Pituitary carcinoma

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]Associate Editor(s)-in-Chief: Masoud Bitarafan, M.D[[2]]

Overview

Historical Perspective

  • pituitary carcinoma was first discovered by Pierre Marie, a French neurologist (Salpetriere Hospital, Paris) in 1886 following his studying in2 patients with clinical findings of what he termed acromegaly and postulated that the pituitary gland was involved in the pathogenesis.[1]
  • The history of pituitary tumor biology is rich. A recent DNA examination from the teeth of an Irish patient with gigantism (7 ft, 7 in in height), who lived from 1761 to 1783 and was housed at the Hunterian Museum in London, revealed the same mutation in the AIP gene (c.910 C- T mutation) present in 4 families with pituitary tumors from Northern Ireland. This patient shared common haplotypes with the recent families studied.[1]

Classification

  • Pituitary carcinoma may be classified according to the type of cells involved into following subtypes:[2][3]
  • Corticotroph carcinoma
  • Prolactin-secreting carcinomas
  • Gonadotroph carcinomas
  • Growth hormone–secreting carcinoma

Pathophysiology

  • Several possible causes have been proposed for pathogenesis of Pituitary carcinoma.[4]The pathogenesis of pituitary carcinoma is characterized by :
  1. consequence of pervious irradiation in a treatment of a pituitary carcinoma
  2. microscopic tumor seeding from a pervious Pituitary surgery
  3. malignant progression of a Pituitary carcinoma
  4. denovo carcinoma
  • The [gene name] gene/Mutation in [gene name] has been associated with the development of [disease name], involving the [molecular pathway] pathway.
  • On gross pathology, [feature1], [feature2], and [feature3] are characteristic findings of pituitary carcinoma
  • On microscopic histopathological analysis, hypochromatasia, [feature2], and [feature3] are characteristic findings of pituitary carcinoma[5]

Associated Conditions

Differentiating pituitary carcinoma from other Diseases

  • pituitary carcinoma must be differentiated from other diseases that cause [clinical feature 1], [clinical feature 2], and [clinical feature 3], such as:
  • [Differential dx1]
  • [Differential dx2]
  • [Differential dx3]

Epidemiology and Demographics

  • The prevalence of pituitary carcinoma is very rare as it accounts for 0.1-0.2% of all pituitary tumors and approximately 4616 individuals worldwide and 207 in US.[5][6]
  • In [year], the incidence of pituitary carcinoma was estimated to be [number or range] cases per 100,000 individuals in [location].

Age

  • Patients of all age groups may develop pituitary carcinoma but typically presents in the third to fifth decade of life in patients with preexisting pituitary adenomas.[7]
  • Pituitary carcinoma is more commonly observed among those in third or fifth decade of life.[8]

Gender

  • Pituitary carcinoma affects men and women equally.[5]

Race

American Blacks have higher incidence rates for pituitary tumors compared with other ethnic groups.[9]

The study of Heshmat et al. supports this possibility with the finding that African Blacks have higher relative proportions of pituitary tumors compared to American Whites (although still not as high as American Blacks)[9]

Risk Factors

  • Common known risk factors in the development of pituitary tumors are[10] :
  1. Multiple endocrine neoplasia type 1 (MEN1).
  2. Families with MEN1 have an increased risk of pituitary gland tumors.
  3. Carney complex. Like MEN1, the Carney complex is a rare genetic condition that can increase the risk of a pituitary gland tumor.
  4. Familial acromegaly. Acromegaly is a condition in adults that is caused by too much growth hormone. Familial acromegaly can occur as part of MEN1, described above, or alone within a family.

Natural History, Complications and Prognosis

  • The majority of patients with pituitary carcinoma remain asymptomatic or latent from a few months to 18 years depending upon the subtype.[5]
  • If left untreated, [#%] of patients with pituitary carcinoma may progress to develop [manifestation 1], [manifestation 2], and [manifestation 3].
  • Common complications of pituitary tumors include blindness,diabetes insipidus, permanent hormone deficiency, pituitary apoplexy.[11]
  • Prognosis is generally [excellent/good/poor], and the [1/5/10­year mortality/survival rate] of patients with pituitary carcinoma is approximately [#%].

