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Basal Cell Carcinoma (BCC)

Basal cell Basal Cell Erythema Multiforme carcinoma is the most common skin Skin The skin, also referred to as the integumentary system, is the largest organ of the body. The skin is primarily composed of the epidermis (outer layer) and dermis (deep layer). The epidermis is primarily composed of keratinocytes that undergo rapid turnover, while the dermis contains dense layers of connective tissue. Skin: Structure and Functions malignancy Malignancy Hemothorax. This cancer arises from the basal layer of the epidermis Epidermis The external, nonvascular layer of the skin. It is made up, from within outward, of five layers of epithelium: (1) basal layer (stratum basale epidermidis); (2) spinous layer (stratum spinosum epidermidis); (3) granular layer (stratum granulosum epidermidis); (4) clear layer (stratum lucidum epidermidis); and (5) horny layer (stratum corneum epidermidis). Skin: Structure and Functions. The lesions most commonly appear on the face as pearly nodules, often with telangiectatic blood vessels and ulceration Ulceration Corneal Abrasions, Erosion, and Ulcers in elderly individuals. Diagnosis is established by tissue biopsy Biopsy Removal and pathologic examination of specimens from the living body. Ewing Sarcoma. Despite having low metastatic potential, basal cell carcinoma should be treated adequately because it is locally aggressive and destructive to tissues. Complete surgical excision is the main treatment method. Long-term prognosis Prognosis A prediction of the probable outcome of a disease based on a individual's condition and the usual course of the disease as seen in similar situations. Non-Hodgkin Lymphomas is excellent with adequate management.

Last updated: 10 Mar, 2022

Editorial responsibility: Stanley Oiseth, Lindsay Jones, Evelin Maza

Contents

Overview

Pathophysiology and Clinical Presentation

Diagnosis and Staging

Management and Prognosis

Differential Diagnosis

References

Overview

Definition

Basal cell Basal Cell Erythema Multiforme carcinoma is a skin Skin The skin, also referred to as the integumentary system, is the largest organ of the body. The skin is primarily composed of the epidermis (outer layer) and dermis (deep layer). The epidermis is primarily composed of keratinocytes that undergo rapid turnover, while the dermis contains dense layers of connective tissue. Skin: Structure and Functions cancer arising from the basal layer of epidermis Epidermis The external, nonvascular layer of the skin. It is made up, from within outward, of five layers of epithelium: (1) basal layer (stratum basale epidermidis); (2) spinous layer (stratum spinosum epidermidis); (3) granular layer (stratum granulosum epidermidis); (4) clear layer (stratum lucidum epidermidis); and (5) horny layer (stratum corneum epidermidis). Skin: Structure and Functions and its appendages.

Epidemiology

Most common cancer worldwide
Most common skin Skin The skin, also referred to as the integumentary system, is the largest organ of the body. The skin is primarily composed of the epidermis (outer layer) and dermis (deep layer). The epidermis is primarily composed of keratinocytes that undergo rapid turnover, while the dermis contains dense layers of connective tissue. Skin: Structure and Functions malignancy Malignancy Hemothorax
Age-adjusted incidence Incidence The number of new cases of a given disease during a given period in a specified population. It also is used for the rate at which new events occur in a defined population. It is differentiated from prevalence, which refers to all cases in the population at a given time. Measures of Disease Frequency in the United States is 226 per 100,000 person-years.
> 1 million basal cell carcinomas are treated annually in the United States.
Men > women
Incidence increases with age.

