Skip to main content
Key Specialties
Cardiology Diabetology Endocrinology Gastroenterology Geriatrics and Gerontology Gynecology and Obstetrics Hematology Infectious Disease Internal Medicine Nephrology Neurology Oncology Pediatrics Respiratory Medicine Rheumatology Surgery
Congress Coverage
2024 ACC Congress 2023 ESMO Congress 2023 EASD Congress 2023 ERS Congress 2023 ESC Congress
Clinical Collections
Advances in Alzheimer’s

Keynote webinar | Spotlight on medication adherence

LIVE: Thursday 27th June 2024, 18:00-19:30 (CEST)
Join our expert panel to discover why you need to understand the drivers of non-adherence in your patients, and how you can optimize medication adherence in your clinics to drastically improve patient outcomes.
ADVANCED SEARCH
Log in
Top
Head and Neck Pathology
Published in: Head and Neck Pathology 4/2022

04-05-2022 | Original Paper

Immunohistochemical Profile of Polymorphous Adenocarcinoma of Minor Salivary Gland: A Systematic Review and Meta-Analysis

Authors: Taichiro Nonaka, Hidehiro Takei

Published in: Head and Neck Pathology | Issue 4/2022

Login to get access

Abstract

Polymorphous adenocarcinoma (PAC) is a rare variant of minor salivary gland tumors. Because of its architectural diversity, histological diagnosis of PAC can be difficult especially for small biopsies, and immunohistochemistry is of great help in differentiating it from its histologic mimics. The aim of this study is to conduct a systematic literature review to identify reliable immunohistochemical markers for PAC. We conducted an electronic literature search of the MEDLINE, ScienceDirect, SpringerLink, and Wiley Online Library databases, covering the literature published in the period between 1988 and 2021. The eligibility criteria included case reports and retrospective studies of PAC cases with details of immunohistochemical markers. Following the search and selection process, 32 studies with 409 cases were included in this systematic review. Overall, > 90% positivity was observed for pan-cytokeratin (CK) (97.3%), CK7 (96.8%), CK7/8 (97.4%), E-cadherin (90.0%), Vimentin (92.5%), S100 (97.0%), p63 (91.7%), and SOX10 (100%), while little to no positivity was observed for CK20 (0.0%), p40 (0.0%), and GFAP (5.0%). The average MIB-1 labeling index was 3.78%. The results of this systematic review indicate that CK7+/CK20−, p63+/p40−, S100+, Vimentin+, and GFAP– immunophenotype have diagnostic value for PAC. In addition, the use of S100, MSA, p40, and c-Kit provide additional layers of information helpful to differentiate PAC from adenoid cystic carcinoma, one of challenging differential diagnoses.
Literature
1.
Barnes L, Eveson JW, Reichart P, Sidransky D. World health organization classification of tumors: pathology and genetics of head and neck tumours. Lyon: IARC Press; 2005.
2.
Evans HL, Batsakis JG. Polymorphous low-grade adenocarcinoma of minor salivary glands. A study of 14 cases of a distinctive neoplasm. Cancer. 1984;53:935–42.CrossRef
3.
El-Naggar AK, Chan JKC, Grandis JR, Takata T, Slootweg PJ. World health organization classification of tumours: WHO classification of head and neck tumours. 4th ed. Lyon: IARC Press; 2017.
4.
Moher D, Liberati A, Tetzlaff J, Altman DG. Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement. PLoS Med. 2009;6:e1000097.CrossRef
5.
6.
Avci N, Deligonul A, Tolunay S, Cubukcu E, Fatih Olmez O, Ulas A, et al. Neoadjuvant chemotherapy-induced changes in immunohistochemical expression of estrogen receptor, progesterone receptor, HER2, and Ki-67 in patients with breast cancer. J BUON. 2015;20:45–9.
