Roderick H W Simpson

The University of Calgary, Calgary, Alberta, Canada

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Publications (20)57.79 Total impact

  • Roderick H W Simpson, Alena Skálová, Silvana Di Palma, Ilmo Leivo
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    ABSTRACT: This review concentrates on the most important developments since the WHO classification of 2005. In particular, the identification of specific translocations is revolutionising the way salivary tumours are considered and will have a major impact on future diagnostic practice. This is true so far in four malignancies: mammary analogue secretory, mucoepidermoid, adenoid cystic and hyalinising clear cell carcinomas. In each, the gene rearrangement is found in 80 % or more of cases. Two 2014 publications have added further possible candidates with molecular abnormalities to the list (cribriform adenocarcinoma of the tongue and minor salivary glands and epithelial-myoepithelial carcinoma), but these findings have yet to be confirmed by other investigators. The advances in molecular pathology have also allowed re-evaluation of the morphology; for example, it is now realised that the histological spectrum of hyalinising clear cell carcinoma includes intracellular mucin in over half of cases, as well as tumours with only scanty clear cells. In a separate development, it is now proposed that salivary duct carcinoma can be subdivided along molecular lines, in ways analogous to breast cancer, suggesting new therapeutic prospects in an otherwise highly aggressive malignancy.
    Virchows Archiv : an international journal of pathology. 08/2014;
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    ABSTRACT: Mammary analogue secretory carcinoma of salivary gland origin (MASC) is a recently described tumor resembling secretory carcinoma of the breast characterized by strong S-100 protein, mammaglobin, and vimentin immunoexpression and which harbors a t(12;15) (p13;q25) translocation resulting in ETV6-NTRK3 fusion product. Histologically, conventional MASC displays bland histomorphology and a lobulated growth pattern and is often composed of microcystic, tubular, and solid structures with abundant eosinophilic homogenous or bubbly secretions. Colloid-like secretory material stains positively for periodic acid-Schiff with and without diastase as well as for Alcian Blue. We present for the first time, 3 patients with MASC of the parotid gland in which high-grade (HG) transformation developed in each case characterized by an accelerated clinical course and poor outcome. The HG component revealed strong membrane staining for EGFR and β-catenin, cytoplasmic/nuclear staining for S-100 protein, and nuclear staining for cyclin-D1, whereas HER-2/neu was absent. Analysis for the presence of the ETV6-NTRK3 fusion transcript revealed positivity in both HG and low-grade component of MASC in 2 of the 3 studied cases. The tumor in case 2 was negative in both its elements for the t(12;15) translocation, but ETV6 gene rearrangement was detected in both components in all 3 cases. Analysis of TP53 and CTNNB1 gene mutations in the HG component of MASCs as well as detection of copy number aberration of EGFR and CCND1 gene did not harbor any abnormalities. All 3 patients with HG-transformed MASC died of disseminated disease within 2 to 6 years after diagnosis. Recognizing HG-transformed MASC and testing for ETV6 rearrangement may be of potential value in patient treatment, because the presence of the ETV6-NTRK3 translocation may represent a therapeutic target in MASC.
