FRCPath Part 1 Dermatopathology Dr Ruth Green Consultant Dermatopathologist Salford Royal Hospital
Single best answer (SBA) questions – Stem – Lead in – Option list
Extended matching questions (EMQ) – 5 sub-question
Questions each have a theme (i.e. speciality) and a focus (e.g. macroscopy, cut up, governance) Likely skin will be a few SBA questions and 1 or 2 EMQs Certain topics keep coming up – Immunobullous disorders – Lichenoid conditions
Useful resources – Robbins or similar – Weedon – McKee – RCPath pathway documents – DermnetNZ – St Johns institute website
Inflammatory Dermatoses
A. Tissue reaction patterns – Spongiotic – Psoriasiform – Lichenoid – Vasculopathic – Granulomatous – Vesiculobullous
B. Patterns of inflammation
Spongiotic reaction
Eczematous dermatitis - Early/’typical’ lesions: spongiosis and lymphocyte exocytosis - Overlying parakeratin, acanthosis - Late lesions: psoriasiform hyperplasia - Always perform a fungal stain for dermatophyte infection
Eosinophilic spongiosis (eosinophils in the epidermis with spongiosis) – Drug reaction – Allergic/contact dermatitis – Insect bite reaction – Pre-bullous bullous pemphigoid
Langerhan cell vesicles – allergic/contact Underlying vascular changes – stasis dermatitis
MCQ 1 33 year old male printer complained of a 3 month history of hand dermatitis. Patch testing was negative. A biopsy showed spongiosis and lymphocyte exocytosis. No Munro’s microabcesses are seen. Identify the most likely diagnosis. A. Prebullous pemiphigoid B. Psoriasis vulgaris C. Irritant/contact eczematous dermatitis D. Mycosis fungoides E. Drug reaction
Answer
C
Psoriasiform reaction
Psoriasiform reaction Regular elongation and broadening of rete
Psoriasis Lichen simplex chronicus Pityriasis rubra pilaris Psoriasiform changes in eczematous dermatitis
Psoriasis Chronic non-infectious inflammatory dermatosis Well demarcated erythematous plaques topped with silvery scales Two peaks 2nd to 3rd and 6th decades FH; HLA Cw6, B13 and B17 Precipitating factors include: Koebner phenomenon, Infection, Drugs, Sunlight, Psychological stress Variants: Plaque, Palmoplantar, Scalp, Guttate, Flexural, Nail
Early – Vascular proliferation in dermal papillae – Slight spongiosis
Established lesions – Regular acanthosis with regular elongation of rete ridges – Thinning of supra-papillary epidermal plate – Parakeratosis – increased mitotic activity at the base – Reduced/absent granular cell layer – Neutrophil pustules
MCQ 2a Which statement is false. Psoriasis: a. Can result in alopecia b. Sacrum affected c. Pustular form exists d. Histologically shows spongiform pustule of Kogoj e. Vascular ectasia is seen with margination of neutrophils
Answer
A
MCQ 2b
a. b. c. d. e.
A 34 year old patient presents with multiple silvery skin plaques. A skin biopsy is performed to confirm the diagnosis. Identify the finding which would not be consistent with a diagnosis of psoriasis. Can result in alopecia Sacrum affected Pustular form exists Histologically shows spongiform pustule of Kogoj Vascular ectasia is seen with margination of neutrophils
MCQ 2c
a. b. c. d. e.
A 34 year old patient presents with multiple silvery skin plaques involving the extensor surface of the limbs, scalp and lower back. The condition is worse after periods of stress and localises to areas of trauma. A skin biopsy is performed to confirm the diagnosis. Identify the finding which would not be expected in this condition. Can result in alopecia Sacrum affected Pustular form exists Histologically shows spongiform pustule of Kogoj Vascular ectasia is seen with margination of neutrophils
MCQ 2d
a. b. c. d. e.
A 34 year old patient presents with multiple silvery skin plaques involving the extensor surface of the limbs, scalp and lower back. The condition is worse after periods of stress and localises to areas of trauma. A skin biopsy is performed to confirm the diagnosis. Identify the finding which would not be expected in this condition. Fibrous replacement of hair follicles Parakeratosis Neutrophilic pustules in the epidermis Vascular ectasia is seen with margination of neutrophils Loss of the granular cell layer
Pityriasis rubrapilaris (PRP) Red-orange well demarcated scaling patches Islands of sparing Can present with erythoderma ‘Alternating orthokeratin and parakeratin’ in a checkerboard pattern Psoriasiform hyperplasia
Lichen simplex chronicus/nodular prurigo Dermatosis related to chronic excoriation without an underlying aetiology Common in practice but a difficult exam question to write Many biopsies show an element of this with other clues to underlying cause
Syphilis Secondary syphilis – Shows a widespread hyperpigmented maculopapular eruption. – Typical copper penny macules with surrounding annular scale (Biette’s collarette) Marked hyperkeratosis and parakeratosis. Epidermis shows psoriasiform hyperplasia. A dense inflammatory cell infiltrate (plasmacytic) in the dermis. Can look like anything (with plasma cells)…..
