Final skin.ppt.29.03.2013.08 08-2014.


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  • Histology review (labels)‏
  • Vitiligo
  • Freckles (ephelis)‏
  • Melasma, also called “mask of pregnancy”
  • What is the ABCDEEFG principle?
    Borders (irregular)
    Color (variegated), and
    Diameter (greater than 6 mm (0.24 in.), about the size of a pencil eraser)
    Evolving over time
    These classifications do not however apply to the most dangerous form of melanoma, nodular melanoma, which has its own classifications:
    Elevated above the skin surface
    Firm to the touch
    Why do only idiots learn the ABCDEEFG acronym? Ans: Because all these features are already basic in understanding malignancy.
  • What kind of malignant cell would have pigment IN it? What could this pigment be?
  • Clark vs. Breslow (better) classification
  • Squamous “horn cysts” in seborrheic keratosis
  • Acanthosis nigricans, often associated with diabetes mellitus
  • Acanthosis nigricans, often associated with diabetes mellitus
  • Fibroepithelial polyp, or “skin tag”
  • Fibroepithelial polyp, or “skin tag”.
    Would you call this a papilloma? Why, or why not?
  • Epidermal inclusion cyst, the overlying skin looks normal.
  • Epidermal inclusion cyst
  • By far, the commonest malignancy of skin, BCC, i.e., Basal Cell Carcinoma, typical appearance.
  • By far, the commonest malignancy of skin, BCC, i.e., Basal Cell Carcinoma, typical appearance. Note the PERIPHERAL PALISADING!!!
  • Merkel cell tumor, very highly malignant RARE and usually fatal, looks EXACTLY like a small cell carcinoma of the lung? Ans: yes.
  • Note the LACK of the term “Fibroma”. Why” Ans: Because tumors of pure “fibroblasts” of the dermis are, somehow, rare.
  • Benign fibrous histiocytoma, or dermatofibroma
  • Benign fibrous histiocytoma, or dermatofibroma
  • Large fibrous histiocytoma, perhaps a dermatofibrosarcoma protuberans?
  • Malignant fibrous histiocytoma.
  • Final skin.ppt.29.03.2013.08 08-2014.

    2. 2. SKINSKIN
    3. 3. Excoriation Traumatic lesion breaking the epidermis and causing a raw linear area (i.e., deep scratch); often self-induced Lichenification Thickened and rough skin characterized by prominent skin markings (as lichen on a tree trunk); usually the result of repeated rubbing Macule Circumscribed lesion, 5 mm or smaller in diameter, characterized by flatness and distinguished by coloration (patch is greater than 5 mm) Onycholysis Separation of nail plate from nail bed
    4. 4. Papule Elevated dome-shaped or flat-topped lesion 5 mm or less across (nodule is greater than 5 mm) Plaque Elevated flat-topped lesion, usually greater than 5 mm across (may be caused by coalescent papules) Pustule Discrete, pus-filled, raised lesion Scale Dry, horny, plate like excrescence; usually the result of imperfect cornification Vesicle Fluid-filled raised lesion 5 mm or less across (Bulla is greater than 5 mm. Blister is the common term for either.) Wheal Itchy, transient, elevated lesion with
    5. 5. Acantholysis Loss of intercellular cohesion between keratinocytes Acanthosis Diffuse epidermal hyperplasia Dyskeratosis Abnormal, premature keratinization within cells below the stratum granulosum Erosion Discontinuity of the skin showing incomplete loss of the epidermis Exocytosis Infiltration of the epidermis by inflammatory cells Hydropic swelling (ballooning) Intracellular edema of keratinocytes, often seen in viral infections Hypergranulosis Hyperplasia of the stratum granulosum, often
    6. 6. Lentiginous A linear pattern of melanocyte proliferation within the epidermal basal cell layer Papillomatosis Surface elevation caused by hyperplasia and enlargement of contiguous dermal papillae Para keratosis Keratinization with retained nuclei in the stratum corneum. On mucous membranes, Para keratosis is normal. Spongiosis Intercellular edema of the epidermis Ulceration Discontinuity of the skin showing complete loss of the epidermis revealing dermis or sub cutis Vacuolization Formation of vacuoles within or adjacent to cells; often refers to basal cell-basement membrane zone area
    7. 7. • Squamous epithelial cells (keratinocytes), in addition to producing protective keratin protein, are major sites for the biosynthesis of soluble molecules (cytokines) that regulate adjacent epidermal cells as well as cells in the dermis. • Melanocytes within the epidermis are cells responsible for the production of melanin, a brown pigment that protects against potentially injurious ultraviolet (UV) radiation in sunlight. • Dendritic cells. Skin is constantly battered with microbial and nonmicrobial antigens that are processed by intraepidermal dendritic Langerhans cells, which interact with the systemic immune system by migrating to regional lymph nodes. • Specialized dendrocytes within the dermis perform similar functions there.
