Chapter 15: Pneumonia in Immunosuppressed; Lung Transplants; Tumors Flashcards
List 3 common causes of diffuse pulmonary infiltrates in an immunocompromised host?
- CMV
- Pneumocystis jiroveci
- Drug rxn
List 5 common causes of focal pulmonary infiltrates in immunocompromised hosts
- Gram-negative bacterial infections
- S. aureus
- Aspergillus
- Candida
- Malignancy
What is the hallmark finding of MAC infections in patients with immunosuppressed (i.e., HIV, elderly, transplant); morphology of the organism?
- Abundant ACID-FAST bacilli within macrophages
- Thin mycobacteria seen as slender red forms

Common sx’s of pt with HIV who become infected with MAC?
Fever + drenching night sweats + weight loss

What is the most common opportunistic infection of AIDS patients?
Pneumocystis jiroveci pneumonia

Opportunistic infections are common causes of pneumonia in HIV pt’s, but what are 4 of the more common “usual” bacteria that may be seen?
- S. pneumoniae
- S. aureus
- -* H. influenzae
- Gram-negative rods
As a general rule of thumb which organisms causing infection in HIV pt’s are more likely with a CD4 count >200, <200, and <50?
- >200 = bacterial and tubercular infections
- <200 = Pneumocystis pneumonia
- <50 = CMV, fungal, and Mycobacterium avium complex
What is most likely seen on CXR of pt with HIV infected with Pneumocystis jiroveci?
- Diffuse BILATERAL interstitial infiltrates
- Can also be focal or show nothing!
What is the characteristic morphology of the yeast, Pneumocystis jiroveci?
Cup-shaped yeast forms

Which type of organism is the most common cause of pulmonary infection in the early post-transplant period (first few weeks)?
Bacterial
Since acute rejection following a lung transplant has a similar picture to infections, diagnosis relies on what?
Transbronchial biopsy
What is the morphology of acute rejection of a lung transplant that differentiates it from an infection?
Rejection shows mononuclear infiltates around small vessels, in submucosa of airways, or both

What is the major morphological pattern of damage seen with chronic rejection following a lung transplant?
Bronchiolitis obliterans –> fibrosis causing partial or complete occlusion of small airways WITH or WITHOUT active inflammation

What age is the peak incidence of lung cancer seen?
50-60 y/o
Large areas of “benign” respiratory mucosa being mutagenized by exposure to carcinogens in tobacco smoke is known as what?
“Field effect“
Deletions of which 3 chromosomal loci and 3 genes are seen as early events in the squamous cell carcinoma of the lung
- 3p and 9p (site of CDKN2A gene –> product = p16)
- -* 17p (site of TP53 gene)
- -* Loss of RB tumor suppressor

Amplification of which gene has been associated with squamous cell carcinoma of the lung?
FGFR1
Which type of lung cancer shows the strongest association with smoking?
Small cell carcinoma
Loss of function mutations in which 2 genes and chromosome are seen with small cell carcinoma of the lung?
- TP53
- RB
- Chromosome 3p deletions

Amplification of which gene is associated with small cell carcinoma of the lung?
MYC family
Oncogenic gain of function mutations in which 5 RTK genes are associated with Adenocarcinoma of the lung?
Tumors without RTK mutations often have mutation in which gene?
- RTK mutation = EGFR + ALK + ROS + MET and RET
- Non-RTK = KRAS

Lung cancers in never smokers are more common in which sex and are most often what type of cancer?
- Women
- Adenocarcinoma
Lung cancers in never smokers are more likely to have mutations in which gene and never have mutations in what?
- More likely to have EGFR mutations; sometimes TP53
- NEVER have KRAS mutations
Which type of lung cancer is more commonly arising in the peripheral lung and which in the central/hilar lung?
- Peripheral = adenocarcinoma
- Central/hilar = squamous cell carcinoma
Which precursor lesion is characterized by dysplastic pneumocytes lining alveolar walls that are mildly fibrotic?
Atypical adenomatous hyperplasia

Which precursor lesion is composed entirely of dysplatic cells growing confluently along pre-existing alveolar septae; and may or may not hav intracellular mucin?
Adenocarcinoma in situ

