Fine-needle aspiration biopsy of mucinous cystic neoplasm of the pancreas: a case study

This report illustrates the cytologic features of well-differentiated cystic adenocarcinoma of the pancreas obtained by fine-needle aspiration biopsy. It also discusses the differentiation of pseudocyst vs neoplastic cyst by this method.     

Undifferentiated carcinoma with osteoclast-like giant cells arising in a mucinous cystic neoplasm of the pancreas

A 26-year-old woman presented with pain in the left hypochondrium, for which pancreatectomy and splenectomy was performed, with total gross excision of a mass. A tumor measuring 11 × 9 cm was found in the pancreas. On cut surface there were two cysts filled with a necrotic substance and hemorrhagic content. Spindle or ovoid-shaped cells, in the sarcomatous component, had diffusely infiltrated along the inner side of the walls of one cyst. Osteoclast-like giant cells (OGC) were also contained in the sarcomatous component. Adenoma components of mucinous epithelium with foci of borderline and adenocarcinomatous components were seen on the inner side of the other cyst. An ovarian-type stroma beneath the epithelial component was seen in the cyst wall. A diagnosis of undifferentiated carcinoma with OGC arising in a mucinous cystic neoplasm (MCN) of the pancreas, was made. Seven months after the initial operation the patient had a local recurrence, and the tumor was removed. One month after the second operation, the patient was free of symptoms. Only four cases of undifferentiated carcinoma with OGC arising in MCN, involving an ovarian-type stroma of the pancreas, have been reported.     

So-called "papillary and cystic neoplasm of the pancreas." An immunohistochemical and ultrastructural study

A case of so-called "papillary and cystic neoplasm of the pancreas" (PCNP) was reported and investigated immunohistochemically and ultrastructurally. A tumor of the pancreatic head in a 21-year-old female was curatively resected. The tumor was cystic and histologically consisted of uniform cells in papillary and solid structure. Although there was no immunoreactivity for pancreaticogut hormones or secretory products of the pancreas in the tumor cells, most of the tumor cells were diffusely immunoreactive for neuron-specific enolase (NSE). Some neurosecretory granules were detected in the tumor cells ultrastructurally. Both facts suggested endocrine cell character of the tumor. Certain cases of PCNP might show a differentiation to endocrine cells.     

胰腺导管内乳头状黏液肿瘤19例的病理学分析

目的 总结并分析胰腺导管内乳头状黏液肿瘤(IPMN)临床病理特征.方法 收集19例IPMN的临床及影像学资料,通过光镜观察及免疫组织化学EnVision法[抗体包括p53、c-erbB-2、Ki-67、p16、Fascin]分析其临床、病理学特征及免疫表型.结果 19例IPMN患者平均年龄59岁,中位年龄61岁,男女比例12:7,6例有长期吸烟史,1例合并结肠腺癌,临床表现为上腹部不适、腹痛、食欲减退、体重下降、脂肪泻等.腹部CT及B超检查多数病例表现为囊性占位性病变,囊内有分隔,囊壁有乳头状回声,个别病例表现为单发或多发实性占位,其中3例行十二指肠镜逆行胰管造影(ERCP)检查见十二指肠乳头处有胶冻样黏液分泌物.18例行肿物及部分胰腺切除术,1例行胰管内肿瘤摘除术,11例主要位于胰头,病理诊断1例为胰腺导管内乳头状黏液腺瘤,3例为交界性IPMN,15例为胰腺导管内乳头状黏液腺癌,其中12例伴有浸润,浸润癌中10例为乳头型和(或)管型,2例为黏液型合并管型,2例为原位癌.大体检杳17例为单发,2例为多发病灶,6例为实性占位,13例表现为囊性或囊实性占位,囊性区部分内肇光滑剑有乳头附着,部分囊腔内充满乳头状组织;镜下检查8例为肠型,7例为胰胆管上皮型,3例为胃型,1例为嗜酸细胞型;导管周围纤维组织均明显增生,16例周围胰腺组织伴有慢性胰腺炎,2例肠壁浸润,淋巴结均未发现转移;术后13例分别随访4～48个月,平均随访20个月,1例术后24个月死于其他原因,1例可疑肝转移,1例姑息手术后胰头占位,10例无复发.免疫组织化学6例p53阳性,5例p16阳性,8例Fascin阳性,c-erbB-2均阴性,Ki-67指数1%～80%,平均38%.结论 IPMN为一组少见的胰腺肿瘤,肿瘤主要位于胰管内,伴有胰管扩张,肿瘤细胞为黏液性,有乳头形成,乳头状黏液腺癌多见,约2/3病例伴有浸润.Ki-67指数超过15%应考虑恶性.肿瘤预后较胰腺导管癌明显要好,治疗主要是局部切除及相应化疗,应长期随访.影像学、ERCP及胰液细胞学检查有助于疾病的早期发现和诊断.     

