the american College of Radiology is pleased to 

present this videotape on granuloma.

Tous diseases of the lung.

Yeah,

by dr Elias 

g lee heroes.

Dr Thoreau's is professor of 

radiological sciences at the Center for 

the Health Sciences recently he 

was registrar of the american registry of radiologic 

pathology and chairman of the Department of 

radiology at the Armed Forces Institute of 

Pathology in Washington,

D.

C.

He also presently continues a long tenure as the 

chairman of the self evaluation and continuing education 

committee of the American College of Radiology.

In his earlier career,

he had been in radiology at the National Naval Medical 

Center in Bethesda Maryland and had preceded 

this with service as a nuclear submarine medical 

officer.

What is a granuloma?

A granuloma is essentially a focal 

reaction of anybody tissue to a low grade 

insult,

sometimes to an organism or perhaps to a grain of dust 

or some unknown offender.

Most commonly,

it is a reaction to a low grade infection 

which causes the tissue to respond in a characteristic 

way.

The common denominator for all types 

is that the reaction must be low grade 

enough that body resources have time 

to marshal into a focus to wall off the 

offender.

We have various names for such granulomas,

depending on whether they have been caused by 

something we can identify such as the 

tobacco back Silas or a fungal organism or 

perhaps a grain of dust that has been 

identified such as silica or beryllium.

Some we can't explain as to specific 

ideology.

For example,

the reaction in sarcoidosis or eosinophilic 

granuloma whose backgrounds are really unknown.

We also more recently have emphasized 

a family of granulomas reactions that are very 

important in the collagen diseases.

We talk about rheumatoid granulomas,

granulomas of pericarditis,

nardoza and also in Vegas granule 

mitosis,

whose very name indicates the granulomas 

response.

In these,

we have an allergic or hypersensitivity response 

to an unknown offender.

Our purpose in this discussion will be 

first to understand some classic 

granulomas caused by known agents 

and then to follow this with a discussion of 

some of those that are unknown.

Let us begin with a lesion that is well 

known to all radiologists,

the histoplasmosis.

With the first two films,

we see a single focus of granule ominous response.

We have a rounded mass which now has reached the 

point in its development when it has become fibrous.

It's six tries and therefore looks rather sharply 

defined against the surrounding lung.

In fact,

this granuloma is old enough so that it now 

has calcification in the center.

This is so easily seen on our toma graham of the specimen.

The central calcification is very typical of a 

granulomas infection and often helps us make the 

diagnosis pre operatively and thus spare the patient any 

concern.

Obviously not all granulomas infections show a 

single focus,

it might be that we would encounter several 

full size similar to this one focus,

but for the moment let's study the single focus.

To see what the general principles are 

next.

We see a pathologic specimen in which the center 

is calcified in the margins shows organization.

We see the whole granuloma and note the darkened 

color in the interior and this represents the 

calcification in the center,

the granuloma that we saw on the radiograph.

Around the outside border we see a peculiar 

bluish cast at the very margin where it 

abuts against the lung.

This bluish cast results from base 

staining aggregates of inflammatory cells 

representing the still smoldering part of the granulomas 

response.

The part in the center is old.

It is so old that it is now.

Destro thick fibrous tissue in which calcium has been 

deposited.

Of course this is what happens in oldest trophic tissue that is 

scarred.

We were able to see this calcification quite easily on the 

radiograph.

As you recall.

As we look at the margin in a close up of the 

nodule,

we see the area where there is still smoldering 

granule,

ominous response and therefore thousands of inflammatory 

cells.

But at the far right of the picture,

we see fibrous tissue which is a cellular and 

represents an older burned out area.

Let's go a little closer and see what a 

granuloma really is.

Notice we don't see cellular detail in the center since it is 

necrotic,

but around the outside of the center.

In the periphery we see a cuff of 

thousands of little black nuclei which 

represent mainly plasma cells and lymphocytes.

This cuff of chronic inflammatory cells is a 

very typical response in a granuloma.

Then we see a giant cell on the left hand side of the 

nodule and this also is a hallmark of 

granulomas response.