    9. 9. Nevus Variant Diagnostic Architectural Features Cytologic Features Clinical Significance Congenital nevus Deep dermal and sometimes subcutaneous growth around adnexa, neurovascular bundles, and blood vessel walls Identical to ordinary acquired nevi Present at birth; large variants have increased melanoma risk
    10. 10. Blue nevus Non-nested dermal infiltration, often with associated fibrosis Highly dendritic, heavily pigmented nevus cells Black-blue nodule; often confused with melanoma clinically Spindle and epithelioid cell nevus (Spitz nevus) Fascicular growth Large, plump cells with pink- blue cytoplasm; fusiform cells Common in children; red- pink nodule; often confused with hemangioma clinically
    11. 11. Halo nevus Lymphocytic infiltration surrounding nevus cells Identical to ordinary acquired nevi Host immune response against nevus cells and surrounding normal melanocytes Dysplastic nevus Coalescent intraepidermal nests Cytological atypia Potential marker or precursor of melanoma
    12. 12.  Melanocytic nevus, junctional type. A, In clinical appearance, lesions are small, relatively flat, symmetric, and uniform. B, On histologic examination, junctional nevi are characterized by rounded nests of nevus cells originating at the tips of rete ridges along the dermoepidermal junction.
    13. 13. Melanocytic nevus, compound type. (A) is more raised and dome-shaped. The symmetry and uniform pigment distribution suggest a benign process. Histologically (B), compound nevi combine the features of junctional nevi (intraepidermal nevus cell nests) with nests and cords of nevus cells in the underlying dermis).
    14. 14. • Dysplastic nevus.  • A, Numerous clinically atypical nevi on the back. • B, One such lesion (inset A) has a compound nevus component (left side of scanning field) and an asymmetric junctional nevus component (right side of scanning field). • The former correlates grossly with the more pigmented and raised central zone and the latter with the less pigmented, flat peripheral rim. • C, An important feature is the presence of cytologic atypia (irregularly shaped, dark-staining nuclei). The dermis underlying the atypical cells characteristically shows linear, or lamellar, fibrosis.
    15. 15. • Potential steps of tumour progression in dysplastic nevi.  • A, Lentiginous melanocytic hyperplasia. • B, Lentiginous junctional nevus. • C, Lentiginous compound nevus with abnormal architectural and cytologic features (dysplastic nevus). • D, Early melanoma, or melanoma in radial growth phase (large dark cells in epidermis). • E, Advanced melanoma (vertical growth phase) with malignant spread into the dermis and vessels. • The risk of malignant transformation of any single dysplastic nevus is extremely low but can occur.
    16. 16. • Clinical and pathologic features are used to gauge the probability of metastatic spread and prognosis. • 1) Tumour Depth (The Breslow Thickness) • (2) Number Of Mitoses; • (3) Evidence Of Tumour Regression (Presumably Due To The Host Immune Response); • (4) The Presence And Number Of Tumour Infiltrating Lymphocytes (Tils); • (5) Gender; And (6) Location (Central Body Or Extremity). • In a retrospective multivariate study by the American Joint Committee on Cancer (AJCC), tumour thickness and presence or absence of ulceration had prognostic significance. • Because most melanomas initially metastasize to regional lymph nodes
    17. 17. BENIGN EPIDERMAL TUMORS • Seborrheic keratosis • Acanthosis nigricans • Fibro epithelial polyp (skin tag) • Epidermal (inclusion) cyst • Adnexal tumors : eccrine, apocrine • Keratoacanthoma.
