dermatology - poliani

• Todays lesson includes the study of dermatitis inflammatory, and autoimmune dermatitis
• Core classification of Dermatopathology (inflammatory skin disease) is based on inflammation definitions and is a series of protective and regenerative responses of the body to insults
• There are three layers of defense against insults: the barrier, innate immunity, and acquired immunity
• The three layers of protection drive the most suitable response against infectious agents and external dangers
• Disorder of the specific layer of the host defense system of the skin can induce an inflammatory skin disease
• Diagnosis and pathology of inflammatory skin diseases are complicated and require an important correlation between the histological and the clinical finding
• Diagnosis includes both clinical and histological finding, for an integrated understanding
• Allergies and autoinflammatory disorders relate to diseases of both acquired and innate immunity, and autoimmune diseases

Inflammatory Skin Diseases: A Differential Diagnosis

• The question will be: which kind of dermatitis are we looking at?
• Clinicians can provide a range of diagnoses to select from; diagnostic power comes from an integrated study of symptoms and pathological findings
• Pathogenesis is usually infectious: bacterial, viral, or fungal infection. Can also be disorders such as traumas, irritants, or UV insults
• Diagnosis proceeds quickly if pathogenesis is known

Diagnosing and Treating Dermatitis

• Acquired immunity defects may result in immunodeficiency, so other causes should be considered for dermatitis
• Systemic and organ-specific immunodeficiencies may cause skin inflammation that relates to the autoimmune reaction with components of the skin layer, such as the epidermal-dermal junction.
• Acquired immunity relates to the acute process
• Innate immunity may result from general hyperactivity or hypersensitivity of the immune system
• Defects in the physical or chemical barrier may cause topic dermatitis, caused by overuse of topic drugs
• Organ-specific autoimmunity, localized on the skin or other specific diseases, may be considered if other causes are absent
• Graft versus host disease (GVHD) presents as a skin rash

Immune System and Clinical Features

• It is not meaningful to check the adaptive immunity because it is suspected in the clinical symptoms
• Pathologic findings may be useful based on where the symptoms occur (clinical features)

Basic Histological Patterns of Inflammatory Skin Disease

• Different entities may each be related with specific features and patterns
• Overlapping exists for the different entities; expect a mixture of different histological patterns

Common patterns encountered

• Perivascular dermatitis: perivascular inflammatory infiltrate without significant involvement of the epidermis, located in the papillary derma and the superficial layer of the derma
• Spongiotic dermatitis: inflammatory infiltrate associated with intracellular epidermal edema (spongiosis), same pattern as a perivascular dermatitis also associated with a spongiosis in the epidermal layer
• Psoriasiform dermatitis: inflammation that may be more intense, with acanthosis and epidermal thickening, as well as long epidermal rete ridges

Disease Prototypes

• Urticaria is a typical disease in the perivascular pathway
• Allergic contact dermatitis refers to the spongiotic pathway
• Psoriasis occurs in the psoriasiform dermatitis pathway

Additional Patterns

• Interface dermatitis: Characterized by cytotoxic inflammatory reaction with prominent changes in the lower epidermis, due to vacuolization of keratinocytes, and inflammation at the epidermal-dermal junction
• Vesiculo-bullous dermatitis: inflammatory reaction associated with intraepidermal or subepidermal cleavage, with bullae (epidermis detachment). Associated with autoimmune disorder, such as bullous pemphigoid
• Vasculitis: inflammatory reaction focused on the walls of cutaneous vessels. It is intensely inflammatory, but is perivascular, and displays an aggressive action against the vessel walls
• Folliculitis: refers to an inflammatory reaction directed against folliculo-sebaceous units, specific to the hair bulb; acne folliculitis is the most common manifestation
• Nodular dermatitis: inflammatory reaction with nodular/diffuse dermal infiltrate with absent epidermal changes; all cutaneous features of granuloma, granulomatous dermatitis pathway
• Panniculitis: inflammatory reaction involving the subcutaneous adipose tissue; the key prototype is erythema nodosum

Biopsies

• Choice of biopsy is based on clinical suspicion such as interface dermatitis. Use shave biopsy because it is superficial; if clinical suspicion is panniculitis then incisional biopsy is needed to view deeper
• Shave biopsy: used for interface dermatitis because it is superficial
• Incisional biopsy: used to look at panniculitis and to reach deeper surfaces
• Punch biopsy: used for other various patterns

