Histopathology of squamous-cell carcinoma

Squamous-cell carcinomas (SCCs), also known as epidermoid carcinomas, comprise a number of different types of

cancer Cancer is a group of diseases involving abnormal cell growth with the potential to invade or spread to other parts of the body. These contrast with benign tumors, which do not spread. Possible signs and symptoms include a lump, abnormal b ...

that begin in

squamous cells Epithelium or epithelial tissue is one of the four basic types of animal tissue, along with connective tissue, muscle tissue and nervous tissue. It is a thin, continuous, protective layer of compactly packed cells with a little intercellu ...

. These cells form on the surface of the skin, on the lining of hollow organs in the body, and on the lining of the

respiratory The respiratory system (also respiratory apparatus, ventilatory system) is a biological system consisting of specific organs and structures used for gas exchange in animals and plants. The anatomy and physiology that make this happen varies grea ...

and

digestive tract The gastrointestinal tract (GI tract, digestive tract, alimentary canal) is the tract or passageway of the digestive system that leads from the mouth to the anus. The GI tract contains all the major organs of the digestive system, in humans a ...

s. Common types include: *

Squamous-cell skin cancer Squamous-cell skin cancer, also known as cutaneous squamous-cell carcinoma (cSCC), is one of the main types of skin cancer along with basal cell cancer and melanoma. It usually presents as a hard lump with a scaly top but can also form an ulcer. O ...

: A type of

skin cancer Skin cancers are cancers that arise from the skin. They are due to the development of abnormal cells that have the ability to invade or spread to other parts of the body. There are three main types of skin cancers: basal-cell skin cancer (BCC) ...

Squamous-cell carcinoma of the lung Squamous-cell carcinoma (SCC) of the lung is a histologic type of non-small-cell lung carcinoma (NSCLC). It is the second most prevalent type of lung cancer after lung adenocarcinoma and it originates in the bronchi. Its tumor cells are characteriz ...

: A type of

lung cancer Lung cancer, also known as lung carcinoma (since about 98–99% of all lung cancers are carcinomas), is a malignant lung tumor characterized by uncontrolled cell growth in tissue (biology), tissues of the lung. Lung carcinomas derive from tran ...

* Squamous-cell thyroid carcinoma: A type of

thyroid cancer Thyroid cancer is cancer that develops from the tissues of the thyroid gland. It is a disease in which cells grow abnormally and have the potential to spread to other parts of the body. Symptoms can include swelling or a lump in the neck. C ...

* Esophageal squamous-cell carcinoma: A type of

esophageal cancer Esophageal cancer is cancer arising from the esophagus—the food pipe that runs between the throat and the stomach. Symptoms often include difficulty in swallowing and weight loss. Other symptoms may include pain when swallowing, a hoarse voice ...

Squamous-cell carcinoma of the vagina Squamous-cell carcinoma of the vagina is a potentially invasive type of cancer that forms in the tissues of the vagina. Though uncommon, squamous-cell cancer of the vagina (SCCV) is the most common type of vaginal cancer. It is further subdivide ...

: A type of

vaginal cancer Vaginal cancer is an extraordinarily rare form of cancer that develops in the tissue of the vagina. Primary vaginal cancer originates from the vaginal tissue – most frequently squamous cell carcinoma, but primary vaginal adenocarcinoma, sarcoma ...

Despite sharing the name "squamous-cell carcinoma", the SCCs of different body sites can show differences in their presented

symptom Signs and symptoms are the observed or detectable signs, and experienced symptoms of an illness, injury, or condition. A sign for example may be a higher or lower temperature than normal, raised or lowered blood pressure or an abnormality showin ...

s, natural history,

prognosis Prognosis (Greek: πρόγνωσις "fore-knowing, foreseeing") is a medical term for predicting the likely or expected development of a disease, including whether the signs and symptoms will improve or worsen (and how quickly) or remain stabl ...

, and response to treatment.

