Small-cell neuroendocrine carcinoma

Chan JK, Suster S, Wenig BM, et al. Cytokeratin 20 immuno-reactivity distinguishes Merkel cell (primary cutaneous neuroendocrine) carcinomas and salivary gland small cell carcinomas from small cell carcinomas of various sites. Am J Surg Pathol. 1997 21 226-234. 

The differential diagnosis for BSCC can be broad, especially in small biopsies where it can be difficult to appreciate all of the histologic features. Included in the differential diagnosis are the two most important mim-ickers adenoid cystic carcinoma and small cell neuroendocrine carcinoma.Immunohistochemical stains are particularly useful in resolving this differential diagnosis (Table 9.2). 

The differential diagnosis for basaloid squamous cell carcinoma (BSCC) includes adenoid cystic carcinoma and small cell neuroendocrine carcinoma. 

Neuroendocrine carcinomas and small cell neuroendocrine carcinomas are almost invariably positive for cytokeratins (such as CAM 5.2 and AE 1/3), synaptophysin, chromogranin, and neuron-specific enolase. A dotlike pattern of positivity may be seen in cytokeratin stains. They are negative for cytokera-tin 20, S-100, and neurofilament.About half of small cell neuroendocrine carcinomas are positive for thyroid transcription factor (TTF-1) and at least one... 

High-grade neuroendocrine carcinomas in the colon and rectum most commonly occur as a component of poorly differentiated adenocarcinomas more than 50% of the tumor should show neuroendocrine differentiation in order to be called a neuroendocrine carcinoma. Both small cell and non-small cell types exist, and both tend to stain with low-molecular-weight cytokeratin (CAM5.2) in a perinuclear dot pattern, as well as with synaptophysin, chromogranin, and/or NSE (Fig. 14.32). ° ° GDI 17 stains a substantial minority of high-grade neuroendocrine carcinomas however, immunoreactivity has not been linked to c-kit juxta-membrane (exon 11) mutations. 

Somatostatin 14,28 Neuroendocrine, small cell lung cancer, medullary thyroid carcinoma, astrocytoma... 

The normal prostate is composed of acinar secretory cells arranged in a radial shape and surrounded by a foundation of supporting tissue. The size, shape, or presence of acini are almost always altered in the gland that has been invaded by prostatic carcinoma. Adenocarcinoma, the major pathologic cell type, accounts for more than 95% of prostate cancer cases.15 Much rarer tumor types include small cell neuroendocrine cancers, sarcomas, and transitional cell carcinomas. 

The monoclonal antibody BER-EP4 recognizes a cell-membrane glycoprotein consisting of two polypeptide chains (mol wt 34 kDa and 39 kDa). Its antigen is expressed on a wide variety of epithelial tumors, including small-cell undifferentiated carcinomas and neuroendocrine tumors. It is not found on nonepithelial or mesothelial tumors. 

Enolase is a glycolytic enzyme also known as phosphopyru-vate hydratase. Neuron-specific enolase (NSE) is the form of enolase found in neuronal tissue and in the cells of the diffuse neuroendocrine system and the amine precursor uptake, and decarboxylation (APUD) tissue. NSE is found in tumors associated with the neuroendocrine origin, including small cell lung cancer (SCLC), neuroblastoma, pheochromocytoma, carcinoid, medullary carcinoma of the thyroid, melanoma, and pancreatic endocrine tumors. 

Small cell neuroendocrine (Merkel cell) carcinoma... 

FIGURE 7.2 Small cell amelanotic melanoma, resembling neuroendocrine carcinoma. 

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. ... 

Poorly differentiated endocrine neoplasms, depending on the site of origin, may produce characteristic peptide hormones. The group of poorly differentiated neuroendocrine tumors and their hormone production include islet cell tumors (insulin, glucagon, somatostatin, gastrin), pulmonary small cell carcinoma (bombesin in 45% of cases), and medullary thyroid carcinoma (calcitonin). 

Nuclear immunostaining of the vast majority of carcinomas of the lung—adenocarcinomas (66%), large cell neuroendocrine and small cell (95%)... 

Thyroid transcription factor-1 (TTF-1), a nuclear tissue-specific protein transcription factor, is found in thyroid and thyroid tumors regardless of histologic type (except anaplastic type), as well as in lung carcinomas including adenocarcinomas (75%), non-small cell carcinomas (63%), neuroendocrine and small cell carcinomas (>90%), and squamous cell carcinomas (10%).258-258 Selectively expressed during embryogenesis in the thyroid, the diencephalon of the brain, and in respiratory epithelium, TTF-1 binds to and activates factors for surfactant protein derived from Clara cells.255 TTF-1 is rarely seen in carcinomas outside of the lung or thyroid... 

