Primary Neuroendocrine Carcinoma Research Articles

Comparison of clinical characteristics and outcomes in primary neuroendocrine breast carcinoma versus invasive ductal carcinoma.

Neuroendocrine breast carcinoma (NECB) is a rare, special histologic type of breast cancer. There are some small sample studies on the clinical outcomes of NECB patients, which are worthy of further discussion. We conducted a retrospective case-control study of clinical characteristics and outcomes among patients with primary NECB versus invasive carcinoma of no special type (NST) between November 2004 and November 2017 in the Peking Union Medical College Hospital, Beijing. NST patients were strictly matched 1:4 during the same period based on the TNM stage. Statistical comparisons were performed to determine the differences in survival between NST and NECB patients and to identify clinical factors that correlate with prognosis. A total of 121 participants affected by primary NECB were included in our analysis from November 2004 to November 2017. Elderly persons (>60 years of age) were more likely to have primary NECB than young persons (p=0.001). In addition, primary NECB patients had significantly higher odds of having tumors 2-5cm (36.5%) and >5cm (6.1%) in size than NST patients. Despite a significant difference in tumor size, the proportion of patients with lymph node metastases showed no difference between the two groups (p=0.021). In addition, the rate of patients with ER-negative tumors in the NECB group (4.2%) was significantly lower than that in the primary NST group (29.8%). Significant differences were noted in the PR-negative (13.3% versus 36.6%, P<0.001) and HER2-negative (90.5% versus 76.4%, P=0.001) expression statuses among these patients. Of 121 primary NECB patients, 11 (9.1%) experienced relapses during the follow-up period. We found that tumor size was an independent risk factor for relapse. For hormone receptors on tumor cells, ER-positive breast cancer patients had significantly lower odds of relapse than receptor-negative patients. Our data demonstrate no significant difference in mortality and relapse between the primary NECB and NST groups. The tumor size in the primary NECB group was significantly larger than that in the NST group. In addition, the absence of ER independently increased the relapse rate for breast carcinoma patients.

HER2 mutations in advanced cervical neuroendocrine carcinoma: implications for trastuzumab deruxtecan therapy.

Recent clinical evidence shows that the antibody-drug conjugate (ADC) trastuzumab deruxtecan (T-DXd) can successfully treat patients with advanced HER2-mutant non-small cell lung cancer (NSCLC). We aimed to characterize HER2 mutations in cervical neuroendocrine carcinoma (NEC) among Taiwanese women to provide the rationale for exploring T-DXd as a tumor-agnostic targeted therapy option. We analyzed 12 archived primary cervical NEC samples from Taiwanese patients. Tumor-rich areas were marked for microdissection on 10 μm unstained sections. DNA was extracted, and HER2 hotspots were sequenced using a targeted panel on the Illumina MiSeq. HER2 missense mutations were identified in 5 of 12 cases (41.7%). Of the 5 cases with mutations, 2 patients (40%) had a single mutation, while 3 patients (60%) had double mutations. We detected 4 substitutions outside the tyrosine kinase domain (non-TKD), which were p.P1170A, p.S305C, p.I655V, and a novel T328K alteration. No mutations were found within the tyrosine kinase domain (TKD). The 41.7% HER2 mutation rate warrants expanded screening and future clinical investigation of the T-DXd targeting HER2 mutations in cervical NEC patients. Overall, this study contributes to the molecular understanding of cervical NEC and lays the groundwork for developing more effective treatment strategies.

Management of Neuroendocrine Breast Carcinoma (NEBC): Review of Literature.

Extra pulmonary high-grade poorly differentiated neuroendocrine carcinomas (EP-NECs) are rare tumors that usually arise in the gastrointestinal and genitourinary tracts. Primary neuroendocrine carcinoma of the breast (NEBC) is extremely rare, representing less than 0.1% of all breast cancers and less than 1% of neuroendocrine neoplasms. Consequently, they can be misdiagnosed as other types of breast cancer, however, proper immunohistochemical (IHC) studies can assist with making the correct diagnosis. Management of NEBC can be challenging given the paucity of evidence-based literature and should not routinely follow the therapeutic guidelines of other breast cancers. In this article, we review the current literature regarding the management of NEBC.

