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Sofia Asioli

Assistant professor

Department of Biomedical and Neuromotor Sciences

Academic discipline: MED/08 Pathology

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ANATOMIC PATHOLOGY 12 cfu (6 per Semester – IV year Medical School) Program for Tracks A, B and C

ANATOMIC PATHOLOGY

12 cfu (6 per Semester – IV year Medical School)

Program for Tracks A e B

(revised July 25, 2017)

LEARNING OUTCOMES

Full knowledge of normal anatomy, histology and embriology are necessary to understand Anatomic Pathology. As Professor Pierre Masson (Montreal, 1968) used to say to understand what is different (Anatomic Pathology) you first need to know the norm. One can not understand specific organ systems disorders if the knowledge of General Pathology is missing. Knowledge of immunology and genetics are also important to understand Anatomic Pathology. Topics discussed during lectures represent an integral part of the program and are the subject of evaluation during exams, including knowledge of tissue fixation and of pathology reporting (biopsies, surgical specimens, autopsies).

Objective of the course is to supply the student with the intellectual tools to understand:

  • The principal epidemiologic, morphologic, phenotypic, clinicopathologic features, as well as the main mechanisms in the etiopathogenesis of the most important neoplasms (including the concepts of grading and staging), and of the most important non neoplastic disorders, of the following organs and systems: cardiovascular, respiratory, gastrointestinal, liver and biliary system, pancreas, kidney, urinary tract, male and female reproductive systems, breast, endocrine system, central and peripheral nervous systems, musculoskeletal and osteoarticular systems, skin, hematopoietic and lymphoid systems.
  • The methods necessary for the processing of tissue samples and for the diagnostic procedures of Anatomic Pathology.

The student at the end of the course should be able to:

  • Correctly interpret the diagnoses of the pathologic conditions mentioned above, with a clear understanding of their value for the definition of patient prognosis and treatment.
  • Be able to appreciate the adequacy of the procedures that have lead to the diagnosis.
COURSE CONTENTS

Cardiovascular Diseases

Congenital heart diseases: principal alterations.

Ischemic heart disease: pathogenesis and morphological features of angina pectoris, chronic ischemic heart disease, myocardial infarction (timing of the progression of ischemic necrosis in myocardial infarction: evaluation methods).

From necrosis to regenerative process: Evolution of morphologic changes in myocardial infarction.

Pericarditis associated with myocardial infarction.

Myocardial rupture: timing and morphology.

Cardiogenic shock (pump failure): principal alterations. Scarring of necrotic myocardium. Ventricular aneurysm as myocardial infarction consequence and complication. Cerebral complications of myocardial infarction.

Sudden cardiac death.

Valvular heart disease: morphology and pathogenesis of: rheumatic heart disease, aortic stenosis, mitral valve prolapse, infective endocarditis, non-bacterial thrombotic endocarditis; artificial valves.

Myocardial diseases: pathogenesis and morphological features of myocarditis and cardiomyopathies, dilated cardiomyopathy, hypertrophic cardiomyopathy, restrictive cardiomyopathy (amyloidosis) and arrhythmogenic cardiomyopathy.

Pericardial disease: pathogenesis and morphological features of percicarditis and pericardial effusion and hemopericardium.

Blood vessel diseases: pathogenesis and morphological features, arteriosclerosis and atherosclerosis, restenosis after endovascular procedures (e.g. ballon angioplasty and endovascular stents), hypertensive vascular disease, autoimmune disease and accelerated atherosclesosis.

The vasculitides, polyarteritis nodosa (principal alterations), ANCA-associated vasculitides, giant cell (temporal) arteritis, Takayasu arteritis, thromboangiitis obliterans (Buerger disease).

Problems in the classification of vasculitides. Pathogenesis of vasculitides.

Aneurysms: congenital and acquired vascular aneurysm (atherosclerotic, aortitis and syphilitic aneurysm).

Aortic dissection and Marfan Disease.

