Clinical Pathology
1. Pathomorphologic diagnosis and epicrisis – main disease as a cause of death, complications of main diseases,
accompanying diseases (co-morbidity), background diseases, cause of death.
Over half of the deaths worldwide are due to the top 10 causes of death. The leading causes of death are ischemic heart
disease and stroke. Chronic obstructive pulmonary disease and lung and other respiratory system cancers and the next
biggest causes of death. This is followed by death due to dementia and Alzheimer’s and the remaining leading causes of
death can be attributed to diabetes, diarrhoea, tuberculosis and road injuries.
2. Biopsy – main method of investigation in the diagnostic process.
A biopsy is a medical test that is commonly performed by. Surgeon, radiologist or cardiologist. It involves extracting
samples of tissue for examintion to determine the presence or absence of disease. After extraction, the tissue is analysed
under a microscope by a pathologist.
3. Inflammatory diseases of the airways – acute and chronic bronchitis, bronchiolitis.
Inflammatory processes can affect all parts of the respiratory system
The diseases can be acute, chronic
Epiglottitis
Acute tracheobronchitis –
• Purulent with pus – due to bacteria: step, staphy, mycotic
Suppurative Bronchitis + bronchiolitis
• Most commonly caused by pneumococcal pneumonia
• Starts at bronchitis, may spread to pulmonary parenchyma
We can have focal pneumonia – only affected some parts = bronchopneumonia
Diffuse pneumonia in form of crupous – affecting whole lobe or lung = lobar pneumonia
• Congestion
• Red hepatization – RBC, neutrophils, fibrin (PTAH stain), erythrocytes
• Grey hepatization – RBC are removed, more and more leukocytes are recruited
o Artificial white yards are due to fibrin retraction – used as good diagnostic
o Two types – deep and superficial
▪ Deep usually affected squamous → deep erosion effects more then one layer
▪ Superficial – columnar → only affects one or two layers, more superficial erosion
• Resolution – formation of granulation tissue which is carnification, which can then lead to fibrosis
o Or the infiltrate can be completely resorbed → complete resolution
Often forms abscess cavity – mostly due to staphylococcal infection
Complications:
• Bacteremia, sepsis
• Lung abscess
• Pleural effusion, empyema (pus in pleura)
• Fibrosis
• Pericarditis
• Atelectasis
• Death
Very often next to fibrous inflammation → inflammation of the pleura, superficial fibrionous inflammation → this acute
inflammation which forms fibrin → turned to fibrosis → adhesions
Pneumonia also exacerbates heart failure
Atelectasis – due to increased pressure, or in CT disorders, EDS, marfan etc
,Aspergillosis
• Fungal infection
• We usually see accumultation of specific granulomas
• The fungi are arranged in hyphi – like rods that are close together and they stain darker – like sunshine rays
• Can be either diffuse or focal depending on persons immunity
• The hyphae are usually surrounded by necrotic tissue, acute inflammatory cells with mixed chronic ones
• The hyphae usually float in the necrotic materials
There are 4 forms:
• Focal infection – aspergillosis
• Diffuse – milliary aspergillosis effect – seems like military tuberculosis
Opportunistic infection – infection occurs due to weakned immune system
Includes:
• Cytomegalovirus – causes cells to enlarge
o Balloon like inclusions
o Can see halo around it
• Herpes simplex virus – usually starts around the mouth
o There are 2 types of HSV
o Then it can spread → multiple sites changed and specific signs for infection with HSV
o Colonies of cells
▪ Can see multiple neutrophils
▪ Perform aspiration of fluid from pleural cavity
• TORCH syndrome
• They all affect majorly glandular structure, brain structures, lymph nodes → glands to be enlarged
• Can see multiple cytoplasmic inclusions
Crupous pneumonia is neither or sometimes superficical
Carnification after crupous pneumonia
• Empty fields – majorly fibrous tissue diffuse
• Can see collapsed alveoli
• Vessels, remnants of hemorrhages, someties calcification
• Alveoli remnants
• Inbetween the alveolar sheets accumulation of fibrous tissue
• Remnants of chronic + acute inflammatory cells
• Can also see some granulation tissue
• Fibrous tissue – fibroblasts + fibrocytes with elongated spindle cells with lots of collagen
• End of chronic process, beginning of fibrosis → loss of function of the lungs
Carnification only happens in the lungs
• Can see yellow small pus leaking out of the bronchi
o Made of neutrophils, desquametd cells, bacteria, inflammatory cells
o Can see thickened septa of the alveoli
Often complication is abscess – can be acute or chronic
• Chronic with pyogenic membrane – granulation tissue, macrophages, lymphocytes
o Needs drainage procedure
• Acute without pyogenic membrane
Epiglotic edema – usually due to allergic reactions
,4. Tumors of the larynx and trachea. Laryngeal cancer.
