Classical Hodgkin lymphoma (CHL) is a lymphoproliferative disorder that has a bimodal age distribution, affecting young and elderly individuals, and is curable in more than 90% of patients. Here we report the coexistence of cutaneous CHL and malignant melanoma as the presentation of papules and a plaque, in an individual with remote history of systemic CHL. One of the biopsies showed a mononuclear cell infiltrate with Reed-Sternberg (RS) like cells that were positive for CD30 and CD15, but negative for CD45. A second concurrent biopsy showed an atypical melanocytic proliferation with significant pagetoid spreading and diffuse Melan-A staining. Based on morphology alone, it is almost impossible to distinguish CHL from other primary cutaneous lymphoproliferative disorders, such as CD30+ lymphoproliferative disorder (lymphomatoid papulosis (LyP) and primary cutaneous anaplastic large-cell lymphoma), or even tumor stage mycosis fungoides when the epidermotropism is minimal. Additionally, bizarre melanocytic cells can also appear similar to RS cells. Our case illustrates the first case report of malignant melanoma and CHL in a patient presenting simultaneously.
The virtual slide(s) for this article can be found here:
Malignant melanoma; Classical Hodgkin lymphoma; Bone marrow transplant
Cancers have a multifactorial etiology a part of which is genetic. Recent data indicate that expression of the tight junction claudin proteins is involved in the etiology and progression of cancer.
To explore the correlations of the tight junction proteins claudin-2,-6, and −11 in the pathogenesis and clinical behavior of gastric cancer, 40 gastric cancer tissues and 28 samples of non-neoplastic tissues adjacent to the tumors were examined for expression of claudin-2,-6, and −11 by streptavidin-perosidase immunohistochemical staining method.
The positive expression rates of claudin-2 in gastric cancer tissues and adjacent tissues were 25% and 68% respectively (P < 0.001). The positive expression rates of claudin-6 in gastric cancer tissues and adjacent tissues were 55% and 79% respectively (P = 0.045 < 0.05). In contrast, the positive expression rates of claudin-11 in gastric cancer tissues and gastric cancer adjacent tissues were 80% and 46% (P = 0.004 < 0.01). Thus in our study, the expression of claudin-2, and claudin-6 was down regulated in gastric cancer tissue while the expression of claudin-11 was up regulated. Correlations between claudin expression and clinical behavior were not observed.
Our study provides the first evidence that claudin-2,-6, and −11 protein expression varies between human gastric cancers and adjacent non-neoplastic tissues.
The virtual slide(s) for this article can be found here:
Gastric cancer; Tight junctions; Claudin-2; Claudin-6; Claudin-11; Immunohistochemistry
This study presents an extremely rare case of constrictive bronchiolitis obliterans (BO) associated with Stevens-Johnson Syndrome (SJS) provides the morphological and immunohistochemical features using histopathological bronchial reconstruction technique. A 27-year-old female developed progressive dyspnea after SJS induced by taking amoxicillin at the age of 10. Finally, she died of exacerbation of type II respiratory failure after 17 years from clinically diagnosed as having BO. Macroscopic bronchial reconstruction of the whole lungs at autopsy showed the beginning of bronchial obliterations was in the 4th to 5th branches, numbering from each segmental bronchus. Once they were obliterated, the distal and proximal bronchi were dilated. Microscopic bronchial reconstruction demonstrated the localization of obliteration was mainly from small bronchi to membranous bronchioli with intermittent airway luminal narrowing or obliteration. Moreover, CD3-, CD20-, and CD68-positive cells were found in the BO lesions. CD34- and D2-40-positive cells were mainly distributed in the peribronchiolar lesions and bronchiolar lumens, respectively. SMA- and TGF-β-positive cells were seen in the fibrous tissue of BO lesions.
The virtual slides
The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/1071703140102601.
Stevens-Johonson syndrome; Bronchiolitis obliterans; Constrictive bronchiolitis obliterans; Bronchial reconstruction; Immunohistochemistry
Hepatocellular carcinoma (HCC) is one of the most common cancers in the world,and the identification of biomarkers for the early detection is a relevant target. The purpose of the study is to discover specific low molecular weight (LMW) serum peptidome biomarkers and establish a diagnostic pattern for HCC.
