Ileal collision tumor associated with gastrointestinal bleeding: A case report and review of literature.

BACKGROUND: Collision tumors involving the small intestine, specifically the combination of a hamartomatous tumor and a lipoma, are extremely rare. To our knowledge, no previous case report has described a collision tumor composed of two benign tumors of different origins in the small intestine. CASE SUMMARY: Here, we present the case of an 82-year-old woman who presented with hemorrhagic shock and was found to have a mass measuring approximately 50 mm × 32 mm × 30 mm in the terminal ileum. Based on computed tomography scan findings, the mass was initially suspected to be a lipoma. A subsequent colonoscopy revealed a pedunculated submucosal elevation consisting of two distinct parts with a visible demarcation line. A biopsy of the upper portion suggested a juvenile polyp (JP). Owing to the patient's advanced age, multiple comorbidities, and poor surgical tolerance, a modified endoscopic submucosal dissection was performed. Histopathological examination of the excised mucosal mass revealed a lipoma at the base and a JP at the top, demonstrating evidence of rupture and associated bleeding. The patient's overall health remained satisfactory, with no recurrence of hematochezia during the six-month follow-up period. CONCLUSION: This case report provides new evidence for the understanding of gastrointestinal collision tumors, emphasizing their diverse clinical presentations and histopathological characteristics. It also offers diagnostic and therapeutic insights as well as an approach for managing benign collision tumors.

Integrating single-cell and spatial transcriptomes reveals COL4A1/2 facilitates the spatial organisation of stromal cells differentiation in breast phyllodes tumours.

BACKGROUND: Breast phyllodes tumours (PTs) are a unique type of fibroepithelial neoplasms with metastatic potential and recurrence tendency. However, the precise nature of heterogeneity in breast PTs remains poorly understood. This study aimed to elucidate the cell subpopulations composition and spatial structure and investigate diagnostic markers in the pathogenesis of PTs. METHODS: We applied single-cell RNA sequencing and spatial transcriptomes on tumours and adjacent normal tissues for integration analysis. Immunofluorescence experiments were conducted to verify the tissue distribution of cells. Tumour cells from patients with PTs were cultured to validate the function of genes. To validate the heterogeneity, the epithelial and stromal components of tumour tissues were separated using laser capture microdissection, and microproteomics data were obtained using data-independent acquisition mass spectrometry. The diagnostic value of genes was assessed using immunohistochemistry staining. RESULTS: Tumour stromal cells harboured seven subpopulations. Among them, a population of widely distributed cancer-associated fibroblast-like stroma cells exhibited strong communications with epithelial progenitors which underwent a mesenchymal transition. We identified two stromal subpopulations sharing epithelial progenitors and mesenchymal markers. They were inferred to further differentiate into transcriptionally active stromal subpopulations continuously expressing COL4A1/2. The binding of COL4A1/2 with ITGA1/B1 facilitated a growth pattern from the stroma towards the surrounding glands. Furthermore, we found consistent transcriptional changes between intratumoural heterogeneity and inter-patient heterogeneity by performing microproteomics studies on 30 samples from 11 PTs. The immunohistochemical assessment of 97 independent cohorts identified that COL4A1/2 and CSRP1 could aid in accurate diagnosis and grading. CONCLUSIONS: Our study demonstrates that COL4A1/2 shapes the spatial structure of stromal cell differentiation and has important clinical implications for accurate diagnosis of breast PTs.

Versican core protein aids in the diagnosis and grading of breast phyllodes tumor.

