Acinic Cell Carcinoma Of Salivary Gland Research Articles

Differential diagnosis between acinic cell carcinoma and pleomorphic adenoma using the quantitative parameters of contrast-enhanced ultrasound.

To investigate the value of differential diagnosis between acinic cell carcinoma (ACC) and pleomorphic adenoma (PA) using the quantitative parameters of contrast-enhanced ultrasound (CEUS). Twenty-two ACC and 98 PA were retrospectively analyzed. These patients had been examined via routine pre-surgical two-dimensional ultrasound and CEUS. The examination results were confirmed by biopsy pathology. Qontrast 4.0 imaging analysis software was applied to obtain the maximum intensity (PEAK), time to peak (TTP), regional blood volume (RBV), regional blood flow (RBF), maximum signal intensity (SImax) and mean signal intensity (SImean) through quantitative analysis. The differences between ACC and PA were compared regarding the conventional ultrasound images and the quantitative parameters of CEUS. ROC curves were drawn to evaluate the diagnostic value of these parameters. There were no statistically significant differences between salivary gland ACC and PA in the manifestations of conventional two-dimensional ultrasound examination regarding morphology, internal echo and the boundary (p > 0.05). However, there were significant differences in PEAK, RBV, RBF, SImax and SImean between ACC and PA (p < 0.05). Additionally, the five quantitative parameters of CEUS were all highly accurate diagnostic indicators. The maximum area under the curve of each parameter was 0.888, sensitivity 72.6%, specificity 90.9% and accuracy 81.8%. The quantitative parameters of CEUS are helpful for differentially diagnosing salivary ACC and PA.

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.

Clinicopathologic Features and Survival Trends for Acinic Cell Carcinoma of the Major Salivary Glands: A Surveillance, Epidemiology, and End Results Population Analysis.

BackgroundWe analyzed a population-based national registry to identify the most influential patient pretreatment and treatment factors affecting overall survival (OS) and cause-specific survival (CSS) in patients diagnosed with acinic cell carcinoma (ACC) of the major salivary glands.MethodsUsing the Surveillance, Epidemiology, and End Results (SEER) database of the US National Cancer Institute (NCI) related to survival, a total of 1,254 patients with diagnosed ACC of the major salivary glands from 1975 to 2016 met inclusion criteria. Factors significant for OS and CSS were determined using univariate and multivariate analysis with the Cox proportional hazards model.ResultsUnivariate OS analysis demonstrated that surgery favorably influenced longer survival compared to no surgery (hazard ratio (HR) 2.35, P < 0.05). Patient age was found to be highly predictive of superior OS (divided into 10-year age bands, P < 0.0001, younger age better). In multivariate OS analysis, there were statistically significant worse outcomes for men (HR 1.54, P < 0.05), grades III/IV (HR 2.5, P < 0.05), and distant disease (HR 3.55, P < 0.05) or regional disease (HR 1.22, P < 0.05). Patients diagnosed during years 1996 - 2016 had better OS when compared to earlier decades 1975 - 1995 (HR 1.38, P < 0.05). In univariate analysis, the mean CSS for grades I, II, and III/IV were 429 months (95% confidence interval (CI), ± 38.39), 426 months (95% CI, ± 25.73) and 198 months (95% CI, ± 66.38). Multivariate analysis of CSS further demonstrated that there were statistically significant worse outcomes for men (HR 1.68, P < 0.05), grade III/IV (HR 3.2, P < 0.05), tumor size greater than 40 mm (P < 0.001), and distant disease (HR 4.48, P < 0.05) or regional disease (HR 1.84, P < 0.05).ConclusionsTo our knowledge, this is the largest population-based study of OS and CSS of major salivary gland ACC. We found that the patient pretreatment and treatment factors including younger age at diagnosis, female sex, early stage, lower grade, surgical excision, and recent year of diagnosis are associated with improved survival in patients diagnosed with ACC of the major salivary glands. We hope that this information will aid in construction of further research projects that better refine optimal treatment protocol of individualized patient care.