    The American journal of surgical pathology 10/2013; · 4.06 Impact Factor
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    ABSTRACT: The recurrent translocations t(11;19) and t(11;15) resulting in CRTC1-MAML2 or CRTC3-MAML2 fusion oncogenes, respectively, are identified in a large proportion of mucoepidermoid carcinomas (MECs) of the salivary gland and have impact on prognosis. However, there are conflicting data on the specificity of this translocation, in particular, on its putative occurrence in Warthin tumor (WT) of the parotid gland as reported in few previous cases. It was speculated that extensive squamous metaplasia could explain the presence of t(11;19) translocation in a subset of WTs. We evaluated 76 salivary gland tumors, including 16 cases of metaplastic WT and 8 cases of pleomorphic adenoma (PA) with squamous and/or mucinous metaplasia, extensive enough morphologically to mimic MEC. Detection of CRTC1-MAML2 and CRTC3-MAML2 fusion transcripts and MAML2 gene break was performed using nested reverse transcription-polymerase chain reaction and fluorescence in situ hybridization (FISH), respectively. None of 16 analyzed metaplastic WTs showed positivity for fusion transcripts CRTC1-MAML2 or CRTC3-MAML2, and none showed rearrangement of the MAML2 gene by FISH. Similarly, we did not detect these transcripts or break of MAML2 gene in any case of PA with extensive squamous/mucinous metaplasia. For comparison, 40 cases of low-grade MEC were also evaluated. CRTC1-MAML2 and CRTC3-MAML2 fusion transcripts were detected in 17 and 5 cases, respectively. The FISH method using break-apart probe demonstrated the MAML2 gene rearrangement in 25 cases of low-grade MEC. In contrast to low-grade MEC, neither metaplastic WTs nor metaplastic PAs harbored translocations t(11;19) and anticipated t(11;15) resulting in CRTC1-MAML2 and CRTC3-MAML2 fusion transcripts, respectively, and/or MAML2 gene rearrangement.
    The American journal of surgical pathology 10/2013; · 4.06 Impact Factor
  • Roderick H W Simpson
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    ABSTRACT: Salivary duct carcinoma (SDC) is an aggressive primary salivary malignancy which microscopically resembles high-grade ductal carcinoma of the breast, with both in situ and invasive patterns. It is typically found in older men, most often in the parotid. It can arise de novo or as the malignant component of carcinoma ex pleomorphic adenoma. SDC is generally a hematoxylin and eosin stain-based diagnosis, with special stains and immunohistochemistry acting mainly in a confirmatory role. Other than epithelial markers, SDC expresses androgen receptors in most cases, with true HER2 positivity seen in about 15 %. Based on these data and analogous to similar schemes in the breast, it is suggested that SDCs can be classified into three main groups: luminal androgen receptor positive, HER2+ and basal phenotype. This may form the basis for prognostic information and new therapeutic possibilities. In addition to the usual type of SDC, a few less common morphological variants have been reported: papillary, micropapillary, mucin-rich, sarcomatoid and oncocytic, as well as pure in situ cases.
    Head and Neck Pathology 07/2013;
  • Alena Skalova, Tomas Vanecek, Roderick H.W. Simpson, Michal Michal
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    ABSTRACT: The review summarizes the new findings in salivary gland pathology with particular reference to molecular genetic developments. In particular, newly recognized entities and specific chromosomal translocations associated with salivary gland carcinomas are discussed. Firstly, there are three types of salivary gland carcinomas which harbour important oncogenic translocations: mucoepidermoid carcinoma with the translocation t(11; 19)(q21; p13) CRTC1-MAML2 (as well as several other less frequent ones), adenoid cystic carcinoma with the translocation t(6; 9)(q22–23; p23–24) MYB-NFIB, and the recently described entity of mammary analogue secretory carcinoma (MASC) characterized by the translocation t(12; 15)(p13; q25) ETV6-NTRK3. Secondly, sclerosing polycystic adenosis was described in 1996 as possibly a salivary counterpart to benign fibrocystic disease of the breast, but recent molecular evidence of clonality suggests it is neoplastic in nature. Finally, new molecular developments in salivary duct carcinoma and molecular mechanisms responsible for high grade transformation and tumour progression in other neoplasms will be addressed.
    Diagnostic Histopathology. 09/2012; 18(9):388–396.
