Solid-pseudopapillary tumor of the pancreas: immunohistochemical localization of neuroendocrine markers and CD10

To clarify the neuroendocrine differentiation and CD10 expression in solid-pseudopapillary tumors (SPTs) of the pancreas, we performed immunohistochemical analysis in 19 such tumors, including one solid-pseudopapillary carcinoma (SPC), along with 20 pancreatic neuroendocrine tumors (PNTs), six acinar cell carcinomas (ACCs), and one pancreatoblastoma (PB). We used antisera directed against CD56, synaptophysin, protein gene product 9.5, the alpha-subunit of Go protein, chromogranin A, CD10, trypsin, chymotrypsin, various cytokeratins (CKs), CA19-9, vimentin, and alpha-1-antitrypsin (AAT). All SPTs exhibited immunoreactivity for CD56 and CD10, and 15 expressed other neuroendocrine markers focally with the exception of chromogranin A. Frequent clustering of synaptophysin-positive cells was noted. Two cases contained a peculiar nodule that cytomorphologically and immunohistochemically resembled PNT. CD10-positive cells were scarce in one SPC. PNTs were CD56-positive, but often with faint intensity, and staining for other neuroendocrine markers, including chromogranin A, was diffusely positive. CD10 was detected, mostly in a focal pattern, in five PNTs. Pan-CK, CK8, CK18, and CK19 were more frequently demonstrated in PNT than SPT. Vimentin and AAT were often identified in PNT as well and were not specific for SPT. ACCs were CD56-negative, with the exception of one case designated as a mixed acinar-endocrine carcinoma. PB was focally positive for CD56 at the periphery of the tumor nests. Four ACCs and one PB exhibited focal CD10 reactivity. This study demonstrated the unique immunohistochemical features of SPT. Our results also suggest that SPT exhibits, at least focally, neuroendocrine differentiation, and that these neuroendocrine markers and CD10 are diagnostically useful.     

The prevalence of pancreatic acinar differentiation in gastric adenocarcinoma: report of a case and immunohistochemical study of 111 additional cases

Although pancreatic acinar metaplasia in the gastric mucosa is well recognized in chronic gastritis, gastric carcinoma with acinar differentiation is very rare. We encountered a case of gastric adenocarcinoma with prominent histologic and immunohistochemical features of pancreatic acinar differentiation in the absence of identifiable heterotopic pancreatic tissue. Distinct glandular and diffuse patterns of adenocarcinoma were also present, and there was focal mucin production. The tumor strongly expressed pancreatic exocrine enzymes trypsin and chymotrypsin, and focal neuroendocrine staining was also present. To investigate the prevalence of acinar differentiation in histologically typical gastric cancers, we performed immunohistochemical staining for trypsin and chymotrypsin on a tissue microarray containing 111 conventional gastric adenocarcinomas (60 intestinal, 28 mixed, 22 diffuse type, and 1 undifferentiated). No obvious morphologic evidence of acinar differentiation was identified in any of the 111 cases. Although some cases showed equivocal staining for at least 1 pancreatic exocrine enzyme on the initial tissue microarray sections, repeat immunohistochemical staining on representative whole-tissue sections failed to reproduce positive staining. Thus, acinar differentiation is rare in gastric adenocarcinomas, other than in histologically unusual cases such as the one we report, and in others from the literature, which are reviewed.     

Papillary cystic tumor of the pancreas. An analysis of cellular differentiation by electron microscopy and immunohistochemistry

Three cases of clinically benign pancreatic papillary cystic tumors in young female patients were studied by immunohistochemistry and electron microscopy in order to define the cellular nature of this type of neoplasm. Two of the tumors showed focal cytokeratin- and desmoplakin-positivity as evidence of focal epithelial differentiation, while the tumor cells were in all cases positive for vimentin--the intermediate filament protein typical of (but not specific for) mesenchymal cells. Electron microscopy showed some cell-cell junctions, but there was no evidence of acinar or islet cell differentiation. The tumors were at least focally positive for neuron-specific enolase, and small clusters of polypeptide hormone immunoreactive cells were present in all cases (glucagon 3/3, somatostatin 2/3, insulin 2/3). However, the tumors were negative for synaptophysin and neurofilament proteins, unlike most islet cell tumors. Trypsin and chymotrypsin immunoreactivity was found in all tumors, but because many nonpancreatic carcinomas were also positive, we doubt whether these two enzyme proteins can act as specific markers for pancreatic acinar cell differentiation. Two of the tumors that were studied immunohistochemically for the presence of nuclear estrogen receptors, were negative. Therefore no proof of the suggested hormone dependence of this tumor could be obtained. We conclude that papillary cystic tumor is a neoplasm of primitive pancreatic epithelial cells, that may exhibit focal endocrine cell differentiation.     