Surgery Alone Is Effective in the Management of Pediatric Salivary Gland Acinic Cell Carcinoma

The treatment strategy for salivary gland acinic cell carcinoma in pediatric patients remains controversial. This retrospective study was undertaken to analyze the role of surgery in the treatment of acinic cell carcinoma of the major salivary gland in pediatric patients. In this retrospective cohort study, we reviewed the medical records of all pediatric patients with acinic cell carcinoma of the major salivary gland who were treated at Beijing Stomatological Hospital of Capital Medical University from 1998 to 2015. The predictor variable was treatment modality. The outcome variables were disease-free survival (DFS), overall survival (OS), local control, and freedom from distant metastasis. Other variables of interest were as follows: age, gender, tumor site, T category, N category, recurrence history, pathologic grade, perineural invasion, extracapsular extension, positive margin, and resection condition. The data analysis methods used were descriptive, bivariate statistics and the Cox proportional hazards regression model. Of the 19 patients, 7 received surgery alone and 12 received initial surgery combined with postoperative radiotherapy (RT). During the median follow-up period of 86months, the overall estimates of DFS, OS, local control, and freedom from distant metastasis were 82.6, 93.3, 89.5, and 94.4%, respectively. Good outcomes were achieved in patients who received surgery alone (100% OS and 85.7% DFS). Initial surgery combined with postoperative RT was appropriate for patients with risk factors (91.7% OS and 83.3% DFS). Surgery alone is appropriate for salivary gland acinic cell carcinoma in pediatric patients without risk factors, even if extracapsular excision is adopted. Preserving the invaded facial nerve during surgery is a good choice because a curative effect can be obtained when adjuvant RT is administered. Older age, high-grade pathology, incomplete resection, recurrence history, and extracapsular extension were identified as risk factors of poor prognosis.

Enhancer hijacking activates oncogenic transcription factor NR4A3 in acinic cell carcinomas of the salivary glands

The molecular pathogenesis of salivary gland acinic cell carcinoma (AciCC) is poorly understood. The secretory Ca-binding phosphoprotein (SCPP) gene cluster at 4q13 encodes structurally related phosphoproteins of which some are specifically expressed at high levels in the salivary glands and constitute major components of saliva. Here we report on recurrent rearrangements [t(4;9)(q13;q31)] in AciCC that translocate active enhancer regions from the SCPP gene cluster to the region upstream of Nuclear Receptor Subfamily 4 Group A Member 3 (NR4A3) at 9q31. We show that NR4A3 is specifically upregulated in AciCCs, and that active chromatin regions and gene expression signatures in AciCCs are highly correlated with the NR4A3 transcription factor binding motif. Overexpression of NR4A3 in mouse salivary gland cells increases expression of known NR4A3 target genes and has a stimulatory functional effect on cell proliferation. We conclude that NR4A3 is upregulated through enhancer hijacking and has important oncogenic functions in AciCC.

Recurrent rearrangements of the Myb/SANT-like DNA-binding domain containing 3 gene (MSANTD3) in salivary gland acinic cell carcinoma.

Pathogenic gene fusions have been identified in several histologic types of salivary gland neoplasia, but not previously in acinic cell carcinoma (AcCC). To discover novel gene fusions, we performed whole-transcriptome sequencing surveys of three AcCC archival cases. In one specimen we identified a novel HTN3-MSANTD3 gene fusion, and in another a novel PRB3-ZNF217 gene fusion. The structure of both fusions was consistent with the promoter of the 5’ partner (HTN3 or PRB3), both highly expressed salivary gland genes, driving overexpression of full-length MSANTD3 or ZNF217. By fluorescence in situ hybridization of an expanded AcCC case series, we observed MSANTD3 rearrangements altogether in 3 of 20 evaluable cases (15%), but found no additional ZNF217 rearrangements. MSANTD3 encodes a previously uncharacterized Myb/SANT domain-containing protein. Immunohistochemical staining demonstrated diffuse nuclear MSANTD3 expression in 8 of 27 AcCC cases (30%), including the three cases with MSANTD3 rearrangement. MSANTD3 displayed heterogeneous expression in normal salivary ductal epithelium, as well as among other histologic types of salivary gland cancer though without evidence of translocation. In a broader survey, MSANTD3 showed variable expression across a wide range of normal and neoplastic human tissue specimens. In preliminary functional studies, engineered MSANTD3 overexpression in rodent salivary gland epithelial cells did not enhance cell proliferation, but led to significant upregulation of gene sets involved in protein synthesis. Our findings newly identify MSANTD3 rearrangement as a recurrent event in salivary gland AcCC, providing new insight into disease pathogenesis, and identifying a putative novel human oncogene.