7.
Gnepp DR, Chen JC, Warren C. Polymorphous low-grade adenocarcinoma of minor salivary gland. An immunohistochemical and clinicopathologic study. Am J Surg Pathol. 1988;12:461–8.CrossRef
8.
Norberg LE, Burford-Mason AP, Dardick I. Cellular differentiation and morphologic heterogeneity in polymorphous low-grade adenocarcinoma of minor salivary gland. J Oral Pathol Med. 1991;20:373–9.CrossRef
9.
Regezi JA, Zarbo RJ, Stewart JC, Courtney RM. Polymorphous low-grade adenocarcinoma of minor salivary gland. A comparative histologic and immunohistochemical study. Oral Surg Oral Med Oral Pathol. 1991;71:469–75.CrossRef
10.
Simpson RH, Clarke TJ, Sarsfield PT, Gluckman PG, Babajews AV. Polymorphous low-grade adenocarcinoma of the salivary glands: a clinicopathological comparison with adenoid cystic carcinoma. Histopathology. 1991;19:121–9.CrossRef
11.
Skalova A, Simpson RH, Lehtonen H, Leivo I. Assessment of proliferative activity using the MIB1 antibody help to distinguish polymorphous low grade adenocarcinoma from adenoid cystic carcinoma of salivary glands. Pathol Res Pract. 1997;193:695–703.CrossRef
12.
Perez-Ordonez B, Linkov I, Huvos AG. Polymorphous low-grade adenocarcinoma of minor salivary glands: a study of 17 cases with emphasis on cell differentiation. Histopathology. 1998;32:521–9.CrossRef
13.
Araujo V, Sousa S, Jaeger M, Jaeger R, Loyola A, Crivelini M, et al. Characterization of the cellular component of polymorphous low-grade adenocarcinoma by immunohistochemistry and electron microscopy. Oral Oncol. 1999;35:164–72.CrossRef
14.
Curran AE, White DK, Damm DD, Murrah VA. Polymorphous low-grade adenocarcinoma versus pleomorphic adenoma of minor salivary glands: resolution of a diagnostic dilemma by immunohistochemical analysis with glial fibrillary acidic protein. Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 2001;91:194–9.CrossRef
15.
Penner CR, Folpe AL, Budnick SD. C-kit expression distinguishes salivary gland adenoid cystic carcinoma from polymorphous low-grade adenocarcinoma. Mod Pathol. 2002;15:687–91.CrossRef
16.
Simpson RH, Pereira EM, Ribeiro AC, Abdulkadir A, Reis-Filho JS. Polymorphous low-grade adenocarcinoma of the salivary glands with transformation to high-grade carcinoma. Histopathology. 2002;41:250–9.CrossRef
17.
Edwards PC, Bhuiya T, Kelsch RD. C-kit expression in the salivary gland neoplasms adenoid cystic carcinoma, polymorphous low-grade adenocarcinoma, and monomorphic adenoma. Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 2003;95:586–93.CrossRef
18.
Edwards PC, Bhuiya T, Kelsch RD. Assessment of p63 expression in the salivary gland neoplasms adenoid cystic carcinoma, polymorphous low-grade adenocarcinoma, and basal cell and canalicular adenomas. Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 2004;97:613–9.CrossRef
19.
Nagao T, Gaffey TA, Kay PA, Minato H, Serizawa H, Lewis JE. Polymorphous low-grade adenocarcinoma of the major salivary glands: report of three cases in an unusual location. Histopathology. 2004;44:164–71.CrossRef
20.
Nikitakis NG, Tosios KI, Papanikolaou VS, Rivera H, Papanicolaou SI, Ioffe OB. Immunohistochemical expression of cytokeratins 7 and 20 in malignant salivary gland tumors. Mod Pathol. 2004;17:407–15.CrossRef
21.
Andreadis D, Epivatianos A, Mireas G, Nomikos A, Poulopoulos A, Yiotakis J, et al. Immunohistochemical detection of E-cadherin in certain types of salivary gland tumours. J Laryngol Otol. 2006;120:298–304.CrossRef
22.
Beltran D, Faquin WC, Gallagher G, August M. Selective immunohistochemical comparison of polymorphous low-grade adenocarcinoma and adenoid cystic carcinoma. J Oral Maxillofac Surg. 2006;64:415–23.CrossRef
