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Examples of well differentiated (4a), poorly differentiated (4b), and moderately differentiated (4c) gastrointestinal neuroendocrine tumors. Photographs courtesy of Nasir Aejaz, MD, Department of Pathology, H. Lee Moffitt Cancer Center and Research Institute, Tampa.
Source publication
Neuroendocrine malignancies of the gastroenteropancreatic axis include carcinoid and pancreatic endocrine tumors. These heterogeneous neoplasms arise from the enterochromaffin cells of the gastrointestinal tract and the islet cells of the pancreas. Histologically, most well-differentiated endocrine tumors consist of small, round, monomorphic cells,...
Contexts in source publication
Context 1
... majority of gastrointestinal neuroendo - crine tumors are described histologically as well-differentiated (Figure 4a). This term identifies tumors with a relatively monomorphic population of small, round cells, a low mitotic rate of < 2 mitoses/10 high powered fields (HPF), a low Ki-67 proliferative index (< 2%), and absence of necrosis. 83-88 Well-differentiated neuroen- docrine tumors (WD-NETs) are clinically indolent and associated with prolonged survivals, even in the metastatic setting. Poorly differentiated (PD) neuroendocrine carcinomas ( Figure 4b) are associated with cellular pleomorphism, a mitotic rate > 10 mitoses/10 HPF, a Ki-67 proliferative index >10%, and tumor necrosis. These are highly aggressive malignancies that closely resemble small-cell carcinoma of the lung, both in morphologic appearance and clinical behavior. 87-89 Intermediate grade or "moderately differentiated" (Figure 4c) tumors of the gastroenteropan- creatic axis are not well defined in the medical literature, but appear to have an intermediate prognosis. 84,86,90 In recent years, the World Health Organi zation (WHO) developed a classifi- cation system for endocrine tumors of the gastrointestinal tract. Using the WHO (2000) nomenclature, 91 the term "carci- noid" is applied to serotonin-producing WD endocrine neoplasms of the small intestine, appendix, and colon. A clinico- pathologic classification has also been proposed by WHO (2004) 92 for pancreatic endocrine neoplasms that distinguishes between WD endocrine tumors (benign or uncertain behavior), WD endocrine carci- nomas, and PD endocrine carcinomas, based on tumor size, local invasion of adjacent organs, angioinvasion, perineural invasion, Ki-67 proliferation index, and the presence of metastases. ...
Context 2
... majority of gastrointestinal neuroendo - crine tumors are described histologically as well-differentiated (Figure 4a). This term identifies tumors with a relatively monomorphic population of small, round cells, a low mitotic rate of < 2 mitoses/10 high powered fields (HPF), a low Ki-67 proliferative index (< 2%), and absence of necrosis. 83-88 Well-differentiated neuroen- docrine tumors (WD-NETs) are clinically indolent and associated with prolonged survivals, even in the metastatic setting. Poorly differentiated (PD) neuroendocrine carcinomas ( Figure 4b) are associated with cellular pleomorphism, a mitotic rate > 10 mitoses/10 HPF, a Ki-67 proliferative index >10%, and tumor necrosis. These are highly aggressive malignancies that closely resemble small-cell carcinoma of the lung, both in morphologic appearance and clinical behavior. 87-89 Intermediate grade or "moderately differentiated" (Figure 4c) tumors of the gastroenteropan- creatic axis are not well defined in the medical literature, but appear to have an intermediate prognosis. 84,86,90 In recent years, the World Health Organi zation (WHO) developed a classifi- cation system for endocrine tumors of the gastrointestinal tract. Using the WHO (2000) nomenclature, 91 the term "carci- noid" is applied to serotonin-producing WD endocrine neoplasms of the small intestine, appendix, and colon. A clinico- pathologic classification has also been proposed by WHO (2004) 92 for pancreatic endocrine neoplasms that distinguishes between WD endocrine tumors (benign or uncertain behavior), WD endocrine carci- nomas, and PD endocrine carcinomas, based on tumor size, local invasion of adjacent organs, angioinvasion, perineural invasion, Ki-67 proliferation index, and the presence of metastases. ...