Risk factors

Ultraviolet (UV) light exposure Exposure ABCDE Assessment:
- Sun exposure Exposure ABCDE Assessment (outdoor workers)
- Tanning beds
- Phototherapy Phototherapy Treatment of disease by exposure to light, especially by variously concentrated light rays or specific wavelengths. Hyperbilirubinemia of the Newborn for psoriasis Psoriasis Psoriasis is a common T-cell-mediated inflammatory skin condition. The etiology is unknown, but is thought to be due to genetic inheritance and environmental triggers. There are 4 major subtypes, with the most common form being chronic plaque psoriasis. Psoriasis
Advanced age
Arsenic Arsenic A shiny gray element with atomic symbol as, atomic number 33, and atomic weight 75. It occurs throughout the universe, mostly in the form of metallic arsenides. Most forms are toxic. According to the fourth annual report on carcinogens, arsenic and certain arsenic compounds have been listed as known carcinogens. Metal Poisoning (Lead, Arsenic, Iron) exposure Exposure ABCDE Assessment (e.g., contaminated drinking water, contaminated seafood)
Ionizing radiation Radiation Emission or propagation of acoustic waves (sound), electromagnetic energy waves (such as light; radio waves; gamma rays; or x-rays), or a stream of subatomic particles (such as electrons; neutrons; protons; or alpha particles). Osteosarcoma
Chronic immunosuppression
Genetics Genetics Genetics is the study of genes and their functions and behaviors. Basic Terms of Genetics:
- Fair complexion
- Personal and family history Family History Adult Health Maintenance of basal cell carcinoma
- Genetic syndromes:
  - Gorlin syndrome (characterized by developmental anomalies and multiple basal cell carcinomas)
  - Xeroderma pigmentosum Xeroderma pigmentosum A rare, pigmentary, and atrophic autosomal recessive disease. It is manifested as an extreme photosensitivity to ultraviolet rays as the result of a deficiency in the enzyme that permits excisional repair of ultraviolet-damaged DNA. Lentigo Maligna ( mutation Mutation Genetic mutations are errors in DNA that can cause protein misfolding and dysfunction. There are various types of mutations, including chromosomal, point, frameshift, and expansion mutations. Types of Mutations in repair of UV-induced DNA DNA A deoxyribonucleotide polymer that is the primary genetic material of all cells. Eukaryotic and prokaryotic organisms normally contain DNA in a double-stranded state, yet several important biological processes transiently involve single-stranded regions. DNA, which consists of a polysugar-phosphate backbone possessing projections of purines (adenine and guanine) and pyrimidines (thymine and cytosine), forms a double helix that is held together by hydrogen bonds between these purines and pyrimidines (adenine to thymine and guanine to cytosine). DNA Types and Structure damage)
  - Bazex–Dupré–Christol syndrome (milia, hypotrichosis, multiple basal cell carcinomas)
  - Oculocutaneous albinism Oculocutaneous albinism Heterogeneous group of autosomal recessive disorders comprising at least four recognized types, all having in common varying degrees of hypopigmentation of the skin, hair, and eyes. The two most common are the tyrosinase-positive and tyrosinase-negative types. Albinism (disorder in melanin Melanin Insoluble polymers of tyrosine derivatives found in and causing darkness in skin (skin pigmentation), hair, and feathers providing protection against sunburn induced by sunlight. Carotenes contribute yellow and red coloration. Seborrheic Keratosis synthesis Synthesis Polymerase Chain Reaction (PCR))

Locally aggressive basal cell carcinoma in a 75-year-old man
Image: “Basalioma” by Klaus D. Peter. License: CC BY 3.0

