Lactotroph (PRL-Producing) Adenomas
Corticotroph (ACTH-Producing) Adenomas
Somatotroph (GH-Producing) Adenomas
Thyrotroph (TSH-Producing) Adenomas
Gonadotroph (FSH-Producing and/or LH-Producing) Adenomas
Plurihormonal Adenomas
Nonfunctioning (Endocrine-Inactive) Adenomas
Oncocytic Tumors
Carcinomas
Metastatic Tumors
Other Tumors

Pituitary adenomas can be classified according to staining affinities of the cell cytoplasm, size, endocrine activity, histologic characteristics, hormone production and contents, ultrastructural features, granularity of the cell cytoplasm, cellular composition, cytogenesis, and growth pattern.[1] Recent classifications, however, omit criteria based on tinctorial stains (i.e., acidophilic, basophilic, and chromophobic) because of the poor correlation between staining affinities of the cell cytoplasm and other pathological features of pituitary tumors, such as the type of hormone produced and cellular derivation.[1,2] A unifying pituitary adenoma classification incorporates the histological, immunocytochemical, and electron microscopic studies of the tumor cells, and stresses the importance of hormone production, cellular composition, and cytogenesis. This classification emphasizes the structure-function relationship and attempts to correlate morphologic features with secretory activity.[1]

Pituitary adenomas are also classified according to size as microadenomas or macroadenomas. Microadenomas are less than 10 mm in their largest diameter, whereas macroadenomas are 10 mm or more in their largest diameter. (See Stage Information for more information.) In addition, pituitary adenomas may be distinguished anatomically as intrapituitary, intrasellar, diffuse, and invasive.[1] Invasive adenomas, which account for approximately 35% of all pituitary neoplasms, may invade into the dura mater, cranial bone, or sphenoid sinus.[3]

Lactotroph adenomas secrete prolactin (PRL) and are typically an intrasellar tumor. In women, these adenomas are often small (<10 mm). In either sex, however, they can become large enough to enlarge the sella turcica. These adenomas represent the most common hormone-producing pituitary tumors and account for 25% to 41% of tumor specimens.[4]

The major manifestation of the corticotroph adenoma is secretion of adrenocorticotropic hormone (ACTH), which results in Cushing syndrome. These tumors are initially confined to the sella turcica, but they may enlarge and become invasive after bilateral adrenalectomy (i.e., Nelson syndrome). These adenomas represent the second or third most common hormone-producing pituitary tumors, depending on the series; in one series, these tumors accounted for 10% of all tumor specimens.[1,4]

Somatotroph adenomas produce growth hormone (GH), resulting in gigantism in younger patients and acromegaly in others. Suprasellar extension is not uncommon. These adenomas represent the second or third most common hormone-producing pituitary tumors, depending on the series; in one series these adenomas accounted for 13% of tumor specimens.[1,4]

Thyrotrophadenomas secrete thyroid-stimulating hormone (TSH), also known as thyrotropin, which results in hyperthyroidism without TSH suppression. Many are large and invasive, may be plurihormonal, and secrete both GH and/or PRL.[5] These tumors are rare and account for ≤2% of tumor specimens.[1,4,5]

Gonadotroph adenomas may secrete follicle-stimulating hormone (FSH) and/or luteinizing hormone (LH), or the alpha or beta subunits that comprise these heterodimers, which, depending on gender, may result in ovarian overstimulation, increased testosterone levels, testicular enlargement, and pituitary insufficiency caused by compression of the pituitary stalk or destruction of normal pituitary tissue by tumor. Many gonadotroph tumors, however, are unassociated with clinical or biochemical evidence of hormone excess and may be considered to be nonfunctioning or endocrine-inactive tumors.[6] Functional, clinically detectable gonadotroph adenomas are rare.[7]

Plurihormonal tumors produce more than one hormone. Morphologically, they can be either monomorphous or plurimorphous. Monomorphous plurihormonal adenomas consist of one cell population that produces two or more hormones. The adenoma cells often differ from nontumorous adenohypophysial cells, and their cellular derivation may remain obscure despite extensive morphological studies. Plurimorphous plurihormonal adenomas consist of two or more distinct cell types, and each produces one hormone.[1] Thyrotroph adenomas are often plurihormonal.[5]

