scholarly journals Metachronous double primary neuroendocrine tumors in larynx and lung: a case report

2020 ◽  
Vol 48 (11) ◽  
pp. 030006052096292
Author(s):  
In Hye Song ◽  
Youn Soo Lee ◽  
Dong-Il Sun ◽  
Yong-Kil Hong ◽  
Kyo-Young Lee
Keyword(s):  
Tumor Cells ◽  
Carcinoid Tumor ◽  
Neuroendocrine Tumors ◽  
Lower Lobe ◽  
Proliferation Index ◽  
Atypical Carcinoid ◽  
Voice Change ◽  
Large Tumor ◽  
Ki 67 ◽  
Primary Tumors

When a patient harbors two or more neuroendocrine tumors (NETs), it can be difficult to determine whether they are double primary tumors or metastases. A 60-year-old man complained of voice change lasting 1 month. On physical examination and imaging, a 1.8-cm mass was observed in his epiglottis, and a laser epiglottectomy was performed. Upon microscopic examination, the tumor consisted of medium-sized ovoid or short spindle cells. Immunohistochemical staining of the tumor cells was positive for synaptophysin, chromogranin, and calcitonin but negative for CD56; the Ki-67 proliferation index was approximately 5%. The patient was diagnosed with atypical carcinoid tumor. In 2015, a hypermetabolic endobronchial tumor was identified in the left lower lobe by positron emission tomography-computed tomography. Bronchoscopic biopsy revealed palisading large tumor cells with high nuclear-cytoplasmic ratio, frequent mitoses, and necrosis. The tumor cells were positive for CD56 and negative for cytokeratin-7, thyroid transcription factor-1, P40, synaptophysin, chromogranin, and calcitonin; the Ki-67 proliferation index was approximately 90%. Overall histologic findings were consistent with large cell neuroendocrine carcinoma rather than metastatic atypical carcinoid tumor. Detailed clinical and pathological review are essential to differentiate between metastatic NET and double primary NETs and, therefore, to provide the best management of the patient.

scholarly journals 26. GENETIC CHARACTERIZATION OF SELLAR METASTASIS FROM PRIMARY BRONCHIAL CARCINOID TUMOR OF NEUROENDOCRINE PATHOLOGY

2020 ◽  
Vol 2 (Supplement_2) ◽  
pp. ii4-ii5
Author(s):  
Christopher Hong ◽  
Declan McGuone ◽  
E Zeynep Erson-Omay ◽  
Sacit Bulent Omay
Keyword(s):  
Pituitary Gland ◽  
Carcinoid Tumor ◽  
Neuroendocrine Tumors ◽  
Large Scale ◽  
Brain Mri ◽  
Genetic Alterations ◽  
Sellar Region ◽  
Ki 67 ◽  
Endoscopic Endonasal ◽  
Primary Tumors

Abstract Metastasis to the pituitary gland and surrounding sellar region from systemic tumors is a rare occurrence. Patients may present with signs of endocrine dysfunction secondary to pituitary involvement, as well as mass effect-related symptoms including headaches and visual deficits. Despite a small but accumulating body of literature describing the clinical and histopathological correlates for sellar metastases from systemic tumors, the genetic alterations underlying sellar spread have not been previously described. We describe a 68 year-old female with history of a resected lung carcinoid tumor, followed by chemoradiation, who was diagnosed with a sellar lesion on surveillance PET-CT and subsequent brain MRI. Her tumor was resected via an endoscopic endonasal approach, and final pathology was consistent with neuroendocrine origin, including positive immunohistochemistry for synpatophysin, CK7, TTF-1, and CAM5.2 with a Ki-67 index of 8–12%. Whole-exome sequencing of the sellar specimen demonstrated large-scale deletions of chromosomes 3, 6, and 9 and focal deletions on chromosomes 1,2, 11, 15, and 16. Mutational signature analysis was enriched for COSMIC Signature 4, seen in multiple primary lung cancers. Among 91 total somatic alterations, 7 had been previously associated with oncogenesis (MYO18A, PTCH1, BCOR, CLIC6, TLL2, COL1A1, PTPRK). Notably, mutations in BCOR and PTCH1 have been previously implicated in both systemic neuroendocrine tumors as well as primary tumors of the pituitary gland, while MYO18A, FGF4, and PTPRK mutations had not been reported in systemic neuroendocrine tumors but have been implicated in tumor migration and pituitary adenoma progression. In summary, these data demonstrated an expected mutational pattern indicating a systemic lung neuroendocrine origin but also revealed new mutations previously implicated in primary pituitary pathologies that may have evolutionarily drove divergence from the primary tumor. Further genome studies of these rare lesions may yield further insight into the genetic alterations underlying metastasis to the sellar region.