Context 3
... majority of gastrointestinal neuroendo - crine tumors are described histologically as well-differentiated (Figure 4a). This term identifies tumors with a relatively monomorphic population of small, round cells, a low mitotic rate of < 2 mitoses/10 high powered fields (HPF), a low Ki-67 proliferative index (< 2%), and absence of necrosis. 83-88 Well-differentiated neuroen- docrine tumors (WD-NETs) are clinically indolent and associated with prolonged survivals, even in the metastatic setting. Poorly differentiated (PD) neuroendocrine carcinomas ( Figure 4b) are associated with cellular pleomorphism, a mitotic rate > 10 mitoses/10 HPF, a Ki-67 proliferative index >10%, and tumor necrosis. These are highly aggressive malignancies that closely resemble small-cell carcinoma of the lung, both in morphologic appearance and clinical behavior. 87-89 Intermediate grade or "moderately differentiated" (Figure 4c) tumors of the gastroenteropan- creatic axis are not well defined in the medical literature, but appear to have an intermediate prognosis. 84,86,90 In recent years, the World Health Organi zation (WHO) developed a classifi- cation system for endocrine tumors of the gastrointestinal tract. Using the WHO (2000) nomenclature, 91 the term "carci- noid" is applied to serotonin-producing WD endocrine neoplasms of the small intestine, appendix, and colon. A clinico- pathologic classification has also been proposed by WHO (2004) 92 for pancreatic endocrine neoplasms that distinguishes between WD endocrine tumors (benign or uncertain behavior), WD endocrine carci- nomas, and PD endocrine carcinomas, based on tumor size, local invasion of adjacent organs, angioinvasion, perineural invasion, Ki-67 proliferation index, and the presence of metastases. ...
Citations
... A recent SEER (Surveillance, Epidemiology, and End Results) study showed a significant increase in the annual incidence of GEP-NENs [2]. Based on histologic differentiation and grade, NENs can be divided into well-differentiated neuroendocrine tumors (NETs) and poorly differentiated carcinomas (NECs) [3,4]. Unlike low-grade welldifferentiated NETs that are generally indolent, poorly differentiated NECs are highly aggressive malignancies. ...
Background:
Neuroendocrine neoplasms (NENs) are a heterogeneous group of cancers that had a significant increase in annual incidence in the last decade. They can be divided into well-differentiated neuroendocrine tumors (NETs) and poorly differentiated neuroendocrine carcinomas (NECs). Poorly differentiated NECs are aggressive forms of cancers with limited therapeutic options. The first line treatment of metastatic poorly differentiated NECs is similar to small cell lung cancer, with cytotoxic chemotherapy (etoposide plus platinum). Patients who progress have limited therapeutic options and poor overall survival, calling for other novel agents to combat this deadly disease. Therefore, in this article, we summarized the effects of a novel component, Thymoquinone (TQ, C10H12O2), which is the main bioactive component of the black seed (Nigella sativa, Ranunculaceae family), plus immunotherapy in case series of patients with refractory metastatic extra-pulmonary NEC (EP-NEC) and one case of mixed neuroendocrine-non-neuroendocrine neoplasm (MiNEN).
Methods:
We report the effect of TQ plus dual immune checkpoint inhibitors (nivolumab plus ipilimumab) in four patients with poorly differentiated gastrointestinal Ep-NEC and MiNEN who progressed on cytotoxic chemotherapy.
Results:
This is the first case series to report the clinical activity of TQ plus dual immune checkpoint inhibitors (nivolumab plus ipilimumab) in patients with refractory metastatic EP-NEC. The four patients showed benefits with the combined regimen TQ plus dual ICPIs with durable response and exceeded the two years of progression-free survival. None of the four patients experienced significant toxicity, and all of them showed improvement in quality of life.
Conclusion:
The reported clinical courses suggest that combined TQ plus ICPIs is a potential promising regimen for refractory EP-NEC and MiNEN that deserves further prospective investigation.
