|Year : 2017 | Volume
| Issue : 2 | Page : 41-46
Prostatic adenocarcinoma and prostatic intraepithelial neoplasia: A tale of the autopsy model in a Nigerian tertiary hospital
Dele Eradebamwen Imasogie1, Akhator Terence Azeke2
1 Department of Morbid Anatomy, University of Benin Teaching Hospital, Benin City, Nigeria
2 Department of Anatomic Pathology, Irrua Specialist Teaching Hospital, Irrua, Edo State, Nigeria
|Date of Web Publication||23-May-2019|
Dr. Dele Eradebamwen Imasogie
Department of Morbid Anatomy, University of Benin Teaching Hospital, P. M. B. 1111, Ugbowo, Benin City
Source of Support: None, Conflict of Interest: None
Introduction: The frequency of clinical prostatic adenocarcinoma and high-grade prostatic intraepithelial neoplasia (HGPIN) in a certain population could be similar to the prevalent model of latent adenocarcinoma as well as to the frequency and extent of HGPIN. The aim of this prospective postmortem study is to determine the prevalence of occult adenocarcinoma and HGPIN and contrasting same with the existing clinical model in the same environment. Subjects and Methods: Adult individuals who died from ailments unrelated to diseases of the prostate glands were the target population using a calculated minimum sample size of 72 cases. The partial sampling method was employed. Sections were assessed for prostatic adenocarcinoma and HGPIN. The biodata and clinical diagnosis were obtained from stored records. Results: Seven patients had occult adenocarcinoma representing 8.1% of the study population of 86 cases. Their median age was 60 years. It had a peak incidence in the sixth decade, with a prevalence of 42.85% in the subset of the study population who had the disease. Gleason's grade 3 and score 6 were the most frequent grades and scores encountered in this study. Those with occult adenocarcinoma were graded International Society of Urological Pathologist (ISUP) 1 using the ISUP grade group system. There were five cases of HGPIN in this study. Their median age was 54 years. It had a peaked incidence in the eighth decade. Conclusion: There exists a subset of the population with occult prostatic adenocarcinoma and HGPIN. These subclinical prostatic lesions may become clinically apparent if these patients had lived long enough, and hence, the prostate should be considered as a possible primary site of metastatic carcinoma because of this concept “occult adenocarcinoma.”
Keywords: Clinical model, high-grade prostatic intraepithelial neoplasia, occult adenocarcinoma, postmortem model, prostatic adenocarcinoma
|How to cite this article:|
Imasogie DE, Azeke AT. Prostatic adenocarcinoma and prostatic intraepithelial neoplasia: A tale of the autopsy model in a Nigerian tertiary hospital. Niger J Surg Sci 2017;27:41-6
|How to cite this URL:|
Imasogie DE, Azeke AT. Prostatic adenocarcinoma and prostatic intraepithelial neoplasia: A tale of the autopsy model in a Nigerian tertiary hospital. Niger J Surg Sci [serial online] 2017 [cited 2019 Sep 15];27:41-6. Available from: http://www.njssjournal.org/text.asp?2017/27/2/41/258799
| Introduction|| |
The earliest documented postmortem studies on occult prostatic adenocarcinoma in the West African subregion (Nigeria and Ghana) were carried out by Jackson et al. in the 1970s. They determined the frequency of carcinoma (micro and invasive) in consecutive necropsy cases from hospitals in Nigeria, Ghana, and Washington DC It was observed that the microcarcinoma (occult) of the prostate gland occurred with a frequency of 11.8% and at an age-adjusted incidence rate of 40.6/1000 necropsies in the sampled African America population while the age-adjusted incidence rate for microcarcinoma in the combined West African (Accra and Ibadan) series was 36.7/1000 necropsies. They concluded that both age-adjusted incidence rates were almost equal. Interestingly, Jackson et al. also noted that clinically, the peak incidence of carcinoma of the prostate in Nigerian males in Ibadan and in American males in Washington DC was in the 65–74 years age groups. While the median age of patients was 66.4 years in Ibadan and 69.2 years in Washington DC In another study by Jackson et al., preliminary analyses suggested that carcinoma of the prostate is a common disease in both African American (196 of 1000 autopsies) and in Nigerian men (67 of 1000 autopsies). The median age of necropsy cases with carcinoma was 50.0 years in Nigeria and 68.3 years in the U. S. Thus, Jackson et al. have set the stage for comparison of data from autopsy and clinical models of prostatic adenocarcinoma in the same environment. There is a paucity of data on occult adenocarcinoma and high-grade prostatic intraepithelial neoplasia (HGPIN) from postmortem studies in Nigeria, other parts of the West African subregion and the African continent; however, a more recent study from University College Hospital Ibadan by Okani et al. looked at occult adenocarcinoma and prostatic intraepithelial lesion in relation to prostatic diseases without reference to the clinical model in their environment.