Pathophysiology and Clinical Presentation

Pathogenesis

UV radiation Radiation Emission or propagation of acoustic waves (sound), electromagnetic energy waves (such as light; radio waves; gamma rays; or x-rays), or a stream of subatomic particles (such as electrons; neutrons; protons; or alpha particles). Osteosarcoma:
- Most significant factor
- UVA and UVB light → DNA DNA A deoxyribonucleotide polymer that is the primary genetic material of all cells. Eukaryotic and prokaryotic organisms normally contain DNA in a double-stranded state, yet several important biological processes transiently involve single-stranded regions. DNA, which consists of a polysugar-phosphate backbone possessing projections of purines (adenine and guanine) and pyrimidines (thymine and cytosine), forms a double helix that is held together by hydrogen bonds between these purines and pyrimidines (adenine to thymine and guanine to cytosine). DNA Types and Structure damage
- Genes most damaged by UV light UV light That portion of the electromagnetic spectrum immediately below the visible range and extending into the x-ray frequencies. The longer wavelengths (near-uv or biotic or vital rays) are necessary for the endogenous synthesis of vitamin D and are also called antirachitic rays; the shorter, ionizing wavelengths (far-uv or abiotic or extravital rays) are viricidal, bactericidal, mutagenic, and carcinogenic and are used as disinfectants. Bullous Pemphigoid and Pemphigus Vulgaris involve the hedgehog signaling pathway.
Common mutations:
- Patched homolog 1 (PTCH1) mutations (found in majority of basal cell carcinoma cases):
  - PTCH1 encodes a protein in the hedgehog pathway.
  - In the resting state, patched homolog 1 (PTCH1) protein normally inhibits smoothened homolog (SMO).
  - When the sonic hedgehog protein binds PTCH1 protein → PTCH1 is degraded → SMO is released
  - This process leads to a series of interacting proteins Proteins Linear polypeptides that are synthesized on ribosomes and may be further modified, crosslinked, cleaved, or assembled into complex proteins with several subunits. The specific sequence of amino acids determines the shape the polypeptide will take, during protein folding, and the function of the protein. Energy Homeostasis → GLI transcription Transcription Transcription of genetic information is the first step in gene expression. Transcription is the process by which DNA is used as a template to make mRNA. This process is divided into 3 stages: initiation, elongation, and termination. Stages of Transcription factors activated → cell proliferation
  - General effect of PTCH1 gene Gene A category of nucleic acid sequences that function as units of heredity and which code for the basic instructions for the development, reproduction, and maintenance of organisms. Basic Terms of Genetics mutations: unbound SMO allows unregulated cell growth
- TP53 mutations also seen in 20%–60% of sporadic Sporadic Selective IgA Deficiency basal cell carcinomas:
  - TP53 normally involved in apoptosis Apoptosis A regulated cell death mechanism characterized by distinctive morphologic changes in the nucleus and cytoplasm, including the endonucleolytic cleavage of genomic DNA, at regularly spaced, internucleosomal sites, I.e., DNA fragmentation. It is genetically-programmed and serves as a balance to mitosis in regulating the size of animal tissues and in mediating pathologic processes associated with tumor growth. Ischemic Cell Damage and DNA DNA A deoxyribonucleotide polymer that is the primary genetic material of all cells. Eukaryotic and prokaryotic organisms normally contain DNA in a double-stranded state, yet several important biological processes transiently involve single-stranded regions. DNA, which consists of a polysugar-phosphate backbone possessing projections of purines (adenine and guanine) and pyrimidines (thymine and cytosine), forms a double helix that is held together by hydrogen bonds between these purines and pyrimidines (adenine to thymine and guanine to cytosine). DNA Types and Structure repair
  - Mutations → cell proliferation and defective DNA DNA A deoxyribonucleotide polymer that is the primary genetic material of all cells. Eukaryotic and prokaryotic organisms normally contain DNA in a double-stranded state, yet several important biological processes transiently involve single-stranded regions. DNA, which consists of a polysugar-phosphate backbone possessing projections of purines (adenine and guanine) and pyrimidines (thymine and cytosine), forms a double helix that is held together by hydrogen bonds between these purines and pyrimidines (adenine to thymine and guanine to cytosine). DNA Types and Structure
- Other genes Genes A category of nucleic acid sequences that function as units of heredity and which code for the basic instructions for the development, reproduction, and maintenance of organisms. DNA Types and Structure: SMO, SUFU

Clinical and histologic features

Disease characteristics:
- Lesion can be a papule Papule Elevated lesion < 1 cm in diameter Generalized and Localized Rashes, patch Patch Nonpalpable lesion > 1 cm in diameter Generalized and Localized Rashes, or plaque Plaque Primary Skin Lesions.
- Most remain localized but can become aggressive
- Rarely metastasize (< 0.05%)
- Slow-growing
Basal cell Basal Cell Erythema Multiforme carcinoma distribution:
- Face: 70% ( nose Nose The nose is the human body’s primary organ of smell and functions as part of the upper respiratory system. The nose may be best known for inhaling oxygen and exhaling carbon dioxide, but it also contributes to other important functions, such as tasting. The anatomy of the nose can be divided into the external nose and the nasal cavity. Nose and Nasal Cavity: Anatomy, cheeks Cheeks The part of the face that is below the eye and to the side of the nose and mouth. Melasma, forehead Forehead The part of the face above the eyes. Melasma, nasolabial folds, and eyelids Eyelids Each of the upper and lower folds of skin which cover the eye when closed. Blepharitis)
- Trunk: 15%
- Remaining body parts: 15%
Histopathology:
- Cells of tumor Tumor Inflammation islands with palisading arrangement at the periphery
- Cellular apoptosis Apoptosis A regulated cell death mechanism characterized by distinctive morphologic changes in the nucleus and cytoplasm, including the endonucleolytic cleavage of genomic DNA, at regularly spaced, internucleosomal sites, I.e., DNA fragmentation. It is genetically-programmed and serves as a balance to mitosis in regulating the size of animal tissues and in mediating pathologic processes associated with tumor growth. Ischemic Cell Damage
- Scattered mitotic activity in the dermis Dermis A layer of vascularized connective tissue underneath the epidermis. The surface of the dermis contains innervated papillae. Embedded in or beneath the dermis are sweat glands; hair follicles; and sebaceous glands. Skin: Structure and Functions
Histologic types:
- Nodular basal cell carcinoma
- Superficial basal cell carcinoma
- Morpheaphorm (sclerosing) basal cell carcinoma
- Other, more rare, types:
  - Basosquamous cell carcinoma
  - Pigmented basal cell carcinoma

