Clinicopathologic features and diagnostic challenges of small cluster pattern appendiceal neuroendocrine tumors.

Appendiceal neuroendocrine neoplasms (NENs) can present with various growth patterns including the traditional triad of histologic patterns-insular, trabecular and tubular. A small cluster pattern was also found in this study and the literature on this specific morphology is limited. In this study, we conducted a comprehensive review of appendiceal NENs from our institution over a ten-year period. Clinical and demographic data were obtained from medical records. Immunohistochemical stains were performed with antibodies specific for synaptophysin, chromogranin, INSM1, CD56, serotonin and peptide YY. The small cluster pattern was found in 29.4 % of all cases evaluated. The tumor cells in these cases were predominantly located at the distal tip of the appendix, associated with fibrous obliteration. These tumors were smaller in size and tended towards less advanced tumor stage, with reduced incidence of lymphovascular and/or perineural invasion. Chromogranin expression was identified in 76 % of these cases. There is a heterogeneous hormone profile with 46.7 % serotonin and 33.3 % peptide YY. In conclusion, the small cluster pattern NENs present with unique histological features and hormone expression profile. Among the various neuroendocrine markers, INSM1 showed superior diagnostic performance, with high sensitivity and minimal non-specific staining.

Appendiceal neoplasms-A practical guide.

Appendiceal neoplasms (ANs) are a diverse group of pathologies that range from benign to malignant with widely varying prognoses. This article serves as an overview of the practical approach to evaluating and managing a patient with AN by reviewing the current literature and guidelines to provide a framework for the management of these nuanced pathologies.

Single-incision laparoscopic ileocecal resection in a 10-year-old child with appendiceal neuroendocrine tumor.

BACKGROUND: In Japan, the majority of gastrointestinal tract neuroendocrine tumors (NETs) have been reported to originate from the rectum, and appendiceal NETs are relatively rare. Preoperative diagnosis is very difficult and it is diagnosed after appendectomy. Pediatric appendiceal NET is a disease with a good prognosis. However, in rare cases, lymph node metastasis could occur and additional resection is required. CASE PRESENTATION: A 10-year-old boy complained of right lower quadrant abdominal pain and underwent an appendectomy under a diagnosis of acute appendicitis in previous hospital. The final diagnosis was appendiceal NET, so he was referred to our department for additional resection. The tumor was found in the base of the appendix and invasively reached the subserosal layer with obvious vascular invasion. His Ki-67 index was 1 to 2%, so we classified it as appendiceal NET G1 according to the WHO 2015 classification. We considered the possibility of a tumor remnant or lymph node metastasis, so we performed single-incision laparoscopy with D3 lymph node dissection. The pathological diagnosis revealed no tumor remnant but metastasis to one lymph node. He was discharged on the 9th postoperative day. There has been no recurrence at 3 years and 7 months after surgery. CONCLUSION: When the tumor size is 10-20 mm, the frequency of lymph node metastasis in some reports is variable, and there is no consensus yet on the indications for additional resection. However, there are definitely a certain number of cases with lymph node metastasis that require additional resection. In the present patient, long-term survival can be obtained by additional resection. At present, factors such as the presence of vascular or lymph node invasion and the malignancy grade and tumor's location must be considered on a case-by-case basis. Although the incidence rate of appendiceal NET is rare, the diagnosis can be made only during postoperative pathological examination; thus, reliable histopathological examination is required.

Appendicular Neuroendocrine Tumours: An Unusual Cause of Hydronephrosis.

Although neuroendocrine tumours (NETs) are predominantly located in the gastrointestinal tract, pancreas, and lungs, they can also occur in uncommon places such as the biliary system, prostate, breast, head, neck, and even the spinal cord. We present the case of a 30-year-old woman who was referred to the urology clinic for right ureterohydronephrosis. Because the contrast-enhanced CT scan did not show signs of kidney stones or an upper urothelial tract cell carcinoma and was combined with renal scintigraphy, the kidney was not functional, and a left nephrectomy was performed. During the surgery, it was observed that the appendix was attached to the ureter by a tiny tumour. In addition, an appendectomy was also conducted. The pathological test indicated the presence of a NET that had invaded the ureter. The diagnosis was confirmed by immunohistochemical staining. The tissue has been positive for chromogranin and synaptophysin staining. Our work highlights the infrequency and difficulty of diagnosing NETs that invade the ureter. Conducting a thorough histological evaluation in patients with uncertain histopathological diagnoses is essential.

Benign or by Chance: A Case Report on Incidental Appendectomy Revealing a Neuroendocrine Tumor During Traumatic Exploratory Laparotomy.

