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ORIGINAL ARTICLE
Year : 2017  |  Volume : 13  |  Issue : 6  |  Page : 1000-1006

A study of the pathological outcome of positron emission tomography-computed tomography 2-(18F)-fluro-2-deoxy-D-glucose avid lesion: A 5 years retrospective study


1 Department of Histopathology and Cytopathology, Rajiv Gandhi Cancer Institute and Research Centre, Rohini, New Delhi, India
2 Department of Radiology, Rajiv Gandhi Cancer Institute and Research Centre, Rohini, New Delhi, India

Date of Web Publication13-Dec-2017

Correspondence Address:
Dr. Jatin S Gandhi
Department of Histopathology and Cytopathology, Rajiv Gandhi Cancer Institute and Research Centre, Sector 5, Rohini, New Delhi - 110 085
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/0973-1482.165874

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 > Abstract 

Introduction: Positron emission tomography-computed tomography (PET-CT) has been commonly used for staging and follow-up in cancer patients. The present study compares radiological and pathological outcomes at all the sites. The benign nonphysiological uptake reduces the specificity of the modality due to high false positive (FP) rate although sensitivity for malignant lesions may be high.
Aims and Objectives: To study the sensitivity, specificity, positive and negative predictive value (PPV and NPV) of PET-CT in the detection of malignant lesions for all sites using pathological and final clinical outcome.
Materials and Methods: A retrospective study of 195 cases of PET-CT detected lesions subjected to pathological diagnosis in the form of fine-needle aspiration cytology (FNAC) and/or Tru-cut biopsies were performed on patients with proven or suspected malignancy over a period of 1-year (2009) with a 5 years follow-up. During the same period, 2900 PET-CT imaging studies were performed, of which 195 were suspected to be malignant or benign. Of these, 193 patients were subjected for tissue diagnosis for confirmation. FNAC smears and Tru-cut biopsy were prepared and examined as per standard protocols.
Results: Of 195 aspirates in 183 aspirates, a conclusive tissue diagnosis was rendered. The follow-up was available in 79 cases of suspicious PET avid lesions for a period of 1–5 years. The PET-CT correlation with the tissue diagnosis and clinical outcome showed the sensitivity of 97.7% and an overall accuracy of 83% for malignant lesions. However, due to a large number of FP (n = 28) the specificity was only 43% and FP rates were 57%. PPV and NPV for malignant lesions was 82.4% and 87.5%, respectively.
Conclusion: PET-CT is a sensitive investigation for detection of malignant lesions in treated and newly diagnosed cases of malignancy.

Keywords: Biopsy, fine needle aspiration cytology, positron emission tomography-computed tomography


How to cite this article:
Gupta G, Gandhi JS, Sharma A, Pasricha S, Mehta A, Rao A, Kamboj M. A study of the pathological outcome of positron emission tomography-computed tomography 2-(18F)-fluro-2-deoxy-D-glucose avid lesion: A 5 years retrospective study. J Can Res Ther 2017;13:1000-6

How to cite this URL:
Gupta G, Gandhi JS, Sharma A, Pasricha S, Mehta A, Rao A, Kamboj M. A study of the pathological outcome of positron emission tomography-computed tomography 2-(18F)-fluro-2-deoxy-D-glucose avid lesion: A 5 years retrospective study. J Can Res Ther [serial online] 2017 [cited 2019 Dec 6];13:1000-6. Available from: http://www.cancerjournal.net/text.asp?2017/13/6/1000/165874


 > Introduction Top


There has been increased popularity and availability of high-speed positron emission tomography-computed tomography (PET-CT) scan for diagnosis, staging, and re-staging of oncology cases. The role of the pathologist is to render tissue diagnosis in cases subjected to fine-needle aspiration with or without Tru-cut biopsy.[1] The present study focuses on the pathological outcome of such cases and correlates them with radiological findings and diagnosis rendered on PET-CT.

