ACINIC CELL CARCINOMA / ACINAR CELL CARCINOMA / ACINIC CELL ADENOCARCINOMA: SPECIFIC CHARACTERISTICS Other Cancer(s) with possible similarities, or sharing these properties Article Title or Source Author(s), Journal Title, Book or Database Publi- cation or conver- sation DATE NOTES      
Note: This document is currently arranged in reverse chronological order, not by subject matter.     Note: This document is currently arranged in reverse chronological order.   Note: This document is currently arranged in reverse chronological order.      
Immunohistochemistry tests performed 10/2002 on Edgar Stroke's tissue from 6/8/99 needle biopsy. Tissue was tested for EGFR and P53. P53 was negative. But EGFR produced a result of “Positive Focally”. Verbal description by pathologist was; “10% of tissue was positive in a specific area. It was on the edge, so I’m not sure how reliable that is. Oncologist needs to decide.”
Other epithelial cancers have shown positivity for EGFR. Surgical Pathology Report UCLA Pathologist: Scott D. Nelson, M.D. Current as of 10/2/2002 A result of positivity for EGFR could make an ACC patient eligible for treatment with IRESSA, a promising new cancer drug. EGFR stands for Epidermal Growth Factor Receptor.      
PANCREATIC CANCER VERSION: The following rare non-endocrine tumors are listed alphabetically: Acinar Cell Carcinomas -
These rare cancerous tumors may produce excess amounts of the digestive enzymes normally produced by the pancreas. This increase in enzymes causes distinct symptoms in 20% of acninar cell carcinoma cases. Symptoms may include unusual skin rashes, joint pain and an increased level of eosinophils, a type of white blood cell.

Microscopically, these tumors have a characteristic grainy appearance. Special tests, including electron microscopy, can often be used to diagnose this type of tumor.
  Pancreas Cancer Web

Johns Hopkins Medical Institutions
Dept. of Pathology
  Current as of 7/15/2002 URL: http://pathology2.jhu.edu/pancreas/QUESTION/TYPTABLE.HTM      
INCIDENCE: 3rd most common epithelial malignancy of the salivary gland.
17% of all primary salivary gland malignancies
6% of salivary gland neoplasms SYNCHRONOUS OR METACHRONOUS: 3% of cases are bilateral.
  Acinic Cell Carcinoma The Doctor's Doctor website page on Acinic Cell Carcinoma Current as of 6/2002 URL: http://www.thedoctorsdoctor.com/diseases/aciniccell_ca.htm      
AGE RANGE-MEDIAN:Mean age is 44 years
12% of patients < 20 years SEX (M:F): 2:3 GEOGRAPHY: No racial predilection.
  Acinic Cell Carcinoma The Doctor's Doctor website page on Acinic Cell Carcinoma Current as of 6/2002 URL: http://www.thedoctorsdoctor.com/diseases/aciniccell_ca.htm      
GROSS APPEARANCE/CLINICAL VARIANTS: Single well circumscribed tumors
1-3 cm
Lobular tan to reddish surface
Solid to cystic
  Acinic Cell Carcinoma The Doctor's Doctor website page on Acinic Cell Carcinoma Current as of 6/2002 URL: http://www.thedoctorsdoctor.com/diseases/aciniccell_ca.htm      
GENERAL: Sheets of polygonal cells with granular, lightly basophilic cytoplasm and uniform nuclei resembling serous acinar cells.
May be separated by thin fibrovascular septa.
Vacuolated cells characteristic.
Clear cells may be abundant.
Usually infiltrate surrounding tissue.
  Acinic Cell Carcinoma The Doctor's Doctor website page on Acinic Cell Carcinoma Current as of 6/2002 URL: http://www.thedoctorsdoctor.com/diseases/aciniccell_ca.htm      
FOLLICULAR: Multiple cystic lumens filled with eosinophilic proteinaceous material, resembling thyroid follicles. PAPILLOCYSTIC: In rare cases, the tumor may dedifferentiate resulting in areas of poorly differentiated or undifferentiated carcinoma. Hemorrhage more common with this type. MICROCYSTIC: SOLID ACINAR: SPECIAL STAINS: Granules PAS positive, diastase resistant. IMMUNOPEROXIDASE: Cytokeratin, transferrin, CD15, CEA
Some positive for S100 and GFAP. ELECTRON MICROSCOPY (EM): Multiple round electron dense secretory granules.

