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.     

Negative 34betaE12 staining in a small focus of atypical glands on prostate needle biopsy: a follow-up study of 332 cases

Atypical glands on prostate needle biopsy with a negative 34betaE12 (cytokeratin 903; CK903) immunostain, indicating a lack of a basal cell layer, are typically diagnostic of prostate cancer. However, in certain cases a negative 34betaE12 immunostain in a small focus of atypical glands is still not convincing enough to make the diagnosis of cancer. This study is the first report to evaluate the incidence of prostate cancer on follow-up biopsy in individuals with this diagnosis. A total of 543 men who had prostate core biopsy specimens diagnosed as a small focus of atypical-appearing glands with a negative 34betaE12 immunostain between January 1, 1997 and December 31, 2000 were selected for study. Some 61% of these 543 individuals (n = 332) had undergone at least one follow-up biopsy procedure. Of these, 43% of repeat biopsy cases (n = 142) were diagnostic of prostate cancer. A total of 46 individuals had at least 2 follow-up biopsy procedures, with 48% of these (n = 22) being diagnosed as cancer. The Gleason grades of the detected carcinomas were broken down as follows: Gleason grade 3 + 2 = 5, 6%; grade 3 + 3 = 6, 86%; grade 3 + 4 = 7, 1%; grade 4 + 3 = 7, 4%; and grade 4 + 4 = 8, 3%. The median amount of time to the first follow-up biopsy was 79 days, with 52% of follow-up biopsies performed within 90 days. A negative 34betaE12 immunohistochemical stain in a small focus of atypical glands is not associated with an increased prediction of prostate cancer on follow-up biopsy (43%), compared with previously published data for "small focus of atypical glands" alone (approximately 45%). Because 48% of men with an initial negative biopsy and multiple follow-up biopsy procedures were found to have cancer, more than one repeat biopsy session or more extensive sampling on the first repeat biopsy procedure may be necessary to maximize the identification of cancer. This finding is similar to that found in men with atypical diagnoses in general, without a negative 34betaE12 immunohistochemical stain. Only half of all individuals with a diagnosis of 34betaE12-negative focus of atypical glands underwent repeat biopsy within 3 months. Urologists need to be educated as to the significance of an atypical diagnosis and the need for repeat biopsy. In a small focus of atypical glands on prostate biopsy, negative staining for 34betaE12 should not necessarily lead to a definitive malignant diagnosis in all cases, because almost half of these biopsies on follow-up sampling are benign.     

粗针活检诊断子宫颈微偏腺癌4例及临床病理分析

目的 总结B超引导下子宫颈微偏腺癌(minimal deviation adenocarcinoma,MDA)的粗针穿刺活检组织病理学形态、免疫组化及组织化学染色、病理诊断和鉴别诊断等要点,结合文献分析粗针穿刺活检方法用于临床早期诊断子宫颈MDA的优势及可行性.方法 对4例临床疑为MDA的患者,在B超引导下进行深部粗针穿刺活检,经常规HE染色、免疫组化及特殊染色后,镜下观察做出病理诊断,与该患者根治切除标本进行对比分析.结果 镜下见子宫颈深部穿刺标本的纤维和平滑肌组织中,散在分化较好的子宫颈型黏液性腺体,但腺体形态不规则,细胞轻至中度异型以及周围纤维组织增生性的间质反应,并且可见腺体邻近大血管;免疫组化染色腺上皮CEA阳性,AB/PAS特殊染色阳性.根治切除标本进一步明确了MDA的诊断,证实术前的子宫颈深部组织粗针穿刺活检获得的组织学证据,足以支持MDA的病理诊断.结论 MDA病变位置较深,间质浸润是明确诊断的最主要依据,粗针穿刺可做到子宫颈深部(深度>5 mm)活检,作为MDA早期诊断的一种方法具有一定的优势和可行性.     

子宫颈黏液腺癌21例病理诊断分析

目的 对子宫颈黏液腺癌病理诊断过程的分析旨在为早期诊断、减少漏诊总结经验.方法 回顾性分析21例子宫颈黏液腺癌的病理诊断过程;采用LABC法免疫组化检测CEA及Ki-67的表达.结果 21例子宫颈黏液腺癌诊断中,漏诊3例(14.3%),其中1例为TCT漏诊,2例为子宫颈活检漏诊;4例(19.0%)子宫颈活检诊断为子宫颈原位腺癌、浸润不能除外,后经LEEP术确诊为子宫颈浸润性黏液腺癌;1例(4.8%)子宫颈活检诊断为慢性子宫颈炎,经LEEP术确诊为子宫颈浸润性黏液腺癌;12例(57.1%)直接由子宫颈活检确诊为子宫颈黏液腺癌;1例(4.8%)经诊刮诊断为腺癌,无法确定组织学类型,术后确诊为子宫颈黏液腺癌.免疫组化染色显示,其中10例CEA表达阳性(47.6%),Ki-67表达均升高(>20%).结论 从细胞学及组织形态学上,掌握子宫颈黏液腺癌的诊断要点,可以减少漏诊,及早做出正确的诊断,为患者赢得宝贵的手术时间.     

