GRANULOMAS IN THE DERMIS
(Use the GlobalSkinAtlas Page link at the top of this website to access Clinical Images of some of these cases.)
(Use the GlobalSkinAtlas Page link at the top of this website to access Clinical Images of some of these cases.)
If you look at the slide and you see in the dermis
collections of epithelioid histiocytes plus or minus surrounding lymphocytes or
giant cells or neutrophils in the centre of these lesions, then you have
granulomas. Granulomas usually occur as part of Infiltrates in the dermis from cells substances or organisms.
Granulomas are
sub-classified into about four types.
They can be tuberculoid, sarcoidal, pallisading or infectious (Suppurative). Various diseases present as different types
of granulomas. Foreign body material can cause any type of granuloma but usually it is sarcoidal. The sarcoidal granuloma
is sometimes called the naked granuloma because basically you just have a collection
of histiocytes without any surrounding lymphocytes or neutrophils. In a tuberculoid granuloma you will have
histiocytes but you will also have some central caseous necrosis. In the pallisading granuloma you will find
that the cells are surrounding denatured collagen which goes under the name of
necrobiosis or sometimes there is mucin or foreign body material at the centre
of a pallisading granuloma. A suppurative
granuloma has centrally numerous neutrophils and they are part of an infected
abscess. Mind you the commonest cause of a suppurative granuloma is a ruptured follicle or cyst.
The granuloma is the body's
immune attempt at isolating this infective or inflammatory process. The common granulomatous diseases you will see will
be secondary to a ruptured follicular cyst, sarcoidosis, granuloma annulare, actinic granuloma, necrobiosis lipoidica,
tuberculosis of the skin and leprosy.
The other condition we have to watch out for is the deep fungal
infection which will have an infective granuloma. Let's look at the histopathology of each of
these conditions in turn.
Granuloma Annulare (See Clinical Images)
This shows a pallisading or interstitial pattern where
you have histiocytes, lymphocytes and some mucin in between collagen fibres in
the dermis and these collagen fibres are necrobiotic. Sometimes this is described as both the
interstitial and the pallisading pattern.
The infiltrating type is the interstitial one and the pallisading pattern
is where you have a central core of collagen with histiocytes surrounding
it. Mucin is seen in granuloma annulare
but it isn't seen in necrobiosis lipoidica, but sometimes you need a colloidal iron stain to show up the mucin.
Granulomas may also have giant cells associated with them and the ones that are classically described are the Toton giant cell where the nuclei are
in a circle; the Langerhans giant cell where the nuclei are peripherally placed and
in a horseshoe shaped pattern and the foreign body giant cell where there is a
diffuse arrangement of the nuclei in the cell.
A deep form of granuloma annulare in which the histiocytes pallisade around fibrin rather than mucin can be indistinguishable from a rheumatoid
nodule.
It is also useful to compare and
contrast granuloma annulare with necrobiosis lipoidica. Essentially in granuloma annulare the
granulomas are focal and patchy whereas necrobiosis lipoidica is diffuse and
often involves the full thickness of the dermis down to and including the fat layer. The
granuloma is pallisading or interstitial in granuloma annulare but in necrobiosis
lipoidica you can have a layered or sandwich granuloma.
Mucin present in granuloma annulare but not in necrobiosis
lipoidica. Plasma cells are common though
in necrobiosis lipoidica but are rare in granuloma annulare and cholesterol
clefts can sometimes be seen in some old lesions of necrobiosis lipoidica but
not in granuloma annulare.
A variant of granuloma annulare that should be recognised is perforating GA. Typically these lesions occur on the back of the hands or feet and the papules have a central crust or small umbilicated area where the abnormal collagenous material is being extruded through the overlying epidermis.
See this Clinical Variant in GlobalSkinAtlas
A variant of granuloma annulare that should be recognised is perforating GA. Typically these lesions occur on the back of the hands or feet and the papules have a central crust or small umbilicated area where the abnormal collagenous material is being extruded through the overlying epidermis.
See this Clinical Variant in GlobalSkinAtlas
This was first described by an Australian, John
O'Brien and it is typically seen on sun exposed areas particularly the
neck. In these lesions there is a
spreading edge with loss of elastic fibres in between so that if a special stain
is done for elastic fibres they won't be there.
Actinic granuloma shows a similar pallisading picture as in granuloma annulare but there is no mucin and it has this
central loss of elastic tissue. Biopsies should be taken from the edge and centre of these lesions or do an ellipse across the edge from normal skin to granulomas to loss of elastic tissue.
The changes in the collagen are necrobiotic changes
extending quite deeply into the reticular dermis in this condition. There is often a layered infiltrate of
lymphocytes and histiocytes in between the damaged collagen. Mucin isn't usually seen. Plasma cells may be seen particularly in the
deep dermis and the degenerate necrobiotic collagen is very prominent. It is probably more prominent in necrobiosis
lipoidica than it is in granuloma annulare.
Many patients with necrobiosis lipoidica have or will develop diabetes
mellitus. The term necrobiosis refers to
alteration in the dermal connective tissue.
There is loss of cellular definition, the area stains quite palely and
as we said before there is an absence of mucin. A deep incisional biopsy is best with primary closure as otherwise healing can be slow.
Though the terminology may seem similar to necrobiosis
lipoidica, the condition is potentially more serious. Again you have broad zones of granuloma formation, may you may also see Toton giant cells and
Langerhans giant cells. In older lesions
cholesterol clefts can also be seen and there may be plasma cells and even
lymphoid follicles. Necrobiotic
Xanthogranuloma typically involves the face and the periocular skin. It may also involve the scalp. The clinical lesions are yellowish with prominent vessels and the patients usually have an abnormal light chain gamma globulin circulating in the blood. Usually it is an IgG kappa light chain and they have a
paraproteinaemia. Note that giant cells
are more common in Necrobiotic xanthogranuloma than in necrobiosis lipoidica.