  Acinic Cell Carcinoma The Doctor's Doctor website page on Acinic Cell Carcinoma Current as of 6/2002 URL: http://www.thedoctorsdoctor.com/diseases/aciniccell_ca.htm      
Most Acinic Cell Carcinomas are LOW GRADE and are associated with less aggressive growth and good survival rates (70% at 10 years). High grade variants have also been described (papillocystic carcinoma) or carcinomas with undifferentiated cells in a medullary pattern. The high grade variants are very uncommon and associated with much poorer survival.   OncoLink - Univ. of Penn. Cancer Center Website   Last reviewed: 11-1-2001        
Acinic Cell Carcinomas are often ENCAPSULATED, and may mistakenly believed to be benign. However, on microscopic analysis there may be extensions of tumour cells into surrounding tissue and metastases may occur over time.   OncoLink - Univ. of Penn. Cancer Center Website   Last reviewed: 11-1-2001        
Edgar's tumor tissue (from 11/99 surgery) was tested for C-Kit overexpression (CD117). It came up negative. Official results were: Slide Block Description: (1) Unstained Slide, pathology report dated 11/22/99. Clinical diagnosis: metastastic adenocarcinoma. Results: Paraffin Immunohistochemistry: CD117 - NEGATIVE.       4/27/01 This was for potential consideration for effectiveness of drug STI-571 / Gleevec.      
OBJECTIVE: CD34-positive dendritic interstitial cells may be associated with the regulation of tumor growth. This association has been studied in various human neoplasms, especially skin tumors. In this study, we evaluated the distribution of dendritic interstitial cells and myofibroblastic cells at the tumor periphery of various benign and malignant salivary gland neoplasms. METHODS: Forty-nine cases of salivary gland tumors were selected: 16 pleomorphic adenomas, 12 Warthin tumors, 8 polymorphous
low-grade tumors, 5 adenoid cystic carcinomas, 6 acinic cell carcinomas, and 2 mucoepidermoid carcinomas. Immunohistochemical analysis was performed by using antibodies for CD34 (dendritic cells) and alpha-smooth muscle actin (myofibroblast) on formalin-fixed, paraffin-embedded archival tissue. Staining intensity was graded as marked (3+), moderate (2+), weak (1+), and absent (0). (more)
  Dendritic interstitial and myofibroblastic cells at the border of salivary gland tumors. Soma L, LiVolsi VA, Baloch ZW
TITLE:Dendritic interstitial and myofibroblastic cells at the border of salivary gland tumors. Arch Pathol Lab Med; 125(2):232-6 2001 UI: 21092141
2001        
(cont'd) RESULTS: Staining intensity for CD34 was 3+ in 24 (86%) of 28 benign tumors (pleomorphic adenomas and Warthin tumors) and 6 (29%) of 21 malignant tumors (polymorphous low-grade tumors, acinic cell carcinomas, adenoid cystic carcinomas, and mucoepidermoid carcinomas) and 2+ in 4 (19%) of 21 malignant tumors. CONCLUSION: We conclude that the dendritic interstitial cells and myofibroblastic cells may be associated with the regulation of tumor growth in salivary gland tumors. polymorphous low-grade tumors, adenoid cystic carcinomas, and mucoepidermoid carcinomas Dendritic interstitial and myofibroblastic cells at the border of salivary gland tumors. Soma L, LiVolsi VA, Baloch ZW
TITLE:Dendritic interstitial and myofibroblastic cells at the border of salivary gland tumors. Arch Pathol Lab Med; 125(2):232-6 2001 UI: 21092141
2001        
Genetic alterations of oncogene MDM2 promote malignant transformation of several human tumors. METHODS AND RESULTS: Benign and malignant tumors of the salivary gland (6 pleomorphic adenomas, 3 Warthin's tumors, 1 adenocarcinoma, 1 basal cell adenocarcinoma, 1 mucoepidermoid carcinoma, 3 acinic cell carcinomas, 2 adenoid cystic carcinoma, 1 squamous cell carcinoma) were analyzed by fluorescence-based PCR techniques and immunochemistry for MDM2 gene amplification, MDM2 gene expression, MDM2 gene mutation, MDM2 RNA splicing and MDM2 accumulation. Data show that all samples contained nonamplified MDM2 genes with nonmutant zinc finger regions. However, in two benign and two malignant samples, novel MDM2 mRNA splicing variant types 1 and 2 were detected. Furthermore, three malignant tumors revealed significant nuclear MDM2 accumulation. Correlation between levels of MDM2 mRNA and MDM2 protein could not be detected in the specimens. (cont'd below)   Genetic analysis of the human oncoprotein MDM2 in benign and malignant tumors of the salivary gland.
Schlott T; Nagel H; Laskawi R; Eiffert H; Droese M
Pathobiology 2001;69(2):67-76
Department of Cytopathology, Georg August University, Gottingen, Germany. tschlott@med.uni-goettingen.de
2001 Check full text for more details.      
(Cont'd) CONCLUSION: The present study suggests that MDM2 gene mutation and gene amplification do not contribute to MDM2 accumulation detected in malignant tumors of the salivary gland. However, the role of novel MDM2 splicing variants in MDM2 expression and malignant transformation must be elucidated further.   Genetic analysis of the human oncoprotein MDM2 in benign and malignant tumors of the salivary gland.
Schlott T; Nagel H; Laskawi R; Eiffert H; Droese M
Pathobiology 2001;69(2):67-76
Department of Cytopathology, Georg August University, Gottingen, Germany. tschlott@med.uni-goettingen.de
2001 Check full text for more details.      
The clinicopathological features of six cases of breast carcinomas showing features of acinic cell differentiation, which are similar to those seen in homologous tumors of salivary glands, are presented. The patients, all women, were 35-80 years of age. One case recurred after 4 years, and in two cases axillary lymph node metastases were found at the time of surgery. Histologically the tumors showed a microglandular pattern merging with solid areas. Cytologically, immunohistochemically, and ultrastructurally the tumors were very similar to cases of acinic cell carcinoma of the parotid gland. The differential diagnostic criteria with microglandular adenosis and carcinomas showing granular cytoplasm are discussed. It seems that acinic cell carcinomas of the breast have to be added to the long list of tumors that affect the salivary glands and can also arise in the breast. Breast Cancers
Acinic cell carcinoma of the breast: an immunohistochemical and ultrastructural study. -
Virchows Arch; 437(1):74-81 2000 UI: 20417373 - Damiani S, Pasquinelli G, Lamovec J, Peterse JL, Eusebi V 2000        
Edgar's tumor tissue (from 11/99 surgery) was tested for carcinoembryonic antigen (CEA) expression. It came up negative.       8/23/00        
Galectins are a family of non-integrin beta-galactosidase-binding lectins. Altered expression of galectins has been associated with neoplastic transformation and progression in several human tumors. In this study, we examined the distribution patterns of galectin-1 and galectin-3 in normal (n=45), benign (n=16), and malignant (n=49) salivary gland specimens using immunohistochemistry to determine their diagnostic and/or biological implications in salivary gland tumorigenesis. In malignant tumors, most of the polymorphous low-grade adenocarcinomas and carcinoma ex-pleomorphic adenomas expressed both galectins, whereas adenoid cystic and acinic cell carcinomas showed dramatically reduced galectin-3 expression and heterogeneous galactin-1 staining. Our data demonstrated altered localization and expression of galectin-3, and to lesser extent, galectin-1 in salivary gland carcinomas. These findings may assist in the differential diagnosis of some salivary gland malignancies, especially when using small and limited fine-needle aspiration materials. adenoid cystic Differential expression of galectin-1 and galectin-3 in benign and malignant salivary gland neoplasms Int J Oncol 2000 Aug;17(2):271-6 - Xu XC, Sola Gallego JJ, Lotan R, El-Naggar AK Aug-00        
OBJECTIVE: To assess the prevalence of activating mutations in K-ras and H-ras genes in salivary gland tumors with ductal or acinar differentiation and to evaluate their potential correlation with clinical parameters. PATIENTS: Twenty-four patients with salivary gland carcinoma were surgically treated. Nine had adenocarcinoma, 1 had adenosquamous carcinoma, 11 had mucoepidermoid carcinoma, and 3 had acinic cell carcinoma. CONCLUSION: Our data suggest that K-ras gene alteration is probably not an important factor in the oncogenesis of human salivary gland tumors. However, mutational activation of the H-ras gene appears to play a role in the development and/or progression of salivary gland mucoepidermoid carcinomas. Other salivary gland cancers ras gene mutations in salivary gland tumors Arch Pathol Lab Med 2000 Jun;124(6):836-9 - Yoo J, Robinson RA Jun-00        
The expression and mutation patterns of p53 were studied in a series of 68 benign pleomorphic adenomas and 237 malignant salivary gland tumors. p53 overexpression (nuclear staining exceeding 10%) was detected in 20% of the malignant salivary gland tumors, with the highest prevalence observed in polymorphous low grade adenocarcinoma, squamous cell carcinoma, and carcinoma ex pleomorphic adenoma and the lowest in adenoid cystic carcinoma and acinic cell carcinoma. Our findings indicate that p53 may be a useful marker to help discriminate between benign and malignant salivary gland tumors. adenoid cystic carcinoma Expression and mutation patterns of p53 in benign and malignant salivary gland tumors. Int J Oncol 2000 Mar;16(3):477-83 - Nordkvist A, Roijer E, Bang G, Gustafsson H, Behrendt M, Ryd W, Thoresen S, Donath K, Stenman G Mar-00        
Report on Edgar's Chemistry: End of April/beginning of May 2000: Edgar's urine was tested for growth factors which could make me a more likely candidate for certain angiogenesis inhibitors (alpha-interferon for example). Edgar's Basic Fibroblast Growth Factor (fGf) was 2690 picograms/liter. Normal levels are less than 4000 (so I was normal). For Vascular Endothelial Growth Factor (veGF), Edgar's levels were 312 picograms/millileter. Normal levels are less than 300, so this was slightlyhigh.     Person who recommended testing, and performed tests at her lab was: Susan Connors (in Judah Folkman's research group) - Children's Hospital, Boston. May-00        
Acinic Cell Carcinoma - Characteristics:
Description of slide on website:
Sheets of large, polygonal cells with granular, basophilic cytoplasm and eccentric nuclei, reminiscent of serous acinar cells. Striated ducts and the normal lobular architecture are absent.
Vacuolated cells and intercalated duct cells are often seen. So are clear cells; these do not contain glycogen.
Note that many tumors have a mixture of cell types and architectural patterns.
All acinic cell carcinomas, however, have at least a focal component of serous acinar differentiation.
  
 

Medscape (www.Medscape.com) - Pathology Case Challenge <http://oncology.medscape.com/Medscape/features/PathCases/
2000/04.00/med0420.14/med0420.14.default.html>

Amir Rahemtulla, MD, MA - clinical pathology instructor at Harvard Medical School. 4/21/00        
Acinic Cell Carcinoma - Characteristics: - The most common malignant epithelial tumor to occur bilaterally (although 97% of acinic cell carcinomas are unilateral).
- Acinic cell carcinoma is the third most common malignant epithelial tumor of the salivary glands.
- It is the third most common epithelial tumor of the salivary gland in children (after pleomorphic adenoma and mucoepidermoid carcinoma).
- Most occur in the parotid gland.
- The papillary-cystic variant reportedly has a worse prognosis.
- The tumor is positive for alpha 1 antitrypsin, alpha 1 antichymotrypsin, PAS with diastase and, sometimes, amylase. Though not typically present, some mucicarmine staining in an otherwise diagnostic case is still compatible with acinic cell carcinoma.
  
  Medscape (www.Medscape.com) - Pathology Case Challenge <http://oncology.medscape.com/Medscape/features/PathCases/
2000/04.00/med0420.14/med0420.14.default.html>
Amir Rahemtulla, MD, MA - clinical pathology instructor at Harvard Medical School. 4/21/00        
Surgical Pathology of Edgar's Sacral Tumor, 11/18/99: Histologic sections reveal a metastatic adenocarcinoma comprising sheets of acinic type cells with abundant eosinophilic and granular cytoplasm and numerous variable sized intracytoplasmic vacuoles. The tumor cells are arranged around fibrovascular cores forming papillary pattern.
  City of Hope Pathologist: Peiguo Chu   11/20/99        
Other Characteristics of Edgar's pelvic tumor, noted during 11/18/99 surgery: Color: Very vascular purplish tumor (noted in left sacral ala). Other areas (more midline, pushing cauda equina posteriorly) were more yellowish.

Texture: Very soft and liquid.