Incidental appendectomies (IAs) are often performed in laparotomies to prevent future complications caused by the buildup of scar tissue. Although neoplastic findings are rare, all appendectomy specimens should be sent for histopathological analysis. We present the case of a 38-year-old man found to have an appendiceal neuroendocrine tumor (NET) after receiving an IA secondary to a traumatic rectal perforation requiring exploratory laparotomy. Well-differentiated NETs isolated to the appendix have an excellent prognosis. Appendectomies are considered curative for NETs smaller than 2 cm that have not metastasized beyond the appendix. Appendiceal NETs are capable of secreting vasoactive substances and, therefore, causing carcinoid syndrome. However, the progression to carcinoid syndrome generally coincides with metastasis to the liver, indicating a poor prognosis. While histopathological analysis of appendectomy specimens rarely yields atypical findings, this analysis is crucial to ensure that the proper treatment is selected based on tumor progression in an appendectomy specimen staining positive for somatotropin and chromogranin.

Hormonally Silent Multifocal Pheochromocytoma in the Setting of a Well-Differentiated Neuroendocrine Tumor of the Appendix: A Case Report.

Pheochromocytomas (PCCs) and paragangliomas (PGLs) represent tumors arising from chromaffin cells of the adrenal medulla and extra-adrenal sympathetic paraganglia, respectively. PCCs commonly produce one or more catecholamines (epinephrine, norepinephrine, and dopamine), but rarely are they biochemically silent. PGLs on the other hand, generally do not produce catecholamines. They have the highest heritability of all adrenal tumors and are known to be associated with genetic mutations. Patients with hereditary tumors typically present at a younger age and with multifocal disease when compared to sporadic disease. Specific genetic mutations have been well established with hereditary syndromes involving PCC/PGLs. Further research has aimed to identify other mutations and delineate specific phenotypes associated with these mutations. A 34-year-old woman presented for evaluation following a laparoscopic appendectomy that identified a 4-cm well-differentiated neuroendocrine tumor on final pathology. Further work-up included a repeat CT scan followed by a Dotatate PET CT scan which revealed a large (7.3 x 5.8 cm) periaortic mass related to the left adrenal gland. Functional adrenal work-up was negative and her Chromogranin A level was 679 ng/mL. She did report intermittent chest tightness and palpitations but was otherwise asymptomatic. The patient subsequently underwent an exploratory laparotomy with left adrenalectomy and adjacent tumor resection as well as completion of right hemicolectomy with ileocolonic anastomosis. Surgical pathology revealed two distinct masses consistent with multifocal PCC. No residual tumor was found in the colectomy specimen and 24 lymph nodes were negative. She had an uneventful recovery and genetic testing showed a variant of uncertain significance for the POLE and VHL genes. She has received genetic counseling and will be enrolled in an appropriate surveillance protocol.

An Amyand Hernia With Concurrent Appendicitis Secondary to a Neuroendocrine Neoplasm: A Case Report.

Amyand's hernia (AH) describes the rare instance of a vermiform appendix within an inguinal hernia. Primary appendiceal neoplasms are also rare with the majority of cases being found incidentally during routine histopathology. This case reports the management of a 15-year-old male, who presented to the emergency department with acute appendicitis located within an indirect right inguinal hernia, which was ultimately secondary to a neuroendocrine tumor (NET) with serosal involvement. Intraoperative findings included macroscopic appendicitis with no evidence of perforation. Histopathology returned as a neuroendocrine tumor (pT4) with involved proximal margin and curative treatment was undertaken with a caecectomy which returned no residual malignancy. Key considerations include management options of peritoneal spread within the inguinal canal and recommended management NET in the context of an AH. It is important to understand the varied presentations of common surgical diagnosis such as appendicitis and underlying malignancy should always be considered a differential.

The Clinicopathological Significance of Tumor Cell Subtyping in Appendiceal Neuroendocrine Tumors: A Series of 135 Tumors.

Appendiceal neuroendocrine tumors (NETs) are common and often are identified as incidental lesions at the time of appendectomy. The guidelines for management are based on tumor size, degree of invasion, and the Ki67 proliferation index. Most small bowel NETs are composed of serotonin-producing EC-cells, but there are multiple other neuroendocrine cell types. In the rectum, there are L-cell tumors that express peptide YY (PYY), glucagon-like peptides (GLPs), and pancreatic polypeptide (PP); they are thought to have a better prognosis than serotonin-producing tumors. We investigated whether the appendix has distinct neuroendocrine tumor types based on cell type and whether that distinction has clinical significance. We collected 135 appendiceal NETs from the pathology archives of UHN Toronto and UHCMC (Cleveland). We analyzed the expression of biomarkers including CDX2, SATB2, PSAP, serotonin, glucagon (that detects GLPs), PYY, and pancreatic polypeptide (PP) and correlated the results with clinicopathologic parameters. Immunohistochemistry identified three types of appendiceal NETs. There were 75 (56%) classified as EC-cell tumors and 37 (27%) classified as L-cell tumors; the remaining 23 (17%) expressed serotonin and one of the L-cell biomarkers and were classified as mixed. EC-cell tumors were significantly larger with more extensive invasion involving the muscularis propria, subserosa, and mesoappendix compared with L-cell tumors. Mixed tumors were intermediate in all of these parameters. Both EC-cell and mixed tumors had lymphatic and/or vascular invasion while L-cell tumors had none. Unlike EC-cell NETs, L-cell tumors were not associated with lymph node metastasis. Tumor type correlated with pT stage and the only patient with distant metastatic disease in this series had an EC-cell tumor. Our study confirms that appendiceal NETs are not a homogeneous tumor population. There are at least three types of appendiceal NET, including EC-cell, L-cell, and mixed tumors. This information is important for surveillance of patients, as monitoring urinary 5HIAA levels is only appropriate for patients with serotonin-producing tumors, whereas measurement of GLPs and/or PP is more appropriate for patients with L-cell tumors. Our data also show that tumor type is of significance with EC-cell tumors exhibiting the most aggressive behavior.