    18. 18. Benign Epithelial Tumours • Benign epithelial neoplasms are common and usually biologically inconsequential, although they may cause significant psychological discomfort for the affected individual. • These tumours, derived from the keratinizing stratified squamous epithelium of the epidermis and hair follicles and the ductular epithelium of cutaneous glands, often recapitulate the structures from which they arise. • They are sometimes confused clinically with malignancy, particularly when they are pigmented or inflamed, and histologic examination of a
    20. 20. • A well-demarcated coin like pigmented lesion containing dark keratin-filled surface plugs (inset) is composed histologically of benign basaloid cells associated with prominent keratin- filled "horn" cysts, some of which communicate with the surface (pseudo-horn cysts).
    21. 21. • On histologic examination, these neoplasms are exophytic and sharply demarcated from the adjacent epidermis. • They are composed of sheets of small cells that most resemble basal cells of the normal epidermis • Variable melanin pigmentation is present within these basaloid cells, accounting for the brown coloration. • Exuberant keratin production (hyperkeratosis) occurs at the surface, and small keratin-filled cysts (horn cysts) and invaginations of keratin into the main mass (invagination cysts) are characteristic feature.
    22. 22. ACANTHOSIS NIGRICANS • Acanthosis nigricans is a condition marked by thickened, hyper pigmented skin with a "velvet-like" texture that most commonly appears in the flexural areas (axillae, skin folds of the neck, groin, and anogenital regions). • It can be an important cutaneous marker of benign and malignant conditions and, accordingly, is divided into two types. • The benign type, which constitutes about 80% of all cases, develops gradually and usually occurs in childhood or during puberty. • It may occur (1) as an autosomal dominant trait with variable penetrance, (2) in association with obesity or endocrine abnormalities (particularly with pituitary or pineal tumors and diabetes), and (3) as part of several rare congenital syndromes
    23. 23. Fibro epithelial Polyp (skin tag) • The fibro epithelial polyp has many names (acrochordon, squamous papilloma, skin tag) and is one of the most common cutaneous lesions. • It is generally detected as an incidental finding in middle- aged and older individuals on the neck, trunk, face, and intertriginous areas as a soft, flesh- coloured, bag-like tumour often attached to the surrounding skin by a slender stalk
    24. 24. • Epithelial cysts are divided into several histologic types. • The epidermal inclusion cyst has a wall resembling normal epidermis and is filled with laminated strands of keratin. • Pilar or trichilemmal cysts have a wall that resembles follicular epithelium, without a granular cell layer and filled by a more homogeneous mixture of keratin and lipid. • The dermoid cyst is similar to the epidermal inclusion cyst, but also contains multiple appendages (such as small hair follicles) budding outward from its wall. • Finally, steatocystoma simplex is a cyst with a wall resembling the sebaceous gland duct, and from which numerous compressed sebaceous lobules originate
    26. 26. • The cylindroma is composed of islands of cells resembling those of the normal epidermal or adnexal basal cell layer (basaloid cells). • These islands fit together like pieces of a jigsaw puzzle within a fibrous dermal matrix . • Trichoepithelioma is a proliferation of basaloid cells that forms primitive structures resembling hair follicles .
    27. 27. • Sebaceous adenoma shows a lobular proliferation of sebocytes with increased peripheral basaloid cells and more mature sebocytes in the central portion, characterized by frothy or bubbly cytoplasm due to lipid vesicle content (Fig. 25-12A). • Pilomatrixomas are composed of basaloid cells that show trichilemmal or hair like differentiation similar to that seen in the germinal portion of the normal hair bulb in the anagen growth phase (Fig. 25-12B). • Apocrine carcinoma shows ductal differentiation with prominent decapitation secretion similar to that seen in the normal apocrine gland (Fig. 25-12C). The infiltrative growth pattern is a hint of malignancy in this otherwise well-differentiated tumour.
    28. 28. • Actinic keratosis are usually less than 1 cm in diameter; are tan-brown, red, or skin-colored; and have a rough, sandpaper-like consistency. Some lesions may produce so much keratin that a "cutaneous horn" develops.
