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Due to the diverse nature of salivary gland tumours, many different terms and classification systems have been used. Perhaps the most widely used currently is that system proposed by the World Health Organization in 2004, which classifies salivary neoplasms as primary or secondary, benign or malignant, and also by tissue of origin. This system defines five broad categories of salivary gland neoplasms:
Benign epithelial tumors
- Pleomorphic adenoma
- Warthin's tumor
- Myoepithelioma
- Basal cell adenoma
- Oncocytoma
- Canalicular adenoma
- Lymphadenoma
- "Sebaceous lymphadenoma"
- "Nonsebaceous lymphadenoma"
- Ductal papilloma
- "Inverted ductal papilloma"
- "Intraductal papilloma"
- "Sialadenoma papilliferum"
- Cystadenoma
- Malignant epithelial tumors
- Acinic cell carcinoma
- Mucoepidermoid carcinoma
- Adenoid cystic carcinoma
- Polymorphous low-grade adenocarcinoma
- Epithelial-myoepithelial carcinoma
- Clear cell carcinoma, not otherwise specified
- Basal cell adenocarcinoma
- Sebaceous carcinoma
- Sebaceous lymphadenocarcinoma
- Cystadenocarcinoma
- Low-grade cribriform cystadenocarcinoma
- Mucinous adenocarcinoma
- Oncocytic carcinoma
- Salivary duct carcinoma
- Salivary duct carcinoma, not otherwise specified
- Adenocarcinoma, not otherwise specified
- Myoepithelial carcinoma
- Carcinoma ex pleomorphic adenoma
- Mammary analogue secretory carcinoma
- Carcinosarcoma
- Metastasizing pleomorphic adenoma
- Squamous cell carcinoma
- Large cell carcinoma
- Lymphoepithelial carcinoma
- Sialoblastoma
- Soft tissue tumors
- Hemangioma
- Hematolymphoid tumors
- Hodgkin lymphoma
- Diffuse large B-cell lymphoma
- Extranodal marginal zone B cell lymphoma
- Secondary tumors (i.e. a tumor which has metastasized to the salivary gland from a distant location)
Others, not included in the WHO classification above, include:
- Intraosseous (central) salivary gland tumors
- Hybrid tumors (i.e. a tumor displaying combined forms of histologic tumor types)
- Hybrid carcinoma
- Others
- Others
- Keratocystoma
- Sialolipoma
The World Health Organization (WHO) classification scheme places neuroendocrine tumors into three main categories, which emphasize the tumor grade rather than the anatomical origin:
- well-differentiated neuroendocrine tumours, further subdivided into tumors with benign and those with uncertain behavior
- well-differentiated (low grade) neuroendocrine carcinomas with low-grade malignant behavior
- poorly differentiated (high grade) neuroendocrine carcinomas, which are the large cell neuroendocrine and small cell carcinomas.
Additionally, the WHO scheme recognizes mixed tumors with both neuroendocrine and epithelial carcinoma features, such as goblet cell cancer, a rare gastrointestinal tract tumor.
Placing a given tumor into one of categories depends on well-defined histological features: size, lymphovascular invasion, mitotic counts, Ki-67 labelling index, invasion of adjacent organs, presence of metastases and whether they produce hormones.
The typical presentation is a rapidly growing mass with associated pain. This may be seen in association with neck lymph node swelling (cervical lymphadenopathy), due to metastases, and facial nerve paralysis.
Traditionally, neuroendocrine tumors have been classified by their anatomic site of origin. NETs can arise in many different areas of the body, and are most often located in the intestine, pancreas or the lungs. The various kinds of cells that can give rise to NETs are present in endocrine glands and are also diffusely distributed throughout the body, most commonly Kulchitsky cells or similar enterochromaffin-like cells, that are relatively more common in the gastrointestinal and pulmonary systems.
NETs include certain tumors of the gastrointestinal tract and of the pancreatic islet cells, certain thymus and lung tumors, and medullary carcinoma of the parafollicular cells of the thyroid. Tumors with similar cellular characteristics in the pituitary, parathyroid, and adrenomedullary glands are sometimes included or excluded.