Perivascular Dermatitis

• Frequently seen reaction pattern in dermatopathology
• Infiltration without significant epidermal involvement, epidermal layer not affected but dermis is inflamed, two types exist
  • Superficial: inflammation in the papillary dermis and superficial dermis, the prototype being urticaria
  • Superficial and deep: inflammation goes down to the reticular layer with connective tissue disease
• The perivascular action does not affect collagen fibers because lymphocytes and granulocytes come from the blood and into the skin, indicating it is acute or subacute, but also could be chronic
• Approximately 75% of urticaria cases have idiopathic etiology, though infections can be viral. Lymphocyte perivascular cuffing is specific to viral infections
• Collagen vascular disorders may be a cause, like lupus or autoinflammatory disorders
• Important entity is also IgE mediated allergies, or spontaneous and inducible hereditary angioedema
• Vessels contain perivascular infiltrates, mononuclear cells such as lymphocytes and RBCs
• A monolayer endothelial layer may be hypertrophic as a reactive change within the endothelial cells, including edema
• Higher magnification may indicate eosinophils with bright eosinophilic cytoplasm and granulocytes; other small cells (lymphocytes) also visible
• Presence of mononuclear cells and granulocytes within the vessel because they originate from blood

Advanced Stages of Perivascular Dermatitis

• Advanced pattern phases can be associated with interstitial infiltration of mononuclear cells, especially lymphocytes in between collagen fibers
• The biopsy location and the stage influence findings
• Superficial and deep dermal infiltrates occur in advanced stages, indicating a severe disease by presence of inflammation both in the dermis and in the deep dermal layer, affecting eccrine glands and other structures of the follicles. Overlapping features with other patterns may well happen
• The deep inflammation prototype is the Dermal hypersensitivity reaction, but clinical and histological features should be investigated because it is nonspecific
• Perivascular and interstitial infiltrates are involved, especially that of the superficial (papillary) plus mid and upper reticular dermis, indicating a more severe infiltration
• Lymphocytic infiltrate with eosinophils, with or without neutrophils, predominates. Granulocytes and neutrophils relate to secondary disease change and probably secondary infection
• Epidermal reactive alterations are: minimal parakeratosis, mild spongiosis, vacuolar interface changes, or secondary crust/excoriation

Spongiotic Dermatitis

• Inflammatory infiltrate associated with intercellular epidermal edema (spongiosis)
• Cell detachment and organization of microcystic changes
• Same pattern as a perivascular inflammation along with these features
• Prototype= atopic dermatitis
• Eczema= most frequently encountered alteration
• Differentiate spongiotic patterns into 3 entities based on time (mild): Subacute eczema (most common), irregular acanthosis and parakeratosis (nuclei in the superficial layer of the skin) among mild to moderate spongiosis in epidermal cell layer with focal spongiotic vesiculation, superficial dermal perivascular lymphohystiocytic infiltrate, endothelial cell swelling, edema
• Subacute eczema’s histological features: mild spongiosis, hyperkeratosis, papillary dermal infiltrate. Eczema is a clinical definition, and the pathological diagnosis is atopic dermatitis
• Acute eczema: There is more severe spongiosis may occur from intracellular edema, intercellular spaces widening, a squamos epithelium, intradermal micro vesicles and dermal edema with mixed infiltrates and histocytes
• Chronic eczema: has different features. The acanthotic changes may be more prominent. Psoriasiform pattern with severe hyperkeratosis, hypogranulosis and minimal parakeratosis may occur with fibrosis of the papillary dermis and secondary spongiosis
  • Neutrophilic crust, from secondary superficial bacteria layer infections can be found on abscesses
  • Spongiosis is prominent, as are Histiocytes

Psoriasiform Dermatitis

• Inflammatory infiltrate associated with epidermal thickening as a result of elongation of rete ridges
• Acanthosis, excoriation, and pustules may be present in the superficial layer
• Spikes of the rete ridges are inserted into the deep derma, with a severe presence of inflammatory components
• Psoriasis occurs commonly, which features demarcated erythematous plaques that have silvery white scales; its pathogenesis depends mostly with autoimmunity and hereditary
• Acanthosis, Lymphocitic perviascular inflammation, and hyper/hypograulosis can be found
• High presence of inflammation is found on deep derma, which consitis of Lymphocitic infiltrate

Interface Dermatitis

• -Characterized by Cytotoxic inflammatory reaction, with lower levels of keratinocytes, as well as cytotoxic and inflammation for reactive basal/low cells
• Cytotoxic inflammatory reaction for Keratinocytes

Lichenoid & Diagnostic

• It needs clinical correlation to perform diagnosis, if erythemia is linked = correct the diagnosis

Vesiculobollis Dermatitis

• Presents as an inflammatory reaction related with separation and creation of (bladder)

Vasculitis

• Inflammtory occurs near vessel areas, along woth cellular levels as well, because it has the cellular
• Clinical and immunflorescense are used for direct diagnosis
• Small cutaneious vasculitis: affects arteries, or cappilarie, usually present on a mid superficial level
• Mediaut cutaneious: involves small ateries
• Classical sign is leuko, which has a lot of alterations to the wall of the vessels

Folliculitis (Infectious vs Non)

• Inflammatory occurs on on either bacterial of fugali
• Acne, rosacea/ supresssative and induced versions are Non infectious, which relate to granulatosis and acne conglobate

Nodular Dermatitis

• Relates to Granuoma with inflammtory diffuse action with absent eperdermal chanegs
• Dermal reaction
• Sarcoidosis

Panniculitis

Composed if inflammatory reaction, on a more adipose tissue, this is a sign of agression. It can then be distingushed by

• Lobo-inflamaion involving fat and luboles
  • Its a diverse amount associated to other diseases in an infection/ inflammtion
  • germ center w lilphoid in infultrate
• Spetal Panniculitis: infalmtion is involved and is a symptom of lobulse.