This particular granuloma Is rather a fresh 

one and sub acute because we still 

have so many cells that are very active in this 

response.

By contrast in the granuloma that we 

saw in our first slides,

we had mostly fibrous tissue in the center 

and the cellular response,

as you may recall,

was only seen as a very scant margin at the 

very periphery of the granuloma.

Another example shows a response that is even fresher 

and is just beginning to form up into a granuloma.

These comparisons give an 

indication which is very valuable for us radiologists.

We have an indication that granulomas do not 

start as modules,

but start as a rather diffuse response,

which then organizes into a nodule 

in the next radiograph.

We see an example of this evolution 

here.

We are privileged to see the evolution of a granuloma.

In the upper left we see the patient in the early 

hours of his infection with a well known 

desert region fungus cox 

opioids impetus notice that at 

the beginning we have what looks like pneumonia,

there is no organization into a rounded mass yet 

this is true of all granulomas responses.

Granulomas at first are a diffuse 

inflammatory response that will look like 

pneumonia.

If the radiologist happens to get a film at that time 

to see such a response.

A few weeks later we go to the lower left 

and see that the pneumonia like response has organized into 

a rounded granuloma a few weeks later.

Still we see in the upper right 

that the rounded area has become a little smaller 

as it organizes and sick actresses,

but also it has broken down so that the center 

has snuffed out and capitated.

This capitation is quite common 

in many granulomas responses because the tissue 

may be destroyed if the early response 

is virulent enough.

Therefore,

in such a case there is no fibrous tissue residual 

to calcify.

But instead the vigor,

the reaction has caused a necrotic or K.

Cious center,

which slips out if it communicates with the broncos 

notice that on the lower right we see that our 

nodule now has a larger cavity.

Actually an air attention cavity has developed 

because of air containing bronchi communicating with the 

inside of this nodule.

After the necrotic tissue has snuffed out,

leaving us with a so called grape skin 

cavity,

which is so common in cox idi.

I don't psychosis.

Now,

the reason we so commonly seek habitation in cox 

video to narcosis is that it is a very 

virulent fungus which causes a lot of 

destruction in the early hours of infection.

It is quite common for such destroyed tissue 

to empty out on communication with the bronchus.

Leaving air inside of the cavity,

which enters easily on inspiration but has 

difficulty exiting because of spasm.

In the secondarily infected communicating bronchus.

This series of events results in an air attention 

cavity.

We now see a very large 

solitary nodule which is associated 

typically with cryptococcus sis.

This peculiar fungus does not cause a 

marked response in the host tissue and allows 

gross proliferation of the fungal organism to the point 

where the granuloma becomes very large before the patient is 

aware of his problem.

So we may see a very large mass in cryptococcus 

infections.

These are puzzling because by the time they get to this 

size the surgeon becomes worried about the 

possibility of primary malignancy or even 

metastases and quite often has to remove 

them because it is difficult to differentiate them.

Radio graphically pre operatively this 

specimen was removed in fact,

and we see a very large mass which even at this stage 

might still puzzle the surgeon about the possibility of 

a tumor.

Actually it is a benign granuloma due to 

cryptococcus Neo foreman's organisms.

This kind of organism may 

indeed result in a very large mass 

because of the proliferation of the organism itself.

When we examine the lungs at low power,

we see thousands of capsules as little 

roundish white areas filling al villa and the 

villa walls.

When we get a closer view,

we see how large the capsules are between 

the bodies of the fungal organisms.

In fact,

most of the space is occupied.

Buy capsules because they look like white 

voids on the photo micrografx.

The proliferation of large capsules may lead to 

large granulomas.

Up to this point,

we have been discussing some general principles about the 

evaluation of granulomas processes 

and to simplify,

we have confined our discussion to solitary 

granulomas,

although such single fosse are common enough 

granulomas often present as multifocal or 

even diffuse lesions in the lung.

And at this point it behooves us to review some 

representative cases of this aspect.

Sometimes granulomas may be quite widespread 

and we see them scattered all over the lung fields.

As in this case.

This too is a case of histoplasmosis.

Like our first solitary nodule,

the close up helps us see the nature of these modules.

