Tumor of skin

SKIN TUMORS

Dr. Ihsan Al-Turfy Consultant Dermatologist College of Medicine/Baghdad MBChB,DDV,FICMS,CABD

Tumor

Definition : Is an abnormal growth of tissue. This abnormal growth usually but not always forms a mass. They can be benign or malignant Any cellular element of the skin can produce tumors

Benign tumors of the skin

1.Hemangioma-. From bv 2. Lymphangioma.- Lymphatics 3.Neuroma. -Nerves 4.lipoma. Adipose tissue 5.Fibroma-- fibrous tissue 6. Epidermal cell tumors(Including its appendages): (Keratinocytes & Melanocytes-mainly)

A. Pigmented nevi.( Melanocytes)

Melanocytic nevi : are benign neoplasms or hamartomas (Hamartoma is Abnormal Collection of normal tissue consituents)composed of melanocytes, {the pigment-producing cells that constitutively colonize the epidermis} ( Melanocytes are present in the basal layer of the epidermis) Melanocytes are derived from the neural crest and migrate during embryogenesis to selected ectodermal sites (primarily the skin and the CNS), but also to the eyes and the ears.

Melanocytic nevi….. They are divided into congenital and acquired types. Conventional or common acquired melanocytic nevi are generally less than 1cm in diameter and evenly pigmented. They are of three types: Junctional ,compound, and dermal

Melanocytic nevi…. Congenital: are thought to represent an anomaly in embryogenesis and, as such, could be considered, at least in a sense, malformations or hamartomas. Melanocytic nevi are common lesions that can be found on the integument of almost all individuals. Some patients present with few lesions, while others have hundreds .Melanocytic nevi represent proliferations of melanocytes that are in contact with each other, forming small collections of cells known as nests.

Congenital melanocytic nevi

They are present since birth( that is why they are called" congenital") Are of 2 types; small and large (bathing trunk), that have deep color(usually ) with irregular border and covered by hair. Larger ones do have a malignant potential.


Types of melanocytic nevi
1.Junctional melanocytic nevi (directly attached to the basal layer) are macular or thinly papular. Junctional lesions typically range from brown to brownish-black. The darker coloration of junctional melanocytic nevi stems from the fact that the surface epidermis is often simultaneously hyperpigmented.

2 & 3 . Compound and intradermal melanocytic nevi

display elevation relative to surrounding uninvolved skin. Compound melanocytic nevi are often lighter in color than junctional nevi and range from tan to light brown. Some compound melanocytic nevi have areas of dark pigmentation, particularly those that have been recently irritated or traumatized. Many wholly intradermal melanocytic nevi display no significant pigmentation.

NB
Compound nevi have both junctional and dermal elements. While dermal nevi have no junctional element.


The development of a new area of pigmentation within a long-standing nonpigmented or lightly pigmented compound or intradermal melanocytic nevus,is a cause for concern. While pigmentary changes could be due to incidental inflammation or recent irritation or trauma, the possibility of evolving melanoma is also a consideration in the differential diagnosis.

Nevi & MM

Signs of suspicion of MM in any pigmented skin lesion (ABCDE): A: Asymmetry in shape, one half of the lesion is unlike the other half. B: Border is irregular C: Color is not uniform; mottled, different shades of black, grey red and white. D: Diameter more than 0.6 mm E: In addtion to increase in size of the lesion( which usually brings the patient to hospital).-Enlargement

Note

Melanocytic nevi never become malignant because of manipulation and trauma. The risk of malignant transformation is very small . Management( of melanocytic nevi): None ,but they can be removed for cosmetic purposes

Epidermal cell tumors-(keratinocytes)

B. Keratoacanthoma( KA): is a relatively common low-grade tumor that originates in the pilosebaceous glands and closely & pathologically resembles squamous cell carcinoma(SCC). Keratoacanthoma is characterized by rapid growth over a few weeks to months, followed by spontaneous resolution over 4-6 months in most cases.


KA….. It typically grows rapidly, reaching 1-2 cm within weeks, followed by a slow involution period lasting up to one year and leaving a residual scar if not excised. Typically are solitary skin-color or red papules(or nodules) with smooth shiny surface and a central crateriform ulceration or keratin plug. Sites:face,neck, and dorsum of the hands.