By body location

Human papillomavirus infection Human papillomavirus infection (HPV infection) is caused by a DNA virus from the ''Papillomaviridae'' family. Many HPV infections cause no symptoms and 90% resolve spontaneously within two years. In some cases, an HPV infection persists and res ...

has been associated with SCCs of the

oropharynx The pharynx (plural: pharynges) is the part of the throat behind the mouth and nasal cavity, and above the oesophagus and trachea (the tubes going down to the stomach and the lungs). It is found in vertebrates and invertebrates, though its struct ...

, lung, fingers, and anogenital region.

Head and neck cancer

About 90% of cases of

head and neck cancer Head and neck cancer develops from tissues in the lip and oral cavity (mouth), larynx (throat), salivary glands, nose, sinuses or the skin of the face. The most common types of head and neck cancers occur in the lip, mouth, and larynx. Symptoms ...

(cancer of the mouth, nasal cavity, nasopharynx, throat and associated structures) are due to SCC.

Skin

Squamous cell carcinoma of the skin Squamous-cell skin cancer, also known as cutaneous squamous-cell carcinoma (cSCC), is one of the main types of skin cancer along with basal cell cancer and melanoma. It usually presents as a hard lump with a scaly top but can also form an ulcer. O ...

is the second most common skin cancer, accounting for over 1 million cases in the United States each year.

Thyroid

Primary squamous-cell thyroid carcinoma shows an aggressive biological phenotype resulting in poor prognosis for patients.

Esophagus

Esophageal cancer Esophageal cancer is cancer arising from the esophagus—the food pipe that runs between the throat and the stomach. Symptoms often include difficulty in swallowing and weight loss. Other symptoms may include pain when swallowing, a hoarse voice ...

may be due to either esophageal squamous cell carcinoma (ESCC) or

adenocarcinoma Adenocarcinoma (; plural adenocarcinomas or adenocarcinomata ) (AC) is a type of cancerous tumor that can occur in several parts of the body. It is defined as neoplasia of epithelial tissue that has glandular origin, glandular characteristics, or ...

(EAC). SCCs tend to occur closer to the mouth, while adenocarcinomas occur closer to the stomach.

Dysphagia Dysphagia is difficulty in swallowing. Although classified under "symptoms and signs" in ICD-10, in some contexts it is classified as a disease#Terminology, condition in its own right. It may be a sensation that suggests difficulty in the passag ...

(difficulty swallowing, solids worse than liquids) and painful swallowing are common initial symptoms. If the disease is localized, surgical removal of the affected esophagus may offer the possibility of a cure. If the disease has spread,

chemotherapy Chemotherapy (often abbreviated to chemo and sometimes CTX or CTx) is a type of cancer treatment that uses one or more anti-cancer drugs (chemotherapeutic agents or alkylating agents) as part of a standardized chemotherapy regimen. Chemotherap ...

and radiotherapy are commonly used.

Lung

When associated with the lung, it is typically a centrally located large-cell cancer (nonsmall-cell lung cancer). It often has a

paraneoplastic syndrome A paraneoplastic syndrome is a syndrome (a set of signs and symptoms) that is the consequence of a tumor in the body (usually a cancerous one), specifically due to the production of chemical signaling molecules (such as hormones or cytokines) by ...

causing ectopic production of

parathyroid hormone-related protein Parathyroid hormone-related protein (PTHrP) is a proteinaceous hormone and a member of the parathyroid hormone family secreted by mesenchymal stem cells. It is occasionally secreted by cancer cells (for example, breast cancer, certain types of ...

, resulting in

hypercalcemia Hypercalcemia, also spelled hypercalcaemia, is a high calcium (Ca2+) level in the blood serum. The normal range is 2.1–2.6 mmol/L (8.8–10.7 mg/dL, 4.3–5.2 mEq/L), with levels greater than 2.6 mmol/L defined as hypercalcemi ...

, but paraneoplastic syndrome is more commonly associated with small-cell lung cancer. It is primarily due to smoking.

