Highlights of the biology of endocrine tumours of the gut and pancreas.

2003 ◽  
pp. 427-436 ◽  
Author(s):  
G Rindi ◽  
C Bordi

Originating from cells of the diffuse endocrine system the endocrine tumours of the gut and the pancreatic tract are rare entities characterized by a common phenotypic aspect and producing several bioactive substances including growth factors. Two major categories are identified: well-differentiated and poorly differentiated tumours. The clinical behaviour varies ranging from benign to low grade malignant for well-differentiated tumours/carcinomas to high grade malignant for poorly differentiated carcinomas. The two major categories of well-differentiated and poorly differentiated tumours display distinct phenotypes and genetic backgrounds possibly supporting distinct histogenesis. Genetic abnormalities associated with either induction or progression of tumours may vary depending on the site of origin.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. e14673-e14673
Author(s):  
Raymond Elsoueidi ◽  
Sabrina Tom ◽  
Eyob Adane ◽  
Mark Dignan

e14673 Background: Colorectal cancer is the third most common cancer worldwide. Smoking has been increasingly reported as a risk factor. Poorly differentiated adenocarcinoma in colorectal cancer has been reported to have a worse outcome. Poorly and moderately differentiated adenocarcinomas in Non Small Cell Lung cancer were more strongly correlated with smoking than well differentiated adenocarcinoma. This study was designed to evaluate the association between cigarette smoking and tumor grade in colorectal cancer. Methods: The medical records of patients diagnosed with colorectal cancer between 2001 and 2011 at the Appalachian Regional Healthcare in Hazard, KY were retrospectively reviewed. Age, gender, pathology and smoking history were obtained. The association between smoking and tumor grade was evaluated by the χ2 test. Results: Three hundred seventeen patients were diagnosed with colorectal cancer between 2001 and 2011. The percentage of male and female patients was 53.3% and 46.7%, respectively. Among these patients, 49.5% (n=157) were smokers and 38.8% were nonsmokers (n=138), while for 11.7% (n=35) of patients smoking history was unknown. In smokers, 17.1% had high grade adenocarcinoma (poorly differentiated) and 82.9% had low grade adenocarcinoma (moderately differentiated + well differentiated) whereas in non-smokers, 13.8% had high grade adenocarcinoma and 86.2% had low grade adenocarcinoma. Although the percentage of high grade adenocarcinoma was higher among smokers this was not statistically significantly (p=0.55). Moreover, tumor grade was not significantly associated with age and gender. Conclusions: Based on these results, there was no association between degree of differentiation of tumor in colorectal cancer and smoking history, age and gender. Although to be noted that the pathologic grading may vary from one pathologist to another.


2009 ◽  
Vol 24 (2) ◽  
pp. 41-42
Author(s):  
Jose M. Carnate

Malignant glandular neoplasms of the sinonasal tract originate either from the respiratory epithelium or the underlying mucoserous glands. They present with a confusing array of morphologic features and this is reflected in the nomenclature of these tumors. These tumors are grouped into three main types: salivary gland-type, intestinal-type and non-intestinal type adenocarcinomas.1 Salivary gland-type adenocarcinomas of the nasal cavity histologically resemble their analogous lesions in the major and minor salivary glands. Adenoid cystic carcinoma is the most common although almost any of those described in the salivary glands can occur in the nasal cavity as well. Intestinal-type adenocarcinomas resemble glandular neoplasms that occur in the small and large intestines. The more well-differentiated ones resemble colonic tubular and villous adenomas while those at the other end of the spectrum resemble moderately to poorly-differentiated colonic adenocarcinomas. Others may be composed of goblet cells or resemble colonic mucinous carcinomas. Nonintestinal-type adenocarcinomas are the most diverse of the lot and are composed of adenocarcinomas whose morphologies do not easily fit in into the previous two categories. For purposes of prognostication, they are divided into low-grade and high-grade categories based on architecture, nuclear features and mitotic activity. Low-grade tumors have uniform cells arranged in compact acini, back to back, confluent glands, cystic spaces and papillae. They maintain tall columnar to cuboidal arrangements without much stratification. Cytoplasm is often abundant but variable in appearance – basophilic, granular, mucinous, eosinophilic and also oncocytic. Nuclear atypia is mild to moderate with few mitoses. High-grade tumors are mostly solid, show prominent nuclear pleomorphism, nucleoli and mitotic activitiy. Signet-ring cells may be seen. Necrosis may often be present.2,3,4 We present the case of a 73 year old female with a destructive left nasal cavity mass. Biopsy shows an infiltrative epithelial tumor with a papillary configuration composed of tumor cells draped around vascular cores (Fig. 1 and Fig. 2). High-power view shows cuboidal to polygonal cells that have large, angular and hyperchromatic nuclei without distinct nucleoli. Mitoses are difficult to come by. Cytoplasm is moderate to abundant and has a dense eosinophilic, somewhat oncocytic quality (Fig. 3 and Fig. 4). Mucin-secreting or other intestinal-type cells are not seen. The case was signed out as a low-grade, papillary, nonintestinal-type adenocarcinoma. Unfortunately, the patient was subsequently lost to follow-up. Among patients with intestinal- and nonintestinal-type adenocarcinomas, histologic grade affects outcome. Well-differentiated tumors with predominantly papillary and tubular configurations do better (80% 5-year survival) while poorly differentiated ones do poorly (40% 5-year survival). Recurrences develop in about 50% and distant metastasis in 15%. Overall survival is about 40% with death occurring in approximately 3 years. Treatment is radical surgical resection with post-operative radiotherapy.1