Histopathological and Clinical Differences Between Primary Breast Carcinomas With Neuroendocrine Features and Primary Breast Carcinomas Mimicking Neuroendocrine Features

2019 ◽  
Vol 27 (7) ◽  
pp. 744-752
Author(s):  
Canan Kelten Talu ◽  
Taha Cumhan Savli ◽  
Gulben Erdem Huq ◽  
Cem Leblebici
Keyword(s):  
Tumor Cells ◽  
Lymphovascular Invasion ◽  
Lymphocytic Infiltration ◽  
Growth Patterns ◽  
Proliferation Index ◽  
Positive Staining ◽  
High Grade ◽  
Breast Carcinomas ◽  
Ki 67 ◽  
Clear Cytoplasm

We aimed to determine the histopathological differences between primary breast carcinomas with neuroendocrine features (NEBC) and carcinomas mimicking neuroendocrine features (NEBC-like). Twenty-three cases with NEBC, all showing positive staining for synaptophysin and/or chromogranin-A in ≥50% of tumor cells and 36 cases with NEBC-like (no staining for neuroendocrine [NE] markers but suspicious for NE morphology in terms of solid/trabecular growth patterns) were included in the study. Significant differences were found between the groups in terms of the patients’ ages, histologic/nuclear grade of tumor, lymphovascular invasion, comedo-type ductal carcinoma in situ (DCIS), microcalcification, Ki-67 proliferation index, nuclear shape, and level of peritumoral lymphocytic infiltration. The presence of large-size solid cohesive groups of tumor cells; plasmocytoid, spindle, and/or columnar shapes of tumor cells; and eosinophilic-granular appearance of cytoplasm were mostly noted in the NEBC group. The presence of small- to medium-sized solid cohesive groups of tumor cells; high-grade histologic and nuclear features; clear cytoplasm; and round to ovoid nucleus were mostly noted in the NEBC-like group. No significant differences were found in terms of tumor size, ER/PR/HER2 status, as well as the presence of DCIS, elastosis, extracellular/intracellular mucin, signet ring cells, apocrine features, and accompanying papilloma or ductal ectasia. In conclusion, small- to medium-sized solid cohesive groups of tumor cells, high-grade features, clear cytoplasm, round to ovoid shape of nucleus, lymphovascular invasion, comedo-type DCIS, microcalcification, high level of Ki-67 proliferation index (≥20%), and moderate/strong level of peritumoral lymphocytic infiltration might support non-NE features in breast carcinomas.

scholarly journals Chromogranin A, Ki-67 index and IGF-related genes in patients with neuroendocrine tumors

2013 ◽  
Vol 2 (4) ◽  
pp. 172-177 ◽  
Author(s):  
R C S van Adrichem ◽  
L J Hofland ◽  
R A Feelders ◽  
M C De Martino ◽  
P M van Koetsveld ◽  
...  
Keyword(s):  
Mrna Expression ◽  
Neuroendocrine Tumors ◽  
Chromogranin A ◽  
Insulin Receptors ◽  
Proliferation Index ◽  
Gastroenteropancreatic Neuroendocrine Tumors ◽  
Ki 67 ◽  
Igf Binding Proteins ◽  
Igf Receptors ◽  
Igf Binding