Blood Supply: Very vascular. Good blood supply (to tumor). On capillary level, seemed average.
  Surgeons: Adam Mamelak, Maria Li, Gary Moscarello.   11/18/99        
Bone morphogenetic protein (BMP-6, also known as vegetal-pale-gene-related and decaplentaplegic-vegetal-related) is a member of the transforming growth factor-beta superfamily of multifunctional signaling molecules. BMP-6 appears to play various biological roles in developing tissues, including regulation of epithelial differentiation. To study the possible involvement of BMP-6 in normal and neoplastic human salivary glands, we compared its mRNA and protein expression in 4 fetal and 15 adult salivary glands and in 22 benign and 32 malignant salivary gland tumors. In situ hybridization and Northern blot analysis indicated that BMP-6 transcripts are expressed at low levels in acinar cells of adult submandibular glands but not in ductal or stromal cells. BMP-6 was immunolocated specifically in serous acini of parotid and submandibular glands. None was found in primitive fetal acini or any other types of cell in adult salivary glands, including mucous acini and epithelial cells of intercalated, striated, and excretory ducts. (more)   Bone morphogenetic protein-6 is a marker of serous acinar cell differentiation in normal and neoplastic human salivary gland. Cancer Res 1999 Nov 15;59(22):5815-21 - Heikinheimo AK, Laine MA, Ritvos OV, Voutilainen RJ, Hogan BL, Leivo IV - Institute of Dentistry, University of Turku, Finland. heikinhe@netlife.fi Nov-99 POSSIBLY VERY IMPORTANT      
(continued): All 16 cases of acinic cell carcinoma consistently exhibited cytoplasmic BMP-6 staining in the acinar tumor cells. Other cell types in these tumors, including intercalated duct-like cells, clear, vacuolated cells, and nonspecific glandular cells, exhibited no cytoplasmic BMP-6 staining. Other benign and malignant salivary gland tumors lacked BMP-6 immunoreactivity, except in areas of squamous differentiation. The results indicate that in salivary glands, BMP-6 expression is uniquely associated with acinar cell differentiation and suggest that BMP-6 may play a role in salivary gland function. More importantly, our experience of differential diagnostic problems related to salivary gland tumors suggests that the demonstration of consistent and specific BMP-6 immunoreactivity in acinic cell carcinoma is likely to be of clinical value.   Bone morphogenetic protein-6 is a marker of serous acinar cell differentiation in normal and neoplastic human salivary gland. Cancer Res 1999 Nov 15;59(22):5815-21 - Heikinheimo AK, Laine MA, Ritvos OV, Voutilainen RJ, Hogan BL, Leivo IV - Institute of Dentistry, University of Turku, Finland. heikinhe@netlife.fi 11/15/99        
The chromosomal locus 9p21 contains the p16 (INK4a/CDKN2/MTS1) tumor suppressor gene that has been implicated in a variety of tumor types, including carcinomas of the head and neck, esophagus, and pancreas. To determine whether the loss of this gene is involved in salivary gland cancers, 35 carcinomas and paired nonneoplastic specimens were analyzed for loss of heterozygosity (LOH) of polymorphic genetic markers located in the region of interest. Loss of heterozygosity was found in 1 of 10 adenoid cystic carcinomas and 1 of 8 mucoepidermoid carcinomas and was absent in the remaining subtypes, including acinic cell carcinoma. These results suggest that inactivation of p16 is important in the development or progression of at least some salivary duct carcinomas, but we found no evidence that its alteration plays a role in the other subtypes examined. mucoepidermoid carcinoma, salivary duct carcinoma, adenoid cystic carcinoma, and polymorphous low-grade adenocarcinoma. Analysis of chromosome 9p21 deletion and p16 gene mutation in salivary gland carcinomas. Hum Pathol 1999 Oct;30(10):1242-6 - Cerilli LA, Swartzbaugh JR, Saadut R, Marshall CE, Rumpel CA, Moskaluk CA, Frierson HF Jr 10/30/99        
Acinic Cell (Adeno)carcinoma - DEFINITION:
A neoplastic growth of epithelial cells showing serous acinar differentiation
GROSS FEATURES: - Single, well circumscribed to multinodular and ill-defined
- Firm to cystic
- 0.5-13 cm
- Lobular, red to tan cut surface
  FRONTIERS IN BIOSCIENCE; LECTURE SERIES:
SALIVARY GLAND TUMORS; CLINICAL AND PATHOLOGICAL FEATURES

Dept of Pathology, Moffitt Cancer Center and University of South Florida, 12902
Magnolia Drive, Tampa, FL 33612
S Tabibzadeh As of 9/19/99 WEBSITE: http://www.bioscience.org/lecture/tabibza/list.htm      
Acinic Cell Carcinoma -
CLINICAL FEATURES:
- Occurs most commonly in parotid gland
- Occurs unilaterally. May occur bilaterally.
- Occurs more frequently in women than men (3:2)
- Occurs in young and old individuals
- Slowly growing, mobile or fixed mass of various durations.
- Asympotatic
- Pain or tenderness
- Facial muscle weakness
  FRONTIERS IN BIOSCIENCE; LECTURE SERIES:
SALIVARY GLAND TUMORS; CLINICAL AND PATHOLOGICAL FEATURES

Dept of Pathology, Moffitt Cancer Center and University of South Florida, 12902
Magnolia Drive, Tampa, FL 33612
S Tabibzadeh As of 9/19/99 WEBSITE: http://www.bioscience.org/lecture/tabibza/list.htm      
Acinic Cell Carcinoma: ULTRASTRUCTUAL FEATURES:  Main epithelial cells, Multiple round, membrane bound, electron dense cytoplasmic granules, Vacuoles, Lumina, Apical junctional complexes, Few microvilli, Clear cells, Dilated ER, Lipid inclusions, Intracytoplasmic pseudolumina, Myoepithelial cells, Elongated, Microfilaments, Dense bodies.   FRONTIERS IN BIOSCIENCE; LECTURE SERIES:
SALIVARY GLAND TUMORS; CLINICAL AND PATHOLOGICAL FEATURES

Dept of Pathology, Moffitt Cancer Center and University of South Florida, 12902
Magnolia Drive, Tampa, FL 33612
S Tabibzadeh As of 9/19/99 WEBSITE: http://www.bioscience.org/lecture/tabibza/list.htm      
Acinic Cell Carcinoma
MICROSCOPIC FEATURES:
Patterns
Sheets
Cysts, some with papillary growth
Microcystic
Acini
Ducts
Glands
Follicles (similar to thyroid)

Epithelium
Large polygonal
Lightly basophilic cytoplasm
Uniform to variable eccentic nuclei (more)
  FRONTIERS IN BIOSCIENCE; LECTURE SERIES:
SALIVARY GLAND TUMORS; CLINICAL AND PATHOLOGICAL FEATURES

Dept of Pathology, Moffitt Cancer Center and University of South Florida, 12902
Magnolia Drive, Tampa, FL 33612
S Tabibzadeh As of 9/19/99 WEBSITE: http://www.bioscience.org/lecture/tabibza/list.htm      
Acinic Cell Carcinoma
MICROSCOPIC FEATURES:
  Acinar epithelium
Large polygonal
Lightly basophilic cytoplasm (blue dot tumors)
Protuberance of luminal membrane producing a tombstone appearance
Uniform to variable eccentic nuclei
Cytoplasmic granules (PAS positive-diastase resistant; mucicarcmine positive)
Hemosiderin

Duct epithelium
Eosinophilic cytoplasm
Variable cell size
Central lumen of various size (more)
  FRONTIERS IN BIOSCIENCE; LECTURE SERIES:
SALIVARY GLAND TUMORS; CLINICAL AND PATHOLOGICAL FEATURES

Dept of Pathology, Moffitt Cancer Center and University of South Florida, 12902
Magnolia Drive, Tampa, FL 33612
S Tabibzadeh As of 9/19/99 WEBSITE: http://www.bioscience.org/lecture/tabibza/list.htm      
Acinic Cell Carcinoma
MICROSCOPIC FEATURES:
Stroma

Delicate fibrovascular tissue
Collagenous tissue
Lymphoid infiltration (in some cases)
Hemorrhage
Hemosiderin
Psammoma bodies
  Vacuolated cells
Eosinophilic to amphophilic cytoplasm
Clear vacuoles
PAS and mucicarmine negative
Clear cells
Lack of glycogen

Glandular cells
Round to polgonal
Eosinophilic to amphophilic cytoplasm
Lack of cytoplasmic granules or PAS positivity
Nuclear pleomorphism
  FRONTIERS IN BIOSCIENCE; LECTURE SERIES:
SALIVARY GLAND TUMORS; CLINICAL AND PATHOLOGICAL FEATURES

Dept of Pathology, Moffitt Cancer Center and University of South Florida, 12902
Magnolia Drive, Tampa, FL 33612
S Tabibzadeh As of 9/19/99 WEBSITE: http://www.bioscience.org/lecture/tabibza/list.htm      
Acinic Cell Carcinoma
IMMUNOHISTOCHEMICAL FEATURES:
Cytokeratin(present)
CEA (present)
alpha 1 antitrypsin (present)
alpha 1 antichymotrypsin (present)
Leu-M1 (present)
Amylase (present)
Transferrin (present)
Lactoferrin (present)
Vasocactive intestinal polypeptide (present)
S-100 (some)
GFAP (some)
  FRONTIERS IN BIOSCIENCE; LECTURE SERIES:
SALIVARY GLAND TUMORS; CLINICAL AND PATHOLOGICAL FEATURES

Dept of Pathology, Moffitt Cancer Center and University of South Florida, 12902
Magnolia Drive, Tampa, FL 33612
S Tabibzadeh As of 9/19/99 WEBSITE: http://www.bioscience.org/lecture/tabibza/list.htm      
Acinic Cell Carcinoma
DIFFERENTIAL DIAGNOSIS:
Papillary-cystic and follicular type
Cystadenocarcinoma (lack of microcycstic and vacuolated cells)
Mucoepidermoid carcinoma (presence of mucous cells)
Metastatic thyroid carcinoma (presence of thyroglobulin)
Polmorphous low-grade adencarcinoma (perineural invasion, homogeneous cell
population, single cell infiltration at the periphery)

Clear cell type
Clear cell carcinoma (lack of glycogen, lack of serous differentiation)
Epithelial-myoepithelial carcinoma (lack of glycogen)
Squamous cell carcinoma (lack of glycogen)
Metastatic renal cell carcinoma (lack of glycogen)
  FRONTIERS IN BIOSCIENCE; LECTURE SERIES:
SALIVARY GLAND TUMORS; CLINICAL AND PATHOLOGICAL FEATURES