Histologic features and clinical presentation Presentation The position or orientation of the fetus at near term or during obstetric labor, determined by its relation to the spine of the mother and the birth canal. The normal position is a vertical, cephalic presentation with the fetal vertex flexed on the neck. Normal and Abnormal Labor of major basal cell carcinoma types
Type	Frequency	Histology	Clinical presentation Presentation The position or orientation of the fetus at near term or during obstetric labor, determined by its relation to the spine of the mother and the birth canal. The normal position is a vertical, cephalic presentation with the fetal vertex flexed on the neck. Normal and Abnormal Labor
Nodular basal cell carcinoma	80%	Nests of basaloid cells in the dermis Dermis A layer of vascularized connective tissue underneath the epidermis. The surface of the dermis contains innervated papillae. Embedded in or beneath the dermis are sweat glands; hair follicles; and sebaceous glands. Skin: Structure and Functions Peripheral palisading of malignant keratinocytes Keratinocytes Epidermal cells which synthesize keratin and undergo characteristic changes as they move upward from the basal layers of the epidermis to the cornified (horny) layer of the skin. Successive stages of differentiation of the keratinocytes forming the epidermal layers are basal cell, spinous or prickle cell, and the granular cell. Skin: Structure and Functions Appearance of “clefts” between tumor Tumor Inflammation stroma and dermis Dermis A layer of vascularized connective tissue underneath the epidermis. The surface of the dermis contains innervated papillae. Embedded in or beneath the dermis are sweat glands; hair follicles; and sebaceous glands. Skin: Structure and Functions	Most common on the face Pink or flesh-colored papule Papule Elevated lesion < 1 cm in diameter Generalized and Localized Rashes Pearly, translucent Rolled border (more raised than the middle) Telangiectatic vessel “Rodent ulcer”: ulcerated nodular basal cell carcinoma
Superficial basal cell carcinoma	15%	Atypical basaloid tumors arise as buds from the epidermis Epidermis The external, nonvascular layer of the skin. It is made up, from within outward, of five layers of epithelium: (1) basal layer (stratum basale epidermidis); (2) spinous layer (stratum spinosum epidermidis); (3) granular layer (stratum granulosum epidermidis); (4) clear layer (stratum lucidum epidermidis); and (5) horny layer (stratum corneum epidermidis). Skin: Structure and Functions	Higher incidence Incidence The number of new cases of a given disease during a given period in a specified population. It also is used for the rate at which new events occur in a defined population. It is differentiated from prevalence, which refers to all cases in the population at a given time. Measures of Disease Frequency in males Most common on the trunk Scaly macule Macule Nonpalpable lesion < 1 cm in diameter Generalized and Localized Rashes, patch Patch Nonpalpable lesion > 1 cm in diameter Generalized and Localized Rashes, or plaque Plaque Primary Skin Lesions Pink or red Center may appear atrophic Scattered dark pigment (may resemble melanoma Melanoma Melanoma is a malignant tumor arising from melanocytes, the melanin-producing cells of the epidermis. These tumors are most common in fair-skinned individuals with a history of excessive sun exposure and sunburns. Melanoma) +/– Telangiectasias Telangiectasias Ataxia-telangiectasia
Morpheaform basal cell carcinoma	5%–10%	Thin cords of basaloid cells penetrating surrounding collagen Collagen A polypeptide substance comprising about one third of the total protein in mammalian organisms. It is the main constituent of skin; connective tissue; and the organic substance of bones (bone and bones) and teeth (tooth). Connective Tissue: Histology Collagen may appear sclerotic, resembling a scar Scar Dermatologic Examination.	Smooth papule Papule Elevated lesion < 1 cm in diameter Generalized and Localized Rashes or plaque Plaque Primary Skin Lesions Light pink or flesh-colored Firm, indurated Ill-defined border

Nodular basal cell carcinoma of the nose Nose The nose is the human body’s primary organ of smell and functions as part of the upper respiratory system. The nose may be best known for inhaling oxygen and exhaling carbon dioxide, but it also contributes to other important functions, such as tasting. The anatomy of the nose can be divided into the external nose and the nasal cavity. Nose and Nasal Cavity: Anatomy:
Pearly nodule Nodule Chalazion with visible telangiectatic vessels
Image: “BCC Nodular type” by M. Sand, D. Sand, C. Thrandorf, V. Paech, P. Altmeyer, F. G. Bechara. License: CC BY 2.0