Is DOG1 really useful in the diagnosis of salivary gland acinic cell carcinoma? - A DOG1 (clone K9) analysis in fine needle aspiration cell blocks and the review of the literature.

Introduction:DOG1 is a transmembrane protein originally “discovered on gastrointestinal stromal tumors,” works as a calcium-activated chloride channel protein. There is a limited number of studies on the potential usage of this antibody in the diagnosis of salivary gland tumors on routine practice in cell blocks. The aim of this study was to search for the usefulness of K9 clone in oncocytic type tumors and review of the literature.Materials and Methods:Sixty-nine fine needle aspiration (FNA) cytologic materials of predominantly oncocytic morphology salivary gland tumors; acinic cell carcinoma (AciCC) (n = 8), adenoid cystic carcinoma (n = 2), pleomorphic adenoma (PA) (n = 22), Warthin tumor (WT) (n = 20), myoepithelioma (ME) (n = 5), benign oncocytoma (BeO) (n = 3), mucoepidermoid carcinoma (MEC) (n = 7), mammary analog salivary gland carcinoma (n = 2) were immunostained with DOG1 (clone K9) stain.Results:Of the 8 AciCCs, 7 were observed apical-luminal positive staining, demonstrating 1–3 + intensity, and involving 40–70% of the tumor cells. One MEC of 7 (14%), 1 ME of 5 (20%), and 4 PA of 22 (18%) showed weak (1+) cytoplasmic granular staining in 5–10% of the tumor cells. Pure oncocytic neoplasms (WT, BeO) showed no expression with DOG1-K9.Conclusions:FNA is a common tool in the diagnosis and management of salivary gland tumors. DOG1-K9 clone was very useful with a unique staining pattern of apical-luminal positivity in the differential diagnosis of AciCC from other oncocytic salivary gland tumors.

Immunohistochemical expression of cytokeratins in human salivary gland acinic cell carcinomas

To compare the expression of cytokeratins (CKs) in the solid, microcystic, follicular, and papillary-cystic subtypes of salivary gland acinic cell carcinoma (AcCC) in order to characterize the cell origin. The expression of CK7, CK14, CK19, CK20, and alpha-smooth muscle actin (α-SMA) in 18 cases of AcCC was assessed with the use of immunohistochemical staining. Ten normal salivary glands were used as controls. The expression of CKs in AcCCs varied according to their growth patterns. CK7 showed strong and diffuse positive staining in the microcystic, follicular, and papillary-cystic subtypes, whereas staining was weakly positive or negative in the solid subtype. CK14 expression was negative in almost all AcCCs. Expression of CK19 was observed in the microcystic, follicular, and papillary-cystic subtypes, but was minimally observed in the solid subtype. No cells positive for CK20 or α-SMA were found in any AcCCs. We demonstrated that the microcystic, follicular and papillary-cystic subtypes of AcCC exhibit features ofductal luminal cells with expression of CK7 and CK19, suggesting their ductal origination. By contrast, the solidsubtype might originate from different cells with no ductal CK expression.

