Neuroendocrine Immunohistochemical Markers Research Articles

Expression of Neuron-Specific Enolase and Other Neuroendocrine Markers is Correlated with Prognosis and Response to Therapy in Non-Hodgkin Lymphoma.

Objective Non-Hodgkin lymphoma (NHL) is a common hematological malignancy. There is very little known about the expression of neuroendocrine immunohistochemical markers and their clinical significance in NHL due to the paucity of studies. Our objective was to study the expression of neuroendocrine immunohistochemical markers in NHL and correlate with clinical parameters. Materials and Methods All cases diagnosed as NHL on morphology and immunohistochemistry (World Health Organization, 2016 classification) were included in the study. Immunohistochemistry for neuron-specific enolase (NSE), synaptophysin, and chromogranin A was performed. The results were correlated with clinical parameters and response to chemotherapy. Results A total of 66 cases were included in the study with a male-to-female ratio of 3.1:1. The most frequent subtypes observed were diffuse large B-cell lymphoma not otherwise specified and follicular lymphoma. Among the neuroendocrine markers, positivity was observed only for NSE, whereas the other markers were uniformly negative. It was positive in both B- and T-cell lymphomas and in many different subtypes. No relation with the age and sex of the patients was observed. However, NSE-positive cases, more frequently, presented in the advanced stage as compared with NSE negative (61 vs. 38%). All NSE-positive cases showed remission with chemotherapy. Conclusion Among the neuroendocrine immunohistochemical markers, positivity was observed only for NSE. This isolated positivity suggests cross-binding of NSE antibodies with some other isoenzyme of NSE. NSE positivity was associated with higher stage and better response to therapy. Despite this apparent paradox, it is recommended that NSE should be part of routine immunohistochemical panel for NHL.

S3570 Incidentally Discovered Multifocal Subclinical Well-Differentiated Neuroendocrine Tumors in the Jejunum Resection of the Bowel for Symptoms of Obstruction

INTRODUCTION: Jejuno-ileal well-differentiated neuroendocrine tumors (WDNET) usually have a relatively high rate of transmural invasion, numerous regional metastases, and advanced stage at the time of presentation. Here we report a rare case of multiple subclinical WDNET that were incidentally discovered after resection of the bowel for an incarcerated intraabdominal hernia. CASE DESCRIPTION/METHODS: The patient is a 69-year-old lady with a longstanding history of uncontrolled diabetes and coronary atherosclerosis who was admitted for cardiac catheterization. However, in the hospital, she complained of abdominal pain, nausea, and vomiting and was diagnosed with incarcerated small bowel hernia with closed-loop obstruction, for which, she underwent segmental resection of the jejunum and hernia repair. Grossly, besides the 35.0 cm of dark-red dull infarcted mucosa, the surgically removed segment of jejunum had up to 37.0 cm of unremarkable velvety tan-pink mucosa, in which there were nine barely visible plaque-like pale-pink lesions ranging from 0.1 × 0.1 × 0.1 cm up to 0.6 × 0.5 × 0.3 cm. The lesions had a white-yellow cut surface. Upon microscopic examination, nests and islets of monomorphic tumor cells with up to 1.6 mitoses per 2 mm2 were noted. The tumor cells expressed neuroendocrine immunohistochemical markers and had a low proliferative index (Ki-67 1%). Tumors were limited to mucosa and submucosa with no muscular propria invasion or lymph node metastases. DISCUSSION: Although rarely, Jejunal WDNET can be incidentally discovered at the early subclinical stage.

Syntaxin 1: A Novel Robust Immunophenotypic Marker of Neuroendocrine Tumors.

Considering the specific clinical management of neuroendocrine (NE) neoplasms (NENs), immunohistochemistry (IHC) is required to confirm their diagnosis. Nowadays, synaptophysin (SYP), chromogranin A (CHGA), and CD56 are the most frequently used NE immunohistochemical markers; however, their sensitivity and specificity are less than optimal. Syntaxin 1 (STX1) is a member of a membrane-integrated protein family involved in neuromediator release, and its expression has been reported to be restricted to neuronal and NE tissues. In this study, we evaluated STX1 as an immunohistochemical marker of NE differentiation. STX1, SYP, CHGA, and CD56 expression was analyzed in a diverse series of NE tumors (NETs), NE carcinomas (NECs), and non-NE tumors. All but one (64/65; 98%) NETs and all (54/54; 100%) NECs revealed STX1 positivity in at least 50% of the tumor cells. STX1 showed the highest sensitivity both in NETs (99%) and NECs (100%) compared to CHGA (98% and 91%), SYP (96% and 89%), and CD56 (70% and 93%), respectively. A wide variety of non-NE tumors were tested and found to be uniformly negative, yielding a perfect specificity. We established that STX1 is a robust NE marker with an outstanding sensitivity and specificity. Its expression is independent of the site and grade of the NENs.

