Mixed exocrine-endocrine tumors of the pancreas

Neoplasms of the pancreas usually show either ductal, acinar, or endocrine differentiation. Mixed exocrine-endocrine pancreatic neoplasms, in which the endocrine component is significant and comprises one-third to one-half of the tumor tissue, are rare. Truly mixed tumors have to be distinguished from exocrine neoplasms with scattered endocrine cells. In ductal adenocarcinomas, the scattered endocrine cells seem to be nonneoplastic. In other malignancies such as acinar cell carcinoma and pancreatoblastoma, scattered endocrine cells most likely represent an integral component of the tumor.     

Alpha-fetoprotein production by pancreatic tumors exhibiting acinar cell differentiation: study of five cases, one arising in a mediastinal teratoma

Five cases of pancreatic neoplasms accompanied by production of alpha-fetoprotein (AFP) and serum elevation of this marker are presented, and the better-documented cases of this phenomenon from the literature are reviewed. Four of the cases originated in the orthotopic pancreas, whereas the fifth arose in the pancreatic component of a mediastinal teratoma. The patients were children or young adults. AFP production in pancreatic tumors is closely linked to acinar differentiation, most cases representing either pancreatoblastoma or acinar cell carcinoma. The distinction between these 2 tumors may be difficult because of the many morphologic and immunohistochemical features they share.     

Ampullary pancreatoblastoma in an elderly patient: a case report and review of the literature

Pancreatoblastoma, generally regarded as a pediatric malignant tumor, is rarely found in the adult population. Only 13 adults with pancreatoblastoma, ranging in age from 19 to 68 years, have previously been reported in the world literature. A diagnosis of pancreatoblastoma relies on characteristic histologic features, including epithelial differentiation and, more importantly, squamoid differentiation. Despite aggressive therapy, adults with pancreatoblastoma have a poor outcome. We describe a 78-year-old woman who presented with painless jaundice and was found on abdominal computed tomographic scan to have a 2.7-cm ampullary mass. The patient underwent successful pancreaticoduodenectomy. Pathologic examination of the resected tumor revealed findings characteristic of pancreatoblastoma. The tumor formed acinar and glandular structures, solid areas, and contained many "squamoid corpuscles," a defining feature of pancreatoblastoma. The tumor cells also showed acinar and ductal phenotype by immunohistochemistry. To the best of our knowledge, this case represents the oldest patient with pancreatoblastoma to be described in the literature to date and the first to occur in the ampulla of Vater. We review previously published cases and discuss the clinical and histopathologic features of adult pancreatoblastoma.     

The fine-needle aspiration biopsy cytology of pancreatoblastoma

We describe the clinical, cytological, histological, and immunohistochemical features of primary and metastatic pancreatoblastoma (PBL), a rare primary pancreatic malignancy of both adults and children. An 18-yr-old male patient presented with abdominal pain, weight loss, and diarrhea and had a 9-cm pancreatic mass that was revealed by CT scan. The fine-needle aspiration biopsy (FNAB) smears from the pancreas specimen and the lung metastasis were cellular and were composed of a combination of solid sheets, three-dimensional, loosely cohesive epithelial groups, and primitive spindled mesenchymal tissue with focal cartilage formation. Acinar formations were best appreciated on cell block preparations, and squamoid corpuscles were seen only on cell block. Zymogen granules were demonstrated in a subset of the epithelial cells using periodic-acid Schiff stains with and without diastase and dual acinar-endocrine differentiation was evident using a focused panel of immunohistochemical stains. Acinar-cell carcinoma (ACC) is the most difficult neoplasm to distinguish from PBL, both clinically and cytologically, especially in young children. The key to distinguishing them is to note the presence of squamous corpuscles and/or heterologous elements such as cartilage. Given the increasing utility of FNAB in the investigation of pancreatic masses, it is important for the pathologist to be familiar with the morphological features of this tumor, especially because preoperative diagnosis provides an opportunity for preoperative therapy before resection.     

Pancreatoblastoma: a histochemical and immunohistochemical analysis.

