I. HISTOPATHOLOGY OF THE HEART 1. Recent myocardial infarction: 50-year-old man with a three-day history of left ventricular myocardial infarct. The patient died of an heart insufficiency. An example of coagulative necrosis. Judging from the lack of staining of the nuclei of cardiac muscle cells (with increased eosinophilia of the cytoplasm) and the diffuse neutrophilic infiltrate in the interstitium, it has to be more than 24 hours old. Subendocardial layers survive (supplied through diffusion through the endocardium). 2. Older myocardial infarction: Clinical history of this patient corresponds with the morphological appearance of his myocardial infarct. The patient died of heart insufficiency in a lung oedema. The heart weighed 420 grams. There was a paler yellowish area in the posterior wall of the left ventricle, surrounded by a darker rim of granulation tissue. A white scar was present in the neighbourhood of this infarct. This infarction may be 2-3 weeks old. Necrotic tissue, now completely devoid of nuclei, is being slowly resorbed by macrophages (see residual granules of lipofuscin from necrotic muscle cells in their lysosomes) and replaced by graulation and by fibrous tissue. 3. Postinfarction scar of the myocardium: 60-year-old patient with a two-month history of a myocardial infarct. The cause of his death was heart insufficiency and lung oedema. The heart weighed 450 grams, the bulging apical part of the left ventricle was of a whitish colour and was about 3mm thick. Necrotic muscle has been completely resorbed and the granulation tissue has been replaced by connective tissue scar. Note residual muscle fibers included in the scar tissue (possible source of arrhythmia). 4. Diphtheric myocarditis: This five-year-old boy died with signs of an heart failure after one week of diphtheria. There was pseudomembranous tracheitis, the heart weighed 120 grams. Left ventricle was markedly dilated. Diffuse infilammation of the myocardial interstitium, consisting of leucocytes and macrophages involved in resorption of disperse necrotic muscle cells.(effect of the exotoxin of corynebacteria. Advanced stage of resorption, almost no necrotic cells remain (pale small foci in the tissue). Similar changes can appear in influenza, polyomyelitis, Coxsackie virus. 5. Rheumatic myocarditis: 30-year-old male patient developed arthralgias and hear failure approximately ten days after tonsillitis (angina). The heart weighed 320 grams, left ventricle was dilated. The myocardial interstitium contains the so-called Aschoff nodules, with eosinophilic necrosis and with the basophilic Aschoff cells (modified macrophages). The muscle cells are undamaged. The nodules may be difficult to find in some of the slides. 6. Bacterial endocarditis: Aortic valve from the heart of a 50-year-old woman with an high septic fever that developed during her pneumonia. The patient died of a complicating brain abscess.The heart weighted 350 grams, left ventricle 12 mm.Trombotic vegetations were present on the surface of aortic valve. Microbiologic examination of vegetations revealed G+ microbes, Staphylococcus epidermidis. Deformed (aortic?) valve is covered by huge thrombotic vegetation with foci of accumulated neutrophils. Finely granular masses of microbial colonis are scattered inside the thrombus. Note small areas of resorbed necrtosis in the adjacent myocardium (possibly from coronary microembolism by fragments of the valvular thrombus). 7. Acute fibrinous pericarditis: This 45-year-old woman had chronic glomerulonephritis and died of renal insufficiency. Serum creatinine was 600 umol/L (normal range 55-110). At autopsy the lungs appeared oedematous, with fibrinous exudate on the pleural surface. Epicardial surface was also covered by fibrinous threads. Causes often unknown (uraemia, viral infections, over myocardial infarction, acute febrile rheumatism, tumours). Epicardial surface is covered by a thin eosinophilic layer of fibrin. 8. Tuberculous pericarditis: A 60-year-old female patient was followed for a destructive pulmonary process predominantly in the upper lobes. The pericardial cavity contained haemorrhagic exudate. The patient died of respiratory insufficiency. A portion of the wall of left atrium shows chronic inflammatory infiltrate in the subepicardial fat, with several epithelioid granulomas, some of them with central caseous necrosis and scattered multinucleated Langhans’ cells. 9. Rhabdomyoma of the heart: A premature newborn died at the age of two days of pneumonia. There were scattered cysts in the liver and in kidneys. The heart muscle contained some ill-circumscribed paler foci, the heart was slightly enlarged. Immature cardiac muscle with smaller and thinner myocytes contains several paler nodules consisting of large cells with watery pale cytoplasm (cytoplasmic glycogen washed out during processing of the tissue) and central nucleus hanging on thin eosinophilic threads of cytoplasm. Some cells can contain fibres of myofibrils. 10. Myxoma, cardiac:A 50-year women with transitory left-sided hemiparesis. Signs of embolisation into the brain, spleen and heart were present. On the dorsal wall of the left atrium, the pedunculated myxoid mass which almost completely occupied left atrium was found. This mass was the source of embolism. The cause of death was massive trombembolism of pulmonary artery. This benign mesenchymal tumor is composed of globular or star-like cells, endothelial cells and smooth muscle cells. The myxoid stroma is composed of acid mucopolysacharides. Locally, glandular formations and vessels may be present. 11. Erdheim’s cystic medionecrosis: This 40-year male patient suffered from severe retrosternal pain that started suddenly, he died 12 hours after the onset of clinical symptoms. Cardiac enzymes (CK, LDH) were negative. Autopsy revealed extensive mediastinal haemorrhage with a rupture in the wall of ascending aorta, the wall of aorta in the neighbourhood of the rupture tore easily on traction. Multifocal necrosis of muscle cells with disappearance of elastic fibres (pale areas) and accumulation of acid mucopolysaccharides (small basophilic areas) (chondroitin-6-suplhate) in the aortic media. Note multifocal laminar splitting of aortic media, the origin of aortic dissection. 12. Arteriosclerosis: 70-year-old patient with a history of stroke and ischaemic heart disease, he was also suffering from renal insufficiency. Grossly the aorta showed severe atherosclerotic changes especially in its descending portion. Principal morphological events: fatty streaks, fibrous plaques, atheromas, ulceration, and dystrophic calcification. Mostly intimal involvement. 13. Arteriolosclerosis of kidney: Kidney tissue from the same patient. Both kidneys were smaller, weighing 100 grams each, their surface was coarsely granulated, thickness of the cortex was reduced to 4 mm. Laboratory: higher serum creatinine and urea. Note obliteration of some of the glomerular and concentric thickening of arterial and arteriolar walls with accumulation of hyaline and fibrinoid masses. Severe vascular atrophy of renal parenchyma with confluent areas of tubular atrophy, hyalinization of gromeruls and increase of the connective tissue interstitium. 14. Polyarteritis nodosa-heart: 40-year-old female patient with signs of ischaemic heart disease. The patient died suddenly of malignant arrhythmia. Grossly, the heart showed slight dilatation of the left ventricle and scattered small subepicardial haemorrhages over the anterior wall of the left ventricle. Systemic disease, which involves mostly small arteries and arterioles. Microscopical findings: segments of fibrinoid necrosis of arterial media, swelling of endothelium, thrombosis, defects in internal elastic membrane. Mixed inflammatory infiltrate. Healing by segmental scar-rosary-like appearance of involved vessels. Complications: thrombosis, aneurysm. II. PATHOLOGY OF BLOOD VESSELS. HAEMATOPATHOLOGY. 1. Myeloproliferative syndrome, polycytemia vera:60-year-old female with several, repeated thromboses of low extremities. During last days anginous pain of the chest. In peripheral blood picture excessive increase of erythrocytes, thrombocytes and neutrophils. MPS is clonal disease of stem cells resulting in increase of one or several cell lines in peripheral blood. The haematopoiesis is effective. Cells are differentiated and have not signs of dysplasia. Hepatosplenomegaly is frequent finding. The bone marrow is hypercellular with hyperplasia of all three major lines – erythropoiesis, granulopoiesis, and megakaryopoiesis. The important finding is lack of hemosiderin. This syndrome may develop into secondary myelofibrosis, sometimes into the blastic acute myeloid leukaemia. 2. Extramedullary haematopoiesis: Description of patient in case 5. Myeloproliferative diseases cause hyperplasia of haematopoiesis, which is disseminated into the liver, spleen, lymphatic nodes and cause hepatosplenomegaly. There are isles of haematopoiesis scattered with different intensity in liver parenchyma. Physiologically is Extramedullary haematopoiesis present during embryogenesis. 3. Myeloproliferative syndrome, chronic myeloid leukaemia (Ph+), liver: 52- years-old male patient with asymptomatic increase of neutrophils in peripheral blood (promyelocytes in 10%). Last examination of the blood revealed leucocytosis of 350×109//L. Physical examination revealed marked hepatosplenomegaly. The patient died of bronchopneumonia. Neoplastic infiltrations both in portal triads and in liver sinusoids, in some areas almost diffuse (cells of the granulocytic lineage in various stage of maturation). 4. Chronic myeloid leukaemia, lymph node:An enlarged lymph node from the same patient. Massive infiltration by the immature cells of myeloid lineage only scattered residual lymphoid follicles. 5. Myelodysplastic syndrome, bone marrow: 76-year-old male with general fatigue. Cytopenia in the peripheral blood especially anaemia. No hepatosplenomegaly. Asymptomatic clinical course. Clonal disease of stem cells with ineffective haematopoiesis, within the hypercellular bone marrow are cell with signs of dysplasia. The presence of blasts is also characteristic. There is poor response to chemotherapy and risk of progression into the acute myeloid/lymphocytic leukaemia. 9 6. Chronic lymphocytic leukaemia, liver: Leuocytosis of 25x10 /L was found in this 60-year-old female patient, with 75 per cent of lymphocytes in the differential. The patient died of a stroke four years later. The liver weighed 1.990 grams, the cut surface showed whitish reticular pattern. Mostly B-cell leukaemia, infiltration of the portal triads by differentiated lymphocytes which express pan-B markers (CD20) and CD23 a CD5. 7. Follicular lymphoma:50-year-old male with left inguinal lymph node enlargement. The most frequent adult lymphoma, almost in all cases nodal. Histologicaly it is nodaly arranged and composed of centrocytes (cells with irregular grooves in nuclear membrane) and centroblasts (larger cells with several nucleoli in hypochrome nuclei). The prognosis is related to number of centroblasts (grading of these neoplasms is mostly based on centroblasts count – grade 1-3). Immunophenotype: pan B+, bcl-2+, CD5-, CD23-. Genetic: t (14; 18). 