Postmortem studies to elucidate occult prostatic adenocarcinoma are not novel to the aforementioned studies,, done in Nigeria; in fact, Rich, in 1935, was the first to have conducted a study that reported that microscopic prostate cancers could be detected at autopsy more commonly than were being diagnosed clinically. In the 1940s and 1950s, high rates of tumor foci in the prostate glands were confirmed by several autopsy studies. One of these autopsy studies was conducted by Franks. Rich and Franks demonstrated 14% of prostatic carcinoma in 292 men and 31% of prostate carcinoma in 220 men at autopsy, respectively. Of the 14% of the carcinoma of the prostate demonstrated by Rich, 5% had been diagnosed clinically while 9% was clinically silent. Other studies have also revealed occult adenocarcinoma in Caucasians at postmortem.,,, None of these studies compared the autopsy models of their findings with the existing clinical models in their respective environments.
It is important to note that prostate cancer is found in all continents and has been noted as the most common male genital cancer in American men. It has also been described as a public health epidemic among African Americans. It is a disease of increasing significance worldwide and among the leading causes of cancer deaths in the United States of America. Prostatic carcinoma is seen more frequently in blacks than Caucasians, and the mortality rate is also higher among blacks. Indeed, data from various clinical studies in Nigeria give a clue to the fact that prostate cancer incidence in Nigeria may have been erroneously underestimated.,,,,,
Some studies have observed associations between HGPIN and prostate cancer on different fronts. HGPIN has been documented to have high predictive value as a marker of prostatic adenocarcinoma. While Jackson et al., did not report on PIN, Okani et al. did. They, however, did not observe any relationship between HGPIN and prostatic adenocarcinoma. Other previous postmortem studies had reported the presence of HGPIN in their respective studies.,, These aforementioned studies did not compare data of HGPIN from their various postmortem studies with data of the same lesion in their respective preexisting clinical studies in their different environments.
Much of what we know today about the prevalence of prostate cancer in various parts of the world comes from autopsy studies. Autopsy performed for epidemiological purposes provides an accurate measure of the occurrence of prostate carcinoma. There is, however, a paucity of epidemiological data from autopsy studies from Nigeria and other Africa populations.
It is likely that the frequency of clinical prostate adenocarcinoma in a certain population could be similar to the prevalent model of latent adenocarcinoma as well as to the frequency and extent of the precancerous lesion. The aim of this prospective postmortem study is, therefore, to determine the prevalence of prostatic adenocarcinoma and high-grade prostatic intraepithelial lesion in adult male who died without overt prostatic disease at the University of Benin Teaching Hospital (UBTH), Benin City and relate the findings to the preexisting clinical data in UBTH.
| Subjects and Methods|| |
This was a prospective postmortem study carried out over a 15-month period (May 1, 2013–July 31, 2014) on adult individuals who died from ailments unrelated to the diseases of the prostate gland. The minimum calculated sample size for this study was 72 adult males. At postmortem, the prostate gland of each recruited case was removed whole, devoid of any nonprostate tissue, weighed and fixed in 10% neutral-buffered formalin. The partial sampling method that guarantees that part of the prostate, usually less than 50%, including all grossly apparent cancers are taken for tissue processing as documented by Bostwick and Meiers was employed in this study. Hematoxylin-and-eosin (H and E) stains were employed to stain the paraffin-embedded sections. These sections were examined under the microscope, and a morphological assessment for HGPIN and prostatic adenocarcinoma was undertaken. The Gleason's grading system was used to grade and score the adenocarcinomas. The corresponding International Society of Urological Society (ISUP) grades were derived using the Gleason's score. The clinical case note of each individual as well as the mortuary/autopsy register was consulted for details of the age and clinical diagnosis. The data obtained were analyzed using the Statistical Package for the Social Sciences, version 16 (SPSS 16, SPSS Inc., Chicago, IL, USA).