Diseases of the respiratory sysetm
Obstructive pulmonary diseases. Pathology and pathogenesis of chronic bronchitis, emphysema, asthma, bronchiectasis.
Restrictive pulmonary diseases. Pathology and pathogenesis of:

- acute restrictive diseases: diffuse alveolar damage (respiratory distress syndrome of adult and infant).

- chronic restrictive diseases: classification of various types of histological patterns in interstitial lung disease. End-stage lung disease: 'honeycomb' lung.

Idiopathic interstitial Pneumonias. Classification and differential diagnosis (usual interstitial pneumonia, non specific interstitial pneumonia, cryptogenic organizing pneumonia).
Pneumoconioses. Pathological findings and differential diagnosis (in particular silicosis and asbestosis).

Hypersensitivity pneumonia.
Granulomatous lung diseases. Sarcoidosis and tuberculosis (and their differential diagnosis).
Non-neoplastic smoke-related lung disease: chronic obstructive pulmonary disease, desquamative interstitial pneumonia, small airways disease/respiratory bronchiolitis, Langerhans cell histiocytosis of the lung.

Pulmonary edema.
Vascular disorders of the lung. Pathology and pathogenesis of: thromboembolism, pulmonary infarction and hemorrhage. Pulmonary hypertension (primary and secondary) and vascular sclerosis.
Lung infections. Pathology and pathogenesis of: acute bacterial pneumonia and bronchopneumonia, primary atypical pneumonia, lung abscesses, Cytomegalovirus and Pneumocistis carinii infections.
Pleural lesions. Pleuritis and pleural tumors (solitary fibrous tumors, malignant mesothelioma and metastatic tumors). The pleural plaque.
Lung tumors.
Molecular pathology and pre-invasive lesions.
Histologic classification of lung carcinomas (according to the World Health Organization-WHO): squamous carcinoma, adenocarcinoma, neuroendocrine tumors, large cell carcinoma, mixed forms, salivary gland-type tumors, pulmonary hamartoma.
Paraneoplastic syndromes.

Pathology and tumours of the naso-pharyngeal region: general features; specifically: naso-pharyngeal carcinoma.

Larynx: general features; specifically: nodules and polyps of the vocal cords; solitary papilloma and papillomatosis; Laryngeal carcinoma and precursor lesions.

Diseases of the Thymus

Developmental disorders.

Thymic hyperplasia.

Thymomas.

(A, AB, B1, B2, B3, C).

Thymic carcinoid.

Salivary gland pathology

Pleomorphic adenoma, Warthin tumor; acinic cell carcinoma; mucoepidermoid carcinoma; adenoid-cystic carcinoma; benign and malignant lympho-epithelial lesions. Cysts of the head and neck region.

Diseases of the Gastro-Intestinal system

Esophageal diseases. Pathology and pathogenesis of: esophagitis, Barrett's esophagus, squamous carcinoma and adenocarcinoma of the esophagus

Non neoplastic gastric diseases. Pathology and pathogenesis of: gastritis (acute and chronic) and gastric ulcer (peptic and acute). Ménétriere's disease.

Tumor and tumorlike conditions of the stomach. Tumors: gastric polyps, gastric carcinoma. Mesenchymal tumors of the gastro-intestinal tract-including GIST

Congenital anomalies. Pathology and pathogenesis of megacolon (congenital and acquired)

Vascular disorders. Ischemic colitis and enteritis.

Enterocolitis. Pathology and pathogenesis of infectious entrocolitis, viral and bacterial gastroenteritis, necrotizing enterocolitis, pseudomembranous colitis (antibiotic-associated)

Malabsorption syndromes. Pathology and pathogenesis of celiac disease and Whipple's disease

Inflammatory bowel disease. Pathology and pathogenesis of ulcerative colitis and Crohn's disease

Neoplasms of the gastro-intestinal tract.

Polyps: general features; specifically: hamartomatous polyps, polyps in Peutz–Jeghers syndrome, hyperplastic and serrated polyps, tubular adenomas, tubule-villous and villous adenomas

Adenoma-carcinoma sequence: pathologic and molecular features.

Cancerized colorectal adenomas.

Colorectal carcinoma: epidemiology, etiology and pathogenesis, pathology.

