Pathology Flashcards
1
Q
Infectious Rhinitis
A
- Caused by one or more viruses
- Adeno
- Echo
- Rhino
- Changes may extend to produce pharyngotonsilitis
- Secondary bacterial infection enhances the inflammatory reaction
- Produces mucopurulent and sometimes suppurative exudate
2
Q
Allergic Rhinitis
A
- Initiated by hypersensitivity reactions to one of a larger group of allergens
- IgE-mediated
3
Q
Nasal Polyps
A
- Focal protrusions of mucosa from recurrent attacks of rhinits
- Polyps histologically consist of edematous mucosa having loose stroma, often harboring hyperplastic or cystic mucous glands, infiltrated w/ a variety of inflammatory cells (neutrophils, eosinophils, and plasma cells w/ occasional clusters of lymphocytes
4
Q
Chronic Rhinitis
A
- Sequel to repeated attacks of acute rhinitis w/ eventual development of superimposed bacterial infection
- Deviated septum or polyps w/ impaired drainage of secretions contribute to increased likelihood of microbial invasion
5
Q
Sinusitis
A
- Most commonly preceded by acute or chronic rhinitis, but maxillary sinusitis occassionally arises by extension of a periapical infection through the bony floor of the sinus
- Impairment of drainage is important contributor to process
- Obstruction of outflow (most often from the frontal, less commonly from anterior ethmoid) occasionally leads to mucocele
- Offending agents often normal inhabitants of oral cavity
- Is a component of Kartegener Syndrome
- Have potential to spread into orbit and penetrate surrounding bone or spread into cranial vault causing septic thrombophlebitis of dural venous sinus
6
Q
Necrotizing Lesions of Nose and Upper Airways
A
- Acute Fungal Infections - Diabetes/Immunosuppressed
- Granulomatosis w/ Polyangitis (Wegener’s)
- Extranodal NK/T-Cell Lymphoma - lymphoma which tumor cells harbor EBV, typically seen in males 5th/6th decade of life most commonly of Asian and Latin American Descent
7
Q
Pharyngitis and Tonsilitis
A
- Most commonly implicated are the rhinoviruses, echoviruses, and adenoviruses
- Less frequently RSV and various strains of influenza virus
- Bacterial infections may be superimposed on viral infections and may be primary invaders
- Most common offenders are the beta-hemolytic streptococci, but sometimes Staph aureus or other pathogens may be implicated
8
Q
Nasopharyngeal Angiofibroma
A
- Nasopharyngeal angio-fibroma is a benign, highly vascular tumor that occurs almost exclusively in adolescent males who are often fair-skinned and red headed
- 75% express androgen receptors
- Also in association w/ familial adenomatous polyps
- Believed to arise w/in the fibrovascular stroma of the posterolateral wall of the roof of the nasal cavity
- Surgical removal is treatment of choice
- Because of locally agressive nature and intracranial expansion, recurrence rates can be as high as 20%
9
Q
Sinonasal Papilloma
A
- Benign neoplasm arising from the respiratory or schneiderian mucosa lining the nasal cavity and paranasal sinuses
- Occur in 3 Forms
- Exophytic (Most Common)
- Endophytic (Most Important Biologically)
- Cylindrical
- HPV DNA, often types 6 and 11, has been identified in the exophytic and endophytic lesions, NOT cylindrical type
- Observed most commonly in adult males b/t ages 30 and 60
10
Q
Olfactory Neuroblastoma (Esthesioneuroblastoma)
A
- “Small round blue cell tumors”
- Arise from neuroectodermal olfactory cells present w/in the mucosa, particularly in the superior aspect of the nasal cavity, and express neuroendocrine markers by immunohistochemistry
- Bimodal age distribution w/ peaks at 15 and 50 years of age
- Typically present w/ nasal obstruction and/or epistaxis
11
Q
Sinonasal Undifferentiated Carcinoma (SNUC)
A
- Anaplastic carcinoma in the skull base of adults
- No histological differentation
- Positive for CK by immunohistochemistry confirming epithelial origin
- Very aggressive w/ 2 year median survival
12
Q
NUT Midline Carcinoma
A
- Uncommon tumor that may occur in the nasopharynx, salivary gland, or in the other midline structures in the thorax or abdomen
- Characteristic transfusion resulting in fusion gene product which may be a future therapeutic target (BRD4-NUT)
- Can occur at any age (infancy to late adulthood)
- Extremely agressive and resistant to conventional therapy
- Most patients survive less than a year following diagnosis
13
Q
Nasopharyngeal Carcinoma
A
- Thought to take 1 of 3 patterns:
- Keratinizing Squamous Cell Carcinomas
- Nonkeratinizing Squamous Cell Carcinomas
- Undifferentiated/Basaloid Carcinomas
- Abundant non-neoplastic, lymphocyte infiltrate
- 3 Factors Influence Origins of These Neoplasms
- Heredity
- Age
- Infection w/ EBV
- As well as diets high in nitrosamines (fermented foods/salted fish)
- Often clinically occult for long periods
- Present w/ nasal obstruction, epistaxis, and often metastases to cervical lymph nodes in as many as 70% of the patients
- Nonkeratinizing Type = better prognosis
- Ketanizing Type = worst prognosis 20% 5-year survival
14
Q
Cholesteatomas
A
- Associated w/ chronic otitis media
- Non-neoplastic, cystic lesions 1-4 cm in diameter
- Lined by keratinizing squamous epithelium or meta-plastic mucus-secreting epithelium, and filled w/ amorphous debris
- Sometimes contain spicules of cholesterol
