bromochloroacetic-acid and Carcinoma--Ductal

The distinction between classic lobular and ductal carcinoma, both in situ and invasive, has important therapeutic and management implications. Most ductal and lobular carcinomas are distinguished readily on hematoxylin-eosin-stained sections because of distinct histomorphologic features. In cases with ambiguous morphologic features, however, categorization in one or another type can be a challenge. Several immunohistochemical markers, including epithelial cadherin, p120, β-catenin, and low-molecular-weight and high-molecular-weight cytokeratins among others, have been introduced to help better discriminate between lobular neoplasia and ductal carcinoma. In this critical review of the literature, we comment about the usefulness and the limitations of these markers to improve the accuracy in the differential diagnosis of breast pathology.

Topics: beta Catenin; Biomarkers, Tumor; Breast Neoplasms; Cadherins; Carcinoma, Ductal; Carcinoma, Lobular; Diagnosis, Differential; Female; Humans; Immunohistochemistry; Keratins; Sensitivity and Specificity; Transcription Factors

We encountered primary ductal adenocarcinoma of the lacrimal gland in a 67-year-old Japanese man. To the best of our knowledge, only three cases of primary ductal adenocarcinoma of the lacrimal gland have been reported in the literature. The patient was admitted because of visual disturbance, and a mass measuring about 3 cm in diameter was revealed in the right orbit. The mass was resected, and primary ductal adenocarcinoma of the lacrimal gland was diagnosed histopathologically. He died from recurrence at the primary site and metastasis to the brain, lungs, liver, common bile duct, and pancreas 2 years and 10 months after surgery although adjunctive orbital radiotherapy was given. Immunohistochemically, the characteristics of cancer cells were similar to those of salivary duct carcinoma, namely positivity for cytokeratin (CK) 7, 10, 17, 18, 19, and 34betaE12, and negativity for CK20. It was not clear whether the ductal adenocarcinoma originated from the ductal or acinar epithelium of the lacrimal gland, because the immunohistochemical features of both epithelia were identical.

Topics: Aged; Carcinoma, Ductal; Eye Neoplasms; Fatal Outcome; Humans; Immunohistochemistry; Keratins; Lacrimal Apparatus Diseases; Male; Neoplasm Recurrence, Local; Radiotherapy, Adjuvant

Feline mammary tumors are usually malignant and aggressive carcinomas. Most cases are simple monophasic carcinomas (1 epithelial population), and additional phenotyping is usually not needed. In this study, we describe 10 malignant mammary tumors from 9 female cats that had unusual histomorphology: they appeared biphasic, with 2 distinct cell populations. Initially, they were morphologically diagnosed as either carcinosarcoma (1/10) or malignant pleomorphic tumor (9/10) of the mammary gland, as the latter did not match any previously described histological subtype. Immunohistochemistry (IHC) was performed for pancytokeratin, cytokeratins 8 and 18, cytokeratin 14, cytokeratins 5 and 6, vimentin, p63, calponin, alpha-smooth muscle actin, Ki-67, ERBB2, estrogen receptor alpha, and progesterone receptor. In 7 of 10 cases, the biphasic nature was confirmed and, on the basis of the IHC results, they were classified as carcinoma and malignant myoepithelioma (4/10), ductal carcinoma (1/10), and carcinosarcoma (2/10). The other 3 of 10 cases were monophasic based on IHC. In the cases of carcinoma and malignant myoepithelioma, the malignant myoepithelial cells were 100% positive for vimentin (4/4) and variably positive for p63, calponin, and cytokeratins (4/4). These findings show that, although rare, biphasic mammary carcinomas do occur in cats. In dogs and humans, tumors composed of malignant epithelial and myoepithelial cells have a less aggressive behavior than certain simple carcinomas, and therefore, their identification might also be clinically significant in the cat.