Juvenile Xanthogranulomas (See Clinical Images) are
not commonly biopsied. They may occur in
young children as the name suggests, but xanthogranulomas can also occur at any
age. The initial lesions look red and
may be confused because of their rapid growth with a Spitz naevus, but over
time they become yellow or yellow/orange.
Histologically there are a lot of histiocytes in the papillary and
reticular dermis and Tuton giant cells may be seen.
Sarcoidal granulomas are regarded as naked granulomas
in that there is just a collection of epithelioid histiocytes. There may be a thin rim of lymphocytes but they don't disperse through the granuloma. Epithelioid means that the histiocytes look
like epidermal keratinocytes. No
necrosis or necrobiosis is usually seen in these lesions.
Sarcoidosis is a great mimic clinically so it may present as a variety of skin diseases and have lung or cardiac problems, or rarely even hypercalcaemia. Sometimes cutaneous lesions are seen in about
25% of patients who don't show any signs of systemic sarcoidosis. It is usually seen histologically as a
diagnosis of exclusion in that infectious causes should be looked at with
special stains and also polarising microscopy should be used to see that this
isn't a sarcoidal reaction to a retained foreign body. Silica material can typically cause
this as can Zirconium and even mercury. Other conditions that can show
naked granulomas include Crohn's disease, the Melkersson Rosenthal syndrome with granulomatous cheilitis, silica granulomas and granulomatous rosacea.
These are sarcoidal reactions at the site of a graze injury. The patient may or may not have systemic sarcoidosis
These are sarcoidal reactions at the site of a graze injury. The patient may or may not have systemic sarcoidosis
Granulomatous rosacea is one of the unusual variants of rosacea. The granulomas are typically tuberculoid
rather than sarcoidal, but there is a degree of overlap. Usually in granulomatous rosacea there are also follicular pustules and telangictasia. The variant perioral dermatitis has a
histopathology just the same as rosacea.
Another condition that is similar is acne agminata or lupus milliarisdisseminatus faceii. These lesions are
firm brownish papules usually found on the forehead.
They will show a pallisading granuloma but in the centre is a large area
of caseous necrosis and hence they look like TB.
However when you do special stains or PCR there is no evidence of tubuculoid organisms.
Rarely drug reactions can cause an interstitial
granulomatous pattern.
In tuberculoid granulomas they are often fairly poorly formed granulomas. You often get central caseous necrosis but not
always. There is usually around the
granuloma a large number of lymphocytes and plasma cells. You may occasionally get some multi-nuclear
giant cells with asteroid and schaumann bodies.
Leprosy also gives a epithelioid granuloma of the
tuberculoid type. There is usually a
prominent rim of lymphocytes with a bit of central ccasseation. The granulomas are particularly localised
around large named nerves and the picture differs a bit depending on the degree
of immunogenicity of the patient. If
there is a fair level of immunity then tuberculoid leprosy will occur with granulomas but few organisms. If there isn't then you will tend to have
lepromatous leprosy in which there are a multitude of organisms and the granulomas
aren't as well formed.
These are due to material such as tattoo pigment or
quartz or glass or even beryllium.
Usually this material is birofringent and polarised to light, but other
foreign bodies even sea urchin spines can give a similar picture. Non-birefringent material includes chromium
seen in deodorants and some tattoo pigments, the commonest of which is red
tattoo containing mercury or cinnabar.
In summary if there is a dermal granulomatous pattern look to see if it is a sarcoidal or tuberculoid or pallisading granuloma or an
infective one. Look to see if you just
have epithelioid histiocytes or a type of giant cell that is there. See if
there is any central caseous necrosis.
See if there are lymphocytes or plasma cells surrounding the granuloma. Look to see if there is any altered collagen . Ask for special stains to look for acid and
alcohol fast bacilli. The Wade Fite stain is better than the Ziel Neilsen. Always do polarising
microscopy to see if there is any birefringence indicating a foreign body.
Infective Granulomas - Deep fungal infections- Sporotrichosis
Here you may as well as seeing a granulomatous process
in the dermis see pseudo epitheliomatous hyperplasia. You get a suppurative granuloma and when
special stains are done you may see the fungal spores of sporotrichosis – these
are usually cigar shaped. Chromoblastomycosis can give a similar picture but here you may get clusters of brown
spores when you use the appropriate stain which are sometimes known as
"copper pennies".
Granulomas
are sometimes seen when you have a ruptured cyst or follicle and these are generally
localised around hair follicles or cystic structures. They are probably the commonest granulomas biopsied in clinical practice.
The condition interstitial granulomatous dermatitis will histologically show pallisading and neutrophilic granulomatous
dermatitis. The lesions are often skin
coloured papules with an umbilicated or crusted surface. Patients with these lesions can often have
autoimmune diseases such as rheumatoid arthritis or lupus or may even have
lymphomas, so this interstitial granulomatous dermatitis is important but it
can also be caused by certain drugs, particularly the calcium channel blockers,
beta blockers, ACE inhibitors and even some antihistamines. The histological picture of the interstitial
granulomatous drug reaction is similar to granuloma annulare with a busy
dermis. There may be epidermotropism
as well and this is what makes you think there may be an underlying
lymphoma. It can also be a lichenoid reaction
with vacuolar changes as well. This is more suggestive of a drug cause. View this link for more details
The last and very rare condition to mention is
granulomatous mycosis fungoides or granulomatous slack skin disease. Here you have a granulomatous infiltrate in
the dermis which also destroys elastic fibres similar to actinic
granuloma. The diagnosis is made on the
basis of the atypical lymphocytes that form these granulomas. View this link for more details.