Neuroendocrine carcinomas of the pancreas with 'Rhabdoid' features

Neuroendocrine carcinomas of the pancreas are rare neoplasms whose morphologic features generally mirror those seen in neuroendocrine tumors in other organs. Rarely, however, they may display unusual morphologic appearances that can introduce difficulties for diagnosis. We report four cases of primary neuroendocrine carcinomas of the pancreas (islet cell tumors) that were characterized by prominent "rhabdoid" features of the tumor cells. The lesions occurred in two men and two women 37-79 years of age who presented with symptoms of biliary obstruction and epigastric pain; one patient had recurrent gastric ulcers and an elevated gastrin level. The tumors were located in the head and tail of the pancreas and measured 2.5-4.5 cm in greatest diameter. Histologic examination revealed sheets of monotonous tumor cells with uniform round nuclei showing dispersed chromatin and containing abundant densely eosinophilic cytoplasmic inclusions that displaced the nuclei toward the periphery. In all cases, the rhabdoid elements appeared to merge with areas showing a more conventional neuroendocrine morphology. Immunohistochemical studies in all cases showed strong cytoplasmic positivity of the rhabdoid tumor cells for chromogranin, synaptophysin, and cytokeratin. Recognition of this unusual morphologic appearance is of importance to avoid mistaking these lesions for other types of malignant neoplasm.     

Prevalence and prognostic significance of acinar cell differentiation in pancreatic endocrine tumors

We have noted that many histologically and immunohistochemically confirmed pancreatic endocrine tumors show immunophenotypic evidence of acinar cell differentiation, but the clinical relevance of this finding is unknown. We performed this study to evaluate the prevalence and prognostic significance of exocrine differentiation by immunohistochemistry in pancreatic endocrine tumors that do not show morphologic features of acinar cell differentiation. Routinely processed tissue sections from 87 pancreatic endocrine tumors were immunohistochemically stained with monoclonal antibodies against acinar (lipase, chymotrypsin, trypsin) and endocrine cell markers (chromogranin A, neuron-specific enolase, synaptophysin, Leu-7) and for the proliferation-associated peptide Ki67. The degree of staining with each marker was graded on a three-tier scale for acinar markers (grade 0, <5%; grade 1, 5-10%; grade 2, 11-25%; and grade 3, >25%) and on a four-tier scale for endocrine markers (grade 0, <5%; grade 1, 5-25%; grade 2, 26-50%; grade 3, 51-75%; and grade 4, >75%), and the results were correlated with clinical outcome (mean follow-up 53 months). Greater than 75% of the tumor cells stained for chromogranin A, neuron-specific enolase, synaptophysin, and Leu-7 in 100%, 96%, 93%, and 27% of cases, respectively. Overall, 66% of tumors stained positively for at least one acinar cell marker, 31% stained for at least two acinar cell markers, and 13% stained for all three acinar cell markers. Forty-seven percent stained for lipase (23 grade 1, 11 grade 2, seven grade 3), 37% for trypsin (22 grade 1, three grade 2, seven grade 3), and 25% stained for chymotrypsin (13 grade 1, five grade 2, four grade 3). No correlation was noted between the presence or extent of expression of any single or combination of acinar cell markers and clinical outcome. However, higher tumor stage correlated with a poor clinical outcome (p = 0.002), and location in the tail of the pancreas was associated with a longer interval to tumor recurrence (p = 0.03). The presence of synaptophysin (p = 0.03) and Leu-7 expression (p = 0.03) correlated significantly with less aggressive clinical behavior. An association was observed between increased Ki67 labeling and poorer clinical outcome, but this was not statistically significant (p >0.05). In conclusion, immunophenotypic evidence of acinar cell differentiation is common in pancreatic endocrine tumors, but this feature does not have any relevance to clinical prognosis. However, in addition to tumor stage, location in the pancreatic tail and the immunohistochemical expression of synaptophysin and/or Leu-7 may be useful prognostic indicators in patients with these lesions.     

