Search

Abstract: A 34-year-old woman who presented with severe psychosis and clinical features of Cushing syndrome underwent 18 F-FDG PET/CT that revealed hypermetabolic lung lesion along with predominantly increased metabolism of bilateral basal ganglia, a scintigraphic correlate of acute psychosis. The lesion was surgically excised and histopathologically proven to be adrenocorticotropic hormone-producing lung carcinoid. Posttreatment 18 F-FDG PET scan showed restoration of normal brain metabolism with complete reversal of psychosis. Even though rare, one should be aware of psychosis as an initial presentation of Cushing syndrome and use of 18 F-FDG PET/CT for mapping brain metabolism as shown in this case., Competing Interests: Conflicts of interest and sources of funding: none declared., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Cushing's syndrome, a clinical condition characterized by hypercortisolemia, exhibits distinct clinical signs and is associated with cyclic cortisol secretion in some patients. The clinical presentation of cyclic Cushing's syndrome can be ambiguous and its diagnosis is often challenging. We experienced a 72-year-old woman with cyclic ACTH-dependent Cushing's syndrome caused by a pulmonary carcinoid tumor. Diagnosis was challenging because of the extended trough periods, and the responsible lesion was initially unidentified. A subsequent follow-up computed tomography revealed a pulmonary lesion, and ectopic ACTH secretion from this lesion was confirmed by pulmonary artery sampling. Despite the short peak secretion period of ACTH (approximately one week), immunostaining of the surgically removed tumor confirmed ACTH positivity. Interestingly, stored plasma chromogranin A levels were elevated during both peak and trough periods. The experience in evaluating this patient prompted us to investigate the potential use of plasma chromogranin A as a diagnostic marker of ACTH-dependent Cushing's syndrome. A retrospective study was conducted to determine the efficacy of plasma chromogranin A in three patients with ectopic ACTH syndrome (EAS), including the present case, and six patients with Cushing's disease (CD) who visited our hospital between 2018 and 2021. Notably, plasma chromogranin A levels were higher in patients with EAS than in those with CD. Additionally, a chromogranin A level in the present case during the trough phase was lower than that in the peak phase, and was similar to those in CD patients. The measurement of plasma chromogranin A levels could aid in differentiating EAS from CD.

Background: Carcinoid tumors are rare neuroendocrine malignancies presenting in an increasing number in our center. The incidence of carcinoid tumors is approximatively between 2.5 and 5 cases per 100,000 people of whom about 50% develop carcinoid syndrome. Once the carcinoid syndrome has developed, a carcinoid cardiomyopathy can occur. Carcinoid heart disease (CaHD) remains a serious and rare complication associated with a significant increase in morbidity and mortality. Although carcinoid tumors have been known and studied for several years, there are still scarce data on the anesthetic management and the peri operative period., Case Presentation: We describe a case of a Caucasian 44-year-old woman with an unusual presentation of left CaHD with an ileal neuroendocrine tumor and liver metastases. Our preoperative somatostatin administration protocol, limit the cardiac damage. The maintenance of stable hemodynamics, the use of balanced anesthetic technique, all along with a good understanding of the pathology, played a major role in the successful management of anesthesia. This case report allows us to introduce our decision algorithm for the management of this type of pathology in our tertiary hospital, Cliniques Universitaires Saint-Luc., Conclusion: Despite the paucity of data, anesthetic management of patients with carcinoid tumor can be safely performed with effective hemodynamic monitoring and a good understanding of the pathophysiology. Knowledge and application of a clear institutional algorithm for octreotide administration and multidisciplinary consultation at a referral center are essential for the management of these patients., (© 2024. The Author(s).)

Background: Mature cystic teratomas (MCT) of the ovary are benign ovarian germ cell neoplasms. Malignant transformation is possible but rare and ovarian carcinoid tumors in MCT are among the most extremely rare subtypes., Case Presentation: We report a case of a 60-year-old Iranian woman suffering from postmenopausal bleeding and hypogastric pain for the last 40 days. An adnexal mass was detected during the physical examination. Ultrasound imaging showed a (55 × 58) mm mass in the left ovary. Total abdominal hysterectomy, bilateral salpingooophorectomy and comprehensive staging surgery were performed for the patient. Intraoperative frozen section of the left ovarian mass was indicative of a malignant tumor. She was diagnosed with a carcinoid tumor with benign mucinous cystadenoma arising on MCT of the ovary, confirmed in the histopathology and immunohistochemistry examination. The tumor was classified as low grade and no chemotherapy cycles were considered. The patient was followed up long-term and no recurrence was observed during 14 months of examinations., Conclusion: Ovarian carcinoids arising from MCT are rare neuroendocrine neoplasms, and proper diagnosis of these tumors requires careful histopathology evaluation and appropriate examination. Therefore, it is necessary to consider these tumors as a possible differential diagnosis and evaluate them in individuals (especially postmenopausal women) who have abdominal pain or abnormal bleeding and a palpable mass., (© 2024. The Author(s).)

Several cases reported in the literature have confirmed the link between pulmonary aspergillosis and various malignant diseases. Furthermore, it has been observed that the correlation between carcinoid tumor and lung adenocarcinoma is quite uncommon. The etiopathogenic mechanisms underlying these correlations remain poorly defined. We present the case of a patient with three of these diseases: a lung adenocarcinoma with a lepidic pattern, a typical carcinoid, and pulmonary aspergillosis. An additional noteworthy aspect of this case pertains to the timely detection of both lung malignancies. Thus, the necessity for further investigation to ascertain the pathogenic connection among the three diseases is underscored. The ultimate objective is to enhance the prognosis of individuals diagnosed with lung cancer, which is a prevailing malignant disease on a global scale.