- Pathogenesis not clear, proposed that chronic inflammation and perforation of the eardrum w/ ingrowth of the squamous epithelium or metaplasia of the secretory epithelial lining of the middle ear are responsible for the formation of a squamous cell nest that becomes cystic
- Can erode into the ossicles, labyrinth, adjacent bone, or surrounding soft tissue and sometimes produce visible neck masses
15
Q
Otosclerosis
A
- Abnormal bone deposition in the middle ear about the rim of the oval window into which the footplate of the stapes fits
- Both ears usually affected
- Fibrous ankylosis of the footplate followed by bony overgrowth anchoring it into the oval window
- Degree of immobilization governs the severity of the hearing loss
- Familial in most instances
- Autosomal dominant transmission w/ variable penetrance
16
Q
Caries
A
- Fermenting sugars by bacteria → acidic metabolites → demineralization of tooth
17
Q
Gingivitis
A
- Inflammation of the gums
- Result of poor oral hygiene and leads to the accumulation of dental plaque and calculus
- Dental plaque is colorless biofilm that collects b/t and on the surface of the teeth
- It contains a mixture of bacteria, salivary protein, and desquamated eptihelial cells
- If not removed mineralized to calculus (tartar)
18
Q
Periodontitis
A
- Inflammation of the supporting structures of the teeth
- Can lead to complete destruction of the periodontal ligament, leading to loosening and eventual loss of teeth
- May be associated w/ underlying systemic disease and may contribute to development of systemic infectious diseases
19
Q
Aphthous Ulcers (Canker Sores)
A
- Painful, superficial oral mucosa ulcerations of unknown etiology
- Tend to be prevalent w/in certain families and may also be associated w/ immunologic disorders
- Celiac Disease
- IBD
- Behcet Disease
- Single or Multiple
- Shallow, hyperemic ulcerations covered by a thin exudate and rimmed by a narrow zone of erythema
20
Q
Irritation Fibroma
A
- Submucosal nodular mass of fibrous connective tissue stroma (reactive), occurs primarily on the buccal mucosa along the bite line or the gingiva
- Tx = Complete Excision
21
Q
Pyogenic Granuloma
A
- Inflammatory lesion typically found on the gingiva of children, young adults, and pregnant women
- Surface of lesion is often ulcerated and red to purple in color
- Histologically, highly vascular proliferation of organizing granulation tissue
- Complete surgical excision is the definitive treatment for these lesions
22
Q
Peripheral Ossifying Fibroma
A
- Reactive in nature
- May arise from a long-standing pyogenic granuloma or develop de novo from cells of the periodontal ligament
- Appear as red, ulcerated, and nodular lesions of the gingiva
23
Q
Peripheral Giant Cell Granuloma
A
- Reactive/Inflammatory process
- Histologically, striking aggregation of multinucleate, foreign body-like giant cells separated by a fibroangiomatous stroma
24
Q
Herpes Simplex Virus Infections
A
- HSV-1 is most common
- Primary infections typically occur in children b/t 2-4 years old
- 10-20% present w/ acute herpetic gingivostomatitis (vesicles and ulcerations of mucosa, lymphadenopathy, fever, anorexia, and irritability)
- Vesicles
- Few millimeters to large bullae filled w/ a clear, serous fluid
- Rupture to yield painful, red-rimmed, shallow ulcerations
- Eosinophilic intranuclear viral inclusions, giant cells, Tzanck test positive
- Clear w/in 3-4 weeks, becomes dormant in trigeminal ganglion
25
Q
Oral Candidiasis (Thrush)
A
- Candida albicans - normal component of the oral flora in approx. 50% of the population
- Immunocompromised individuals, diabetics and patients on broad spectrum antibiotics
- Most Common Clinical Form: Pseudomembranous Form (Thrush)
- Characterized by a superficial, gray to white inflammatory membrane composed of matted organisms enmeshed in a fibrnosuppurative exudate that can be readily scraped off to reveal an underlying erythematous inflammatory base
26
Q
Raspberry/Strawberry Tongue
A
Scarlet Fever
27
Q
Koplik Spots
A
Measles
28
Q
Acute Pharygitis
Enlargement of Lymph Nodes in the Neck
Palatal Petechiae
A
Infectious Mononucleosis
29
Q
Pseudomembrane
A
Diptheria
30
Q
Reticulate
Lacelike
White Keratotic
A
Lichen Planus
31
Q
Vesicles and Bullae Prone to Rupture
A
Pemphigus
Bullous Pemphigoid resembles but can be differentiated histologically (Not Inside the Mouth)
32
Q
Maculopapular, Vesiculobullous Eruption
A
Erythema Multiforme
33
Q
Hairy Leukoplakia
A
- In pts w/ HIV and may portend the development of AIDS
- Caused by EBV
- Takes form of white, confluent patches of fluffy (“hairy”), hyperkeratotic thickenings, almost always situated on the lateral border of the tongue
- CANNOT be scraped off
- Distinctive microscopic appearance consists of hyperparakeratosis and acanthosis w/ “balloon cells” in the upper spinous layer
34
Q
Leukoplakia and Erythroplakia
A
- Leukoplakia
- White patch or plaque that cannot be scraped off and cannot be characterized clinically or pathologically as any other disease
- Up to 25% are premalignant
- Erythroplakia
- Red, velvety, possibly eroded area w/in the oral cavity that usually remains level w/ or may be slightly depressed in relation to the surrounding mucosa
- Epithelium in such lesions tends to be markedly atypical, and the risk of malignant transformation is much higher than is leukoplakia