Chromogranin A (CgA) and the Ki-67 proliferation index are considered as important biochemical and pathological markers for clinical behaviour of gastroenteropancreatic neuroendocrine tumors (GEP NETs), respectively. The IGF system has been suggested as an important regulator of GEP NET proliferation and differentiation. A possible relationship between serum CgA (sCgA), Ki-67 proliferation index, and expression of IGF-related genes in patients with GEP NETs has not been demonstrated yet. This study investigates the relationship between sCgA, the Ki-67 proliferation index, and the expression of IGF-related genes in GEP NET tissues and their relation with 5-year survival. Tumor and blood samples from 22 GEP NET patients were studied. Tumoral mRNA expression of IGF-related genes (IGFs: IGF1, IGF2; IGF receptors: IGF1R, IGF2R; insulin receptors: subtype A (IR-A) and B (IR-B); IGF-binding proteins (IGFBPs): IGFBP1, IGFBP2, IGFBP3, and IGFBP6) was measured using quantitative RT-PCR. Ki-67 proliferation index was determined using immunohistochemistry. sCgA was measured with ELISA. Five-year survival in patients with nonelevated sCgA (n=11) was 91 vs 46% in patients with elevated sCgA (n=11) (P=0.006). IR-A mRNA expression was significantly higher in tumors obtained from patients with elevated sCgA than in those from patients with nonelevated sCgA (6.42±2.08 vs 2.60±0.40; P=0.04). This data suggests that sCgA correlates well with 5-year survival of GEP NET patients, and that IR-A mRNA expression correlates well with tumor mass in GEP NET patients.

Relationship of Ki-67 proliferative index and metastatic tumor of breast cancer.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. e22190-e22190
Author(s):  
Kokoro Kobayashi ◽  
Yoshinori Ito ◽  
Akiko Ogiya ◽  
Naoya Gomi ◽  
Rie Horii ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Primary Tumor ◽  
Metastatic Tumor ◽  
Labeling Index ◽  
Proliferation Index ◽  
Luminal Breast Cancer ◽  
Line Treatment ◽  
Metastatic Tumors ◽  
Ki 67 ◽  
Primary Tumors

e22190 Background: The metastatic breast tumor tends to be more aggressive with high proliferation, but this has not been proven in clinical sampling of metastatic tumors. Methods: Forty-eight patients who had histological specimens of both primary and metastatic sites of luminal breast cancer (ER and/or PgR positive and HER2 negative) were examined. We classified them as luminal A (LA) with Ki-67 labeling index of less than 14% and as luminal B (LB) with Ki-67 labeling index of more than 14%. We analyzed their overall survival (OS) and progression free survival (PFS) of 1st line treatment of each subtype of primary and metastatic tumors. Results: Subtypes of primary tumors and metastatic tumors were as follows; the primary tumor: LA; 34 patients (70.8%), LB; 14 (29.2%), metastatic tumors: LA; 21 (43.8%), LB; 27 (56.2%). Patients with LA of the primary tumor demonstrated statistically longer OS (LA; 72.5 months, LB 39.6 months, p=0.009). OS depended on the subtype of the primary tumor. In contrast, patients with LB of a metastatic tumor showed a statistically worse PFS (LA; 20.5 months, LB; 11.5 months, p=0.040). PFS of the 1st line treatment for MBC depended on the subtype of the metastatic tumor. Conclusions: The frequency of LB was increased on metastatic tumors and tended to acquire a higher proliferation index. This suggests that characterization of metastatic tumors could be better as an indicator of subsequent treatment for MBC. [Table: see text]

scholarly journals The association of the angiopoietin/Tie-2 system with the development of metastasis and leukocyte migration in neuroendocrine tumors

2010 ◽  
Vol 17 (4) ◽  
pp. 897-908 ◽  
Author(s):  
Nicté Figueroa-Vega ◽  
Ángel Díaz ◽  
Magdalena Adrados ◽  
Cristina Álvarez-Escolá ◽  
Amalia Paniagua ◽  
...  
Keyword(s):  
Tumor Cells ◽  
Neuroendocrine Tumors ◽  
Serum Levels ◽  
Soluble Form ◽  
Blood Monocytes ◽  
Rt Pcr ◽  
Gastroenteropancreatic Neuroendocrine Tumors ◽  
Primary Tumors ◽  
Enhanced Expression ◽  
And Function