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    ABSTRACT: Di Palma S, Simpson R H W, Marchiò C, Skálová A, Ungari M, Sandison A, Whitaker S, Parry S & Reis-Filho J S (2012) Histopathology Salivary duct carcinomas can be classified into luminal androgen receptor-positive, HER2 and basal-like phenotypes Aims:  The aim of this study was to devise a molecular classification for salivary duct carcinomas (SDCs) based on the similarities between SDCs and breast carcinomas and on characteristics of the microarray-based gene expression profiling-defined molecular subtypes of breast cancer. Methods and results:  Forty-two pure salivary duct carcinomas, 35 of which contained an in-situ component as defined by histological review and/or immunohistochemical analysis, were stained with antibodies for oestrogen receptor (ER), progesterone receptor (PR), androgen receptor (AR), human epidermal growth factor receptor 2 (HER2), epidermal growth factor receptor (EGFR) and cytokeratin (CK) 5/6. Based on these markers, tumours were classified into HER2, luminal androgen receptor-positive, basal-like, luminal and indeterminate phenotype. Analysis revealed that 16.7%, 69%, 4.8%, 9.5% and 0% were of HER2, luminal androgen receptor-positive, basal-like, indeterminate and luminal phenotype, respectively. The in-situ and invasive components displayed the same molecular subtype in all but one case. Conclusions:  Salivary duct carcinomas can be classified into molecular subgroups approximately equivalent to those in the breast. We also report on the existence of a subgroup of bona fide pure salivary duct carcinomas that have a 'basal-like' phenotype. Understanding the phenotypic complexity of SDCs may help to expedite the identification of novel therapeutic targets for these aggressive tumours.
    Histopathology 08/2012; · 2.86 Impact Factor
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    ABSTRACT: Lymphadenomas (LADs) are rare salivary gland tumors. Their clinicopathologic characteristics and etiopathogenesis are poorly understood. We examined 33 LADs in 31 patients (17 women and 14 men) aged 11-79 years (median 65 years). There were 22 sebaceous LADs in 21 patients (9 women and 12 men) and 11 non-sebaceous LADs in 10 patients (8 women and 2 men). Two patients had synchronous double tumors. Twenty-six tumors (79%) arose in parotid, three in the neck, and two each in submandibular gland and oral cavity. Extraparotid tumors were seen in 2 of 21 (10%) patients with sebaceous and 4 of 10 (40%) patients with non-sebaceous LADs. Seven of twenty-three (30%) patients had immunosuppressive therapy for unrelated diseases. The tumors were well circumscribed, encapsulated (n=28, 84%) painless masses, varying in size from 0.6 to 6 cm (median 2.2). The cut surfaces were gray-tan to yellow, homogeneous and multicystic (n=24, 72%). The epithelial cells were basaloid, squamous and glandular, forming solid nests, cords, tubules, and cysts. Sebaceous differentiation was restricted to sebaceous lymphadenoma. The epithelial cells expressed basal cell markers (p63, 34BE12, and/or CK5/6, 18/18, 100%) and the luminal glandular cells expressed CK7 (12/12, 100%). Myoepithelial cells were absent (n=10/16, 63%) or focal. The lymphoid stroma was reactive, with germinal centers in 28 (84%). There was no evidence of HPV (0/11), EBV (0/7), and HHV-8 (0/8). Malignant transformation to sebaceous and basal cell adenocarcinoma was seen in one patient each. None of the 11 patients with follow-up (1-8 years) recurred. In summary, sebaceous and non-sebaceous LADs are benign, encapsulated, solid and cystic tumors affecting older adults. Non-sebaceous LADs affect women and extraparotid sites more frequently than sebaceous LADs. Altered immune status may have a role in their etiopathogenesis. Multiple synchronous tumors, origin in buccal mucosa, and malignant transformation may rarely occur.