Ruptured mucinous cystic neoplasm with an associated invasive carcinoma of pancreatic head in a pregnant woman: report of a case and review of literature

Mucinous cystic neoplasm (MCN) of the pancreas is characterized by mucin-producing columnar epithelium and an ovarian-type stroma. It occurs almost exclusively in women and is almost always located in the pancreatic body or tail. Here, we report a case of large MCN located in the pancreatic head but not in the body nor tail in a 32-year-old pregnant woman, which was thought to have grown rapidly during pregnancy. It was ruptured at 34 weeks of gestation and the patient was admitted to the emergency department of the University of Fukui Hospital with an acute abdomen. Emergency cesarean section followed by pancreaticoduodenectomy was performed. The tumor consisted of many small cysts lined by a single-layer of mucinous epithelium with papillary growth and partial solid parts showing invasive growth and sarcomatoid changes, indicating mucinous cystic neoplasm with an associated invasive carcinoma (previously referred as mucinous cystadenocarcinoma). Thickened septa revealed ovarian-type stroma strongly positive for α-inhibin and partly positive for progesterone receptor immunohistochemically. We also review and discuss previous reports of MCNs including those with an associated invasive carcinoma in pregnant patients.     

Intraductal papillary–mucinous neoplasm of the pancreas associated with polycystic liver and kidney disease

A case of intraductal papillary–mucinous neoplasm (IPMN) of the pancreas associated with polycystic liver and kidney disease is reported. A 63-year-old man was admitted to hospital with heartburn and upper abdominal pain. CT indicated multiple cysts in the liver and bilateral kidneys, and also showed multiple cystic lesions in the pancreatic head. Pancreatoduodenectomy was performed, and a pathological diagnosis of intraductal papillary–mucinous adenoma of branch duct type of the pancreas was made. He died of renal failure and hepatic failure due to recurrent cholangitis 12 years after the operation. An autopsy confirmed multiple cysts in the liver and kidneys. Multiple hepatic cysts were lined by biliary-type epithelium with no connection to the bile ducts. Peribiliary cysts were observed, and histology of the liver indicated von Meyenburg complexes. The kidneys showed that the cysts originated from all segments of the renal tubule. The autopsy findings suggested that the patient had suffered from autosomal-dominant polycystic kidney disease (ADPKD), but he did not have a family history of ADPKD. This case demonstrates that IPMN of the pancreas can occur as an extrarenal complication in patients with polycystic liver and kidney disease.     

Gastrointestinal mixed adenoneuroendocrine carcinoma (MANEC): An immunohistochemistry study of 13 microsatellite stable cases

BackgroundMixed adenoneuroendocrine carcinoma (MANEC) is currently included in the category of neuroendocrine carcinomas but the therapeutically management is not yet defined.AimsTo present the immunohistochemical (IHC) features of the epithelial mesenchymal transition (EMT) of MANEC.Materials and methodsThe clinicopathological features of 13 consecutive cases of MANEC (6 gastric and 7 colorectal) were correlated with the IHC expression of the biomarkers E-cadherin, β-catenin, N-cadherin, vimentin, maspin, CD44 and S100. In all of the cases open surgery was performed.ResultsAll of the cases showed microsatellite stable status, expressed E-cadherin and membrane β-catenin in both components (neuroendocrine and adenocarcinoma) and were negative for N-cadherin, vimentin and S-100. The colorectal MANECs were negative for maspin. In gastric MANECs, maspin showed cytoplasm positivity in the neuroendocrine component and nuclear translocation in the adenocarcinoma cells. CD44 was positive in all of the cases, in both components. No tumor buddings were identified. Three of the 13 patients survived for at least 32 months, all of them showing lymphatic emboli but not lymph node metastases. Pure neuroendocrine lymph node metastases were seen in only four of the cases: one from stomach, two of the ascending colon and two cases of the upper rectum.ConclusionsGastrointestinal MANEC is a microsatellite stable tumor with nodular growth, which components might originate from a CD44-positive stem-like precursor cell. Lymph node status remains the most reliable prognostic parameter and agressivity seems to not be influenced by tumor budding degree or EMT-related features. The histologic aspect of metastatic component (neuroendocrine versus adenocarcinoma) should be included in the histopathological reports and might be used for establishing the proper-targeted therapy of MANEC.     

