CELLULAR PATHOLOGY #2.

BENIGN CONDITIONS OF THE RESPIRATORY TRACT
Recognition of benign conditions essential to to avoid false negative and false suspicious reports. (1) Proliferative abnormalities, (2) Inflammatory processes (Bacterial and fungal: Squamous epithelial changes and Pulmonary changes; Viral diseases), (3) Cytological changes due to therapy.
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Proliferative Abnormalities

Hyperplasia: Abnormal multiplication of the basal or germinative cells. The epithelium thickens to several layers, usually with a surface layer of ciliated columnar epithelium. The cells are uniform. Cytology: Cells from such an area may be present after (prolonged) bronchial intubation. Cells may show the following features: Clusters of small dark nuclei tightly packed with scanty basophilic cytoplasm. (Not so superimposed as adenocarcinoma) Size of about a leucocyte. Usually find an occasional columnar cell in the area. Bronchial Epithelial Hyperplasia: A columnar, triangular, or cubic shape; A palisade arrangement of the cells (cells are palisading); Eccentrically located nuclei, A distinct terminal plate or suggestion of such a plate (i.e. a dome-shaped end of the cell); NB: More or less well preserved cilia. Only remnants of cilia may be of great aid in identifying the cell as benign – regardless of nuclear abnormality.

The above findings may occur particularly in chronic bronchitis and bronchiectasis. Differential diagnosis: Oat cell carcinoma in which cells lie loosely. Broncheolo-alveolar carcinoma. Small histiocytes: Occasionally have scanty cytoplasm which may not be finely vacuolated. Usually one or more nuclei may show kidney shape. Squamous Metaplasia: Similar process to that of the endocervix. (See http://www.scribd.com/doc/14693767/Basic-Concepts-in-Cytopathology ) Columnar epithelium is replaced by squamous epithelium. Reflects chronic irritation of the respiratory mucosa and an attempt at defence. Epithelium may be replaced in small areas or extensive areas by metaplastic tissue which may be partially or wholly squamous. If often coexists with basal hyperplasia which may be a stepping stone between squamous metaplasia and carcinoma. Metaplasia is found in many chronic diseases of the lungs, e.g. bronchitis, abcess, chronic interstitial pneumonia, tuberculosis, radiation and chemotherapy and bronchogenic

regular nuclear margin. 4.g. bronchitis.) Heart failure cells: In conditions of pulmonary congestion due to heart failure. e. Prussian blue stain for iron is diagnostic. which is opposite of pathology in the uterine cervix. Heavily purulent exudate will be found in all disorders associated with tissue breakdown. which is usually eosinophilic and not as dense as cancer cells. 1. Hyperchromasia. There may be a proteinaceous debris on the smear in any of these conditions. Hyperchromasia may be quite alarming. pneumonia from any cause. ● – Cytology of Inflammatory Processes Bacterial and Fungal: Note: There are normally polymorphs in sputum. the macrophages may contain hemosiderin – a breakdown product of hemoglobin from degenerate red blood cells. There is usually a heavy mixed bacterial flora. Larger than basal cells with more cytoplasm. It is dark brown and the macrophages have a granular appearance. Upper respiratory tract infections may be associated with so-called PAP. 3. Degenerative changes are frequent. (Cytoplasm contains discrete round vacuoles. chromatin irregularity becomes more disturbed as the atypia becomes more marked. Asbestosis : Later discussed. Nucleoli may be present. smoke. Blastomyces dermatiidis: may be mistaken for human cells. Variation in size and shape is important.: 1. stain strongly with Sudan's stain.g. Size and shape are regular. cells: small squamous cells with abundant cytoplasm. Atypical metaplasia changes are very similar to such changes in the endocervix and similar diagnostic rules apply. Edges of a group may be flat with regular arrangement of nuclei.carcinoma. 3. Diagnosis of specific inflammatory reactions is possible though in a few conditions.g. e. Occasionally sausage shaped epitheloid cells may be found. 2. Cytology: Metaplastic cells are usually smaller than (normal) squamous epithelial cells. Abnormal pulmonary macrophages may be present in many inflammatory conditions. Fungi : Candida albicans most frequent fungal infection. Nuclei size and shape varies. Note: Both hyperplasia and metaplasia may result from a variety of irritant: fumes. TB. Tuberculosis : Lymphocytes may be very numerous. including Lipoid pneumonia (inhalation of oily substances into lungs). in granuloma with caseous necrosis. Single or budding spherical . and cancer. trauma. inside Langhans cells. In most cases specific diagnosis cannot be made on cytological specimens. Nuclei may be large. 2. e. Cytoplasmic staining from being delicate in the non-atypical metaplasia becomes denser and more eosinophilic with atypical metaplasia. abscesses. Alteration in N/C ratio occurs but the amount of cytoplasm may be increased with increasing degrees of atypia. dark round or oval nuclei. There may be some columnar appearance.