    Modern Pathology 09/2011; 25(1):26-35. · 5.25 Impact Factor
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    ABSTRACT: We present a series of 23 cases of a distinctive, hitherto poorly recognized low-grade adenocarcinoma, with several histologic features reminiscent of papillary carcinoma of the thyroid, and which mostly but not exclusively occurs in the tongue. All the tumors were unencapsulated and were divided into lobules that were composed mainly of cribriform and solid growth patterns. Therefore, we propose the name "cribriform adenocarcinoma of minor salivary gland origin (CAMSG)." All the patients were adults with a mean age at diagnosis of 55.8 years (range, 25 to 85 y). Fourteen of the 23 tumors were localized in the tongue, 3 in the soft palate, 2 in the retromolar buccal mucosa, 3 in the lingual tonsils, and 1 in the upper lip. Fifteen patients of 23 had synchronous metastases in the cervical lymph nodes at the time of diagnosis, bilateral in 3 cases. In 3 patients, the nodal metastasis was the first evidence of disease, later investigation revealing primary neoplasms in the base of tongue and tonsil, respectively. In addition, 1 patient developed a cervical lymph node metastasis 8 years after excision of a primary tumor of the tongue. Data on treatment and follow-up were available in 14 cases. The patients were treated by radical excision with clear margins (12 cases) or by simple excision (2 cases). Neck dissection was performed in 10 patients; 9 received radiotherapy, but none were treated by chemotherapy. Clinical follow-up ranged from 2 months to 13 years (mean, 6 y and 5 mo). Twelve patients are alive with no evidence of recurrent or metastatic disease after treatment, 1 patient died 2 years after surgery without evidence of tumor, and 1 patient is alive with recurrent tumor of the palate.
    The American journal of surgical pathology 06/2011; 35(8):1168-76. · 4.06 Impact Factor
  • Roderick H.W. Simpson, Silvana Di Palma
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    ABSTRACT: This review concentrates on significant developments in salivary pathology since the 2005 WHO classification was written.•Sclerosing polycystic adenosis is a rare lesion often mistaken histologically for carcinoma. Previously thought to be a reactive fibro-inflammatory process, recent evidence of clonality suggests it may be neoplastic.•Histological grading of mucoepidermoid carcinoma has been shown to have clinical relevance, but it is not clear yet which is the best method. Also, other prognostic indices, particularly MIB1 proliferation may be useful in practice.•Epithelial–myoepithelial carcinoma has been known as mainly a clear cell tumour, but it has now been recognized to have a much wider spectrum of histological appearances.•Various morphological variants of salivary duct carcinoma have been described, and a possibly clinically significant molecular classification has been proposed.•The relationship between low-grade cribriform cystadenocarcinoma and salivary duct carcinoma remains unclear.
    Diagnostic Histopathology. 01/2010;
  • R H W Simpson, S Desai, S Di Palma
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    ABSTRACT: To describe three cases of purely in situ salivary duct carcinoma, so as better to define the entity. Three primary tumours of the parotid gland are presented, in each case composed of cysts and ducts and lined by high nuclear grade epithelial cells. All parts of each tumour were surrounded by a myoepithelial cell rim and there was no evidence of invasion. The tumour cells expressed immunohistochemical markers seen in invasive salivary duct carcinoma of usual (high-grade) type. In two cases the androgen receptor (AR) reaction was strong, but there was no immunohistochemical expression of HER2 protein or gene amplification by in situ hybridization. In the remaining case, fewer nuclei stained for AR, but both HER2 protein and gene amplification were demonstrated. Salivary duct carcinoma in situ is morphologically similar to breast ductal carcinoma in situ and, although our cases are few, salivary duct carcinoma in situ can possibly be subdivided into luminal and non-luminal cell types, as can analogous mammary neoplasms. The present study cannot determine whether low-grade cribriform cystadenocarcinoma, architecturally similar but immunohistochemically different, is part of the spectrum of salivary duct carcinoma in situ, or whether it represents a separate entity.
    Histopathology 11/2008; 53(4):416-25. · 2.86 Impact Factor
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    ABSTRACT: Sclerosing polycystic adenosis (SPA) is a recently described, rare lesion of the salivary glands that bears a resemblance to epithelial proliferative lesions of the breast. The true nature of the lesion is unknown, but up to now it has been generally believed to represent a pseudoneoplastic sclerosing and inflammatory process. However, local recurrence developed in about one-third of the cases. Superimposed dysplastic changes ranging from low-grade dysplasia to carcinoma in situ were described in SPA. Although no metastases-related and/or disease-related patient deaths were documented, these clinical and histopathologic features raise the possibility that SPA might represent a neoplastic lesion. Polymorphism of the human androgen receptor locus is most frequently used to assess whether the pattern of X-chromosome inactivation is random or nonrandom, the latter strongly indicating clonality. In this study, the assay was applied to tissue from 12 examples of SPA. Three cases (males) were noninformative and 3 cases (females) could not be analyzed owing to poor quality of DNA, but all the remaining 6 lesions satisfied the criteria for monoclonality. We therefore conclude that the findings in the present study are further supporting evidence that SPA is a neoplasm, and not just a reactive process.