P-68 Misdiagnosed calcitonin negative Medullary thyroid carcinoma as Hurthle cell thyroid adenoma with fine needle aspiration biopsy

Abstract Introduction Medullary carcinoma is a rare thyroid carcinoma, that originates from the malignant proliferation of parafollicular C cells. Medullary thyroid cancer produces calcitonin, and elevated calcitonin level is an essential feature of this tumor, so, most of them are associated with high levels of calcitonin. Calcitonin-negative medullary carcinoma of the thyroid gland is an extremely rare entity and poorly understood primary neuroendocrine carcinoma that is characterized by classic medullary carcinoma of the thyroid morphology without raised serum calcitonin levels. Fine needle biopsy (FNAB) is a diagnostic test done in people with suspected thyroid cancer and it is very important for timely diagnosis and treatment of medullar thyroid cancer, especially when calcitonin levels are in normal range. Clinical Case A 35-year-old woman visited an endocrinologist due to swelling on the left side of the neck. Thyroid ultrasound showed hypoechogenic, heterogenous nodule in the left lobe with dimensions 29×28×35 mm and calcifications. Laboratory tests were normal: thyroid stimulating hormone (TSH) 3,0 mlU/ml; free T4 14,3 pmol/l; anti –thyroid peroxidase antibody (ATPO) 20IU/ml; human thyroglobulin 35IU/ml; calcitonin &amp;lt;2 pg/ml; carcinoembryonic acid (CEA) 0.742ng/ml. The FNAB were performed, with cytological finding for classification group I. Four months after the first biopsy, the FNAB was repeated and Hürthle cells were found, with pronounced degenerative changes as well as pronounced cytological atypia, cytological findings correspond to classification group III. Computed tomography of the neck was performed preoperatively and it showed hypodense nodule (slightly smaller than 4 cm) with numerous calcifications, and no significantly enlarged lymph nodes. Left lobectomy was performed with histopathological findings for Medullary thyroid carcinoma. Immunohistochemical tumor cells were positive for chromogranin A, CD56, focally for thyroglobulin and CK 19, and negative for S-100 and NSE. RET gene mutation analysis was performed and it was negative. Additional diagnostic tests were performed for MEN2A and MEN 2B and they were excluded. Postoperative levels of calcitonin and CEA were in normal range. Conclusion Normal calcitonin levels do not exclude medullar carcinoma. Follow-up and monitoring of the patients with thyroid nodules is very important for timely diagnososis and treatment of medullar carcinoma.

Carboplatin and Etoposide for the Treatment of Metastatic Prostate Cancer with or without Neuroendocrine Features: A French Single-Center Experience.

Chemotherapy using carboplatin and etoposide (CE) is frequently pragmatically proposed to treat metastatic prostate cancer (mPC), both primary small-cell neuroendocrine (PSC-NE) carcinoma and adenocarcinoma with or without neuroendocrine (NE) marker elevation. However, the real benefit of CE is poorly reported in the recent therapeutic context. We retrospectively analyzed the efficacy and tolerance of CE chemotherapy in these three different groups of mPC patients. Efficacy endpoints included radiological response, progression-free survival (PFS), and overall survival (OS), as well as PSA response and PFS2/PFS1 ratio in patients with adenocarcinoma. Sixty-nine patients were included in this single-center study (N = 18 with PSC-NE carcinoma and 51 with adenocarcinoma with (N = 18) or without (N = 33) NE marker elevation). Patients with adenocarcinoma were highly pretreated with next-generation hormonal agents (NHAs) and taxanes. In patients with adenocarcinoma, a PSA response ≥50% was observed in six patients (15.8%), four of whom had NE marker elevation. The radiological response was higher in PSC-NE and tended to be higher in adenocarcinoma when NE marker elevation was present. Comparing patients with adenocarcinoma with vs. without NE marker elevation, the median PFS was 3.7 and 2.1 months and the median OS was 7.7 and 4.7 months, respectively. Overall, 62.3% of patients experienced grade 3-4 adverse events (mainly hematological), and three treatment-related deaths were recorded. Reports of the clinical results of CE suggest that we should not mix PSC-NE and castration-resistant adenocarcinoma of the prostate. In patients with heavily pretreated adenocarcinoma, the benefit/risk ratio of CE chemotherapy seems unfavorable due to poor response and high toxicity.

Long‐term survival of a cat diagnosed with primary hepatic neuroendocrine carcinoma treated with surgical resection and several adjuvant chemotherapies

AbstractPrimary hepatic neuroendocrine carcinoma, previously referred to as carcinoid, is a malignant tumour arising from neuroendocrine cells and is a rare form of hepatic neoplasia in cats. This case report describes primary hepatic neuroendocrine carcinoma in a cat, with weight loss and vomiting as its primary clinical signs. Definitive diagnosis was made following surgical excision and histopathology of the affected liver lobes in addition to immunohistochemistry staining. Following surgery, the cat received different chemotherapy agents due to observation of progressive disease at restaging visits. The cat is currently receiving metronomic chemotherapy of cyclophosphamide and has no evidence of metastatic disease present 1009 days after initial presentation. Primary hepatic neuroendocrine carcinoma can occur in cats and should be a differential diagnosis for a hepatic mass in this species. Primary hepatic neuroendocrine carcinomas are rare in cats, and there is no standard of care for treatment in companion animals.