Superficial basal cell carcinoma — Nodular basal cell carcinoma of the nose Nose The nose is the human body’s primary organ of smell and functions as part of the upper respiratory system. The nose may be best known for inhaling oxygen and exhaling carbon dioxide, but it also contributes to other important functions, such as tasting. The anatomy of the nose can be divided into the external nose and the nasal cavity. Nose and Nasal Cavity: Anatomy:
Pearly nodule Nodule Chalazion with visible telangiectatic vessels
Image: “BCC Nodular type” by M. Sand, D. Sand, C. Thrandorf, V. Paech, P. Altmeyer, F. G. Bechara. License: CC BY 2.0

Diagnosis and Staging

Diagnosis

History:

Family history of genetic diseases
Personal history of previous skin Skin The skin, also referred to as the integumentary system, is the largest organ of the body. The skin is primarily composed of the epidermis (outer layer) and dermis (deep layer). The epidermis is primarily composed of keratinocytes that undergo rapid turnover, while the dermis contains dense layers of connective tissue. Skin: Structure and Functions cancers
History of excessive sun exposure Exposure ABCDE Assessment
HIV HIV Anti-HIV Drugs-positive status or other forms of immunocompromise

Physical exam:

Thorough skin Skin The skin, also referred to as the integumentary system, is the largest organ of the body. The skin is primarily composed of the epidermis (outer layer) and dermis (deep layer). The epidermis is primarily composed of keratinocytes that undergo rapid turnover, while the dermis contains dense layers of connective tissue. Skin: Structure and Functions examination should be performed.
Assess for palpable lymphadenopathy Lymphadenopathy Lymphadenopathy is lymph node enlargement (> 1 cm) and is benign and self-limited in most patients. Etiologies include malignancy, infection, and autoimmune disorders, as well as iatrogenic causes such as the use of certain medications. Generalized lymphadenopathy often indicates underlying systemic disease. Lymphadenopathy.

Dermoscopy Dermoscopy A noninvasive technique that enables direct microscopic examination of the surface and architecture of the skin. Seborrheic Keratosis:

Arborizing vessels
Blue-gray ovoid nests
Ulceration Ulceration Corneal Abrasions, Erosion, and Ulcers
Lack of pigmented network (unlike melanocytic lesions)

Biopsy Biopsy Removal and pathologic examination of specimens from the living body. Ewing Sarcoma:

Establishes definitive diagnosis
Shave, punch, or excisional technique can be used.

Staging Staging Methods which attempt to express in replicable terms the extent of the neoplasm in the patient. Grading, Staging, and Metastasis

