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This rare malignant salivary gland tumor has an aggressive clinical course. It is distinctive in its histopathologic appearance, resembling the infiltrating ductal carcinoma of the breast. The tumor arises almost exclusively in the major salivary glands.


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Range 22-91 years



Salivary duct carcinoma--a highly aggressive salivary gland tumour with overexpression of c-erbB-2.

Hellquist HB, Karlsson MG, Nilsson C.

Department of Pathology, Orebro Medical Center Hospital, Sweden.

J Pathol 1994 Jan;172(1):35-44 Abstract quote

The clinicopathological and immunocytochemical features of nine cases of salivary duct carcinoma are described.

This relatively rare tumour, which only recently has been widely recognized as a separate entity, is highly malignant and caused the death in eight of the patients. The tumour cells are arranged in cribriform and solid growth patterns, where the solid tumour nests frequently have comedo necrosis, and a fibrous, often sclerotic, stroma is present. The infiltrating desmoplasmic component and the diffuse invasive growth into adjacent adipose parotid tissue have similarities to ductal breast carcinoma. Immunocytochemical investigation of salivary duct carcinoma showed constant overexpression of c-erbB-2 as detected by membrane accentuation, and high proliferative activity as detected by nuclear positivity for MIB 1 (Ki-67). Changes in the expression of p53 and retinoblastoma gene product do not constitute a constant event in salivary duct carcinoma. A few of the tumours showed scattered cells with distinct nuclear positivity for both progesterone and oestrogen receptors.

We emphasize that this highly malignant salivary gland tumour has a characteristic morphology, may not be as rare as previously considered, and that prompt and aggressive therapy is needed.



Salivary duct carcinoma.

Delgado R, Vuitch F, Albores-Saavedra J.

Department of Pathology, University of Texas Southwestern Medical Center, Dallas 75235-9072.

Cancer 1993 Sep 1;72(5):1503-12 Abstract quote

BACKGROUND. Salivary duct carcinoma (SDC) is a distinctive salivary gland neoplasm morphologically characterized by intraductal and infiltrating components. Most tumors occur in the major salivary glands and demonstrate a propensity for invasive growth with early regional and distant metastases. Therefore, SDC is regarded as a high-grade malignancy in the current classification of salivary gland neoplasms.

METHODS. In an effort to identify clinically relevant prognostic features, we studied the clinicopathologic and immunohistochemical findings in 15 SDC, with ultrastructural evaluation of three tumors.

RESULTS. Thirteen SDC occurred in the parotid gland, one in the Stensens duct, and one in the palate. Twelve patients were men (ratio of men to women = 4:1). Patients ranged in age from 39 to 81 years (mean = 59 years). Tumor size varied from 1.2 to 6.5 cm (mean = 3.1 cm). An intraductal component was identified in 10 of 14 primary SDC that made up 10% to 95% of the tumor. In three SDC a preexisting pleomorphic adenoma was identified. Immunohistochemical and electron microscopic evaluation showed the SDC to be composed entirely of ductal cells, and one tumor exhibited features of striated duct differentiation.

CONCLUSIONS. SDC show a broader clinicopathologic spectrum than previously described. The tumor may arise in a pleomorphic adenoma. The proportion of intraductal and extraductal growth is variable and of prognostic significance. Although the majority of SDC behave in a high-grade fashion, those with a predominant intraductal component of greater than 90% (PID-SDC) and minimally invasive (< 8 mm) SDC in pleomorphic adenoma appear to have a more favorable prognosis.

Salivary duct carcinoma: a clinicopathologic study of three cases with a review of the literature.

Minamiguchi S, Iwasa Y, Shoji K, Higuchi K, Watanabe C, Haga H, Nakashima Y, Yamabe H.

Laboratory of Anatomic Pathology, Kyoto University Hospital, Japan.

Pathol Int 1996 Aug;46(8):614-22 Abstract quote

Three cases of salivary duct carcinoma are presented. They occurred in a 60 year old man, a 66 year old man and a 57 year old woman. All of the lesions were located in the parotid gland. The tumor size ranged from 3 to 5 cm across the largest diameter. Facial paralysis was observed in two cases.

Histologically, intraductal and invasive adenocarcinoma showing papillary, cribriform, and solid patterns with comedolike necrosis was observed. Immunohistochemically, the tumor cells were positive for keratin and epithelial membrane antigen. No myoepithelial cells were demonstrated within the tumor by staining for S-100 protein, alpha-smooth muscle actin or muscle specific actin. Ultrastructurally, intracytoplasmic lumina with microvilli, a moderate number of mitochrondria, lysosomes, and tight junctions were found. Regional lymph node metastasis was observed in one case, and distant metastasis developed in two cases. All of the patients were treated with adjuvant postoperative irradiation. One patient died of disease at 11 months after the initial diagnosis, another was alive with disease at 8 months, and the third patient was alive without disease at 2 years and 3 months.

Salivary duct carcinoma should be differentiated from low-grade salivary gland carcinomas using morphologic and clinical criteria because of its poor prognosis even with aggressive therapy.


Salivary duct carcinoma in the mandible: report of a case with immunohistochemical studies.

Suzuki H, Hashimoto K.

Department of Oral and Maxillofacial Surgery, Hamamatsu University School of Medicine, Hamamatsu City, Shizuoka Prefecture, Japan.