... Poorly-differentiated extra-pulmonary neuroendocrine carcinomas (EP-NECs) are a group of neoplasms with highly aggressive behavior, defined by ki-67 proliferative index more than 20% and limited therapeutic options [1][2][3]. Treatment for EP-NECs has been adapted from small cell lung cancer (SCLC), with platinum etoposide doublet chemotherapy utilized as the standard first-line regimen [4,5]. In the later-line setting, very few treatments have been prospectively validated in patients with EP-NECs, with most treatment recommendations stemming from small retrospective studies. ...
Simple Summary
Extrapulmonary neuroendocrine carcinomas (EP-NEC) are a group of tumors which are often metastatic and characterized by poor outcomes. Platinum-etoposide chemotherapy is the current front-line therapy for metastatic EP-NEC, and has been adapted from small cell lung cancer. There are limited treatment options for patients with platinum-resistant EP-NEC, with no current established second-line standard of care. Recently, there has been mixed evidence for the role of immunotherapy in EP-NEC, with limited existing prospective data. In this multicenter retrospective analysis, we compared outcomes between patients with refractory EP-NEC who received single, dual immune check point inhibitors (ICPIs) and cytotoxic chemotherapy in the second-line setting. This real world experience suggests that utilizing ipilimumab and nivolumab in patients with second-line pretreated EP-NEC may be more effective than other existing treatment options.
Abstract
Background: Dual utilization of the immune checkpoint inhibitors (ICPIs) nivolumab plus ipilimumab has demonstrated clinical promise in the treatment of patients with refractory high-grade neuroendocrine neo-plasms (NENs) in phase II clinical trials (DART SWOG 1609 and CA209), while single agent ICPIs have largely been ineffective for these types of tumors. While both trials demonstrated promising results in high grade NENs, there was no adequate description of the association between tumor differentiation (high-grade well-differentiated neuroendocrine tumor vs poorly-differentiated extra-pulmonary neuroendocrine carcinoma (EP-NEC) and ICPI outcomes in the DART SWOG 1609 trial. Our study reports on the effectiveness and toxicity profile of dual ICPIs in a real world second-line EP-NEC patient population. Methods: Data on metastatic EP-NEC patients, treated with either ICPIs (single and dual ICPIs) or chemo-therapy in the second-line setting, were retrieved from databases of three comprehensive cancer centers. Associations between treatment characteristics and outcomes, including progression-free survival (PFS) and overall survival (OS), were evaluated. Results: From 2007 to 2020, we identified 70 patients with metastatic EP-NEC (predominantly of gastro-enteropancreatic origin), of whom 42 patients (23 males, 19 females, median age 62 years old) were eligible for the final analysis. All patients were refractory to platinum etoposide doublet chemotherapy in the first-line setting. The median PFS for patients who received dual ICPIs (11 patients), single agent ICPI (8 patients), and cytotoxic chemotherapy (23 patients) was 258 days, 56.5 days, and 47 days, respectively (p = 0.0001). Median overall survival (OS) for those groups was not reached (NR), 18.7 months, and 10.5 months, respectively (p = 0.004). There were no significant differences in treatment outcomes in patients according to tumor mismatch repair (MMR) or tumor mutational burden (TMB) status. Grade 3–4 adverse events (AEs) were reported in 11.1% of the patients who received dual ICPIs; however, none of these AEs led to permanent treatment discontinuation. Conclusions: In the second-line setting, patients with EP-NECs treated with dual ICPIs (nivolumab plus ipilimumab) experienced improved PFS and OS compared to patients treated with single agent ICPI or cytotoxic chemotherapy. These results echo some of the current evidence for ICPIs in grade 3 NENs and need to be validated in future prospective studies.
... Generally, GI-NETs often show hematogenous metastases, and the most frequent sites of distant spread are the liver, bones, and peritoneal cavity [13][14][15][16]. According to some reports, the tumor size, depth of invasion, and lymph node involvement are all significant predictors of malignant behavior in rectal NETs [17]. ...
