Diagnostic Discrepancies between Intraoperative Cytological Frozen Section and Permeant Histopathological Diagnosis of Brain Tumors

Keywords

Brain tumor • Histopathology • Frozen section • Diagnostic compatibility

Introduction

Brain tumors, known as intracranial tumors, are abnormal masses of tissue with cells that continuously grow and multiply. More than 150 types of brain tumors have been documented by the World Health Organization (WHO) [1]. They can be categorized as primary and metastatic tumors. Primary tumors arise from brain tissue or surrounding structures, which include neuroglial cells, meninges, or the ependymal layer. They can be benign (low-grade) or malignant (high-grade). Secondary metastatic brain tumors include any systemic organ cancer that hematogenously spreads to the brain. To distinguish primary from secondary brain tumors, a detailed clinical history and body imaging are important to identify the origin of the tumor but not the exact histological subtype. Furthermore, intraoperative examination of tumor tissue is the gold diagnostic tool to differentiate the two types and to determine the surgical treatment plan.

Intraoperative frozen section (IOFS) diagnosis of brain tumors plays an important role in assessing the adequacy of the specimen, determining the surgical treatment plan, improving surgical procedures, and facilitating postoperative follow-up. In certain cases, when unexpected lesions cannot be identified by radiological imaging, the surgeon can determine the best procedure and endpoint of the operation [2,3]. This can reduce the incidence of surgical complications and avoid unnecessary second surgical procedures. The key criteria and indications for requesting an intraoperative diagnosis by the surgeon are as follows:

(i) intraoperative surgery would be affected by the diagnosis,

(ii) an unexpected lesion appears during surgery that is different from what was clinically suspected,

(iii) the primary goal is to obtain a biopsy diagnosis, and

(iv) the necessity to assess the margins if a total resection is planned [4-6].

The distinction between primary tumor, lymphoma, metastatic tumor, or unusual lesions are considered the main reasons for requesting intraoperative diagnosis of brain tumors. Sometimes, the tumor is not accessible by surgery, and thus a stereotactic biopsy with IOFS is recommended. The assessment of brain tumors through IOFS is commonly used in clinical practice to verify the origin and type of tumor; however, the final diagnosis should be reported later after the permanent section [4,6].

Several studies have discussed the diagnostic accuracy of IOFS in assessing brain tumor type and grading, and inconsistencies were found between IOFS diagnosis and permanent diagnosis. Nevertheless, permanent paraffinembedded examination remains the gold standard in diagnosing brain tumors.

In Saudi Arabia, no publications have discussed the diagnostic accuracy between IOFS and permanent tissue diagnosis of brain tumors. In this study, we aimed to assess the compatibility between the results of frozen sections and permanent sections in patients diagnosed with brain tumors. We also discuss the reasons attributed to the lack of diagnostic accuracy between the two diagnostic methods.

Materials and Methods

Case Stratification

In this retrospective study, we reviewed the histopathological reports of 383 primary and secondary brain tumors between 2013 and 2019 from two medical institutions in Saudi Arabia. The study was ethically approved by the National Biomedical Ethics Committee at King Abdulaziz University (HA- 02-J-008) under general ethical approval. Patient age, gender, intraoperative and permanent histological diagnosis and grading, and recurrence rate were used as statistical factors. The permanent section result was used as a primary criterion, and the frozen section diagnosis was compared with the final diagnosis.

Histopathological Confirmation

The histopathological report of IOFS and permanent paraffin-embedded section of each patient with a brain tumor was examined. The diagnostic compatibility between the two diagnostic methods was determined on the basis of tumor type and grading. The cases were classified into three degrees of diagnostic compatibility as follows:

i) the diagnosis of IOFS was identical to the final diagnosis (perfect fit);

ii) the diagnosis of IOFS was not incorrect but was too broad to be considered fully compatible (partial compatibility); and

iii) the diagnosis of IOFS were incorrect and differs from the final diagnosis (conflict).

