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Introduction <p>High-grade transformation (HGT) in salivary gland carcinomas is an abrupt shift from a low-grade, often indolent tumor to an aggressive high-grade variant. What makes this phenomenon critical is its association with rapid disease progression, increased metastasis, and poor patient prognosis. Despite its clinical importance, diagnosing HGT remains challenging due to its sudden morphological changes and overlapping features with conventional high-grade carcinomas. The rationale behind this study is to address the diagnostic gaps by integrating histopathological, immunohistochemical, and molecular markers to improve accuracy in detecting HGT.</p> <p>Rationale: The need is multifold: Diagnostic gaps in HGT of salivary gland carcinomas exist at morphological, molecular, and clinical levels. Morphologically, subtle shifts such as abrupt atypia, necrosis, or rising Ki-67 may be missed without extensive sampling.</p> <p>Molecularly, alterations like TP53 mutations, CDKN2A/PTEN loss, and chromosomal instability are under-recognized. Clinically, delayed detection leads to inaccurate prognostication and suboptimal therapy. Hence, careful pathological assessment with proliferation indices and architecture is critical.</p> <p>Integrating molecular profiling into routine practice can refine diagnosis and guide targeted treatment.</p> Conclusion <p>From a pathologist’s perspective, precise diagnosis of HGT can better inform surgeons regarding the aggressive nature of the tumor, aiding clinical decision-making and surgical planning. Moreover, molecular findings offer promising avenues for future targeted therapies, potentially improving patient outcomes. This study emphasizes the critical role of pathologists in bridging morphological assessment with molecular insights, ultimately guiding multidisciplinary management of salivary gland carcinomas undergoing high-grade transformation.</p>

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High-Grade Transformation in Salivary Gland Carcinomas: Current Concepts on Diagnosis and Targeted Therapy

  • 期刊论文

  • 发表日期：

    2025年12月4日

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  • Sharon John,
  • Arushi Tomar,
  • Prashasti Chundawat,
  • Saloni Verma,
  • Shivanjali Raghuvanshi,
  • Shalini Gupta

摘要

Introduction

High-grade transformation (HGT) in salivary gland carcinomas is an abrupt shift from a low-grade, often indolent tumor to an aggressive high-grade variant. What makes this phenomenon critical is its association with rapid disease progression, increased metastasis, and poor patient prognosis. Despite its clinical importance, diagnosing HGT remains challenging due to its sudden morphological changes and overlapping features with conventional high-grade carcinomas. The rationale behind this study is to address the diagnostic gaps by integrating histopathological, immunohistochemical, and molecular markers to improve accuracy in detecting HGT.

Rationale: The need is multifold: Diagnostic gaps in HGT of salivary gland carcinomas exist at morphological, molecular, and clinical levels. Morphologically, subtle shifts such as abrupt atypia, necrosis, or rising Ki-67 may be missed without extensive sampling.

Molecularly, alterations like TP53 mutations, CDKN2A/PTEN loss, and chromosomal instability are under-recognized. Clinically, delayed detection leads to inaccurate prognostication and suboptimal therapy. Hence, careful pathological assessment with proliferation indices and architecture is critical.

Integrating molecular profiling into routine practice can refine diagnosis and guide targeted treatment.

Conclusion

From a pathologist’s perspective, precise diagnosis of HGT can better inform surgeons regarding the aggressive nature of the tumor, aiding clinical decision-making and surgical planning. Moreover, molecular findings offer promising avenues for future targeted therapies, potentially improving patient outcomes. This study emphasizes the critical role of pathologists in bridging morphological assessment with molecular insights, ultimately guiding multidisciplinary management of salivary gland carcinomas undergoing high-grade transformation.