Morphologic criteria for the diagnosis of prostatic adenocarcinoma in needle biopsy specimens. A study of 250 consecutive cases in a routine surgical pathology practice

CONTEXT: The diagnosis of prostate adenocarcinoma in needle core biopsy specimens is based on multiple diagnostic criteria and supportive features, most of which have been defined mainly from observations in transurethral resection and prostatectomy specimens. There is little information on the frequency with which diagnostic and supportive features of prostate cancer occur within benign glands. The few reports dealing with diagnostic criteria of cancer in needle biopsies have been largely confined to analysis of selected cases that posed particular diagnostic difficulty. OBJECTIVE: To analyze the frequency with which numerous diagnostic or supportive features of prostate cancer occur in an unselected, consecutively performed series of 18-gauge prostate needle biopsy specimens. DESIGN: Two hundred fifty consecutive 18-gauge prostate needle biopsy specimens (150 malignant and 100 benign) were evaluated, using hematoxylin-eosin-stained histologic sections. RESULTS: The frequency of the histologic features in malignant and benign glands was as follows: prominent nucleoli (94% and 25% of malignant and benign specimens, respectively), marginated nucleoli (88% and 7%), multiple nucleoli (64% and 0%), blue-tinged mucinous secretions (52% and 0%), intraluminal crystalloids (40.6% and 1%), intraluminal amorphous eosinophilic material (86.7% and 2%), collagenous micronodules (2% and 0%), glomerulations (15.3% and 0%), perineural invasion (22% and 0%), retraction clefting (38.6% and 7%), and invasion of fat (0.7% and 0%). CONCLUSIONS: Since not all diagnostic or supportive features of cancer are evident in any single case of cancer, particularly in needle biopsy specimens in which sampling is limited, awareness of these data would be helpful in the assessment of small foci of atypical glands being considered for cancer.     

Identification of isolated and early prostatic adenocarcinoma in radical prostatectomy specimens with correlation to biopsy cores: clinical and pathogenetic significance

Prostatic adenocarcinoma (PAC) is a multifocal disease. In this study, we identified isolated and small foci of PAC (ISPAC) in radical prostatectomy specimens, described the histopathologic features, investigated their zonal distribution in the prostate and their relationship with large tumor nodules, and correlated the findings with those of preceding biopsy cores. One hundred and thirty radical prostatectomy specimens performed for PAC or for urothelial carcinoma of the urinary bladder with incidental PAC were reviewed for identification of ISPAC. Prostates were serially sectioned in the horizontal plane and submitted in toto for microscopic examination. ISPAC were defined as foci of PAC measuring less than 3 mm in maximum diameter. There were 461 ISPAC identified in 114 cases. They were distributed in the transitional zone (TZ) (18 foci), the apex (73 foci), the anterior horn of the non-TZ (NTZ) (118 foci), the base (8 foci), and the remaining NTZ (244 foci). ISPAC usually consisted of groups of small acini with a GS ranging from 2 to 7 (3 + 4). GSs of ISPAC consisted of single grade or two consecutive grades equal to or lower than those of the main PAC. ISPAC were more often located in close proximity to large tumor nodules. The number of ISPAC increased with the tumor volume up to 3 cm3, then decreased as the PAC became more extensive (p value = 0.02, statistically significant). Prostates with NTZ PAC <1.5 cm3 and TZ PAC or prostates containing 4 or more than 4 ISPAC tended to be frequently associated with small foci of PAC in biopsy cores In this study, we identified ISPAC that likely represent foci of PAC in early development and account for the multicentricity and heterogeneity of PAC. ISPAC in the NTZ were common and may account for small foci of PAC or atypia in biopsy cores. Although these small foci of PAC or atypia in biopsy cores without accompanying higher GS PAC were often associated with significant PAC, they may also occasionally represent insignificant or vanishing PAC in subsequent radical prostatectomies.     