Ductal adenocarcinoma of the pancreas with huge cystic degeneration: a lesion to be distinguished from pseudocyst and mucinous cystadenocarcinoma

Cystic neoplasms of the pancreas are rare and often mistaken for pseudocyst by imaging studies and macroscopic examination. We describe an unusual tumor of the pancreas composed of a mural nodule of anaplastic carcinoma arising from a huge ductal adenocarcinoma undergoing cystic degeneration. The cyst measured 27 x 13 x 4 cm. Light microscopy showed that the cyst was partly lined by a single layer of cuboidal to columnar tumor cells with focal mucin production and was surrounded by hyalinized connective tissue. Most lining epithelial cells were absent owing to extensive degenerative process. Immunohistochemical studies showed positive staining of cytokeratin and vimentin for pleomorphic giant tumor cells, which were negative for leukocyte common antigen (CD45), KP-1 (CD68), epithelial membrane antigen (EMA), and carcinoembryonic antigen (CEA). The ductal adenocarcinoma stained strongly positive for cytokeratin and EMA, and negative for vimentin, CD45, CD68, and CEA. The clinical course of the current case was extremely poor and the prognosis resembled that of an anaplastic carcinoma. Therefore, we like to emphasize the importance of complete excision and extensive sampling of any cystic neoplasms in the pancreas including those with large cystic component to avoid missing the malignant elements.     

Intraductal tubular adenoma (pyloric gland-type) of the pancreas: a reappraisal and possible relationship with gastric-type intraductal papillary mucinous neoplasm

Aims:  Intraductal tubular adenoma (ITA) is an uncommon intraluminal polypoid lesion that occurs in the main pancreatic duct and involves the main pancreatic duct in the region of head or body. Three cases of ITA are presented, the literature reviewed and their association with intraductal papillary mucinous neoplasm (IPMN) is postulated.
Methods and results:  ITA is composed of tightly packed tubular structures with focal cystic dilation and papillary areas lined by gastric/pyloric epithelium showing minimal to mild cytological atypia. Pancreatic intraepithelial neoplasia (PanIN) 1A and B was present in smaller ducts of all cases. In addition, in the cases in this report and 50% of cases reported in the literature, an associated gastric-type IPMN was present in the same duct as the ITA or in adjacent ducts. The coexistence of ITA and IPMN and the similarities of their epithelial lining (gastric/pyloric mucosa) suggest a possible pathogenic link.
Conclusions:  ITA can occur without (type A) or with (type B) an associated gastric-type IPMN. ITA could represent a localized, polypoid form of gastric-type IPMN.It is a benign lesion with no evidence of invasion and no direct tumour-related deaths. Its relationship to intraductal tubular carcinoma remains to be elucidated.     

Immunohistochemical analysis of steroidogenic enzymes in ovarian‐type stroma of pancreatic mucinous cystic neoplasms: Comparative study of subepithelial stromal cells in intraductal papillary mucinous neoplasms of the pancreas

Mucinous cystic neoplasms (MCNs) are generally defined as cyst‐forming epithelial neoplasms that arise in the pancreas and harbor characteristic ovarian‐type stroma beneath the epithelium. In this study, we compared the immunoreactivity of steroid‐related factors in these subepithelial stromal cells in MCNs to those in intraductal papillary mucinous neoplasms (IPMNs) to further characterize this unique MCN ovarian‐type stroma through evaluation of sex steroid biosynthesis. Twenty MCNs and twenty IPMNs were examined. Immunoreactivity of steroid hormone receptors, including estrogen receptor (ERα and ERβ), progesterone receptor (PR, PR‐A, and PR‐B), and androgen receptor (AR), was more frequently detected in MCN ovarian‐type stromal cells than in IPMN stromal cells (P < 0.01). The H‐scores (mean ± SD) of steroidogenic factor (SF)‐1 were also significantly higher in MCNs (112.3 ± 33.1) than in IPMNs (0.9 ± 1.2) (P < 0.01). The steroidogenic enzymes cytochrome P450 cholesterol side‐chain cleavage enzyme (P450scc), cytochrome P450 17 alpha‐hydroxylase (P450c17) and 3β‐hydroxysteroid dehydrogenase (3β‐HSD) showed immunoreactivity in 9/20 (45.0 %), 15/20 (75.0 %) and 13/20 (65.0 %), respectively, of ovarian‐type stroma from MCN cases. These results demonstrate that the ovarian‐type stroma of MCNs can express steroidogenic enzymes. Thus, the ovarian‐type stroma of MCNs can produce sex steroids that may also act on these cells.     

