[Extemporaneous examination in lung pathology: the pathologist's view]. / L'examen extemporané en pathologie thoracique. Le point de vue du pathologiste.

Extemporaneous examination of a thoracopulmonary lesion has an unquestionable interest when pre-surgical diagnostic workup has not allowed determining its exact nature. This examination, the sole objective of which is to guide the surgical approach, is especially important in lung pathology, due to the limited non-surgical access to thoracic lesions and the morbidity and mortality of repeated surgery. Its yield as a decision-making procedure is of utmost importance in many clinical situations, and a close collaboration between thoracic surgeons and pathologists is required to ensure its quality, in a context of mutual confidence that requires time and experience. After a presentation of the indications and practical modalities of extemporaneous examination, we will underline its limitations and insist on difficult situations for the pathologist and inadequate indications.

[Appendiceal mucoceles, pseudomyxoma peritonei and appendiceal mucinous neoplasms: update on the contribution of imaging to choice of surgical approach]. / Mucocèles appendiculaires, pseudomyxomes péritonéaux et tumeurs mucosécrétantes du carrefour iléocaecal: apport de l'imagerie dans la stratégie thérapeutique et le choix de la voie d'abord laparoscopique ou classique.

INTRODUCTION: The treatment of pseudomyxoma peritonei (PMPs) and appendiceal mucocele (AM) has changed radically. To assess the contribution of preoperative imaging to the treatment strategy and choice of approach, a surgeon and a radiologist different from the initial radiologist examined the files of all patients treated for PMP or AM in four facilities in one district from January 1, 1996, through December 31, 2008. PATIENTS AND METHODS: The study included 27 patients (20 men and seven women, mean age: 63+/-13 years). Eleven patients had an intact AM, seven synchronous PMP (malignant appendiceal lesion in two of seven), six metachronous PMP (five with peritoneal mucinous carcinomatosis and one with diffuse peritoneal adenomucinosis) and three a ruptured AM but not PMP. The incidence of mucin-secreting tumors observed (27 cases in 12 years in a region of 500 000 inhabitants) corresponds to a prevalence of approximately five cases per year per million inhabitants. Acute clinical pictures (7/27) were significantly more frequent for the malignant forms (5/7) (p<0,02). RESULTS AND DISCUSSION: The overall sensitivity of computed tomography (CT) for all the criteria studied was 93%. The predictive value for AM rupture of visualization of thick calcifications was 100%. On the other hand, rupture never occurred when the CT showed an AM under pressure, with thin walls and septa. The predictive value for PMP of "scalloping" was 100%. The diagnostic accuracy of the initial reading was 25/27 for the imaging overall and 25/25 for the CT. Preoperative visualization of the exact size of the intact AM or of diagnostic information about ruptured AM and PMP helped to select an appropriate approach in 25 of 27 cases.

[Giant colonic or ileo-jejunal diverticulum and infra-mesocolic abdomial pseudocysts: diagnosis, pathalogical and clinical analysis]. / Diverticules géants du grêle et du côlon et formations pseudo kystiques sous-mésocoliques.

Giant diverticula of the small intestine and colon are rare. Four cases treated at our institution in the last year are reported and compared to published cases; specific features and those which differentiate them from abdominal pseudocysts are described. They most commonly present a clinical tableau similar to commonplace diverticular disease. Awareness of this unusual condition and a good CT study are the keys to diagnosis. Giant diverticula may be acquired or congenital. The acquired type is simply a more spectacular version of commonplace diverticulosis while the congenital type, having a muscular wall and myenteric plexus, is more akin to intestinal duplications. Treatment is surgical and, in the case of sigmoid giant diverticula, usually requires a colon resection similar to that required for sigmoid diverticulitis.

[Imaging of pancreatic adenocarcinoma]. / Imagerie de l'adénocarcinome du pancréas.

Pancreatic cancer remains the fourth most common cause of cancer death. Surgery remains the only option for cure. Accurate diagnosis and staging are essential for appropriate management of patients with pancreatic cancer. This paper reviews the state of the art for imaging modalities in the diagnosis and staging of pancreatic adenocarcinoma. The crucial role of CT has increased with the new generation of multidetector CT.

[HER2 gene amplification assay: is CISH an alternative to FISH?]. / Recherche de l'amplification du gène HER2: la CISH est-elle une alternative à la technique FISH?