Lichenoid reaction
Lichenoid reaction Lichen planus Lichenoid keratosis Lichen nitidus Erythema multiforme/Stephen Johnson syndrome/toxic epidermal necrosis - Lupus erythematosus - Graft versus host disease - Lichen sclerosus -
Interface change – Basal cell vacuolation – Apoptotic cells – Pigment incontinence
Band like lymphocytic infiltrate obscuring the dermo-epidermal junction = associated lichenoid inflammation
Lichen Planus Violaceous, flat-topped papules, which are usually pruritic Flexor surfaces of wrists, trunk, thighs, and genitalia Histopathology Typical lichenoid features No parakeratosis ‘Saw tooth’ acanthosis Wedge shaped hypergranulosis
Lichen planus – like keratosis (lichenoid keratosis) Solitary discrete slightly raised lesions Arms and presternal area of middle aged and elderly women Clinically diff. diagnosis: BCC ? Bowen’s Histopathology Lichenoid reaction Thought to be an inflamed/regressing seborrheic keratosis
Lichen nitidus Rare, chronic eruption, multiple small flesh coloured papules Upper extremities, chest, abdomen and genitalia of children and young adults Histopathology Dense, well circumscribed sub-epidermal infiltrate, sharply limited to one or two adjacent dermal papillae. Claw-like acanthotic rete ridges, which appear to grasp the infiltrate
Erythema multiforme spectrum Erythema multiforme: Targetoid lesions central blister surrounded by an outer erythematous border Stevens–Johnson syndrome: mucosal involvement with <30% skin involved Toxic epidermal necrolysis: >30% skin involvement
Erythema multiforme spectrum Causes: idiopathic, viral, bacterial, fungal, drugs (antibiotics, NSAIDs), other Oral, conjunctival, genital lesions not uncommon Interface change >lichenoid infammation
MCQ 3 A 44 year old taxi-driver presents with an sudden eruption on the trunk and limbs. Target lesions are present on the hands and feet. His skin biopsy shows basal cell damage with apoptotic keratinocytes. Identify the most likely diagnosis. a. Lichen planus b. Dermatomyositis c. Erythema multiforme d. Chronic graft versus host disease e. Lichen nitidus
Answer
C
Toxic epidermal necrolysis Sub-epidermal blisters with necrotic overlying epidermis Medical emergency Treated as a burns patient Main clinical differential – staphylococcal scalded skin
Lupus erythematosus Clinically: Sharply demarcated erythematous, scaly patches with follicular plugging. Characterised by 1. Interface change +/- lichenoid reaction 2. Superficial and deep perivascular and periadnexal chronic inflammatory cell infiltrate. 3. Hyperkeratosis, follicular plugging and epidermal atrophy. 4. Thickening of basement membrane 5. Increased dermal mucin
Graft versus host disease Usually a clinical diagnosis Following transplantation the donor's immune cells in the transplant (graft) make antibodies against the patient's tissues (host). Organs most often affected include the skin, gastrointestinal (GI) tract and the liver.
Interface dermatosis DD – Erythema multiforme – Dermatomyositis – Lupus erythematosus
Lichen sclerosus Pale atrophic patches Clinical DD often morphoea Lichenoid reaction (often subtle) Homogenisation of dermal collagen Thickening of basement membrane Ectatic vessels Underlying inflammatory infiltrate – often contains eosinophils
Vasculopathic conditions Vasculopathic just means it involves the blood vessels. Conditions include: – Inflammation of vessels – vasculitis. – Changes in the walls – porphyria, amyloid. – Something in the lumen – thrombosis. – More widespread changes – stasis dermatitis, arteriopathic changes.