Within the broad category of neuroendocrine tumors there are many different tumor types: this outline is presented to facilitate retrieving information. Neuroendocrine tumors are uncommon in many of these areas, and frequently represent only a very small proportion of the tumors or cancers at these locations.
- Pituitary gland: Neuroendocrine tumor of the anterior pituitary
- Thyroid gland: Neuroendocrine thyroid tumors, particularly medullary carcinoma
- Parathyroid tumors
- Thymus and mediastinal carcinoid tumors
- Pulmonary neuroendocrine tumors
- bronchus
- pulmonary carcinoid tumors: typical carcinoid (TC; low-grade); atypical carcinoid (AC; intermediate-grade)
- small-cell lung cancer (SCLC)
- large cell neuroendocrine carcinoma of the lung (LCNEC)
- Extrapulmonary small cell carcinomas (ESCC or EPSCC)
- Gastroenteropancreatic neuroendocrine tumors (GEP-NET)
- Foregut GEP-NET (foregut tumors can conceptually encompasses not only NETs of the stomach and proximal duodenum, but also the pancreas, and even thymus, lung and bronchus)
- Pancreatic endocrine tumors (if considered separately from foregut GEP-NET)
- Midgut GEP-NET (from distal half of 2nd part of the duodenum to the proximal two-thirds of the transverse colon)
- appendix, including well differentiated NETs (benign); well differentiated NETs (uncertain malignant potential); well differentiated neuroendocrine carcinoma (with low malignant potential); mixed exocrine-neuroendocrine carcinoma (goblet cell carcinoma, also called adenocarcinoid and mucous adenocarcinoid)
- Hindgut GEP-NET
- Liver and gallbladder
- Adrenal tumors, particularly adrenomedullary tumors
- Pheochromocytoma
- Peripheral nervous system tumors, such as:
- Schwannoma
- paraganglioma
- neuroblastoma
- Breast
- Genitourinary tract
- urinary tract carcinoid tumor and neuroendocrine carcinoma
- ovary
- neuroendocrine tumor of the cervix
- testes
- Merkel cell carcinoma of skin (trabecular cancer)
- Several inherited conditions:
- multiple endocrine neoplasia type 1 (MEN1)
- multiple endocrine neoplasia type 2 (MEN2)
- von Hippel-Lindau (VHL) disease
- neurofibromatosis type 1
- tuberous sclerosis
- Carney complex
SDC are diagnosed by examination of tissue, e.g. a biopsy.
Their histologic appearance is similar to ductal breast carcinoma.
Ductal carcinoma is a type of tumor that primarily presents in the ducts of a gland.
Types include:
- Mammary
- Ductal carcinoma in situ
- Invasive ductal carcinoma
- Pancreatic ductal carcinoma
Presents as painless, slow-growing mass that is firm or hard. Most appear clinically as mixed tumors.
Salivary gland tumours usually present as a lump or swelling in the affected gland which may or may not have been present for a long time. The lump may be accompanied by symptoms of duct blockage (e.g. xerostomia). Usually, in their early stages it is not possible to distinguish a benign tumour from a malignant one. One of the key differentiating symptoms of a malignant growth is nerve involvement. For example signs of facial nerve damage (e.g facial palsy) are associated with malignant parotid tumours. Facial pain, and paraesthesia are also very often associated with a malignant tumours. Other red flag symptoms which may suggest malignancy and warrant further investigation are fixation of the lump to the overlying skin, ulceration and induration of the mucosa.
Some PanNETs do not cause any symptoms, in which case they may be discovered incidentally on a CT scan performed for a different purpose. Symptoms such as abdominal or back pain or pressure, diarrhea, indigestion, or yellowing of the skin and whites of the eyes can arise from the effects of a larger PanNET tumor, either locally or at a metastasis. About 40% of PanNETS have symptoms related to excessive secretion of hormones or active polypeptides and are accordingly labeled as "functional"; the symptoms reflect the type of hormone secreted, as discussed below. Up to 60% of PanNETs are nonsecretory or nonfunctional, in which there is no secretion, or the quantity or type of products, such as pancreatic polypeptide (PPoma), chromogranin A, and neurotensin, do not cause a clinical syndrome although blood levels may be elevated. In total, 85% of PanNETs have an elevated blood marker.