Cowden syndrome (CS) is a rare genetic condition due to the various germline mutations in the phosphatase and tensin homologue on chromosome ten (PTEN) tumour suppressor gene. As a result, CS is characterised by an increased risk of developing various benign and malignant tumours, such as thyroid, breast, endometrial and urogenital neoplasms, as well as gastrointestinal tract tumours. However, the neuroendocrine tumour association with CS is not elucidated yet. We present a case of a 46-year-old male patient diagnosed with testicular seminoma and follicular thyroid cancer in his medical history. Our patient met the clinical diagnostic criteria of Cowden syndrome. Genetic analysis established the clinical diagnosis; a known heterozygous PTEN mutation was detected [PTEN (LRG_311t1)c.388 C > T (p.Arg130Ter)]. Incidentally, he was also seen with multiple pulmonary lesions during his oncological follow-up. A video-assisted thoracoscopic left lingula wedge resection and later resections from the right lung were performed. Histological findings revealed typical pulmonary carcinoid tumours and smaller tumorlets. Somatostatin receptor SPECT-CT, 18 F-FDG-PET-CT and 18 F-FDOPA-PET-CT scans and endoscopy procedures could not identify any primary tumours in other locations. Our patient is the first published case of Cowden syndrome, associated with multifocal pulmonary carcinoids. Besides multiple endocrine neoplasia type 1, we propose Cowden syndrome as another hereditary condition predisposing to multiple pulmonary tumorlets and carcinoid tumours., (© 2024. The Author(s).)

Carcinoid syndrome is caused by the release of serotonin and other substances, which commonly occurs due to liver metastasis of neuroendocrine tumors. It rarely occurs due to liver metastasis of neuroendocrine carcinoma. We report the case of a patient with liver metastasis of neuroendocrine carcinoma who suffered from acute abdominal pain and diarrhea triggered by hemodialysis. Various differential diagnoses were considered, but we concluded these symptoms to be probably caused by exacerbation of carcinoid syndrome, as the serum 5HIAA level was markedly elevated, and a drug with anti-serotonin activity was effective. Prochlorperazine maleate, which has anti-serotonin activity, was effective for these symptoms, and the patient was able to continue maintenance hemodialysis, which contributed to his quality of life and prognosis. We speculated the mechanism of carcinoid exacerbation was that substances such as serotonin had entered the systemic circulation via the increased extrahepatic shunt of the portal venous blood flow, entering the inferior vena cava and that this condition had been triggered by hemodialysis via the same mechanism as portal systemic encephalopathy., (© 2023. The Author(s), under exclusive licence to Japanese Society of Nephrology.)

A 50-year-old male was referred to our hospital for the further evaluation and treatment of abdominal pain. He was diagnosed with complicated appendicitis using computed tomography. After conservative treatment, he underwent an interval appendectomy. A histopathological examination revealed a goblet cell carcinoid(GCC)of the appendix with subserosal invasion. He underwent laparoscopic ileocecal resection with D3 lymph node dissection. Histopathological findings showed neither residual tumor nor lymph node metastasis. The patients is currently followed as an outpatient without recurrence. Here we report our experience with GCC, a rare disease.

Carcinoid tumors (CT) are among the least studied tumors. It is a relatively rare and slow-growing tumor with good survival in its primary form. However, metastatic carcinoid tumor comes up with many different complications contributing to increased morbidity and mortality. Metastatic form of the disease has a wide spectrum of clinical manifestations and multisystem involvement including cardiovascular manifestations, neurological manifestations, and psychiatric manifestations and so on. In this review, we are centered towards the cardiovascular manifestations of the disease, which, by far, is one of the commonest causes of death in these patients. Being a neuroendocrine tumor, cardiovascular manifestations are mainly because of biologically active substances, produced by the tumor cells, remodeling the heart. Development of targeted therapies against carcinoid heart diseases is currently limited by lack of understanding of pathophysiology of the disease processes. In this review, we aim to figure out the spectrum of carcinoid heart diseases, along with the molecular biology of the changes going on, which, in turn, will not only pave a way to the development of targeted therapies but will also extend opportunities for molecular screening of the tumor and diagnosis at an early stage, thereby, reducing the morbidity and mortality., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2023 the Author(s). Published by Wolters Kluwer Health, Inc.)

Background: Pulmonary carcinoid is a rare diagnosis with surgery remaining the standard treatment of choice. However, resection may impact patients' daily activities due to decreased lung volume reserve and postoperative pain. Our study aims to compare the impact of different types of surgical resection on the post-operative quality of life with the application of a strict peri-operative pulmonary care program., Methods: Patients who underwent surgery for bronchopulmonary carcinoid tumors in a tertiary cancer center between August, 2017 and March, 2020 were identified and demographic data was collected. Patients were contacted via phone for the qualitative and quantitative assessment of pain and quality of life, utilizing the Arabic version of Short-form McGill Pain Questionnaire and Activity of Daily Living (ADL) instrument respectively. Lung reserve was assessed before and after surgery. Statistical analysis used Chi-Square for categorical variables and ANOVA for continuous variables., Results: A total of 16 patients underwent different type of resection. The majority were male (n = 10; 63%) with a mean age of 44 years (19-81). Most common clinical stage was stage I (n = 12, 75%) with typical carcinoid features recorded in more than half of the cases (n = 11, 69%). Almost all patients underwent surgical excision (n = 15, 94%) with negative resection margin and no major post-operative complications. Bilobectomy was the most frequent procedure (n = 6, 40%) and video-assisted thoracoscopic surgery (VATS) was utilized in 8 patients (50%). Expected changes were recorded in pre- and postoperative pulmonary function test with an average drop of 10 in FEV1 and 14 mL/min/mmHg in DLCO. The majority of patients (n = 15, 94%) were totally independent doing daily activities. Mild intermittent pain was found in 7 patients (44%) who scored an average intensity of 1.6 out of 10., Conclusions: Excellent long-term outcomes can be achieved following surgical resection of pulmonary carcinoid tumors with little to no effect on patients' lung function and quality of life in regard to performance status and post-operative pain when a good peri-operative pulmonary, physical rehabilitation, and pain management programs are adopted and strictly implemented., (© 2023. The Author(s).)

Purpose: The incidence of small intestinal cancer (SIC) is increasing, however, its aetiology remains unclear due to a lack of data from large-scale prospective cohorts. We examined modifiable risk factors in relation to SIC overall and by histological subtype., Methods: We analysed 450,107 participants enrolled in the European Prospective Investigation into Cancer and Nutrition cohort. Cox proportional hazards models were used to estimate univariable and multivariable hazard ratios (HRs) and 95% confidence intervals (CIs)., Results: During an average of 14.1 years of follow-up, 160 incident SICs (62 carcinoids, 51 adenocarcinomas) were identified. Whilst univariable models revealed a positive association for current versus never smokers and SIC (HR, 95% CI: 1.77, 1.21-2.60), this association attenuated in multivariable models. In energy-adjusted models, there was an inverse association across vegetable intake tertiles for SIC overall (HR T3vsT1 , 95% CI: 0.48, 0.32-0.71, p-trend: < 0.001) and for carcinoids (HR T3vsT1 , 95% CI: 0.44, 0.24-0.82, p-trend: 0.01); however, these attenuated in multivariable models. Total fat was also inversely associated with total SIC and both subtypes but only in the second tertile (SIC univariable HR T2vsT1 , 95% CI: 0.57, 0.38-0.84; SIC multivariable HR T2vsT1 , 95% CI: 0.55, 0.37-0.81). Physical activity, intake of alcohol, red or processed meat, dairy products, or fibre were not associated with SIC., Conclusion: These exploratory analyses found limited evidence for a role of modifiable risk factors in SIC aetiology. However, sample size was limited, particularly for histologic subtypes; therefore, larger studies are needed to delineate these associations and robustly identify risk factors for SIC., (© 2023. The Author(s).)