Topics: Animals; Biomarkers, Tumor; Calcium-Binding Proteins; Calponins; Carcinoma; Carcinoma, Ductal; Carcinosarcoma; Cat Diseases; Cats; Dogs; Female; Immunohistochemistry; Keratins; Mammary Neoplasms, Animal; Microfilament Proteins; Myoepithelioma; Sarcoma; Vimentin

Anal duct carcinoma is an uncommon malignancy of the glands of the anal duct. This entity poses a diagnostic challenge, both clinically and histologically. This article describes histopathologic findings in a case of anal duct carcinoma, including the initial diagnosis on biopsy and subsequent cytology specimens. Additionally, differential diagnoses of this neoplasm are discussed. With a high index of suspicion, and attention to histological and immunohistochemical features, anal duct carcinoma can be accurately diagnosed both on biopsy and on cytology.

Topics: Abdominal Pain; Anus Neoplasms; Ascites; Biopsy; Carcinoma, Ductal; Constipation; Cytodiagnosis; Diagnosis, Differential; Female; Hospice Care; Humans; Keratins; Middle Aged; Paracentesis; Peritoneal Neoplasms

This study aimed to identify modules associated with breast cancer (BC) development by constructing a gene co-expression network, and mining hub genes that may serve as markers of invasive breast cancer (IBC).We downloaded 2 gene expression datasets from the Gene Expression Omnibus (GEO) database, and used weighted gene co-expression network analysis (WGCNA) to dynamically study the changes of co-expression genes in normal breast tissues, ductal carcinoma in situ (DCIS) tissues, and IBC tissues. Modules that highly correlated with BC development were carried out functional enrichment analysis for annotation, visualization, and integration discovery. The hub genes detected by WGCNA were also confirmed using the Oncomine dataset.We detected 17 transcriptional modules in total and 4 - namely tan, greenyellow, turquoise, and brown - were highly correlated with BC development. The functions of these 4 modules mainly concerned cell migration (tan module, P = 3.03 × 10), the cell cycle (greenyellow module, P = 3.08 × 10), cell-cell adhesion (turquoise module, P = .002), and the extracellular exosome (brown module, P = 1.38 × 10). WGCNA also mined the hub genes, which were highly correlated with the genes in the same module and with BC development. The Oncomine database confirmed that the expressions levels of 6 hub genes were significantly higher in BC tissues than in normal tissues, with fold changes larger than 2 (all P < .05). Apart from the 2 well-known genes EPCAM and MELK, during the development of BC, KRT8, KRT19, KPNA2, and ECT2 also play key roles, and may be used as new targets for the detection or treatment of BC.In summary, our study demonstrated that hub genes such as EPCAM and MELK are highly correlated with breast cancer development. However, KRT8, KRT19, KPNA2, and ECT2 may also have potential as diagnostic and prognostic biomarkers of IBC.

Topics: alpha Karyopherins; Biomarkers, Tumor; Breast Neoplasms; Carcinoma, Ductal; Cell Adhesion; Cell Cycle; Cell Movement; Epithelial Cell Adhesion Molecule; Exosomes; Gene Expression Profiling; Gene Regulatory Networks; Humans; Keratins; Oligonucleotide Array Sequence Analysis; Protein Serine-Threonine Kinases; Proto-Oncogene Proteins

Terminal duct lobular unit (TDLU) is widely accepted as the origin of ductal carcinoma in situ of breast. The differentiation states of myoepithelial cells of breast ductal system hint the development of breast hyperplastic lesions. Basal cytokeratin (CK) phenotypes indicate the differentiation of myoepithelial cells. Using antibodies of CK5/6, CK14, and CK17, this study reports the basal CK phenotypes of myoepithelial cells in 20 foci of normal breast, 20 usual ductal hyperplasias, 36 ductal carcinomas in situ (DCIS), and 28 sclerosing adenosis (SA). The results showed that the positive staining of basal CKs of myoepithelial cells in normal ducts were significantly higher than those in normal lobules. The basal CK expression of myoepithelial cells of DCIS and usual ductal hyperplasia was similar to that of normal duct, whereas that of SA was similar to that of normal lobule. We propose a modified model of TDLU origin of intraductal carcinoma that most of DCIS originate from terminal ducts of TDLU, whereas most SA originate from lobules.