We undertook this pilot study using a combined application of magnetic beads with Matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) technique and ClinPro Tools v2.2 to detect 32 patients with HCC, 16 patients with chronic hepatitis (CH), 16 patients with liver cirrhosis (LC) and 16 healthy volunteers.
The results showed 49, 33 and 37 differential peptide peaks respectively appeared in HCC, LC and CH groups. A Supervised Neural Network (SNN) algorithm was used to set up the classification model. Eleven of the identified peaks at m/z 5247.62, 7637.05, 1450.87, 4054.21, 1073.37, 3883.64, 5064.37, 4644.96, 5805.51, 1866.47 and 6579.6 were used to construct the peptides patterns. According to the model, we could clearly distinguish between HCC patients and healthy controls as well as between LC or CH patients and healthy controls.
The study demonstrated that a combined application of magnetic beads with MALDI-TOF MB technique was suitable for identification of potential serum biomarkers for HCC and it is a promising way to establish a diagnostic pattern.
The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/1503629821958720.
Hepatocellular carcinoma; Chronic hepatitis; Liver cirrhosis; Magnetic beads; Matri-assisted laser desorption/ionization time-of-flight mass spectrometry; Serum biomarkers
STAT is the backward position of cytokine and growth factor receptors in the nucleus, STAT dimers could bind to DNA and induce transcription of specific target genes. Several lines of evidence support the important roles of STAT, especially STAT5, in carcinogenesis. The overexpression of STAT 5 is related to the differentiation and apoptosis of tumor cells. However, the role of STAT5 in esophageal squamous cell carcinoma remains unclear.
The siRNA vectors aiming to STAT5 gene were constructed. STAT5 siRNA was transfected into Eca-109 cells by Lipofectamine™2000. Expression of STAT5、Bcl-2 and Cyclin D1 were analyzed by Western blot and RT-PCR. Eca-109 cells proliferation was determined by MTT. Eca-109 cell cycle and apoptosis were detected by the flow cytometry. Boyden chamber was used to evaluate the invasion and metastasis capabilities of Eca-109 cells.
The double strands oligonucleotide of siRNA aiming to STAT5 was successfully cloned into the pRNAT-U6.1 vector, and the target sequence coincided with the design. RT-PCR and Western blotting detection demonstrated that the expression levels of STAT5、Bcl-2 and Cyclin D1 gene were obviously decreased in Eca-109 cells transfected with STAT5 siRNA. STAT5 siRNA could suppress the proliferation of Eca-109 cells. The proportion of S and G2/M period frequency was significantly decreased (p < 0.05). The proportion of G0/G1 period frequency was significantly increased (p < 0.05). The average amount of cells penetrating Matrigel was significantly decreased (p < 0.05).
STAT5 silenced by siRNA could induce the apoptosis and suppress the proliferation、invasion and metastasis of esophageal carcinoma cell line Eca-109, which indicated STAT5 might be a novel therapeutic strategy for the human ESCC.
The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/1351913072103000
STAT5; siRNA; Proliferation; Cell cycle; Apoptosis
The virtual slide(s) for this article can be found here:
Since first reported in 1986, 14 cases of extrauterine adenomyoma have been
reported in the English literature, most often occurring in the ovaries. In this
report, we present the first case of extrauterine adenomyoma involving the liver
in a 29-year-old woman who presented with a 2-year history of low back pain with
recent worsening and a history of laparoscopic myomectomy 5 years
previously. Gross inspection of the specimen revealed a subcapsular mass that
had a well-circumscribed margin with the adjacent liver tissue. By
histopathologic examination, the multilobular mass was composed of a smooth
muscle component and benign endometrioid glands and stroma. The smooth muscle
component was focally cellular, and the endometrioid glands had secretory
features. Both the smooth muscle component and endometrioid tissue were positive
for ER and PR. The smooth muscle component was also positive for desmin and SMA,
while the endometrioid stroma was positive for CD10. Other extrauterine lesions
composed of a mixture of smooth muscle tissue and heterotopic endometrioid
tissue, including endometriosis with a smooth muscle component,
leiomyomatosis/leiomyomas associated with endometriosis and uterus-like masses,
should be included in differential diagnoses. The patient was free from
recurrence 5 months after liver tumor resection.
