Diagnosis of adenocarcinoma in prostate needle biopsy tissue

Prostate cancer is a major public health problem throughout the developed world. For patients with clinically localised prostate cancer, the diagnosis is typically established by histopathological examination of prostate needle biopsy samples. Major and minor criteria are used to establish the diagnosis, based on the microscopic appearance of slides stained using haematoxylin and eosin. Major criteria include an infiltrative glandular growth pattern, an absence of basal cells and nuclear atypia in the form of nucleomegaly and nucleolomegaly. In difficult cases, basal cell absence may be confirmed by immunohistochemical stains for high-molecular-weight cytokeratins (marked with antibody 34betaE12) or p63, which are basal cell markers. Minor criteria include intraluminal wispy blue mucin, pink amorphous secretions, mitotic figures, intraluminal crystalloids, adjacent high-grade prostatic intraepithelial neoplasia, amphophilic cytoplasm and nuclear hyperchromasia. Another useful diagnostic marker detectable by immunohistochemistry is alpha-methylacyl coenzyme A racemase (AMACR), an enzyme selectively expressed in neoplastic glandular epithelium. Cocktails of antibodies directed against basal cell markers and AMACR are particularly useful in evaluating small foci of atypical glands, and in substantiating a diagnosis of a minimal adenocarcinoma. Reporting of adenocarcinoma in needle biopsy specimens should always include the Gleason grade and measures of tumour extent in the needle core tissue. Measures of tumour extent are (1) number of cores positive for cancer in the number of cores examined, (2) percentage of needle core tissue affected by carcinoma and (3) linear millimetres of carcinoma present.     

Minimal focus of adenocarcinoma on prostate biopsy: clinicopathological correlations

AIMS: To establish the clinicopathological features of minimal volume prostate adenocarcinoma on prostate biopsy. METHODS: Twenty four cases of minimal adenocarcinoma diagnosed on prostate biopsy and treated by radical prostatectomy were reviewed. RESULTS: The major microscopic criteria were nuclear enlargement (22 of 24), infiltrative pattern (19 of 24), prominent nucleoli (19 of 24), intraluminal eosinophilic secretions (15 of 24), and high grade intraepithelial neoplasia associated (11 of 24). Sixteen of 24 cases were assigned a Gleason score 6 on biopsy. When the whole gland was assessed, 22 of these tumours were localised to the prostate (stage pT2), and only two cases were stage pT3. CONCLUSIONS: Minimal focus of adenocarcinoma on prostate biopsy is not an uncommon finding. It is usually an intermediate grade and localised stage neoplasm.     

Predictive factors in prostate needle biopsy

Prostate cancer (PCa) is a leading cause of morbidity and mortality in men, accounting for approximately 30% of all new cases of cancer and approximately 14% of cancer deaths. Despite considerable advances achieved in the ability to detect and treat PCa, there have not been significant corresponding decreases in PCa-related morbidity and mortality. Proper examination of prostate biopsy specimens by pathologists is critical in determining the type of treatment and predicting patient outcome. The goal is to tailor the therapeutic approach to the clinical, morphological and molecular features of each patient.     

Inflammation and focal atrophy in prostate needle biopsy cores and association to prostatic adenocarcinoma

The possible origin of proliferative inflammatory atrophy in the regenerative proliferation of prostate epithelial cells in response to injury caused by inflammation, and their relation to prostate adenocarcinoma have not been defined. Inflammation and focal atrophy are common pathological findings in prostate biopsies, currently not routinely included in surgical pathology reports. The objective of the study was to determine the correlation between inflammation and focal atrophy with prostate adenocarcinoma. Prostate needle biopsies from 203 patients with clinical parameters suspicious for malignancy were evaluated for the presence and extent of chronic inflammation, type and grade of focal atrophy, high-grade intraepithelial neoplasia, and adenocarcinoma. Relations among them and with age were also analyzed. χ² tests and binary logistic regression were used to estimate associations. Chronic inflammation was observed in 77.3% of the biopsies, significantly associated to adenocarcinoma (P = .031). Moderate/severe inflammation in at least 1 biopsy core increased the risk of prostate adenocarcinoma (odds ratio, 2.94; 95% confidence interval, 1.27-6.8), whereas glandular localization of inflammation decreased the risk. Focal atrophy was present in 72.9% of the biopsies, proliferative inflammatory atrophy was the most common type, and its grade was significantly associated to inflammation (P < .0001) and inflammation intensity (P = .003). An association between prostate adenocarcinoma and inflammation was found, with higher odds in presence of moderate/severe inflammation in at least 1 biopsy core. Increasing grades of proliferative inflammatory atrophy were associated to high levels of inflammation, supporting its previously proposed inflammatory nature.     