The HER2 proto-oncogene encodes a transmembrane protein, which is considered to function as a growth factor receptor. Overexpression of this protein found by immunohistochemistry in about 20% of infiltrating breast carcinomas, has a predictive value of response to treatment by trastuzumab, an anti-HER2 humanized monoclonal antibody. Search for HER2 gene amplification is necessary to adapt the immunohistochemical technique quality and also in the cases of delicate analysis or weak overexpression. It is usually carried out by Fluorescence In Situ Hybridization (FISH). A more recent hybridization technique, named CISH because of its chromogenic revelation is an alternative method, which gives highly correlated results with FISH. We present details of this technique, which may be more familiar for the pathologists than FISH, because reading analysis is similar to that of immunohistochemical staining.

[2001 Standards, Options and Recommendations: practice guidelines for difficult diagnoses in surgical pathology or cytopathology in cancer patients]. / Standards, Options et Recommandations 2001 bonnes pratiques pour la conduite à tenir devant une lésion de diagnostic anatomocytopathologique difficile en cancérologie.

CONTEXT: The Standards, Options and Recommendations (SOR) project, which started in 1993, is a collaboration between the Federation of French Cancer Centers (FNCLCC), the 20 French Regional Cancer Centers, and specialists from French public universities, general hospitals and private clinics. The main objective is the development of clinical practice guidelines to improve the quality of health care and the outcome of cancer patients. OBJECTIVES: To elaborate practice guidelines for difficult diagnoses in surgical pathology or cytopathology in cancer patients. METHODS: The methodology is based on a literature review and critical appraisal by a multidisciplinary group of experts who define the CPGs according to the definitions of the Standards, Options and Recommendations project. Once the guidelines has been defined, the document is submitted for review by independent reviewers. RESULTS: The main recommendations to prevent and reduce the number of difficult diagnoses in surgical pathology or cytopathology are: The main recommendations to detect lesions associated with difficult diagnosis in surgical pathology or cytopathology are: The main recommendations to solve difficult diagnosis in surgical pathology or cytopathology are:

Primary squamous cell carcinoma of the endometrium: case history, pathologic findings, and discussion.

Primary squamous cell carcinoma of the endometrium (PSCCE) is an exceedingly rare tumor. Rarely are cytological criteria discussed. We report our experience in the cytological diagnosis of a case. A postmenopausal, 64-yr-old woman suffered from pyometria. An endometrial Pap smear displayed some malignant squamous cells. Curettage of the cervix and the uterine cavity only recovered some fragments of atypical squamous epithelium whose origin could not be precisely identified. A hysterectomy with bilateral adnexectomy was decided upon. Pathological study evidenced a primary squamous cell carcinoma in the uterine cavity while the cervix was tumor-free and the lymph nodes were devoid of metastases (pT1, pN0, pM0). The patient died 46 mo PO with multiple pulmonary and renal metastases. The histological feature of PSCCE is identical to that of any tumor of a similar nature, whatever the site, especially the cervix. Confirmation of the primary endometrial nature is only possible on the hysterectomy specimen.

Interpretation and quantification of immunostains.

Despite the fact that immunohistochemistry is widely used in routine diagnostic work and is a very common part of scientific reports in pathology and cytology, its standardization still lags behind. Interpretation of immunostains should be based on microanatomic distribution of the staining, proportion of positively stained cells, staining intensity, if relevant, and cutoff levels. These parameters should be shown to be reasonably reproducible and should be clearly defined in publications. Uniformity in the setting of thresholds could probably benefit from interlaboratory control materials containing defined amounts of the target antigen. Reliable and precise quantitative immunohistochemistry requires the use of control materials containing defined amounts of the target antigen and processed alongside the specimen combined with automated computer-assisted microspectrophotometry. Application of these suggestions is hoped to improve standardization and to facilitate communication in the field of immunohistochemistry.

[Standards, options and recommendations: practice guidelines for difficult diagnosis in surgical pathology or cytopathology in cancer patients]. / Standards, options et recommandations: conduite a tenir devant une lésion de diagnostic anatomo-cyto-pathologique difficile en cancérologie.

