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Year of Publication
1.  Radiological and pathological characteristics of giant cell tumor of bone treated with denosumab 
Diagnostic Pathology  2014;9:111.
Abstract
We describe a case of giant cell tumor of the proximal tibia with skip bone metastases of the ipsilateral femur in a 20-year-old man. After the neoadjuvant treatment with denosumab, plain radiographs and computed tomography showed marked osteosclerosis and sclerotic rim formation, and 18F-FDG PET/CT showed a decreased standardized uptake value, whereas magnetic resonance imaging showed diffuse enhancement of the tumor, nearly the same findings as those at pretreatment. Pathological findings of the surgical specimen after the denosumab treatment showed benign fibrous histiocytoma-like features with complete disappearance of both mononuclear stromal cells and multinuclear osteoclast-like giant cells.
Virtual Slides
The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/1090602085125068
doi:10.1186/1746-1596-9-111
PMCID: PMC4057823  PMID: 24906559
Giant cell tumor of bone; Denosumab; Neoadjuvant chemotherapy; Receptor activator of nuclear factor-κB ligand (RANKL); Plain radiograph; MRI; 18F-FDG PET/CT; Benign fibrous histiocytoma
2.  An unusual case of Acanthamoeba Polyphaga and Pseudomonas Aeruginosa keratitis 
Diagnostic Pathology  2014;9:105.
Virtual Slides
The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/5168343391150859
A 56-year-old woman with a history of disposable soft contact lens wear was referred to our university eye center for a corneal ulcer. Based on the microbial culture, the initial diagnosis was bacterial keratitis, which was unresponsive to topical fortified antibiotics. The patient was then examined using in vivo confocal microscopy, which revealed Acanthamoeba infection. This case emphasizes the need to suspect Acanthamoeba infection in soft contact lens wearers who present with progressive ulcerative keratitis or progressively worsening corneal ulcers that are not responsive to the usual antimicrobial therapy. It is also important to consider the possibility of a coinfection with bacterial and Acanthamoeba species.
doi:10.1186/1746-1596-9-105
PMCID: PMC4051961  PMID: 24894486
Contact lens; Acanthamoeba species; Pseudomonas aeruginosa
3.  The NQO1 Pro187Ser polymorphism and breast cancer susceptibility: evidence from an updated meta-analysis 
Diagnostic Pathology  2014;9:100.
Background
NAD(P)H: quinone oxidoreductase 1 (NQO1) plays a central role in catalyzing the two-electron reduction of quinoid compounds into hydroquinones. The NQO1 Pro187Ser polymorphism was found to correlate with a lower enzymatic activity, which may result in increased incidence of carcinomas including breast cancer. Previous studies investigating the association between NQO1 Pro187Ser polymorphism and breast cancer risk showed inconsistent results. We performed a meta-analysis to summarize the possible association.
Methods
All studies published from January 1966 to February 2014 on the association between NQO1 Pro187Ser polymorphism and breast cancer risk were identified by searching electronic databases PubMed, EMBASE, Cochrane library, and Chinese Biomedical Literature database (CBM). The association between NQO1 Pro187Ser polymorphism and breast cancer risk was assessed by odds ratios (ORs) together with their 95% confidence intervals (CIs).
Results
Ten studies with 2,773 cases and 4,076 controls were finally included in the meta-analysis. We did not observe a significant association between NQO1 Pro187Ser polymorphism and breast cancer risk when all studies were pooled into the meta-analysis. In subgroup analysis by ethnicity, significant increased breast cancer risk was found in Caucasians (Ser/Pro vs. Pro/Pro: OR = 1.145, 95% CI = 1.008–1.301, P = 0.038; Ser/Ser + Ser/Pro vs. Pro/Pro: OR = 1.177, 95% CI = 1.041–1.331, P = 0.009). When stratified by source of control, significant increased breast cancer risk was found in population-based studies (Ser/Pro vs. Pro/Pro: OR = 1.180, 95% CI = 1.035–1.344, P = 0.013; Ser/Ser + Ser/Pro vs. Pro/Pro: OR = 1.191, 95% CI = 1.050–1.350, P = 0.007). However, in subgroup analyses according to menopausal status, quality score, and HWE in controls, no any significant association was detected.
Conclusions
Our meta-analysis provides the evidence that the NQO1 Pro187Ser polymorphism contributed to the breast cancer susceptibility among Caucasians. Further large and well-designed studies are needed to confirm this association.
Virtual slides
The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/1248639991252504
doi:10.1186/1746-1596-9-100
PMCID: PMC4041044  PMID: 24884893
NQO1; Polymorphism; Breast cancer; Meta-analysis
4.  Immunohistochemical assessment of a unique basal pattern of p53 expression in ulcerative-colitis-associated neoplasia using computer-assisted cytometry 
Diagnostic Pathology  2014;9:99.
Background
The basal pattern of p53 expression, defined as its immunoreactivity confined to the basal half of the glands, is associated with early neoplastic lesions in ulcerative colitis (UC). However, their clinical utility of this finding is limited by the use of “visual estimation” (approximate immunoreactivity on the basis of scanning the stained slide, without formal counting). This study was designed to analyze the basal pattern of p53 using computer-assisted cytometry and to identify the optimal cutoff value for discriminating between UC-associated early-stage neoplasia and regenerative atypia.