PET-CT in Oncology makes use of injected 2-(18F)-fluro-2-deoxy-D-glucose (18F-FDG), for imaging the rates of glucose metabolism. The malignant tissue typically exhibits markedly increased rates of glucose metabolism by inefficient anaerobic pathway (Warburg effect). The physiological basis is that that FDG is transported actively like D-glucose and is phosphorylated by hexokinase as the first step in glycolytic pathway. This FDG-6-phosphate cannot enter glycolytic pathway, like phosphorylated glucose and hence is effectively trapped intracellularly (metabolic trapping). The tumor cells also express increased number of glucose transporter proteins and increased levels of hexokinase and phosphofructokinase. These combined mechanisms allow tumor cells to take up and retain higher levels of FDG when compared to normal tissue.[1],[2]

Although, used for detecting malignant lesions with high sensitivity, FDG is not cancer specific and will accumulate in areas of high rates of metabolism and glycolysis. Pitfalls are the physiologic and nonphysiologic uptake of 18F-FDG.[3] These lead to a false positivity (FP) on PET-CT. Tuberculosis is an important cause for the same and when extensive, can mimic malignancy.[4],[5] Other causes include benign bone lesions such as fibromas, fibrous cortical defect, healing fractures and benign bone-forming tumors, inflammatory or infections processes such as abscesses, pneumonia, sinusitis, osteomyelitis, prosthetic joint infection, infectious mononucleosis, and fungal or granulomatous diseases.[6],[7],[8],[9]

Physiological uptake is seen in brain, normal lymphatic tissue, tonsils and Waldeyers ring, salivary gland, thymus heart, breast, diffuse uptake in gastrointestinal tract, liver, spleen, significant uptake in urinary tract, testis, and brown fat at various sites.[3],[6],[7],[8]

The false-negative cases are due some non-FDG avid tumors and their metastasis. Examples include bronchioloalveolar carcinoma lung, prostatic adenocarcinoma, and mucinous carcinoma.[10],[11]

Thus combined PET and CT data are reported to be more accurate in accessing lesions.[1] The role of PET-CT established for neoplasm at various sites is as follows.

In breast carcinoma, the modality is very useful for follow-up, especially in detection of recurrence and distant metastasis.[12],[13] The role is limited for detecting small new primary breast tumors. FP may be observed in presence of fibrocystic change, atypical ductal hyperplasia, ductal ectasia, mastitis, and phyllodes tumor.[12] The sensitivity and specificity of PET to detect the primary lesion range from 80% to 100%.[14] In colorectal carcinoma the role of PET-CT is in assessing regional nodal involvement and distant metastases.[14] In lung carcinoma the PET-CT is an integral part of staging, response assessment and mediastinal nodal staging of nonsmall cell carcinoma. For evaluation of solitary pulmonary nodule, high standardized uptake value is taken as malignant, however infective and granulomatous lesions can show intense FDG uptake. Whereas cancers like lepidic predominant adenocarcinomas may show poor or no FDG uptake.[15],[16],[17]

In lymphomas, PET-CT has high sensitivity (97%) and specificity (100%) for staging. The PET is recommended for staging of potentially curable lymphomas like diffuse large B-cell lymphoma and Hodgkin lymphoma, and is now routinely recommended for indolent histologic subtypes like low grade B-cell lymphomas (including gastric mucosa-associated lymphoid tissue lymphoma) and especially follicular lymphomas-Grade 1.[15],[16],[18],[19],[20]

In thyroid gland, the uptake of FDG is variable; any pet avid focal asymmetric lesions should be subjected to tissue diagnosis. The common causes had been benign lesions like adenomatous change and follicular adenoma.[21] FDG-PET plays a complementary role with conventional radioiodine whole body scan due to flip-flop phenomenon, which is uptake of radioiodine with no FDG uptake and vice versa. This means that FDG uptake is relatively increased in less well-differentiated thyroid cancers.[22] In preoperative setting, PETCT was more reliable at identifying positive disease from CT or MRI alone.[23]

PET-CT identifies a significant number of additional 18F-FDG avid primary cancers on the PET-CT study of patients with known cancer.[24] PET-CT has a high sensitivity and specificity for differentiation of benign from malignant adrenal lesions and is useful in staging also. A 5% of FP rate for PET-CT has been reported secondary to a variety of causes including adrenal adenomas, inflammatory, and infectious lesions. Furthermore, false-negative small (<10 mm) metastatic nodules, and metastases from pulmonary carcinoma or carcinoid tumors. Furthermore, PET-CT cannot offer tissue characterization or differentiate among malignant lesion types.[25],[26]

PET-CT is equally useful in pediatric malignancies with some limitations of FDG-PET that relate to physiologic variations in FDG distribution in children.[7],[27] The aim of this study was to correlate radiological diagnosis with tissue diagnosis and to determine the accuracy of same in detecting malignant and benign lesions.