Introduction: Ectopic Cushing's syndrome (CS) is a rare condition nevertheless well-known to endocrinologists. The pneumologist may be called upon to treat CS not only because bronchial carcinoid tumors are the most frequent source of ectopic ACTH secretion, but also due to the fact that the immunosuppression induced by hypercorticism favors lower respiratory tract infections., Case Report: We report the case of a female patient presenting with acute respiratory failure secondary to Enterobacter cloacae pneumonia exacerbated by SC. Further investigations confirmed ectopic ACTH secretion and revealed a right upper lobe pulmonary nodule. After appropriate antibiotic therapy, the patient received preoperative adrenolytic treatment. Management by right upper lobectomy resulted in the extraction of a 12mm tumor. Pathological analysis was consistent with the diagnosis of a typical carcinoid tumor. Immunohistochemistry confirmed ACTH secretion by the tumor. Even though the postoperative course showed CS regression, the patient developed adrenal insufficiency., Conclusion: Ectopic CS induces immunosuppression, which aggravates lower respiratory tract infections. Search for a pulmonary neuroendocrine tumor should be systematic. Following control of the secretory syndrome by adrenolytic treatment, and if the diagnosis of carcinoid tumor is confirmed, surgical treatment is the preferred option., (Copyright © 2023 SPLF. Published by Elsevier Masson SAS. All rights reserved.)

Diffuse idiopathic pulmonary neuroendocrine cell hyperplasia (DIPNECH) is a rare, but increasingly recognized entity that primarily affects middle-aged and elderly women. It is characterized by abnormal proliferation of pulmonary neuroendocrine cells (PNECs) and is considered a preinvasive lesion for carcinoid tumorlets/tumors. Sometimes, DIPNECH is accompanied by constrictive bronchiolitis which usually manifests as chronic cough and/or dyspnea, along with airflow limitation on spirometry. The telltale imaging sign of DIPNECH is the presence of multiple noncalcified pulmonary nodules and mosaic attenuation on CT. However, these clinico-radiologic features of DIPNECH are characteristic but nonspecific; thus, histopathologic confirmation is usually necessary. DIPNECH has an indolent course and only rarely leads to respiratory failure or death; progression to overt neuroendocrine tumor (carcinoid) of the lung occurs in a minority of patients. Of available therapies, somatostatin analogs and mechanistic target of rapamycin inhibitors are the most promising. In this review, we provide an update regarding the diagnosis and management of DIPNECH and describe critical gaps in our understanding of this entity, including the central terms 'diffuse' and 'idiopathic.' We also summarize the inconsistencies in definitions employed by recent studies and discuss the pitfalls of the DIPNECH definitions proposed by the World Health Organization in 2021. In this context, we propose an objective and reproducible radio-pathologic case definition intended for implementation in the research realm and seeks to enhance homogeneity across cohorts. Furthermore, we discuss aspects of PNECs biology which suggest that PNEC hyperplasia may contribute to the pathogenesis of phenotypes of lung disease aside from constrictive bronchiolitis and carcinoid tumorlets/tumors. Finally, we steer attention to some of the most pressing and impactful research questions awaiting to be unraveled.

Rationale: Carcinoid tumors, derived from the cells of the disseminated neuroendocrine system, are rare, slow-growing neuroendocrine neoplasms that display a relatively indolent disease course. The majority of carcinoids are found within the gastrointestinal tract and bronchopulmonary system. Primary ovarian carcinoids are rare and account for merely 1% of all carcinoid tumors. We describe our experience of a rare case of primary ovarian carcinoid, presenting as chronic constipation, with no other carcinoid symptoms such as flushing, diarrhea, and wheezing., Patient Concerns: A 51-year-old postmenopausal woman with chronic constipation visited the clinic for routine check-up of her preexisting uterine fibroids. She had undergone hemorrhoidectomy 3 years ago. Physical examination revealed a soft abdomen without direct or rebound tenderness. Transvaginal ultrasonography revealed two subserosal fibroids, which had increased in size compared with previous ultrasonographic findings. A 3 cm hyperechoic mass was also detected in the right ovary. Her blood and urine tests were unremarkable, with no ascites in the pelvic cavity. She had a normal CA-125 level of 5.5 units/mL., Diagnosis, Interventions, and Outcomes: The patient underwent a robot-assisted hysterectomy and right salpingo-oophorectomy because of enlarging fibroids and the right ovarian mass. Subsequently, based on the pathological and immunohistochemical findings, she was diagnosed with a primary ovarian carcinoid. The mass consisted of the insular and trabecular types of tumor cells. It was positive for pan-cytokeratin and synaptophysin, and the Ki-67 proliferation index was less than 1%. A follow-up positron emission tomography-computed tomography revealed no distant metastasis. Six months postoperatively, the patient was doing well without any signs of recurrence., Lessons: Primary ovarian carcinoids without teratoma components are rare. It is crucial to make an accurate diagnosis based on the immunohistochemical staining results. Diagnosis in the early stages of the disease are associated with a favorable prognosis, but regular follow-up is mandatory., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2023 the Author(s). Published by Wolters Kluwer Health, Inc.)