Searching for mammary analog secretory carcinoma of salivary gland among its mimics

Mammary analog secretory carcinoma of salivary gland is a recently described entity with unique morphologic, clinical, and genetic characteristics, including the characteristic t(12;15)(p13;q25) with ETV6-NTRK3 translocation found in secretory carcinomas of the breast. Before their initial description, these salivary gland tumors were generally diagnosed as acinic cell carcinoma or adenocarcinoma. For the purpose of this study, all cases of salivary gland acinic cell carcinoma, cribriform cystadenocarcinoma, and adenocarcinoma, not otherwise specified (NOS), diagnosed over a 10-year period were retrieved from our surgical pathology files. There were a total of 11 cases diagnosed as acinic cell carcinoma, 10 cases of adenocarcinoma, NOS, and 6 cases of cribriform cystadenocarcinoma. All slides were reviewed by two pathologists (AP, CGF) and tumors that show morphologic features of mammary analog secretory carcinoma according to the recent literature were selected. This process narrowed down the initial number to six cases originally diagnosed as acinic cell carcinoma, three cases originally diagnosed as adenocarcinoma, NOS, and one case originally diagnosed as cribriform cystadenocarcinoma. The 10 cases were subjected to immunohistochemistry for S-100, mammaglobin, and ANO1, as well as fluorescence in situ hybridization analysis for t(12;15)(p13;q25) with ETV6-NTRK3 fusion rearrangement. The ETV6-NTRK3 gene rearrangement was detected in three tumors. These three tumors, initially diagnosed as acinic cell carcinomas, stained positive for S-100 and mammaglobin, and negative for ANO1 by immunohistochemistry. Two of the three patients were male (2/3). In summary, mammary analog secretory carcinoma is a newly described diagnostic entity that should be in the differential diagnosis of salivary gland tumors that morphologically mimic other neoplasms, mainly acinic cell carcinomas. They differ from conventional acinic cell tumors immunohistochemically and molecularly. Positivity for mammaglobin and S-100, and negativity for ANO1 are useful screening tools before confirmatory molecular studies.

Widely Metastatic Parotid Acinic Cell Carcinoma to Bone and Liver: A Case Report, Review of Literature, and Review of Diagnostic Challenges

Distant metastasis of salivary gland neoplasms is a rare occurrence. Generally, high-grade salivary malignancies such as salivary duct carcinoma and high-grade mucoepidermoid carcinoma, as well as tumors located in the submandibular gland, show a higher likelihood of metastasizing. Acinic cell carcinoma is an uncommon salivary gland neoplasm that typically occurs in the parotid gland and is considered a low-grade malignancy. Metastasis is unusual and, if present, predominantly involves the lung and bones. However, vertebral metastasis is exceedingly rare. Here, we describe a rare case of recurrent acinic cell carcinoma of the parotid gland with widespread metastases to multiple bones, including the vertebrae, and to the liver, which was diagnosed in part by cytology. To our knowledge, this is the first report in the cytology literature to describe salivary gland acinic cell carcinoma with metastases to such distant sites and to discuss the resulting cytologic differential diagnoses.

PP017: Clinicopathologic factors affecting outcome in salivary gland Acinic Cell Carcinoma and newly described mammary analogue secretory carcinoma

Purpose Mammary Analogue Secretory Carcinoma (MASC) is a newly characterized neoplastic process commonly misdiagnosed as Acinic Cell Carcinoma. Although well-characterized genetically, little information exists regarding the clinicopathologic factors affecting outcome in patients with this disease process. Acinic Cell Carcinoma is a rare entity, and clinicopathologic data has been elucidated from studies with relatively small patient populations. We aim to better understand the characteristics affecting outcome in Acinic Cell Carcinoma patients, and to compare these with patients that have been re-classified with MASC. Materials and Methods Twenty-one patients diagnosed with Acinic Cell Carcinoma were identified from the Medical University of South Carolina cancer registry. Pathological specimens from each patient were then analyzed using fluorescence in situ hybridization (FISH) to detect the ETV6-NRTK3 (12;15) (p13;q25) translocation, which is diagnostic of MASC. Furthermore, radiographic findings were also reviewed for each patient. Demographic information, primary site, presenting symptoms and tumor staging characteristics were obtained along with treatment, recurrence and outcome data for each identified case. Results All patients were treated with primary surgical excision, eleven of which also received adjuvant treatment. The average age at diagnosis was 50.4 years. Parotid glad was the most common site (95%), with one patient demonstrating disease in a minor salivary gland. The majority of patients were female (76%), and most patients were stage I (48%). However, 60% of male patients, and 19% of female patients demonstrated Stage IV disease. Eight patients from our cohort showed increased s100 reactivity, thus making them candidates for FISH analysis. At this point, one case of MASC has been identified with two more cases still to be analyzed. Our confirmed case of MASC was Stage I, which received only primary surgical treatment. Conclusions Although thought to be slightly more aggressive, MASC may have similar clinical outcomes compared to Acinic Cell Carcinoma.

