Histopathology of squamous-cell carcinoma

Squamous-cell carcinoma (SCC), also known as epidermoid carcinoma, comprises a number of different types of

cancer Cancer is a group of diseases involving Cell growth#Disorders, abnormal cell growth with the potential to Invasion (cancer), invade or Metastasis, spread to other parts of the body. These contrast with benign tumors, which do not spread. Po ...

that begin in squamous cells. 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 gr ...

and

digestive tract The gastrointestinal tract (GI tract, digestive tract, alimentary canal) is the tract or passageway of the Digestion, digestive system that leads from the mouth to the anus. The tract is the largest of the body's systems, after the cardiovascula ...

s. The squamous-cell carcinomas of different body sites can show differences in their presented symptoms,

natural history Natural history is a domain of inquiry involving organisms, including animals, fungi, and plants, in their natural environment, leaning more towards observational than experimental methods of study. A person who studies natural history is cal ...

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

, 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 ...

has been associated with SCCs of the

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

, lung, fingers, and anogenital region.

Head and neck cancer

About 90% of cases of

head and neck cancer Head and neck cancer is a general term encompassing multiple cancers that can develop in the head and neck region. These include cancers of the mouth, tongue, gums and lips (oral cancer), voice box ( laryngeal), throat ( nasopharyngeal, orophary ...

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

Skin

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

Thyroid

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

Esophagus

Esophageal cancer Esophageal cancer (American English) or oesophageal cancer (British English) is cancer arising from the esophagus—the food pipe that runs between the throat and the stomach. Symptoms often include dysphagia, difficulty in swallowing and weigh ...

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 condition in its own right. It may be a sensation that suggests difficulty in the passage of solids or l ...

(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 chemo, sometimes CTX and CTx) is the type of cancer treatment that uses one or more anti-cancer drugs (list of chemotherapeutic agents, chemotherapeutic agents or alkylating agents) in a standard chemotherapy re ...

and radiotherapy are commonly used.

Lung

When associated with the lung, it is typically a centrally located large-cell cancer (

non-small-cell lung cancer Non-small-cell lung cancer (NSCLC), or non-small-cell lung carcinoma, is any type of epithelial lung cancer other than small-cell lung cancer (SCLC). NSCLC accounts for about 85% of all lung cancers. As a class, NSCLCs are relatively insensitiv ...

). It often has a paraneoplastic syndrome 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 for total calcium 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 def ...

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

Penis

Human papillomavirus 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 r ...

(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 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 an male accessory gland, accessory gland of the male reproductive system and a muscle-driven mechanical switch between urination and ejaculation. It is found in all male mammals. It differs between species anatomically, chemica ...

, squamous-cell carcinoma is very aggressive in nature. It is difficult to detect as no increase in prostate-specific antigen levels is seen, meaning that the cancer is often diagnosed at an advanced stage.

Vagina and cervix

Squamous cell carcinoma of the vagina spreads slowly and usually stays near the vagina, but may spread to the lungs and liver. This is the most common 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 of the vagina, squamous cell carcinoma, but p ...

Ovary

Ovarian squamous cell carcinoma (oSCC) or ''squamous ovarian carcinoma'' (SOC) is a rare tumor that accounts for 1% of

ovarian cancer Ovarian cancer is a cancerous tumor of an ovary. It may originate from the ovary itself or more commonly from communicating nearby structures such as fallopian tubes or the inner lining of the abdomen. The ovary is made up of three different ...

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 neglected tropical helminthiasis, disease caused by parasitism, parasitic Schistosoma, flatworms called schistosomes. It affects both humans and animals. It affects ...

is often SCC.

Eye

Conjunctival squamous cell carcinoma and corneal intraepithelial neoplasia comprise ocular surface squamous neoplasia (OSSN).

Diagnosis

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 a set of information the physicians collect over medical interviews. It involves the patient, and ev ...

physical examination In a physical examination, medical examination, clinical examination, or medical checkup, a medical practitioner examines a patient for any possible medical signs or symptoms of a Disease, medical condition. It generally consists of a series of ...

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 revea ...

may suggest a squamous-cell carcinoma, but a

biopsy A biopsy is a medical test commonly performed by a surgeon, interventional radiologist, an interventional radiologist, or an interventional cardiology, interventional cardiologist. The process involves the extraction of sampling (medicine), sample ...

for

histopathology Histopathology (compound of three Greek words: 'tissue', 'suffering', and '' -logia'' 'study of') is the microscopic examination of tissue in order to study the manifestations of disease. Specifically, in clinical medicine, histopatholog ...

generally establishes the diagnosis. TP63 staining is the main histological marker for squamous-cell carcinoma. In addition, TP63 is an essential transcription factor to establish identity of the squamous cells. File:Squamous Cell Carcinoma well differentiated Left upper paraspinal back with adjacent actinic keratosis.jpg, SCC well-differentiated, left upper paraspinal back marked for biopsy with adjacent actinic keratosis File:Squamous Cell Carcinoma Left Lateral Canthus.jpg, SCC, left lateral canthus marked for biopsy File:Squamous Cell Carcinoma Left Ventral Forearm.jpg, SCC, 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 change into various types of cells and proliferate indefinitely to produce more of the same stem cell. They are the earliest type of cell ...

of epithelial lineage or characteristics. SCCs arise from

squamous cell Epithelium or epithelial tissue is a thin, continuous, protective layer of Cell (biology), cells with little extracellular matrix. An example is the epidermis, the outermost layer of the skin. Epithelial (Mesothelium, mesothelial) tissues line ...

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, also known as base 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 epithelial tis ...

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 spreading 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, ...

, 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 ICD, International Statistical Classification of Diseases and Related Health Problems for tumor diseases. This classification is widely used by ...

(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; the term is most familiar as a characterization of cancer. A ''malignant'' tumor contrasts with a non-cancerous benign tumor, ''benign'' tumor in that a malig ...

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 (papillary thyroid carcinoma, PTC) 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 ...

(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.

Other histopathologic subtypes

* Erythroplasia of Queyrat * Marjolin's ulcer 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 sloughin ...

or burn wound. More recent evidence, however, suggests that genetic differences exist between SCC and Marjolin's ulcer, 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 found in the epidermis, the outermost layer of the skin. In humans, they constitute 90% of epidermal skin cells. Basal cells in the basal layer (''stratum basale'') of the skin are sometimes referre ...

acantholysis. * basaloid squamous-cell carcinoma is mostly found in or near the tongue, tonsils, or larynx, but may also occur in the lung or elsewhere. * 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. * 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 cell, plant and Fungus, fungal Cell (biology), cells and some protist, animal, and bacterial cells. Vacuoles are essentially enclosed compartments which are filled with water ...

s corresponding to markedly dilated

endoplasmic reticulum The endoplasmic reticulum (ER) is a part of a transportation system of the eukaryote, eukaryotic cell, and has many other important functions such as protein folding. The word endoplasmic means "within the cytoplasm", and reticulum is Latin for ...

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

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 Nucleu ...

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