Diagnosis Of Acinic Cell Carcinoma Research Articles

Diagnosis of acinic cell carcinoma of the salivary gland on cytology specimens: Role of NOR-1 (NR4A3) immunohistochemistry.

Acinic cell carcinoma (AcCC) is often a challenging diagnosis on cytology. Recently, NOR-1 (NR4A3) has been demonstrated as a sensitive and specific marker for AcCC. Therefore, we conducted this study to evaluate NOR-1 expression in AcCC cytology specimens and to compare its reactivity in other salivary gland tumours (non-AcCC). We retrospectively reviewed our database and selected cytology cases with available cell blocks, including 10 AcCC and 24 non-AcCC tumours (12 benign tumours and 12 malignant tumours). NOR-1 (1:50 dilution; SC393902 [H-7]; Santa Cruz Biotech) immunohistochemistry (IHC) was performed on all cases. All AcCC cases except two (2/10, 80%) showed positive nuclear staining of variable intensity for NOR-1, with the majority of cases (75%) demonstrating at least moderately intense nuclear expression. All non-AcCC cases were negative for NOR-1, demonstrating a specificity of 100%. We conclude that NOR-1 IHC is sensitive and very specific on cytology specimens and is able to distinguish AcCC from its mimickers reliably and classify them appropriately for further management.

Submandibular Secretory Carcinoma in a 10-year-old Filipino

Secretory carcinoma is a recently described salivary gland neoplasm reported in the fourth edition of World Health Organization classification of head and neck tumors.1 We report a case of a primary secretory carcinoma arising from the submandibular gland that was completely excised in a 10-year-old. The histomorphologic features and the immunophenotype studies are compatible with secretory carcinoma. Unless proven otherwise by immunohistochemical stains and cytogenetics, secretory carcinoma should be included as a differential in cases of lesion of the major and minor salivary glands that has the primary differential diagnosis of acinic cell carcinoma. This case report aims to contribute to the limited literature about this disease entity and would be one of the few reported cases of the disease in a school-age child.

NOR-1 (NR4A3) immunostaining on cytologic preparations for the preoperative diagnosis of acinic cell carcinoma of the salivary gland.

Acinic cell carcinoma of the salivary gland (ACC-SG) is characterized by recurrent rearrangements in the nuclear receptor subfamily 4 group A member 3 (NR4A3). Immunostaining using an antibody targeting this rearrangement, neuron-derived orphan receptor 1 (NOR-1), has been recently studied on surgical specimens and cell block material of fine-needle aspirates for the diagnosis of ACC-SG. Our goal was to evaluate whether NOR-1 immunostaining could reliably be performed on destained cytologic preparations. This was a retrospective multi-institutional study. Immunostaining with the NOR-1 antibody (sc-393902 [H-7], Santa Cruz Biotechnology Inc.) was performed at a titer of 1:30 on destained cytologic preparations. ACC-SG cases (n = 17) were represented by twelve cases with alcohol-fixed preparations (n = 12), including direct smears and SurePath preparations, as well as 5 cases with air-dried preparations (n = 5). These were compared to 27 mimicker lesions (n = 27): normal acini (4), chronic sialadenitis (3), oncocytoma (2), pleomorphic adenoma (6), Warthin tumor (8), mucoepidermoid carcinoma (1), secretory carcinoma (2), and salivary duct carcinoma (1). The positivity of NOR-1 in ACC-SG cases was 100% on destained alcohol-fixed preparations (12/12) and 60% on air-dried preparations (3/5). All 27 mimicker lesions were negative for NOR-1 (0/27). Evaluation of 2 ACC-SG cases with both types of cytologic preparations showed that NOR-1 was positive on the alcohol-fixed slides but negative on the air-dried slides. NOR-1 immunostaining can reliably be performed on alcohol-fixed direct smears and liquid-based preparations for the diagnosis of ACC-SG. Air-dried preparations show a lower positivity rate and may be less suitable for diagnostic immunostaining.

Cystic Salivary Gland Neoplasms: Diagnostic Approach With a Focus on Ancillary Studies.