Malignant pancreatic tumors in childhood and adolescence: The Memorial Sloan-Kettering experience, 1967 to present

Background: Malignant tumors of the pancreas are uncommon in children and adolescents and only recently have the most common tumor types been well characterized. As a result, the treatment approach to these patients has yet to be standardized, and much of the information available in the literature, particularly with regard to the role of chemotherapy and radiation, is anecdotal. Methods: A retrospective review was undertaken of all patients less than 21 years of age with malignant pancreatic tumors who were cared for at Memorial Sloan-Kettering since 1967. Results: Seventeen patients were identified. The pathologic types were pancreatoblastoma, 5; solid pseudopapillary tumor, 7; acinar cell carcinoma, 1; nonfunctioning pancreatic endocrine neoplasm, 1; malignant VIPoma, 1; and PNET, 2. A complete resection of the primary tumor was achieved in 82%, and 12 of 15 are alive, 10 with no evidence of disease. Chemotherapy or radiation were used in selected cases. Conclusions: Unlike malignant pancreatic tumors in adults, tumors in children and adolescents usually are resectable, and long-term survival is likely. However, the risk of recurrence for pancreatoblastoma is high. The roles of chemotherapy and radiation remain undefined. J Pediatr Surg 37:887-892.     

胰腺囊性肿瘤的临床分析

目的：总结胰腺囊性肿瘤的诊治经验，提高对该疾病的认识和诊治水平。方法：对1986—2004年中24例胰腺囊性肿瘤的临床病例资料作回顾性分析。结果：全组中胰腺囊腺瘤10例，胰腺囊腺癌6例，胰腺导管内乳头状黏液性腺癌3例。实性假乳头瘤2例，胰腺腺泡细胞囊腺癌、胰岛细胞癌囊性变及胰腺继发性囊性肿瘤各1例。全组男8例，女16例，平均年龄51岁。肿瘤位于胰头部8例，胰体尾部16例。手术方式为胰十二指肠切除4例，胰体尾切除15例，内引流2例，活检3例。胰腺囊腺瘤、囊腺癌、导管内乳头状黏液性腺癌、实性假性乳头瘤等的临床表现、病理特征、手术方式和预后显著不同。结论：不同病理类型的胰腺囊性肿瘤之临床特征和预后显著不同。提高对胰腺囊性肿瘤的认识对指导临床治疗具有重要意义。     

Lysozyme Expression Can be Useful to Distinguish Mammary Analog Secretory Carcinoma from Acinic Cell Carcinoma of Salivary Glands

Lysozyme is an enzymatic marker of acinar and intercalated duct cells of normal salivary glands. The aim of this study was to verify whether lysozyme expression could be useful to distinguish acinic cell carcinoma (ACC) from its main mimic, mammary analog secretory carcinoma (MASC). For comparison, DOG1 expression was analyzed as well. Seventeen cases of ACC, 15 MASC, and 125 other salivary tumors were studied. Lysozyme expression was found in tumor cells as well as in secreted material of MASC (86.6 % of cases) and in ductal cells of epithelial–myoepithelial carcinoma (EMC-53.8 %), pleomorphic adenoma (PA-29.1 %) and polymorphous low-grade adenocarcinoma (PLGA-23.8 %). However, in ACC, lysozyme was not expressed. Three patterns of DOG1 staining were seen: apical–luminal, cytoplasmic, and mixed cytoplasmic/membranous. The apical–luminal pattern was detected in ductal cells of ACC (58.8 % of cases), EMC (38.4 %), adenoid-cystic carcinoma (AdCC-35.3 %), PA (8.3 %), and PLGA (4.8 %). These tumors also showed mixed membranous/cytoplasmic staining for DOG1. MASC, mucoepidermoid, and salivary duct carcinomas exhibited only DOG1 cytoplasmic staining. In conclusion, lysozyme cannot be used as a marker of acinar differentiation in salivary tumors. However, lysozyme expression can be helpful to distinguish MASC from ACC due to its high frequency in the former and absence in ACC. It is likely that in MASC, lysozyme expression may reflect a lactational-like secretory differentiation since lysozyme belongs to breast milk proteins. Regarding DOG1 expression, the apical–luminal pattern is related to acinar and intercalated duct differentiation whereas the cytoplasmic staining does not seem to be associated with a specific cellular phenotype.     