Treatment of KA

Many consider surgical treatment of KA to be equivalent to treatment of SCC.

Other benign tumors(keratinocytes)

C. Seborrheic keratoses are the most common benign tumor in older individuals (usually never appear before the age of 30). Seborrheic keratoses have a variety of clinical appearances that begin with the appearance of one or more sharply defined, light brown, flat macules. The lesions may be sparse or numerous, asymptomatic or itchy .

SK… The color May become dark brown to black with warty stuck on appearance Sites: face, upper trunk & scalp are the commonest They are NOT premalignant that is why treatment should be simple like curettage or cryotherapy. We can apply topical AHA or Retinoids. NB being colored they should be differentiated from malignant melanoma(ABCDE).

Histopathology of Seb K.

Epidermal proliferating cells with basaloid appearance. The lesions are raised above skin surface with papilomatosis and horn cyst formation. No tendency toward malignancy.

Treatment of seb. keratosis

Can be removed easily by curettage,cryotherapy or electrodessication Others :AHA, TCA,Tazarotene cr.

Other benign tumors

D. Trichelemmal cysts(pilar cyst)-- from hair(External Root sheet):Arise on the scalp, similar to sebaceous cyst but has no opening( punctum) may be single or multiple( usually familial),surgical removal is easier than that for sebaceous cysts. E.sebaceous gland tumors--- benign seb hyperplasia,and seb.cyst


Benign sebaceous hyperplasia
: Is a common, benign condition of sebaceous glands in adults of middle age or older. Lesions can be single or multiple and manifest as yellowish, soft, small papules on the face (particularly nose, cheeks, and forehead).often with an umblicated center. It may occasionally be confused with BCC Can be removed by simple shave excision

Benign sebaceous hyperplasia..

NB occasionally oral isotretinoin may be needed for wide spread disfiguring lesions.

F. Syringoma

Is a sweat duct tumor: are skin-colored or yellowish, generally small, dermal papules Most commonly, syringomas are limited to the upper parts of the cheeks and lower eyelids.They are only of cosmetic importance

Premalignant skin conditions

Any skin condition that will lead ultimately to frank malignancy if left untreated. The classic example is actinic (senile,solar) keratosis(AK)-AKs are amongst the most frequently encountered skin lesions in clinical practice. They present on sun-damaged skin of the head, neck, upper trunk and extremities. Individuals at higher risk of developing AKs include the elderly, lighter skin phototypes and history of chronic sun exposure.

AK…. They present with rough erythematous papule with white to yellow scale. size from a few millimeters to large confluent patches several centimeters in diameter surrounded by photodamaged skin(wrinkled, telangiectatic with dyspigmentation) Sites: face,ears,bald scalp, and dorsa of hands.

Treatment

1.5-FU– TOPICAL.2. Topical imiquimod.3.Topical diclofenac.4. PTD with topical delta-aminolevulinic acid(generation of oxygen free radicals).

Important malignant tumors of the skin

1. Related to basal cells.-- BCC2. Originating from keratinocytes.-- SCC3 Originating from melanocytes-- MM4. Mycosis fungoides(MF) originating from T cells( T cell lymphoma)NB: recently kaposi’s sarcoma(malignant vascular tumor) is raising concern in our country .


General causes of malignant tumors
1.Sun exposure. 2.Chronic skin disease or irritation Including old burns 3. X rays and ionizing radiation. 4. Genitic diseases like xeroderma pigmentosa-- in ability to repair Sundamaged DNA 5. Exposure to Some chemicals Like arsenic. 6. The presence of some immune defects(Genitic , Aquired"HIV" ,and drug induced"For organ transplants") 7. HPV (Human papIlloma virus" certain types")

NB: susceptibility to UVR damage

Well-known markers for UVR vulnerability include the following: Fair skin (or a history of repeated sunburns) Hazel or blue eyes Blonde or red hair Albinism (NOT Vitiligo)

Basal cell carcinoma (BCC)

a nonmelanocytic skin cancer (ie, an epithelial tumor) that arises from basal cells ( small, cuboidal cells found in the lower layer of the epidermis)--???. The prognosis for patients with BCC is excellent, but if the disease is allowed to progress, it can cause significant morbidity. NB: Many believe that BCCs arise from pluripotential cells in the basal layer of the epidermis or follicular structures.

