Defining clinically significant prostate cancer on the basis of pathological findings

The definition of clinically significant prostate cancer is a dynamic process that was initiated many decades ago, when there was already evidence that a great proportion of patients with prostate cancer diagnosed at autopsy never had any clinical symptoms. Autopsy studies led to examinations of radical prostatectomy (RP) specimens and the establishment of the definition of significant cancer at RP: tumour volume of 0.5 cm³, Gleason grade 6 [Grade Group (GrG) 1], and organ‐confined disease. RP studies were then used to develop prediction models for significant cancer by the use of needle biopsies. The first such model was used to delineate the first active surveillance (AS) criteria, known as the ‘Epstein’ criteria, in which patients with a cancer Gleason score of 3 + 3 = 6 (GrG1) involving fewer than two cores, and <50% of any given core, and a prostate‐specific antigen density of <0.15 ng/ml per cm³ had a minimal risk of significant cancer at RP. These were adopted as components of the ‘very‐low‐risk category’ of the National Comprehensive Cancer Network guidelines, in which AS is supported as a management option. With the increase in the popularity of AS, much research has been carried out to better define significant/insignificant cancer, in order to be able to safely offer AS to a larger proportion of patients without the risk of undertreatment. Research has focused on allowing higher volume tumours, focal extraprostatic extension, and a limited amount of Gleason pattern 4, and the significance of different morphological patterns of Gleason 4. Other areas of research that will probably impact on the field but that are not covered in this review include the molecular classification of tumours and imaging techniques.     

Diagnostic utility of immunohistochemical markers alpha methyl acyl coA racemase (AMACR) and Ets related gene (ERG) in prostate cancer

Objectives: To study the sensitivity and specificity of IHC markers AMACR and ERG in prostatic adenocarcinoma. Methods: The study was a prospective one and samples were collected from August 2014 to June 2016. A total of 186 samples were obtained from the Department of Urology, in which 112 of these were benign prostatic hyperplasia (BPH), and 71 were prostatic adenocarcinoma. The adenocarcinoma cases were evaluated by two histopathologists, and appropriate Gleason score was given according to the modified ISUP Gleason grading system (2016). IHC markers AMACR & ERG were performed on the adenocarcinoma cases and their sensitivity and specificity were calculated. Results: AMACR was a highly sensitive and specific marker for detecting prostatic carcinoma with a sensitivity and specificity of 95.8% and 96.5% respectively. ERG was a very specific marker with poor sensitivity in detecting prostate cancer. The sensitivity and specificity of ERG were 35.2% and 100% respectively. ERG expression decreased with increasing Gleason grade, PSA level, and tumour volume, which was statistically significant while the association of AMACR with Gleason grade or with tumor volume was not significant. Conclusion: ERG is a marker of early prostatic carcinogenesis and tumors may be positive or negative subtypes. Special histomorphologic features like perineural invasion, glomerulations, and intraluminal blue mucin were also studied. AMACR was a highly sensitive marker for detecting prostatic adenocarcinoma, while ERG was highly specific.     

Decreased annexin I expression in prostatic adenocarcinoma and in high-grade prostatic intraepithelial neoplasia

AIMS: To analyse annexin I expression in prostatic carcinoma. Annexin I belongs to a family of structurally related calcium and phospholipid-binding proteins implicated in signal transduction, DNA replication, cell proliferation and apoptosis. The decreased expression of annexin I, II and VII proteins has been reported in different types of cancer. METHODS AND RESULTS: Using immunohistochemistry, we analysed annexin I expression in 77 cases of prostatic adenocarcinoma (Gleason score 6, N = 40; Gleason scores 7-8, N = 27; and Gleason scores 9-10, N = 10) and high-grade prostatic intraepithelial neoplasia (PIN, N = 50). Immunoreactivity of annexin I in tumour cells was evaluated as negative (< 5% of cells), focally positive (5-25% of cells) or positive (> 25% of cells). In contrast to positive staining in adjacent benign prostatic epithelium, annexin I expression was decreased (focally positive) in 76% of cases of high-grade PIN (P < 0.0001) and was decreased or absent in 81% of prostatic adenocarcinomas (P < 0.0001). Annexin I expression in all higher grade tumours (Gleason scores 7-10) was only focally positive or absent. CONCLUSIONS: Expression of annexin I inversely correlates with the increasing histological grade of prostatic adenocarcinoma. By showing a progressive loss of annexin I expression in high-grade PIN, intermediate-grade and high-grade cancer, our findings suggest that the loss of annexin I expression occurs early in prostatic tumorigenesis and becomes more prominent throughout tumour progression. The loss of expression of annexin I may serve as a useful marker of prostate cancer development and progression.     

