MARIA SAMARA, THOMOPOULOU ELENI GEORGIA

Face-to-Face:

Teaching of DIAGNOSTIC CYTOLOGY IN CLINICAL PRACTICEB consists of lectures, tutorials and laboratory practice. Attendance of Laboratory Practice and Tutorials is obligatory.

The lectures content is described above.

Tutorials (in 1-2 student groups with 1 instructor per group) review and extend the lectures into knowledge and fundamentals of cytology methodologies used.

Laboratory exercises (in 1-2 student groups, 1 instructor per group of 8-10 students) composing the students’ practical are complementary to the lectures and they aim to familiarize the student with clinical methods for obtaining cellular material,with the application ofoptical microscope for diagnosis, the operation of simple laboratory instruments and the procedures that are used
in aCytology laboratory as well as to help the students comprehend concepts that are not easily presented theoretically (learning based on practical experience).

MANDATORY ATTENDANCES – LECTURES: NO

Information and Communication Technologies are used for the preparation of the lecture material, the online information and provision of supplementary learning material to students.
Specifically:
• Common software (e.g. MS power-point) is used to prepare lecture material and display slides and videos.
• The study guide (detailed supplementary material & additional bibliography), the tutorial material (clinical cases), the theory and protocols of the laboratory exercises, the slides of each lecture as well as relevant videos and scientific articles made available electronically and online to students through the e-class system of our university.
• Information about the course, instructors andtheir research interests and in general the Pathology Department of the Faculty of Medicine are available online
• Common software (e.g.MS excel) is used to statistically process student assessment.
Announcements, information etc. are available online and via eclass. Communication is also done via e-mail.

The language of assessment is Greek.
Evaluation methods

A. For the laboratory practical: Laboratory Assignment Reports,Written Examination with short answer and problem-solving questions. Students’ participation in the exercises is mandatory. Successful examination of the Laboratory after presentation of laboratory work.

B. For the Tutorials:
The material of the tutorials is examined together with the lectures.

C. For the lecture material: Written Exams with multiple choice and True/False questions, short questions, oral examination of students with special needs.
The course exams are written, last 2 hours and consist of multiple choice or True/False questions and short questions. The material to be examined is lectures and tutorial material as described above.

Final Grade:
The final grade of the course is calculated as the sum of 60%of the grade of the written course exams and 40%of the grade of  the Laboratory work presentation.
All of the above are presented in detail to all students and posted electronically in e-class

Aims of the course
The aim of the course is to introduce students to the diagnostic approach of various pathological entities, inflammatory, precancerous lesions, benign and malignant neoplasms through the study of cytomorphological features. Furthermore, the course intends to provide students with knowledge and skills on the methods of obtaining cytological specimens and its laboratory management techniques, in order to understand its diagnostic capabilities and limitations. Teaching of individual pathological entities is based on the presentation of clinical cases (case-based learning), combining clinical presentation, laboratory and imaging findings with cytological diagnosis and correlation with the corresponding histology. The Classification Systems of cytological reports, widely used in contemporary everydaypractice, are also introduced. Emphasis is also given to immunocytochemical and molecular profile of neoplasms for diagnosis and therapeutic treatment.
The course aims students to understand cytological reports and include them in the context of diagnostic thinking. The course also aims to provide students with a thorough understanding of the ways in which Cytology actively intervenes in the clinical management of patients, with diagnosis, prevention of pathological conditions as well as study of prognostic and predictive biomarkers.