23.
Furuse C, Cury PR, Altemani A, dos Santos Pinto D, de Araujo NS, de Araujo VC. Beta-catenin and E-cadherin expression in salivary gland tumors. Int J Surg Pathol. 2006;14:212–7.CrossRef
24.
Curran AE, Allen CM, Beck FM, Damm DD, Murrah VA. Distinctive pattern of glial fibrillary acidic protein immunoreactivity useful in distinguishing fragmented pleomorphic adenoma, canalicular adenoma and polymorphous low grade adenocarcinoma of minor salivary glands. Head Neck Pathol. 2007;1:27–32.CrossRef
25.
Epivatianos A, Poulopoulos A, Dimitrakopoulos I, Andreadis D, Nomikos A, Vlahou S, et al. Application of alpha-smooth muscle actin and c-kit in the differential diagnosis of adenoid cystic carcinoma from polymorphous low-grade adenocarcinoma. Oral Oncol. 2007;43:67–76.CrossRef
26.
Meer S, Altini M. CK7+/CK20- immunoexpression profile is typical of salivary gland neoplasia. Histopathology. 2007;51:26–32.CrossRef
27.
Vargas PA, Cheng Y, Barrett AW, Craig GT, Speight PM. Expression of Mcm-2, Ki-67 and geminin in benign and malignant salivary gland tumours. J Oral Pathol Med. 2008;37:309–18.CrossRef
28.
Schwarz S, Muller M, Ettl T, Stockmann P, Zenk J, Agaimy A. Morphological heterogeneity of oral salivary gland carcinomas: a clinicopathologic study of 41 cases with long term follow-up emphasizing the overlapping spectrum of adenoid cystic carcinoma and polymorphous low-grade adenocarcinoma. Int J Clin Exp Pathol. 2011;4:336–48.
29.
Dultra FK, Barros AC, Schaer-Barbosa H, Figueiredo AL, Gurgel CA, Ramos EA, et al. Immunohistochemical assessment of CD1a-positive Langerhans cells and their relationship with E-cadherin in minor salivary gland tumors. J Oral Pathol Med. 2012;41:47–53.CrossRef
30.
Schwartz LE, Begum S, Westra WH, Bishop JA. GATA3 immunohistochemical expression in salivary gland neoplasms. Head Neck Pathol. 2013;7:311–5.CrossRef
31.
Argyris PP, Gopalakrishnan R, Pambuccian SE, Tosios KI, Koutlas IG. Polymorphous low-grade adenocarcinoma of the upper lip with metachronous myoepithelioma of the buccal mucosa. Oral Surg Oral Med Oral Pathol Oral Radiol. 2014;117:e441-448.CrossRef
32.
Zaib N, Mushtaq S, Mamoon N, Akhter N, Ayaz B. Immunohistochemical pattern of pleomorphic adenoma, polymorphous low grade adenocarcinoma and adenoid cystic carcinoma in minor salivary glands. J Dent (Tehran). 2014;11:38–46.
33.
Projetti F, Lacroix-Triki M, Serrano E, Vergez S, Barres BH, Meilleroux J, et al. A comparative immunohistochemistry study of diagnostic tools in salivary gland tumors: usefulness of mammaglobin, gross cystic disease fluid protein 15, and p63 cytoplasmic staining for the diagnosis of mammary analog secretory carcinoma? J Oral Pathol Med. 2015;44:244–51.CrossRef
34.
Rooper L, Sharma R, Bishop JA. Polymorphous low grade adenocarcinoma has a consistent p63+/p40- immunophenotype that helps distinguish it from adenoid cystic carcinoma and cellular pleomorphic adenoma. Head Neck Pathol. 2015;9:79–84.CrossRef
35.
Argyris PP, Wetzel SL, Greipp P, Wehrs RN, Knutson DL, Kloft-Nelson SM, et al. Clinical utility of myb rearrangement detection and p63/p40 immunophenotyping in the diagnosis of adenoid cystic carcinoma of minor salivary glands: a pilot study. Oral Surg Oral Med Oral Pathol Oral Radiol. 2016;121:282–9.CrossRef
36.
Xu B, Aneja A, Ghossein R, Katabi N. Predictors of outcome in the phenotypic spectrum of polymorphous low-grade adenocarcinoma (PLGA) and cribriform adenocarcinoma of salivary gland (CASG): a retrospective study of 69 patients. Am J Surg Pathol. 2016;40:1526–37.CrossRef