This report describes the case of a 46-year-old non-smoker housewife. She presented to our attention with a diagnosis of "difficult asthma" from another center in the previous two years. She had no allergies and had not been exposed to an excessive amount of noxious stimuli. Her chronic respiratory symptoms (dyspnea on exertion with wheezing) remained uncontrolled despite maximal anti-asthmatic inhaled therapy. A high-resolution computed tomography scan was performed to further investigate other pulmonary diseases that mimic asthma. It revealed a pedunculated endotracheal lesion with regular borders that obstructed 90% of the tracheal lumen. The lesion was removed via rigid bronchoscopy with laser endobronchial; histological examination revealed the presence of an atypical carcinoid. Atypical carcinoids are a rare subtype of neuroendocrine lung tumor that accounts for 2% of all thoracic malignancies. They frequently arise from the central airways and cause obstructive symptoms such as coughing, wheezing, chest pain, or recurrent obstructing pneumonia, which is caused by central airway obstruction. Clinical onset is gradual and characterized by non-specific symptoms, which frequently result in misdiagnosis. As a result, in a young patient with progressive dyspnea, chronic cough, and wheezing that is not responding to anti-asthmatic treatment, second-level investigations are required and may lead to a definite diagnosis, allowing the appropriate course of treatment to begin.

Rationale: Atypical thymic carcinoid tumor is an exceedingly rare thymic neuroendocrine tumor derived from the cells of neuroendocrine system. Misdiagnosis or delayed diagnosis may result in disease progression to advanced stages and eventually leads to a poor prognosis. It is therefore necessary to make a correct diagnosis and provide an adequate treatment., Patient Concerns: A 33-year-old Chinese male presented with numbness in bilateral lower extremities and general fatigue for a month. Chest computed tomography revealed a superior anterior mediastinal mass. Thymoma was initially considered, given the location of the mass and radiographic presentation., Diagnosis: Microscopic findings showed that the tumor cells are arranged in pseudoepitheliomatous growth or irregular nested growth pattern in a background of fibroconnective tissue, with focal infiltration into adipose tissue. The chrysanthemum-like structure or beam-like structure seen often in typical carcinoid tumor was not identified in this case. The tumor cells are spindled or oval, with focal active mitosis. The immunohistochemical staining showed strong positivity for CD56, CgA and Syn, positivity for CK, ACTH, and TTF-1, negativity for Vimentin, and ki67 labeled proliferation index was up to 10% in focal areas. According to the radiological and pathological findings, the diagnosis of atypical thymic carcinoid was made., Interventions: The patient underwent surgical resection of the mass., Outcome: No recurrence or metastasis was identified during the follow up., Lessons: Because of its low incidencen, onspecific clinical symptoms, tissue location, and radiological findings, atypical thymic carcinoid tumor may sometimes be misdiagnosed as thymoma. Attention should be paid to avoid misdiagnosis., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2023 the Author(s). Published by Wolters Kluwer Health, Inc.)

A 76-year-old woman was admitted to our hospital for refractory diarrhea with a poor antidiarrheal effect. Chest and abdominal computed tomography revealed a 24×22-mm mass in the left upper lobe of lung and multiple masses in the liver. Urine 5-Hydroxy indol acetic acid was markedly elevated. A liver biopsy revealed large-cell neuroendocrine carcinoma with serotonin production, suggestive of a lung origin, and a lung biopsy revealed combined large-cell neuroendocrine carcinoma and squamous cell carcinoma. Therefore, we made a definitive diagnosis of carcinoid syndrome caused by large-cell neuroendocrine carcinoma of the lung. Although chemotherapy was performed after diagnosis, the patient died 50 days postadmission.

Purpose: We aimed to evaluate and compare the clinical, biochemical and radiological profile and outcomes of patients with ectopic ACTH syndrome (EAS) and Cushing disease (CD) treated over a period of 10 years (2013-2022)., Methods: In this ambispective observational study, we collected data for 146 patients with ACTH-dependent CS (EAS, n = 23; CD, n = 94; occult ACTH source, n = 29). Relevant details were filled in a predesigned proforma and outcomes were ascertained at the most recent visit., Results: EAS was more common in males (65.2 vs. 27.6%, p < 0.001). Patients with EAS had a shorter duration of symptoms [12 (6-12) vs. 31.5 (15-48) months, p < 0.001] and were more likely to have hypokalemia (82.6 vs. 21.0%, p = 0.001), pedal edema (65.2 vs. 34.2%, p = 0.015), weight loss (34.8 vs. 4.0%, p < 0.001) and systemic infection (30.4 vs. 6.5%, p = 0.006). They also had significantly higher 8 a.m. serum cortisol, midnight serum and salivary cortisol and 8 a.m. plasma ACTH levels. Bronchial carcinoid (n = 10, 43.5%) was the most common etiology of EAS. Bilateral adrenalectomy was performed in 11 (47.8%) patients with EAS. Eight patients (34.8%) with EAS died at the last follow-up, of whom 7 (87.5%) had metastatic disease. In CD group, overall remission rate was 69.4% (56.1%, early and 13.3%, delayed) and 26.3% of patients with an initial remission had recurrence., Conclusions: Bronchial carcinoid was the most common cause of EAS in our cohort. Bilateral adrenalectomy was performed in approximately every 1 in 2 patients with EAS and approximately every 1 in 3 patients expired till the last follow-up., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

The carcinoid syndrome (CS) is a constellation of symptoms attributed to hypersecretion of amines, prostaglandins and polypeptides. The cardinal symptoms of CS are flushing, diarrhea and bronchospasm; however, CS may present with various symptoms and signs, as: Skin: cutaneous flushes, cyanosis, pellagra, Gastrointestinal: diarrhea, nausea, abdominal cramps, vomiting, Heart: tricuspid and pulmonic valve thickening causing right heart failure, edema, Respiratory: wheezing, dyspnea.

Although Cushing's Syndrome (CS) is usually caused by pituitary/adrenal adenomas, in the remaining few cases, Adrenocorticotrophic hormone (ACTH) is secreted by extrapituitary neuroendocrine tumors (NET). In typical pulmonary / bronchial carcinoid tumors leading to ectopic ACTH syndrome (EAS). The main principle of treatment is the localization of the ACTH-secreting tumor and its surgical removal. In this case report, we aimed to present two typical carcinoid cases, whose ACTH and cortisol levels returned to normal after lung surgery for ectopic ACTH. One of the cases, a 32-year-old female patient with CS symptoms and signs, was referred to our department after detecting a lesion in the left lower lobe in the thorax CT, which did not show an obvious focus on cranial MRI. The other patient, a 36-year-old male, had previously undergone adrenalectomy for Cushing's syndrome and was admitted to the emergency department due to adrenal insufficiency. The lesion seen in the right lower lobe on thorax CT was evaluated as an ectopic ACTH focus. After the tumors of the patients were resected according to surgical principles, CS clinic regressed, and ACTH and cortisol values returned to normal. Pathological examinations of the surgically resected tumors were reported as typical carcinoid. With surgically removed typical carcinoids tumors, excellent longterm survival results can be achieved and hypercortisolism can be controlled.

Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Background: Pulmonary carcinoid tumorlet (PCT) is defined as small proliferation of neuroendocrine cells that invade the adjacent basement membrane. It is often associated with chronic pulmonary inflammatory processes. However, the characteristics of PCT in end-stage lung diseases remain unclear., Methods: We conducted a retrospective cohort study of the explanted lungs after transplantation at our institution between January 1999 and October 2020. Patients who underwent re-transplantation were excluded., Results: Pulmonary carcinoid tumorlet was incidentally discovered in the explanted lungs from 15 patients (1.1%) out of 1367 lung transplants performed during the study period. Nine patients (60.0 %) were women, with a median age of 59 years (IQR: 57-62) at transplant. Underlying pulmonary indications for lung transplantation were chronic obstructive pulmonary disease (9/15, 60.0%), interstitial lung disease (2/15, 13.0%), pulmonary vascular disease (2/15, 13.0%), alpha-1 antitrypsin deficiency (1/15, 7.0%), and bronchiectasis (1/15, 7.0%). Of the patients who underwent bilateral lung transplantation (13/15, 86.7%), PCT was found in the right lung in 10 patients (10/13, 76.9%). Thirteen patients had one lesion, 1 patient had 2 lesions and 1 patient had multiple lesions., Conclusion: Our study shows that PCT is generally uncommon, but when it occurs, it occurs more frequently on the right side and in female patients with end-stage pulmonary disease. Chronic obstructive pulmonary disease may be a predisposing factor for developing PCT., Competing Interests: DISCLOSURE The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Inc. All rights reserved.)

N-of-1 trials can serve as useful tools in managing rare disease. We describe a patient presenting with a typical clinical picture of Cushing's Syndrome (CS). Further testing was diagnostic of ectopic Adrenocorticotropic Hormone (ACTH) secretion, but its origin remained occult. The patient was offered treatment with daily pasireotide at very low doses (300 mg bid), which resulted in clinical and biochemical control for a period of 5 years, when a pulmonary typical carcinoid was diagnosed and dissected. During the pharmacological treatment period, pasireotide was tentatively discontinued twice, with immediate flare of symptoms and biochemical markers, followed by remission after drug reinitiation. This is the first report of clinical and biochemical remission of an ectopic CS (ECS) with pasireotide used as first line treatment, in a low-grade lung carcinoid, for a prolonged period of 5 years. In conclusion, the burden of high morbidity caused by hypercortisolism can be effectively mitigated with appropriate pharmacological treatment, in patients with occult tumors. Pasireotide may lead to complete and sustained remission of hypercortisolism, until surgical therapy is feasible. The expression of SSTR2 from typical carcinoids may be critical in allowing the use of very low drug doses for achieving disease control, while minimizing the risk of adverse events.

Background: Paragangliomas in the central nervous system account for 0.6% of all head and neck neoplasms, with glomus tympanicum being the most common middle ear tumor. Carcinoid tumors are neuroendocrine tumors, representing less than 1% of neuroendocrine neoplasms in the middle ear. Misdiagnoses have been reported in the literature regarding glomus and carcinoid tumors, however, none have been in the central nervous system or middle ear., Case Description: A 70-year-old female with a history of left temporal lobe tumor underwent unsuccessful resection due to intraoperative bleeding at an outside institution. However, biopsy prior to aborting the case led to the diagnosis of paraganglioma. Eight years postoperatively, the patient presented at our institution with acute confusion, aphasia, and altered mental status. Imaging revealed a 4cm left temporal intraparenchymal hematoma at the known tumor site with concern for intracranial tumor extension. Surgical resection was performed and previous symptoms resolved. Final pathology revealed a Grade II atypical carcinoid tumor with an unusually high Ki-67 of 50%., Conclusions: Carcinoid tumors of the middle ear constitute a differential diagnosis for patients presenting with temporal lobe hemorrhage. A combination of immunohistochemical staining with electron microscopy can assist in differentiating the tumor types. This atypical presentation for a carcinoid tumor in the middle ear suggests the need to consider carcinoid as the diagnosis in patients with a middle ear tumor invading into the temporal lobe and causing hemorrhage. These tumors may demonstrate an unusually high Ki-67 rate, in which case they should be treated aggressively., (Copyright © 2022 Elsevier Masson SAS. All rights reserved.)

Background: Bronchopulmonary carcinoids (BPCs) are rare malignancies but are known to be one of the most common causes of the ectopic adrenocorticotropic hormone (ACTH) syndrome. Surgery is the mainstay of therapy and one key question considering surgical treatment is the impact of local lymph node metastases. We sought to determine the risk factors and prognosis of LN metastases in resected carcinoid patients., Methods: Data of 42 patients of BPCs with lymph node metastasis who received radical surgery in Peking Union Medical College Hospital (PUMCH) from Jan 2000 to Dec 2021 were retrospectively analysed. Overall survival (OS) and progression-free survival (PFS) were analyzed using Kaplan-Meier curves. Independent prognostic factors were assessed by COX hazard proportion model., Results: It was indicated that in patients received radical surgery with local lymph node positive of BPCs, the 5-year OS and PFS rate was 74.5%, 68.3%, respectively. Multivariate Cox regression indicated that ectopic ACTH syndrome (EAS) could predict significantly to a better OS and PFS. In the subgroup analysis, the age, tumor size, Ki-67 index, histology and postoperative chemotherapy in patients with EAS had significantly differences with those without EAS., Conclusions: Our study certified R0 resection with lymphadenectomy was effective in patients with lymph nodal positive. The ectopic ACTH syndrome was a protective factor for a better prognosis, which could provide clear evidence for operations., (© 2022. The Author(s).)