Primary Acinic Cell Carcinoma of the Breast: A Clinicopathological and Immunohistochemical Study

Acinic cell carcinoma of the breast is an extremely rare, malignant neoplasm characterized by widespread acinar cell-like differentiation and clinically low-grade malignancy. Herein, we report a case of acinic cell carcinoma of the breast in a 41-year-old woman. The tumor was poorly demarcated but had a firm consistency. It was removed with lumpectomy, and sentinel lymph node biopsy was performed to check for metastasis. Microscopically, the tumor showed an infiltrative growth pattern with a combination of solid, trabecular, and microglandular areas. Many of the tumor cells had abundant clear vacuolated cytoplasm containing zymogen-typed granules which resemble acinar cells of the salivary glands. The immunohistochemical profile of the tumor was also similar to that of salivary gland acinic cell carcinoma: the tumor cells were positive for amylase, lysozyme, α-1-antichymotrypsin, S-100 protein, and epithelial membrane antigen and negative for estrogen receptor, progesterone receptor, and human epidermal growth factor receptor 2. She received postoperative chemoradiation therapy and has been well for 3 years since surgery. As studies on large series are lacking, further studies are needed to elucidate the biological characteristics of acinic cell carcinoma of the breast.

P63 Expression Can Be Used in Differential Diagnosis of Salivary Gland Acinic Cell and Mucoepidermoid Carcinomas

Differentiation of salivary gland acinic cell carcinoma from mucoepidermoid carcinoma can be diagnostically challenging as both may have prominent mucin production. P63 is a p53 homologue required for limb and epidermal morphogenesis. Itis expressed in basal and myoepithelial cells of normal salivary gland tissues. In this immunohistochemical study, we examined the expression of p63 in salivary gland acinic cell and mucoepidermoid carcinomas (MEC) and its use in differentiating these two entities. A search was performed and appropriate cases were selected from Lifespan Hospital System archives as well as the consult archives of one author (DRG). 31 salivary gland acinic cell carcinomas (ACC) and 24 MEC were examined for p63 expression by immunohistochemistry. The nuclear immunoreactivity was examined by both authors and was graded semi-quantitatively with negative being less than 10% of cells staining. Positive staining was graded as follows: 10-25% of tumor cells staining was weakly positive, 26-75% of tumor cells staining was moderately positive, and 76-100% of tumor cells staining was strongly positive. Negative nuclear staining of the tumor cells was seen in 30/31 (96%) of salivary gland ACC while 1/31 (3%) showed diffuse nuclear staining of the tumor cells. This latter case was later reclassified as mammary analogue secretory carcinoma following confirmatory molecular testing for the ETV6-NTRK3 fusion gene. Strong positive nuclear staining of the tumor cells was seen in 24 (100%) of salivary gland MEC cases. P63 is an immunohistochemical stain that can potentially aid in differentiating unusual ACC with prominent mucin production from MEC of the salivary gland. According to this study, acinic cell carcinoma is always negative for p63 immunoreactivity while mucoepidermoid carcinoma is always positive.

Acinic cell carcinoma of the retromolar trigone region: expanding the tumor phenotype in Cowden syndrome?

