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Cytologic diagnosis of salivary duct carcinoma: a review of seven cases.

The cytomorphologic findings in fine-needle aspirates from 7 cases of salivary duct carcinoma (SDC) are reviewed and correlated with the histologic features. Malignant cytologic characteristics are clear in this tumor, and no false-negative results were obtained. But the absence of cribriform or papillary groups suggests an inconclusive diagnosis and sometimes the need to establish a differential diagnosis with other salivary tumors, and in particular with adenocarcinoma not otherwise specified (ADC-NOS) and high-grade mucoepidermoid carcinoma (h-g MEC). The pitfalls in the cytologic diagnosis of this tumor are discussed. In addition, the literature on the subject is reviewed.

Adult↗

Salivary duct carcinoma: cytokeratin 14 as a marker of in-situ intraductal growth.

AIMS: The aim of this study was to determine the immunoprofile of salivary duct carcinoma and to differentiate intraductal growth from invasive growth. METHODS AND RESULTS: We applied a panel of antibodies (cytokeratins 7, 8, 13, 14, 19, vimentin and alpha-smooth muscle actin) in five cases of salivary duct carcinoma. This panel is currently used for identification of different components of salivary gland tumours in our laboratory. All tumour cells were positive for cytokeratins 7 and 8. Few neoplastic structures expressed cytokeratin 14 in cells surrounding tumour islands. CONCLUSION: The finding of cytokeratin 14 was important to confirm the in-situ intraductal growth, which probably characterizes this low-grade neoplasm.

Adenocarcinoma↗

Salivary duct carcinoma: ultrastructural and histogenetic considerations.

Two cases of salivary duct carcinoma were examined by light and electron microscopy. Histologically, the tumor presented cribriform and papillary patterns together with comedonecrosis. Electron microscopy revealed duct cells with microvilli, interdigitations, and apical vesicles. No myoepithelial cells were observed. These findings suggest a ductal origin other than from the intercalated duct or its precursor element. The importance of separating the salivary gland adenocarcinomas is discussed.

Adenocarcinoma↗

An electron microscopic radioautographic study of the uptake of tritiated serotonin by nerve fibres in the posterior salivary duct and gland of cephalopods.

In the posterior salivary duct and gland of Octopus vulgaris and of Eledone cirrhosa, the duct secretory nerve trunks and their ramifications in the gland tubules include many fibres that incorporate labelled serotonin. However, there are also unlabelled secretory fibres, which cannot be discriminated from incorporating fibres on morphological grounds. Neuroglandular junctions are not apparently established by incorporating fibres. In the duct, the motor nerve trunks contain a small number of labelled fibres, and nerve bundles supplying the duct muscle contain, in variable proportions, serotonin incorporating fibres. Both labelled and unlabelled nerve fibres reach the duct muscle fibres, but neuromuscular junctions involve only unlabelled presynaptic fibres. The nerve fibres which join the gland muscle are usually unlabelled, and the small quota of incorporating fibres in the motor trunks apparently supply only duct tissues. Both secretory and motor trunks, originating from different ganglia, can be considered to contain heterogeneous fibres, releasing different neurotransmitters at the terminals. Certain of these fibres could be serotoninergic.

Animals↗

Shockwave lithotripsy of salivary duct stones.