Dept of Pathology, Moffitt Cancer Center and University of South Florida, 12902
Magnolia Drive, Tampa, FL 33612
S Tabibzadeh As of 9/19/99 WEBSITE: http://www.bioscience.org/lecture/tabibza/list.htm      
We report a rare case of acinic cell carcinoma of the palate in a 63-year-old Japanese woman. Clinical examination demonstrated a firm, mobile mass without regional lymph-adenopathy. Histopathologically, the tumor was composed of large, polyhedral or round cells with basophilic granular cytoplasm (serous acinar-like cells) and reticular or clear cytoplasmic cells. These tumor cells were positive for the periodic acid-Schiff reaction, but negative for alcian blue. The tumor nests were separated by thin vascular tissue and incompletely encapsulated. Immunohistochemically, the tumor cells exhibited positive reactivity for alpha-amylase, lactoferrin, secretory component, S100 protein, and epithelial membrane antigen, but were negative for actin, glial fibrillary acidic protein, keratin, and carcinoembryonic antigen. These results suggest that this tumor is well differentiated into serous acinar cells and that the reticular and clear cytoplasmic cells are a modified form of these cells.   Acinic cell carcinoma of the palate: case report and immunohistochemical observation. Arch Otolaryngol Head Neck Surg 1999 Sep;125(9):1025-8 - Utsunomiya T, Yamamoto H, Kuyama K, Itami M, Asanuma K - Department of Pathology, Nihon University School of Dentistry at Matsudo, Chiba, Japan. Sep-99        
Immunohistochemistry Report on Edgar's Biopsy Tissue of 6/8/99: Tests for Her2Neu overexpression, Estrogen Receptors and Progesterone Receptors ALL CAME BACK NEGATIVE. It HAS been reported that some salivary gland cancers (and some Acinic Cells) have been positive for these tests. UCLA Pathologist: Scott D. Nelson M.D. & Andrea Chang M.D. - Resident   7/27/99 According to Scott Nelson, results are completely reliable.      
Conversation with authority: In salivary gland cancers (mucoepidermoid carcinomas) he studied (together with MD Anderson), Her2Neu was overexpressed in 20-30% of cases. They found that when Her2neu gene is amplified/ overexpressed, cancers are more aggressive and prone to higher rate of metastatic disease (and higher death rate). mucoepidermoid carcinomas Pathologist: Mike Press - USC, Norris Cancer Center   7/12/99        
Conversation with authority: There are similarities between salivary glands and mammary glands Mammary glands /breasts. Pathologist: Mike Press - USC, Norris Cancer Center   7/12/99        
Conversation with authority: My case: Unusual; torpid but persistent pattern of growth. Slow growth / slow "turnover". Very long G1 Phase of growth. Most Breast Cancers have similar characteristics. See Waterhouse. (also adenocarcinomas) Oral Pathologist: J. Sciubba - LI Jewish (soon Johns Hopkins)   7/7/99        
Cytogenetics Report of Edgar's Biopsy - Metastatic Site, Pelvic Recurrence, Needle Biopsy 6/8/99: ANALYSIS:
Metaphases counted: 15 Colonies Counted:
Metaphases analyzed: 15 Banding Technique: GPG
Metaphases karotyped: 3 Banding Resolution: 450
RESULTS:
KARYOTYPE: 46, XY, der(1) add (1p), -3, del(4) q(12), del(6) (q21), del(10q), der(11) add(11p), der (12q), der(18q) [cp15]
INTERPRETATION: Highly abnormal * male chromosome analysis with several unusual abnormalities, suggestive of an aggressive phase. The most relevant of these abnormalities are deletion 4q and 6q, both consistent with tumors of the salivary glands.
  UCLA Pathologists: Wayne W. Grody, M.D. P. Nagesh Rao, Ph.D.   7/2/99        
* Conversation with authority: Re: Edgar's Cytogenetics Report - The cells are highly abnormal as compared with normal cells. But it is NOT atypical for salivary gland cancer. Don't put TOO much weight on "aggressive" part. However, it COULD be, if Edgar's experience backs that up. There ARE similarities with Breast CancersŠin the normal biology;glandular structure. But he doesn't know much about. It's not his area. UCLA Pathologist: Scott D. Nelson, M.D. - Wrote Edgar's Pathology Report 6/99, and ordered cytogenetics study.   7/15/99        
P53 protein and vascular endothelial growth factor (VEGF) expression, and mean intratumoral microvessel density (IMVD) were studied by immunohistochemistry in 31 salivary gland carcinomas, consisting of 11 adenoid cystic carcinomas (AdCCs), 10 mucoepidermoid carcinomas (MECs), 7 acinic cell carcinomas (AcCCs), and 3 squamous cell carcinomas (SCCs). Cases with p53 protein in more than 20% of tumor cells were detected in one AdCC, four MECs, one AcCC, and two SCCs. Both frequency of p53 and VEGF expression, and mean IMVD, were higher in the MECs and SCCs than in the AdCCs and AcCCs. Similarly, both VEGF expression and mean IMVD were significantly higher (P<0.05) in the eight p53-positive tumors than in the 23 negative tumors. Six cases with survival periods less than 5 years showed significantly higher frequency of p53 and VEGF expression and of mean IMVD than those with longer survival periods. These results indicate that p53 expression might partly correlate with VEGF expression and mean IMVD, and be a factor in the survival of patients with salivary gland carcinomas.
Adenoid cystic carcinomas showed similar traits (lower frequency of P53 protein, VEGF expression, and mean IMVD). Expression of p53 oncoprotein increases intratumoral microvessel formation in
human salivary gland carcinomas.
Doi R, Kuratate I, Okamoto E, Ryoke K, Ito H - First Department of Pathology, Faculty of Medicine, Tottori University, Japan - J Oral Pathol Med 1999 Jul;28(6):259-63
Jul-99        
Conversation with authority: Acinic Cell of salivary glands is similar to Acinic Cell Pancreatic Cancer (only one he can think of). But that lesion is almost as rare as salivary gland Acinic Cell. (Probably more literature on Pancreatic version.) Pancreas and Parotid are similar glands. Pancreatic Acinic cell is ALSO SLOW GROWING. Many salivary gland cancers DO have Estrogen Receptors or Progestin Receptors. Radiation Therapy in general will control, but never cure. Radiation AND Chemotherapy generally prefer something LESS DIFFERENTIATED for successful treatment. Acinic Cell is rather "torpid" (sluggish). Pancreatic Acinic Cell Type, not ductal. They have similar type of gland. John Batsakis - ex. MD Anderson, now retired (major authority)   6/30/99        
Conversation with authority: Acinic cell falls into larger salivary gland group of Adenocarcinomas. Adenoid Cystic in same family. His experience is that Adenoid Cystic has some response to chemotherapy, and that it will react similarly to ACC as far as treatments. Acinic cell falls into larger salivary gland group of Adenocarcinomas. Adenoid Cystic in same family. It's a sister disease, but not quite as slow growing. It is also well-differentiated though. Acinic Cell and Adenoid Cystic attack different sections of glands. George J. Bosl - Chair, Dept. of Medicine, Clinical Oncology/Head and Neck Cancers, Medical Oncology   6/29/99        
Conversation with authority: Acinic Cell is most similar acting to Breast Cancer. You CAN get Acinic Cell in Breast! Breast Cancers. Gary Clayman - MD Anderson; rec. by John Batsakis; Head, neck and Oral Surgeon and Researcher. "cutting edge"   6/29/99        
Conversation with authority: Edgar's tumor is VERY WELL DIFFERENTIATED, which means that it closely mimics normal tissue. One interesting note about HIS TUMOR: Lots of times cancers get more poorly differentiated over time and metastases. But Edgar's hasn't changed much. But that's a double edged sword... It's good because it's slow-moving. But it also means things like chemo are LESS EFFECTIVE. LOW GRADE / WELL-DIFFERENTIATED mean same thing. Will act like other WELL DIFFERENTIATED cancers. Pancreatic is similar, but more aggressive. Pancreas is closest cousin. UCLA Pathologist: Scott D. Nelson, M.D. - Wrote Edgar's Pathology Report 6/99, and ordered cytogenetics study.   6/24/99        
Transgenic mice overexpressing transforming growth factor-alpha (TGF-alpha) display an expansion of intrapancreatic fibroblasts and a progressive accumulation of extracellular matrix. This massive fibrosis is associated with an increase in pancreatic size and weight. In parallel, tubular complexes appear that are composed of acinar cells with a decreased height. These acinar cell lose zymogen granules and become transitional cells, which subsequently gain duct cell features. In animals older than one year dysplastic lesions develop, which originate from tubular complexes. Occasionally these dysplastic foci transform to papillary and cystic pancreatic carcinoma. These tumors are positive for the duct-specific antigen Duct-1 and carbonic anhydrase activity indicative of ductal differentiation. Tumors overexpress the epidermal growth factor (EGF)-receptor and p53, but lack K-ras mutations.  These data suggest an acinar-ductal-carcinoma sequence in TGF-alpha transgenic mice.   Acinar-ductal-carcinoma sequence in transforming growth factor-alpha transgenic
mice.
Schmid RM, Kloppel G, Adler G, Wagner M - Ann N Y Acad Sci 1999 Jun 30;880:219-30 6/30/99        
Pathology of Edgar's Biopsy - Metastatic Site, Pelvic Recurrence, Needle Biopsy 6/8/99: Sections show a tumor with a prominent microcystic and focally solid pattern. The tumor cells have abundant granular, basophilic cytoplasm, small round nuclei with prominent nucleoli. Mitotic figures are present.   UCLA Pathologist: Scott D. Nelson, M.D.   6/10/99        
Conversation with authority: Acinic cell mostly in 2 organ systems: Salivary Gland and Pancreas. Acinic Cell is part of family of adenocarcinomas, which make a glandular structure. There are two types of adenocarcinomas; those with mucous granules, and those with serrous granules. Acinic Cell has SERROUS GRANULES. Acinic Cell is also special because it has LARGE GRANULES... specifically called ZYMOGEN GRANULES. The entire Parotid Gland, when normal, is made up of ACINOUS GRANULES. One day they can become cancerous, leading to "Acinic Cell Carcinoma". In Pancreatic Cancer, the most common type is cancer of duct (ductal). A small # of pancreatic cancers may be Acinic Cell. Acinic Cell is also special because it can look quite similar over long period of time, and at various metastastatic sites. (Many other cancers change over time.) Pancreatic Cancer - Acinic Cell Type, not ductal. Sunita Bhuta, UCLA Pathologist   Jun-99        
Immunoreactivity of prostate-specific antigen (PSA), a kallikrein-like enzyme present in the seminal plasma, was demonstrated by indirect immunoperoxidase staining using a PSA antiserum in the apical cytoplasm along the luminal border of small-sized duct epithelial cells of the major salivary (parotid and submandibular) gland of both sexes (56/56, 100%). No PSA-like immunoreactivity was seen in large-sized duct epithelial cells and acinar cells. Minor salivary gland ducts were negative. When inflammatory and atrophic changes were observed, ductal expression of PSA-like immunoreactivity was decreased (12/37, 32%) and the site of intracellular localization often became diffusely cytoplasmic. The immunoreactivity was absorbed by human seminal plasma. Immunoreactivities of prostatic acid phosphatase and sex hormone receptors were undetectable in the salivary gland. Twenty-nine (34%) of 86 salivary gland tumors with ductal differentiation were immunoreactive for PSA mainly in the cytoplasm. (more) No PSA-like immunoreactivity was seen in large-sized duct epithelial cells and acinar cells. Localization of prostate-specific antigen-like immunoreactivity in human salivary gland and salivary gland tumors. Tazawa K, Kurihara Y, Kamoshida S, Tsukada K, Tsutsumi Y -Pathol Int 1999 Jun 18;49(6):500-505 Jun-99        
(cont'd): A PSA monoclonal antibody ER-PR8 detected immunoreactivity in the prostate but not in the salivary glands or their tumors. Prostate-specific antigen-like immunoreactivity in small-sized (intercalated) duct epithelial cells of the major salivary gland and their tumors may be due to cross-reactivity of the antiserum with kallikrein-like substances. No PSA-like immunoreactivity was seen in large-sized duct epithelial cells and acinar cells. Localization of prostate-specific antigen-like immunoreactivity in human salivary gland and salivary gland tumors. Tazawa K, Kurihara Y, Kamoshida S, Tsukada K, Tsutsumi Y -Pathol Int 1999 Jun 18;49(6):500-505 Jun-99        
Acinic cell carcinomas arise from pluripotential stem cells found at the acinar-intercalated duct junctions and/or in the intercalated ducts proper of mature salivary glands. Multiple growth patterns are possible, with the most common growth patterns being solid-lobular and acinar-microcystic. In contrast to most other salivary gland tumors, acinic cell carcinomas normally produce large lobules or nests with little intervening stroma. Cytoplasmic basophilic granules and vacuolated cells are characteristic of these tumors; immunohistochemical staining and electron microscopy are normally not necessary for diagnosis.   Pathologic Diagnosis: Acinic cell carcinoma of the deep lobe of the parotid gland involving the right parapharyngeal space. References: Batskis JG, Luna MAA, El-Naggar AK. Histopathologic grading of salivary gland neoplasms, II: acinic cell carcinomas. Ann Otol Rhinol Laryngol. 1990;99:929-933. Archives of Otolaryngology ­ Head and Neck Surgery: Vol. 125 No. 6, June 1999
Also online at: http://archotol.ama-assn.org/issues/v125n6/ffull/orp0699-1b.html
Jun-99        
There is no conclusive evidence to correlate the histopathologic characteristics of acinic cell carcinomas and overall prognosis. However, larger, poorly circumscribed tumors with both solid and cystic areas, high degrees of mitotic activity, and atypia with lymph node involvement are associated with a worse prognosis. Also, Lewis et al  found that the presence of desmoplastic stromal reaction is associated with a poor outcome. Other studies have shown a worse prognosis for tumors with a papillary-cystic pattern. Perzin and LiVolsi found an association between tumor involvement of the deep lobe of the parotid gland and local recurrence and metastasis.

