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Table of Contents
ORIGINAL ARTICLE
Year : 2020  |  Volume : 12  |  Issue : 2  |  Page : 50-55

Spectrum of histological diagnoses among clinically suspected PLCC patients in a Nigerian teaching hospital


1 Department of Pathology, University College Hospital, Ibadan, Nigeria
2 Department of Pathology, Faculty of Basic Medical Sciences, College of Medicine, University of Ibadan/University College Hospital, Ibadan, Nigeria
3 Department of Medicine, Faculty of Clinical Sciences, College of Medicine, University of Ibadan/University College Hospital, Ibadan, Nigeria

Date of Submission14-May-2020
Date of Decision26-Jul-2020
Date of Acceptance12-Sep-2020
Date of Web Publication10-Dec-2020

Correspondence Address:
Prof. Samuel Olawale Ola
Department of Medicine, Faculty of Clinical Sciences, College of Medicine, University College Hospital, University of Ibadan, Ibadan
Nigeria
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/NJGH.NJGH_18_20

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  Abstract 


Background and Objective: Hepatocellular carcinoma (HCC) is a common rapidly growing tumor with poor outcomes and hence requires precise, accurate, and timely diagnosis for early intervention. Although it may be suspected clinically and by imaging investigation such as ultrasound scan (USS) of the liver, there are insufficient data correlating these two modalities with histological diagnosis. This study aims at determining the relevance of liver biopsy in the diagnostic confirmation of HCC in clinically suspected Nigerian patients.
Materials and Methods: This is a retrospective cross-sectional study of 105 clinically diagnosed Nigerian patients with HCC who had liver biopsy between January 1, 2001 and December 31, 2017 at the GIT/liver Unit of UCH, Ibadan. After securing the appropriate ethical clearance from the UI/UCH Ibadan ERC, relevant data were collected from patients' Pathology Departmental records and analyzed using appropriate statistical instruments.
Results: There were 105 cases of clinically diagnosed HCC patients, 45 of which had imaging (USS/or computerized tomography scan) diagnosis. The mean age of the patients was 44 ± 14.8 years, ranging from 0.25 to 85 years. They consisted of 69 males and 36 females with M:F ratio of 1.9:1. Histological diagnosis was not ascertained in 8 cases (7.6%), while 97 cases (92.4%) had varied diagnoses. Malignant neoplasms, benign neoplasms, liver dysplasia, and nonneoplastic liver diseases were established in 74.1%, 2%, 9.6%, and 14.5% of cases, respectively. Primary liver cancers accounted for 62.8% of cases and included HCC (59.8%), cholangiocarcinoma (1%), hepatoblastoma (1%), and NHL (1%). The sensitivities of clinical and USS diagnoses were 100% and 93%, respectively. The positive and negative predictive values for USS were 65.1% and 0%, respectively. The overall clinical and USS diagnostic accuracies for HCC were 59.8% and 62.2%, respectively.
Conclusion: The clinical accuracy for the diagnosis of HCC among clinically suspected and USS diagnosed HCC is limited in comparison to histological diagnosis by liver biopsy. Hence there should be the utilization of liver biopsies for confirmation of HCC in such suspected Nigerian patients.

Keywords: Clinical accuracy, HCC, histological diagnosis


How to cite this article:
Mashor MI, Oluwasola AO, Ola SO. Spectrum of histological diagnoses among clinically suspected PLCC patients in a Nigerian teaching hospital. Niger J Gastroenterol Hepatol 2020;12:50-5

How to cite this URL:
Mashor MI, Oluwasola AO, Ola SO. Spectrum of histological diagnoses among clinically suspected PLCC patients in a Nigerian teaching hospital. Niger J Gastroenterol Hepatol [serial online] 2020 [cited 2021 Jun 25];12:50-5. Available from: https://www.njghonweb.org/text.asp?2020/12/2/50/302901




  Introduction Top


Hepatocellular carcinoma (HCC) is the most common cancer in males <45 years and the fifth after prostate (21.7%), colorectal (7.6%), nonmelanoma skin cancer (6.4%), with a relative frequency of 6.1%, among all males in Ibadan, Southwest Nigeria.[1] Worldwide, it is the 6th most commonly diagnosed cancer and the 4th most common cause of cancer death.[2] The male-to-female incidence ratio of HCC varies between 2:1 and 4:1 across different populations.[3],[4],[5],[6],[7],[8],[9],[10] The peak age of incidence of HCC in Nigeria is 30–59 years in males and 30–49 in females but in countries of Africa is 60–65 years in males and 65–75 years in females, whereas in other parts of the world like the United States, Canada, and United Kingdom, Hong Kong and Shanghai the peak incidence age is ≥75 years.[4],[5],[6],[7],[8],[9],[10],[11] It is a rapidly growing tumor with poor outcomes and hence requires precise, accurate, and timely diagnosis in all suspecting patients to enhance appropriate early intervention.[5],[6],[7],[12]

