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Global Translational Medicine Immunohistochemistry in pituitary adenomas

PAs are broadly categorized into two types: functioning 2. Materials and methods
PAs (FPAs) and non-FPAs (NFPAs). FPAs are characterized
by excess hormone production, often leading to distinct 2.1. Patients
clinical syndromes such as acromegaly, Cushing disease, A total of 40 patients diagnosed with PAs were included
or prolactinomas, depending on the type of hormone in the study. These patients were followed up in the
secreted. In contrast, NFPAs do not cause hormone Endocrinology and Diabetology Department of Farhat
4
hypersecretion and are typically diagnosed due to mass Hached University Hospital, Sousse. Each patient underwent
effects, such as visual disturbances or headaches. Larger pituitary neurosurgery, and the surgical specimens were
4
NFPAs may compress nearby structures, including the analyzed in the Pathology Department of the same hospital.
optic chiasm, leading to neuro-ophthalmologic symptoms. Only cases that were histologically confirmed as PAs after
The 2017 WHO classification incorporates a complete pathological examination were included in the
immunohistochemical (IHC) staining and ultrastructural study. Written informed consent was obtained from all
features, categorizing PAs into five subtypes based on participants for the use of their clinical data and specimens.
hormone immunostaining: prolactin (PRL)-secreting, Patients with histologically confirmed pituitary carcinomas
growth hormone (GH)-secreting, adrenocorticotropic or other non-adenoma pituitary diseases were excluded from
hormone (ACTH)-secreting, thyroid-stimulating the study. All procedures were conducted in accordance
hormone (TSH)-secreting, and gonadotroph adenomas with the ethical standards of the Declaration of Helsinki and
expressing follicle-stimulating hormone (FSH) and approved by the Institutional Ethics Committee.
luteinizing hormone (LH). Non-functioning adenomas 2.2. Clinical identification of PAs
5-7
may express hormone markers without clinical signs of
hormone overproduction, whereas null cell adenomas Patients were classified into two groups based on their
exhibit no detectable hormone production. 4 clinical and biochemical profiles. FPAs were identified in
cases with clinical and biochemical evidence of endocrine
Recent research has highlighted that tumor behavior, syndromes associated with hormone hypersecretion.
including growth potential and recurrence risk, can NFPAs were diagnosed in patients without clinical or
be better predicted through the integration of clinical, biochemical signs of hormone overproduction and were
biochemical, radiological, and IHC profiles with primarily identified through neuro-ophthalmological
molecular and genetic markers. Atypical adenomas, or radiological manifestations. Tumor size was assessed
characterized by more aggressive clinical behavior, often using magnetic resonance imaging and classified as
exhibit features such as a high mitotic rate, increased microadenomas (<10 mm in diameter) or macroadenomas
Ki-67 proliferation index, and p53 overexpression. (≥10 mm). Tumor invasiveness was graded according to
2
This comprehensive approach is crucial in enhancing Hardy’s classification, with Grade I-III being non-invasive
diagnostic precision and optimizing therapeutic and Grade IV classified as invasive. 8
strategies, including surgery, pharmacological treatment,
and radiation therapy. 2.3. Hormonal assessment
Previous studies have emphasized the complementary Serum levels of FSH, LH, PRL, and TSH were measured
roles of histopathology and IHC in diagnosing PAs. using a chemiluminescence immunoassay (Diasorin,
Histopathology evaluates cellular morphology and growth Italy). ACTH and GH levels were determined using
patterns, while IHC facilitates precise identification immunoradiometric assay techniques with commercially
of hormone expression, even in clinically silent or available kits (Beckman Coulter, United States).
ambiguous cases. For instance, NFPA, which constitutes a
significant proportion of pituitary tumors, often exhibits 2.4. Pathological examination
immunoreactivity for pituitary hormones without The pathological examination of the tumor specimens
associated clinical syndromes. Despite these diagnostic consisted of two main steps: tissue processing and
advancements, discrepancies between histopathological histopathological examination. In the tissue processing
classifications and IHC profiles persist, underscoring the phase, tumor specimens were fixed in 10% buffered
need for an integrated diagnostic approach. formalin for 48 h to preserve tissue integrity, followed by
This study aimed to characterize the clinical and embedding in paraffin blocks to facilitate sectioning.
hormonal profiles of PAs and compare their clinical and For histopathological examination, serial sections of
biochemical classifications with histopathological findings 4 µm in thickness were cut from each paraffin block and
to improve diagnostic and management approaches. mounted onto glass slides. Hematoxylin and eosin staining

Volume 4 Issue 2 (2025) 97 doi: 10.36922/gtm.8474