Composite glandular and endocrine tumors of the stomach with pancreatic acinar differentiation

Composite tumors of the stomach consisting of mixed glandular and endocrine components are rare. We report 3 cases of composite glandular and endocrine tumors with pancreatic acinar differentiation in the stomach with their clinicopathologic findings. The patients' presenting symptoms were variable and included abdominal pain, gastrointestinal hemorrhage, and weight loss. One patient with abdominal pain also had an elevated serum lipase level, clinically mimicking acute pancreatitis. The histology of these tumors was similar. They showed admixture of well-differentiated endocrine components with acinar and glandular components. The glandular component consisted of columnar epithelial cells resembling gastric foveolar or intestinal goblet cells, consistent with a well-differentiated adenocarcinoma. A panel of histochemical and immunohistochemical stains was performed, which included PAS, Alcian blue, Mib1, CEA, cytokeratin 7, cytokeratin 20, Muc2, Muc5AC, chromogranin, synaptophysin, trypsin, chymotrypsin, lipase, insulin, gastrin, serotonin, and pancreatic polypeptide. While the immunoreactivity for cytokeratin 7, cytokeratin 20, Muc2, Muc5AC, and CEA was largely restricted to the glandular component, the endocrine and pancreatic acinar markers showed marked variability and overlap. All cases showed immunoreactivity for at least one of the exocrine pancreatic enzymes, and all expressed endocrine differentiation. Some degree of amphicrine differentiation was suggested in all cases. Two cases showed metastases in perigastric lymph nodes, which histologically resembled the primary tumor. In summary, these tumors represent another distinct type of composite glandular and endocrine gastric neoplasm with pancreatic acinar differentiation.     

Desmoplastic small cell tumor in the pancreas

Desmoplastic small cell tumor (DSCT) is a distinct type of small blue cell tumors and is characterized by the unique karyotypic aberration involving the fusion of the Ewing's sarcoma (EWS) gene and Wilms' tumor (WT1) gene. Typically, it grows along serosal surfaces; however, in some cases, the tumor presents as a dominant mass in an internal organ. Examples of DSCT forming a primary mass in ovary, testes, and brain have been described, but its presentation as a primary pancreatic mass has not been reported previously. The case reported here is a 31-year-old woman who presented with a 14-cm mass in the pancreas. There were smaller nodules on the peritoneal surfaces that were regarded clinically as metastasis from a primary pancreatic tumor. During the frozen section, the diagnosis of a poorly differentiated endocrine carcinoma of pancreatic origin was rendered and patient underwent subtotal pancreatectomy. On microscopic examination, the tumor was composed of large nests and broad bands of small blue cells, separated by fibrous stroma. Immunohistochemical stains showed positivity of the tumor cells for cytokeratins (AE1:AE3 and CAM5.2), neuron specific enolase, desmin and WT1, whereas chromogranin, S-100, and CD99 were negative. Since this immunoprofile is characteristic of DSCT, molecular analysis was performed which revealed the presence of EWS-WT1 gene fusion characteristic of DSCT. This case shows that in addition to primary pancreatic tumors characterized by prominent cellularity such as solid pseudopapillary tumors, acinar cell carcinoma, pancreatoblastoma, endocrine tumors, and other small blue cell tumors, the differential diagnosis of cellular, stroma-poor neoplasia in the pancreas also includes DSCT. This case is also another demonstrative example of how DSCT may form a dominant mass in intraabdominal organs.     

Hyaline globules in neuroendocrine and solid-pseudopapillary neoplasms of the pancreas: a clue to the diagnosis

Distinguishing between solid-pseudopapillary neoplasms (SPNs) and pancreatic neuroendocrine tumors (PanNETs) may pose a diagnostic dilemma. Both can demonstrate solid growth patterns, and both can be immunoreactive with neuroendocrine markers such as synaptophysin and CD56. One well-established feature of SPNs is the presence of hyaline globules, which in contrast has only rarely been reported in PanNETs. Clinicopathologic features of 361 cases originally classified as PanNETs were examined. Of these, 24 tumors (6.6%) had hyaline globules, raising the possibility of SPN. Immunohistochemistry for β-catenin was performed on these 24 neoplasms, and showed nuclear labeling in 6 cases. These 6 cases, which also demonstrated cytoplasmic CD10 staining, were reclassified as SPNs. The remaining 18 cases maintained their original diagnosis as PanNETs, and the hyaline globules in these cases were periodic acid-Schiff (PAS) positive, diastase resistant, and immunoreactive with α-1-antitrypsin. All 24 cases were histologically re-evaluated, and the pattern of invasion, presence of clear cells, and nuclear grooves were found to be helpful in distinguishing SPNs from PanNETs. We conclude that the presence of hyaline globules should raise SPNs in the differential diagnosis of a solid cellular neoplasm of the pancreas. However, this should not be used as the sole criterion in the diagnosis of SPNs, as hyaline globules may also be seen in 5% of PanNETs. Immunohistochemical and histologic features supporting the diagnosis of SPNs over PanNETs include CD10 and nuclear β-catenin labeling, an insidious pattern of invasion, clear cells, and nuclear grooves.     