 > Materials and Methods Top


A retrospective review of 195 cases of PET-CT detected lesions subjected to pathological diagnosis in form of fine-needle aspiration cytology (FNAC) and/or Tru-cut biopsies performed on patients with proven or suspected malignancy over a period of 1-year (between January and December 2009). During the same period 2900 PET-CT imaging studies were performed, of which 195 lesions, suspected to be malignant or benign, from 193 patients were subjected for tissue diagnosis for confirmation. Of 195 aspirates in 183 (including repeat aspirations) (93%), a conclusive cytological/tissue diagnosis was rendered. The patients included both follow-up cases (n = 111) (56%) who were treated by chemotherapy, radiation, surgery or any combination of these modalities and newly diagnosed/suspected cases (n = 72) (36%). The newly diagnosed group was evaluated for staging of disease [Table 1]. The most common indications for tissue diagnosis in PET-CT detected lesion was breast cancer (n = 47), lymphoma (n = 31), metastasis of unknown origin (n = 13), and in new cases (no prior diagnosis n = 31) for staging. The 31 patients with “no prior diagnosis” were subjected for PET-CT to evaluate lung mass (n = 14), lymph nodes (n = 8), pancreas (n = 2), vertebral lesions (n = 2) and one each of liver, adnexal mass, breast, and anterior mediastinal. One hundred and seventy-seven cases were from PET avid hyper-metabolic lesions and only 9 cases were from hypo metabolic lesions. The patients included 107 females and 86 males who ranged in age from 9 to 93 years (median age 54.5 years). The radiological impression was indicated on the request form, and cases stratified as malignant (high index of suspicion for malignancy), benign (features favor benign pathology). The lesions were sampled under CT guidance (n = 145), ultrasonography guidance (n = 30), and without guidance (n = 11). The most common sites for aspiration was lung (n = 35), 19%, liver (n = 28) 15%, abdominal lymph nodes (n = 17), 9%, and upper deep cervical lymph nodes (n = 15), 8%. Overall the most common organ was lymph node at various sites [Table 2].
Table 1: Indications for performing PET/CT

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Table 2: Site of aspiration

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 > Results Top


The PET-CT correlation with the tissue diagnosis showed sensitivity of 97.7% and an overall accuracy of 83% for malignant lesions. However, due to large number of FP (n = 28) 14%, the specificity was only 43% and FP rate was 57%. The radiological diagnosis and final tissue diagnosis was evaluated and compared [Table 3]. The malignant 87% (n = 159)/benign 12% (n = 24) diagnosis as rendered on radiological examination were compared with tissue diagnosis, malignant 67% (n = 131) and benign 26% (n = 52). In most of the benign cases follow-up PET-CT and clinical follow-up further confirmed the radiological and tissue diagnosis. Barring six cases which were reported benign on FNAC, on subsequent clinical follow-up turned out to be malignant. The cases are included with malignant final diagnosis, the cases included: (1) A case of epithelial myoepithelial carcinoma of parotid with flap thickening, with clinic radiological suspicion of recurrence, FNAC reported negative. On follow-up, recurrence at same site after 1-year (tumor excised) final diagnosis was acinic cell carcinoma. (2) Carcinoma breast with hepatic nodules, FNAC reactive hepatocytes. After a year of follow-up of persistence of lesions with increase in size of few, patient was treated by chemotherapy. (3) Carcinoma breast operated site lesion reported fat necrosis and in year 2010 FNAC same site reported positive after 8 months of follow-up. (4) Carcinoma sigmoid colon, liver lesion reported negative, follow-up after 1-year revealed metastatic adenocarcinoma. (5) Carcinoma stomach, node reported negative, same/different site metastasis 2013 on follow-up. (6) Carcinoma vocal cord, lung lesion reported as reactive and in 2010 malignant. One case of carcinoma stomach failed on further follow-up at 4 years. This was taken as true positive on FNAC. The positive predictive value (PPV) and negative predictive value (NPV) for malignant lesions were 82.4% and 87.5%, respectively.
Table 3: Comparison of diagnosis provided by PET/CT and final tissue diagnosis

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The 28 FP cases on PET-CT [Table 4], 13 cases were inflammatory lesion: Chronic granulomatous inflammation (n = 5), acute and chronic nonspecific inflammation (n = 8) and five nodal masses were reported as reactive. Rest of the cases were from lung, operative site, or liver that showed reactive changes only, same was confirmed by follow-up PET-CT and clinical follow-up. The common sites were lymph nodes (n = 10), lung (n = 4), and liver (n = 3).
Table 4: Cases with PET/CT diagnosis of malignant and reported as benign on FNAC

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In 12 (out of 186) inconclusive cases repeat procedure was carried out.