1989 ◽  
Vol 103 (4) ◽  
pp. 420-423 ◽  
Author(s):  
V. L. Cumberworth ◽  
A. Narula ◽  
K. A. MacLennan ◽  
P. J. Bradley

AbstractWe report two cases of poorly differentiated mucoepidermoid carcinoma of the larynx which both remain well after surgical management. The first underwent a radical neck dissection for recurrent disease following radiotherapy and the second a total laryngectomy with elective post-operative radiotherapy.Although well differentiated (‘low grade’) mucoepidermoid tumours of the larynx may respond to radiotherapy surgical management is generally recommended for all grades of such tumours especially for poorly differentiated (‘high grade’) tumours. Elective post-operative radiotherapy is often advocated for high grade tumours; radical neck dissection is generally undertaken only in the presence of lymphadenopathy, although elective radical neck dissection has been proposed for high grade tumours. These cases emphasise the value of comprehensive surgical management for this condition.Such laryngeal tumours are difficult to diagnose histologically from biopsy and are often initially reported as squamous cell carcinoma.


Cancers ◽  
2021 ◽  
Vol 13 (6) ◽  
pp. 1453
Author(s):  
Chiara Fabbroni ◽  
Giovanni Fucà ◽  
Francesca Ligorio ◽  
Elena Fumagalli ◽  
Marta Barisella ◽  
...  

Background. We previously showed that grading can prognosticate the outcome of retroperitoneal liposarcoma (LPS). In the present study, we aimed to explore the impact of pathological stratification using grading on the clinical outcomes of patients with advanced well-differentiated LPS (WDLPS) and dedifferentiated LPS (DDLPS) treated with trabectedin. Patients: We included patients with advanced WDLPS and DDLPS treated with trabectedin at the Fondazione IRCCS Istituto Nazionale dei Tumori between April 2003 and November 2019. Tumors were categorized in WDLPS, low-grade DDLPS, and high-grade DDLPS according to the 2020 WHO classification. Patients were divided in two cohorts: Low-grade (WDLPS/low-grade DDLPS) and high-grade (high-grade DDLPS). Results: A total of 49 patients were included: 17 (35%) in the low-grade cohort and 32 (65%) in the high-grade cohort. Response rate was 47% in the low-grade cohort versus 9.4% in the high-grade cohort (logistic regression p = 0.006). Median progression-free survival (PFS) was 13.7 months in the low-grade cohort and 3.2 months in the high-grade cohort. Grading was confirmed as an independent predictor of PFS in the Cox proportional-hazards regression multivariable model (adjusted hazard ratio low-grade vs. high-grade: 0.45, 95% confidence interval: 0.22–0.94; adjusted p = 0.035). Conclusions: In this retrospective case series, sensitivity to trabectedin was higher in WDLPS/low-grade DDLPS than in high-grade DDLPS. If confirmed in larger series, grading could represent an effective tool to personalize the treatment with trabectedin in patients with advanced LPS.