- Both found in persons aged 40-70
- 2:1 Male Preponderance
- Although these lesions have multifactorial origins, the use of tobacco is a common antecedent
35
Q
Squamous Cell Carcinoma
A
- 95% of cancers of the head and neck are SCCs
- Pathogenesis is multifactorial
- North America and Europe - chronic abusers of smoked tobacco and alcohol
- India and Asia - chewing of betel quid and paan
- Actinic radiation (sunlight) and, particularly, pipe smoking are known predisposing influences for cancer of the lower lip
- In oropharynx, 70% of SCCs, particularly those involving the tonsils, the base of the tongue, and the pharynx, harbor oncogenic variants of HPV, particularly HPV-16
- Patients w/ HPV-positive SCC have greater long-term survival than those w/ HPV-negative tumors
- Typically create ulcerated and protruding masses that have irregular and indurated borders
- As a group these tumors tend to infiltrate locally before they metastasize to other sites
36
Q
Verrucous Carcinoma
A
- SCCA w/ a very “wart-like” appearance and more insidious growth pattern
- Usually blander than typical SCCA but has a “pushing” pattern or growth
- Treated w/ laser instead of surgery
37
Q
Dentigerous Cyst
A
- Cyst that originates around the crown of an unerupted tooth
- Radiographically
- Unilocular lesions most often associated w/ impacted third molar teeth
- Complete removal is curative
38
Q
Odontogenic Keratocyst
A
- Aggressive behavior
- Diagnosed in male patients b/t ages 10 and 40 w/in the posterior mandible
- Radiographically
- Present as well-defined unilocular or multilocular radiolucencies
- Treatment requires complete removal of the lesion, because OKCs are locally aggressive and recurrence rates for inadequately removed lesions can reach 60%
39
Q
Periapical Cyst
A
- Inflammatory in origin
- Found at apex of teeth
- Develop as a result of long-standing inflammation of the tooth (pulpitis), which may be caused by advanced carious lesions or by trauma to the tooth
40
Q
Ameloblastoma
A
- Arises from odontogenic epithelium
- Commonly cystic, slow growing, and locally invasive but has an indolent course in most cases
- Typically requires wide surgical resection
41
Q
Odontoma
A
- Most common type of odontogenic tumor, arises from epithelium but shows extensive depositions of enamel and dentin
- Odontomas are probably hamartomas rather than true neoplasms and are cured by local excision
42
Q
Laryngotracheobronchitis (Croup)
A
- Parainfluenza Virus
- Nonspecific respiratory symptoms (rhinorrhea, sore throat, cough) and low grade fever
- 1-2 Days
- Characteristic Signs
- Hoarseness
- Barking Cough
- Inspiratory Stridor
43
Q
Reactive Nodules
A
- Vocal Cord Nodules and Polyps
- Sometimes develop on the vocal cords, most often in heave smokers or in individuals who impose great strain on their vocal cords
- Smooth, rounded, sessile, or pedunculated excrescences, generally only a few millimeters in the greatest dimension
- Located usually on the true vocal cords
- Renke’s edema cuases edematous thickening of the vocal cords
- Characteristically change the character of the voice and often cause progressive hoarseness
- Virtually never give rise to cancers
44
Q
Squamous Papilloma
A
- Benign located on the true vocal cords
- Soft, raspberry-like rearely more than 1 cm in diameter
- Histologically
- Multiple slender, finger-like projections supported by central fibrovascular cores and covered by an orderly stratified squamous epithelium
- Traumatized, may lead to ulceration that can be accompanied by hemoptysis
45
Q
Papillomatosis
A
- Juvenile laryngeal papillomatosis
- Multiple in children, caused by HPV types 6 and 11
- Do NOT become malignant, but frequently recur
- Often spontaneously regress at puberty, but some affected patients endure numerous surgeries before this occurs
46
Q
Carcinoma of the Larynx
A
- Typically squamous cell carcinoma seen in male chronic smokers
- Vary from smooth, white or reddened focal thickenings, sometimes roughened by keratosis, to irregular verrucous or ulcerated white-pink lesions
- Commonly seen in men in the sixt decade of life and often manifests clinically as persistent hoarseness, dysphagia, and dysphonia
- Prognosis dependent on clinical staging
47
Q
Branchial Cyst (Cervical Lymphoepithelial Cyst)
A
- Arise from remnants of the second branchial arch in young adults (20-40 years)
- Benign cysts on the upper lateral aspect of the neck along the sternocleidomastoid muscle
- Morphology: fibrous wall lined by stratified squamous or psuedostratified columnar epithelium w/ lymphoid tissue w/ prominent germinal centers
- Readily excised
48
Q
Thyroglossal Duct Cyst
A
- Embryologically the thyroid anlage begins in the region of the foramen cecum at the base of the tongue; as the gland develops it descends to its definitive midline location in the anterior neck
- Remnants of this developmental tract may persist, producing cysts
- 1-4 cm in diameter
- May be lined by stratified squamous or psuedostratified columnar epithelium
- Connective tissue wall of the cyst may harbor lymphoid aggregates or remnants of recognizable thyroid tissue
- Treatment = excision
49
Q
Paraganglioma (Carotid Body Tumor)
A
- Clusters of neuroendocrine cells associated w/ the sympathetic and parasympathetic nervous systems
