PULMONARY PATHOLOGY OF IMMUNOCOMPROMISED HOSTS Flashcards
Cough in the immunosuppressed? What information is needed? What is the risk in this population?
Cough (or other standard ‘chronic’ pulmonary symptoms) and a pulmonary infiltrate, sometimes even without fever, developing in patients with suppressed immune function for whatever reason is an immediate cause for concern. In other types of patients, fever may be the only symptom of a very serious and catastrophic process. Overall, a high index of suspicion is needed in an immunocompromised patient, because symptoms may atypical, muted, or absent. A constellation of clinicopathologic findings may be needed to correctly identify the organisms below:
x Type of immunodeficiency (neutrophil abnormality, antibody deficiency, lymphocyte issues, etc.) present in the patient
x Imaging findings
x State of oxygenation
x Sputum sampling, which may require bronchoscopy
x Blood cultures and serology testing
Of course, with all these infections, the risk is dissemination given the immunosuppression. In the setting of dissemination, these become much more than just a pulmonary disease process.
What are atypical Mycobacterium?
Atypical (non-tuberculous)mycobacteria are common in the environment and can be found in water (including tap water), soil, food, and on animals. Spread of atypical mycobacteria can be due to respiratory routes, ingestion, and/or direct inoculation. The most common of these atypical species are M. avium and M. intracellulare(and sometimes M. chimaera), and because they are difficult to separate and often are co-infecting a patient, we often just lump them together as M.avium-intracellulare complex(MAC).
In patient’s with T-cell deficiences like respiratory symptoms may include?
In patients with T-cell deficiencies (like HIV), respiratory symptomatology may also be accompanied by fever and night sweats. Dissemination includes:
x GI tract –diarrheaand/or malabsorption,abdominal pain, and weight loss, as the organism(s) use the mucosal surface as a point of entry
x Lymph nodes –possible lymphadenitis
x Bone marrow –anemia as a possible symptom
What is the image showing?
Image: Affected tissues will show ingested organisms within macrophages, and these are sometimes found throughout the reticuloendothelial system (lymph nodes, spleen, liver, bone marrow) with disseminated disease. Granulomas would not be typically seen.
Explain Pneumocystis Jirovecii? Presentations? Diagnosis? Dissemination?
Pneumocystis pneumonia (PCP) can occur in the severely immunosuppressed, such as those with advanced HIV/frank AIDS or bone marrow transplant patients.
x Presentations can include atypical symptomatology, including normal chest x-rays with severe hypoxia
x Diagnosis is often with bronchoalveolar lavage/washing –effectively squirting fluid into the bronchi and alveoli, and then collecting and examining the fluid
x Dissemination isn’t that common; PCP is primarily a lung disease
The pathophysiology revolves around
1) the proliferation of the Type 1 and Type 2 pneumocytes that contribute to alveolar filling, and 2) leaky vessels allowing proteins and exudate to collect in alveolar spaces. Both of these lead to severe oxygenation diffusion difficulty and/or asphyxiation.
Pathophysiology of Pneumocystis Jirovecii?
The pathophysiology revolves around
1) the proliferation of the Type 1 and Type 2 pneumocytes that contribute to alveolar filling, and 2) leaky vessels allowing proteins and exudate to collect in alveolar spaces. Both of these lead to severe oxygenation diffusion difficulty and/or asphyxiation.
what are the images showing?
Left image: Fluffy, delicate appearing (‘cotton candy’) protein and exudate at the arrow is seen filling the alveoli. Some pneumocyte hyperplasia is likely also present.
Right image: In the same exudate are numerous, round-slightly compressedtrophozoite forms of P. jirovecii, which are slightly smaller than an RBC (usually 4-6 microns); silver stain.
Explain CMV infections? where is it most active?