Chromosome 14q LOH in localized clear cell renal cell carcinoma

The progression of a malignant tumour is understood to be the result of the accumulation of multiple genetic aberrations. As up to 14% of organ-confined renal cell carcinomas will recur after surgery, tumour clones with metastatic potential must already be present in some of these localized tumours. The association of 14q LOH with high-grade tumours and advanced tumour stage suggests an important role for the gene in tumour progression. Chromosome 14q LOH has been analysed in microdissected specimens from 130 organ-confined (UICC TNM stage 1 and 2) clear cell renal cell carcinomas using three microsatellite markers (D14S588, D14S617, GATA136B01). Tumours were classified as 14q LOH or not on the basis of LOH at one or more of the markers. The allelic imbalance ratio was used to determine both LOH and LOH proportion and the association between LOH and mortality, tumour size, histological grade and growth kinetics, measured by quantification of nucleolar organizer regions, was analysed. 14q LOH was present in 35.4% of informative cases at marker D14S588, 24.4% at D14S617, 36.4% at GATA136B01 and 39.5% for any one of the three markers. The mean 14q LOH proportion was 0.24 (range 0.009-0.80). LOH proportion correlated significantly with tumour size, AgNOR score and histological grade. It was also significantly associated with disease-specific mortality; (hazard ratio 1.22; 95% CI 1.02-1.45; p = 0.039). LOH proportion did not remain significant after adjusting for tumour size (hazard ratio 0.98; 95% CI 0.76-1.27; p = 0.90). These results indicate that the proportion of cells with 14q LOH in the tumour is associated with tumour aggressiveness; while this is not an independent predictor of survival, it may have some utility as a marker of latent metastatic potential.     

Patho-anatomical characteristics of renal cell cancer]

A total of 61 observations on nephrocellular cancer were carried out. It was established that the tumour was not uniform by its histological structure neither in the primary node nor in metastases. Four variants of a histological structure of the cancer were identified: clear-cell, granular, sarcoma-like, and grandular. The one-type histological structure (one variant) in the primary node and in the most common metastases was identified nearly with the same frequency--in 60-66% of the cases. In the rest of the cases the tumour was of a mixed structure; more often there were observed combinations of 2 variants and more seldom--of 3 or 4 combinations. As a rule, metastases histologically corresponded to the primary node, but had peculiar features of their own depending on their localization. Divercity of morphological structures of tumours should be born in mind in making the histological diagnosis of nephrocellular cancer, partitularly if the volume of tissues obtained is small.     

Numerical chromosomal aberrations in prostate cancer: correlation with morphology and cell kinetics

Eleven routinely processed radical prostatectomy specimens were studied for the presence of numerical chromosomal aberrations by means of in situ hybridization with nucleic acid probes specific for chromosomes 7, 10, 17, X, and Y. Cytogenetic information was correlated with morphology, tumour stage and volume as well as with cell kinetics, the latter being assessed by immunohistochemistry with antibodies raised against the proliferative cell nuclear antigen (PCNA) and against a formalin-resistant epitope of the Ki-67 antigen, MIB 1. In 5 of 11 cases, numerical aberrations of at least one chromosome were found. The cases with normal chromosome numbers were those with the smallest volumes of Gleason grade 4 and/or 5 tumour (mean 0.5 cm³) and represented tumours restricted to the prostate. Tumours with aberrations in the number of detected chromosomes showed advanced stages and large volumes of high-grade tumour (mean 12.5 cm³). All 4 tumours with positive surgical margins were recruited from a group with marked local heterogeneity in chromosome numbers. Immunostaining with MIB 1 and PCNA was most intense in areas of high-grade tumour and was positively correlated with the emergence of chromosomal aberrations. The data suggest that the appearance of numerical chromosomal aberrations in prostate cancer coincides with aggressive tumour behaviour and could be used as an additional prognostic marker.This work is part of E.K.'s doctoral thesis     