Neuromyelitis optica spectrum disorder (NMOSD) is an autoimmune inflammatory disease, occasionally accompanied by malignant tumors. Immunosuppressive therapy is the mainstay treatment for idiopathic NMOSD; no guidelines have been published for paraneoplastic NMOSD because it is rarely reported in the literature. We report a rare case of a 67-year-old man with paraneoplastic NMOSD associated with thymic carcinoid whose cells expressed aquaporin-4 antibody. After surgical resection, the patient's symptoms improved, and serum aquaporin-4 autoantibody turned negative. We believe that radiographic examination for mediastinal tumors in patients with NMOSD is necessary because thymic epithelial tumors could have a role in the pathogenesis of paraneoplastic NMOSD. After mediastinal tumor has been detected, they should be surgically resected to improve neurological symptoms.

BACKGROUND Carcinoid heart disease typically occurs in the presence of metastatic carcinoid tumor deposits in the liver, as vasoactive substances access the systemic circulation through the hepatic vein. Primary ovarian carcinoid tumors are rare neuroendocrine tumors, and can be associated with carcinoid syndrome and carcinoid heart disease. CASE REPORT We describe the case of a 40-year-old woman who presented with secondary amenorrhea, acne, hirsutism, and diarrhea. She was found to have a heart murmur on exam in the absence of severe symptoms of heart failure. Her investigations demonstrated elevated urinary 5-hydroxyindoleacetic acid (5-HIAA), chromogranin A, and free testosterone. Abdominal computed tomography enterography showed a large and hypervascular pelvic mass. Octreotide scintigraphy confirmed the diagnosis of primary ovarian carcinoid tumor in the setting of an intensely octreotide-avid mass with no evidence of distant metastases. Transesophageal echocardiography showed severe tricuspid regurgitation with severe dilation of the right heart chambers. She underwent a total abdominal hysterectomy and bilateral salpingo-oophorectomy. The pathology demonstrated a 14-cm carcinoid tumor of 'insular' type confined to the ovary, pT1apNX, grade 1, positive for chromogranin and synaptophysin (neuroendocrine markers) and positive mib-1 (Ki-67). Postoperatively, clinical and biochemical parameters improved significantly but her cardiac function regressed over time, resulting in a tricuspid valve replacement 6 years later. CONCLUSIONS Primary ovarian carcinoid tumors can result in carcinoid heart disease, even in the absence of liver metastases. Early diagnosis and treatment contribute to favorable outcomes.

Introduction: Diffuse idiopathic pulmonary neuroendocrine cell hyperplasia (DIPNECH) is considered to be a rare condition associated with lung neuroendocrine tumours (NET), and its natural history is poorly described. We aimed to assess the prevalence and clinicopathologic characteristics of DIPNECH in the lung NET population, and to investigate predictors of time-to-progression (TTP) and overall survival (OS)., Methods: We retrospectively identified patients diagnosed with DIPNECH between April 2005 and December 2020. Clinical data were collected from medical records. The relationship between baseline characteristics and TTP and OS was analysed using the Kaplan-Meier method. Univariate analysis was performed using the Cox proportional hazards model., Results: Of 311 patients with well-differentiated lung NETs, 61 (20%) had DIPNECH and were included in the study. Baseline demographics described 95% female, 59% never smokers and mean body mass index 34.4 kg m -2 ; 77% were typical carcinoids (TC), 13% atypical carcinoids (AC), and 10% both TC and AC (multicentric). At presentation, 54% of patients were asymptomatic. Multicentric NETs were demonstrated in 16 (26%) on histopathology, and a further 32 (52%) had synchronous NETs suggested on imaging (multiple nodules ≥ 5 mm). Seven (11%) patients developed metastases and the median OS from time of first metastasis was 37 months. AC histopathology and NET TNM stage ≥ IIA were associated with poorer TTP and OS. Of the DIPNECH cohort, the 15-year survival rate was 86%., Conclusions: DIPNECH may be more prevalent in the lung NET population than previously appreciated, especially in women. Although our results confirm that DIPNECH is predominantly an indolent disease associated with TC, 23% developed AC and these patients may warrant closer observation., (© 2022 British Society for Neuroendocrinology.)

Background: Ectopic Cushing syndrome (ECS) is a sporadic condition. Even uncommon is an ECS that derives from a carcinoid tumor of the thymus. These tumors may pose several diagnostic and therapeutic conundrums. This report discusses the differential diagnosis, clinicopathological findings, and effective treatment of a rare case of ECS using a minimally invasive approach., Case Presentation: A 29-year-old woman with Cushing syndrome presented with facial flushing. Physical examination revealed hypertension (blood pressure: 141/100 mmHg). A mediastinal tumor was discovered to be the cause of the patient's chronic hypokalemia and hypercortisolemia. Cortisol levels increased in the morning, reaching 47.7 ug/dL. The levels of the hormones ACTH, aldosterone, and renin were determined to be 281 pg/mL, 3.0 ng/dL, and 2.1 pg/mL, respectively. The presence of hypertension, hypokalemia, and alkalinity suggested Cushing's syndrome, which was proven to be ACTH-dependent ECS by a dexamethasone suppression test. A chest CT scan revealed inflammation in the posterior basal region of the right lower lobe. The superior anterior mediastinum was characterized by round-shaped isodensity lesions with distinct borders. She underwent thoracoscopic anterior mediastinal tumor excision via the subxiphoid technique (R0 resection); following surgery, her blood pressure returned to normal, and the hypernatremia/hypopotassemia resolved. The tumor was determined to be a thymic carcinoid. Most notably, cortisol levels fell to half of their presurgical levels after one hour of surgery, and other abnormalities corrected substantially postoperatively., Conclusion: Thoracoscopic excision of thymic tumors by subxiphoid incision may be a useful treatment option for ECS caused by neuroendocrine tumors of the thymus., (© 2022. The Author(s).)

Competing Interests: Competing interests: None declared.

Background: Multiple endocrine neoplasia (MEN) is divided into MEN type 1 (MEN-1) and MEN type 2 (MEN-2). MEN-1 may be associated with thymic carcinoid tumors. We present a case of the surgical removal of a thymic carcinoid associated with MEN-1 via a single-incision port RATS., Case Presentation: A 39-year-old male patient with multiple endocrine neoplasia type 1 (MEN-1) who had an anterior mediastinal mass was referred to our hospital. The patient had undergone total parathyroidectomy and auto-transplantation of a partial parathyroid for hyperparathyroidism 6 years ago. Chest computed tomography revealed an isolated anterior mediastinal mass on the thymic gland with a maximum diameter measuring 22 mm. Thymic carcinoid tumor is classified as MEN-1 and has a poor prognosis, so we decided to remove the tumor. Single-incision port RATS was performed, and thymic carcinoid was confirmed in pathology., Conclusions: This report demonstrates that thymic carcinoid tumor removal is feasible and easy to perform via single-incision port RATS., (© 2022. The Author(s).)