After the successful completion of this course, the students will be able to:
• Identify pathological entities based on their cytological diagnostic criteria
• Understand the cytological reports and integrates them into complex diagnostic thinking
• Understand the importance of clinical practice in Cytology (taking material from patients)
• Use the basic equipment of a Cytology laboratory and perform basic cytological techniques.
• Collaborate with fellow students in a laboratory environment

Α. LECTURES: The theoretical clinical skills that students must acquire to succeed in the course

1. Introduction to Cytology:
Definition and purpose of Cytology – differences from Pathological Anatomical – Historical overview–Methods of obtaining samples: Exfoliative Cytology, Fine Needle Assay (FNA), Endoscopic Cytology
Techniques for processing cytological materials: smears, Liquid phase cytology, Cytocentrifuge, cell block (techniques), Stains: Papanicolaou -Giemsa –Immunocytochemistry

2. The role of cytology in the prevention and diagnosis of lesions of the cervix:
Pap smears, past and current application. Sample collection and processing Morphology of normal cells – correlation with histology Diagnosis of inflammatory diseases correlation with clinical findings
Low-grade squamous intraepithelial lesions (LSIL), high-grade squamous cell carcinoma (HSIL),
Squamous carcinoma, Adenocarcinoma in situ of the cervix (AIS), Adenocarcinoma of the cervix:

Cytology correlation with clinical – colposcopic findings and with histology (with presentation of clinical cases)
Significance of the presence of endometrial cells in pap smears after menopause
The Bethesda system for classification of cytological reports and clinical management

3. HPV and oncogenesis
High and low risk subtypes, mechanisms of HPV oncogenesis, neoplasms associated with HPV infection
Population screening with HPV TEST
Molecular detection techniques (HPV DNA TEST, mRNA TEST, methylation),
HPV vaccine, age application and results

4. Cytological diagnosis of the respiratory system lesions
Sampling methods: sputum, bronchoscopy, EBUS TBNA, Percutaneous FNA
Importance of rapid on-site evaluation of the cytological specimen (ROSE) –utility of cell block
Morphology of normal cells – correlation with histology
Diagnosis of inflammatory diseases: Fungal infections, viral infections, Granulomatous inflammations – Cytology, correlation with clinical and imaging findings and with histology (with presentation of clinical cases)
Malignant neoplasms: Squamous carcinoma, Adenocarcinoma, Large cell carcinoma, Carcinoid, Small cell carcinoma – Cytology, correlation with clinical and imaging findings and with histology (with presentation of clinical cases)
Metastatic neoplasms in the lung-correlation with clinical and imaging findings (with presentation ofclinical cases)
WHO Reporting System for Lung Cytopathology
Investigation of molecular biomarkers in cytological material for targeted therapy.

5. Urine cytology and its role in the diagnosis of urothelial carcinoma
Historical overview- Methods of obtaining cytological material – Methods of processing samples
Clinical guidelines for urine cytology
Normal cells and correlation with histology
Regenerative changes in inflammation, Diagnosis of viral infections, Radiation and chemotherapy changes.-Cytology correlation with clinical and histological findings (with presentation of clinical cases)
Cytology of high-grade urothelial carcinoma and carcinoma in situ – correlation with histology – clinical and imaging findings (with presentation of clinical cases)
Squamous carcinoma, Adenocarcinoma Cytology – correlation with histology and clinical findings (with presentation of clinical cases)
The Paris system for reporting urinary cytology and its importance in clinical practice
Atypical urothelial cells – auxiliary methods for further investigation

6. Cytology of effusions – clinical significance in the diagnosis of neoplastic and non-neoplastic diseases
Physiology of fluid cavities: transudate, exudate
Method of obtaining effusions – management and processing methods
Normal cells and correlation with histology
Diagnosis of non-neoplastic diseases: Empyema, Eosinophilic pleuritis, Rheumatoid arthritis, Systemic lupus erythematosus – Cytology, correlation with clinical and imaging findings (with presentation of clinical cases),
Boerhaves syndrome (esophageal rupture): cytological diagnosis -correlation with clinical and imaging  findings (with presentation of a case)
Neoplastic diseases:
Mesothelioma, differential diagnosis from reactive mesothelial cells and from adenocarcinoma – Cytology, immunocytochemistry
Metastatic carcinomas – investigation of unknown primary site – Cytology, immunocytochemistry
correlation with clinical picture and imaging findings (with presentation of clinical cases)
Primary effusion lymphoma (PEL)
Clinical significance of cytological diagnosis of metastatic malignancy in pleural effusions for staging and therapeutic approach