Br J Oral Maxillofac Surg 1999 Feb;37(1):67-9 Abstract quote

Salivary duct carcinoma is rare.

We describe a 56-year-old man who developed salivary duct carcinoma in the mandible 10 years after removal of the right second and third molars. The tumour originated in the retromolar gland or the ectopic minor salivary gland in the mandible. The panoramic radiograph showed a radiolucent, poorly circumscribed area about 40 x 30 mm in size and distal to the lower right first molar. This tooth, together with all neoplastic tissue, was removed, and histopathological examination showed it to be a salivary duct carcinoma in the mandible. On immunohistochemical staining, keratin antibodies stained the ductal structure, 1A4 antibody stained myoepithelial cells, but S-100 protein and vimentin were not seen.

The patient was well and with no sign with recurrence 6 years postoperatively.


Intraoral salivary duct carcinoma: case report with immunohistochemical observations.

Lopes MA, de Abreu Alves F, Levy BA, de Almeida OP, Kowalski LP.

Oral Diagnosis, School of Dentistry of Piracicaba, University of Campinas-UNICAMP, Sao Paulo, Brazil.

Oral Surg Oral Med Oral Pathol Oral Radiol Endod 2001 Jun;91(6):689-92 Abstract quote

Salivary duct carcinoma is an uncommon malignant salivary gland tumor that occurs predominantly in the parotid gland. Oral involvement is extremely rare, with few cases having been reported in the literature. The tumor is characterized by an aggressive behavior and has a poor prognosis.

We describe a case of salivary duct carcinoma arising in the hard palate of a 63-year-old man. Immunohistochemical analysis revealed that tumor cells tested positive for cytokeratin, epithelial membrane antigen, proliferating cell nuclear antigen, Ki67, p53, laminin, and collagen IV.

Despite radical surgical resection, bilateral neck dissection, and postoperative radiotherapy, liver metastases developed, and the patient subsequently died of his disease.

Salivary duct carcinoma of the parotid gland metastasizing to the skin: a case report and review of the literature.

Aygit AC, Top H, Cakir B, Yalcn O.

Department of Plastic and Reconstructive Surgery, Trakya Universitesi, Edirne, Turkey.
Am J Dermatopathol. 2005 Feb;27(1):48-50. Abstract quote

Salivary duct carcinomas of parotid gland are rare, as are the skin metastases from them. Four cases are reported with metastases to the skin.

We present an additional case, with subcutaneous metastases of the back and leg.

To our knowledge, this is the first case reported in the literature in which the nodule on an extremity was the metastasis of a salivary duct carcinoma of parotid gland.



Infiltrating salivary duct carcinoma. A clinicopathologic study of five cases.

Chen KT, Hafez GR.

Arch Otolaryngol 1981 Jan;107(1):37-9 Abstract quote

The clinicopathologic features of five cases of salivary gland carcinoma characterized by the presence of intraductal components of the carcinomatous process were studied and compared with those of other types of salivary gland carcinoma.

The term "infiltrating salivary duct carcinoma" seems to be appropriate for this type of tumor because of its morphologic resemblance to the infiltrating ductal carcinomas of the breast.

Its biologic behavior is highly aggressive; the metastatic and tumor-related death rates were 75% and 73%, respectively.


Intraductal Carcinoma of the Oral Cavity: A Case Report and a Reappraisal of the Concept of Pure Ductal Carcinoma In Situ in Salivary Duct Carcinoma

Cheuk, Wah MD*; Miliauskas, John R MD†; Chan, John K.C MD*

From the *Department of Pathology, Queen Elizabeth Hospital, Hong Kong and †Clinpath Laboratories Pty. Ltd, Kent Town, S.A., Australia.


The American Journal of Surgical Pathology : Volume 28(2) February 2004 pp 266-270 Abstract quote

The pure in situ form of salivary duct carcinoma, also known as intraductal carcinoma, is very rare, and its existence is controversial.

We describe a case arising from the minor salivary glands. The patient was a 44-year-old woman who presented with a painless mass in the buccal mucosa. On microscopic examination, the tumor comprised crowded and smooth-contoured epithelial units exhibiting a fenestrated or cribriform pattern, occasionally punctuated by comedonecrosis. An attenuated layer of myoepithelial cells could be demonstrated around all the islands by immunostaining for p63 and actin, indicating absence of an invasive component. The patient remained well following local excision.

This case, together with other reported cases, suggests that intraductal carcinoma is a distinct entity. It may represent the preinvasive phase of some invasive salivary duct carcinomas but by itself is nonmetastasizing and associated with an excellent prognosis.

Low-grade Intraductal Carcinoma of Salivary Gland: Report of 3 Cases With Marked Apocrine Differentiation.

Weinreb I
Tabanda-Lichauco R, Van der Kwast T, Perez-Ordonez B.

*Department of Pathology, University Health Network daggerDepartment of Laboratory Medicine and Pathobiology, University of Toronto double daggerDepartment of Pathology, St John Regional Hospital and St John, New Brunswick section signDepartment of Pathology and Laboratory Medicine, Mount Sinai Hospital, Toronto, Ontario, Canada.


Am J Surg Pathol. 2006 Aug;30(8):1014-1021 Abstract quote

Low-grade intraductal carcinomas (LG-IDCs) of salivary gland are rare neoplasms that resemble atypical ductal hyperplasia or LG-IDCs of the breast. They have been referred to as "low-grade salivary duct carcinomas" or "low-grade cribriform cystadenocarcinomas."

