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Global Translational Medicine Immunohistochemistry in pituitary adenomas

both tumor size and histological subtype serve as key technique is semi-quantitative and is subjected to
predictors of aggressive behavior and clinical outcomes. observer-dependent variations. This variability, along
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with its reliance on specific antibodies, introduces bias
4. Discussion into IHC results. The effectiveness of IHC is compromised
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In this study, we conducted a comparative analysis of in cases where adenomas secrete hormone isoforms that
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histological examination and immunohistochemistry to are not recognizable by the chosen antibodies. Petrus
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characterize PAs. A notable strength of this research is et al. noted the potential underestimation of FSH levels
the comprehensive inclusion of radio-clinical, hormonal, when using monoclonal antibodies, particularly in altered
and IHC assessments for all patients, all performed in a isoform balances. 16
single laboratory. Despite numerous publications on PAs, Plurihormonal adenomas are characterized by the
there is a scarcity of large-scale studies scrutinizing both production of multiple hormones, with combinations
morphologic and IHC features. However, a key limitation such as GH-PRL or GH-TSH being common. Our study
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of our study is the absence of molecular analysis, which identified a plurihormonal frequency of 28.9%, which
could provide further insights into tumor behavior. aligns with findings from other studies where over 30% of
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NFPAs often present as macroadenomas and can adenomas expressed multiple hormones. The cytogenesis
exhibit invasiveness. The primary therapeutic approach of these tumors remains poorly understood, but they can
involves surgery, with radiotherapy employed in cases of significantly impact clinical management, especially in
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recurrence or persistence. In contrast to FPAs, medical somatotroph adenomas, where up to 50% may exhibit
interventions for NFPAs are generally less effective, as plurihormonal activity. 13
their management often focuses on alleviating mass effects In a study of 143 plurihormonal PAs, 29 IHC subtypes
rather than hormonal control. The prognosis for NFPAs were recognized, highlighting the complexity of tumor
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depends on the efficacy of these treatments. Although classification. In another study by Balinisteanu et al.,
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most PAs are benign and slow-growing, clinical follow-up only 9.1% of adenomas were found to be plurihormonal.
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is infrequent when no residual tumor is evident post- The differences in reported frequencies may arise from
surgery or irradiation. 10 variations in quantification methods for hormone
Our hormonal findings revealed that prolactinomas, immunoreactivity, emphasizing the need for standardized
somatotroph adenomas, Cushing disease, and NFPAs protocols in IHC analysis. 11
accounted for 57.5% of the cohort, aligning with existing This study has several limitations, including the absence
literature that highlights prolactinomas as the most of molecular analyses, which restricts the ability to explore
common pituitary tumors. Interestingly, our IHC analysis genetic and epigenetic alterations that could provide deeper
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showed that LH and TSH adenomas each represented only insights into the pathogenesis and heterogeneity of PAs,
5% of cases. This lower prevalence may be attributed to the particularly plurihormonal tumors. Without techniques
fact that gonadotroph adenomas are often not surgically such as next-generation sequencing or RNA sequencing,
removed due to their indolent nature. In addition, the study was not able to identify potential biomarkers or
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certain assays, such as alpha subunit measurement, may therapeutic targets.
be necessary to accurately detect these adenomas, which
could contribute to discrepancies. 9 Overall, our findings contribute to the evolving
understanding of PAs, underscoring the importance of
Histologically, eosinophilic adenomas are traditionally integrating histopathological and IHC data for accurate
associated with acromegaly, basophilic adenomas with diagnosis and management. Further research, particularly
Cushing syndrome, and chromophobe adenomas with incorporating molecular analyses, is needed to enhance
non-functionality. However, our findings suggest our understanding of the pathogenesis and behavior of
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that not all acidophilic tumors produce GH, nor are all these tumors.
GH-producing tumors eosinophilic. Similarly, some
basophilic tumors may not cause Cushing syndrome, and 5. Conclusion
many chromophobic tumors exhibit hormonal activity. 11,12 The comparison between pathology examination and IHC
These results align with findings in recent literature that in our study highlights that prolactinomas are the most
emphasize the need for a nuanced understanding of PA prevalent pituitary tumors in our cohort. The critical role of
classification. 13 comprehensive IHC staining for all pituitary hormones is

The IHC classification of PAs has several limitations. underscored, as it is essential for accurately characterizing
Despite its advancements in tumor classification, the the secretory or non-secretory behavior of tumors,

Volume 4 Issue 2 (2025) 100 doi: 10.36922/gtm.8474