecific glandular
Papillay peninsulasimasses with secondary patterns:
microcystic, follicular, etc.
Fills and distends (expands1 cystic spaces
Acinar, clear, intercalatedduct-like, nonspecific glandular,
vacuolated, oncocpic
Prominent nucleoli
Readily identifiablr mitotic figures
Derived from acinar cells, loose lreticulatedi macrovaciioles
coalescing into mirrorystic spares
Cplogic features of nunvacuolated ducral cells
Cplogic features of vacuolated cells
ldrntifiable nucleoli
Infrequent iniitotic figures
Derived from apocrine cells, well defined, crowded and refraclile intracellular
Features shared by both entities: Secondary changes such as squamous
nietaplasia of cyst lining, stromal fibrosis, sclerosis, remote heniorrhage
with cholesterol cleftsigranulomaa.psammonia body-like and dystrophic
calcification, marked lymphoid illfiltrate
SDC: saliun duct carcinoma; ACC: acinic cell carcinoma.
as salivary duct and not acinic cell neoplasms. Of
interest, this immunohistochemical profile contrasts
with that of high grade salivary duct carcinoma3,"
(Table 3 ) .
Complete clinical information was available for
6 patients, none of whom showed local recurrence
or metastatic disease at 2 (3 patients), 6 , 11, and 12
years following total parotidectomy. Only one had
received postoperative radiotherapy based o n the
diagnosis of ACC and positive surgical margins.
Three patients were lost to follow-up. The last and
most recent case in our series with only 9 months
of follow-up was significant for exhibiting a focus of
invasive ductal carcinoma extending to the surgical
margin, for which postoperative radiotherapy was
given. These clinical findings contrast with those of
HG-SDC which has been reported to have a death
rate of 70 to 75%, with a mean survival of 3 years
after diagnosis.'
We conclude that LG-SDC represents the low
grade end of the spectrum of salivary duct neoplasms. LG-SDC appears to be primarily an in situ
(intraductal) process and should be distinguished
from the better known HG-SDC which is usually invasive, carries a poor prognosis, and warrants aggressive therapy.
Furthermore, we especially emphasize the distinguishing features from an ACC, with which it is
often confused. Recognition will enable further
definition of this entity and of its natural course,
given the protracted disease progression that characterizes many of the low grade salivary gland malig-
Low Grade Salivary Duct Carcinoma/Delgado et al.
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become invasive an d/or to evolve to a HG-SDC also
needs to be addressed.
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