Adenocarcinoma and mucinous adenocarcinoma (with production of extracellular mucin), signet-ring adenocarcinoma, and adenocarcinomas with neuroendocrine features.

Mesenchymal neoplasms of the gastro-intestinal tract.

Neoplasms of the anal canal: basaloid carcinoma, verrucous carcinoma, squamous carcinoma.

Neuroedocrine gastro-intestinal tumors.

Vermiform appendix. Acute appendicitis, mucocele, adenoma and adenocarcinoma of the appendix, Pseudomyxoma peritonei, appendiceal carcinoid tumor.

Diseases of the Liver and Biliary system

Cirrhosis. Liver pathology and pathogenesis. Pathology of systemic complications.

Viral hepatitis. Etiology, pathogenesis and pathology in the different clinical syndromes. Fulminant hepatitis, acute hepatitis, chronic hepatitis.

Liver disorders not related to viral infection. Pathology and pathogenesis of: alcoholic liver disease, autoimmune hepatitis, drug and toxin related hepatitis, hemochromatosis, Wilson's disease, alpha-1 antitrypsin liver disease, neonatal hepatitis. Liver abscess.

Intrahepatic biliary diseases. Pathology and pathogenesis of: biliary cirrhosis (primary and secondary), primary sclerosing cholangitis.

Tumors and tumorlike conditions. Hepatic angioma. Pathology, predisposinig conditions and evolution of: focal nodular hyperplasia, hepatocellular adenoma, hepatocellular carcinoma, cholagiocarcinoma, hepatoblastoma.

Metastatic tumors.

Extrahepatic biliary diseases. Pathology and pathogenesis of extrahepatic biliary tract obstruction; classification, pathology, predisposinig conditions and evolution of extrahepatic cholangiocarcinoma and of carcinoma of the ampulla of Vater.

Gallbladder. Pathology of: cholecistitis; carcinoma of the gallbladder.

Diseases of the Pancreas

Diseases of the exocrine pancreas. Pathology and pathogenesis of: acute and chronic pancreatitis.

Tumors of the exocrine pancreas. Ductal and acinar carcinomas.

Diseases of the endocrine pancreas. Classification, pathology, pathogenesis, natural history and complications of diabetes mellitus. Classification, pathology, and clinical features of insular pancreatic tumors. Pathology of insulinomas and gastrinomas (Zollinger-Ellison syndrome).

Diseases of the Kidney

Renal pathophysiology. The podocyte, the epithelial and non-epithelial cells of the renal parenchyma: their role in the development of renal failure.

Renal biopsy: indications, preservation of the specimen, criteria to evaluate its adequacy; mandatory techniques for a consistent diagnosis.

Histopathological diagnosis in glomerular pathology as established for the major glomerulopathies: IgA nepropathy, focal segmental glomerulosclerosis, diabetic glomerulopathy, nephrotic syndromes, C3 glomerulopathies.

Systemic lupus erythematosus.

Thrombotic microangiopathy - hemolytic uremic syndrome (HUS) in the infancy.

Shock-kidneys.

Macroscopic changes in chronic pyelonephritis and in the Renal Vascular Disease.

Tubulointerstitial pathology: principal alterations,

Renal failure. Renal and systemic alterations. Morphological indicators to predict evolution to end-stage renal disease.

Renal tuberculosis: classic and current forms of the disease.

Adult polycystic kidney.

Alport's syndrome.

Tumors of the Kidney. Clear cell renal cell carcinoma: unique entity in oncology. Natural history. description and sampling of the surgical specimen. Histopathological diagnosis and critical evaluation of prognostic and predictive criteria. Renal cancer and cystic disease of the kidney.

Nephroblastoma (Wilms' tumor). Natural history. Sampling for histopathological diagnosis. Prognostic and predictive criteria. Predictable sequelae in long-term survivors to Wilms' tumor oncological therapy.

Diseases of the urinary tract

Congenital anomalies of the urinary bladder.

Acute and chronic cystitis, and specific variants (e.g. Malakoplakia).