No hyphae. Cryptococcus neoformans: Usually a secondary invader in the dehibilitated. Aspergillus spp. Silver stains reveal no internal structure. Viral diseases: May affect any part of the body including respiratory tract and affected cells may be present in washings from the sinuses. Viral pneumonia: → Possible appearances of altered bronchial cells include: – Loss of cytoplasmic borders – clusters. 8 – 15 µm in diameter.C. Soc. 1. 98. Indicates a mass destruction of ciliated cells. interstisioned gram +ve filaments which may terminate in eosin-staining enlargement or clubs. but the daughter cell pinches off leaving attenuated isthmus of attachment to the mother cell assuming a tear drop shape. Pulmonary actinomycosis may develop from a sub-diaphragmatic hepatic abscess. NB: The cell is thick walled. Differential diagnosis: Adenocarcinoma. Budding: single bud is characteristic. It is not classified as a fungi but as bacteria which display branching. Pneumocystis carinii: A frequently fatal complication of some severe underlying disease. Note: The organism must be seen inside histiocytes to be diagnostic. These can be seen with the naked eye in the pus as grey or yellow “sulphur granules”.: Thick septate hyphae with 450 angle brush-like branching. Occurrence: Inflammatory viral pneumonia Bronchogenic carcinoma – relative frequent association. Occasional spore heads resemble a brush. Bud remains in close position to mother cell. Cells found associated with marked inflammatory reactivity. The nucleus may show karyorrhexis-like degeneration. Thick refractile walls gives a double contoured appearance. Acidophilic (eosinophilic) cytoplasmic inclusion may be present. Experimental work done by Cynthia Pierce (Proc. 489. 1958). with flattening where the two cells contact. – Nucleoli may be present. NB: if ciliated cells are present with similar atypias – . – Nuclear enlargement. Golden-brown irregularly septated forms which look rather like seeds. Buds may remain attached producing a short chain.P. – Hyperchromasia. Experimental Biol. in patients undergoing corticosteroid or immunosuppressive therapy. Cytoplasm varies and may see scattered brownish red granules. Single budding is also a characteristic. This can be seen with Giemsa. or by aspiration. They break in half and one sees anucleated ciliated tufts and the nuclei with fragmented cytoplasm. Loss of cilia and rounding of cells: Ciliocytophora (C. Chronic abscesses develop and the organism in the lesion occur as colonies which are termed “grains”. Inflammatory reaction may be extremely slight. Actinomyces: Caused by the anaerobic organism Actinomyces israeli is of world wide occurrence.) is a term from Papanicolaou. Med. Microscopically these are delicate branching.cells. Cyst forms are small round. disc shaped or crescentic. May be basophilic. 5 – 20 µm in diameter (very small). The septate hyphae are strong morphological evidence of infection. Multinucleated giant cells engulf the organism. Alternaria species: Non-pathogenic. PAP stain frothy and structureless. Aspergillomes of the lung may produce marked cellular atypia which may be mistaken for cancer.