Bacterial/Fungal/Viral Infections

• Bacterial Infection : Commonly comes iwth netrophills can create absyssess, along w/ granulocyte
  • Impetrigo: is a form of positive cocvi which causes infection
  • staphylo scalad syndrome : causes infecftillitration and a spread of the epidermis form toxicity can be used from slides
  • Rhinoscleoma; if inflammation exists it will underly the submucsa, it trigger is klebsilla
  • Erhtracsa; is triggered by patches/erhyhtmus, the trigger is corynebacteria

Viral Infection: is composted of inflammatory cells that can drive change - Herples Virus: its a surface infection, composed of inflammatory cells that drive different changes. One of the changes will be a spongiotic change. It presents multinucleated keratinocytes with chromatin margination and molding, mucosal sites (HSV1 / 2) or dermatome distribution (varicella zoster virus). - Epstein-Barr virus (EBV): Infectious mononucleosis, oral hairy leukoplakia

• EB virus: inctuous mono can be detected by hybnization Fungal Infection: Can range in difficlty or is not severe depending if fungal formation

ARTHROPODS and PARASITES

arthropod - parasite infections; Demoded: - incidental infection - it can relate to immunodeficiency. Scabies: are 8 legged - they invest layer of the skin, and intense itchiness.

Neoplastic Dermatopathology

• The WHO classification of tumors is the reference for neoplastic pathology of all organs.
• The WHO classification of skin tumors includes many entities such as epidermal and melanocytic tumors.
• Soft tissue tumors and lymphoid and hematopoietic tumors are rarer entities.
• The most recent tumor classification dates to 2018.
• Epidermal tumors arise in the epidermal cell layer and are epithelial tumors.
• Precursor lesions are benign entities often related to subsequent disease progression

Actinic Keratosis

• A common neoplastic intraepidermal proliferation.
• A squamous proliferative lesion associated with ultraviolet light exposure.
• Actinic keratosis is a precursor lesion, where this kind of insult will be related to dysplasia.
• Dysplasia grades range in severity.
• Progression to neoplasia occurs in epithelial cell layers with unique features.
• Located in the basal epidermal layer, atypical cells lose polarization and proliferate.
• Atypia may be present.
• Damage is confined to the basal cell layer without atypia in higher levels.
• Variants include hyperplastic, hypertrophic, atrophic, acantholytic, pigmented, proliferative, and pagetoid
• Histological features relate to these variants.
• Pagetoid refers to linear diffusion along the basal epidermal layer.
• Pigmented refers to lesions with melanin.
• Actinic keratoses are benign lesions and precursor lesions
• Histologically and clinically, they appear as poorly circumscribed erythematous lesions.
• Dermoscopically, actinic keratosis has a strawberry pattern.
• Basal atypia, including irregularly distributed cells leads to crowding of the lesion.
• Lymphocytic infiltrate and dermis elastosis are ancillary histological features.
• Elastosis in the dermis occurs due to UV and solar radiation exposure.
• Severe inflammation may occur in the dermis, though is usually confined to superficial dermis.
• Flattened epidermis and larger basal layer nuclei occur.
• The pagetoid variant exhibits aggregates of cells diffusing linearly along the epidermal cell layer.
• Acanthotic or microcystic features may be present.
• Upregulation and overexpression of p53 occurs in actinic keratosis, which is detectable by staining for p53.
• p53 mutations are a driver mutation in squamous cell carcinoma, so its expression is a warning sign of high-grade dysplasia and potential progression to squamous cell carcinoma.
• Toxic arsenical keratosis appears as lesions on the hands
• Hyperkeratotic cutaneous lesions are related to ultraviolet treatment.
• Mild to moderate dysplasia is typical.
• The final endpoint can be squamous cell carcinoma in situ, also called Bowen disease.

