International Cytology Guidelines

The following international standardised systems for cytopathology reporting have been endorsed by the RCPA Cytopathology Advisory Committee and the Cancer Services Advisory Committee.

These international standards are currently not the subject of any published or planned RCPA Structured Pathology Reporting of Cancer protocols.

Laboratories should reference the reporting system in their report.


Development of the Milan System was initially proposed in 2015, with the support of the American Society of Cytopathology and the International Academy of Cytology. The system aims to enable triage of salivary gland lesions by identifying those requiring significant clinical management. A unique category in the system is “neoplasm” which is subdivided into benign and uncertain malignant potential groups. These categories address the limitations in cytological diagnosis of some salivary gland neoplasms which have overlapping morphological features. The aims are to optimise patient management. Aggressive surgery would be avoided in equivocal cases. Risk of malignancy ranges are provided for each category based on the currently available literature; these parameters may be modified as further evidence is available following implementation of the Milan System.



Faquin WC, Rossi ED, Baldoch Z (Eds.). The Milan System for Reporting Salivary Gland Cytopathology. Bazel, Switzerland: Springer International Publishing AG; 2018.


Accurate cytological assessment of urine and communication of results allow for optimal management pathways for patients. A perceived lack of clinical application of urine cytology reports led to the concept of an improved reporting system at the International Academy of Cytology Congress in Paris May 2013. An international working group followed, led by Drs Rosenthal and Wojcik.

The main goal of the Paris System is detection of the clinically important high-grade urothelial carcinoma. The shortcomings of cytological diagnosis of low-grade urothelial neoplasia are acknowledged in this system, with strict criteria required for diagnosis. Indiscriminate use of equivocal categories has also been an issue in urine cytology. Standardised morphological criteria are provided in the atypical and suspicious categories in this system.



Rosenthal DL, Wojcik EM, Kurtycz DFI (Eds.). The Paris System for Reporting Urinary Cytology. 1st ed. Cham, Switzerland: Springer International Publishing AG; 2016.


The development of this system began with a meeting, sponsored by the International Academy of Cytology (IAC), of a group of cytopathologists with an interest in breast fine needle aspiration biopsy cytology at the International Congress of Cytology in Yokohama in May 2016. The System defines five categories for reporting breast cytology, each with a clear descriptive term for the category, a definition, a risk of malignancy and a suggested management algorithm. The System is intended for global use, is based on cytomorphology and includes key diagnostic cytological criteria for each of the many lesions and tumours found in the breast. The System emphasizes that biopsy and smear making techniques of a high standard are essential to optimize quality and enhance breast fine-needle aspiration biopsy (FNAB) diagnosis.

The five categories are:

  • Insufficient/Inadequate
  • Benign
  • Atypical
  • Suspicious of malignancy.
  • Malignant

The standardized structured report should state one of these five descriptive terms as a diagnostic heading, then include a brief cytological description, noting the presence or absence of key diagnostic features, and follow with a conclusion or summary providing as specific a diagnosis of the lesion as possible. If the diagnosis is uncertain, the most likely differential diagnoses should be provided. A category number, 1, 2, 3, 4 or 5 for insufficient, benign, atypical, suspicious of malignancy and malignant respectively, can be stated in the body of the report to assist with quality assurance and research, but not as a replacement for the actual diagnosis or the descriptive category terminology.


The smears are too sparsely cellular or too poorly smeared or fixed to allow a cytomorphological diagnosis.

 A laboratory and its cytopathologists should select either ‘insufficient’ or ‘inadequate’ and use this term consistently. FNAB smears are regarded as adequate or inadequate based on the assessment of the material on the slides. This may not require epithelial material to be present if the cytological findings correlate with the clinical and imaging findings (the triple test).
If there is a mass lesion on palpation or imaging, which does not decrease in size on FNAB, the presence of seven tissue fragments, each of 20 or more epithelial cells, are suggested as a measure of adequacy. If there are any atypical features or necrosis, even if there are fewer than 7 tissue fragments, the case should be reported as atypical. The reason for the categorization as insufficient/inadequate should always be stated in the report.

Definition BENIGN

Unequivocally benign cytological features, which may or may not be diagnostic of a specific benign lesion.

Definition ATYPICAL

The presence of cytological features seen predominantly in benign processes or lesions, but with the addition of some features that are uncommon in benign lesions and which may be seen in malignant lesions.

The decision was made to include an ‘atypical’ category in order to maximize the negative predictive value (NPV) of a ‘benign’ diagnosis and a ‘suspicious of malignancy’ category to maximize the positive predictive value (PPV) of a ‘malignant’ diagnosis. The majority of ‘atypical’ cases will be benign proliferative lesions and the majority of suspicious lesions will be in situ or low grade carcinomas.


The presence of some cytomorphological features which are usually found in malignant lesions, but with insufficient malignant features, either in number or quality, to make a definitive diagnosis of malignancy. The type of malignancy suspected should be stated whenever possible.

 Low-grade Ductal carcinoma in situ (LGDCIS) most typically produces highly cellular smears, a pattern of large tissue fragments showing a cribriform, micropapillary or papillary architecture, a variable but often marked increase in dispersed single cells showing mild to moderate nuclear atypia, a greatly reduced number or total lack of myoepithelial cells associated with the epithelial tissue fragments, and scanty or absent bare bipolar nuclei in the background. Recognition of these features prevents undercalling LGDCIS as a proliferative lesion, and overcalling LGDCIS as invasive carcinoma. Although controversial in relation to the specific diagnosis of LGDCIS, the categorization of these lesions as ‘suspicious of malignancy’ is recommended.