  Pathologic Diagnosis: Acinic cell carcinoma of the deep lobe of the parotid gland involving the right parapharyngeal space. References: Yokoyama M, Nomura Y, Semba T. Acinic cell carcinoma of the parapharyngeal space: case report. Head Neck. 1993;15:67-69.

Perzin KH, LiVolsi VA. Acinic cell carcinomas arising in salivary glands: a clinicopathologic study. Cancer. 1979;44:1434-1457.

Lewis JE, Olsen KD, Weiland LH. Acinic cell carcinoma: clinicopathic review. Cancer. 1991;67:172-179.
Archives of Otolaryngology ­ Head and Neck Surgery: Vol. 125 No. 6, June 1999
Also online at: http://archotol.ama-assn.org/issues/v125n6/ffull/orp0699-1b.html
Jun-99        
Telomerase activity can be detected in most human cancers. This is consistent with the telomere hypothesis, which predicts upregulation of telomerase expression after a number of mitotic divisions to prevent the progressive and catastrophic loss of telomeres. In this report, telomerase activity was analyzed in 31 human oral malignant tumors, 11 leukoplakias, three pleomorphic adenomas, and 40 samples taken from normal tissues of the oral cavity, using a polymerase chain reaction (PCR)-based telomeric repeat amplification protocol assay. Telomerase activity was detected in most oral cancers [squamous cell carcinoma (SCC), non-Hodgkin's lymphoma, adenoid cystic carcinomas, mucoepidermoid carcinoma, osteosarcoma, acinic cell carcinoma, rhabdomyosarcoma]. None of the normal tissues or pleomorphic adenomas displayed telomerase activity. These results suggest that detection of telomerase activity in oral tissues could be used to differentiate malignant from benign or normal tissues. squamous cell carcinoma, non-Hodgkin's lymphoma, adenoid cystic carcinomas, mucoepidermoid carcinoma, osteosarcoma, rhabdomyosarcoma Telomerase activity in oral cancer. Oral Oncol 1999 May;35(3):283-9 - Miyoshi Y, Tsukinoki K, Imaizumi T, Yamada Y, Ishizaki T, Watanabe Y, Sasakura Y, Lin Y, Hosaka M, Kubota Y May-99        
A dedifferentiated acinic cell carcinoma (AciCC) of the right parotid gland with lymph node metastases occurred in a 36-year-old woman. The tumour was associated with a bilateral well-differentiated AciCC. The two components of this tumour had different (high and low) proliferative activity measured by Mib-1 and different (aneuploid and diploid) DNA content. Despite the presence of a high-grade component, TP53 mutations, microsatellite instability (MSI) and/or loss of heterozygosity (LOH) at the p53 locus were not detected. Although the follow-up of the patient is very short, the aggressiveness of the tumour is shown by a recurrence in the right parotid within 4 months and by the rapid development of regional metastases.
  Unilateral aneuploid dedifferentiated acinic cell carcinoma associated with
bilateral-low grade diploid acinic cell carcinoma of the parotid gland.
Di Palma S, Corletto V, Lavarino C, Birindelli S, Pilotti S - Division of Pathology and Cytopathology, Istituto Nazionale per lo Studio e la Cura dei Tumori, Milano, Italy. dipalma@istitutotumori.mi.i - Virchows Arch 1999 Apr;434(4):361-5 Apr-99        
This study is to investigate some characteristics of lung tumor associated with exposure to coal combustion emissions. In Xuan Wei (XW) county, China, lung cancer mortality in females (99% nonsmokers) is the highest in China and has been associated with exposure to indoor smoky-coal emissions which contain high concentrations of carcinogenic PAHs. Expression of the proliferation nuclear antigen, Ki-67 and accumulation of p53 protein were investigated by immunohistochemistry in 33 XW nonsmoking female patients with non-small cell lung cancer. The mean Ki-67 index was 24.9% in acinar adenocarcinoma, 6.87% in papillary adenocarcinoma, 38.6% in solid adenocarcinoma, 24.1% in adenosquamous carcinoma, 3.23% in squamous carcinoma and 21.88% in bronchioloalveolar carcinoma. The above subtypes showed positive in p53 staining in 4/6, 1/2, 2/5, 1/2, 2/2, and 13/16, respectively. Among the subtypes of adenocarcinomas, bronchioloalveolar carcinoma was most frequently found, as high as 55% (16/29), which is much higher than published reports. (more below)
Acinar adenocarcinoma of the LUNG. (also mentioned by other physician sources)... Adenosquamous carcinoma had almost the same Ki-67 index. Cell proliferation related antigen Ki-67 and p53 protein accumulation in non small-cell lung cancer from nonsmoking females exposed to indoor coal emissions. [PROC. AMER. ASSOC. CANCER RES. 40, March 1999] Copyright © 1999 by the American Association for Cancer Research - Tian, D., Feng, Z., Li, X. Mumford, J. L. - University of North Carolina, Chapel Hill, NC 27599, Institute of Environmental Health and Engineering, Beijing, China. U.S. Environmental Protection Agency, Research Triangle Park, NC 27711. Mar-99        
(no abstract available) Acinar adenocarcinoma of the LUNG. (also mentioned by other physician sources) Cell proliferation related antigen Ki-67 and p53 protein accumulation in non small-cell lung cancer from nonsmoking females exposed to indoor coal emissions. [PROC. AMER. ASSOC. CANCER RES. 40, March 1999] Copyright © 1999 by the American Association for Cancer Research - Tian D., Feng Z., Li X. Mumford J. L. - University of North Carolina, Chapel Hill, NC 27599, Institute of Environmental Health and Engineering, Beijing, China. U.S. Environmental Protection Agency, Research Triangle Park, NC 27711. Mar-99        
The purpose of this study was to determine the estrogen and progesterone receptor status of a selection of salivary tumours. Using immunohistochemistry, we detected nine oestrogen receptor and six progesterone receptor positive tumours from a sample of 36.  One acinic cell carcinoma and two mucoepidermoid carcinomas demonstrated positivity for both receptors. We suggest that there may be role for oestrogen manipulation in the management of some salivary tumours. mucoepidermoid & maybe more? (need full text) Immunohistochemical detection of oestrogen and progesterone receptors in salivary tumours. Clin Otolaryngol 1999 Feb;24(1):52-4 - Jeannon JP, Soames JV, Bell H, Wilson JA Feb-99        
The tumor was considered to be the recurrence 22 years after initial surgery... Although this tumor is of low grade malignancy, complete resection with adequate surgical margins is advisable due to high incidence of this tumor to recur after long periods of time.   Acinic Cell carcinoma of maxillary sinus Fujii M, Kumanomidou H, Ohno Y, Kanzaki J - Auris Nasus Larynx, 25(4): 451-7 Dec-98        
The purpose of this study was to determine the oestrogen and progesterone receptor status of a selection of salivary tumours. Using immunohistochemistry, we detected nine oestrogen receptor and six progesterone receptor positive tumours from a sample of 36.  One acinic cell carcinoma and two mucoepidermoid carcinomas demonstrated positivity for both receptors.  We suggest that there may be role for oestrogen manipulation in the management of some salivary tumours. Mucoepidermoid carcinomas also demonstrated positive estrogen and progesterone receptors. Immunohistochemical detection of oestrogen and progesterone receptors in
salivary tumours.
Jeannon JP, Soames JV, Bell H, Wilson JA -
Clin Otolaryngol 1999 Feb;24(1):52-4
Nov-98        
PURPOSE: To investigate the effects of increasing concentrations of cholecystokinin octapeptide (CCK-8) on a
pancreatic acinar adenocarcinoma. METHODS: Growth of the tumour was estimated in vivo on rats bearing a
subcutaneous pancreatic carcinoma, and in vitro on primary cultured tumour cells. CCK receptors were characterized
by binding assays. RESULTS: CCK-8, administered for 12 successive days, exerted a biphasic action on tumour
growth: a dose-dependent stimulation with low doses (0.1 and 0.5 microg/kg) and inhibition with high doses (2 and 4
microg/ kg) as shown by respective increases and decreases in tumor volume, protein, RNA and amylase contents. In
cell cultures, [3H]thymidine incorporation was dose-dependently increased with 10-(10) to 10(-8) M CCK-8 and
inhibited with 10(-7) M. Both effects were completely suppressed by the CCK-receptor antagonists CR 1409 and L
364,718 (10(-4) M). Binding studies showed the overexpression of two classes of CCK-A receptors of low and high affinity when compared to the normal pancreas which was less sensitive to CCK-8. (more below)
Effects of cholecystokinin octapeptide on a pancreatic acinar carcinoma in the rat. Hajri A, Damge C: Pharm Res 1998 Nov;15(11):1767-74 Nov-98        
(cont'd):   CONCLUSIONS: CCK-8 exerts a biphasic growth response on the acinar pancreatic carcinoma, mediated by two classes of CCK-A receptors overexpressed in the tumour.