A case of pancreatoblastoma arising in a five year old girl was analysed using histochemical and immunohistochemical methods. The tumour was composed of tubular gland-like structures, squamoid components and some small round cells surrounding tubular structures. The cytoplasm of the small round cells and a few of the squamoid cells was positive on staining with Grimelius argyrophil stain. Immunohistochemically, tumour tissue was positive for neurone specific enolase. The cytoplasm of some of the small round cells was positive for insulin, glucagon, somatostatin, pancreatin polypeptide, thyroid stimulating hormone, follicle stimulating hormone, and neurotensin. These results suggest that this tumour arose from primitive multipotential stem cells, showing exocrine and neuroendocrine differentiation.     

Genetic and immunohistochemical analysis of pancreatic acinar cell carcinoma: frequent allelic loss on chromosome 11p and alterations in the APC/beta-catenin pathway

Acinar cell carcinomas (ACCs) are rare malignant tumors of the exocrine pancreas. The specific molecular alterations that characterize ACCs have not yet been elucidated. ACCs are morphologically and genetically distinct from the more common pancreatic ductal adenocarcinomas. Instead, the morphological, immunohistochemical, and clinical features of ACCs overlap with those of another rare pancreatic neoplasm, pancreatoblastoma. We have recently demonstrated a high frequency of allelic loss on chromosome arm 11p and mutations in the APC/beta-catenin pathway in pancreatoblastomas, suggesting that similar alterations might also play a role in the pathogenesis of some ACCs. We analyzed a series of 21 ACCs for somatic alterations in the APC/beta-catenin pathway and for allelic loss on chromosome 11p. In addition, we evaluated the ACCs for alterations in p53 and Dpc4 expression using immunohistochemistry, and for microsatellite instability (MSI) using polymerase chain amplification of a panel of microsatellite markers. Allelic loss on chromosome 11p was the most common genetic alteration in ACCs, present in 50% (6 of 12 informative cases). Molecular alterations in the APC/beta-catenin pathway were detected in 23.5% (4 of 17) of the carcinomas, including one ACC with an activating mutation of the beta-catenin oncogene and three ACCs with truncating APC mutations. One ACC (1 of 13, 7.6%) showed allelic shifts in four of the five markers tested (MSI-high), two (15.4%) showed an allelic shift in only one of the five markers tested (MSI-low), and no shifts were detected in the remaining 10 cases. The MSI-high ACC showed medullary histological features. In contrast, no loss of Dpc4 protein expression or p53 accumulation was detected. These results indicate that ACCs are genetically distinct from pancreatic ductal adenocarcinomas, but some cases contain genetic alterations common to histologically similar pancreatoblastomas.     

Mosaic paternal haploidy in a patient with pancreatoblastoma and Beckwith–Wiedemann spectrum

Pancreatoblastoma is a rare type of pancreatic cancer in children. Here, we describe a case in which Beckwith‐Wiedemann syndrome (BWS) was first suspected because of placental mesenchymal dysplasia. Although the baby did not show the stigmata characteristic of BWS or abnormal peripheral blood methylation, she developed a massive pancreatoblastoma 2 months later. She survived after partial excision of the tumor and chemotherapy. The methylation pattern of the pancreatoblastoma tissue was typical of BWS. Single nucleotide polymorphism (SNP) array analyzes revealed that the pancreatoblastoma tissue had genome‐wide loss of maternal alleles. Peripheral blood and nontumor pancreatic tissue showed normal biparental genomic contribution. Interphase fluorescence in situ hybridization analysis with centromeric probes for chromosomes 2 and 11 revealed haploid pancreatoblastoma cells, whereas the placental mesenchymal dysplasia tissue and nontumor pancreas tissue showed diploidy. SNP genotype analysis suggested the presence of mosaicism with the pancreatoblastoma tissue having a different paternal haplotype than that of the peripheral blood and nontumor pancreatic tissue. We report for the first time mosaic paternal haploidy associated with pancreatoblastoma. Babies with placental mesenchymal dysplasia, even those without a definitive diagnosis of BWS, need to be closely followed for the occurrence of embryonic tumors.     