Herein, we describe 3 additional cases of LG-IDCs, 2 were pure intraductal carcinomas, although 1 demonstrated increasing cytologic atypia and progression to an invasive adenosquamous carcinoma. The latter had been present for 7 years before demonstrating clinical and pathologic progression to a widely invasive malignancy. The intraductal component in all cases exhibited a remarkable degree of apocrine differentiation. The tumor cells were positive for AE1:AE3, Cam 5.2, high molecular weight keratin, CK7, CK19, BRST-2, and androgen receptors (ARs). S-100 was positive in 2 cases and negative in 1 case.

The intraductal neoplastic cells were surrounded by myoepithelial cells positive for CK14, actins, calponin, high molecular weight keratin, and p63. All the tumors were negative for CK20, estrogen and progesterone receptors, Her2Neu, and p53. Extensive apocrine differentiation, expression of ARs, CK7, and CK19, and progression to a widely invasive carcinoma after a long clinical latency have not been reported in LG-IDCs previously. These tumors share some histopathologic features with salivary duct carcinoma including apocrine differentiation, and expression of ARs and BRST-2.

The terms "low-grade salivary duct carcinomas" and "low-grade cribriform cystadenocarcinomas" should be abandoned in favor of LG-IDC of salivary gland, which better reflects their predominantly noninvasive, intraductal nature.
Low-Grade Salivary Duct Carcinoma: Description of 16 Cases.

Brandwein-Gensler M, Hille J, Wang BY, Urken M, Gordon R, Wang LJ, Simpson JR, Simpson RH, Gnepp DR.

*Departments of Otolaryngology and Pathology, Mount Sinai School of Medicine, New York, NY; the daggerDepartment of Pathology, Rhode Island Hospital, Brown University, Providence, RI; double daggerSt. Richard's Hospital, Chichester, Sussex, UK; and the section signRoyal Devon and Exeter Hospital, Exeter, UK. Jos Hille is a research fellow from the University of the Western Cape, Cape Town, South Africa.
Am J Surg Pathol. 2004 Aug;28(8):1040-1044. Abstract quote

Low-grade salivary duct carcinoma is a rare neoplasm. We report on 16 patients, with a median age of 64 years. All but one tumor arose from the parotid gland, including one tumor that arose in an intraparotid lymph node; one arose in the submandibular gland.

Tumors consist of single to multiple dominant cysts, accompanied by adjacent intraductal proliferation. Cysts are lined by small, multilayered, proliferating, bland ductal cells with finely dispersed chromatin and small nucleoli. Separate, smaller ductal structures are variably filled by proliferating ductal epithelium with cribriform, micropapillary, and solid areas. The overall appearance is very similar to breast atypical ductal hyperplasia and low-grade ductal carcinoma in situ. Foci of definitive stromal invasion were seen in four tumors. Two tumors demonstrated transition from low- to intermediate- or high-grade cytology, with scattered mitotic figures and focal necrosis. S-100 revealed diffuse strong expression in all 9 cases studied. Myoepithelial markers (calponin) highlighted supportive myoepithelial cells rimming the cystic spaces, confirming the intraductal nature of most, or all, of six tumors studied. Nine tumors studied for Her2-neu antigen were uniformly negative. Follow-up was obtained on 13 of our 16 patients. All patients were disease-free after surgery 6 to 132 months (median 30 months).

Low-grade salivary duct carcinoma is a low-grade neoplasm with an excellent prognosis; it may be treated by conservative but complete resection. Its resemblance to atypical breast ductal hyperplasia, or micropapillary/cribriform intraductal carcinoma, distinguishes it from high-grade salivary duct carcinoma, papillocystic acinic cell carcinoma, and cystadenocarcinoma.

Low grade salivary duct carcinoma. A distinctive variant with a low grade histology and a predominant intraductal growth pattern.

Delgado R, Klimstra D, Albores-Saavedra J.

Department of Pathology, University of Texas Southwestern Medical Center, Dallas 75235-9072, USA.

Cancer 1996 Sep 1;78(5):958-67 Abstract quote

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 (LG) counterpart of SDC. Immunoperoxidase stains were performed on five cases, and electron microscopy on three.

RESULTS: All 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 cm. The gross appearance was focally to predominantly cystic. Microscopically, the tumors were characterized by intraductal proliferative lesions exhibiting three main patterns: (1) cystic ducts with micropapillary, tufted, and plaque-like intraluminal 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 and 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 confirmed the ductal phenotype of the tumors and supported an in situ process evidenced by the presence of native myoepithelial cells. Nine patients underwent total parotidectomy and one superficial parotidectomy. One patient received radiation therapy following total parotidectomy. 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 and exhibits differentiation towards an intercalated duct-like cell phenotype. Its relationship to HG-SDC should be further explored.


Invasive Micropapillary Salivary Duct Carcinoma: A Distinct Histologic Variant With Biologic Significance

Nagao, Toshitaka MD; Gaffey, Thomas A MD*; Visscher, Daniel W MD*; Kay, Paul A MD*; Minato, Hiroshi MD; Serizawa, Hiromi MD†; Lewis, Jean E MD*

From the *Division of Anatomic Pathology, Mayo Clinic, Rochester, MN; and the †Department of Surgical Pathology, Tokyo Medical University Hospital, Tokyo, Japan. Drs. Nagao and Minato are Visiting Clinicians at the Division of Anatomic Pathology.