  Effects of cholecystokinin octapeptide on a pancreatic acinar
carcinoma in the rat.
Hajri A, Damge C: Pharm Res 1998 Nov;15(11):1767-74 Nov-98 possibly IMPORTANT?      
Human acinic cell adenocarcinoma cell (HACC) line was established from the pleural effusion that contain metastatic tumor cells of acinic cell adeno-carcinoma of papillary and microcystic type originating from the parotidgland. The HACC cells grew in an adherent monolayer with a doubling time of 66 h. Implanted tumor of SCIDmice revealed similar histological findings to that of the primary tumor. The HACC cells produced mucin and expressed epithelial markers as well as alpha1-antitrypsin and lysozyme, whereas salivary peptide P-C was expressed in cultured HACC cells but not in the primary and implanted HACC cell tumors. S-100 protein was also expressed in both the primary tumor and HACC cell line. Neither amplification of common oncogenes nor expression of p53 was observed. The receptor for epidermal growth factor (EGF) was expressed, indicating EGF and transforming growth factor-alpha (TGF-alpha) enhanced the growth of the HACC line. Unexpectedly, tumor necrosis factor-a (TNF-alpha) also enhanced the growth of the HACC line significantly.  (more below)
  Characterization of a newly established human acinic cell
adenocarcinoma cell line (HACC) originating from the salivary gland: morphological features and role of various growth factors on the growth of the HACC cell line.
Fukuda T; Tominaga K; Abe M; Kusakabe T; Yamaki T; Hiraki H; Itoh S; Suzuki T - Pathol Int, 48(10): 791-9 Oct-98        
(cont'd)  However, there was no evidence of autocrine growth using these growth factors. In contrast, TGF-beta1 inhibited the growth of the HACC cell line through apoptosis. The HACC cell line has features similar to both acinar and intercalated ductal cells of the salivary gland. Epidermal growth factor, TGF-alpha and TNF-alpha are potential growth factors for the HACC cell line. The HACC cell line may be a good model for studying the biological behavior of salivary gland neoplasms.
a biphasic growth response on the acinar pancreatic carcinoma, mediated by two classes of CCK-A receptors Characterization of a newly established human acinic cell
adenocarcinoma cell line (HACC) originating from the salivary gland: morphological features and role of various growth factors on the growth of the HACC cell line.
Fukuda T; Tominaga K; Abe M; Kusakabe T; Yamaki T; Hiraki H; Itoh S; Suzuki T - Pathol Int, 48(10): 791-9 Oct-98        
ACINIC CELL CARCINOMA - STATISTICS: The National Cancer Institute Data Base (NCDB) identified 1353 cases of acinic cell carcinoma of the head and neck for years 1985 to 1995. (Cells below provide various statistics from this report.)   National Cancer Data Base Report on Cancer of the Head and Neck: Acinic Cell Carcinoma (1985-1995) Henry T. Hoffman M.D., Lucy Hynds Karnell PhD, Robert A. Robinson MD, John A. Pinkston M.D., Herman R. Menck, MBA 8/27/98 (submitted) July 1999 published        
ACINIC CELL CARCINOMA - OCCURRENCE STATISTICS: The National Cancer Institute Data Base (NCDB) identified 1353 cases of acinic cell carcinoma of the head and neck for years 1985 to 1995. Salivary gland cancers comprise between 0.3% and 0.9% of all cancers in the United States. Acinic cell carcinomas account for approximately 5% to 11% of these salivary gland cancers. The Armed Forces Institute of Pathology (AFIP) Salivary Gland Registry (having the largest series of salivary gland tumors to date) identified acinic cell carcinoma as the third most common epithelial malignancy of the salivary glands (after mucoepidrmoid and adenocarcinoma NOS (not otherwise specified). In AFIP series, acinic cell represented 17% of primary malignant salivary gland neoplasms and 6% of all (including benign) salivary gland neoplasms. Note: Data from the distant past may not be accurate, due to the past practice of classifying poorly differentiated acinic cell carcinomas as "unspecified adenocarcinomas", or "undifferentiated carcinomas".   National Cancer Data Base Report on Cancer of the Head and Neck: Acinic Cell Carcinoma (1985-1995) Henry T. Hoffman M.D., Lucy Hynds Karnell PhD, Robert A. Robinson MD, John A. Pinkston M.D., Herman R. Menck, MBA 8/27/98 (submitted) July 1999 published        
ACINIC CELL CARCINOMA HISTOLOGY: According to Batsakis et al, acinic cell carcinoma derives from progenitor reserve cells of the terminal tubules and intercalated ducts of salivary tissue. Batsakis et al demonstrated that varieties of acinic cell carcinoma occur within a histomorphologic spectrum defined by the lowest and highest grades. Low grade acinic cell carcinomas are broadly interpreted as those most closely resembling the architecture of a normal salivary lobule. High grade acinic cell carcinomas are poorly differentiated and resemble the early phases of embryonic development of acini. Although a single pattern usually dominates, mixtures of grades may be apparentwithin a single tumor. Solid, solid-lobular, papillary-cystic, follicular, microcystic, tubuloductal, and solid undifferentiated patterns have also been reported. Controversy persists regarding the prognostic value of assigning grade by histological analysis of acinic cell carcinoma.   National Cancer Data Base Report on Cancer of the Head and Neck: Acinic Cell Carcinoma (1985-1995) Henry T. Hoffman M.D., Lucy Hynds Karnell PhD, Robert A. Robinson MD, John A. Pinkston M.D., Herman R. Menck, MBA 8/27/98 (submitted) July 1999 published Some quoted from Batsakis JG (et al) - The pathology of head and neck tumors; salivary glands, Part 2: Head and Neck Surgery 1978;1: 167-171      
ACC HISTOLOGY AND PRIMARY SITE:  Although serous-type cells do not necessarily predominate in all cases, acinic cell carcinomas are commonly characterized by cytologic differentiation toward the serous acinar cells.  The parotid gland, which is dominated by serous cells, and is the largest of the major salivary glands, is also the most common site of acinic cell carcinoma. Acinic cell carcinomas are distinctly less common in the mixed serous and mucous submandibular and sublingual glands and in the predominantly mucous minor salivary glands.   National Cancer Data Base Report on Cancer of the Head and Neck: Acinic Cell Carcinoma (1985-1995) Henry T. Hoffman M.D., Lucy Hynds Karnell PhD, Robert A. Robinson MD, John A. Pinkston M.D., Herman R. Menck, MBA 8/27/98 (submitted) July 1999 published        
ACC Patient Profiles: Most reports have identified that acinic cell carcinoma presents at an earlier age than other salivary gland cancers, and affects women more commonly than men. Income grouping reflected a disproportionately large number of high-income cases (12.3%) relative to low-income cases (8.2%). Cases were predominantly white non-Hispanic (86.0%). ACC was more common in women (58.8%) than in men (42.2%). The median age at diagnosis was approximately 52 years, with 16.2% of cases among patients younger than 30 years. Women comprised a significantly larger proportion of this younger group (64.4%), than in older group (57.7%).   National Cancer Data Base Report on Cancer of the Head and Neck: Acinic Cell Carcinoma (1985-1995) Henry T. Hoffman M.D., Lucy Hynds Karnell PhD, Robert A. Robinson MD, John A. Pinkston M.D., Herman R. Menck, MBA 8/27/98 (submitted) July 1999 published        
ACC Tumor Statistics - SITE: The tumors arose in the parotid gland in 1167 cases (86.3%), and the submandibular gland in 37 cases (2.7%). 26 cases (1.9%) were recorded as arising in the major salivary glands, but without a specific gland identified. Only one case was identified as arising in the sublingual gland. The remaining 122 cases (9.0%) arose in sites other than the major salivary glands, which presumably reflect involvement of the minor salivary glands.   National Cancer Data Base Report on Cancer of the Head and Neck: Acinic Cell Carcinoma (1985-1995) Henry T. Hoffman M.D., Lucy Hynds Karnell PhD, Robert A. Robinson MD, John A. Pinkston M.D., Herman R. Menck, MBA 8/27/98 (submitted) July 1999 published        
