Thursday, April 3, 2014

Diagnosis by the most obvious dermpath feature

Often when you look at a path slide an obvious histopath feature or pattern of inflammation catches your eye. It is quite useful to have a list of differential diagnoses for these features. You should still systematically examine a slide in case a less obvious feature is actually present and is of even more importance!

I also like to look at a slide and immediately state whether I think this is an Epidermal or a Dermal histological pattern. I then assign a couple of mnemonics as follows
If Epidermal then the diagnosis will be one of the Red Scaly or Skin Coloured scaly diagnoses and the mnemonic will be the PMsPET a little cat called PETAL

If dermal then the mnemonic will be CUL DVA EVIE   (See You Later at the Department of Veterans Affairs EVIE ) where EVIE is your girlfriend

If pustules obvious us II  and if vesicles or blisters use ICI   (See explanation for these mnemonics below.)

So look at the slide, look for features and patterns, decide whether Epidermal or Dermal or Both, Go through the diseases in the relevant mnemonic and then look for Specific histological features, patterns or clues to decide on the likeliest diagnosis. If you need more information on a histopath feature  look in the posts opposite and for patterns see DermatopathologyMadeSimple. If you want to see clinical pictures of the skin diseases go to GlobalSkin Atlas. If you need more information on the mnemonics look at Differential Diagnosis

Try some of the test cases in the post opposite


Epidermis.
Parakeratosis
Parakeratotic column
Alternating Ortho and Parakeratosis
Abscent stratum corneum
Neutrophils in the stratum corneum
Collections of cells in the epidermis
Thickened epidermis
Thinned epidermis
Thickened basement membrane
Epidermis with Atypical keratinocytes
Dyskeratotic cells
Pale cells in the epidermis
Epidermotropism
Basal layer damage
Pagetoid spread of cells or nests
Follicular pathology

Dermis 
Grenz zone
Papillary oedema
Material laid down
Black staining
Pink staining
Blue staining
Clear cells
Clear spaces between cells
Indian filing of cells between collagen
Cells with anything within them
Papillary microabscesses
Flame figures in the dermis
Busy dermis
Giant cells
Ectopic tissue
Lichenoid infiltrate
Perivascular infiltrate
Mid dermal infiltrate
Desmoplasia
Involvement of fat

Tumours
Blue cells in dermis
Spindled cells
Granular cells
Clear cells
Balloon cells
Excess eccrine ducts
Excess Sebaceous glands
Excess vascular spaces
Keratin cysts in the dermis
Indian filing
Atypical cells with prominent nucleoli

Adapted from Dermatopathology - Diagnosis by first impression. Christine J Ko and Ronald Barr Wiley-Blackwell

The conventional approach to teaching the pathological diagnosis of inflammatory skin disease has been to assign the slide to a particular reaction pattern and look for the subtle features that distinguish one disease from another that conventionally are known to cause that reaction pattern. This works quite well but if you get the reaction pattern wrong you will have trouble arriving at the correct diagnosis. You can combine the first obvious feature with reaction patterns to minimise this risk.





1. Diagnosing skin diseases is not difficult. You look at a rash and decide if it is red and scaly or red and non scaly. If it is red and scaly you use the mnemonic PMs PET (PET is Psoriasis, Eczema and Tinea. This is the Prime Minister'S Pet ( I used to always think of Kevin Rudd with a Siamese cat called Petal sitting on his lap!) The first P of PM is for Pityriasis rosea or Pityriasis versicolour, Pityriasis rubra pilaris, Pityriasis lichenoides and the M is for Mycosis fungoides, a T cell lymphoma of the skin.) The S is for Solar damage and Scabies

 Now we know that his pet cat is called PETAL. This helps us to remember Psoriasis, Eczema and Tinea but also the less common red scaly diseases of A for Annular erythemas and L for Lupus erythematosus ,Lichen Planus, Light eruption and Lues (an old name for syphilis)

2. If it is red but not scaly consider Cellulitis, Urticaria, Lupus, Light eruption, Drug reaction, Viral exanthem or Annular erythema .The mnemonic is C U L at the Department of Veterans Affairs EVIE(your girlfriend Evie) (CUL DVA EVIE) where EVIE stands for Erythema multiforme, Vasculitis and Erythema nodosum and Infiltrates

3. If there are Pustules then the mnemonic is II
(aye aye) Infective( viral, bacterial, fungal) or Inflammatory eg psoriasis or a pustular drug reaction or Sweet's syndrome. Common causes include Staph folliculitis , modified fungal infection or if the vesicles are grouped herpes simplex. Pustules on the face are Acne, Rosacea, Staph folliculitis or H Simplex if grouped.