Cowden syndrome (CS) is a cancer predisposition syndrome caused by germline mutations in the PTEN tumor suppressor gene. It is associated with an increased risk of thyroid, breast and endometrial cancer but many manifestations can be found in the head and neck region, some of which are pathognomonic. Here we report a 35-year-old male referred by his dentist for evaluation of a lesion located near the retromolar trigone. Comprehensive clinical examination revealed papillomatous skin lesions, macrocephaly and gingival hypertrophy. Histopathological examination of the lesion showed an acinic cell carcinoma (ACC) of minor salivary gland origin. Analysis of the PTEN gene identified a germline R130Q mutation in exon 5, confirming the diagnosis of CS, but no loss of heterozygosity was seen in DNA extracted from tumor tissue. This is to our knowledge the first case describing an association of ACC of the minor salivary gland with a PTEN-gene related disorder. It emphasizes the importance of head and neck examination in these patients.

Mammalian Target of Rapamycin–Dependent Acinar Cell Neoplasia after Inactivation of Apc and Pten in the Mouse Salivary Gland: Implications for Human Acinic Cell Carcinoma

Cross-talk between the canonical Wnt and mammalian target of rapamycin (mTOR) signaling pathways occurs at multiple levels in the cell and likely contributes to the oncogenic effects of these pathways in human cancer. To gain more insight into the interplay between Wnt and mTOR signaling in salivary gland tumorigenesis, we developed a mouse model in which both pathways are constitutively activated by the conditional inactivation of the Apc and Pten tumor suppressor genes. Loss of either Apc or Pten alone did not cause tumor development. However, deletion of both genes resulted in the formation of salivary gland tumors with 100% penetrance and short latency that showed a remarkable morphologic similarity to human acinic cell carcinoma. Treatment of tumor-bearing mice using the mTOR inhibitor rapamycin led to complete regression of tumors, indicating that tumor growth was dependent on continued mTOR signaling. Importantly, we found that human salivary gland acinic cell carcinomas also express markers of activated mTOR signaling. Together, these results suggest that aberrant activation of mTOR signaling plays a pivotal role in acinar cell neoplasia of the salivary gland. Because rapamycin analogues are approved for treating other types of human malignancies, our findings suggest that rapamycin therapy should be evaluated for treating patients with salivary gland acinic cell carcinoma.

Acinic Cell Carcinoma of Minor Salivary Glands: A Clinicopathologic Study of 21 Cases

Acinic cell carcinoma (ACC) is an infrequent type of malignant salivary gland tumor. Approximately 16% of all ACCs occur in the mouth according to several small studies. This study was undertaken to 1) report on the clinicopathologic characteristics of 21 intraoral examples, 2) reconfirm the reported indolent behavior of these tumors, and 3) verify the synchronous or metachronous occurrence of other malignancies with ACC. Twenty-one patients with intraoral ACC were identified in the previous 27 years. Demographic data and histomorphologic characteristics were evaluated and follow-up information was sought. Fifteen patients (68%) were male and 6 female. Seven cases (33.3%) occurred in the buccal mucosa, 6 in the palate (28.6%), 5 involved the upper lip (23.8%), 2 the retromolar mucosa (9.5%), and 1 the lower lip (4.8%). The mean age of patients was 50 years, with the youngest being 13 and the oldest 73. The duration was known in 9 patients and varied from 4 months to longer than 15 years. The size of the tumors varied from 0.6 to 1.6 cm. Where reported, lesions were asymptomatic. Histologically, different patterns that included microcystic, papillary cystic, follicular and solid, and combinations of these types characterized the lesions. Follow-up information was obtained in 12 patients. Eleven patients did not report recurrence or metastatic disease. The follow-up extended from 10 months to 17 years. One patient had 2 recurrences due to erroneous diagnosis that led to inappropriate treatment. After properly diagnosed and treated, this patient has been free of tumor for 4 years. Of interest were the metachronous occurrence of lymphoma in 1 patient and the synchronous occurrence of renal cell carcinoma in another. This study confirms the indolent behavior of ACC of minor salivary glands and previous reports on the occasional synchronous or metachronous association of malignant salivary gland tumors with other malignancies.