Topics: Actins; Adult; Breast Neoplasms; Calcium-Binding Proteins; Calponins; Carcinoma, Ductal; Carcinoma, Intraductal, Noninfiltrating; Female; Humans; Immunohistochemistry; Keratins; Microfilament Proteins; Middle Aged; Transcription Factors; Tumor Suppressor Proteins

Parotid gland carcinomas are rare. Among them, the epithelial-myoepithelial carcinoma (EMC) is extremely rarely diagnosed. This case report was based on a female with a history of 17 years of recurrent EMC of the parotid and evidence of distant metastasis over a period of 2 years. During debulking procedures of her extensive facial tumour, small tumour samples were transplanted to nude mice. The tumours grew well on the mice and were characterized morphologically and immunohistochemically after explantation. Cellularity per mm(2) ranged between 3,470 and 7,410. The tumours were characterized by the typical bipolar pattern of tumour cells and broad stromal septae. All but one of 7 transplanted tumours were positive for pan-cytokeratin marker KL-1. The proliferation index in terms of MIB-1-stained nuclei increased from 2% to 20% and was correlated positively to the expression of EGFR. IGF-1R-, VEGF- and FLK1-stained cells were found in all cases. The increase in EGFR- and MIB-1-positive cells correlated with the clinical course of the patient, who showed shorter periods of tumour recurrence prior to her death. These findings in EMC transplanted to the nude mouse demonstrate the feasibility of growing EMC in vivo.

Topics: Animals; Biomarkers, Tumor; Carcinoma, Ductal; Epithelium; ErbB Receptors; Immunohistochemistry; Keratin-8; Keratins; Ki-67 Antigen; Mice; Mice, Nude; Neoplasm Transplantation; Neoplasms, Glandular and Epithelial; Receptors, Growth Factor; Salivary Gland Neoplasms; Tomography, X-Ray Computed

A very rare case of intraductal oncocytic papillary carcinoma of the liver is reported. A 63-year-old Japanese man was admitted to our clinic because of abdominal pain and jaundice. Imaging techniques revealed a unilocular cystic neoplasm of 14 cm diameter in the medial segment of the left hepatic lobe. Combined percutaneous and endoscopic retrograde cholangiographies revealed the unilocular cystic neoplasm contained a lot of mucus and communicated with the left segmental intrahepatic bile duct, and that mucus filled the left segmental and hepatic ducts. Left lobectomy was performed. The postoperative course was good, and the patient is free of disease 30 months after operation. Pathological examination revealed that the cavity of the neoplasm was continuous with the left segmental intrahepatic bile duct, and that a lot of mucus was present in the neoplasm, as well as in the left segmental and hepatic ducts. The neoplasm consisted of papillary growth of atypical epithelial cells with oncocytic changes. Atypical goblet cells were also recognized. No invasion into the surrounding liver was noted. Non-tumorous intrahepatic bile ducts near the lesion occasionally showed epithelial dysplasia and contained a lot of mucus. Immunohistochemically, the tumor cells were rich in mitochondria and were immunoreactive for cytokeratins 7, 18 and 19, carbohydrate antigen 19-9, and hepatocyte-specific antigen. Some tumor cells were immunoreactive for pancreatic alpha-amylase and lipase. Ultrastructurally, the tumor cells showed numerous mitochondria and mucus droplets. Intraductal neoplasm communicating with the intrahepatic bile ducts has rarely been reported. The present case suggests that intraductal oncocytic papillary neoplasm, as described in the pancreas, may also occur in the intrahepatic bile ducts, and that such hepatic intraductal neoplasm may express hepatocellular and pancreatic acinar phenotypes.

Topics: Adenoma, Oxyphilic; Bile Ducts, Intrahepatic; Biomarkers, Tumor; Carcinoma, Ductal; Carcinoma, Papillary; Humans; Keratins; Liver Neoplasms; Male; Middle Aged; Mitochondria; Radiography

Cytokeratins (CKs) have been recognized for >20 years as structural marker proteins specific for epithelial cells. Recent expression profiling analyses indicate, however, that CK down-regulation may occur in breast cancer.. Here we evaluated the expression pattern of CK18 by immunohistochemical analysis of primary breast carcinomas (n = 1458) spotted on a high-density tissue microarray. The findings were correlated to histopathological risk factors and clinical outcome.. Down-regulation of CK18 (as compared to normal breast tissue) was observed in 25.4% of the tumors with a lower rate in lobular carcinomas (17.0%) than in ductal carcinomas (25.4%) or other histological entities (32.5%). CK down-regulation was significantly correlated to advanced tumor stage and high grade but not to axillary lymph node status. Kaplan-Meier survival analysis revealed CK18 as a prognostic indicator of overall survival (P = 0.015) and cancer-specific survival (P = 0.005).. Down-regulation of the luminal CK18 is not rare and a clinically relevant event in breast cancer. This finding has important implications for the use of CK18 as epithelial tumor marker. The correlations with clinical follow-up suggest that CK18 might suppress tumor progression.