Leukocytoclastic vasculitis Intramural neutrophils Red blood cell extravasation Fibrinoid necrosis Leukocytoclasis
• Leukocytoclastic vasculitis – “Tissue reaction pattern which can be idiopathic or have underlying associations including drugs, connective tissue disease, infection and systemic vasculitis”
Polyarteritis nodosa (PAN) Necrotising vasculitis of medium sized vessels Uncommon Tender nodules May develop hypertension, renal failure and neuropathy
Polyarteritis nodosa versus Microscopic polyangiitis (MPA) Polyarteritis nodosa – Cutaneous lesions more common
Microscopic polyangiitis – Not associated with glomerulonephritis – ANCA positive
Wegener’s granulomatosis/Granulomatosis with polyangiitis Multiple purpuric macules and papules – Possible to have ulcerating plaques and nodules. Histology – Leukocytoclastic vasculitis. – May see ill-defined granulomatous infiltrate surrounding vessels. c-ANCA positive Respiratory tract (nasal and lung) biopsies show necrosis associated with a granulomatous infiltrate
MCQ 4a Which of the following conditions does not show a leukocytoclastic vasculitis? A. Erythema nodosum B. Microscopic polyangiitis C. Wegeners granulomatosis D. Polyarteritis nodosa E. Urticarial vasculitis
Answer
A
MCQ 4b A 42 year old patient presents with purpuric lesions involving both limbs. Inflammatory markers are raised. A skin biopsy is taken and shows features of a leukocytoclastic vasculitis. Identify the condition which does not show this feature. A. Erythema nodosum B. Eosinophilic granulomatosis with polyangiitis C. Granulomatosis with polyangiitis D. Polyarteritis nodosa E. Urticarial vasculitis
MCQ 4c A 42 year old patient presents with purpuric lesions involving both limbs. Inflammatory markers are raised. A skin biopsy is taken and shows fibrinoid necrosis of vessel walls with leukocytoclasis and red blood cell extravasation. Identify the condition which would not show these features. A. Erythema nodosum B. Eosinophilic granulomatosis with polyangiitis C. Granulomatosis with polyangiitis D. Polyarteritis nodosa E. Urticarial vasculitis
MCQ 4d A 42 year old patient presents with purpuric lesions involving both limbs. Inflammatory markers are raised. A skin biopsy is taken and shows fibrinoid necrosis of vessel walls with leukocytoclasis and red blood cell extravasation. Identify the most likely diagnosis. A. Erythema nodosum B. Eczematous dermatitis C. Epidermolysis bullosa acquista D. Erythema multiforme E. Polyarteritis nodosa
Granulomatous inflammation/reaction
Types of granulomatous inflammation - Sarcoidal - Foreign body - Suppurative - Tuberculoid - Necrobiotic - “Interstitial”
Differential always includes infection in all patterns of granulomatous inflammation
Sarcoidal granulomas – Sarcoidosis – Reaction to foreign materials – Secondary Syphilis – Infection – Crohn’s disease
Sarcoidosis Multisystem disorder Skin, liver, spleen, lung, eyes, lymph nodes 10-35% patients with systemic sarcoid have cutaneous lesions
Sarcoidal granulomas are composed of epithelioid cells and giant cells, some containing asteroid bodies or other inclusions.
Foreign Body Granulomas Seen every day – Scar/re-excision specimens – Ruptured epidermoid cysts/follicles
Suppurative Granulomas Neutrophils within and sometimes surrounding the granuloma. The granulomatous component is not always well defined. Infection needs to be excluded – special stains don’t necessarily do this.
- Blastomycosis - Blastomycosis-like pyoderma - Botryomycosis - Mycetoma – Chromomycosis – Phaeohyphomycosis – Sporotrichosis
- Non-tuberculous mycobacterial - Tuberculoid mycobacterial - Nocardiasis - Actinomycosis - Lymphogranuloma venereum - Ruptured cysts and follicles
Fungi/yeasts Coccidioides
Histoplasma
Cryptococcus
Mucormycosis
Blastomycosis
Candida
Tuberculoid granulomas Tuberculoid granulomas resemble those of tuberculosis Caseation not always seen Langerhans giant cells often present
Tuberculosis Primary tuberculosis Miliary tuberculosis of skin Lupus vulgaris Scrofuloderma Tuberculous gumma Tuberculosis cutis orificialis Papulonecrotic tuberculid
Necrobiotic granulomas Palisading of histiocytes around degenerate collagen
Necrobiotic Granulomas Granuloma Annulare – palpable annular lesions on hands, feet or face Necrobiosis lipoidica – shiny atrophic yellowish red plaques on shins (62% in diabetics) Rheumatoid nodule - a local swelling or tissue lump, over bony prominences which occurs almost exclusively in association with rheumatoid arthritis
Granuloma annulare – Superficial/mid dermis – Often intersitial (‘incomplete’) – No plasma cells – Eosinophils – Mucin stain
Necrobiosis lipoidica – Diabetes – Mid to deep dermis – Linear pattern – Plasma cells
Rheumatoid nodules – History – Over joints – Deep dermis to subcutis – Palisading of histiocytes around eosinophilic material – Fibrin/Trichrome stain
Granuloma annulare
Rheumatoid nodule
MCQ 5a Which of the following conditions is not associated with granulomatous inflammation. A. Sarcoidosis B. Granuloma annulare C. Pemphigus vulgaris D. Fungal infection E. Tuberculosis
