Skin Carcinoma – Basal And Squamous Cell  Carcinoma

Basal Cell  Carcinoma

The most prevalent non-melanotic skin cancer is basal cell carcinoma, which nearly exclusively affects people with white skin. Older adults or those in their middle years (40–60 years) are typically affected. Hair follicles and pluripotent epithelial cells of the stratum basale (non-keratinizing basaloid cells) are the primary sources of basal cell carcinoma, which affects men more frequently than women. 
It is a locally invasive malignancy with a sluggish growth rate. Because of this, it is also referred to as a rodent ulcer. It hardly ever spreads. The Hedgehog signaling pathway mutations are the primary cause of it. 

Risk Factors For Basal Cell Carcinoma

Sun exposure, UV light exposure, these are the two main risk factors for basal cell cancer. Contact with substances such as coal tar, aromatic hydrocarbons, and arsenical compounds. Immunosuppression in transplant recipients may possibly be the cause. 
An additional risk factor for basal cell carcinoma is the human papillomavirus. Additionally, basal cell cancer can result from PUVA (psoralen plus ultraviolet-A radiation). 

Genetic Syndromes Associated with Basal Cell Carcinoma

1. Gorlin Syndrome       
   • Necessitated basal cell carcinoma syndrome is another name for Gorlin syndrome. It is an autosomal dominant condition that is inherited.
   • Basal cell carcinoma can result from abnormalities in the human patched gene PTCH-I, a tumor suppressor gene located on chromosome 9q22–31. Ninety percent of people with Gorlin syndrome may have more than one basal cell carcinoma. 
   • It is possible to see phenotypic characteristics such as hypertelorism, large nasal ridges, and overdeveloped supraorbital ridges. Molar odontogenic cysts present. Skeletal deformities such as brachy metacarpals, scoliosis, and bifid ribs are observed. Palmar and plantar pits are visible, as well as calcifications associated with Fallx cerebri. 
2. Xeroderma Pigmentosum
   • The primary cause of this autosomal recessive disorder is faulty nucleotide excision repair that takes place during cellular DNA maintenance. Patients develop numerous neoplasms and premature skin aging as a result of their insensitivity to UV light. Chorionic villi sample and amniocentesis can be used to diagnose xeroderma pigmentosum in utero. 
3. Bazex Syndrome
   • Follicular atrophoderma, hypotrichosis, and basal cell carcinoma are the trio of follicular atrophoderma, an X-linked dominant hereditary condition.It also has the following characteristics:
   • Dermatosis with acne-like psoriasis.
   • A cyst on the epidermoid.
   • Bazax syndrome is primarily linked to malignancies of the upper aerodigestive tract, such as squamous cell carcinoma. 

Subtypes of Basal Cell Carcinoma

Two general categories exist for basal cell carcinoma: diffuse and localized/circumscribed. The following subtypes of basal cell carcinoma can be distinguished from the localized or circumscribed type: 

• Nodular - It is the most common type of basal cell carcinoma and is seen in 50 to 60 percent of the cases. 
• Nodulocystic. 
• Cystic. 
• Pigmented. 
• Naevoid. 
• Keratotic. 
• Fibroepithelioma of pinkus. 

Clinical Features Of The Nodular Type Of Basal Cell Carcinoma

The head and neck area is where nodular or nodulocystic basal cell carcinoma is most frequently found.  The lesion appears as a well-defined, raised pink lesion that has a waxy texture.  Pearly opalescent nodules form along the edges of the lesion as it progresses.
There is a central depression that has the traditional characteristics of rolled-out edges and umbilication or ulceration.  Elangiectasia is visible at the margins or on the surface.  An ulcerative lesion that is persistent and bleeds sporadically is another possible presentation.

Diffuse or Generalised Type

The superficial or spreading type, which is localized to the epidermis as a flat, pink, scaling or crusting lesion, is the initial subtype of diffuse or generalized basal cell carcinoma.  The trunk and extremities are where it is most frequently observed. It progresses slowly and has an ulcerable center with ill-defined or irregular edges. 
Eczema or psoriasis may be the differential diagnosis. The second subtype is called micronodular, and it is an aggressive kind with several slightly elevated pink or red lesions. Micronodular type extends considerably beyond the surface changes that are readily noticeable.
The infiltrative type, an aggressive kind, is the third subtype.

The site of embryonic fusion in the head and neck is where infiltrative type is observed. It appears as a white, opaque lesion that mixes in with the skin around it. There are no visible elevated edges, and they don't have a good future. The other subtype of basal cell carcinoma is called morpheaform or morphoeic type, and it is the most aggressive and locally invasive subtype. 

It produces type 4 collagenase, which aids in its quick dissemination.
The growth pattern appears as white scars.  The clinical borders are vague or poorly defined; it is an indurated macula or papule that resembles an expanding scar. 