Although HCC may be suspected clinically, many imaging techniques have been developed for the diagnosis and staging of liver diseases, including assessment of the severity of the chronic liver disease, screening of patients at risk of developing HCC, noninvasive diagnosis of HCC and other nodules that can develop in cirrhotic livers.[13],[14],[15] Ultrasound scan (USS) is the key modality for the screening of individuals at risk and it has a sensitivity of 60%–90% and a specificity of 90%. However, USS is highly operator dependent with a sensitivity of 63% for nodules <2 cm and has low performance in obese patients, though it is also dependent on the type of available machine. Ultrasound features of HCC include the presence of early nodular lesions showing areas of hypervascularity due to tumor angiogenesis or hypo-vascularity due to loss of portal blood supply resulting in hypo-enhancement in the late washout phase.[16],[17] The presence of these characteristic nodular lesions, elevated alpha-fetoprotein levels >400 ng/ml, and the presence of risk factors such as infection by hepatitis B, hepatitis C viruses and/or liver cirrhosis are considered diagnostic for HCC.[18],[19],[20],[21],[22] Alternatively, the presence of characteristic nodules using two imaging modalities and elevated alpha-fetoprotein levels >400 ng/ml is also considered diagnostic for HCC.[21] However, the sensitivity and specificity of these features are poor in small nodules measuring <2 cm.[22] There are, however, newer imaging modalities such as the computerized tomography scan (CTs), magnetic resonance imaging , and contrast-enhancing USS that aim at overcoming the malady in the early detection of malignant liver nodules <2 cm in diameter.[20],[23]

Tissue biopsy is however, the gold standard investigation for the diagnosis of HCC, although there may be false-negative results due to difficulty in targeting small nodules.[15],[24] Another drawback of tissue biopsy is the reported risk of tumour seeding although the evidence for this remains controversial.[25] There are no sufficient data correlating clinical, other minimally invasive laboratory and imaging diagnostic criteria with tissue histological diagnoses in this environment. There is, therefore, a need to determine the sensitivity, specificity, and accuracy of these diagnostic criteria in comparison with histologic tissue diagnoses. Hence, this study is a presentation of the relevance of liver biopsy in histological confirmation of clinically suspected Nigerians patients of HCC.


  Materials and Methods Top


This is a retrospective study of 105 clinically diagnosed Nigerian patients with HCC who had liver biopsy between January 1, 2001 and December 31, 2017 at the GIT/liver Unit, Department of Medicine, UCH, Ibadan. Their age and sex data as well as the presence of other investigations such as Liver USS and CTs, were collected in addition to their histological diagnoses of the liver biopsy specimen sent to the Pathology Department of the Hospital from their histology request cards and results. The study was conducted consequent to the collection of clearance from the University of Ibadan/University College Hospital Ibadan Ethical Review Committee. The data collected were entered into IBM SPSS version 23 and analyzed for frequencies, and Z test was used to find out if the difference in the proportion of cases diagnosed by USS and that by clinical criteria was significant. Two by two tables were used to determine the sensitivities, specificities, positive and negative predictive values, and overall accuracies. The level of significance was set at P< 0.05.


  Results Top


There were 105 cases of clinically diagnosed HCC patients, 45 of which had imaging (43 had USS only and 2 had both CTS and USS) done to arrive at the diagnosis. The studied subjects had a mean age of mean age of 44 ± 14.8 years, ranging from 3 months to 85 years. They consisted of 69 males and 36 females with a male-to-female ratio of 1.9:1 [Table 1]. The histological diagnosis could not be ascertained in 7.6% (8 cases) of cases due to inadequate tissue while the remaining 97 eventually had a variety of diagnoses [Table 2]. The diagnoses of malignant neoplasms, benign neoplasms, liver dysplasia, and nonneoplastic liver diseases were made in 74.1%, 2%, 9.6%, and 14.5% of cases, respectively [Figure 1]. Primary liver cancer made up 61 patients (62.8%) and are composed of HCC (59.8%), cholangiocarcinoma (1%), hepatoblastoma (1%), and NHL (1%). Out of the 58 patients who had HCC, 34.5% had background liver cirrhosis. Metastatic liver cancers were found in 11.3% of cases, comprising metastatic adenocarcinoma (10.3%) and Wilm's tumor (1%). Therefore, the clinical diagnostic accuracy for HCC diagnosis in this study was 59.8%.
Table 1: Age group and sex distribution of clinically diagnosed primary liver cell carcinoma patients at the Gastrointestinal Tract/Liver Unit, Department of Medicine, University College Hospital, Ibadan, 2001–2017