Basal cell Basal Cell Erythema Multiforme carcinoma metastasis Metastasis The transfer of a neoplasm from one organ or part of the body to another remote from the primary site. Grading, Staging, and Metastasis is rare and is thus not usually staged.
Often, the cancer is treated before it spreads.
Sites of metastasis Metastasis The transfer of a neoplasm from one organ or part of the body to another remote from the primary site. Grading, Staging, and Metastasis:
- Regional lymph nodes Lymph Nodes They are oval or bean shaped bodies (1 – 30 mm in diameter) located along the lymphatic system. Lymphatic Drainage System: Anatomy
- Lungs Lungs Lungs are the main organs of the respiratory system. Lungs are paired viscera located in the thoracic cavity and are composed of spongy tissue. The primary function of the lungs is to oxygenate blood and eliminate CO2. Lungs: Anatomy
- Bones
- Liver Liver The liver is the largest gland in the human body. The liver is found in the superior right quadrant of the abdomen and weighs approximately 1.5 kilograms. Its main functions are detoxification, metabolism, nutrient storage (e.g., iron and vitamins), synthesis of coagulation factors, formation of bile, filtration, and storage of blood. Liver: Anatomy
- Skin
Imaging: CT or MRI used for evaluation of metastasis Metastasis The transfer of a neoplasm from one organ or part of the body to another remote from the primary site. Grading, Staging, and Metastasis
Staging Staging Methods which attempt to express in replicable terms the extent of the neoplasm in the patient. Grading, Staging, and Metastasis follows that for cutaneous squamous cell carcinoma Squamous cell carcinoma Cutaneous squamous cell carcinoma (cSCC) is caused by malignant proliferation of atypical keratinocytes. This condition is the 2nd most common skin malignancy and usually affects sun-exposed areas of fair-skinned patients. The cancer presents as a firm, erythematous, keratotic plaque or papule. Squamous Cell Carcinoma (SCC) but is applicable only to head and neck Neck The part of a human or animal body connecting the head to the rest of the body. Peritonsillar Abscess lesions (American Joint Committee on Cancer, 8th edition).
Stages:
- Stage 0: cancer involves only the epidermis Epidermis The external, nonvascular layer of the skin. It is made up, from within outward, of five layers of epithelium: (1) basal layer (stratum basale epidermidis); (2) spinous layer (stratum spinosum epidermidis); (3) granular layer (stratum granulosum epidermidis); (4) clear layer (stratum lucidum epidermidis); and (5) horny layer (stratum corneum epidermidis). Skin: Structure and Functions (in situ)
- Stage I:
  - Cancer is not large (≤ 2 cm).
  - No spread to the lymph nodes Lymph Nodes They are oval or bean shaped bodies (1 – 30 mm in diameter) located along the lymphatic system. Lymphatic Drainage System: Anatomy or other organs
- Stage II:
  - Cancer is large (>2 cm but ≤ 4 cm).
  - No spread to lymph nodes Lymph Nodes They are oval or bean shaped bodies (1 – 30 mm in diameter) located along the lymphatic system. Lymphatic Drainage System: Anatomy or other organs
- Stage III:
  - Cancer > 4 cm or cancer of any size with deep, perineural or minor bone Bone Bone is a compact type of hardened connective tissue composed of bone cells, membranes, an extracellular mineralized matrix, and central bone marrow. The 2 primary types of bone are compact and spongy. Bones: Structure and Types invasion and/or spread to 1 ipsilateral lymph Lymph The interstitial fluid that is in the lymphatic system. Secondary Lymphatic Organs node (no extranodal extension Extension Examination of the Upper Limbs)
  - No spread to other organs
- Stage IV: lesions of any size; spread to other organs (distant metastasis Metastasis The transfer of a neoplasm from one organ or part of the body to another remote from the primary site. Grading, Staging, and Metastasis)

Management and Prognosis

Treatment approach

Assess risk of recurrence:

Helps determine treatment of choice
Inadequate treatment of high-risk lesions can result in recurrence and complications (e.g., deformities).
High-risk features:
- Location: face, ears, hands, and feet
- Size:
  - ≥ 10 mm MM Multiple myeloma (MM) is a malignant condition of plasma cells (activated B lymphocytes) primarily seen in the elderly. Monoclonal proliferation of plasma cells results in cytokine-driven osteoclastic activity and excessive secretion of IgG antibodies. Multiple Myeloma on head, neck Neck The part of a human or animal body connecting the head to the rest of the body. Peritonsillar Abscess, and pretibia
  - ≥ 20 mm MM Multiple myeloma (MM) is a malignant condition of plasma cells (activated B lymphocytes) primarily seen in the elderly. Monoclonal proliferation of plasma cells results in cytokine-driven osteoclastic activity and excessive secretion of IgG antibodies. Multiple Myeloma in other areas
- Aggressive variants: morpheaform, basosquamous, micronodular
- Recurrent lesions
- Perineural invasion
- Poorly defined borders
- Basal cell Basal Cell Erythema Multiforme carcinomas in previous radiation Radiation Emission or propagation of acoustic waves (sound), electromagnetic energy waves (such as light; radio waves; gamma rays; or x-rays), or a stream of subatomic particles (such as electrons; neutrons; protons; or alpha particles). Osteosarcoma sites
- Immunocompromised patient Immunocompromised patient A human or animal whose immunologic mechanism is deficient because of an immunodeficiency disorder or other disease or as the result of the administration of immunosuppressive drugs or radiation. Herpes Zoster (Shingles)

Surgery:

Standard surgical excision:
- 1st-line treatment for low-risk lesions
- Margins: 4–5 mm MM Multiple myeloma (MM) is a malignant condition of plasma cells (activated B lymphocytes) primarily seen in the elderly. Monoclonal proliferation of plasma cells results in cytokine-driven osteoclastic activity and excessive secretion of IgG antibodies. Multiple Myeloma
Mohs micrographic surgery:
- 1st-line treatment for high-risk lesions
- For facial lesions/cosmetically sensitive areas (less normal tissue resected)