Methods
The specimens were obtained from eight UC patients undergoing colectomy and were classified according to the criteria by the Research Committee of Inflammatory Bowel Disease of the Ministry of Health and Welfare in Japan. Patients with classes UC-IIa (indefinite for dysplasia, probably regenerative), UC-IIb (indefinite for dysplasia, probably dysplastic), and UC-III (definitive dysplasia) were enrolled in the study. Based on the percentage of immunoreactive cells in the basal half of the crypt with visual estimation, basal positivity of p53 was classified into three categories: grade 1 (1 - 9%), grade 2 (10 - 19%), and grade 3 (≥20%). Next, crypts classified as grade 3 by visual estimation were analyzed by computer-assisted image analysis.
Results
Using visual estimation, grade-3 p53 basal positivity was observed in 46.0% of UC-IIa crypts (128 of 278), 61.9% of UC-IIb crypts (39 of 63), and 94.2% of UC-III crypts (81 of 86). Using image analysis, the median p53 basal positivities were 30.3% in UC-IIa, 52.3% in UC-IIb, and 65.4% in UC-III (P ≤0.002). A receiver operating characteristics curve was generated to determine the method’s diagnostic utility in differentiating UC-IIa from UC-III. In this cohort, the sensitivity was 0.78; the specificity was 0.98; the negative predictive value was 87.4%; the positive predictive value was 95.5%, and the accuracy was 90.2% with a cutoff value for p53 basal positivity of 46.1%.
Conclusions
Our findings indicate that assessing p53 basal positivity by image analysis with an optimal threshold represents an alternative to visual estimation for the accurate diagnosis of UC-associated early-stage neoplasia.
Virtual Slides
The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/3588120501252608
doi:10.1186/1746-1596-9-99
PMCID: PMC4047002  PMID: 24886509
Ulcerative colitis; p53; Immunohistochemistry; Computer-assisted cytometry; Dysplasia
5.  Association between STAT3 gene Polymorphisms and Crohn’s disease susceptibility: a case–control study in a Chinese Han population 
Diagnostic Pathology  2014;9:104.
Background
Crohn’s disease (CD) is an immune-related disease with genetic predisposition. This study aimed to investigate the association of three polymorphisms in the signal transducer and activator of transcription 3 (STAT3) gene with CD risk in a Chinese population.
Methods
We conducted a hospital-based case–control study involving 232 CD patients and 272 controls. Genotyping was performed using polymerase chain reaction with sequence-specific primer method. Statistical analyses were conducted using logistic regression and genotype risk scoring.
Results
Significant differences were found between patients and controls in allele/genotype distributions of rs744166 (Pallele = 0.0008; Pgenotype = 0.003) and allele distributions of rs4796793 (P = 0.03). The risk for CD associated with the rs744166-A mutant allele decreased by 37% [95% confidence interval (CI): 0.48–0.83] under the additive model, 39% (95% CI: 0.43–0.81) under the dominant model and 57% (95% CI: 0.24–0.77) under the recessive model. Carriers of the rs4796793-G mutant allele exhibited 25% (95% CI: 0.58–0.98; P = 0.03) and 47% (95% CI: 0.30–0.95) decreased risks of developing CD under the additive and recessive models, respectively.
Conclusions
STAT3 rs744166 and rs4796793 polymorphisms may be associated with CD occurrence and used as a predictive factor of CD in Chinese Han populations.
Virtual Slides
The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/2169674321122294
doi:10.1186/1746-1596-9-104
PMCID: PMC4047544  PMID: 24885273
STAT3; Polymorphism; Crohn’s diseases; Susceptibility; Association study
6.  Erythrodermic psoriasis with bullous pemphigoid: combination treatment with methotrexate and compound glycyrrhizin 
Diagnostic Pathology  2014;9:102.
We report a case of erythrodermic psoriasis with bullous pemphigoid (BP) in a 68-year-old male. The patient had a history of psoriasis for 35 years and tense, blisterlike lesions for 4 months. He presented with diffuse flushing, infiltrative swelling, and tense blisterlike lesions on his head, trunk, and limbs. This patient was successfully treated by a combination of methotrexate and compound glycyrrhizin. We also discuss the clinical manifestations, histopathological features, and differentiation of erythrodermic psoriasis with BP and present a review of the pertinent literature.
Virtual Slides
The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/1853737109114076
doi:10.1186/1746-1596-9-102
PMCID: PMC4047554  PMID: 24885087
Erythrodermic psoriasis; Bullous pemphigoid; Methotrexate; Compound glycyrrhizin
7.  Berberine inhibits the expression of hypoxia induction factor-1alpha and increases the radiosensitivity of prostate cancer 
Diagnostic Pathology  2014;9:98.
Abstract
Background
The radiation resistance of prostate cancer remains the primary obstacle to improve patient survival. This study aimed to investigate the effects of berberine, a commonly used natural product, on the radiosensitivity of prostate cancer.
Methods
Prostate cancer cell line LNCaP and DU-145 were subjected to hypoxia and/or ionizing radiation (IR), in the presence or absence of berberine treatment. Cell growth and colony formation, and apoptosis were evaluated. Moreover, LNCaP cells were xenografted into nude mice and subjected to IR and/or berberine treatment. The expression of HIF-1α and VEGF in prostate cancer cells and xenografts was detected by Western blot analysis.
Results
Berberine increased radiosensitivity of prostate cancer cells and xenografts in a dose dependent manner, and this was correlated with the inhibition of HIF-1α and VEGF expression.
Conclusions
Berberine may inhibit the expression of HIF-1α and VEGF and thus confer radiosensitivity on prostatic cancer cells. Berberine has potential application as an adjuvant in radiotherapy of prostatic cancer.
Virtual Slides
The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/1519827543125021.
doi:10.1186/1746-1596-9-98
PMCID: PMC4051149  PMID: 24886405
Berberine; Radiosensitivity; Prostate cancer; HIF-1α
8.  Primary extranodal NK/T cell lymphoma, nasal-type of uterus with adenomyosis: a case report 
Diagnostic Pathology  2014;9:95.