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Table 2: Sex and histological diagnoses of 97 liver biopsies in clinically diagnosed primary liver cell carcinoma patients at the Gastrointestinal Tract/Liver Unit, Department of Medicine, University College Hospital, Ibadan, 2001–2017

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Figure 1: Histological patterns of liver biopsy specimen in 97 clinically diagnosed patients with primary liver cell carcinoma

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Benign neoplasms were composed of epithelioid hemangioendothelioma (1.03%) and sinusoidal hemangioendothelioma (1.03%). Nonneoplastic liver diseases were made up of cirrhosis with specified (3%) and unspecified etiology (4.12%), chronic hepatitis (1.03%), chronic active hepatitis (3.2%), and cholestatic liver disease (1.03%). Liver dysplastic nodules were seen in 9.6% of the patients, 2 of which were without coexisting pathology, while other patients with liver dysplasia had coexisting nonneoplastic liver diseases. The male-to-female ratio for HCC, primary liver cancers and metastatic liver cancers are 1.5:1, 1.5:1, and 4.5:1, respectively, while that of other noncancer lesions is 3.2:1 [Table 3].
Table 3: Age group and gender distribution of diseases through liver biopsies in clinically diagnosed primary liver cell carcinoma patients at the Gastrointestinal Tract/Liver Unit, Department of Medicine, University College Hospital, Ibadan, 2001–2017

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Although 45 of the patients also had USS, only 43 patients (95.6%) had USS diagnosis of HCC, out of which 28 patients (65.1%) were confirmed histologically as HCC. The remaining 35.9 % had histological diagnoses of non-neoplastic liver diseases (20.9%) and metastatic adenocarcinoma (14%), [Table 4] [Figure 1]. In addition, the two patients that USS did not diagnose as HCC, but as liver cirrhosis and metastatic carcinoma were confirmed as HCC histologically. The sensitivity for USS diagnosis was 93.3%, and the specificity was 0% because there was no true negative result identified by USS in this study. The positive predictive value for USS was 65.1%. The negative predictive value was 0% because there were no true negative results by USS and the overall accuracy or efficiency of USS was 65.1%. Comparing the role of clinical assessment and liver USS of patients to the histology of their liver biopsy specimen, misdiagnosis of HCC occurred in 39 (40.2%) and 17 (37.8%) patients, respectively. The difference was insignificant (P = 0.85).
Table 4: Liver biopsy histology in 43 clinically and ultrasound scan diagnosed primary liver cell carcinoma patients

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  Discussion Top


Definite diagnosis of a disease, not to mention a malignancy, is tantamount to good treatment, and this is the cornerstone of appropriate medical care hence the need for the role of liver biopsy in ascertaining diagnosis of HCC in our clinically suspected patients. Adequate liver biopsy tissue for the diagnosis of HCC obtainable in 92% of our specimen is similar to previous studies among patients with HCC in Nigeria, but is higher than the 81.5% adequacy reported by Caturelli et al. in Italy.[26],[27],[28] In the study by Caturelli et al. each biopsy sample was smeared for cytological examination before fixation of the biopsy tissue, making accurate diagnosis possible in 97.3% of their cases.[28] Therefore, in addition to the need for improvement in carrying out liver biopsy, cytological smear taken before the fixation of the biopsy specimen is capable of increasing its definitive diagnostic yield and thus improving the efforts at surmounting the diagnostic difficulties associated with inadequate liver biopsy tissue.

From our study, the age distribution of patients with histological diagnosis of HCC is peaked at 30–39 and 50–59 years, which are like previous reports among Nigerians from the different parts of Nigeria.[4],[5],[6],[7],[8],[9],[10] Apart from HCC, three patients with other primary liver cancers and 11 patients with metastatic liver cancers were within 40–49 years and 40–59 years, respectively; an observation that has been scarcely previously documented among Nigerians though not unexpected in view of Nigeria's slight rise in life expectancy to 54.8 years in 2020.[29] Furthermore, our patients below the age of 30 years had more HCC without cirrhosis than other age groups. This is similar to findings by Okuda et al. in a study among the Japanese who found lower rates of cirrhosis among younger patients with HCC.[30] Similar to global trends, this study shows that patients with chronic liver disease were predominantly males, especially those with HCC without cirrhosis.[4],[5],[6],[7],[8],[9],[10],[15],[31],[32],[33],[34] This study further shows that benign vascular neoplasms of the liver are predominated by females, which could be consequences of contraception.[35]

