Prostate cancer stands as the most prevalent malignant tumor among men; with its incidence increasing with advancing age. The spectrum of patient care options for this disease is broad, encompassing approaches such as "active surveillance," definitive radiation therapy, robot-assisted surgery, among others. These diverse modalities afford opportunities for cure or successful management in the majority of cases. It is paramount to underscore that optimal treatment hinges upon a multidisciplinary framework, wherein the coordinated efforts of allied healthcare professionals yield the highest standard of patient care. Hence, it is imperative for pathologists to keep abreast of contemporary processing and specimen collection protocols, as well as the potential necessity of supplementary investigations and their clinical significance. The latest Hungarian guideline on prostate cancer care features a dedicated chapter delineating the pivotal role and responsibilities of pathologists. Through this discourse, we aim to consolidate and disseminate pertinent insights, thereby fostering the continuing enhancement of pathologists' knowledge and elucidating the intricacies of histological processing to our clinical counterparts.

Invasive lobular carcinoma of the breast has different mammographic appearances, including spiculated or lobulated masses, architectural distortion, increased breast density, and the possibility of also being occult. Histologically, the morphology is also variable, as several patterns have been described beside the classical one, including the solid, the alveolar, the trabecular, the one with tubular elements, and others. Of 146 ILC cases, 141 were reviewed for mammographic appearance and 136 for histological patterns by two radiologist and two pathologists, respectively; 132 common cases were analyzed for possible associations between mammographic presentation and the histological patterns. Interobserver agreement on the presence or absence of a given mammographic morphology ranged from 45% (increased density) to 95% (occult lesion); the most common radiomorphology was that of a spiculated mass. Interobserver agreement on the presence or absence of a given histological pattern ranged between 79% (solid) and 99% (classical) but was worse when semi-quantification was also included. The mammography–pathology correlation was less than optimal. Multifocality was more commonly detected by histology. The identification of a mammographic mass lesion often coincided with a mass-like lesion on the histological slides and vice versa, but nearly half of the mammographically occult lesions were felt to have masses on histological slides assessed grossly. Histological patterns showed no obvious associations with one or the other mammographic appearance.

Tumour-infiltrating lymphocytes (TILs) reflect antitumour immunity. Their evaluation of histopathology specimens is influenced by several factors and is subject to issues of reproducibility. ONEST (Observers Needed to Evaluate Subjective Tests) helps in determining the number of observers that would be sufficient for the reliable estimation of inter-observer agreement of TIL categorisation. This has not been explored previously in relation to TILs. ONEST analyses, using an open-source software developed by the first author, were performed on TIL quantification in breast cancers taken from two previous studies. These were one reproducibility study involving 49 breast cancers, 23 in the first circulation and 14 pathologists in the second circulation, and one study involving 100 cases and 9 pathologists. In addition to the estimates of the number of observers required, other factors influencing the results of ONEST were examined. The analyses reveal that between six and nine observers (range 2–11) are most commonly needed to give a robust estimate of reproducibility. In addition, the number and experience of observers, the distribution of values around or away from the extremes, and outliers in the classification also influence the results. Due to the simplicity and the potentially relevant information it may give, we propose ONEST to be a part of new reproducibility analyses.

Histological grade is one of the most important prognosticators of breast cancer which is available for nearly all cases. It also makes part of several multivariable analysis derived combined prognostic profiles despite concerns about its reproducibility. The aims included a reproducibility study of grading in the light of a recently described statistical approach, ONEST (Observers Needed to Evaluate Subjective Tests) and review earlier reproducibility studies in the light of the ONEST analysis. Nine pathologists reviewed 50 core needle biopsies and 50 slides from different excision specimens and recorded the scores for gland (tubule) formation, nuclear pleomorphism and mitotic activity as well as histological grade. Overall percent agreement, Fleiss kappa and the intraclass correlation coefficient (ICC) were used for the analysis of reproducibility. ONEST data and curves were generated from 100 random permutations of the participants. ONEST suggested a minimum of 4 observers for the reliable evaluation of reproducibility for both the scored components and grade in either type of specimen. Our results suggested moderate or moderate to good reproducibility of grading (kappa values of 0.51 for excisions, and 0.54 for biopsies and ICCs of 0.70 and 0.69, respectively) with gland formation being the most and nuclear pleomorphism the worst consistently evaluated feature. In studies with sufficient participants (at least 4) and non-pairwise comparisons in the analysis, the reproducibility of histological grading is fair to moderate, whereas studies with fewer participants or pairwise kappa analysis suggest moderate to almost prefect agreement of the results. ONEST is a valuable complementation of reproducibility analyses.