    30. 30. • A, Excessive scale formation in this lesion has produced a "cutaneous horn." • B, Basal cell layer atypia (dysplasia) is associated with marked hyperkeratosis and Para keratosis. • C, Progression to full-thickness nuclear atypia, with or without the presence of superficial epidermal maturation, heralds the development of squamous cell carcinoma in situ.
    32. 32. GENERAL COMMENTS • BOTH SCC and BCC related to SUN (i.e., radiation) exposure. • SCC also related to As, carcinogens, chaw, betel nut, HPV, familial, etc. • BOTH SCC and BCC can do local damage but very rarely metastasize. • MERKEL CELL tumors metastasize early and extensively, like melanomas.
    33. 33. Diseases: Ataxia-telangiectasia Nevoid basal cell carcinoma syndrome Cowden syndrome• Familial melanoma syndrome • Muir-Torre syndrome • Neurofibromatosis I • Neurofibromatosis II • Tuberous sclerosis • Xeroderma pigmentosum
    34. 34. SQUAMOUS CELL CARCINOMA • Squamous cell carcinoma is the second most common tumour arising on sun-exposed sites in older people, exceeded only by basal cell carcinoma. • Except for lesions on the lower legs, these tumours have a higher incidence in men than in women. • Invasive squamous cell carcinomas are usually discovered while they are small and resectable. • Less than 5% of these tumours metastasize to regional nodes; these lesions are generally deeply invasive and involve the sub cutis.
    35. 35. • A.Lesions are often nodular and ulcerated as seen in this scalp tumour. • B, Tongues of atypical squamous epithelium have transgressed the basement membrane, invading deeply into the dermis. • C, A magnified image reveals invasive tumour cells showing enlarged nuclei with angulated contours and prominent nucleoli.
    36. 36. • Squamous cell carcinomas that have not invaded through the basement membrane of the dermoepidermal junction (termed in situ carcinoma) appear as sharply defined, red, scaling plaques. • More advanced, invasive lesions are nodular, show variable keratin production (appreciated grossly as hyperkeratosis scale), and may ulcerate .
    37. 37. • The most important cause of cutaneous squamous cell carcinoma is DNA damage induced by exposure to UV light. • Tumour incidence is proportional to the degree of lifetime sun exposure. • A second common association is with immunosuppression, most notably chronic immunosuppression as a result of chemotherapy or organ transplantation. • Immunosuppression may contribute to carcinogenesis by reducing host surveillance and increasing the susceptibility of keratinocytes to infection and transformation by oncogenic viruses,
    38. 38. • Other risk factors for squamous cell carcinoma include industrial carcinogens (tars and oils), chronic ulcers and draining osteomyelitis, old burn scars, ingestion of arsenicals, ionizing radiation, and (in the oral cavity) tobacco and betel nut chewing .
    39. 39. • Basal cell carcinoma is the most common invasive cancer in humans, with nearly 1 million estimated cases per year . • These are slow-growing tumours that rarely metastasize. They have a tendency to occur at sun-exposed sites and in lightly pigmented people. • As with squamous cell carcinoma, the incidence of basal cell carcinoma rises sharply with immunosuppression and in people with inherited defects in DNA repair such as xeroderma pigmentosum
    40. 40. Basal cell carcinoma. Pearly, telangiectatic nodules (A) are composed of nests of uniformly atypical basaloid cells within the dermis (B) that are often separated from the adjacent stroma by thin clefts (C), an artefact of sectioning.
    41. 41. • Histologically, • the tumour cells resemble those in the normal basal cell layer of the epidermis. They arise from the epidermis or follicular epithelium and do not occur on mucosal surfaces. Two patterns are seen: • Multifocal growths originating from the epidermis and sometimes extending over several square centimeters or more of skin surface (multifocal superficial type) and nodular lesions growing downward deeply into the dermis as cords and islands of variably basophilic cells with hyper chromatic nuclei, embedded in a mucinous matrix, and often surrounded by many fibroblasts and lymphocytes. • The cells at the periphery of the tumour cell islands tend to be arranged radially with their long axes in parallel alignment (palisading). In sections, the stroma retracts away from the carcinoma
    43. 43. • Benign fibrous histiocytoma refers to a heterogeneous family of morphologically and histogenetically related benign dermal neoplasms of uncertain lineage. • These tumours are usually seen in adults and often occur on the legs of young to middle-aged women.