8. Mantle cell lymphoma (only DIA): Often extranodal lymphoma of elderly males. Prognosis is poor due to aggressive behaviour and chemoresistance. It arises from small mantle cells localised around germinal centre. It is arranged nodulary in the early phases, diffusely in the late phases. Immunophenotype: pan B+, CD5+, cyclin D1+, CD23-. Genetic: t (14; 18) 9. Diffuse large B cell lymphoma:75-year-old male with general lymphadenopathy, fatigue and subfebrilias. Often extranodal lymphoma of various age groups. Many subtypes exists (mediastinal large cell B lymphoma, large cell B lymphoma rich of T cells, etc.). Treatable but highly aggressive tumour. Original structure of lymph node is substituted by infiltration of large lymphoid cells with high mitotic activity. Immunophenotype: pan B+. Genetic: in 30% t(14;18). 10. Non-specified peripheral T cell lymphoma (only DIA): Tumour is composed of small, medium and large cells with irregular nuclei together with venules, plasmocytes, eosinophils. So called Lennert`s lymphoepitheloid lymphoma is characterised by presence of numerous epitheloid histiocytes. Aggressive behaviour. Relatively often in Far East. Immunophenotype: various T antigens, most often CD3, CD4, less often CD8. 11. Anaplastic large cell T lymphoma: 30-year-old male with peripheral and abdominal lymphadenopathy with skin infiltrates. Subfebrilias and night sweats. This tumour appears both in the childhood and elderly and is often extranodal (skin). Histologicaly it may resemble undifferentiated carcinoma or malignant lymphoma. Immunophenotype: CD30+, EMA+-, T markers +-, B markers always negative! Sometimes expression of ALK (anaplastic lymphoma kinase). Genetic: t (2,5). 12. Nodular lymphocytic-predominance Hodgkin`s lymphoma (NLPHL): 22-year-old female patient was suffering from fatigue and night sweats. Physical examination revealed enlarged cervical lymph nodes, otherwise it was unremarkable. Fine needle aspiration biopsy of a node was positive. There was slight eosinophilia in peripherial blood. Disease of various age groups. Classic Hodgkin lymphoma (CHL) Types: nodular sclerosis (NSCL) mixed cellularity (MCHL) lymphocyte rich classic HL (LRCHL) lymphocyte depletion (LDHL) The tumour cell is HRS – Hodgkin mononuclear or Reed-Sternberg binuclear cell, both with characteristic inclusiform nucleolus. The background is filled with various inflammatory cells (see slide) – T cells, B cells, eosinophils, histiotyocytes. Prognosis depends on morphological type (LRCHL has best prognosis), NSCL is most common type with predilection in mediastinal nodes. III. PATHOLOGY OF THE RESPIRATORY TRACT, PART ONE 1. Nasal polyp: This 45-year-old patient was suffering from nasal obstruction. Personal history included repeated bouts of chronic rhinitis and sinusitis. Multiple polypous formations, pedunculated and sessile, were excised from the nasal cavities. Increased level of IgE should confirm allergic origin of the patient’s problems. Inflammatory pseudotumour (chronic allergic hypertrophic rhinitis), oedematous, sometimes resembling myxoma. Uneven cellularity, with few cells in some areas and more cellular, infiltrating with eosinophils, lymphocytes and plasma cells elsewhere. 2. Laryngeal (singer’s or preacher’s) nodule: 20-year-old patient, 2 years singing in a choir, had a 3month history of hoarseness. A small polyp on the right vocal cord was excised. The lesion is lined by metaplastic squamous stratified epithelium; sub-epithelial stroma consists of eosinophilic and vacuolated poorly cellular collagenous fibrous tissue, with a fibrin content, in which there are thin-walled blood vessels. 3. Laryngeal carcinoma: 57-year-old patient who had suffered for some month from afonia, ORL examination revealed a tumour located in the supraglottic portion of the larynx, the patient underwent partial laryngektomy. The tumour exhibits papillary growth and there is ulceration and infiltration of the underlying tissues, too. It consists of sheets of moderate or low-differentiated squamous epithelial cells with only minimal foci of keratinisation. At the margin the non-neoplastic metaplastic squamous epithelium is visible. 4. Pseudomembranous tracheitis: 79-year-old man with clinical symptoms of influenza suffering from distressed breathing died of pneumonia. The patient’s larynx and trachea were severely congested and oedematous, with an adherent pseudomembrane on the mucosal surface. Cross section of tracheal wall formed from a superficial part of fibrinous exsudate and a deeper portion formed by necrotic mucosa permeated by fibrin. There is erythrostasis in mucosa and submucosa, blood vessels are dilated. It is an examle of superficial (croupous) pseudomembranous inflammation. 5. Bronchial asthma: This 38-year-old male patient had a history of an atopic eczema, allergic rhinitis, dyspnoea with a "wheezing breath", dyspnoea and cough. His IgE was elevated and the white blood cell differential revealed eosinophilia. The patient was admitted for bronchospasm with suspicion of pneumonia. He died four days later. Lungs are oedematous, heavy. Bronchi are dilated, with hypertrophic muscular layer and mucinous glands, hyperaemia and thick basemembrane. There is infiltration of lymphocytes, plasma cells and eosinophils in the wall. Many bronchi are filled with thick mucus containing numerous eosinophils. Note scattered Curshmann’s spirals and Charcot-Leyden’s crystals. 6. Chronic bronchitis (hypertrophic type) with emphysema (COPD), exacerbating: A man of 65, cigarette smoker, living in an industrial town had a chronic productive cough for several years. Recently he had been suffering from exertional dyspnoea, he died of cardial insufficiency. Lungs have emphysematous configuration with perivasal and peribronchial antrakosis. The bronchi are lined by hypertrophic mucosa with an increase in goblet cells. Bronchial walls are oedematous, thickened by hyperplastic and hypertrophic mucus-secreting glands, increase amounts of smooth muscle and capillaries. Basement membranes are also thickened. An increase in chronic inflammatory infiltration has been documented (lymphocytes, plasma cells, eosinophils). In airways there is excess mucus with small amount of polymorphonuclear leukocytes. 7. Silicosis of the lungs: This 50-year-old glass cutter had a long history of lung fibrosis died form pneumonia that complicated exacerbating bronchitis. Both lungs were tough, with small, sometimes coalescing nodules that reached several centimetres in diameter. Some nodules contained a necrotic centre, some were calcified. Regional lymph nodes showed similar changes. Nodules are formed from fibrous tissue with low content of fibrocytes, increased hyalinization, antracotic pigment and SiO2 crystals /evidenced by polarised light/. Coniofibrosis with three stages: 1-stigmatization with SiO2 crystals in similar location as antracotic pigment. 2-formation of silicotic nodules, 3-massive fibrosis. 8. Lung emphysema: Same patient as above. There is emphysematous configuration of lung parenchyma next to the above described nodules. Alveoli are extended with destruction of septa together with thickening of arterial wall as the sign of pulmonary hypertension. Various types: senile, centroacinar, paraseptal, panacinar, bullous. 9. Atelectasis of the lung: This asfyxiated stiiborn fetus died during a complicated prolong labour. Noninflated lungs can’t swim after immersion into water. There are collapsed or slit shaped alveoli. 10. Lung oedema: 70-year-old patient with a history of ischemic heart disease was coughing a frothy pink sputum. At autopsy both lungs were heavy, weighing 950 and 820 grams, with pink watery fluid running from the cut surface. Hyperaemia of lung tissue. Eosinophilic fluid in the alveoli,variable etiology. IV. PATHOLOGY OF THE RESPIRATORY TRACT, PART TWO 1. Acute catarrhal-suppurative bronchopneumonia: This 87-year-old female patient underwent osteosynthesis after a fracture of her left femur. An x-ray revealed bilateral shadows in the lower lobes of her lungs. At autopsy both lower lobes were congested and oedematous, with disperse consolidation of the lung tissue on palpation. Both main bronchi contained mucus while peripheral bronchial branches were filled with pus. Acute superficial inflammation of the lungs, spreading from minor bronchi and bronchioles, aetiology variable. Alveoli are filled with polymorphonuclear leukocytes, little fibrin can be seen. The appearance of exudate may differ in various parts of the inflamed area. 2. Lobar pneumonia: 45-year-old male patient with a short history of malaise, fever and dyspnoea. In spite of an antibiotic treatment, the patient died in respiratory and circulatory failure. The upper lobe of the left lung showed fibrinous pleuritis, the parenchyma of the lobe was consolidated, resembling on cut surface liver tissue (grey hepatisation). Mostly infection with Diplococcus pneumoniae. Fibrinous inflammation, involving major areas of lung parenchyma, spreading quickly through neighbouring alveoli. Several stages: inflammatory oedema, grey hepatisation (grossly resembles liver tissue), red hepatisation, and resolution. 3. Lung carnification (caro = meat): This 68-year-old patient had a history of ischaemic heart disease and pneumonia died of cardiorespiratory failure. The surface of the posterior segment of the left upper lobe showed organizing fibrinous pleuritis. The segment itself showed hypoventilation, on section the parenchyma appeared rubbery, resembling skeletal muscle in consistency. Caused by incomplete resolution and organisation of the intraalveolar exudate with formation of non-specific granulation tissue (concentric arrangement of fibroblasts and collagen fibres in the alveoli). 4. Nonsuppurative interstitial pneumocystis pneumonia: This 58-year old patient with history of carcinoma showed signs of a pulmonary infiltrate. Pneumocystis carini was found in the bronchopulmonary lavage. At autopsy non-specific finding. Microorganism Pneumocystis carinii (fungus, yeast-like) can be visualised in the spumoid masses in alveoli. Alveolar septa are thickened with mononuclear (plasmocytic and lymphocytic) infiltrate. Typical in immunocompromised patients, sensitivity to UV light. 5. Lung abscess: This 59-yeard old female patient was suffering from repeated inflammation of veins in her lower extremities; she died of massive pulmonary embolism. The lungs showed several subpleural infarcts, one of them with gangrenous destruction of the necrotic tissue. Acute abscess: irregular shape, peripheral zone of hemorrhagic lung and area of inflammatory oedema. Possibility of further spreading. Chronic abscess: regular shape, its wall composed of pyogenic membrane, impossibility of collapse (cavitary abscess). Three ways of spreading: bronchogenous, haematogenous, lymphogenous. 