37.
Adkins BD, Geromes A, Zhang LY, Chernock R, Kimmelshue K, Lewis J Jr, et al. SOX10 and GATA3 in adenoid cystic carcinoma and polymorphous adenocarcinoma. Head Neck Pathol. 2020;14:406–11.CrossRef
38.
Atiq A, Mushtaq S, Hassan U, Loya A, Hussain M, Akhter N. Utility of p63 and p40 in distinguishing polymorphous adenocarcinoma and adenoid cystic carcinoma. Asian Pac J Cancer Prev. 2019;20:2917–21.CrossRef
39.
Varadhachary GR, Abbruzzese JL, Lenzi R. Diagnostic strategies for unknown primary cancer. Cancer. 2004;100:1776–85.CrossRef
40.
Kim JH, Rhee YY, Bae JM, Cho NY, Kang GH. Loss of CDX2/CK20 expression is associated with poorly differentiated carcinoma, the CpG island methylator phenotype, and adverse prognosis in microsatellite-unstable colorectal cancer. Am J Surg Pathol. 2013;37:1532–41.CrossRef
41.
Gleason BC, Fletcher CD. Myoepithelial carcinoma of soft tissue in children: an aggressive neoplasm analyzed in a series of 29 cases. Am J Surg Pathol. 2007;31:1813–24.CrossRef
42.
Yu G, Ma D, Sun K, Li T, Zhang Y. Myoepithelial carcinoma of the salivary glands: behavior and management. Chin Med J (Engl). 2003;116:163–5.
43.
Foschini MP, Gaiba A, Cocchi R, Pennesi MG, Pession A. p63 expression in salivary gland tumors: role of DeltaNp73L in neoplastic transformation. Int J Surg Pathol. 2005;13:329–35.CrossRef
44.
Ianez RF, Buim ME, Coutinho-Camillo CM, Schultz R, Soares FA, Lourenco SV. Human salivary gland morphogenesis: myoepithelial cell maturation assessed by immunohistochemical markers. Histopathology. 2010;57:410–7.CrossRef
45.
Seethala RR, LiVolsi VA, Zhang PJ, Pasha TL, Baloch ZW. Comparison of p63 and p73 expression in benign and malignant salivary gland lesions. Head Neck. 2005;27:696–702.CrossRef
46.
Evans HL, Luna MA. Polymorphous low-grade adenocarcinoma: a study of 40 cases with long-term follow up and an evaluation of the importance of papillary areas. Am J Surg Pathol. 2000;24:1319–28.CrossRef
47.
Nonaka D. A study of DeltaNp63 expression in lung non-small cell carcinomas. Am J Surg Pathol. 2012;36:895–9.CrossRef
48.
Bishop JA, Teruya-Feldstein J, Westra WH, Pelosi G, Travis WD, Rekhtman N. p40 (DeltaNp63) is superior to p63 for the diagnosis of pulmonary squamous cell carcinoma. Mod Pathol. 2012;25:405–15.CrossRef
Metadata
Title
Immunohistochemical Profile of Polymorphous Adenocarcinoma of Minor Salivary Gland: A Systematic Review and Meta-Analysis
Authors
Taichiro Nonaka
Hidehiro Takei
Publication date
04-05-2022
Publisher
Springer US
Published in
Head and Neck Pathology / Issue 4/2022
Electronic ISSN: 1936-0568
DOI
https://doi.org/10.1007/s12105-022-01453-6

Other articles of this Issue 4/2022

Head and Neck Pathology 4/2022 Go to the issue

Original Paper

Immunohistochemical Expression Pattern of Theragnostic Targets SSTR2 and PSMA in Endolymphatic Sac Tumors: A Single Institution Case Series

Original Paper

Evaluation of Expression Of ADAM 10 as a Predictor of Lymph Node Metastasis in Oral Squamous Cell Carcinoma—An Immunohistochemical Study

Original Paper

NKX3.1 Expression in Salivary Gland “Intraductal” Papillary Mucinous Neoplasm: A Low-Grade Subtype of Salivary Gland Mucinous Adenocarcinoma

Original Paper

Basal Cell Adenoma and Basal Cell Adenocarcinoma: a 50-year Experience From a Single Institution

Case Reports

Intrathyroidal Plasmacytoma with Pleomorphic Multilobated Bizarre Cells: A Rare Primary Clinicopathological Presentation Mimicking Anaplastic Carcinoma of Thyroid

Original Paper

Metastases to the Parotid Gland: Study from a Tertiary Care Centre