Primitive neuroectodermal tumors of the pancreas: a report of seven cases of a rare neoplasm

Primitive neuroectodermal tumors (PNETs) have rarely been described in solid organs. We report a series of seven PNETs of the pancreas. The clinical, gross, microscopic, and immunohistochemical features of these seven PNETs of the pancreas are described, as are the genetic analyses in five cases. The patients ranged in age from 6 to 25 years (mean 18 years). Four of the patients were male. All of the patients presented with jaundice and/or abdominal pain. All of the tumors were located in the head of the pancreas, and they ranged in size from 3.5 to 9.0 cm. Light microscopy revealed the typical morphologic features of PNETs. By immunohistochemistry the neoplastic cells in all seven cases expressed O13 (CD99, p30/32MIC2). In five of six tested cases, the neoplastic cells also expressed cytokeratin. All of the tumors expressed neural-neuroendocrine markers. Two of the three cases examined ultrastructurally showed prominent epithelial features. There was cytogenetic or molecular genetic evidence of the t(11;22)(q24;q12) in four of five cases examined. Clinical follow-up was available in five cases. Two of the patients were alive with no evidence of disease at 33 and 43 months. One patient was alive with disease at 27 months. One patient died of postoperative complications. Another patient died of disease 4 years after diagnosis. PNET can sometimes arise as a primary neoplasm of the pancreas. Like PNETs arising in more conventional sites, pancreatic PNETs occur in the pediatric and adolescent population, show the characteristic staining with O13, and typically harbor the t(11;22)(q24;q12) chromosomal translocation. PNETs should be included in the differential diagnosis of poorly differentiated small round cell tumors of the pancreas. Moreover, they should not be confused with pancreatic endocrine tumors, which also demonstrate dual epithelial and neuroendocrine differentiation by immunohistochemistry and express O13 in 30% of cases.     

Diagnostic utility of thymic epithelial markers CD205 (DEC205) and Foxn1 in thymic epithelial neoplasms

Foxn1 and CD205 (DEC205) are novel thymic epithelial markers that are important for thymic organogenesis and the positive selection process for thymocytes, respectively. These markers were immunohistochemically applied to a total of 77 cases of thymic epithelial neoplasms comprised of 58 cases of thymomas, 17 cases of thymic carcinomas, and 2 cases of thymic neuroendocrine carcinomas. Foxn1 was diffusely expressed in nuclear staining in all cases of type B thymoma and all but 1 case of type A thymoma, whereas the expression was generally focal in thymic carcinoma (76%). The expression was identified in all cases of mixed AB thymoma, with the expression in type A component being more variable than the one in type B component. CD205 cytoplasmic expression in the form of coarse granular staining with membranous accentuation was strong and diffuse in all cases of type B thymoma (100%), and a majority of type A thymoma (89%), and focal with variable intensity in thymic carcinoma (59%). Mixed AB thymoma demonstrated diffuse expression in type B component (100%), and variable expression in type A component (94%). Neither Foxn1 nor CD205 was expressed in 2 cases of thymic neuroendocrine carcinoma. Foxn1 was focally expressed in 13% of cutaneous squamous cell carcinoma and completely negative in cutaneous basal cell carcinoma, whereas it was completely negative in squamous cell carcinoma from head and neck, esophagus and uterine cervix, and normal tissue and malignant neoplasms from all other organs other than thymus. CD205 was expressed in 4% of nonsmall cell carcinomas of lung, 27% of squamous cell carcinoma of head and neck, and 10% of squamous cell carcinoma of esophagus, but the staining pattern was different from that of thymic epithelial neoplasm and was characterized by rather homogeneous and amorphous quality without granularity or membranous reaction. CD205 was expressed in myeloid dendritic cells of various organs and tissues as well. Foxn1 is a sensitive and specific marker for thymoma and thymic carcinoma, and it appears to be superior to CD5 and CD117 for the diagnosis of thymic carcinoma. CD205 is a sensitive and specific marker for thymoma but its sensitivity to thymic carcinoma is lower than CD5 and CD117.     