Neuroendocrine Carcinoma of Esophagus: A Case Series

Esophageal Neuroendocrine carcinoma (NECs) are rare and aggresive type of esophageal carcinoma with positive neuroendocrine markers. The esophageal NECs present most commonly with gastrointestinal symptoms such as dysphagia and/or abdominal discomfort. They have the potential for distant metastasis. In the present case series, all the patients present with symptoms of dysphagia and ulcerative growth pattern with positive neuroendocrine immunohistochemical markers.

Colorectal large-cell neuroendocrine carcinoma with lymphoid stroma: further evidence confirming a unique subtype associated with MLH1/PMS2 loss, BRAF mutation, Epstein-Barr virus negativity, and the possibility of a better prognosis.

Pure large-cell neuroendocrine carcinoma (LCNEC) is an uncommon but well-recognised primary tumour of the colorectum. It is characterised by large cells organised in a discernible neuroendocrine pattern with >20 mitoses per 10 high-power fields (HPFs), and/or a Ki67 index of >20%, and coagulative tumour necrosis is invariably present. These features are supplemented by positivity for neuroendocrine immunohistochemical markers. The aim of this study was to highlight three primary LCNECs of the colorectum. All three patients were elderly females, aged 79, 85 and 89years, who presented with ascending colon (two) tumours and a rectal tumour. All three tumours were large, ulcerated, polypoid masses (85, 76 and 55mm; average size 72mm) and were pT3N2. Histologically, the tumours were composed of packets and nests of cells with rosettes; other areas were in sheets composed of large cells. The mitotic counts were 23/10 HPFs, 27/10 HPFs and 24/10 HPFs, respectively. There was no mucosal dysplasia, precursor adenoma or associated adenocarcinoma component. All cases contained mainly peritumoral lymphoid aggregates, with smaller numbers of intratumoral lymphocytes. Synaptophysin, chromogranin (less intensely) and epithelial markers were expressed in all cases in the majority of the tumour cells. The Ki67 proliferative indices were 95%, 100%, and 80%, respectively. Two patients survived for 48 and 72months, whereas the third is alive after 12months without evidence of recurrence. These unusual primary colorectal LCNECs with an accompanying lymphoid component are characterised by loss of MLH1/PMS2, BRAF mutation, microsatellite instability, and Epstein-Barr virus negativity. The patients also have better overall survival than those with LCNECs lacking an accompanying lymphoid component.

Contribution of Human papillomavirus in neuroendocrine tumors from a series of 10,575 invasive cervical cancer cases

AimsNeuroendocrine tumors (NET) of the cervix are rare tumors with a very aggressive course. The human papillomavirus (HPV) has been linked to its etiology. The objective of this study is to describe HPV prevalence and genotype distribution of NET. Methods and ResultsForty-nine tumors with histological neuroendocrine features were identified among 10,575 invasive cervical cancer (ICC) cases from an international study. HPV DNA detection was done using SPF10/DEIA /LiPA25 system. Immunohistochemical (IHC) staining for neuroendocrine markers (chromogranin A, synaptophysin, CD56) and for p16INK4a as a surrogate for HPV transforming infection was performed. In 13 samples with negative IHC for all 3 neuroendocrine markers studied, it was possible to conduct electron microscopy (EM).NET represented 0.5% of the total ICC series and HPV was detected in 42 out of 49 samples (85.7%, 95%CI:72.8%,94.1%). HPV16 was the predominant type (54.8%), followed by HPV18 (40.5%). p16INK4a overexpression was observed in 38/44 cases (86.4%). Neuroendocrine IHC markers could be demonstrated in 24/37 (64.9%) cases. EM identified neuroendocrine granules in 8 samples with negative IHC markers. ConclusionsOur data confirms the association of cervical NET with HPV and p16INK4a overexpression. Specifically, HPV16 and 18 accounted together for over 95% of the HPV positive cases. Current HPV vaccines could largely prevent these aggressive tumors.