Larynx
The most common disorders of the larynx are inflammatory. Tumors are uncommon but are amenable to resection,
though often at the price of loss of natural voice.
Reactive Nodules (Vocal Cord Nodules and Polyps)
Reactive nodules, also called polyps, sometimes develop on the vocal
cords, most often in heavy smokers or in individuals who impose great
strain on their vocal cords (singer’s nodules)
By convention, singers’ nodules are bilateral lesions and polyps are
unilateral.
These nodules are smooth, rounded, sessile or pedunculated
excrescences, generally only a few millimeters in the greatest dimension,
located usually on the true vocal cords.
They are typically covered by squamous epithelium that may become keratotic, hyperplastic, or even slightly dysplastic.
The core of the nodule is a loose myxoid connective tissue that may be variably fibrotic or punctuated by numerous
vascular channels.
When nodules on opposing vocal cords impinge on each other, the mucosa may undergo ulceration. Because of their
strategic location and accompanying inflammation, they characteristically change the character of the voice and often
cause progressive hoarseness.
They never give rise to cancer!
Squamous Papilloma and Papillomatosis
Laryngeal squamous papillomas are benign neoplasms, usually located on the true vocal cords, that form soft, raspberry-
like proliferations rarely more than 1 cm in diameter.
On histologic examination, the pap-illomas are made up of multiple slender, finger-like projections supported by central
fibrovascular cores and covered by an orderly stratified squamous epithelium. When the papillomas are on the free edge
of the vocal cord, trauma may lead to ulceration that can be accompanied by hemoptysis.
Papillomas are usually single in adults but are often multiple in children, in whom they are referred to as juvenile
laryngeal papillomatosis.
The lesions are caused by HPV types 6 and 11. They do not become malignant, but frequently recur.
Carcinoma of the Larynx
Carcinoma of the larynx is typically a squamous cell carcinoma seen in male chronic smokers.
Sequence of Hyperplasia-Dysplasia-Carcinoma
A spectrum of epithelial alterations is seen in the larynx. They range from hyperplasia, atypical hyperplasia, dysplasia, and
carcinoma in situ to invasive carcinoma. Grossly, the epithelial changes vary from smooth, white or reddened focal
thickenings, sometimes roughened by keratosis, to irregular verrucous or ulcerated
white-pink lesions.
There are all gradations of epithelial hyperplasia of the true vocal cords, and the
likelihood of the development of an overt carcinoma is directly proportional to the
grade of dysplasia when the lesion is first seen.
Orderly hyperplasias have almost no potential for malignant transformation, but the risk
rises to 1% to 2% during the span of 5 to 10 years with mild dysplasia and 5% to 10%
with severe dysplasia. Only histologic evaluation can determine the gravity of the
changes.
The epithelial alterations described above are most often related to tobacco smoke, the
risk being proportional to the level of exposure. Indeed, up to the point of cancer, the
changes often regress after cessation of smoking. Together smoking and alcohol
increase the risk substantially. Other factors that may contribute to increased risk include nutritional factors, exposure to
asbestos, irradiation, and infection with HPV.
, Morphology
About 95% of laryngeal carcinomas are typical squamous cell tumors. The tumor usually develops on the vocal cords, but
it may also arise above or below the cords, on the epiglottis or aryepiglottic folds, or in the pyriform sinuses. Those
confined within the larynx proper are termed intrinsic, whereas those that arise or extend outside the larynx are called
extrinsic. Squamous cell carcinomas of the larynx follow the growth pattern of other squamous cell carcinomas. They
begin as in situ lesions that later appear as pearly gray, wrinkled plaques on the mucosal surface, ultimately ulcerating
and fungating. The degree of anaplasia of the laryngeal tumors is highly variable. Sometimes massive tumor giant cells
and multiple bizarre mitotic figures are seen. As expected with lesions arising from recurrent exposure to environmental
carcinogens, adjacent mucosa may demonstrate squamous cell hyperplasia with foci of dysplasia or even carcinoma in
situ.