Natural killer (NK)/T cell lymphoma of the female genital tract is extremely rare. We here report a case of ‘nasal type’ NK/T cell lymphoma arising in the uterus with adenomyosis in a 41-year-old woman with fever and hypogastralgia. The histologic analysis demonstrated a highly aggressive tumor with characteristic angiocentric/angiodestructive growth pattern and focal necrosis. The lymphoma cells displayed a CD3ϵ/CD56/TIA-1/granzyme-B/Perforin-positive and CD20/CD79a/CD4/CD8-negative immunophenotype and positive for Epstein-Barr virus by EBER in situ hybridization. Clinically, the disease was limited to the uterus at the initial diagnosis, but progressed rapidly. The patient died on day 54 after hysterectomy, irrespective of intensive chemotherapy.
Virtual Slides
The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/1323474831125945
doi:10.1186/1746-1596-9-95
PMCID: PMC4052815  PMID: 24886075
Uterus; NK/T cell lymphoma; Extranasal type
9.  Current evidences on XPC polymorphisms and gastric cancer susceptibility: a meta-analysis 
Diagnostic Pathology  2014;9:96.
Background
Reduced DNA repair capacities due to inherited polymorphisms may increase the susceptibility to cancers including gastric cancer. Previous studies investigating the association between Xeroderma Pigmentosum group C (XPC) gene polymorphisms and gastric cancer risk reported inconsistent results. We performed a meta-analysis to summarize the possible association.
Methods
All studies published up to January 2014 on the association between XPC polymorphisms and gastric cancer risk were identified by searching electronic databases PubMed, EMBASE, Cochrane library, and Chinese Biomedical Literature database (CBM). The association between XPC polymorphisms and gastric cancer risk was assessed by odds ratios (ORs) together with their 95% confidence intervals (CIs).
Results
Six studies with 1,355 gastric cancer cases and 2,573 controls were finally included in the meta-analysis. With respect to Lys939Gln polymorphism, we did not observe a significant association when all studies were pooled into the meta-analysis. When stratified by ethnicity, source of control, and study quality, statistical significant association was not detected in all subgroups. With respect to Ala499Val and PAT−/+polymorphisms, we also did not observe any significant association with gastric cancer risk in the pooled analysis.
Conclusions
This meta-analysis based on current evidences suggested that the XPC polymorphisms (Lys939Gln, Val499Arg, and PAT−/+) did not contribute to gastric cancer risk. Considering the limited sample size and ethnicity included in the meta-analysis, further larger scaled and well-designed studies are needed to confirm our results.
Virtual Slides
The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/1485880312555069
doi:10.1186/1746-1596-9-96
PMCID: PMC4053311  PMID: 24886180
XPC; Polymorphism; Gastric cancer; Meta-analysis
10.  Polypoid nodular histiocytic hyperplasia associated with endometrioid adenocarcinoma of the endometrium: report of a case 
Diagnostic Pathology  2014;9:93.
A 45 year old woman underwent Laparoscopy-assisted total hysterectomy with staging procedure following a diagnosis of endometrial endometrioid adenocarcinoma on her endometrial biopsy. The hysterectomy specimen showed a FIGO I stage 1a, endometrioid carcinoma. A separate polypoid lesion in the endometrium, distinct from the carcinoma, was also identified. Microscopically the polypoid lesion was “nodular histiocytic hyperplasia”. The H&E, immunohistochemical staining findings and the differential diagnoses are discussed in this report. Although description of similar lesions is available in the literature, the current lesion is unique as it is identified in a hysterectomy specimen in its entirety and its association with an endometrial endometrioid carcinoma.
Virtual Slides
The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/1060511915121922
doi:10.1186/1746-1596-9-93
PMCID: PMC4041356  PMID: 24885845
Endometrium; Nodular histiocytic hyperplasia; Endometrioid carcinoma
11.  Objective assessment of changes in nuclear morphology and cell distribution following induction of apoptosis 
Diagnostic Pathology  2014;9:92.
Background
To objectively measure changes in nuclear morphology and cell distribution following induction of apoptosis.
Methods
A spontaneously immortalized retinal pigment epithelial cell line (ARPE-19) was cultured for three days in DMEM/F12 with 10% fetal bovine serum followed by 24 hours incubation in staurosporine to induce apoptosis. Cells that were not incubated in staurosporine served as control. Caspase-3 expression in apoptotic cells was demonstrated by quantitative immunofluorescence. Nuclei were counterstained with DAPI. Assessments of nuclear morphology and cell distribution were performed using ImageJ software. Statistical analyses included Student’s t-test and Pearson’s correlation coefficient. Nearest neighbor analysis was used to assess cell nuclei distribution.
Results
Caspase-3 expression in staurosporine-incubated cells increased by 471% ± 182% compared to control (P = 0.014). Relative to the control, cells in the staurosporine-incubated cultures had smaller average nuclear area (68% ± 5%; P < 0.001) and nuclear circumference (78 ± 3%; P < 0.001), while nuclear form factor was larger (110% ± 1%; P < 0.001). Cell nuclei from the staurosporine-group (R = 1.12 ± 0.04; P < 0.01) and the control (R = 1.28 ± 0.03; P < 0.01) were evenly spaced throughout the cultures, thereby demonstrating a non-clustered and non-random cell distribution. However, the staurosporine-incubated group had a significantly lower R-value compared to the control (P = 0.002), which indicated a move towards cell clustering following induction of apoptosis. Caspase-3 expression of each individual cell correlated significantly with the following morphological indicators: circumference of the nucleus divided by form factor (r = -0.475; P < 0.001), nuclear area divided by form factor (r = -0.470; P < 0.001), nuclear circumference (r = -0.469; P < 0.001), nuclear area (r = -0.445; P < 0.001), nuclear form factor (r = 0.410; P < 0.001) and the nuclear area multiplied by form factor) (r = -0.377; P < 0.001).