The reproducibility of assessing potential biomarkers is crucial for their implementation. ONEST (Observers Needed to Evaluate Subjective Tests) has been recently introduced as a new additive evaluation method for the assessment of reliability, by demonstrating how the number of observers impact on interobserver agreement. Oestrogen receptor (ER), progesterone receptor (PR), and Ki67 proliferation marker immunohistochemical stainings were assessed on 50 core needle biopsy and 50 excision samples from breast cancers by 9 pathologists according to daily practice. ER and PR statuses based on the percentages of stained nuclei were the most consistently assessed parameters (intraclass correlation coefficients, ICC 0.918–0.996), whereas Ki67 with 5 different theoretical or St Gallen Consensus Conference–proposed cut-off values demonstrated moderate to good reproducibility (ICC: 0.625–0.760). ONEST highlighted that consistent tests like ER and PR assessment needed only 2 or 3 observers for optimal evaluation of reproducibility, and the width between plots of the best and worst overall percent agreement values for 100 randomly selected permutations of observers was narrow. In contrast, with less consistently evaluated tests of Ki67 categorization, ONEST suggested at least 5 observers required for more trustful assessment of reliability, and the bandwidth of the best and worst plots was wider (up to 34% difference between two observers). ONEST has additional value to traditional calculations of the interobserver agreement by not only highlighting the number of observers needed to trustfully evaluate reproducibility but also by highlighting the rate of agreement with an increasing number of observers and disagreement between the better and worse ratings.

Bevezetés: Hohenberger 2009-ben a totális mezorectális excízió (TME) elvét átültette a kolonsebészetbe, és az új műtétet komplett mezokólikus excíziónak nevezte el (CME). A CME lényege az érintett kolonszakasz eltávolítása a viszcerális peritoneum sérülése nélkül az ellátó erek centrális lekötésével a viszcerális és parietális fascia közötti embrionális rétegben preparálva. Ez nyitottan és laparoszkóppal is végezhető. Célkitűzés: Válogatás nélküli beteganyagon meggyőződni arról, hogy elvégezhető-e a CME laparoszkóppal hasonló eredménnyel, mint nyílt műtét során. Eredmények: 2016. 09. 01. és 2019. 06. 30. között 156 műtét történt jobb oldali malignus vastagbéldaganat miatt. 143 esetben végeztünk kuratív reszekciót, 63 férfi és 80 nőbetegnél. Az átlagéletkor férfi aknál 71,5 évnek, míg nőknél 73 évnek bizonyult. 84 műtétet laparoszkóppal, 59 műtétet nyitottan végeztünk. Konvencionális műtét 56 esetben, míg CME 87 esetben történt. Az átlagos kolonhossz konvencionális műtétnél 22,34 cm, míg CME esetén 24,97 cm volt (p = 0,18). A nyirokcsomók átlagos száma a hagyományos műtétnél 15,4, míg CME esetén 16,9 volt (p = 0,24). Az átlagos műtéti idő nyitott műtétnél 111, míg laparoszkópos műtétnél 136 perc volt (p = 0,0014), az átlagos ápolási idő pedig a szövődményes esetek nélkül a nyitott csoportban 7,47, míg a laparoszkópos csoportban 5,65 napnak bizonyult (p = 0,0004). Megbeszélés: A korai eredmények alapján az mondható, hogy laparoszkóppal is elvégezhető a műtét hasonló eredményekkel, valamivel rövidebb ápolási idővel.

