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 Necrotic muscle has been completely resorbed and the granulation tissue has been replaced by connective tissue scar.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.
6. Chronic lymphocytic leukaemia, liver: Leuocytosis of 25x109/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`slymphoma (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 3-month 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.