Neuroendocrine markers

Although there has been a substantial body of pharmacological evidence in support of the monoamine theory of depression, clinical biochemical data have been less convincing (Luchins, 1976) this is where differences in the concentrations of NA and 5-HT and their metabolites or hormones, which are ultimately under the control of brain monoaminergic neurons (neuroendocrine markers), have been compared between depressed patients and normal controls. However, by the early 1970s a major difficulty with the theory was becoming apparent this was the time lag between the immediate... 

The initial panel of antibodies described above is also useful in discriminating among small cell tumors, except that a few additional markers are needed. A panel of neuroendocrine markers (chromogranin A, synaptophysin, and CD57) should be used to differentiate neuroendocrine tumors. The use of a panel rather than just one of these markers is recommended to maximize the ability to detect poorly differentiated neuroendocrine tumors that lose the... 

Large cell undifferentiated neuroendocrine carcinoma (LCNEC) can present as CUPS, and it is easy to miss the diagnosis without applying the appropriate neuroendocrine markers. The correct diagnosis of LCNEC is an important distinction because it carries the same dismal prognosis as does small cell carcinoma, whether in the lung or gastrointestinal tract. 776 Synaptophysin may be the most frequent positive marker in LCNEC. ... 

Kayser K, Schmid W, Ebert W, Wiedenmann B. Expression of neuroendocrine markers (neuronspecific enolase, synaptophysin and bombesin) in carcinoma of the lung. Pathol Res Pract. 1988 183 412-417. 

The best markers to differentiate these are p63 and neuroendocrine markers BSCC will be positive for cyto-keratin and p63 and negative for most neuroendocrine markers. 

The tumor cells are positive for neuroendocrine markers, and up to 30% can be positive for cytokeratin. 

Neuroendocrine markers are rarely positive when they are, staining should be only focal. 

Neuroendocrine carcinomas are positive for cytokeratins and for typical neuroendocrine markers, such as chromogranin and synaptophysin. 

These three neuroendocrine tumors of the larynx all display positivity for typical neuroendocrine markers such as chromogranin, synaptophysin, and neuron-specific enolase. They may also be positive for carcinoembryonic antigen (CEA) or epithelial membrane antigen (EMA). Atypical carcinoid and SCNEC can also express other neuroendocrine markers such as serotonin, calcitonin, and somatostatin. TTE-1 is probably not a useful marker to distinguish metastatic pulmonary small cell carcinoma from primary tumors in the head and neck because up to 50% of extrapulmonary small cell carcinomas are positive for TTR-l.i 8... 

The immunophenotype of these tumors includes positivity for neuroendocrine markers and for cytokeratins. 

Generic neuroendocrine markers, including chromogra-nins A and B and secretogranin II, are present in medullary carcinomas. 

Normal parathyroid chief cells and hyperplastic and neoplastic parathyroids are positive for parathyroid hormone and a variety of neuroendocrine markers including synap-tophysin and chromogranin A. 

Neuroblastomas and pheochromocytomas are positive for a wide spectrum of neuroendocrine markers. 

Neuroendocrine markers, including synaptophysin, chromogranin, and CD56... 

Other neuroendocrine markers that are occasionally used to identify normal neuroendocrine lung cells and neoplastic neuroendocrine cells include neurofilaments,neural cell adhesion molecules (N-CAM),A77 and Leu7. The most frequent neuropeptides, neuroamines, and hormones found in neuroendocrine lung neoplasms are listed in Table 12.11. TTF-1 is found in a high percentage of small cell carcinomas, atypical carcinoids, and large cell neuroendocrine carcinomas, but in less than 50% of typical carcinoids. 

The immunophenotype of large cell undifferentiated neoplasms of lung is unpredictable. Most large cell undifferentiated neoplasms are carcinomas and coexpress keratin and vimentin. Some express only vimentin. There are large cell neoplasms that look like carcinomas but, in fact, are not. Another area of potential confusion is related to observations that non-neuroendocrine, non-small cell carcinomas as determined by histologic appearances express neuroendocrine markers by immunohistochemistry. We will discuss this concept later in this chapter. 

A. Zero of 10 squamous carcinomas, 4 of 26 adenocarcinomas, and 0 of 11 large cell undifferentiated carcinomas showed immunostaining for Leu7. Six of 10 squamous carcinomas, 15 of 26 adenocarcinomas, and 7 of 11 large cell undifferentiated carcinomas showed immunostaining for neuron-specific enolase. Six of 10 squamous carcinomas, 16 of 26 adenocarcinomas, and 7 of 11 large cell undifferentiated carcinomas showed immunostaining for synaptophysin. Overall, 34 of 47 (79%) carcinomas without neuroendocrine features expressed at least one neuroendocrine immunohistochemical marker. Nineteen of 19 (100%) of neuroendocrine carcinomas expressed at least one neuroendocrine marker. 

The bottom line for pathologists is that lung neoplasms that are not classified by histologic criteria as being a neuroendocrine neoplasm may express neuroendocrine markers by immunohistochemistry. A summary of these studies showing the frequency of expression of chromogranin A, synaptophysin, neuron-specific enolase, and Leu7 is shown in Fig. 12.41. 

FIGURE 12.41 Summary of expression of neuroendocrine markers in histologically diagnosed non-neuroendocrine neoplasms. Neuroendocrine expression in non-neuroendocrine lung neoplasms is usually focal and is usually of low intensity. 

Chromogranin and synaptophysin can aiso be positive in typicai adenocarcinomas. Thus, staining with neuroendocrine markers is not sufficient evidence for the diagnosis of neuroendocrine carcinoma. 

By definition, they need to have morphologic features of a neuroendocrine carcinoma and stain with neuroendocrine markers such as synaptophysin or chromogranin. 

Mertz EE, Vyberg M, Paulsen SM. Immunohistochemical detection of neuroendocrine markers in tumors of the lungs and gastrointestinal tract. Appl Immunohistochem. 1998 6 175-180. 

Endocrine component is very commonly present and shows immunoreactivity for chromogranin orsynapto-physin as well as other neuroendocrine markers. 

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