Fibroepithelioma of Pinkus

It is a rare form that often manifests as a solitary, raised polypoidal pink or erythematous nodule with a smooth surface.  It is an indolent tumor that usually appears over the limbs and torso. 
Lymph node involvement is infrequent with basal cell carcinoma; Metastasis is uncommon; The most prevalent place is the back skin.
An excision, an incisional, or a shave biopsy (including the base) can be used to confirm the diagnosis. 

Histological Picture of Basal Cell Carcinoma

The classic characteristic of basal cell cancer is peripheral palisading. • Round or ovoid basophilic cells in epidermal nests.  Only the outer layer of cells actively divides; palisading of tumor nuclei can be seen near the margin, when the outer layer separates from the stroma. 

High-Risk Features Or Prognostic Factors For Basal Cell Carcinoma       

The tumor's site or location is a significant prognostic factor. The mask area of the face, which includes the mandible, hands, feet, genital areas, periorbital nose, lips, chin, and eyelids and eyebrows, is represented by the alphabet "H." * The pretibial area, scalp, forehead, and cheekbones are all represented by the letter "M."  The basal cell carcinoma found on the trunk or extremities is denoted by the letter "L."

Treatment Options For Basal Cell Carcinoma  

There are non-surgical and surgical treatment options. The non-surgical alternatives are referred to as field therapies and comprise the following:
1. Cryotherapy.
2. Electrostatic and capacitance sensing.
3. Imiquimod/5FU (fluorouracil) topically applied to treat minor superficial basal cell carcinoma of the neck, trunk, and extremities.
4. The use of photodynamic treatment. 

Cryotherapy                                          

The use of extremely low temperatures created by cryogens to kill aberrant tissues is known as cryotherapy. Liquid air and carbon dioxide snow were the first cryogens to be employed.  In the 1940s, liquid nitrogen became accessible. 
The second mechanism of cryotherapy is ischemia necrosis of the tissue, which results in the creation of ice crystals that break cell membranes. The ideal temperature for benign lesions is -20 degrees Celsius, and the ideal temperature for carcinomas is between 50 and 60 degrees Celsius.  For carcinomas, two free thaw cycles are necessary.
It takes between 40 and 90 seconds to reach this temperature. 

Methods of Cryotherapy

 Cryotherapy techniques consist of the following:
• Open method: After applying pressure, liquid nitrogen is sprayed on the tumor.
• Semi-open method: The liquid nitrogen in the target region is covered and targeted by a cone or plate.
• Closed or touch method: The skin is probed with a liquid nitrogen-cooled instrument. 

The following are possible cryotherapy side effects:
• Anguish.
• Radiation.
• Injuries.
• Hyperpigmentation.
• Skin-implanted veins. 

Curettage and Electrodessication

• Curette the lesion down to 4 mm beyond its edge, then apply electrodessication.
• Electrocautery is used at a depth of 1 mm on the tumor's deep margins.
• Curettettage and electrodesiccation are used three times.
• It is applied to superficial lesions that are wide and low-risk. 

Photodynamic Therapy

One can apply a photosensitizing agent topically or systemically.  Tumor foci are irradiated using the proper wavelength of light.  In the presence of molecular oxygen, radiation activates the photosensitizer, starting a photochemical reaction. As a result, singlet oxygen is produced, which has the following effects:
• Direct killing of tumor cells.
• Damage to the tiny blood vessels.
• Provocation of an inflammatory response locally. 

Another kind of photodynamic therapy is radiotherapy.  A tumor that is radiosensitive is basal cell carcinoma.  Patients who are elderly, frail, or have low performance status undergo radiation therapy.  The drawbacks include an inability to obtain sufficient margins, an elevated chance of developing another cancer, and a lack of tissue accessible for histology. 

Surgery for Basal Cell Carcinoma

Basal cell carcinoma may be treated with wide local excision.  A margin of 4 mm should be used when the tumor is smaller than 2 cm.  A margin of 6 to 10 mm should be used when the tumor is larger than 2 cm. 
Frederick Mohs wrote a 1938 description of Mohs micrographic surgery. It is a surgical treatment that is performed in stages, with excision continuing until a negative margin is reached, and then reconstruction taking place. 

The benefit of Mohs micrographic surgery is that it provides the best possible margin in locations where tissue preservation is challenging from a cosmetic standpoint.  Following excision, tissue mapping, a quick on-site assessment, and a review of the margin site are completed. 
The Mohs micrographic surgery has a recurrence rate of just 1.When it comes to treating basal cell carcinoma, Mohs micrographic surgery has the lowest recurrence rate—1 percent—of all the available methods. 
Mohs micrographic surgery should be considered for the patients listed below:  Aggressive characteristics in morpheaform or other basal cell carcinomas.  Marginally defined poorly.tumor recurrence.  Sensitive regions of the body like the eyes or nose. 