Some of the nodules are about one centimeter in diameter 

and some of them smaller.

Many are very sharply defined,

while others are ill defined and shaggy at the 

margins.

This tells us that in some cases the 

na jules have already organized and become 

psychiatrist and therefore have sharp 

margins,

whereas others still have considerable surrounding reaction 

in the lung and because of that looks shaggy 

radia graphically notice that we are not 

aware of any calcification in any of the modules in 

this case,

When biopsy was done.

In this case we saw a slight calcification 

in the center of the modules notice the purplish 

area in the center of the nodule.

This represents early classification that is yet too 

little for us to be aware of it on the radiograph.

This evokes an important principle in 

radiologic diagnosis.

It takes considerable classification to reach the 

visual threshold.

Radio graphically later the 

calcification becomes so intense 

as the disease heals that we effectively see the 

lungs full of calcifications.

Here we see a margin of one of the granulomas.

We just saw notice again the 

thousands of cells at the very periphery of the nodule 

toward the inside and lower.

We see fibrosis.

We also see the elevator walls and the lung 

interface that surround the nodule.

And we can see that this can be very sharp 

because there is a very neat border at the periphery of the 

granuloma.

The airspace around it gives us a sharp 

air water density interface and 

gives sharpness to our nodule.

Now this nodule will become even sharper 

at its margins as it ages and becomes 

more and more psychiatrist and retracts from the 

surrounding lung and thus leave a cuff of 

air around itself,

so called perry focal emphysema,

on the next to radiographs of a full 

chest and a close up.

We see a patient at a quite acute stage in his 

granulomas response.

This patient came to us very ill in the early 

days of his disease and thus these nachos 

are very ill defined.

It is very difficult to pick out the margins.

They tend to merge into each other and tend 

to coalesce.

We see ill defined modules,

Shaggy modules and several emerging ones 

indicating we are somewhere between the pneumonia stage 

and the organization stage.

Microscopically we see such nah 

jewels as very small granulomas beginning to 

form while around the na jules.

We see involvement of the elevator walls 

which are full of cells and inflammation 

so that in effect we have a surrounding 

storm around the nodule.

This complex leads to an ill defined 

appearance so that we tend to see a 

patch rather than a nodule radia graphically.

Thus,

in this case we encountered the disease early 

and our margins are not yet sharp.

This poor definition and diffused quality 

reaches an extreme in this unfortunate 

patient who has a remarkable accidentally 

response to such an infection.

It has overwhelmed him and we observe a 

hemorrhagic pneumonia which spread throughout the lung 

fields and resulted in a fatal outcome.

This patient has poor resistance to the cock city 

oil organism in it has disseminated 

as the X ray shows there was an overwhelming 

infection and we can see air braca grams in 

profusion as we look through the 

infiltrations and realized that his lungs are 

flooded with fluid,

plasma and blood.

This patient never had a chance to organize 

his disease.

We have now reviewed widespread lesions 

in granulomas processes and at this 

point it is vital to emphasize another 

important principle in these diseases.

Up to now we have examined only bronco 

jealously delivered or airborne entry of 

granuloma causing agents 

granulomas may also reach the lung hematology,

nestle or lymph obviously as we will see in 

the next examples 

Another example of widespread disease 

in this case,

all the infiltrations are made up of thousands 

upon thousands of tiny little fosse of 

granulomas.

This is a blood barn or hematology nous 

miliary tuberculosis.

We see the tiny little na jules as points 

because they are so small that usually it 

takes two or three na jewels in an agglomeration 

or perhaps several modules summiting 

in order to see even a point of density on the X ray.

Effectively,

we don't see a single granuloma on the X ray and miliary 

tuberculosis because it is so tiny,

we rather see groups of them which simulate a single 

nodule notice that there are hundreds of 

thousands of these granulomas that are in the interstitial 

of the lung.

For the most part they are peri vascular and 

location in keeping with their hematology.

This route to the lung.

If we were to examine such a tiny nodule 

more closely,

we would see a single granuloma with tremendous 

numbers of lymphocytes and plasma cells ringing the 

periphery and with giant cells 

which are a hallmark of this disease.