The American Journal of Surgical Pathology : Volume 28(3) March 2004 pp 319-326 Abstract quote

An invasive micropapillary component has been described in tumors of several organs and is nearly always associated with aggressive biologic behavior.

We present 14 cases of salivary duct carcinoma (SDC) with an invasive micropapillary component (invasive micropapillary SDC) and compare the clinicopathologic findings of these cases with those of cases of conventional SDC. The mean age of the 14 patients (10 men, 4 women) was 65.8 years (range, 26-80 years). The mean size of the tumors was 2.4 cm (range, 1.3-5 cm). The parotid gland was involved in 12 patients and the submandibular gland in 2.

Histologically, all tumors had an invasive micropapillary architecture admixed with features typical for SDC. Invasive micropapillary carcinoma was characterized by morula-like small cell clusters without fibrovascular cores, surrounded by a clear space. Tumor cells exhibited moderate- to high-grade nuclear features, conspicuous nucleoli, and eosinophilic cytoplasm. This component was distributed diffusely in 9 tumors and focally in 5. Angiolymphatic and perineural invasion was seen in all tumors. A residual pleomorphic adenoma was detected in four tumors. Of the 12 tumors examined, all were diffusely positive for cytokeratin 7 and epithelial membrane antigen (with a distinctive inside-out pattern) but negative for cytokeratin 20. Tumors were frequently immunoreactive for BRST-2 (gross cystic disease fluid protein-15) and androgen receptor protein. Aberrant expression of HER-2/ neu or p53 was detected in seven tumors each. The mean Ki-67 labeling index was 33.1% (range, 6.3%-61.6%). All 14 patients with invasive micropapillary SDC had cervical or periglandular lymph node metastasis, and this value was significantly higher than for conventional SDCs. Local recurrence developed in 4 patients and distant metastatic disease in 9.

Clinical follow-up (mean, 25.5 months) was available for 13 patients: 9 died of disease within 24 months after the diagnosis (mean, 17.6 months), 1 was alive with metastatic disease at 19 months, and 3 were free of disease. Overall survival of these patients with invasive micropapillary SDC was significantly shorter than that of patients with conventional SDC (n = 49) in our series ( P = 0.031).

Our results suggest that invasive micropapillary SDC is a distinct, aggressive variant of SDC, with a propensity for extensive lymph node metastasis and rapid disease progression.


Mucin-rich variant of salivary duct carcinoma: a clinicopathologic and immunohistochemical study of four cases.

Simpson RH, Prasad AR, Lewis JE, Skalova A, David L.


Am J Surg Pathol. 2003 Aug;27(8):1070-9. Abstract quote

Salivary duct carcinoma is a relatively uncommon aggressive neoplasm, typically found in the parotid glands of older men. The histologic appearance is that of an in situ and invasive high-grade adenocarcinoma, and it closely resembles ductal carcinoma of the breast. Several variants of the latter are very well known, but only papillary, sarcomatoid, and low-grade subtypes have so far been reported in salivary duct carcinoma.

This study describes the clinicopathologic and immunohistochemical findings in four examples of an additional previously undescribed variant, rich in mucin. Each tumor showed areas of typical salivary duct carcinoma, but in addition there were lakes of epithelial mucin-containing malignant cells, i.e., mucinous (colloid) carcinoma.

All four tumors expressed androgen receptors, cytokeratins, epithelial membrane antigen, gross cystic disease fluid protein-15, and carcinoembryonic antigen, but S-100 protein, other myoepithelial markers, and estrogen and progesterone receptors were negative. The mucin antigen profile showed positivity for MUC2, MUC5B, and MUC6 in all cases but only rare staining with MUC5AC and MUC7. Strong immunohistochemical overexpression of HER2/neu was demonstrated in one tumor, together with amplification by fluorescence in situ hybridization; another case was weakly positive with just one antiserum, but the remaining two tumors were completely negative.

Small quantities of mucin have often been described in salivary duct carcinoma but not large extracellular mucinous lakes, which though prominent in the present series, were not as extensive as in mucinous adenocarcinoma.

The relatively poor clinical outcome of the patients in our study mirrored that seen in usual-type salivary duct carcinoma and emphasizes the importance of differentiating mucin-rich salivary duct carcinoma from pure mucinous (colloid) adenocarcinoma, a tumor not fully defined, but possibly with a better prognosis.

Sarcomatoid Variant of Salivary Duct Carcinoma
Clinicopathologic and Immunohistochemical Study of Eight Cases With Review of the Literature

Toshitaka Nagao, MD, etal.
Am J Clin Pathol 2003;122:222-231 Abstract quote

Salivary duct carcinoma (SDC) is an uncommon, high-grade tumor.

We present 8 cases of sarcomatoid SDC, which has been defined recently as a rare variant of SDC. The 8 patients (5 men, 3 women) had a mean age of 63.6 years.

Histologically, all tumors were characterized by a biphasic neoplasm composed of both SDC and sarcomatoid elements. In 3 cases, sarcomatoid components showed osteosarcomatous heterologous differentiation. A residual pleomorphic adenoma was detected in 5 tumors. The sarcomatoid component showed focal immunoreactivity for cytokeratin in 4 cases and epithelial membrane antigen in all 8 cases. Diffuse p53 immunostaining was detected in 3 cases, and it was coexpressed in both components.