The aim of this study was to explore the possible involvement of the angiopoietin (Ang)-1, -2/Tie-2 system in the development, growth, and metastases evolution of gastroenteropancreatic-neuroendocrine tumors (GEP-NETs). We prospectively examined the serum levels of Tie-2, Ang-1, and Ang-2 by ELISA in 42 patients with proven GEP-NETs and 27 controls. We also determined the expression of the Ang/Tie-2 system in freshly isolated peripheral blood monocytes and in tumor cells from malignant primary tumors and/or liver metastases samples from GEP-NET patients by flow cytometry and/or RT-PCR. Furthermore, the function of the Ang/Tie-2 system in monocytes from controls and patients was assessed by a chemotaxis assay. GEP-NET patients showed enhanced serum levels of soluble form of Tie-2 (sTie-2), Ang-1, and Ang-2 (P<0.05 in all cases), compared to controls. sTie-2 and Ang-2 levels were significantly higher in GEP-NETs with metastases compared to those with no metastases. In addition, a significant correlation was detected between Ang-2 levels and chromogranin A or sTie-2 concentrations or 5-hydroxy-indole acetic acid excretion (r=0.71, r=0.60, and r=0.81 respectively, P<0.01 in all cases). Furthermore, we observed an enhanced expression of Ang-1, Ang-2, and Tie-2 in freshly isolated tumor cells from GEP-NET both by immunohistochemistry and by RT-PCR. Interestingly, an enhanced expression and function of Tie-2 was detected in monocytes from GEP-NET patients. Our data suggest that the Ang/Tie-2 system is involved in the growth and development of metastases of GEP-NETs, and that favors the recruitment of Tie-2+ monocytes to the tumor site, where they can promote inflammation and angiogenesis.

Canine Neuroendocrine Tumors of the Pancreas: A Study Using Image Analysis Techniques for the Discrimination of Metastatic Versus Nonmetastatic Tumors

1997 ◽  
Vol 34 (2) ◽  
pp. 138-145 ◽  
Author(s):  
G. Minkus ◽  
U. Jütting ◽  
M. Aubele ◽  
K. Rodenacker ◽  
P. Gais ◽  
...  
Keyword(s):  
Image Analysis ◽  
Neuroendocrine Tumors ◽  
Nucleolar Organizer ◽  
Biological Behavior ◽  
Proliferation Index ◽  
Nucleolar Organizer Regions ◽  
Ki 67 ◽  
Analysis Techniques ◽  
Significant Difference ◽  
Image Analysis Techniques

Canine pancreatic neuroendocrine tumors were studied using different image analysis techniques (nuclear image histometry, analysis of argyrophilic proteins of nucleolar organizer regions, determination of the mouse anti-Ki 67 antigen proliferation index, and DNA densitometry) to correlate their biological behavior with objective phenotypic markers. The methods were compared to determine the best method for distinguishing between metastatic and nonmetastatic tumors. Discrimination between the two types of tumor was possible using nuclear image histometry in combination with morphometric analysis of argyrophilic proteins of nucleolar organizer regions. In contrast, the mouse anti-Ki 67 antigen proliferation index, DNA measurement, and immunohistochemical parameters revealed no significant difference between the two types of tumors.

scholarly journals Albumin to alkaline phosphatase ratio: does it predict survival in grade 1 and grade 2 neuroendocrine tumors?

2019 ◽  
Author(s):  
Yusuf Acikgoz ◽  
Öznur Bal ◽  
Mutlu Doğan
Keyword(s):  
Alkaline Phosphatase ◽  
Neuroendocrine Tumors ◽  
Prognostic Value ◽  
Proliferation Index ◽  
Rank Test ◽  
P Value ◽  
Albumin Concentration ◽  
Ki 67 ◽  
Registration Data ◽  
Well Differentiated

