High molecular weight cytokeratin antibody (clone 34betaE12): a sensitive marker for differentiation of high-grade invasive urothelial carcinoma from prostate cancer

AIMS: There is no well-established positive immunomarker for urothelial carcinoma. We evaluated the diagnostic utility of high molecular weight cytokeratin (HMWCK) antibody clone 34betaE12 in differentiating high-grade invasive urothelial carcinoma from prostate cancer. METHODS AND RESULTS: Formalin-fixed paraffin-embedded sections from 28 cases of high-grade invasive urothelial carcinoma (20 not otherwise specified (UC-NOS), eight with glandular differentiation) and 20 cases of poorly differentiated prostate carcinoma were immunostained with a monoclonal antibody to carcinoembryonic antigen (CEA), clone 85A12 and with HMWCK antibody clone 34betaE12 after microwave pretreatment or protease 24 predigestion. All cases of UC-NOS expressed HMWCK on 34betaE12 immunostaining after microwaving or enzyme predigestion. Immunoreactivity was intense and diffuse in all the cases after microwave pretreatment, whilst with enzyme predigestion immunoreactivity was sometimes patchy with <50% tumour cells positive in 20% of cases. In comparison with 34betaE12, 85A12 was insensitive with 15% of UC-NOS cases totally CEA-negative and <50% tumour cell immunoreactivity in 60% of cases. Rare positive cells were present in two (10%) cases of prostate cancer with monoclonal anti-CEA and 34betaE12 on microwaved sections, but all the cases were HMWCK-negative using 34betaE12 on sections pretreated by enzyme digestion. CONCLUSIONS: HMWCK antibody clone 34betaE12, particularly when used with microwave heat retrieval, is a very sensitive positive marker for high-grade invasive urothelial carcinoma.     

Validation of cytokeratin 5/6 as an effective substitute for keratin 903 in the differentiation of benign from malignant glands in prostate needle biopsies

AIMS: Keratin 903 (also known as anti-cytokeratin antibody 34betaE12) is widely used to differentiate benign glands from malignant glands in prostate needle biopsies. However, it is subject to considerable staining heterogeneity. We sought to evaluate the use of cytokeratin 5/6 (CK5/6) as an effective alternative to K903 in the evaluation of prostate needle biopsies in clinical practice. METHODS AND RESULTS: Thirty Hollandes-fixed prostate needle biopsies were randomly selected over a period of 2 months from the surgical specimens accessioned over that period of time. Twelve cases had diagnosed prostatic adenocarcinoma (Gleason scores 3 + 3, 3 + 4 and 4 + 4) and the remaining cases (n = 18) were negative for carcinoma. Four sequential sections were stained with H&E (x2), K903, and CK5/6. Care was taken to preserve tissue so that matching glands were evaluated on all four sections. All cases were run routinely over a period of 3 weeks on a daily basis with matching positive controls. All slides were evaluated in a blinded fashion independently by two pathologists using a semiquantitative analysis of staining: <25%, 25-50%, 50-75%, >75% and >95% of benign glands (verified on H&E). Cases that showed no staining were repeated to ensure no false negatives. Both observers agreed with respect to percentage of staining in 96% of the cases. Twenty-nine of 30 cases (97%) showed staining in >95% of benign glands with CK5/6. In contrast, K903 staining was seen in <50% of benign glands in five of 30 (17%), 50-75% in nine of 30 (30%), and >75% in 10 of 30 (33%), with only two cases (7%) showing >95% staining for K903. In four cases (13%) the K903 failed to stain any tissue even after repeat staining. K903 was conspicuously negative in atrophic glands in three of 30 cases (10%). Neither K903 nor CK5/6 stained malignant glands. Using a cut-off of >75% staining in benign glands the sensitivity of CK5/6 and K903 was 97% and 40%, respectively. CONCLUSIONS: CK5/6 has superior sensitivity and reliability compared with that of K903 when evaluating routine prostate needle biopsies, including improved staining of atrophic prostatic glands. While K903 is traditionally used to differentiate benign glands from malignant glands, these results support the use of CK5/6 as an effective and reliable substitute for K903 in routine clinical practice.     

