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World Journal of Gastrointestinal... May 2021Several benign conditions such as chronic pancreatitis, autoimmune pancreatitis, and paraduodenal pancreatitis can present as mass lesions and may mimic pancreatic... (Review)
Review
Several benign conditions such as chronic pancreatitis, autoimmune pancreatitis, and paraduodenal pancreatitis can present as mass lesions and may mimic pancreatic ductal adenocarcinoma (PDAC) clinically and radiologically. Thorough histologic examination with attention to certain morphologic features can assist in deciphering neoplastic from reactive, however small biopsies often remain a challenge. Variable histologic patterns in conventional PDAC may also confound the diagnosis of PDAC. Uncommon subtypes of pancreatic carcinoma such as adenosquamous and squamous cell carcinoma, colloid carcinoma, medullary carcinoma, hepatoid carcinoma and signet ring cell carcinoma necessitate excluding metastasis from other sites prior to rendering the diagnosis of pancreatic carcinoma. The use of immunohistochemical staining and molecular markers can aid in separating benign from malignant and PDAC from metastasis. PDAC expresses a few non-specific epithelial and mucin immunomarkers such as CK7, CK19, MUC1, MUC4 and MUC5AC. However, the only immunohistochemical marker that is specific for PDAC in the right clinical context is SMAD4. Loss of SMAD4 within atypical glands and ducts supports the diagnosis of PDAC in a limited sample. Unfortunately, this finding is seen only in 50% of PDAC cases. The identification of certain mutations can help support a diagnosis of PDAC when benign conditions are in the differential. At the molecular level, oncogene mutations are seen in approximately 93% of PDACs. Subsequent neoplastic progression is driven by additional mutations of tumor suppressor genes, such as , , and . Molecular markers can also provide an insight to the prognosis. For instance, the loss of is associated with a poor outcome whereas mutations in , , , and are associated with improved survival.
PubMed: 34122731
DOI: 10.4240/wjgs.v13.i5.406 -
Journal of Veterinary Diagnostic... Nov 2022A 12-y-old, castrated male Weimaraner dog was presented for a wellness examination. A 7-cm, firm mass was palpated on the left, ventral, mid-lateral neck. The neck mass...
A 12-y-old, castrated male Weimaraner dog was presented for a wellness examination. A 7-cm, firm mass was palpated on the left, ventral, mid-lateral neck. The neck mass was removed surgically and submitted for histopathology. A thyroid carcinoma was diagnosed based on microscopic examination. Immunohistochemistry for chromogranin-A, calcitonin, and thyroglobulin identified dual immunoreactivity of the latter two, and a final diagnosis was of a well-differentiated, compact, mixed medullary and follicular cell thyroid carcinoma. These neoplasms are rare in humans and have not been reported in dogs, to our knowledge.
Topics: Humans; Dogs; Male; Animals; Thyroglobulin; Calcitonin; Carcinoma, Medullary; Chromogranins; Adenocarcinoma, Follicular; Thyroid Neoplasms; Dog Diseases
PubMed: 36127830
DOI: 10.1177/10406387221126655 -
Cleveland Clinic Journal of Medicine Oct 2015Sickle cell disease is a common genetic disorder characterized by sickling of red blood cells under conditions of reduced oxygen tension. In turn, sickling leads to... (Review)
Review
Sickle cell disease is a common genetic disorder characterized by sickling of red blood cells under conditions of reduced oxygen tension. In turn, sickling leads to intravascular hemolysis and vaso-occlusive events with subsequent tissue ischemia-reperfusion injury affecting multiple organs, including the genitourinary system. Our review of the genitourinary manifestations of sickle cell disease focuses on sickle cell nephropathy, priapism, and other genitourinary complications such as papillary necrosis and renal medullary carcinoma.
Topics: Anemia, Sickle Cell; Female; Humans; Ischemia; Kidney Diseases; Kidney Medulla; Kidney Neoplasms; Kidney Papillary Necrosis; Male; Penis; Priapism
PubMed: 26469825
DOI: 10.3949/ccjm.82a.14029 -
Frontiers in Endocrinology 2021Medullary thyroid carcinoma is a rare neuroendocrine neoplasm that originates from thyroid C cells. Surgery, with complete resection of the tumor, is the only curative... (Review)
Review
Medullary thyroid carcinoma is a rare neuroendocrine neoplasm that originates from thyroid C cells. Surgery, with complete resection of the tumor, is the only curative approach. However, in most cases, the tumor recurs at locoregional or metastatic level. In this setting, the management remains challenging. In recent years, the immune checkpoint inhibitors have provided promise for changing the cancer treatment paradigm through the application of new approaches that enhance the body's natural antitumor defenses. The aim of this review is to summarize and discuss available data on efficacy and safety of the Food and Drug Administration-approved immune checkpoint inhibitors in patients with medullary thyroid carcinoma. After an extensive search, we found 7 useful data sources (one single-case report, one short article with very preliminary data, five ongoing registered clinical trials). Despite the lack of published evidence regarding the use of immune check point inhibitors, it must be considered that all the ongoing registered clinical trials saw first light in the last three years, thus indicating a growing interest of researchers in this field. Results coming from these trials, and hopefully, in the next future, from additional trials, will help to clarify whether this class of drugs may represent a new weapon in favor of patients with medullary thyroid carcinoma.