So again,

each one of these thousands upon thousands of military 

tuberculosis granulomas still has 

the organization that we saw in the single 

large granuloma.

At the very beginning of our discussion.

Another case of military granulomas,

widespread throughout the lung fields,

but now interestingly in a limb 

fogginess disease.

Sarcoidosis.

The radiologist can also see the 

concomitant findings of marked lymphedema apathy 

in the Hyler and para trickier areas which is 

so characteristic of sarcoidosis that we would be 

hard pressed to offer any differential diagnosis.

This constellation of at anapa.

These is almost pathetic demonic for 

sarcoidosis interestingly 

in this case the lung fields are shot through 

with millions of military granulomas which 

again,

we can correlate with biopsies 

because they are lim fogginess.

We can see the sarcoidosis granulomas lining 

up in the sub pleural space along 

the septa,

in the pre bronc Euler and peri arterial 

spaces,

All areas rich in emphatic six.

So we may call sarcoidosis lymphoma,

Jenness rather than heterogeneous.

We referred to blood borne diseases when 

we talked about military tuberculosis,

but here we will refer to the lymph ah Jenness 

location.

Actually with most inhaled 

agents such as the fungus spores 

and the dust.

We are talking about bronco genius disease 

deposit in the lungs through the airways.

Here we are talking about a disease that follows the 

lymphatic six radiographic lee.

We cannot see the difference between these 

all.

We are aware of radiographic lee is a marked 

military pattern of thousands of granulomas 

scattered through the lung fields.

Let us examine sarcoidosis,

granulomas more closely.

We see that the cells in these granulomas are loosely 

arranged and very viable appearing.

We can see that the central cells are not 

broken down but seem well formed and 

intact.

These are the macrophages or the history of sites.

Again we see the cuff of lymphocytes and plasma 

cells around the periphery,

the nodule and many giant cells which 

are so characteristic.

However,

if we examine this nodule,

we see that the cells have been replaced by 

fibroblasts and fibrous tissue.

This unfortunate patient is beginning to 

fibrosis,

his na jules as he goes into 

progressive fibrosis,

the non regular pattern that we indicate it was military,

will give way to a particular modular pattern 

because the septa become 

involved.

Note the pseudo paddle extension in the 

lower right into a septum 

we then see linear patterns,

not just modular ones.

The linear patterns represent involvement of the lymphatic 

sex in the interlocutor septa,

so that we begin to see a reticulated appearance radia 

graphically.

This becomes very striking in some of these 

diseases.

Where the disease may start with a multi modular 

pattern,

it may evolve if the patient is so 

unfortunate and to a reticulated pattern 

which indicates that fibrosis is ensuing in the 

interstitial of the lung.

This is seen in sarcoidosis in perhaps a third 

of patients,

but in silicosis,

which we will now review it is seen 

eventually,

nearly always,

a case of silicosis in which we not 

only see nodule or granulomas throughout the lung fields,

but also are already aware,

particularly as we view the close up of 

a reticulated pattern which has been 

caused by extension of the silica reaction 

into the lymphatic of the interlocutor septa and 

other interstitial tissues of the lung,

A biopsy shows nodule in the lower part of the 

specimen which are seeing close up as markedly 

fiber optic modules in walls of fibrous 

tissue.

But we also see the reorganization of the architecture of the 

lung in the upper part of the specimen,

where actually we can visualize the articulation.

Even on this microscopic specimen,

you can see tiny elevator walls at the lower 

left and can then appreciate by contrast 

with the upper central part where they are missing,

how much such elevator walls have been 

destroyed.

What is left in the upper area are larger 

septa that have been rearranged by 

secularizing fibrosis.

The lung structures have been reorganized by 

secret rising retraction and delicate l 

villa walls have not been able to withstand the 

pull of such retraction in so many areas.

In this way we begin to see more and more 

ridiculous in radiographic lee as the silicosis 

progresses in this patient 

finally,

we reached a stage where the lung is so damaged 

that the lung organizes into practically fibrous 

knots with great air voids and emphysema 

between them.