Trends in prostate needle biopsy diagnosis. A ten year experience of a medical center in Taiwan

Prostate cancer has seen a rapid rise in Taiwanese men. The current study was undertaken to evaluate trends of the disease diagnosed on prostate needle biopsy during a ten-year period at the Department of Pathology, Taipei Veterans General Hospital. The study included 8236 men who underwent a total of 9995 prostate needle biopsies at this institute from 1994 to 2003. Pathologic features pertinent to diagnosis of cancer were reviewed and compared for cases diagnosed before and after 1999. There were statistically significant increases of the overall cancer detection rate (from 17.6% to 19.9%), proportion of cases with a Gleason score ≤ 6 (from 16.6% to 40.9%) and focal adenocarcinoma (from 3.0% to 12.8%) in the latter 5 years. The incidence of high-grade prostatic intraepithelial neoplasia (HGPIN) increased from 0.1% to 1.5%. Patients with HGPIN had a significantly higher risk for subsequent cancer discovered on repeat biopsy than did those with a primary benign diagnosis (29.9% versus 13.7%). Despite a relatively lower incidence of cancer and HGPIN in Taiwanese men compared with that reported in Western studies, in recent years we have found an increase of relevant diagnoses, especially cancer of limited extent and lower grade, which may represent the progress in prostate cancer diagnosis.     

Performance of combined clinical mammography and needle biopsy: a nationwide study from Denmark

Clinical mammography and needle biopsy are key tools for non-operative assessment of breast lesions. We evaluated the performance of all combined tests undertaken in Denmark in 2000. Clinical mammography and needle biopsy data were collected and linked to final cancer outcome, to determine sensitivity, specificity, and predictive values of clinical mammography, needle biopsy, and combined test. In 2000, 6709 combined tests were performed in 36 mammography clinics in Denmark. The combined test was consistently more sensitive than any single test, increasing the proportion of women correctly identified with breast cancer by 9% compared with clinical mammography alone. For concordant combined tests (i.e. either both benign or both malignant), specificity and positive predictive value were 100%, sensitivity was 99.1%, and positive predictive value was 99.6%. Therefore, Danish patients with a malignant concordant combined test can proceed directly to definitive surgery without fear of a false-positive diagnosis, and Danish women with a concordant benign combined test can omit surgery without fear of a false-negative diagnosis. In discordant cases, our results showed that any of the two tests with a suspicious or malignant result indicated a high risk of cancer, and excisional diagnostic biopsy therefore still has an important role to play.     

Prospective evaluation of AMACR (P504S) and basal cell markers in the assessment of routine prostate needle biopsy specimens

Distinguishing benign prostate glands from malignant ones, based purely on morphology, on prostatic core needle biopsy specimens (PNBs) may prove difficult, particularly if the suspicious focus is small. In recent years, several immunohistochemical markers, including the basal cell cocktail (BCC), 34betaE12 and p63, and the prostate cancer (PCa) biomarker alpha-methylacyl-CoA-racemase (AMACR), have been used as adjuvants to morphology, in these diagnostically challenging cases. We prospectively address the diagnostic utility of using the BCC, in combination with the commercially available AMACR monoclonal antibody, P504S, on PNBs that required immunohistochemistry (IHC) studies to make a diagnosis. The goals of this prospective study were to assess the day-to-day practice in an academic setting, to determine how often these IHC tests were used on routine PNBs, and to establish how often a combination of the BCC and P504S were helpful in diagnosing prostate cancer. A total of 772 prospectively collected PNB cases were examined over a 7-month period. IHC staining was performed in 171 cases (22%); 123 cases were stained with the BCC in addition to the commercially available monoclonal AMACR antibody. In 86 of these 123 cases (70%), both stains contributed to the final diagnosis: PCa in 44 cases, benign in 33 cases and high-grade prostatic intraepithelial neoplasia in 9 cases. Of the remaining 37 cases (30%), 18 were called benign or PCa, based solely on appropriate staining with the BCC, with AMACR being noncontributory because the focus of interest had been cut through (12 cases), there was negative staining with AMACR (in 4 PCa cases), or there was positive staining with AMACR (in 2 benign cases showing atrophy). Nineteen of 37 cases were diagnosed as atypical small acinar proliferation. In these 19 cases either the focus had been cut through on one or both of the stains (11 cases), both AMACR and BCC failed to work (2 cases), AMACR was positive in the presence of patchy BCC staining (1 cases), AMACR was negative in the absence of BCC staining (3 cases), or despite appropriate staining the focus consisted of 1 gland and was considered too small to call carcinoma (2 cases). Additional IHC stains were performed in 171 of 772 cases; of these, 123 had sufficient material to perform both the BCC and P504S. The BCC when used in combination with AMACR rendered a diagnosis in almost 70% of cases. Using these stains in combination may be a better approach in diagnostically difficult cases as it increases the likelihood that a definitive diagnosis can be rendered while decreasing the likelihood of an equivocal diagnosis. However, a limitation of this approach is the loss of tissue in these small lesions, suggesting that combining AMACR and the BCC on a single slide would be superior to using either marker separately.     