Majority of adenocarcinomas of the lung express which transcription factor required for normal lung development?
Thyroid transcription factor-1
Which tumor of the lung tends to spread aerogenously, forming satellite tumors and may consolidate an entire lobe mimicking lobar pneumonia?
Mucinous ADENOCARCINOMA

What is the characteristic histologly of squamous cell carcinoma?
Keratin pearls and/or intracellular bridges

Via cytology which color will the cytoplasm be if keratin is present and is indicative of SCC?
Orange cytoplasm

Which type of lung tumor is almost always metastatic at time of presentation and is best treated with specific chemotherapies/radiation?
Small cell *neuroendocrine* carcinoma
What is the most aggressive lung tumor with no known preinvasive phase?
Small cell *neuroendocrine* carcinoma
What is the histology of the chromatin, cytoplasm, nucleus, and nucleoli like with small cell carcinoma of the lung?
- Small cells w/ scant cytoplasm
- Finely granular (BLUE) nuclear chromatin (salt and pepper pattern)
- Absent nucleoli
- Necrosis is COMMON and often extensive

What is a more ominous change squamous metaplasia or dysplasia?
Dysplasia
Basophilic staining of vascular walls due to encrustation by DNA from necrotic tumor cells (Azzopardi effect) is common with what lung tumor?
Small cell carcinoma

Which 3 markers are found in the neurosecretory granules of small cell carcinomas of the lungs?
- Chromogranin
- Synaptophysin
- CD57
Via immunohistochemistry high levels of which anti-apoptotic protein can be demonstrated in small cell carcinomas of the lung?
BCL2
Early distant spread of lung carcinoma generally occurs via which 2 pathways; which carcinoma specifically metastasizes late?
- Lymphatic and hematogenous
- Squamous cell carcinoma spreads late
What are the 4 favored sites of metastasis for lung carcinomas?
- Adrenals
- Liver
- Brain
- Bone
Which 3 LN’s are common sites of metastasis for lung carcinoma?
- Bronchial
- Tracheal
- Mediastinal
What may partial or total obstruction caused by a lung carcinoma cause?
- Partial –> focal emphysema
- Total –> atelectasis
Impaired drainage of the airways caused by lung carcinomas is a common cause of what?
SEVERE suppurative or ulcerative bronchitis or bronchiectasis
Venous congestion of the head and arm w/ circulatory compromise caused by an underlying lung carcinoma is known as what?
SVC syndrome
Phrenic nerve invasion by lung tumor is associated with what?
Diaphragm paralysis
Activating mutations of which gene in lung cancers is associated with a worse prognosis regardless of tx?
KRAS
Release of PTHrP leading to paraneoplastic hypercalcemia is associated with what type of lung tumor?
Squamous cell carcinoma
Which 2 hormones may be secreted by small cell carcinomas and what does each cause
- ADH —> SIADH
- ACTH —> Cushing Syndrome
What are 2 systemic nervous system related syndromes that may be associated with lung tumors?
- Lambert-Eaton myasthenic syndrome –> auto-abs against Ca2+ channels –> muscle weakness
- Peripheral neuropathy –> usually purely sensory
What is a dermatologic manfiestation that may be associated with lung tumors?
Acanthosis nigricans
What characteristic of Lambert-Eaton Syndrome distinguishes it from Myasthenia Gravis?
Sx’s IMPROVE w/ more movement throughout the day

Apical lung cancers (pancoast tumors) in the superior pulmonary sulcus tend to invade which neural structures around the trachea and produce what signs/sx’s?
- Invade cervical sympathetic plexus
- Severe pain in the distribution of the ulnar nerve
- Horner syndrome –> enophthalmos + ptosis + miosis + anhidrosis

What are 2 hematologic abnormalities that may be assocaited with lung tumors?
- Leukemoid rxns
- Trousseau syndrome (DVT and thromboembolism)
What is a peculiar abnormality of connective tissue associated with lung tumors and what is seen with this?
Hypertrophic pulmonary osteoarthropathy –> clubbing of fingers
Lambert-Eaton Syndrome is most often associated with what tumor of the lung?
Small cell carcinoma
Trousseau sign (migratory thrombophlebitis) is most often associated with what type of lung tumor?
Adenocarcinoma
What is the main difference between Diffuse Idiopathic Pulmonary Neuroendocrine Cell Hyperplasia (DIPNECH) and Carcinoid tumors?
- SIZE!!!
- DIPNECH = very small, <5mm —> “Tumorlets”
- Carcinoid tumor = 5mm or larger