Functional tumors are often classified by the hormone most strongly secreted, for example:
- gastrinoma: the excessive gastrin causes Zollinger–Ellison syndrome (ZES) with peptic ulcers and diarrhea
- insulinoma: hypoglycemia occurs with concurrent elevations of insulin, proinsulin and C peptide
- glucagonoma: the symptoms are not all due to glucagon elevations, and include a rash, sore mouth, altered bowel habits, venous thrombosis, and high blood glucose levels
- VIPoma, producing excessive vasoactive intestinal peptide, which may cause profound chronic watery diarrhea and resultant dehydration, hypokalemia, and achlorhydria (WDHA or pancreatic cholera syndrome)
- somatostatinoma: these rare tumors are associated with elevated blood glucose levels, achlorhydria, cholelithiasis, and diarrhea
- less common types include ACTHoma, CRHoma, calcitoninoma, GHRHoma, GRFoma, and parathyroid hormone–related peptide tumor
In these various types of functional tumors, the frequency of malignancy and the survival prognosis have been estimated dissimilarly, but a pertinent accessible summary is available.
PanNETs are sometimes abbreviated as PETs or PNETs: such use should not to be confused with the primitive neuroectodermal tumor (PNET).
The majority of PanNETs are benign, while some are malignant. The World Health Organization (WHO) classification scheme places neuroendocrine tumors into three main categories, which emphasize the tumor grade rather than the anatomical origin. In practice, those tumors termed well or intermediately differentiated PanNETs in the WHO scheme are sometimes called "islet cell tumors." The high grade subtype, termed neuroendocrine cancer (NEC) in the WHO scheme, is synonymous with "islet cell carcinoma".
The most common clinical features of MEN2B are:
Unlike Marfan syndrome, the cardiovascular system and the lens of the eye are unaffected.Mucosal neuromas are the most consistent and distinctive feature, appearing in 100% of patients. Usually there are numerous yellowish-white, sessile, painless nodules on the lips or tongue, with deeper lesions having normal coloration. There may be enough neuromas in the body of the lips to produce enlargement and a "blubbery lip" appearance. Similar nodules may be seen on the sclera and eyelids.
Histologically, neuromata contain a characteristic adventitious plaque of tissue composed of hyperplastic, interlacing bands of Schwann cells and myelinated fibers overlay the posterior columns of the spinal cord. Mucosal neuromas are made up of nerve cells, often with thickened perineurium, intertwined with one another in a plexiform pattern. This tortuous pattern of nerves is seen within a background of loose endoneurium-like fibrous stroma.
Adrenocortical carcinoma may present differently in children and adults. Most tumors in children are functional, and virilization is by far the most common presenting symptom, followed by Cushing's syndrome and precocious puberty. Among adults presenting with hormonal syndromes, Cushing's syndrome alone is most common, followed by mixed Cushing's and virilization (glucocorticoid and androgen overproduction). Feminization and Conn syndrome (mineralocorticoid excess) occur in less than 10% of cases. Rarely, pheochromocytoma-like hypersecretion of catecholamines has been reported in adrenocortical cancers. Non-functional tumors (about 40%, authorities vary) usually present with abdominal or flank pain, varicocele and renal vein thrombosis or they may be asymptomatic and detected incidentally.
All patients with suspected adrenocortical carcinoma should be carefully evaluated for signs and symptoms of hormonal syndromes. For Cushing's syndrome (glucocorticoid excess) these include weight gain, muscle wasting, purple lines on the abdomen, a fatty "buffalo hump" on the neck, a "moonlike" face, and thinning, fragile skin. Virilism (androgen excess) is most obvious in women, and may produce excess facial and body hair, acne, enlargement of the clitoris, deepening of the voice, coarsening of facial features, cessation of menstruation. Conn syndrome (mineralcorticoid excess) is marked by high blood pressure which can result in headache and hypokalemia (low serum potassium, which can in turn produce muscle weakness, confusion, and palpitations) low plasma renin activity, and high serum aldosterone. Feminization (estrogen excess) is most readily noted in men, and includes breast enlargement, decreased libido and impotence.