Phyllodes tumors (PTs) are biphasic fibroepithelial lesions that occur in the breast. Diagnosing and grading PTs remains a challenge in a small proportion of cases, due to the lack of reliable specific biomarkers. We screened a potential marker versican core protein (VCAN) through microproteomics analysis, validated its role for the grading of PTs by immunohistochemistry, and analyzed the correlation between VCAN expression and clinicopathological characteristics. Cytoplasmic immunoreactivity for VCAN was identified in all benign PT samples, among which 40 (93.0 %) showed VCAN-positive staining in ≥50 % of tumor cells. Eight (21.6 %) borderline PT samples showed VCAN-positive staining in ≥50 % of the cells with weak to moderate staining intensity, whereas 29 samples (78.4 %) showed VCAN-positive staining in <50 % of the cells. In malignant PTs, 16 (84.2 %) and three (15.8 %) samples showed VCAN-positive staining in <5 % and 5-25 % of stromal cells, respectively. Fibroadenomas showed a similar expression pattern to benign PTs. Fisher's exact test showed that the percentages of positive cells (P < .001) and staining intensities (P < .001) of tumor cells were significantly different between the five groups. VCAN positivity was associated with tumor categories (P < .0001) and CD34 expression (P < .0001). The expression of VCAN gradually decreases as the tumor categories increases, following recurrence. To the best of our knowledge, our results are the first in the literature to reveal that VCAN is useful for diagnosing and grading PTs. The expression level of VCAN appeared to be negatively associated with PT categories, suggesting that dysregulation of VCAN may be involved in the tumor progression of PTs.

Artemether ameliorates adriamycin induced cardiac atrophy in mice.

Adriamycin is a widely used and effective antitumor drug; however, its application is limited by various side effects, including irreversible cardiotoxicity. The central role of cardiac atrophy in Adriamycin­induced cardiotoxicity has been revealed; however, the underlying mechanism of this process remains unclear. Artemether is a well­known Chinese herbal medicine, and its pharmacological action is related to the regulation of mitochondrial function and redox status. The present study determined the effects of artemether on Adriamycin­induced cardiotoxicity and investigated the underlying mechanisms. After mouse model establishment and artemether intervention, experimental methods including pathological staining, immunohistochemistry, immunofluorescence, immunoblotting, ELISA and reverse transcription­quantitative PCR were used to evaluate the therapeutic effect. The results demonstrated that artemether prevented Adriamycin­induced cardiac atrophy and recovered the intercombination of connexin 43 and N­cadherin at the intercalated discs. Artemether also regulated the autophagy pathway and restored the unbalanced ratio of Bax and Bcl­2 in myocardial cells. In addition, the increased serum H2O2 levels after Adriamycin exposure were significantly decreased by artemether, and the mitochondrial alterations and redox imbalance in myocardial cells were also improved to varying degrees. In summary, the findings of the present study provide reliable evidence that artemether could ameliorate cardiac atrophy induced by Adriamycin. This therapeutic approach may be translated to the clinic for preventing drug­induced heart diseases.

Signet ring cell-like diffuse large B-cell lymphoma involving the breast: a case report.

BACKGROUND: Diffuse large B-cell lymphoma (DLBCL) with signet ring cell components is extremely rare. Here, we present a case of DLBCL with signet ring cell components involving the breast, which can be easily confused with invasive lobular carcinoma of the breast or metastatic signet ring cell carcinoma of gastrointestinal origin. CASE PRESENTATION: A 66-year-old woman presented with a painless mass in her left breast. Enhanced magnetic resonance imaging (MRI) of the breast revealed a 42 × 29 × 28 mm mass in the left breast. Histological examination revealed a diffuse or scattered arrangement of round cells mixed with signet ring-like cells. Immunohistochemically, the neoplastic cells were positive for PAX-5, CD79a, CD20, Bcl-6, and MUM-1 but and negative for cytokeratin, ER, PR, E-cadherin, and P120. The Ki-67 proliferation index was approximately 70%. Fluorescence in situ hybridisation (FISH) demonstrated non-rearrangement of Bcl-2, Bcl-6, and c-MYC genes. Immunohistochemistry and FISH examination confirmed the diagnosis of DLBCL. Subsequently, immunofluorescence showed both IgM and IgG deposits in the signet ring-like lymphocytes. After confirming the diagnosis, the patient received four courses of CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisolone) chemotherapy in a specialist hospital and achieved partial remission; however, she unfortunately died of secondary pneumocystis pneumonia infection 3 months later. CONCLUSION: Malignant lymphoma with signet ring cell morphology is quite uncommon, and this variant can be a diagnostic pitfall. We emphasise that pathologists should consider lymphoma in the differential diagnosis of malignant breast tumours.

Resection of an anal fistula with endoscopic submucosal dissection.