Cystic salivary gland cytology can be challenging due to the fact that a cystic mass can be the clinical presentation of both non-neoplastic and neoplastic conditions. Neoplastic lesions consist of both benign and malignant neoplasms. The cytomorphologic features of these entities can overlap and the cystic background may additionally contribute to the complexity of these lesions and their interpretation. Ancillary studies have been reported in several studies to be beneficial in further characterization of the cellular components and subsequent diagnosis of the cystic lesions of the salivary gland. Fluorescence in situ hybridization, real-time polymerase chain reaction, and next-generation sequencing are now being utilized to detect molecular alterations in salivary gland neoplasms. MALM2 rearrangement is the most common gene fusion in mucoepidermoid carcinoma. PLAG1 rearrangement is present in more than half of pleomorphic adenomas. AKT1:E17K mutation is the key diagnostic feature of the mucinous adenocarcinoma. NR4A3 overexpression is highly sensitive and specific for the diagnosis of acinic cell carcinoma. MYB fusion is noted in adenoid cystic carcinoma. ETV6:NTRK3 fusion is helpful in diagnosis of secretory carcinoma. p16 and human papillomavirus (HPV) studies differentiate HPV-related squamous cell carcinoma from non-HPV-related neoplasms with overlapping features. NCOA4:RET fusion protein is the main fusion in intraductal carcinoma.

Diagnostic Value of Nuclear Receptor Subfamily 4 Group A Member 3 in Salivary Gland Carcinomas

Salivary gland carcinomas are diagnostically challenging lesions in heterogeneous groups. However, recently described genomic alterations may be helpful and have future therapeutic implications. The molecular investigation is becoming useful tool to help diagnosis and provide prognostic information. Diagnosis of acinic cell carcinoma (AcCC) is challenging due to its rarity and similarity with other SGCs or normal acinar cells.
 Herein, the diagnostic performance of transcription factor nuclear receptor subfamily 4 group A member3 (NR4A3) was analysed immunohistochemically. This study was done on 68 cases of SCCs, including 32 of AcCC, 14 of adenoid cystic carcinoma (AdCC), 8 of mucoepidermoid carcinoma (MEC), 7 of epithelial myoepithelial carcinoma (EMC), 4 of salivary duct carcinoma (SDC), and only one case from each of carcinoma ex pleomorphic adenoma (CXPA), polymorphous adenocarcinoma (PAC) and secretory carcinoma (SC) for detecting NR4A3.
 All stained samples of AcCC (100%) responded positively to the NR4A3 antibody. However, only one case of AdCC and MEC demonstrated NR4A3 immunostaining in less than 10% of cells. On the other hand, the different types of SGCs, including EMC, SDC, CXPA, PAC, and SC, revealed negative expressions. Therefore, we can conclude that NR4A3 can be used as a potential marker for AcCC rather than other SGCs.

Cytopathology of acinic cell carcinoma: A study of 50 cases, including 9 with high-grade transformation.

Although largely readily recognizable in tissue sections, acinic cell carcinoma (ACC) remains diagnostically problematic in fine-needle aspiration (FNA) cytopathology. The authors undertook an analysis of a large series of ACC aspirates, including acinic cell carcinoma with high-grade transformation (ACC-HGT). The authors searched their cytopathology files for ACC cases with histopathologic confirmation. FNA biopsy was performed according to standard techniques. Fifty FNA biopsy cases of ACC (including 36 of parotid origin [72%]) from 41 patients (female to male ratio, 1.4:1; age range, 23-84 years; average, 54 years) met the study inclusion requirements. Primary neoplasm aspirates were most common (72%), and they were followed by recurrent tumors (16%) and metastases (12%). A precise cytologic diagnosis was made for 64%. Three of 9 ACC-HGT cases (33%) were correctly interpreted as such; 98% of conventional ACC cases were correctly graded as low-grade. With the Milan classification system, 74% fit into the malignant category. Ancillary testing was performed for only 36%. Conventional ACC had moderately to highly cellular smears; monotonous cells in aggregates and single forms; rounded nuclei; and microvacuolated, finely granular, oncocyte-like, or nonspecific cytoplasm. ACC-HGT smears contained larger nuclei, high nuclear to cytoplasmic ratios, coarse nuclear chromatin, and a loss of cytoplasmic granules/vacuoles. A correct diagnosis of ACC via FNA biopsy was made in almost two-thirds of the cases. With the Milan classification, 84% of the cases would have been classified as malignant or suspicious for malignancy. An absence of conventional serous acinar cell morphology in some cases as well as an absence of ancillary immunohistochemistry testing in almost two-thirds of the cases prevented even better diagnostic performance.

