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International Journal of Molecular... Dec 2018Gastric cancer has reduced prevalence, but poor prognoses. To improve treatment, better knowledge of carcinogenesis and cells of origin should be sought. Stomach cancers... (Review)
Review
Gastric cancer has reduced prevalence, but poor prognoses. To improve treatment, better knowledge of carcinogenesis and cells of origin should be sought. Stomach cancers are typically localized to one of the three mucosae; cardial, oxyntic and antral. Moreover, not only the stem cell, but the ECL cell may proliferate and give rise to tumours. According to Laurén, the classification of gastric carcinomas seems to reflect biological important differences and possible different cell of origin since the two subtypes, intestinal and diffuse, do not transform into the other and show different epidemiology. The stem cell probably gives rise to the intestinal type, whereas the ECL cell may be important in the diffuse type. Elevation of gastrin may be the carcinogenic factor for as well as the recently described increased risk of gastric cancer due to proton pump inhibitor treatment. Therefore, it is essential to determine the role of the gastrin target cell, the ECL cell, in gastric carcinogenesis. Clinical trials with gastrin antagonists could improve prognoses in those with gastrin receptor positive tumours. However, further studies on gastric carcinomas applying relative available methods and with the highest sensitivity are warranted to improve our knowledge of gastric carcinogenesis.
Topics: Carcinogenesis; Carcinoma; Cell Proliferation; Gastric Mucosa; Gastrins; Helicobacter Infections; Helicobacter pylori; Humans; Stomach Neoplasms
PubMed: 30567376
DOI: 10.3390/ijms19124109 -
Modern Pathology : An Official Journal... Jan 2021Immunohistochemistry is an essential component of diagnostic breast pathology. The emergence of novel assays and applications is accompanied by new interpretation... (Review)
Review
Immunohistochemistry is an essential component of diagnostic breast pathology. The emergence of novel assays and applications is accompanied by new interpretation criteria and potential pitfalls. Immunohistochemistry assists in supporting breast origin for primary or metastatic carcinomas and identifying non-mammary metastases to the breast; however, no single immunostain is perfectly sensitive nor specific. GATA3 and Sox10 are particularly useful immunostains to identify triple negative breast carcinoma, which are often negative for other markers of mammary differentiation. Sox10 labeling is a major potential diagnostic pitfall, as Sox10 and S-100 label both triple negative breast carcinoma and metastatic melanoma; a pan-cytokeratin immunostain should always be included for this differential diagnosis. Novel immunohistochemistry serves as surrogates for the molecular alterations unique to several of special-type breast carcinomas, including the use of MYB in adenoid cystic carcinoma, pan-TRK in secretory carcinoma, and mutant IDH2 in tall cell carcinoma with reversed polarity (TCCRP). In addition, PD-L1 immunohistochemistry is an emerging, albeit imperfect, biomarker for breast cancer immunotherapy, with different assay parameters and scoring criteria in breast carcinoma compared to other tumor types. The expanding repertoire of novel immunohistochemistry provides additional diagnostic tools and biomarkers that improve diagnostic breast pathology and patient care.
Topics: B7-H1 Antigen; Biomarkers, Tumor; Breast; Breast Neoplasms; Carcinoma; Carcinoma, Adenoid Cystic; Carcinoma, Ductal, Breast; Diagnosis, Differential; Female; GATA3 Transcription Factor; Humans; Immunohistochemistry; SOXE Transcription Factors; Triple Negative Breast Neoplasms
PubMed: 33110239
DOI: 10.1038/s41379-020-00697-3 -
Head and Neck Pathology Mar 2011Papillary thyroid carcinomas are the most common thyroid cancers and constitute more than 70% of thyroid malignancies. The most common etiologic factor is radiation, but... (Review)
Review
Papillary thyroid carcinomas are the most common thyroid cancers and constitute more than 70% of thyroid malignancies. The most common etiologic factor is radiation, but genetic susceptibility and other factors also contribute to the development of papillary thyroid carcinoma. The most common variants include conventional, follicular variant and tall cell variant. However, many other uncommon variants have been described including oncocytic, columnar cell, diffuse sclerosing and solid forms. Immunohistochemical staining with TTF-1 and thyroglobulin is very useful in confirming the diagnosis of papillary thyroid carcinoma especially in metastatic sites. Markers such as HBME-1 and CITED1 can assist in separating some difficult cases of follicular variants of papillary thyroid carcinomas from follicular adenomas. Molecular studies have shown that the BRAF V600E mutation is found mainly in papillary and anaplastic thyroid carcinomas. Other molecular markers such as HMGA2 and insulin-like growth factor II mRNA binding protein 3 have been used recently as molecular tests to separate papillary thyroid carcinoma and its variants from follicular adenomas and other benign thyroid nodules.