Topics: Animals; Carcinoma, Neuroendocrine; Humans; Immune Checkpoint Inhibitors; Thyroid Neoplasms
PubMed: 33935977
DOI: 10.3389/fendo.2021.667784 -
Scientific Reports May 2024Medullary Carcinoma of the Colon (MCC) is a rare histological subtype of colon cancer, and there is currently no recognized optimal treatment plan for it, with its...
Medullary Carcinoma of the Colon (MCC) is a rare histological subtype of colon cancer, and there is currently no recognized optimal treatment plan for it, with its prognosis remaining unclear. The aim of this study is to analyze the independent prognostic factors for MCC patients and develop and validate nomograms to predict overall survival (OS). A total of 760 patients newly diagnosed with MCC from 2004 to 2020 were selected from the Surveillance, Epidemiology, and End Results (SEER) database. All patients were randomly allocated to a training group and a validation group in a 7:3 ratio. Univariate and multivariable Cox regression analyses were conducted to identify prognostic factors and construct nomograms. The nomogram prediction model was evaluated and validated using receiver operating characteristic (ROC) curves, calibration curves, and decision curve analysis (DCA). The study found that elderly women are more susceptible to MCC, and the ascending colon and cecum are the most common sites of involvement. MCC is poorly differentiated, with stages II and III being the most common. Surgery is the primary treatment for MCC. The prognosis for patients with stage IV MCC is poor, with a median survival time of only 10 months. Independent prognostic factors for MCC include age, N stage, M stage, surgery, chemotherapy, and tumor size. Among them, age < 75 years and completion of chemotherapy were protective factors for colon medullary carcinoma, while N2 (HR = 2.18, 95%CI 1.40-3.38), M1 (HR = 3.31, 95%CI 2.01-5.46), no surgery (HR = 27.94, 95%CI 3.69-211.75), and tumor diameter > 7 cm (HR = 1.66, 95%CI 1.20-2.30) were risk factors for colon medullary carcinoma. The results of ROC, AUC, calibration curves, and DCA demonstrate that the nomogram prediction model exhibits good predictive performance. We have updated the demographic characteristics of colon medullary carcinoma and identified age, N staging, M staging, surgery, chemotherapy and tumor size as independent prognostic factors for colon medullary carcinoma. Additionally, we have established nomograms for prognostic prediction. These nomograms can provide personalized predictions and serve as valuable references for clinical decision-making.
Topics: Humans; Nomograms; Female; Male; Colonic Neoplasms; SEER Program; Aged; Middle Aged; Risk Factors; Prognosis; Carcinoma, Medullary; Neoplasm Staging; ROC Curve; Adult
PubMed: 38763982
DOI: 10.1038/s41598-024-61354-2 -
Nature Reviews. Nephrology Mar 2015Sickle cell disease (SCD) substantially alters renal structure and function, and causes various renal syndromes and diseases. Such diverse renal outcomes reflect the... (Review)
Review
Sickle cell disease (SCD) substantially alters renal structure and function, and causes various renal syndromes and diseases. Such diverse renal outcomes reflect the uniquely complex vascular pathobiology of SCD and the propensity of red blood cells to sickle in the renal medulla because of its hypoxic, acidotic, and hyperosmolar conditions. Renal complications and involvement in sickle cell nephropathy (SCN) include altered haemodynamics, hypertrophy, assorted glomerulopathies, chronic kidney disease, acute kidney injury, impaired urinary concentrating ability, distal nephron dysfunction, haematuria, and increased risks of urinary tract infections and renal medullary carcinoma. SCN largely reflects an underlying vasculopathy characterized by cortical hyperperfusion, medullary hypoperfusion, and an increased, stress-induced vasoconstrictive response. Renal involvement is usually more severe in homozygous disease (sickle cell anaemia, HbSS) than in compound heterozygous types of SCD (for example HbSC and HbSβ(+)-thalassaemia), and is typically mild, albeit prevalent, in the heterozygous state (sickle cell trait, HbAS). Renal involvement contributes substantially to the diminished life expectancy of patients with SCD, accounting for 16-18% of mortality. As improved clinical care promotes survival into adulthood, SCN imposes a growing burden on both individual health and health system costs. This Review addresses the renal manifestations of SCD and focuses on their underlying mechanisms.
