Morbid anatomy

pT staging of melanoma depends on:

A. Breslow thickness and ulceration

B. Clark level and number of mitoses

C. Breslow thickness and number of mitoses

D. Breslow thickness and satellite metastases

E. Clark level and ulceration

A. Breslow thickness and ulceration

Melanocytomas are:

A. Intermediate lesions characterized by atypical histologic features but indolent behavior with more than one driver mutation

B. Intermediate lesions characterized by typical histologic features but malignant behavior with more than one driver mutation

C. Intermediate lesions characterized by typical histologic features but malignant behavior with more than one driver mutation

D. Intermediate lesions characterized by atypical histologic features but indolent behavior with only one driver mutation

E. Intermediate lesions characterized by typical histologic features and indolent behavior with only one diver mutation

A. Intermediate lesions characterized by atypical histologic features but indolent behavior with more than one driver mutations

Melanoma is usually characterized by:

A. Ill-defined border, absence of maturation of melanocytes, increased dermal mitotic activity, pagetoid melanocytes.

B. Well-defined borders, hypermaturation of melanocytes, increased dermal mitotic activity, pagetoid melanocytes.

C. Ill-defined border, hypermaturation of melanocytes, increased dermal mitotic activity, pagetoid melanocytes.

D. Ill-defined border, absence of maturation of melanocytes, reduced dermal mitotic activity, pagetoid melanocytes.

E. Ill-defined border, absence of maturation of melanocytes, increased dermal mitotic activity, absence of pagetoid melanocytes.

A. Ill-defined border, absence of maturation of melanocytes, increased dermal mitotic activity, pagetoid melanocytes.

What is the correct sequence of the epidermal layers from outermost to innermost?

A) Spinosum, Granulosum, Corneum, Basale

B) Corneum, Granulosum, Spinosum, Basale

C) Basale, Spinosum, Corneum, Granulosum

D) Granulosum, Corneum, Basale, Spinosum

B) Corneum, Granulosum, Spinosum, Basale

Which epidermal cell presents antigens to lymphocytes and plays a role in the immune response?

A) Melanocytes

B) Merkel cells

C) Langerhans cells

D) Keratinocytes

C) Langerhans cells

Which area of the body contains Moll, Zeis, and Meibomian glands?

A) Palms

B) Scalp

C) Eyelid

D) Neck

C) Eyelid

Which of the following is considered a precancerous lesion?

A) Wart

B) Solar lentigo

C) Seborrheic keratosis

D) Actinic keratosis

D) Actinic keratosis

What is the typical histological feature of solar lentigo?

A) Horn pseudocysts

B) Reticular dermal hyperpigmentation

C) Elongation of rete ridges

D) Atrophy of the granular layer

C) Elongation of rete ridges

Which clinical sign may suggest an underlying malignancy associated with seborrheic keratosis?

A) Basophilic sign

B) Leser-Trélat sign

C) Flag sign

D) Crater sign

B) Leser-Trélat sign

Which histological finding is typical of HPV-induced warts?

A) Multinucleated giant cells

B) Pseudocysts

C) Koilocytosis

D) Melanin deposits

C) Koilocytosis

Which epidermal layer typically shows atypia in actinic keratosis?

A) Corneum

B) Granulosum

C) Basal

D) Spinosum

C) Basal

What is a distinguishing feature of Bowen disease compared to actinic keratosis?

A) Involvement of the basal layer

B) Full-thickness atypia

C) Presence of the flag sign

D) Absence of “monster” cells

B) Full-thickness atypia

Which of the following statements about basal cell carcinoma is true?

A) It is a systemic cancer

B) It frequently metastasizes

C) It has no TNM classification

D) It originates from Merkel cells

C) It has no TNM classification

Which histological clue helps in diagnosing basal cell carcinoma?