Penis

Human papillomavirus (HPV), primarily HPV 16 and 18, are strongly implicated in the development of SCC of the penis. Three carcinomas ''in situ'' are associated with SCCs of the penis: #

Bowen's disease Squamous-cell skin cancer, also known as cutaneous squamous-cell carcinoma (cSCC), is one of the main types of skin cancer along with basal cell cancer and melanoma. It usually presents as a hard lump with a scaly top but can also form an ulcer. ...

presents as leukoplakia on the shaft. Around a third of cases progress to SCC. # Erythroplasia of Queyrat, a variation of Bowen's disease, presents as erythroplakia on the glans. # Bowenoid papulosis, which histologically resembles Bowen disease, presents as reddish papules.

Prostate

When associated with the

prostate The prostate is both an Male accessory gland, accessory gland of the male reproductive system and a muscle-driven mechanical switch between urination and ejaculation. It is found only in some mammals. It differs between species anatomically, ...

, squamous-cell carcinoma is very aggressive in nature. It is difficult to detect as no increase in

prostate-specific antigen Prostate-specific antigen (PSA), also known as gamma-seminoprotein or kallikrein-3 (KLK3), P-30 antigen, is a glycoprotein enzyme encoded in humans by the ''KLK3'' gene. PSA is a member of the kallikrein-related peptidase family and is secreted b ...

levels is seen, meaning that the cancer is often diagnosed at an advanced stage.

Vagina and cervix

Vaginal SCC spreads slowly and usually stays near the vagina, but may spread to the lungs and liver. This is the most common type of

Bladder

Most bladder cancer is transitional cell, but bladder cancer associated with

schistosomiasis Schistosomiasis, also known as snail fever, bilharzia, and Katayama fever, is a disease caused by parasitic flatworms called schistosomes. The urinary tract or the intestines may be infected. Symptoms include abdominal pain, diarrhea, bloody s ...

is often SCC.

Diagnosis

Oral cancer (1) squamous cell carcinoma histopathology

Cytopathology of nonkeratinizing squamous cell carcinoma

Medical history The medical history, case history, or anamnesis (from Greek: ἀνά, ''aná'', "open", and μνήσις, ''mnesis'', "memory") of a patient is information gained by a physician by asking specific questions, either to the patient or to other peo ...

physical examination In a physical examination, medical examination, or clinical examination, a medical practitioner examines a patient for any possible medical signs or symptoms of a medical condition. It generally consists of a series of questions about the patien ...

and

medical imaging Medical imaging is the technique and process of imaging the interior of a body for clinical analysis and medical intervention, as well as visual representation of the function of some organs or tissues (physiology). Medical imaging seeks to rev ...

may suggest a squamous cell carcinoma, but a

biopsy A biopsy is a medical test commonly performed by a surgeon, interventional radiologist, or an interventional cardiologist. The process involves extraction of sample cells or tissues for examination to determine the presence or extent of a diseas ...

for

histopathology Histopathology (compound of three Greek words: ''histos'' "tissue", πάθος ''pathos'' "suffering", and -λογία '' -logia'' "study of") refers to the microscopic examination of tissue in order to study the manifestations of disease. Spe ...

generally establishes the diagnosis.

TP63 Tumor protein p63, typically referred to as p63, also known as transformation-related protein 63 is a protein that in humans is encoded by the ''TP63'' (also known as the '' p63'') gene. The ''TP63'' gene was discovered 20 years after the discove ...

staining is the main histological marker for Squamous cell carcinoma. In addition, TP63 is an essential transcription factor to establish squamous cell identity. File:Squamous Cell Carcinoma well differentiated Left upper paraspinal back with adjacent actinic keratosis.jpg, Squamous cell carcinoma, well differentiated, left upper paraspinal back marked for biopsy with adjacent actinic keratosis File:Squamous Cell Carcinoma Left Lateral Canthus.jpg, Squamous cell carcinoma, left lateral canthus marked for biopsy File:Squamous Cell Carcinoma Left Ventral Forearm.jpg, Squamous cell carcinoma, left ventral forearm

Classification

Cancer can be considered a very large and exceptionally heterogeneous family of malignant diseases, with squamous cell carcinomas comprising one of the largest subsets. All SCC lesions are thought to begin via the repeated, uncontrolled division of cancer

stem cells In multicellular organisms, stem cells are undifferentiated or partially differentiated cells that can differentiate into various types of cells and proliferate indefinitely to produce more of the same stem cell. They are the earliest type o ...