... Tumors smaller than 1 cm are rarely metastatic, with only 3.7% of rectal NETs that are 0.5 cm or smaller being metastatic at the time of diagnosis; rates of metastatic disease increase to 13.2% in tumors 0.5 to 1.0 cm in size, and to 26-28% in tumors 1 to 2 cm in size [18]. Up to 70% of tumors larger than 2 cm may be metastatic [14,19]. In addition, many previous studies have reported that the presence of muscularis propria or lymphovascular invasion in a rectal NET is a strong risk factor for metastasis [20][21][22]. ...
Background:
The incidence of synchronous gastrointestinal neuroendocrine tumors (GI-NETs) and colorectal cancer is very low.
Case presentation:
We present a 72-year-old man diagnosed with a rectal neuroendocrine tumor (NET) with multiple organ metastases and simultaneous sigmoid colon cancer. Although the NET was his prognostic factor, he underwent a laparoscopic sigmoidectomy at first because it was expected that the colon cancer would cause obstruction or bleeding during NET treatment. Subsequently, he started taking everolimus.
Conclusions:
We should consider surgical resection of the synchronous cancer before systemic therapy for a GI-NET regardless of the difference in prognosis between synchronous tumors, if the cancer may impair the continuation of systemic therapy.
... In an analysis of nationwide Swedish registers by Riihimaki et al. [16] to assess the distribution of metastatic sites of NETs among 7334 patients, 568 with primary rectal cancer, metastatic disease was evident in 1842 patients (25%) and in 71 patients with NETs of the rectum (12.5%). The risk of metastases development was higher in primary tumors of the small intestine or pancreatic-hepatobiliary tract, and lower with appendiceal and rectal NET, and the liver was the most common metastatic site [54][55][56]. Specifically, among 71 metastatic rectal tumors, 80% involved liver; bone was the second most frequent metastatic site, followed by lung, central nervous system, pleura or mediastinum [16]. ...
Background:
Neuroendocrine tumors (NETs) are heterogeneous, widely distributed tumors arising from neuroendocrine cells. Gastrointestinal (GI)-NETs are the most common and NETs of the rectum represent 15, 2% of gastrointestinal malignancies. Poorly differentiated neuroendocrine carcinomas of the GI tract are uncommon. We report a rare case of poorly differentiated locally advanced rectal neuroendocrine carcinoma with nodal and a subcutaneous metastasis, with a cytoplasmic staining positive for Synaptophysin and Thyroid Transcription Factor-1.
Case presentation:
A 72-year-old male presented to hospital, due to lumbar, abdominal, perineal pain, and severe constipation. A whole-body computed tomography scan showed a mass of the right lateral wall of the rectum, determining significant reduction of lumen caliber. It also showed a subcutaneous metastasis of the posterior abdominal wall. Patient underwent a multidisciplinary evaluation, diagnostic and therapeutic plan was shared and defined. The pathological examination of rectal biopsy and subcutaneous nodule revealed features consistent with small-cell poorly differentiated neuroendocrine carcinoma. First line medical treatment with triplet chemotherapy and bevacizumab, according to FIr-B/FOx intensive regimen, administered for the first time in this young elderly patient affected by metastatic rectal NEC was highly active and tolerable, as previously reported in metastatic colo-rectal carcinoma (MCRC). A consistent rapid improvement in clinical conditions were observed during treatment. After 6 cycles of treatment, CT scan and endoscopic evaluation showed clinical complete response of rectal mass and lymph nodes; patient underwent curative surgery confirming the pathologic complete response at PFS 9 months.
Discussion and conclusions:
This case report of a locally advanced rectal NEC with an unusual subcutaneous metastasis deserves further investigation of triplet chemotherapy-based intensive regimens in metastatic GEP NEC.
... Well-differentiated NETs often secrete hormones or vasoactive substances that can be measured by serum or urinary analysis, with the elevated hormone pattern suggestive of a particular NET subtype. [15][16][17] Testing for 5-hydroxyindoleacetic acid is usually recommended regardless of the suspected subtype, with additional tests done according to clinical presentation. 16,18 Plasma chromogranin A and serotonin and urinary or plasma 5-hydroxyindoleacetic acid are often elevated in several NET subtypes (eg, well-differentiated NET, pancreas, and thyroid medullar carcinoma). ...