- Can be seen in many places throughout the body, most commonly located in the adrenal medulla (pheochromocytoma)
- Slow-growing and painless masses that usually arise in the fifit and sixth decades of life
- May be associated w/ MEN 2 syndrome
- More common in people living at high altitudes
- Frequently recur after incomplete resection and may metastasize to regional lymph nodes and distant sites
- Nests (zellballen) of round to oval chief cells (neuroectodermal in origin) that are surrounded by delicate vascular septae and bound by sustentacular cells
- Stain positive for neuroendocrine lineage immunohistological stains
- Frequently harbor loss of function mutations in genes encoding succinate dehydrogenase subunits
50
Q
Xerostomia
A
- Dry mouth resulting from a decrease in the production of saliva
- Causes:
- Old Age
- Sjogren Syndrome - autoimmune
- Complication of radiation therapy
- Side-effect of many commonly prescribed classes of medications
51
Q
Sialadenitis
A
- Trauma, viral, or bacterial infection or autoimmune disease causing inflammation of salivary glands
- Mumps particularly effects the parotid
- Pancreas and testes may also be involved
52
Q
Mucocele
A
- Most common lesion of the salivary gland
- Caused by either blockage or rupture of a salivary gland duct w/ consequent leakage of saliva into the surrounding CT stroma
- Most often found on the lower lip and are the result of trauma
- Clinically, they present as fluctuant swellings of the lower lip that have a blue translucent hue
- May change in size, particularly in association w/ meals
- Histologically
- Pseudo cysts w/ cyst-like spaces lined by inflammatory granulation tissue or by fibrous connective tissue
- Incomplete excision may lead to recurrence
53
Q
Ranula
A
- Epithelial-lined cysts that arise when the duct of the sublingual gland has been damaged
- May become so large that it develops into a “plunging ranula”
54
Q
Sialolithiasis and Nonspecific Sialadenitis
A
- Nonspecific bacterial sialadenitis, most often involving major salivary glands (particularly submandibular) is a common condition
- Usually secondary to ductal obstruction produced by stones
- Sialolithiasis may be secondary to duct trauma/edema or blockage by food debris
- Common offenders are s. aureus and strep viridans
- Decreased secretory function
- Secondary bacterial invasion
- In pts receiving long-term phenothiazines that suppress salivary secretion and dehydration in elderly patients w/ a recent history of surgery
- Kuttner Tumor (KT)
- Chronic Sclerosing Sialadenitis
- Clinically produces a firm swelling of the glands and may be difficult to distinguish from neoplasia
- Diagnosis can ONLY be made histologically
55
Q
Pleomorphic Adenoma (Benign Mixed Tumor)
A
- Most common salivary gland tumor in adults and children
- Benign, tends to recur
- Malignant transformation is rare
- Mainly affects parotid gland 60%, can occur in submandibular and minor salivary glands
- Presents as rounded, well-demarcated masses rarely exceeding 6 cm in the greatest dimension
- Cut surface is gray-white w/ myxoid and blue translucent areas of chondroid (cartilage-like)
- Histological Features
- Epithelial elements resembling ductal cells and myoepithelial cells are arranged in duct formations, acini, irregular tubules, strands, or sheets of cells
- Typically disperesed w/in mesenchyme-like background of loose myxoid tissue containing islands of cartilage and, rarely, foci of bone
- Clinical Features
- Present as painless, slow-growing, mobile, discrete masses w/in the parotid or submandibular areas in the buccal cavity
- Carcinoma arising in a pleomorphic adenoma is referred to as a carcinoma ex pleomorphic adenoma or a malignant mixed tumor
- Among the most aggressive of all salivary gland malignant neoplasms, producing mortality rates of 30-50% at 5 years
56
Q
Warthin Tumor
A
- Benign, bilateral, most common in smokers, “motor oil” cyst fluid
- Exclusively in parotid gland, more commonly in males 5th-7th decade of life
- About 10% are multifocal and 10% bilateral
- Smokers have eight times the risk of nonsmokers for developing
- Most are round to oval encapsulated masses, 2-5cm in diameter, usually arising in the superficial parotid gland, where they are readily palpable
- Transection reveals a pale gray surface puncuated by narrow cystic or cleftlike spaces filled w/ mucinous or serous secretions
- Cystic spaces lined by double layer of neoplastic eosinophilic epithelial cells, embedded in lymphoid stroma sometimes bearing germinal centers
- Granular appearance of the cytoplasm of the upper layer of the cells is due to the presence of numerous mitochondria, a feature referred to as “oncocytic”
57
Q
Oncocytoma
A
- Benign, peak occurrence in the elderly
- Primarily affects the parotid gland
- Large granular appearing eosinophilic staining epithelial cells
58
Q
Mucoepidermoid Carcinoma
A
- Most common form of primary malignant tumor of the salivary glands
- Composed of variable mixtures of squamous cells, mucus-secreting cells, and intermediate cells
- Behavior varies from indolent to highly agressive
- Tumors w/ greater number of epidermoid cells and non-parotid tumors tend to be more agressive
- Primarily affects the parotid gland