Primary small cell neuroendocrine carcinoma of the gallbladder: an extremely rare case

Primary small cell neuroendocrine carcinoma of the gallbladder: an extremely rare case

Computed tomographic findings in a canine ovarian teratoma.

A 2-year-old, intact female, Labrador Retriever was referred for progressive abdominal distension, assessed by emergency clinicians as being extrauterine in origin on AFAST. Abdominal radiographs and ultrasound identified a large, lobulated, partially mineralized, soft tissue, mid-abdominal mass and gravid uterus. Contrast-enhanced CT identified a mixed fat to soft tissue attenuating mass with a complex internal mineralized matrix, heterogeneous contrast enhancement, receiving blood from the left ovarian artery. Histology confirmed a left ovarian teratoma, diffuse endometrial hyperplasia, and fetal implantation. The patient had a good post-operative outcome for 2 years, but was later diagnosed with primary cranial mediastinal neuroendocrine carcinoma.

Primary neuroendocrine carcinoma of cervical lymph node masquerading as non-Hodgkin lymphoma: A diagnostic challenge

ABSTRACT A large extended family of tumors classified as neuroendocrine tumors most commonly occurs in the gastrointestinal tract and bronchus pulmonary tree. It is extremely unusual for a primary neuroendocrine tumor to present as a cervical lymph node mass at initial presentation. We discuss the rare case of a 55-year-old man who initially complained of a right neck mass that was misinterpreted as non-Hodgkin lymphoma on fine needle aspiration cytology. By integrating clinical findings, radiography, fine-needle aspiration cytology, histomorphology, and immunohistochemistry analysis, a definitive diagnosis of primary neuroendocrine carcinoma of the cervical lymph node was made. He received chemotherapy and decompressive radiation as treatment. Regarding the course of disease in the present case, the patients underwent a distant subcutaneous metastasis over the right anterior chest wall 10 months after the initial manifestation. The patient is still alive, albeit his general condition has gotten deteriorated, and he is getting regular follow-ups.

WITHDRAWN: Primary large cell neuroendocrine carcinoma of the bladder: A case report and review of the literature

Large cell neuroendocrine carcinoma (LCNEC) of the bladder is a rare bladder tumor. Due to its invasive clinical behavior, most patients already have muscle layer invasion and/or metastasis at the time of diagnosis. We report a 72-year-old female patient who presented with gross hematuria. A solitary tumor located in the anterior wall of the bladder was found by cystoscopy. Biopsy pathological examination suggested urothelial carcinoma (UC) of the bladder. The patient underwent partial cystectomy and was eventually diagnosed as LCNEC (pT2bN0M0) based on the results of postoperative immunohistochemical examination.

Primary Small Cell Neuroendocrine Carcinoma of the Tonsil: A Rare Case Report and Review of Literature

Neuroendocrine tumors of the head and neck region are extremely infrequent. Small cell neuroendocrine carcinoma (NEC) of the tonsil is almost unheard of and carries a poor prognosis. There is no standard treatment protocol with regard to this tumor type. We present a 74-year-old male with complaints of odynophagia and swelling on the right side of the neck for one month. Physical examination showed a right neck level II lymph node with an ulceroproliferative mass involving the (R) tonsillar fossa, uvula, soft palate, and obstructing the oropharynx. MRI showed a right tonsillar mass measuring 3.4 × 3.3 × 1.4 cm with an ipsilateral level II lymph node measuring 2.7 × 1.9 cm. PET-CT scan showed a metabolically active right tonsillar lesion with a right level II lymph node. Histopathological examination revealed small cell NEC. On immunohistochemistry, tumor cells were strongly positive for PanCK, synaptophysin, chromogranin, CD56, and p16. Tumor cells were negative for CD45, CK7, CK20, and EBV-LMP. Ki-67 was 80%. The patient was treated with cisplatin and etoposide-based chemotherapy, and the tumor showed a very good response.