Carcinoma of the larynx is most commonly seen in men in the sixth decade of life and often manifests clinically as
persistent hoarseness, dysphagia, and dysphonia. Prognosis is highly dependent on clinical staging.
Tracheal tumor
Tracheal neoplasms occur infrequently, accounting for fewer than 1% of all malignancies.
Patients with tracheal tumors can present with catastrophic airway obstruction. In addition to primary neoplasms of the
trachea, secondary tracheal involvement can occur from tumors of surrounding tissues such as thyroid, esophagus,
larynx, and lung.
Of all primary tumors of the trachea, 80% are malignant; squamous cell carcinoma (SCC) was the predominant histology
type at 259 (44.3%) tumors, followed by adenoid cystic carcinoma (ACC) at 16.3%. The remaining tumors are widely
varied and include both malignant and benign histotypes.
Pathophysiology
The tracheal mucosa is columnar and ciliated. It is closely apposed to the tracheal cartilages and to the interannular
tissues between them. Mucous glands are liberally present. In patients with chronic bronchitis, particularly those who
smoke heavily, squamous metaplasia may occur.
Typically, tracheal tumors grow slowly. Benign neoplasms tend to be smooth, rounded masses less than 2 cm in length.
The presence of calcium seen on plain radiography films, though common, does not reliably differentiate benign and
malignant tumors. Malignant tumors, specifically SCCs, may be exophytic or ulcerative.
Singer’s Nodule
• Benign small laryngeal polyp
• Usually induced by chronic irritation e.g. excessive voice use, heavy ciggarete smoking
• Usually localized to the true vocal cords
Squamous Papilloma
• Benign neoplasms, usually centred around the true vocal cords, rarely undergo malignant change
• Usually due to low risk HPV infections (type 6 + 11)
• In children and adolescents, multiple lesions may be seen sometimes with airway threatening extension into the
trachea and bronchi – juvenile laryngeal papillomatosis – reccurance after resection is cmmon
Squamous Cell carcinoma
• Most common malignant tumor or larynx
• usually seen in men older than 40
• associated with the combination of alcoholism + cigarette smoking
• usually not associated with HPV
• initially presents with persistant horseness
o Glottic carcinoma – arises from true vocal cords, most common type, with best prognosis
o Supraglotic and subglottic carcinoma – less common, have poorer prognosis.
1. Pathomorphologic diagnosis and epicrisis – main disease as a cause of death, complications of main diseases,
accompanying diseases (co-morbidity), background diseases, cause of death.
Over half of the deaths worldwide are due to the top 10 causes of death. The leading causes of death are ischemic heart
disease and stroke. Chronic obstructive pulmonary disease and lung and other respiratory system cancers and the next
biggest causes of death. This is followed by death due to dementia and Alzheimer’s and the remaining leading causes of
death can be attributed to diabetes, diarrhoea, tuberculosis and road injuries.
2. Biopsy – main method of investigation in the diagnostic process.
A biopsy is a medical test that is commonly performed by. Surgeon, radiologist or cardiologist. It involves extracting
samples of tissue for examintion to determine the presence or absence of disease. After extraction, the tissue is analysed
under a microscope by a pathologist.
