Introduction:
Many diseases can impact the pituitary gland, or hypophysis, and surrounding structures in the sellar area, resulting in neurological and endocrine disorders. These comprise tumors of the neurohypophysis and pituitary stalk (pituicytoma, granular cell tumor), neoplasms of the parasellar bone (chordoma), and neoplasms originating from remnants of Rathke's pouch (Rathke's cleft cyst, craniopharyngioma). Furthermore, these tumors may be connected to specific endocrine disorders such as acromegaly or Cushing's disease. Pituitary neoplasms are often mistaken for illnesses such as lymphocytic or granulomatous hypophysitis. This article will summarize these frequent lesions' neuropathological characteristics and molecular pathophysiology.
What Are Pituitary Adenomas?
Pituitary adenomas are noncancerous (benign) growths of the pituitary gland. The neuroendocrine epithelial cells of the adenohypophysis are the source of benign clonal neoplasms. Pituitary adenomas are similar to other endocrine gland adenomas in that they have granular cytoplasm, round nuclei with finely dispersed chromatin, and multiple distinct nucleoli. In addition, they typically express markers of both epithelial differentiation (cytokeratins) and neurosecretory granules (synaptophysin and chromogranin). However, based on hormonal or genetic subtypes, or as a consequence of therapeutic effects, they can present with a broad range of morphological traits. Pituitary adenomas, despite being referred to as benign, can be locally invasive and destructive, or because of the excess hormone secreted and its metabolic effects, they can develop into a clinical malignancy.
There are two types of pituitary adenomas: those that are clinically functioning and those that are clinically not functioning. TSH-secreting adenomas (TSHomas), ACTH-secreting adenomas (ACTHomas), FSH-secreting adenomas (FSHomas), prolactin (PRL) secreting adenomas (PRLomas), and GH secreting adenomas (GHomas) are included in the former. LHomas are not very common. GHomas and PRLomas are the most common adenomas; the other tumors are uncommon. Clinically, the remaining adenomas are "non-functioning." The fact that the majority of clinically nonfunctioning adenomas are positive for gonadotropin subunits (SUs) should be highlighted in particular.
Pituitary adenomas are common intracranial neoplasms that usually remain silent and are diagnosed postmortem (14 percent) or coincidentally discovered on brain MRI scans (22 percent). They account for about 25 percent of all intracranial neoplasms that exhibit clinical symptoms.
How Is Pituitary Adenomas Classified?
Pituitary adenomas can be categorized based on several factors: size, histologic characteristics, hormone or cytokeratin expression profile, clinically functioning or silent manifestation, and defining somatic mutations. The primary classification in the 2004 edition of the WHO classification system for endocrine tumors is cytodifferentiation markers. It also established the idea of "atypical pituitary adenoma" in addition to the categories of "pituitary carcinoma" and "typical pituitary adenoma." Nonetheless, the latter is debatable since the standards are somewhat arbitrary, and longitudinal research is still needed to establish the clinical importance of "atypia" as it is now described. The current classification is as follows:
1. GH-Producing Adenoma (Growth Hormone Producing Adenomas):
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Sparsely granulated somatotroph adenoma.
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Densely granulated somatotroph adenoma.
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Mixed somatotroph and lactotroph adenoma.
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Mammosomatotrop adenoma.
2. PRL-Producing Adenoma (Prolacting Producing Adenomas):
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Densely granulated lactotroph adenoma.
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Sparsely granulated lactotroph adenoma.
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Acidophil stem-cell adernoma.
3. TSH-Producing Adenoma (Thyroid Stimulating Hormone Producing Adenoma):
- Thyrotroph Adenoma.
4. ACTH-Producing Adenoma:
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Densely granulated corticotroph adenoma.
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Sparsely granulated corticotroph adenoma.
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Crooke’s cell adenoma.
5. Gonadotrophin Producing Adenoma:
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Gonadotroph adenoma.
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Plurihormonal adenomas.
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Silent type III adenoma.
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Unusual plurihormonal adenoma (NOS).
6. Hormone Negative Adenoma:
- Null-cell adenoma
What Are the Histopathological Features of Pituitary Adenomas?
Pituitary adenomas are noncancerous tumors that grow in the pituitary gland, a tiny gland the size of a pea near the base of the brain. These tumors are usually benign, and depending on the types of cells present, the hormones they produce, and the way they grow, they may show various histological characteristics. Below is an overview of the histological characteristics that are frequently linked to pituitary adenomas:
Cell Types:
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Somatotroph Adenomas: These tumors comprise Growth Hormone (GH)-producing cells.
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Lactotroph Adenomas: These are standard cells that release prolactin and are frequently linked to hyperprolactinemia.
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Corticotroph Adenomas: Adrenocorticotropic hormone (ACTH) is produced by corticotroph adenomas associated with Cushing's disease.
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Thyrotroph Adenomas: Thyroid-stimulating hormone-secreting rare adenomas (TSH).
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Gonadotroph Adenomas: Less common tumors that produce gonadotropins (FSH and LH) are called gonadotroph adenomas.
Hormone Immunostaining:
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The use of immunohistochemistry helps to determine which tumor cells produce hormones. Hormones such as growth hormone, prolactin, ACTH, TSH, FSH, and LH can be found using various stains.
Growth Patterns and Architecture:
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Microadenomas: Small tumors with a diameter of less than 10 mm.
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Macroadenomas: Macroadenomas are larger tumors with a more than 10 mm diameter.
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Invasive Adenomas: Tumors that penetrate nearby areas like the cavernous sinus or sphenoid bone are called invasive adenomas.
Cytological Atypia :
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Benign pituitary adenomas typically have very little cellular atypia. Significant atypia could indicate a malignant or aggressive lesion.
Mitotic Activity:
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Benign pituitary adenomas are characterized by low mitotic activity. More mitotic figures may indicate a more aggressive tumor.
Vascularization:
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The capacity for tumor growth may be influenced by the vascularity of the growth, which can be evaluated by parameters such as angiogenesis.
Dystrophic Calcifications:
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On imaging tests, calcifications may be seen in some pituitary adenomas. Areas of increased density characterize these.
Conclusion:
In conclusion, the microscopic analysis, supported by immunohistochemical methods, helps distinguish between microadenomas and macroadenomas, providing important information about the size and potential invasiveness of the tumor in addition to defining the hormone profile. Layers of complexity are added by cytological atypia, mitotic activity, and dystrophic calcifications, which may indicate the aggressiveness of some adenomas. When it comes to pituitary adenomas, where hormonal abnormalities can present in a variety of ways, histopathology becomes the key that helps doctors make sense of the confusing array of therapy options. The histological landscape of pituitary adenomas continues to open up new possibilities for better treatment, diagnosis, and, eventually, better patient care as study and understanding expand.