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.     

磁共振与经直肠超声认知融合引导的经直肠前列腺靶向穿刺活检614例单中心临床研究

本研究旨在探索磁共振(MRI)-经直肠超声(TRUS)认知融合引导下的,经直肠前列腺靶向穿刺活检与经直肠前列腺系统穿刺活检对前列腺癌的检出率的差异性。回顾性纳入自2016年-2018年于我院行前列腺多参数MRI检查后行前列腺穿刺活检的患者614例。对于根据PI-RADS V2评分≥3分的患者同时行MRI-TRUS认知融合靶向活检和系统活检,对PI-RADS V2评分≤2分的患者只行系统活检,比较靶向活检和系统活检在前列腺癌检出率方面的差异。结果显示认知融合靶向活检检出肿瘤342例(75.7%),系统活检检出肿瘤358例(79.2%),二者对于前列腺癌的检出率无显著差异(χ^2=1.621,P=0.203)。靶向活检穿刺针数显著低于系统穿刺活检针数,减少了(9.3±0.11)针(P <0.001)。靶向穿刺活检阳性针中肿瘤组织平均占比比系统穿刺活检多10.8%(P <0.001)。研究结果表明MRI-TRUS认知融合引导的靶向穿刺与系统穿刺对于前列腺癌都具有较高的检出率。MRI-TRUS有望减少穿刺针数,并能提供更多肿瘤组织。     

Efficacy of fine‐needle aspiration biopsy in diagnosis of breast cancer: A retrospective study of 303 cases in Bahrain

Breast cancer is a leading cause of death in many countries worldwide and breast lesions remain a common diagnostic dilemma. Fine‐needle aspiration biopsy (FNAB) has been suggested as the most important, first line, minimally invasive measure in the management of patients with breast lesions. The aim of this study is to evaluate the efficacy of FNAB in patients with breast lesions by comparing the diagnostic accuracy of cytology results with that of the definitive histological examination outcome and also to investigate the added value of a single aspirator experience to the overall diagnostic precision and compared with the internationally published results. A retrospective study of 303 breast FNAB samples were carried out by a single experienced cytopathologist with complete comparison records. The prevalence of positive cytologic diagnosis for the breast cancer was determined to be 20.4%. The overall diagnostic accuracy of FNAB was 97.9%, with a specificity and sensitivity of 98.3 and 96.5%, respectively. The overall positive and negative predictive values were determined to be 93.2 and 99.2%, respectively. In addition, the sensitivity was comparable in cases that have been attempted by palpation‐guided sampling compared with those aspirations that were carried out under US guidance. Results from this study confirm that FNAB biopsies performed and reported by a dedicated, single, skilled cytopathologist are highly effective in diagnosis of breast lesions and reliable in differentiating benign and malignant breast lesions with an overall high efficacy in a specialized laboratory‐based FNAB clinic. Diagn. Cytopathol. 2009. © 2009 Wiley‐Liss, Inc.     

The Symphony protocol for H&E staining of prostatic adenocarcinoma on needle biopsy: a multicentre analysis of 120 cases

AIMS: The diagnosis of prostate carcinoma is based on a constellation of architectural, nuclear, cytoplasmic, and ancillary features. The aim of this study was to determine if the Ventana Symphony H&E protocol can improve on the detection of prominent nucleoli in foci of prostate cancer. METHODS: One hundred and twenty cases of Gleason score 3 + 3 = 6 cancers involving 10-30% of one core were retrieved from four academic institutions and two large laboratories (20 cases per institution). The routine H&E and Symphony H&E protocol stained slides from the same case were reviewed centrally in a blinded fashion at the Johns Hopkins Hospital. The mean percentages of prominent nucleoli in malignant and benign glands by visual estimation were recorded for each case. After unblinding, the routine H&E slides were compared in a pair-wise t-test with the corresponding Symphony stained slide. RESULTS: Within all sites, the Symphony slides showed statistically significantly more prominent nucleoli in the malignant glands than the routine slides. CONCLUSIONS: The Symphony H&E staining protocol consistently highlights nucleoli in cancer to a greater extent than routine H&E stains and may increase the likelihood of making a diagnosis of limited adenocarcinoma of the prostate in challenging cases.     