Diagnosis

Diagnostic Criteria

  • The diagnosis of pituitary carcinoma is made when at least [number] of the following [number] diagnostic criteria are met:
  • [criterion 1]
  • [criterion 2]

Symptoms

A pituitary tumor causes symptoms in 3 different ways, which are:[12]

  • By producing too much of 1 or more hormones:
  1. Growth hormone. The symptoms depend on a patient’s age. In children, before the bone plates have closed, increased growth can cause gigantism, which is excessive body size and height. In adults, increased growth hormone causes acromegaly, a syndrome that includes excessive growth of soft tissues and bones, high blood sugar, high blood pressure, heart disease, sleep apnea, increased snoring, carpal tunnel syndrome, and pain, including headaches
  2. Thyroid stimulating hormone (TSH). Too much TSH causes increased production of thyroid hormone. This can lead to nervousness and irritability, fast heart rate and high blood pressure, heart disease, increased sweating, thin skin, and weight loss.
  3. Prolactin. Too much prolactin, a hormone that stimulates lactation and the secretion of progesterone, causes inappropriate secretion of breast milk, even in men. It can also cause osteoporosis, which is weakening of the bones; loss of sex drive; infertility; irregular menstrual cycles; and the inability to have an erection.
  4. Adrenocorticotropic hormone (ACTH). Too much of this hormone causes weight gain, particularly in the body’s trunk. It can also cause high blood pressure, high blood sugar, brittle bones, emotional changes, stretch marks on the skin, and easy bruising.
  5. Gonadotropins (FSH and LH). These are usually not high enough to cause symptoms but can, in rare cases, cause infertility and irregular menstrual cycles in women.
  • By pressing on the pituitary gland, causing it to make too little of 1 or more hormones:
  1. Growth hormone. Not enough growth hormone causes late growth in children, poor muscle strength, irritability, weakening of bone strength, and an overall unwell feeling.
  2. TSH. Low TSH causes fatigue, low energy, sensitivity to cold temperatures, constipation, and weight gain.
  3. Prolactin. Too little prolactin causes an inability to breastfeed after a woman gives birth to a baby.
  4. ACTH. Too little of this hormone causes fatigue and low energy, low blood pressure, low blood sugar, and upset stomach.
  5. Gonadotropins. Low levels of gonadotropins cause infertility, decrease in sex drive, an inability to have an erection, and irregular menstrual cycles.
  • By pressing on the optic nerves or, less commonly, the nerves controlling eye movements, and causing either loss of part or all of a person’s sight, or double vision.


Examination

  • Patients with pituitary carcinoma usually appear [general appearance].
  • Physical examination may be remarkable for:
  • [finding 1]

Laboratory Findings

  • There are no specific laboratory findings associated with pituitary carcinoma
  • A [positive/negative] [test name] is diagnostic of pituitary carcinoma
  • An [elevated/reduced] concentration of [serum/blood/urinary/CSF/other] [lab test] is diagnostic of pituitary carcinoma
  • Other laboratory findings consistent with the diagnosis of pituitary carcinoma include [abnormal test 1], [abnormal test 2], and [abnormal test 3].

Imaging Findings

  • There are no [imaging study] findings associated with pituitary carcinoma
  • [Imaging study 1] is the imaging modality of choice for pituitary carcinoma
  • On [imaging study 1], pituitary carcinoma is characterized by [finding 1], [finding 2], and [finding 3].
  • [Imaging study 2] may demonstrate [finding 1], [finding 2], and [finding 3].

Other Diagnostic Studies

  • pituitary carcinoma may also be diagnosed using [diagnostic study name].
  • Findings on [diagnostic study name] include [finding 1], [finding 2], and [finding 3].

Treatment

Pituitary carcinomas are generally associated with a poor prognosis despite administration of maximal multimodal therapies . Patients with systemic metastases have a median survival of 12 months,whereas those with metastases confined to the central nervous system live longer with an average of 2.6 yr.[7]

Treatment options for Pituitary carcinoma include[13]:

  • surgery
  • external radiotherapy
  • medical treatment
  • peptide receptor radionuclide therapy.