Merkel cell carcinoma: literature review

Merkel cell carcinoma (MCC) was given a such name after the German histopathologist Friedrich Merkel, who first in 1875, described the Merkel cells, as small round or oval basophilic cells located at the end of nerve axons and within the basal layer of the epidermis. The current agreement about the function of Merkel cells they are associated with the nerve terminals acting as mechanoreceptors. MCC is a clinically aggressive uncommon, cutaneous neuroendocrine neoplastic tumour with a high mortality rate. Clinically may be presented as a painless, rapidly growing, dome-shaped red or purplish nodule. Usually in a sun-exposed area of the head and neck or upper limbs. Tremendous effort has been done in the last few years for a better understanding of the pathogenesis behind the MCC and the discovery of the Merkel cell polyomavirus suggests another clue to its pathogenesis. The expression of both epithelial and neuroendocrine immunohistochemical markers in the malignant cells, gives the tumour a unique feature that helps differentiate this neoplasm from other entities.

Neuroendocrine carcinoma of the breast - a pilot study of a Danish population of 240 breast cancer patients

Neuroendocrine carcinoma of the breast - a very recent diagnosis, which was not recognized by WHO until 2003 - has lately been the subject of increasing attention. It is defined as a primary breast cancer with morphologic features similar to other types of neuroendocrine tumors of the lung and gastrointestinal tract combined with positive neuroendocrine immunohistochemical markers. While much information has been gathered during the last decade, most studies suffer from poor statistics due to a low incidence, and there are still fundamental open questions regarding etiology and prognosis. Furthermore, apparent limitations of the WHO definition appear to influence diagnosis. Here, we present our own results obtained from 13 cases and furthermore review previous reports with particular reference to incidence, clinical, histological, and prognostic features.

Colorectal mixed adeno-neuroendocrine carcinomas

Mixed adeno-neuroendocrine carcinomas (MANEC) are rare gastrointestinal neoplasms most commonly diagnosed in the large bowel. They contain mixed exocrine and endocrine components and for diagnosis at least 30% of either component must be identi-fied. We present two recent cases, the first of which was a 69-year-old male who presented with anaemia and weight loss and was found to have a rectal tumour. He received combined chemo-radiotherapy and subsequent surgery revealed a 15 mm MANEC invading into the perirectal tissue. The tumour showed radiation-induced changes with neuroendocrine carcinoma adjacent to ad-enocarcinoma. The second case was a 75-year-old male who presented with obstructive symptoms and a palpable abdominal mass. Following surgery, he was found to have a 95 mm MANEC in the ascending colon invading into the pericolic tissue. Both cases were confirmed using neuroendocrine immunohistochemical markers. Positive staining of the neuroendocrine components was seen with at least two of CD56, synaptophysin and chromogranin. The current World Health Organization (2010) classification recognises that size >20 mm, invasion of the muscularis propria, lymphatic invasion and atypical histology are significant risk factors for malignant behaviour. The two cases presented contain most, if not all of these factors.

Merkel Cell Carcinoma

Abstract Merkel cell carcinoma is a rare, highly aggressive neuroendocrine cutaneous neoplasm with a variable clinical presentation. Histologically, it is a predominantly dermal-based lesion composed of monotonous small round cells with scanty cytoplasm, often difficult to differentiate from small round cell tumors, metastatic small cell carcinoma, blastic hematologic malignancies, and melanoma. The malignant cells express both epithelial and neuroendocrine immunohistochemical markers, a unique feature that helps differentiate this neoplasm from other entities. The pathogenesis of Merkel cell carcinoma has remained a mystery despite its association with various chromosomal abnormalities and with growth signaling and apoptotic pathways. The discovery of the Merkel cell polyomavirus suggests another clue to its pathogenesis. This virus integrates into band 3p14 and promotes carcinogenesis by altering the activity of tumor suppressor and cell cycle regulatory proteins. This discovery of the Merkel cell polyomavirus may greatly enhance our understanding of this rare aggressive neoplasm and allow further advancements in treatment.

Merkel cell carcinoma.

Merkel cell carcinoma is a rare, highly aggressive neuroendocrine cutaneous neoplasm with a variable clinical presentation. Histologically, it is a predominantly dermal-based lesion composed of monotonous small round cells with scanty cytoplasm, often difficult to differentiate from small round cell tumors, metastatic small cell carcinoma, blastic hematologic malignancies, and melanoma. The malignant cells express both epithelial and neuroendocrine immunohistochemical markers, a unique feature that helps differentiate this neoplasm from other entities. The pathogenesis of Merkel cell carcinoma has remained a mystery despite its association with various chromosomal abnormalities and with growth signaling and apoptotic pathways. The discovery of the Merkel cell polyomavirus suggests another clue to its pathogenesis. This virus integrates into band 3p14 and promotes carcinogenesis by altering the activity of tumor suppressor and cell cycle regulatory proteins. This discovery of the Merkel cell polyomavirus may greatly enhance our understanding of this rare aggressive neoplasm and allow further advancements in treatment.