4. If there are Blisters or vesicles The mnemonic is ICI(Imperial Chemical Industries) Inflammatory including Immunological, Contact dermatitis and Infective.
Inflammatory causes can include drugs but remember Immunological causes in the elderly particularly bullous pemphigoid. Contact dermatitis usually gives smaller vesicles rather than blisters but individual vesicles can join up into blisters. If blisters are linear and itchy it is probably a Plant contact dermatitis. Infective blisters are usually bullous impetigo due to a staph infection. If in a dermatomal distribution blisters are likely to be Herpes Zoster.

5. If Skin Coloured and Scaly The mnemonic is ( I am coming Don't go away) Ichthyosis, Acanthosis nigricans, Confluent and Reticulate papillomatosis, Dariers, Grovers and Acrokeratosis verruciformis) but these are mostly uncommon conditions.

6. Skin coloured and Non scaly  No good mnemonic except ICS (Infiltrates of cells or substances)     Most cases are Infiltrates of cells or substances  eg Granuloma annulare, Sarcoidosis, Mucinosis, Scleromyxedema, Scleredema, Scleroderma,  Metastases,

TEST CASES

Try this case. Biopsy papular lesion on the face.

 
 
Dermal process Therefor CUL DVA EVIE
 
These are granulomas. See the link on this below in the DERMIS section or go to the Dermatopathology Made Simple tab above for more information on the different types of granulomatous diseases and their histopathology.
 
See the video of the analysis below. Click to view it on YouTube then click on the circular motive at the base to increase the resolution to 1080 HD and click the outside box to view full screen.
 
 
 
This is the clinical picture
 
 
 

EPIDERMIS

Epidermal diseases usually show psoriasiform or spongiotic reaction patterns with varying degrees of hyperkeratosis and hyperplasia or acanthosis. The archetypical examples are psoriasis and eczema but the many diseases seen with an epidermal histology reaction pattern are best remembered by the mnemonic PMs PET a small cat called PETAL

P - Pityriasis rosea, P versicolor, P rubra pilaris, P lichenoides,
M - Mycosis fungoides
s - Solar damage, Scabies

P - Psoriasis
E - Eczema
T - Tinea and other fungi
A - Annular erythema
L - Lupus erythematosus, Lues (syphilis). Lichen planus, Light exacerbated Darier's, Linear verrucous epidermal nevus, Lichen striatus,

Some interface pathology diseases can involve the epidermis sufficiently to cause epidermal changes eg Erythema multiforme  and also dermal processes which perforate will cause epidermal changes eg Perforating folliculitis in renal failure, perforating deep fungal infections and TB or elastosis perforans serpiginosa with perforating elastic fibres.

Elastosis perforans serpiginosa


So look at a slide.

Is the pathology Epidermal or Dermal or Both. If Epidermal use the Mnemonic PMs PETAL
If dermal use the mnemonic CUL DVA EVIE (See DERMIS) link opposite.

If Both then use both mnemonics.
Look for any other epidermal or dermal features or clues and then work through the diseases in the mnemonics to see which might best fit the histology in front of you.

If you see Pustules in the epidermis the mnemonic is II

I - Infective  Viral, Bacterial, Fungal, Rickettsial, Protozoa
I Inflammatory eg Drugs, Pustular psoriasis, Rare ( Scabies, Necrolytic migratory erythema, Subcorneal pustular dermatosis, Erosive pustular dermatosis, Acrodermatitis enteropathica)

If you see Vesicles or Blisters the mnemonic is ICI

I - Infective Viral Bacterial Fungal
C - Contact Dermatitis
I - Inflammatory - Drugs, Porphyria, Insect bite, Genetic bullous diseases
I - Immunological - The immune bullous diseases

View a video on this topic

Parakeratosis

Parakeratosis                            See DX Path for details of the conditions below

Parakeratosis refers to retained keratinocytic nuclei in the stratum corneum. It is seen in proliferating keratinocytic disorders such as psoriasis, and in keratinocytic malignancies and premalignant conditions such as Bowen's disease and Solar keratosis. The nuclei are flattened and run  parallel to the epidermal surface.
When you see it look carefully at the underlying epidermis. You may see hyperkeratosis, hypogranulosis and acanthosis.  Histological parakeratosis usually equates to surface scale so think of the mnemonic for the red scaly diseases PMs PETAL for likely diseases.



