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Pituitary incidentalomas are pituitary tumors that are characterized as an incidental finding. They are often discovered by computed tomography (CT) or magnetic resonance imaging (MRI), performed in the evaluation of unrelated medical conditions such as suspected head trauma, in cancer staging or in the evaluation of nonspecific symptoms such as dizziness and headache. It is not uncommon for them to be discovered at autopsy. In a meta-analysis, adenomas were found in an average of 16.7% in postmortem studies, with most being microadenomas (<10mm); macrodenomas accounted for only 0.16% to 0.2% of the decedents. While non-secreting, noninvasive pituitary microadenomas are generally considered to be literally as well as clinically benign, there are to date scant studies of low quality to support this assertion.
It has been recommended in the current Clinical Practice Guidelines (2011) by the Endocrine Society - a professional, international medical organization in the field of endocrinology and metabolism - that all patients with pituitary incidentalomas undergo a complete medical history and physical examination, laboratory evaluations to screen for hormone hypersecretion and for hypopituitarism. If the lesion is in close proximity to the optic nerves or optic chiasm, a visual field examination should be performed. For those with incidentalomas which do not require surgical removal, follow up clinical assessments and neuroimaging should be performed as well follow-up visual field examinations for incidentalomas that abut or compress the optic nerve and chiasm and follow-up endocrine testing for macroincidentalomas.
Unlike tumors of the posterior Pituitary, Pituitary adenomas are classified as endocrine tumors (not brain tumors). Pituitary adenomas are classified based upon anatomical, histological and functional criteria.
- Anatomically pituitary tumors are classified by their size based on radiological findings; either microadenomas (less than <10 mm) or macroadenomas (equal or greater than ≥10 mm).
- Histological classification utilizes an immunohistological characterization of the tumors in terms of their hormone production. Historically they were classed as either basophilic, acidophilic, or chromophobic on the basis of whether or not they took up the tinctorial stains hematoxylin and eosin. This classification has fallen into disuse, in favor of a classification based on what type of hormone is secreted by the tumor. Approximately 20-25% of adenomas do not secrete any readily identifiable active hormones ('non-functioning tumors') yet they are still sometimes referred to as 'chromophobic'.
- Functional classification is based upon the tumors endocrine activity as determined by serum hormone levels and pituitary tissue cellular hormone secretion detected via immunohistochemical staining. The "Percentage of hormone production cases" values are the fractions of adenomas producing each related hormone of each tumor type as compared to all cases of pituitary tumors, and does not directly correlate to the percentages of each tumor type because of smaller or greater incidences of absence of secretion of the expected hormone. Thus, nonsecretive adenomas may be either "null cell adenomas" or a more specific adenoma that, however, remains nonsecretive.
A physician's response to detecting an adenoma in a patient will vary according to the type and location of the adenoma among other factors. Different adenomas will grow at different rates, but typically physicians can anticipate the rates of growth because some types of common adenomas progress similarly in most patients. Two common responses are removing the adenoma with surgery and then monitoring the patient according to established guidelines.
One common example of treatment is the response recommended by specialty professional organizations upon removing adenomatous polyps from a patient. In the common case of removing one or two of these polyps from the colon from a patient with no particular risk factors for cancer, thereafter the best practice is to resume surveillance colonoscopy after 5–10 years rather than repeating it more frequently than the standard recommendation.
Craniopharyngiomas are usually successfully managed with a combination of adjuvant chemotherapy and neurosurgery. Recent research describes the rare occurrence of malignant transformations of these normally benign tumors. Malignant craniopharyngiomas can occur at any age, are slightly more common in females, and are usually of the adamantinomatous type.
The malignant transformations can take years to occur (although 1 in 5 of the diagnosed cases were de novo transformations), hence the need for lengthier follow up in patients diagnosed with the more common benign forms.
There was no link found between malignancy and initial chemo-radiotherapy treatment, and the overall survival rate was very poor with median survival being 6 months post diagnosis of malignancy.
There are a few scans and tests that the physician can conduct in order to diagnose a person with craniopharyngioma. Your doctor may order a high-resolution magnetic resonance imaging (MRI) scan. This test is valuable because it allows the neuroradiologist to view the tumor from different angles.
In some cases, a powerful 3T (Tesla) MRI scanner can help define the location of critical brain structures affected by the tumor.The histologic pattern consists of nesting of squamous epithelium bordered by radially arranged cells. It is frequently accompanied by calcium deposition and may have a microscopic papillary architecture.A computed tomography (CT) scan is also a good diagnostic tool as it detects calcification in the tumor.
Two distinct types are recognized:
- Adamantinomatous craniopharyngiomas, which resemble ameloblastomas (the most common type of odontogenic tumor), are characterized by activating CTNNB1 mutations; and,
- Papillary craniopharyngiomas are characterized by BRAFv600E mutations.