A 34-year-old man presented with paroxysmal hypogastralgia during defecation for 2 weeks. Physical and laboratory examination findings were unremarkable, other than a depression located 1 cm above the dentate line, accompanied by mild tenderness and a clubbed induration extending to the rectum. Colonoscopy showed a 2.0×0.8 cm longitudinal, protruding mass in the posterior wall of the lower rectum. Endosonography revealed a mixed echogenic mass originating from the rectal submucosa, with no sign of muscular wall disruption. There was no evidence of Crohn's or other diseases. Following anorectal consultation, we suspected a submucosal or internal blind fistula since the patient was symptomatic with a superficial mass which communicated to the rectum. The location and depth of the mass indicated that endoscopic resection might allow for removal of the lesion without impairment of the anorectal anatomy and function. After obtaining the patient's consent, endoscopic submucosal dissection (ESD) was performed. En bloc resection was achieved using a disposable, high-frequency knife (Micro-Tech, China). No adverse events occurred. Histopathological examination revealed a benign fistula composed of local submucous granulomatous tissue proliferation and a focal mucous epithelial defect. The patient's symptoms were relieved postoperatively, and no recurrence was evident after 6 months.

Artemether attenuates renal tubular injury by regulating iron metabolism in mice with streptozotocin-induced diabetes.

OBJECTIVES: Renal tubular injury plays an important role in the progression of diabetic kidney disease. Previous studies demonstrated that artemether, an antimalarial agent, exerts renal tubular protection in diabetes. However, the detailed mechanisms remain unclear. Several studies have indicated that disorders of iron metabolism have a great impact on renal tubular injury. Therefore, this study was performed to explore whether the therapeutic effects of artemether on diabetic renal tubular injury are related to iron metabolism. METHODS: Male C57BL/6 J mice were randomly divided into three groups. Mice in the type 1 diabetic (T1D) control and streptozotocin (STZ) groups were fed a regular diet; mice in the STZ plus artemether (STZ+Art) group were treated with artemether. RESULTS: Artemether significantly reduced the urinary albumin:creatinine ratio and tubular injury in mice with T1D. Artemether also restored the energy imbalance and restored the changes of mitochondrial cristae in mice with T1D. Increased protein and mRNA levels of ferritin heavy chain (FTH) and ferritin light chain (FTL) were observed in renal tubules of diabetic mice. In response to iron overload, levels of iron transport-related proteins and the antioxidant system related to iron metabolism were abnormal in diabetic mice. Artemether significantly restored the protein and mRNA expression levels of both FTH and FTL. Both the iron transport and antioxidant systems were also restored by artemether to varying degrees. CONCLUSIONS: Artemether attenuates renal tubular injury in diabetic mice; this effect might be related to its regulation of iron metabolism.

Morphological features of 52 cases of breast phyllodes tumours with local recurrence.

Typical phyllodes tumours (PTs) of the breast are fibroepithelial neoplasms characterised histologically by stromal hypercellularity and leaf-like structures. However, morphological changes may be atypical in some cases, increasing the difficulty of diagnosis and the likelihood of misdiagnosis. To provide more morphological clues for pathological diagnosis of PTs, we retrospectively analysed 52 PT cases with typical morphological features after recurrence, and summarized the clinicopathological characteristics of the paired primary tumours. We found five special histological features in the primary tumours distinct from classic PTs, namely (1) PTs with epithelioid feature (three cases); (2) PTs with gland-rich feature (eight cases); (3) PTs with fibroadenoma-like feature (20 cases); (4) PTs with myxoid fibroadenoma-like feature (five cases); and (5) PTs with pseudohemangiomatoid stromal hyperplasia-like feature (four cases). All the features can exist independently, and a few cases displayed more than two distinctive features at the same time. In this cohort of recurrent PTs, all the primary tumours were absent of recognisable stromal hypercellularity and leaf-like structures that are the critical diagnostic criteria of PTs; however, they showed some other non-classic characteristics which may provide significant clues for the diagnosis of PTs. Particularly, tumours with epithelioid feature displayed high grade at earlier stages, tumours with fibroadenoma-like feature were most likely to be confused with classical fibroadenomas, and tumours with myxoid feature were prone to be neglected because of their hypocellularity.