... A diagnostic imaging plan to identify the neuroendocrine subtype often starts with CT, followed by MRI if liver metastasis is suspected, and then functional imaging in tumors with SR expression. 16,17 Endoscopy and endoscopic ultrasound can be effective at identifying NETs originating from the gastrointestinal tract. For localized and SR-positive tumors, first-generation imaging methods such as scintigraphy may be sufficient to determine the subtype based on the anatomic primary site to guide subsequent treatment. ...
Neuroendocrine tumors (NETs) comprise a heterogeneous group of neoplasms in which tumor staging/prognosis and response to treatments depend heavily on accurate and timely identification of the anatomic primary site or NET subtype. Despite recent technological advancements and use of multiple diagnostic modalities, 10% to 14% of newly diagnosed NETs are not fully characterized based on subtype or anatomic primary site. Inability to fully characterize NETs of unknown primary may cause delays in surgical intervention and limit potential treatment options. To address this unmet need, clinical validity and utility are being demonstrated for novel approaches that improve NET subtype or anatomic primary site identification. Functional imaging using Ga-radiolabeled DOTATATE positron emission tomography/computed tomography has been shown to overcome some false-positive and resolution issues associated with octreotide scanning and computed tomography/magnetic resonance imaging. Using a genomic approach, molecular tumor classification based on differential gene expression has demonstrated high diagnostic accuracy in blinded validation studies of different NET types and subtypes. Given the widespread availability of these technologies, we propose an algorithm for the workup of NETs of unknown primary that integrates these approaches. Including these technologies in the standard workup will lead to better NET subtype identification and improved treatment optimization for patients.
... These heterogeneous tumors are classified by the primary tumor site, grade, and functional status. As most NETs are slow growing and lack obvious symptoms, they often present with locally advanced or metastatic disease by the time patients are accurately diagnosed (2)(3)(4). The overall median survival of patients with NETs is estimated to be 9.3 years, but survival varies considerably by tumor stage and grade (1). ...
Background:
Octreotide has been used for decades in the United States (US) and Europe to treat patients with advanced neuroendocrine tumors (NETs). Lanreotide was approved in 2014 to improve progression-free survival (PFS) in patients with unresectable, well- or moderately-differentiated, locally advanced or metastatic gastroenteropancreatic NETs. Therefore, clinicians and patients may consider sequencing therapy from octreotide to lanreotide. However, current real-world outcomes data on patients who have made this transition is limited.
Methods:
We conducted a multicenter, noninterventional, retrospective medical record review of patients with locally advanced or metastatic gastroenteropancreatic NETs (NCT03112694). Included patients had been treated with long-acting octreotide monotherapy for ≥90 days before transitioning to lanreotide monotherapy and continued on lanreotide for ≥90 days. Abstractors entered patient demographic and clinical data into a customized, web-based case report form. We assessed clinically defined PFS and other tumor-related outcomes while patients were treated with lanreotide. Outcomes were analyzed according to level of response at the time of transition from octreotide to lanreotide: progressive disease, nonprogressive disease, or unknown. Statistical analyses were descriptive. Clinically defined PFS and duration of treatment with lanreotide were estimated using the Kaplan-Meier method.