In the next specimens,

we can see how this reaction can cause a glam aeration 

into ever larger masses,

smaller masses pulled together by secularizing 

fibrosis into practically a solid mass.

This results in the well known radiologic 

picture we see next in two further cases of 

silicosis.

Here we see large masses in the upper parts of the 

lung fields.

The so called progressive,

massive fibrosis of silicosis 

notice that in the lower lung fields we still 

see some nodule scattered around,

but these have been all pulled together into a 

glamorous masses above the highly a 

very classic picture in end stage silicosis 

we have seen in both sarcoidosis 

now thought possibly to be a type for immunological 

response expressed unfortunately,

and in silicosis,

an airborne dust and Helen disease,

that a granuloma.

This change in the lung can evolve 

from modular patterns to interstitial reticulated 

patterns.

This evolution from a modular into articulated 

pattern is an important diagnostic 

criterion for radiologists since 

They mainly occur in five major disease 

categories.

The pneumoconiosis or dust fungus 

diseases,

tuberculosis,

sarcoidosis and in the history of 

psychosis.

Now,

let us review a case of histiocytosis.

Eosinophilic granuloma of the lung,

the ideology of eosinophilic granuloma is still 

not understood,

but it is suspected to be a type for immunological 

response,

much as sarcoidosis triggered by 

chronic infection.

No definite pathogen has been isolated.

However,

Here we see a patient with eosinophilic granuloma in 

1957 notice any 

close up that nearly all the change at this time is a 

modular pattern.

Now,

let's look at the patient in about a year and a half as his disease 

progresses.

In addition to Na Jules,

we begin to see articulation in 1958,

this indicates that this patient with eosinophilic 

granuloma is responding with interstitial 

fibrosis.

This has brought out very poignantly as we go to the 

same patient in another five years in 

1963 to see how it is progressed.

Now,

we have reached the stage where the nodules are no longer the 

prominent part of our pattern.

We see instead mostly 

articulation and in fact the 

change is not advanced enough that we might refer to 

this as honeycomb lung.

This patient has gone from a larger infiltration 

to an involvement by extension into lymphatic sin,

the interlocutor septa to articulation 

as fibrosis ensues and causes 

reorganization and rearrangement of the septa.

We get a chaotic pattern of arba rising lines 

which give us the texture of a honeycomb lung.

If we look at the gross specimens in such patients,

we see the remarkable quality of honey combing.

We see how the septa have become 

enlarged and rearranged and 

resulted in large air containing 

voids.

As we look at the surfaces,

we see blood formation,

enlarged,

cyst like structures,

voids of error,

which can easily break down and cause 

pneumothorax.

We of course,

realize that pneumothorax finds its highest 

rate in eosinophilic granuloma,

in fact higher than in any other interstitial 

disease of the lung,

as in the other granulomas diseases.

If we happen to see a patient early in the course of 

eosinophilic granuloma.

We will see an ill defined modular pattern.

Here's a case that fortuitously was seen 

early during the clinical course 

and this is not too common,

since these patients tend to be asymptomatic.

Here we see that the nodules are ill defined and 

shaggy and tend to coalesce.

This again is the pattern of early granulomas 

infiltration such as we saw when we were 

looking at certain early cases of fungus infection 

earlier.

This shows us that even here we 

progress from an infiltration into an 

organized nodule,

which then goes on to a smaller fibrous nodule 

and then in some cases will extend into the intersection 

and result in the patterns we saw in our previous patient.

We see in a biopsy from this case,

one of the ill defined modules notice that we 

see soft edges,

a kind of storm in the surrounding lung,

which makes the nodule look shaggy and coalescence on the 

radiograph 

before closing.

We should talk about some more recent concepts in 

granulomas disease.

It is very important to consider the granulomas response 

in collagen disease.

First let us study some rheumatoid granulomas,

in which we see that the nodules are discreet in 

size,

Usually one or 2 cm.

We see that they are very smooth and 

aspect there are usually 

a few scattered around the lung fields and they are 

primarily peripheral.

In fact most of them may be sub plural,

and they tend to cavett ate quite easily.

