Psoriasiform Reaction Pattern

EXAMINING HISTOLOGICAL SLIDE


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Examining a histological slide starts by not  looking at the patient's history but instead starts with an examination of the slide itself. You look to see what type of biopsy has been done and how many cuts have been taken. Remember to look at all of them!

Assuming that it is a skin biopsy the first thing you do is look at the epidermis, specifically at the stratum corneum.  Look to see whether there is orthokeratosis or parakeratosis.  Orthokeratosis is the normal type of scale that is found on the skin surface.  It can be exaggerated in certain conditions and  it is obviously thickened in certain areas of the skin, such as the palms of the hands and the soles of the feet.  Parakeratosis, when nuclei are retained within the stratum corneum, indicates a hyperproliferative disorder.  This can be an inflammatory disorder associated with overgrowth of keratinocytes such as psoriasis or it can be a skin malignancy such as Bowen's Disease.  There is a characteristic pattern of alternating ortho and parakeratosis  that is seen in a condition called pityriasis rubra pilaris, and parakeratosis is seen in many of the other red scaly diseases. You can also have the sandwich sign of vertical layers of ortho and parakeratosis  seen in dermatophyte infections. See the clinical image of this and the histology image.

The next step is to look and see if the stratum granulosum is there or not.  There are some conditions in which the stratum granulosum is in fact absent and this is the case in psoriasis.  Also look at the stratum corneum and see if there is any sign of fungal hyphae or yeast forms.  These can be subtle and unless you specifically look at the top layers of the stratum corneum you are not going to see these unless you subsequently have the tissue stained with a PAS stain, when these organisms will stand out more prominently. 

You then look at the epidermis itself and see if it has thinned, if it is intact, if there is hyperplasia or acanthosis.  Acanthosis is seen a variety of benign skin proliferations such as seborrhoeic keratoses, but it is also seen in inflammatory disease such as psoriasis.  All the other red scaly diseases can have a degree of acanthosis as well, but there is a form in psoriasis that goes under the name of psoriatic hyperplasia in which, not only is there prominent acanthosis but there are also prominent rete ridges and the dermal papillae are also seen higher up in the epidermis. 

These are the base line changes that are common in all the scaly disorders.  In the red scaly disorders there is usually some degree of inflammation as well, which is why there is redness associated with them.  All those conditions that are seen in the PMs PETAL will have some degree of the changes that have been mentioned already.  So, anytime you see acanthosis, anytime you see parakeratosis, anytime you see some degree of psoriatic epidermal hyperplasia with inflammation you have to think of the conditions that are part of the PMs PETAL and then you look for the characteristic histological features of each of the conditions that are in that mnemonic and try to either count them in or count them out.  All we are going to do now is to look at some of the additional histological features that you will see in each of those conditions. 

The Psoriasiform Reaction Pattern

 

If the granular layer is absent Consider Psoriasis ord pustular psoriasis if intraepidermal pustules 

If the granular layer is diminished Consider Ilven (alternating parakeratosis) Seborrhoeic dermatitis (spongiosis and follicular shoulder parakeratosis) 

If the granular layer is increased Consider Lichen simplex chronicus and prurigo nodule 

Plaque Psoriasis Back

In psoriasis you see,  starting from the top, confluent parakeratosis.  It is not focal, in other words there is parakeratosis all the way along.  In looking at that top layer there may also be neutrophils in the stratum corneum and these are called Munro micro abscesses.  Neutrophils or some degree of neutrophilic infiltration is a feature of psoriasis all the way through to pustular psoriasis.  In the spinous layer there may also be some neutrophils in groups and here it is known as the spongiform pustule of Kogoj.  The epidermis itself will show a regular acanthosis. What this means is that the rete ridges tend to be much the same length.  They may well be elongated and they are also  clubbed at the base.  The granular layer is reduced and may in fact be absent and above the dermal papillae you have a really very thin epidermal plate with  dilated vessels within the dermal papillae.  There may in fact be neutrophils all the way right through to the stratum corneum.  We have talked of them already being in little abscesses but sometimes they dont form abscesses and you just have neutrophils all the way through.  In the upper portion of the dermis there will be dilated vessels and there may be some extravasation of neutrophils here as well and this partly relates to the colour changes that you are going to see in psoriasis.