BCC.. Signs and symptoms

BCC occurs mostly on the face, head (scalp included), neck, and hands.Other characteristic features of BCC tumors include the following: Waxy papules with central depression Pearly appearance Erosion or ulceration: Often central and pigmented Bleeding: Especially when traumatized

BCC features… Oozing or crusted areas: In large BCCs Rolled (raised) border (often inetrrupted) Translucency Telangiectases over the surface Slow growing: 0.5 cm in 1-2 years Black-blue or brown areas

Clinicopathologic types of BCC

Each of which has a distinct biologic behavior, include the following: Nodular,morpheaform, superficial, Cystic, pigmented, keratotic .The most common type of BCC; usually presents as a round, pearly, flesh-colored papule with telangiectases Infiltrative: Tumor infiltrates the dermis in thin strands between collagen fibers, making tumor margins less clinically apparent

OTHER TYPES of BCC

Morpheaform: Appears as a white or yellow, waxy, sclerotic plaque that rarely ulcerates; is flat or slightly depressed, fibrotic, and firm. Superficial: Seen mostly on the upper trunk or shoulders; appears clinically as an erythematous, well-circumscribed patch or plaque, often with a whitish scale


Diagnosis
Clinical plus histopathological. Given that BCC rarely metastasizes, laboratory and imaging studies are not commonly clinically indicated in patients presenting with localized lesions. Imaging studies may be necessary when involvement of deeper structures, such as bone, is clinically suspected. In such cases, computed tomography scans or radiography can be used.

Biological behavior according to type

Nodular, Cystic, pigmented, keratotic; the most common type of BCC; usually presents as a round, pearly, flesh-colored papule with telangiectasesInfiltrative: Tumor infiltrates the dermis in thin strands between collagen fibers, making tumor margins less clinically apparentMicronodular: Not prone to ulceration; may appear yellow-white when stretched,…

is firm to the touch, and may have a seemingly well-defined border Morpheaform: Appears as a white or yellow, waxy, sclerotic plaque that rarely ulcerates; is flat or slightly depressed, fibrotic, and firm. Superficial: Seen mostly on the upper trunk or shoulders; appears clinically as an erythematous, well-circumscribed patch or plaque, often with a whitish scale.

Biopsy Types of skin biopsy that may be used to confirm the diagnosis and determine the histologic subtype of BCC include the following: Shave biopsy: Most often, the only biopsy that is required

Punch biopsy: May be indicated in the case of a pigmented lesion if there is difficulty distinguishing between pigmented BCC and melanoma; ensures that the depth of the lesion can be determined if it proves to be a malignant melanoma.

proliferation of basiloid( similar to basal cells) cells within the dermis forming a peripheral palisade appearance( like a fence), presence of tumour retraction and stroma are the main features. It can be undifferentiated or differrentiated (towrd hair, sebaceous gland or tubular glands).
Histology of BCC

Management

1.Surgery In nearly all cases of BCC, surgery is the recommended treatment modality. Techniques used include the following: a.Electrodesiccation and curettage b.Excisional surgery c.Mohs micrographically controlled surgery

2.Cryosurgery-freezing the skin to about 180 c 3.Radiation therapy BCCs are usually radiosensitive; radiation therapy (RT) can be used in patients with advanced and extended lesions, as well as in those for whom surgery is not suitable. Postoperative radiation can also be a useful adjunct when patients have aggressive tumors that were treated surgically or when surgery has failed to clear the margins of the tumor.


RX…. 4.Photodynamic therapy (PDT)(( application of a photosensitizer plus UV light )) is a reasonable choice in Certain conditions . 5.Pharmacologic therapy: Topical agents used in the treatment of superficial BCC include the following :

RX…. Topical 5-fluorouracil 5%: May be used to treat small, superficial BCCs in lowrisk areas Imiquimod: Approved by the US Food and Drug Administration for the treatmentof nonfacial superficial BCC Tazarotene ( is a tpoical retinoid): Can also be used to treat small, low-risk BCCs

Squamous cell CA (SCC)

Squamous cell Ca (SSC) is the second most common skin cancer, after basal cell carcinomas(BCC) Site - mostly on head and neck ( development in non-sun exposed skin usually follows chronic skin inflammtion" old burn, lupus vulgaris, DLE" ). Signs and symptoms The classic presentation of a SCC is that of a shallow ulcer with heaped-up edges, often covered by a plaque, usually in a sun-exposed area.