SYNCHRONOUS OCCURRENCE OF ACINIC CELL CARCINOMA OF SOFT PALATE AND SQUAMOUS CELL CARCINOMA OF LUNG: A CASE REPORT

Acinic cell carcinoma (AcCC) is a low-grade malignant salivary neoplasm and constitutes approximately 6% to 8% of all salivary gland neoplasms. Although it has low-grade histology, AcCC has a significant tendency to metastasize. We report the first case of AcCC in our facility of a 74-year-old man who presented with a slow-growing mass on the left soft palate. A diagnosis of AcCC was made based on the characteristic histologic features of an infiltrative tumor of large polygonal cells with dark, round, eccentric nuclei and having PAS-D-positive basophilic granules along with immunohistochemical findings positive for CK7. The presence of intravascular invasion was evident. Concurrently, contrast-enhanced computed tomography of the thorax showed a suspicious nodule at the right upper lobe of the lung. Initially we suspected lung metastatic tumor based on the fact that AcCC has a significant tendency to metastasize to the lung and cervical lymph nodes. A wedge biopsy from the lung was done and revealed squamous cell carcinoma. Immunohistochemical studies on this tumor also showed different findings with immunopositivity with P63 and negativity for CK7. A probability of tumor metastasis to the lung was ruled out with the finding of a new primary tumor of the lung. AcCC can be misinterpreted due to its benign appearance, absence of malignant features, and histologic similarity to normal acinar cells. Pathologists should be aware and vigilant when reporting this entity. AcCC of the soft palate in this case is relatively rare and synchronous occurrence of other primary tumors makes it extremely unusual.

NR4A3 (NOR-1) Immunostaining Shows Better Performance than DOG1 Immunostaining in Acinic Cell Carcinoma of Salivary Gland: a Preliminary Study.

ABSTRACTObjectivesAcinic cell carcinoma of salivary gland harbours recurrent and specific chromosomal rearrangement [t(4;9)(q13;q31)], resulting in the translocation of secretory calcium-binding phosphoprotein gene cluster at 4q13 to nuclear receptor subfamily 4 group a member 3 at 9q31. This upregulates the transcription factor nuclear receptor subfamily 4 group A member 3, which can be detected by immunohistochemistry. The purpose of this pilot study is to evaluate the performance of nuclear receptor subfamily 4 group A member 3 immunostaining on whole-slide acinic cell carcinoma tissue, in comparison with discovered on GIST-1 immunostaining.Material and MethodsWe retrieved 6 cases of acinic cell carcinoma (AciCC), including 5 conventional low-grade and 1 dedifferentiated high-grade. Immunohistochemistry (IHC) for nuclear receptor subfamily 4 group A member 3 (NR4A3) and discovered on GIST-1 (DOG1) were performed at the University of Pittsburgh Medical Centre in Pittsburgh, Pennsylvania on all retrieved cases.ResultsThe result shows that NR4A3 IHC shows better performance than DOG1 IHC: 5 of the 6 (83.3%) AciCC cases (including the dedifferentiated high-grade) demonstrated strong diffuse nuclear staining for NR4A3, also five AciCC cases (including the dedifferentiated high-grade) demonstrated weak to moderate membranous staining with variable distribution for DOG1. Moreover, only 3 (50%) cases showed complete membranous staining with DOG1.ConclusionsThis pilot study showed that nuclear receptor subfamily 4 group A member 3 immunostaining is a sensitive marker for acinic cell carcinoma and of better utility than discovered on GIST-1 immunostaining in making a diagnosis of acinic cell carcinoma.

NR4A3 Immunohistochemistry Reliably Discriminates Acinic Cell Carcinoma from Mimics