Introduction: In 2009, Hohenberger translated the concept of total mesorectal excision to colon cancer surgery and he named it complete mesocolic excision (CME). The principle of CME is based on wide mesenteric excision in the embriologic plane to remove mesenteric lymph nodes, central vascular ligation without damage of the peritoneal layer. CME can be performed by laparoscopic and open methods. Aim: To make sure that we are capable of performing right laparoscopic hemicolectomy with similar results to the open method. Results: A cohort of 156 consecutive patients were operated on with malignant right-sided colon tumours from 01.09.2016 to 30.06.2019. 143 curative resections were performed in 63 men and 80 women. The average age of men and women were 71.5 and 72.75 years, respectively. 84 laparoscopic and 59 open operations were performed. 84 patients underwent CME surgery and 56 conventional resections. The average length of the specimen was 22.34 cm in the conventional and 24.97 cm in CME surgery (p = 0.18) and the average lymph node number were 15.4 and 16.9, respectively (p = 0.24). The average duration of the operation was 111 minutes for the conventional and 136 minutes for the CME group (p = 0.0014), while the average length of stay were 7.47 days and 5.65 days (p = 0.0004) respectively for the cases without complications. Conclusion: We are yet in the learning period, but based on the early results, it might be concluded that the operation can be performed by laparoscopic methods as well with similar results to the open operation but with shorter length of stay.

A prognostic index (Petersen index, PI) was created for patients with pT3-4 pN0 M0 (Stage II, Dukes' B) colon cancers to distinguish between patients with better and worse outcome, and to help in recommending adjuvant chemotherapy for high risk patients in this stage. The prognostic value of the PI was evaluated in two independent retrospective series of stage II (Dukes' B) colon cancer patients. The parameters defining the PI (venous invasion, peritoneal involvement, circumferential margin involvement, perforation through the tumour) and performance of the PI were compared in two institutions. The two series of patients consisted of 127 and 87 patients. Venous invasion was more frequently detected at one of the centres (p<0.01) and tumour perforation was more frequent at the other (p<0.01). There were no significant differences in the 5-year survival estimates of all patients (p=0.19), and of either the low PI value groups (p=0.52) or that of the high PI value groups (p=0.99) between the two sites. In contrast, there were significant differences in the survival estimates between patients of the low PI category and those of the high PI category altogether (p<0.01) and in either centre. Although, it was expected that differences in the frequency of the parameters involved in the PI would influence its performance, this was not confirmed by the data. Our results suggest that using the PI may be of value in prognostic factor based therapy selection of colon carcinoma patients.

BACKGROUND:Sentinel lymph node biopsy (SLNB) is a standard procedure in women with breast cancer. The risk of morbidity related to axillary lymph node dissection (ALND) is similar for men and women with breast cancer and SLNB could minimize this risk.METHODS:Between January 2004 and August 2013, 25 men with primary breast cancer were operated on at the Bács-Kiskun County Teaching Hospital. These were reviewed retrospectively. SLNB was performed following lymphoscintigraphy with intraoperative gamma probe detection and blue dye mapping.RESULTS:SLNB was successful in all 16 male patients (100 %), in whom it was attempted. The SLNs were negative in 4 cases (25 %) and were involved in 12. Intraoperative imprint cytology was positive in 9 of the 12 involved cases (75 %) and resulted immediate completion ALND. In 7 patients, the intraoperative imprint cytology was negative, with 3 false-negative results that resulted in delayed completion ALND. After a median follow-up of 48 months, there was only one axillary recurrence after ALND and none in the SLNB group.CONCLUSIONS:SLNB is successful and accurate in male breast cancer patients too. Although compared to women a larger proportion of men have positive nodes, for men with negative nodes, ALND-related morbidity may be reduced by SLNB. We recommend SLNB in male patients with breast cancer and clinically negative axilla.

INTRODUCTIONGleason grading is the most common method of prostate cancer classification.AIMThe aim of the authors was to assess the reproducibility of Gleason grading among pathologists using the same needle biopsy samples.METHOD23 pathologists examined 37 prostate cancer biopsies stained with hematoxylin and eosin. Gleason scores were categorised into 4 groups (2-4, 5-6, 7 and 8-10). Kappa statistics were used to reflect interobserver agreement.RESULTSConsidering all participating pathologists, grouping into one of the 4 categories resulted in an overall kappa value of 0.49. For the individual categories, the worst agreement (kappa = 0.15) was seen with well differentiated carcinomas, and the best (kappa = 0.65) with poorly differentiated ones.CONCLUSIONSThese results suggest that Gleason grading in biopsy samples is moderately reproducible. The kappa values vary according to the differentiation of the cancer, and there is not much difference between the results of the present study and those published in the literature. To increase reproducibility, trainings should be organised, and this could improve the quality of grading.