Extrauterine adenomyoma; Liver; Differential diagnosis; Pathogenesis
Coactivator-associated arginine methyltransferase 1 (CARM1) belongs to the protein arginine methyltransferase family. CARM1 has been reported to be associated with high grade tumors in breast cancer. It still remains unknown the expression pattern of CARM1 in breast cancer and its relationships with clinicopathological characteristics and molecular subtypes.
Two hundred forty-seven invasive breast cancer cases were collected and prepared for tissue array. There were thirty-seven tumors with benign glandular epithelium adjacent to the tumors among these cases. Molecular subtype and CARM1 expression were investigated using immunohistochemistry.
Cell staining was observed in the cytoplasm and/or nucleus. Staining for CARM1 was significantly stronger in adenocarcinoma compared with adjacent benign epithelium. There is a significant correlation between CARM1 overexpression with young age, high grade, estrogen receptor (ER) and progesterone receptor (PR) negative, increased p53 expression, and high Ki-67 index. Our study demonstrated CARM1 overexpression was associated with an increase in the protein expression of HER2. Furthermore, our data indicated CARM1-overexpression rate were remarkably higher in HER2 subtype (69.6%), luminal B subtype (59.6%) and TN subtype (57.1%) compared with luminal A subtype (41.3%).
CARM1 expression was increased in invasive breast cancer. CARM1 overexpression was associated with poorly characterized clinicopathologic parameters and HER2 overexpression. There were significant differences between different molecular subtypes in their relationship to CARM1 overexpression. Our results support the value of using CARM1 in prognostic stratification of breast cancer patients and its potential therapeutic implications in targeting treatment.
The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/4116338491022965
CARM1; Breast cancer; Clinicopathologic parameters; HER2; Molecular subtype
Intra-abdominal fibromatosis (IAF) commonly develops in patients who had abdominal surgery. In rare instances, it occurs subsequent to gastrointestinal stromal tumor (GIST). This special situation has clinical significance in imatinib era. About 1000 patients with GIST in our institution from 1993 to 2010 were re-evaluated based on their clinical and pathological data, the treatment strategies and the follow-up information. We identified 2 patients who developed IAF after GIST resection. Patient 1 was a 54 year-old male and had 5 cm × 4.5 cm × 3.5 cm jejunal GIST excised on February 22, 1994. Three years later, an abdominal mass with 7 cm × 6 cm × 3 cm was identified. He was diagnosed as recurrent GIST from clinical point of view. After excision, the second tumor was confirmed to be IAF. Patient 2 was a 45-year-old male and had 6 cm × 4 cm × 3 cm duodenal GIST excised on August 19, 2008. One year later, a 4 cm mass was found at the original surgical site. The patient refused to take imatinib until the tumor increased to 8 cm six months later. The tumor continued to increase after 6 months’ imatinib therapy, decision of surgical resection was made by multidisciplinary team. The second tumor was confirmed to be IAF with size of 17 cm × 13 cm × 11 cm. Although IAF subsequent to GIST is very rare, it is of clinical significance in imatinib era as an influencing factor for making clinical decision.
The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/1076715989961803
GIST; Intra-abdominal fibromatosis (IAF); Imatinib
The novel pandemic A (H1N1) pdm09 virus was first identified in Mexico in April 2009 and since then it spread worldwide over a short period of time. Although the virus infection is generally associated with mild disease and a relatively low mortality, it is projected that mutations in specific regions of the viral genome, especially within the receptor binding domain of the haemagglutinin (HA) protein could result in more virulent virus stains, leading to a more severe pathogenicity.
To monitor the genetic polymorphisms at position 222 of Haemagglutinin of influenza A(H1N1)pdm09 viruses from both outpatients with mild influenza and individuals with severe disease requiring hospitalization, during 2009–2010 and 2010–2011 seasons, a sequence-based genotypic assessment of viral populations to understand the prevalence of D222G mutation.