Treatment Of Locally Advanced Basal Cell Carcinoma

The characteristics of a locally progressed basal cell carcinoma are as follows:
• There is cranial nerve involvement.
• The head is involved.
• The tumor is larger than 4 centimeters.
• Involvement of vital components, such as the eyes. 
Vismodegib is a tiny molecule inhibitor of the hedgehog signaling pathway that can be used in systemic therapy for locally progressed basal cell carcinoma based on this route. 
Sonidegib is the second medication that functions as an inhibitor of the hedgehog signaling pathway; studies have showed a 33 percent response rate in locally advanced basal cell carcinoma and a 43 percent response rate in metastatic basal cell carcinoma. 

Follow Up

The patient needs to have six to twelve monthly skin exams as part of a routine follow-up, particularly in the following situations:
• Cancers in high-risk regions
• Skin affected by the sun everywhere.
• Syndromes linked to basal cell carcinoma
• Those who say no to additional surgery.
• Inadequate removal. 
Forty percent of cases following treatment can evolve into a second primary basal cell carcinoma. Sixty-six percent of basal cell carcinoma recurrences happen within three years, and the remainder occurrences happen within five years. 

Squamous Cell Carcinoma

This is the second most prevalent type of skin cancer. It is a malignant tumor that originates from the epidermis' keratinizing cells.  Compared to women, men are more likely to be impacted.  As people age, squamous cell carcinoma incidence rises.  The greatest risk factor for squamous cell carcinoma is the accumulation of solar damage and exposure. 
On regularly dividing keratinocytes, UV light has direct carcinogenic consequences.  Tumor development and multiplication can be accelerated by unrepaired mutations.  People with fair skin who live close to the equator are more susceptible to squamous cell carcinoma; • Continuous UV exposure contributes significantly more to the disease than intense, sporadic exposure.

Etiology  

• Rays of ionizing radiation encountered.
• Past and present smoking history.
• Mutations in genes.
• The p53 gene is silenced by UV radiation.
• Immunosuppression in those undergoing transplants.
• Other autoimmune diseases, lymphomas, and leukemias are also associated with an increased risk of squamous cell carcinoma. 

Subtypes 5 and 16 of the human papillomavirus are among the risk factors.  Infections with the human immunodeficiency virus (HIV).
Chemicals such as arsenical compounds, coal tar, petroleum, and PUVA (psoralen plus ultraviolet-A radiation) therapy can predispose people to squamous cell carcinoma. 

Long-term burn scars, chronic venous ulcers, chronic osteomyelitis sinuses, vaccination sites, and Marjolin's ulcers can all develop squamous cell carcinoma.  Vemurafinib is used to suppress BRAF in BRAF-positive melanomas. 

 The following genetic disorders are linked to squamous cell carcinoma:
- Albinism; Xeroderma pigmentosum. 

Precursor Lesions For Squamous Cell Carcinoma

Actinic keratosis is currently categorized as a continuum of lesions. It is thought to be a precursor lesion for squamous cell cancer. Actinic keratosis is characterized by the following features:
• Dyskeratosis.
• Atypia of partial thickness of cells.
• Inflammation beneath the skin. The basement membrane is intact. 
Actinic keratosis, which can appear macroscopically as a papular or macular lesion with or without keratinous surfaces (20% will become an SCC). 

 A keratin horn is a keratinous surface that is taller than its base diameter (10% contain underlying SCC). Actinic keratosis is linked to it. 

Treatment of Actinic Keratosis

The most popular treatment for actinic keratosis is cryotherapy. Imiquimod and 5 Fluorouracil can be used topically. Actinic keratosis can be treated with photodynamic treatment. One of the therapy options is electrodesiccation and cauterization. 
Chemical peels, dermabrasion, and carbon dioxide lasers are some more treatment options. Squamous cell carcinoma in situ, often known as Bowen's disease, is another significant ailment that does not penetrate the basement membrane.  The most typical site of Bowen's disease observation is a slowly growing erythematous scaly plaque on the mucocutaneous surfaces. 

Topical therapy options include imiquimod and 5 fluorouracil.
If a lesion is big or recurrent, Mohs micrographic surgery can be performed (4mm).

Clinical Features of Invasive Squamous Cell Carcinoma

On surfaces exposed to the sun, invasive squamous cell carcinoma is observed.  The lesions may appear as smooth nodules, verrucous, papillomatous, or ulcerating.  Eventually, erosion and ulceration become apparent.  The skin around the inflamed and indurated edges is everted.