A Case of Familial Appendiceal Neuroendocrine Tumor.

The risk of developing appendiceal neuroendocrine tumor (aNET) may be attributed to multiple factors. A familial clustering is found in less than 1% of the cases. We report the case of a 25-year-old woman who initially presented with a clinical presentation of acute appendicitis and was subsequently diagnosed with aNET by histopathological examination after an emergency appendectomy. While revealing the result to the patient, she was found to have a positive family history of appendiceal carcinoid tumor. Although rare and only found in 1% of the cases, aNET found in family history should raise the suspicion of neuroendocrine tumors in other family members.

Diagnosis of Appendiceal Neuroendocrine Tumors Following Incidental Appendectomy During Benign Gynecologic Laparoscopic Surgeries: A Case Series.

Gastrointestinal neuroendocrine tumors, although relatively rare, are one of the most common appendiceal neoplasms. Patient symptoms can range from asymptomatic to acute appendicitis, and these tumors are often diagnosed after histopathological evaluation. This case series describes five separate cases of appendiceal neuroendocrine tumors diagnosed by histopathological review following incidental appendectomy during benign gynecologic laparoscopic surgeries at a single multispecialty group. Each case had a preoperative diagnosis of chronic pelvic pain. Intraoperatively, the appendix appeared scarred, adhered, or nodular. Two patients required a right laparoscopic hemicolectomy for the management of the appendiceal neuroendocrine tumor. As a result of these findings, it is recommended that the appendix be routinely evaluated during gynecologic surgeries and, if abnormal in appearance, appendectomy should be performed. Additionally, laparoscopic gynecologic surgeons should receive appendectomy training to aid with the early diagnosis and treatment of appendiceal neuroendocrine tumors.

An unusual case of appendicitis due to appendiceal neuroendocrine tumor in a patient: A case report.

Appendiceal neuroendocrine tumor (NET) is the most common type of appendiceal cancer and is rare in the pediatric population. The clinical characteristics of this cancer are not specific and are highly similar to those of acute appendicitis. By contrast, acute appendicitis is a common surgical indication that is caused by obstruction of the appendix lumen. With a detection rate of 0.5-1% in all appendectomy specimens, appendiceal NET is rare histopathologically and can easily be missed. However, detecting an appendiceal NET in a patient with appendicitis is highly difficult. Therefore, clinicians must be aware of this much under-reported and rare tumor in children. In the present report, a case was reported, of a 13-year-old female child who initially presented with clinical presentation of acute appendicitis, but was subsequently diagnosed with appendiceal NET by histopathological examination after an emergency appendectomy. Follow-up examination including abdominal enhanced CT and enteroscopy 2 years after surgery revealed normal results.

Appendiceal Neuroendocrine Tumor Is a Rare Cause of Ectopic Adrenocorticotropic Hormone Syndrome With Cyclic Hypercortisolism: A Case Report and Literature Review.

OBJECTIVE: Ectopic adrenocorticotropic hormone (ACTH) syndrome (EAS) is a condition of hypercortisolism caused by non-pituitary tumors secreting ACTH. Appendiceal neuroendocrine tumor as a rare cause of ectopic ACTH syndrome was reported scarcely. We aimed to report a patient diagnosed with EAS caused by an appendiceal neuroendocrine tumor and summarized characteristics of these similar cases reported before. CASE REPORT AND LITERATURE REVIEW: We reported a case with Cushing's syndrome who was misdiagnosed as pituitary ACTH adenoma at first and accepted sella exploration. Serum and urinary cortisol decreased, and symptoms were relieved in the following 4 months after surgery but recurred 6 months after surgery. The abnormal rhythm of plasma cortisol and ACTH presented periodic secretion and seemingly rose significantly after food intake. EAS was diagnosed according to inferior petrosal sinus sampling (IPSS). Appendiceal mass was identified by 68Ga-DOTA-Tyr3-octreotate (DOTATATE)-PET-CT and removed. The pathological result was consistent with appendiceal neuroendocrine tumor with ACTH (+). The literature review demonstrated 7 cases diagnosed with EAS caused by appendiceal neuroendocrine tumor with similarities and differences. CONCLUSION: The diagnosis of an ectopic ACTH-producing tumor caused by the appendiceal neuroendocrine tumor can be a challenging procedure. Periodic ACTH and cortisol secretion may lead to missed diagnosis and misdiagnosis. IPSS is crucial in the diagnosis of EAS and 68Ga-DOTATATE-PET-CT plays an important role in the identification of lesions.