Mucoepidermoid carcinoma is the most common type of minor salivary gland malignancy in adults. Mucoepidermoid carcinoma can also be found in other organs, such as bronchi, lacrimal sac and thyroid.
Mucicarmine staining is one stain used by pathologist for detection.
While most carcinoids are asymptomatic through the natural lifetime and are discovered only upon surgery for unrelated reasons (so-called "coincidental carcinoids"), all carcinoids are considered to have malignant potential.
About 10% of carcinoids secrete excessive levels of a range of hormones, most notably serotonin (5-HT), causing:
- Flushing (serotonin itself does not cause flushing). Potential causes of flushing in carcinoid syndrome include bradykinins, prostaglandins, tachykinins, substance P, and/or histamine, diarrhea, and heart problems. Because of serotonin's growth-promoting effect on cardiac myocytes,[14] a serotonin-secreting carcinoid tumour may cause a tricuspid valve disease syndrome, due to the proliferation of myocytes onto the valve.
- Diarrhea
- Wheezing
- Abdominal cramping
- Peripheral edema
The outflow of serotonin can cause a depletion of tryptophan leading to niacin deficiency. Niacin deficiency, also known as pellagra, is associated with dermatitis, dementia, and diarrhea.
This constellation of symptoms is called "carcinoid syndrome" or (if acute) "carcinoid crisis". Occasionally, haemorrhage or the effects of tumor bulk are the presenting symptoms. The most common originating sites of carcinoid is the small bowel, particularly the ileum; carcinoid tumors are the most common malignancy of the appendix. Carcinoid tumors may rarely arise from the ovary or thymus.
They are most commonly found in the midgut at the level of the ileum or in the appendix. The next most common affected area is the respiratory tract, with 28% of all cases — per PAN-SEER data (1973 – 1999). The rectum is also a common site.
Basophilic, bland cells similar to acinar cells. Growth pattern: solid - acinar cells, microcytic - small systic spaces mucinous or eosinophilic, papillary-cystic - large cystic lined by epithelium, follicular - similar to thyroid tissue.
These tumors which resemble serous acinar cells vary in their behavior from locally aggressive to blatantly malignant.
It can also appear in the breast. The pancreatic form of acinic cell carcinoma is a rare subtype of exocrine pancreatic cancer. Exocrine pancreatic cancers are the most common form of pancreatic cancer when compared to endocrine pancreatic cancer.
Acinic cell carcinomas arise most frequently in the parotid gland. Other sites of primary tumors have included the submandibular gland and other major and minor salivary glands. There have been rare cases of primary tumors involving the parapharyngeal space and the sublingual gland.
In many cases, ductal carcinoma is asymptomatic, and detected as abnormal results on mammography. When symptoms occur, a painless, enlarging mass that does not fluctuate with the menstrual period may be felt. Pinching of the overlying skin may also be seen. Certain subtypes, such as inflammatory carcinomas, may result in a swollen, enlarged and tender breast. All variants of cancer, if there is metastatic spread, may cause enlarged lymph nodes and affect other organs.
Invasive carcinoma of no special type (NST) is the most common form of invasive breast cancer. It accounts for 55% of breast cancer incidence upon diagnosis, according to statistics from the United States in 2004. On a mammogram, it is usually visualized as a mass with fine spikes radiating from the edges. On physical examination, this lump usually feels much harder or firmer than benign breast lesions such as fibroadenoma. On microscopic examination, the cancerous cells invade and replace the surrounding normal tissues. IDC is divided in several histological subtypes.
Acinic cell carcinoma is a malignant tumor representing 2% of all salivary tumors. 90% of the time found in the parotid gland, 10% intraorally on buccal mucosa or palate. The disease presents as a slow growing mass, associated with pain or tenderness in 50% of the cases. Often appears pseudoencapsulated.
Cystic nephromas are often asymptomatic. They are typically discovered on medical imaging incidentally (i.e. an incidentaloma).
Epithelial-myoepithelial carcinoma of the lung (EMECL) is a very rare histologic form of malignant epithelial neoplasm ("carcinoma") arising from lung tissue.