Patterns of parakeratosis can be helpful.
Confluent in Bowen's disease and Psoriasis
Alternating in Solar keratosis







Parakeratosis in a heaped up column in the cornoid lamellae of DSAP


Checkerboard parakeratosis in PRP







Sandwich parakeratosis over orthokeratosis in Tinea corporis




There is also the unusual axillary granular parakeratosis with granules in the stratum corneum.


Papillomatosis

Papillomatosis                               See DX Path for details of the conditions below

This occurs with the surface projection of the dermal papillae high up towards the skin surface with resultant irregular undulation of the epidermal surface and often  overlying hyperkeratosis. It is commonly seen with warts, solar keratosis, epidermal nevi and some seborrhoeic keratoses. It is a major feature of a verrucous carcinoma..



Other rarer disorders to consider

Acanthosis nigricans


Nevus sebaceous



Syringocystadenoma papilliferum Usually head and neck warty lesion, invagination of the epidermis with papillary structures lined by cuboidal or low columnar epithelial cells showing decapitation secretion.Numerous plasma cells in the fibrin core of the papillary structures.


Tuberculosis verrucosa cutis 

  Papillomatosis

This occurs with the surface projection of the dermal papillae high up towards the skin surface with resultant irregular undulation of the epidermal surface and often  overlying hyperkeratosis. It is commonly seen with warts, solar keratosis, epidermal nevi  Virtual Slide  and some seborrhoeic keratoses.

 It is a major feature of a verrucous carcinoma..  Virtual Slide

Other rarer disorders to consider

Acanthosis nigricans   Virtual Slide

Nevus sebaceous         Virtual Slide

Linear Verrucous Epidermal nevus

Syringocystadenoma papilliferum  Virtual Slide

Tuberculosis verrucosa cutis          Virtual Slide

Acrokeratosis verruciformis (Acral Dariers)

View the Video of this Topic



Follicular plugging

The follicular opening is plugged with excess keratin        See DX Path for details of the conditions below

It is seen in discoid lupus and in lichen sclerosus and also PRP as the major disorders.





  but also in Darier's disease, Keratosis pilaris, Lichen spinulosis and perforating folliculitis.






Absent stratum granulosum

Absent Stratum Granulosum                            See DX Path for details of the conditions below

This is seen in ichthyosis vulgaris and under a porokeratotic cornoid lamella.





There is also hypogranulosis seen in any disorder with marked parakeratosis particularly psoriasis. It is also seen in Necrolytic migratory erythema, Acrodermatitis enteropathica and Pellagra. It is also a feature of normal mucous membranes.


Neutrophils in stratum corneum

Neurophils in the Stratum Corneum                  See DX Path for details of the conditions below

Whenever I see this I think of Impetigo, Fungi or Pustular psoriasis and would order a PAS stain.
Munro microabscesses are collections of neutrophils in the stratum corneum.








Neutrophils in the epidermis can be seen in a variety of inflammatory conditions but remember Acne and folliculitis, Gonococcemia, Necrolytic migratory erythema, Pemphigus erythematosus or foliaceous, Neonatal pustular melanosis, Scabies and Halogenodermas.




If you see Pustules in the epidermis the mnemonic is II

I - Infective  Viral, Bacterial, Fungal, Rickettsial, Protozoa
I Inflammatory eg Drugs, Pustular psoriasis, Rare ( Scabies, Necrolytic migratory erythema, Subcorneal pustular dermatosis, Neonatal pustular melanosis, Erosive pustular dermatosis, Acrodermatitis enteropathica, Halogenodermas)

Collections of cells in the epidermis

Collections of cells in the Epidermis             See DX Path for details of the conditions below

They can be neutrophils, eosinophils, lymphocytes, melanocytes or histiocytes plus Paget cells. They all form collections within the epidermis and clinically appear as pustules or they induce scale. So the red scaly mnemonic PMs PETAL  or the Pustule mnemonic II should pick them up.