This β-group herpesvirus causes a variety of symptoms depending upon when, how, and what body part becomes infected, but also the immunologic status of the individual. The vast majority of humans are infected by the time of adulthood, as CMV infects monocytes, macrophages, and their bone marrow precursors. Reactivation of CMVis an important diagnostic consideration among HIV+ patients, bone marrow transplant recipients, chronic dialysis patients, and those taking long-term steroids. With reactivation, CMV tends to be most evident in the macrophagesand endothelial cells of the respiratoryand GI tracts.
x Aninterstitial pneumonitiscan quickly progress to acute respiratory distress (see ARDS lecture)
x Colitiscan progress into mucosal ulceration, mucosal necrosis, pseudomembrane formation, and severe diarrhea/intravascular volume depletion
what is this image showing?
CMV infected pneumocytes (box) with characteristic large intranuclear inclusion, pneumocyte hyperplasia, and septal/interstitial expansion and inflammation are apparent.
What is Candida? who is most at risk? what can happen?
Candida species (particularly C. albicans) are commensal organisms on mucosal surfaces, and are the most common fungal pathogen of humans. Neutrophils (and macrophages) are particularly active against candida, therefore neutropenia (leukemia patients, patients undergoing chemotherapy, and/or hematopoietic stem cell transplant patients), orkilling mechanisms difficulties, such asNADPH oxidase deficiency(chronic granulomatous disease)and myeloperoxidase deficiency,are susceptible to defective Candida killing and increased risk of the organism gaining access to the bloodstream (disseminating).
Dissemination of Candida can result when it invades into the bloodstream. Involvement of one or many major organs is possible: heart, lungs, liver, kidney, meninges, etc. In dissemination, candida has a tendency to form collections of organisms, and along with some inflammation, likely will appear as an abscess(es).
What are these images depicting?
Left image: Candida as a microabscess in the lung, with filamentous extensions present at lowpower.
Right image: the classic dimorphic pseudohyphae(linear forms) andyeasts(round forms) of Candida –AKA: the spaghetti and meatballs appearance. Pseudohyphae represent yeast forms that are joined end-to-end, and often have periodic narrowing wherethe ends touch.
Explain cryptococcus? who is at risk? Can go where? classic?
This soil-located opportunist can affect individuals with all types of immunosuppression, and those taking high-dose corticosteroids(SLE, sarcoidosis, transplant patients, etc.) are also at greater risk. Cryptococcus can disseminate to many different organs (lungs, liver, bone, adrenals, spleen), but brain involvement is particularly classic.
Cryptococcus invades the brain how? what happens? how do we seen?
In the brain, the yeast forms will collect in/invade the brain through the VirchowRobin perivascular spaces (left image, mucin stain staining yeasts red, arrow at vessel), produce abundant capsular mucin material, and overall produce small, bubbly appearing lesions filled with gelatinous material (so-called soap-bubble lesions, arrows middle image). Finally, on India ink preps, the capsule will show a negative image of where ink can’t penetrate, creating a clear haloaround the yeasts’ external membrane (right image)
what does the image show?
Image: The yeast form of Cryptococcus is about 5-10 microns, and contains a thick, visible,mucopolysaccharide capsule. The interstitium/septum is expanded by the organisms (arrows) and accompanying inflammation.
Explain Aspergillus?
A ubiquitous mold/filament that is transmitted by airborne spore fragments of conidia, growing off the stalks of a conidiaphore (see schema to right and nice micro image below of it).
x Spore fragments are 2-3 μm and can reach alveoli
x In immunosuppressed (particularly those with neutropenia or on corticosteroids), spores can germinate into hyphae (septate filaments)
x Hyphae can grow in airways or in cavities, such old infarcts, abscesses, prior TB, etc.,and is then calledan aspergilloma–masses of hyphae plugging or occupying a space (lung, below left and middle images)
x In immunocompromised, hyphae can disseminate, often causing an invasive sinusitis or an invasive pneumonia, may involve the heart or CNS, and has a tendency to invade blood vesselscausing hemorrhagic infarction(bottom left image, brain, silver stain)
Branch at 45 degrees aka acute angle branching