Etiology of granulomatous lobular mastitis based on metagenomic next-generation sequencing.

OBJECTIVES: We aimed to comprehensively explore the etiology of granulomatous lobular mastitis (GLM) to optimize treatment programs. METHODS: We collected 30 fresh mastitis samples for metagenomic next-generation sequencing, morphological observation, and analysis of the clinical information. RESULTS: Of the 30 samples, 25 were GLM; pathogens were detected in 17, these were: Corynebacterium kroppenstedtii (10 of 25, 40%); C. kroppenstedtii and Pseudomonas oleovorans (3 of 25, 12%); C. kroppenstedtii and human gammaherpesvirus 4 (1 of 25, 4%); Acinetobacter baumannii and C. kroppenstedtii (1 of 25, 4%); P. oleovorans (1 of 25, 4%); and Tepidiphilus thermophilus (1 of 25, 4%). Abnormal sex hormone levels (mainly prolactin) and/or autoimmune function were found in 12 of the 25 samples. Lipophilic antibiotics (rifampicin) were found to work effectively in patients with slow-healing wounds after surgery. CONCLUSIONS: The main pathogenic factor of GLM is C. kroppenstedtii infection, but other unusual pathogens (P. oleovorans, human gammaherpesvirus 4, A. baumannii, T. thermophilus) are likely to be closely related to GLM, particularly human gammaherpesvirus 4 (Epstein-Barr virus)-associated mastitis, which may be a new entity of mastitis. Abnormal levels of sex hormones and autoimmune function are also common causes. Therefore, lipophilic antibiotics (rifampicin) and prolactin inhibitors may be an effective treatment.

Pathogens in patients with granulomatous lobular mastitis.

OBJECTIVE: Granulomatous lobular mastitis (GLM) is a rare inflammatory disease of the breast that clinically mimics breast cancer. However, its etiology is not completely defined. The purpose of this study was to systematically study the bacteriology of GLM using advanced detection technology. METHODS: Paraffin-embedded tissue from patients with GLM was collected. DNA was extracted from the samples and analyzed using next-generation sequencing (NGS) technology, and the data were processed using bioinformatics analyses. RESULTS: A total of 40 patients were recruited into the study. A bioinformatics analysis revealed that a total of 17 genera or 19 species of pathogens were present in 39 of the GLM patients (97.5%). These included bacteria, fungi, and Mycobacterium tuberculosis complex group. Bacteria were found in 39 of the patient cases, while fungi were present in five. Only one case tested positive for M. tuberculosis complex. In addition, a single genus of pathogen was found in nine patients (23.1%), whereas 30 patients (76.9%) tested positive for multiple pathogens. CONCLUSIONS: This study profiled the microbiota of patients with GLM using NGS technology, which provides more useful information for establishing patient treatment plans.

Clinical and histopathological features of chronic hepatitis B virus infected patients with high HBV-DNA viral load and normal alanine aminotransferase level: A multicentre-based study in China.

BACKGROUND: The aim of this study is to reveal the clinical and histopathological features of HBsAg-positive and HBeAg-positive chronic hepatitis B infected patients with high level of HBV DNA, from 17 hospitals and medical centres in China, with alanine aminotransferase levels within the lower region of normal range versus those with levels within the upper region of normal range and to investigate the clinical risk factors for the requirement of treatment through the examination of liver biopsy. METHODS: Liver biopsy was performed on high level of HBV DNA of 455 patients with HBsAg-positive and HBeAg-positive chronic hepatitis B infection and persistently normal alanine aminotransferase level. Liver necroinflammation and fibrosis were graded per the Knodell histological activity index and Ishak's fibrosis score, respectively. Univariate analysis of the clinical parameters versus necroinflammation and fibrosis was carried out. RESULTS: Of the subjects in this multicentre-based study, 5.49% and 10.11% had significant necroinflammation with Knodell histological activity index ≥ 9 and hepatic fibrosis stages with Ishak scores ≥ 3, respectively. The subjects were stratified into three age groups (30-39, 40-49 and ≥ 50 years), and our data clearly suggested that age, particularly in the age group over 50, was an independent predictor of liver necroinflammation and fibrosis. Lower HBV-DNA viral levels were found in patients with Knodell histological activity index ≥ 9 or advanced fibrosis (Ishak scores ≥ 3). CONCLUSION: Our results showed that histological changes in liver tissues were observed in a significant proportion of patients with persistently normal alanine aminotransferase level. According to the data evaluation results, liver biopsy is advisable for HBeAg-positive chronic hepatitis B infected patients aged older than 40 and high HBV-DNA viral load in China.