Answer
C
MCQ 5b A 58 year year old woman presents with itchy annular skin lesions. She has a history of Crohn’s disease for which she is on systemic therapy. A skin biopsy show aggregates of histiocytes. A Grocott silver stain is positive. Identify the most likely diagnosis. A. Sarcoidosis B. Granuloma annulare C. Necrobiosis lipoidica D. Fungal infection E. Metastatic Crohn’s disease
MCQ 5c A 59 year old lady presents with annular lesions over the dorsal surfaces of both hands. A biopsy shows an interstitial infiltrate of histiocytes with mucin deposition and focal necrobioisis. No plasma cells are seen. Identify the most likely diagnosis Necrobiosis lipoidica Sarcoidosis Granuloma annulare Fungal infection Rheumatoid nodules
Approach to bullous disorders 1. Anatomical level of split 2. Mechanism responsible 3. Nature of inflammatory cell infiltrate
Anatomical Level of Split Intracorneal/ subcorneal Intraepidermal (within stratum spinosum) Suprabasal Sub-epidermal Correlates with clinical type of blister
Mechanism responsible Cytopathic Spongiotic Autoimmune - immunobullous Vasculitic Trauma
Intracorneal/ Subcorneal Subcorneal – Impetigo – Dermatophytosis – Staphylococcal scalded skin – Superficial variants of pemphigus
Intraepidermal Intraepidermal – – – –
Herpes Infection Spongiotic blistering disease Friction blister Acantholytic disorders
Suprabasal Acantholytic
Differential Diagnosis Suprabasal – Pemphigus vulgaris
Suprabasal/intraepidermal – Hailey-Hailey – Darier’s Disease – Grover’s Disease (transient acantholytic dermatosis) – Acantholytic actinic keratosis – Paraneoplastic pemphigus
Acantholytic disorders Loss of cell-to-cell adhesion in epidermis Immune mediated Blisters tend to be fragile as suprabasal or above Immunofluoresence helps distinguish the pemphigus variants from other conditions
Differential Diagnosis – Pemphigus Vulgaris – Hailey-Hailey
• • • • • •
– Darier’s Disease
• • •
Acantholysis Intracellular IgG and C3c on IMF Mucosal involvement
Acantholysis Autosomal dominant, flexural Dilapidated brick wall/intraepidermal Spares adnexal epithelium Negative IMF ATP2C1 gene
• • • • • •
Acantholysis Autosomal dominant, sebaceous areas Suprabasal and intraepidermal Dyskeratotic cells = corps ronds and grains Involves adnexal epithelium Negative IMF
Differential Diagnosis – Grover’s Disease (transient acantholytic • Acantholysis dermatosis) • Itchy papules trunk • • •
Can show similar findings to HH, Dariers or PV) Negative IMF Multiple tissue reaction patterns now recognised
– Acantholytic actinic keratosis •
Epidermal dysplasia
– Paraneoplastic pemphigus • • •
Blistering Acantholytic Both intercellular and linear (BMZ) IgG and C3c on IMF
Subepidermal Immunobullous – Bullous pemphigoid – Dermatitis herpetiformis – Epidermolysis bullosa – Linear IgA ( = Chronic bullous disease of childhood) Traumatic Vasculitis Lichenoid/interface dermatoses Bullous diabeticorum Bullous amyloidosis
Bullous pemphigoid Large often tense blisters with a predilection for trunk and flexural extremities Subepidermal blister with eosinophils ‘Eosinophilic spongiosis’ Diagnosis can be confirmed by immunofluorescence.
Linear IgG and C3c along BMZ – Bullous pemphigoid – Epidermolysis bullosa acquista – Pemphigoid gestationalis – Paraneoplastic pemphigus (+chicken wire pattern of intercellular deposition)
Dermatitis herpetiformis Young adults Intense pruritic vesicles with excoriation Predilection for extensor surfaces Invariably associated with gluten enteropathy although often subclinical
Sub-epidermal neutrophil-rich blister Dermal neutrophil-rich infiltrate with leukocytoclasis Neutrophil micro-abscess in adjacent dermal papillae Granular IgA in the tips of the dermal papillae on direct immunofluorescence. Vesiculo-bullous eruption of hepatobiliary disease may also present with dermatitis herpetiformis-like features
Linear IgA disease (and chronic bullous disease of childhood) show similar morphology Older individuals – present with blisters Distinguish by immunofluoresence
MCQ 6 A 68 year old female has a 1/52 history of tense large blisters arising on erythematous skin. A skin biopsy shows a subepidermal blister containing eosinophils. Identify the most likely diagnosis. A.Pemphigus vulgaris B.Pemphigus foliaceus C.Darier’s disease D.Bullous pemphigoid E.Grover’ Disease
Answer
D
Cell poor subepidermal blisters – Bullous pemphigoid – Porphyria cutea tarda – Burns – Toxic epidermal necrolysis – Suction blister – Drugs – Bullous amyloid – Bullous diabeticorum
Porphyria cutea tarda Increasingly fragile skin hands and feet Fluid filled blisters (vesicles and bullae) Tiny cysts (milia) arising as the blisters heal Increased sensitivity to the sun
Cell poor subepidermal blister Deposition of basement membrane material in epidermis – ‘caterpillar bodies’ Thickening and increased eosinophilic in dermal vessels – PAS and DPAS
A. Tissue reaction patterns – Spongiotic – Psoriasiform – Lichenoid – Vasculopathic – Granulomatous – Vesiculobullous
B. Patterns of inflammation