Predictors for axillary lymph node metastasis in primary neuroendocrine carcinomas of the breast and neuroendocrine differentiated breast cancers

Aims: Primary neuroendocrine carcinomas of the breast (NEC) and neuroendocrine differentiated breast cancers are rare entities. The aim of this study was to investigate clinical and histopathological findings and predictors for axillary lymph node metastasis (ALNM) in primary neuroendocrine carcinomas of the breast (NEC) and neuroendocrine differentiated breast cancers (NEBC).&#x0D; Methods: Patients with a diagnosis of breast cancer with histopathological neuroendocrine features between the years 2015 and 2022 were retrospectively screened. The patients were divided into two main groups, the NEC and NEBC groups. The two groups were evaluated in terms of their clinical and histopathological characteristics and predictive factors for axillary lymph node.&#x0D; Results: A total of 35 patients [NEBC group: 24 patients, NEC group: 11 patients) were evaluated. At the time of diagnosis, the median age was 57 (NEC: 49 years, NEBC: 57.5). Of the 35 patients, 15 (57.1%) had ALNM, and lymphovascular invasion was detected in 16 (45.7%). When the whole patient population was evaluated for ALNM, it was found that lymphovascular invasion had an effect on ALNM (p=0.005). In the NEBC group, the rate of ALNM was associated with an increase in tumor diameter (p=0.035). Additionally, the tumor diameter was found to be predictive of ALNM in the ROC analysis (AUC: 0.753, 95% CI: 0.557-0.950, cut-off: 2.35 cm, p=0.035). Analyses of correlation revealed a low-level correlation between age and Ki-67 in the study cohort ( ρ= -0.341, p=0.45).&#x0D; Conclusion: NECs and NEBCs of the breast are uncommon tumors with a high ALNM potential. Patients with lymphovascular invasion and a large tumor diameter should be carefully evaluated for ALNM. Further research is required to determine the most appropriate treatment strategy for these rare subtypes of breast cancers.

Neuroendocrine Carcinoma of the Hypopharynx - An Elusive Clinical Rarity.

Neuroendocrine carcinoma originating from neuroendocrine cells is typically linked to unfavourable survival rates. We are introducing an exceptional case of neuroendocrine carcinoma occurring in the hypopharynx. To date, only a handful of instances involving primary neuroendocrine carcinoma of the hypopharynx have been documented. Advanced age, being male, a history of chronic alcoholism, smoking, and previous radiation are all risk factors associated with this condition. The majority of patients present with distant metastases and are not amenable to a complete cure. As there are no guidelines for the treatment of this rare tumour, various treatment modalities have been tried. Here, we are reporting one such case which was diagnosed as small-cell neuroendocrine carcinoma of the hypopharynx on the basis of histopathological cues and received concurrent chemoradiotherapy.

A clinical and pathologic study of muscle invasive urothelial carcinoma. Does the grade really matter?

PurposeThe purpose of our study is to correlate grade of Muscle invasive urothelial carcinoma with prognosis of patients in terms of disease recurrence, metastasis and death. Materals and methodsWe retrieved 48 cases of invasive urothelial carcinomas which on initial presentation had invaded muscularis propria (pT2) or beyond muscularis propria (pT3 or pT4), diagnosed and treated in Shaukat Khanum Memorial hospital Lahore and whose 8–20 years follow up data was available in hospital archives received either as Transurethral resection or cystectomy specimens from 2002 to 2015. Cases diagnosed as primary adenocarcinomas, Neuroendocrine carcinomas or other bladder malignancy other than urothelial carcinoma were excluded. ResultsAll 48 pT2 and higher stage patients were high grade. 34/48(70.8%) patients had disease recurrence, 11/48(22.9%) had no recurrence of disease and 3 patients lost to follow up. 43/48(89.5%) patients developed disease metastasis while 5/48(10.4%) did not develop metastatic disease. 39/48(81.2%) died of disease, 3 patients lost to follow up while 6/48(12.5%) patients survived. 5 out of 6 patients who survived had underwent cystectomy while 6 more underwent cystectomy but still died of disease. ConclusionMuscle invasion is itself an independent prognostic factor in predicting prognosis of patients and grade of such tumors is not much helpful as either majority of tumors are high grade or even if they are low grade, the prognosis is not good.

Combined Hepatocellular Neuroendocrine Carcinoma: A Rare Tumor

ABSTRACT Neuroendocrine tumors originate from neuroendocrine cells primarily located in the gastrointestinal tract. These tumors often metastasize to the liver. Primary hepatic neuroendocrine carcinomas are uncommon, and combined hepatocellular neuroendocrine carcinomas are exceedingly rare. There is a lack of data on the management of these rare tumors. Most cases have very poor prognosis secondary to aggressive behavior of the neuroendocrine tumor component. It is important for clinicians to be aware of this rare carcinoma to allow for early diagnosis and optimize potential treatment options.