Current therapeutic modalities are mainly palliative, and once metastases develop, the prognosis of these tumors is relatively poor.

Medical Therapy

  • Medicines are used to manage hormone levels in functional pituitary carcinomas.
  • These are the same drugs used to treat pituitary adenomas, but higher doses and combinations of drugs may be needed.[14]
  • some medicine which is used are listed below:[15]
  1. drugs for prolactin-secreting tumors:dopamine agonists such as cabergoline and bromocriptine
  2. drugs for growth hormone- secretings timors:somatostatin analogs such as octreotide or lanreotide.
  3. drugs for corticotropin-secreting tumors:somatostatin analog such as pasireotide or cortisol receptor blocker such as mifepristone.

Surgery

  • Surgery and radiation therapy are the main forms of treatment used for pituitary carcinoma.
  • . They may decrease tumor size, slow tumor growth, and help prevent or relieve symptoms. Surgery may be repeated, if needed.[14]
  • for surgery there is two common ways:[16]
  1. Transsphenoidal surgery
  2. craniotomy(for larger or more complicated pituitary tumors.

Radiation therapy

  • Radiation therapy may be considered if surgery isn't an option, if some of a pituitary tumor remains or comes back after surgery, or if the tumor causes symptoms that aren’t controlled with medicines.[17]
  • There are some Newer techniques help lower the risks of radiation therapy which is listed below:
  1. Intensity modulated radiation therapy (IMRT)
  2. Stereotactic radiosurgery/stereotactic radiation therapy
  3. Proton beam radiation therapy

Prevention

  • pituitary tumors have not been linked with any known outside risk factors. As a result, there is no known way to prevent these tumors at this time.[18]

References

  1. 1.0 1.1 "Pituitary Tumors: Background, Pathophysiology, Epidemiology".
  2. Ragel BT, Couldwell WT (April 2004). "Pituitary carcinoma: a review of the literature". Neurosurg Focus. 16 (4): E7. PMID 15191336.
  3. Scheithauer BW, Kovacs KT, Laws ER, Randall RV (December 1986). "Pathology of invasive pituitary tumors with special reference to functional classification". J. Neurosurg. 65 (6): 733–44. doi:10.3171/jns.1986.65.6.0733. PMID 3095506.
  4. "Pituitary carcinoma: a review of the literature in: Neurosurgical Focus Volume 16 Issue 4 (2004)".
  5. 5.0 5.1 5.2 5.3 5.4 Pernicone PJ, Scheithauer BW, Sebo TJ, Kovacs KT, Horvath E, Young WF, Lloyd RV, Davis DH, Guthrie BL, Schoene WC (February 1997). "Pituitary carcinoma: a clinicopathologic study of 15 cases". Cancer. 79 (4): 804–12. PMID 9024719.
  6. Daly AF, Tichomirowa MA, Beckers A (October 2009). "The epidemiology and genetics of pituitary adenomas". Best Pract. Res. Clin. Endocrinol. Metab. 23 (5): 543–54. doi:10.1016/j.beem.2009.05.008. PMID 19945022.
  7. 7.0 7.1 "Clinical Review: Pituitary Carcinoma: Difficult Diagnosis and Treatment".
  8. Kontogeorgos G (October 2005). "Classification and pathology of pituitary tumors". Endocrine. 28 (1): 27–35. doi:10.1385/ENDO:28:1:027. PMID 16311407.
  9. 9.0 9.1 "Demographic Differences in Incidence for Pituitary Adenoma".
  10. "Pituitary Gland Tumor: Risk Factors | Cancer.Net".
  11. "Pituitary Tumor Complications".
  12. "Pituitary Gland Tumor: Symptoms and Signs | Cancer.Net".
  13. "Pituitary Carcinoma | American Journal of Neuroradiology".
  14. 14.0 14.1 "Treatment of Pituitary Carcinomas".
  15. "Medicines to Treat Pituitary Tumors".
  16. "Surgery for Pituitary Tumors".
  17. "Radiation Therapy for Pituitary Tumors".
  18. "www.cancer.org" (PDF).


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