Salivary Gland Cytology: A Clinical Approach to Diagnosis and Management of Atypical and Suspicious Lesions

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Salivary Gland Cytology: A Clinical Approach to Diagnosis and Management of Atypical and Suspicious Lesions W.C. Faquin, M.D., Ph.D. Massachusetts General Hospital Harvard Medical School, USA Marc Pusztaszeri, MD, Geneva, Switzerland Esther Diana Rossi, MD, Rome, Italy

Reporting System for Salivary Gland FNA Why do we need a new reporting system for salivary gland cytology?

Salivary Gland FNA Diagnostic Terminology Current reporting confusion: Diversity of diagnostic categories, vs. Descriptive reports (no categories), vs. Surgical pathology terminology General agreement on the need for a defined set of diagnostic categories for salivary gland FNA

The Milan System for Reporting Salivary Gland Cytopathology Proposed Classification Scheme 1) Non-Diagnostic 2) Non-Neoplastic 3) Atypia of undetermined significance 4) Neoplastic: a) Benign b) Uncertain malignant potential 5) Suspicious for Malignancy 6) Malignant

The Benefits of a Uniform Reporting System for Salivary Gland Cytopathology Improve communication between pathologists and clinicians Improve patient care Facilitate cytologic-histologic correlation Facilitate research into the epidemiology, molecular biology, pathology, and diagnosis of salivary gland diseases Facilitate sharing of data from different laboratories for collaborative studies

The Milan System for Reporting Salivary Gland Cytopathology Sponsored by the ASC and the IAC The goal is to produce a practical classification system that will be user-friendly and internationally accepted. The system will be evidence-based, and will provide a useful & uniform format for clinicians who treat salivary gland disease.

The Milan System for Reporting Salivary Gland Cytopathology Core Group and over 40 Participants from 14 Countries Co-Chairs: Bill Faquin, MD, PhD & Diana Rossi, MD Zubair Baloch, MD, PhD Guliz Barkan, MD Maria Pia Foschini, MD Daniel Kurtycz, MD Marc Pusztaszeri, MD Philippe Vielh, MD

The Milan System for Reporting Salivary Gland Cytopathology Dr. Marc Pusztaszeri Geneva University Hospitals Switzerland

Non-Diagnostic Insufficient quantitative and/or qualitative cellular material to make a cytologic diagnosis. At present no set validated adequacy criteria has been established in the literature. This diagnostic category should only be used when the entire material is processed and examined.

Non-Neoplastic Specimens lacking cytomorphologic evidence of a neoplastic process; consisting of benign acinar and/or ductal epithelium with or without inflammatory component, metaplastic and reactive changes (includes benign entities such as: acute and chronic and granulomatous sialadenitis, sialolithiasis, sialadenosis, etc ) Specimens showing evidence of reactive lymphoid tissue (flow cytometry is recommended based on clinical and morphologic suspicion). The ROM for this category is expected to be low (0-20%) if strict criteria are used for inclusion Clinico-radiological correlation is essential to ensure that the specimen is representative of the lesion.

Atypia of Undetermined Significance Cytologic features of greater dysmorphology than those assigned to the Non Neoplastic category but falling qualitative or quantitative short of those assigned to the Suspicious for Malignancy category, and an insufficient number of features for diagnosis of a Neoplasm (Neoplastic category). AUS favors a benign-non neoplastic process, but cannot entirely exclude a neoplasm (benign or malignant) after examination of all the cellular material. These samples are therefore indeterminate for a neoplasm. A majority of these samples will represent reactive atypia or poorly sampled neoplasms. A contributing factor to the uncertainty is often (but not always) specimens that are compromised due to scant cellularity and/or preparation artifacts (eg, air-drying, blood clot). The AUS diagnostic category is needed to accommodate certain FNA samples, but should be used rarely (<10 % of all salivary gland FNAs).

Neoplasm i) Benign Neoplasm: Reserved for clear-cut benign neoplasms diagnosed based on established cytologic criteria This category will include classic cases of PA, WT, lipoma, etc ii) Salivary Gland Neoplasm of Uncertain Malignant Potential: Reserved for FNA specimens which are diagnostic of a neoplasm; however, a diagnosis of a specific entity cannot be made. This diagnosis should be used for cases where a malignant neoplasm cannot be excluded. A majority of these cases will include cellular benign neoplasms, neoplasms with atypical features, and low grade carcinomas (eg, basaloid tumors, oncocytic tumors, atypical PAs, etc ).

Suspicious for Malignancy This category is for aspirates of neoplasms which show features that are highly suggestive of carcinoma but are not unequivocal for carcinoma (ROM: 70-80%). An attempt should be made to sub-categorize these FNA specimens as suspicious for low grade vs high grade carcinoma. A majority (but not all) of specimens in this category will be high grade carcinomas.

Malignant This category is for aspirates which are diagnostic of malignancy. An attempt should be made to sub-classify these aspirates into specific types and grades of carcinoma: eg, low grade (low grade mucoepidermoid carcinoma) vs high grade (salivary duct carcinoma). Other malignancies such as lymphomas, sarcomas and metastases are also included in this category and should be specifically designated.

SALIVARY workshop Esther Rossi MD PhD MIAC Division of Anatomic Pathology and Cytology Catholic University of Sacred Heart Rome, Italy

LIQUID-BASED CYTOLOGY (LBC) Collect all the aspirated material in the same vial Rinse the needle and the syringe in a hemolytic and preservative solution (skip the smearing step) Obtain a slide made up of an uniform layer of the cells present in the vial

RINSE IN THE HEMOLYTIC SOLUTION THE NEEDLE IS LEFT IN THE SOLUTION THE THIN PREP 2000 TM DEVICE COMPARISON BETWEEN LBC AND CONV.

LIQUID-BASED CYTOLOGY (LBC):ADVANTAGES All the material is processed and the procedure is standardized The cells are immediately preserved and the erythrocytes with the fibrin are lysated The cells are layered on a single slide Store a variable amount of cells for being used for further investigations (up to six months after the FNAB)

LIQUID-BASED CYTOLOGY (LBC): LIMITS It is not cost-effective in the short term The technical work is higher than conventional Some morphological features are different in conventional smears compared to LBC The on-site assessment of the material adequacy is not possible

Conventional FNAB and LBC 1) Background (less tissue fragments in LBC) 2) Stromal material: denser, in fragments and small droplets in LBC 3) Cells: slightly smaller and uniform cytoplasms, better nuclear details in LBC

WHAT S ABOUT LBC?

LBC of salivary glands Red blood cells, lymphocytes, infammatory cells may be filtered and minimally represented Larger clusters of cells broken into smaller or single Reduced complexity of cellular groups Cells may appear relatively smaller and more spherical Nucleoli are more conspicuous Chromatin detail is not always crisp Extracellular matrix is altered in quality and quantity Rarick JM et al, Acta Cytol 2014; 58: 552-62

What s about LBC?

WHICH EXAMINATION CAN BE CARRIED OUT ON THE CELLULAR MATERIAL? Immunocytochemistry molecular biology