TUMOURS OF THE SKIN
Primary v metastasis Epithelial – Squamous – Adnexal- follicles, eccrine/apocrine glands, sebaceous glands
Melanocytic Dermal – Mesenchymal
Deep soft tissue Benign v malignant
Primary v metastasis Epithelial – Squamous – Adnexal- follicles, eccrine/apocrine glands, sebaceous glands
Melanocytic Dermal – Mesenchymal
Deep soft tissue Benign v malignant
Adnexal neoplasms
Tumours with differentiation towards hair structures Trichofolliculoma Trichilemmoma Trichoepithelioma Desmoplastic trichoepithelioma Pilomatricoma Proliferating trichilemmal cyst Basal cell carcinoma
Trichilemmoma Benign neoplasm with differentiation toward pilosebaceous follicular epithelium. Association with Cowden disease Asymptomatic papules on face Epidermal proliferation Clear cells (PAS positive) Thickened basement membrane CD34 positive
Trichoepithelioma Well circumscribed superficial tumour Composed of basaloid islands with peripheral palisading Lack high grade atypia, mitoses and retraction artifact Keratinisation is abrupt and complete – ‘trichilemmal keratinisiation’ Papillary mesenchymal bodies Multiple associated with Brooke-Spiegler syndrome
Pilomatricoma Also known as calcifying epithelioma of Malherbe Tumour with differentiation towards hair cells Solitary lesion on the face or upper extremities Rarely malignant transformation can occur
Tumours/lesions with sebaceous differentiation Naevus Sebaceous Sebaceous Hyperplasia Sebaceous Adenoma Sebaceoma Sebaceous Carcinoma
Sebaceous adenoma Can be sporadic or associated with the MuirTorre syndrome Sporadic located on the head and neck region. Those not on head and neck more commonly associated with Muir-Torre. A multilobulated tumour sharply demarcated from the surrounding tissue. Two types of cells: sebocytes and undifferentiated basaloid cells in the periphery
Sebaceoma
Muir-Torre syndrome Muir in 1967 and Torre in 1968 Sebaceous neoplasms – most commonly sebaceous adenoma Carcinomas of the endometrium, ovary, breast, parotid, upper GI tract and larynx, and haematological malignancies Autosomal dominant inherited germline mutation in one of the DNA mismatch repair genes, most commonly hMSH2. The male:female ratio is 3:2.
Sebaceous carcinoma Ocular & Extraocular. Sebaceous carcinoma is rarely associated with Muir-Torre syndrome than benign sebaceous neoplasms. Histology reveals irregular lobular growth pattern with atypical cells. The undifferentiated cells show eosinophilic cytoplasm with fine lipid globules.
Tumours with eccrine/apocrine differentiation Eccrine Hidrocystoma Syringoma Eccrine Poroma Porocarcinoma Spiradenoma Spiradenocarcinoma Chondroid Syringoma - Benign mixed tumour of the skin
Syringoma A benign adnexal tumour Common in patients with trisomy 13. Clear cell syringoma are commonly associated with diabetes mellitus. Multiple papules on the lower eyelids and cheeks of adolescent females Dermal tumours are composed of small ducts lined by two layers of cuboidal epithelium ; ducts have a comma-like tail ; solid nests and strands of basaloid cells may be present in the dermis.
Spiradenoma This lesion often coexists with cylindroma. Usually presents as a painful or tender solitary nodule (less than 1cm in diameter). Tumour consists of sharply demarcated lobules located in the dermis with pale and more basaloid cells. Eosinophilic PAS positive basement membrane-like material may be present around the lobules
Brooke-Spiegler syndrome – Autosomal dominant – Development of multiple cylindromas, trichoepitheliomas, and spiradenomas. – Cylindromatosis (CYLD) gene on chromosome 16q12 – Can get salivary (esp parotid) neoplasms
Cylindroma Apocrine and trichoepitheliomatous differentiation has been noted indicating complex hair follicle (folliculosebaceous-apocrine) rather than eccrine differentiation. Clinically a solitary, slow growing rubbery lesion. The multiple form is autosomal dominant inherited on CYLD1 gene on chromosome 16. Composed of numerous oval and polygonal nests arranged in an interlocking 'jigsaw-like' pattern.
Chondroid syringoma Cutaneous counterpart of mixed tumor ("pleomorphic adenoma") of salivary glands, therefore it is also termed 'mixed tumour of the skin’. Rarely recurs even if inadequately excised. Occurs mainly in the head and neck region and rarely in the distal extremities. Tumour consists of epithelial component set in a chondroid, myxoid and fibrous stroma with epithelial nests, islands, ducts and tubular structures.
Poroma Monomorphous proliferation of epithelial cells from the epidermis that show ductal differentiation.
Question EMQ 1 Options A. Trichoepithelioma B. Basal cell carcinoma C. Halo naevus D. Compound melanocytic naevus E. Intradermal melanocytic naevus F. Blue naevus G. Keratoacanthoma H. Lichen planus I. Malignant melanoma J. Trichilemmoma K. Seborrhoeic keratosis L. Simple lentigo M. Squamous cell carcinoma
Question 1 A 55 year old female present with a pigmented lesion on the hand. Histology shows naevus cells in the dermis with pigmented dendritic processes with overlying normal epidermis.