骨转移性小细胞癌11例穿刺病理的鉴别诊断

目的：探讨骨转移性小细胞癌穿刺病理的诊断与鉴别诊断,尤其是与骨原发Ewing肉瘤的鉴别诊断。方法收集11例骨转移性小细胞癌和20例骨原发Ewing肉瘤的临床病理资料,并采用免疫组化EnVision两步法检测两组病例中相关标志物的表达。结果11例骨转移性小细胞癌中,CD99阳性率27．3%,FLI-1阳性率54．5%;20例骨原发Ewing肉瘤中,CK阳性率15．0%。患者年龄、单发病灶、免疫组化标志物CK、vimentin、CD99、FLI-1、CD56的表达在两组间差异具有显著性。结论骨转移性小细胞癌与骨原发Ewing肉瘤的组织形态相似,免疫组化标志物的表达也有重叠,正确诊断需结合临床资料及免疫组化染色综合分析。     

Computer-aided diagnosis of breast cancer based on fine needle biopsy microscopic images

Prompt and widely available diagnostics of breast cancer is crucial for the prognosis of patients. One of the diagnostic methods is the analysis of cytological material from the breast. This examination requires extensive knowledge and experience of the cytologist. Computer-aided diagnosis can speed up the diagnostic process and allow for large-scale screening. One of the largest challenges in the automatic analysis of cytological images is the segmentation of nuclei. In this study, four different clustering algorithms are tested and compared in the task of fast nuclei segmentation. K-means, fuzzy C-means, competitive learning neural networks and Gaussian mixture models were incorporated for clustering in the color space along with adaptive thresholding in grayscale. These methods were applied in a medical decision support system for breast cancer diagnosis, where the cases were classified as either benign or malignant. In the segmented nuclei, 42 morphological, topological and texture features were extracted. Then, these features were used in a classification procedure with three different classifiers. The system was tested for classification accuracy by means of microscopic images of fine needle breast biopsies. In cooperation with the Regional Hospital in Zielona Góra, 500 real case medical images from 50 patients were collected. The acquired classification accuracy was approximately 96–100%, which is very promising and shows that the presented method ensures accurate and objective data acquisition that could be used to facilitate breast cancer diagnosis.     

Secondary prostatic adenocarcinoma: a cytopathological study of 50 cases

Positive diagnosis of metastatic prostate adenocarcinoma (PAC) can be made by microscopic examination of the cytologic specimens and immunostaining for prostate-specific antigen (PSA) and prostate acid phosphatase (PAP). Immunohistochemical markers have been known to display negative, weak, or focal staining in poorly differentiated PAC and in patients with prior hormonal and/or radiation therapy. The purpose of this study is to characterize the cytopathology of metastatic PAC as it has not been documented in large series. Fifty cases of metastatic PAC with cytological specimens consisting of 41 fine-needle aspiration biopsies (FNAB), 6 pleural fluid aspirates, and 3 catheterized urine samples were reviewed and correlated with the surgical specimens and the clinical charts. Immunostaining for PSA, PAP, cytokeratin AE1/3, cytokeratin 7 (CK7), cytokeratin 20 (CK20), vimentin, and carcinoembryonic antigen (CEA) was done. Mean patient age was 77 +/- 8 yr; serum PSA, 4.1 +/- 2.3; and primary PAC Gleason score, 8.1 +/- 1.5. Cytologically, the specimens consisted of cell clusters or cell sheets with overlapping uniform hyperchromatic nuclei with or without nucleoli. Twelve cases were not reactive to PSA and PAP and 44 cases displayed negative immunoreactivity to both CK7 and CK20. Carcinoid-like lesions and small cell carcinomas were seen in 4 cases and were misdiagnosed as nonprostatic origin based on the following features: negative immunoreactivity to PSA and PAP with or without positive reactivity to CEA, and different histopathological features when compared with the primary PAC. In addition to the frequency of high-grade PAC, awareness of the negative immunoreactivity to PSA and PAP, the discrepancy in the histopathological patterns between the primary and secondary tumors, especially the frequent neuroendocrine differentiation, are helpful features for the diagnosis of metastases of prostatic origin.     

The use of a decremental dose regimen in patients treated with a chronic low-dose step-up protocol for WHO Group II anovulation: a prospective randomized multicentre study