Alternative therapies:

Options for patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship who are poor surgical candidates or who prefer not to have surgery:
- Topical chemotherapy Chemotherapy Osteosarcoma (e.g., imiquimod Imiquimod A topically-applied aminoquinoline immune modulator that induces interferon production. It is used in the treatment of external genital and perianal warts, superficial carcinoma, basal cell; and actinic keratosis. Hypertrophic and Keloid Scars or fluorouracil Fluorouracil A pyrimidine analog that is an antineoplastic antimetabolite. It interferes with DNA synthesis by blocking the thymidylate synthetase conversion of deoxyuridylic acid to thymidylic acid. Bowen Disease and Erythroplasia of Queyrat):
  - Low-risk sites
  - 6-week treatment
  - Skin irritation is a side effect.
- Electrodesiccation Electrodesiccation Seborrheic Keratosis and curettage Curettage A scraping, usually of the interior of a cavity or tract, for removal of new growth or other abnormal tissue, or to obtain material for tissue diagnosis. It is performed with a curet (curette), a spoon-shaped instrument designed for that purpose. Benign Bone Tumors:
  - Can be used for small low-risk basal cell carcinomas
  - Risk of incomplete tumor Tumor Inflammation removal
- Cryosurgery:
  - Not for high-risk lesions
  - Can result in scarring Scarring Inflammation and hypopigmentation Hypopigmentation A condition caused by a deficiency or a loss of melanin pigmentation in the epidermis, also known as hypomelanosis. Hypopigmentation can be localized or generalized, and may result from genetic defects, trauma, inflammation, or infections. Malassezia Fungi
- Radiotherapy: for high-risk lesions in poor surgical candidates

Therapy for advanced disease:

For metastasis Metastasis The transfer of a neoplasm from one organ or part of the body to another remote from the primary site. Grading, Staging, and Metastasis or locally advanced basal cell carcinoma that is not amenable to radiotherapy or surgery
Inhibitor of sonic hedgehog pathway: vismodegib, sonidegib

Prognosis Prognosis A prediction of the probable outcome of a disease based on a individual’s condition and the usual course of the disease as seen in similar situations. Non-Hodgkin Lymphomas

Overall prognosis is excellent.
Metastatic potential: 0.05%–0.1%.
Population-based case mortality Mortality All deaths reported in a given population. Measures of Health Status: 0.05%.