Topics: Aged; Biomarkers, Tumor; Breast Neoplasms; Carcinoma; Carcinoma, Ductal; Carcinoma, Lobular; Disease Progression; Down-Regulation; Humans; Immunohistochemistry; Keratins; Lymphatic Metastasis; Middle Aged; Prognosis; Protein Array Analysis; Risk Factors; Time Factors

Topics: Biomarkers, Tumor; Breast Neoplasms; Carcinoma, Ductal; Cell Nucleus; Cytological Techniques; Data Interpretation, Statistical; Demography; DNA; Female; Flow Cytometry; Humans; Keratins; Ploidies; Predictive Value of Tests; Prognosis; Prospective Studies; Reproducibility of Results; Sample Size

Tubulolobular carcinoma (TLC) is a rare subtype of mammary carcinoma that has eluded precise classification, exhibiting features of both ductal and lobular differentiation. The clinicopathologic features of 27 cases of TLC were analyzed by both hematoxylin and eosin and immunohistochemical stains for E-cadherin and 34betaE12 (high molecular weight cytokeratin). Five cases of both pure tubular and classic lobular carcinoma were included as controls. Patients with TLC ranged in age from 43 to 79 years (median, 60 years). Tumor characteristics were as follows: size, 0.5 cm to 2.5 cm (median, 1.4 cm); bilaterality, 1 of 27 (4%); and multifocality, 5 of 27 (19%). Twenty-two of the 27 cases (81%) contained an in situ component: 8 (36%) lobular (LIN); 4 (18%) ductal (DIN); and 10 (46%) mixed. All 27 cases were intensely positive (3+) for E-cadherin, a feature of ductal differentiation, while 25 of 27 (93%) cases showed variable positivity for 34betaE12 (1 to 3+), a feature far more common in tumors with lobular differentiation. Clinical follow-up was available on 25 of 27 (93%) patients. Three of 24 (13%) patients developed axillary lymph node metastases and 1 of 25 (4%) patients developed a local recurrence over a follow-up period of 2 to 91 months (median, 39 months). In conclusion, TLCs are a distinct subtype of mammary carcinoma with overlapping morphologic features that are mirrored by a hybrid immunohistochemical profile. The uniform 3+ expression of E-cadherin in TLC supports the ductal differentiation of these tumors, despite a dominant lobular growth pattern. The prognosis of these tumors appears to be excellent, especially in those cases that are unilateral and less than 2 cm in size.

Topics: Adult; Aged; Biomarkers, Tumor; Breast Neoplasms; Cadherins; Carcinoma, Ductal; Carcinoma, Lobular; Female; Humans; Immunohistochemistry; Keratins; Lymphatic Metastasis; Middle Aged; Neoplasm Recurrence, Local; Prognosis

Carcinoma with osteoclast-like giant cells (OCGC) is an uncommon neoplasm characterized by giant cells, prominent vascularization, haemorrhage and areas of cribriform epithelial growth with moderate atypia. Multinucleated giant cells (MGC) have been described in several other breast lesions raising an interesting differential diagnosis, mainly with benign disorders. Due to its rarity few cases have been described cytologically. We retrospectively reviewed 13 fine needle aspiration samples from nine patients with this variant of carcinoma. Nine corresponded to breast tumours and four to axillary, liver, subcutaneous and mediastinal metastatic lesions. The expression of CD68 by giant cells was evaluated immunocytochemically in six cases. All patients had a complete pathological study of the breast neoplasm. Smears showed a double component of epithelial and giant cells. Epithelial clusters were predominantly of intermediate size with irregular contours. Most were cohesive but others showed cellular dissociation with scarce to moderate cellular pleomorphism. Giant cells had well defined, deeply stained cytoplasm and round to elongated morphology. Two metastatic cases were devoid of them. Haemosiderin-laden macrophages were common in smears from breast tumours. In the six cases tested CD68 was expressed in MGC. Cytological features of mammary carcinoma with OCGC correlate closely with the histological ones. Most cases are clearly recognizable as malignant but in others cytological atypia may be minimal, mimicking a benign lesion. In difficult cases the presence of haemosiderin-laden macrophages and the histiocytic nature of the MGC are helpful diagnostic features.