7. Fine needle aspiration (FNA) cytology in the diagnosis and clinical management of thyroid lesions.
FNA techniques – Clinical and ultrasound criteria for selecting a nodule for FNA
Benign diseases: Nodular disease, Hashimoto’s thyroiditis, de Quervain’s thyroiditis – Cytology
correlation with histological clinical features and ultrasound findings (with case presentations)
Follicular neoplasm and Follicular neoplasm of acidophilic cells – Cytological features correlation with histology, clinical presentation and ultrasound findings (with case presentation)
Malignant neoplasms: Papillary carcinoma, Myeloid carcinoma, Anaplastic carcinoma, Lymphoma:
cytological picture correlation with histological with clinical picture and ultrasound findings (with presentation of clinical cases)
Metastatic neoplasms in the thyroid: most common types-cytological picture-immunocytochemistry,
correlation with clinical history (case presentations)
The Bethesda system for reporting thyroid cytopathology–adequacy, diagnostic categories and clinical management
Application of molecular tests in thyroid FNA, for the clarification of categories III, IV, V of the Bethesda system

8. Cytology in the clinical management of breast lesions
Nipple cytology, secretions and imprints: papillary neoplasm, Paget’s disease
Contribution of FNA to the triple diagnostic test: palpation-imaging-cytology
Normal breast: histology-cytology
Benign lesions: Fibrocystic disease, Breast cyst, Subareolar abscess, Gynecomastia, Fat necrosis –
Cytology correlation with histology, clinical and imaging findings (with presentation of clinical cases)
Neoplasms: Fibroadenoma, Phylloides tumor: Cytology correlation with histological with clinical and imaging findings(with case presentations)
Malignant neoplasms: Ductal carcinoma, Lobular carcinoma, Metaplastic carcinoma, -Cytology correlation with histology clinical and imaging findings (with presentation of clinical cases)
The IAC-Yokohama system for reporting breast cytopathology – diagnostic categories and clinical management
FNA of axillary lymph nodes for staging
Use of cell block in breast cytology for biomarkers (ER, PR, HER2)

9.Fine needle aspiration (FNA) cytology in the diagnosis and clinical management of salivary gland lesions
Salivary gland FNA – indications.
Normal tissue (cytology-histology)
Inflammatory lesions: Acute and Chronic sialadenitis, Granulomatous sialadenitis
Cystic lesions: a) with squamous epithelium (D/D branchial cyst, squamous carcinoma) b) with mucinous content: (D/D Retention cyst, well differentiated mucoepidermoid carcinoma)
Benign neoplasms: pleomorphic adenoma, Warthin’s tumor-Cytology correlation with histology with clinical and imaging findings (with presentation of clinical cases).
Basaloid neoplasms: Adenoma D/D Carcinoma (cytology-histology)
Malignant neoplasms: Mucoepidermoid carcinoma, Acinic cell carcinoma, Adenoid cystic carcinoma
Carcinoma ex pleomorphic adenoma, Salivary duct carcinoma, MALT lymphoma-Cytology, immunocytochemistry correlation with histology, clinical and imaging findings (with presentation of clinical cases).
The Milan system for reporting salivary gland cytopathology – adequacy, diagnostic categories and clinical management