Use of enzyme histochemistry in the diagnosis of pancreatoblastoma

The macroscopic, light microscopic and ultrastructural findings in a case of pancreatoblastoma in a neonate are presented. No evidence for exocrine or endocrine secretion could be found by histochemistry, immunocytochemistry or electron microscopy. However, enzyme histochemical techniques to localize activity of 'glucose-6-phosphatase', acid phosphatase, esterase and esteroprotease supported both a pancreatic origin for the tumour and a biphasic pattern of differentiation.     

Fine-needle aspiration cytology of pancreatoblastoma

Pancreatoblastoma is a rare pancreatic neoplasm seen most commonly in the pediatric age group. We report on the aspiration cytology and immunohistochemical findings of a pancreatoblastoma in a 16-yr-old male.     

Synchronous ectopic pancreatoblastoma in a child: a case report

Pancreatoblastoma is a rare primary pancreatic neoplasm of children that may arise in any portion of the pancreas. We report a case of a 3-yr-old boy who presented to with abdominal pain our hospital and a progressive bulge in his right abdomen. Biochemical evaluation and serum levels of tumoral markers were within reference limits. On the computed tomography, two tumors were found. One located in the head of the pancreas; however, a laparotomy revealed that the head of pancreas was compressed but normal. The other was in the left abdomen near the spleen and the tail of the pancreas. The diagnosis of two synchronous pancreatoblastoma originating from the omentum was confirmed by pathology. Therefore, a pancreatoblastoma should be considered when a large well-defined, lobulated, and heterogeneous mass is identified in the pancreas of children. In addition, an ectopic pancreatoblastoma should be considered when identified within or near the ectopic pancreatic tissue.     

Cystic pancreatic schwannoma in a 46-year-old man

Pancreatic schwannomas are a rare benign mesenchymal neoplasm of the pancreas. They are thought to arise from the epineurium of either autonomic sympathetic or parasympathetic fibers, which course through the pancreas with the vagus nerve. Large pancreatic schwannomas often undergo cystic change, which causes them to be often confused with other more common cystic pancreatic neoplasms preoperatively. The radiological, histologic, and immunohistochemical findings of pancreatic schwannomas are consistent with those of neoplasms found in other sites. Treatment is by surgical resection, and the prognosis is excellent. The awareness and, to some extent, knowledge of less common tumors in the pancreas are needed to achieve the diagnosis. We discuss the clinical and pathologic features and differential diagnosis of cystic pancreatic tumors.     

Immunohistochemical study of pancreatoblastoma

Three cases of pancreatoblastoma in children were examined immunohistochemically and the results were compared with those of pancreatic duct carcinoma in adults. The pancreatoblastoma demonstrated positive reactions to alpha-fetoprotein (AFP) (67%: 2/3), alpha-1-antitrypsin (AAT) (100%: 3/3), carcinoembryonic antigen (CEA) (67%: 2/3) and keratin (33%: 1/3), although CEA was only weakly positive in both cases. On the other hand, adult pancreatic duct carcinoma showed positive reactions as follows; AFP: 3% (1/29), AAT: 21% (6/29), CEA: 97% (28/29) and keratin: 93% (27/29). Also, endocrine substances including insulin, glucagon and somatostatin were all negative in the pancreatoblastomas. Two cases of pancreatoblastoma which were immunohistochemically positive for AFP also showed elevation of the serum AFP level clinically. The different expressive pattern of oncofetal antigens in pancreatoblastoma as compared with pancreatic duct carcinoma in adults may provide further supporting evidence for the embryonic nature of pancreatoblastoma, and suggests that such a pattern might be used as a tumor marker for pancreatoblastoma.     