of epithelial lineage or characteristics. SCCs arise from

squamous cell Epithelium or epithelial tissue is one of the four basic types of animal tissue, along with connective tissue, muscle tissue and nervous tissue. It is a thin, continuous, protective layer of compactly packed cells with a little intercellula ...

s, which are flat cells that line many areas of the body. Some of which are keratinocytes. Accumulation of these cancer cells causes a microscopic focus of abnormal cells that are, at least initially, locally confined within the specific tissue in which the progenitor cell resided. This condition is called squamous cell carcinoma ''in situ'', and it is diagnosed when the tumor has not yet penetrated the

basement membrane The basement membrane is a thin, pliable sheet-like type of extracellular matrix that provides cell and tissue support and acts as a platform for complex signalling. The basement membrane sits between Epithelium, epithelial tissues including mesot ...

or other delimiting structure to invade adjacent tissues. Once the lesion has grown and progressed to the point where it has breached, penetrated, and infiltrated adjacent structures, it is referred to as " invasive" squamous cell carcinoma. Once a carcinoma becomes invasive, it is able to spread to other organs and cause the formation of a

metastasis Metastasis is a pathogenic agent's spread from an initial or primary site to a different or secondary site within the host's body; the term is typically used when referring to metastasis by a cancerous tumor. The newly pathological sites, then, ...

, or "secondary tumor".

Tissue of origin

The

International Classification of Diseases for Oncology The International Classification of Diseases for Oncology (ICD-O) is a domain-specific extension of the International Statistical Classification of Diseases and Related Health Problems for tumor diseases. This classification is widely used by canc ...

(ICD-O) system lists a number of morphological subtypes and variants of

malignant Malignancy () is the tendency of a medical condition to become progressively worse. Malignancy is most familiar as a characterization of cancer. A ''malignant'' tumor contrasts with a non-cancerous ''benign'' tumor in that a malignancy is not s ...

squamous cell

neoplasm A neoplasm () is a type of abnormal and excessive growth of tissue. The process that occurs to form or produce a neoplasm is called neoplasia. The growth of a neoplasm is uncoordinated with that of the normal surrounding tissue, and persists ...

s, including: *

Papillary thyroid carcinoma Papillary thyroid cancer or papillary thyroid carcinoma is the most common type of thyroid cancer, representing 75 percent to 85 percent of all thyroid cancer cases.Chapter 20 in: 8th edition. It occurs more frequently in women and presents in th ...

(code 8050/3) * Verrucous squamous cell carcinoma (code 8051/3) * Papillary squamous cell carcinoma (code 8052/3) * Squamous cell carcinoma (code 8070/3) * Large-cell keratinizing squamous cell carcinoma (code 8071/3) * Large-cell nonkeratinizing squamous cell carcinoma (code 8072/3) * Small-cell keratinizing squamous cell carcinoma (code 8073/3) * Spindle-cell squamous cell carcinoma (code 8074/3) It is also known as spindle-cell carcinoma, and is a subtype characterized by spindle-shaped atypical cells. * Adenoid/pseudoglandular squamous cell carcinoma (code 8075/3) * Intraepidermal squamous cell carcinoma (code 8081/3) * Lymphoepithelial carcinoma (code 8082/3) Other variants of SCCs are recognized under other systems, such as

keratoacanthoma Keratoacanthoma (KA) is a common low-grade (unlikely to metastasize or invade) rapidly-growing skin tumour that is believed to originate from the hair follicle (pilosebaceous unit) and can resemble squamous cell carcinoma. The defining characteris ...