Kaufmann O, Dietel M. Expression of thyroid transcription factor-1 in pulmonary and extrapulmonary small cell carcinomas and other neuroendocrine carcinomas of various primary sites. Histopathology. 2000 36 415-420. 

Agoff SN, Lamps LW, Philip AT, et al. Thyroid transcription factor-1 is expressed in extrapulmonary small cell carcinomas but not in other extrapulmonary neuroendocrine mmors. Mod Pathol. 2000 13 238-242. 

TABLE 9.2 Differentiating Basaloid Squamous Cell Carcinoma from Adenoid Cystic and Small Cell Neuroendocrine Carcinoma ... 

Many of the tumors of the nasal cavity and paranasal sinuses fall under the category of round cell neoplasms. Among these are olfactory neuroblastoma, sinonasal undifferentiated carcinoma, malignant melanoma, neuroendocrine carcinoma-small cell neuroendocrine carcinoma, malignant lymphoma, extramedullary plasmacytoma, invasive-ectopic pituitary adenoma, rhabdomyosarcoma, and Ewing s sarcoma (ES)-peripheral neuroectodermal tumor (ES/ PNET). But there is also a host of other epithelial lesions that are unique to the sinonasal tract. 

TABLE 9.6 Sinonasal Undifferentiated Carcinoma (SNUC) versus Small Cell Neuroendocrine Carcinoma (SCNEC) ... 

Small Cell Neuroendocrine Carcinoma and Neuroendocrine Carcinoma... 

The differential diagnosis for neuroendocrine tumors in the sinonasal tract will include olfactory neuroblastoma, small cell neuroendocrine carcinoma, carcinoid, atypical carcinoid, paraganglioma, and possibly even sinonasal undifferentiated carcinoma. Once these more specific neuroendocrine entities have been excluded, there remains a small group of tumors that cannot be further classified. These should be referred to as neuroendocrine carcinoma, not otherwise specified. These tumors can be graded using standard morphologic features. 

Small cell neuroendocrine carcinomas similar to those seen in the lung are exceptionally rare in the nasal cavity and paranasal sinuses. They affect both sexes equally and occur over a broad age range (38 to 68 years in one studyThey may arise either in the nasal cavity or in the paranasal sinuses, especially the ethmoid and maxilla. Though some tumors will remain localized to the site of origin, higher grade tumors are likely to invade into adjacent structures such as the orbit, cribriform plate, or cranial cavity. 

Microscopically, small cell neuroendocrine carcinomas are identical to their pulmonary counterparts and, as such, are composed primarily of round to short spindle cells with sparse, poorly defined cytoplasm and hyperchromatic nuclei without nucleoli. Nuclear molding, frequent mitoses, necrosis, and single-cell apoptosis are common. 

The classification of neuroendocrine tumors of the head and neck has been controversial.The WHO classification has divided the tumors into four categories typical carcinoid, atypical carcinoid, small cell neuroendocrine carcinoma, and paraganglioma. Each of these tumor types is discussed separately. Immunohisto-chemical stains will not easily separate the four types of... 

Small cell neuroendocrine carcinoma (SCNEC) of the larynx is rare, representing less than 1% of all laryngeal carcinomas. These tumors have been categorized in a similar fashion to lung tumors, into oat cell type, intermediate, and combined. The first two tumor types have typical neuroendocrine differentiation and show... 

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 three categories of neuroendocrine tumors (carcinoid, atypical carcinoid, and small cell neuroendocrine carcinoma) are distinguished from one another mainly on the basis of histologic appearance. 

Paragangliomas located in the usual or unusual locations in the neck must be differentiated from other epithelial neuroendocrine tumors such as carcinoids, atypical carcinoids, small cell neuroendocrine carcinoma, and medullary thyroid carcinoma.The staining panel that will differentiate these tumors is... 

Perez-Ordonez B, Caruana SM, Huvos AG, et al. Small cell neuroendocrine carcinoma of the nasal cavity and paranasal sinuses. Hum Pathol. 1998 29(8) 826-832. 

Gnepp DR. Small cell neuroendocrine carcinoma of the larynx A critical review of the literature. ORL. 1991 53 210-219. 

FIGURE 10.52 A, Small cell (neuroendocrine) carcinoma of the breast (H E). B, Immunoperoxidase stain for chromogranin A shows moderately intense cytoplasmic staining. 

LaPoint RJ, Bourne PA, Wang HL, Xu U. Coexpression of c-kit and bcl-2 in small cell carcinoma and large cell neuroendocrine carcinoma of the lung. Appl Immunohistochem Mol Morph. 2007 15 401-406. 

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