Cilia persist. Cells are often more degenerate. 3. Cytoplasmic vacuolation. Herpes simplex: Cell appearance: similar changes to those seen in genital system. Herpes simplex changes: Nuclear enlargement and multiplication. ● Cytological Changes due to Therapy RADIATION THERAPY: – Squamous epithelial changes: Similar to genital tract description. Eosinophilic intra-nuclear inclusion may be seen. The enlarged nuclei tend to be irregular in form and markedly hyperchromatic. Wrinkled-empty looking finely granular nuclei. Adenovirus: Eosinophilic intra nuclear inclusions. Large central inclusion bodies in the nuclei. Opaque homogenization of nuclei (“ground glass” appearance of nuclei). Appearance: Marked cellular and proportionate nuclear enlargement. Chromatin clumping and margination beneath the nuclear membrane (nuclear halo). 2. the cytological interpretation may be very difficult. . May occur in debilitated adults. The chromatin is uniformly coarsely granular. Enlargement of all cell components. Degenerative vacuoles of cytoplasm and nuclei are features. occasionally eosinophilic inclusion bodies in cells both in the cytoplasm and nucleus. – Columnar changes: Multinucleation. Large bizarre cells with malignant-looking features may be present. Crowding and moulding and “ground glass” opaque nuclei are features. Enlarged nucleoli. Reagan & Ng. Multinucleation. 4. the cytoplasm of these cells is less homogenous and does not keratinise. The cytoplasm is moderately abundant and vacuolated. Measles: Large multinucleated giant cells in nasal secretions. This is a fatal disorder in infants when cytomegalic cells may be isolated in the urine.: The abnormal cells associated with cancer chemotherapy are normally limited in number. Multi-nucleation may be observed. Nuclear crowding and moulding. They appear pleomorphic and bizarre forms are frequent. 5. Cytomegalic Inclusion Disease: Characterised by basophilic. BISULFAN (Myleran) is a cytotoxic drug used in treatment of cancer. In general. Unless the history is given of use of such drugs.the condition is benign.

hemoptysis in 50% of cases. pleuritic pain. Occupational hazards e. night sweats. Local spread: 1) Progressive spread. Pathology: Extensive caseation (necrosis with cheese-like appearance). cough: muco-purulent. Miliary TB: TB scattered throughout the body (like millet seed) – often fatal. Diabetes. South India and Asia. Clinically: May be asymptomatic.g. Prognosis: Usually good if confined to the lungs. coal miners and laboratory workers. Consequences: Healing: viable bacteria may remain in the calcified focus. The nuclei may appear pyknotic and the changes have some features of irradiation changes. fibrosis and progressive disease with little or no lymph node involvement.g. can spread throughout the body. PULMONARY TUBERCULOSIS Incidence: Extremely common in South Africa. Poor general health (e. or Malaise. . Cytology: Granuloma consisting of epitheloid cells (altered macrophages). Primary infection: Usually in childhood. TB meningitis. Acid fast rods with Ziehl Nielson. Hypersensitivity is induced. called Ghon focus. Steroid therapy – long term.: Reactivation of organisms or infection due to lowered resistance or overwhelming infection. 2) TB pneumonia. Hematogenous dissemination: 1) If it invades a branch of the pulmonary artery.g.Prominent chromocentres of nucleoli are evident.B. Post Primary Pulmonary T. low grade fever. 2) If it invades the sub-clavian vein. Aetiology: Mycobacterium tuberculosis – usually inhaled. usually asymptomatic. Langhans giant cells with multiple nuclei in a horse-shoe arrangement. with central casceous necrosis. lymphocytes and fibrous tissue. the condition may be confined to the lung. Predisposing factors: Increased susceptibility caused by Malnutrition / alcoholism. HIV+). Elderly with weakened defences. anorexia. Form grey / white foci of consolidation. e.

Spread may however occur in children and debilitated people. 7. ACUTE BRONCHITIS This is inflammation of the large and medium bronchi. the following may be present in sputum: 1. 6. NB: In asthma. 2. Bronchiolitis and bronchopneumonia result and can prove fatal. Curschmann's spirals: appear (macroscopically) as small white granules in sputum. The condition is usually mild and spread to the bronchioles is unusual in healthy adults due to effective ciliary action of the bronchial epithelium. The lung is rather voluminous but without any real emphysema. The difficulty in breathing is mainly related to exhalation due to the plugging of bronchioles with viscid mucus. the result of prolonged spasm. Coughing which is non-productive may occur. Ciliated epithelium lining the bronchi aids passage of the exudate upward and helps prevent spread down to the bronchioles. Charcot-Leyden crystals (diamond shaped) in association with eosinophils. This initial phase is followed by bacterial invasion. Inspissated core of structure with coiled sheath of mucus containing small round cells. Degenerate balls of cells forming a Creola body. Equally important is the serious effect of repeated attacks of acute infection in patients with chronic bronchitis. Many leukocytes including eosinophils (produce histaminase to regulate hypersensitivity reaction). Streptococcus pneumoniae and Haemophilus influenzae are most common but Staphylococcus aureus and Streptococcus pyogenes may be found especially in infants. 4. Hypersecretory goblet cells with prominent nucleoli. Often metaplastic cells which may be atypical. Thickened and hyalinised basement membrane overlies oedematous (edematous) submucosa (many eosinophils present) and congested blood vessels and hypertrophic muscle. It is a common complication of influenza and measles. At the end of the attack thick viscid sputum is produced.BRONCHIAL ASTHMA This condition. In most cases the process is initiated by a viral or mycoplasmal infection. The asthmatic attack begins with difficulty in breathing. 5. producing loud wheezing noises. 3. Histological changes are a combination of allergic reaction and muscular hypertrophy. Mucous and serous glands in tme walls of the bronchi provide abundant mucoid secretion during the inflammation. . of allergic nature is characterised by spasmodic attacks of severe dyspnoea with some coughing. The condition may be serious if associated with pre-existing respiratory disease. Large number of histiocytes. Viscid secretion composed of eosinophils and desquamated epithelium in thick mucus. particularly exhalation.