View this Virtual slide of Psoriasis

Guttate Psoriasis

The above description is mainly for plaque psoriasis.  If you look at guttate psoriasis it is a little bit different.  Here you can get what are called focal mounds of parakeratosis with some orthokeratosis in between and also there is less acanthosis of the epidermis than you see in ordinary psoriasis.  You will still see some neutrophils and they can extend all the way through to the stratum corneum.  We will deal with pustular psoriasis later because from a morphological point of view it is going to come under the pustular disorders and it is best described there in association with the other pustular disorders.

View this Virtual Slide of Guttate Psoriasis

Note the prominent follicular papules

Pityriasis Rubra Pilaris

Pityriasis rubra pilaris.  I am going to talk about the histopathology of this condition  here because again it is a red scaly disease but it begins with follicular papules. Clinically you have islands of sparing. It begins typically in the scalp with a psoriatic picture and then extends acrally.  A characteristic feature is thickening of the palms and soles and it also shows  ectropion.  Histopathologically it is similar to psoriasis but when you are looking from the top down, what you get is an alternating orthokeratosis and parakeratosis in both a vertical and horizontal direction.  There is still quite marked acanthosis but instead of hypogranulosis in this condition there is often hypergranulosis, ie prominence of the stratum granulosum.  You may well see some follicular plugging and a degree of parakeratosis on the lip of these hair follicles.  There still can be some degree of clubbing of the acanthotic epidermis.  There also still can be thinish suprapapillary plates but they are usually thicker than in psoriasis.  There is not the same degree of vascular dilatation of the vessels in the dermal papillae and if you look at the infiltrating cells in pityriasis rubra pilaris they are often lymphocytes with occasionally eosinophils and plasma cells rather than the neutrophils that you see in psoriasis.

View this virtual Slide of PRP

Thinking along the mnemonic of the PMs PETAL we will come to E for eczema.  The form of eczema that is very similar to psoriasis is lichen simplex chronicus.  Normally the histological hallmark of eczema is that you have some degree of spongiosis i.e. a little bit of fluid in between the keratinocytes in the epidermis.  But in lichen simplex chronicus what you get is really quite prominent psoriasiform hyperplasia, but instead of hypogranulosis or loss of the granular layer you still have quite a prominent granular layer, and you have compact orthokeratosis overlying this acanthotic epidermis.  When you have a little look in the papillary dermis as well you will see there is vertical streaking of collagen.  The dermal collagen is more prominent in these areas and it gives an almost papillomatosis appearance looked at histologically.  The degree of spongiosis in lichen simplex chronicus can be quite minimal because of the chronic nature of this condition, so remember the hypergranulosis and the compact orthokeratosis for the stratum corneum in lichen simplex chronicus.  Some acute eczema will have more spongiosis and because there may be oozing on to the surface, you may get a little bit of scale crust as well, which is a mixture of serum and cells and sometimes some parakeratosis.  The more chronic the process is the more psoriasiform the changes are going to be in the epidermis and also remember a few eosinophils and plasma cells are more likely in a spongiotic dermatitis in it's chronic form and this is not often seen in psoriasis.