SCC … Typical surface changes may include the following: Scaling,ulceration, crusting,and a cutaneous horn Less commonly, SCC presents as a pink cutaneous nodule without overlying surface changes.Regional spread of head and neck :SCC may result in enlarged preauricular, submandibular, or cervical lymph nodes.

Diagnosis

The workup of suspected SCC may include the following: Biopsy: Indicated for any lesion suspected of being a cutaneous neoplasm Computed tomography (CT) scanning: To evaluate for bone or soft tissue invasion and cervical lymph nodes at risk for metastasis Magnetic resonance imaging (MRI): Preferred for evaluation of perineural invasion and orbital or intracranial extension.

Pathology

Nuclear atypia Frequent mitoses Cellula pleomorphism Parakeratosis and hyperkeratosis. A disorganized progression of cells from the basal to apical layers of the epidermis. When cells break the basal layer and invades the dermis it is called invasive SSC With invasive SCC, nests of atypical cells are found within the dermis, surrounded by an inflammatory infiltrate.

Pathology… The presence of malignant appearing cells.SSC can be well differentiated moderately differentiated or poorly differentiated.( The first one has better prognosis). Squamous cell carcinoma in situ (CIS){ malignant cells are still within the epidermis}, sometimes referred to as Bowen disease, is a precursor to invasive SCC.

DD of SCC

1.AK 2.BCC 3.Bowenoid papulosis and bowens disease. 4. Amelanotic MM. 5. any chronic skin conditions that presents with ulceration and induration.



Management
Treatment options include the following: 1.Electrodessication and curettage: Low-risk SCC on the trunk and extremities 2. Mohs micrographic surgery: Invasive SCC 3.Radiation therapy: As an adjuvant to surgery, to provide improved regional control, or as primary therapy in patients who are unable to undergo surgical excision

Rx..

Oral 5-fluorouracil (5-FU) and epidermal growth factor receptor (EGFR) inhibitors: Adjuvant therapy for select highest-risk cases Systemic chemotherapy: A consideration for metastatic SCC

Malignant melanoma

is a neoplasm of melanocytes. Although it was once considered uncommon, the annual incidence has increased dramatically over the past few decades. Surgery is the definitive treatment for early-stage melanoma, with medical management generally reserved for adjuvant treatment of advanced melanoma.

History

The history should address the following: Family history of melanoma or skin cancer Family history of irregular, prominent moles Previous melanoma (melanomas are sometimes multiple); patients have reported as many as 8 or more primary melanomas)

History… Previous sun exposure Changes noted in moles (eg, size, color, symmetry, bleeding, or ulceration) History or family history of multiple nevus syndrome


Physical examination includes the following: Total-body skin examination, to be performed on initial evaluation and during all subsequent visits Serial photography, epiluminescence microscopy, dermoscopy ,and computerized image analysis, to be considered as adjuncts Skin examination involves assessing the number of nevi present

and distinguishing between typical and atypical lesions. Early melanomas may be differentiated from benign nevi by the ABCDs, as follows:A - AsymmetryB - Border irregularityC - Color that tends to be very dark black or blue and variableD - Diameter ≥ 6 mm

If a patient is diagnosed with a melanoma, examine all lymph node groups. NB: Dermoscopy: (a hand held device for the examination and differentiation of pigmented lesions Including MM) may be a useful tool.


Clinical types:
1- Lentigo maligna melanoma: Affects the face in elderly people, irregular in shape and pigmentation grows for years in situ before invasion. 2- Superficial spreading melanoma: There is a radial growth phase into the epidermis before invading the dermis.