Our observations support the histogenetic theory of a common origin of the carcinomatous and sarcomatoid populations. Of the 13 patients, including our 8, reported to have sarcomatoid SDC arising in a major salivary gland and for whom long-term follow-up data were available, 7 have died of disease (mean survival, 15.6 months).

These results indicate that sarcomatoid SDC is a highly aggressive tumor, similar to conventional SDC.

Sarcomatoid salivary duct carcinoma of the parotid gland.

Henley JD, Seo IS, Dayan D, Gnepp DR.

Department of Pathology, Wishard Memorial Hospital, Indiana University School of Medicine, Indianapolis 46202-5280, USA.

Hum Pathol 2000 Feb;31(2):208-13 Abstract quote

Salivary duct carcinoma (SDC) is a high-grade neoplasm known to histologically resemble high-grade ductal carcinoma in situ of the breast.

We describe 3 cases of sarcomatoid salivary duct carcinoma, a heretofore unreported variant of SDC. Each case was a composite of SDC and sarcomatoid carcinoma and histologically similar to reported cases arising in the breast. The clinicopathologic features, including immunohistochemistry, of 3 cases were investigated. In the 3 men, ages 56, 68, and 70 years, the resected parotid tumors measured 1.5, 3.5, and 1.5 cm, respectively. Only the 3.5-cm tumor extended beyond the parotid gland into soft tissue. This patient died at 3 years with pulmonary metastases. The other patients were free of disease at 6 and 12 months.

Histologically, each case was a composite of usual-type SDC and sarcomatoid carcinoma. SDC showed typical cribriform architecture, whereas anaplastic, spindled cells constituted the sarcomatoid areas. Immunohistochemically, epithelial elements stained as follows: cytokeratin (AE1/AE3 & CAM 5.2) positive in 3 of 3 cases, EMA positive in 3 of 3 cases, vimentin negative in 3 of 3 cases, desmin negative in 3 of 3 cases, c-erbB-2 positive in 1 of 2 cases. Sarcomatoid elements stained as follows: AE1/AE3 negative in 3 of 3 cases, CAM 5.2 rare positive cell in 1 of 3 cases, EMA focally positive in 3 of 3 cases, vimentin positive in 3 of 3 cases, desmin negative in 3 of 3 cases, c-erbB-2 negative in 2 of 2 cases. Electron microscopy, performed in one case, showed scattered junctional complexes congruent with epithelial differentiation. Immunohistochemical results, EMA and CAM 5.2 positivity, and ultrastructural findings supported our belief that these unique biphasic tumors represented SDC with sarcomatoid carcinoma.

We conclude an element of sarcomatoid carcinoma rarely may arise in association with SDC, and it is erroneous to diagnose such tumors as "carcinosarcoma."


Differential Expression of Hormonal and Growth Factor Receptors in Salivary Duct Carcinomas: Biologic Significance and Potential Role in Therapeutic Stratification of Patients.

Williams, Michelle D. MD *; Roberts, Dianna PhD +; Blumenschein, George R. Jr MD ++; Temam, Stephane MD ++; Kies, Merrill S. MD ++; Rosenthal, David I. MD [S]; Weber, Randal S. MD +; El-Naggar, Adel K. MD, PhD * +


American Journal of Surgical Pathology. 31(11):1645-1652, November 2007. Abstract quote

Salivary duct carcinoma (SDC), a rare malignancy, manifests remarkable morphologic and biologic resemblance to high-grade mammary ductal carcinoma. We contend that, similar to mammary ductal carcinoma, hormones and growth factors may play a role in SDCs.

Our aim was to determine the incidence and clinical significance of the expression of several hormone and growth factor receptors and evaluate their potential in therapeutic stratification of SDC patients in the largest cohort studied to date. Eighty-four archived tumor tissue blocks were analyzed immunohistochemically for expression of estrogen receptor-[beta] (ER[beta]), androgen receptor (AR), and proline, glutamic acid, and leucine-rich protein-1 and growth factor receptors HER-2 and epidermal growth factor receptor. The results were correlated with available pathologic, demographic, and clinical data from 59 of 84 cases. Proline, glutamic acid, and leucine-rich protein-1, ER[beta], and AR were expressed individually in 94% (71/76), 73% (57/80), and 67% (56/84) of SDCs, respectively, and coexpressed in 45% (34/75). AR was expressed significantly more often in SDCs of men than in SDCs of women [79% (35/57) vs. 33% (9/27), P<0.001]. Epidermal growth factor receptor and HER-2 were overexpressed individually in 48% (40/83) and 25% (21/84), respectively, and co-overexpressed in 12% (10/83). Survival decreased significantly in patients with lymph node metastasis (P=0.002) and positive surgical margins (P=0.006). Lack of ER[beta] expression correlated with increased local and regional recurrence (P=0.05 and P=0.002, respectively).

Together, these results indicate that (a) ER[beta] down-regulation is associated with adverse clinical features, (b) lymph node and surgical margin status are significant survival factors, and (c) the differential expression of these hormones and growth factor receptors may assist in triaging patients with SDC for novel therapies.

Salivary duct carcinoma. Clinicopathologic and immunohistochemical review of 26 cases

Lewis JE, McKinney BC, Weiland LH, Ferreiro JA, Olsen KD.

Division of Anatomic Pathology, Mayo Clinic, Rochester, Minnesota 59505, USA.