Although axillary lymph node dissection (ALND) has been the standard intervention in breast cancer patients with sentinel lymph node (SLN) metastasis, only a small proportion of patients benefit from this operation, because most do not harbor additional metastases in the axilla. Several predictive tools have been constructed to identify patients with low risk of non-SLN metastasis who could be candidates for the omission of ALND. In the present work, predictive nomograms were used to predict a high (>50 %) risk of non-SLN metastasis in order to identify patients who would most probably benefit from further axillary treatment. Data of 1000 breast cancer patients with SLN metastasis and completion ALND from 5 institutions were tested in 4 nomograms. A subset of 313 patients with micrometastatic SLNs were also tested in 3 different nomograms devised for the micrometastatic population (the high risk cut-off being 20 %). Patients with a high predicted risk of non-SLN metastasis had higher rates of metastasis in the non-SLNs than patients with low predicted risk. The positive predictive values of the nomograms ranged from 44 % to 64 % with relevant inter-institutional variability. The nomograms for micrometastatic SLNs performed much better in identifying patients with low risk of non-SLN involvement than in high-risk-patients; for the latter, the positive predictive values ranged from 13 % to 20 %. The nomograms show inter-institutional differences in their predictive values and behave differently in different settings. They are worse in identifying high risk patients than low-risk ones, creating a need for new predictive models to identify high-risk patients.

Blood and lymphatic vessel invasion (BLVI) has been long recognised as a category I prognostic factor in colorectal carcinomas (CRC) along with the pT and pN categories of the Tumour-Node-Metastasis system, preoperative carcinoembryonal antigen levels and the residual tumour (R) classification.1 Small vessel involvement includes the invasion of capillary-type vessels (figure 1A), where a reliable distinction between lymphatic and blood capillaries cannot be made on H&E-stained or general endothelial marker (eg, CD31, CD34) immunostained sections. Theoretically, the two types of capillary invasion lead to different consequences: lymphatic vessel invasion (LI) precedes and may be predictive of lymph node metastasis, whereas blood capillaries may be the source of systemic dissemination.2–4 The development of lymphatic endothelial markers like podoplanin (D2-40) or lymphatic endothelial hyaluronan receptor (LYVE-1) enables a distinction between lymphatic and blood capillaries: lymphatics can be defined as D2-40, LYVE-1, CD31 and CD34 positive capillaries, whereas blood capillaries are D2-40 and LYVE-1 negative but can be highlighted by CD31 or CD34 antibodies.4–7 Without such a distinction, small vessel invasion is best recorded as (lympho-)vascular invasion (LVI) or angiolymphatic invasion.1 The impact of LI or LVI is mainly seen in patients with conservative removal (eg, polypectomy) of invasive carcinomas without a resection allowing the histopathologic assessment of the lymph nodes. Figure 1 Types of vessel invasion in colorectal carcinomas. (A) Small vessel (ie, capillary) invasion corresponding to (lympho-)vascular invasion. (B and C) Venous invasion (VI) stained by orcein and elastica van Gieson, respectively. Right to the vein invaded by carcinoma is an accompanying artery, which helps the recognition of VI. (D) Invasion of an artery. ((A) CD34 ×400, (B) Orcein ×100, (C) Elastica van Gieson ×100, (D) Orcein ×100). This figure is only reproduced in colour in the online version. By contrast, large vessel invasion includes venous invasion (VI) …

AIMS:To assess the reliability of nodal staging in colorectal carcinomas (CRCs) when only lymph nodes close to the tumour are recovered and examined histologically.METHODS:Lymph nodes from CRC resection specimens were recovered into two fractions: one from around the tumour and the 3 cm sidelong bowel segment associated with it in the proximal and distal directions, and another from the remaining part of the resection specimen.RESULTS:Of the 762 CRCs (239 right colon, 251 left colon, 257 rectum, 15 unspecified localisation) there were 393 node-negative and 369 node-positive cases. The median number of LNs examined was 18. The assessment of the LNs located in the close fraction (median 13) yielded an adequate qualitative nodal status in 756 patients (99.2%). In four cases (two rectal and two right colic), no LN metastases could be identified in the close-fraction lymph nodes, but nodes from the distant fraction contained metastases. Of the node-positive carcinomas which had at least one positive lymph node in the close fraction, 203 belonged to the pN1 category and 162 to the pN2 category of the Tumour Node Metastasis staging system. Only 14 cases (10 rectal, two right and two left colic tumours) were misclassified as pN1 (on the basis of lymph nodes recovered from the close fraction) although they were of the pN2 category.CONCLUSIONS:In general, nodal status of CRCs may be adequately assessed by examining the lymph nodes from the close fraction around the tumour and the 3 cm sidelong bowel segment in both directions.