Other histopathologic subtypes

* Erythroplasia of Queyrat *

Marjolin's ulcer Marjolin's ulcer refers to an aggressive ulcerating squamous cell carcinoma presenting in an area of previously traumatized, chronically inflamed, or scarred skin.Freedberg, et al. (2003). ''Fitzpatrick's Dermatology in General Medicine''. (6th ed ...

is a type of SCC that arises from a nonhealing

ulcer An ulcer is a discontinuity or break in a bodily membrane that impedes normal function of the affected organ. According to Robbins's pathology, "ulcer is the breach of the continuity of skin, epithelium or mucous membrane caused by sloughing o ...

or burn wound. More recent evidence, however, suggests that genetic differences exist between SCC and

, which were previously underappreciated. One method of classifying squamous cell carcinomas is by their appearance under microscope. Subtypes may include: * Adenoid squamous cell carcinoma (also known as pseudoglandular squamous cell carcinoma) is characterized by a tubular microscopic pattern and

keratinocyte Keratinocytes are the primary type of Cell (biology), cell found in the epidermis (skin), epidermis, the outermost layer of the skin. In humans, they constitute 90% of epidermal skin cells. Basal cells in the stratum basale, basal layer (''str ...

acantholysis Acantholysis is the loss of intercellular connections, such as desmosomes, resulting in loss of cohesion between keratinocytes,Kumar, Vinay; Fausto, Nelso; Abbas, Abul (2004) ''Robbins & Cotran Pathologic Basis of Disease'' (7th ed.). Saunders. ...

. * Basaloid squamous cell carcinoma is characterized by a predilection for the tongue base. * Clear-cell squamous cell carcinoma (also known as clear-cell carcinoma of the skin) is characterized by keratinocytes that appear clear as a result of

hydropic swelling Hydropic swelling is intracellular edema of keratinocytes, often seen with viral infections. See also * Skin lesion * Skin disease * List of skin diseases Many skin conditions affect the human integumentary system—the organ system coverin ...

. * Signet ring-cell squamous cell carcinoma (occasionally rendered as signet ring-cell squamous cell carcinoma) is a histological variant characterized by concentric rings composed of keratin and large

vacuole A vacuole () is a membrane-bound organelle which is present in plant and fungal cells and some protist, animal, and bacterial cells. Vacuoles are essentially enclosed compartments which are filled with water containing inorganic and organic mo ...

s corresponding to markedly dilated

endoplasmic reticulum The endoplasmic reticulum (ER) is, in essence, the transportation system of the eukaryotic cell, and has many other important functions such as protein folding. It is a type of organelle made up of two subunits – rough endoplasmic reticulum ( ...

. These vacuoles grow to such an extent that they radically displace the

cell Cell most often refers to: * Cell (biology), the functional basic unit of life Cell may also refer to: Locations * Monastic cell, a small room, hut, or cave in which a religious recluse lives, alternatively the small precursor of a monastery ...

nucleus Nucleus ( : nuclei) is a Latin word for the seed inside a fruit. It most often refers to: *Atomic nucleus, the very dense central region of an atom *Cell nucleus, a central organelle of a eukaryotic cell, containing most of the cell's DNA Nucle ...

toward the cell membrane, giving the cell a distinctive superficial resemblance to a "signet ring" when viewed under a

microscope A microscope () is a laboratory instrument used to examine objects that are too small to be seen by the naked eye. Microscopy is the science of investigating small objects and structures using a microscope. Microscopic means being invisibl ...

. File:SkinTumors-P6070232.JPG, Adenoid squamous-cell carcinoma File:SkinTumors-P6020140.JPG, Basaloid squamous-cell carcinoma File:SkinTumors-P5290109.JPG, Clear-cell squamous-cell carcinoma File:SkinTumors-P5300131.JPG, Spindle-cell squamous-cell carcinoma

Prevention

Studies have found evidences for an association between diet and skin cancers, including SCC. The consumption of high-fat dairy foods increases SCC tumor risk in people with previous skin cancer. Green leafy vegetables may help prevent development of subsequent SCC and multiple studies found that raw vegetables and fruits are significantly protective against SCC risk. On the other hand, consumption of whole milk, yogurt, and cheese may increase SCC risk in susceptible people. In addition, meat and fat dietary pattern can increase the risk of SCC in people without a history of SCC, but the association is again more prominent in people with a history of skin cancer. Tobacco smoking and a dietary pattern characterized by high beer and liquor intake also increase the risk of SCC significantly.

References

{{Authority control Cancer Oncology Epithelium