Statistical Analysis

Statistical analysis was performed using SPSS software (version 20). To describe the data, we used means, frequencies, and percentages. To assess the diagnostic compatibility of different methods, we used the linear model, ANOVA and people’s Chi-square test. The number and types of discrepancies were identified.

Results

The mean age of the 383 patients was 37.6 + 23.1 years (females: 212 (55.4%); males: 171 (44.6%)). Around 84% of the patients underwent craniotomy and tumor resection, while 15% only underwent tumor biopsy (open or stereotactic biopsy). Most of the tumors were grade IV (n=177, 46.2%), followed by grade II (n=105, 27.4%) (Table 1). Tumour locations are summarized in Figure 1.

Figure 1. Diagnostic compatibility between intraoperative frozen sections and permanent-paraffine embedded sections in all brain tumors enrolled in this study.

Diagnostic compatibility between IOFS and permanent sections

The diagnostic compatibility between IOFS and permanent section showed comprehensive variability, as 53.8% (n=206) of the cases showed perfect match between IOFS and permanent section diagnosis, while 16.2% (n=62) cases showed complete mismatch. Furthermore, 30% (n=115) of the cases showed partial compatibility between the two diagnostic methods (Table 1, Figure 2). For example, the cases diagnosed as glioblastoma with IOFS were also diagnosed as glioblastoma with permanent section; however, these cases represented 13% perfect compatibility among all investigated brain tumors (Table 2). In a few cases, glioblastomas were misdiagnosed with IOFS as low-grade gliomas, necrotic cells, or glioneuronal tumors (Table 3). Hemangioblastomas, schwannomas, pilocytic astrocytomas, and metastatic carcinomas had perfectly matching diagnoses on both sections (Tables 2,3 & Figure 2).

Figure 2. Tumour locations of all cases enrolled in this study. There is 0.25% of cases did not have specific location or the location was not mentioned in the report.

Diagnostic compatibility of low-grade and high-grade gliomas

Approximately 9% of the cases diagnosed as low-grade gliomas with IOFS were diagnosed as high-grade gliomas with permanent sections, and one case was found to be a meningioma (Table 2). Conversely, 17% of the cases diagnosed as high-grade gliomas with IOFS were diagnosed on permanent sections as either low-grade gliomas or a different histological subtype such as medulloblastoma or metastasis. Furthermore, 19% of the cases diagnosed with infiltrating glioma with IOFS showed partial compatibility on permanent sections. The final diagnosis was grade II, such as cases of oligodendrogliomas (Table 2).

Diagnostic compatibility between atypical, reactive, and necrotic cells

From the 22 cases diagnosed as atypical glial cells with IOFS, two of them were permanently diagnosed as mature teratoma and hemangioblastoma. The remaining 20 cases of atypical glial cells were compatible with the same glioma histogenesis, regardless of the grading. These cases were considered partially compatible. The cases that were diagnosed as showing reactive cells with IOFS (n=6, 9.6%) were diagnosed differently from permanent sections (Table 2). These cases included teratoma, hemangioblastoma, germinoma, ganglioglioma, pilocytic astrocytoma, and pituitary adenoma. Cases for which IOFS revealed necrotic cells were diagnostically deferred at the time of surgery. Their permanent sections revealed malignant tumors except one case (pilocytic astrocytoma in the brainstem), which was rediagnosed as diffuse midline glioma.

Relationship between recurrence status and diagnostic compatibility

There was no significant relationship between the recurrence rates and the diagnostic compatibilities of different brain tumors (P=0.54) (Table 4). Cases that showed conflicts in diagnostic compatibility showed no significant differences in recurrence rates compared to cases with perfect diagnosis matches.

Conclusion

The role of frozen sections during intraoperative consultation is important. Our results showed some diagnostic discrepancies between the intraoperative diagnosis of brain tumors and permanent final diagnosis. Appropriate knowledge of pathologists regarding radiological findings and microscopic interpretation with proper communication with neurosurgeons are required to minimize IOFS misdiagnosis. Further studies should be conducted to determine the reasons for this discrepancy and to solve the problems related to this incompatibility.

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