The D222G was identified in clinical specimens from 3 out of 42 cases analyzed in Tunisia with severe outcome (7%). Interestingly, in one fatal case out of four viruses taken from fatal cases studied (25%). Also this mutation was found in one mild case out of 8 mild cases studied (0.1%). D222E substitution was found in virus taken from one patient with severe clinical syndrome (2%) out of 42 severe cases analyzed and E374K substitution was found in two severe cases (4%) out of 42 severe cases studied.
A specific mutation in the viral haemagglutinin (D222G) was found in fatal, severe and mild case. Further virological, clinical and epidemiological investigations are needed to ascertain the role of this and other mutations that may alter the virulence and transmissibility of the pandemic influenza A (H1N1)pdm09.
The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/1027334947811255
D222G substitution; Haemagglutinin; Influenza A(H1N1)pdm09 virus; Pandemic; Severe respiratory infection
Spinal motoneuron neuroprotection by vitaminB12 was previously reported; the present study was carried out to evaluate neuroprotectivity in the dorsal root ganglion sensory neuron.
In present study thirty-six Wister-Albino rats (aged 8–9 weeks and weighing 200–250 g) were tested. The animals were randomly divided into 6 groups which every group contained 6 rats. Group A: received normal saline (for 42 days); Group B: vitamin B12 was administered (0.5 mg/kg/day for 21 days); Group C: received vitamin B12 (1 mg/kg/day for 21days); Group D: received vitamin B12 (0.5 mg/kg/day for 42 days); Group E; received vitamin B12 (1 mg/kg/day for 42 days); Group F; received no treatment. The L5 Dorsal Root Ganglion (DRG) neurons count compared to the number of left and right neurons .Furthermore, DRG sensory neurons for regeneration were evaluated 21 or 42 days after injury (each group was analyzed by One-Way ANOVA test).
(1): The comparison of left crushed neurons (LCN) number with right non-crushed neurons in all experimental groups (B, C, D and C), indicating a significant decline in their neurons enumeration (p<0/05). (2): The comparison of test group’s LCN with the control group’s LCN revealed a significant rise in the number of experimental group neurons (p<0/05). (3): Moreover, comparing the number of right neurons in experimental groups with the number of neurons in crushed neurons indicated that the average number of right neurons showed a significant increase in experimental groups (p<0/05).
Consequently, the probability of nerve regeneration will be increased by the increment of the administered drug dosage and duration. On the other hand, the regeneration and healing in Dorsal Spinal Ganglion will be improved by increase of administration time and vitamin B12 dose, indicating that such vitamin was able to progress recovery process of peripheral nerves damage in experimental rats. Finally, our results have important implications for elucidating the mechanisms of nerve regeneration. Moreover, the results showed that vitaminB12 had a proliferative effect on the dorsal root ganglion sensory neuron.
The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/7395141841009256
Dorsal root ganglion; Rat; Surgery; Sciatic nerve; Vitamin B12
The histological grade is the gold standard for the evaluation of prognosis of astrocytic tumors. Nevertheless, morphologic criteria are not always accurate prognostic indicators.
The research investigates the expression of MIB-1 and DJ-1 in different grades of astrocytomas and evaluates the possible prognostic role of DJ-1 in these tumors in relation to other prognostic parameters including the MIB-1 labeling index.
Materials and methods
Immunohistochemical expression of MIB-1 and DJ-1 was evaluated in 111 samples of astrocytic tumors comprising 28 diffuse astrocytomas, 38 anaplastic astrocytomas and 45 glioblastomas. The univariate survival analysis was done using the Kaplan-Meier method and the multivariate survival analysis was done using Cox proportional hazard model.
The statistical analysis revealed a significant correlation between each of DJ-1 and MIB-1 and the histological grade of astrocytomas. The univariate analysis showed that high grade, high DJ-1 score and MIB-1 labeling index ≥ 10.1 were associated with poor survival. Multivariate analysis for all the studied astrocytomas proved the independent prognostic significance of the histological grade and DJ-1 score. Meanwhile, the multivariate analysis for each grade emphasized that DJ-1 was the only independent prognostic indicator in high-grade astrocytomas.
This study emphasized the effectiveness of high DJ-1 expression in predicting poor survival of astrocytoma patients, when compared to MIB-1. DJ-1 could be particularly important in cases with discrepancies between the morphologic criteria and clinical parameters.