Abstract BACKGROUND: Neuroendocrine tumors (NETs) are very heterogeneous tumors. Although it is classified according to Ki-67 proliferation index and mitotic count, their behavior may greatly vary even in the same group. Therefore, more accurate prognostic markers are required to predict prognosis in patients with well differentiated NETs. This study is aimed to evaluate prognostic value of albumin to alkaline phosphatase ratio (AAPR) in patients with well differentiated neuroendocrine tumors. PATIENTS AND METHODS: A total of 110 patients included in this study. Patients' data were obtained from registration data-base of the hospital and reviewed retrospectively. AAPR was calculated by dividing albumin concentration (g/dl) to alkaline phosphatase level (U/L). Cut off value for AAPR was determined by Receiver Operating Characteristic (ROC) analysis. Survival analysis was performed by Kaplan-Meier method with the Long-rank test. We reported two-sided p value and p<0.05 was considered statistically significant.RESULT: The calculated optimum cut-off value for AAPR was 0.028. Patients were divided into two groups as patients with AAPR ≤0.028 (n:22, 20%) and, with AAPR >0.028 (n:88, 80%). Patients with AAPR >0.028 had statistically longer overall survival (OS) compared with patients with ≤0.028 ( NR vs 96,8 months, p=0.001). Additionally, AAPR has been shown to be an independent prognostic factor for OS in in multivariate analysis (HR=4.942, 95% CI=1.693-14.420, p=0.003).CONCLUSION: Patients with higher AAPR had more favourable prognosis compared to patients with lower AAPR. We demonstrated that AAPR can be of prognostic value in well-differentiated NETs.

scholarly journals Expression of Estrogen and Progesterone Receptors in a Tailgut Cyst with Carcinoid Tumor

2021 ◽  
Vol 156 (Supplement_1) ◽  
pp. S76-S77
Author(s):  
N Mohamed ◽  
D Rampisela ◽  
L M Lopez
Keyword(s):  
Carcinoid Tumor ◽  
Pelvic Pain ◽  
Rare Complication ◽  
Progesterone Receptors ◽  
Cystic Mass ◽  
Proliferation Index ◽  
Presacral Space ◽  
Tailgut Cyst ◽  
Ki 67 ◽  
Female Predominance

Abstract Introduction/Objective Tailgut cysts (TC) are congenital lesions that arise in the presacral space. They originate from the embryonic hindgut and usually present between the ages of 30-60, with female predominance. TCs are usually asymptomatic or can present with lower back, perianal or pelvic pain. Malignant transformation of a TC is a rare complication, with adenocarcinoma being the most common, followed by carcinoid tumor. About thirty cases of carcinoid tumors arising in a TC have been reported in the literature so far with a slight female predominance (1.5:1). Methods/Case Report We describe a 40-year-old Hispanic woman with a 9-year history of cyclic pelvic pain related to her menstrual cycles. She was diagnosed with adenomyosis and underwent hysterectomy that did not completely resolve her symptoms. Follow-up serial imaging showed a growing complex-cystic presacral mass, which was eventually excised. Grossly, there was a 3.6×3.1×2.5 cm multiloculated cystic mass filled with mucoid material. Microscopically, there were multiple cystic spaces lined by benign squamous and mucinous columnar epithelium and surrounded by smooth muscle cells. A 6-mm carcinoid tumor was found within a cyst wall and confirmed by positive synaptophysin and chromogranin staining with a Ki-67 proliferation index of &lt;2%. Estrogen and progesterone receptor immunostains were positive in the epithelial cyst linings and the stromal cells but not in the carcinoid tumor cells. Results (if a Case Study enter NA) NA Conclusion We conclude that the diagnosis of TC should be considered in the differential of gynecologic patients with unresolved cyclic pelvic pain and that estrogen and progesterone could have an important role in the pathogenesis of TCs. Furthermore, estrogen receptors can be a therapeutic target in patients with this entity.

scholarly journals Sexual dimorphism in small-intestinal neuroendocrine tumors: lower prevalence of mesenteric disease in premenopausal women