In the adamantinomatous type, calcifications are visible on neuroimaging and are helpful in diagnosis.
The papillary type rarely calcifies. A vast majority of craniopharyngiomas in children are adamantiomatous whereas both subtypes are common in adults. Mixed type tumors also occur.
On macroscopic examination, craniopharyngiomas are cystic or partially cystic with solid areas. On light microscopy, the cysts are seen to be lined by stratified squamous epithelium. Keratin pearls may also be seen. The cysts are usually filled with a yellow, viscous fluid which is rich in cholesterol crystals. Of a long list of possible symptoms, the most common presentations include: headaches, growth failure, and bitemporal hemianopsia.
A recommend surveillance program for Multiple Endocrine Neoplasia Type 1 has been suggested by the International Guidelines for Diagnosis and Therapy of MEN syndromes group.
The diagnosis of salivary gland tumors utilize both tissue sampling and radiographic studies. Tissue sampling procedures include fine needle aspiration (FNA) and core needle biopsy (bigger needle comparing to FNA). Both of these procedures can be done in an outpatient setting. Diagnostic imaging techniques for salivary gland tumors include ultrasound, computer tomography (CT) and magnetic resonance imaging (MRI).
Fine needle aspiration biopsy (FNA), operated in experienced hands, can determine whether the tumor is malignant in nature with sensitivity around 90%. FNA can also distinguish primary salivary tumor from metastatic disease.
Core needle biopsy can also be done in outpatient setting. It is more invasive but is more accurate compared to FNA with diagnostic accuracy greater than 97%. Furthermore, core needle biopsy allows more accurate histological typing of the tumor.
In terms of imaging studies, ultrasound can determine and characterize superficial parotid tumors. Certain types of salivary gland tumors have certain sonographic characteristics on ultrasound. Ultrasound is also frequently used to guide FNA or core needle biopsy.
CT allows direct, bilateral visualization of the salivary gland tumor and provides information about overall dimension and tissue invasion. CT is excellent for demonstrating bony invasion. MRI provides superior soft tissue delineation such as perineural invasion when compared to CT only.
Fine Needle Aspiration Cytology (FNAC) is a cheap, simple, and safe method in obtaining cytological specimens for diagnosis by using a needle and a syringe. The "Bethesda System for Reporting Thyroid Cytopathology" is the system used to report whether the thyroid cytological specimen is benign or malignant. It can be divided into six categories:
Repeated FNAC is recommended for Category I, followed by clinical follow-up in Category II, repeat FNAC for Category III, and lobectomy for Category IV, near total-thyroidectomy/lobectomy for Category V, and near total thyroidectomy for Category VI. The risk of malignancy in a malignant FNAC report is 93.7% while for suspicious FNAC report, it is 18.9%.
Immunohistochemistry is performed as additional test. The strong positive expression of cytokeratin 19 was showed in primary SCTC, and negative in metastatic SCTC.
Ultrasound-guided FNAC should be performed for verification of SCTC.
Blood tests may be done prior to or in lieu of a biopsy. The possibility of a nodule which secretes thyroid hormone (which is less likely to be cancer) or hypothyroidism is investigated by measuring thyroid stimulating hormone (TSH), and the thyroid hormones thyroxine (T4) and triiodothyronine (T3).
Tests for serum thyroid autoantibodies are sometimes done as these may indicate autoimmune thyroid disease (which can mimic nodular disease).
Parathyroid carcinoma is sometimes diagnosed during surgery for primary hyperparathyroidism. If the surgeon suspects carcinoma based on severity or invasion of surrounding tissues by a firm parathyroid tumor, aggressive excision is performed, including the thyroid and surrounding tissues as necessary.
Agents such as calcimimetics (for example, cinacalcet) are used to mimic calcium and are able to activate the parathyroid calcium-sensing receptor (making the parathyroid gland "think" we have more calcium than we actually do), therefore lowering the calcium level, in an attempt to decrease the hypercalcemia.
The first step in diagnosing a thyroid neoplasm is a physical exam of the neck area. If any abnormalities exist, a doctor needs to be consulted. A family doctor may conduct blood tests, an ultrasound, and nuclear scan as steps to a diagnosis. The results from these tests are then read by an endocrinologist who will determine what problems the thyroid has.
Hyperthyroidism and hypothyroidism are two conditions that often arise from an abnormally functioning thyroid gland. These occur when the thyroid is producing too much or too little thyroid hormone respectively.
Thyroid nodules are a major presentation of thyroid neoplasms, and are diagnosed by ultrasound guided fine needle aspiration (USG/FNA) or frequently by thyroidectomy (surgical removal and subsequent histological examination). FNA is the most cost-effective and accurate method of obtaining a biopsy sample. As thyroid cancer can take up iodine, radioactive iodine is commonly used to treat thyroid carcinomas, followed by TSH suppression by high-dose thyroxine therapy.