| Results|| |
The study population had 86 patients. The distribution of the 86 patients seen in this study from the fourth to ninth decade was 15, 19, 27, 14, 10, and 1, respectively [Table 1]. Seven of these patients had occult adenocarcinoma representing 8.1% of the study population. The most common cause of death in these patients was cardiac-related death [Table 2]. The age in those cases with occult adenocarcinoma ranged from 52 to 85 years with a mean age of 65.29 years, a median age of 60 years, and a modal age of 52 years [Table 3]. Occult adenocarcinoma was seen from the sixth to the ninth decade. It peaked in the sixth decade accounting for 42.85% in the subset of the study population who had disease [Table 4]. The prevalence of occult adenocarcinoma in the sixth, seventh, eighth, and ninth decades was 11.11%, 7.15%, 20%, and 100%, respectively [Table 5]. There was a significant increase in the frequency of occult adenocarcinoma with age, P = 0.02. At this level of statistical significance (P = 0.02), 42.85% (three cases) of those with concealed adenocarcinoma were 59 years and below while 57% (four cases) were 60 years and above. Gleason's grade 3 was the most common histologic grade. It was observed in six of the seven cases accounting for 85.71% of those with adenocarcinoma. This was followed by Gleason's grade 2 in a patient (14.29%). Gleason score 6 was the most frequent score encountered in this study. It accounted for five (71.4%) of the seven cases of occult adenocarcinoma diagnosed histologically. Three (42.86%) of these patients with Gleason score 6 were in their sixth decade while the seventh and ninth decades each accounted for the other two cases (i.e., one case/14.29% in each decade). This is followed by Gleason score 4 (14.29%) and 5 (14.29%). The former and latter were seen in the eighth decade [Table 6]. The International Society of Urological Pathologist (ISUP) grade group system of prostatic adenocarcinoma had a 100% (7 cases) of those with occult adenocarcinoma in ISUP grade Group 1 [Table 7]. The weight of the prostate glands in those cases with occult adenocarcinoma ranged from 15 to 130 g, with a mean weight of 48.57 g, a median weight of 40 g, and modal weight of 30 g [Table 3].
|Table 2: The cause of death in cases with occult adenocarcinoma and high-grade prostatic intraepithelial neoplasia|
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|Table 3: The P value, age, and weight characteristics in those with occult adenocarcinoma and high-grade prostatic intraepithelial neoplasia|
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|Table 4: The prevalence of occult adenocarcinoma and high-grade prostatic intraepithelial neoplasm in those with the disease|
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|Table 6: The age distribution of Gleason's score in patients with occult prostatic adenocarcinoma|
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|Table 7: The International Society of Urological Pathologist grade of those cases with occult adenocarcinoma|
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The HGPIN accounted for five cases of the study population. The most common cause of death in these patients was cardiac-related death [Table 2]. Their ages ranged from 36 to 74 years with a mean age of 55.40 years, a median age of 54 years, and a modal age of 36 years [Table 3]. It was seen in the fourth to sixth and eighth decades. It peaked in the eighth decade which accounted for 40% (2 cases) [Table 4]. The fourth to sixth decade accounted for 20% (a case) each [Table 4]. The frequency of HGPIN increases with age, and this was statistically significant P = 0.05. At this level of statistical significance (P = 0.05), 40% (2 cases) of those with HGPIN were 49 years and below while 60% (3 cases) were 50 years and above. The weight in those with HGPIN ranged from 20 to 55 g, with a mean weight of 36.16 g, a median weight of 35 g, and modal weight of 20 g [Table 3].
| Discussion|| |
Autopsy series has been a valuable part of understanding the natural history of prostate cancer. Majority of the epidemiological studies associated with prostate carcinoma and PIN are based on the biopsy outcomes obtained from symptomatic patients and prostatic-specific antigen (PSA) screenings. The specificity and sensitivity of these studies in showing the prevalence of prostate carcinoma are lower than those of autopsy studies. This can be attributed to latent (occult) and incidental (unsuspected) prostate carcinoma. It is important to note that while the term “latent prostate carcinoma” is used to define prostate carcinoma that is clinically silent and determined during postmortem examination, the “unsuspected” or “incidental prostate carcinoma” refers to prostate carcinoma cases showing no abnormalities in the digital rectal examination, routine PSA analysis, or transrectal ultrasonography.