Ki67 LABELLING INDEX: AN INDEPENDENT PREDICTOR OF PROGRESSION IN PROSTATE CANCER TREATED BY RADICAL PROSTATECTOMY

The clinical course of prostate cancer is highly variable and cannot satisfactorily be predicted by histological criteria alone. Both tumour cell proliferation and neuroendocrine differentiation have been suggested as additional prognostic parameters, neuroendocrine differentiation being considered to enhance tumour cell proliferation. This study investigated the prognostic value of tumour cell proliferation [Ki67 labelling index (LI), MIB 1] and neuroendocrine differentiation and their relationship to each other. One hundred and thirty-seven paraffin-embedded radical prostatectomy specimens were examined. Neuroendocrine differentiation was found in 58 per cent of cases, but was not associated with pTN stage, Gleason score, Ki67 LI, or tumour progression. Ki67 LI was not significantly associated with pTN stage or with Gleason score. High grade ( P =0·0005), advanced local stage ( P =0·0004), positive lymph nodes ( P =0·02), and high Ki67 LI ( P =0·0203) were predictors of tumour progression if univariate analysis was performed, but Cox stepwise regression showed that only advanced local stage ( P =0·0025) and Ki67 LI ( P =0·0105) were independent predictors of tumour progression, the relative risk being 3·6 and 2·5, respectively. It is concluded that Ki67 is an important prognostic marker in prostate cancer with a potential for routine application.     

Expression of E-cadherin in prostate cancer in formalin-fixed,paraffin-embedded tissues: correlation with pathological features

AIMS: E-cadherin has been studied recently as a potential marker for tumour progression. The present study aimed to assess the expression of E-cadherin in formalin-fixed and paraffin-embedded radical prostatectomy specimens and to compare its expression with the pathological stage and Gleason score. METHODS: This study comprised a total of 58 men who were selected on the basis of the negative surgical margins of surgical specimens from radical retropubic prostatectomies and concomitant pelvic lymph node dissections. Indirect immunoperoxidase staining was performed as described previously using HECD-1 monoclonal antibody with the retrieval of antigen by treatment of the paraffin-embedded tissue with microwaves in citrate buffer. RESULTS: Aberrant staining patterns of E-cadherin were observed in 18 (64%) and in 25 (83%) of cases with pathological stages pT2 and pT3a, respectively (P>0.05). Immunohistochemical examination also revealed aberrant staining patterns of E-cadherin in 16 (89%) of specimens with Gleason score > or =7 and in 27 (68%) of specimens with Gleason score <7 (P>0.05). Biochemical recurrence was identified in three (5%) patients and immunohistochemical examination of their specimens revealed aberrant staining patterns of E-cadherin molecule in all of them. CONCLUSION: Our preliminary results indicate that, even though we could not demonstrate any significant correlation between E-cadherin staining pattern and tumour invasion and Gleason scores, aberrant staining patterns of E-cadherin may be a significant predictor for disease recurrence following radical prostatectomies if supported by large scale studies.     

Transition zone carcinoma of the prostate gland: a common indolent tumour type that occasionally manifests aggressive behaviour

AIMS: Tumours arising in the transition zone (TZ) of the prostate gland are often well differentiated and considered clinically unimportant. We have observed examples of high-grade TZ cancers that prompted this study. METHODS: Review of 654 radical prostatectomy specimens previously assessed by systematic whole organ histology identified 187 (29%) TZ cancers of which 76 (11.6%) represented the index (main) tumour. These were compared with a volume-matched group of 76 peripheral zone (PZ) carcinomas. RESULTS: Fifty-nine of 76 TZ index carcinomas had additional minor tumours mainly located in the PZ. Compared to PZ tumours of similar size, TZ tumours had significantly lower Gleason scores, less Gleason grade 4/5 and lower rates of capsular penetration and positive surgical margins. However, within this TZ tumour group, seven carcinomas had a major Gleason grade 4 or 5 component with high rates of capsular penetration (57%) and positive surgical margins (43%). Positive anterior and bladder neck margins were more common in TZ carcinoma than peripheral tumours and transperineal biopsy was the method of choice for TZ cancer diagnosis. CONCLUSIONS: A subset of TZ carcinoma characterised by high tumour grade has a significant risk of extraprostatic spread, margin positivity and possible biochemical failure. We recommend transperineal prostate biopsy for TZ tumour diagnosis and histological sampling of the anterior TZ at radical prostatectomy, even if macroscopically normal, to detect patients at risk from aggressive TZ carcinoma.     