Each of these subjects has a skin biopsy. For each one, select the most likely condition form the list of options. Each may be use once, more than once, or not at all.
Question EMQ 1 Options A. Trichoepithelioma B. Basal cell carcinoma C. Halo naevus D. Compound melanocytic naevus E. Intradermal melanocytic naevus F. Blue naevus G. Keratoacanthoma H. Lichen planus I. Malignant melanoma J. Trichilemmoma K. Seborrhoeic keratosis L. Simple lentigo M. Squamous cell carcinoma
Question 2 A 35 year old man present with a pigmented lesion on the arm with an outer hypo-pigmented area. Biopsy shows a band of inflammatory cells at the dermo-epidermal junction with scattered bland nests of naevus cells.
Each of these subjects has a skin biopsy. For each one, select the most likely condition form the list of options. Each may be use once, more than once, or not at all.
Question EMQ 1 Options A. Trichoepithelioma B. Basal cell carcinoma C. Halo naevus D. Compound melanocytic naevus E. Intradermal melanocytic naevus F. Blue naevus G. Keratoacanthoma H. Lichen planus I. Malignant melanoma J. Trichilemmoma K. Seborrhoeic keratosis L. Simple lentigo M. Squamous cell carcinoma
Question 3 A 28 year old female with a papule on the nose. Histology shows islands of basaloid cells with occasional mitotic activity and papillary mesenchymal bodies.
Each of these subjects has a skin biopsy. For each one, select the most likely condition form the list of options. Each may be use once, more than once, or not at all.
Question EMQ 1 Options A. Trichoepithelioma B. Basal cell carcinoma C. Halo naevus D. Compound melanocytic naevus E. Intradermal melanocytic naevus F. Blue naevus G. Keratoacanthoma H. Lichen planus I. Malignant melanoma J. Trichillemmoma K. Seborrhoeic keratosis L. Simple lentigo M. Squamous cell carcinoma
Question 4 A 70 year old man presents with a ulcerated lesion on the face. Skin biopsy shows squamous islands in the dermis with atypia and dyskeratosis.
Each of these subjects has a skin biopsy. For each one, select the most likely condition form the list of options. Each may be use once, more than once, or not at all.
Question EMQ 1 Options A. Trichoepithelioma B. Basal cell carcinoma C. Halo naevus D. Compound melanocytic naevus E. Intradermal melanocytic naevus F. Blue naevus G. Keratoacanthoma H. Lichen planus I. Malignant melanoma J. Trichilemmoma K. Seborrhoeic keratosis L. Simple lentigo M. Squamous cell carcinoma
Question 5 A 68 year old man with multiple papules on the face. Histology shows epidermal proliferation with glycogenated keratinocytes, peripheral palisade and thickened basement membrane. No atypia or mitoses are seen.
Each of these subjects has a skin biopsy. For each one, select the most likely condition form the list of options. Each may be use once, more than once, or not at all.
Malignant epithelial entities
Squamous Cell Carcinoma May occur anywhere on the skin Sun damaged skin Site of Scar Venous Ulcers Burns
High risk sites – Ear – Lip – Perineum
Variants – Acantholytic – Verrucous – Follicular
MCQ 7a Predisposing factors for squamous cell carcinoma are all the following except: a. UVB exposure b. HPV Infection c. Immunosuppression d. Scarring e. HHV-8 Infection
Answer
E
MCQ 7b A 35 year old presents with an invasive poorly differentiated squamous cell carcinoma of the scalp. Identify the most likely aetiological factor. A- Solar damage/sun exposure B- Immunosuppression C- HHV8 infection D- Previous radiotherapy E- Idiopathic
Answer
B
MCQ 8 A 72 year old presents with a squamous cell carcinoma of the scalp. An excision biopsy is performed and reported as per the RCPath dataset. Identify which feature would upstage the tumour to pT3. A- Perineural invasion –subcutis nerves B- Location in head and neck C- Depth of invasion 5.5mm D- Clinical diameter >20mm E- Lymphovascular invasion
Answer
A
Keratoacanthoma Classic History Crateriform squamoproliferative lesion Epithelial Collarette Bulbous nested downgrowths with well defined borders Neutrophil microabscesses Abundant glassy cytoplasm
Differential Diagnoses Well Differentiated SCC Keratoacanthoma Inverted Follicular Keratosis Nodular prurigo Pseudoepitheliomatous Hyperplasia Verrucous carcinoma
Basal Cell Carcinoma Predisposing factors – Solar damage – Xeroderma pigmentosum – Nevoid BCC syndrome – Bazex syndrome – Burns
MCQ 9 A 72 year old presents with an ulcerating tumour of the scalp. He has had androgenetic alopecia for many years. A biopsy shows basaloid nests of atypical cells infiltrating the dermis. Identify the most likely predisposing factor in this case. A- Solar damage B- Immunosuppression C- Gorlins syndrome D- Xeroderma pigmentosum E- Underlying lichen planopilaris
Answer
A
Merkel cell carcinoma Primary cutaneous neuroendocrine carcinoma UV radiation Clonal integration of Merkel cell polyomavirus (MCPyV) x10 in HIV +ve x5-10 in solid organ recipients x40 in patients with chronic lymphocytic lymphoma