Why is it important to differentiate DIPNECH from Carcinoid tumors?
Carcinoid tumors have ability to metastasize
Which tumor of the lungs grows as fingerlike or spherical polypoid masses that commonly project into the lumen of the bronchus and may produce so-called collar-button lesions?
Carcinoid tumor

Which lung tumor is characterized by organoid, trabecular, palisading, ribbon, or rosette-like arrangements of cells w/ uniform round nuclei and abundant cytoplasm separated by a delicate fibrovascular stroma?
Carcinoid tumor

What are features of atypical carcinoid tumors (neuroendocrine tumor grade 2) which differ from typical carcinoid tumors (grade 1)?
- ↑↑↑ mitotic activity
- NECROSIS (typical carcinoids lack necrosis)
- Disordered growth
- ↑↑↑ rate of metastasis w/ LOWER survival

Immunohistochemical stains of carcinoid tumors may be positive for what 4 markers?
- Serotonin
- Neuron-specific enolase
- Calcitonin
- Bombesin
What are clinical features of carcinoid tumors which may result from their intraluminal growth?
- Persistent cough
- Hemoptysis
- Impairment of drainage of resp. pathways –> 2’ infections
- Bronchiectasis
- Emphysema
- Atelectasis
What are the sx’s of Carcinoid Syndrome?
- Flushing
- Diarrhea
- Cyanosis
What is the prognosis like for typical carcinoid vs. atypical carinoid tumors?
- Typical have 5-year survival of 95%
- Atypical have 5-year survival of 70%
What is a feature that can be seen on CXR and CT that points to metastasis TO the lung?
Multiple discrete nodules (cannonball lesions) scattered throughout all lobes

How are lung hamartomas most often discovered and how do they appear?
- Incidental finding on CXR
- Appear as rounded, radio-opacity (“coin lesion”)

What do pulmonary hamartomas consist of?
Nodules of CT; most often cartilage, also fat and fibrous tissue; intersected by epithelial clefts

Which 2 chromosomal aberrations are associated with lung hamartomas?
- 6p21
- 12q14-q15

Lymphangioleiomyomatosis is a lung disorder occurring almost exclusively in whom?
Young women
Which markers are expressed by Lymphangioleiomyomatosis?
Melanoma, like HMB-45 and smooth muscle cells
Lymphangioleiomyomatosis is characterized by proliferation of which cells and what does this create morphologically?
Perivascular epithelioid cells –> CYSTIC, emphysema-like dilation of terminal air spaces, thickening of interstitium, and obstruction of lymph vessles

Lymphangioleiomyomatosis is associated with loss of function of which tumor suppressor; this tumor suppressor is normally a negative regulator of what?
TSC2 –> neg. regulator of mTOR activity

What is the only definitive tx currently available for Lymphangioleiomyomatosis?
Lung transplant
Diffuse involvement of both lungs with cystic, emphysem-like dilation of airspaces in Lymphangioleiomyomatosis, may present with what complication?
Pneumothorax

The strong tendency for Lymphangioleiomyomatosis to affect young women suggests what hormone contributes to proliferation of perivascular epithelioid cells?
Estrogen
Inflammatory myofibroblastic tumors, though rare, is more common in whom; presents how?
- Children
- Fever + cough + chest pain + hemoptysis
- May be asymptomatic
Imaging of a child with suspected Inflammatory myofibroblastic tumor will show what?
Single (rarely multiple) round, well-defined, peripheral mass that often has calcium deposits
Inflammatory myofibroblastic tumors are associated with activating rearrangements of which gene and on which chromosome?
ALK gene on chromosome 2p23
Growth of contiguous tumors (aka direct continuity) into the lungs most often occurs with what 2 types of tumors?
- Esophageal carcinomas
- Mediastinal lymphomas