Apoptosis induced by 9,11­dehydroergosterol peroxide from Ganoderma Lucidum mycelium in human malignant melanoma cells is Mcl­1 dependent.

9,11-Dehydroergosterol peroxide [9(11)-DHEP] is an important steroid from medicinal mushroom, which has been reported to exert antitumor activity in several tumor types. However, the role of 9(11)­DHEP toward the malignant melanoma cells has not been investigated. In the present study, the steroid from Ganoderma lucidum was purified on a submerged culture, and its antitumor mechanisms on A375 human malignant melanoma cells was investigated by MTT, flow cytometry and western blotting. The studies demonstrated that apoptotic mechanisms of the steroid were caspase­dependent and mediated via the mitochondrial pathway. The steroid did not cause significant changes in the expression levels of B­cell lymphoma 2 (Bcl­2) family proteins, Bcl­2­like protein 11, p53 upregulated modulator of apoptosis, Bcl­2­associated X protein, BH3 interacting­domain death agonist, Bcl­2­associated death promoter and Bcl­2, but it significantly downregulated induced myeloid leukemia cell differentiation protein Mcl­1 (Mcl­1) in melanoma cells, suggesting the key role of Mcl­1 in regulating apoptosis of melanoma cells induced by the steroid. These properties of 9(11)­DHEP advocate its usage as supplements in human malignant melanoma chemoprevention. The present study also suggests that mycelium of G. lucidum has a potential for producing bioactive substances and extracts with applications in medicine.

GATA-3 is superior to GCDFP-15 and mammaglobin to identify primary and metastatic breast cancer.

PURPOSE: Despite numerous studies on the utility of GATA-3 as breast cancer marker, its comparison with other breast markers, its concordance between primary and metastatic tumors and its expression in primary cancers from sites with frequent breast metastases remains unclear. METHODS: To address these questions, totally 993 invasive breast cancers (IBC), 254 paired nodal metastases, 23 distant metastases, and 208 lung carcinomas were included. GATA-3 expression was analyzed by immunohistochemistry and compared to other breast markers [gross cystic disease fluid protein 15 (GCDFP-15) and mammaglobin (MGB)]. RESULTS: GATA-3 was expressed in 82.5% of IBC, predominantly in luminal (93.9%), and lower in non-luminal cancers [59.6% of HER2 overexpressing (HER2-OE) and 38.1% of triple negative breast cancer (TNBC) subtypes]. GATA-3 identified more IBC than GCDFP-15 (23.9%) and MGB (46.6%). However, MGB showed a comparable sensitivity for non-luminal cancers to GATA-3. Combining MGB and GATA-3 improved sensitivity for both HER2-OE (80.8%) and TNBC cases (55.4%). GATA-3 showed a high sensitivity for nodal metastases and distant metastases, with good concordance with primary tumors. GATA-3 was expressed in 1.0% of lung carcinomas, with sensitivity and specificity of 82.5 and 99.0% in differentiating IBC and lung carcinoma. CONCLUSIONS: GATA-3 expression was the highest in luminal breast carcinomas, and showed higher sensitivity than GCDFP-15 and MGB. However, in the poorly differentiated IBC, its utility was still limited. One should be aware of the possible GATA-3 expression in lung carcinomas.

Renalase overexpression in ER-positive breast cancer.