ACC Extent of Disease: Among cases submitted by hospitals using the 3rd and 4th editions of the AJCC staging manual *: The median tumor size at the time of diagnosis was 2.0 cm. Approx. two thirds (67.4%) were stage I. The remainder were distributed between stage II (14.4%), stage III (11.0%), and stage IV (7.1%). At the time of initial presentation, disease was confined locally for 88% of the patients classified. Regional metastasis was identified in 9.9%, and distant metastasis in 2.1% of patients. Regional metastases, distant metastases and large tumor size were all more common among patients 30 years of age and older. Incidence of regional node involvement and cervical metastases are discussed, but not with an overall accurate rate. A previous study of 42 patients, which ended in 1978, had a median follow-up of 11 years. That review identified an overall regional metastatic rate of 11%, occuring either at presentation or as a recurrence. Distant metastases were identified in 13% of patients.   National Cancer Data Base Report on Cancer of the Head and Neck: Acinic Cell Carcinoma (1985-1995) Henry T. Hoffman M.D., Lucy Hynds Karnell PhD, Robert A. Robinson MD, John A. Pinkston M.D., Herman R. Menck, MBA 8/27/98 (submitted) July 1999 published        
* Over the time period covered, classification frequently employed editions of the AJCC staging manual that were outdated, which confounds comparisons of populations across different periods. Advances in imaging technology may also affect these statistics. Additionally, some systems employ three separate grade categories, whereas others employ four. There is also a recognized subjective nature of staging.   National Cancer Data Base Report on Cancer of the Head and Neck: Acinic Cell Carcinoma (1985-1995) Henry T. Hoffman M.D., Lucy Hynds Karnell PhD, Robert A. Robinson MD, John A. Pinkston M.D., Herman R. Menck, MBA 8/27/98 (submitted) July 1999 published        
ACC Grade of Disease: * Among those cases with recorded grade, grade I (57.8%) was most common, and grade 4 (4.6%) was least. Higher grade cancers were significantly associated with age 30 years or greater (p=.0024), advanced stage (p=.0002), and the presence of metastatic disease at presentation (p<.0001). This report also identifies a strong correlation between grade and aggressive behavior.   National Cancer Data Base Report on Cancer of the Head and Neck: Acinic Cell Carcinoma (1985-1995) Henry T. Hoffman M.D., Lucy Hynds Karnell PhD, Robert A. Robinson MD, John A. Pinkston M.D., Herman R. Menck, MBA 8/27/98 (submitted) July 1999 published        
ACC High Grade Variety: An aggressive subset of acinic cell carcinoma which is characterized by high grade and advanced stage rarely occurs in patients younger than 30 years old. The association between advanced grade and greater extent of disease at presentation clearly identifies this subset of acinic cell carcinomas with aggressive behavior and histologically determined differences. It is noteworthy that, although this higher grade did not appear to compromise the surgeons' capacity to obtain negative surgical margins, treatment with postoperative radiotherapy was used nearly three times more commonly for high grade than low grade varieties.   National Cancer Data Base Report on Cancer of the Head and Neck: Acinic Cell Carcinoma (1985-1995) Henry T. Hoffman M.D., Lucy Hynds Karnell PhD, Robert A. Robinson MD, John A. Pinkston M.D., Herman R. Menck, MBA 8/27/98 (submitted) July 1999 published        
Acc High Grade Variety:  The association between advanced grade and greater extent of disease at presentation clearly identifies a subset of acinic cell carcinomas with aggressive behavior and histologically determined differences. It is noteworthy that, although this higher grade did not appear to compromise the surgeons' capacity to obtain negative surgical margins, treatment with postoperative radiotherapy was used nearly three times more commonly for high grade than for low-grade acinic cell carcinomas.   National Cancer Data Base Report on Cancer of the Head and Neck: Acinic Cell Carcinoma (1985-1995) Henry T. Hoffman M.D., Lucy Hynds Karnell PhD, Robert A. Robinson MD, John A. Pinkston M.D., Herman R. Menck, MBA 8/27/98 (submitted) July 1999 published        
ACC Grade:  The association between tumor grade and biologic behaviorhas been well documented for many neoplasms but has remained controversial for acinic cell carcinoma. The assertion is made in the 1972 WHO mongraph that it is not possible to identify the small subset of acinic cell neoplasms that are likely to metastasize based on histologic features alone. Wide acceptance of this concept has resulted in the practice of lumping all acinic cell carcinomas into the same favorable prognostic group as low-grade mucoepidermoid carcinoma and low-grade adenocarcinoma without further segregating acinic cell carcinoma cases according to grade. This broad grouping has not notably affected most analyses, possibly because of the minor contribution made by the addition of the small number of cases of high-grade acinic cell carcinoma.   National Cancer Data Base Report on Cancer of the Head and Neck: Acinic Cell Carcinoma (1985-1995) Henry T. Hoffman M.D., Lucy Hynds Karnell PhD, Robert A. Robinson MD, John A. Pinkston M.D., Herman R. Menck, MBA 8/27/98 (submitted) July 1999 published        
ACINIC CELL CARCINOMA  TREATMENT STATISTICS:  Single modality treatment with surgery was employed in 64% of cases. Surgery with radiotherapy was employed in 30.1% of cases. Chemotherapy was used as adjuvant therapy along with surgery or radiotherapy in 1.0% of cases. Among patients receiving treatment of known type, surgery (alone or with adjuvant therapy) was employed in 1285 of 1345 cases (95%). Advanced stage and grade were highly associated with the more common use of surgery and radiotherapy. Lower stage and grade were most commonly treated with surgery alone.   National Cancer Data Base Report on Cancer of the Head and Neck: Acinic Cell Carcinoma (1985-1995) Henry T. Hoffman M.D., Lucy Hynds Karnell PhD, Robert A. Robinson MD, John A. Pinkston M.D., Herman R. Menck, MBA 8/27/98 (submitted) July 1999 published        
ACINIC CELL CARCINOMA TREATMENT PROTOCOLS: General guidelines for management of salivary gland cancer support surgical excision as the primary treatment. Supplemental irradiation has been reserved for those case with indicators of poor prognosis. Although better outcome was not statistically demonstrated for combined therapy, surgery with irradiation is the most common management in the United States for cases with regional metastases, high grade and microscopic positive margins. Although it is widely accepted that surgical excision is the preferred treatment for acinic cell carcinoma, debate continues regarding the extent of resection needed, as well as the role for neck dissection and adjuvant radiotherapy.   National Cancer Data Base Report on Cancer of the Head and Neck: Acinic Cell Carcinoma (1985-1995) Henry T. Hoffman M.D., Lucy Hynds Karnell PhD, Robert A. Robinson MD, John A. Pinkston M.D., Herman R. Menck, MBA 8/27/98 (submitted) July 1999 published        
ACC Treatment Protocols, contd - Neck Dissection: The practice of elective neck dissection in the treatment of high-grade salivary gland cancers has been widely advocated in the past. Others have suggested that an elective staging supraomohyoid selective neck dissection was useful not only for all high-grade salivary gland cancers, but also for those with primary tumors larger than 4 cm, regardless of grade. The weight of more recent publications appears to support a less aggressive surgical approach to the uninvolved neck. These reports propose that the few occult metastases that exist will be adequately addressed by postoperative radiotherapy.   National Cancer Data Base Report on Cancer of the Head and Neck: Acinic Cell Carcinoma (1985-1995) Henry T. Hoffman M.D., Lucy Hynds Karnell PhD, Robert A. Robinson MD, John A. Pinkston M.D., Herman R. Menck, MBA 8/27/98 (submitted) July 1999 published        
ACC Treatment Protocols, contd - Radiation: Some have recommended postoperative radiation for ALL cases of salivary gland cancer except for those tumors staged as T1N0 or T2N0 with low grade histology, which were excised with negative margins. Factors that have been reported as useful in supporting postoperative radiotherapy have been listed as: skin invasion, high grade, facial nerve paralysis, advanced stage (III or IV), and the presence of neck metastases. Salivary gland cancers in general and acinic cell in particular have traditionally been considered radioresistant. Over the past two decades, reports of improved locoregional control through use of postoperative radiotherapy have provoked a wider acceptance of the value of administering radiotherapy after surgery for cases with poor prognosis. Authors Note: This review does not mention Fast Neutron Radiation separately from all other forms of radiotherapy. (more below)   National Cancer Data Base Report on Cancer of the Head and Neck: Acinic Cell Carcinoma (1985-1995) Henry T. Hoffman M.D., Lucy Hynds Karnell PhD, Robert A. Robinson MD, John A. Pinkston M.D., Herman R. Menck, MBA 8/27/98 (submitted) July 1999 published        
