Review Article

VOLUME: 39 | ISSUE: 2 | Jun 25, 2023 | PAGE: (46 - 49) | DOI: 10.24911/BioMedica/5-339

Will Adding Michel’s Solution to the Laboratory Reagents do Any Good for the Neuropathologists?


Authors: Tuaha Amjad , Muhammad Hassan Malik , Ghulam Rasool , Shameen Shoaib


Authors

Tuaha Amjad

M. Phil Scholar, MLS (Histotechnology), Department of Histopathology, University of Health Sciences, Lahore, Pakistan.

Muhammad Hassan Malik

Student, Masters of Science in MLS, Riphah College of Rehabilitation & Allied Health Sciences, Lahore Campus-Pakistan.

Ghulam Rasool

Lecturer, Department of Histopathology, University of Health Sciences, Lahore, Pakistan.

Shameen Shoaib

Senior Demonstrator, Department of Pathology, Akhtar Saeed Medical and Dental College, Lahore, Pakistan.

Publication History

Received: April 18, 2023

Revised: May 29, 2023

Accepted: June 07, 2023

Published: June 25, 2023


Abstract


The importance of intraoperative consultation through frozen sections can hardly be over-emphasized. The overall accuracy of frozen section diagnosis falls within the range of 92% to 97.98%; however, in brain tissues, the diagnostic accuracy is debatable, considering the artifacts due to ice crystal formation, crushing, and overstretching resulting in impaired histomorphology. On the other hand, reliance on immunohistochemistry on a frozen brain section is even more challenging because of reported interpretational problems. Hence, preserving the histomorphology of brain tissues and optimizing preanalytical variables is crucial for the accurate diagnosis of the patients.


Keywords: Brain, fixation, fixatives, frozen section, histomorphology, immunnohistochemistry, diagnosis.


Pubmed Style

Tuaha Amjad, Muhammad Hassan Malik, Ghulam Rasool, Shameen Shoaib. Will Adding Michel’s Solution to the Laboratory Reagents do Any Good for the Neuropathologists?. BioMedica. 2023; 26 (October 2023): 46-49. doi:10.24911/BioMedica/5-339

Web Style

Tuaha Amjad, Muhammad Hassan Malik, Ghulam Rasool, Shameen Shoaib. Will Adding Michel’s Solution to the Laboratory Reagents do Any Good for the Neuropathologists?. https://biomedicapk.com/articles/online_first/339 [Access: December 11, 2023]. doi:10.24911/BioMedica/5-339

AMA (American Medical Association) Style

Tuaha Amjad, Muhammad Hassan Malik, Ghulam Rasool, Shameen Shoaib. Will Adding Michel’s Solution to the Laboratory Reagents do Any Good for the Neuropathologists?. BioMedica. 2023; 26 (October 2023): 46-49. doi:10.24911/BioMedica/5-339

Vancouver/ICMJE Style

Tuaha Amjad, Muhammad Hassan Malik, Ghulam Rasool, Shameen Shoaib. Will Adding Michel’s Solution to the Laboratory Reagents do Any Good for the Neuropathologists?. BioMedica. (2023), [cited December 11, 2023]; 26 (October 2023): 46-49. doi:10.24911/BioMedica/5-339

Harvard Style

Tuaha Amjad, Muhammad Hassan Malik, Ghulam Rasool, Shameen Shoaib (2023) Will Adding Michel’s Solution to the Laboratory Reagents do Any Good for the Neuropathologists?. BioMedica, 26 (October 2023): 46-49. doi:10.24911/BioMedica/5-339

Chicago Style

Tuaha Amjad, Muhammad Hassan Malik, Ghulam Rasool, Shameen Shoaib. "Will Adding Michel’s Solution to the Laboratory Reagents do Any Good for the Neuropathologists?." 26 (2023), 46-49. doi:10.24911/BioMedica/5-339

MLA (The Modern Language Association) Style

Tuaha Amjad, Muhammad Hassan Malik, Ghulam Rasool, Shameen Shoaib. "Will Adding Michel’s Solution to the Laboratory Reagents do Any Good for the Neuropathologists?." 26.October 2023 (2023), 46-49. Print. doi:10.24911/BioMedica/5-339

APA (American Psychological Association) Style

Tuaha Amjad, Muhammad Hassan Malik, Ghulam Rasool, Shameen Shoaib (2023) Will Adding Michel’s Solution to the Laboratory Reagents do Any Good for the Neuropathologists?. , 26 (October 2023), 46-49. doi:10.24911/BioMedica/5-339


Biomedica - Official Journal of University of Health Sciences, Lahore, Pakistan

Volume 39(2):46-49

MINI REVIEW

Will adding Michel’s solution to the laboratory reagents do any good for the neuropathologists?