Conclusions
Caspase-3 positive apoptotic cells demonstrate morphological features that can be objectively quantified using freely available ImageJ software. A novel morphological indicator, defined as the nuclear circumference divided by form factor, demonstrated the strongest correlation with caspase-3 expression.
Virtual Slides
The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/3271993311662947
doi:10.1186/1746-1596-9-92
PMCID: PMC4048047  PMID: 24885713
12.  Adult primary paratesticular mesenchymal tumors with emphasis on a case presentation and discussion of spermatic cord leiomyosarcoma 
Diagnostic Pathology  2014;9:90.
Background
The aim of this report is related to adult primary paratesticular mesenchymal tumors with emphasis on a case presentation and discussion of the spermatic cord leiomyosarcoma. Primary paratesticular tumors are rare, only accounting for 7% to 10% of all intrascrotal tumors. In adults, more than 75% of these lesions arise from the spermatic cord, 20% being leiomyosarcoma. Tumor grade, stage, histologic type, and lymph node involvement are independently predictive of prognosis.
Findings
The case report concerns a 81-year-old man presented with a 3-year history of painless lump in the right hemiscrotum. Scrotal examination demonstrated a 5.1-cm, firm-to-hard mass attached to the spermatic cord. Scrotal ultrasound scan revealed a heterogeneous mass separate from the testis. He was treated with an radical orchi-funicolectomy. Histologically the lesion is composed of spindled cells with often elongated, blunt-ended nuclei and variably eosinophilic cytoplasm. Areas with pleomorphic morphology are present. The level of mitotic activity is equal to 3/10 HPF in the areas with spindle cell morphology and to 12/10 HPF in the areas with pleomorphic morphology. The final diagnosis was that a leiomyosarcoma of the spermatic cord, with grade 1 and grade 2 areas, stage pT2b cN0 and cM0. The patient has been followed up for 3 months with CT scans and shows no signs of recurrence.
Conclusions
Spermatic cord leiomyosarcoma, although rare, should be one of the first differential diagnoses for a firm-to-hard lump in the cord. Apart from radical orchi-funicolectomy, there has been added benefit of adjuvant radiotherapy to prevent any loco-regional lymph node recurrence.
Virtual Slides
The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/1613030331125632
doi:10.1186/1746-1596-9-90
PMCID: PMC4039061  PMID: 24885500
Leiomyosarcoma of the spermatic cord; Mesenchymal tumors of the scrotum; Spermatic cord; Liposarcoma; Malignant fibrous histiocytomas; Rhabdomyosarcoma
13.  Submandibular gland cystadenocarcinoma with mucinous adenocarcinoma-like areas: a case report 
Diagnostic Pathology  2014;9:87.
Abstract
Cystadenocarcinoma is primarily characterized by cystic structures of varying sizes, that are lined by epithelial cells. As a rare neoplasm, only four cases of cystadenocarcinoma of submandibular glands have been previously reported. Herein, we reported a unique case of submandibular gland cystadenocarcinoma in a 44-year-old man. By in large, this case had typical morphologic cystadenocarcinoma features. However, mucinous adenocarcinoma-like areas were additionally observed in the tumor tissues. This case was initially misdiagnosed as mucinous adenocarcinoma due to the low incidence of submandibular gland cystadenocarcinoma and the presentation of mucinous adenocarcinoma-like areas in the tumor tissues. Histopathology of additional tumor tissues revealed that mucinous adenocarcinoma-like areas accounted for only a small percentage of the tumor tissues, confirming the submandibular gland cystadenocarcinoma diagnosis.
Virtual slides
The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/1387916949121142
doi:10.1186/1746-1596-9-87
PMCID: PMC4012165  PMID: 24774077
Cystadenocarcinoma; Submandibular gland; Cysts; Papillary; Mucus-like materials
14.  Down regulation of miR-143 is related with tumor size, lymph node metastasis and HPV16 infection in cervical squamous cancer 
Diagnostic Pathology  2014;9:88.
Objective
This study is to investigate the role of miR-143 expression in cervical squamous cell carcinoma (SCC).
Methods
The expression level of miR-143 was examined by quantitative real-time PCR. Human papillomavirus (HPV) genotype was detected by HPV genotype detection kit. The expression level of bcl-2 was detected by immunohistochemistry.
Results
The positive rate of HPV was 78% in the patients of cervical SCC. The most prevalent genotype was HPV16, with a positive rate of 42%. The expression level of miR-143 was significantly lower in the cervical SCC tissues than that in the normal cervical tissues (Z = −2.180, P = 0.029). Down-regulated miR-143 expression was associated with tumor size, lymph node metastasis and HPV16 infection in cervical cancer patients. No significant associations were found between the expression levels of miR-143 and age, clinical stage, differentiation or lymph vascular space invasion. And, in cervical SCC patients after treatment with Taxol chemotherapy, the expression level of miR-143 was higher and the positive expression of bcl-2 protein was lower. However, the differences in expression changes of miR-143 and bcl-2 were not statistically significant (miR-143, Z = −0.763, P = 0.446; bcl-2 protein, χ2 = 2.277, P = 0.131).