OBJECTIVES: To explore the expression and pathologic significance of renalase in tumor tissues of different molecular subtypes of breast cancer. DESIGN: Immunofluorescence methods and laser confocal scanning microscope observations were used to detect expression of renalase, estrogen receptor (ER), phospho-extracellular signal-regulated kinase 1 and 2 (p-ERK1/2), and phospho-signal transducer and activator of transcription (p-STAT3) in 58 cases of breast cancer tissue, 11 normal tissues, and 14 benign fibroadenomas. Statistical analysis of its expression in different molecular subtypes of breast cancer was employed. RESULTS: Compared with control tissue (benign lesions and normal breast tissue), renalase was highly expressed in invasive breast cancer and the difference was significant (P<0.0001). Renalase was also expressed significantly higher in ER-positive breast cancer, compared with control tissue (P<0.0001). There was a positive correlation between renalase and ER expression in breast cancer tissues (R=0.7246, P<0.0001) and a positive correlation between renalase and p-ERK 1/2 expression (R=0.6599, P<0.0001). Renalase had no significant correlation with p-STAT3 protein expression. CONCLUSION: Renalase is a new molecular marker for ER-positive breast cancer and may become a potential therapeutic target for the ER-positive/HER2-negative subtype breast cancer. Renalase may promote high ER expression and breast cancer cell proliferation and growth through the p-ERK1/2 pathway.

Astragaloside IV ameliorates renal injury in db/db mice.

Diabetic nephropathy is a lethal complication of diabetes mellitus and a major type of chronic kidney disease. Dysregulation of the Akt pathway and its downstream cascades, including mTOR, NFκB, and Erk1/2, play a critical role in the development of diabetic nephropathy. Astragaloside IV is a major component of Huangqi and exerts renal protection in a mouse model of type 1 diabetes. The current study was undertaken to investigate the protective effects of diet supplementation of AS-IV on renal injury in db/db mice, a type 2 diabetic mouse model. Results showed that administration of AS-IV reduced albuminuria, ameliorated changes in the glomerular and tubular pathology, and decreased urinary NAG, NGAL, and TGF-ß1 in db/db mice. AS-IV also attenuated the diabetes-related activation of Akt/mTOR, NFκB, and Erk1/2 signaling pathways without causing any detectable hepatotoxicity. Collectively, these findings showed AS-IV to be beneficial to type 2 diabetic nephropathy, which might be associated with the inhibition of Akt/mTOR, NFκB and Erk1/2 signaling pathways.

Immunohistochemistry in the diagnosis of papillary lesions of the breast.

AIMS: Many immunohistochemical markers have been studied for differentiating papillary lesions. However, their differentiating power has not been evaluated comprehensively. Additionally, assessment of some markers will require the difficult task of identifying different cell types. In the current study, we aimed to devise a simple papillary panel which can aid in diagnosis irrespective of architectural pattern and cell type differentiation. METHODS AND RESULTS: Immunohistochemical analysis of papillary lesions using myoepithelial markers [p63 and smooth muscle actin (SMA)], high molecular weight cytokeratins (HMWCKs: CK5, CK5/6, CK14 and 34ßE12), hormone receptors (ER and PR) and neuroendocrine markers (chromogranin and synaptophysin) was performed. Among them, neuroendocrine markers showed high specificity but low sensitivity. HMWCK specificity was better than that for myoepithelial markers. Homogeneous staining pattern for hormonal receptors rather than their percentage positivity was more effective in identifying malignant lesions. Negative staining for two or more of HMWCKs, namely CK5/6, CK14 and 34ßE12, achieved the best overall specificity and sensitivity of 87.8% and 94.1%, respectively, irrespective of the architecture. Their discriminatory power was validated with an independent cohort of core needle biopsies. CONCLUSIONS: A marker panel with HMWCKs could be used in differentiating papillary lesions irrespective of architectural pattern or cell type differentiation.

Androgen receptor expression shows distinctive significance in ER positive and negative breast cancers.