Positive for neuroendocrine markers (chromogranin, synaptophysin, CD56)
Main clinical difficulty: Is it primary skin tumour or metastasis? – Panel of immunohistochemistry – CK7 –ve, CK20 +ve, TTF1 -ve
?? CM2B4 immunohistochemistry as surrogate for MCPyV
Pigmented lesions inc melanocytic tumours
Derived from epidermal melanocytes Freckles Solar lentigines Melanotic macules of Albright’s syndrome Becker’s melanosis Café-au-lait patches of neurofibromatosis
Derived from dermal melanocytes Mongolian spot Naevi of Ota and Ito Blue naevus
Blue Naevi Three types – usually occur on the skin Common Blue Naevus Cellular Blue Naevus Combined Naevus
Common blue naevus Dorsum of hands and feet Slate blue nodule Melanocytes are of the same appearance as naevus of Ito/Ota but show much greater density Epidermis normal Melanocytes contain fine granules of melanin
Cellular blue naevus Usually larger than a common blue naevus (1-3 cms) 50% over the buttocks Histopathology – Areas similar to blue naevus admixed with more cellular islands composed of closely aggregated, rather larger spindle shaped cells with ovoid nuclei and abundant pale cytoplasm. – Extends into the superficial subcutis – May have atypical features
Special variants of melanocytic naevi
Halo Naevus Spitz naevus Pigmented spindle cell naevus of Reed BAPoma Deep penetrating naevus Dysplastic naevus
Halo Naevus Clinical appearance Nest of naevus cells in the papillary dermis associated with a lympho-histiocytic inflammatory cell infiltrate
Spitz naevus Children and young to early middle aged adults Solitary, lower limbs and face Histopathology – Small, symmetrical and well circumscribed – Usually compound – Epithelioid and spindled cells – Maturation can be hard to assess – Kamino bodies
Pigmented Spindle Cell Naevus of Reed ?Variant of Spitz naevus Young adults, lower extremities Spindle shaped cells in nests. Prominent vertical orientation of cells are noted. Heavily pigmented + melanophages. Junctional clefting is noted in some cases.
Differential diagnosis Includes melanoma Unlike melanoma these are symmetrical lesions and display maturation of cells in the deeper part of the lesion Pagetoid spread of cells is limited to the lower half of the epidermis
BAPoma = BAP-1 negative melanocytic tumour Relatively recently described melanocytic tumour Characterised by mutation in the BAP-1 gene (BRCAAssociated protein 1 on chromosome 3) Can occur sporadically or as part of a syndrome Typical morphological findings
Wiesner T, et al. Nat Genet. 2011;43(10):1018-21. Wiesner T, et al. Am J Surg Pathol. 2012;36(6):818-30
Familial cases: – Autosomal dominant – Patients with germline mutation in BAP-1 are at increased risk of cutaneous melanoma, uveal melanoma, mesothelioma and meningioma
Wiesner T, et al. Nat Genet. 2011;43(10):1018-21
Both sporadic and syndrome related cases have similar distinctive features Bland clinical lesion(s) – fleshy polypoidal tumour Histopathological features – Polypoidal – Limited junctional component – Mixed population of epithelioid ‘Spitzoid’ cells and bland naevoid cells – Characteristic features of Spitzoid lesions (e.g. Kamino bodies) absent – and typically BRAF positive – Multinucleate and floret cells – Lymphocytic infiltrate – Can show pleomorphism and atypia – “MELTUMP”
Images from BSD meeting presentation 2015, Virtual Pathology leeds.ac.uk
Deep penetrating naevus First described by Helwig et al and 1989 Dermal based melanocytic lesion composed of pigmented spindled and/or epithelioid cells with deep architecture Melanocytes maintain size and pigmentation throughout the dermis (i.e. don’t mature) Morphological overlap with conventional, blue and Spitz naevi If atypical features – melanocytoma Rarely progress to melanoma Significance Frequent simulation of melanoma Frequent uncertainty regarding malignant potential Rare metastatic progression
Fourchardiere et al, Nature Communications, 2017 8:644 /
Dysplastic Naevus Clinically and histologically form a continuum extending from common naevus to a superficial spreading melanoma Histopathology – Architectural atypia Lentiginous proliferation of melanocytes Bridging between adjacent rete ridges
– Lamellar fibroplasia – Cytological atypia – Shouldering of dermal component
Dysplastic Naevus Syndrome Familial or sporadic occurrence of multiple dysplastic naevi in an individual Originally called B-K Mole Syndrome and FAMMM syndrome
Malignant Melanoma Superficial Spreading Melanoma Lentigo Maligna Melanoma Acral Lentiginous Melanoma Nodular Melanoma Desmoplastic Melanomas Metastatic Melanoma
Useful Pointers to MM Ulceration Asymmetrical Lesion Architectural Atypia Pagetoid Spread Diffuse cytological atypia with prominent eosinophilic nucleolus Dermal Mitoses Lack of Maturation Regression Factor in age!