Conclusion
Down-regulated miR-143 is related with tumor size, lymph node metastasis and HPV16 infection in cervical SCC, but miR-143 does not participate in the Taxol sensitivity response.
Virtual slides
The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/1401279451112150.
doi:10.1186/1746-1596-9-88
PMCID: PMC4039059  PMID: 24774218
15.  Follow-up of breast papillary lesion on core needle biopsy: experience in African-American population 
Diagnostic Pathology  2014;9:86.
Background
The optimal course of clinical follow-up after a diagnosis of breast papillary lesion on a core needle biopsy (CNB) remains elusive. In particular, no reports in literature have addressed this question in African-American population. We describe our experience with breast papillary lesions in a primarily African-American population.
Methods
A search of our database for breast papillary lesions diagnosed on CNB between September 2002 and September 2012 was conducted. Cases were categorized into benign, atypical, and malignant. CK5/6 and CK903 stains were performed when necessary.
Results
A total of 64 breast papillary lesions were diagnosed on CNB, including 55 (86%) benign papillary lesions, 6 (9%) atypical lesions, and 3 (5%) intraductal papillary carcinomas. Of these 64 patients, 29 patients (25 African-Americans, 3 Hispanics, 1 Asian American) underwent lumpectomy within 6 months after CNB. Pathology of the lumpectomy showed: five of the 25 (20%) benign papillary lesions on needle biopsy were upgraded to intraductal or invasive papillary carcinoma; 2 of the 3 atypical papillary lesion cases on core biopsy were upgraded (67%), one into intraductal papillary carcinoma, the other invasive papillary carcinoma; the only case of malignant papillary lesion on CNB remained as intraductal papillary carcinoma on lumpectomy. The rate of upgrade in lumpectomy/mastectomy was 25%. CK5/6 and CK903 immunostains were performed on all seven core needle biopsies that were later upgraded.
Conclusions
In our predominantly African-American urban population, 25% of benign or atypical papillary lesions diagnosed on CNB was upgraded in the final excisional examination. Early excision of all papillary lesions diagnosed on CNB may be justified in this patient population.
Virtual Slides
The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/7950117821177201
doi:10.1186/1746-1596-9-86
PMCID: PMC4039081  PMID: 24762090
Breast papillary lesion; Core needle biopsy; Immunostains; African-Americans
16.  Inhibitory receptor immunoglobulin-like transcript 4 was highly expressed in primary ductal and lobular breast cancer and significantly correlated with IL-10 
Diagnostic Pathology  2014;9:85.
Background
Immunoglobulin-like transcript 4 (ILT4) is an inhibitory molecule involved in immune response and has recently been identified to be strongly inducible by IL-10. The aim of the present study was to examine the associations of ILT4 expression with clinicopathological characteristics and IL-10 expression in primary ductal and lobular breast cancer.
Methods
We studied the expression of ILT4 in 4 cancer cell lines, 117 primary tumor tissues and 97 metastatic lymph nodes from patients with primary ductal and lobular breast cancer by reverse transcription-polymerase chain reaction, western blot or immunohistochemistry analysis. Additionally, IL-10 expression was also investigated using immunohistochemistry in primary tumor tissues. Then the relationship between ILT4 expression and clinicopathological characteristics/IL-10 expression was evaluated.
Results
ILT4 was highly expressed in all 4 human breast cancer cell lines on both mRNA and protein levels. In primary tumor tissues, ILT4 or IL-10 was expressed in the cell membrane, cytoplasm, or both; the positive rate of ILT4 and IL-10 expression was 60.7% (71/117) and 80.34% (94/117), respectively. ILT4 level was significantly correlated with IL-10 (r =0.577; p < 0.01). Furthermore, the expression of ILT4 or IL-10 was associated with less number of Tumor Infiltrating Lymphocytes (TILs) (p = 0.004 and 0.018, respectively) and more lymph node metastasis (p = 0.046 and 0.035, respectively).
Conclusion
Our data demonstrated the association of ILT4 and IL-10 expression in human breast cancer, suggesting their important roles in immune dysfunction and lymph node metastases.
Virtual Slides
The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/1692652692107916
doi:10.1186/1746-1596-9-85
PMCID: PMC4045966  PMID: 24762057
Immunoglobulin-like transcript 4; Interleukin-10; Tumor infiltrating lymphocytes; Immunohistochemistry; Breast cancer
17.  Kallikrein 3 and vitamin D receptor polymorphisms: potentials environmental risk factors for prostate cancer 
Diagnostic Pathology  2014;9:84.
Objective
To investigate the relationship and interaction of the single nucleotide polymorphisms (SNPs) of KLK3 and VDR and environmental factors with the predisposition to prostate cancer within Chinese population.
Methods
The comparison between 108 patients and 242 healthy people was carried out by using the TaqMan/MGB Probe Technology to determine the genotypes of KLK3(rs2735839 is located between KLK2 and KLK3) and VDR (rs731236 is located exon 9). Univariate and multivariate logistic regression model were used to assess the connection of genetic polymorphisms and environmental risk factors with PCa by collecting demographic information, as well as BMI, consumption of cigarettes, alcohol, and tea, exercise, and other environmental risk factors.
Results
The appearing frequencies of AA, AG, and GG genotypes at the SNPs rs2735839 (A/G) for KLK3 were 13.89%, 62.96% and 23.15% in PCa and 37.19%, 44.63%, 18.18% in control, respectively; these two groups are statistically different (P = 0.00). While the appearing frequencies of TT, TC, and CC genotypes at the SNPs rs731236 (T/C) for VDR were 88.89%, 9, 26%, 1.85% and 90.50%, 9.10%, 0.40% in control, respectively, with no significant statistical difference between the two group. The study confirmed decreasing risk in tea drinkers (OR = 0.58, 95% CI = 0.35-0.96).