6. Squamous cell carcinoma: This 65-year old patient had been treated unsuccessfully for chronic cough by his physician. He had been smoking 20 cigarettes/day for about 40 years. Hospital check-up revealed dysplastic squamous cells in his sputum and chest x-ray showed suspicious lesion in the upper lobe of his left lung. A greyish-white nodule was found in the wall of the main bronchus for the upper lobe. Hilar nodes were free of tumour. Most frequent histological form of bronchial carcinoma, especially in smokers (preceding squamous cell metaplasia and dysplasia of the bronchial epithelium). Various degree of differentiation with keratinisation and formation of keratin pearls in the differentiated forms. 7. Small cell cancer of the lungs: A 52-year-old smoker with a history of shortness of breath and expectoration of purulent sputum with occasional streaks of blood. A forceps biopsy from the bronchus for the right upper lobe confirmed the diagnosis of cancer. The patient died 10 months later with extensive dissemination of the tumour. The hilar region of the right lung was infiltrated by whitish tumorous masses that were encircling and compressing the aortic arch, distal oesophagus, and the origin of the left main bronchus. Bilateral hilar lymph nodes were infiltrated by the tumour. Second in frequency, this is the most malignant histological type. Oat cell, round cell type, with occasional neurosecretory granules on electron microscopy. Sometimes accompanied by paraneoplastic syndromes (Cushing’s syndrome, hypercalcemia, carcinoid syndrome). 8. Adenocarcinoma: This 57-year-old female patient had had a history of hysterectomy for cervical carcinoma ten years ago. Recently, she became dyspnoeic and anaemic, with a considerable weight loss. The patient died from cardiorespiratory failure. At autopsy the right pleural cavity was massively filled by tumour masses that focally appeared gelatinous and caused severe compression of the totally collapsed lung. Metastases in lymphatic nodes, opposite lung, suprarenal glands and in other organs were found. Tumour rises from bronchial epithelium or bronchial glands, but also without connection with bronchus. 9. Bronchioloalveolar carcinoma: Special form of adenocarcinoma (10%). Tumour cells lining alveolar ducts and alveoli without destruction of their septa. The most frequent localization is the periphery of bronchial tree – terminal bronchioli and alveolar ducts. 10. Large cell carcinoma: Non-differentiated variant of carcinoma, without morphology of squamous, small cell and adenocarcinoma. V. PATHOLOGY OF THE GASTROINTESTINAL TRACT, PART I 1. Epulis gigantocellularis: A 26-year-old female patient noticed a swelling in the retromolar region of her upper jaw, sitting on the surface of the alveolar processus. The excised white round formation measured 1.5cm in the greatest diameter and was of a firm consistence, it was covered with an unchanged mucosa. Tumoriform formation with markedly vaskularised stroma, focally looking like non-specific granulating tissue, contents multiple multinucleated giant cells /most common type of epulis in childhood and middle age/. 2. Leukoplakia: (see the slides). 3. Carcinoma of the oral cavity: (see the slides) 4. Radicular cyst: This 53-year-old lady had a history of chronic periodontitis. Lateral x-ray revealed focal lucidity next to the root of one of her molars. Surgical excision revealed whitish tissue specimen with a small collapsed cavity. A cyst resulting form epithelisation of a chronic apical root abscess. Squamous epithelium derives from the cell rests of Malassez, stimulated by the inflammatory process. There is dense chronic inflammatory infiltrate under the epithelial lining. 5. Ameloblastoma: This 40-year-old male patient had a polycystic lesion of the alveolar processus excised. The specimen for histology was formed by a whitish firm tissue with fragments of bone. The patient noticed loosening of his teeth on the site of the polycystic growth. Epithelial tumour of borderline biological behaviour, developing in the processus alveolaris of the jaw. Slowly growing with bone destruction, grossly solid or polycystic. Microscopically reticular arrangement of loosely arranged stellate epithelial with interposition of islands of vascularised oedematous stroma. 6. Pleiomorphic adenoma: A 61-year-old female patient with a recurring growth in her right parotid eight years following the original excision. Fragments of tissue with white firm stripes were removed; together with the rest of the gland 2×4×3 cm. Previously called myxochondroepithelioma for its microscopical appearance (only the epithelial and myxoid structure is visible in our slide). Epithelial, with locally variable differentiation, cells form stripes, glandular and solid structures. Benign but poorly outlined, without capsule (frequent recurrences with incomplete excision). 7. Adenoid cystic carcinoma: This 37-year-old female patient developed a slowly growing tumorous lesion on the right side of her hard palate. A whitish tough formation was excised and sent for histological examination. Former cylindroma, malignant. Lace-like arrangement of epithelium, what appears like adenoid glandular structures is actually oedematous stroma. 8. Cystic adenolymphoma of parotid (Warthin’s tumour): An 87-year-old lady had a swelling in her right parotid excised. The specimen consisted of a round whitish piece of tissue, grossly resembling a lymph node. Less frequent, localized in the parotid gland. Glandular and papillary formations are lined by tall columnar epithelium with apically located nuclei. Dense lymphoid infiltrate in the stromal septa, sometimes with formation of lymphoid follicle. 9. Chronic gastritis: A 39-year old woman had a 20-year history of pernicious anaemia. A biopsy was taken from her gastric mucosa for assessment of cellular dysplasia. Two main forms – atrophic and hypertrophic gastritis. In hypertrophic g. there is thickening of the mucosa with dense chronic inflammatory infiltrate, appearance of lymphoid follicles, possibility of intestinal metaplasia. Atrophic gastritis – grossly the mucosal layer is thinned and smoothened, disappearance of gastric glands, intestinal metaplasia. 10. Acute peptic ulcer of stomach: (see the slide). 11. Chronic peptic ulcer of stomach: This 68-year-old lady died from ischaemic heart disease. She had a history of rheumatoid arthritis that was treated with nonsteroidal antiphlogistic drugs. A mucosal defect with slightly raised margins was found in the pyloroduodenal transition. The defect measured 2 cm in diameter and its base was formed by the submucosal connective tissue. Chronic peptic ulcer, note three layers at the base – necrotic debris with leukocytes, layer of fibrinoid necrosis, layer of non-specific granulation tissue, then peripheral fibrosis. Thickened walls of adjacent arteries, hyperthrophy of nervous fibres and fibrosis in the basal part of wall are signs of chronicity. 12. Adenocarcinoma of the stomach – well differentiated: This 60-year-old male patient had a history of dysorexia with weight loss (8 kilograms in two months) and anaemia. Ulceration with elevated margins was found on the major curvature and an excision was taken for histological examination. Transmural infiltrative adenocarcinoma, microscopically tubular and acinar structure. Laurén’s classification: intestinal form producing extracellular and intracellular acid mucin (this case), and diffuse type with less tendency to produce mucin (HE and PAS stain). (Note - sample of adenocarcinoma originates from large intestine, greading in this localization is identical). 13. Adenocarcinoma of the stomach – moderately differentiated: Same patient as above; endoscopy established thickened wall with smooth mucous in great curvature. Neoplastic cells grove in stripes and solid formations, glandular formations are not apparent. 14. Adenocarcinoma of the stomach – poorly differentiated – scirrhous carcinoma: This 70-year-old female patient was thoroughly examined for anorexia, severe weight loss and fatigue. Sonography showed small-constricted stomach of a "leather bottle" shape. Biopsy confirmed cancer of the stomach. Dissociated, less differentiated epithelial cells with mucus production (HE and PAS stain - presence of signet ring cells) with rich desmoplasia. 15. MALT lymphoma of the stomach: This 55-year old male patient with a past history of chronic gastritis had been loosing weight for about four months. He had crampy epigastric pains and was vomiting several times. Endoscopy revealed a tumour mass on the lesser curvature of the stomach. The patient was treated by gastrectomy. The resection specimen revealed whitish tumour measuring approximately 3 cm in diameter. Regional lymph nodes were enlarged. Malignant B lymphoma of low-grade malignity. Arising from lymphatic tissue of GIT mucosa. An excision from the tumour is totally infiltrated by slightly pleiomorphic neoplastic cells with irregular nuclei and scanty cytoplasm. There are many apoptotic cells. The tumour cells are CD20 and CD79a positive, CD45RO, CD5, CD10, CD23 negative. Note that may be preceded by Helicobacter gastritis. VI. PATHOLOGY OF THE GASTROINTESTINAL TRACT, PART II 1. Haemorrhagic infarction of the intestine: Similar morphology with arterial or venous occlusion, haemorrhagic necrosis and oedema of the intestinal wall, fibrinous exudate on the peritoneal surface. Causes paralytic ileus. By arterial occlusion is necrotic part well defined, by venous occlusion is margin worse defined. 2. Acute catarrhal enteritis: Severe diarrhoea appeared in this 13-year-old boy after one week in a summer camp, the diarrhoea was accompanied by vomiting and gradual development of fever. The stools showed admixture of mucus and blood. Microbiological culture grew Shigella sonnei. Variable causes (cholera nostras), the serosa is pink, intestinal content is aqueous, hyperaemia and odema of the mucosal stroma and of tunica propria. Grundhagen’s spaces - separation of the superficial epithelium from the basement membrane, sometimes eosinophils in the infiltrate. 3. Pseudomembranous colitis: Some patients develop colitis after treatment with broad-spectrum antibiotics, such as lincomycin and clindamycin, which depress the normal flora. The disease is caused by anaerobic organism, Clostridium difficile, the toxin of which damages the wall of the bowel to cause superficial necrosis of the mucous membrane. The deeper parts of the colonic glands remains. The severity can vary widely, from mild colitis to fulminating pseudomembranous, haemorragic necrosis with ulcers of the mucosa. 4. Ulcerative colitis: 35-year-old woman suffering from diarrhoea (15 bloody stools daily), lost of weight, low-grade fever. A biopsy of rectal mucosa was required to establish the diagnosis. In the hyperaemic mucosa there is dense infiltrate of inflammatory cells (neutrophil prevalence), several glands are distended with mucus and inflammatory cells,(the contents appearing pus-like) - crypt abscess. 