The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/1070116023943146
DJ-1; MIB-1; Immunohistochemistry; Prognosis; Astrocytoma
The “proximal-type” epithelioid sarcoma is a very rare kind of mesenchimal tumor characterized by the difficulty in histological diagnosis and the very aggressive biological behavior.
We report of a case of a 63 years old woman with a vulvar “proximal-type” epithelioid sarcoma that underwent a radical surgical staging followed by an adjuvant radiotherapy. She is on follow-up care for 14 months and there is no clinical evidence of disease.
Even if quite rare the proximal type epithelioid sarcoma should be regarded as a separate entity of particularly aggressive biologic behaviour. Its diagnosis attracts controversies and criticism related to the surgical approach and the choice of an adjuvant therapy.
The virtual slide(s) for this article can be found here:
Vulvar “proximal-type” epithelioid sarcoma; Radical vulvectomy; Vulvar cancer
BRAF mutation is an important diagnostic and prognostic marker in patients with papillary thyroid carcinoma (PTC). To be applicable in clinical laboratories with limited equipment, diverse testing methods are required to detect BRAF mutation.
A shifted termination assay (STA) fragment analysis was used to detect common V600 BRAF mutations in 159 PTCs with DNAs extracted from formalin-fixed paraffin-embedded tumor tissue. The results of STA fragment analysis were compared to those of direct sequencing. Serial dilutions of BRAF mutant cell line (SNU-790) were used to calculate limit of detection (LOD).
BRAF mutations were detected in 119 (74.8%) PTCs by STA fragment analysis. In direct sequencing, BRAF mutations were observed in 118 (74.2%) cases. The results of STA fragment analysis had high correlation with those of direct sequencing (p < 0.00001, κ = 0.98). The LOD of STA fragment analysis and direct sequencing was 6% and 12.5%, respectively. In PTCs with pT3/T4 stages, BRAF mutation was observed in 83.8% of cases. In pT1/T2 carcinomas, BRAF mutation was detected in 65.9% and this difference was statistically significant (p = 0.007). Moreover, BRAF mutation was more frequent in PTCs with extrathyroidal invasion than tumors without extrathyroidal invasion (84.7% versus 62.2%, p = 0.001). To prepare and run the reactions, direct sequencing required 450 minutes while STA fragment analysis needed 290 minutes.
STA fragment analysis is a simple and sensitive method to detect BRAF V600 mutations in formalin-fixed paraffin-embedded clinical samples.
The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/5684057089135749
BRAF; Mutation; Termination assay; Sequencing; Thyroid; Papillary carcinoma
Collecting duct carcinoma (CDC) with a mass of coagulative necrosis is very rare. We report here a case of CDC with extensive geographic coagulative necrosis mimicking anemic infarct with tumor cells embedded around the necrotic foci in a 73-years-old man. Histopathological examination showed that tumor nests near the necrotic foci were arranged as angulated tubules, tubulopapillary and glandular structures. Neoplastic cells had moderate to abundant eosinophilic cytoplasm and large hyperchromatic nuclei with prominent nucleoli as Fuhrman nuclear grade 3 or 4. The tumor cells were positive for pan-Cytokeratin, Vimentin, E-cadherin, CD10, and CK7, confirming the diagnosis as CDC. The patient is still alive 6 months later from nephrectomy, a long time following up is needed to learn the prognosis. Conclusively, morphology from different portions of the lesion, immunohistochemical stain and the combination analysis of the radiological features is essential to make a precise pathological diagnosis of CDC. And CDC should also be distinguished from clear cell renal cell carcinoma, renal medullary carcinoma, urothelial carcinoma with glandular differentiation, renal neuroendocrine tumor, renal epithelioid angiomyolipoma, renal pigmented paraganglioma and renal mesenchymal chondrosarcoma etc.
The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/1264270525975030
Collecting duct carcinoma (CDC); Renal epithelial tumors; Extensive coagulative necrosis; Anemic infarct; Differential diagnosis
Primary lymphoepithelial-like carcinoma of the parotid gland is a rare tumour with an increased incidence among Eskimos and Orientals. In these populations, it is usually associated with Epstein-Barr virus. In Western countries, salivary gland lymphoepithelial-like carcinomas are uncommon and only 14 cases have been described so far; among these, only five cases showed Epstein-Barr virus positivity.