Acinic Cell Carcinoma of Salivary Gland With Massive Deposits of Globular Amyloid

We present the case of a 23-year-old woman with a parotid gland tumor, the fine-needle aspiration biopsy smears of which showed epithelial cells with wide cytoplasm, isolated or arranged in micropapillary groups together with psammoma bodies. The surgical specimen contained a 5-cm tumor with the histologic features of an acinic cell carcinoma (ACC) with papillary areas. Notably, the cells of the tumor seemed to follow a sequence from large cells with rounded nuclei with open chromatin and prominent nucleoli to vacuolated cells with granular material, and finally to cells undergoing apoptosis. This finding was followed by the appearance of concentrically laminated, round to polygonal, Congo red-positive, birefringent bodies that in areas accumulated and formed extensive areas with massive deposits. The picture suggested that those amyloid bodies (psammoma bodies) resulted from the accumulation of residual masses of apoptotic cells. Huge globular amyloid deposits, the suggested name for this material irrespective of the type of amyloid, have not been previously reported in ACC of salivary gland.

Poster 060: Acinic Cell Carcinoma of Minor Salivary Glands: A Clinicopathologic Study of 22 Cases

Poster 060: Acinic Cell Carcinoma of Minor Salivary Glands: A Clinicopathologic Study of 22 Cases

Morphometric analysis using automated image analysis of CD34-positive vessels in salivary gland acinic cell carcinoma

Conclusions. In computer-assisted analysis of acinic cell cancer (ACC) morphological characteristics of CD34 immunoreactivity were detected. Bigger vessel size, vessel irregularity, and lower intensity of CD34-positive vessel staining may indicate unfavorable prognosis. Objectives. Salivary gland cancer (SGC) is a morphologically diverse group of malignancies, the most common histological types being mucoepidermoid, adenoid cystic and ACC, which has the most favorable prognosis of the three. The aim of this research was to study the applicability of automated image analysis as prognostic criteria in ACC. Patients and methods. In a nationwide study covering SGC patients in Finland during 1991–1996, 34 patients with ACC (15 males, 19 females, aged 19–95 years, mean 55 years) were included. Parameters were measured from CD34-stained samples. Results. In all, 10 385 vessels were measured, of which 9873 were from specimens from patients who were alive 5 years after treatment (n=32, group I) and 512 were from patients who died of disease (n=2, group II). The following results were found in group II versus group I: mean vessel size 469 µm vs 272 µm (p=0.024); vessel irregularity 28.3 µm vs 22.3 µm (p<0.001); CD34 staining intensity 0.555 µm vs 0.584 µm (p=0.024).

Abnormal expression of Rb pathway–related proteins in salivary gland acinic cell carcinoma

Salivary gland acinic cell carcinoma (ACC) is a relatively rare neoplasm, and limited information is available regarding its molecular pathogenesis. Because the deregulation of Rb pathway is common to most human tumors, we immunohistochemically investigated the expression of Rb pathway–related proteins, including Rb, Rb proteins phosphorylated at serine 780 and 795 (pRb-S780 and pRb-S795, respectively), cyclin D1, and p16 INK4a in 18 cases of ACC. The expression of topoisomerase II– α and Ki-67 was also examined to evaluate cell proliferation. All the ACCs exhibited substantial numbers of positive cells against Rb antibody that recognizes both unphosphorylated and phosphorylated Rb proteins. The numbers of positive cells for pRb-S795 and cyclin D1 significantly increased in ACCs as compared with normal salivary glands. Double immunofluorescent staining demonstrated that pRb-S795 was colocalized with cyclin D1 in most tumor cells. However, neither significant change of the expression of Rb protein phosphorylated at serine 780 nor its colocalization with cyclin D1 was observed. The loss of p16 INK4a is infrequent, but its expression was correlated with phosphorylated Rb proteins. Our results suggest that serine 795 but not serine 780 is the preferred phosphorylation site induced by cyclin D1. This phosphorylation appeared to be critical for inactivation of Rb-mediated growth suppression and may play an important role in the pathogenesis of ACC.