Papillary cystic tumours of the pancreas: An analysis by nuclear morphometry

Papillary cystic tumour (PCT) is a rare, low-grade malignant pancreatic neoplasm, in which the histological criteria for malignancy are still uncertain. We performed a histological examination of 3 metastasizing PCTs, while comparing them with 18 non-metastasizing PCTs, using a computed image analyser. The mean maximum nuclear diameter, the mean standard deviation (SD) of the nuclear diameter, the mean nuclear area and the nuclear-nonnuclear (N/NN) ratio obtained by the image analyser of the metastasizing PCTs (7.23 m, 2.21 m, 30.45 m², 36.41%) were all significantly larger than those of the non-metastasizing PCT (6.34 m, 1.59 m, 23.66 m², 23.74%;P<0.005,P< 0.005,P<0.005,P<0.001 respectively). However, there were no statistical differences in either the nuclear ellipsoidity or nuclear regularity. These results suggested that nuclear morphometry might be a useful parameter to define metastatic potential, in addition to histological variables such as venous invasion, nuclear grade and mitotic rate.     

Classification of types of intraductal papillary-mucinous neoplasm of the pancreas: a consensus study

Now that more than two decades have passed since the first reports of intraductal papillary-mucinous neoplasms (IPMNs), it has become clear that IPMN consists of a spectrum of neoplasms with both morphological and immunohistochemical variations. At a meeting of international experts on pancreatic precursor lesions held in 2003, it was agreed that a consensus classification of IPMN subtypes should be established to enable a more detailed analysis of the clinicopathological significance of the variations. Based on our experience and on information from the literature, we selected representative histological examples of IPMNs and defined a consensus nomenclature and criteria for classifying variants as distinctive IPMN subtypes including gastric type, intestinal type, pancreatobiliary type, and oncocytic type. These definitions can be used for further analyses of the clinicopathological significance of the variations of IPMN. This work was supported in part by a Grant-in-Aid from the Ministry of Education, Culture, Sports, Science and Technology of Japan, the Pancreas Research Foundation of Japan, the Gonryo Medical Foundation, and NIH SPORE (Specialized Programs of Research Excellence) in Gastrointestinal Cancer Grant CA62924.     

Ciliated carcinoma of the endometrium associated with mucinous and neuroendocrine differentiation: A case report with immunohistochemical and ultrastructural study

A case of endometrial ciliated carcinoma mixed with foci of mucinous adenocarcinoma and argyrophil cells is described. The patient suffered from diabetes mellitus, hypertension and obesity, but had no history of estrogen use. Although the tumor presented well differentiated histologic features, it showed complete diffuse, endophytic extension. Approximately half of the cilia had abnormal inner structures, with 8 + 2 microtubular pattern. Some ciliated cells contained intracytoplasmic mucin, while others contained neurosecretory granules. These findings suggest that malignant ciliated cells have the capacity of further transformation into mucinous or endocrine cells.     

Angiogenesis in the progression of cutaneous squamous cell carcinoma: an immunohistochemical study of endothelial markers

OBJECTIVE:

To demonstrate the role of angiogenesis in the progression of cutaneous squamous cell carcinoma.

INTRODUCTION:

Angiogenesis is a pivotal phenomenon in carcinogenesis. Its time course in cutaneous squamous cell carcinoma has not yet been fully established.

METHODS:

We studied the vascular bed in 29 solar keratoses, 30 superficially invasive squamous cell carcinomas and 30 invasive squamous cell carcinomas. The Chalkley method was used to quantify the microvascular area by comparing panendothelial (CD34) with neoangiogenesis (CD105) immunohistochemical markers. The vascular bed from non-neoplastic adjacent skin was evaluated in 8 solar keratoses, 10 superficially invasive squamous cell carcinomas and 10 invasive squamous cell carcinomas.

