Cutaneous Squamous Cell Carcinoma (images and abstracts):

Squamous cell carcinoma  is the second most common form of skin cancer. It is usually noted on sun damaged skin in elderly patients. 

Visit:  Bowen's Disease ;  Actinic Keratosis ;  Epidermal Tumours .

Etiological factors may be intrinsic, extrinsic or both.
The extrinsic factors are  ultraviolet sunlight exposure , chemicals (arsenic, polycyclic aromatic hydrocarbons and those found in tobacco product), Human papilloma virus (HPV-16 is present in squamous cell carcinoma of genital and  periungual areas). The intrinsic factors include skin pigmentation, primary dermatoses and hereditary conditions like xeroderma pigmentosa and oculocutaneous albinism.
There is an increased incidence of squamous cell carcinoma in immunosuppressed patients . These tumours seem to  behave more aggressively when present in organ transplant recipients and HIV postive patients.

HISTOLOGIC SUBTYPES OF SQUAMOUS CELL CARCINOMA:

 CONVENTIONAL  SQUAMOUS CELL CARCINOMA:

There are nests of atypical squamous cell which arise from the epidermis and extends into the dermis.The atypical squamous cells are large with pleomorphic nuclei. Intercellular bridges are present. Numerous atypical mitotic figures are noted. There are large amounts of keratin with keratin pearl formation depending on the differentiation of the tumour. There is  evidence of individual cell keratinization.
Presence of invasion of is essential for the  diagnosis.
Immunohistochemistry reveals positivity with EMA and cytokeratin. Vimentin may be positive in poorly differentiated tumour.
Clue to diagnosis:  Evidence of perineural lymphocytes is suggestive of perineural invasion in deeper sections.  

IMAGE LINKS:  Image1 ;  Image2 ; Image 3

 SPINDLE  CELL /PLEOMORPHIC/SARCOMATOID VARIANT:

This rare variant  usually presents as an exophytic mass on  sun exposed skin, in elderly patients. Microscopically,  there are whorls and fascicles of atypical squamous cells intermingled with collagen fibres. Pleomorphic giant cells may be present. The spindle cells display elongated pleomorphic, vesicular nuclei and eosinophilic cytoplasm. Numerous mitotic figures are present. Presence of dyskeratotic cells and evidence of continuity with the epidermis assist in the diagnosis of squamous cell carcinoma.  Image Link
Differential diagnosis include melanoma , atypical fibroxanthoma , leiomyosarcoma.
Immunohistochemistry reveals that the tumour stains postively with EMA , cytokeratin and vimentin. These lesions are negative with S100 and other  mesenchymal markers.

ADENOID/ACANTHOLYTIC/PSEUDOGLANDULAR:

Clinically, the lesion  usually presents as an ulcer or crusted nodule  on the head and neck region. Microscopically,  the tumour cells are arranged in nests and cords and there are clefts produced by acantholysis of cells. These spaces resemble glandular structures. Dysplastic cells may be present within  the spaces.  CASE LINK
This variant often arises from acantholytic solar keratosis.

VERRUCOUS CARCINOMA:

These are slow growing large warty tumours usually noted at sites of chronic irritation.
There are three clinical variants- oral , plantar and anogenital.
Microscopicaly verrucous carcinoma are exophytic or endophytic masses characterized by hyperkeratosis, parakeratosis and nests of well differentiated squamous epithelium with little atypia
extending into the dermis. The rete ridges have  a bulbous appearance. There is low mitotic activity.        IMAGE LINK
This lesion slowly invades into underlying soft tissue and bone, if left untreated.

SMALL CELL  NONKERATINIZING VARIANT:

Small cell nonkeratinizing variant of squamous cell carcinoma  may be associated with overlying in-situ sqamous cell carcinoma  and the tumour infiltrates in cohesive nests in a backround of dense inflammation and desmoplasia. Microscopically  the  lesion may resemble merkel cell carcinoma.

OTHER RARE VARIANTS:

Clear cell or signet ring
Bowenoid  
Pigmented
Pseudovascular Image1 ;  Image2 ;  Image3 ; Image4 ; Image5 .
Desmoplastic
Infiltrative
Rhabdoid differentiation

HISTOLOGICAL  PARAMETERS:

Site of tumour-
Tumour on the lip,eyelid,nose and ear are associated with high incidence of recurrence and metastasis.

Size of tumour-   IMAGE LINK
Tumour more than 20mm in diameter is at greater risk of recurrence and metastasis.  

Grading- 
                     Broder's Classification:

Well differentiated (Grade I)-   < 25% undifferentiated cells
Moderately differentiated (Grade II)- <50% undiff. cells
Poorly differentiated (Grade III)- <75% undiff. cells
Anaplastic/pleomorphic (Grade IV)- >75% undiff. cells

Histologic subtypes-
Verrucous carcinoma has a high recurrence rate but rarely metastasises.
Spindle cell variant with desmoplasia and pseudo-angiosarcomatous squamous cell carcinoma has a higher metastatic rate.

Growth pattern-
Tumour infiltrating in small nests, isolated strands, clusters and single cells are at higher risk for recurrence and metastasis than those with broad pushing borders.

Tumour thickness and risk of recurrence and metastasis -
2mm or less- Low risk
4mm and above- High risk
More than 10mm- Very high risk