Clinical types… 3- Nodular melanoma: No radial growth phase, early invasion, very aggressive. 4- Acral lentigenous melanoma: Most common type in Iraq, affects the palms and soles, presents as irregularly pigmented macule or patch. presence of nodule indicates invasion

laboratory studies

The following laboratory studies are indicated: Complete blood count Complete chemistry panel (including alkaline phosphatase, hepatic transaminases, total protein, and albumin) Lactate dehydrogenase

imaging modalities

Chest radiography Magnetic resonance imaging of the brain Ultrasonography (possibly the best imaging study for diagnosing lymph node involvement) Computed tomography of the chest, abdomen, or pelvis Positron emission tomography (PET; PET-CT may be the best imaging study for identifying other sites of metastasis)---???

Histopathology

Characteristic histologic findings include the following: Cytologic atypia, with enlarged cells containing large, pleomorphic, hyperchromic nuclei with prominent nucleoli Numerous mitotic figures Pagetoid growth pattern with upward growth of the melanocytes

DD of MM

1.BCC 2.Lentigo maligna. 3.Mycosis fungoides. 4.Subungual hematoma 5. Bleeding inside a benign pigmented nevus.

Procedural management

Complete excisional biopsy of a suggestive lesion with wide safe margin Surgical excision or re excision after biopsy Elective lymph node dissection (ELND) for patients with clinically enlarged nodes and no evidence of distant disease Sentinel lymph node biopsy .


Management
Surgery (wide local excision ) is the definitive treatment for early-stage melanoma. Medical management is reserved for adjuvant therapy of patients with advanced melanoma.

Mycosis Fungoides (MF):

It is primary T-cell lymphoma of the skin. There is clonal proliferation of CD 4 positive T-cells while CD 8 positive T-cells represent the antitumor response. Clinical manifestations: The disease arises in mid to late adulthood. It has four stages.

Stages

Symptoms
pruritus, which may be severe.

Dermatopathology

Atypical lymphocytes with large cerebriform (Convoluted) nuclei are gathered in the dermis at the dermo-epidermal junction. Some of these cells invade the epidermis in collections called Pautrier's micro-abscesses. Staging: TNM

Treatment

According to the stage Topical steroids Topical retinoids Topical chemotherapy - Eg, nitrogen mustard or bischloroethylnitrosourea (BCNU) Ultraviolet B (UV-B) light treatment or UV-A light treatment enhanced with psoralen (PUVA)

RX..

Total-body electron beam radiation These modalities are also used in combination with systemic modalities (eg, PUVA plus interferon) for higher-stage disease. Course and prognosis: The course is slow. The prognosis depends on the stage Survival May be for 10 to 15 years.


Kaposi’s sarcoma It is a spindle-cell tumor thought to be derived from endothelial cell lineage. It is controversial whether Kaposi sarcoma (KS) represents neoplasia or hyperplasia; all clinical variants are viewed as a virally induced disease, with human herpesvirus-8 (HHV-8) the implicated agent.


KS…. A multifocal systemic disease with four principal clinical variants:(1) chronic or classic KS; (2) African endemic KS, including a fulminant lymphadenopathic type; (3) KS due to iatrogenic immunosuppression; and (4) AIDS-related epidemic KS(male homosexuals).


KS……… Cutaneous lesions can vary from pink patches to dark violet macules,plaques, nodules or polyps, depending on clinical variant and stage. Most cases in children, with or without HIV infection, are of the lymphadenopathic type and are rapidly fatal due to visceral dissemination but this type is NOT seen in Iraq(usually starting in the 5th decade and up)

KS…. Classic KS usually starts as a bluish-red macule on the distal portions of the lower extremities the lesions progress very slowly and may coalesce to form large plaques and finally it may form nodular and fungiform tumors. It may start unilaterally but eventually becomes bilateral. It may ulcerate.

KS…. While early,angiomatous “lesions” are soft and spongy to the touch, the older tumors are firm. Edema of the surrounding tissue is often present and may occasionally antedate the cutaneous lesionsIn addition to cutaneous lesions, KS may develop on various mucous membranes, especially in the oral cavity and within the gastrointestinal tract.

DD of KS

Bacillary angiomatosis Stasis dermatitis Lichen planus

KS… Classic KS usually develops very slowly and therefore runs a rather benign course, even when extracutaneous sites are involved. Because of multifocality, treatment with chemotherapy and/or radiation is favored over surgery. Others :cryotherapy ,laser, intralesional vincristine ,and even topical retinoids.