BACKGROUND: In women with chronic anovulation, the choice of the FSH starting dose and the modality of subsequent dose adjustments are critical in controlling the risk of overstimulation. The aim of this prospective randomized study was to assess the efficacy and safety of a decremental FSH dose regimen applied once the leading follicle was 10-13 mm in diameter in women treated for WHO Group II anovulation according to a chronic low-dose (CLD; 75 IU FSH for 14 days with 37.5 IU increment) step-up protocol. METHODS: Two hundred and nine subfertile women were treated with recombinant human FSH (r-hFSH) (Gonal-f) for ovulation induction according to a CLD step-up regimen. When the leading follicle reached a diameter of 10-13 mm, 158 participants were randomized by means of a computer-generated list to receive either the same FSH dose required to achieve the threshold for follicular development (CLD regimen) or half of this FSH dose [sequential (SQ) regimen]. HCG was administered only if not more than three follicles >or=16 mm in diameter were present and/or serum estradiol (E(2)) values were <1200 pg/ml. The primary outcome measure was the number of follicles >or=16 mm in size at the time of hCG administration. RESULTS: Clinical characteristics and ovarian parameters at the time of randomization were similar in the two groups. Both CLD and SQ protocols achieved similar follicular growth as regards the total number of follicles and medium-sized or mature follicles (>/=16 mm: 1.5 +/- 0.9 versus 1.4 +/- 0.7, respectively). Furthermore, serum E(2) levels were equivalent in the two groups at the time of hCG administration (441 +/- 360 versus 425 +/- 480 pg/ml for CLD and SQ protocols, respectively). The rate of mono-follicular development was identical as well as the percentage of patients who ovulated and achieved pregnancy. CONCLUSIONS: The results show that the CLD step-up regimen for FSH administration is efficacious and safe for promoting mono-follicular ovulation in women with WHO Group II anovulation. This study confirms that maintaining the same FSH starting dose for 14 days before increasing the dose in step-up regimen is critical to adequately control the risk of over-response. Strict application of CLD regimen should be recommended in women with WHO Group II anovulation.     

Cytologic features of prostatic adenocarcinoma in urine: a clinicopathologic and immunocytochemical study

Cells of adenocarcinoma of the prostate (ACP) are infrequently shed in urine. We examined the clinicopathologic features of 22 patients with ACP and tumor cells in urine. Patients typically were clinical stage C or D and had hematuria (13 cases, 59%) and/or obstruction (11 cases, 50%). Prostatic palpation or instrumentation preceded collection of 15 urine specimens. Histologically, tumors were high grade (Gleason score 7-10) and extensive, with involvement of prostatic ducts and acini (10 cases, 45%) and prostatic urethra (5 cases, 23%). Cytologically, the background was clean, and neoplastic cells appeared singly, in loose clusters, as large "casts," or, rarely, in papillary structures. The cells were small, round to oval, with a moderate amount of finely granular or vacuolated cytoplasm; nuclei were generally round with a thin, often irregular membrane, finely granular chromatin, and a single prominent nucleolus. Immunoperoxidase staining for prostatic acid phosphatase and prostate-specific antigen was useful in distinguishing ACP from transitional cell carcinoma.     

Current prostate biopsy protocols cannot reliably identify patients for focal therapy: correlation of low-risk prostate cancer on biopsy with radical prostatectomy findings

Focal therapy appears to be an attractive alternative approach for patients with localized prostate cancer (PCa). Identifying suitable candidates is crucial to the success of focal therapy. Currently, standard transrectal ultrasound (TRUS)-guided prostate biopsy remains the widespread approach to evaluate patient suitability. In this study, we evaluated the ability of current biopsy protocols to predict cancer characteristics in radical prostatectomy (RP) specimens. We reviewed 4437 cases from 2000 to 2008 in our PowerPath database, and identified 158 patients with low-risk cancer, defined as a pre-biopsy PSA level ≤ 10 ng/mL, unilateral, low tumor volume (≤5%) and low to intermediate Gleason score (GS≤6) on first positive prostate biopsy. The pathological characteristics of subsequent RP specimens were reviewed. We found that, of 158 patients with these criteria, 117 (74%) had bilateral cancer, 49 (31%) had increased tumor volume (≥ 10%), and 46 (29%) were upgraded to GS ≥ 7 at RPs. When patients were stratified by total biopsy core numbers, extended biopsy core protocols were not significantly more reliable in identifying unilateral and low volume prostate cancer patients. One core positive on biopsy was not significantly superior to > 2 positive cores in predicting unilateral, low volume, low stage cancer at prostatectomy. These findings indicate that current standard prostate biopsy protocols have limited accuracy in identifying candidates for focal therapy.     

Desquamating apoptotic variant of high-grade prostatic intraepithelial neoplasia: a possible precursor of intraductal prostatic carcinoma

Various patterns of high-grade prostatic intraepithelial neoplasia have been have been described, many of which show morphologic similarity to patterns of prostatic intraductal carcinoma, which is thought to develop either directly from high-grade prostatic intraepithelial neoplasia or by invasion of existing ducts by Gleason pattern 4 or 5 carcinoma. We document a rare and previously unreported "desquamating apoptotic variant" of high-grade prostatic intraepithelial neoplasia where desquamating cells containing apoptotic nuclear material coalesce in the gland lumens to form basophilic intraluminal masses in up to one third of involved acini. This lesion shares features of both high-grade prostatic intraepithelial neoplasia and prostatic intraductal carcinoma and supports the hypothesis that some forms of prostatic intraductal carcinoma evolve directly from high-grade prostatic intraepithelial neoplasia.     

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.