Squamous cell carcinoma adheres to the tissues beneath it and grows both vertically and horizontally. It is possible for squamous cell carcinoma to spread lymphatically.  Twenty percent is the local recurrence rate.  Squamous cell carcinomas are more likely than basal cell carcinomas to metastasize. 

Histology of Squamous Cell Carcinoma

Keratin pearls are a distinctive trait of squamous cell carcinoma, which is characterized by irregular masses of proliferating epidermal cells entering the dermal layer. 

Squamous cell carcinoma can be histologically classified using Broader's grading system; it also dyes positive for cytokeratin 1 and 10. 

Subtypes Of Squamous Cell Carcinoma

• Keratoacanthoma. 
• Verrucous. 
• Spindle cell. 
• Acantholytic. 
• Desmoplastic. 
• Adeno squamous. 

Keratoacanthoma                             

Keratoacanthoma is now recognized as a self-healing squamous cell carcinoma, while it was formerly thought to be a precursor lesion for the disease.  With a 2:1 male-to-female ratio, it is more common in men than in women.  Sun-exposed areas are the site of occurrence; • Individuals with lighter skin tones and those between the ages of 50 and 70 are more susceptible. 
The cause may be related to smoking and exposure to chemicals that cause cancer, as well as human papillomavirus infection in the hair follicle during the growth phase.  Keratoacanthoma has symmetry surrounding a crater filled with keratin in the center. 

Keratoacanthoma grows quickly at first, then stabilizes and then starts to recede.
• The preferred course of treatment for keratoacanthoma is excision.
• Differential diagnosis for SCCs that are anaplastic.
• An excision scar looks better on the outside.

Verrucous Carcinoma

 It grows extremely slowly, is a very low-grade carcinoma, and progresses slowly without spreading. Since verrucous carcinoma takes on an aggressive behavior, radiation therapy is not recommended for this condition. 

Prognostic Factors for Squamous Cell Carcinoma

There is no risk of metastasis if the invasion depth is less than 2 mm, but the risk increases if the invasion thickness is greater than 2 mm.  There is a 15–20 percent likelihood of metastasis if the lesion is thicker than 6 mm.  The worst prognosis is for lesions larger than 2 centimeters.  As the Broader's rating rises, the outlook gets worse.  There is a significant chance of a tumor recurrence in the ear and lip. 
The worse prognosis is associated with immunosuppression and squamous cell carcinoma with poorly defined borders.  The prognosis is poor for the following histological subtypes of squamous cell carcinoma:
• Cathexolytic.
• Scleroderma.
• Subtypes that are metaplastic or desmoplastic.
• Both lymphovascular and perineural invasion.

Treatment of Squamous Cell Carcinoma

The two types of treatment for squamous cell carcinoma are surgery and field therapy.  The primary mode of treatment is wide local excision.  Four to six millimeters of the margin must be removed from low-risk lesions when the tumor size is less than two centimeters. 

One centimeter of the margin must be removed from high-risk lesions with tumor sizes larger than two centimeters, poor differentiation, and high-risk locations.  If lymph nodes are palpable or show up on a biopsy, lymph node dissection is performed. 
The following is a list of squamous cell carcinoma indications for adjuvant therapy:
• The positive margin.
• Intrineural encroachment.
• Severe nerve damage.
• Several recurrences at the same location.
• Big lesions. 

Field Therapies 

For minor superficial lesions, cryotherapy combined with curettage and electrodesiccation can be employed;  Radiotherapy can be used for locoregional control in squamous cell carcinomas.
• Limitations associated with outdoor therapy:
• Greater, thicker SCC
• Areas on the central face
• Dense regions that bear hair 

Treatment   

Palliative radiation therapy is an option for squamous cell carcinoma that is incurable.  Squamous cell carcinoma with distant metastases may be treated with radiation and surgery. 

• Below is a list of medications used to treat squamous cell carcinoma:
• Pembrolizumab; nivolumab; cetuximab.
• Cemiplimab, an inhibitor of PD 1.
• Systemic chemotherapy with platinum.
• Agents that target the epidermal growth receptor.
• Squamous cell carcinoma may be treated with chemotherapy-preventive drugs such as isotretinoin.
• Regional metastases and local recurrence.
• Remainder: five years.
• Retinoids

Transplant Related Squamous Cell Carcinoma 

Depending on the degree, kind, and length of immunosuppression; duration—after ten years; forty–six percent after twenty years; skin cancer in immunocompromised people is always more aggressive; solid organ versus hematopoietic transplant; sun-exposed areas; use of sirolimus; lessening of the risk of SCC; prevention—retinoids and sun exposure.

Hope you found this blog helpful for your NEET SS Surgery Skin and Subcutaneous preparation. For more informative and interesting posts like these, keep reading PrepLadder’s blogs.