The Expression of Chromogranin A, Syanptophysin and Ki67 in Detecting Neuroendocrine Neoplasma at High Grade Colorectal Adenocarcinoma

BACKGROUND: Neuroendocrine neoplasm (NEN) is an epithelial cell neoplasm that can give a histopathological appearance resembling high-grade colorectal adenocarcinoma. Immunohistochemical assays with specific neuroendocrine markers of chromogranin A and synaptophysin are required to establish a definite diagnosis of NEN. AIM: This study aimed to determine whether there was an expression of chromogranin A, synaptophysin and Ki67 which indicated the presence of neuroendocrine neoplasms in samples that have been diagnosed as high-grade colorectal adenocarcinoma. MATERIALS AND METHODS: A study of the expression of chromogranin A, synaptophysin and Ki67 in paraffin blocks was carried out as a result of biopsy and tissue surgery of 70 samples of colorectal tumor specimens diagnosed with colorectal adenocarcinoma. Descriptive analyses were used to assess the study results of the amount of chromogranin A, synaptophysin, and sample characteristics. RESULTS: We discovered that eight (8) samples (11.4%) were NEN from 70 previously diagnosed samples as high-grade colorectal adenocarcinoma using immunohistochemical assay with neuroendocrine markers, namely chromogranin A and synaptophysin. CONCLUSION: The final diagnosis obtained from 8 samples diagnosed as NEN were Neuroendocrine tumor (NET) G1, G2, and G3, respectively 1.4% and LCNEC 7.1% based on the specific neuroendocrine markers of chromogranin A, synaptophysin and Ki67.

Expanding the Immunophenotype Spectrum of SMARCA4-Deficient Non-Small Cell Lung Carcinomas: A Case Series with Neuroendocrine Markers Expression

Aims. In recent years, SMARCA4-deficient nonsmall cell lung cancer (NSCLC) has been recognized as a distinct new subtype of lung cancer, which is characterized by loss of SMARCA4 (Brahma-related gene-1 [BRG1]) protein expression. Only a limited number of SMARCA4-deficient NSCLC case series have been reported, and their clinicopathological features have not yet been fully elucidated. Our main aim was to analyze the clinical history, histology, immunohistochemistry, and molecular pathology of 5 SMARCA4-deficient NSCLC patients with poorly differentiated or undifferentiated histology and neuroendocrine markers expression. Methods and results. Five patients with complete loss of nuclear BRG1 immunostaining were identified among 53 patients of poorly differentiated/undifferentiated NSCLC. We then performed immunohistochemical staining and gene mutation analysis using a real-time polymerase chain reaction. All patients were male aged between 58 and 82 years (average 67.6 years), with smoking exposure. Histologically, the tumors had a relatively monotonous morphology and showed solid nest-like, sheet-like growth, and geographic necrosis. Thyroid transcription factor 1, cytokeratin 7, and Napsin A were all negative (5 of 5). Moreover, all tumors showed a variable expression of neuroendocrine markers, including synaptophysin, chromogranin A and CD56. Hot spot epidermal growth factor receptor/anaplastic large-cell lymphoma kinase/c-ros oncogene 1 mutations were not detected in any of the 5 tumors. Conclusions. To the best of our knowledge, this is the first study that has reported the poorly differentiated morphology with a frequent expression of neuroendocrine markers. Our results have expanded the immunophenotype spectrum of SMARCA4-deficient NSCLC. However, the clinicopathological significance of this subset of SMARCA4-deficient NSCLC should be further clarified in larger series studies.

Prognostic significance of the aberrant expression of neuroendocrine markers in melanomas

Background Melanoma is a highly malignant tumor with diverse histopathological morphology and frequent aberrant expression of immunohistochemical markers. An occasionally reported phenomenon is the abnormal expression of neuroendocrine markers. Awareness of this situation is essential because such tumors need to be differentiated from neuroendocrine tumors because of their significant therapeutic and prognostic implications. Methods We retrospectively analyzed the expression of chromogranin A (CgA), synaptophysin (Syn) and CD56 as neuroendocrine markers in 308 cases with melanomas. Kaplan-Meier curves and Cox regression analyses were used for overall survival (OS) and progression-free survival (PFS) evaluation and comparison between neuroendocrine markers expression status in all melanoma cases or stage I–II cases. Results The expression of neuroendocrine markers in melanomas is not uncommon. CgA was positive in 6/304 (2.0%) cases, Syn in 26/304 (8.6%), and CD56 in 56/189 (29.6%). None of the cases co-expressed all the three markers. Focal or weak expression of at least one neuroendocrine marker was identified in 70/188 (37.2%) cases. The expression of CgA was correlated with age (p = 0.019), while the positive expression of Syn and CD56 showed borderline significance (p = 0.078 and 0.083, respectively), but not for any neuroendocrine marker expression. The expression of any neuroendocrine marker showed borderline significance with staging (p = 0.066). The expression of CgA, Syn, CD56, or any neuroendocrine marker did not correlate with clinicopathological features including sex, specimen type, origin, location, and histology subtype. Survival analyses revealed that the expression of neuroendocrine markers was not associated with OS or PFS. Conclusions Our study confirms that neuroendocrine marker expression is a common phenomenon in melanomas, but it has no prognostic significance. Nevertheless, awareness can avoid misdiagnosis in cases of melanomas with unusual morphology and immunophenotypes.

Neuroendocrine Differentiation in Non-Small Cell Lung Cancer and its Relation to Different Pathologic Features: An Immunohistochemical Study

Objectives: To identify the relevance of neuroendocrine differentiation in non-small cell lung cancer and its correlation with different pathological features. Materials and Methods: A total number of 30 cases of per cutaneous CT guided biopsies of primary non-small lung cancer were collected in the pathology department of Misr University for Science and Technology Giza, Egypt and private practice in the time period from January 2018 till December 2020. Immunohistochemical study for neuroendocrine differentiation was performed using mono clonal antibodies against synaptophysin, chromogranin A and CD56. For all selected cases, clinical and pathological data such as age, gender, histologic types, grade and clinical stage were collected, tabulated and statistically analyzed with the results of neuroendocrine markers expression. Cases with incomplete pathological data and cases with histologic picture of neuroendocrine differentiation were excluded. Results: A total number of 30 cases of primary non-small lung cancer were enrolled in this study. The median age of patients was 61.5 years. There were 21 (70%) males and 9 (30%) females. Regarding neuroendocrine markers, positivity for either marker was identified in 23.3% of non-small cell lung cancer. Chromogranin A was positively expressed in 9 (30%) of cases, synaptophysin was positively expressed in 7 (23.3%) of cases and CD56 was positively expressed in 5 (16.7%) of cases. Only 2 cases (6.7%) showed co-expression of two markers. It was found that there was a high significant relation between chromogranin A expression and clinical stage. Chromogranin A expression was significantly higher in stage III than stage I and II (P<0.001). There was no statistical significant difference between synaptophysin, chromogranin A and CD56 expressions and the rest of the studied pathologic data. Conclusion: A considerable number of non-small cell lung cancer has neuroendocrine differentiation for at least one neuroendocrine marker despite absence of morphologic features. Much less number of cases showed expression of two markers. A reasonable panel of neuroendocrine markers is recommended to detect this differentiation which may have a clinical impact and optimize an alternative therapeutic option.