Cancer 1996 Jan 15;77(2):223-30 Abstract quote

BACKGROUND. Salivary duct carcinoma (SDC) is a high grade aggressive malignancy of the major salivary glands. Clinical and pathologic features that may be predictive of survival are not well delineated. The microscopic features of SDC are remarkably similar to those of mammary ductal carcinoma, raising the question of whether these tumors share antigenic or hormonal features.

METHODS. We reviewed the clinical and pathologic characteristics of 26 cases of SDC treated at the Mayo Clinic from 1960 to 1989. Immunoperoxidase studies and flow cytometry were performed in 25 and 24 cases, respectively.

RESULTS. The study population consisted of 22 men and 4 women (mean age, 66 years). The parotid gland was involved in 23 patients and the submaxillary gland in 3. Five of 24 tumors studied were diploid (21%), and 19 (79%) were nondiploid. Nine tumors (35%) recurred locally and 16 (62%) metastasized distantly; 20 patients (77%) died of disease at a mean interval of 3 years after diagnosis. Female sex was the only significant negative prognostic factor analyzed, but positive nodal status approached significance. Paraffin-section immunostaining showed positive reactions for epithelial membrane antigen (100%), keratin (AE1/AE3) (88%), alpha-lactalbumin (88%), GCDFP-15 (76%), and carcinoembryonic antigen (72%); S-100 protein was rarely detected (4%). Stains for estrogen receptor were uniformly negative, but one tumor was positive for progesterone receptors.

CONCLUSIONS. The prognosis for SDC is dismal, and clinically useful prognostic factors were not found. Our results do not confirm hormonal concordance between SDC and breast carcinoma.

Salivary duct carcinoma of the parotid gland. Report of a case with cytologic and immunocytochemical findings on fine needle aspiration biopsy.

Colecchia M, Frigo B, Leopardi OM.

Division of Anatomical Pathology and Cytology, Ospedale Maggiore di Lodi, Milan, Italy.

Acta Cytol 1997 Mar-Apr;41(2):593-7 Abstract quote

BACKGROUND: Salivary duct carcinoma (SDC) is a rare high grade neoplasm arising from the larger ducts of the major salivary glands, most frequently in the parotid glands in the elderly. It is important to identify some characteristics that allow differentiating SDC from the other salivary gland adenocarcinomas, which have different prognoses.

CASE: A 63-year-old, white male presented with an indolent swelling in the left parotid gland, the retromandibular angle. Fine needle aspiration biopsy (FNAB) showed polygonal or cuboidal, medium-sized, moderately pleomorphic cells with round to oval nuclei in cytocentrifuge preparations. Small tissue fragments with a prominent cribriform pattern and an area of comedocarcinoma were observed in the cytocentrifuged material. Tumor cells were diffusely immunoreactive for low- and high-molecular-weight cytokeratins, and strong positivity was observed with 115D8 and Ber-EP4 antibodies. Overexpression of c-ERB B-2 was absent, and < 5% of the nuclei were immunoreactive for p53.

CONCLUSION: The cytologic and immunocytochemical appearance of SDC are characteristic, and FNAB results provide the surgeon with useful information for planning surgical therapy.

Novel estrogen receptor coactivator PELP1/MNAR gene and ERbeta expression in salivary duct adenocarcinoma: Potential therapeutic targets.

Vadlamudi RK, Balasenthil S, Sahin AA, Kies M, Weber RS, Kumar R, El-Naggar AK.

Hum Pathol. 2005 Jun;36(6):670-5. Abstract quote  

Summary Salivary duct carcinoma (SDC) is a high-grade neoplasm with marked morphological resemblance to mammary duct carcinoma.

The novel estrogen receptor (ER)-interacting protein and the proline-, glutamic acid-, and leucine-rich protein 1 ( PELP1 ), also called the modulator of nongenomic activity of ER ( MNAR ), have been shown to activate steroid hormone receptors in mammary carcinomas by nongenomic and genomic mechanisms. The expression and the relationship of this gene to the ER status in SDCs are unknown.

We investigated the differential expression of the PELP1 / MNAR and the ERs alpha and beta proteins in SDCs, using Western blotting and immunohistochemistry. Western blot analysis of 7 paired normal and tumor specimens showed increased expression of PELP1 / MNAR and ER beta in 3 and 4 of the SDCs, respectively. No detectable expression of ER alpha in any normal or SDC specimens was noted. Immunohistochemical staining performed on 70 SDCs revealed strong expression of PELP1 / MNAR in 51 (73%) and ER beta in 52 (74%) tumors. PELP1 / MNAR and ER beta were coexpressed in 35 (50%), individually in 17 (24.2%), and negative in 18 (25.7%) tumors. PELP1 / MNAR staining was predominantly cytoplasmic whereas ER beta staining was nuclear and occasionally cytoplasmic in tumor cells.

Our results indicate that PELP1 / MNAR and ER beta are coexpressed in most SDCs and may play a role in the pathobiology of these tumors.

Expression of peroxisome proliferator-activated receptor gamma in salivary duct carcinoma: immunohistochemical analysis of 15 cases.

Mukunyadzi P, Ai L, Portilla D, Barnes EL, Fan CY.