5. Crohn´s disease: 23 –year-old man with recurrent abdominal pain, diarrhoea (3-6 stools per a day) and fever. Bioptic examination revealed mixed (lymphocytes) transmural inflammation all layers of the bowel wall are affected, non-caseating epitheloid cell granulomas and presence of fussuration in the wall. 6. Diverticulitis of the large bowel: A 56-year old man developed acute GI symptoms during ski-vacation in Austrian Alps (abdominal cramps in left hypogastrium, nausea, vomiting, constipation). Guarding and a painful resistance in the left lower abdomen were found during physical examination. The temperature was 39°C. Surgery revealed multiple prolapses of the intestinal mucosa through the intestinal wall into mesosigmoideum. One of these diverticles was distended and inflamed. Low-power view of the section shows (pseudo)diverticulum with mucosa and tunica propria protruding through the muscularis layer into the fibrotic and inflamed subserosal fat tissue. The mucosal surface is ulcerated in the proximal part of the diverticulum. 7. Meckel’s diverticulum: This 40-year-old lady underwent urgent laparotomy with symptoms of acute appendicitis and beginning peritonitis. Her appendix and the right-sided adnexa were grossly normal. An inflamed Meckel’s diverticulum (ductus omphaloentericus remnant) was found 20 cm proximal to the ileocaecal valve. Cross section through a diverticulum with small bowel-type mucosa, slightly fibrotic tunica propria and thickened muscularis layer. Gastric mucosa can occur heterotopically – common complicated by ulcer. 8. Intestinal tubulovillous adenoma: A 61-year old man was suffering from anal bleeding, feeling of fullness, flatulence and abdominal cramps. Endoscopy revealed multiple polypoid lesions in his whole large intestine, some of them on a narrow stalk, other sessile. Most frequent in the large intestine, with narrow elongated or broad and short stalk, tubular, villous or tubulovillous, some dedifferentiation of the superficial epithelium (disappearance of goblet cells). Possible dysplastic changes or cancerization. 9. Ulcerophlegmonous appendicitis: A 29-year-old febrile woman with acute abdominal symptomatology, signs of peritoneal irritation and positive rebound phenomenon. Laboratory examination showed leukocytosis with neutrophilia and a left shift. Appendix with congestion a partial adhesion to neighbourhood. Diffuse transmural leukocytic (polymorphonuclear) infiltrate, ulceration od the mucosa, suppurative exudate in the lumen, fibrinous layer on the serosal surface. Complications: gangraene, periappendiceal abscess (localized peritonitis). 10. Carcinoid of the appendix: A 52-year-old man was complaining of an occasional pain in his right hypogastrium. An appendectomy was performed and the appendectomy specimen showed signs of chronic inflammation. A greyish intramural nodule was found, measuring 1 cm in diameter. Epithelial tumour consisting of cells of the diffuse endocrine system of gastrointestinal tract. Solid alveolar arrangement of small regular cells with small amount of cytoplasm. Benign if localized in appendix. 11. Chronic cholecystitis: This 53-year-old female patient had a history of biliary stones, intermittent pain under the right costal margin related to meals. Episodes of tremor, fever with sweating occasional moderate jaundice, skin prurience. Laboratory tests revealed leukocytosis. Gall bladder is reduced, adherent to liver, contents number of mixed stones. His wall is thick, whitish, firm. Scattered chronic inflammatory infiltrate in the thickened mucosa focal forms lymphatic follicles, atrophic forms with smooth mucosa. 12. Absceding cholangitis: 65-year-old woman with a history of bile stones and repeated inflammation of the extrahepatic biliary tract. The patient refused surgical intervention. Following a biliary colic, she developed high fever and was icteric and confused. Laboratory tests indicated failing liver and kidneys. At autopsy the liver showed greenish discoloration and small abscesses on cut surface. Ascending bacterial infection (E. coli) usually accompanying obturation of the biliary tract. Choleangiogenic sepsis. Portal fields and adjacent parenchyma are infiltrated by neutrophils, necrosis of hepatocytes are common. 13. Cystic fibrosis of the pancreas: This 28-year-old asthenic male patient with markedly enlarged abdomen was treated for sterility. His personal history reveals tabescence in despite to good appetite, steatorrhoea. Analysis of duodenal secretion provided extreme viscosity and absence of proteases, lipases and amylases. In sweat extremely elevated levels of Na, Cl and K. Pancreas is firm with large cysts contenting dense mucus. Note marked reduction in the acinar secretory part of the gland, the ducts are present, some of the wide dilated with inspissated secretion, fibrotisation and chronic inflammation in surrounding tissue. Langerhans’ islets are preserved. Frequently complicated by diabetes. Disappearing exocrine parenchyme replaced by the newly formed connective tissue with scattered lymphocytic infiltrate. Sometimes increased fat tissue - lipomatous atrophy. Islets of Langerhans often well preserved. 14. Acute haemorrhagic necrosis of pancreas: This 40-year-old obese male patient developed severe abdominal pain after a celebration with consumption of fatty meals and alcoholic beverages. The pain was located in the epigastrium and was radiating towards his the back. Meteorismus appeared after a few hours and the abdomen was painful on palpation. The patient had leukocytosis and laboratory examination revealed raised serum amylase. Pancreas is slightly enlarged, oedematous. Combination of necrosis of the pancreatic parenchyme, necrosis of the fat tissue, haemorrhage. Intraglandular activation of pancreatic enzymes (proteo- and lipolytic). 15. Colorectal adenocarcinoma: 78-year-old woman was complaining of constipation, weight loss. Laboratory examination revealed hypochromic, microcytic anemia. Colorectal cancer is common in developed counties; adenomatous polyps and ulcerative colitis belong to the most important risk factors. Macroscopically this tumour took the form of an ulcer, visible also histologically, in cross-section in this field. Carcinomatous tissue, consisting of malignant cells of adenocarcinoma (more basophilic), which are invading downwards, destroying muscle fibres, pericolic fat and affects lymph nodes, too. (Dukes C). VII. PATHOLOGY OF THE LIVER 1. Haemochromatosis: This 35-year-old patient was suffering from refractory anaemia that required multiple transfusions. The patient’s skin was dark, she also had diabetes. At autopsy the liver was harder and nodular, of a rusty brown colour. Lysosomal storage of an iron-positive (Pearls’ reaction) pigment in the lysosomes of hepatocytes and Kupffer cells. Associated micronodular cirrhosis. Unregulated absorption of iron from the intestine. Compare with haemosiderosis (caused by accelerated red blood cells breakdown in haemolytic anaemias, repeated blood transfusions), here haemosiderin appears primarily in the Kupffer cells. 2. Congestion of the liver: This 65-year-old patient was treated for cardiac failure. He was short of breath and had hepatosplenomegaly and ankle oedema. The liver was enlarged, with "congestion lines". Most pronounced in the lobular centers, sometimes accompanied by centrilobular steatosis and by zonal fibrosis. 3. Viral hepatitis: Activation (swelling) of Kupffer cells, baloon degeneration and monocellular necrosis (apoptosis, eosinophilic cytoplasm, Councilman bodies) of hepatocytes. Predominantly small cell inflammatory infiltrate in the portal fields. Chronic hepatitis: persistent (benign course) or active (with piecemeal necrosis). Ground-glass appearance of cytoplasm of hepatocytes with HBsAg storage in the tubules of endoplasmic reticulum. 4. Massive necrosis (hepatodystrophy, yellow atrophy): This 26-year-old technician was exposed to chlorinated hydrocarbons, and to aniline derivatives. She suddenly became icteric and laboratory tests indicated severe damage to the liver. The patient died in hepatorenal syndrome. At autopsy the liver was slightly paler and softer. Massive necrosis of the liver parenchyma sparing portal areas, from which regeneration may start. Smaller and flabby liver, yellow at the beginning, turning red (resorption of necrotic parenchyma and congestion) and then gray (reparative fibrosis). 5. Atrophic (micronodular, Laennec’s) cirrhosis: This 55-year-old patient was admitted because of bleeding from his oesophageal varices. Physical examination revealed gynaecomastia, ascites and signs of haemorrhagic diathesis. The liver was smaller and nodular. Often caused by chronic alcohol cnsumption. Nodular regeneration of the liver tissue with displacement and compression of the veins, fibrosis with inflammatory infiltration, and proliferation of small bile ducts. Grossly small, hard liver. 6. Zonal (centroacinar) necrosis of the liver. A 74-year-old man operation of oesophageal carcinoůma died of hepatorenal failure. At autopsy liver showed signs of an acute congestion. The liver tissue shows severe centrilobular congestion with necrosis of hepatocytes, with infiltration by neutrophils and with activation of endothelial and Kupffer cells. 7. Cavernous haemangioma: A 63-year-old woman died of cardiac failure. A circumscribed dark red area measuring 3 cm in diameter was founds in the right lobe of her liver (incidental finding). The most frequent liver neoplasm (except for the metastases). Benign, but danger of haemorrhage in diagnostic liver needle biopsy – absence of myoepitelial cells. Scattered thrombi in various stages of organization are present in the wide vascular spaces, otherwise filled with blood. 8. Hepatocellular carcinoma: This 49-year-old male patient had a history of B hepatitis and liver cirrhosis. He was losing weight in the last six months and developed icterus and ascites. Liver was enlarged, with coarsely nodular surface. The patient died of pulmonary embolism. At autopsy the liver had an ill-defined area measuring five cm in diameter in the right lobe. The tissue of the nodule was more friable than the surrounding liver parenchyma. Frequently as complication of liver cirrhosis. Solitary or multicentric. Invasive growth into hepatic vessels, haematogenous metastases into lungs and bones. Note irregular arrangement of the tumour cells, with occasional glandular formations and with production of bile. 9. Cholangiocellular carcinoma of the liver dia VIII. PATHOLOGY OF KIDNEYS 1. Microcystosis: Recessive mode of inheritance, leads to death in renal insufficiency in newborns. Grossly enlarged kidneys with smooth surface, sponge-like appearance on section. Note multiple small cysts with renal parenchyma and primitive tubules in between. This newborn boy died of renal insufficiency. At autopsy both kidneys were enlarged, grossly of spongy appearance. 