Nodules are of particular concern when they are found in those under the age of 20. The presentation of benign nodules at this age is less likely, and thus the potential for malignancy is far greater.
Common diagnostic techniques include:
- MRIs
- CAT scans
- blood samples.
Blood samples are assessed for the absence or presence of aldosterone and cortisol. Physical examinations are also useful in patients in order to examine vision, skin pigmentation, how the body replaces steroids, and the cranial nerves. Recent advancements in high-resolution MRIs allow for adenomas to be detected during the early stages of Nelson syndrome. Physical examination including height, weight, vital signs, blood pressure, eye examination, thyroid examination, abdominal examination, neurological examination, skin examination and pubertal staging needs to be assessed. Through blood pressure and pulse readings can indicate hypothyroidism and adrenal insufficiency. Hyper-pigmentation, hyporeflexia, and loss of vision can also indicate Nelson's syndrome when assessed together. Specifically for a child who might have Nelson's syndrome, the patient should be questioned about the symptoms of the disease, and well as symptoms of other diseases to narrow down which disease the patient presents with. The patient should be questioned about how often and to what degree headaches, visual disturbances, and symptoms associated with pituitary malfunction occur. Additionally, adrenal steroid replacement should be assessed, especially in children who have prior insufficiency associated wit
There are many diagnostic methods that can be used to determine the type of salivary gland tumour and if it is benign or malignant. Examples of diagnostic methods include:
Physical exam and history: An exam of the body to check general signs of health. The head, neck, mouth, and throat will be checked for signs of disease, such as lumps or anything else that seems unusual. A history of the patient's health habits and past illnesses and treatments will also be taken.
Endoscopy: A procedure to look at organs and tissues inside the body to check for abnormal areas. For salivary gland cancer, an endoscope is inserted into the mouth to look at the mouth, throat, and larynx. An endoscope is a thin, tube-like instrument with a light and a lens for viewing.
MRI
Biopsy: The removal of cells or tissues so they can be viewed under a microscope by a pathologist to check for signs of cancer.
Fine needle aspiration (FNA) biopsy: The removal of tissue or fluid using a thin needle. An FNA is the most common type of biopsy used for salivary gland cancer, and has been shown to produce accurate results when differentiating between benign and malignant tumours.
Radiographs: An OPG (orthopantomogram) can be taken to rule out mandibular involvement. A chest radiograph may also be taken to rule out any secondary tumours.
Ultrasound: Ultrasound can be used to initially assess a tumour that is located superficially in either the submandibular or parotid gland. It can distinguish an intrinsic from an extrinsic neoplasm. Ultrasonic images of malignant tumours include ill defined margins.
Overall, the mainstay of the treatment for salivary gland tumor is surgical resection. Needle biopsy is highly recommended prior to surgery to confirm the diagnosis. More detailed surgical technique and the support for additional adjuvant radiotherapy depends on whether the tumor is malignant or benign.
Surgical treatment of parotid gland tumors is sometimes difficult, partly because of the anatomical relationship of the facial nerve and the parotid lodge, but also through the increased potential for postoperative relapse. Thus, detection of early stages of a tumor of the parotid gland is extremely important in terms of prognosis after surgery.
Generally, benign tumors of the parotid gland are treated with superficial(Patey's operation) or total parotidectomy with the latter being the more commonly practiced due to high incidence of recurrence. The facial nerve should be preserved whenever possible. The benign tumors of the submandibular gland is treated by simple excision with preservation of mandibular branch of the trigeminal nerve, the hypoglossal nerve, and the lingual nerve. Other benign tumors of minor salivary glands are treated similarly.
Malignant salivary tumors usually require wide local resection of the primary tumor. However, if complete resection cannot be achieved, adjuvant radiotherapy should be added to improve local control. This surgical treatment has many sequellae such as cranial nerve damage, Frey's syndrome, cosmetic problems, etc.
Usually about 44% of the patients have a complete histologic removal of the tumor and this refers to the most significant survival rate.
Treatment of a thyroid nodule depends on many things including size of the nodule, age of the patient, the type of thyroid cancer, and whether or not it has spread to other tissues in the body.
If the nodule is benign, patients may receive thyroxine therapy to suppress thyroid-stimulating hormone and should be reevaluated in 6 months. However, if the benign nodule is inhibiting the patient's normal functions of life; such as breathing, speaking, or swallowing, the thyroid may need to be removed.
Sometimes only part of the thyroid is removed in an attempt to avoid causing hypothyroidism. There's still a risk of hypothyroidism though, as the remaining thyroid tissue may not be able to produce enough hormones in the long-run.
