Morphofunctional characteristics of pituitary adenomas

Pituitary adenoma is a benign glandular tumor that develops from the tissue of the anterior pituitary. It is characterised by uncontrolled cell expansion. According to the WHO, adenomas represent 80% of all pituitary tumors. In 2021, 2,3 million cases were registered around the world. Nowadays, progression of pituitary adenoma is considered to be caused by monoclonal somatic mutations and developmental disorders during intrauterine growth. Pituitary tumor occurs mainly in a sporadic way, but inheritance is also possible. There are many complementary classifications of pituitary adenomas according to the size, location, and direction of expansion, as well as aggressiveness. Besides, they may be categorised by cytological features, functional and hormonal activity. According to the cell type, tumors may be classified into chromophobe, acidophilic, basophilic, and mixed. Depending on their size, microadenomas and macroadenomas are distinguished. Microadenomas measure up to 1 centimeter in diameter and do not involve surrounding tissues. Macroadenomas are larger than 1 centimeter, manifest with hypopituitarism and can potentially compress adjacent tissues. Microscopically, these tumors may have sinusoidal architecture or diffuse type. Pituitary adenomas may have expansive growth or low proliferative activity; be non-invasive or invasive, the latter invading local tissues. Depending on their location in relation to sella turcica and nearby anatomical structures, they are divided into endosellar adenomas and endo-extrasellar adenomas. Besides, it is necessary to mention the Hardy and the Knosp classifications due to their clinical importance. However, the Zurich pituitary score has a higher scientific impact. The score is based on the ratio between the maximum horizontal tumor diameter and the minimum intercarotid distance. Depending on the tumor size and expansion, several surgical approaches might be used: transsphenoidal approach, transcranial approach and combined approach. In 36-54% of cases, adenomas do not produce any hormones, being known as non-functional. Hormonally active tumors are called functional. Tumors are also classified based on the secreted hormone. In this article, we rely on the 1980 R. Aldman’s classification, which includes the following types: somatotropinoma, prolactinoma, corticotroph adenoma, thyrotropinoma, gonadotropinoma, mixed adenoma, and non-functional tumors – oncocytoma and non-oncocytic adenoma. Somatotropinoma is a pituitary adenoma characterised by excessive production of growth hormone. Two types are distinguished according to the granularity – sparsely and densely granulated. Somatotropinoma may manifest with gigantism or acromegaly before and after the closure of the epiphyseal growth plates, respectively. Prolactinoma results in common neuroendocrine disorders. The cells have a monomorphic appearance and are arranged in sheets or cords. Cytoplasm may be acidophilic or chromophobic, containing a small number of secreted granules, which allows to evaluate tumor aggressiveness. Corticotroph adenoma is a pituitary adenoma producing adrenocorticotropic hormone. This type is subdivided into sparsely granulated, densely granulated, and silent. Gonadotropinoma secrets luteinizing hormone and follicle-stimulating hormone. The detection of gonadotropinoma may be challenging due to the biological inactivity of its secretions. Most gonadotropic adenomas contain some chromophobe cells that give a positive periodic acid Schiff (PAS) staining. Thyrotropinoma represents a benign pituitary adenoma which expresses and secretes thyroid-stimulating hormone. These tumors tend to be large and invade adjacent structures. Plurihormonal adenomas express more than one pituitary hormone. In addition, multiple pituitary adenomas may occur, able to produce several types of hormones. Carcinoma, or adenocarcinoma, is uncommon. Generally, it produces hormones and resembles adenomas on morphology. As a result, it demands a multifaceted approach, including the consultations of endocrinologist, neurologist, radiologist, pathologist, neurosurgeon, and ophthalmologist. 

An expert should know structural and functional features of pituitary adenomas to guarantee a precise differential diagnosis, deliver an efficient symptomatic and definitive treatment and facilitate daily patient care. Keywords: pituitary adenoma, somatotropinoma, prolactinoma, corticotropinoma, thyrotropinoma, gonadotropinoma, microadenoma, macroadenoma, morphology, functions Financing. The work has no sources of funding. Conflict of interest. The authors declare no conflict of interest.