Conclusions
Our studies indicate that environmental factor-tea drinking is associated with the development of PCa. The habit of drinking tea is a protective factor against PCa. The SNPs rs2735839 for KLK3 is strongly related to the development of PCa, while the SNPs rs731236 for VDR is not.
Virtual slides
The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/9759981571058803.
doi:10.1186/1746-1596-9-84
PMCID: PMC4022449  PMID: 24755043
Prostate cancer; Nucleotide polymorphisms; Environmental risk factor
18.  Adenovirus36 infection expresses cellular APMI and Visfatin genes in overweight Uygur individuals 
Diagnostic Pathology  2014;9:83.
Objective
This study is to determine if Adenovirus type 36 (Ad36) infection is related to macrophage infiltration in the obese group and non-obese group and the related molecular mechanisms.
Methods
Ninety obesity patients and 95 non-obesity Uygur individuals were enrolled in this study. CD68 levels in abdominal subcutaneous and omental adipose tissues were detected by immunohistochemistry. The cytokine expression levels of adiponectin (APMI) and visfatin in serum were measured by enzyme-linked immunosorbent assay. Infection of 3T3-L1 cells with Ad36 was performed. Real-time PCR was performed to determine expression levels of APMI and Visfatin genes in the 3T3-L1 preadipocytes infected with Ad36.
Results
In the obese individuals infected with Ad36, the expression levels of adiponectin and visfatin in serum was elevated. For the individuals infected with Ad36, the macrophage infiltration (as indicated by CD68 level) in the obese group was also significantly higher than that in the non-obese group (P < 0.05) in both abdominal subcutaneous and omental adipose tissues. The real-time PCR results indicated that APMI mRNA levels and Visfatin mRNA levels in Ad36 infected cells were significantly increased.
Conclusions
Ad36 infection may be a factor related with macrophage infiltration in adipose tissues of the obese patients. The APMI and Visfatin genes may be involved in the mechanism underlying the effect of Ad36 infection on the obese patients.
Virtual Slides
The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/1849614638119816
doi:10.1186/1746-1596-9-83
PMCID: PMC3996488  PMID: 24739504
Adenovirus 36; Adipocytokines; Obesity; Adiponectin; Visfatin
19.  Immunohistochemical analysis of PDK1 expression in breast cancer 
Diagnostic Pathology  2014;9:82.
Background
3-phosphoinositide-dependent protein kinase-1 (PDK1) functions downstream of phosphoinositide 3-kinase (PIK3) and activates members of the AGC family of protein kinases that are known to play crucial roles in physiological processes associated with cell metabolism, growth, proliferation and survival. Changes in the expression and activity of PDK1 and several AGC kinases have been linked to human disease, including cancer.
Methods
We used immunohistochemical analysis to determine PDK1 expression in 241 tumors from patients with breast cancer in which we had previously analyzed PIK3CA mutation status.
Results
Moderate or high expression of PDK1 was observed in 213 of the 241 cases (88%). There was no correlation between PIK3CA mutation status and PDK1 overexpression.
Conclusion
Our findings indicate that PDK1 is independently activated in breast cancer and not only as part of the PIK3CA pathway, suggesting that PDK1 plays a specific and distinct role from the canonical PIK3/Akt pathway and promotes oncogenesis independently of AKT. Our data implicate PDK-1 and downstream components of the PDK-1 signaling pathway as promising therapeutic targets for the treatment of breast cancer.
doi:10.1186/1746-1596-9-82
PMCID: PMC4005628  PMID: 24739482
PDK1; PIK3CA; Breast cancer
20.  Melanotic Xp11 translocation renal cancer: report of a case with a unique intratumoral sarcoid-like reaction 
Diagnostic Pathology  2014;9:81.
Background
Melanotic Xp11 translocation renal cancer is a rare tumor belonging to the family of microphthalmia-associated transcription factor (MiTF)/transcription factor E (TFE) neoplasms. This tumor family also includes alveolar soft part sarcoma, perivascular epithelioid cell neoplasms, Xp11 translocation renal cell carcinoma, and melanoma. To date, six confirmed melanotic Xp11 translocation cancers (five renal, one ovarian) have been reported in the literature.
Case Report
Here, we report the clinical, histologic, immunohistochemical, and molecular features of a unique melanotic Xp11 translocation renal cancer arising in a 34-year-old African-American female. Histologically, the tumor was composed of epithelioid tumor cells arranged in a nested pattern. The cells had clear to eosinophilic granular cytoplasm, vesicular nuclear chromatin, and prominent nucleoli. Multifocal intracytoplasmic deposits of granular brown melanin pigment were identified and confirmed by Fontana-Masson stain. An unusual histologic feature, not previously reported in melanotic Xp11 translocation renal cancer, was a sarcoid-like granulomatous reaction consisting of tight epithelioid granulomas with lymphocytic cuffing, numerous giant cells, and calcifications. Nuclear transcription factor E3 expression was identified by immunohistochemistry and TFE3 rearrangement was confirmed by fluorescence in situ hybridization. Additional immunohistochemical findings included immunoreactivity for HMB45, cathepsin K, and progesterone receptor; negative staining was seen with actin, desmin, cytokeratins, epithelial membrane antigen, CD10, vimentin, and PAX-8. The patient is currently free of disease, two years following initial clinicoradiologic presentation and twenty-two months following partial nephrectomy without additional therapy.