ACC Treatment Protocols, contd - Radiation: It is noteworthy that NCDB reveals 5-year disease-specific survival for patients treated with surgery only was 96.8% compared with 88.2% for those receiving combined surgery and radiotherapy. HOWEVER, it is difficult to determine the true efficacy of radiotherapy based on this sampling becasue of the clear selection bias influencing use of postoperative radiotherapy. Despite the lack of data supporting its use for acinic cell carcinoma, in the United States, cases characterized by high grade, positive margins or nodal metastases are most commonly treated with combined surgey and postoperative radiotherapy. ACCIC Authors Note: This review does not mention Fast Neutron Radiation separately from all other radiotherapy.   National Cancer Data Base Report on Cancer of the Head and Neck: Acinic Cell Carcinoma (1985-1995) Henry T. Hoffman M.D., Lucy Hynds Karnell PhD, Robert A. Robinson MD, John A. Pinkston M.D., Herman R. Menck, MBA 8/27/98 (submitted) July 1999 published        
ACC Treatment Protocols, contd - Radiation: Salivary gland cancers in general and acinic cell carcinoma in particular have traditionally been considered radioresistant. Over the past two decades, reports of improved locoregional control through the use of postoperative radiotherapy have provoked a wider acceptance of the value of administering radiotherapy after surgery for cases with poor prognosis. It is noteworthy that the NCDB reveals 5-year disease-specific survival for patients treated with surgery only was 96.8%, compared with 88.2% for those receiving combined surgery and radiotherapy. It is difficult to determine the efficacy of radiotherapy based on this sampling because of the clear selection bias influencing postoperative radiotherapy.   National Cancer Data Base Report on Cancer of the Head and Neck: Acinic Cell Carcinoma (1985-1995) Henry T. Hoffman M.D., Lucy Hynds Karnell PhD, Robert A. Robinson MD, John A. Pinkston M.D., Herman R. Menck, MBA 8/27/98 (submitted) July 1999 published        
ACC Treatment Protocols, contd - Radiation: In the effort to address this bias, comparative analyses of subsets of patients with poor prognosis were performed to analyze for the impact of postoperative radiotherapy. Unfortunately, the numbers of evaluable cases was too small to offer definitive statements regarding the value of postoperative radiotherapy for cancers characterized by high grade, positive margins, or regional spread of disease at the time of presentation. The relative rarity of acinic cell carcinoma has prevented the execution of a study capable of statistically demonstrating improved survival for patients treated with postoperative radiotherapy. Despite the lack of data supporting its use for acinic cell carcinoma, in the United States, cases characterized by high grade, positive margins, or nodal metastases are most commonly treated with combined surgery and postoperative radiotherapy.   National Cancer Data Base Report on Cancer of the Head and Neck: Acinic Cell Carcinoma (1985-1995) Henry T. Hoffman M.D., Lucy Hynds Karnell PhD, Robert A. Robinson MD, John A. Pinkston M.D., Herman R. Menck, MBA 8/27/98 (submitted) July 1999 published        
Treatment Protocols, contd - Surgery: It is clear from reports of salivary gland cancer treated in the remote past that recurrence and survival is compromised when treatment is limited to excision by enucleation. Spiro et al indentified that among 67 cases of acinic cell carcinoma,the best results were observed in patients receving conservative operations. These investigators concluded that outcome was more dependent on the extent of of the tumor than the type of operation performed.   National Cancer Data Base Report on Cancer of the Head and Neck: Acinic Cell Carcinoma (1985-1995) Henry T. Hoffman M.D., Lucy Hynds Karnell PhD, Robert A. Robinson MD, John A. Pinkston M.D., Herman R. Menck, MBA 8/27/98 (submitted) July 1999 published        
ACC Recurrence Statistics: Because of limited data, and inaccuracies in record-keeping, this report did not provide overall statistics on recurrence. Some data is provided in report, but it cannot be used to determine an accurate overall percentage. (See "ACC Outcome" section later.)   National Cancer Data Base Report on Cancer of the Head and Neck: Acinic Cell Carcinoma (1985-1995) Henry T. Hoffman M.D., Lucy Hynds Karnell PhD, Robert A. Robinson MD, John A. Pinkston M.D., Herman R. Menck, MBA 8/27/98 (submitted) July 1999 published        
ACC Survival Statistics: Five year survival was 83.3% (observed) and 91.4% (disease specific) in this review. Worse survival was associated with high grade (p<.0001), age greater or equal to 30 years (p+.0055), the presence of metastatic disease (p,.0001) (regional or distant at presentation), and site of cancer in the submandibular gland. In this review, overall survival has been crudely estimated to be about 84%. But survival analyses should be interpreted with the understanding that 10 to 20 years follow-up is needed to identify the full impact of acinic cell carcinoma on extended survival. The indolent behavior of this cancer is underscored by reports that recurrent tumor has been identified up to 30 years after initial treatment.   National Cancer Data Base Report on Cancer of the Head and Neck: Acinic Cell Carcinoma (1985-1995) Henry T. Hoffman M.D., Lucy Hynds Karnell PhD, Robert A. Robinson MD, John A. Pinkston M.D., Herman R. Menck, MBA 8/27/98 (submitted) July 1999 published        
ACC Outcome:  Acinic cell carcinoma has been identified as the least aggressive of the salivary gland cancers. From a review of multiple reports, the most recent AFIP fascicle addressing salivary gland cancer identifies the overall recurrence rate for acinic cell carcinoma to be 35%. These investigators identified that death from persistent or recurrent disease occurred in 16%. Other reports have identified similar statistics, with the observation that prolonged survival despite persistence of disease is possible. The prolonged survival that may occur despite persistent disease appears to support the practice of managing incurable disease with aggressive treatment as needed for palliation. Disease characteristics reported to indicate a poor prognosis include location of tumor in the deep lobe of the parotid gland and presence of infiltrative margins, presumably because these factors influence completeness of excision. The current results demonstrate that incomplete excision is associated with a lower chance of survival.   National Cancer Data Base Report on Cancer of the Head and Neck: Acinic Cell Carcinoma (1985-1995) Henry T. Hoffman M.D., Lucy Hynds Karnell PhD, Robert A. Robinson MD, John A. Pinkston M.D., Herman R. Menck, MBA 8/27/98 (submitted) July 1999 published        
ACC Overview Conclusion: Survival was best for cases characterized by younger age and lower stage. Although better outcome was not statistically demonstrated for cases treated with combined therapy, surgery with radiotherapy is the most common management for cases with regional metastases, grades 3 or 4, and microscopic positive margins. The clear association identified between higher grade and aggressive behavior supports the wider application of a standardized approach to grading acinic cell carcinoma.   National Cancer Data Base Report on Cancer of the Head and Neck: Acinic Cell Carcinoma (1985-1995) Henry T. Hoffman M.D., Lucy Hynds Karnell PhD, Robert A. Robinson MD, John A. Pinkston M.D., Herman R. Menck, MBA 8/27/98 (submitted) July 1999 published        
The paradigm that human malignancies are monoclonal has been questioned during recent years by the finding of unrelated, cytogenetically aberrant clones in short-term cultures from certain tumour types, notably carcinomas of the breast, skin and upper aerodigestive tract. In order to analyse whether cytogenetically unrelated clones are also unrelated at the molecular level, we analysed the X-chromosome inactivation status in cell cultures from a cytogenetically highly polyclonal acinic cell carcinoma of the parotid gland. By using cell cultures dominated by a single abnormal clone, obtained through in vitro culturing for 3-5 passages, we showed that the different clones must indeed have originated from different cells.
  Cytogenetic and molecular genetic demonstration of polyclonality in an
acinic cell carcinoma.

Author: Jin C; Jin Y; Hšoglund M; Wennerberg J; Akervall J; WillŽen R; Dictor M; Mandahl N; Mitelman F; Mertens F
Address:
Department of Clinical Genetics, University Hospital, Lund, Sweden.
Source: Br J Cancer, 78(3):292-5
1998 Aug
Aug-98        
The mo