The presence of benign prostatic glandular tissue at surgical margins does not predict PSA recurrence

BACKGROUND: Serum prostate specific antigen (PSA) increases after radical prostatectomy are thought to indicate recurrent disease, although some suggest they result from benign prostatic epithelial tissue left at surgical margins. AIMS: To investigate whether presence, location, and extent of benign prostatic tissue at radical prostatectomy surgical margins influence patient outcome. METHODS: One hundred and ninety nine patients with prostate cancer and negative surgical margins were studied. The prostectomy specimens were totally embedded using the whole mount technique. The apex and bladder neck, dissected as a cone from the specimen, were serially sectioned. The total length of benign prostatic tissue at the margins, measured for each location using an ocular micrometer, was obtained by summing the length of all positive sites. The presence, anatomical location, and extent of benign prostatic tissue at the margin were correlated with clinicopathological characteristics and postoperative PSA increases. RESULTS: Fifty five cases had benign prostatic glandular tissue at the surgical margin. The mean length was 2.19 mm (0.1-14.7). The most frequent location of benign prostatic tissue was the apex (40 patients). Presence, anatomical location, and length of benign prostatic tissue at the margin were not significantly associated with age, preoperative PSA, prostate weight, pathological stage, tumour volume, largest tumour dimension, Gleason score, extraprostatic extension, seminal vesical invasion, tumour multifocality, perineural invasion, or PSA recurrence. CONCLUSIONS: Benign prostatic tissue was frequently found in margins of apex and bladder base, but uncommon in the anterior or posterior prostate. The presence of benign prostatic tissue at surgical margins had no prognostic relevance.     

Caspase-3/CPP32 immunoreactivity and its correlation with frequency of apoptotic bodies in human prostatic carcinomas and benign nodular hyperplasias

AIMS: Apoptosis is mediated by apoptosis-specific genes, certain oncogenes and tumour suppressor genes. Caspase-3, a group of cystein proteases, is involved in the induction of apoptosis and has been considered to correlate with apoptosis. The aim of this study was to determine whether caspase-3 is expressed in prostatic carcinoma and benign prostatic hyperplasia, and correlated with the apoptosis. METHODS AND RESULTS: We studied the apoptotic index and caspase-3 immunoreactivity in 40 cases of benign nodular hyperplasia (BPH) and 40 cases of prostate carcinoma (PCA) by in-situ labelling and immunohistochemistry. The mean number of apoptotic bodies in cases with BPH was not significantly different from cases with PCA I (Gleason score 2-4), but samples from patients with PCA II (Gleason score 5-7) and PCA III (Gleason score 8-10) showed a significantly higher apoptotic number than cases with BPH. Positive staining for caspase-3 was seen in 42.5% (17/40) of the BPH, and 27.5% (11/40) of the PCA: PCA I was 41.7% (5/12), PCA II 14.3% (2/14) and PCA III was 28.6% (4/14). CONCLUSIONS: Based on our results, the number of apoptotic bodies was not correlated with the caspase-3 expression and there was no relationship between caspase-3 expression and Gleason score. However, the number of apoptotic bodies was significantly higher in cases with intermediate (Gleason score 5-7) and high-grade (Gleason score 8-10) PCAs than cases with BPH and low-grade PCAs (Gleason score 2-4).     