Differential Diagnosis

Squamous cell carcinoma: second most common skin Skin The skin, also referred to as the integumentary system, is the largest organ of the body. The skin is primarily composed of the epidermis (outer layer) and dermis (deep layer). The epidermis is primarily composed of keratinocytes that undergo rapid turnover, while the dermis contains dense layers of connective tissue. Skin: Structure and Functions cancer: Squamous cell carcinoma usually presents as a firm, erythematous, keratotic plaque Plaque Primary Skin Lesions or papule Papule Elevated lesion < 1 cm in diameter Generalized and Localized Rashes. Diagnosis is through biopsy. Histopathologic examination confirms the diagnosis by showing findings such as atypical keratinocytes Keratinocytes Epidermal cells which synthesize keratin and undergo characteristic changes as they move upward from the basal layers of the epidermis to the cornified (horny) layer of the skin. Successive stages of differentiation of the keratinocytes forming the epidermal layers are basal cell, spinous or prickle cell, and the granular cell. Skin: Structure and Functions infiltrating into the dermis Dermis A layer of vascularized connective tissue underneath the epidermis. The surface of the dermis contains innervated papillae. Embedded in or beneath the dermis are sweat glands; hair follicles; and sebaceous glands. Skin: Structure and Functions.
Dermatofibroma: a common mesenchymal growth of the skin Skin The skin, also referred to as the integumentary system, is the largest organ of the body. The skin is primarily composed of the epidermis (outer layer) and dermis (deep layer). The epidermis is primarily composed of keratinocytes that undergo rapid turnover, while the dermis contains dense layers of connective tissue. Skin: Structure and Functions where skin Skin The skin, also referred to as the integumentary system, is the largest organ of the body. The skin is primarily composed of the epidermis (outer layer) and dermis (deep layer). The epidermis is primarily composed of keratinocytes that undergo rapid turnover, while the dermis contains dense layers of connective tissue. Skin: Structure and Functions fibroblasts Fibroblasts Connective tissue cells which secrete an extracellular matrix rich in collagen and other macromolecules. Sarcoidosis are the major constituents: Dermatofibroma usually presents as a firm, indurated, mobile nodule Nodule Chalazion measuring about 0.5–1 cm. Upon lateral compression Compression Blunt Chest Trauma, a dimple-like depression in the overlying skin Skin The skin, also referred to as the integumentary system, is the largest organ of the body. The skin is primarily composed of the epidermis (outer layer) and dermis (deep layer). The epidermis is primarily composed of keratinocytes that undergo rapid turnover, while the dermis contains dense layers of connective tissue. Skin: Structure and Functions appears (“buttonhole” sign).
Melanoma: skin Skin The skin, also referred to as the integumentary system, is the largest organ of the body. The skin is primarily composed of the epidermis (outer layer) and dermis (deep layer). The epidermis is primarily composed of keratinocytes that undergo rapid turnover, while the dermis contains dense layers of connective tissue. Skin: Structure and Functions malignancy Malignancy Hemothorax arising from melanocytes Melanocytes Mammalian pigment cells that produce melanins, pigments found mainly in the epidermis, but also in the eyes and the hair, by a process called melanogenesis. Coloration can be altered by the number of melanocytes or the amount of pigment produced and stored in the organelles called melanosomes. The large non-mammalian melanin-containing cells are called melanophores. Skin: Structure and Functions: Melanoma presents as irregular pigmented lesions and can resemble pigmented variants of basal cell carcinoma. Diagnosis is confirmed by biopsy. This condition carries a significantly worse prognosis than basal cell carcinoma.
Actinic keratosis Actinic keratosis Actinic keratosis (AK) is a precancerous skin lesion that affects sun-exposed areas. The condition presents as small, non-tender macules/papules with a characteristic sandpaper-like texture that can become erythematous scaly plaques. Actinic Keratosis: benign Benign Fibroadenoma keratinocytic lesion considered a precursor to squamous cell carcinoma Squamous cell carcinoma Cutaneous squamous cell carcinoma (cSCC) is caused by malignant proliferation of atypical keratinocytes. This condition is the 2nd most common skin malignancy and usually affects sun-exposed areas of fair-skinned patients. The cancer presents as a firm, erythematous, keratotic plaque or papule. Squamous Cell Carcinoma (SCC): Lesions of actinic keratosis present as scaly erythematous macules. Diagnosis is established by biopsy.
Inflammatory skin Skin The skin, also referred to as the integumentary system, is the largest organ of the body. The skin is primarily composed of the epidermis (outer layer) and dermis (deep layer). The epidermis is primarily composed of keratinocytes that undergo rapid turnover, while the dermis contains dense layers of connective tissue. Skin: Structure and Functions conditions: Psoriasis and eczema Eczema Atopic dermatitis, also known as eczema, is a chronic, relapsing, pruritic, inflammatory skin disease that occurs more frequently in children, although adults can also be affected. The condition is often associated with elevated serum levels of IgE and a personal or family history of atopy. Skin dryness, erythema, oozing, crusting, and lichenification are present. Atopic Dermatitis (Eczema) can present with erythematous papules and plaques and clinically resemble superficial basal cell carcinoma. Diagnosis is made with a thorough exam, dermoscopy, and biopsy.

References

Aasi SZ. (2020). Treatment and prognosis of basal cell carcinoma at low risk of recurrence. Retrieved January 19, 2021, from https://www.uptodate.com/contents/treatment-and-prognosis-of-basal-cell-carcinoma-at-low-risk-of-recurrence
Aasi SZ. (2020). Treatment of basal cell carcinomas at high risk for recurrence. Retrieved January 19, 2021, from https://www.uptodate.com/contents/treatment-of-basal-cell-carcinomas-at-high-risk-for-recurrence
Bader R. (2020). Basal cell carcinoma. Medscape. Retrieved February 3, 2021, from https://emedicine.medscape.com/article/276624-overview
Curti BD, Leachman S, Urba WJ. (2018). Cancer of the skin. Jameson J., et al. (Eds.). Harrison’s Principles of Internal Medicine, 20th ed. McGraw-Hill.
Lazar A. (2020). The skin. In Kumar V, et al. (Eds.). Pathologic Basis of Disease (10th ed.). Elsevier.
Wu PA. (2019). Epidemiology, pathogenesis, and clinical features of basal cell carcinoma. Retrieved January 19, 2021, from https://www.uptodate.com/contents/epidemiology-pathogenesis-and-clinical-features-of-basal-cell-carcinoma

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Basal Cell Carcinoma (BCC)

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