Results:
Data were abstracted for 91 patients with gastroenteropancreatic NETs who received long-acting octreotide followed by lanreotide at six US based sites. At initial diagnosis, 71.4% of patients had stage IV disease. Small intestine (63.7%) and pancreas (14.3%) were the most common primary tumor sites. Mean [standard deviation (SD)] duration of follow-up from diagnosis was 70.6 (41.3) months. Patients received long-acting octreotide for a mean (SD) of 38.4 (32.8) months. When patients transitioned to lanreotide, 57.1% had nonprogressive disease on octreotide, 30.8% had progressive disease, and the remainder had unknown disease status. The most common reasons for switching from octreotide to lanreotide were progressive disease (22.0%), formulary change (15.4%), and patient preference (9.9%). Patients received lanreotide for a median (95% CI) duration of 24.7 (16.7-59.9) months. At the end of follow-up, 74% of patients remained on lanreotide monotherapy. Progression occurred in 24.2% of patients during lanreotide treatment. Overall median (95% CI) clinician-defined PFS following the transition to lanreotide was estimated to be 23.7 months [20.2 months-NE (not estimable)]. Patients with nonprogressive disease when they transitioned to lanreotide experienced a median clinician-defined PFS of 24.7 (17.0-NE) months. Among patients reported to have progressive disease when they transitioned to lanreotide, median (95% CI) clinician-defined PFS was estimated to be 15.2 (11.4-NE) months. There were no material differences in adverse events recorded during the long-acting octreotide and lanreotide treatment periods.
Conclusions:
Our study suggests that lanreotide monotherapy is well tolerated and may contribute to stabilization of disease in a subset of patients with locally advanced or metastatic gastroenteropancreatic NETs previously treated with long-acting octreotide.
... The gastrointestinal tract is the most common site of origin (70%) followed by the lungs (25%). Other less common sites include kidneys, thymus and larynx [5]. Neuroendocrine tumors have a proclivity for hepatic metastasis, with up 90% of patients having hepatic involvement at the time of diagnosis [6]. ...
... The presence of hepatic metastases is a poor prognostic factor with a median survival of 2-4 years. By extension, significant burden of hepatic metastases portends for increased morbidity due to symptoms from mechanical compression from the lesions, hepatic synthetic dysfunction as the liver is gradually replaced by tumor or hypersecretion of hormones which may lead to episodic flushing, cardiac failure from valvular damage, profuse diarrhea and bronchospasm (carcinoid syndrome) [5,6,7,8]. ...
While tumor lysis syndrome is a relatively common oncologic emergency that may occur spontaneously or resulting from cancer directed therapy, it is relatively unusual occurrence in solid tumors, especially neuroendocrine tumors. It is also particularly rare after hepatic trans-arterial embolization. We report a case of a 60-year-old man who had hepatic trans-arterial embolization for metastatic neuroendocrine tumor of the liver of unknown primary, who developed tumor lysis along with post-embolization syndrome. He received aggressive intravenous fluid resuscitation, allopurinol and rasburicase for his tumor lysis syndrome but subsequently had acute renal failure for which he underwent renal replacement therapy. The patient responded well to treatment with complete resolution of his post-embolization syndrome, tumor lysis syndrome and acute renal failure. Our case report highlights the need to consider tumor lysis syndrome in solid tumors. It should be readily recognized and treated given the associated high risk of morbidity and mortality.
... Differentiation refers to the extent to which neoplastic cells resemble endocrine cells of origin. Poorly differentiated tumors tend to be highly aggressive malignancies, whereas well-differentiated tumors tend to progress more indolently (4). Tumor grade refers to the proliferative activity of tumor cells, measured using either mitotic rate or Ki-67 index. ...
Gastroenteropancreatic neuroendocrine tumors are relatively rare neoplasms, characterized by a propensity to secrete hormones that cause distinct clinical syndromes. During the past decade, the systemic treatment landscape has improved significantly: new options include everolimus, an inhibitor of the mammalian target of rapamycin; sunitinib, an angiogenesis inhibitor; and cytotoxic regimens such as capecitabine and temozolomide. Moreover, the recent approval of the radiolabeled somatostatin analog 177Lu-DOTATATE has had a significant impact on management of neuroendocrine malignancies. In this review, we discuss advances in the medical management of gastroenteropancreatic neuroendocrine tumors within the context of the larger multidisciplinary approach to these diseases.
... NETs are probably one of the most heterogeneous group of cancers and difficult to grasp into a universally accepted classification system for more than 3 decades 5 . Indeed, all commonly used classification systems using proliferation markers, tumor stage, and primary tumor localization [GEP-NET's (gastric mucosa, the small and large intestine, the rectum and pancreas) and lung] aim to establish clear epidemiologic view and precision in treatment decision [6][7][8] . Recent epidemiological studies showed increase rate of NETs in Europe and United States and now, prevalence of NETs is higher than all gastrointestinal cancers except colon cancer 5 . ...