A 45-year-old woman was admitted to Siena Hospital for evaluation of a pre-existent (2 years) painless and tender submandibular mass, rapidly enlarging since two months. On physical examination, a 2.5-cm mass was found in the right parotid. It was firm, mobile and non-tender. Laboratory data were within reference range. Nuclear magnetic resonance detected a 2,5×1,5×1-cm well-circumscribed mass in the deep lobe of the right parotid. A total right paroditectomy with dissection of a satellite lymph node was performed. On the basis of morphological, immunohistochemical and molecular biology findings, a diagnosis of stage II (according to TNM7) Epstein Barr-virus positive, undifferentiated lymphoepithelial-like carcinoma of the parotid gland was made. Twenty months after surgery the patient was free of disease.
Further studies seem to be necessary to completely elucidate the oncogenic role of Epstein Barr-virus in these tumors, which have identical morphology but different prognosis and variable presence of the virus.
The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/1260381551000616
The polymorphism Pro12Ala in peroxisome proliferator-activated receptorγ2 gene (PPARγ2) has been reported to be associated with diabetic nephropathy (DN) in some studies, though the results remain inconclusive. To explore this relationship between PPARγ2 Pro12Ala polymorphism and the susceptibility for DN, a cumulative meta-analysis was performed in this study.
PubMed, Medline, Embase and Web of Science databases have been systematically searched to identify relevant studies. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated.
18 studies were included in this meta-analysis, involving 3,361 cases and 5,815 controls. The PPARγ2 Ala12 allele was significantly associated with decreased risk of DN based on dominant model (OR=0.778; 95%CI=0.618–0.981; Pheterogeneity=0.008; P=0.034). In the stratified analysis by ethnicity, significantly decreased risks were found among Caucasians for dominant model (OR=0.674; 95%CI=0.500–0.909; Pheterogeneity=0.079; P=0.010), while there was no significant association was found in Asians.
The results from the present meta-analysis indicated that the Pro12Ala polymorphism in PPARγ2 gene is not a risk factor for DN in type 2 diabetes (T2D). Further large and well-designed studies are needed to confirm this conclusion.
The virtual slides for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/7491348341027320.
PPARγ2; Meta-analysis; Diabetic nephropathy; Polymorphisms
We observed an unusual case of Lipofibroadenoma (LFA) in the anterior mediastinum with a 21-year-old man, who was detected with a mass on a chest X-ray scan for one month. Thymothymectomy was then performed and the mass was excised completely, in which the tumor was histologically composed of epithelial cells, lymphocytes, mature adipose and fibrous tissue. Within the tumor, the fat cells was distributed singly or multifocally under the ground of fibro tissue with hyaline degeneration, and the epithelial cells were arranged as crack structure with lymphocytes infiltrated sparsely. By immunohistochemical staining assay, the epithelial cells were positive for AE1/AE3 and CK19, and the lymphocytes were CD3 and CD20 positive. Based on the histological characters, a diagnosis of LFA was made, and the total follow-up period was determined to be forty six months. The final repeated CT scan revealed no recurring or residual lesions were detected during the post-surgical course.
The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/1500429801911703
Lipofibroadenoma; Thymic tumor
Lymphomas account for less than 5% of thyroid malignant lesions. Vast majority of them are B-cell non-Hodgkin lymphomas (NHL), while Hodgkin lymphoma (HL) is extremely rare. Here we present two cases of HL, at baseline manifesting as a thyroid lesion. First patient, 29-year-old pregnant female, initially suspected for metastatic medullary thyroid cancer, was eventually diagnosed with mixed cellularity type of thyroid HL. Second patient, 22-year-old woman with suspicion of advanced thyroid cancer, was in the end diagnosed with an extra-lymphatic classical HL of the thyroid. In both cases, despite repeated fine-needle aspiration biopsy, cytological examination gave inconclusive or misleading results. On histopathological examination, thyroid tumor cells were positive for CD15 and CD30 antigen, which is typical for Reed-Sternberg cells. In the report authors also discuss difficulties in management as well as potential importance of novel methods such as FISH, PCR and other molecular techniques in diagnostics of thyroid lymphomas.