2020 ◽  
Vol 153 (6) ◽  
pp. 811-820 ◽  
Author(s):  
Kelsey E McHugh ◽  
Sanjay Mukhopadhyay ◽  
Erika E Doxtader ◽  
Christopher Lanigan ◽  
Daniela S Allende

Abstract Objectives INSM1 has been described as a sensitive and specific neuroendocrine marker. This study aims to compare INSM1 with traditional neuroendocrine markers in gastrointestinal neuroendocrine neoplasms. Methods Retrospective review (2008-2018) was used to retrieve paraffin-embedded tissue from 110 gastrointestinal neuroendocrine neoplasms and controls that was subsequently stained with INSM1, synaptophysin, chromogranin, CD56, and Ki-67. Results INSM1 was positive in 16 of 17 (94.1%) gastric, 17 of 18 (94.4%) pancreatic, 13 of 18 (72.2%) small bowel, 17 of 21 (81.0%) colonic, and 26 of 36 (72.2%) appendiceal tumors. INSM1 was positive in 58 of 70 (82.9%) well-differentiated neuroendocrine tumors, 17 of 20 (85.0%) poorly differentiated neuroendocrine carcinomas, 8 of 11 (72.7%) low-grade goblet cell adenocarcinomas (grade 1), and 6 of 9 (66.7%) high-grade goblet cell adenocarcinomas (grade 2/3). INSM1 sensitivity for neuroendocrine neoplasms (80.9%) was less than that of synaptophysin (99.1%), chromogranin (88%), and CD56 (95.3%); specificity was higher (95.7% vs 86.0%, 87.3%, and 86.0%, respectively). Conclusions INSM1 is a useful marker of neuroendocrine differentiation in gastrointestinal neuroendocrine and mixed neuroendocrine neoplasms. Compared with traditional neuroendocrine markers, INSM1 is less sensitive but more specific.


Folia Medica ◽  
2020 ◽  
Vol 62 (1) ◽  
pp. 17-22
Author(s):  
Artur Kowalik ◽  
Andrzej Wincewicz ◽  
Sebastian Zięba ◽  
Janusz Kopczynski ◽  
Mariusz Koda ◽  
...  

We examined a status of fibrosarcoma arising in dermatofibrosarcoma protuberans of 64-year-old male patient. A dermal, solid, grayish-yellow, desmin-negative trichrome-bluish tumor measured 1.5 cm in diameter pT1a (edition 8 pTNM). It was composed of spindle cells. It was consistent with dermatofibrosarcoma protuberans (ICD-O3: 8832/3) in areas of low mitotic activity, low atypia and sustained CD34 positivity. CD34-negative texture with high mitotic index and atypia was consistent with the high grade sarcoma apparently of fibrous origin, given category of poorly differentiated fibrosarcoma. The high grade component was graded (G3) and scored according to French Federation of Cancer Centers Sarcoma Group (FNCLCC): total score of 6 points: tumor differentiation: 3 points + Mitotic count: 3 points (up to 26 mitoses/ 10HPF in high-grade fields), + no necrosis: 0 points. In low grade sarcomatous component ADAMTS20 (NM_025003: c.1661C>T, p.P554L) NF1 (NM_001042492: c. 2173G>T, p.E725X) and PKHD1 (NM_138694: c. 11074C>T, p.R3692X) were revealed with following allelic frequencies: 25%, 27% and 17%. In high grade component allelic frequencies of the same mentioned mutations were 30%, 30% and 14% respectively. In the light of our findings, none of detected mutations can be regarded as a mutation that would definitely induce phenotype of high malignancy, because ADAMTS20, NF1 and PKHD1 mutations were detected both in high grade sarcoma and in low grade areas of dermatofibrosarcoma protuberans. It also points that these mutations appeared on early stages of tumor development.


2009 ◽  
Vol 27 (15_suppl) ◽  
pp. 1061-1061
Author(s):  
R. Santana-Davila ◽  
D. W. Visscher ◽  
C. M. Vachon ◽  
M. Frost ◽  
R. A. Vierkant ◽  
...  