3. Inflammatory diseases of the airways – acute and chronic bronchitis, bronchiolitis.
Inflammatory processes can affect all parts of the respiratory system
The diseases can be acute, chronic
Epiglottitis
Acute tracheobronchitis –
• Purulent with pus – due to bacteria: step, staphy, mycotic
Suppurative Bronchitis + bronchiolitis
• Most commonly caused by pneumococcal pneumonia
• Starts at bronchitis, may spread to pulmonary parenchyma
We can have focal pneumonia – only affected some parts = bronchopneumonia
Diffuse pneumonia in form of crupous – affecting whole lobe or lung = lobar pneumonia
• Congestion
• Red hepatization – RBC, neutrophils, fibrin (PTAH stain), erythrocytes
• Grey hepatization – RBC are removed, more and more leukocytes are recruited
o Artificial white yards are due to fibrin retraction – used as good diagnostic
o Two types – deep and superficial
▪ Deep usually affected squamous → deep erosion effects more then one layer
▪ Superficial – columnar → only affects one or two layers, more superficial erosion
• Resolution – formation of granulation tissue which is carnification, which can then lead to fibrosis
o Or the infiltrate can be completely resorbed → complete resolution
Often forms abscess cavity – mostly due to staphylococcal infection
Complications:
• Bacteremia, sepsis
• Lung abscess
• Pleural effusion, empyema (pus in pleura)
• Fibrosis
• Pericarditis
• Atelectasis
• Death
Very often next to fibrous inflammation → inflammation of the pleura, superficial fibrionous inflammation → this acute
inflammation which forms fibrin → turned to fibrosis → adhesions
Pneumonia also exacerbates heart failure
Atelectasis – due to increased pressure, or in CT disorders, EDS, marfan etc
,Aspergillosis
• Fungal infection
• We usually see accumultation of specific granulomas
• The fungi are arranged in hyphi – like rods that are close together and they stain darker – like sunshine rays
• Can be either diffuse or focal depending on persons immunity
• The hyphae are usually surrounded by necrotic tissue, acute inflammatory cells with mixed chronic ones
• The hyphae usually float in the necrotic materials
There are 4 forms:
• Focal infection – aspergillosis
• Diffuse – milliary aspergillosis effect – seems like military tuberculosis
Opportunistic infection – infection occurs due to weakned immune system
Includes:
• Cytomegalovirus – causes cells to enlarge
o Balloon like inclusions
o Can see halo around it
• Herpes simplex virus – usually starts around the mouth
o There are 2 types of HSV
o Then it can spread → multiple sites changed and specific signs for infection with HSV
o Colonies of cells
▪ Can see multiple neutrophils
▪ Perform aspiration of fluid from pleural cavity
• TORCH syndrome
• They all affect majorly glandular structure, brain structures, lymph nodes → glands to be enlarged
• Can see multiple cytoplasmic inclusions
Crupous pneumonia is neither or sometimes superficical
Carnification after crupous pneumonia
• Empty fields – majorly fibrous tissue diffuse
• Can see collapsed alveoli
• Vessels, remnants of hemorrhages, someties calcification
• Alveoli remnants
• Inbetween the alveolar sheets accumulation of fibrous tissue
• Remnants of chronic + acute inflammatory cells
• Can also see some granulation tissue
• Fibrous tissue – fibroblasts + fibrocytes with elongated spindle cells with lots of collagen
• End of chronic process, beginning of fibrosis → loss of function of the lungs
Carnification only happens in the lungs
• Can see yellow small pus leaking out of the bronchi
o Made of neutrophils, desquametd cells, bacteria, inflammatory cells
o Can see thickened septa of the alveoli
Often complication is abscess – can be acute or chronic
• Chronic with pyogenic membrane – granulation tissue, macrophages, lymphocytes
o Needs drainage procedure
• Acute without pyogenic membrane
Epiglotic edema – usually due to allergic reactions
,4. Tumors of the larynx and trachea. Laryngeal cancer.
Larynx
The most common disorders of the larynx are inflammatory. Tumors are uncommon but are amenable to resection,
though often at the price of loss of natural voice.
Reactive Nodules (Vocal Cord Nodules and Polyps)
Reactive nodules, also called polyps, sometimes develop on the vocal
cords, most often in heavy smokers or in individuals who impose great
strain on their vocal cords (singer’s nodules)
By convention, singers’ nodules are bilateral lesions and polyps are
unilateral.
These nodules are smooth, rounded, sessile or pedunculated
excrescences, generally only a few millimeters in the greatest dimension,
located usually on the true vocal cords.
They are typically covered by squamous epithelium that may become keratotic, hyperplastic, or even slightly dysplastic.
The core of the nodule is a loose myxoid connective tissue that may be variably fibrotic or punctuated by numerous
vascular channels.
When nodules on opposing vocal cords impinge on each other, the mucosa may undergo ulceration. Because of their
strategic location and accompanying inflammation, they characteristically change the character of the voice and often
cause progressive hoarseness.
They never give rise to cancer!
Squamous Papilloma and Papillomatosis
Laryngeal squamous papillomas are benign neoplasms, usually located on the true vocal cords, that form soft, raspberry-
like proliferations rarely more than 1 cm in diameter.
On histologic examination, the pap-illomas are made up of multiple slender, finger-like projections supported by central
fibrovascular cores and covered by an orderly stratified squamous epithelium. When the papillomas are on the free edge
of the vocal cord, trauma may lead to ulceration that can be accompanied by hemoptysis.
Papillomas are usually single in adults but are often multiple in children, in whom they are referred to as juvenile
laryngeal papillomatosis.
The lesions are caused by HPV types 6 and 11. They do not become malignant, but frequently recur.
Carcinoma of the Larynx
Carcinoma of the larynx is typically a squamous cell carcinoma seen in male chronic smokers.