Multiple endocrine neoplasia type 2B (also known as "MEN2B", "Mucosal neuromata with endocrine tumors", "Multiple endocrine neoplasia type 3", and "Wagenmann–Froboese syndrome") is a genetic disease that causes multiple tumors on the mouth, eyes, and endocrine glands. It is the most severe type of multiple endocrine neoplasia, differentiated by the presence of benign oral and submucosal tumors in addition to endocrine malignancies. It was first described by Wagenmann in 1922, and was first recognized as a syndrome in 1965-1966 by E.D. Williams and D.J. Pollock.
MEN 2B typically manifests before a child is 10 years old. Affected individuals tend to be tall and lanky, with an elongated face and protruding, blubbery lips. Benign tumors (neoplasms) develop in the mouth, eyes, and submucosa of almost all organs in the first decade of life.
Medullary thyroid cancer almost always occurs, sometimes in infancy. It is often aggressive. Cancer of the adrenal glands (pheochromocytoma) occurs in 50% of cases.
A variety of eponyms have been proposed for MEN 2B, such as Williams-Pollock syndrome, Gorlin-Vickers syndrome, and Wagenmann-Froboese syndrome. However, none ever gained sufficient traction to merit continued use, and are no longer used in the medical literature.
The prevalence of MEN2B is not well established, but has been derived from other epidemiological considerations as 1 in 600,000 to 1 in 4,000,000. The annual incidence has been estimated at 4 per 100 million per year.
Carcinoid (also carcinoid tumor) is a slow-growing type of neuroendocrine tumor originating in the cells of the neuroendocrine system. In some cases, metastasis may occur. Carcinoid tumors of the midgut (jejunum, ileum, appendix, and cecum) are associated with carcinoid syndrome.
Carcinoid tumors are the most common malignant tumor of the appendix, but they are most commonly associated with the small intestine, and they can also be found in the rectum and stomach. They are known to grow in the liver, but this finding is usually a manifestation of metastatic disease from a primary carcinoid occurring elsewhere in the body. They have a very slow growth rate compared to most malignant tumors. The median age at diagnosis for all patients with neuroendocrine tumors is 63 years.
Pulmonary neuroendocrine tumors are neuroendocrine tumors localized to the lung: bronchus or pulmonary parenchyma.
Pulmonary neuroendocrine tumors include a spectrum of tumors from the low-grade typical pulmonary carcinoid tumor and intermediate-grade atypical pulmonary carcinoid tumor to the high-grade pulmonary large cell neuroendocrine carcinoma (LCNEC) and pulmonary small cell carcinoma (SCLC), with significant clinical, epidemiologic and genetic differences.
Adrenal tumors are often not biopsied prior to surgery, so diagnosis is confirmed on examination of the surgical specimen by a pathologist. Grossly, adrenocortical carcinomas are often large, with a tan-yellow cut surface, and areas of hemorrhage and necrosis. On microscopic examination, the tumor usually displays sheets of atypical cells with some resemblance to the cells of the normal adrenal cortex. The presence of invasion and mitotic activity help differentiate small cancers from adrenocortical adenomas.
There are several relatively rare variants of adrenal cortical carcinoma:
- Oncocytic adrenal cortical carcinoma
- Myxoid adrenal cortical carcinoma
- Carcinosarcoma
- Adenosquamous adrenocortical carcinoma
- Clear cell adrenal cortical carcinoma
Lung cancer is an extremely heterogeneous family of malignant neoplasms, with well over 50 different histological variants recognized under the 4th revision of the World Health Organization (WHO) typing system ("WHO-2004"), currently the most widely used lung cancer classification scheme. Because these variants have differing genetic, biological, and clinical properties, including response to treatment, correct classification of lung cancer cases are necessary to assure that lung cancer patients receive optimum management.
The WHO-2004 scheme groups lung carcinomas into 8 major types:
- Squamous cell carcinoma
- Small cell carcinoma
- Adenocarcinoma
- Large cell carcinoma
- Adenosquamous carcinoma
- Sarcomatoid carcinoma
- Carcinoid tumor
- Salivary gland-like carcinoma
EMECL is considered a subtype of salivary gland-like carcinoma, tumors so named because their histological appearance and characteristics closely resemble malignant neoplasms arising in the major and minor salivary glands.