A) Papillomatous growth

B) Keratin-filled crater

C) Cleft between tumor nest and stroma

D) Hypergranulosis

C) Cleft between tumor nest and stroma

Why is micronodular BCC considered high risk?

A) It is highly metastatic

B) It always involves the epidermis

C) It grows along neurovascular bundles

D) It has a bluish color

C) It grows along neurovascular bundles

When is TNM classification used for SCC?

A) Always

B) Only in young patients

C) Only for lesions on the head and neck

D) Only if larger than 2 cm

C) Only for lesions on the head and neck

Which grade corresponds to a poorly differentiated squamous cell carcinoma?

A) G1

B) G2

C) G3

D) G0

C) G3

Which immunohistochemical marker is characteristic of Merkel cell carcinoma diagnosis?

A) HMB-45

B) CD1A

C) CK20

D) Ki67

C) CK20

What histological feature is typical of well-differentiated SCC (G1)?

A) Lack of keratinization

B) Keratin-filled crater with minimal atypia

C) Full-thickness loss of epidermal structure

D) Absence of neutrophils

B) Keratin-filled crater with minimal atypia

What distinguishes a G3 squamous cell carcinoma from G1 and G2?

A) Clear epidermal layering

B) Crateriform growth

C) Very undifferentiated cells, hard to identify as keratinocytes

D) Presence of horn pseudocysts

C) Very undifferentiated cells, hard to identify as keratinocytes

What is the main pathogenic agent involved in Merkel cell carcinoma?

A) HPV

B) Epstein-Barr virus

C) Human polyomavirus

D) HHV-8

C) Human polyomavirus

What is the typical microscopic appearance of Merkel cell carcinoma?

A) Granular eosinophilic cytoplasm

B) "Salt and pepper" chromatin and nuclear molding

C) Keratin-filled crater

D) Blue basaloid palisading nodules

B) "Salt and pepper" chromatin and nuclear molding

Which marker shows a dot-like paranuclear staining pattern specific for Merkel cell carcinoma?

A) CK20

B) Synaptophysin

C) Chromogranin

D) HMB-45

A) CK20

Which of the following is a characteristic of a common nevus?

A) Diameter over 20 mm

B) Asymmetry

C) Sharp borders and symmetry

D) Irregular pigmentation

C) Sharp borders and symmetry

What is meant by “maturation” in a common nevus?

A) Presence of mitotic figures

B) Melanocytes become larger with depth

C) Melanocytes become smaller deeper in the dermis

D) Loss of pigment with depth

C) Melanocytes become smaller deeper in the dermis

What causes the blue appearance of a blue nevus?

A) Hemorrhage

B) Tyndall effect due to deep melanin

C) Loss of keratinocytes

D) High vascularity

B) Tyndall effect due to deep melanin

Which of the following is a typical feature of special site nevi?

A) Uniform appearance across all sites

B) Bridging of rete ridges and pagetoid scatter

C) Always associated with BRAF mutations

D) Common mitotic figures

B) Bridging of rete ridges and pagetoid scatter

What is a key histologic feature of melanoma?

A) Presence of nested melanocytes with maturation

B) Decrease in dermal mitotic activity

C) Pagetoid scatter of melanocytes

D) Round nests along rete ridges

C) Pagetoid scatter of melanocytes

Which type of melanoma is most often found on sun-damaged skin?

A) Nevoid melanoma

B) Lentigo maligna melanoma

C) Acral lentiginous melanoma

D) Nodular melanoma

B) Lentigo maligna melanoma

What defines a high-grade dysplastic nevus in the WHO system?

A) Absence of mitoses

B) Cytomorphological uniformity

C) Melanocytes > 1.5x size of basal keratinocytes

D) Lack of architectural disorder

C) Melanocytes > 1.5x size of basal keratinocytes

Which mutation is commonly seen in BAP1-inactivated melanocytoma (BIM)?

A) NRAS

B) HRAS

C) BRAF + BAP1 loss

D) ALK translocation

C) BRAF + BAP1 loss

Spitz nevi typically show which mutation?