CONTEXT: The "Standards, Options and Recommendations" (SOR) project, started in 1993 is a collaboration between the Federation of the French Cancer Centres (FNCLCC), the 20 French Cancer Centres and specialists from French Public Universities, General Hospitals and Private Clinics. The main objective is the development of clinical practice guidelines to improve the quality of health care and outcome for cancer patients. The methodology is based on literature review and critical appraisal by a multidisciplinary group of experts, with feedback from specialists in cancer care delivery. OBJECTIVES: To develop clinical practice guidelines according to the definitions of the Standards, Options and Recommendations project for difficult diagnoses in surgical pathology or cytopathology in cancer patients. METHODS: Data were identified by searching Medline and using the personal reference lists of members of the expert groups. Once the guidelines were defined, the document was submitted for review to 71 independent reviewers. RESULTS: The main recommendations to prevent and reduce the number of difficult diagnoses in surgical pathology or cytopathology are: 1) The development of quality insurance programs with use of written procedures in each pathology laboratory (standard). 2) The knowledge of clinical data in order to explain surgical pathology or cytopathology results (standard). 3) The availability of complementary patient informations (radiologic data . . .) can be useful to explain surgical pathology or cytopathology results (option). The main recommendations to detect lesions associated with difficult diagnosis in surgical pathology or cytopathology are: 1) Tumor types known as potential difficult diagnosis in surgical pathology or cytopathology should be reviewed by a second pathologist. 2) The systematic second reviewing for every case is expensive but has to be done when the difficulty is know (sarcoma, lymphoma . . .) by experienced pathologists. The main recommendations to solve difficult diagnosis in surgical pathology or cytopathology are: 1) Block recuts, use of special techniques (immunocytohistochemistry and molecular biology), additional data from clinicians, second opinion by a local pathologist, or new specimen can be required for establishing the diagnosis (options). 2) Outside second opinion by expert pathologist has to be considered once the other steps did not allow to establish surgical or cytopathology diagnosis (recommendations, expert agreement).

Study of interlaboratory reliability and reproducibility of estrogen and progesterone receptor assays in Europe. Documentation of poor reliability and identification of insufficient microwave antigen retrieval time as a major contributory element of unreliable assays.

Immunohistochemical assays for estrogen receptors (ERs) and progesterone receptors (PRs) have not been surveyed for technical validity. In the present study, the reliability of the immunohistochemical assay for ER and PR was evaluated using data from 105 laboratories participating in external quality assessment (EQA) during a 2-year period. Technical variables associated with reliable immunostaining were analyzed. The efficiency of the antigen retrieval step was identified as the single most important contributory factor influencing the overall reproducibility of the assays. Reliable assays were found in 24 (36%) of 66 laboratories participating in continual EQA, including the majority of centers known to have clinically validated results. Inadequate assay sensitivity, with subsequent weak staining, was the main cause of poor and variable results by laboratories using microwave antigen retrieval; too short a heating time was identified as the principal contributory factor. Extension of the heating time resulted in significant improvement regardless of all other variables in the immunohistochemical protocol. Continual participation in EQA is an effective means for identifying and ameliorating variables that influence the reliability of immunohistochemical assays for predictive markers, thereby assisting in technical validation and standardization.

[Monoclonal antibodies in oncology: applications in diagnosis, prognosis and prediction of response to therapy on tissue specimens]. / Anticorps monoclonaux en oncologie: applications diagnostiques, pronostiques et prédictives sur coupes tissulaires.

Immunohistochemistry (IHC) is the application of antibody methods to slide-based material i.e. cells and tissues. No other technique has so revolutionised the field for the past 50 to date. IHC has become a staple of the histopathology laboratory. The advantages of this technique are obvious: it is simple, fast and cost-effective. IHC is of great help in oncology: to classify a tumor in its category, to identify the origin of a metastasis and in some cases to establish the malignancy of a lesion. The implications of IHC in the determination of prognostic and predictive factors in oncology are still limited, but start to develop, particularly in the field of the detection of hormon receptors and of the overexpression of HER2/neu in breast cancer. Although IHC lacks of reproducibility, the development of quality assurance programs will contribute to the development of IHC in predictive oncology.

Frequency of oestrogen and progesterone receptor positivity by immunohistochemical analysis in 7016 breast carcinomas: correlation with patient age, assay sensitivity, threshold value, and mammographic screening.