Sequence of Hyperplasia-Dysplasia-Carcinoma
A spectrum of epithelial alterations is seen in the larynx. They range from hyperplasia, atypical hyperplasia, dysplasia, and
carcinoma in situ to invasive carcinoma. Grossly, the epithelial changes vary from smooth, white or reddened focal
thickenings, sometimes roughened by keratosis, to irregular verrucous or ulcerated
white-pink lesions.
There are all gradations of epithelial hyperplasia of the true vocal cords, and the
likelihood of the development of an overt carcinoma is directly proportional to the
grade of dysplasia when the lesion is first seen.
Orderly hyperplasias have almost no potential for malignant transformation, but the risk
rises to 1% to 2% during the span of 5 to 10 years with mild dysplasia and 5% to 10%
with severe dysplasia. Only histologic evaluation can determine the gravity of the
changes.
The epithelial alterations described above are most often related to tobacco smoke, the
risk being proportional to the level of exposure. Indeed, up to the point of cancer, the
changes often regress after cessation of smoking. Together smoking and alcohol
increase the risk substantially. Other factors that may contribute to increased risk include nutritional factors, exposure to
asbestos, irradiation, and infection with HPV.
, Morphology
About 95% of laryngeal carcinomas are typical squamous cell tumors. The tumor usually develops on the vocal cords, but
it may also arise above or below the cords, on the epiglottis or aryepiglottic folds, or in the pyriform sinuses. Those
confined within the larynx proper are termed intrinsic, whereas those that arise or extend outside the larynx are called
extrinsic. Squamous cell carcinomas of the larynx follow the growth pattern of other squamous cell carcinomas. They
begin as in situ lesions that later appear as pearly gray, wrinkled plaques on the mucosal surface, ultimately ulcerating
and fungating. The degree of anaplasia of the laryngeal tumors is highly variable. Sometimes massive tumor giant cells
and multiple bizarre mitotic figures are seen. As expected with lesions arising from recurrent exposure to environmental
carcinogens, adjacent mucosa may demonstrate squamous cell hyperplasia with foci of dysplasia or even carcinoma in
situ.
Carcinoma of the larynx is most commonly seen in men in the sixth decade of life and often manifests clinically as
persistent hoarseness, dysphagia, and dysphonia. Prognosis is highly dependent on clinical staging.
Tracheal tumor
Tracheal neoplasms occur infrequently, accounting for fewer than 1% of all malignancies.
Patients with tracheal tumors can present with catastrophic airway obstruction. In addition to primary neoplasms of the
trachea, secondary tracheal involvement can occur from tumors of surrounding tissues such as thyroid, esophagus,
larynx, and lung.
Of all primary tumors of the trachea, 80% are malignant; squamous cell carcinoma (SCC) was the predominant histology
type at 259 (44.3%) tumors, followed by adenoid cystic carcinoma (ACC) at 16.3%. The remaining tumors are widely
varied and include both malignant and benign histotypes.
Pathophysiology
The tracheal mucosa is columnar and ciliated. It is closely apposed to the tracheal cartilages and to the interannular
tissues between them. Mucous glands are liberally present. In patients with chronic bronchitis, particularly those who
smoke heavily, squamous metaplasia may occur.
Typically, tracheal tumors grow slowly. Benign neoplasms tend to be smooth, rounded masses less than 2 cm in length.
The presence of calcium seen on plain radiography films, though common, does not reliably differentiate benign and
malignant tumors. Malignant tumors, specifically SCCs, may be exophytic or ulcerative.
Singer’s Nodule
• Benign small laryngeal polyp
• Usually induced by chronic irritation e.g. excessive voice use, heavy ciggarete smoking
• Usually localized to the true vocal cords
Squamous Papilloma
• Benign neoplasms, usually centred around the true vocal cords, rarely undergo malignant change
• Usually due to low risk HPV infections (type 6 + 11)
• In children and adolescents, multiple lesions may be seen sometimes with airway threatening extension into the
trachea and bronchi – juvenile laryngeal papillomatosis – reccurance after resection is cmmon
Squamous Cell carcinoma
• Most common malignant tumor or larynx
• usually seen in men older than 40
• associated with the combination of alcoholism + cigarette smoking
• usually not associated with HPV
• initially presents with persistant horseness
o Glottic carcinoma – arises from true vocal cords, most common type, with best prognosis
o Supraglotic and subglottic carcinoma – less common, have poorer prognosis.