Acinic cell carcinoma (AciCC) harbors a recurrent t(4;9)(q13;q31) translocation, which leads to upregulation of Nuclear Receptor Subfamily 4 Group A Member 3 (NR4A3). Previous work on tissue microarrays suggests that NR4A3 immunohistochemistry (IHC) may be useful in the diagnosis of AciCC. Thus far, only a single study has evaluated the utility of NR4A3 immunohistochemistry (IHC) in the diagnosis of AciCC, using a tissue microarray to assess most non-AciCC tumor types. Herein we evaluate the diagnostic performance of NR4A3 IHC for AciCC in a large cohort of 157 salivary gland tumors, using whole tissue sections. The cohort consisted of 37 AciCC (6 of them (16%) with high grade transformation), 30 secretory carcinomas (SC), and 90 additional salivary gland tumors, including mucoepidermoid carcinomas (MEC), polymorphous adenocarcinomas (PAC), pleomorphic adenomas (PA), salivary duct carcinomas (SDC), and adenoid cystic carcinomas (AdCC). NR4A3 nuclear staining by IHC was considered positive if present in more than 5% of tumor cells. Overall, 92% of AciCC (34/37) expressed NR4A3 by IHC, with strong (89%) or moderate (3%) nuclear staining, yielding a sensitivity of 92%. IHC detected NR4A3 expression in all cases of recurrent/metastatic AciCC and tumors with high grade transformation. Importantly, all SC were negative for NR4A3 IHC, with no staining in 28/30 cases and weak focal staining, in < 5% of cells, in 2/30 (7%). Similarly, all MEC (20/20), SDC (20/20) and AdCC (10/10) were negative for NR4A3 by IHC, as were most PA (18/20; 15%) and PAC (18/20; 5%). Two PA and two PAC showed multifocal expression of NR4A3 in more than 5% of cells, of weak intensity in 3 cases and moderate in 1 PAC, yielding an overall specificity of 97% for NR4A3 IHC for the diagnosis of AciCC. In conclusion, NR4A3 is a highly sensitive and specific immunohistochemical marker for AciCC; moderate to strong and/or diffuse NR4A3 expression is a consistent and diagnostic feature of AciCC.

Perithyroidal Salivary Gland Acinic Cell Carcinoma: Morphological and Molecular Attributes of a Unique Lesion

Rarely, salivary gland tumors such as mucoepidermoid carcinoma, mammary analogue secretory carcinoma and mucinous carcinoma arise as primary tumors from ectopic or metaplastic salivary gland tissue adjacent to or within the thyroid gland. We report for the first time a case of primary salivary acinic cell carcinoma (AcCC) adjacent to the thyroid gland in a 71-year-old female patient with Crohns disease and a previous history of malignant melanoma. Following the development of a nodule adjacent to the left thyroid lobe, a fine-needle aspiration biopsy was reported as consistent with a follicular lesion of undetermined significance (Bethesda III). A left-sided hemithyroidectomy was performed. A circumscribed lesion measuring 33 mm was noted adjacent to the thyroid and trapping parathyroid, it was composed of solid nests and glands with microcystic and follicular patterns. The tumor was negative for thyroid, parathyroid and paraganglioma markers, but positive for pan-cytokeratins, CK7, CD10, CD117, androgen receptor and HNF-beta. A metastasis of a thyroid-like renal cell carcinoma was suspected but ruled out, and the patient had no evident lesions on extensive radiology of the urogenital, pulmonary and GI tracts. Based on the morphology, a diagnosis of AcCC was suggested, and confirmed with DOG1 and PAS-diastase staining. Molecular analyses pinpointed a constitutional ASXL1 variant of uncertain significance, but no fusion events. The patient had no radiological or clinical evidence of parotid, submandibular or sublingual tumors postoperatively, and the excised lesion was therefore assumed to be a primary tumor. We here detail the morphological and immunophenotypic profile of this previously undescribed perithyroidal tumor.

Acinic cell carcinoma of the parotid gland: from pathogenesis to management: a literature review.

Acinic cell carcinoma (ACCs) is uncommon malignant epithelial neoplasm of the salivary glands; the most common presentation is a well-defined painless solid mass. Diagnosis of ACCs is frequently complicated, due to its similarity with benign tumors. A review of the literature available on ACCs was carried out. Studies were sourced from PubMed with searching of relevant headings and sub-headings and cross-referencing. There are no clear characteristics of ACCs found on CT, MRI and ultrasound imaging. The management of the ACC, a rare malignancy of the parotid gland, is often difficult and controversial. Radical surgery is the best treatment option. The role of radiotherapy remains controversial: the precise indications and oncologic effects of adjuvant radiotherapy in ACC of the parotid gland are not well known. There is insufficient literature regarding the chemotherapy for metastatic ACC. Knowledge about ACC, a rare malignancy of parotid gland, has changed over the past few decades. More clinical randomized works would be needed, both to assess the real effectiveness of radio and chemotherapy and to have an unanimous consensus about their indications.