View this Virtual Slide of Lichen Simplex Chronicus

Small Plaque Parapsoriasis

Large Plaque Parapsoriasis

Parapsoriasis -  small plaque parapsoriasis can clinically look like psoriasis but there are  few very definitive histological features unlike the zebra striped pattern that we see clinically.  Again there is quite a bit of surface scale, but when this is histologically examined it looks more like a chronic superficial dermatitis with a mild eczema , a bit of spongiosis, and a degree of psoriasiform change, but there are no abnormal lymphocytes within the epidermis itself. This is possibly an early form of mycosis fungoides or T-cell lymphoma, the M in the PMs PETAL.  It is a difficult diagnosis to make for the pathologist, and almost certainly they will put it out as a chronic superficial dermatitis, but the lesions may not respond all that well to topical steroids.  There is a variant called large plaque parapsoriasis which certainly looks more psoriasiform and depending on the stage at which it is examined, more atypical lymphocytes may invade the epidermis and you may start to get little collections of them.  If you get true collections of abnormal lymphocytes in the epidermis, called Pautrier microabscesses, then it is mycosis fungoides or T-cell lymphoma. 

So in summary, if you have the M of PMs PETAL mycosis fungoides then you are going to see a degree of psoriasiform hyperplasia but there are going to be lymphocytes that invade into the epidermis.  This is known as epidermotropism and these lymphocytes will show varying sized nuclei and some atypia. The more lymphocytes that invade into the epidermis the thicker the epidermis becomes and so patch mycosis fungoides will change into plaque mycosis fungoides and it is much easier for the pathologist to make the diagnosis in these circumstances.  There is usually preservation of the stratum granulosum and generally you have overlying orthokeratosis rather than the parakeratosis you would expect in psoriasis.

Mycosis Fungoides patch stage

Pautrier Microabscesses

Tinea Corporis (Ringworm)

Tinea  We have dealt with psoriasis.  We have dealt with eczema.  We have dealt a bit with the M of mycosis fungoides.  What about tinea the T of PMs PETAL.  In tinea the dermatophyte infection involves the stratum corneum because it is made of keratin.  This is what the fungal organism lives on, so the area to look for it is at the top of the stratum corneum.  What you will see though is some degree of psoriasiform hyperplasia.  There may be neutrophils in the stratum corneum as well, much the same as in psoriasis and when you see this phenomenon of neutrophils in the stratum corneum it is called neuts in the horn. Sure it can be seen in psoriasis but it is also a feature of tinea infection. So when you see it you should go looking for  evidence of fungal hyphae or yeasts in the top layers of the stratum corneum. What you may get is alternating compact and basket weave layers of the stratum corneum itself.  Though there may be hyperplasia of the epidermis the rete ridges aren't as extensive and deep as you would see in psoriasis.

Eryhtema Annulare Centrifugum

 

Continuing with the PMs PETAL the A stands for Annular Erythemas such as Erythema annulare centrifugum.  It certainly is a red scaling disorder but it has a  trailing scale and the scale is not a major feature of the rash.  Many presentations of EAC actually don't have much in the way of scale.  When you look on the histopathology of this  is that there isn't the degree of psoriasiform hyperplasia that we see in  psoriasis, or  eczema for that matter or tinea.  You may just get a small area of spongiosis and a little bit of parakeratosis that is associated with this trailing edge scale.  The major changes that you are going to see are actually in the superficial vessels of the dermis where you will get a fairly tight cuffing of lymphocytes around these vessels.  This is the feature that is going to catch your eye more than anything else.  You may see that little bit of parakeratosis corresponding to the trailing scale but it is going to be the prominence of the perivascular or coat sleeve appearance of lymphocytes that is going to catch your eye histologically.  There is a deeper variant of EAC as well and in this one there is often no scale at all, so there is sparing of the epidermis, there is no spongiosis and you tend to get just a spreading erythematous edge where lesions join up to give an arcuate shaped lesion. In this variant there is  both a deep and superficial perivascular cuffing with lymphocytes.

The other Ls in PMs PETAL are lupus, lichen planus, polymorphic light eruption, the L for syphilis or Lues, the old name for syphillis.  Now of these four conditions, the first three don't give rise to much psoriasiform hyperplasia, however, syphilis may and remember syphilis, especially secondary syphilis will give the salmon red scaly patches on the skin that can be mistaken for pityriasis rosea and sometimes can even be mistaken for guttate psoriasis. So it probably wouldn't surprise you clinically and shouldn't surprise you histologically that these other Ls may at times have a psoriasiform picture associated with them.  