The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/2896947559559648
Thyroid nodule; Hodgkin lymphoma; Fine-needle aspiration biopsy (FNAB); Reed-Sternberg cells
The distinction between lobular neoplasia of the breast and ductal carcinoma in situ has important therapeutic implications. In some cases, it is very difficult to determine whether the morphology of the lesion is ductal or lobular. The aim of this study was to evaluate the value of E-cadherin and β-catenin expression through the immunophenotypical characterization of carcinoma in situ with mixed pattern (CISM).
A total of 25 cases of CISM were analyzed considering cytology/mixed architecture (ductal and lobular), nuclear pleomorphism, loss of cell cohesion, and presence of comedonecrosis. The immunophenotype pattern was considered E-cadherin positive and β-catenin positive, or negative.
Nineteen (76%) cases presented a mixed cytology and / or architectural pattern, two (8%) presented nuclear pleomorphism, two (8%) presented mixed cytology and nuclear pleomorphism, and two (8%) presented comedonecrosis and nuclear pleomorphism. A complete positivity for E-cadherin and β-catenin was observed in 11 cases (44%). In one case, the lesion was negative for both markers and showed nuclear pleomorphis. Thirteen lesions showed negative staining in areas of lobular cytology and positive staining in cells presenting the ductal pattern.
The expression of E-cadherin and β-catenin, combined with cytological and architectural analysis, may highlight different immunophenotypes and improve classification of CISM.
The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/1693384202970681
E-cadherin; β-catenin; Breast cancer; Lobular neoplasia; Ductal carcinoma in situ; Immunohistochemistry
The early phase of salivary gland carcinomas with high-grade transformation (HGT) is extremely rare. We reported one case of adenoid cystic carcinoma (AdCC) with early HGT, herein.
The patient was a 27-year-old Japanese woman who suffered from swelling of the left parotid region. Most of this tumor consisted of typical AdCC histology, whereas the central area of this tumor was composed of solid growth component by atypical cells with clear cytoplasm and marked nuclear atypia. Immunohistochemically, this area was strongly and diffusely positive for epithelial membrane antigen, p53, p16, Her-2, cyclin A and cyclin B1. The Ki-67 labeling index of this area was high, entirely different from that of AdCC area.
Overall, this area was an early phase of AdCC-HGT. This case is the second case of early AdCC-HGT. We discuss the development of salivary gland carcinoma with HGT.
High-grade Transformation; Adenoid Cystic Carcinoma; Salivary Gland; Early Phase; Immunohistochemstry
Gastric carcinoma development is a multi-stage process that involves more than one gene. Aberrant changes in DNA methylation are considered as the third mechanism that leads to anti-oncogene inactivation, which plays an essential role in tumor development. In this study, we assessed the relationship among the aberrant methylation of the promoter CpG islands of tissue inhibitor of metalloproteinase 3 (TIMP3) gene, its protein expression, and the clinicopathological features of gastric adenocarcinoma.
The methylation status of the promoter CpG islands and the protein expression of TIMP3 gene in tumors and adjacent normal mucosal tissues of 78 patients with gastric adenocarcinoma were detected by methylation-specific PCR (MSP) and immunohistochemistry.
The CpG island methylation of TIMP3 was detected in tumor tissues, cancer-adjacent tissues, and lymph nodes with metastasis. In increasing order, the hypermethylation frequency of these tissues were 35.9% (28 of 78 non-neoplastic tissues), 85% (17 of 20 early-stage cases), 89.7% (52 of 58 progressive-stage cases), and 100% (78 of 78 metastatic lymph node). A marked difference was found between tumors and non-neoplastic tissues (P < 0.05), but no difference existed among the subgroups of tumors (P > 0.05). Immunohistochemistry analysis confirmed TIMP3 down-regulation in tumor tissues. The rate of TIMP3 gene expression was 100% in non-neoplastic tissues but apparently decreased to various extents at different stages, i.e., decreased to 30% (6/20) at the early stage, to 3.4% (2/58) at the progressive stage, and to 0% (0/78) in metastatic lymph nodes. Among the 70 tumor tissues with negative TIMP3 expression, 64 (91.4%) were hypermethylated and 6 were unmethylated (8.6%), indicating a significant association between hypermethylation and reduced or negative TIMP3 expression (P < 0.01).