Topics: Biomarkers, Tumor; Carcinoma; Carcinoma, Papillary; Carcinoma, Papillary, Follicular; Humans; Immunohistochemistry; Thyroid Cancer, Papillary; Thyroid Neoplasms
PubMed: 21221869
DOI: 10.1007/s12105-010-0236-9 -
Turk Patoloji Dergisi 2015Parathyroid carcinoma is a rare type of endocrine cancer, with significant morbidity and mortality associated with parathyroid hormone (PTH)-mediated hypercalcemia.... (Review)
Review
Parathyroid carcinoma is a rare type of endocrine cancer, with significant morbidity and mortality associated with parathyroid hormone (PTH)-mediated hypercalcemia. Concerning clinical features for parathyroid cancer include severe hypercalcemia (albumin-corrected calcium > 3 mmol/L), a palpable neck mass ( > 3 cm), 3rd/2nd generation PTH assay ratio ( > 1), and intraoperative suspicion of local invasion or regional metastasis. A definite diagnosis of malignancy is rendered when a parathyroid tumor presents one of the following clinicopathological features: (1) vascular invasion, (2) perineural invasion, (3) gross invasion into adjacent anatomical structures, and/or (4) metastasis. In difficult cases, the use of ancillary biomarkers is critical to establish an accurate diagnosis. Recent advances in molecular pathology have uncovered the important role of CDC73/HRPT2, a tumor suppressor gene deregulated in parathyroid carcinomas. Loss of nuclear and/or nucleolar expression of parafibromin (the gene product of CDC73/HRPT2) is now regarded as a diagnostic, prognostic and predictive biomarker for parathyroid carcinoma. Furthermore, over 15-20% of seemingly sporadic parathyroid carcinomas have underlying germline CDC73/HRPT2 mutations. As a result, many centers have integrated the use of ancillary biomarkers, notably parafibromin staining, in their routine practise. Radical surgery with en bloc resection has emerged as a primary treatment modality in parathyroid cancer, achieving cure in some patients. However, in those with inoperable disease, there remains a dire need for new therapies, as current treatments are largely ineffective. This review provides an update on the current knowledge of parathyroid carcinoma and highlights its exciting changes in endocrine practice.
Topics: Biomarkers, Tumor; Biopsy; Carcinoma; DNA Mutational Analysis; Genetic Predisposition to Disease; Humans; Immunohistochemistry; Mutation; Neoplasm Invasiveness; Parathyroid Neoplasms; Phenotype; Predictive Value of Tests; Prognosis; Signal Transduction
PubMed: 26177319
DOI: 10.5146/tjpath.2015.01316 -
World Journal of Gastroenterology Nov 2015The outcome of gallbladder carcinoma is poor, and the overall 5-year survival rate is less than 5%. In early-stage disease, a 5-year survival rate up to 75% can be... (Review)
Review
The outcome of gallbladder carcinoma is poor, and the overall 5-year survival rate is less than 5%. In early-stage disease, a 5-year survival rate up to 75% can be achieved if stage-adjusted therapy is performed. There is wide geographic variability in the frequency of gallbladder carcinoma, which can only be explained by an interaction between genetic factors and their alteration. Gallstones and chronic cholecystitis are important risk factors in the formation of gallbladder malignancies. Factors such as chronic bacterial infection, primary sclerosing cholangitis, an anomalous junction of the pancreaticobiliary duct, and several types of gallbladder polyps are associated with a higher risk of gallbladder cancer. There is also an interesting correlation between risk factors and the histological type of cancer. However, despite theoretical risk factors, only a third of gallbladder carcinomas are recognized preoperatively. In most patients, the tumor is diagnosed by the pathologist after a routine cholecystectomy for a benign disease and is termed ''incidental or occult gallbladder carcinoma'' (IGBC). A cholecystectomy is performed frequently due to the minimal invasiveness of the laparoscopic technique. Therefore, the postoperative diagnosis of potentially curable early-stage disease is more frequent. A second radical re-resection to complete a radical cholecystectomy is required for several IGBCs. However, the literature and guidelines used in different countries differ regarding the radicality or T-stage criteria for performing a radical cholecystectomy. The NCCN guidelines and data from the German registry (GR), which records the largest number of incidental gallbladder carcinomas in Europe, indicate that carcinomas infiltrating the muscularis propria or beyond require radical surgery. According to GR data and current literature, a wedge resection with a combined dissection of the lymph nodes of the hepatoduodenal ligament is adequate for T1b and T2 carcinomas. The reason for a radical cholecystectomy after simple CE in a formally R0 situation is either occult invasion or hepatic spread with unknown lymphogenic dissemination. Unfortunately, there are diverse interpretations and practices regarding stage-adjusted therapy for gallbladder carcinoma. The current data suggest that more radical therapy is warranted.