Surgical extirpation of the affected gland has been necessary for cases of sialolithiasis in which the stone cannot be removed by dilatation or dissection of the salivary duct. The ability of the piezoelectric lithotripter to deliver shockwaves to a small focus makes extracorporeal shockwave lithotripsy of salivary gland stones potentially safe. Its safety and efficacy have been assessed in 51 patients with symptomatic solitary salivary stones that could not be removed by conservative measures. The stones had a median diameter of 8 (range 4-18) mm and were located in the submandibular gland in 69% of patients and in the parotid gland in 31%. A total of 72 shockwave treatment sessions (maximum 3 per patient) were given under continuous sonographic monitoring. In 45 patients (88%) complete fragmentation (fragments less than or equal to 3 mm) of the concrements was achieved. No patient needed anaesthesia, sedatives, or analgesics. The only untoward effects were localised petechial haemorrhages after 10 (13%) out of 72 treatments and transient swelling of the gland immediately after delivery of shockwave in 2/72 (3%) sessions. 20 weeks after the first session 90% (46/51) of patients were free of discomfort, and 53% (27/51) were stone free. Stone-clearance rate was higher among patients with stones in the parotid gland (81%) than among those with stones of the submandibular gland (40%). Auxiliary measures such as dilatation or dissection of the salivary duct were required only in patients with stones in the submandibular gland (20%). No long-term damage to the treated salivary gland or to adjacent tissue structures was noted during the median follow-up of 9 (1-24) months. Extracorporeal piezoelectric shockwave therapy seems likely to be safe, comfortable, and effective minimally-invasive, non-surgical treatment for salivary stones.

Adolescent↗

Salivary duct carcinoma: cytologic characteristics and application of androgen receptor immunostaining for diagnosis.

BACKGROUND: Although there have been several reports of cytologic features for salivary duct carcinoma (SDC), it still can be difficult to diagnose patients with these tumor accurately at the time of fine-needle aspiration (FNA). Review of the literature indicates that, immunohistochemically, SDC expresses androgen receptor (AR) in the majority of patients. The authors investigated the cytologic characteristics and utility of AR immunostaining on cytologic smears for the diagnosis of patients with SDC. METHODS: FNA and imprint smears from four patients with SDC were stained with Papanicolaou and periodic acid-Schiff (PAS). Immunostaining for AR on paraffin sections and imprint smears of SDC was performed, including 51 benign and other malignant salivary gland tumors. RESULTS: The smears were cellular and contained three-dimensional clusters, flat sheets, and scattered epithelial cells with necrotic backgrounds. A cribriform architectural pattern was noted in many of the tumor sheets. The tumor cells were large polygonal, spindle, and round to oval, and had abundant, finely granular, or vacuolated cytoplasm. Intracytoplasmic vacuoles were PAS negative. The nuclei were hyperchromatic, medium to large in size, round to oval in shape, and often had prominent nucleoli. All SDC tumors expressed AR. Two patients with carcinoma in (pleomorphic adenoma) showed a focal, comedo carcinoma pattern in which AR positive nuclei were observed. Other salivary gland tumors were completely negative for AR. CONCLUSIONS: The cytologic features of high-grade adenocarcinoma with a variety of cell morphologies, flat sheets of tumor cells with a cribriform pattern, and necrotic backgrounds are characteristic findings in patients with SDC. Immunostaining for AR on cytologic smears is useful for the diagnosis of these patients.

Adenocarcinoma↗

[Salivary duct carcinoma of the parotid gland: report of two cases and literature review].

Salivary duct carcinomas are scarce tumour developed mainly in the male in the 6th or 7th decades of their life. Authors report two new cases developed 43 and 60 years-old in females. Because this tumour was localised, a radical treatment associating surgery and radiotherapy was performed. Follow-up were 115 and 137 months, and the two patients remain free of disease. These two cases were opportunity to discuss literature data.

Adult↗

Salivary duct carcinoma. Clinicopathologic and immunohistochemical review of 26 cases.

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.

Adenocarcinoma↗

Salivary duct carcinoma: report of a case and review of the literature.

Salivary duct carcinoma is a rare primary tumour of the salivary glands arising most frequently in the parotid gland. It has a male preponderance and occurs most often in patients over the age of 50 years. Its distinctive histological features include dilated ducts containing cells arranged in cribriform, papillary or solid patterns often with central necrosis and reminiscent of intraduct carcinoma of the breast. These features are associated with an obvious invasive component. It is an aggressive neoplasm and may metastasize widely, causing death in a high proportion of cases.

Carcinoma↗

Regulation of [Na+]i in resting and stimulated submandibular salivary ducts.