Gleason grading: past, present and future

In 1966 Donald Gleason developed his grading and scoring system for prostatic adenocarcinoma. This classification was refined in 1974 and gained almost universal acceptance, being classified as a category 1 prognostic parameter by the College of American Pathologists. Modifications to the classification were recommended at a conference convened by the International Society of Urological Pathology (ISUP) in 2005. This modified classification has resulted in a significant upgrading of tumours, although some studies have shown a greater concordance between needle biopsy and radical prostatectomy scores when compared to classical Gleason (CG) grading. The ISUP consensus conference recommended that for needle biopsies higher tertiary patterns should be incorporated into the final Gleason score, and this has been correlated with biochemical failure, tumour volume and mortality. Recently the validity of including cribriform glands as a component of Gleason pattern 3 has been questioned and it has been recommended that all tumours showing cribriform architecture should be classified as Gleason pattern 4. The recommendations arising from the 2005 Consensus Conference were largely unsupported by validating data, yet this new grading system has achieved widespread usage. It is unfortunate that recent suggestions for further modification are similarly lacking in supporting evidence. In view of this it is recommended that the Modified Gleason Scoring Classification should continue to be utilized in its original (2005) format and that any future alterations should be implemented only when mandated by tumour-related outcome studies.     

The relationship between the extent of surgical margin positivity and prostate specific antigen recurrence in radical prostatectomy specimens

The presence of positive surgical margins is a negative prognostic indicator in patients undergoing prostatectomy for prostate cancer; whether the extent of the positive margins affects the clinical outcome with regards to prostate-specific antigen (PSA) recurrence remains uncertain. We evaluated the linear extent of margin positivity as a prognostic indicator in a series of radical prostatectomy specimens. One hundred seventy-four consecutive margin-positive prostatectomy specimens were evaluated. The linear extent of margin positivity was measured with an ocular micrometer and ranged from 0.05 to 75.0 mm (mean, 8.94; median, 5.0). The linear extent of margin positivity was associated with tumor volume (P = .03) but was not associated with patients' age at surgery, preoperative PSA level, prostate weight, pathologic stage, Gleason score, extraprostatic extension, seminal vesicle invasion, perineural invasion, high-grade prostatic intraepithelial neoplasia, or PSA recurrence. In the full model multiple Cox regression, significant predictors for PSA recurrence were Gleason score (P = .001) and preoperative PSA (P = .01); extent of margin positivity was not predictive of PSA recurrence (hazard ratio, 1.00; 95% confidence interval, 0.98-1.02; P = .97) nor was tumor volume a significant factor when adjusted for other covariates (P = .27). Preoperative PSA, tumor stage, and Gleason score remained significant prognostic factors in evaluating the likelihood of PSA recurrence in patients with positive surgical margins; the extent of margin positivity, however, is not a prognostic factor for PSA recurrence and should, therefore, not necessarily be included in the final report for radical prostatectomy specimens.     

Feasibility of percutaneous organ biopsy as part of a minimally invasive perinatal autopsy

To determine the feasibility of percutaneous fetal organ biopsies in the context of a ‘minimally invasive’ perinatal autopsy after stillbirth and termination for abnormality is the aim of this study. We assessed successful biopsy rate and the proportion adequate for histological examination in 30 fetuses undergoing organ sampling before autopsy. The relationship between gestational age, body weight, death–biopsy interval, operator experience and successful biopsy rate was investigated. Significant findings from conventional block histology were compared with corresponding percutaneous biopsies. Of 210 organ biopsies attempted from seven target organs, 107 were obtained, of which 94 were adequate for pathological comment. The median delivery–autopsy interval was 4 (range 2–11) days. Adequate samples were obtained from the lung in 86% cases (95% CI 68, 96%), liver 76% (95% CI 56, 90%) and less frequently for the myocardium, kidney, adrenal, thymus and spleen. There was no relationship between biopsy success and time to biopsy, gestational age, body weight and user experience. No histological abnormalities found at autopsy were diagnosed from needle biopsies. Although targeted percutaneous biopsies appear feasible for some organs, fewer than 50% of all biopsies are adequate for histological examination. This technique cannot be considered to provide useful clinical information as part of a ‘minimally invasive’ perinatal autopsy.     