    American Journal of Surgical Pathology 09/2006; 30(8):939-44. · 4.87 Impact Factor
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    ABSTRACT: We present the largest series of mucinous carcinoma involving the skin, describing the histopathologic, immunohistochemical, electron microscopic, and cytogenetic findings. Our aim was fully to characterize the clinicopathologic spectrum and compare it with that seen in the breast. In addition, we wished to reevaluate the differential diagnostic criteria for distinguishing primary mucinous carcinomas from histologically similar neoplasms involving the skin secondarily, and study some aspects of their pathogenesis. We demonstrate that primary cutaneous mucinous carcinomas span a morphologic spectrum compatible to their mammary counterparts. Both pure and mixed types can be delineated morphologically, and some lesions have mucocele-like configurations. Most lesions seem to originate from in situ lesions that may represent, using mammary pathology terminology, ductal hyperplasia, atypical ductal hyperplasia, or ductal carcinoma in situ or a combination of the three. Inverse cell polarity appears to facilitate the progression of the changes similar to lesions in the breast. The presence of an in situ component defines the neoplasm as primary cutaneous, but its absence does not exclude the diagnosis; although for such neoplasms, full clinical assessment is essential. Mammary mucinous carcinoma involving the skin: all patients presented with lesions on chest wall, breast, axilla, and these locations can serve as clue to the breast origin. Microscopically, cutaneous lesions were of both pure and mixed type, and this correlated with the primary in the breast. Dirty necrosis was a constant histologic finding in intestine mucinous carcinomas involving the skin, and this feature may serve as a clue to an intestinal origin.
    American Journal of Surgical Pathology 07/2005; 29(6):764-82. · 4.87 Impact Factor
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    ABSTRACT: Reported here are 18 cases of hidradenoma papilliferum with oxyphilic metaplasia. All patients were women ranging in age from 29 to 74 years. Each presented clinically with a small, solitary tumor in the anogenital region. Microscopically, in addition to classic histopathological features, in every case there was oxyphilic metaplasia of the constituent epithelial cells. This finding could be likened to apocrine metaplasia, a term used in breast pathology. Other histopathological findings observed in this series, analogous to benign breast disease, included sclerosing adenosis-like changes, atypical apocrine adenosis-like changes, changes corresponding to usual ductal epithelial hyperplasia, epitheliomatosis with a streaming growth pattern, lamprocyte-like changes, clear cell change of the myoepithelium, foamy histiocyte reaction, and stromal fibrosis. Immunohistochemistry inferred that in the majority of cases oxyphilic metaplasia resulted from more lysosomes, whereas numerous mitochondria were detected in only 3 cases. Using 2 different PCR methods we identified HPV in 4 of 15 cases of hidradenoma with oxyphilic metaplasia. In addition, HPV was detected in 3 of 16 conventional papillary hidradenomas used as a control group. The following HPV types were identified: 16, 31, 33, 53, and 56. The last type was found in 5 cases. More than one HPV type from a single lesion was seen in 5 cases. Our observations are consistent with previous publications noting similarities between tumors of the breast and sweat glands. Oxyphilic metaplasia, areas with solid growth, and changes simulating atypical apocrine adenosis are rare and poorly recognized in hidradenoma papilliferum and may cause diagnostic difficulties; in our cases several submitting pathologists suspected malignancy. A causal role for HPV in hidradenoma papilliferum cannot be confirmed from our results, as the detection rate is too low. The exact role of the HPV in etiology and pathogenesis of this neoplasm has yet to be determined.
