Az emlő in situ carcinomáinak/intraepithelialis neoplasiáinak legújabb patológiai vonatkozásai = Pathological aspects of in situ carcinoma/intraepithelial neoplasia of the breast

Az elmúlt évtizedekben az emlőpatológia mind klasszikus, mind modern, molekuláris patológiai értelemben óriási fejlődésen ment keresztül. Ismereteink gyarapodását az előbbi vonatkozásában a széles körű szűrővizsgálatok bevezetése, az utóbbi vonatkozásában a patológiában zajló molekuláris technikai „forradalom” segítette elő. Ez az állandóan gyarapodó tudás a fogalmaink, a régóta használt osztályozások és legfőképpen a szemléletünk változását eredményezte. A ductalis és lobularis in situ carcinomák, vagy a ma egyre inkább terjedő szóhasználattal intraepithelialis neoplasiák összefoglaló ismertetésével a patológiában jelenleg érvényes nézeteket és álláspontokat szeretném közreadni. | Dramatic development has happened in the field of classical and molecular breast pathology in the recent three decades. Introduction of systematic screening programs induced our increasing knowledge in the field of classical surgical pathology, while molecular technical revolution resulted in dramatic improvement of our understanding of molecular pathology of breast tumors and precursor lesions. This continuous increase of our knowledge results in the change of our concepts, classifications and approach. In this review, I would like to share the new and recently adapted views regarding intraepithelial neoplastic lesions of the breast

Expression of claudin-1, -3, -4, -5 and -7 proteins in low grade colorectal carcinoma of canines

The aim of the present study was to characterise the expression pattern of claudin-1, -3, -4, -5 and -7 tight junction proteins in canine normal colorectum and in the low-grade, tubulopapillary colorectal carcinoma in canines. Methods and results: The biopsy samples included 10 canine normal colorectal tissues and 20 canine low grade colorectal carcinomas (CLGCCs). The canine normal colorectal mucosa was negative for claudin-1. Claudin-1 was detected as a non-diffuse intense membrane labelling of neoplastic epithelial cells in low grade colorectal cancer in canines. Fifty five per cent of all tumours showed a weak cytoplasmic pattern of staining for claudin-1 protein. The normal colorectal mucosa showed diffuse punctate positivity for claudin-3. Claudin-3 was detected as an intense lateral membrane labelling of tumour cells in CLGCCs. Claudin-4 expression in surface and crypt epithelial cells of the intact colorectal mucosa in canines was punctate. Claudin-4 molecule was detected as a lateral membrane labelling of neoplastic cells in CLGCCs. The epithelium of the CLGCCs and the low grade colorectal carcinoma were negative for claudin-5. The surface and crypt epithlial cells of the canine normal colorectal mucosa showed a diffuse lateral membranous pattern of staining for claudin-7. Claudin-7 molecule was detected as an intense membrane labelling of neoplastic cells in CLGCCs. Seventy per cent of all tumours showed weak cytoplasmic positivity for claudin-7. Conclusion: Consequently, we hypothesize that claudin-1 plays a role in the progression of CLGCCs. Further functional studies are needed to clarify the biological role of the mislocalization of the claudin-1 molecule from cell membrane to the cytoplasm in CLGCCs. Lower claudin-4 expression suggests that reduced expression of claudin-4 molecule may lead to cellular disorientation, detachment and invasion of CLGCCs. Further functional studies are needed to clarify the biological role of overexpression and mislocalisation of claudin-7 in CLGCCs