Tuaha Amjad1*, Muhammad Hassan Malik2, Ghulam Rasool3†, Shameen Shoaib4

Received: 18 April 2023 Revised date: 29 May 2023 Accepted: 07 June 2023

Correspondence to: Tuaha Amjad

*M. Phil Scholar, Medical Laboratory Sciences (Histotechnology), Department of Histopathology, University of Health Sciences, Lahore, Pakistan.

Late

Email: tahaamjad477@gmail.com

Full list of author information is available at the end of the article.


ABSTRACT

The importance of intraoperative consultation through frozen sections can hardly be over-emphasized. The overall accuracy of frozen section diagnosis falls within the range of 92% to 97.98%; however, in brain tissues, the diagnostic accuracy is debatable, considering the artifacts due to ice crystal formation, crushing, and overstretching resulting in impaired histomorphology. On the other hand, reliance on immunohistochemistry on a frozen brain section is even more challenging because of reported interpretational problems. Hence, preserving the histomorphology of brain tissues and optimizing preanalytical variables is crucial for the accurate diagnosis of the patients.


Keywords:

Brain, fixation, fixatives, frozen section, histomorphology, immunnohistochemistry, diagnosis.


Appropriate fixation of tissues for histological examination is extremely important. The major objective of fixation in pathology is to maintain clear and consistent morphological features. In order to visualize the microanatomy of tissue, its stained sections must maintain the original microscopic relationships among cells, cellular components, in particular, the cytoplasm, nuclei, and extracellular material, with little disruption of the organization of the tissue along with maintenance of tissue’s local chemical composition.1,2

Fixation of tissue can be accomplished by physical or chemical methods. Formaldehyde has been the “gold standard” fixative for decades. It is cheap, enables long-term storage of surgical material, preserves morphologic features well, allows special histologic stains, and in combination with antigen retrieval, allows for immunohistochemical analysis.3 However, formaldehyde was classified as “carcinogenic to humans” by the International Agency for Research on Cancer and, therefore, represents a risk to anyone handling the solution. Furthermore, it is cross-linking masks antigens, which may hamper immunohistochemical analysis and cause fragmentation of nucleic acids that, in turn, impairs extraction of deoxyribonucleic acid (DNA) and ribonucleic acid. Other effects of using formaldehyde as a fixative include hardening, shrinkage, and color variation in the tissue sections.4-6

The frozen section for intraoperative consultation is widely used to assist in timely treatment decisions. Primary diagnosis, assessment of margins of excision, and nodal status assessment are the major indications for intraoperative consultations on several types of tissues.7,8 Several studies have been conducted worldwide to assess the diagnostic accuracy of frozen sections in general, and the overall accuracy of frozen section diagnosis has been extensively studied. This accuracy rate falls within the range of 92% to 97.98%.9,10 The diagnostic process can be greatly affected by the technical errors in frozen sections. Freezing artifacts due to the ice crystals introduced into the examined tissue, crushing artifacts, and overstretching artifacts seen in frozen preparations are common technical errors faced in the intraoperative consultations performed on specimens.11

Fresh frozen specimens are a better source of template DNA compared to archived formalin-fixed specimens.8,12 Immunohistochemistry (IHC) on a frozen section material has the potential to reduce the number of late positive lymph nodes, especially concerning micro-metastasis and single-cell infiltration.13,14 An interpretational problem with IHC on frozen sections is impaired morphology combined with the presence of endogenous peroxidase, which might give false positive staining results, but snap freezing to reduce freezing artifacts and blocking endogenous peroxidase activity greatly reduces these artifacts.15-17