2. Vascular nephrosclerosis: Scattered scars in arteriosclerosis, smaller kidneys with granular surface and extensive glomerular obsolescence and hyalinization in arteriolosclerosis of the kidneys. Sometimes with fibrinoid deposition in the walls of small arteries and arterioles, especially with arterial hypertension. Note splitting of elastic fibers in arterial walls. This 75-year-old female patient was suffering from a slowly progressing deterioration of renal function over a period ov several years. At ysotupsy both kidnexys were symmetrical and smaller, with coarsely granular surface and several depressed scars. 3. Diabetic glomerulosclerosis (Kimmelstiel-Wilson): Nodular (this slide) or diffuse form. Segmental accumulation of mesangium, mostly mesangial matrix, usually also hyaline, PAS-positive thickening of the walls of afferent arterioles.Other forms of diabetic involvement of the kidneys: accelerated arteriosclerosis, pyelonephritis, necrosis of renal papillae, Armani’s cells (glycogen accumulation in cells of tubular epithelium). This 45-year-old femmale patient with type I diabetes and progressing renal failure during last year. There were signs of diabetic angiopathy. At autopsy both kidneys were slightly enlarged, reddishbrown, with some granularity on the surface. 4. Armani’s cells: In pars recta of proximal tubules, deposition of glycogen in the water-clear cytoplasm, PAS-positive, amylase-digestible. Same patient. PAS staining for the demonstration of glycogen. 5. Non-suppurative interstitial nephritis: Variable aetiology (scarlet fever, cytomegaloviral infection, transplant rejection etc.). Interstitial chronic inflammatory infiltrate, with time leading to interstitial fibrosis with tubular atrophy. 6. Acute diffuse glomerulonephritis: Most frequently poststreptococcal (ASLO-positive, 1 to 2 weeks after infection), diffuse involvement of glomeruli that are hypercellular (polymorphonuclear leucocytes and macrophages with proliferating endothelial cells blocking lumina of the gloimerular capillaries).On immunohistology and electron microscopy focal deposition of immunocomplexes on the outer surface og the glomerular basement membranes ("humps"). Numerous casts in the tubular lumens. Very good prognosis, usually heals without any residues. This 19-year-old young man developed suddenly oliguria and hypertension two weeks following an angina. He noticed dark urine and puffing oedema of the face. There was high titre of ASLO. Renal biopsy revealed IgG and C3 complement deposits in the glomerular loops, electron microscopy showed subepithelial deposits (humps). 7. Chronic (membranoproliferative) glomerulonephritis: Pronounced lobularity and hypercellularity of some glomeruli, the rest of glomeruli show fibrosis and hyaline change. Tubules extensively atrophic, interstitial connective tissue increase, with occasional inflammatory infiltrate. This 48-year-old man had had failing kidneys for about 10 years. Laboratory revealed haematuria and proteinuria, decreased C3 complement. Renal biopsy showed subendothelia deposits and splitting of the glomerular basement membrane. 8. Focal glomerulonephritis: Focal proliferation and fibrotic obsolescence of scattered glomeruli, other glomeruli are of normal appearance. 45-year-old patient with haematuria and proteinuria. Renal biopsy revealed lesions in a minority of glomeruli.The patient was suffering from infective endocarditis and died of a brain haemorrhage. 9. Rapidly progressing (crescentic) glomerulonephritis: The slide represents a more advanced stage of the disease, where all glomeruli present in the section show some degree of fibrosis. There is only disperse presence of cellular crescents in some of the Bowman spaces. Tubules show variable degree of fibrosis, with a general increase in the connective tissue interstitium. This 55-year-old patient had haematuria, proteinuria and severe hypertension of an acute onset, he died af a complicating brain haemorrhage. Both kidney showed multiple disseminated subcapsular small haemorrhages and whitish small nodules. 10. Acute suppurative pyelonephritis: Ascending infection, with inflammatory infiltrate in the tubules and in the connective tissue interstitium, with focal formation of abscessses. In chronic pyelonephritis interstitial fibrosis with chronic inflammatory infiltrate and hyaline casts in areas of the cortical tubules with atrophy of the epithelium ("thyreoidisation"). This 73-year male patient had a history of prostate hypertrophy with repeated bouts of ascending urinary infection. The patient died of urosepsis. Autopsy revealed small contracted kidneys with scarring and suppurative inflammation. 11. Amyloid nephropathy: Deposition of amyloid in the walls of arteries and arterioles, less in the glomeruli and under the tubular epithelium. AA = secondary amyloidosis.This 53-year-old male patient had been treated for multiple myeloma. He developed progressive renal insufficiency with severe proteinuria in the last years of his disease. 12. Biliary nephrosis: Secondary to severe obstructive jaundice 9conjugated bilirubin excreted in the urine). Look for pigmented casts in the renal tubules, pigmentation of epithelium of the proximal tubules. This 63-year-old female patient had generalized carcinoma of the head of her pancreas that caused compression of the common bile duct and severe cholestatic jaundice. At autopsy both kidneys showed greenish discoloration. 13. Chronic hydronephrosis: Severe pressure atrophy of the renal parenchyma caused by obstruction of the ourflow of urine (renal stones, ureteral obstruction by stones, tumours, compression, diseases of the urinary bladder, in males often hypertrophy of prostate). May be complicated by (usually ascending) infection hydropyelonephritis. Numerous hyaline casts in the atrophic tubules, glomerular obsolescence, thickening of arterial walls. A 58-year-old female patient with cancer of the right ovary compressing the neighbouring right ureter. Both proximal ureter and the right renal plevis were severely dilated and the thickness of the parenchyma of right kidney was reduced. 14. Wilms’ tumour (nephroblastoma): Typical for small children, malignant, fast growing but curable by radiation and surgery. Cellular immature tissue resembling renal blastema, with focal differentiation of tubules, glomeruloid structures, cartilage, muscle etc. This two-year old boy was admitted for haematuria. CT examination revealed a large tumour in his right kidney. 15. Renal cell carcinoma, clear cell type: Assesment of malignancy unreliable on morphological grounds, malignant tumours may appear differentiated and encapsulated. Small tumours (under 2cm in diameter) considered benign (clear cell adenoma). Vascular, sometimes cystic, consisting mostly of lear ccells containing glycogen. Sometimes with oxyphilic cells, sarcomatoid variant. This 60-year- old man had had intermittent haematuria for several months but did not visit his physicians. He came only later because of a flank pain and a palpable tumor on the right side. The nephrectomy specimen revealed an round circumscribed pale-yellow tumour which did not penetrate into the pelvis and did not grow into the renal vein. IX. PATHOLOGY OF THE URINARY OUTFLOW TRACT, MALE AND FEMALE GENITAL TRACT 1. Chronic follicular urocystitis: A 75-year-old male patient, parlyzed after a stroke, immobile, was repeatedly catethrised, and was complaining of dysuria. The patient died of bronchopneumonia. The mucosa of the urinary bladder was congested, with small whitish nodules. Chronic inflammation with accumulation of lymphocytic infiltrate in follicles, usually grossly visible under the superficial epithelium. Other frequent findings in chronic inflammation – squamous metaplasia of the superficial epithelium, hypertrophy of the muscular layer (obstruction). 2. Papillary carcinoma of the urinary bladder: This 50-year old heavy smoker with severe dysuria and haematuria, fatigue. A large papillary growth is found at cystoscopy. Tumours are most common derivated from trigonum urethrae. Epithelial layer thicker than in papilloma (over 6 layers), less differentiated cells, disperse mitoses. May show infiltrative growth into the bladder wall. 3. Testicular fibrosis (atrophy): This 22-year old patient had been treated for infertility. His right testis was undescended. A small sample was taken for peroperative biopsy during surgical intervention and revealed atrophy and fibrosis. Marked thickening of the basement membranes of seminiferous tubules, atrophy or total disappearance of the seminiferous epithelium. Sometimes increase in number of the interstitial Leydig cells. Another case stained by the green trichrome stain (unfortunately bleached out) shows interstitial fibrosis and the Leydig cell hyperplasia. In old patients, in liver cirrhosis, after radiation, in some genetic defects, cryptorchism, cytostatics, chronic inflammation, etc. 4. Seminoma: This 36-year-old man noticed gradual enlargement of his left testis which was painful. The most frequent tersticular tumour of midle age, consists of nests of large cells with large nuclei and prominent nucleoli and with a glycogen-rich cytoplasm in the connective tissue stroma showing lymphocytic infiltration, sometimes even formation of granulomas. 5. Adenomyomatous hyperplasia of the prostate: A 57-year old patient is coming because of progressing problems with urination. He has had repeated bladder inflammation. Rectal examination reveals symmetrical enlargement of the prostate which feels hard, slightly nodular. Some degree of hyperplasia in practically all males more than fifty years old. Microscopically variable proportion of hyperplastic fibrous, muscular and glandular tissue, typically nodular. Often leads to urethral obstruction and ascending infection. Carcinoma of prostate usually does not originate from the hyperplastic areas. 6. Carcinoma of prostate: This 76-year-old patient is complaining of severe pain in the lumbar region, the pain has lasted for the last two months. Rectal examination reveals enlarged, rock-hard prostate. PSA 15.4 (normal up to 4.0 g/l). A variety of differentiation degrees (Gleason’s classification with prognostic significance). Our case shows microacinal glandular formations. Direct continual progression into adjacent structures. Metastases: regional lymph nodes, often bones (osteoplastic metastases). 7. Mucinous cystadenoma of ovary: This 36-year-old female patient comes with diffuse abdominal pain. Palpation of the hypogastrium reveals a resistance in the region of the right ovary, measuring approximately 15x7cm. Sonography reveals multicystic ovarian tumour. Large cysts with mucinous content, lined by tall columnar epithelium positive with the mucin stain. Usually multicystic (20-30 cm), internal surface is smoth (in proliferative form formation of pseudopapillar structures) malignant transformation in 10 per cent of cases. 