Primary neuroendocrine tumor of the breast - report of 2 cases

BACKGROUND Primary neuroendocrine tumor of the breast is rare, although 20-30% of primary breast carcinomas show neuroendocrine differentiation to some degree. According to the 2012 WHO Classification of Tumours of the Breast the current classification recognizes 3 subgroups of breast tumors with neuroendocrine features: Neuroendocrine tumor, well-differentiated; Neuroendocrine tumor, poorly-differentiated; Invasive breast carcinoma with neuroendocrine differentiation. Due to the low prevalence of this disease our understanding of its development, prognosis and effective therapy is limited. Up to date there are approximately 125 cases reported in the English and non-English literature. Here we report two further cases. MATERIAL-METHODS Our first patient was 63 years old and presented with a 3 cm large mobile nodule in the upper outer quadrant of her right breast. After a complete clinicopathological work-up of imaging techniques and core needle biopsy with an initial diagnosis of invasive carcinoma of no special type (IBC NST), lumpectomy and sentinel node biopsy was recommended by the institutional tumor board. The second patient was 75 years old and presented with a 2 cm large mobile nodule in the upper outer quadrant of her left breast. Lumpectomy was performed based on fine needle aspiration cytology results that revealed the malignant proliferation. RESULTS Histological examination of the surgical specimens revealed neuroendocrine differentiation in approximately 90% of the tumor cells in both cases. Immunohistochemical studies and additional imaging studies disclosed the possibility of metastasis to the breast. DISCUSSION Neuroendocrine differentiation of breast tumors is a controversial issue and there are numerous questions in terms of histogenesis, diagnostics and clinical considerations. To establish the correct diagnosis, characteristic growth patterns and cytological and immunohistochemical features of neuroendocrine differentiation should be carefully evaluated

Claudin-7 protein differentiates canine cholangiocarcinoma from hepatocellular carcinoma

The aim of the present study was to characterise the expression pattern of claudin-7 tight junction protein in canine normal liver, hyperplastic and primary neoplastic lesions of the canine liver and whether this tight junction protein can help differentiate canine cholangiocarcinomas from canine hepatocellular carcinomas. Methods and results: Necropsy samples included 15 canine normal liver tissue samples, 10 hepatocellular nodular hyperplasias, 6 hepatocellular adenomas, 15 well-differentiated and 6 poorly differentiated hepatocellular carcinomas, 6 cholangiocellular hyperplasias, 10 cholangiocellular adenomas, 15 well-differentiated and 6 poorly differentiated cholangiocarcinomas, 6 normal extrahepatic bile ducts, 8 normal gall bladder tissue samples, and 5 cystic mucinous hyperplasias of the gall bladder. In all canine normal liver tissue samples the hepatocytes were negative for claudin-7 and the normal biliary epithelial cells showed intense basolateral membrane claudin-7 positivity. In all cholangiocellular hyperplasia samples and in all cholangiocellular adenoma samples the benign cholangiocytes showed intense basolateral membrane positivity for claudin-7. In all samples of the well-differentiated and poorly differentiated cholangiocarcinomas, the malignant neoplastic biliary epithelial cells showed intense basolateral membrane positivity for claudin-7. Neither the hyperplastic nodules of the liver cells nor the hepatocellular adenomas reacted with claudin-7. The well-differentiated and poorly differentiated hepatocellular cancers were negative for claudin-7. The epithelial cells of canine normal extrahepatic bile ducts, gall bladder and cystic mucinous hyperplasias of the gall bladder showed intense basolateral membrane positivity for claudin-7. Differences in the intensity of claudin-7 reaction were not apparent among different types of proliferative lesions of cholangiocytes or degrees of cellular differentiation of neoplastic biliary epithelial cells. Conclusion: Consequently, we hypothesize that claudin-7 is an excellent immunohistochemical marker of the cholangiocellular differentiation in canines and can be used to detect benign and malignant proliferative lesions of the canine biliary tract. It can also help to differentiate canine cholangiocarcinomas from hepatocellular carcinomas

Az emlőrák patológiai diagnosztikája, feldolgozása és kórszövettani leletezése. Szakmai útmutatás a III. Emlőrák Konszenzus Konferencia alapján

There have been relevant changes in the diagnosis and treatment of breast cancer to implement the updating of the 2010 recommendations made during the 2nd national consensus conference on the disease. Following a wide interdisciplinary consultation, the present recommendations have been finalized after their public discussion at the 3rd Hungarian Consensus Conference on Breast Cancer. The recommendations cover non-operative and intraoperative diagnostics, the work-up of operative specimens, the determination of prognostic and predictive markers and the content of the cytology and histology reports. Furthermore, it touches some special issues such as the current status of multigene molecular markers, the role of pathologists in clinical trials and prerequisites for their involvement, some relevant points about the future