Neutrophils in the epidermis can be seen in a variety of inflammatory conditions but remember Acne and folliculitis, Gonococcemia, Necrolytic migratory erythema, Pemphigus erythematosus or foliaceous, Neonatal pustular melanosis, Scabies and Halogenodermas.


If you see Pustules in the epidermis the mnemonic is II

I - Infective  Viral, Bacterial, Fungal, Rickettsial, Protozoa
I Inflammatory eg Drugs, Pustular psoriasis, Rare ( Scabies, Necrolytic migratory erythema, Subcorneal pustular dermatosis, Neonatal pustular melanosis, Erosive pustular dermatosis, Acrodermatitis enteropathica, Halogenodermas)

Eosinophils in the Epidermis

This is known as eosinophilic spongiosis  and is commonly seen in Pemphigoid and Pemphigus, Acute Contact Dermatitis, Arthropod bites, Eosinophilic pustular Folliculitis, Incontinentia pigmenti and Erythema toxicum Neonatorum
Still remember the Pustular Mnemonic II Infective and Inflammatory. Most of the eosinophilic pustules come under the inflammatory list of diseases.



Lymphocytes in the Epidermis

These can be small normal looking lymphocytes in PMLE, Acute dermatitis, Pityriasis rosea, Pityriasis lichenoides, Graft versus host disease and Erythema multiforme and collections of atypical lymphocytes (Pautrier microabscesses) in Mycosis fungoides. They tend not to form pustules but either cause keratinocyte necrosis, or spongiosis or irritate the keratinocytes causing scale so most are caught by the red scaly mnemonic PMs PETAL



Melanocytes in the Epidermis

Melanocytes in the Epidermis can be as single cells in Superficial spreading melanoma  showing Pagetoid spread or as nests as in Spitz and Reed nevi or as single cells in neonatal congenital nevi, recurrent nevi and acral nevi.




Histiocytes in the Epidermis

These are really Langerhans cells. They occur in nests and cause a red scaly rash.



Epidermal invasion by other cells

Pagetoid spread of cells or nests in the Epidermis.

Pagetoid spread is the upward movement of atypical melanocytes into the upper spinous or sub granular layers of the epidermis and is seen in melanoma. However it is also seen in the centre of Spitz nevi, in Reed or spindled cell nevi and in some acral nevi where the lesions are benign. Some nevi of special sites will also show this phenomenon. Usually though these are single cells rather than nests but Spitz nevi do have nests high up in the epidermis.

Other tumours showing Pagetoid  spread.

Paget's disease of the nipple
Extramammary Pagets
Bowen's disease
Intra epidermal sebaceous carcinoma
Intraepidermal Merkel cell carcinoma




Rarely T cell lymphoma and histiocytosis will show pale cells in the epidermis in nests

To separate out these conditions you need to undertake immunofluorescence studies with specific cell marker antibodies.

Last thing to mention is the Borst- Jadassohn phenomenon

These are usually discrete clones of pale keratinocytes in the epidermis in irritated seborrheoic keratosis. However they can be malignant keratinocytes in Bowen's disease and rarely can also be seen in hidroacanthoma simplex, a form of eccrine poroma confined to the epidermis.


Thickened epidermis

Thickened Epidermis                       See DX Path for details of the conditions below

This usually results from keratinocyte hyperplasia and features acanthosis of the epidermis. Often there is associated hyperkeratosis.

Check it to see if there is any cytological atypia of the keratinocytes to indicate Bowen's disease.

 Otherwise a lot of chronic diseases eg Lichen simplex and Psoriasis will show a thickened epidermis but look out for some Deep fungal infections, TB of the skin and Reactive perforating collagenosis and the much rarer halogenodermas.





Thinned epidermis

Thinned Epidermis                           See DX Path for details of the conditions below

This suggests partial epidermal destruction as occurs in erythema mutiforme , graft versus host disease,  lupus erythematosus, dermatomyositis and in lichen sclerosus. It can also be a feature of Degos disease. Epidermal consumption can also be a feature of melanoma.