Conclusion
This report further expands the spectrum of morphologic and clinical findings previously described in melanotic Xp11 translocation renal cancer, a distinctive tumor showing overlapping features between Xp11 translocation renal cell carcinoma, melanoma, and perivascular epithelioid cell neoplasms.
Virtual slides
The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/7225796341180634
doi:10.1186/1746-1596-9-81
PMCID: PMC4003493  PMID: 24735727
Melanotic Xp11 translocation; TFE3; HMB-45; Renal cell carcinoma; Sarcoid-like reaction
21.  Use of a standardized diagnostic approach improves the prognostic information of histopathologic factors in pancreatic and periampullary adenocarcinoma 
Diagnostic Pathology  2014;9:80.
Background
Variability in reported histopathology parameters in operated periampullary adenocarcinomas may affect the prognostic weight of the parameters. Standardized axial sectioning produces a higher incidence of involved margins and also seems to produce a lower relative incidence of pancreatic compared with distal bile duct origin and a higher incidence of involved lymph nodes, compared with non-standardized procedure. The aims of this study were to 1) assess how a previously not described standardized pathology procedure, with longitudinal sectioning along the distal bile duct, affects reported tumour origin, margin status and involved lymph nodes, compared with non-standardized procedure, 2) assess if re-evaluation of microscopic slides affects the prognostic value of margin status and 3) compare the results of this standardized procedure with reported results of other standardized and non-standardized procedures.
Methods
One hundred seventy-five consecutive pancreaticoduodenectomy specimens with primary adenocarcinomas, operated during 2001 – 2011 at the University hospitals of Lund and Malmö, Sweden, were re-evaluated histologically, and parameters relevant for classification and prognosis were assessed, with 1 mm as a threshold for involved or uninvolved margins. Follow-up lasted until 31 December 2013. Five-year overall survival (OS) and hazard ratios (HR) were calculated for the margin status stated in the original reports and margin status after re-evaluation.
Results
Compared with non-standardized cases (n = 129), standardized cases (n = 46) had more involved lymph nodes in the specimens (median 3 vs 1), a higher fraction of distal bile duct origin (39% vs 21%) and a higher fraction of involved margins (74% vs 47%). The prognostic value of uninvolved margins increased by re-evaluation of slides (p < 0.001) and the adjusted HR for involved margins increased from 1.6 (95% CI 1.1 - 2.4) to 3.3 (95% CI 1.5 – 7.0). Uninvolved margins remained a significant predictor of OS in adjusted analysis.
Conclusions
Both the method of sectioning the specimen and the microscopic assessment affect prognostic pathology parameters significantly. The results of the herein described standardized method are similar to the results of other standardized procedures. The 1-mm threshold for involved margins in pancreaticoduodenectomies is relevant for OS, and margin status is an independent prognostic parameter.
Virtual slides
The virtual slides for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/1056639379120615
doi:10.1186/1746-1596-9-80
PMCID: PMC3999361  PMID: 24731283
Carcinoma; Pancreatic ductal; Common bile duct neoplasms; Duodenal neoplasms; Pathology; Surgical; Pancreaticoduodenectomy; Prognosis
22.  HMG-CoA reductase expression in primary colorectal cancer correlates with favourable clinicopathological characteristics and an improved clinical outcome 
Diagnostic Pathology  2014;9:78.
Background
An association between tumor-specific HMG-CoA reductase (HMGCR) expression and good prognosis has previously been demonstrated in breast and ovarian cancer. In this study, the expression, clinicopathological correlates and prognostic value of HMGCR expression in colorectal cancer was examined.
Findings
Immunohistochemical expression of HMGCR was assessed in tissue microarrays with primary tumours from 557 incident cases of colorectal cancer in the Malmö Diet and Cancer Study. Pearson’s Chi Square test was applied to explore the associations between HMGCR expression and clinicopathological factors and other investigative biomarkers. Kaplan Meier analysis and Cox proportional hazards modeling were used to assess the relationship between HMGCR expression and cancer-specific survival (CSS) according to negative vs positive HMGCR expression.
A total number of 535 (96.0%) tumours were suitable for analysis, of which 61 (11.4%) were HMGCR negative. Positive cytoplasmic HMGCR expression was associated with distant metastasis-free disease at diagnosis (p = 0.002), lack of vascular invasion (p = 0.043), microsatellite-instability (p = 0.033), expression of cyclin D1 (p = <0.001) and p21 (p = <0.001). Positive HMGCR expression was significantly associated with a prolonged CSS in unadjusted Cox regression analysis in the entire cohort (HR = 1.79; 95% CI 1.20-2.66) and in Stage III-IV disease (HR = 1.71; 95% CI 1.09-2.68), but not after adjustment for established clinicopathological parameters.
Conclusions
Findings from this prospective cohort study demonstrate that HMGCR is differentially expressed in colorectal cancer and that positive expression is associated with favourable tumour characteristics and a prolonged survival in unadjusted analysis. The utility of HMGCR as a predictor of response to neoadjuvant or adjuvant statin treatment in colorectal cancer merits further study.
Virtual slides
The virtual slides for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/2115647072103464.
doi:10.1186/1746-1596-9-78
PMCID: PMC4000148  PMID: 24708688
HMG-CoA reductase; Immunohistochemistry; Colorectal cancer; Prognosis
23.  Distribution of estrogen and progesterone receptors isoforms in endometrial cancer 
Diagnostic Pathology  2014;9:77.