- Morphology
- Can grow as large as 8 cm in diameter
- Lack well defined capsules, often infiltrative at the margins
- Basic histologic pattern is that of cords, sheets, or cystic configurations
59
Q
Adenoid Cystic Carcinoma
A
- Relatively uncommon tumor, which in approximately 50% of cases is found in minor salivary glands (particularly palatine glands)
- Tends to infiltrate perineural spaces and cause pain; slow growing malignancy w/ late metastasis and are stubbornly recurrent
- Most characteristic appearance consists of cribiform pattern w/ masses of small, dark staining cells arrayed around cystic spaces
- Morphology
- Composed of small cells having dark, compact nuclei and scant cytoplasm
- Cells tend to be disposed in tubular, solid, or cribrifrom patterns
- Spaces b/t tumor cells are often filled w/ a hyaline material
60
Q
Acinic Cell Carcinoma
A
- Second most common malignant salivary gland of children following mucoepidermoid carcinoma
- Most arise in parotid gland
- Neoplastic cells resemble normal serous acinar cells
- Recurrence after resection is uncommon, but about 10-15% metastasize to lymph nodes
61
Q
Salivary Duct Carcinoma
A
- Uncommon malignant tumor of elderly males
- Affects the parotid gland or submandibular glands
- Histologically, resembles in-situ and invasive ductal carcinoma of the breast
- 40% Express HER2/neu
- 90% Express Androgen Receptors
62
Q
Polymorphous Low Grade Adenocarcinoma
A
- Slow growing
- Affects minor salivary glands, which typically occurs on the palate where it is second only to adenoid cystic carcinoma in that location
- Variable histology, but deceptively bland malignant glands are characteristic (perineural invasion is diagnostic clue to malignant nature)
63
Q
Emphysema
A
- Irreversible airspace enlargment distal to terminal bronchiole w/ destruction of airspace walls
- Small airway fibrosis significantly contributes to airflow obstruction
- Classification
- Centriacinar (95% of Cases)
- Panacinar
- Paraseptal
- Irregular
64
Q
Centriacinar Emphysema
A
- Occurs most commonly in heavy smokers
- Affects central and proximal acinus (respiratory bronchioles)
- Spares distal alveoli, so has normal tissue and emphysematous changes w/in same lobule
- More common in upper lobe apices
- When severe, can be difficult to differentiate from panacinar
65
Q
Panacinar Emphysema
A
- Enlarged acini from level of respiraotry bronchiole to terminal alveoli
- Tends to affect different anatomic regions than centrilobular - panacinar emphysema usually found in lower lungs and anterior margins
- Associated w/ alpha-1 antitrypsin deficiency
66
Q
Paraseptal Emphysema
A
- Predominately involves distal acinus
- Subpleural tissue at margins of lobules more affected
- Occurs near areas of fibrosis or atelectasis mostly in upper half of lungs
- Thought to be an underlying factor in cases of spontaneous pneumothorax in young adults
67
Q
Irregular Emphysema
A
- Associated w/ scarring
- Usually in small foci and not clinically significant
68
Q
Emphysema Pathogenesis
A
- Smoke and toxic particles damage lung tissue and cause inflammation
- Numerous inflammatory mediators are increased and recruit inflammatory cells from circulation, increasing inflammation and inducing structural changes
- Proteases are released from inflammatory cells, resulting in protease-antiprotease imbalance and breakdown of tissue
- Imbalance may also have a genetic basis
- Oxidative stress results, resulting in even more inflammation and damage
- NRF2 gene codes for a transcription factor activated by oxidants that upregulates other genes that protect from oxidant damage
- Mice lacking NRF2 are more sensitive to smoke
- Infections probably dont initiate the process but may exacerbate it
69
Q
Gross Findings of Emphysema
A
- Large lungs, may overlap heart
- Upper portions of lungs most affected
- Often see apical blebs and bullae
- Cut sections of parenchyma show enlarged airspaces
70
Q
Alpha-1 Antitrypsin
A
- Encoded by Pi locus on chromosome 14
- PiMM = Normal
- PiZZ = Severely Decreased AAT
- PiSZ = Increased Riske of Emphysema
- PiSS = NO Increased Risk
71
Q
Microscopic Findings of Emphysema
A
- Enlarged alveoli
- Thin septa
- Loss of attachments of alveoli to small airways
- Septa look like they end blindly into alveolar spaces (blunted alveolar septa)
72
Q
In emphysema, how much of the parenchyma is damaged before symptoms occur?
A
1/3
73
Q
Clinical Findings of Emphysema
A
- Dyspnea that steadily progresses
- Some patients present w/ cough or wheezing, which may make you think of asthma
- Cough and expectoration depend on degree of chronic bronchitis
- Sometimes barrel-chested
- May develop cor pulmonale and congestive heart failure related to secondary pulmonary htn
74
Q
Compensatory Hyperinflation
A
Dilation of alveoli as a response to tissue loss elsewhere; e.g. following surgical lobectomy
75
Q
Obstructive Overinflation
A
E.g. airway obstruction by tumor
76
Q
Bullous Emphysema
A
- Large subpleural blebs and bullae (>1 cm)
- May result from any type of emphysema
- May rupture and cause pneumothorax
77
Q
Interstitial Emphysema
A
- Air in connective tissue in lung, mediastinum, or subcutaneous tissue
- E.g. w/ chest wounds
78
Q
Chronic Bronchitis Pathogenesis
A
- Can occur in smokers or as result of pollution or other irritating inhaled substances