1061 Background: Benign breast disease (BBD) is a significant risk factor for breast cancer (BC); however little is known about the aggressiveness of the BCs these patients develop. Shared features between select atypias and low-grade DCIS have led some to speculate that a history of BBD portends the development of well-differentiated BCs. Methods: The Mayo BBD cohort includes 9,376 women who had benign breast biopsies from 1967–1991. Data on BC events were obtained from medical records and questionnaires. Tissue from the BCs was reviewed by a single breast pathologist (DWV). Results: Our cohort included 6,244 patients with nonproliferative disease (NP), 2,801 women with proliferative disease without atypia (PDWA), and 331 with atypical hyperplasias (AH). With a median of 18 years of follow-up, 799 patients with BBD have developed breast cancer, 416 initially had NP, 313 had PDWA, and 70 AH. BC tissue was available for 703 of the women. The cancers were invasive ductal in 76.1% (n = 535), invasive lobular in 9.4% (n = 66), and DCIS alone in 14.5% (n = 102) patients. Grade is currently available for 500 women, and is well differentiated in 29.4% (n = 150), moderately differentiated in 42.7% (n = 218) and poorly differentiated in 27.8% (n = 142). In 537 cases the malignant tissue had a concurrent benign component consisting of NP in 24% (n = 129), PDWA in 25.1% (n = 135), and AH in 50.8% (n = 273). In regards to tumor size, 69.6% had T1 tumors, 24.9% T2 tumors, and 5.5% T3 disease. Metastasis to lymph nodes occurred in 25% of patients. Median time to BC was 12.3 years and did not differ across the different benign entities. Breast cancer developed within 5 years from the initial BBD in 163 women (20%). In this group, tumor size was greater (p = 0.02), and there were more poorly differentiated tumors (p = 0.006) than in those who later developed BC. Conclusions: In the BCs that have developed in our BBD cohort, we do not see a preponderance of well-differentiated, good-risk BCs. Patients diagnosed within 5 years of BBD appear to have BCs with more aggressive features. No significant financial relationships to disclose.


2020 ◽  
Vol 38 (15_suppl) ◽  
pp. e15038-e15038
Author(s):  
Aman Chauhan ◽  
Alexandre Prieur ◽  
Jill Kolesar ◽  
Susanne M. Arnold ◽  
Léa Payen ◽  
...  

e15038 Background: Neuroendocrine neoplasms (NENs) are heterogeneous tumors which originate from various organs and are of variable aggressiveness based on grade and morphology. Current biomarkers for NENs lack sensitivity and specificity, especially for high-grade NENs (small and large cell neuroendocrine carcinomas). hPG80, progastrin, is a novel bio-marker which is easily measured in plasma using an ELISA test. Physiologically, hPG80, an 80 amino acid protein, is the precursor of the gastrointestinal hormone gastrin. It is synthetized by gastric antrum G cells, and then processed into gastrin by multiple enzymatic processes. In pathological conditions, the GAST gene, which encodes hPG80, was shown to be over-expressed in human solid tumors from various primary sites. hPG80 is unprocessed and released from the tumor cells and becomes detectable in the blood. This study is the first to explore hPG80 in NENs. Methods: hPG80 was quantified in the plasma from 31 NEN patients using DxPG80 technology (ECS-Progastrin, Switzerland). Additional 69 samples are currently undergoing analysis. Progastrin concentrations in 18-70 YO (n = 557) and 18-25 YO (n = 137) healthy blood donors were compared to 31 stage IV NENs patients. The study was IRB approved. Results: Current data are for 31 patients. Data on total 100 patients will be presented at ASCO 2020. Mean age of study cohort at the time of blood collection was 60.9 years. 21 patients had grade 1 and 2 well differentiated NET. 10 patients had high grade NEN (Small cell, large cell and poorly differentiated NEC). High grade sub cohort also included two well differentiated grade 3 NET patients. Mean hPG80 in NENs was 14.17 pM as compared to 2.04 pM and 0.99 pM in 18-70 and 18-25 YO control groups (p < 0.0001), respectively. Subgroup analysis of NENs revealed mean hPG80 of 24.61 pM in high-grade NENs (n = 10) vs 10.88 pM in G1/2 NETs (n = 21). Conclusions: This first-ever study of plasma hPG80 in NENs suggests hPG80 may be a diagnostic blood-based biomarker in both low and high-grade NENs and further study is warranted. A prospective trial is ongoing in high-grade NEN to evaluate its role in monitoring of disease (NCT03958045) and further studies in low-grade NETs are underway. This research was supported by Cancer Center Support Grant (CCSG) from the National Cancer Institute (P30 CA177558) and ECS Progastrin.