Secondary Syphilis

So histopathologically with syphilis you are going to see some psoriasiform hyperplasia, especially in the late lesions of secondary syphilis.  You are not going to see a lot of change in the stratum corneum, most of it is going to be orthokeratosis rather than parakeratosis.  You will though see changes in the vasculature in the upper dermis where you will get a superficial and deep dermal infiltrate, but when you look the cells you will see will be mainly plasma cells. Sometimes these plasma cells may even invade into the epidermis itself.  In some cases because of the nature of the inflammation there may even be a sort of lichenoid like infiltrate, where there are a lot of lymphocytes arranged along the base of the basement membrane, but if you look there is certainly going to be plasma cells there as well and this is what is going to alert you that you may be dealing with secondary syphilis.

Pityriasis Rosea

Pityriasis Rosea is one of the first Ps in PMs PETAL.  It is a red scaly disease but the degree of scale is not great, so you are not going to expect a lot of changes in the stratum corneum.  In pityriasis rosea you tend to get a rather undulating epidermis and you will get focal areas of parakeratosis, but you will also get little bits of spongiosis in the epidermis as well.  There can be some lymphocytic extravasation into the epidermis and so it may look like small Pautrier microabscesses but, the lymphocytes won't look abnormal.  You are also going to get changes in the vessels in the upper dermis where there may be a degree of perivascular cuffing with lymphocytes as in erythema annulare centrifugum and there is also often some extravasated red blood cells.  The epidermis itself may show a bit of psoriasiform thickening because, as you know, clinically the lesions can look like psoriasis, but it is a combination of the spongiosis, the focal parakeratosis and the vascular changes with a bit of red cell extravasation that allow you to make the diagnosis histologically of pityriasis rosea.  You will know clinically that there are a variety of clinically atypical forms of pityriasis rosea, so each of these elements can be exaggerated sometimes depending on the form that you are seeing.  Some can also be drug induced and in these circumstances you may get an increase in eosinophils.  This may make you think that it is more a dermatitic process but it may be that the eosinophils are there as part of a drug reaction.

Extensive Pityriasis versicolor

Pityriasis Versicolor is normally a fairly easy clinical diagnosis.  Either you will get red, slightly scaly areas on a background of white skin or you will get white or paler hypopigmented areas on the background of a tanned skin.  To induce the scale you often have to take your fingernail and roughen up the surface and it gives this very fine pityriasis like scale.  Histologically when you look at this what you will see are changes in the stratum corneum.  Now initially you might think that this is parakeratosis but when you look under higher magnification you will see that it is a mixture of hyphae and yeast forms in the orthokeratotic stratum corneum.  This sometimes goes by the name of spaghetti and meatballs appearance of both spores and hyphae.  If you look at the epidermis there may be a degree of psoriasiform hyperplasia there and also sometimes be a little bit of spongiosis, but it is the presence of these organisms that is the giveaway for pityriasis versicolor.

Pityriasis Alba

Pityriasis Alba is really a very low grade form of eczema that presents particularly in tanned individuals, on the face and upper arms.  Again it has a  degree of hypopigmentation with very fine scale and it can sometimes be mistaken for pityriasis versicolor.  Generally though there is an atopic background in these individuals.  If it is biopsied and one looks at it histologically then there is just minimal parakeratosis in the hypopigmented areas and a little bit of spongiosis is sometimes seen in the epidermis, in other words it has the same basic histological pattern you would expect in an eczema, but it is the clinical features that really allow you to make this diagnosis, so you sometimes need the clinical information to be able to make the specific diagnosis of pityriasis alba but it is still an eczematous reaction pattern.

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