A) TP53 deletion

B) ROS1 or ALK translocation

C) CDKN2A loss

D) TERT amplification

B) ROS1 or ALK translocation

Which combination of mutations is typical of PEM?

A) HRAS + ALK

B) BRAF + PRKAR1A

C) MITF + MC1R

D) TERT + CDK4

B) BRAF + PRKAR1A

Which marker, when lost, suggests potential melanoma progression?

A) S100

B) SOX10

C) P16

D) HMB45

C) P16

What is the hallmark histological feature of trichilemmoma?

A) Koilocytosis

B) Inverted nuclear polarization in the basal layer

C) Clefting between tumor and stroma

D) Suprabasal detachment

B) Inverted nuclear polarization in the basal layer

The presence of multiple trichilemmomas suggests possible:
A) Birt-Hogg-Dubé syndrome
B) Muir-Torre syndrome
C) Cowden syndrome
D) Gardner syndrome

C) Cowden syndrome

What key feature distinguishes trichoblastoma from basal cell carcinoma?

A) Necrosis

B) Stromal clefting

C) Papillary mesenchymal bodies

D) Hypergranulosis

C) Papillary mesenchymal bodies

Brooke-Spiegler syndrome is most strongly associated with:

A) Sebaceous adenomas

B) Cylindromas and spiradenomas

C) Epidermoid cysts

D) Bowen disease

B) Cylindromas and spiradenomas

What mutation is commonly associated with Muir-Torre syndrome?

A) APC

B) PTEN

C) FLCN

D) MSH2

B) PTEN

What histological clue is characteristic of pilomatricoma?

A) Palisading nuclei

B) Shadow (ghost) cells

C) Necrobiotic granulomas

D) Pautrier’s abscesses

B) Shadow (ghost) cells, which are necrotic keratinocytes

Which of the following is NOT typically associated with Gardner syndrome?

A) Pilomatricomas

B) Desmoid tumors

C) Multiple sebaceous adenomas

D) APC mutation

C) Multiple sebaceous adenomas

What distinguishes fibrofolliculoma from trichodiscoma histologically?

A) Location of lesion

B) Amount of sclerotic stroma vs. epithelial component

C) Mitotic rate

D) Size of sebocytes

B) Amount of sclerotic stroma vs. epithelial component:

stroma > epithelial =

epithelial > stroma =

Which of the following is NOT typically associated with Birt-Hogg-Dubé syndrome?

A) Pulmonary cysts

B) Chromophobe renal tumors

C) Sebaceous adenomas

D) Spontaneous pneumothorax

C) Sebaceous adenomas

What is the main histological feature of spongiotic dermatitis?

A) Lichenoid infiltrate

B) Basilar vacuolar degeneration

C) Intraepidermal edema with lymphocyte exocytosis

D) Suprabasal detachment

C) Intraepidermal edema with lymphocyte exocytosis

Which histological feature is characteristic of psoriasis?

A) Bullous detachment

B) Mucin deposition

C) Confluent parakeratosis and Munro abscesses

D) Basal layer dyskeratosis

C) Confluent parakeratosis and Munro abscesses

Which disease is characterized by wedge-shaped hypergranulosis and band-like infiltrate?

A) Psoriasis

B) Lichen planus

C) Bullous pemphigoid

D) Seborrheic keratosis

B) Lichen planus

What is the hallmark histological feature of mycosis fungoides?

A) Pautrier’s abscesses with spongiosis

B) Epidermotropism without spongiosis

C) Vacuolar degeneration of basal layer

D) Diffuse eosinophilia

B) Epidermotropism without spongiosis ?

Which triad of findings is typical of leukocytoclastic vasculitis?