Topics: Adult; Aged; Aged, 80 and over; Antigens, CD; Antigens, CD34; Antigens, Differentiation, Myelomonocytic; Biopsy, Fine-Needle; Breast Neoplasms; Carcinoma, Ductal; Carcinoma, Lobular; Cytodiagnosis; Female; Giant Cells; Hemosiderin; Humans; Keratins; Macrophages; Middle Aged; Osteoclasts; Retrospective Studies

A case of salivary duct carcinoma arising in the submandibular region of an 83-year-old man is presented. Histologically, the tumour consisted of solid cell nests with ductal structures. Tumour cell nests showed central comedonecrosis. Immunohistochemically, the tumour cells were positive for keratin and epithelial membrane antigen but negative for S-100 protein and calponin. Clinical features as well as pathological examinations based on haematoxylin-eosin and immunohistochemical stainings were important in the diagnosis of this case.

Topics: Aged; Aged, 80 and over; Apolipoproteins; Apolipoproteins D; Carcinoma, Ductal; Carrier Proteins; Glycoproteins; Humans; Keratins; Male; Membrane Transport Proteins; Mucin-1; Neoplasm Proteins; Salivary Ducts; Submandibular Gland Neoplasms

Our previous studies detected focal disruptions in myoepithelial cell layers of several ducts with carcinoma in situ. The cell cluster overlying each of the myoepithelial disruptions showed a marked reduction in or a total loss of immunoreactivity for the estrogen receptor (ER). This is in contrast to the adjacent cells within the same duct, which were strongly immunoreactive for the ER. The current study attempts to confirm and expand previous observations on a larger scale.. Paraffin sections from 220 patients with ER-positive intraductal breast tumors were double immunostained with the same protocol previously used. Cross-sections of ducts lined by > or = 40 epithelial cells were examined for myoepithelial cell layer disruptions and for ER expression. In five selected cases, ER-negative cells overlying the disrupted myoepithelial cell layer and adjacent ER-positive cells within the same duct were separately microdissected and assessed for loss of heterozygosity and microsatellite instability.. Of the 220 cases with 5698 duct cross-sections examined, 94 showed disrupted myoepithelial cell layers with 405 focal disruptions. Of the 94 cases, 79 (84%) contained only ER-negative cell clusters, nine (9.6%) contained both ER-negative and ER-positive cell clusters, and six (6.4%) contained only ER-positive cell clusters overlying disrupted myoepithelial cell layers. Of the 405 disruptions, 350 (86.4%) were overlain by ER-negative cell clusters and 55 (13.6%) were overlain by ER-positive cell clusters (P < 0.01). Microdissected ER-negative and ER-positive cells within the same duct from all five selected cases displayed a different frequency or pattern of loss of heterozygosity and/or microsatellite instability at 10 of the 15 DNA markers.. Cells overlying focally disrupted myoepithelial layers and their adjacent counterparts within the same duct displayed different immunohistochemical and molecular features. These features potentially represent an early sign of the formation of a biologically more aggressive cell clone and the myoepithelial cell layer breakdown possibly associated with tumor progression or invasion.

Topics: Breast; Breast Neoplasms; Carcinoma in Situ; Carcinoma, Ductal; Collagen Type IV; Disease Progression; DNA Mutational Analysis; DNA, Neoplasm; Epithelial Cells; Female; Humans; Immunohistochemistry; Keratins; Laminin; Loss of Heterozygosity; Microsatellite Repeats; Muscle, Smooth; Neoplasm Invasiveness; Receptors, Estrogen