    American Journal of Dermatopathology 05/2005; 27(2):102-10. · 1.42 Impact Factor
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    ABSTRACT: Non-invasive carcinoma ex pleomorphic adenoma is defined as a carcinoma arising within the boundaries of a pleomorphic adenoma (PA), but which fails to display invasion beyond the capsule of host PA. Alternative names are intracapsular, in situ, or focal carcinoma. The true nature of non-invasive carcinoma ex-PA is still controversial; for example, it is not clear whether it represents early but genuine carcinomatous changes with the genetic make-up of malignant cells, or simply cytological, possibly metaplastic or 'bizarre' changes in PA. Strong overexpression and amplification of HER-2/neu protein has recently been demonstrated in invasive carcinoma ex-PA. In addition, data from breast cancer studies suggest that amplification of HER-2/neu and overexpression of its gene product is mainly involved in the initiation of breast oncogenesis. We sought to establish whether this method could help to demonstrate that what is described as non-invasive carcinoma ex-PA is really a genuine malignancy, albeit in an early phase. Eleven cases of non-invasive carcinoma (in situ) ex-PA were studied for HER-2/neu status using immunohistochemistry and fluorescent in-situ hybridization (FISH). Cells of focal non-invasive carcinoma ex-PA were strongly positive for HER-2/neu protein, while the cells of the maternal PA were always negative. Two cases of low-grade non-invasive myoepithelial carcinoma ex-PA were negative. In four cases out of a total of six tumours studied by FISH, we detected amplification of HER-2/neu gene signals in tumour cells of focal, non-invasive, carcinoma. The current data suggest that non-invasive carcinoma ex PA is a genuine carcinoma within a PA. However, the presence of cyto-nuclear atypia is not sufficient to make a definite diagnosis of malignant change, which requires a combination of morphology and immunohistochemistry.
    Histopathology 03/2005; 46(2):144-52. · 2.86 Impact Factor
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    ABSTRACT: Mixed epithelial and stromal tumor of the kidney (MESTK) is a recently described subset of renal neoplasm that tends to occur in middle-aged and older women and is characterized by a distinctive histological appearance. To further characterize this lesion, we report the clinicopathological and immunohistochemical features of 22 additional cases from our institutional files. Grossly, the tumors ranged in size from 1 cm to 14 cm (mean 6.7 cm), were well circumscribed but unencapsulated, and showed a cystic cut surface. The tumors were composed of a spindle cell proliferation that resembled ovarian stroma, as well as an epithelial component lining the cystic structures, which usually consisted of flat to hobnailed cells typical of collecting-duct epithelium. Areas displaying features of Mullerian differentiation were also documented in 6 cases, including epithelium of endometrioid, tubal, clear cell and squamous cell type as well as one case showing an architecture that closely resembled Mullerian adenofibroma and adenosarcoma. Follow-up in 14 patients (average 4.4 years) showed no evidence of recurrence or metastasis. We believe these tumors represent the renal counterpart of similar mixed epithelial and stromal neoplasms occurring in the biliary tract and pancreas, which is also characterized by cystic structures lined by epithelium, admixed with ovarian-type stroma. The differential diagnosis for these tumors includes cystic nephroma and cystic partially differentiated nephroblastoma, which we believe to represent clinically and morphologically distinct entities from MESTK. In particular, the distinction from cystic nephroma in adult male patients is emphasized, and two cases of this entity are included in the study for comparison.
    Archiv für Pathologische Anatomie und Physiologie und für Klinische Medicin 11/2004; 445(4):359-67. · 2.68 Impact Factor
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    ABSTRACT: 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.
    American Journal of Surgical Pathology 09/2004; 28(8):1040-4. · 4.87 Impact Factor
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    ABSTRACT: 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.