BACKGROUND Carcinoid tumors are well-differentiated tumors that develop from neuroendocrine cells. They are rare tumors and occur most commonly in the gastrointestinal tract, followed by the pulmonary system. They usually present with abdominal pain or cough or persistent pneumonia. They are usually diagnosed with computed tomography (CT) or magnetic resonance imaging (MRI) of the chest or abdomen. The cornerstone of treatment is surgical resection. There are rare reported cases of carcinoid tumor presenting in the pancreas as gastrinoma or insulinoma and are associated with multiple endocrine neoplasia type 1 (MEN1). CASE REPORT We report a case of an otherwise healthy 9-year-old girl who presented with manifestations of Cushing syndrome (easy fatigability, weakness, back pain, easy bruising, hirsutism, acne, skin discoloration [pigmentation], and blurred vision). She was diagnosed with incidental carcinoid tumor in the pancreas based on hypertension and typical stigmata. She underwent distal pancreatectomy and splenectomy. The histopathology showed a well-differentiated neuroendocrine tumor with G2. The diagnosis of concurrent Cushing syndrome and carcinoid syndrome can be challenging, as it is rare. It is important to screen for MEN syndrome when Cushing syndrome occurs in a child, as there is a high rate of transition to malignancy. They are usually diagnosed with ACTH, cortisol, and imaging. CONCLUSIONS Incidental hypertension in children is not common and mandates further investigation and clinical work-up to look for endocrinopathies such as Cushing syndrome and carcinoid syndrome. As the literature on such cases is scant, further reporting of cases is needed.

We have read with interest the article by Pérez Montiel CA et al., in which goblet cell adenocarcinoma (GCA) is described as a cause of acute appendicitis. Although the article is brilliant in terms of histopathological description of the appendiceal GCA, the surgical indication for right hemicolectomy should be analyzed in depth due to the great controversy that exists in the scientific literature.

Background: Pulmonary carcinoid tumors rarely coexist with non-small cell lung carcinoma, and only nine cases have been reported previously. The pathogenesis and origin of these combined tumors remain unclear because of its rarity., Case Presentation: We examined two cases of adenocarcinoma coexisting with a typical or atypical carcinoid tumor: Case 1 was a 77-year-old woman and Case 2 was an 83-year-old woman. Both of these cases had no respiratory symptoms, and underwent pulmonary lobectomies due to incidentally detected lung nodules. Recurrence and metastases were not detected after the surgery. Histologically, carcinoid and adenocarcinoma components were present in both cases. The two components coexisted without mixing with each other. Next-generation sequencing was performed on the two components in these cases. In each case, no common genetic variants were detected., Conclusion: We considered that our cases could histologically and genetically represent collision tumors that did not share common progenitor cells. Comprehensive analyses such as whole genome sequencing could provide important information for elucidating the pathogenesis of adenocarcinoma and carcinoid components., (© 2022. The Author(s).)

Objective: To determine the main forms of primary tracheal cancer (PTC), to specify the indications for various surgeries in these patients depending on extent and localization of lesion., Material and Methods: There were 263 PTC patients. Benign tumors were diagnosed in 68 (25.9%) patients, malignancies - in 195 (74.1%) cases. Tracheal cancer includes 3 basic morphological variants - adenocystic cancer (49.7%), carcinoid (18.7%) and squamous cell carcinoma (19.0%). Other forms of malignancies were much less common. We applied endoscopic intraluminal and open surgeries. In malignant PTC, open surgeries were performed in 165 (84.6%) out of 195 patients. Baseline palliative endoscopic treatment was performed in 30 patients. They underwent airway recanalization (with subsequent tracheal stenting in 19 patients). Endoscopic resection was preferred for benign tumors., Results: Twenty (12.1%) patients died after open surgery, and 1 (3.3%) patient died after endoscopic procedure. Most lethal outcomes occurred in early years of development of tracheal surgery. The causes of mortality were tracheal anastomotic failure in 12 patients, pneumonia in 6 patients, and arterial bleeding in 2 patients. Severe postoperative period was observed in all 3 patients after tracheal replacement with a silicone prosthesis. Long-term treatment outcomes depended on morphological structure of PTC. Favorable results were observed in patients with neuroendocrine tumor (carcinoid), worse outcomes in adenocystic cancer and unfavorable results in squamous cell carcinoma ( p <0.0013). Five-year survival rates were 75%, 65.6%, and 13.3%; 10-year survival rates were 75%, 56.2%, and 13.3%, respectively. These outcomes after combined treatment of primary tracheal cancer were significantly better compared to lung cancer ( p <0.05 when compared to global data)., Conclusion: Treatment of primary tracheal cancer should be based on classical principles of modern oncology (combined therapy, tumor resection with lymphadenectomy). Open and endoscopic interventions are justified. PTC is characterized by more favorable outcomes compared to lung cancer. It is difficult to analyze long-term results in tracheal cancer depending on various features of tumor process due to small number of observations. Accurate conclusions require multiple-center studies, preferably with international participation, which can convincingly prove certain concept.

Neuroendocrine tumors (NETs, originally termed &#8220;carcinoids&#8221;) create a relatively rare group of neoplasms with an approximate incidence rate of 5 to 8 cases per 10 000 persons. NETs predominantly demonstrate indolent disease biology for many years. They become symptomatic when they are large enough or when they metastasize to the liver or the lungs, bones, or other sites. Roughly 30% to 40% of subjects with NETs develop carcinoid syndrome. Signs and symptoms of carcinoid syndrome are bronchospasm, flushing, diarrhea and cramping, cyanosis and pellagra. White plaque-like deposits on the endocardial surface of heart structures are characteristic for carcinoid heart disease. The treatment of patients with carcinoid syndrome is multi-faceted due to the necessity to manage simultaneously the systemic cancer disease as well as the signs of carcinoid syndrome and includes resection or debulking of tumor mass, biological treatment with somatostatin analogues and peptide receptor radionuclide treatment.