The diagnosis of high-grade ductal carcinoma in situ (HGDCIS) by FNAB is also controversial. FNAB cannot diagnose HGDCIS to the exclusion of invasive carcinoma. In FNAB cytology smears HGDCIS has been reported to be associated with necrosis, calcifications and high grade nuclear atypia seen in dispersed single cells and in both small and larger crowded epithelial tissue fragments. The smears are often of low cellularity. These findings cannot exclude high grade invasive carcinomas.
Definition MALIGNANT

A malignant cytological diagnosis is an unequivocal statement that the material is malignant, and the type of malignancy identified should be stated whenever possible.



Field AS, Raymond WA, Rickard M et al. The International Academy of Cytology Yokohama System for Reporting Breast Fine Needle Aspiration Biopsy Cytopathology. Acta Cytologica 2019;63:257-273.
Field AS, Raymond WA, Schmitt F (Eds.). The International Academy of Cytology Yokohama System for Reporting Breast Fine Needle Aspiration Biopsy Cytopathology. Springer Nature Switzerland AG 2020.


A structured reporting system for pancreas and biliary tract cytology was developed by the Papanicolaou Society in 2014 with the aim to provide a standardised scheme to clearly communicate cytological results to clinicians, including implied risk of malignancy. The system also facilitates clinical audit and comparison of results with other centres. When indicated, the system incorporates ancillary studies, including biochemistry, imaging and molecular studies, to improve test performance.  Investigation of pancreatic and biliary abnormalities, including pancreatic cysts, has increased over recent years, in part due to more frequent and improved imaging studies, as well as the introduction of endoscopic ultrasound (EUS) guided biopsy. EUS cytology has revolutionised the assessment of such lesions. The guidelines for Pancreaticobiliary cytology developed by the Papanicolaou Society of Cytopathology appear to be readily adaptable to the Australasian setting. It is recommended reports have 3 sections: Specimen quality, Cytological interpretation, and specific diagnosis (where possible). Cytological interpretation comprises 6 categories and includes a novel split category of Neoplastic (Neoplastic Benign or Neoplastic Other).
Cases insufficient for diagnosis (qualitative and/or quantitative). Reserved only for those specimens in which no useful information about the lesion can be obtained.  Any cytological atypia precludes use of this category. For cystic lesions, placing an acellular specimen in this category may be avoided by incorporating mucin stains, biochemistry, imaging, and/or molecular studies. See reference (Chai et al, 2013) for a suggested triage protocol for fluid samples.
Adequate cellular or non-cellular material to define a non-neoplastic lesion. No specified minimum material is required. Included are findings of benign pancreatic tissue, pancreatitis (acute, chronic, autoimmune), pseudocyst, lymphoepithelial cyst, splenule or accessory spleen. Imaging findings must be considered when normal pancreas is present; a negative diagnosis may be appropriate when there is no distinct mass on imaging, but the sample would be more appropriately designated as non-diagnostic in the setting of a mass lesion.
A heterogeneous category which includes atypia in excess of reactive change, atypia in a low cellularity sample, premalignant changes (eg dysplasia in bile duct brushings) or features suggestive, but not diagnostic, of a low grade neoplasm such as a pancreatic neuroendocrine tumour or solid pseudopapillary neoplasm.

NEOPLASTIC BENIGN. Samples recognised to originate from benign neoplasms, including serous cystadenoma, neuroendocrine microadenoma (<5mm) and lymphangioma.

NEOPLASTIC OTHER. Samples recognised to originate from neoplasms that are premalignant or of low malignant potential.  Included are well differentiated neuroendocrine tumour, intraductal papillary mucinous neoplasm (IPMN), mucinous cystic neoplasm (MCN) and solid pseudopapillary neoplasm. Determination of mucinous aetiology by CEA analysis of cyst fluid assists identification of neoplastic mucinous cysts.

Grading of dysplasia in IPMN and MCN is performed to help determine management, as high grade dysplasia is typically treated surgically.
Specimens with features concerning for malignancy but insufficient (qualitative or quantitative reasons) for a definitive diagnosis of malignancy.
Clear malignant morphology is present. Diagnoses include ductal adenocarcinoma, cholangiocarcinoma, acinar cell carcinoma, poorly differentiated neuroendocrine carcinoma, lymphoma and metastatic malignancy.



Pitman MB, Layfield L. The Papanicolaou Society of Cytopathology System for Reporting Pancreaticobiliary Cytology. Definitions Criteria and Explanatory Notes. Springer Nature 2015.
Pitman MB, Layfield LJ. Guidelines for Pancreaticobiliary Cytology from the Papanicolaou Society of Cytopathology: A Review. Cancer Cytopathology 2014;122:399-411.
Chai SM, Herba K, Kumarasinghe MP et al. Optimizing the Multimodal Approach to Pancreatic Cyst Fluid Diagnosis. Developing a Volume-Based Triage Protocol. Cancer Cytopathol. 2013;121:86-100.
McKinley M, Newman M. Observations on the application of the Papanicolaou Society of Cytopathology standardised terminology and nomenclature for pancreaticobiliary cytology. Pathology 2016; 48(4): 353-6.

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