8. Serous cystadenoma (border-line): A regular checkup of this 48-year-old woman revealed a painless tumour measuring 5 by 4 cm in her right ovary. At operation the tumour is cystic, with some warty excrecences in some of the cysts. Often unilocular, with many irregular papillary formations protruding into the lumina of the cysts, content is serous. Malignant transformation in 25 per cent of cases. 9.Tumors metastatic to the ovary: Approximately 8% of ovarian tumors, mostly breast and GIT adenocarcinomas. Krukenberg tumors – (bilateral less common ubilateral) metastases in which the tumor appears as nests of mucin-filled “signet-ring“ cells within a cellular stroma. The stomach is the primary site in 75% of cases, the colon is a less common primary site. 10. Granulosa cell tumour: Derivated from gonadal stroma. Consists of small cells with coffee-bean nuclei and scattered lipid vacuoles in the cytoplasm. May show hormonal activity – production of oestrogens. Forms - adult (common postmenopausal) and juvenile (children and young women). 11. Ovarian teratoma, immature: Variable degree of differentiation, with structures derived from all three germ layers. Note presence of various kinds of epithelium, cartilage etc., including embryonal tissues. Almost always is in the form of solid teratoma. 12. Dermoid cyst, mature teratoma: This 30-year-old woman was complaining of hypogastric pain. Surgery revealed an unilocular cyst 5×5 cm in her left ovary. The cyst contained a fatty matter and with a convolute of hairs. The most frequent type of ovarian teratoma, benign. Unilocular cyst filled with keratin and hairs, islands of tissues derived from the three germ layers can be found in the wall of the cyst. 13. Chronic salpingitis (only a slide): This 29-year-old woman has been treated for infertility. Personal history reveals recurrent adnexal inflammation and an ectopic (tubar) pregnancy. Fibrous thickening of the wall with chronic inflammatory infiltrate. May lead to stricture and adhesions, danger of extrauterine pregnancy. Possibility of pyosalpinx when exudate is colected, risk of rupture into peritoneal cavity and peritonitis. X. PATHOLOGY OF THE FEMALE GENITAL TRACT II, PATHOLOGY OF BREAST 1. Cervical polyp: This 40-year-old patient had a history of occasional postcoital bleeding during last three months. Colposcopy revealed a polypoid growth protruding from the external os of the cervical canal. 2. Condyloma accuminatum of vulva: This 25-year-old female patient had several wart-like polypoid soft growths in endocervical epithelium, measuring up to 0,5 centimeters in the greatest dimension, focally hyperkeratotic rough cover. Polypoid lesion with papillary, wart-like arrangement, covered by squamous epithelium with the presence of koilocytes – epithelia with waterclear cytoplasm and shrunken hyperchromatic nucleus-related to HPV (human papillomavirus 6,11) infection. Stroma with inflammatory infiltrate, acantosis. 3. Poorly differentiated (nonkeratinizing) squamous cell carcinoma of the cervix: A routine checkup revealed an exocervical ulcerative lesion with bulging margins and indurated base in this 52-year-old patient. In the greatest diameter 1cm. More common in women with history of delivery. Cytology – evidence of precancerosis. Forms: exophytic and endophytic. Metastasis – in lymphatic nodes, risk of ureteral stenosis, later hydronephrosis. Importance of HPV virus in oncogenesis of this tumour. Moderately differentiated, nonkeratinizing carcinoma showing both superficial growth min the glands (replacing the original columnar epithelium) and intralymphatic invasion. 4. Dysfunctional hyperplastic proliferative endometrium: A 49-year-old patient with metrorrhagia. Uterine currettings contained voluminous fragments of endometrium. Last menstruation three months ago. From overwhelming oestrogenic influence, hyperproliferation. Mitotic activity both in the gnandular epithelium and in the stromal cells. Sometimes cystic dilatation of some of the glands – "swiss-cheese hyperplasia"- glandular cystic hyperplasia. 5. Leiomyoma of the uterus: A nodular enlarged uterus was palpated in this 58-year-old patient. The hysterectomy specimen showed multiple round hard grayish-white nodes inside the myometrium and bulging under the serosal surface. The most frequent of all the uterine tumours, benign, consists of smooth muscle cells mostly in fascicular arrangement, with variable admixture of fibroblasts (secondary change). Solitary or multiply, subserosal, intramural, submucosal, well circumscribed, may calcify. Low number of mitoses (contrary to leiomyosarcoma). 6. Endometrial adenocarcinoma: . This 63-year-old patient presented with a metrorrhagia of 3 days. Uterine curettage revealed endometrial carcinoma. This diagnosis was followed by an urgent hysterectomy. Possibly originating in an endometrial polyp (overall arrangement with abundant non-neoplastic stroma containing larger vessels). Back-to-back glands with high mitotic activity of the epithelium. Many areas of squamous metaplasia (adenoacanthoma). Appears at higher age than cervical cancer, more frequently in nulliparous women 7. Residua post abortum: This 19-year-old student has been bleeding for 8 days. Last menses before two months, before bleeding he had spastic pain in lower abdomen. Orifice is open, degrease of basal temperature. Note secretory endometrium with ferning (zig-zag pattern) of glands containing secretion, foetal remnants. Placental villi are immature, slightly oedematous, mostly avascular, there are foci of accumulation of the trophoblast. Look for the nucleated red blood cells in the placental vessels - normal up to the 10th week of gestation. 8. Hydatidiform mole: This 38-year-old woman with rapid growth of uterus after conception had an abortion of an hydatidiform mole in 5th month. Friable grape-like structures consisting of enlarged markedly oedematous avascular villi mostly with flattened trophoblastic lining. Foetus is not present. There is marked proliferation of trophoblast in between the villi. Dysplastic changes in the epihtelium, risk of development of choriocarcinoma (residual mole or CHC- persisting high level of HCG). 30% risk for choriocarcinoma 9. Chorionepithelioma (choriocarcinoma): This 29-year-old patient had her hydatidiform mole removed six months ago. After an intermittent drop in the serum HCG the values are raising again. Malignant tumour of trofobloast, deeply invading the myometrium, angioinvasion, focal necrotizing. Tumour doesn’t have own stroma. Early haematogenous metastases in lungs and brain. Diagnose: levels of HCG in blood. Treatment: Chemotherapy is successful nearly 100% of cases. 10. Ectopic (tubal) pregnancy: This 21-year-old woman had a history of repeated adnexal inflammation. After about three months following conception she suddenly felt severe hypogastric pain on the left side. Culdecentesis revealed blood in the space of Douglas. The wall of the Fallopian tube is only paritally present in the section. Note immature placentar tissue with signs of trophoblastic invasion into the mucosa and muscularis layers of the tube. Danger of: tubar abortion, rupture of the tube and peritoneal bleeding. 11. Fibrocystic changes: 49-year-old patient has multiple hard, painful nodules in the upper lateral segments of both breasts. Very frequent, with combination atrophy, hyperplasia, and metaplasia of both the ducts and the lobules. Caused predominantly by hormonal dysbalance and infalammation. Simple dysplasia: fibroproliferation predominates, fibrous dysplasia, or fibrocystic dysplasia (cystic dilatation of some of the ducts). Sclerosing adenosis – accompanied by proliferation of the myoepithelial cells (can be erroneously diagnosed as cancer!) Proliferative dysplasia – predominating epithelial proliferation. With cellular atypia – atypical proliferative dysplasia, risk of cancer development. 12. Fibroadenoma: This 28-year.-old female patient noticed for 2 month a slowly growing hard, indolent nodular hazelnut-size formation in the upper lateral segment of her right breast. The most frequent neoplasia of breast in young women, benign. Combined proliferation of ductal epihtelium and epiductal stroma. Two histological forms – peri- and intracanalicular. 13. Commedocarcinoma (IDC): This 61-year-old patient noted a centrally located tangerine-size hard node in her left breast. Frozen sections from a diagnostic excision reveald carcinoma. The mastectomy specimen contained a nodular growth measuring approximately 4 cm in diameter. The cut surface was grayish-white, with yellow necrotic commedo-like areas of necrosis. Intraductal necrotizing carcinoma, noninvasive at the beginning. Central necrosis evidence pure differentiated type of intraductal carcinoma, that can develop in to pure differentiated ductal carcinoma (there are integrated different mutations of genetic sequences compared to low and intermediate grade carcinomas. Occasional microcalcification of the necrotic material – visible on mammography. XI. PATHOLOGY OF THE NERVOUS SYSTEM 1. Cerebral infarct (encephalomalacia): A 75-year-old patient had been admitted with an anterior myocardial infarct four weeks ago. Just before release from the hospital for further outpatient care, he became unconscious and hemiplegic. Ischemic colliquative necrosis, vital reaction – activated microglia (enlarged cells with vacuolated cytoplasm) so called “granular cells” (rich in lipids), healing by formation of a pseudocyst. Causes: thrombosis, embolism. Hemorrhagic infarct (usually caused by embolism, small, cortical) through reflux of blood into the necrotic focus – red encephalomalacia. Diagnostic features – leucostasis, diapedesis of leukocytes and erythrocytes, activated microglia disintegration of necrotic tissue. 2. Cerebral hemorrhage: This 60-year-old woman had a history of arterial hypertension of many years. She was admitted because of a severe headache with progression of neurological symptomatology two weeks ago. CT scan of the head showed a suspicious area measuring 1 cm in diameter in the right basal ganglia. Intracerebral -possible causes: hypertension, most common in basal ganglia. Extracerebral - subarachnoid – possible causes: aneurysm, atherosclerosis, most common basis of brain with progression in to parenchyma. In subdural localization (between dura mater and arachnoidea) risk of hygroma, expansion and increase of intracranial pressure. Epidural localization (between dura mater and bone) – at least dangerous. Small hemorrhages scattered through the nervous tissue - cerebral purpura (bleeding disorders, sepsis). 3. Suppurative leptomeningitis: This 20-year-old male patient had been on his compulsory military service. An inflammation of upper respiratory tract was complicated by a febrile state with headache and with nuchal stiffness. A sample of cerebrospinal liquor was obtained through lumbar puncture and was send for biochemical and for microbiological examination. Cultures grew Neisseria meningitidis. Ours slide: enlargement of leptomeningeal space which is filled with neutrophils. Cortical oedema. Healing by resorption, formation of adhesions (epilepsy, hydrocephalus). 