Seepage and retention of exudate in alveoli → patches of pneumonia during acute exacerbations. With repeated acute exacerbations of the inflammation and increasing retention of secretion. The respiratory bronchioles are lined with non-ciliated cuboidal epithelium. oedema (edema) and congestion. spread of the chronic changes along the bronchial tree is encouraged. Stenosis of bronchioles → obstruction to expiration → emphysema The causes of chronic bronchitis are multiple and form an interacting complex. chemical vapours. The lack of ciliary action makes it difficult to get rid of exudate and renders resolution. Goblet cells appear in the terminal bronchioles. At first the bronchial wall is thickened due to the increase in glandular tissue. At later stage it may become thin as a result of atrophy of all structures. When the terminal bronchioles are affected more serious changes can take place: Ciliated columnar cells normally found untill the small bronchi and bronchioles (single layer. Healing is by organisation: 1. Increase in goblet cells + increase of mucous glands with loss of serous glands + loss of ciliated epithelium → Large quantity of viscid secretion difficult to eliminate. sulphur dioxide) Metaplasia of epithelium Irritation Loss of ciliated epithelium Stimulation of secretion Retention of secretion Mucous gland hyperplasia Chronic Bronchitis Bacterial proliferation Retention of secretion . Atmospheric pollution Tobacco smoke Repeated attacks of acute (Particulate matter. bronchitis exhaust fumes. no goblet cells). The tendency to retention of secretion encourages bacterial growth creating a vicious circle: Chronic bronchitis Repeated attacks of acute inflammation Bacterial infections Continued chronic irritation may result in squamous metaplasia of the bronchial epithelium.CHRONIC BRONCHITIS The essential feature is a change in the epithelial structure of the bronchus. Obliteration of some alveoli and bronchioles 2.

X-ray may be mistaken for carcinoma. indurated and yellowish. – Fibrosis commences in subpleural zone of lower lobe (i. Spreading occurs inwards and upwards. In its serious form it occurs in males over the age of 40 but the onset can be dated many years earlier. ● Asbestosis This term is generally reserved for a process which affects both lungs and leads to progressive destruction of respiratory tissue. all of them may occur in the same patient. Spread occurs to ducts and alveoli. Diffuse type: Focal lesions commonly in lower lobes. 3. Fat cells form in situ. Foamy. carcinoma or abscess.wikipedia. Vegetable oils are relatively innocuous but mineral oils are especially irritant. – Destruction of lung tissue and contraction of fibrous tissue cause shrinkage of lobe. lymphocytes and fibrocytes replace macrophages. The particles particularly affect the lower lobes and produce a spreading fibrosis.e.Chronic bronchitis is most common in industrial areas with a high rainfall. usually an adenocarcinoma. pale color. – Fibrosis first affects respiratory bronchioles. Progressively increasing dyspnoea appears ending in respiratory failure. Asbestosis. Also see: http://en. Localised type: Single rounded indurated mass. 2. arises commonly in the fibrotic lower . due to fatty residues of necrotic tissue. Pulmonary hypertension and right heart failure complicate the process. Bronchial carcinoma. 1. These tend to coalesce until a whole lobe becomes solid. – Unaffected bronchioles may undergo compensatory dilation → one type of honeycomb lung. lipid filled macrophages seen with multinucleated giant cells. 2. regurgitated oily medicine. ASBESTOSIS Asbestos dust causes severe pulmonary disease. Pleural fibrous plaques.org/wiki/COPD PNEUMONIA – SPECIAL TYPES LIPID PNEUMONIA This is a non-infective pneumotic condition usually of iatrogenic origin (medication): Inhaled oily nose drops. Three distinct lesions can be identified. Later. A similar type of lesion may also form in cases of non-resolving pneumonia. Malignant mesothelioma. outer periphery of lung). Sequelae: The process is slow and symptoms may be delayed for years. Microscopically the process exhibits two phases: 1.