Although the parameters for clinical diagnosis of primary liver cell carcinoma (PLCC) were not documented in the histology request cards, the histology reports of the clinically diagnosed PLCC showed that primary liver cancer, metastatic liver cancer, benign liver neoplasm liver dysplasia, and nonneoplastic diseases accounted for 62,8%, 11.3%, 9.4%, 2%, and 14.5% respectively, a report similar to the plethora of various liver pathologies from the histology of liver biopsies performed previously in Nigerians.[10],[27],[36],[37] The florid pattern of different histopathological diagnoses from the liver biopsy of our clinically suspected HCC patients illustrates the progression of diseases from chronic hepatitis to liver cirrhosis, dysplasia, and then HCC or from chronic hepatitis to dysplasia and ultimately to PLCC without cirrhosis, a finding also previously highlighted by Abdulkareem et al. among Nigerians.[38],[39],[40],[41] Furthermore, among the 62.8% histologically diagnosed primary liver cancers in our study, only 58% were HCC which is 95% of the PLCCs, a value comparable to the finding of Ugiagbe and Udoh and Vhriterhire et al. of 83.3% and 91% among their patients with histologically diagnosed primary liver cancers.[10],[37] It is worthy of note that only 34.5% of our subjects with histological diagnosis of HCC had associated liver cirrhosis, a value lower than previous reports of 81% and 78% by Olubuyide and Ndububa et al. at Ibadan and Ile-Ife, respectively, but higher than 23.7% reported by Vhriterhire et al. at Jos.[4],[5],[36] This study shows that not all clinically diagnosed HCC patients are truly definite until confirmed by histology.

Similarly, even though the criteria for USS diagnosis of HCC among our clinically diagnosed HCC subjects were unknown, Park et al. in South Korea reported a sensitivity of 95.2%, similar to the 93% in our study but a positive predictive value of 93.7% which is remarkably higher than the 65.1% from our result.[42] However, USS missed the diagnosis in two of our patients and also wrongly diagnosed HCC in 17 patients. This illustrates the limitation of USS in the diagnosis of HCC, affirming the earlier remark by Maàji et al. that liver biopsy remains the gold standard for its diagnosis.[15]

From the clinical diagnosis of our patients versus the outcome from histological diagnoses, various diseases could mimic HCC and these could range from malignant to benign neoplasms and inflammatory lesions as earlier illustrated by previous studies in Nigeria as well as the findings by Kim et al. from a study in Canada.[4],[10],[27],[36],[37],[38],[39] Thus, the possible neoplastic differential diagnoses of HCC include cholangiocarcinoma, metastatic carcinoma, and NHL while benign disorders range from hemangioma to liver cell dysplasia and other nonneoplastic liver diseases. These differential diagnoses should be considered in the clinical evaluation of suspected HCC patients. It is of great importance that nonneoplastic diseases formed 14.5% of all our clinically diagnosed HCC reinforcing the need to ensure precision in the diagnosis of such patients by liver biopsy before declaring them as having a malignancy of the liver. This uncertainty in such diagnosis will obviously cause unnecessary physical, social, psychological, and spiritual sequelae aside from the side effects from inappropriate therapy to such patients.[43],[44]

Furthermore, the accuracies of 59.8% and 65.1% found in this study for the clinical and USS diagnosis of HCC, respectively, are low. Our study shows that not all patients with clinical and radiological diagnosis of HCC may actually have the malignancy in view of our possible illustrated differentials of the malignancy.[38] It further re-emphasizes that liver biopsy is of premium value in making the diagnosis of HCC over clinical and radiological diagnoses in all suspecting patients to spare patients with benign liver disease from wrong diagnosis as well as the agony of inappropriate therapy.[45] It is also pertinent that not all patients with hepatomegaly that simulate HCC on clinical evaluation are always HCC.[15] Therefore, patients should be better clinically diagnosed as liver tumors instead of HCC. The patients can then be subjected to image-guided liver biopsy, especially with image guidance (when available) to ensure exact targeting of suspicious nodules and definitive diagnosis histologically, thus providing room for possible multi-disciplinary team management.[46],[47]


  Conclusion Top


This study shows that the clinical and imaging diagnostic accuracy for HCC is limited in Nigeria with high rates of misdiagnosis and a diverse spectrum of histologic diagnostic outcomes. There is, therefore, a need for more utilization of liver biopsies for the confirmation of diagnosis of suspected HCC patients in Nigeria.

The limitation of this study is the difficulty in assessing the case notes to ascertain the criteria used to arrive at the clinical and USS diagnosis as well as the absence of controls; hence, further prospective study with a larger population incorporating controls is advocated.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
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