The hypermethylation of the promoter region in CpG islands is the main mechanism of TIMP3 gene expression and may provide evidence for the molecular diagnosis and stage evaluation of gastric cancer.
The virtual slides for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/1756134016954958
Gastric Adenocarcinoma; Tissue Inhibitor of Metalloproteinase 3 (TIMP3); Methylation
Numerous epidemiological studies have been conducted to explore the association between the Lys939Gln polymorphism of Xeroderma pigmentosum group C (XPC) gene and urinary bladder cancer susceptibility. However, the results remain inconclusive. In order to derive a more precise estimation of this relationship, a large and update meta-analysis was performed in this study.
A comprehensive search was conducted through researching MEDLINE, EMBASE, PubMed, Web of Science, China Biomedical Literature database (CBM) and China National Knowledge Infrastructure (CNKI) databases before June 2013. Crude odds ratios (ORs) with 95% confidence intervals (CIs) were calculated to estimate the strength of the association.
A total of 12 studies with 4828 cases and 4890 controls for evaluating the XPC Lys939Gln polymorphism and urinary bladder cancer were included. Overall, there was significant associations between the XPC Lys939Gln polymorphism and urinary bladder cancer risk were found for homozygous model (OR = 1.352, 95% CL = 1.088-1.681), heterozygous model (OR = 1.354, 95% CL = 1.085-1.688), and allele comparison (OR = 1.109, 95% CL = 1.013-1.214). In subgroup analysis by ethnicity and source of controls, there were still significant associations detected in some genetic models.
Our meta-analysis suggested that the XPC Lys939Gln polymorphism contributed to the risk of urinary bladder cancer.
The virtual slide(s) for this article can be found here: .
Bladder cancer; XPC; Polymorphism; Susceptibility; Meta-analysis
Thyroid-like follicular carcinoma of the kidney (TLFC), a rare neoplasm with low malignant potential, is histologically similar to primary thyroid follicular carcinoma, but characteristically lacks thyroid immunohistochemical markers. We report a case of 34-year old patient with nephrolithiasis. Ultrasound revealed hepatorenal cysts consistent with adult type polycystic kidney disease (ATPKD) and a cytologically confirmed left kidney tumor. Nephrectomy specimen contained sharply demarcated lesion of unusual morphology. Tubular and cystic structures lined by mostly cuboidal cells and filled with amorphous eosinophillic material, reminiscent of follicular carcinoma of the thyroid gland, were diagnostic for TLFC. Thyroid markers were negative. To our knowledge this is the first report of TFLC associated to ATPKD. Brief review of previously published TFLCs, possible relationship between entities and differential diagnosis are discussed.
The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/8067946569612694
Renal cell carcinoma; Thyroid-like follicular carcinoma; Pathology-cytology; Immunohistochemistry; Polycystic kidney disease
Previous studies have shown that membranous expression of podocalyxin-like protein (PODXL) is associated with poor prognosis in colorectal cancer (CRC). In this study, we compared PODXL expression in primary CRC and synchronous lymph node metastases. We further analyzed whether its expression changed in rectal tumours after neoadjuvant radiation therapy.
Methods and results
The studied cohort consists of 73 consecutive patients from the South-Swedish Colorectal Cancer Biobank. Immunohistochemical PODXL expression was examined on full-face sections from all primary tumours and all 140 available lymph node metastases from 31 cases. Membranous PODXL expression was denoted in 18/73 (24,7%) primary tumours, with a high concordance between primary and metastatic lesions. While all negative primary tumours had negative metastases, some PODXL positive primaries had a varying proportion of positive and negative metastatic lymph nodes. PODXL expression was also found to be mainly unaltered in pre- and post-irradiation surgically resected tumour specimens in rectal cancer patients (n=16).
The findings in this study suggest that analysis of PODXL expression in the primary tumour is sufficient for its use as a prognostic and treatment predictive biomarker in CRC, also in patients with metastatic disease.
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