Forae et al. carried out a 20-year retrospective clinical study on the pattern of the prostatic lesion at the UBTH. They reported that prostatic adenocarcinoma was the second most common disease of the prostate after benign prostatic hyperplasia (BPH) accounting for 30% (252 cases of the 813 prostatic lesions) of all prostatic lesions. Similarly, occult adenocarcinoma in this study was the second most common lesion after BPH representing 8.1% of the study population. The sample size especially in favor of the middle age and elderly in those with clinical suspicion of prostatic adenocarcinoma and nodular prostatic hyperplasia in the study done by Forae et al. might be responsible for the wide disparity in the incidence (30%/8.1%) of prostatic adenocarcinoma in both studies. Forae et al. reported an age range of 50–102 years with the observation that the frequency of prostatic adenocarcinoma increases with age despite a sharp decline in frequency from the ninth to eleventh decades. This decline Forae et al. opined might be related to the reduced life expectancy in Africans in general and Nigerians in particular. The peak age was noted in the eighth decade, thus accounting for 38% of prostatic adenocarcinoma. In this study, the age range for those with prostatic adenocarcinoma was 52–85 years. The peak age was in the sixth decade, thus accounting for 42.85% of prostatic adenocarcinoma with a decline in the frequency thereafter. Despite this decline, this study has shown that the frequency of concealed adenocarcinoma increases with age (P = 0.02).
The decline in frequency of concealed adenocarcinoma after the sixth decade might be due to a reduction in life expectancy in Nigerian males which according to the World Health Organization is 53 years of age., This is further compounded by the fact that the frequency of other prostatic lesions (HGPIN and BPH) increase with age, thus competing with adenocarcinoma for the rate of occurrence as age increases. The ISUP grade was not used for the clinical study. This may be because this grading system was not in use as at the time of the clinical study. The majority (48.41%) of the patients in the clinical study had a Gleason's score of ≤6, thus corresponding to an ISUP grade of 1. Gleason's score 7 (ISUP 2 or 3 depending on whether the Gleason's score was 3 + 4 or 4 + 3), 8 (ISUP 4), 9 and 10 (ISUP 5) accounted for 7.9%, 11.11%, and 15.87% of the patients in the clinical study. The ISUP grade 1 was the sole and most common grade in this study, thus making it the most common in both studies.
PIN comprises lesions in which the lining epithelium of preexisting ducts and acini undergoes architectural and cytological atypia. The relationship between HGPIN and prostate cancer has been reported. HGPIN has a high predictive value as a marker of adenocarcinoma; however, it was not found coexisting with the observed cases of occult adenocarcinoma in this study. Forae et al. did not report any incidence of the isolated PIN in their study; however, they noted that it occurs as an incidental finding in prostate glands removed with a clinical diagnosis of BPH which was subsequently confirmed by histology. This lesion was associated with 2% of BPH, and no association with adenocarcinoma was noted. In this study, although 5.8% of the study population had HGPIN, it, however, did not coexist with adenocarcinoma, a finding similar to that of Forae et al.
The clinical study and autopsy study rate of occurrence of prostatic carcinoma increase with age (middle age and elderly), with a decline in the frequency in both studies immediately after the peak age. Both studies showed that prostatic carcinoma is the second most common prostatic lesion after nodular prostatic hyperplasia. The incidence of adenocarcinoma at the peak age closely approximates in both studies, i.e., 38% and 43% for the clinical and autopsy studies, respectively. More so, HGPIN has no relationship with prostatic carcinoma in both studies. This latter observation was also noted in work done by Okani et al. The postulate that “it is likely that the frequency of clinical prostate cancer in a certain population could be related to the prevalent model of latent cancer as well as to the frequency and extent of HGPIN is to a large extent true.
| Conclusion|| |
There exist subsets of the postmortem population in particular and the living population in general with occult adenocarcinoma and HGPIN. It, therefore, follows that it was only a matter of time for these subclinical prostatic lesions to become clinically apparent if these patients had lived long enough. It stands to reason that metastatic prostatic adenocarcinoma in the absence of clinically apparent prostatic lesion should be entertained in the middle aged and the elderly when considering differentials of possible metastatic sites in cases of metastases because of the concept of occult adenocarcinoma and HGPIN.
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