- Mucus hypersecretion
- Earliest feature
- Associated w/ submucosal gland hypertrophy in trachea and bronchi and also eventually bronchioles
- Inflammation
- Both acute and chronic w/ neutrophils, lymphocytes, macrophages
- Chronic Inflammation
- Leads to fibrosis of small airways, which contributes to airway obstruction
79
Q
Gross Findings of Chronic Bronchitis
A
- Hyperemia, swelling, edema of mucosa
- Increased mucinous secretions, sometime mucopurulent
80
Q
Microscopic Findings of Chronic Bronchitis
A
- Submucosal mucus gland hyperplasia is the major feature
- Reid Index
- Ratio of thickness of mucus gland layer to thickness of tissue b/t epithelium and cartilage
- Normal is 0.4; higher in chronic bronchitis
- Reid Index
- Increased numbers of goblet cells
- Chronic inflammation of airways (mostly lymphocytes)
- Thickened basement membrane
- Epithelium may show squamous metaplasia or dysplasia
81
Q
Reid Index
A
Ratio of thickness of mucus gland layer to thickness of tissue b/t epithelium and cartilage
82
Q
Asthma
A
- Chronic disorder of conducting airways w/ episodic bronchoconstriction, bronchial wall inflammation, and increased mucus secretion
- Episodes of wheezing, dyspnea, chest tightness, cough
- At least partly reversible
- Can be fatal
- Categories
- Atopic
- Non-Atopic
- May also classify as seasonal, exercise-induced, drug-induced, occupational, or asthmatic bronchitis (smokers)
83
Q
Atopic Asthma
A
- Type I hypersensitivity (IgE-Mediated)
- Usually begins in childhood; various triggers
- Often have allergic rhinitis and eczema
- Skin test may identify antigen(s)
- High total serium IgE or RAST (serum radioallergosorbent test) may help w/ dx
- Pathogenesis
- TH2 and IgE response in genetically predisposed patients
84
Q
Adenocarcinoma
A
- Glandular differentiation and mucin production
- Most common type in non-smokers and women
- Gross
- Peripheral scar w/ pleural puckering
- Tend to grow more slowly than SCC
- Precursor Lesions
- Atypical Adenomatous Hyperplasia
- 5 mm or less w/ moderate cytologic atypia
- Adenocarcinoma In-Situ
- Less than 3 cm
- Lipedic
- Atypical Adenomatous Hyperplasia
- Immunohistochemistry
- TTF-1 and Napsin A Positive
- P40 and p63 Negative
- +/- PD-L1 Expression
- Molecular Genetics
- Mutations in multiple genes encoding receptor tyrosine kinases, including EGFR, ALK, ROS, MET, and RET
85
Q
Squamous Cell Carcinoma
A
- Invasive epithelial tumor characterized by evidence of squamous differentiation
- Most highly associated w/ male smokers
- Risk of serious pulmonary hemorrhage w/ bevacizumab
- Gross
- Growth Patterns
- Exophytic Endobronchial Mass
- Obstruction, Atelectasis, Infection
- Peribronchiolar Spread
- Mediastinal Disease
- Nodular Intraparanchymal Mass
- Exophytic Endobronchial Mass
- Grey-white firm cut surface, often centrally necrotic +/- cavitation
- Growth Patterns
- Histological
- Keratinization
- Keratin Pearls
- Dyskeratosis
- Intracellular Bridges
- Keratinization
- Immunohistochemistry
- p40 and p63 Positive
- TTF-1 and Napsin A Negative
- +/- PD-L1
- Molecular
- Highest TP53 Mutations of All Histologic Types
86
Q
(Undifferentiated) Large Cell Carcinoma
A
- Undifferentiated non-small cell carcinoma which lacks morphologic and immunohistochemical evidence of other differentiated forms of lung cancer
- Pathologic diagnosis of exclusion
- Histologically
- Large nuclei, prominent nucleoli, moderate amount of cytoplasm
- No pearls, no bridges, no glands, no mucin
- Immunohistochemistry
- NO TTF-1, Napsin A, p40, or p63
- +/- PD-L1
87
Q
Small Cell Carcinoma
A
- Most aggressive lung tumor w/ strong relationship to smoking
- Virtually always fatal
- >90% DOD in 5 Years
- 6-17 Month Median Survival
- Virtually always fatal
- Thought to derive from neuroendocrine progenitor cells present in bronchial epithelium
- Staged as Limited or Extensive
- Gross
- Central or Peripheral
- Histologically
- “Relatively” small cells
- Scant cytoplasm
- Nuclear Molding
- Finely granular “salt and pepper” chromatin
- Absent or inconspicuous nucleoli
- Brisk mitotic activity
- Extensive necrosis
- Crush artifact
- Azzopardi effect
- “Relatively” small cells
- Immunohistochemistry
- Chromogranin (high specificity, low sensitivity)
- Synaptophysin
- CD56 and 57
- +/- TTF-1
- Electron Microscopy
- Dense Core Neurosecretory Granules (Neuroendocrine Origin)
88
Q
Carcinomas Clinical Course
A
- Spread w/ direct extension to surrounding structures
- >50% local node involvement at presentation
- Distant metastases
- Adrenals >50%
- Liver 30-50%
- Brain 20%
- Bone 20%
- Cough, chest pain, weight loss, dyspnea, hemoptysis, pleural effusion, SVC syndrome, symptoms related to Pancoast tumor (miosis, ptosis, anhidrosis, enophthalmos, ulnar pain)
- Often discovered in areas of direct extension or metastatic sites
- Prognosis is improving
- Adenocarcinoma and squamous tend to stay localized longer
89
Q
Cushing Syndrome
A
- Underlying Cancer
- SCC or Lung
- Pancreatic Carcinoma
- Neural Tumors
- Causal Mechanism
- ACTH or ACTH-Like Substance
90
Q
SIADH
A
- Underlying Cancer
- SCC of Lung
- Intracranial Neoplasms
- Mechanism
- ADH
- Atrial Natriuretic Hormones
91
Q
Hypercalcemia
A
- Underlying Cancer
- SCC of lung
- Breast Carcinoma
- Renal Carcinoma