An Accuracy Comparison of SOX10 with DOG1 Immunohistochemistry in Diagnosing Acinic Cell Carcinoma of Salivary Gland in Paraffin Tissue Samples

BackgroundMorphological diversity is a challenge in establishing diagnosis of malignant tumor originated from salivary gland, especially Aciniccell carcinoma (ACC). Immunohistochemical (IHC) staining using DOG1 is often used to help diagnosis of ACC. Lately, IHC SOX10has been reported to have almost the same accuracy to DOG1 staining. This evidence-based case report aims to determine theaccuracy of SOX10 to DOG1 immunohistocheinstry staining in establishing a diagnosis of ACC.MethodsLiterature searches were carried out on the Pubmed, Clinical key, Proquest, ScienceDirect, Scopus, SpringerLink and Wileydatabases. Two journals were relevant to the clinical scenario, then a critical review is carried out using the Diagnostic StudyAppraisal Worksheet from the Center for Evidence-based Medicine, University of Oxford, 2010.ResultsThe accuracy of SOX10 in diagnosing ACC was slightly better than DOG1, with sensitivity reaching 100% and specificity reaching87.76%. The sensitivity of SOX10 and DOG1 is the same, but SOX10 is more specific, and positive predictive value is also betterthan DOG1.ConclusionThe accuracy of SOX10 is better than DOG1 in diagnosing ACC of salivary gland. However, the intensity of SOX10 staining tends tobe rather low compared to DOG1. Therefore, further research is still needed to recommend SOX10 staining in daily practice.

Cytological Diagnosis of Acinic Cell Carcinoma. A Study of Four Cases with Emphasis on Differential Diagnosis and DOG1 Expression.

Cytological Diagnosis of Acinic Cell Carcinoma. A Study of Four Cases with Emphasis on Differential Diagnosis and DOG1 Expression.

Clinical characteristics of acinic cell carcinoma and secretory carcinoma of the parotid gland

Mammary analogue secretory carcinoma (SC) of the parotid gland is a relatively uncommon cancer associated with the ETV6-NTRK3 fusion product similar to breast cancer. The clinical characteristics and outcome of treatment were reviewed for patients with this tumor at our hospital. In this retrospective case series, 24 patients with a diagnosis of acinic cell carcinoma (AcCC) of the parotid gland were classified as having either SC or AcCC based on analysis of the ETV6-NTRK3 fusion gene. These two groups were compared with respect to their clinical and imaging characteristics (MRI/US), cytologic findings, accuracy of fine-needle aspiration cytology and frozen section, treatment outcomes, and immunohistochemical findings. Based on re-classification by ETV6-NTRK3 fusion gene analysis, the diagnosis was SC in 14 patients and AcCC in 10 patients. The SC group had a significantly higher proportion of male patients and was also significantly younger than the AcCC group. Imaging studies revealed that SC was significantly more likely to show internal heterogeneity. Correct grading of both tumors was comparable by fine needle aspiration, with the rate being 60% for AcCC and 50% for SC. Diagnosis by frozen section biopsy diagnosis obtained the correct grade in 90% of the AcCC group and 93% of the SC group. In 24 patients previously diagnosed with AcCC, re-analysis of the ETV6-NTRK3 fusion product indicated that 14 patients actually had SC. Although AcCC and SC show similarities of their biological aggressiveness and prognosis, patients with SC were significantly more likely to be male and younger.

Acinic Cell Carcinoma of the Parotid Gland in Children and Adolescents.

Acinic cell carcinoma of the parotid gland is a rare low-grade malignant neoplasm. Data on children are sparse. For the present study, the database of a tertiary pediatric medical center was reviewed for all patients with parotid gland acinic cell carcinoma diagnosed and treated between 2004 and 2013. Clinical, histologic, treatment, and outcome parameters were collected from the medical files. Four patients were identified, 3 female and 1 male, aged 13.5 to 18 years (median 15.7) at diagnosis. One patient had a family history of parotid tumor and 1 of hypothyroidism/hyperthyroidism. Two patients had L-thyroxin-treated Hashimoto thyroiditis, and 1 had a thyroid nodule. All presented with a localized parotid mass and negative lymph nodes. Treatment consisted of partial parotidectomy, with no damage to the facial nerve. Histology confirmed the diagnosis of acinic cell carcinoma with low proliferation rate (Ki67 immunostaining 1% to 8%). No evidence of disease was found on any patient with a median follow-up at 83 months (range, 32 to 93 mo) from presentation. In our experience, the prognosis of pediatric parotid gland acinic cell carcinoma is good, and surgery alone is sufficient for treatment of early stage tumors. This is the first report of findings of a family history of thyroid disease and/or thyroid abnormalities in patients with parotid gland acinic cell carcinoma.