Neoplasms of the urinary bladder. Urothelial neoplasms. Papillomas and papillary carcinomas: differential diagnosis; frequent occurrence of multicentricity and recurrence. Macroscopic features of urothelial carcinoma. Flat urothelial carcinoma. Importance of grading. Staging: relevance of the degree of tumor infiltration of the bladder wall.

Diseases of the male reproductive system

Non neoplastic diseases and congenital anomalies.

Testicular tumors. Classification (according to the WHO). Pathology and evolution of: germ cell tumors (seminoma and non-seminomatous germ cell tumours), gonadal stromal tumors, testicular lymphoma.

Diseases and tumors of the prostate gland. Pathology and pathogenesis of: prostatitis, benign prostatic stromal and glandular hyperplasia, prostatic carcinoma (including staging; Gleason’s grade and score).

Penis: congenital anomalies, inflammatory disorders and tumors.

Breast pathology

Male breast. Gynecomastia and male breast carcinoma.

Female breast. Mastitis. Cystic disease and its components: cysts, apocrine metaplsaia, fibrosis. Intraductal proliferative lesions and their relationship with breast carcinoma.

Breast calcifications: epidemiology and diagnosis of microcalcifications.

Breastcancer. Epidemiology and impact of early diagnosis. In situ carcinoma: all morphological variants.

Invasive carcinoma: most frequent variants (ductal and lobular)

Prognostic factors of breast cancer: TNM.

Predictive factors of breast cancer: importance of oestrogen and progesterone receptors; molecular features of breast carcinoma.

Paget's disease of the breast.

Breast carcinoma special types: main features.

Benign breast lesions: sclerosing adenosis; radial scar and sclero-elastotic lesion; nipple adenoma.

Fibroadenoma. Benign and malignant phyllodes tumours.

Intraductal papilloma: differential diagnosis with in situ carcinoma.

Diseases of the female reproductive system

Neoplastic and pre-neoplastic diseases of vulva, vagina and uterine cervix. Pathology and pathogenesis of: human papillomavirus infection and correlation with intraepithelial vulvar neoplasia (VIN), intraepithelial vaginal neoplasia (VAIN), intraepithelial cervical neoplasia (CIN and SIL). Squamous carcioma of the female genital tract (vulva, vagina, uterine cervix): pathology, natural history, diagnosis and staging.

Endometritis.

Endometriosis and Adenomyosis

Neoplastic and pre-neoplastic diseases of the uterine corpus.

Pathology, pathogenesis of endometrial hyperplasia and its correlation with endometrial carcinoma. Endometrial polyps. Classification, pathology, staging of endometrial carcinoma. Uterine leiomyoma and leiomyosarcoma.

Ovarian cysts and tumors. Pathology and pathogenesis of: follicular and lutein cysts. Polycystic ovary. Classification, pathology and evolution of ovarian tumors (serous, mucinous, endometrioid, Brenner tumor, gonadal stromal tumors and germ cell tumors).

Trophoblastic pathology. Pathology and pathogenesis of: partial and complete hydatidiform mole, invasive mole, choriocarcinoma.

Diseases of the endocrine system

Pituitary gland. Pathology and clinical features of pituitary adenoma.

Craniopharyngioma.

Thyroid gland.

Congenital anomalies.

Hyper- e hypothyroidism.

Thyroiditis (Hashimoto’s thyroiditis, subacute thyroiditis).

Diffuse and multinodular hyperplasia: Graves-Basedow disease, multinodular goiter.

The thyroid nodule.

Thyroid neoplasms: molecular pathology, classification and general features, clinical manifestations; differential diagnosis between benign and malignant lesions.

Well differentiated malignant neoplasms: follicular and papillary carcinoma. Poorly differentiated carcinoma (insular carcinoma). Anaplastic carcinoma. Sporadic and familial medullary carcinoma.

Parathyroid: hypoparathyroidism; primary and secondary hyperparathyroidism. Parathyroid hyperplasia, adenoma and carcinoma.

Adrenal gland. Adrenocortical hyper- and hypofunction. Adrenocortical neoplasms. Pheochromocytoma. Neuroblastoma.