4. Multiple sclerosis: This 50-year-old patient developed first signs of multiple sclerosis 23 years ago. She was suffering from paresthesias of upper extremities, occasional vertigo, and general apathy. This was followed by remission of several years’ duration, then by elapses with ever shorter symptom free-intervals. Now the patient is bedridden, with continuing progression of her symptoms. She died of bronchopneumonia. Complex pathogenesis: genetic, environment, immunity. Typical gross appearance with greyish-brown areas scattered irregularly in the white matter. Histology: periventricular located areas of demyelization are revealed by the myelin stain, axons without damage. Principe: direct destruction of myelin or destruction of oligodendroglial cells, which produce myelin. There is no cellular reaction. 5. Meningeoma: This 50-year-old female patient was suffering from headaches and epileptic paroxysms. Xray examination showed a density of 2cm in diameter in connection with dura mater, dilatation of vessel at cranium. Frequent, originates from leptomeninx. Benign, well circumscribed, may cause impression (local pressure atrophy) of the brain tissue. Variable morphology, most frequent is the epithelioid type with formation of whorls , onion-like structures of tumour cells. Calcification is common. 6. Astrocytoma: A 45-year-old man with a two month’s history of headaches and occasional epileptic paroxysms. CT examination of the brain shows a circumscribed lesion in the left frontal and parietal lobes. Progression of malignancy from differentiated astrocytoma through anaplastic astrocytoma to glioblastoma. Signs of malignancy - cellular pleiomorphism, necroses, neovascularization. Sometimes formation of cysts. Gemistocytic astrocytoma - consists of plump enlarged astrocytes. 7. Ependymoma: This 17-year-old boy suffered from headaches, vomitus, and ataxia. CT scan revealed a tumor in the 4th ventricle. Most frequently in the 4th ventricle in children. Is formed of regular oval cells arising from ventricular ependymoma. Note characteristic formation of rosettes and pseudorosettes (perivascular arrangement) of tumour cells. In 50% GFAP positive. 8. Glioblastoma multiforme: This 45-year-old patient had a history of changing behaviour and occasional confusion for several months, these led to his hospitalization in a psychiatric clinic. Examination at the clinic revealed an ill-circumscribed tumor in the left frontoparietal lobe, measuring 4 cm in the greatest dimension. Marked cellular pleiomorphosm, scattered necroses (compared to astrocytoma), highly vascularized. Malignant. 9. Neurinoma (Schwannoma): A 40-year-old man was complaining of vertigo, instability and hearing loss. Audiological examination supported a diagnosis of a retrocochlear lesion. Typical location – cerebellopontine angle. Benign, but unfavourable site. Histologically typical structure Apalisading of nuclei, structure B-less cellular, with round cells, remind of myxoma, probable degenerative changes. Cells build whorls and fascicules. 10. Alzheimer’s disease: A 60 year old male, progressive deterioration of psychical functions, neurologic symptomatology Degenerative disorder of brain, changes visible in cerebral cortex (especially hippocampus) – senile plaques and neurofibrillary tangles, decrease in number of neurons. XII. PATHOLOGY OF THE MUSCULOSKELETAL SYSTEM. ENDOCRINE PATHOLOGY. 1.Gout: This 52-year-old slightly obese man with a history of a sudden onset of pain in his right big toe during the night. The pain lasted for several days. The metatarsophalangeal joint was reddened, swollen and very painful on palpation. Laboratory: increased serum uric acid, relief of pain 24 hours after a dosage of colchicin. An excision has been taken from a paraarticular nodule. Sections show loose connective tissue forming septa with fibroblasts and some giant cells. The septa surround deposits of urates, most of them dissolved during processing of the specimen. The rest of the deposits can be visualized in polarized light. 2. Osteochondroma (exostosis): This 20-year-old football player has been feeling pain in the distal part of left tibia. X-ray shows an area of bone formation, perpendicular to the surface of the tibia. The lesion results from a local displacement of epiphyseal cartilage that grows perpendicular to the normal growth plate. According to the age of the lesion (and the patient) is the surface of osteochondroma covered by cartilaginous cup of variable thickness that undergoes enchondral ossification. Deeper parts are formed by bone trabeculae and by fatty bone marrow. 3. Gigant cell tumour of the bone: A 30-year-old young lady with a five-month history of pain in the distal left femur. X-ray examination reveals a lucent area next to the distal epiphysis of the femur. Also called giant cell tumour or brown tumour (haemosiderin deposits). In younger patients (3rd and 4th decade), distal femur and proximal tibia, highly vascular, predominant spindle pulpy cells with scattered multiple multinucleated giant cells. Osteolytic aggressive growth, but almost always benign. Healing after extirpation but recurrence is also possible. 4. Osteogenic sarcoma: This 20-year-old man was suffering from a growing pain in his left distal femur. The pain was more severe at night and during walking. Physical examination showed dense swelling without fixation of the overlying skin and soft tissue. X-ray: Signs of bone destruction and neoformation in the metaphyseal region. Highly malignant, most frequent in young patients. Haematogenous metastases in the lungs. Variable histology – osteoplastic, osteolytic osteosarcoma. Malignant bone aneurysm. 5. Sarcoma of Ewing/PNET (primitive neuroendocrine tumour): A 10-year-old boy was intermittently febrile and had leukocytosis, increased sedimentation rate and slightly painful region of the fibular diaphysis on the right side. X-ray examination revealed central osteolysis with thinning of the corticalis and some periostal aposition of new bone. A haematogenous osteomyelitis was suspected and the patient was treated with antibiotics without effect. Angiographic examination revealed malignant character. Diaphysis of long bones, in children, insidious beginning in the bone marrow cavity. Microscopy: small cells ("small blue cell tumour"), occasionally rosettes, glycogen in the cytoplasm of the neoplastic cells, large necrotic areas. Ewing’s sarcoma is histogeneticaly close to PNET and microscopic picture is similar, tharefore they are uvažují togeather. Tumour is radiosensitive. 6. Pituitary adenoma: This 40-year-old male patient was complaining of growing headaches. He had some vision problems, impotence and noticed swelling of his breasts. X-ray showed widening of sella turcica with 1cm lesion. Laboratory: raised serum level of prolactin. May cause pressure atrophy of sella turcica and of the prechiasmatic part of the optic nerves. Endocrine effect according to the cell of origin: gigantism or adromegaly in eosinophilic adenoma - STH, basophilic adenoma – Cushing syndrome, ACTH hypersecretion. Most frequent chromophobe adenoma without endocrine symptoms. Microscopy: uniform ovoid cells with hyperchromic nuclei, make palisade structures around vessels. 7. Craniopharyngeoma: An eight-year-boy was complaining of headaches, he also had vision problems and signs of retarded growth and maturation. X-ray revealed a suprasellar tumour measuring 3.5 centimeters in diameter at the base of the brain, the formation was partly cystic. Erdheim’s tumour, benign, usually arise ftom the intermediary part of hypophysa or hypothalamus. Expansive and destructive growth at the skull base compression of hypophysis, resembles adamantinoma. Cysts with epithelial nonkeratinizating squamous cell layer. 8. Pheochromocytoma: A 35-year-old woman has been complaining of intermittent epigastric pains, palpitation and anxiosity. Physical examination reveals hypertension of 210/100 mmHg, sometimes raising up to 240mmHg systolic pressure. Laboratory: Marked increase in the urinary vanilmandelic acid. Benign tumour arises in medulla of adrenal glands, with paroxysmal, less frequently continuous hypertension. 90 per cent isolated, 10 % in the MEN II a, b syndrome. Highly vascular, with large and scattered bizzare giant cells. Chromogranin positivity, ultrastructureally catecholamine granules in the cytoplasm, secreting epinephrine and norepinephrine. 9. Hashimoto’s thyroiditis: A 30-year-old woman comes to her physician with a painless symmetrical enlargement of her thyroid gland. Laboratory examination reveals hypothyroidism, fine-needle aspiration biopsy shows lymphocytic infiltration and serum examination reveals high titre of antithyreoglobulin antibodies. Thyreoidectomy specimen shows symmetrical enlargement of the gland, the cut surface is yellowish-white, the gland is well circumscribed. Autoimmune pathogenesis, well circumscribed, usually enlarged thyroid gland. Microscopically marked lymphocytic interstitial infiltrates (struma lymphomatosa) with formation of lymphatic follicles. Focal oxyphilic metaplasia of the follicular epithelium. Most frequent in middle age female patients. Increased risk of MALT lymphoma and carcinoma. 10. Diffuse colloid goiter: This 50-year-old patient visits her physician complaining of enlargement of her thyroid gland. Laboratory examination is unremarkable. Grossly the gland is symmetrical. Partial strumectomy is done. The specimen consists of a yeallowish-brown gland tissue. Symmetrical enlargement of both lobes (contrary to nodular goiter), large follicles with flat epithelium and abundant eosinophilic colloid. Usually euthyroid, occasionally signs of hypo- (especially in children) or hyperthyroidism. Nodular structures are not present. 11. Hyperthyroidism – thyreotoxicosis: A 40-year-old female patient comes with enlargement of her thyroid. She is complaining of irritability and increased sweating. Further examination shows tachycardia and tremor of her fingers. The skin is warm and moist. The patient has some orbital pain. Laboratory examination reveals increased TSH. Graves’ (Basedow) disease. Parenchymatous (diffuse) goiter. Highly cuboidal to columnar epithelium focally arches into folicules (Sandersen’s pillows), decreased eosinophilia of colloid with signs of resorption, lymphoid interstitial infiltrates. Forms: diffuse or nodular (hyperfuncional adenomatous nodules). 12. Follicular adenoma of thyroid: This 45-year-old man came for a regular checkup. A painless nodule measuring 1 cm in diameter was found in the right lobe of his thyroid. The nodule was excised; it was well circumscribed, yellowish-brown on cut surface with pressure atrophy of surrounding tissue. Variable microscopic appearance (makrofollicular, microfollicular (fetal), trabecular (embryonal), oxyphilic /Hürtle cell/ adenoma). Common regressive changes, without fibrous capsule. Toxic adenoma – hyperfunctional. Cystopapillary adenoma – danger of malignant transformation. 