Radiation damage gives epidermal atrophy and it is a rare feature of Sezary syndrome and Mycosis fungoides.



The commonest cause of epidermal thinning is ageing and sun damage but remember the regional differences in the body with eyelid skin epidermis being particularly thin relative to other areas.

Thickened basement membrane

Thickened Basement Membrane                     See DX Path for details of the conditions below

An obviously thickened basement membrane has me thinking of lupus erythematosus. You do not usually see this feature in Dermatomyositis which is a common differential diagnosis. Also lupus tends to have a greater dermal inflammatory response than dermatomyositis. Rarely lichen sclerosus can show a thickened basement membrane.


Epidermis with atypical keratinocytes

Epidermis with Atypical Keratinocytes        See DX Path for details of the conditions below

Be certain they are atypical keratinocytes and not melanocytes , lymphocytes or Paget cells!
If primarily in the lower two thirds of the epidermis then we call these solar keratoses. If full thickness atypia we call these scc in situ.



You may need to do immunoperoxidase studies to determine the true nature of some of these other cells.

There can be clear cell change in keratinocytes due to glycogen in the cells. 

Some variants of Seborrhoeic keratoses can have large cells (large cell acanthoma) clear cells (Clear cell acanthoma) and Clonal seborrhoeic keratosis. Areas of Bowen's disease can occur within seborrhoeic keratoses.

Epidermolytic hyperkeratosis changes can also look atypical as are the changes of warts with koilocytosis.



Dyskeratotic cells

Dyskeratotic cells                        See DX Path for details of the conditions below

What is a dyskeratotic cell down the microscope? In the epidermis it is pink because of either early or abnormal keratinisation .Ocassionally a bit of a basophilic nucleus may persist. Unfortunately a variety of other terms are used in describing these cells in different conditions.

Dyskeratotic cells high up in the epidermis are a feature of Adult onset Still's disease. Multiple dyskeratotic cells scattered throughout an acanthotic epidermis is seen in incontinentia pigmenti

Kamino bodies - definitely basement membrane
Civatte bodies - dyskeratotic cells in the upper dermis
Colloid bodies - interface dermatitis, may be basement membrane and immunoglobulin
Cytoid bodies - same as colloid bodies
Corps ronds  and Grains  - acantholytic dyskeratotic cells seen in Dariers and other acantholytic disorders

Apoptotic, dyskeratotic and necrotic keratinocytes can all look the same!

You come across these terms most in Darier's disease, Lichen planus, Graft versus Host disease, Erythema multiforme,  PLEVA, Warty dyskeratoma, Spitz nevi (Kamino bodies) and Incontinentia pigmenti


Pale cells in the epidermis

Pale cells in the Epidermis              See DX Path for details of the conditions below




For me I think of Acrodermatitis enteropathica, Necrolytic migratory erythema, Necrolytic acral erythema, Pellagra and Epidermolytic hyperkeratosis.
Here the clear cells are usually in the upper third of the epidermis.



You can also get clear cell neoplasms where processing removes glycogen, mucin or lipid from the cells. eg Clear cell acanthoma and clear cell variants of other tumours or nevi.
Sebaceous gland tumours and metastatic renal tumours are also clear celled but the pale cells are in the dermis although some may appear to invade the epidermis in a pagetoid fashion.



Vacuolisation of keratinocytes can simulate pale cells but this usually occurs because of a processing artefact but remember papilloma virus causing this (koilocytosis around a shrunken raisin like nucleous in the upper spinous layer.)


Individual and nests of pale cells can be seen in the epidermis with the conditions causing Pagetoid spread.( Melanoma, Mammary and Extra mammary Pagets, Pagetoid reticulosis (T cell lymphoma) Bowen's disease, Sebaceous carcinoma and rarely Merkel cell carcinoma)




Check GlobalSkinAtlas for the Clinical images of these conditions

View the video of this topic

Epidermotropism

Epidermotropism and Exocytosis                See DX Path for details of the conditions below

Exocytosis refers to the migration of inflammatory cells into the epidermis whereas Epidermotropism refers to the migration of malignant cells into the epidermis.