If the nodule is malignant or has indeterminate cytologic features, it may require surgery. A thyroidectomy is a medium risk surgery that can result complications if not performed correctly. Problems with the voice, nerve or muscular damage, or bleeding from a lacerated blood vessel are rare but serious complications that may occur. After removing the thyroid, the patient must be supplied with a replacement hormone for the rest of their life. This is commonly a daily oral medication prescribed by their endocrinologist.
Radioactive iodine-131 is used in patients with papillary or follicular thyroid cancer for ablation of residual thyroid tissue after surgery and for the treatment of thyroid cancer. Patients with medullary, anaplastic, and most Hurthle cell cancers do not benefit from this therapy. External irradiation may be used when the cancer is unresectable, when it recurs after resection, or to relieve pain from bone metastasis.
Adrenal adenomas are common, and are often found on the abdomen, usually not as the focus of investigation; they are usually incidental findings. About one in 10,000 is malignant. Thus, a biopsy is rarely called for, especially if the lesion is homogeneous and smaller than 3 centimeters. Follow-up images in three to six months can confirm the stability of the growth.
While some adrenal adenomas do not secrete hormones at all, often some secrete cortisol, causing Cushing's syndrome, aldosterone causing Conn's syndrome, or androgens causing hyperandrogenism.
An endocrine gland neoplasm is a neoplasm affecting one or more glands of the endocrine system.
Examples include:
- Adrenal tumor
- Pituitary adenoma
The most common form is thyroid cancer.
Condition such as pancreatic cancer or ovarian cancer can be considered endocrine tumors, or classified under other systems.
Pinealoma is often grouped with brain tumors because of its location.
Common treatments for Nelson's syndrome include radiation or surgical procedure. Radiation allows for the limitation of the growth of the pituitary gland and the adenomas. If the adenomas start to affect the surrounding structures of the brain, then a micro-surgical technique can be adapted in order to remove the adenomas in a transsphenoidal (bone at base of the skull) process. Death may result with development of a locally aggressive pituitary tumor. However, does not commonly occur with pituitary diseases. In the rare case, ACTH-secreting tumors can become malignant. Morbidity from the disease can occur due to pituitary tissue compression or replacement, and compression of structures that surround the pituitary fossa. The tumor can also compress the optic apparatus, disturb cerebrospinal fluid flow, meningitis, and testicular enlargement in rare cases.
Multiple Endocrine Neoplasia type 1 (MEN1) is a rare hereditary endocrine cancer syndrome characterized primarily by tumors of the parathyroid glands (95% of cases), endocrine gastroenteropancreatic (GEP) tract (30-80% of cases), and anterior pituitary (15-90% of cases). Other endocrine and non-endocrine neoplasms including adrenocortical and thyroid tumors, visceral and cutaneous lipomas, meningiomas, facial angiofibromas and collagenomas, and thymic, gastric, and bronchial carcinoids also occur. The phenotype of MEN1 is broad, and over 20 different combinations of endocrine and non-endocrine manifestations have been described. MEN1 should be suspected in patients with an endocrinopathy of two of the three characteristic affected organs, or with an endocrinopathy of one of these organs plus a first-degree relative affected by MEN1 syndrome.
MEN1 patients usually have a family history of MEN1. Inheritance is autosomal dominant; any affected parent has a 50% chance to transmit the disease to his or her progeny. MEN1 gene mutations can be identified in 70-95% of MEN1 patients.
Many endocrine tumors in MEN1 are benign and cause symptoms by overproduction of hormones or local mass effects, while other MEN1 tumors are associated with an elevated risk for malignancy. About one third of patients affected with MEN1 will die early from an MEN1-related cancer or associated malignancy. Entero-pancreatic gastrinomas and thymic and bronchial carcinoids are the leading cause of morbidity and mortality. Consequently, the average age of death in untreated individuals with MEN1 is significantly lower (55.4 years for men and 46.8 years for women) than that of the general population.
Treatment may include the following:
- Surgery with or without radiation
- Radiotherapy
Fast neutron therapy has been used successfully to treat salivary gland tumors, and has shown to be significantly more effective than photons in studies treating unresectable salivary gland tumors.
- Chemotherapy
Surgical excision is the preferred method of treatment for benign glomus tumors.
Parathyroid cancer occurs in midlife at the same rate in men and women.
Conditions that appear to result in an increased risk of parathyroid cancer include multiple endocrine neoplasia type 1, autosomal dominant familial isolated hyperparathyroidism and hyperparathyroidism-jaw tumor syndrome (which also is hereditary). Parathyroid cancer has also been associated with external radiation exposure, but, most reports describe an association between radiation and the more common parathyroid adenoma.
In a diagnostic workup individuals with a combination of endocrine neoplasias suggestive of the "MEN1 syndrome" are recommended to have a mutational analysis of the MEN1 gene if additional diagnostic criteria are sufficiently met, mainly including:
- age <40 years
- positive family history
- multifocal or recurrent neoplasia
- two or more organ systems affected