A new method of grading malignancy of prostate carcinoma using quantitative microscopic nuclear features

A morphometrical assessment of nuclear features and a DNA study were performed on prostate tissue specimens from 33 patients with prostate carcinoma using an image analysing computer. Six nuclear geometric variables were measured and their mean, standard deviation (SD) and standard error (SE) were calculated for each case. The data on nuclear DNA content obtained by static cytometry were processed using an algorithm which provided a DNA grade of malignancy (DNA MG). Using the stepwise multiple regression, we found a significant correlation (p less than 0.01) between the DNA MG, chosen as the dependent variable in the statistical model, and the following nuclear features in decreasing order of importance: area SD, convex perimeter SE, and the mean of maximum diameter. From the correlation coefficients of the variables an equation was built up which provided a geometric nuclear grade of malignancy (GNMG) on a morphometrical basis more closely related to the clinical stage of the tumour (r = 0.75) than the visually assessed histological grade (r = 0.68) based on the Gleason score. This new method of grading malignancy allows an objective and quantitative evaluation to be made of the biological behaviour of the tumour, as measured by the patient's clinical stage.     

HISTOLOGICAL GRADE HETEROGENEITY IN MULTIFOCAL PROSTATE CANCER. BIOLOGICAL AND CLINICAL IMPLICATIONS

In order to understand the clinical and biological implications of prostate cancer multifocality and heterogeneity, we investigated their occurrence in relation to variables such as tumour volume, local invasion, and biopsy findings. In a series of 61 completely sectioned whole-mount radical prostatectomy specimens with clinical stage T2 prostate cancer, we mapped histological grade heterogeneity and tumour multifocality. We also evaluated 55 prostate biopsy cases to assess the accuracy of pre-operative grading. Among all of the prostates, only 28 per cent had a single tumour and in 16 per cent one histological grade of cancer was evident. Extracapsular invasion was not restricted to the largest tumour in each case, but also occurred in tumours of relatively small volume and low histological grade. Variability of histological grade was directly proportional to tumour volume. Both grade heterogeneity and tumour multifocality of the prostatectomy specimen showed no significant relationship to the grade accuracy of biopsies. Biopsy grading error proved greatest among small, well-differentiated tumours. Whole-mount sectioning of prostatectomy specimens in patients with clinically localized adenocarcinoma demonstrates that grade heterogeneity is most closely related to tumour volume; that the largest (index) tumour lesion may not be representative of the pathological stage; and that grading error in prostate needle biopsies can be only partly explained by grade heterogeneity or tumour multifocality.     

Peripheral neuroblastic tumours in eastern Denmark 1972-2002

The peripheral neuroblastic tumour group includes neuroblastoma, ganglioneuroblastoma and ganglioneuroma. Neuroblastoma is the most common extracranial solid tumour of childhood. We have evaluated the histological presentation, MYCN gene status, and clinical course of peripheral neuroblastic tumours diagnosed and treated in eastern Denmark from 1972-2002. 125 patients were diagnosed with peripheral neuroblastic tumour during this 30-year period. The histological material was reviewed and classified into three categories in accordance with the Shimada system: unfavourable histology, favourable histology, and benign tumours. MYCN status was determined by fluorescent in situ hybridization (FISH) on paraffin sections from the primary tumour. Clinical information was obtained from hospital records. Diagnostic likelihood ratios in the two groups were calculated to compare the ability of MYCN status and histological classification to predict 5-year outcome. 41 tumours showed unfavourable histology, 30 tumours showed favourable histology, 11 were benign, and 43 were unclassifiable due to limited amounts of primary tumour, bad preservation or inaccessibility of the primary tumour necessitating metastatic tumour biopsy for diagnosis. Unfavourable histology was associated with widespread disease (p<0.001). The overall 5-year survival rate was 45%, which correlates well with the European survival rate reported for this time period. The 5-year survival rate in the unfavourable group was 30% as compared to 100% in the favourable histology group (p<0.001). The survival rate in the unclassifiable group was 13%. 26% of the neuroblastomas were MYCN amplified. MYCN amplification was associated with undifferentiated histology, a histological subtype of the unfavourable histology group (p<0.001). For unfavourable histology the positive diagnostic likelihood ratio was 2.9 as compared to 4.7 for MYCN amplification. The study has confirmed the prognostic significance of the Shimada system in the peripheral neuroblastic tumour group in a retrospective material, and has also demonstrated the prognostic superiority of MYCN compared to histological classification, thus reducing the necessary amounts of tumour tissue.     