Mikroszatellita-instabilitás előfordulása, intratumoralis heterogenitása, prognosztikus és prediktív potenciálja primer colorectalis carcinomák és párosított májáttéteik sebészi kezelését követően

Absztrakt Bevezetés: A vastagbéldaganatokra jellemző genetikai instabilitás megnyilvánulhat több úton: kromoszomális instabilitás, mikroszatellita-instabilitás, illetve „CpG-island methylator phenotype”. Ezek pontosabb karakterizálásával a rendelkezésre álló kezelések elviekben optimalizálhatók lehetnek. Célkitűzés: A szerzők a mikroszatellita-instabilitás előfordulását, heterogenitását, prognosztikus és prediktív potenciálját vizsgálták 122 primer colontumor szisztematikusan szelektált régióiban és 69 párosított májmetasztázisban. Módszer: Szöveti multiblokkok kialakítása után az MLH1, MSH2, MSH6 és PMS2 kifejeződését vizsgálták immunhisztokémiai módszerrel. Eredmények: A betegek 11,5%-a (14/122) rendelkezett mikroszatellita-instabil fenotípusú daganattal. A különböző tumorrégiók fehérjekifejeződésében nem volt jelentős különbség. A primer tumor–májmetasztázis párok esetében 20,2%-ban a kettő más mismatch repair státusba volt sorolható. A relapsusmentes és teljes túlélést tekintve a mismatch repair státus nem volt prognosztikus. Az 5-fluorouracil-, oxaliplatin-, irinotecan-, bevacizumab-, cetuximab-, panitumumabterápia hatékonyságát tekintve mismatch repair státus nem volt prediktív a progressziómentes és teljes túlélés adatai alapján. Következtetések: A prognosztikus faktorok pontosabb meghatározása nagyobb esetszámú, pontosan szelektált vizsgálat keretében hatékonyabbá teheti a kezelés megválasztását. Orv. Hetil., 2015, 156(36), 1460–1471

Morphological and pathological response in primary systemic therapy of patients with breast cancer and the prediction of disease free survival

AIM: To identify breast cancer subtypes likely to respond to primary systemic therapy (PST or neoadjuvant therapy) and to assess the accuracy of physical examination (PE) and breast ultrasonography (US) in evaluating and predicting residual size of breast carcinoma following PST. METHODS: 116 patients who received at least two cycles of PST between 1998 and 2009 were selected from a prospectively collected clinical database. Radiological assessment was done by mammography and US. Prior to PST, tumors were subclassified according to core biopsy (NCB) and/or fine-needle aspiration-based immunohistochemical profiles of NCB. Pathological response rates were assessed following the surgeries by using Chevallier classification. Tumor measurements by PE and US were obtained before and after PST. Different clinical measurements were compared with histological findings. Disease-free survival (DFS) was assessed. RESULTS: Pathological complete remission (pCR=Chevallier I/II) was observed in 25 patients (21.5%), 44% of whom had triple negative histology, 28% Her2 positive and 76% had high-grade tumor. Of 116 patients, 24 received taxane-based PST, 48 combined taxane + anthracycline treatment, 8 trastuzumab combinations, 21 anthracycline-based treatments, and 15 other treatments. In the taxane treated group, the pCR rate was 30%, in the taxane + anthracycline group 25%, in the anthracycline group 9.5%, and in trastuzumab group 37.5%. After PST, PE and US were both significantly associated with pathology (P<0.001 and P=0.004, respectively). Concerning OS, significant difference was observed between the Chevallier III and IV group (P=0.031) in favor of Chevallier III group. In the pCR group, fewer events were observed during the follow-up period. CONCLUSIONS: Our results show that even limited, routinely used immunohistochemical profiling of tumors can predict the likelihood of pCR to PST: patients with triple negative and Her2-positive cancers are more likely to achieve pCR to PST. Also, PE is better correlated with pathological findings than US