- Adult T-Cell
- Leukemia/Lymphoma
- Mechanism
- PTHRP
- TGF-alpha
- TNF
- IL-1
92
Q
Carcinoid Tumors
A
- Low grade malignancies w/ limited potential for spread
- Most Common Pediatric Lung Tumor
- Central or Peripheral
- Polypoid, Mucosal Covered, Intraluminal Masses
- Typically Confined to Bronchus
- Clinical
- Hemoptysis, infection distal to tumor
- Carcinoid Syndrome
- Secretion of serotonin and other vasoactive substances
- Intermittent diarrhea, flushing, cyanosis
- Gross
- Gray-yellow cut surface
- Histologically
- Small uniform cells
- Central nuclei
- Moderate amount of fine granular cytoplasm
- Distinct “organoid” architecture - nests, ribbons, rosette-like arrangements
- Prominent fibrovascular stroma
- Typical vs. Atypical
- Typical (Grade I Neuroendocrine Tumor)
- <2 Mitoses/10hpf
- No necrosis
- 95% 5 Year Survival
- Atypical
- 2-10 Mitoses/10hpf and/or
- Necrosis
- 70% 5 Year Survival
- “Tumorlets”
- Peri-bronchiolar
- 4mm or less
- Typical (Grade I Neuroendocrine Tumor)
- Immunohistochemistry
- Serotonin
- Chromogranin
- Synaptophysin
- TTF-1 Positive in 50%
- Electron Microscopy
- Dense Core Neurosecretory Granules
93
Q
Pulmonary Hamartoma
A
- Benign connective tissue w/ epithelial clefts
- Cartilage Most Common
- Ciliated or Non-Ciliated
- Clonal
- Incidental “coin lesion” on XR
- <3-4 cm
94
Q
Lymphangiomyomatosis
A
- Young women of childbearing age, +/- tuberous sclerosis
- Pulmonary architecture distorted by cyst formation w/ emphysema-like change of terminal airspaces, interstitial thickening, and lymphatic obstruction
- Underlying lesion is proliferation of perivascular epithelioid cell
- Express melanocytic and muscle markers
- TSC2 LOF Mutations
- Generally considered benign, but death can ensue from respiratory insufficiency
95
Q
Non-Atopic Asthma
A
- No allergen sensitization/Negative skin tests
- Viral respiratory infections are common triggers
96
Q
Drug-Induced Asthma
A
- Several possible causitive agents
- Uncommonly, people have “aspirin-senstive asthma”
97
Q
Occupational Asthma
A
- May be associated w/ fumes, dusts, gases, other chemicals
- Usually after repeated exposures
98
Q
Asthma Pathophysiology
A
- Airway inflammation leads to release of inflammatory mediators
- Airway wall remodeling
- Growth factors lead to goblet cell hyperplasia, smooth muscle hypertrophy, angiogenesis, fibrosis
- Exaggerated TH2 response to antigens in asthma
99
Q
Genetic Susceptibility to Asthma
A
- Many genetic polymorphisms associated w/ asthma
- Chromosome 5q in IL13 gene
- Some class II HLA alleles
- Adam33 metalloproteinase
- Beta 2 adrenergic receptor variants
- IL4 receptor gen variants associated w/ atopy
100
Q
Environmental Factors in Asthma
A
- Industrialized environments have many airborne pollutants
101
Q
Gross Findings of Asthma
A
- In autopsy cases of acute asthma exacerbation
- Severely hyperinflated lungs w/ areas of atelectasis
- Often see gross mucus plug
- In less severe or well-controlled
- May not see any gross abnormalities
102
Q
Microscopic Findings of Asthma
A
- Thickened airway wall w/ increased vessels
- Goblet cell hyperplasia and increased size of submucosal glands
- Thickened basement membranes
- Submucosal inflammation including many eosinophils
- Smooth muscle hypertrophy
- Sputum or brochoalveolar lavage specimens often sho Curschmann spirals from extruded mucus plugs
- Charcot-Leyden crystals (from eosinophil protein)
103
Q
Bronchiectasis
A
- Not a specific disease, but the result of other disease processes
- Chronic infections lead to destruction of smooth muscle and elastic tissue and permanent dilation of bronchi and bronchioles
- Relatively uncommon today because of better treatment of lung infections
- Associations
- Congenital or Hereditary Conditions: CF, Primary Ciliary Dyskinesia
- Infections: Necrotizing Pneumonia
- Bronchial Obstruction: Tumors, Foreign Bodies, Mucus Impaction
104
Q
Bronchiectasis Pathogenesis
A
- Obstruction and Infection
- Obstructions impair normal clearing
- Severe infections lead to necrosis, fibrosis, and eventually dilation
105
Q
Gross Findings of Bronchiectasis
A
- Usually lower lobes
- More severe in distal bronchi and bronchioles
- Severely dilated airways, may appear cystic and contain mucopurulent secretions
- Sometimes so dilated they can be followed all the way to the visceral pleura
106
Q
Microscopic Findings of Bronchiectasis
A
- Varies w/ severity, activity, and chronicity
- Active case have acute and chronic inflammation walls of bronchi and bronchioles
- May have desquamation of epithelium and ulceration
- May lead to necrosis of airway walls and lung abscess
- Chronic cases have fibrosis of bronchial and bronchiolar walls as well as peribronchiolar fibrosis
- May obliterate bronchiolar lumens
- Bacteria and/or fungi may be present
107
Q
Bronchiectasis Clinical Findings
A
- Severe, persistent cough
- Foul smelling sputum, sometimes bloody
- Symptoms often episodic, triggered by respiratory infections
- Changes in position cause secretions and pus to drain into bronchi, so coughing paroxysms in the morning are common
108
Q
Pulmonary Embolism Pathogenesis
A
- Usually have predisposing condition that results in hypercoagulable state
- Primary: Factor V Leiden Mutation, Prothrombin Mutation, Antiphospholipid Syndrome