Mycobacterium avium complex infection in a neck abscess: A diagnostic pitfall in fine‐needle aspiration biopsy of head and neck lesions

Fine‐needle aspiration biopsy (FNAB) is a useful tool in the diagnosis of mycobacterial disease, especially Mycobacterium tuberculosis. However, nontuberculous mycobacterial infection diagnosed with FNAB material is much rarer, with Mycobacterium avium complex being the most common. In this report, we present the case of a 21‐year‐old HIV positive man, who presented with a unilateral, tender, enlarging cervical neck mass. FNAB had revealed acute inflammation. Mycobacterium avium complex grew in culture from the material that was aspirated and was confirmed by DNA probe. Because of the paucity of articles on this subject in the cytology literature, it is important to reiterate the value of the material aspirated at the bedside and the clinic in the diagnosis of infectious disease. When faced with antibiotic‐resistant cellulitis and abscesses, the FNAB material must be sent for acid fast bacteria smears and culture. Diagn. Cytopathol. 2009. © 2009 Wiley‐Liss, Inc.     

Adenosquamous carcinoma of the head and neck: criteria for diagnosis in a study of 12 cases

AIMS: Adenosquamous carcinoma (ASC) of the head and neck is an unusual neoplasm in which a general consensus with regard to diagnostic criteria has not yet been reached. In this study we report the clinicopathological results of 12 ASCs, with special attention to their histological and immunohistochemical characteristics in order to define this neoplasm more precisely. METHODS AND RESULTS: All the patients were male with a peak incidence in the sixth decade of life. The tumours were located most frequently in the larynx and oral cavity, followed by the nasal cavity and pharynx. ASCs had two distinct histological components. The most extensive one was an usual keratinizing squamous cell carcinoma, arising from the surface epithelium, where characteristically severe dysplasia or carcinoma in situ was found in all cases. The second component was an adenocarcinoma, usually displayed in the deepest areas of the tumour. Evidence of origin from salivary or seromucinous glands was not found. Immunohistochemical studies demonstrated in most cases positivity of glandular differentiated areas for carcinoembryonic antigen (CEA) (11/12), CK7 (9/12) and CAM5.2 (7/12), whereas the squamous cell component was unreactive or reacted only focally for these markers. High-molecular-weight cytokeratin 34BE12 was positive in both components and CK20 was always negative. All cases showed high expression of Ki67 antigen. Most of them had overexpression of p53 (8/12) and DNA aneuploidy (10/12). Fifty percent of patients with ASC died of disease after a mean period of 23 months (range 12-35 months). CONCLUSIONS: ASC of the head and neck is an aggressive neoplasm that originates in the surface epithelium of the upper respiratory tract. Severe dysplasia or carcinoma in situ is usually found and its recognition helps to make the diagnosis. In addition to mucin stains, positive immunoreactivity for CEA, CK7 and CAM5.2 helps to identify the glandular component.     

Diagnostic value of fine needle aspiration biopsy in non-thyroidal head and neck lesions: a retrospective study of 866 aspiration materials

Aim: We aimed to investigate the diagnostic value of fine needle aspiration biopsy (FNAB) and compared our FNAB results of non-thyroidal head and neck lesions with excisional biopsy results. Materials and methods: A total of 866 aspiration material taken from different parts of head and neck region out of thyroid were evaluated at Haydarpasa Numune Training and Research Hospital Pathology Laboratory, between January 2002 and May 2013 and 248 of which has histopathologic response were included in the study. Patients depending on origin of the masses were divided into three categories as; salivary gland, lymph nodes and soft tissue/cystic lesions. The sensitivity, specificity, diagnostic accuracy values of fine needle aspiration biopsies have been investigated for all the series and individually for each category. Findings: Diagnostic sensitivity, specificity, accuracy, positive predictive value and negative predictive values of non-thyroidal head and neck masses were respectively; For all of the series; 94.6%, 97.9%, 96.7%, 95.9%, 97.2%, Salivary gland: 88.9%, 100%, 98.8%, 100%, 98.7%, Lymph nodes: 94.7%, 89.3%, 92.9%, 94.7%, 89.2%, Soft tissue/cystic lesions: 100%, 100%, 100%, 100%, 100%. For all of the series; there were 4 false negative (FN) cases; and 3 false positive (FP) cases. Conclusion: FNAB in the diagnosis of head and neck masses; it is an easy, cheap and usefull procedure.