胰体尾占位病变的手术切除

目的探讨胰体尾占位病变切除的手术路径。方法采用最先探查横断胰颈的方法,对5例胰体尾占位患者实施胰体尾切除。其中2例胰体尾癌及1例实性假乳头瘤患者实施胰体尾联合脾脏切除,1例无功能胰岛细胞瘤患者接受保留脾脏及脾动静脉的胰体尾切除,1例潴留性囊肿患者实施保留脾脏、联合睥动静脉切除的胰体尾切除。结果手术用时2.0～5.5h,术中出血200～1000ml。术后均恢复顺利,未发生任何并发症。结论从探查横断胰颈开始的胰体尾切除术,综合满足了疗效、安全与保脾的需要,具有优势。     

Acinar cell carcinoma of the pancreas metastatic to the ovary: a report of 4 cases

We report 4 cases of acinar cell carcinoma of the pancreas, 3 presenting as metastases in the ovary, the first report of this circumstance, which may pose a broad differential diagnosis and caused significant diagnostic difficulty in all the cases. The average patient age was 57 (range: 28 to 81) years. In 3 cases, the ovarian tumors were detected before the pancreatic tumor; in 1 case, a large abdominal mass and ovarian tumors were discovered synchronously. The ovarian tumors were large, solid, white-tan on gross examination, and bilateral in 3 cases; the single case involving only 1 ovary had 2 discrete masses of tumor. Microscopic examination showed highly cellular neoplasms with a small amount of fibrous stroma. Two cases had a predominant acinar growth pattern of cells with brightly eosinophilic, granular cytoplasm. In 2 cases, the pattern was predominantly solid-cribriform with areas of comedolike necrosis, and the cells had pale eosinophilic, finely granular cytoplasm. Nuclei in all cases were uniform with prominent nucleoli. The main differential diagnostic consideration was well-differentiated neuroendocrine neoplasm (carcinoid tumor); positive immunostaining with antibodies against chymotrypsin and trypsin and negative immunostaining with antibodies against synaptophysin and chromogranin helped exclude this diagnosis. We observed focal alpha-inhibin immunostaining in 2 cases, which may represent a potential diagnostic pitfall, as a Sertoli cell tumor or unusual granulosa cell tumor may also enter the differential diagnosis. Inclusion of antibodies against the pancreatic enzymes chymotrypsin and trypsin in the immunohistochemical panel is critical in establishing the correct diagnosis and should be considered when evaluating ovarian tumors with architectural (mainly acinar) and cytologic (granular eosinophilic cytoplasm) characteristics that should bring a metastatic acinar cell carcinoma into consideration.     

Neuroendocrine secretory protein-55 (NESP-55) expression discriminates pancreatic endocrine tumors and pheochromocytomas from gastrointestinal and pulmonary carcinoids

Neuroendocrine secretory protein-55 (NESP-55), the latest addition to the chromogranin family, is a product of a genomically imprinted gene transcribed exclusively from the maternal allele. Initial studies have shown it to have a less widespread distribution than that of chromogranin A in normal tissues. It has also been suggested that NESP-55 may be a marker of neuroendocrine tumors differentiating toward the adrenal chromaffin and pancreatic islet cells. Metastatic gastrointestinal and pulmonary carcinoids may occasionally be difficult to distinguish from pancreatic endocrine tumors (PETs) and pheochromocytomas on morphologic grounds alone. We studied neuroendocrine tumors from these sites to see if NESP-55 expression could reliably discriminate pulmonary and gastrointestinal carcinoids from neuroendocrine tumors arising in the pancreas or the adrenal medulla. Sixty-three neuroendocrine tumors positive for one or more immunohistochemical marker of neuroendocrine differentiation (chromogranin A, chromogranin B, synaptophysin, secretogranin II, neuron-specific enolase) were selected for the study and consisted of 34 typical carcinoids (15 pulmonary, 11 ileal, 4 gastric, and 4 rectal), 19 PETs, and 10 pheochromocytomas (4 sporadic, 3 MEN-2, 2 neurofibromatosis type 1, and 1 VHL). All cases were stained for NESP-55 after microwave antigen retrieval using a rabbit polyclonal antibody at a dilution of 1:1000. Sections of normal adrenal medulla were used as positive controls for NESP-55 staining. Negative controls consisted of omission of primary antibody and replacement with normal rabbit serum at an equivalent concentration. NESP-55 immunoreactivity was seen as brown finely granular cytoplasmic staining with prominent perinuclear accentuation. All gastric and ileal carcinoids studied were completely negative for NESP-55. One of four rectal and 1 of 15 pulmonary carcinoids showed focal positivity for it in less than 5% of tumor cells. In contrast, all 10 pheochromocytomas and 14 of 19 PETs showed strong immunohistochemical staining in a variable proportion of tumor cells. Diffuse positivity (>75% of tumor cells) was seen in 6 of 14 PETs and 8 of 10 pheochromocytomas. Our results indicate that, in contrast to the other granins, NESP-55 reactivity is restricted to endocrine tumors of the pancreas and the adrenal medulla. Immunohistochemical expression of NESP-55 may thus be useful in assigning a pancreatic or adrenal origin to metastatic endocrine tumors of unknown origin.     