13. Papillary carcinoma of the thyroid gland: A 15-year-old boy has swollen nodes along the left sternocleidomastoid muscle. Further examination reveals a "cold nodule" in the thyroid on the same side. A biopsy of the lymph node shows metastasis of a papillary carcinoma. Total thyroidectomy is performed and the thyroid nodule examined. Most common thyroid tumour type, almost all cases are carcinomas, mostly papillary, less often follicular, undifferentiated, 5 per cent medullary (from C cells, calcitonin production, amyloid in the stroma). Predominantly in middle-aged females, occasionally in children. Radiation danger (increased frequency in children after the Tchernobyl accident). Papillary formations, often psammoma bodies in papillary carcinoma, cellular atypias. Focally cells with groundglass-grows nuclei, nuclear pseudoinclusions and grooves in longitudinal axis. 14. Adenoma of parathyroid: This 40-year-old woman suffers from fatigue, muscle weakness, nycturia and obstipation. Laboratory examination reveals hypercalcaemia, hypofosfataemia, there are signs of an increased bone resorption on x-ray exmination. A small greyish-brown nodule measuring less than 1 cm is found on the dorsal side of the left thgyroid lobe. Partial thyroidectomy containing the nodule is performed. Most frequent cause of the primary hyperparathyroidism. Benign, usually solitary, sometimes cystic, variable size and cell composition (chief cells, oxyphilic, water-clear cells), nuclei are common irregular, some can be enlarged. Well circumscribed, with signs of compressive atrophy of the surrounding parathyroid parenchyma (in contrast to parathyroid hyperplasia). Imunohistochemical staining evidences parathormone. Carcinoma – extremely rare. 15. Nesidioma: Benign, solitary or multiple, originating from the cells of the Langerhans’ islets. Endocrine activity and symptoms according to the cell(s) of origin (A,B,D,G). Tumour originating from B cells is called inzulinoma, from G cells is called gastrinoma, from A cells glucagonoma and from D cells somatinostatinoma. Vipoma is tumour characterized by production of vasoaktiv intestine peptide (VIP). Some tumours can produce more hormons simultanously. Their size is usually small. Carcinoma – often without endocrine secretory activity. XIII. PATHOLOGY OF THE SKIN. PERINATAL PATHOLOGY, PATHOLOGY OF THE NEWBORN AND INFANT 1. Inflammatory dermatosis – overview. 2. Spongiotic dermatitis (subacute eczema dermatitis): A 32-year-old female, several months anamnesis of recidiving confluent red maculae, papulae and vesiculae localized on fingers and palms. In the period of inactivity these lesions are only slightly red and covered by scales. Combination of chronic changes (psoriasiform dermatitis with hyperplasia of epidermis, hyper- and parakeratosis) with acute changes (intracellular edema-spongiosis, formation of blisters). Perivascular lymphocytic infiltrates in papillary corium with exocytosis into the epidermis. 3. Psoriasis vulgaris: A 22-year-old student with multiple reddish-brown plaques and papules predominantly over the extensor regions of extremities. In some areas there is whitish scaling on the surface of the spots, removal of scrapes by superficial gentle scraping here results in appearance of small bleeding points (Ausspitz phenomenon). Histological examination shows acanthosis with elongation and widening of the basal parts of the interpapillar epidermal areas (rete ridges) with suprapapillar thinning of epidermis. There is marked parakeratosis on the surface, with occasional formation of the Munro abscesses (accumulation of pyknotic nuclei of neutrophils). Oedema and some chronic inflammatory infiltrate can be seen in the dermal papillae, in older lesion also fibrosis of papillae. 4. Psoriasis pustulosa: A 19-year-old male with small pustules on plants and palms, sterile content. During course their extinction, atrophy of the skin and new attack with new pustules. The same picture as in psoriasis vulgaris, moreover the presence of typical intraepidermal pustule – Kogoj`s spongiform pustules. 5. Lupus vulgaris: This 30-year-old patient has multiple yellowish-brown spots on the skin of his face. Proliferative form of skin TBC with epitheloid granulomas with small caseification. Small number of Mycobacterium tuberculosis in Ziehl-Neelsen staining, PCR more sensitive. Differential diagnosis: sarcoidosis (deeper in the dermis) lepra. 6. Atheroma of the skin with inflammatory and giant cell reaction: A middle aged man visits his dermatologist with a slowly growing soft circumscribed lump under the skin of his scalp. The lump is not fixed to the surface and measures about 1 centimetre in diameter. A small cystic lesion is present in the dermis. It is filled with keratin and sebum. Atrophy of the wall of cyst. A rim of granulomatous resorptive inflammatory reaction can be seen around the cyst, the infiltrate consists of lymphocytes, epithelioid and multinucleated giant cells. 7. Verruca vulgaris: This 12-year-old boy has some small rubbery papules with rough segmented surface on fingers of his right hand. Akanthosis, papillomatosis, hyperkeratosis and parakeratosis. In superficial layer of stratum spinosum there is presence of koilocytes and pale cells with oxyphilic cytoplasmic inclusions. The effect human papilloma viruses (HPV type 2, 4, 7). Verruca palmaris, plantaris – with marked hyperkeratosis. 8. Molluscum contagiosum: A 13-year-old girl comes with a waxy, centrally slightly depressed papule on the skin of her face. A cheesy material appears on gentle pressing of the papule. Endophytic circumscribed pear-shaped formation of hyperplastic confluent follicular infundibles. Infection by poxvirus - enlarged cells with cytoplasmic inclusions turning more distinct and slightly more eosinophilic towards the surface – molluscum bodies. 9. Seborrhoic keratosis (seborrhoic verruca): This 60-yea-old man comes with some brownish warty growths on the skin of his back. Verrucous and partially endophytic proliferation of bazaloid cells with abrupt keratinization and formation of keratin pearls, without transitional zone accordant with stratum spinosum and granulosum.. Differential diagnosis – keratoakanthoma. 10. Bowen’s dermatosis: A 65-yea-old man with a sharply demarcated greyish-brown lesion on the trunk. The surface of the lesion is uneven, scaly, with scattered small ulcerations. The lesion is enlarging. A variant of intraepithelial squamous cell carcinoma. Varied cellular composition with giant cells, base membrane is not broken. Note cellular atypias and increased mitotic activity and intact basal membrane. Sometimes present in sun exposed areas of solar keratosis. The presence of HPV (type 16, 18) was detected in lesions in anogenital region. 10% risk of development of invasive squamous cell carcinoma. 11. Keratinizing squamous cell carcinoma: An 80-year-old woman comes with a warty growth on the skin of her forehead; the lesion grows slowly over years and is fixed to its indurate base. These tumours usually arise on the basis of solar keratosis and neoplastic cell are similar to ones in stratum spinosum. Differentiation (grading) is based on the presence of cell polymorphism, mitotic activity and keratinization. In well differentiated forms the presence of keratinization - cancroid pearls, is typical. Slow destructive growth and late formation of metastases. More malignant than basal cell carcinoma. 12. Basal cell carcinoma: 75-year-old man with an ulcerated lesion above his left eyebrow. Ulceration has rigid with raised margins. Slow growth. Most frequent tumour in elderly, arise in the areas of solar keratosis. Often on the face, nose, eyelids. Slow progress, with destructive growth. Various histological types, sometimes multicentric origin. Basic type consists of small basophilic cells, palisading of tumour cells at the periphery of the tumour cell islands. Resembles cells of the basal layer of epidermis. Sometimes ulcerate. Typically without metastasis. 13. Junctional nevocellular nevus: A 12-year-old boy with several light brown well demarcated flat lesions not exceeding 5mm. Usual nevus in children and young adults. Melanocytes are present in the border epidermis-corium, especially in the tips of interpapillar epithelial interdigitations. There is also lentiginous hyperplasia of stratum basale (i.e. increased number of typical melanocytes in stratum basale). 14. Intradermal nevocellular nevus: A 42-year-old female has some flat and slightly elevated pale or dark brown lesions on her skin, predominantly on the trunk. The lesions measure mostly 0.5 to 1 cm in dimension. Most frequent pigmented nevus in the adulthood. Nevus cells (melanocytes) located in the corium, in deeper parts they change into spindle shaped cells similar to Meissner tactile bodies or neurofibroma. 15. Malignant melanoma: This 32-year-old man noticed an irregular, ill-circumscribed dark brown flat lesion 1cm in diameter on the skin of his waist region. The lesions are sometimes painful and itching, there is some occasional spotty bleeding from the surface. Nodular melanoma with vertical growth. Two types of cells – epitheloid cells with prominent nucleoli and spindle shaped cells without nucleoli. Variable presence of melanin. Typical immunohistochemical positivity in S100, HMB 45 and Melan A. Prognosis depends of vertical invasion (Clark, Breslow classification). 16. Aspiration of amniotic fluid: This hypotrophic male baby was born by cesarean section during complicated delivery at the end of week 40. Apgar score was 5, 5, 6. The baby died after three hours with signs of respiratory insufficiency. Macroscopically there are areas of collapsed lung and areas of emphysematous configuration. The immature lung tissue shows alveolar distension. Bronchi, bronchioles and partially alveoli are filled with keratinized cells from aspirated amniotic fluid (vernix, mekonium, epithelial skin cells). Aspiration results from intrauterine irritation of respiratory centre due to asphyxia. 17. Respiratory distress syndrome – hyaline membranes: Immature baby, born in week 28, weight 1600g. Immediately after delivery resuscitate with quick improvement of breathing and pink skin. During 2 hours worsening dyspnoe, cyanosis, died three days after delivery. Within the alveoli and bronchioli there are homogeneous eosinophilic membranes, partially fixed to the wall. Majority of alveoli are atelectatic. 18. Respiratory distress syndrome – acute catarrhal bronchopneumonia: New born baby delivered in term, weight 4500 g, mother suffering from diabetes mellitus. Half an hour after delivery development of dyspnoea and cyanosis. Five days of intensive therapy (oxygen), than increase of temperature, exitus. Within the alveoli and bronchioli residua of hyaline membranes and rich inflammatory exsudate with neutrophil leukocytes. Infection complication of respiratory distress syndrome.