Melanoma associated with CSD – Superficial spreading melanoma – Lentigo maligna melanoma – Desmoplastic melanoma
Melanoma not associated with CSD – – – – – –
Spitzoid Acral Mucosal Uveal Melanoma arising in congenital naevi Melanoma arising within blue naevi
Nodular melanoma
Superficial spreading melanoma May develop in any part of the body and at any age. It is commonly noted on the trunk and lower extremities. Episodic skin damage – episodes of sun burn Histologically , the lesion is characterized by proliferation of atypical melanocytes at all levels in the epidermis. The tumour cells are present singly and in nests. Pagetoid spread in the epidermis (buckshot spread).
Lentigo Maligna In 1969, Clark and Mihm described LM Most frequently occurs on the sun-exposed face and upper extremities of elderly people (chronic sun exposure) Histologically, there is proliferation of atypical melanocytes singly and in nests along the basal layer of the epidermis.
Nodular melanoma 2nd most common subtype of melanoma. It represents 15% of all melanomas. The most common sites for nodular melanoma are the trunk, head, and neck. Macroscopically, the lesion presents as a nodular, polypoid or pedunculated dark brown or blue black lesion. May also present as an amelanotic nodule.
MCQ 10 All the following lesions are benign except A. Spitz naevus B. Lentigo maligna C. Cellular blue naevus D. Naevus of ota E. Freckles
Answer
B
MCQ 11 A 27 year old man presents with a pigmented lesion on the upper arm. An excision biopsy is performed. The lesion is compound in nature with prominent Pagetoid ascent in the epidermis and multiple dermal mitoses (3 per mm2). Identify the most important prognostic factor. A- Depth of invasion B- Macroscopic diameter C- Presence of dermal mitoses D- Pagetoid ascent E- Absence of tumour infiltrating lymphocytes
Answer
A
Acral lentiginous melanoma The most common type of malignant melanoma in skin type 3+ Peak incidence in the seventh decade for males and in the sixth decade for females. These lesions are usually located on palmar, plantar and subungual skin. Lentiginous and some nesting proliferation of atypical melanocytes. Perineural invasion not uncommon Genetic mutation in cKIT most common
MCQ 12 A 23 year old woman presents with a changing melanocytic lesion on the sole of the foot. An excision biopsy shows malignant melanoma. Identify the most likely genetic mutation. A- cKIT B- BRAF C- ALK D- k-RAS E- Tyrosine kinase
Answer
A
Breslow Thickness Most important prognostic factor Only for invasive lesions Measure from Granular cell layer If Ulcerated; base of ulcer
Clark’s Levels I – Insitu II – Papillary Dermis III – Border of Papillary with reticular dermis IV- Reticular dermis V - Subcutis
Microsatellite – Foci of metastatic tumour cells in the skin or subcutis adjacent or deep to but discontinuous from the primary tumour detected in microscopic examination of tissue Satellite metastasis – Foci of clinically evident cutaneous and/or subcutaneous metastasis occurring within 2cm of but discontinuous from the primary melanoma
In-transit metastasis – Clinically evident cutaneous and/or subcutaneous metastasis occurring >2cm from the primary melanoma in the region between the primary and the regional lymph node basin Any cutaneous metastasis that does not fall into the above categories is considered distant metastasis and staged under the M category
Sarcoma and soft tissue tumours involving the skin Dermatofibrosarcoma protuberans Angiosarcoma Clear cell sarcoma (melanoma of soft tissue)
Dermatofibrosarcoma protuberans (DFSP) Superficial fibroblastic neoplasm Prone to local recurrence Characteristic storiform arrangement of monomorphic spindled cells strongly positive for CD34 t(17;22)(q21.3;q13.1) results in COL1A1PDGFB fusion
CD34
Angiosarcoma Malignant neoplasm of blood vessels Head and neck of elderly patients In areas of lymphoedema Post-radiotherapy MYC positive in >90% cases related to lymphoedema and radiotherapy
Clear cell sarcoma (melanoma of soft tissue parts) Morphologically and immunohistochemistry profile same as a melanoma Can involve dermis (but coming from below) Characteristic t(12,22)(q13,q12) EWSR1ATF translocation
5: Sarcoma and soft tissue neoplasms
Benign epithelial entities
Inverted Follicular Keratosis Variant of seborrhoeic keratosis Numerous whorls/ eddies – eosinophilic flattened squamous cells arranged in an onion-peel fashion No cytological atypia
Clear Cell Acanthoma Arise on the shin of elderly females Distinctive tumour Collarette often seen at periphery Pale cells Intraepidermal neutrophils PAS and EMA positive
Cutaneous Horn Viral Wart Seborrhoeic keratosis Actinic keratosis Lichenoid keratosis Squamous cell carcinoma
Thank you and good luck! Acknowledgment to Dr Mikheil and Dr Iskander H Chaudhry