Background
70–80% of sporadic endometrial carcinomas are defined as endometrioid carcinoma (EC). Early-stage, well differentiated endometrial carcinomas usually retain expression of estrogen and progesterone receptors (ER and PR, respectively), as advanced stage, poorly differentiated tumors often lack one or both of these receptors. Well-described EC prognosis includes tumor characteristics, such as depth of myometrial invasion. Therefore, in the current study, we evaluated the expression profile of ER and PR isoforms, including ER-α, PR-A and PR–B, in correlation to EC tumor histological depth.
Methods
Using immunohistochemistry and image analysis software, the expression of ER-α, PR-A, PR–B and Ki67 was assessed in endometrial stroma and epithelial glands of superficial, deep and extra-tumoral sections of 15 paraffin embedded EC specimens, and compared to 5 biopsies of non-malignant endometrium.
Results
Expression of PR-A and ER-α was found to be lower in EC compared to nonmalignant tissue, as the stromal expression was dramatically reduced compared to epithelial cells. Expression ratios of both receptors were significantly high in superficial and deep portions of EC; in non-tumoral portion of EC were close to the ratios of nonmalignant endometrium. PR-B expression was low in epithelial glands of EC superficial and deep portions, and high in the extra-tumoral region. Elevated PR-B expression was found in stroma of EC, as well.
Conclusions
The ratio of ER-α and PR-A expression in the epithelial glands and the stroma of EC biopsies may serve as an additional parameter in the histological evaluation of EC tumor.
Virtual slides
The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/1155060506119016
doi:10.1186/1746-1596-9-77
PMCID: PMC4022268  PMID: 24684970
Endometrial carcinoma; Estrogen receptor; Progesterone receptor
24.  Prognostic value of miR-96 in patients with acute myeloid leukemia 
Diagnostic Pathology  2014;9:76.
Objective
Aberrant expression of miRNA (miR)-96 is associated with tumorigenesis and tumor progression in several solid cancers. However, little is known about the expression and prognostic value of miR-96 in acute myeloid leukemia (AML). Therefore, the aim of this study was to investigate the correlation of miR-96 expression with clinicopathological features and prognosis of AML.
Methods
Real-time quantitative RT-PCR assay was performed to evaluate the expression levels of miR-96 in mononuclear cells from bone marrow or peripheral blood specimens in 86 patients with newly diagnosed AML.
Results
Compared with normal controls, miR-96 expression was significantly downregulated in patients with newly diagnosed AML (P < 0.001). In analysis of 14 diagnosis/CR-paired samples, the expression level of miR-96 was found markedly elevated in patients after treatment than before (P < 0.001). Moreover, lower levels of miR-96 were associated with a higher white blood cell count, bone marrow blast count (P < 0.001 and 0.022, respectively), and lower hemoglobin and platelet count (P = 0.036 and 0.033, respectively). Although the low-expression group seemed to have a lower CR rate (53.85% vs 70.0%), there was no significant difference between the two groups (P = 0.213). The low-expression group had a lower relapse-free survival (RFS) (P = 0.038) and overall survival (OS) (P = 0.022) compared with the high-expression group during a median follow-up of 20 months.
Conclusion
Our data demonstrated that the expression of miR-96 was downregulated in newly diagnosed AML patients and associated with leukemic burden, as well as RFS and OS. This suggests that miR-96 detection might become a potential biomarker of prognosis and monitoring in AML.
Virtual slides
The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/1434808553949498
doi:10.1186/1746-1596-9-76
PMCID: PMC3975266  PMID: 24678958
miR-96; Acute myeloid leukemia; Real-time quantitative RT-PCR assay; Prognosis
25.  Two cases of multiple ossifying fibromas in the jaws 
Diagnostic Pathology  2014;9:75.
Background
The clinicopathologic characteristics of multiple ossifying fibroma (OF) are unclear due to the condition’s rarity, making diagnosis challenging. Sporadic multiple OFs must be distinguished from hyperparathyroidism-jaw tumour syndrome (HPT-JT) related OF and other fibro-osseous lesions.
Methods
Multiple OF cases were identified from ossifying fibroma cases. Clinical data including age, sex, anatomic site, radiographic features, clinical impression, treatment and available follow-up data as well as serum calcium, phosphorus, and parathyroid hormone (PTH) were recorded. GNAS and HRPT2 genetic mutations were examined in the two present cases. Case reports of sporadic multiple ossifying fibroma and HPT-JT-related OF were also reviewed.
Results
The two present cases were confirmed as sporadic multiple OF, with no genetic GNAS and HRPT2 mutations found. The incidence of sporadic multiple ossifying fibroma was 2.0% (2/102). The total 18 sporadic multiform OF cases were characterized as followed: 13 (72.2%) female; 5 (27.8%) male; mean age 28.6 years; 2/16 (11.1%) cases only in the mandible; 4/18 (22.2%) cases only in the maxilla; and 12/18 (66.7%) cases in both the maxilla and mandible. Radiographically, the lesions were radiolucent in 5/18 (27.8%) cases and mixed density in 13/18 (72.2%) cases. Along with 24 cases of HPT-JT related OF were reviewed, sixteen (66.7%) patients were diagnosed with a single lesion, and 8 patients (33.3%) were diagnosed with multiple jaw lesions.
Conclusions
Sporadic multiple OFs are very rare, but must be distinguished from HPT-JT related OF. We strongly recommend that patients diagnosed with multiple ossifying fibromas receive serum PTH testing and mutation screening of HRPT2.
Virtual slides
http://www.diagnosticpathology.diagnomx.eu/vs/1194507146115753
doi:10.1186/1746-1596-9-75
PMCID: PMC3974450  PMID: 24678936
Multiple ossifying fibroma; HPT-JT; Fibrous dysplasia; GNAS gene; HRPT2 gene; Osseous dysplasia

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