DOG1, alpha-amylase and p63 expression in acinic cell carcinoma of salivary gland; immunohistochemical, clinical and radiological study

Abstract Introduction: Identification of serous acinar differentiation is the basic step for the diagnosis of acinic cell carcinoma (ACC). α-amylase was described to be specific for normal acinar cell but its

Diagnosis of a case of papillary-cystic variant of acinic-cell carcinoma on fine needle aspiration cytology: Myriad of cytomorphological features

Introduction: the diagnosis of papillary-cystic variant of acinic-cell carcinoma (Acc-PcV) is easy on histology. However, the diagnosis on cytology usually poses a problem because of the cytoarchitecture which is different from classic type. case report: A 39-year-old male presented with left parotid swelling for last four months. Fine needle aspiration cytological smears revealed papillary fragments and tumor cells with varied morphological features. cell block prepared from the fluid aspirates confirmed the diagnosis of papillary-cystic variant of aciniccell carcinoma. Histological study of the excised specimen confirmed the diagnosis of acinic cell carcinoma, papillary cystic variant. conclusion: this case describes papillary-cystic variant of acinic-cell carcinoma and discusses the myriad of cytological features exhibited by it.

DOG1 for the Diagnosis of Acinic Cell Carcinoma in Cytology

DOG1 for the Diagnosis of Acinic Cell Carcinoma in Cytology

Skull Base Involvement by Acinic Cell Carcinoma of the Parotid Gland

Objective Describe the clinical course and outcomes of patients with primary acinic cell carcinoma (ACC) of the parotid gland with skull base invasion or metastasis. Design Retrospective case series (1995-2011) at a single institution. Results Ten patients met study criteria. Mean and median time from initial diagnosis of parotid ACC to development of skull base disease were 14.6 and 10.2 years, respectively. Two patients demonstrated skull base disease on initial presentation. Those who pursued further treatment after developing disease at the skull base underwent surgery (4/7), stereotactic radiosurgery (4/7), or external beam radiation (3/7). The 10-year Kaplan-Meier estimated overall survival after initial diagnosis of parotid ACC was 80%. Once skull base invasion occurred, 2-year estimated overall survival was 50%. Conclusion Although primary ACC of the parotid generally caries an excellent prognosis, tumor control with cranial base disease is difficult and the majority of patients present with late aggressive recurrences. Our observations underscore the importance of long-term follow-up in this patient group.

DOG1: a novel marker of salivary acinar and intercalated duct differentiation

AbstractAnoctamin-1 (ANO1) (DOG1, TMEM16a) is a calcium-activated chloride channel initially described in gastrointestinal stromal tumors, but now known to be expressed in a variety of normal and tumor tissues including salivary tissue in murine models. We herein perform a comprehensive survey of DOG1 expression in 156 cases containing non-neoplastic human salivary tissues and tumors. ANO1 mRNA levels were significantly higher (8-fold increase, P<0.0001) in normal parotid tissue (n=6) as compared with squamous mucosa (n=15). By immunohistochemistry, DOG1 showed a diffuse moderate (2+) apical membranous staining pattern in normal serous acini, 1+ apical membranous pattern in mucous acini, and variable 1–2+ apical staining of distal intercalated ducts. Myoepithelial cells, striated and excretory ducts were invariably negative. All acinic cell carcinomas (n=28) were DOG1 positive demonstrating a complex mixture of intense (3+) apical membranous, cytoplasmic and complete membranous staining. Most ductal tumor types were negative or only showed a subset of positive cases. Within the biphasic tumor category, adenoid cystic carcinomas (18/24 cases) and epithelial–myoepithelial carcinomas (8/15 cases) were frequently positive, often showing a distinctive combined apical ductal and membranous/cytoplasmic myoepithelial staining profile. Thus, DOG1 staining is a marker of salivary acinar and to a lesser extent intercalated duct differentiation. Strong staining can be used to support the diagnosis of acinic cell carcinoma. DOG1 may also be a marker of a ‘transformed' myoepithelial phenotype in a subset of biphasic salivary gland malignancies.