The capitation,

however,

is not due to the destruction of the tissue by infection,

as we have noted in the fungus diseases and in 

tuberculosis,

but rather is due to the 

hypersensitivity response of the tissue,

including a vasculitis.

The vasculitis may lead to infarction of the tissue 

dependent on the involved vessel.

This is seen nicely when we look at one of the 

nodules in the gross specimen 

on the left,

we see the hemorrhagic content in the cavity of the 

granuloma.

It is easily recognized by its intense red 

color as breakdown products of blood 

around it is the familiar fibers tissue 

and again around the very periphery of the fibrous nodule.

We see the bluish haze caused once more 

by the thousands of tiny lymphocytes and plasma cells.

It is the same classical organization we 

saw in the infectious granulomas.

This higher power view shows that the 

fibrous tissue strands 

tend to be oriented around the center 

and they catch up the cells and macrophages in what we 

call a police aided effect because of the 

degree of fibrous tissue retraction.

In this case,

we see hundreds of rheumatoid granulomas 

peppering the lung fields in a multifocal 

display.

Each granuloma is organized like the 

few granulomas we saw in the previous case.

Another interesting disease in which we see 

capitated granulomas in a hypersensitivity 

or allergic response is vacationers 

granuloma ketosis,

not the size of these granulomas in this 

disease,

they tend to be variable in size but are often very 

large,

much larger than we would ever expect to see in 

any of the diseases we have studied up to this point,

break down with necrosis and subsequent 

capitation are paramount in this disease.

Here to the breakdown is caused by a marked 

vasculitis,

which leads to thrombosis of arteries as well 

as veins and causes destruction of the tissue 

dependent on the involved blood supply.

Therefore,

we see marked breakdown of tissue 

with huge cavities and air fluid levels 

caused by either super infection in the 

granuloma or by the bleeding caused by the 

vasculitis.

Close ups allow us to see the degree of this 

capitation and the natural quality of the wall 

of the granuloma.

When we study the tissue,

we see its breakdown in the center of the beginner's 

granuloma,

which is already beginning to slough to form a cavity.

Very little substance is left,

the peculiar dark color is caused by the 

necrosis.

On the right slide,

a vessel is becoming fibrosis and the lumen of the 

vessel is nearly constricted,

closed by the remarkable granulomas response to the tissue.

This will eventually lead to ischemia and 

infarction in these collagen 

diseases are granulomas response is 

really centered on the blood vessels causing 

infarction,

then capitation and often 

air blood fluid levels.

In this remarkable process.

Here is a case in which we see a remarkable 

change.

In one week,

The patient has a few scattered capitated 

granulomas fosse on 

14 June 1971 

they look somewhat shaggy because of the storm of 

reaction in surrounding lung tissue.

In one week,

by 21 June,

his whole lung is flooded by what 

appears to be numerous shaggy.

Fosse on pathologic 

inspection.

These indeed were infections.

Nothing else could account for the remarkable change in this 

patient.

In one week he has had several 

infractions in various parts of the vascular 

distribution of his lung,

causing a flooding of the lungs with el valor filling 

by hemorrhage and edema.

Another case of vegans,

granuloma ketosis,

in which we see hundreds of shaggy nah jewels,

many of them capitated.

They can best be appreciated in the topographic close 

ups which show the capitation so 

vividly in our discussion today,

we have covered not only the classic granulomas 

in solitary or multifocal distribution,

but have also attempted to look at some of the latest 

concepts of granulomas associated with college 

and diseases.

All of these are related by a similar organization of 

cells and responses which lead to nausea,

Lafosse,

which may either fibrosis calcify or 

cavett eight depending upon the vigor of the 

reaction during the course of the disease.

We have also seen how we can radio graphically 

trace the evolution of a granuloma from 

early infiltrated pneumonia to an organized 

nodule.

We have also seen how these modules may give way to a 

reticulated pattern or even a honeycomb 

lung if the disease extend sufficiently 

into interstitial structures.

Through such general principles we are able 

to predict more what we should see radio graphically 

depending upon the nature and timetable of the 

disease we may be discussing.

Mhm