Topics: Carcinoma; Cholecystectomy; Gallbladder Neoplasms; Humans; Neoplasm Staging; Risk Factors; Treatment Outcome
PubMed: 26604631
DOI: 10.3748/wjg.v21.i43.12211 -
Turk Patoloji Dergisi 2015Thyroid cancer is the most common endocrine malignancy and its incidence goes on increasing worldwide. The majority of thyroid tumours comprise well-differentiated... (Review)
Review
Thyroid cancer is the most common endocrine malignancy and its incidence goes on increasing worldwide. The majority of thyroid tumours comprise well-differentiated (papillary and follicular) thyroid carcinomas that usually carry an excellent prognosis, while a minority progress to poorly differentiated carcinoma (PDTC) and, ultimately, to the highly aggressive and lethal undifferentiated carcinoma (UTC). Recently, some major advances have been made on the histologic and imunohistochemical identification, as well as on the molecular characterization of PDTC and UTC. In this review we summarize the most recent immunohistochemical and molecular findings in PDTC and UTC, giving a particular emphasis to the diagnostic and prognostic meaning of the genetic alterations.
Topics: Biomarkers, Tumor; Biopsy; Carcinoma; Cell Differentiation; Humans; Immunohistochemistry; In Situ Hybridization, Fluorescence; Molecular Diagnostic Techniques; Predictive Value of Tests; Prognosis; Thyroid Neoplasms
PubMed: 26177317
DOI: 10.5146/tjpath.2015.01314 -
International Journal of Surgery... Mar 2016The incidence of thyroid carcinoma is increasing worldwide. Graves' disease is the most common hyperthyroid disease. Studies have suggested an increased risk of thyroid... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
The incidence of thyroid carcinoma is increasing worldwide. Graves' disease is the most common hyperthyroid disease. Studies have suggested an increased risk of thyroid malignancy in Graves' disease: there has not yet been a meta-analysis to allow quantitative comparison. The purpose of this study was to determine the risk of thyroid carcinoma in Graves' disease, and to gather information on the histological subtypes of carcinoma and the co-existence of thyroid nodules.
METHODS
Several databases and article reference lists were searched. Inclusion criteria included appropriate diagnostic criteria for thyroid conditions and a diagnoses of carcinoma based on histology.
RESULTS
33 studies were selected, all reporting on surgically-resected specimens. The event rate of thyroid carcinoma in Graves' disease was 0.07 (95% CI 0.04 to 0.12). There was no data to allow comparison with patients without hyperthyroid diseases. There was no increase in the odds of developing carcinoma in Graves' disease compared to toxic multinodular goitre and toxic uninodular goitre. 88% of thyroid carcinomas in Graves' disease were papillary, with solitary papillary micro-carcinoma (diameter 10 mm or less) comprising 23% of all detected thyroid carcinomas. Patients with Graves' disease and co-existing thyroid nodules were almost 5 times more likely to be diagnosed with thyroid carcinoma than those without nodules.
CONCLUSION
Thyroid malignancy in Graves' disease requiring surgical treatment should be considered as likely as in other hyperthyroid diseases needing surgical treatment. Clinicians should consider screening selected patients with Graves' disease for nodules whilst being aware of potentially over-diagnosing papillary micro-carcinoma.