These tumors arise from the adenohypophysis and cause symptoms when they extend beyond the sella, which results in pressure on the surrounding structures rather than secretion of a hormonally active substance. Endocrine-inactive adenomas show positive immunostaining for one or more pituitary hormones;[1] however, they are not associated with clinical and biochemical evidence of hormone excess. Gonadotrophic hormones, as detected by antisera to beta-FSH and beta-LH, are present in many clinically nonfunctioning adenomas. Some of these adenomas are recognized by electron microscopy to have gonadotrophic differentiation, but some have characteristics of less well-differentiated cells and resemble the null cells that were initially thought to be undifferentiated precursors of adenohypophysial cells.[7] Endocrine-inactive pituitary adenomas comprise approximately 30% to 35% of the pituitary tumors in most series and are the most common type of macroadenoma.[8]

Oncocytic tumors of the pituitary, also known as pituitary oncocytomas, are characterized by an abundance of mitochondria, which may fill up to 50% of the cytoplasmic area, which is normally around 8%, and obscure other organelles. These tumors are usually unassociated with clinical and biochemical evidence of hormone excess; in some cases, they may be accompanied by various degrees of hypopituitarism and/or mild hyperprolactinemia. Oncocytic change may occur in several other pituitary tumor types.[1]

Pituitary carcinomas are usually endocrinologically functional, and ACTH-producing and PRL-producing tumors are the most frequent.[2,9] The histological and cytological characteristics of pituitary carcinomas vary from bland and monotonous to frankly malignant.[10] Carcinomas show a variable degree of nuclear atypia and cellular pleomorphism, but they also show significantly higher mitotic rates and cell proliferation indices than adenomas.[2] Carcinomas account for 0.1% to 0.2% of all pituitary tumors.[9,11]

Breast and lung cancer are the most common primary neoplasms metastasizing to the pituitary. Although tumors that are metastatic to the pituitary have been reported to be as high as 28% in autopsy series, the majority of metastatic tumors are clinically silent.[12]

Other tumors that arise in the pituitary include craniopharyngiomas, meningiomas, and germ cell tumors; the rare granular cell tumors, pituicytomas, and gangliogliomas; and the even rarer gangliocytomas, lymphomas, astrocytomas, and ependymomas.[2]

References

1. Kovacs K, Horvath E, Vidal S: Classification of pituitary adenomas. J Neurooncol 54 (2): 121-7, 2001.  [PUBMED Abstract]
   
   
2. Ironside JW: Best Practice No 172: pituitary gland pathology. J Clin Pathol 56 (8): 561-8, 2003.  [PUBMED Abstract]
   
   
3. Scheithauer BW, Kovacs KT, Laws ER Jr, et al.: Pathology of invasive pituitary tumors with special reference to functional classification. J Neurosurg 65 (6): 733-44, 1986.  [PUBMED Abstract]
   
   
4. Ezzat S, Asa SL, Couldwell WT, et al.: The prevalence of pituitary adenomas: a systematic review. Cancer 101 (3): 613-9, 2004.  [PUBMED Abstract]
   
   
5. Teramoto A, Sanno N, Tahara S, et al.: Pathological study of thyrotropin-secreting pituitary adenoma: plurihormonality and medical treatment. Acta Neuropathol (Berl) 108 (2): 147-53, 2004.  [PUBMED Abstract]
   
   
6. Snyder PJ: Extensive personal experience: gonadotroph adenomas. J Clin Endocrinol Metab 80 (4): 1059-61, 1995.  [PUBMED Abstract]
   
   
7. Asa SL, Ezzat S: The cytogenesis and pathogenesis of pituitary adenomas. Endocr Rev 19 (6): 798-827, 1998.  [PUBMED Abstract]
   
   
8. Yeh PJ, Chen JW: Pituitary tumors: surgical and medical management. Surg Oncol 6 (2): 67-92, 1997.  [PUBMED Abstract]
   
   
9. Ragel BT, Couldwell WT: Pituitary carcinoma: a review of the literature. Neurosurg Focus 16 (4): E7, 2004.  [PUBMED Abstract]
   
   
10. Pernicone PJ, Scheithauer BW: Invasive pituitary adenoma and pituitary carcinoma. In: Thapar K, Kovacs K, Scheithauer BW, et al., eds.: Diagnosis and Management of Pituitary Tumors. Totowa, NJ: Humana Press, 2001, pp 369-86. 
    
    
11. Pernicone PJ, Scheithauer BW, Sebo TJ, et al.: Pituitary carcinoma: a clinicopathologic study of 15 cases. Cancer 79 (4): 804-12, 1997.  [PUBMED Abstract]
    
    
12. Komninos J, Vlassopoulou V, Protopapa D, et al.: Tumors metastatic to the pituitary gland: case report and literature review. J Clin Endocrinol Metab 89 (2): 574-80, 2004.  [PUBMED Abstract]
    
    

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