One of the other imperative considerations while performing IHC, especially on frozen sections, is the time consumption and cost of the procedure. Nowadays, intraoperative IHC examination methods have been developed. The use of IHC results in higher detection rates of metastases and fewer re-operations. A study conducted to evaluate the clinical and economic implications of intraoperative IHC showed an overall cost saving of approximately 40%.18,19 The central nervous system (CNS) tumors pose diagnostic challenges because tumors of varying histogenesis show divergent differentiation and overlap in morphological features.20 IHC is done, in addition to the routine histopathologic examination, to overcome the diagnostic difficulties since an accurate histologic diagnosis helps in predicting the clinical outcome of various CNS tumors.21 The diagnosis of progressive glioblastoma is aided by the use of immunohistochemical stains. Specific genetic alterations that have been most thoroughly documented include isocitrate dehydrogenase 1 and 2 mutations, and promoter methylation status of methylguanine-DNA methyltransferase can also be determined by antigenic expression on tissues.22

Unfortunately, freezing of brain tumor tissue samples impairs histomorphology, and diagnostic tumor typing remains conclusive on the basis of tissues that are formalin-fixed and paraffin-embedded.9,23 Thus, histomorphology and molecular analyses have to be performed from two different tissue samples, which could hamper a direct comparison of results.24 Moreover, the maintenance of a frozen tissue bank is complex and costly. The collection of frozen brain tumor samples in the frame of multi-centric clinical trials with companion tissue-based translational research has proven problematic, in particular for logistic and economic reasons.25 Alternative methods that do not impair nucleic acid quality and at the same time warrant high-quality histopathology and facilitate molecular analysis are needed. In recent years, several new fixatives and transport media have been proposed as an alternative to formalin fixation.8,26,27 Among these alternatives, Michel’s transport medium (MTM) seems to be a promising option. This medium, initially described by Michel et al.28 has been simplified by Niedecken and Lange29 and is currently used by most of the laboratories for the transport and detection of tissue-bound immune reactants by direct immunofluorescence microscopy and molecular analysis30,31 and was subsequently used for transport of renal biopsy specimens for evaluation of immunoglobulin and complement deposition and even lymph nodes for detection of lymphocyte surface markers.32 The MTM has not yet been extensively tested for brain biopsies but is recommended, in a single study, for use in a study for transporting small brain tissue sections which were 0.2 cm thick for long-term preservation in autopsy specimens.33

From a neurosurgical viewpoint, intraoperative consultation on neurosurgical specimens is a valuable guide for the best intra-or post-operative patient management. In addition, tumors such as astrocytomas and oligodendrogliomas can be intraoperatively diagnosed if artifacts and background staining in IHC can be knocked down.34 Direct freezing of tissues leads to antigenic cryo-precipitation that can be a major issue in false positive/negative reporting of brain biopsies. Hence, the development of new fixatives and/or methods must be explored to minimize these artifacts and to maximize the retention of morphological details as well as antigenicity for reaching a conclusive diagnosis and differential diagnosis, which is critical for patients with CNS lesions, including tumors.


Limitations of the Review

This review could not include data and efficacy statistics of MTM on different tissues as reported in the literature. A comprehensive systematic review should be carried out to generate reliable and authentic data regarding the utility of this fixative in routine labs.


Acknowledgement

The principal author is grateful to the Head of the Histopathology Department, University of Health Sciences, Lahore, Pakistan, Prof. Nadia Naseem, for guiding and mentoring during the finalization of the research proposal from which this review article has been derived.


List of Abbreviations

CNS Central nervous system
DNA Deoxyribonucleic acid
IHC Immunohistochemistry
MTM Michel’s transport medium

Conflict of interests

None to declare.


Grant support and financial disclosure

None to disclose.


Ethical approval

Not applicable.


Authors’ contribution

ALL AUTHORS: Conception, critical intellectual input, drafting of manuscript. Approval of the final version of the manuscript to be published.

GR: Conception and design of study. Acquisition of literature, critical intellectual input. He was co-supervisor of the M.Phil research project of the Principal author.


Authors’ Details

Tuaha Amjad1, Muhammad Hassan Malik2, Ghulam Rasool3†, Shameen Shoaib4

  1. M. Phil Scholar, Medical Laboratory Sciences (Histotechnology), Department of Histopathology, University of Health Sciences, Lahore, Pakistan
  2. Student, Masters of Science in Medical Laboratory Sciences, Riphah College of Rehabilitation & Allied Health Sciences, Lahore Campus, Riphah International University, Islamabad, Pakistan
  3. Lecturer, Department of Histopathology, University of Health Sciences, Lahore, Pakistan (From 29-09-2015 till 22-09-2023)
  4. Senior Demonstrator, Department of Pathology, Akhtar Saeed Medical and Dental College, Lahore, Pakistan

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