Three cases of primary small cell neuroendocrine carcinoma of the upper urinary tract and review of the literature

Three cases of primary small cell neuroendocrine carcinoma of the upper urinary tract and review of the literature

Clinicopathological Features of Primary Small Cell Neuroendocrine Carcinoma of the Bladder

Objective To investigate the clinicopathological features,immunohistochemical features,diagnosis,and relationship with sporadic prostate cancer in primary small cell neuroendocrine carcinoma of the bladder. Methods We retrospectively analyzed the clinical characteristics of 12 patients with primary small cell neuroendocrine carcinoma of the bladder diagnosed at Beijing Chao-Yang Hospital affiliated to Capital Medical University from January 2013 to September 2022.The histological features of primary small cell neuroendocrine carcinoma of the bladder were re-evaluated by two pathologists according to the 2022 revision of the World Health Organization Classification of Tumors of the Urinary System and Male Genital Organs.Electronic medical records were retrieved,and telephone follow-up was conducted from the time of histopathological diagnosis to the death or the end of the last follow-up until January 31,2023. Results The 12 patients include 7 patients in pT3 stage and 1 patient in pT4 stage.Eight patients were complicated with other types of tumors,such as high-grade urothelial carcinoma of the bladder and squamous cell carcinoma.Five patients had sporadic prostate cancer.Immunohistochemical staining showed that 12 (100.0%),10 (83.3%),and 8 (66.7%) patients were tested positive for CD56,Syn,and CgA,respectively.The Ki67 proliferation index ranged from 80% to 90%.Five patients with urothelial carcinoma were tested positive for CK20,GATA3,and CK7.P504S was positive in all the 5 patients with prostate cancer,while P63 and 34βE12 were negative.The follow-up of the 12 patients lasted for 3-60 months.Eight of these patients died during follow-up,with the median survival of 15.5 months.Four patients survived. Conclusions Primary small cell neuroendocrine carcinoma of the bladder is a rare urological tumor with high aggressiveness and poor prognosis.In male patients with bladder prostatectomy,all prostate tissue should be sampled.If prostate cancer is detected,the prostate-specific antigen level should be monitored.

Primary multiple carcinomas: Papillary thyroid carcinoma and primary neuroendocrine liver carcinoma

Searchable abstracts of presentations at key conferences in endocrinology ISSN 1470-3947 (print) | ISSN 1479-6848 (online)

Association of Merkel Cell Polyomavirus Status With p53, RB1, and PD-L1 Expression and Patient Prognosis in Merkel Cell Carcinomas: Clinical, Morphologic, and Immunohistochemical Evaluation of 17 Cases.

Merkel cell carcinoma (MCC) is a rare, aggressive, primary neuroendocrine carcinoma of the skin whose main risk factors are immunosuppression, UV radiation exposure, and Merkel cell polyomavirus. Programmed death-1/programmed death ligand-1 (PD-L1)-based immunotherapy is currently the first choice for treating patients with metastatic MCC. MCC biopsies (17) were evaluated for their nucleus and cytoplasm characteristics and growth patterns, as well as for intratumor lymphocytes, mitotic number, and lymphovascular invasion. Paraffin-embedded tissue samples of the biopsies were stained with MCPyV large T-antigen (LTag), RB1, p53, and PD-L1. We observed MCPyV LTag expression in 9 out of the 17 tumors, and all 9 cases were positive for RB1 ( P <0.000). p53 staining was not significantly correlated with MCPyV LTag. We observed no relationship between p53 expression and any other parameters, and PD-L1 expression was low in the MCC samples. We evaluated PD-L1 using both the combined positive score and tumor proportion score (TPS), and found that TPS was correlated with MCPyV LTag expression ( P =0.016). Tumors with tumor-infiltrating lymphocytes showed a better prognosis than those without these lymphocytes ( P =0.006). Our data demonstrated that RB1 was effective for immunohistochemically investigating the MCPyV status of tumors. TPS was superior to the combined positive score in evaluating PD-L1 in MCC. Tumor-infiltrating lymphocytes were the only parameters that were associated with survival. Further studies with larger series are required to confirm these results.

A tale of multiple primaries: Primary neuroendocrine carcinoma, vaginal vault and renal cell carcinoma in a 52 years old female

Cancer patients have 15-25% higher risk of second malignancy compared to general population. We hereby describe an extremely unusual case of 52-years-old-female with Neuroendocrine Carcinoma (NEC) of vaginal vault developing 4