Background : Ectopic Cushing's syndrome is a very rare condition caused by an ACTH-secreting tumor outside the pituitary or adrenal glands, and the majority of these cases are encountered in the context of paraneoplastic syndromes. The ectopic source of ACTH secretion is not always obvious to detection and can be challenging. We report a rare case, in which a hidden ACTH-secreting carcinoid tumor of the lung caused a severe refractory hypokalemia, leading us to a race against time to locate the tumor. Case presentation : A 33-year-old young male was admitted to the ICU for the management of a severe hypokalemia, and complains from several months of depression, increased weight, disabling non-radiating dorsal lower back pain and refractory arterial hypertension. The physical examination immediately suggested a Cushing's syndrome. The 24-h cortisoluria confirmed hypercortisolism and the increased ACTH level was oriented towards ACTH-dependent Cushing's syndrome. Thereafter, a dexamethasone suppression test was negative, indicating in favor of ectopic ACTH secretion. The etiological assessment via imaging and isotopes revealed a solitary pulmonary nodule at the right lower lobe estimated at 18 mm, the resection and anatomopathological analysis of which led to the diagnosis of carcinoid pulmonary tumor, and resolved hypercortisolism and its complications. Conclusion : A delayed diagnosis of Cushing's syndrome result in a consequent morbi-mortality, mainly due to cardiovascular events. The optimal treatment for ectopic Cushing's syndrome is surgical resection, thus making the localization of the tumor a key element.

Background: A rare appendiceal malignancy is characterized by both glandular and neuroendocrine histology. It often presents with dissemination of the perforated tumor to peritoneal surfaces. Current treatments involve systemic chemotherapy, cytoreductive surgery and perioperative intraperitoneal chemotherapy., Methods: The impact of clinical, histological and treatment-related characteristics on survival were evaluated and subjected to univariate statistical analyses. All patients had stage IV disease and were treated by a uniform treatment strategy. Survival was determined from onset of disease until death or most recent follow-up., Results: There were 47 patients available for study of whom 17 were male. Median age was 48 with a range of 27-65. None or a single symptom vs. 2 or more symptoms had a significant effect on survival. Median survival of the entire cohort was 45 months and 34.88% and 8.72% of patients survived 5 and 10 years, respectively. The use of neoadjuvant chemotherapy showed no impact on survival. Patients with a peritoneal cancer index (PCI) of 0-20 as compared to PCI > 20 survived longer (p = 0.012). The survival of patients able to have a complete resection as compared to an incomplete resection of disease was significant (p = 0.0087). The type of perioperative chemotherapy did not alter survival., Conclusions: These data show that patients with a lesser extent of disease with a complete cytoreduction had an improved prognosis. No benefit from systemic or perioperative regional chemotherapy was apparent. With long-term follow-up, patients with the combined glandular and neuroendocrine histology exhibiting peritoneal metastases have a guarded prognosis., Competing Interests: Declaration of competing interest For our manuscript entitled, “Appendiceal Tumors with Glandular and Neuroendocrine Features Exhibiting Peritoneal Metastases - Critical Evaluation of Outcome Following Cytoreductive Surgery with Perioperative Chemotherapy”, we do not have any disclosures to declare., (Copyright © 2021 Elsevier Ltd, BASO ~ The Association for Cancer Surgery, and the European Society of Surgical Oncology. All rights reserved.)

Background: Postural tachycardia syndrome (POTS) is a heterogenous disorder of the autonomic nervous system that is commonly associated with small fiber neuropathy, Ehlers-Danlos Syndrome and autoimmune disorders, but association with rare conditions may also occur., Methods: Reported here are clinical features, diagnostic tests and treatment outcomes of 6 unique patients who presented with POTS and were subsequently diagnosed with Fabry disease, McArdle disease, Complex V mitochondrial disease, carcinoid tumor, Hodgkin's lymphoma and chemotherapy-induced neuropathy., Results: All patients (age range 15-57 years, 3 females, 3 males) presented with orthostatic intolerance of at least 6 months duration, and all patients had co-morbid small fiber neuropathy. Five patients presented with symptoms of POTS months to years before the underlying or associated medical condition was discovered, and three out of six patients experienced either complete resolution or significant improvement of POTS after treatment of the underlying or associated medical condition., Conclusion: In rare cases, POTS can present as a possible manifestation of genetic, neoplastic or neurotoxic disorders. Unusual clinical features that fall outside of the typical spectrum of dysautonomia can point toward the presence of another disorder and help guide further diagnostic investigation.

Carcinoid tumors are relative rare neuroendocrine tumors of the lung. Bronchial obstruction's symptoms as cough, hemoptysis and pneumonia may be present when they are centrally located and lung-sparing surgery is usually preferred. We describe the case of an adult patient with a central right upper lobe carcinoid tumor and a concurrent tracheal bronchus malformation. This peculiar bronchial malformation allowed a sleeve S2 segmentectomy sparing the S1-S3 segments and the middle and lower lobes. The patient was discharged on day 4 without complications.

Objectives: Little is known about the etiology of pulmonary carcinoids (PC). Associations with other types of cancer may identify shared risk factors but results from earlier studies were inconclusive. The aim of the present study was to explore the association between PC and other primary malignancies for identifying risk factors., Methods: A query of the nationwide Netherlands Cancer Registry generated data about patients diagnosed with PC from 1989 to 2018. The occurrence of second primary malignancies was evaluated separately for year 1 and years 2-30. The expected numbers of second primary malignancies were calculated using incidence reference tables, controlling for age, gender and period. Confidence intervals (95 % CI) for the ratio between observed and expected numbers (SIR: standardized incidence ratio) were calculated using Poisson distributions., Results: In a total of 2933 patients with PC, 425 consecutive primary malignancies were observed in 376 patients. Concomitant diagnoses in the first year mainly comprised lung (n = 59) and renal cancer (n = 14). Metachronous malignancies beyond the first year were most common for breast (n = 50), colorectal (n = 41), prostate (n = 32), and lung cancer (n = 29). Beyond year 1, the overall risk of second primary cancer in patients with PC was similar to the risk within the general population (n = 256, SIR = 1.12, 95 % CI 0.99-1.27). Increased risks were observed for soft tissue sarcoma (n = 5, SIR = 3.52, 95 % CI 1.14-8.22) and GEPNET (n = 4, SIR = 4.30, 95 % CI 1.17-11.01)., Conclusions: Concomitant diagnosis of PC with other cancers is common, reflecting surveillance diagnostics. Apart from MEN-1 family history, no shared risk factors could be identified., (Copyright © 2020 Elsevier B.V. All rights reserved.)