BACKGROUND: Androgen receptor (AR), a nuclear steroid hormone receptor, is differentially expressed in breast cancer subgroups with distinct clinical implications. METHODS: To investigate the clinical significance of AR in breast cancers more precisely, the expression of AR in a large cohort of breast cancer was correlated with clinicopathological features, biomarker expression, and patients' survival according to different molecular groupings in this study. RESULTS: Higher AR expression was found in ER+ (57.8 %) than in ER- (24.7 %) cancers. In the ER+ cancers, AR expression was associated with favorable clinicopathological features, including lower grade (p < .001), lower pT stage (p < .001), and positivity for PR (p < .001). It was an independent prognostic factor for longer disease-free survival, mainly in the HER2+ luminal B cancers (hazard ratio [HR] = 0.251, 95 % CI 0.065-0.972, p = .045). In ER- cancers, AR expression was associated with features distinct from basal-like breast cancer, and such features were found in molecular apocrine (MA) cancers. AR correlated with presence of extensive in situ component (p = .006) and apocrine phenotype (p < .001), HER2 (p = .026), and EGFR (p = .048), but negatively with c-kit (p = .041), CK5/6 (p < .001), CK14 (p = .002), and αB-crystallin (p = .038). However, AR expression was found only in 37.8 % of immunohistochemically defined MA. Of note, AR-MA appeared to have a trend of worse overall survival than AR+MA. CONCLUSIONS: AR expression was different in ER+ and ER- cancers and had different clinical implications. AR alone may not be a good marker for MA subtype. Its expression in MA may have substantial prognostic implication and as such warrants further validation.

TTF-1 expression in breast carcinoma: an unusual but real phenomenon.

AIMS: To evaluate thyroid transcription factor-1 (TTF-1) expression in a large cohort of invasive breast carcinomas (IBCs) using two commercially available monoclonal antibody clones (8G7G3/1 and SPT24). METHODS AND RESULTS: Nuclear and cytoplasmic TTF-1 expression was evaluated in 1132 primary IBCs and 208 primary pulmonary carcinomas using tissue microarray (TMA) sections. TTF-1 nuclear expression was detected in one of 1132 (0.09%) IBCs by 8G7G3/1. In pulmonary carcinoma, TTF-1 expression was detected in 149 (71.6%) and 147 (70.6%) cases by 8G7G3/1 and SPT24, respectively, with no significant difference being seen between the two clones (P = 0.839), and there was good consistency between these two antibodies in differentiating breast and pulmonary carcinomas (kappa value 0.905; P < 0.001). Both clones showed high specificity but relatively low sensitivity. Cytoplasmic TTF-1 expression was detected in 44 IBCs by 8G7G3/1, and this particular expression pattern was an independent adverse prognostic factor. CONCLUSIONS: Both TTF-1 antibodies (clones 8G7G3/1 and SPT24) were useful in differentiating breast from pulmonary carcinomas. Nuclear expression of TTF-1 was detected in IBCs by 8G7G3/1, but not by SPT24. Cytoplasmic expression of 8G7G3/1 was seen in IBC for the first time, and was an independent unfavourable prognostic factor.

Columnar cell-like changes in the male breast.

AIMS: Columnar cell lesions are known as a link between normal breast and low grade neoplastic lesions in female, but have not been established in the male breast. This study evaluated the presence of ducts showing columnar cell-like features in the male breast. METHODS: Seventy-one consecutive surgical resections from men (6 invasive breast carcinoma of grade 3, 1 atypical ductal hyperplasia and 64 other lesions) were reviewed to identify foci of dilated ducts with columnar epithelial cells, and their morphological features including apical snouts, intraluminal secretions and calcifications were assessed. The expression of CK5/6 and estrogen receptor (ER) was evaluated immunohistochemically. Clinicopathological features including patients' age, histological diagnosis and gynaecomastoid hyperplasia were documented. RESULTS: Ducts showing columnar cell-like features were identified in 39 cases, morphologically as distended ducts with round or undulating outline. There was an outer layer of myoepithelial cells and an inner layer of columnar luminal cells showing apical snouts, but without intraluminal secretions or calcifications. Immunohistochemically, these columnar epithelial cells were negative for CK5/6 in 38/39 cases and all were ER heterogeneously positive. These changes were associated with older age, but their incidence did not differ whether they were associated with invasive breast carcinoma, atypical ductal hyperplasia and other lesions. CONCLUSIONS: In the male breast, there is an entity sharing morphological features and immunohistochemical profile of columnar cell lesions.