    44. 44. • The most common form of fibrous histiocytoma is referred to as a dermatofibroma. • These tumours are formed by benign, spindle- shaped cells arranged in a well-defined, nonencapsulated mass within the mid-dermis. • Extension of these cells into the subcutaneous fat is sometimes observed. • Many cases demonstrate a peculiar form of overlying epidermal hyperplasia, characterized by downward elongation of hyper pigmented rete ridges (a pseudo- epitheliomatous pattern).
    45. 45. • Dermatofibrosarcoma protuberans is best regarded as a well-differentiated, primary fibro sarcoma of the skin. • These tumours are slow growing, and although they are locally aggressive and can recur, they rarely metastasize. • Clinically they are firm, solid nodules that arise most frequently on the trunk. They often develop as aggregated "protuberant" tumours within a firm (indurated) plaque or nodule that may sometimes ulcerate.
    46. 46. Benign fibrous histiocytoma (dermatofibroma). This firm, tan papule on the leg (A) shows a localized proliferation of benign- appearing spindle cells within the dermis (B). C, Note the characteristic overlying epidermal hyperplasia and the tendency of fibroblasts to surround individual collagen bundles.
    47. 47. • These neoplasms are cellular, composed of fibroblasts arranged radially, reminiscent of blades of a pinwheel, a pattern referred to as storiform. • Mitoses are rare. In contrast to that in dermatofibroma, the overlying epidermis is generally thinned. • Deep extension from the dermis into subcutaneous fat, producing a characteristic "honeycomb" pattern, is frequently present . • These tumours may extend down fibrous septae in the subcutis and thus require wider excision than would appear to be necessary to prevent local recurrence
    48. 48. Cellular “Immigrants” • Langerhans cells (Histiocytosis) • Mycosis Fungoides (T-Cell cutaneous lymphoma) • Mastocytosis (mast cell tumors)
    49. 49. • Cutaneous T cell lymphoma (CTCL) represents a spectrum of lymph proliferative disorders affecting the skin • Two different clinical types of malignant T-cell disorders were originally recognized: mycosis fungoides, a chronic proliferative process; and a more aggressive nodular eruptive variant, mycosis fungoides. • It is now known that a variety of presentations of T-cell lymphoma occur in the skin, but this section will focus on mycosis fungoides.
    50. 50. A, Several ill-defined, erythematous, often scaling, and occasionally ulcerated plaques. B, Microscopically, there is an infiltrate of atypical lymphocytes that show a tendency to accumulate beneath the epidermal layer and to invade the epidermis.
    51. 51. •  The histologic hallmark of CTCL of the mycosis fungoides type is the presence of the Sézary- Lutzner cells. • These are T-helper cells (CD4+) that characteristically form band-like aggregates within the superficial dermis (Fig. 25-19B) and invade the epidermis as single cells and small clusters (Pautrier micro abscesses).
    52. 52. • The term mastocytosis refers to a spectrum of rare disorders characterized by increased numbers of mast cells in the skin and, in some instances, in other organs. • A localized cutaneous form of the disease that affects predominantly children and accounts for more than 50% of all cases is termed urticaria pigmentosa. • These lesions are multiple, although solitary mastocytomas may also occur, usually shortly after birth.
    53. 53. A, Solitary mastocytoma in a 1-year-old child. B, By routine histology, numerous ovoid cells with uniform, centrally located nuclei are observed in the dermis. C, Giemsa staining reveals purple, "metachromatic" granules within the cytoplasm of the cells.
    54. 54. • The histologic picture in urticaria pigmentosa or solitary mastocytoma varies from a subtle increase in the numbers of spindle-shaped and stellate mast cells around superficial dermal blood vessels, to large numbers of tightly packed, round to oval mast cells in the upper to mid-dermis • Variable fibrosis, edema, and small numbers of eosinophils may also be present. • Mast cells may be difficult to differentiate from lymphocytes in routine, hematoxylin and eosin- stained sections, and special metachromatic stains (toluidine blue or Giemsa) must be used to visualize their granules .