Departments of Pathology and Nephrology, University of Arkansas for Medical Sciences, Little Rock, Arkansas 72205, USA.
Mod Pathol. 2003 Dec;16(12):1218-23. Abstract quote  

Salivary duct carcinoma is a rare but highly aggressive tumor of the salivary glands that has poor prognosis. There is no effective cure for this tumor. Peroxisome proliferator-activated receptor gamma (PPARgamma) is a member of the nuclear receptor family with diverse biological functions that include mediation of adipocyte differentiation, regulation of the monocyte-macrophage anti-inflammatory activity, and inhibition of tumor cell proliferation.

Natural (prostaglandin J2, PG-J2) and synthetic (thiazolinediones) PPARgamma ligands with anti-proliferative agonist activity have been identified. The expression of PPARgamma has been demonstrated in human colorectal, pancreas, breast, and prostate cancers but has never been explored in salivary duct carcinoma. The aim of our study was to investigate the expression patterns of PPARgamma in salivary duct carcinoma, a finding that may provide a mechanism for treating patients with this highly aggressive tumor. Archival formalin-fixed tissues from 15 salivary duct carcinoma cases were analyzed for PPARgamma expression by an immunohistochemical staining method using a monoclonal antibody against the PPARgamma. The tissue sections were subjected to antigen retrieval by a steam heat method. All the cases of salivary duct carcinoma originated from the parotid gland. Immunohistochemistry analyses showed positive expression of PPARgamma in 12 (80%) cases, whereas 3 (20%) were negative. Of the positive cases, 9 (75%), 2 (17%) and 1 (8%) showed strong, moderate, and weak staining, respectively. All staining was cytoplasmic. Nuclear staining was not observed.

We conclude that PPARgamma is frequently (80%) expressed in salivary duct carcinoma, often at high levels, and is topographically located in the cytoplasm. The high-level expression of PPARgamma may provide a potential molecular target for the treatment of salivary duct carcinoma using agonist ligands.

Ultrastructural and immunohistochemical study of salivary duct carcinoma of the parotid gland.

Yoshihara T, Shino A, Ishii T, Kawakami M.

Department of Otolaryngology, Tokyo Women's Medical College, Japan.

Ultrastruct Pathol 1994 Nov-Dec;18(6):553-8 Abstract quote

A case of salivary duct carcinoma of the parotid gland found in an 81-year-old man was studied by light microscopy, immunohistochemistry, and electron microscopy.

Histologically, the tumor was composed of elongated cords of cells and ductal structure with desmoplastic stromal reaction. Tumor cell nests sometimes showed central comedonecrosis.

Immunohistochemically, the tumor cells were positive for cytokeratin and epithelial membrane antigen, and they were negative for S-100 protein and muscle-specific actin.

Electromicroscopically, two cell types were identified. The first cell type showed electron-lucent cytoplasm with scant organelles. The second type cell contained numerous mitochondria. Neither acinar nor myoepithelial cell differentiation was observed. These findings suggest that salivary duct carcinoma originates from the interlobular or excretory ducts.


Metastatic carcinoma Especially breast cancer



Salivary duct carcinoma. Part I. A clinicopathologic evaluation and DNA image analysis of 13 cases with review of the literature.

Barnes L, Rao U, Krause J, Contis L, Schwartz A, Scalamogna P.

Department of Pathology, University of Pittsburgh Medical Center, Pa.

Oral Surg Oral Med Oral Pathol 1994 Jul;78(1):64-73 Abstract quote

Salivary duct carcinoma is an uncommon and relatively unknown clinically aggressive adenocarcinoma of salivary origin that histologically demonstrates a remarkable resemblance to invasive carcinoma of the breast.

We report the clinicopathologic features of 13 cases that were also examined by image analysis for DNA ploidy. The results were then analyzed collectively with the less than 100 cases of salivary duct carcinoma reported in the English-language literature to define the characteristics of this unusual neoplasm. The 12 men and one woman averaged 68 years of age (range, 49 to 90 years). All tumors arose in the parotid (10 cases) or submandibular glands (three cases). Nine tumors were aneuploid, three diploid, and one was indeterminate because of insufficient tissue. Follow-up (median, 24 months) was available in 12 cases: three patients died of disease, six were alive without disease, and three died of other causes.

Combining our cases with those in the literature, a total of 104 cases, confirms that salivary duct carcinoma is a highly malignant neoplasm with distinctive clinical and pathologic features. It arises almost exclusively in the major salivary glands (96% of cases), is three times more common in men, and usually occurs in patients over 50 years of age (range, 22 to 91 years). One-third of patients experience local recurrences, 59% develop positive regional lymph nodes, 46% have systemic metastases (lungs and bones), and 65% die of their disease, usually within 4 years of diagnosis. Determination of tumor ploidy has no prognostic significance.

The presence of distant metastasis was the only clinicopathologic feature that was statistically associated with prognosis (p = 0.02); all patients with systemic metastasis died of disease.

Salivary duct carcinoma.

Grenko RT, Gemryd P, Tytor M, Lundqvist PG, Boeryd B.

Department of Pathology, University Hospital, Linkoping, Sweden.

Histopathology 1995 Mar;26(3):261-6 Abstract quote

Twelve cases of salivary duct carcinoma were examined clinically, pathologically and by flow cytometry to quantify their histological features as well as attempt to identify factors predictive of patient outcome.