A) Vacuolar degeneration, necrosis, parakeratosis

B) Fibrinoid necrosis, nuclear dust, RBC extravasation

C) Spongiosis, edema, neutrophil infiltrate

D) Eosinophils, mucin, dermal fibrosis

B) Fibrinoid necrosis, nuclear dust, RBC extravasation

What feature is typical of necrobiotic granulomas in necrobiosis lipoidica?

A) Central mucin accumulation

B) Naked granulomas

C) Plasma cells and collagen degeneration

D) Acid-fast bacilli

C) Plasma cells and collagen degeneration

What distinguishes pemphigus foliaceus from pemphigus vulgaris?

A) Subepidermal blistering

B) Superficial detachment without mucosal involvement

C) Mitosis and hypergranulosis

D) Direct IgA deposition

B) Superficial detachment without mucosal involvement (PF)

What is the key immunofluorescence finding in bullous pemphigoid?

A) Granular deposits in upper dermis

B) Linear C3 and IgG at dermo-epidermal junction

C) Intercellular IgA deposits

D) None

B) Linear C3 and IgG at dermo-epidermal junction

What is a defining histological feature of erythema nodosum?

A) Vasculitis of small vessels

B) Septal panniculitis without vasculitis

C) Bullous epidermal detachment

D) Lobular panniculitis with necrosis

B) Septal panniculitis without vasculitis

Differences (2) between actinic keratosis and Bowen disease:

1. AK = precancerous lesion that can lead to SCC; BD = SCC in situ

2. AK = ONLY basal layer atypia; BD: the whole epidermis is disrupted, but the basal layer is preserved (eyeliner sign)

SK acanthotic VS SK irritated

ACANTHOTIC: horn pseudocysts + thickened epidermis

IRRITATED: parakeratosis + lymphocytic infiltration

Features of solar lentigo:

1. UV-related

2. Solar elastosis

3. Elongation of rete ridges

4. Hyperplasia of normal keratinocytes

DD between SK and AK

SK: proliferation of normal keratinocytes

AK: proliferation of atypical keratinocytes (basal layer atypia) + ABNORMAL maturation

Warts features (5)

1. Papillomatosis

2. Hypergranulosis

3. Dilated blood vessels

4. Koilocytes

5. Inward growth of rete ridges

Where do we find the flag sign?

Flag sing (parakeratosis - normal keratosis - parakeratosis) is fiund in AK.

Merkel cell carcinoma: histological features (3)

1. Basaloid cells growing in sheets/nests/trabeculae

2. Nuclear molding

3. Salt and pepper pattern (finely dispersed chromatin)

What is the immunohistochemical marker and pattern for MCC?

The marker is CK20 (+) with a paranuclear dot-like staining pattern.

What is the syndrome associated with presence of many BCCs in a patient?

Gorlin syndrome (PTCH1 germline mutation)

Low-risk (4) and High-risk (2) BCC

LOW RISK:

1. Superficial

2. Nodular

3. Adenoid —> mucin (lake-like aspect)

4. Fibroepithelioma of Pinkus

HIGH RISK:

1. Infiltrative

2. Micronodular: tends to ulcerate

BCC: histological features (4)

1. Peripheral basaloid proliferation

2. Peripheral nuclear palisades (keratinocytes)

3. Mucin production

4. Cleft formation (artifact) between basaloid lobules and stroma

Is SCC UV-related?

YES

TNM system in SCC

• Used only in head and neck SCC

• Takes into account DEPTH and PERINEURAL INVASION

T3: perineural invasion

T4: skull base invasion

Keratoacanthoma (G1 Keratoacanthoma-like SCC):

1. Central crater of keratin

2. Dermal infiltration by squamous cells

3. Glassy cytoplasm

4. Well-differentiated SCC

5. Intraepidermal neutrophils

6. Epidermal dysplasia of basal layer

7. Very good epidermal differentiation (we recognize all the layers)

Epidermis and Dermis in SCC:

Epidermis: full-thickness keratinocyte atypia

Dermis: infiltration by islands of squamous cells