Diagnosis and reporting of limited adenocarcinoma of the prostate on needle biopsy.

The diagnosis of limited adenocarcinoma of the prostate is one of the more difficult challenges in surgical pathology. This paper highlights the methodological approach to diagnosing limited cancer, based on a constellation of features more commonly present in adenocarcinoma than benign glands. In assessing small foci of atypical glands on needle biopsy, one looks for differences between the benign glands and the atypical glands in terms of nuclear features, cytoplasmic features, and intraluminal contents. Only a few features, such as glomerulations, mucinous fibroplasia (collagenous micronodules), and perineural invasion are diagnostic in and of themselves for prostate cancer. Immunohistochemistry may be a useful adjunct in the diagnosis of limited adenocarcinoma of the prostate, although as with any immunohistochemical studies, there are problems with both sensitivity and specificity. Basal cell markers, such as high molecular weight cytokeratin and more recently, p63, highlight basal cells found in benign glands, yet are absent in adenocarcinoma of the prostate. However, not all benign glands label uniformly with basal cell markers. Certain mimickers of adenocarcinoma of the prostate are even less frequently labeled uniformly with these stains. Consequently, negative staining in a small focus of atypical glands for basal cell markers is not diagnostic of adenocarcinoma of the prostate. More recently, a marker has been identified that relatively selectively labels adenocarcinoma of the prostate. AMACR will label the cytoplasm of approximately 80% of limited adenocarcinoma of the prostate cases on needle biopsy. In positive cases, not all of the glands will be positive and those that are positive are often not intensely positive. Certain variants of adenocarcinoma of the prostate that are a little more difficult to recognize, such as foamy glands adenocarcinoma, pseudohyperplastic adenocarcinoma, and atrophic adenocarcinoma, are labeled with AMACR in only approximately 60-70% of cases. In addition to problems with sensitivity, AMACR is not entirely specific for adenocarcinoma, and will label almost all cases of high-grade prostatic intraepithelial neoplasia, some foci of adenosis, and even some entirely benign glands. Finally, this paper will briefly cover the significance of atypical or suspicious prostate needle biopsies, and how to report the key diagnostic and prognostic information on needle biopsy.     

Use of interphase fluorescence in situ hybridization in prostate needle biopsy specimens with isolated high-grade prostatic intraepithelial neoplasia as a predictor of prostate adenocarcinoma on follow-up biopsy

Isolated high-grade prostatic intraepithelial neoplasia (HGPIN) on needle biopsy confers an increased risk of prostate carcinoma (CaP) on follow-up biopsy. The aim of this study is to determine whether paraffin-section fluorescence in situ hybridization (FISH) of specific chromosome/oncogene copy number abnormalities (CNAs) in biopsy specimens with isolated HGPIN increases the predictive value for CaP on repeat biopsy. Cases were divided into 3 groups: controls (n=8) and sextant biopsy specimens with isolated HGPIN without CaP (group A; n=11) and with CaP (group B; n=14) on follow-up biopsy. Dual-color FISH assessing c-myc, HER-2/neu, chromosome region 7q31 (D7S486), and corresponding chromosome centromeres was performed. An amplification ratio (AR) for each marker centromere was derived for each biopsy specimen, with AR ranges designated as no/low, low-intermediate, and high. Also calculated for each marker were the percentage of cells with marker amplification, hyperdiploidy, and monosomy. A composite score for each biopsy specimen was calculated based on these parameters, with a possible range of 0 to 15. The specific chromosomal oncogene CNAs were as follows: for chromosome 7/7q31, 2 of 11 (18%) in group A and 6 of 14 (43%) in group B; for chromosome 8/c-myc, 4 of 11 (36%) in group A and 9 of 13 (69%) in group B; and for chromosome 17/HER-2/neu, 10 of 10 (100%) in group A and 13 of 14 (93%) in group B. The mean composite score was 0 for controls, 2.5 for group A, and 4.7 for group B. Composite scores > or =4 for the 3 groups were 0 of 9 (0%) for controls, 1 of 11 (12%) for group A, and 8 of 14 (57%) for group B. These differences were statistically significant (P=0.015). One group A patient with a high composite score (6) had atypical small glands on follow-up biopsy at <1 year. Chromosome/oncogene CNAs are uncommon in control patients, occurring with increasing frequency and magnitude in patients with isolated HGPIN without and with follow-up CaP. Chromosome/oncogene CNAs in HGPIN are mostly of the low to intermediate level and display intercellular heterogeneity. HER-2/neu amplification is common in HGPIN with and without follow-up CaP. Chromosome 7 and 8 aneusomy and 7q31 and c-myc amplification are greater in HGPIN with follow-up CaP. Patients with isolated HGPIN and high composite score without follow-up CaP are uncommon; these patients may have a small, unsampled CaP. Although patients with HGPIN without CaP are more likely to have a low composite score, a subset of patients with follow-up CaP have low composite score, suggesting (1) mutational pathways independent of chromosomes 7, 8, and 17 and HER-2/neu, c-myc, and chromosome region 7q31 CNAs; (2) CaP derived from an independent, unsampled focus of HGPIN; or (3) CaP not derived from HGPIN.     