Amaç: Nöroendokrin tümörler (NET) tümör ve hasta özellikleri, muhtemelen tüm dünyada çevresel ve genetik faktörlerin yol açtığı coğrafi alanlar arasında önemli değişiklik göstermektedir. Bu nedenle, tek merkez deneyimi bildirmek, epidemiyolojik görüşleri açıklığa kavuşturmaya ve karar verme sürecini geliştirmeye yardımcı olabilirGereç ve Yöntem: Başkent Üniversitesi Tıbbi Onkoloji Anabilim Dalına başvuran ve takip edilen, tümör özelliklerini, tedavi yöntemlerini, sağkalım oranlarını ve prognostik faktörlerini kaydettiğimiz 82 NET tanılı hastanın retrospektif analizi yapılmıştır.Bulgular: Tüm grup ve lokal evredeki NET'lerin genel sağkalım süresi, sırasıyla 44 ve 24 aydır. En sık görülen primer tümör alanı gastrointestinal sistem ve daha sonra pankreas bölgesi olarak bulundu. Küratif cerrahi rezeksiyon oranı karsinoid sendrom ile başvuran hastaların%46'sında ve %8.5'inde idi. Karaciğer metastazı akciğer, kemik ve lenf nodu metastazı ile karşılaştırıldığında en yaygın metastatik bölge idi. Hastaların %70'inden fazlası kemoterapi ve somatostatin analoğu ile tedavi edildi. Sonuç: Daha yüksek greydli, erkek cinsiyeti olan ve ileri yaşta (>65 yaş) hastalarda sağkalım oranı düşüktür. Bununla birlikte, nispeten düşük hasta sayısı ve yeni tedavi yöntemlerinin (<%10) daha az kullanımı, çalışmamızın gelecek için yönermeler üretebilmesi için sınırlamalar getirdi.
... Gastrointestinal neuroendocrine tumors (GI-NETs) often show hematogenous metastasis, with the liver being the most common and pancreas being a rare metastatic site [1][2][3][4]. There are few reports on pancreatic metastasis of GI-NETs; thus, the clinical course and the indication for resection in such cases are unknown. ...
... Pancreatic metastasis from a rectal NET is rare. According to the autopsy data on the prevalence of metastatic pancreatic tumors, 3%-12% of malignant pancreatic tumors are metastatic [1][2][3][4]. In addition, among 690 autopsy cases with malignant tumors, 103 cases had metastatic pancreatic tumors. ...
Introduction:
Gastrointestinal neuroendocrine tumors (GI-NETs) often show hematogenous metastasis, with the liver being the most common metastatic site; however, metastasis to the pancreas is rare.
Case presentation:
We report a rare case of rectal NETs with pancreatic metastases in a 75-year-old man who presented with a chief complaint of constipation. Imaging and endoscopic findings revealed a rectal submucosal tumor, a pancreatic hypovascular mass, and multiple liver masses. The rectal lesion and pancreatic lesions were diagnosed as neuroendocrine tumors using biopsy and endoscopic ultrasound fine-needle aspiration, respectively. Synchronous rectal NET and pancreatic NET (P-NET) with liver metastasis of either of these two were preoperatively diagnosed. A two-stage surgery was performed, comprising abdominoperineal resection and distal pancreatectomy. Pre-operative imaging findings showed a solitary mass in the pancreas, although the resected specimen contained multiple lesions. Immunohistochemical staining of the resected rectal and pancreatic lesions showed that both were synaptophysin positive and chromogranin A (CgA) negative. Generally, rectal NET cells are positive for synaptophysin and negative for CgA, while the majority of P-NETs are positive for both. The final diagnosis was rectal NETs with pancreatic and liver metastases. Till date, there have been no reports on the outcomes in patients with pancreatic metastasis of GI-NETs.
Conclusions:
More case reports on metastatic NETs are needed to arrive at a consensus for a standardized treatment regimen.