Squamous Cell Carcinoma In Situ (Bowen Disease)

• A malignant tumor confined within the epidermal cell layer.
• Full thickness keratinocytes atypia is the most important difference from actinic lesions.
• Atypia extends from the basal layer to superficial cell layers.
• Atypical cells occur across the epidermal cell layer.
• Main differential diagnosis includes severe dysplasia versus carcinoma
• Carcinoma cells are more atypical, with atypical mitotic figures, which are not present in benign lesions.
• Epidermal cell layer maturation ceases, but hyperkeratosis and parakeratosis may be present.
• Nuclei are very hyperchromatic.
• Features relate to malignancy and presence of in-situ carcinoma.
• Severe typical cells and inflammation are visible in biopsy and ulceration can begin.
• Diagnosing requires anamnesis, including previous UV exposure, and is a histological definition.
• The tumor is confined in the epidermal cell layer.
• Hyperproliferative hyperplasia may occur in the epidermal cell layer.
• Severe atypia occurs in the lower part plus parakeratotic features.
• Ulceration of granulocytes and secondary infection of the lesion surface is possible.
• Lichenoid distribution of inflammatory cells is a typical reaction of the immune system trying to confine neoplastic proliferation.

Verruca Vulgaris

• A benign lesion related to papilloma virus infection.
• HPV-induced benign epidermal squamous proliferation.
• HPV1, 2, 4, and 7 are frequent viruses, while HPV16 is rarely detected in the skin, which is the one encountered in gynecological lesions ,has oncogenic potential.
• Koilocytes are typical features of cells infected by the virus.
• Keratotic nodules are present on the scalp.
• Hyperkeratotic features increase the thickness of the epidermal cell layer.
• Papillomatosis is typical Histological samples may have secondary features like inflammation.

Seborrheic Keratosis

• Common in older people typically after 60-70 years of age.
• An epidermal proliferation with acanthotic and keratotic features.
• Acanthosis is a main histological feature.
• Variants include adenoid seborrheic keratosis, which presents with a cribriform feature.
• Diagnosing is easy based on histological characteristics.
• An intraepithelial neoplastic proliferation confined within the epidermal cell layer.
• Lesions are usually sharply circumscribed with elevated seborrheic keratosis.
• Papillomatous features are evident.
• Mutations such as GFR3 and PIT3CA may occur, but are not related to disease progression, instead being self-limited and benign.
• Cells possess mild atypical features, nuclei are not prominent and borders are regular.

Other Benign Keratosis

• Lesions are characterized by acanthotic change.
• Includes solar lentigo, lichen planus-like keratosis, clear cell acanthoma, large cell acanthoma, and warty dyskeratoma.
• Solar lentigo presents as hyperpigmentation of the basal layer where keratinocytes pick up melanin.
• Inflammation may or may not be present.
• Lichen Planus-like keratosis- inflammation occurs along the epidermal and dermal junction where distribution of inflammatory cells on the most superficial papillary dermal layer.

Acanthoma

• It is frequently found
• It resembles keratocytes of basal proliferation
• Main diagnosis of differential will come from acell carciinoma.
• Main difference is we will not see major atypia will be regularly cells w/ a Hyperkertatotic layer + Acanthosis.

Malignant Epidermal Proliferation

• Has 3 main classes of epithelial prolifereation
  • BCC BASAL cell cars
  • Squamous cellCars
  • Merkel Cell Carcinomas
    • very rare and agressieve for these three.

Basal Cell Carcioma

• A Malignant cells Local proliferation w/o meta statis
• Squamous Aggresive/ w meta. Basal-epidermis and the intrafollicial is from the basil layer of the epithelium. Its a common malignent tumor mostly with elderly. Usually comes w syndromes like gorvin and others , has multiple BCC w/ Tumors.

Diagnostic staining

• We start with p63 in squam, P53 a driver.

Variants

• Nodular SCC common
• superface.

Squamous Cell Carcioma

• It’s a malignant tumor, meta possible, mortality possible.
• Tight related UV exposure.
• Arose with Epithelial cell and then goes down to the dermis , infiltration takes places.
• Grade I = Low different.
• HI grade Tumors don’t have maturity
• Sarcamoit has aggresisve behavior
• If tumor is Cyotkereatin this helps Dtermitne the orgingin.
• Prollfertion/ Keratinization, the cells that show this prolifreation are less, the immune system could be fighting.
• Grade 1 well differentt Gradde 2 meddium different. Grade 3 underdiff
• Cyokeratin possitve Especially Ctyokreatin 5.6. and aE1 aE2

Merkel Cell Carcioma MCC

• It’s a tumor NE features, of the skin
• May ormaynot come from polyvirus/ we subclassify the tumor based on virus infection.
• A NE CARCINOMA, aggresive mostly oldies/ immuno supressed.
• They might MIMIC benign / malgent lesions, biopsy.
• Hisotlogical: Small - Med cell, proliferation, to stablish, we IHC/ NE tumor we have cystoker /Synaphtysin; to detect Polyoma.
• Higgh rate metasti, hard to distinct if primer or metstatic .

Pegimtented lesions / melanoma

They all come with benign/meg lesions. Important we do Histlogy and Patholo.