Paraganglioma.

MEN Syndromes.

Skin diseases

Acute and chronic inflammatory dermatoses and Systemic Lupus Erythematosus (SLE)

Blistering (Bullous) diseases.

Infectious diseases (verrucae, molluscum contagiosum, Syphilis).

Epithelial tumors. Morphology of: benign and premalignant epithelial tumors (actinic keratosis, seborrheic keratosis, Bowen's disease). Warts. Malignant epithelial tumors: squamous cell carcinoma, basal cell carcinoma.

Disorders of pigmentation and tumors. Clinicopathological aspects of: melanocytic nevi (junctional, dermal, and compound), dysplastic nevi, malignant melanoma. Histology and prognostic significance of malignant melanoma (in situ melanoma, superficial melanoma, nodular melanoma, Clark's level and Breslow's depth staging system).

Diseases of the osteoarticular system

Bone fractures.

Osteonecrosis.

Infections.

Bone tumors and tumorlike lesions:

Fibrous dysplasia and syndrome of McCune-Albright.

Benign neoplasms of bone and cartilage, including chondroma and osteochondroma, osteoma, osteoblastoma, chondroblastoma. Maffucci syndrome and Ollier disease. Aneurysmal bone cyst.

Giant cell tumor of bone.

Bone sarcomas: general features, grading and staging.

Osteosarcoma: clinical features and site of origin. Correlation with body growth and bone metaphyses. Radiographic and macroscopic features. Codman triangle.

Chondrosarcoma.

Ewing sarcoma and PNET.

Arthropathies: general features; reumatoid arthritis, gout and pseudogout.

Tumors and tumorlike lesions of the joints.

Soft tissue tumors and tumorlike lesions

Benign tumors:

Lipoma and variants.

Leiomioma.

Fibromatosis. Fibrohistiocytic tumors. Dermatofibroma. Dermatofibrosarcoma protuberans.

Benign vascular tumors and tumorlike vascular lesions, including Kaposi's sarcoma.

Benign neoplasms of peripheral nerves.

Soft tissue sarcomas:

General features, grading and staging.

Fibrosarcoma.

Malignant fibrous hystiocytoma.

Liposarcoma.

Leiomyosarcoma.

Rhabdomyosarcoma and variants, including alveolar rhabdomyosarcoma and sarcoma botryoides.

Angiosarcoma.

Synovial sarcoma.

Malignant Peripheral Nerve Sheath Tumor.

Skeletal muscle and peripheral nervous system diseases

Main forms of neuropathy.

Classification of myopathies.

Diseases of the central nervous system

Cerebral edema.

Hydrocephalous.

Trauma and traumatic vascular lesions (epi and sub-dural hematoma)

Vascular lesions. Morphological features and pathogenesis of: hypoxic-ischemic encephalopathy; cerebral infarct, intracranial haemorrhages; primitive intraparenchymal haemorrhages; saccular aneurysms; sub-arachnoid haemorrhages; vascular malformations.

Brain infections. Morphological features and pathogenesis of epidural and subdural infections. Meningitis (acute, chronic and lymphocytic). Intraparenchymal infections (general introduction of encephalitis); abscesses; encephalitis.

Tumors. Morphological features and classification of brain tumours: gliomas (astrocytoma, oligodendroglioma, ependymoma) neuroectodermal tumours, meningiomas. Brain metastases.

Degenerative and demyelinating disorders. Multiple sclerosis; Alzheimer disease; Parkinson disease; Huntington’s disease; spongiform encephalopathy: clinico-pathological correlation. Lateral amiotrophyc sclerosis. Leucodystrophies.

Diseases of the hematopoietic and lymphoid systems
Introduction and overview of the classification of tumors of lymphoid tissues (WHO classification): Hodgkin's lymphoma, non-Hodgkin B-cell lymphomas (chronic lymphocytic leukaemia, follicular lymphoma, marginal zone lymphomas, mantle zone lymphoma, large B-cell lymphoma, Burkitt lymphoma).
Lymphadenitis (including HIV and AIDS infection).

Splenomegaly and Ruptured spleen.

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