10. The role of cytology in the diagnosis and clinical management of pancreatic lesions
Methods of obtaining cytology specimens: Endoscopic Ultrasound (EUS) FNA, Endoscopic Retrograde Cholangiopancreatography (ERCP)-laboratory management of cytological samples of solid and cystic lesions
Normal pancreatic tissue (cytology-histology)
Benign lesions: Acute, Chronic pancreatitis, Autoimmune pancreatitis, Cystic lesions: Pseudocyst, Lymphoepithelial cyst- Cytology correlation with histology, clinical and imaging findings (with presentation of clinical cases).
Benign neoplasms: serous cystadenoma
Malignant solid neoplasms: Pancreatic ductal adenocarcinoma, Acinar cell carcinoma, Neuroendocrine tumors (PAN NETS), Pancreatic neuroendocrine carcinoma (PAN NEC), Solid pseudopapillary tumor- cytology correlation with histological and clinical and imaging findings (with presentation of clinical cases).
Malignant cystic neoplasms: Intraductal papillary mucinous neoplasm (IPMN), Mucinous cystic neoplasm (MCN) -Cytology correlation with histological and clinical and imaging findings (with presentation of clinical cases).
GIST cytological picture, correlation with histological and clinical and imaging findings (with presentation of case).
WHO Reporting System for Pancreaticobiliary Cytopathology and corresponding clinical management.

11. Fine needle aspiration (FNA) cytology in the diagnostic approach of lympadenopathy
Indications for lymph node FNA in correlation with clinical and laboratory findings
Normal lymph node tissue (cytological-histological)
WHO Reporting System for Lymph Node, Spleen and Thymus Cytopathology for classification of cytological responses and corresponding clinical management
Benign diseases: Acute lymphadenitis, Lymphoid hyperplasia, Granulomatous lymphadenitis (TB, sarcoidosis, nail fungus)-Cytology, correlation with histological and clinical and laboratory findings, (with presentation of clinical cases).
Non-Hodgkin lymphomas: Follicular lymphoma, Small cell lymphoma/chronic lymphocytic leukemia,
Lymphoma from cells mantle, B-cell lymphoma from large cells, Burkitt lymphoma, Anaplastic large cell lymphoma-Cytology correlation with histological and with clinical and laboratory findings, (with presentation of clinical cases).
Hodgkin lymphoma Cytology correlation with histological and with clinical and laboratory findings, (with presentation of clinical cases).
Metastatic neoplasms -Cytological picture, correlation with histological, with clinical and laboratory findings,(with presentation of clinical cases).
The importance of flow cytometry and immunohistochemistry in the diagnosis ofneoplastic lesions of lymph nodes 
WHO Reporting System for Lymph Node Cytopathology

12. Fine needle aspiration (FNA) cytological examination in the diagnostic approach of soft tissue and bone tumors
Obtaining and handling the material. The importance of correlation with the clinical picture and imaging findings. The importance of obtaining material for immunocytochemistry and cytogenetic analysis (FISH).
Soft tissue tumors: Lipoma, Liposarcoma, Nodular Fasciitis, Schwannoma, Solitary fibrous tumor,
Synovial sarcoma, Granular cell tumor, Epithelioid hemangiosarcoma -Cytology, correlation with histology with clinical and imaging findings, (with presentation of clinical cases).
Bone tumors: Ewing sarcoma, Osteosarcoma, Chondrosarcoma, Chordoma, Langerhans’ histiocytosis,
Multiple Myeloma – Cytology, correlation with histology and with clinical and imaging findings, (with presentation of clinical cases).

13. Molecular test on cytological material-liquid biopsy
Detection and assessment of molecular biomarkers in clinical practice. Molecular techniques (PCR, FISH, NGS) – Role in diagnosis, prognosis, and treatment. Liquid biopsy – applications in the diagnosis and monitoring of common neoplasms.

B. TUTORIALS-LABORATORY PRACTICE
In the mandatory tutorials-laboratories learning is based on practical experience with the aim of acquiring general and specific practical & clinical skills:
• using optical microscope for diagnostic purposes
• familiarity with clinical methods for obtaining cellular material
• operating basic Cytology laboratory equipment
• familiarity with basic laboratory cytology techniques
• working as a team
• following safety regulations
• receiving and following instructionsdiagnosis using an optical microscope