IMMUNOHISTOCHEMICAL STUDY OF PANCREATOBLASTOMA

Three cases of pancreatoblastoma in children were examined immunohis-tochemically and the results were compared with those of pancreatic duct carcinoma in adults. The pancreatoblastoma demonstrated positive reactions to α-fetoprotein (AFP) (67%: 2/3), α-1-antitrypsin (AAT) (100%: 3/3), carcinoembryonic antigen (CEA) (67% : 2/3) and keratin (33% : 1/3), although CEA was only weakly positive in both cases. On the other hand, adult pancreatic duct carcinoma showed positive reactions as follows; AFP: 3% (1/29), AAT: 21% (6/29), CEA: 97% (28/29) and keratin: 93% (27/29). Also, endocrine substances including insulin, glucagon and somatostatin were all negative in the pancreatoblastomas. Two cases of pancreatoblastoma which were immunohistochemically positive for AFP also showed elevation of the serum AFP level clinically. The different expressive pattern of oncofetal antigens in pancreatoblastoma as compared with pancreatic duct carcinoma in adults may provide further supporting evidence for the embryonic nature of pancreatoblastoma, and suggests that such a pattern might be used as a tumor marker for pancreatoblastoma. ACTA PATHOL. JPN. 37 : 1581-1590, 1987.     

2例婴幼儿胰母细胞瘤临床病理分析

目的：探讨婴幼儿胰母细胞瘤（pancreatoblastoma，PBL）的临床病理特征以及诊断与鉴别诊断。方法：回顾分析2例PBL患儿的临床资料、病理学特征、免疫组织化学结果，并复习相关文献。结果：2例PBL患儿均为无意中发现腹部肿块。组织学可见肿瘤细胞由上皮和数量不等的间质组成，密集的上皮被纤维间质分隔，形成巢状或器官样结构。肿瘤显示腺泡、导管和片状排列，排列成片状的瘤细胞中可见特征性的鳞状上皮岛。免疫组织化学结果显示2例角蛋白均阳性表达，抗胰糜蛋白酶局灶性阳性；嗜铬粒素A、神经元特异性烯醇化酶及CD99各1例局灶性阳性；2例导管分化的细胞癌胚抗原阳性表达；甲胎蛋白和突触素均阴性。结论：PBL是一种罕见的胰腺低度恶性肿瘤，多发生于婴幼儿。鳞状上皮岛为其组织学特征性改变，在诊断时应与其他胰腺肿瘤及畸胎瘤鉴别。     

Pancreatic acinar cell carcinoma

Acinar cell carcinomas (ACCs) are rare neoplasms that represent less than 2% of all exocrine tumors of the pancreas. Although they occur more often in adults between the 5th and 7th decades of life, a few cases have been reported in children. Histologically, ACCs can resemble islet cell tumors, but they differ in their ultrastructural and immunohistochemical features. Although ACCs present a bland histology, they are highly malignant and the survival of patients with these tumors, even though better than that of those with ductal cell carcinomas, is generally poor.     

Granulomatous lymphadenitis in children

The spectrum of granulomatous inflammation in peripheral lymph nodes in 85 children over the previous decade was systematically investigated. A variety of histopathologic features were examined and correlated with the epidemiologic, clinical, and microbiologic information, in addition to the long-term outcome. Sixty children had head or neck involvement, with atypical mycobacteria accounting for the vast majority of confirmed causes. It was most frequent in cervical and submandibular glands of children aged between 1 and 10 years (35 of 44 patients), peaking between age 2 and 5 years, and was more common in girls (male:female ratio, 1:3). Mycobacterium avium-intracellulare was the predominant pathogen, accounting for 75% of the mycobacteria that could be characterized. Granulomatous inflammation in other sites (axilla and upper extremity, 16 patients; inguinal, nine patients), or older than age 10 years rarely yielded a cause. Such patients had no recurrent or persistent clinical problems following surgical excision. Histopathologic features were extremely variable, and no consistent patterns were discerned that could reliably be related to either cause or time course. The clinical features and bacteriologic investigations were the most useful for establishing a diagnosis.     

Ezrin--a useful factor in the prognosis of nephrotic syndrome in children: an immunohistochemical approach