Fine needle aspiration biopsy of the prostate gland

With the worldwide acceptance of mechanically assisted, ultrasound guided thin needle biopsy of the prostate gland, prostate fine needle aspiration (FNA) has fallen out of favor with both urologists and cytopathologists. Nonetheless, given today's trend to submit from 12 to 18 core biopsies per patient, prostate FNA remains less expensive, more expedient and more economical than any other sampling method so far developed. This short overview presents prostate FNA as a sensitive, specific and reliable diagnostic modality that should not be dismissed, as an anachronism, from the diagnostic armamentarium of either the urologist or the pathologist.     

Number and location of nucleoli and presence of apoptotic bodies in diagnostically challenging cases of prostate adenocarcinoma on needle biopsy

There is limited published data regarding the significance of the number or position of nucleoli and the presence of apoptotic bodies in diagnostically challenging cases of adenocarcinoma of the prostate on needle biopsy material. One hundred consecutive prostate cancers on needle biopsy were sent because of diagnostic difficulty to an expert in urological pathology, and the remaining normal benign prostatic glands on the same core were evaluated for the number and location of nucleoli and for the presence of mitotic figures and apoptotic bodies. The Gleason scores of the cases were 6 (86%), 7 (9%), and 8 to 10 (5%). For comparison, the same parameters were evaluated in mimickers of cancer on needle biopsy from other cases, including partial atrophy (n = 135), fully developed atrophy (n = 89), adenosis (n = 50), prostate glands with acute inflammation (n = 50), and high-grade prostatic intraepithelial neoplasia (n = 100). Findings were recorded under high dry magnification (x40) using hematoxylin and eosin-stained sections. Although the number and position of nucleoli did not discriminate between cancer and benign mimickers, mitotic figures and apoptotic bodies were more commonly seen in cancer. Apoptotic bodies in particular were seen fairly frequently (34%) in prostatic adenocarcinoma (also seen in 13% of high-grade prostatic intraepithelial neoplasia), yet rarely in benign mimickers on needle biopsy. Our findings indicate that the presence of apoptotic bodies should be added to the list of histological features that are helpful in the diagnosis of challenging cases of prostate cancer on needle biopsy.     

Carcinoma extent in prostate needle biopsy tissue in the prediction of whole gland tumor volume in a screening population

Increasing prostate tumor volume has been shown to correlate with numerous adverse prognostic indicators for patients with prostate carcinoma The ability to predict tumor volume from pretreatment parameters is potentially critical in the stratification of patients for different management strategies. We assessed the capacity of preoperative variables to predict tumor volume in 100 men diagnosed with prostate cancer in a prostate-specific antigen (PSA)-based screening program. Preoperative information included total serum PSA concentration and needle biopsy tissue variables, including Gleason score, number of positive cores, linear extent of carcinoma in millimeters, greatest percentage of carcinoma (in a single core), total percentage of carcinoma (all cores), presence of perineural invasion, and percentage of high-grade carcinoma. The postoperative end point was total tumor volume in radical prostatectomy tissue, calculated by image analysis. We determined independently significant factors and generated a predictive modelfor whole gland tumor volume. Total tumor volume was related significantly in multivariate analysis to 3 preoperative variables: linear extent of carcinoma, exponential number of positive cores, and serum PSA. A predictive model generated based on these 3 variables accounted for only 65% of the natural deviance of the data owing to data-point scatter for individual patients, suggesting that additional variables are needed to more accurately predict tumor volume. Findings highlight the importance of reporting quantitative measures of tumor amount in prostate needle biopsy specimens; several measures of tumor extent (vs 1 measure) provide maximal information on prostate cancer size.     