Exocytosis occurs in inflammatory diseases such as Eczema and Psoriasis but also in Erythema multiforme and graft versus host disease. Sweet's syndrome is another condition showing exocytosis  but here the cells are neutrophils. Plasma cells can be seen in secondary syphilis. Eosinophils are prominent in the epidermis in bullous pemphigoid, allergic contact dermatitis, insect bite reactions, scabies, where they may form eosinophilic spongiosis.

Epidermotropism- We particularly think of epidermotropism and T cell lymphoma with atypical lymphocytes being found in the epidermis sometimes in nests as in Pautrier microabscesses. Histiocytoses can also be seen in the epidermis and the various conditions showing Pagetoid spread may sometimes also be exhibiting epidermotropism when the cell of oprigin is not a normal inhabitant of the epidermis.


Basal layer damage

Basal Layer Damage                              See DX Path for details of the conditions below

Marked basal layer damage is a feature of Erythema multiforme and its variants Stevens Johnson syndrome and Toxic epidermal necrolysis. We call this interface reaction pattern. It may also be seen to a lessor degree in lupus erythematosus and lichen planus and in the PLEVA variant of Pityriasis lichenoides.
Older terms for these changes were liquifactive degeneration and hydropic degeneration.




Lichenoid reaction pattern may overlap here but usually gives less vacuolar changes at the DEJ than interface damage and a more florid lichenoid infiltrate.



Pagetoid spread of cells or nests

Pagetoid spread of cells or nests in the Epidermis.  See DX Path for details of the conditions below

Pagetoid spread is the upward movement of atypical melanocytes into the upper spinous or sub granular layers of the epidermis and is seen in melanoma. However it is also seen in the centre of Spitz nevi, in Reed or spindled cell nevi and in some acral nevi where the lesions are benign. Some nevi of special sites will also show this phenomenon. Usually though these are single cells rather than nests but Spitz nevi do have nests high up in the epidermis.




Other tumours showing Pagetoid  spread.

Paget's disease of the nipple
Extramammary Pagets
Bowen's disease
Intra epidermal sebaceous carcinoma
Intraepidermal Merkel cell carcinoma




Rarely T cell lymphoma and histiocytosis will show pale cells in the epidermis in nests

To separate out these conditions you need to undertake immunoperoxidase studies with specific cell marker antibodies.

Pagetoid spread of cells or nests

Pagetoid spread of cells or nests in the Epidermis.

Pagetoid spread is the upward movement of atypical melanocytes into the upper spinous or sub granular layers of the epidermis and is seen in melanoma. However it is also seen in the centre of Spitz nevi, in Reed or spindled cell nevi and in some acral nevi where the lesions are benign. Some nevi of special sites will also show this phenomenon. Usually though these are single cells rather than nests but Spitz nevi do have nests high up in the epidermis.




Other tumours showing Pagetoid  spread.

Paget's disease of the nipple
Extramammary Pagets
Bowen's disease
Intra epidermal sebaceous carcinoma
Intraepidermal Merkel cell carcinoma




Rarely T cell lymphoma and histiocytosis will show pale cells in the epidermis in nests

To separate out these conditions you need to undertake immunoperoxidase studies with specific cell marker antibodies.

Follicular pathology

Follicular Pathology                          See DX Path for details of the conditions below

Big topic but put simply if a follicle ruptures you get surrounding granulomas.



Collections of neutrophils suggest a bacterial folliculitis.
Fungal folliculitis needs a PAS stain



Follicular plugging suggests lupus erythematosus or lichen sclerosus.

Clear cells in the follicular epithelium suggests follicular mucinosis.


Spread of melanocytes down a follicle suggests Lentigo maligna and if atypical keratinocytes then Bowen's disease is the likely diagnosis.
Occasionally unusual things such as Mollusca can be found in follicles.
Follicular variants of T cell lymphoma may also be seen.



Darier's disease and Pityriasis rubra pilaris are based around follicles

Follicular derived tumours are numerous and include Trichoepithelioma, Trichilemmoma, Pilomatricoma, Proliferating Trichilemmal cyst, Fibrofolliculoma, Trichodiscoma and Trichoblastoma.



Some of these tumours are associated with the Birt Hogg Dube syndrome and renal carcinomas.
Trichilemmoma is seen in Cowdens syndrome