These bodies are found in the sputum of individuals exposed to asbestos dust. They occur in the lung tissue where whichever asbestosis lesions exist. Antinuclear antibody and rheumatoid factor are found in a quarter of all patients. They produce no symptoms and are not a precursor to mesothelioma. An immunological mechanism may operate. roofing felt. Simple coal worker's anthracosis and Progressive massive fibrosis. Crocidolite (blue asbestos) and Amosite (brown iron-rich asbestos): both are in the form of rigid fibres which reach the periphery of the lung and are associated with all three types of lesion. ● Malignant mesothelioma This tumor can occur even if the individual was only exposed to a low concentration of asbestos dust for a relatively short space of time. ASBESTOS BODIES: Asbestos fibres become coated with mucopolysaccharide and iron. particularly coal miners and is comparable to “hut lung” (people around indoor fire to keep warm). They are irregular in shape but well-defined and circumscribed calcification may follow. tiles. nl. insulation. ● Pleural fibrous plaques Bilateral pearly white plaques of acellular collagen form on the parietal pleura and upper surface of the diaphragm. Crocidolite is especially associated with mesothelioma. Macrophages which have ingested asbestos fibres may form a fibrogenic substance. There is however a long interval between exposure to the dust and the time of appearance of the tumor. The intervening (rod-like) part is segmented. brake and clutch linings. Types of asbestos fibres and their industrial use as at 2001 Chrysolite (white asbestos): occurs as soft curly fibres generally retained in the upper respiratory tract. Mechanism of fibrogenesis: Unknown. 2. gaskets. ANTHRACOSIS This indicates an accumulation of carbon particles in the lung. Two forms are recognised. but two suggestions have been made: 1. A typical body is brown in color with bulbous ends. Used in making textiles. It is found in a marked form in those who handle soft butiminous coal. yet are rarely if ever found within the pleural fibrous plaques or in mesothelioma tumor tissue. It causes asbestosis.lobe and is the cause of death in 50 % of cases. ● Simple coal miner's anthracosis . but rarely mesothelioma or pleural plaques. Both are highly resistant to acids and alkalis and are used in insulation work.

Lecture 3 – Bronchogenic Carcinoma.Changes most marked in upper half of lung but also found in lower lobes. Look out for it at: http://www. ● Progressive massive fibrosis In a small percentage of workers with simple anthracosis this further serious change may develop: Irregular masses of black fibrous issue in the upper lobes. the alveoli are obliterated and the specialised structures such as muscle in the broncheolar wall atrophy. Fibrosis of lung tissue Reduction in functional tissue Hypoxia Respiratory failure Pulmonary hypertension Right ventricular failure Secondary emphysema ? Tuberculosis Vascular obliteration Notes from Cape Tech. 2002 Next notes : Cell. This results in focal dust emphysema which itself has no significant effect on respiratory function. Path. Thickened pleura often adhere to the chest wall. According to some observers all the changes – fibrous and cavitation – are due to tuberculosis. The functional effects are severe. especially those around respiratory bronchioles. Lower parts of lung show simple anthracotic changes. called “carbon cells”) accumulate and adhere to alveolar walls. Tuberculosis infection can be demonstrated in 40 % of cases. This may be the cause of cavitation in some of the fibrous nodules. Macrophages (now clogged with carbon particles. The macrophages die and a limited degree of fibrosis develops around the particles. Black lines and small nodules of carbon deposit.scribd. In other instances cavitation may be due to necrosis following the obliteration of blood vessels. Respiratory bronchioles become surrounded by a cuff of alveoli filled by carbon-laden macrophages. The respiratory bronchiole becomes inelastic and with thw obliteration of alveoli the air pressure from inhalation causes dilation of the bronchioles. (Cape Peninsula University of Technology). The fibrous tissue is rubbery. Alveolar epithelium grows over the fibrous masses.com/people/documents/2135965/folder/83622 . Carbon particles of less than 5 µm are taken up by macrophages and transported to the alveolar spaces. Cavities are filled with black fluid in central nodules.

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