- Secondary: Obesity, Recent Surgery, Cancer, Oral Contraceptive Use, Pregnancy, Immobilization, Burns, Trauma, Fractures
109
Q
PE Clinical Findings
A
- Pathophysiology
- Respiratory comrpomise because of non-perfused but ventilated portion of lung
- Hemodynamic compromise because of obstruction of blood flow
- Death may be caused by blockage of blood flow or acute cor pulmonale
- Large PE can cause essentially instantaneous death
- Small PEs (60-80% of cases) may have no symptoms, chest pain, or cough
- Infacts: dyspnea, tachypnea, fever, chest pain, cough, hemoptysis
110
Q
PE Gross Finding
A
- May lodge in main pulmonary arter or branches
- Saddle embolus when lodges at bifurcation of main pulmonary artery
- Smaller peripheral emboli can cause hemorrhage or infarction
- If good CV function, bronchial arteries keep lung parenchyma viable — hemorrhage
- If not — infarction
- Infarctions are typicallly wedge shaped
- Extend to periphery of lung
- Initially red-blue then paler and red-brown after RBCs lyse and hemosiderin is produced
- Eventually becomes scar
111
Q
PE Microscopic Findings
A
- Laminations called Lines of Zahn
- Infarct
- Hemorrhagic area w/ ischemic necrosis of alveolar walls, airways, vessels
112
Q
Other Types of PEs
A
- Fat and bone marrow
- Trauma
- After chest compressions
- After long bone or pelvic fractures
- Air Embolism
- Trauma
- Surgery
- IV Catheters
- Septic Embolism
- From tricuspid valve vegetation
- Neutrophilic inflammatory reaction, sometimes see bacteria, can turn into abscess
- Tumor Embolism
- Amniotic Fluid Embolism
113
Q
Pulmonary Hypertension
A
- Mean pulmonary artery pressure > or = 25 mmHg at rest
- Pathogenesis
- Because of diverse causes, depends on underlying condition
- Chronic obstructive or interstitial lung disease
- Obliteration of alveolar capillaries, increases resistance to blood flow
- Heart Disease
- Increased pressure transmitted to pulmonary arteries
- Recurrent Thromboemboli
- Reduced area of pulmonary vasculature, increased resistance
- Autoimmune Disease
- When involves pulmonary vasculature
114
Q
Idiopathic Pulmonary Arterial Hypertension (Group 1)
A
- Uncommon
- Up to 80% have genetic defect
- Most common is BMPR2 mutation
- Autosomal Dominant w/ Incomplete Penetrance
- Most common is BMPR2 mutation
115
Q
Gross Finding of Pulmonary Hypertension
A
- Pulmonary Artery Atherosclerosis
- R Ventricular Hypertrophy
116
Q
Microscopic Findings of Pulmonary Hypertension
A
- Vascular changes can be anywhere in the arterial tree
- Medial hypertrophy of arterioles and small arteries
- Intimal fibrosis (may result in pinpoint lumen)
- Atheromatous deposits in pulmonary artery and major branches may be seen in severe cases
- Plexiform lesions in extreme cases; tuft of capillary channels
- Most common in idiopathic and familial cases
- Etiology Clues
- Many organized and recanalized thrombi, probably due to chronic thromboemboli
- If present w/ emphysema and chronic bronchitis, probably due to COPD
117
Q
Clinical Findings of Pulmonary Hypertension
A
- Idiopathic most common in 20-40 yo women, also sometimes in children
- Initially dyspnea, fatigue, sometimes anginal chest pain
- Progression to severe resp. distress, RVH, and cor pulmonale
- Tx
- Therapy for triggers in secondary cases
- Vasodilators for Group 1 or Refractory dz
- Lung Transplant
118
Q
Goopasture Syndrome
A
- Lung and kidney injury due to autoantibodies against type IV collagen alpha3 chain
- If kidneys only, called anti-glomerular basement membrane dz
- Inflammatory destruction of basement membranes in glomeruli and alveoli
- RPG
- Necrotizing hemorrhagic interstitial pneumonitis
- Mostly teens or 20s, males, smokers
- Gross Findings
- Heavy lungs w/ red-brown consolidation
- Microscopic
- Necrosis of alveolar walls
- Alveolar hemorrhage
- Often hemosiderin-laden macrophages in alveoli
- Later stages may have septal fibrosis, type II pneumocyte hypertrophy
- Many cases have immunofluorescent linear Ig deposits along septal wall basement membranes
- Clinical Findings
- Hemoptysis
- Evidence of glomerulonephritis then rapidly progressive renal failure
- Tx
- Plasmapheresis and Immunosupression
119
Q
Idiopathic Pulmonary Hemosiderosis
A
- Intermittent diffuse alveolar hemorrhage
- Mostly young children but can occur in adults
- Cough, hemoptysis, anemia
- Pulmonary findings similar to Goodpasture
- Pathogenesis unknown but responds to immunosuppressive therapy
120
Q
Polyangiitis w/ Granulomatosis (aka Wegener Granulomatosis)
A
- Autoimmune dz of upper respiratory tract and/or lungs
- Probably a T-cell mediated hypersensitivity to normally innocuous inhaled agents
- Responds to immunosuppressive therapy
- PR3-ANCAs present in vast majority of cases
- Hemoptysis
- Necrotizing vasculitis w/:
- Necrotizing granulomas of upper or lower respiratory tracts, or both
- Necrotizing or granulomatous vasculitis of small to medium vessels
- Focal necrotizing glomerulonephritis often crescenteric
- Small biopsies my not show necrosis and granulomatous vasculitis
- Inflammatory sinusitis w/ mucosal granulomas
- Ulcers of nose, palate, pharynx w/ associated granulomas in geographic pattern w/ central necrosis and associated vasculitis
- Granulomas resemble those in mycobacterial or fungal infection
- Alveolar hemorrhage