Cutaneous perineurioma: a poorly recognized tumour often misdiagnosed as epithelioid histiocytoma

AIMS: Eleven cases of cutaneous perineurioma were studied to further characterize the histological features of this entity. METHODS AND RESULTS: The histological and immunocytochemical features of 11 cases of cutaneous perineurioma were studied and detailed by two pathologists. Clinical data were obtained from the referring clinician. Seven patients were female and four were male with ages ranging from 19 to 67 years (median 41 years). Six lesions arose on the leg. Macroscopically lesions ranged from 4 mm to 14 mm in maximum diameter (median 7 mm). Diagnostic histological features included a nonencapsulated but sharply demarcated tumour with a dumbbell architecture. The tumour cells were spindle-shaped with delicate inconspicuous cytoplasm and arranged in sheets, whorls or with a vague fascicular pattern. Epithelioid cells with moderate amounts of eosinophilic cytoplasm were frequently admixed with the spindle cells. One tumour had trabeculae of cells embedded within a dense collagenous stroma as described in sclerosing perineurioma. One case displayed a prominent myxoid stroma. Three further cases contained small foci of fibrosis or myxoid change suggesting a morphological spectrum exists in cutaneous perineurioma. Mitoses were exceptionally rare and necrosis and significant cytonuclear pleomorphism was not found. All tumours were epithelial membrane antigen (EMA) positive. Six cases showed focal positivity for factor XIIIa. Follow-up ranged from 5 months to 6 years (median 1 years). No tumour recurred or metastasized. CONCLUSIONS: The histological appearance of this tumour is broader than hitherto realized. Several cases in this series were misdiagnosed histologically and cutaneous perineuriomas may be more common than currently appreciated.     

Light and electron microscopic investigation of parathyroid carcinoma during differentiation

Summary A case of parathyroid carcinoma in a 74-year-old female patient was studied by light and electron microscopy.The malignancy of the parathyroid tumour was confirmed by local recurrence and infiltration of adjacent structures. The tumour was composed of uniform chief cells without mitoses. Ultrastructurally, the cells were characterized by tortuous plasma membranes, numerous secretion granules, an extensive rough endoplasmic reticulum and lack of lipid vacuoles, all indicating hyperactivity, but not malignancy.At death, the autopsy revealed local recurrence of tumour tissue, but no distant metastases. Both light and electron microscopy showed that considerable dedifferentiation of the tumour tissue had occurred. The tumour cells were now characterized by a marked nuclear pleomorphism and a coarse clumping of the chromatin. The presence of secretion granules alone suggested a parathyroid origin.Thus, at death there was unequivocal histological evidence of a carcinoma, whereas no such diagnosis could be made from the early biopsy. The clinical course alone indicated the malignant nature of the lesion.     

Bedeutung der Zweitmeinung bei Prostatabiopsien

Objective

The significance of a second opinion on the histological findings of prostate carcinomas as well as suspicious lesions on core needle biopsy specimens was studied in cases from the year 2008.

Study design

A total of 920 core needle biopsy specimens of the prostate were stained with H &; E and when necessary immunohistochemical analyses were performed with basal cell markers p63, 34?E12, PSA and AMACR (P504?S) and neuroendocrine markers such as synaptophysin and chromogranin. The modified Gleason grading system was used.

Results

In 43.5% of suspicious lesions adenocarcinomas of the prostate were found. In 53.2% the findings of atypical small acinar proliferations or high-grade prostatic intraepithelial neoplasia (HGPIN) were confirmed with a recommendation of serum PSA and morphological controls. The suspicion of prostatic carcinoma could be confirmed in 87.2% by the diagnosis of adenocarcinoma. After Gleason grading 82.8% of all diagnosed carcinomas had scores 6 or 7(3?+?4) and belonged to the group of low grade carcinomas. High grade carcinomas were without diagnostic problems.

Conclusion

A second opinion on the histological analysis of suspicious lesions of the prostate as well as of confirmation of Gleason grading is a very important point of quality management of diagnostic steps of prostate carcinomas and may be helpful for different therapeutic strategies.