BACKGROUND: Minimal change disease (MCD) and diffuse mesangial proliferation (DMP) are the most common pathomorphological forms of nephrotic syndrome glomerulopathies in children. The clinical course of DMP can be characterised by either DMP-sensitivity (DMP-S) or DMP-resistance (DMP-R) to steroids, resulting in an unfavourable course of the glomerulopathy. Although the clinical processes of DMP-S and DMP-R are initially identical, resistance to steroids may be foreseen by the immunohistochemical expression of cytoskeleton-associated proteins in podocytes. AIMS: To estimate the immunohistochemical expression of ezrin in children with MCD, DMP and focal segmental glomerulosclerosis (FSGS) and to evaluate its usefulness in predicting resistance to steroids. MATERIALS AND METHODS: Renal biopsy specimens of patients with MCD (n = 15), DMP (n = 16) and FSGS (n = 6) were taken. The control tissue consisted of normal-appearing cortex taken from kidneys resected for localised neoplasms (n = 6). The indirect immunohistochemical protocol for the use of a monoclonal antibody directed against ezrin was used. RESULTS: The immunohistochemical expression of ezrin in cases progressively reduced from MCD to DMP-S to DMP-R to FSGS. Except for DMP-R and FSGS (p>0.05), the difference in ezrin expression in podocytes was significant. CONCLUSION: Ezrin can be a potent marker of podocyte injury (podocytopathy) and may help in the histological qualification of MCD, DMP and FSGS. The increased permeability of the filtration barrier in steroid-resistant and proteinuric glomerulopathies may be a consequence of subcellular changes in podocyte-associated proteins following decreased expression of ezrin.     

Insulinoma with Fibrillar Inclusions and Acinar Cell Elements

Islet cell tumors associated with exocrine elements are rare. An insulinoma was removed from the head of the pancreas of a 33 -year-old woman. Ultrastructural and immunohistochemical studies demonstrated that, in addition to the endocrine cells, the tumor had a small population of cells with an acinar cell morphology. Rare cells exhibiting both endocrine and exocrine features (amphicrine cells) were also identified. Another unusual finding in this case was the presence of a large number of intracytoplasmic filamentous inclusions that, even though they have been observed in other neoplasms, have not previously been reported in endocrine tumors of the pancreas. The demonstration of cells with mixed endocrine features supports the concept that both the endocrine and exocrine portions of the components of the pancreas have a common embryologic origin.     

Insulinoma with Fibrillar Inclusions and Acinar Cell Elements

Islet cell tumors associated with exocrine elements are rare. An insulinoma was removed from the head of the pancreas of a 33 -year-old woman. Ultrastructural and immunohistochemical studies demonstrated that, in addition to the endocrine cells, the tumor had a small population of cells with an acinar cell morphology. Rare cells exhibiting both endocrine and exocrine features (amphicrine cells) were also identified. Another unusual finding in this case was the presence of a large number of intracytoplasmic filamentous inclusions that, even though they have been observed in other neoplasms, have not previously been reported in endocrine tumors of the pancreas. The demonstration of cells with mixed endocrine features supports the concept that both the endocrine and exocrine portions of the components of the pancreas have a common embryologic origin.     

High-grade myoepithelial carcinoma can show histologically undifferentiated/anaplastic features

High grade malignant tumors with a poorly-/un-differentiated morphology pose significant diagnostic challenges. Increasingly, the use of adjunct immunohistochemical and molecular tests to characterize and delineate the histopathologic phenotype of these tumors has become necessary, particularly in head and neck tumors. Recently, several entities with a poorly-/un-differentiated light microscopic morphology have been defined based on specific immunohistochemical and genetic characteristics. We herein describe two cases of high-grade myoepithelial carcinoma, one occurring in the submandibular gland and the other occurring in the left nasal cavity, both showing undifferentiated histological and anaplastic cytomorphological features. This led to very broad differential diagnostic considerations and the diagnosis was only established after extensive immunohistochemical studies. Molecular testing for HPV was negative in both cases. Gene fusion analysis using a targeted sequencing assay (Archer® FusionPlex® system) did not identify fusions involving PLAG1, HMGA2, EWSR1 or ALK genes in either case. The submandibular tumor showed an aggressive clinical course, with diffuse pulmonary metastases at presentation, whilst the nasal cavity tumor showed only localized disease. Awareness of a subcategory of high-grade myoepithelial carcinomas with undifferentiated light microscopical features is of significant importance in antibody selection for immunohistochemical investigation of poorly-/undifferentiated malignant tumors in the head and neck region. This histological variant of myoepithelial carcinoma adds to the growing list of differential diagnoses in this diagnostically complex and multifaceted field.