In the preceding manuscript (Zhao, H., Xu, X., Diaz, J., and Muallem, S. (1995) J. Biol. Chem. 270, 19599-19605), we described a Kout(+)-dependent H+/HCO3- and Na+ influx pathway in the luminal membrane of salivary duct cells. In the present studies, we further characterized this pathway to show that the Kout(+)-dependent Na+ influx was not mediated by the luminal amiloride-sensitive Na+ channel, the Na+/H+ exchangers, or any electroneutral or conductive Cl(-)-dependent transport pathway. Thus, K+ efflux probably maintained electroneutrality during Na+ influx induced by removal of Kout+. Accordingly, Na+ influx was largely inhibited by 2.5mM external Ba2+. The K+ site of the Kout(+)-dependent Na+ influx showed the selectivity sequence Cs+ > K+ > NH4+ >> > Li+ which is different from that of several known K+ channels. More importantly, Na+ influx is 50% inhibited at about 20 mM Kout+, and significant Na+ influx occurred even at 80 mM Kout+. This is a critical property for the pathway to play a role in Na+ reabsorption and K+ secretion by the duct. The large Na+ influx in resting duct cells is matched by high activity of the ductal Na+ pump which is about 8-fold faster than that of acinar cells. Stimulation of submandibular ducts with various agonists increased [Na+]i in an agonist-specific manner. The parasympathetic agonist epinephrine was more effective than isoproterenol and sympathetic agonist carbachol. The use of various inhibitors of Na+ and K+ transporters suggests that different pathways mediate Na+ influx in stimulated acinar and duct cells of the gland. In duct cells, Na+ influx was inhibited only by extracellular Cs+ and Ba2+. The overall findings support a significant role for the Kout(+)-dependent pathway(s) in Na+ reabsorption and K+ and HCO3- secretion and explain several features of transepithelial electrolyte transport by salivary ducts.

Amiloride↗

Invasive micropapillary salivary duct carcinoma: a distinct histologic variant with biologic significance.

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.

Adult↗

Dopamine-induced graded intracellular Ca2+ elevation via the Na+Ca2+ exchanger operating in the Ca2+-entry mode in cockroach salivary ducts.

Stimulation with the neurotransmitter dopamine causes an amplitude-modulated increase in the intracellular Ca(2+) concentration ([Ca(2+)](i)) in epithelial cells of the ducts of cockroach salivary glands. This is completely attributable to a Ca(2+) influx from the extracellular space. Additionally, dopamine induces a massive [Na(+)](i) elevation via the Na(+)K(+)2Cl(-) cotransporter (NKCC). We have reasoned that Ca(2+)-entry is mediated by the Na(+)Ca(2+) exchanger (NCE) operating in the Ca(2+)-entry mode. To test this hypothesis, [Ca(2+)](i) and [Na(+)](i) were measured by using the fluorescent dyes Fura-2, Fluo-3, and SBFI. Inhibition of Na(+)-entry from the extracellular space by removal of extracellular Na(+) or inhibition of the NKCC by 10 microM bumetanide did not influence resting [Ca(2+)](i) but completely abolished the dopamine-induced [Ca(2+)](i) elevation. Simultaneous recordings of [Ca(2+)](i) and [Na(+)](i) revealed that the dopamine-induced [Na(+)](i) elevation preceded the [Ca(2+)](i) elevation. During dopamine stimulation, the generation of an outward Na(+) concentration gradient by removal of extracellular Na(+) boosted the [Ca(2+)](i) elevation. Furthermore, prolonging the dopamine-induced [Na(+)](i) rise by blocking the Na(+)/K(+)-ATPase reduced the recovery from [Ca(2+)](i) elevation. These results indicate that dopamine induces a massive NKCC-mediated elevation in [Na(+)](i), which reverses the NCE activity into the reverse mode causing a graded [Ca(2+)](i) elevation in the duct cells.