All of the tumours arose in the parotid gland. Eight of the twelve patients were male. Four patients died of disease (median survival 12.5 months); three are alive with disease; and five are alive with no evidence of disease (mean follow-up of 50 months). Two tumours arose in a pre-existing pleomorphic adenoma. Positive lymph nodes were present in eight of ten patients sampled; patients with two or more positive lymph nodes tended to die of their disease or be alive with metastases. Comedo necrosis, perineural invasion and vascular invasion were common findings by light microscopy. Ten of the twelve tumours were aneuploid. Neither clinical stage, tumour size, aneuploidy nor histological features correlated with patient outcome.

This study confirms the aggressive nature of salivary duct carcinoma.

Salivary duct carcinoma: clinicopathological and immunohistochemical studies.

Martinez-Barba E, Cortes-Guardiola JA, Minguela-Puras A, Torroba-Caron A, Mendez-Trujillo S, Bermejo-Lopez J.

Pathology Service, Virgen de la Arrixaca University Hospital, El Palmar, Murcia, Spain.

J Craniomaxillofac Surg 1997 Dec;25(6):328-34 Abstract quote

Nine cases of salivary duct carcinoma were reviewed clinically, histologically and immunohistochemically, with special evaluation of biomarkers with prognostic significance (p53, Ki67, c-erbB-2 and DNA content).

Eight tumours occurred in the parotid gland and one in the submandibular gland. The average age of the patients (8 males and 1 female) was 62.8 years (range = 47-74 years). Tumour size ranged from 1 to 6 cm (mean = 3.46 cm). Recurrences were found in 33.3% (3 patients), regional metastases in 44.4% (4 patients) and systemic metastases in 33.3% (3 patients). Three patients died of their disease (median survival = 12.3 months), one is alive with the disease (follow-up of 222 months) and 5 are alive without evidence of disease (mean follow-up of 75 months). p53 protein nuclear immunostaining was positive in 66.6% and c-erbB-2 overexpression was observed in 100% of the tumours. Ki 67 positivity ranged from 6.75% to 47.5% of tumour cells (mean = 21.3%). DNA aneuploidy was found in 4 tumours (44.4%) and DNA diploidy in 5 (55.5%).

Our results seem to indicate that Ki67 immunostaining can be useful in the evaluation of the biological behaviour of these tumours, as well as the presence of a high proliferative index of aneuploid cells and the presence of distant metastases.

Salivary duct carcinoma: an unusual case of long-term evolution.

Madrigal B, Garcia J, De Vicente JC.

Department of Pathology, Hospital Central de Asturias, University of Oviedo, Spain.

Oral Surg Oral Med Oral Pathol Oral Radiol Endod 1999 Nov;88(5):597-602 Abstract quote

Salivary duct carcinoma is a highly malignant adenocarcinoma of salivary origin. Its pathologic features are distinct from the other salivary gland tumors and bear a remarkable histologic resemblance to ductal breast carcinoma. The clinical course is rapid and the prognosis is dismal. Aggressive therapy is warranted, including primary tumor resection, cervical neck dissection, and radiotherapy.

We present a case of salivary duct carcinoma of parotid origin with a very long-term evolution in clear contrast to its supposed aggressiveness. Tumor cells expressed low- and high-molecular-weight cytokeratins, epithelial membrane antigen, carcinoembryonic antigen, and c-erbB-2 but not estrogen and progesterone receptors, actin, and S-100.


Salivary duct carcinoma metastasizing to the small bowel.

Kruslin B, Scukanec-Spoljar M, Separovic V, Manojlovic S, Jankovic D, Danilovic Z.

Department of Pathology, School of Medicine, University of Zagreb, Croatia.

Tumori 1996 Sep-Oct;82(5):502-4 Abstract quote

We report a case of salivary duct carcinoma in a 47-year-old woman. The patient presented with symptoms simulating acute appendicitis. Surgery revealed metastatic tumor in the wall of the small bowel. Two months later, a tumor of the right parotid gland was resected, and histologic analysis revealed a salivary duct carcinoma.

To our knowledge, this is the first case of salivary duct carcinoma metastasizing to the small bowel with manifestations of metastatic disease as the prominent symptom.


Salivary duct carcinoma: clinical characteristics and treatment strategies.

Guzzo M, Di Palma S, Grandi C, Molinari R.

Maxillo-Facial Surgery and Otolaryngology, Instituto Nazionale Tumori, Milan, Italy.

Head Neck 1997 Mar;19(2):126-33 Abstract quote

BACKGROUND: Salivary duct carcinoma (SDC) is a highly malignant tumor of the salivary gland.

METHODS: Twenty-six cases observed during the period 1975 to 1994 were selected from the pathology archives of the Instituto Nazionale Tumori of Milan. A review of all the similar cases published in the literature and comparison with the present series was performed.

RESULTS: SDC was mainly a parotid gland tumor diagnosed at an advanced stage. Lymphatic involvement seems to be related to T stage. Distant spread was evidently related to the presence of lymph node metastasis. Surgery with radiotherapy was the standard treatment. The only demonstrable negative prognostic factor was the presence of node metastases (p = 0.01).

CONCLUSIONS: Most patients died of disseminated disease in spite of an aggressive and often successful local-regional treatment. The role of a prophylactic ipsilateral neck dissection and adjunctive systemic treatment should be investigated.

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Weedon D. Weedon's Skin Pathology Second Edition. Churchill Livingstone. 2002
Fitzpatrick's Dermatology in General Medicine. 6th Edition. McGraw-Hill. 2003.
Weiss SW and Goldblum JR. Enzinger and Weiss's Soft Tissue Tumors. Fourth Edition. Mosby 2001.

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