Histopathological changes in thyroid tissue after fine needle aspiration biopsy

Fine needle aspiration biopsy (FNAB) is a method that is frequently used in the diagnosis for neoplastic and non-neoplastic thyroid lesions. However, despite the contribution of this method to diagnosis, varying degrees of histopathological alterations in thyroid tissue occur due to the trauma caused by the aspiration needle. In this study, we compared the histopathology of the thyroidectomy specimens obtained by FNAB with the specimens obtained without the use of FNAB. A hundred and fifty thyroidectomy specimens obtained by FNAB were compared histopathologically with 150 thyroidectomy specimens (control group) obtained without a FNAB procedure. The thyroidectomy specimens were evaluated for hemorrhage, fibrosis, siderophagia, vascular thrombosis, vascular proliferation, infarction, granulation tissue, cystic degeneration, papillary hyperplasia, nuclear atypia, mitosis, calcification, vascular invasion, capsular distortion (pseudoinvasion), cholesterol clefts, and the presence of metaplasia. The thyroidectomy specimens obtained by FNAB had rates of hemorrhage, siderophagia, granulation tissue, papillary hyperplasia, fibrosis, calcification, capsular distortion, cholesterol clefts (P<0.001), and vascular thrombosis (P=0.001) that were statistically significantly higher than those obtained without FNAB. However, there were no clinically significant differences between the two groups in terms of vascular proliferation, nuclear atypia, mitosis, infarction, and oncocytic and squamous metaplasia. Alterations in thyroid tissue in association with FNAB show a considerable variation. Some of the alterations make diagnosis difficult, even leading to misdiagnosis in favor of carcinoma. Therefore, a thorough knowledge of possible alterations is essential to the differential diagnosis.     

The complete prostate needle biopsy submission during grossing and embedding

The completion of prostate needle biopsy submission in the histology laboratory during grossing and embedding is a topic of interest worth discussion. Flattening the cores can contribute to the completeness of biopsy presentation on the microscope slide. The use of polyester pads is controversial due to a possible ‘compression artifact’ of thin and fragmented areas of the core during vacuum and pressure tissue processing. Two randomly selected cases demonstrated that many core areas are comparable with the holes in the sponge net. If the cores were placed between the sponges and prevented from direct contact with the sponge by porous lens paper, such a ‘sandwich’ would be optimal for keeping the cores flat and would secure completeness of submission. The specimens with fragmented cores require filtration during sampling. Filtration directly into a processing cassette could be faster, if an absorbent material were placed beneath the cassette. The use of a tamper to flatten the cores during embedding should be the standard procedure. Flattening the cores is only one of the particularities during embedding. For example, placing the cores parallel to each other and following the longest axis of the processing cassette can contribute to the completeness of the submission on the microscope slide.     

前列腺摘除病检和穿刺活检的形态学差异

目的：探讨前列腺摘除病检和穿刺活检的形态学差异。方法：对340例穿刺标本和280例因良性前列腺增生（BPH）而摘除的前列腺标本进行形态学对比分析。结果：在穿刺活检中,前列腺癌,上皮内新生物（PIN）和非特异性肉芽肿性前列腺炎（NSGP）的检出率明显高于摘除者,在前列腺摘除的标本中,梗死,磷化,间质增生性结节,腺性尿道炎和非典型性腺瘤样增生（AAH）的检出率明显市政地穿刺活检,结论：形态学差异是由于穿刺和摘除标本分别取自前列腺不同解剖并且并且部位所致,对穿刺和摘除前列腺的病理诊断,应该有不同的鉴别诊断思路。     

Sclerosing adenosis of the prostate. Histologic features in needle biopsy specimens

Sclerosing adenosis of the prostate is a pseudoneoplastic lesion that can mimic prostate cancer. Because the lesion is more common in the transition zone, which is only rarely sampled in needle biopsy, it is uncommon to see examples of this lesion in biopsy specimens. Because sampling of the transition zone of the prostate is likely to become more frequent, practicing surgical pathologists must be aware of the morphologic features of sclerosing adenosis of the prostate in needle biopsy specimens, in order to avoid misinterpretation of sclerosing adenosis of the prostate, a benign lesion, as prostate adenocarcinoma. We report the morphologic findings of sclerosing adenosis of the prostate in 3 needle biopsy specimens from 2 patients diagnosed as having sclerosing adenosis. We found a combination of histologic (mainly a cellular myxoid stroma and a double-cell population of acinar cells) and immunohistochemical features demonstrating a continuous basal cell layer with myoepithelial differentiation to be diagnostic.