Animals↗

Antibodies to AB blood group antigens mimic anti-salivary duct autoantibodies in patients with limited sicca symptoms.

OBJECTIVE: We evaluated the clinical relevance and pathogenic significance of anti-salivary duct autoantibodies (ASDA) in Sjögren's syndrome (SS) and rheumatoid arthritis (RA) by examining (1) their frequency in healthy controls, patients with sicca symptoms, and patients with various autoimmune and infective disorders; (2) their localization by confocal microscopy; and (3) their tissue distribution and cross reactivity with blood group antigens. METHODS: Indirect immunofluorescence (IF) was performed on commercial cryostat sections of monkey parotid salivary gland. Sections were examined by fluorescence and confocal laser scanning microscopy. Sera giving positive staining on the ducts were tested by IF on a range of monkey tissues and salivary glands from several mammalian species. Blocking experiments were performed with human erythrocytes of different ABO blood groups and AB antigens. RESULTS: We identified 2 distinct ductal staining patterns. The first resembled ASDA described in earlier studies and showed patchy bright staining of the apical (luminal) surfaces of the ducts and staining of apical cytoplasmic vesicles. The other was only observed with anti-mitochondrial antibody positive sera and stained the mitochondrial-rich ductal epithelium in a distinctive punctate pattern. Antibodies staining the apical surface of ducts were detected rarely in patients with antiRo/La autoantibody-positive primary SS (1/76) and RA (1/36) and were found in only 1115 with RA and secondary SS. ASDA were detected in sera from 13/51 (25.5%) of patients referred to our clinic with limited sicca symptoms who were anti-Ro/La antibody-negative and had no typical clinical or laboratory features of classical primary SS. The apical ductal staining pattern was not observed with sera from 63 healthy controls without sicca symptoms or in patients with autoimmune and infective disorders. Twelve of the 13 patients whose sera gave ASDA-like staining were blood group O and one group A. Ductal staining was abolished in all sera after absorption with blood group AB erythrocytes or AB antigen. In 5 patients ductal staining was removed by absorption with B erythrocytes but not with A erythrocytes; in the remainder ductal reactivity was abolished by both A and B erythrocytes. CONCLUSION: ASDA seem to occur rarely in patients with primary SS and RA. However, isotype-switched IgG AB blood group antibodies cross react with primate salivary ducts and may produce false positive ASDA staining. Detection of ASDA may be of value in identifying a subset of patients who present with mild sicca symptoms without other autoimmune features.

ABO Blood-Group System↗

Salivary duct carcinoma: a report of nine cases.

Nine cases of salivary duct carcinoma are presented. Eight lesions were located in the parotid gland and one in the submandibular gland. Tumor size was greater than 3 cm in four cases (44%), and facial paralysis was observed in five tumors (62.5%). Lymph node metastases were observed macroscopically or microscopically in seven patients. Perineural and lymphatic invasion were detected in eight and seven cases, respectively. Free surgical margins were obtained in eight of the nine patients (88%). Adjuvant postoperative irradiation was delivered in eight patients. Five patients died of disease in spite of the different clinicopathologic characteristics and aggressiveness of the surgery and irradiation. None of the parameters studied correlated with the final outcome.

Adenocarcinoma↗

[Salivary duct carcinoma (clinicopathologic study of 11 cases)].

Eleven cases of salivary duct carcinoma were studied clinicopathologically. The clinical features are as follows: men outnumber women; arise most frequently within the parotid glands; rapidly enlarging mass; obvious symptoms of invading nerves; high rates of cervical lymph node and distant metastases; poor patient's prognosis. Its histologic features were shown by the various stages of development of duct carcinoma including dysplasia, carcinoma in situ, papillary, cribriorm, solid and commedo patterns. In addition to the intraductal carcinoma, there is the invasive carcinoma with obvious infiltration into the surrounding tissues. Its treatment requires the combination of radical surgery with postoperative radiotherapy.

Adenocarcinoma↗