Appendiceal Neuroendocrine Tumors: Does Colon Resection Improve Outcomes?

BACKGROUND: Appendiceal neuroendocrine tumors (A-NETs) are rare neoplasms of the GI tract. They are typically managed according to tumor size; however, the impact of surgical strategy on the short- and long-term outcomes is unknown. METHODS: All patients who underwent resection of A-NET at 8 institutions from 2000 to 2016 were analyzed retrospectively. Patient clinicopathologic features and outcomes were stratified according to resection type. RESULTS: Of 61 patients identified with A-NET, mean age of presentation was 44.7 ± 16.0 years and patients were predominantly Caucasian (77%) and female (56%). Mean tumor size was 1.2 ± 1.3 cm with a median of 0.8 cm. Thirty-one patients (51%) underwent appendectomy and 30 (49%) underwent colonic resection. The appendectomy group had more T1 tumors (87% vs 42%, p < 0.01) than the colon resection group. Of patients in the colon resection group, 27% had positive lymph nodes and 3% had M1 disease. R0 resections were achieved in 90% of appendectomy patients and 97% of colon resection patients. Complications occurred with a higher frequency in the colon resection group (30%) compared with those in the appendectomy group (6%, p = 0.02). The colon resection group also had a longer length of stay, higher average blood loss, and longer average OR time. Median RFS and OS were similar between groups. CONCLUSION: A-NET RFS and OS are equivalent regardless of surgical strategy. Formal colon resection is associated with increased length of stay, OR time, higher blood loss, and more complications. Further study is warranted to identify patients that are likely to benefit from more aggressive surgery.

Sixty-One-Year-Old Female With Metastatic Poorly Differentiated Carcinoma of the Appendix With Omental Metastasis.

Neuroendocrine tumors (NETs) are rare tumors that are often asymptomatic and were once considered benign. A specific subtype that we will dive into in this article is appendiceal neuroendocrine tumors (ANETS). ANETs are the most common tumors located within the appendix. Most often, they present as acute appendicitis and are found incidentally on pathology reports status post appendectomy. The objective of this article is to show that even though most of the ANETs are benign and fully treated via surgery, ANETs still have the potential to become malignant and metastasize. Our patient fits the common features seen in ANETS. She is a middle-aged woman with vague abdominal pain and no clear diagnosis on gastrointestinal (GI) workup. Computed tomography (CT) confirmed appendicitis, and pathology reports status post-surgery confirmed stage IV, pT4, Nx, M1 - poorly differentiated neuroendocrine carcinoma of the appendix with omental metastases.

Double intestinal duplication and incidental neuroendocrine tumor of appendix, a rare case of acute abdomen.

INTRODUCTION: Intestinal duplication is rarely reported in adulthood and often remains undiagnosed until onset of complications. We describe the case of a 39 year old woman who came to our observation for acute abdomen due to a combination of double intestinal duplication (colon and ileum) and an incidental neuroendocrine tumor of the appendix. MATERIALS AND METHODS: A 39 year old woman who was admitted at with upper abdominal pain. Multisliced spiral CT scan showed a cystic lesion suggestive of an inflammed Meckel's diverticulum.The patient was underwent an urgent explorative laparoscopy. The intraoperative findings revealed a cystic lesion of the anti-mesenteric side of transverse colon, apparently dissectable from the bowel and a second lesion with a strongly adherent and unresectable from the anti-mesenteric aspect of the small bowel. A combined appendectomy was also performed. The histological diagnosis was consistent with a typical intestinal duplication for both intestinal lesionsand an incidental 2mm carcinoid tumor was also found in the appendix. The postoperative course was uneventful and the patient was discharged on p.o. day 5. At the presenttime she is well and following a regular oncologic follow-up. DISCUSSION: The rarity of this case is due to the concomitant presence of an incidental, sincronous, appendiceal NET. The elective treatment is surgical resection. CONCLUSION: Intestinal duplication in the adulthood is extremely rare and may either have an acute presentation as acute abdomen or represents an incidental finding of mass. We suggest that, once the diagnosis is suspected patient must undergo surgery.