Topics: Anemia, Sickle Cell; Disease Progression; Humans; Kidney Diseases; Renal Insufficiency, Chronic
PubMed: 25668001
DOI: 10.1038/nrneph.2015.8 -
Human Pathology Apr 2017Colorectal medullary carcinoma, recognized by the World Health Organization as a distinct histologic subtype, is commonly regarded as a specific entity with an improved...
Colorectal medullary carcinoma, recognized by the World Health Organization as a distinct histologic subtype, is commonly regarded as a specific entity with an improved prognosis and unique molecular pathogenesis. A fundamental but as yet unaddressed question, however, is whether it can be diagnosed reproducibly. In this study, by analyzing 80 colorectal adenocarcinomas whose dominant growth pattern was solid (thus encompassing medullary carcinoma and its mimics), we provided a detailed description of the morphological spectrum from "classic medullary histology" to nonmedullary poorly differentiated histologies and demonstrated significant overlapping between categories. By assessing a selected subset (n=30) that represented the spectrum of histologies, we showed that the interobserver agreement for diagnosing medullary carcinoma by using 2010 World Health Organization criteria was poor; the κ value among 5 gastrointestinal pathologists was only 0.157 (95% confidence interval, 0.127-0.263; P=.001). When we arbitrarily classified the entire cohort into "classic" and "indeterminate" medullary tumors (group 1, n=19; group 2, n=26, respectively) and nonmedullary poorly differentiated tumors (group 3, n=35), groups 1 and 2 were more likely to exhibit mismatch repair protein deficiency than group 3 (P<.001); however, improved survival could not be detected in either group compared with group 3. Our findings suggest that the diagnosis of medullary carcinoma, as currently applied, may only serve as a morphological descriptor indicating an increased likelihood of mismatch-repair deficiency. Additional evidence including a more objective classification system is needed before medullary carcinoma can be regarded as a distinct entity with prognostic relevance. Until such evidence becomes available, caution should be exercised when making this diagnosis, as well as when comparing results across different studies.
Topics: Adult; Aged; Aged, 80 and over; Biomarkers, Tumor; Biopsy; Carcinoma, Medullary; Cell Differentiation; Colorectal Neoplasms; DNA Mismatch Repair; DNA Repair Enzymes; Female; Humans; Immunohistochemistry; Male; Middle Aged; Observer Variation; Predictive Value of Tests; Prognosis; Reproducibility of Results; Terminology as Topic; Young Adult
PubMed: 28034727
DOI: 10.1016/j.humpath.2016.12.013 -
Oncotarget Jun 2019
PubMed: 31258836
DOI: 10.18632/oncotarget.26970 -
Current Colorectal Cancer Reports 2015Colorectal cancer is not just one type of cancer. Differences in outcome and reaction to treatment can at least be partly explained by different histological and... (Review)
Review
Colorectal cancer is not just one type of cancer. Differences in outcome and reaction to treatment can at least be partly explained by different histological and molecular subtypes. Recognition of these differences may influence treatment decisions. However, there is huge variation in the amount of information that is available. Several tumour types such as mucinous carcinoma, signet ring cell carcinoma, neuroendocrine carcinoma and adenosquamous carcinoma have such a distinct phenotype that they are readily recognised. However, due to the rarity of signet ring cell carcinoma and adenosquamous carcinoma, limited data are available. More recently defined subtypes, like medullary carcinoma, serrated adenocarcinoma and micropapillary carcinoma, are not adequately diagnosed, which limits research possibilities using large-scale data from registries. In the current review, we systematically describe the histologic subtypes with the clinical and molecular background. We evaluate their prognosis compared to adenocarcinoma not otherwise specified and speculate about the clinical relevance.
PubMed: 26321889
DOI: 10.1007/s11888-015-0280-7 -
Cancers Jul 2019Several histopathological variants of colorectal carcinoma can be distinguished, some associated with specific molecular profiles. However, in routine practice,... (Review)
Review
Several histopathological variants of colorectal carcinoma can be distinguished, some associated with specific molecular profiles. However, in routine practice, ninety/ninety-five percent of all large bowel tumors are diagnosed as conventional adenocarcinoma, even though they are a heterogeneous group including rare histotypes, which are often under-recognized. Indeed, colorectal cancer exhibits differences in incidence, location of tumor, pathogenesis, molecular pathways and outcome depending on histotype. The aim is therefore to review the morphological and molecular features of these rare variants of intestinal carcinomas which may hold the key to differences in prognosis and treatment.
PubMed: 31340478
DOI: 10.3390/cancers11071036