AimsTo assess venous invasion (VI) and its relation to distant metastases in colorectal cancer (CRC).MethodsPrimary untreated CRC cases were assessed for VI. All tumour blocks were stained with H&E and orcein. The presence of VI and nodal status were then correlated with the presence of synchronous or metachronous distant metastases.ResultsVI was detected more frequently with the orcein stain (18% versus 71%). Eleven tumours (nine node-positive tumours, all VI positive) were associated with synchronous distant metastasis. During a median follow-up of 17 months nine further cases were diagnosed with distant metastasis (six node-positive tumours, all VI positive). The specificity and sensitivity of the presence of nodal metastasis for predicting distant metastasis were 0.56 and 0.75, respectively. The same values for orcein-detected VI were 0.39 and 1, respectively.ConclusionsElastic stains such as the orcein stain enable the detection of clinically relevant VI with greater frequency than conventionally stained histological slides. If nodal involvement is an indication for systemic chemotherapy, the data presented here suggest that VI detected by the orcein stain should also be an indication for systemic chemotherapy.

Colorectal carcinomas (CRCs) infiltrating through the muscularis propria layer without infiltration of adjacent structures, organs or the serosa-i.e. the pT3 tumors, compose the largest subset of large intestinal carcinomas treated by surgical resection. They are heterogeneous in terms of prognosis. CRCs treated by surgery in a period of 69 months were prospectively classified as pT3a tumors (invading to a maximum of 5 mm beyond the muscularis propria) and pT3b tumors (invading deeper). Their nodal status, incidence of vascular invasion and the presence or absence of distant metastases were analyzed in relation to the depth of invasion. Of the 593 CRCs primarily treated by surgery 429 were pT3 tumors. CRCs categorized as pT3a had significantly lower rates of nodal involvement (44% vs 75%), massive nodal involvement (pN2) (9% vs 39%), venous invasion (17% vs 30%) and distant metastasis (11% vs 28%) than pT3b tumors. Significant differences in these prognostic variables in pT3a and pT3b cancers were observed both for carcinomas of the colon and those of the rectum. Such differences were not obvious in further 66 ypT3 cases of rectal carcinoma receiving neoadjuvant treatment before surgery. Tumors in the pT3a category are associated with a better prognostic profile than pT3b tumors. This subdivision might be useful in both prognostication and treatment planning.

Breast cancer in the young is considered a special clinical presentation of the disease. Sixty-nine breast cancer cases diagnosed at or before the age of 35 were analyzed for common morphological and immunophenotypical features of basal-like carcinomas. Sixteen carcinomas displayed the immunophenotypical characteristics (estrogen receptor and HER2 negativity and positivity for at least one of the following basal markers: cytokeratin 5 or 14, epidermal growth factor receptor, p63) of basal-like carcinomas, and most of them demonstrated characteristic histological features (pushing borders, lymphocytic peritumoral infiltrate, central hypocellular zone or necrosis, high mitotic rate) too. These tumors were more likely to be high-molecular-weight cytokeratin: 34betaE12 and p53 positive by immunohistochemistry. The presence of a basal-like phenotype can be important as concerns systemic treatment issues and could theoretically be associated with a higher rate of BRCA1 mutations in the young, because of the overlap of BRCA1 mutation associated breast carcinomas and the basal-like phenotype.

Granular cell tumor is generally benign, but rare malignant cases have been documented. Features of malignancy include necrosis, cellular spindling, vesicular nuclei with large nucleoli, increased mitotic activity, high nuclear to cytoplasmic ratio, and pleomorphism, but not vascular invasion. Venous invasion was incidentally identified with the orcein elastic stain in an otherwise benign granular cell tumor (propositus case). Four further benign granular cell tumors were also analyzed; venous invasion was discovered in three. It is suggested that vascular invasion is not uncommon in granular cell tumors and should not lead to the classification of the tumor as malignant or atypical. It is likely that in most cases there is only invasion of the vascular wall. It is also suggested that some cases of vascular invasion identified by elastic stains in tumors such as colorectal carcinomas (where these stains are recommended for routine use) may also represent invasion of vascular structures without the propensity of metastasis.