2018 ◽  
Vol 108 (1) ◽  
pp. 54-62 ◽  
Author(s):  
Halfdan Sorbye ◽  
Eric Baudin ◽  
Ivan Borbath ◽  
Martyn Caplin ◽  
Jie Chen ◽  
...  

Gastroenteropancreatic (GEP) neuroendocrine neoplasms (NEN) are classified based on morphology and graded based on their proliferation rate as either well-differentiated low-grade (G1 to G2) neuroendocrine tumors (NET) or poorly differentiated high-grade (G3) neuroendocrine carcinomas (NEC). Recently, a new subgroup of well-differentiated high-grade pancreatic tumors (NET G3) has been defined. The GEP NEN G3 group consisting of both NEC and NET G3 has recently been shown to be a quite heterogeneous patient group concerning prognosis and treatment benefit, depending on factors such as the primary tumor site, differentiation, proliferation rate, and molecular alterations. In this review we discuss the existing data on diagnostics, treatment, and biomarkers in this patient group, the unmet needs, and the future perspectives.


2010 ◽  
Vol 63 (8) ◽  
pp. 708-713 ◽  
Author(s):  
Matthew R Lindberg ◽  
Cyril Fisher ◽  
Khin Thway ◽  
Dengfeng Cao ◽  
John C Cheville ◽  
...  

BackgroundLeiomyosarcomas of the urinary bladder (LMS-UB) are rare, usually aggressive neoplasms. Owing to their rarity, only a limited number of cases with clinical follow-up information have been published. There is no current consensus on LMS-UB grading, and it is unknown whether the widely accepted Fédération Nationale des Centres de Lutte Contre le Cancer (FNCLCC) and National Cancer Institute (NCI) grading systems of soft-tissue sarcomas are applicable to LMS-UB.MethodsThe authors studied 34 well-characterised LMS-UB and compared the prognostic power of the FNCLCC and NCI systems with that of one published grading scheme for LMS-UB (Mayo). All available slides from 34 LMS-UB were retrieved and evaluated with regards to degree of differentiation, mitotic rate/10 high-powered fields (HPF), and % necrosis. Cases were graded using published criteria for the FNCLCC, NCI and Mayo schemes. Follow-up information was obtained.ResultsThe tumours occurred in 17 females and 17 males, ranging from 31 to 91 years (median 65), and measured 2–12 cm in size. One tumour was well differentiated, 17 tumours were moderately differentiated, and 16 tumours were poorly differentiated. Mitotic rates ranged from 1 to >30/10 HPF (median 12/10 HPF), and tumours showed 0–60% necrosis (median 25%). FNCLCC grades were 1 (3), 2 (12) and 3 (19). NCI grades were 1 (2), 2 (11) and 3 (21). Mayo grades were low (7) and high (27). FNCLCC and NCI grades were identical in 23/34 cases (68%). Four cases were FNCLCC/NCI grade 2 or 3 and Mayo low-grade. Clinical follow-up was available for 25 of 34 patients (74%). Clinical follow-up of ≥12 months was available for 17 of these 25 cases (68%) with a median follow-up duration of 52 months (range 12–120 months). Adverse outcome was seen in nine of these 17 patients (53%). Seven of the eight cases (88%) with a clinical follow-up duration of <12 months died of their disease. Overall, adverse outcome was documented in 16 of 25 (64%) cases. Metastatic disease was seen in 13 of 25 (52%) cases, with the lungs being the most common site of metastasis (62%). Adverse outcome was noted in 15 of 23 (65%) of FNCLCC grade 2 or 3 LMS-UB, as compared with zero of two (0%) FNCLCC grade 1 tumours (p=0.15), in 15 of 23 (65%) NCI grade 2 or 3 LMS-UB, versus zero of two (0%) NCI grade 1 sarcomas (p=0.17) and in 13 of 20 (65%) Mayo high grade LMS-UB, as opposed to two of five (40%) low-grade lesions (all results not statistically significant).ConclusionsThe authors conclude that LMS-UB occurs in older adults of either sex and is characterised by aggressive behaviour, with adverse outcome in >60% of cases. Certain advantages of the FNCLCC system may support its more widespread adoption for future studies.


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