2022 ◽  
Author(s):  
Anela Blažević ◽  
Anand M Iyer ◽  
Marie-Louise F van Velthuysen ◽  
Johannes Hofland ◽  
Lindsey Oudijk ◽  
...  
Keyword(s):  
Estrogen Receptor ◽  
Sexual Dimorphism ◽  
Tumor Cells ◽  
Neuroendocrine Tumors ◽  
Estrogen Receptor Alpha ◽  
Premenopausal Women ◽  
Primary Tumors ◽  
Tertiary Center ◽  
Male Patients ◽  
Small Intestinal

Abstract Context Small intestinal neuroendocrine tumors (SI-NETs) have a modest but significantly higher prevalence and worse prognosis in male patients. Objective This work aims to increase understanding of this sexual dimorphism in SI-NETs. Patients and Methods Retrospectively, SI-NET patients treated in a single tertiary center were included and analyzed for disease characteristics. Estrogen receptor 1 (ESR1) and 2 (ESR2), progesterone receptor (PGR) and androgen receptor (AR) mRNA expression was assessed in primary tumors and healthy intestine. Estrogen receptor alpha (ERα) and AR protein expression was analyzed by immunohistochemistry in primary tumors and mesenteric metastases. Results Of the 559 patients, 47% were female. Mesenteric metastasis/fibrosis was more prevalent in men (71/46%) than women (58/37%, P=0.001 and P = 0.027). In women, prevalence of mesenteric metastases increased gradually with age from 41.1% in women &lt;50 years to 71.7% in women &gt;70 years. Increased expression of ESR1 and AR mRNA was observed in primary tumors compared to healthy intestine (both P &lt; 0.001). ERα staining was observed in tumor cells and stroma with a strong correlation between tumor cells of primary tumors and mesenteric metastases (rho=0.831, P=0.02), but not in stroma (rho=-0.037, P=0.91). AR expression was only found in stroma. Conclusion Sexual dimorphism in SI-NETs was most pronounced in mesenteric disease and the risk of mesenteric metastasis in women increased around menopause. The combination of increased ERα and AR expression in the SI-NET microenvironment suggests a modulating role of sex steroids in the development of the characteristic SI-NET mesenteric metastasis and associated fibrosis.

Comparison of Manual and Digital Assessment of KI-67 in Neuroendocrine Tumors

2020 ◽  
Vol 154 (Supplement_1) ◽  
pp. S125-S125
Author(s):  
B S Raju ◽  
M Quinton ◽  
L Hassell
Keyword(s):  
Image Analysis ◽  
Neuroendocrine Tumors ◽  
Digital Image ◽  
Digital Image Analysis ◽  
Hot Spot ◽  
World Health ◽  
Proliferation Index ◽  
Digital Analysis ◽  
Ki 67 ◽  
Digital Assessment

Abstract Introduction/Objective Proliferative activity is an essential prognostic and treatment indicator for neuroendocrine tumors (NET). Ki-67 proliferation index, if reported by unaided microscopic estimation on hot-spot locations could lead to variability and inconsistencies. This study aims to compare the Ki-67 assessment of NETs by visual estimation versus automated digital image analysis (Roche iCoreo/Virtuoso). Methods 212 patients with Ki-67-graded GI NETs (117 G1; 61 G2; 34 G3) from 2010 to 2019 were reassessed using digital image analysis quantification of hot spot areas of at least 500 cells (average 800 cells). Revised tumor grades were assigned according to the European Neuroendocrine Tumor Society guidelines and the 2010 World Health Organization classification and compared to initially reported grade. Results We found 75% concordance for G1, with 22% of cases upgraded to G2 and 3% of cases upgraded to G3. For G2, there was 70.5% agreement, with 13.1% of cases downgraded to G1 and 16.4% upgraded to G3. For G3, there was 100% agreement, (kappa=0.64, overall). Retrospective review of discordant G3 cases revealed cases with known metastasis, small fragments of tissue, or polyps. Scanning and scoring required approximately 10 minutes per case. Conclusion Our data shows the time/effort difference of visually estimating versus automated digital analysis may lead to significant classification errors in these tumors. Although digital analysis has limitations, including tumor heterogeneity, misidentification of tumor cells, and poor immunostaining which could require manual counting by a pathologist, this rigor should be reinforced and explicitly stated to increase accuracy and reproducibility of grading.

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