Topics: Adult; Carcinoma; Carcinoma, Papillary; Female; Graves Disease; Humans; Incidence; Male; Odds Ratio; Thyroid Neoplasms; Thyroid Nodule
PubMed: 26626367
DOI: 10.1016/j.ijsu.2015.11.027 -
Clinical Cancer Research : An Official... Apr 2019Cutaneous squamous cell carcinoma (cSCC) and basal cell carcinoma (BCC) are keratinocyte carcinomas, the most frequently diagnosed cancers in fair-skinned populations.... (Review)
Review
Cutaneous squamous cell carcinoma (cSCC) and basal cell carcinoma (BCC) are keratinocyte carcinomas, the most frequently diagnosed cancers in fair-skinned populations. Ultraviolet radiation (UVR) is the main driving carcinogen for these tumors, but immunosuppression, pigmentary factors, and aging are also risk factors. Scientific discoveries have improved the understanding of the role of human papillomaviruses (HPV) in cSCC as well as the skin microbiome and a compromised immune system in the development of both cSCC and BCC. Genomic analyses have uncovered genetic risk variants, high-risk susceptibility genes, and somatic events that underlie common pathways important in keratinocyte carcinoma tumorigenesis and tumor characteristics that have enabled development of prediction models for early identification of high-risk individuals. Advances in chemoprevention in high-risk individuals and progress in targeted and immune-based treatment approaches have the potential to decrease the morbidity and mortality associated with these tumors. As the incidence and prevalence of keratinocyte carcinoma continue to increase, strategies for prevention, including effective sun-protective behavior, educational interventions, and reduction of tanning bed access and usage, are essential. Gaps in our knowledge requiring additional research to reduce the high morbidity and costs associated with keratinocyte carcinoma include better understanding of factors leading to more aggressive tumors, the roles of microbiome and HPV infection, prediction of response to therapies including immune checkpoint blockade, and how to tailor both prevention and treatment to individual risk factors and needs.
Topics: Carcinoma; Carcinoma, Basal Cell; Carcinoma, Squamous Cell; Cell Transformation, Neoplastic; Disease Management; Disease Susceptibility; Humans; Keratinocytes; Papillomavirus Infections; Primary Prevention; Research; Risk Factors
PubMed: 30523023
DOI: 10.1158/1078-0432.CCR-18-1122 -
Archives of Pathology & Laboratory... Aug 2018- Lung tumors are histologically heterogeneous, but classification of lung carcinoma has prognostic impact and increasingly, specific molecular correlates. (Review)
Review
CONTEXT
- Lung tumors are histologically heterogeneous, but classification of lung carcinoma has prognostic impact and increasingly, specific molecular correlates.
OBJECTIVE
- To update the gross, microscopic, and molecular pathology of unusual lung carcinomas to assure accurate classification. In entities with mixed histology, the recognition of specific features or rare patterns is critical to diagnosis. These diagnoses can identify tumors with aggressive clinical behavior, and diagnostic pitfalls can therefore result in underdiagnosis of these already rare entities. Incorrect classification of more indolent tumors into the more aggressive categories can also occur. In the area of molecular pathology, these unusual tumors have a specific spectrum of molecular alterations.
DATA SOURCES
- PubMed searches for lung and sarcomatoid carcinoma, pleomorphic carcinoma, blastoma, carcinosarcoma, and adenosquamous and mucoepidermoid carcinoma were undertaken and this information was integrated with clinical experience of the author.
CONCLUSIONS
- These uncommon carcinomas have specific clinicopathologic features, and attention to their gross and microscopic pathology leads to classification with important associated molecular findings.
Topics: Carcinoma; Humans; Lung Neoplasms; Neoplasms, Complex and Mixed
PubMed: 30040455
DOI: 10.5858/arpa.2017-0584-RA -
Expert Opinion on Therapeutic Targets Sep 2008NF-kappaB includes a family of signal-activated transcription factors that normally regulate responses to injury and infection but which are aberrantly activated in many... (Review)
Review
BACKGROUND
NF-kappaB includes a family of signal-activated transcription factors that normally regulate responses to injury and infection but which are aberrantly activated in many carcinomas.
OBJECTIVE
To review the activation and role of NF-kappaB in pathogenesis and as a target for treatment and prevention in carcinoma.
METHODS
Evidence from experimental, epidemiological, preclinical studies and clinical trials cited in the literature are reviewed.
RESULTS/CONCLUSION
Cumulative evidence implicates NF-kappaB in cell survival, inflammation, angiogenesis, spread and therapeutic resistance during tumor development, progression and metastasis of carcinomas. Non-specific natural and synthetic agents that inhibit NF-kappaB have demonstrated activity and safety in prevention or therapy. NF-kappaB-activating kinases and the proteasome are under investigation for targeted prevention and therapy of carcinoma.
Topics: Animals; Antineoplastic Agents; Carcinoma; Humans; Mice; NF-kappa B
PubMed: 18694378
DOI: 10.1517/14728222.12.9.1109