Nonductal Pancreatic Cancers

Nonductal pancreatic neoplasms, including solid pseudopapillary neoplasms, acinar cell carcinomas, and pancreatoblastomas, are uncommon. These entities share overlapping gross, microscopic, and immunohistochemical features, such as well-demarcated solid neoplasms, monotonous cellular tumor cells with little intervening stroma, and abnormal beta-catenin expression. Each tumor also has unique clinicopathologic characteristics with diverse clinical behavior. To differentiate nonductal pancreatic neoplasms, identification of histologic findings, such as pseudopapillae, acinar cell features, and squamoid corpuscles, is important. Immunostainings for acinar cell or neuroendocrine markers are helpful for differential diagnosis. This article describes the clinicopathologic and immunohistochemical features of nonductal pancreatic cancers.     

Non-Small Cell Neuroendocrine Carcinoma of the Sinonasal Tract and Nasopharynx. Report of 2 Cases and Review of the Literature

Non-small cell neuroendocrine carcinomas (NSNECs) of the sinonasal tract are rare. Due to their rarity, the clinical and pathologic characteristics of these neoplasms are not adequately understood. We report two additional examples of NSNEC. The patients were male, 67- and 34-year-old. The first had a tumor involving left ethmoid sinus and nasal cavity and the second, a neoplasm involving nasopharynx, sphenoid sinus, with bilateral involvement of cavernous sinuses. Both tumors were composed of small to medium size cells showing round nuclei with finely dispersed chromatin and small to inconspicuous nucleoli. One case was characterized by variable size individual and confluent nests while the second demonstrated patternless sheets only. One case had punctate necrosis and a mitotic rate of 10–11/10 hpf whereas the second did not have necrosis and the mitotic rate was only 1–2/10 hpf. Both tumors were positive for keratins, CD56, and NSE. One case was positive for chromogranin and the second for synaptophysin. One patient is alive and free of disease 4 years after external beam radiotherapy. The second is alive with locally advanced disease 7 years after radiotherapy and chemotherapy. The literature suggests that NSNECs are a heterogenous group of neoplasms with a morphologic spectrum encompassing tumors resembling “atypical carcinoids”, neoplasms composed of large cells akin to large cell neuroendocrine carcinomas, and tumors with glandular and goblet cell differentiation reminiscent of “goblet cell carcinoids”. Other cases do not show specific features and are probably best regarded as “neuroendocrine carcinoma, NOS”. More studies are needed to better define the histopathologic spectrum of these lesions and to develop a clinically relevant classification.     

Pancreatic Neuroendocrine Tumors

Pancreatic neuroendocrine neoplasms include well-differentiated pancreatic neuroendocrine tumors (PanNETs) and neuroendocrine carcinomas (NECs) with well-differentiated PanNETs accounting for most cases. Other pancreatic primaries and metastatic carcinomas from other sites can mimic pancreatic neuroendocrine neoplasms. Immunohistochemical studies can be used to aid in the differential diagnosis. However, no specific markers are available to differentiate PanNETs from NETs of other sites. Although NECs are uniformly deadly, PanNETs have variable prognosis. Morphology alone cannot predict the tumor behavior. Although some pathologic features are associated with an aggressive course, Ki67 is the only prognostic molecular marker routinely used in clinical practice.