    American Journal of Surgical Pathology 09/2003; 27(8):1070-9. · 4.87 Impact Factor
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    ABSTRACT: Polymorphous low-grade adenocarcinoma of the minor salivary glands is an infiltrative neoplasm characterized by bland-looking tumour cells arranged in diverse architectural patterns. It is considered to be of low-grade malignant potential in that nodal metastases are seen in only a minority, and distant spread is rare. Even more unusual is the transformation of polymorphous low-grade adenocarcinoma to a histologically high-grade carcinoma, i.e. dedifferentiation. In this paper, we describe the clinicopathological and immunohistochemical findings in two further examples. Two patients presented each with a tumour of the palate. Histopathological examination showed the typical morphological, cytological and immunohistochemical features of a polymorphous low-grade adenocarcinoma. In one case there was a second component of high-grade carcinoma showing nuclear atypia, markedly increased mitotic activity and MIB1 index, as well as prominent zones of necrosis. It expressed epithelial markers and androgen receptors, and thus resembled salivary duct carcinoma. Similar tumour tissue was observed in one of the cervical nodal metastases, which was biopsied at the same time as the palate. In the second patient, a high-grade component was discovered when the tumour recurred in the palate 13 years after the initial biopsy. Whilst morphologically similar to that in first case, there were significant immunohistochemical differences such as retention of some of the polymorphous low-grade adenocarcinoma profile and absence of androgen receptor expression. Polymorphous low-grade adenocarcinoma was first described relatively recently, and as experience with it continues to accumulate, it is becoming clear that late recurrences and metastases, whilst still infrequent, may not be quite as rare as previously thought. Reports of histological transformation are even scarcer, and most occurred at least 13 years after the polymorphous low-grade adenocarcinoma was initially recognized. It is a real possibility that this phenomenon, like clinical progression, may also be encountered more often as time passes. Therefore, we believe that, whilst polymorphous low-grade adenocarcinoma is certainly far less aggressive than, for example, adenoid cystic carcinoma, it nevertheless remains a true malignancy with a potential to prove fatal in a minority of patients.
    Histopathology 10/2002; 41(3):250-9. · 2.86 Impact Factor
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    ABSTRACT: We describe three cases of sclerosing polycystic adenosis (SPA) of the parotid gland, a salivary condition analogous to fibrocystic disease of the breast. For the first time, immunoreactivity for oestrogen and progesterone receptors was demonstrated, suggesting a possible participation of hormone stimulation in its pathogenesis. In addition, all our cases showed foci of dysplasia of the ductal epithelium, which in one case was severe enough to amount to carcinoma in situ. This feature that has not previously been reported in SPA.
    Archiv für Pathologische Anatomie und Physiologie und für Klinische Medicin 02/2002; 440(1):29-35. · 2.68 Impact Factor
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    ABSTRACT:  Twenty oncocytic myoepitheliomas (MEs) and pleomorphic adenomas (PAs) were composed of interlacing fascicles of swollen spindle-shaped or/and epithelioid oncocytic myoepithelial cells showing intense finely granular immunoreactivity with anti-mitochondrial antibody. Focal vacuolation of the cytoplasm of oncocytic myoepithelial cells and their gradual transition into sebaceous metaplasia were observed in 3 cases. Another unusual feature found in 5 cases was the presence of slit-like adenomatoid spaces lined with double-layered oncocytic myoepithelium closely resembling Warthin’s tumour. The nuclei of oncocytic cells were characterized by enlargement, hyperchromasia and polymorphism, which should not be confused with malignancy. Oncocytic change in myoepithelial cells in MEs and PAs can cause pitfalls in the differential diagnosis of salivary gland tumours. We describe some unusual histological features associated with onococytic metaplasia in benign myoepithelial cell-derived salivary gland tumours, hoping to help to avoid the overdiagnosis of malignancy.
    Archiv für Pathologische Anatomie und Physiologie und für Klinische Medicin 01/1999; 434(6):537-546. · 2.68 Impact Factor

Publication Stats

350 Citations
57.79 Total Impact Points


  • 2013
    • The University of Calgary
      Calgary, Alberta, Canada
  • 2002–2012
    • Royal Devon and Exeter NHS Foundation Trust
      Exeter, England, United Kingdom
  • 2005–2011
    • Charles University in Prague
      • Ústav patologie (3. LF)
      Praha, Hlavni mesto Praha, Czech Republic
  • 1999
    • University of Exeter
      Exeter, England, United Kingdom