Lecture 8 - Radiotherapy & Chemotherapy Changes .pdf

RADIOTHERAPY AND CHEMOTHERAPY CHANGES INTRODUCTION Radiotherapy and chemotherapy are modalities in treating malignancies including cervical carcinoma. Follow up vault or cervical smears are inecessary in monitoring the area for the possibility of local recurrence Produce cytologica...

RADIOTHERAPY AND CHEMOTHERAPY CHANGES INTRODUCTION Radiotherapy and chemotherapy are modalities in treating malignancies including cervical carcinoma. Follow up vault or cervical smears are inecessary in monitoring the area for the possibility of local recurrence Produce cytological changes on both benign and malignant cells which can mimic malignant squamous or glandular lesions in pap smears RADIOTHERAPY Disrupts cell function and division – Destroys nuclear DNA – Inhibits cell synthesis – Denaturing and coagulating cell proteins and enzymes. Results in a spectrum of degenerative and regenerative changes. Irradiated malignant cells usually disappear within 1 month after termination of radiotherapy Cellular changes may eventually disappear or may persist, for many years. RADIOTHERAPY Differential diagnosis to consider: 1. Radiation changes 2. Post radiation dysplasia Appearance of abnormal cellular changes in benign epithelial cell (1- 3mths after) 3. Persistent carcinoma 4. Recurrent cancer RADIATION CHANGES 2 phases – Acute radiation changes – Chronic radiation changes ACUTE RADIATION CHANGES Develop within 2 days after radiotherapy Continue for 6-8 weeks and disappear gradually subsequently Effect the malignant cells as well as cervical and vaginal epithelium. Cytological features: Marked cellular enlargement ( macrocyte ) Nuclear and cytoplasmic vacuolation. Acute inflammation. Multinucleated giant cells. Epithelial repair. ACUTE RADIATION CHANGES These parabasal cells show repair reaction, post-radiation. Marked cellular enlargement ACUTE RADIATION CHANGES NUCLEAR CHANGES: 1. Enlargement ( maintain normal N:C ratio) 2. Chromatin finely granular and bland 3. Hypochromasia/ normochromasia ACUTE RADIATION CHANGES NUCLEAR CHANGES: 4. Multinucleation/ binucleation 5. Intranuclear vacuoles ACUTE RADIATION CHANGES CYTOPLASMIC CHANGES: 1. Vacuolisation in cells 2. Cannibalism of cells 3. Perinuclear halos or vacuoles 4. Hyalinisation of cytoplasm with cell death ACUTE RADIATION CHANGES CYTOPLASMIC CHANGES: 5. Biphasic staining 6. Cytoplasmic enlargement 7. Bizarre shapes with cytoplasmic tails Endocervical cells ACUTE RADIATION CHANGES BACKGROUND CHANGES: 1. Exudate neutrophils, histiocytes, cell debris, blood, lymphocytes, giant cells 2. Radiosensitive malignant cells Degenerative changes Effect on malignant cells CHRONIC RADIATION CHANGES Develop 6 months or more after cessation of therapy May persist more than 20 years Reparative process Cytological features: Sheets of cells with multiple tails An atrophic pattern ( basal and parabasal) Multinucleation Nuclear and cytoplasmic vacuoles less prominent Nuclear and cytoplasmic enlargement Nuclei hyperchromatic, chromatin homogeneous Background of amorphous acellular pink material (replacing the acute inflammatory background) CHRONIC RADIATION CHANGES Cellular enlargement with nuclear hyperchromasia and cytoplasmic rills. CHRONIC RADIATION CHANGES Sheets of cells with multiple tails Less nuclear and cytoplasmic vacoulation Nuclei hyperchromatic, chromatin homogeneous CHRONIC RADIATION CHANGES Persistent radiation effect – Seen in cases 5 to 6 months after completion of radiotherapy – Cytological features: shows more crowded, atypical and hyperchromatic nuclei. – A diagnosis of atypical repair, a form of ASCUS, could be considered. CHRONIC RADIATION CHANGES Persistent radiation effect Endocervical cells with persistent large cytoplasmic vacuoles and distortion of cells configuration Atypical squamous cells with nuclear enlargement and nucleoli