In hypometabolic lesions [Table 5], out of 9 cases only 2 were malignant (one case of nodal large B-cell lymphoma) recurrence and second case was of a metastatic adenocarcinoma to liver in a proven case of carcinoma breast. Radiological evaluation was accurate in 8 cases, as shown in [Table 5].
Table 5: Hypo metabolic lesions

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In cases with no prior diagnosis [Table 6], the most common sites for aspirate were lung (n = 15). This is explained by the fact that lung is the most common site for detection of lesions (masses in our study), in 13 cases the aspirates were done for primary lung lesions and in two cases it was for staging work up for other suspected primary. Of 15 cases two turned out to be benign (aspergillosis and granulomatous lesions-acid-fast bacilli positive).
Table 6: Different sites with no prior diagnosis

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Sensitivity, specificity, overall accuracy, PPV, and NPV for malignant lesions was, 97.8%, 43%, 83.1%, 82.4%, and 87.5%, respectively.

Twenty-one cases reported as benign on both PET-CT and tissue diagnosis, follow-up was available for 11 cases (ranging from 1 to 4 years) and none failed.

In our study, most of the breast carcinomas with recurrences were of intermediate to high grade with lymphomas too following a similar trend [Table 7].
Table 7: Grades of different tumor with recurrences in breast and NHL

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 > Discussion Top


The present study is one of the few studies comparing the radiological evaluation, pathological diagnosis and clinical follow-up of 5 years in the case of benign diagnosis at the initial cytological examination.

The overall accuracy of 83.1% for PET-CT for diagnosing malignant lesion is comparable to other studies [Table 8]. Nguyen et al. reported PET PPV for malignancy of 72%, which was less than our study (82.4%), exclusion of pulmonary lesions may explain the lower PPV.[28] They also studied PPV for specific sites and reported high PPV for bone (96%) and liver (90%). The high sensitivity of 97.8% is limited by high FP rate of 57%, thereby low specificity of 43%.
Table 8: Comparison of sensitivity and specificity of PET, PET/CT reported for various sites in literature

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This when compared to other studies the specificity is lower in our case. The high FP rate in a the present study is because of inflammatory and reactive changes, presenting as PET avid lesions in treated/newly diagnosed oncology patients, raises suspicion of recurrence/malignancy. In 28 cases, PET-CT diagnosis of malignant was benign on tissue diagnosis. All of these cases were confirmed on follow-up imaging and the clinical absence of disease. The the most common causes are listed. The presence of solitary noninflammatory lesions in liver and lung lead to suggested diagnosis of malignancy on radiology.

In treated cases breast carcinoma was the commonest indication for PET-CT, followed by lymphoma. Compared to other studies, lymphoma was the most common indication.[2] Hence, requisite experience and knowledge for same is mandatory for correct and useful interpretation of PET-CT findings. However, appearances of avid lesions supported by morphology in CT in follow-up cases of treated cases of oncology are common cause for FP diagnosis on PET-CT.

In our study, all such lesions (suspected benign and suspected malignant) were subjected to tissue diagnosis to confirm or to rule out malignancy. This was needed for clinical decision about further chemotherapy and prognosis. However, a close follow-up of the suspected cases with repeat aspiration or increased symptoms/size of lesion were helpful in detecting malignant lesions in cytological negative cases.


 > Conclusion Top


PET-CT is a sensitive investigation for detection of malignant lesions in treated and newly diagnosed cases of malignancy. High FP is mainly due to nonphysiological uptake of FDG by inflammatory conditions such as tuberculosis, fungal infection, abscess, chronic inflammatory lesions and granulation tissue (operative site). Thus, PET-CT fulfills criterion for screening test because of high sensitivity for malignant lesions (97.8%) and low false-negative rate. In suspicious cases, clinical and radiological correlation needs to be done to rule out benign lesions. A tissue diagnosis confirmation helps in accurate diagnosis, management and detection of new second primaries. Although FNAC and biopsy may fail to detect malignancy in minority of cases, clinicoradiological follow-up and repeat biopsy may confirm malignancy. As in our study, six cases reported benign turned out to be malignant on follow-up.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.[31]

 
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  [Table 1], [Table 2], [Table 3], [Table 4], [Table 5], [Table 6], [Table 7], [Table 8]



 

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