AIMS: A routine immunohistochemical (IHC) assay is now commonly used for determining the oestrogen receptor (ER) and progesterone receptor (PR) status of women with breast cancer. To date, no large studies have been conducted that report the expected frequency of receptor positivity in relation to patient age and sensitivity of the IHC assay. Data on 7016 breast carcinomas from 71 laboratories were analysed to determine the frequency of receptor positivity and investigate possible causes of the observed variation in detection rates. METHODS: Members of UK NEQAS-ICC (UK National External Quality Assessment Scheme for Immunocytochemistry) provided data on the receptor status of cases routinely assayed in their departments over a period of two to 26 months between June 1996 and September 1998. Data on 7016 breast carcinomas were stratified according to patient age and receptor status. Frequency of receptor positivity was correlated with IHC assay sensitivity, the threshold value used to determine receptor positivity, and the presence or absence of mammographic screening in the hospitals or clinics served by the laboratories. RESULTS: The highest proportion of receptor positive cases occurred in patients in the age ranges > 65 years for ER and 41-50 years for PR. There was a significant positive correlation between frequency of receptor positivity and the sensitivity of the IHC assay, for both ER (rs = 0.346; p = 0.019; two tailed) and PR (rs = 0.561; p = 0.003; two tailed). The mean frequency of receptor positivity for laboratories using the same 10% threshold value was 77% for ER (95% confidence interval (CI), 74% to 80%) in laboratories with high sensitivity and 72% (95% CI, 68% to 76%) for those with low assay sensitivity (p = 0.025). For PR, the mean frequency of receptor positivity for laboratories using the same 10% threshold value and having high assay sensitivity was 63% (95% CI, 57% to 69%), and 51% (95% CI, 38% to 65%) for laboratories with assays of low sensitivity (p = 0.022). The mean frequency of ER positivity for laboratories serving hospitals and clinics where mammographic screening does and does not take place was 73.4% and 75.7%, respectively (p = 0.302; two tailed). CONCLUSIONS: Of the parameters investigated, patient age and IHC assay sensitivity were found to be the main variables influencing the frequency of receptor positivity. We recommend the range of receptor values obtained by laboratories achieving high assay sensitivity as a useful guide against which all laboratories can gauge their own results.

Immunohistochemical demonstration of oestrogen and progesterone receptors: correlation of standards achieved on in house tumours with that achieved on external quality assessment material in over 150 laboratories from 26 countries.

AIMS: To investigate the sensitivity of immunohistochemical (IHC) assays for oestrogen receptors (ER) and progesterone receptors (PR) achieved by laboratories on breast tumours fixed and processed in their own department, and to compare this with the degree of sensitivity they achieve on tumours circulated as part of an external quality assessment (EQA) programme. METHODS: On 10 occasions between April 1994 and June 1998, histological sections from breast cancers showing various degrees of expression of ER and PR were circulated for IHC staining to laboratories participating in the UK national external quality assessment scheme for immunocytochemistry (UK NEQAS-ICC). The staining of these tumours, in addition to that of tumours fixed and processed in the participants own laboratories (in house tumours), was assessed by a panel of four assessors, using the established UK NEQAS-ICC scoring system. For a selected assessment run, the degree of expression of participants in house tumours was evaluated by means of the semiquantitative quick score method. RESULTS: Although the scores awarded for the staining of in house tumours were generally higher than those awarded for the staining of UK NEQAS tumours, there was also a significant positive correlation between the two sets of scores. Using the quick score method of evaluation for one of the assessment runs, 47% of in house tumours were classified as having a high degree of ER expression. Of the remaining cases, a significant proportion initially classified as having only low or medium expression of ER were found to have higher expression when stained by the organising laboratory. The UK NEQAS-ICC centre's routine assay for hormonal receptors was found to be 90-100% efficient in achieving optimal demonstration of breast tumours from over 150 different laboratories. CONCLUSIONS: The significant positive correlation between the results obtained on the UK NEQAS tumours and the in house tumours provides evidence for the view that results achieved on EQA material are accurate indicators of in house laboratory performance. Although most laboratories adequately detected tumours with high receptor expression, a large proportion of in house tumours classified initially by participants' staining as being of low or medium ER expression had a higher degree of expression when stained by the UK NEQAS-ICC centre. The efficiency of the organising centre's routine IHC method for ER and PR in optimally demonstrating participants in house breast tumours shows that variations in fixation and tissue preparation are not limiting factors preventing a different laboratory achieving optimal demonstration.

[Antigenic retrieval using a pressure cooker]. / Restauration antigénique à l'aide d'un autocuiseur.

This technical note describes antigen retrieval procedures using a pressure cooker. These procedures are perfectly adapted to routine immunohistochemistry and improve the overall quality of immunostaining.