CHRONIC RADIATION CHANGES Persistent radiation effect Bizzare squamous cells seen 6 months after completion of radiotherapy Malignant cells after 4 months completion of radiotherapy CHRONIC RADIATION CHANGES Persistent radiation effect – The outcome: If absent of malignant cells; – Successful treatment If present of malignant cells; – Persistent carcinoma (never cured) – Post radiation dysplasia – Recurrent carcinoma POST RADIATION DYSPLASIA Develop after a latent period varying from several months to 20 years. Literature review: -18 to 26% of patient who received radiotherapy, develop dysplasia usually within 3 years of treatment. -About 30% of cases will regress. Majority either persist or progress. POST RADIATION DYSPLASIA Cytological features: Sheets or isolated squamous cells with slightly enlarged and hyperchromatic nucleus Chromatin finely granular, crysp, well preserved Micronucleoli may be present Multinucleation common Nucleo-cytoplasmic ratio increased Cytoplasm has indistinct cell borders, irregular cell contours and shapes (polygonal to oval or round), usually eosinophilic but may show biphasic staining POST RADIATION DYSPLASIA Cell Radiation changes Dysplasia Enlarged Normal size Cytoplasm Biphasic staining Cyanophilic or eosinophilic Vacuoles Absent in sq cells N:C ratio Normal increased Multiple, bland nuclei Single nucleus Hypo/normochromic Usually Nucleus hyperchromatic Homogeneous Granular, coarse or chromatin fine chromatin Vacuoles No vacuoles POST RADIATION DYSPLASIA Singly dysplastic cells with enlarged nuclei Sheet of dysplastic cells showing large granular nuclei with prominent nucleoli and mitoses PERSISTENT CARCINOMA Malignant cells seen during the course of treatment or shortly after cessation These cells have hyperchromatic and pleomorphic nuclei and well preserved chromatin May exhibit nuclear and cytoplasmic radiation changes RECURRENT CARCINOMA Malignant cells detected after a tumour free interval of 6 months or more. In patients with squamous cell carcinoma, presence of atypical cells within 3 years of disease may strongly suggests a recurrent carcinoma. Cytological features: Presence of HSIL cells with no evidence of radiation changes. RECURRENT CARCINOMA Large dark nuclei Nuclei variation in size and shaped, sometime showing moulding Abnormal chromatin pattern Prominent nucleoli Background of rbcs M1 RECURRENT CARCINOMA Smear from a known of SCC of cervix, treated with radiation. This smear is taken 15 years after radiptherapy. CHEMOTHERAPY Used in treatment of certain disease or condition. Alone or with radiotherapy Chemotherapy causes systemic effect, hence affect multiple tissues. Changes can be seen in cervical, vaginal, urinary and bronchopulmonary epithelium CHEMOTHERAPY Cytological features: – Nuclei - large and hyperchromatic - chromatin may be coarsely granular or smudged - nuclear membrane smooth - N:C ratio normal - multinucleation, binucleation - Vacuoles – Cytoplasm - vacuoles Changes revert to normal after cessation of treatment CHEMOTHERAPY Examples of chemotherapy: 1. Cytotoxic drugs Used in treatment of certain tumour like hematological malignancy and also as palliative treatment of advanced inoperable tumour Cytological changes similar to radiotherapy Large abnormal nuclei Multinucleation CHEMOTHERAPY Examples of chemotherapy: 1. Cytotoxic drugs Nuclear enlargement and hyperchromasia in an atrophic cervical smear in women treated with busulfan for CML CHEMOTHERAPY Examples of chemotherapy: 2. Immunosuppressive drugs – Inhibits immunological defence mechanism of the body – Used as treatment for many condition and also in organ transplant – Increase the risk of HPV infection CHEMOTHERAPY Examples of chemotherapy: 2. Immunosuppressive drugs Atypical squamous cells in a transplant patient. The changes vanished after reduced the dosage of immunosuppressive drugs. THANK YOU