RESULTS:

The microvascular area in CD105-stained specimens significantly increased in parallel with cutaneous squamous cell carcinoma progression. However, no differences between groups were found in CD34 sections. Solar keratosis, superficially invasive squamous cell carcinoma and invasive squamous cell carcinoma samples showed significant increases in microvascular area for both CD34- and CD105-stained specimens compared with the respective adjacent skin.

DISCUSSION:

The angiogenic switch occurs early in the development of cutaneous squamous cell carcinoma, and the rate of neovascularization is parallel to tumor progression. In contrast to panendothelial markers, CD105 use allows a dynamic evaluation of tumor angiogenesis.

CONCLUSION:

This study demonstrated the dependence of skin carcinogenesis on angiogenesis.     

胰腺黏液性囊性肿瘤临床病理分析

目的；探讨胰腺黏液性囊性肿瘤（MCN）的临床病理学特点。方法：6例MCN均行B超或CT检查。除1例外，均作了手术切除治疗。对6例（MCN）作常规HE及免疫组织化学染色观察。结果：6例MCN中，女性4例，男性2例，平均年龄47岁，均位于胰腺体尾部。黏液性囊腺瘤（MCA）3例，囊壁内衬高柱状黏液上皮，上皮周围可见卵巢样间质组织；黏液性囊腺癌（MCC）3例，黏液上皮 有不典型增生，均有囊壁或胰腺组织的浸润，1例上皮周围可见卵巢样间质。CEA和CK 7在上皮中均阳性，c-erbB－2均阴性，间质SMA均阳性。结论：胰腺MCN是好发于中年女性的少见肿瘤，绝大多数发生于胰腺体尾部。MCA内衬高柱状上皮，上皮外来卵巢样间质包绕；MCC上皮细胞有不典型增生， 浸润性生长。MCN手术切除率高。     

Differential expression of CD44v6 in adenocarcinoma of the pancreas: an immunohistochemical study

Alternative splicing gives rise to numerous CD44 isoforms, some of which seem to have a role in tumour metastasis. Specifically, a variant form of CD44 with sequences encoded by exon v6 (CD44v6) confers metastatic potential when transfected into a nonmetastasizing cell line of rat pancreatic adenocarcinoma. This study has investigated standard CD44 (CD44s) and CD44v6 expression immunohistochemically in 6 samples of normal pancreatic tissue, 4 of tissue affected by chronic pancreatitis, and 24 of tissue from metastasizing and nonmetastasizing pancreatic adenocarcinomas. In addition, 18 samples from lymph node or visceral metastases were included in the study. CD44s was expressed in nonneoplastic tissue and in tissue from pancreatic adenocarcinomas. In contrast, CD44v6 was not detected in any of the normal tissue or chronic pancreatitis specimens, whereas 54% of pancreatic adenocarcinomas and 55% of metastases expressed this variant exon. Although it is not clear whether CD44 isoforms containing exon v6 play a part in malignant progression in the human exocrine pancreas, it seems plausible that the expression of multiple isoforms containing this and other variant exon confers a selective advantage on pancreatic adenocarcinoma.     

The chronically pilocarpine-treated rat in the study of cystic fibrosis: investigations on submandibular gland and pancreas

The chronically pilocarpine-treated rat has been proposed as an animal model for the disease cystic fibrosis, a generalized exocrinopathy. The effect of chronic pilocarpine treatment on structure, composition, and function of the acinar cells of rat submandibular gland and pancreas was investigated by electron microscopy, X-ray microanalysis, and biochemical analysis. The morphological effects of chronic pilocarpine treatment were most pronounced in the pancreas. The number and size of the zymogen granules was increased, and the granules had a less electron-dense appearance. X-ray microanalysis at the cellular level showed in both the submandibular gland and the pancreas a significant increase in calcium and a decrease in sodium. The increase in cellular calcium concentrations can be explained by an increase in the relative volume of secretory material in the cell (assessed by morphometry) and an increase in the local calcium concentration in the secretory material (assessed by X-ray microanalysis at the subcellular level). Chronic pilocarpine treatment caused a disturbance of glycolysis and energy metabolism in the submandibular gland, but no significant effects in this respect were noted in the pancreas. On the other hand, a nearly twofold increase of the pancreatic amylase activity was noted. The pancreas appeared somewhat hyperreactive towards cholinergic stimulation.     

CD117 immunoreactivity in high-grade neuroendocrine tumors of the lung: a comparative study of 39 large-cell neuroendocrine carcinomas and 27 surgically resected small-cell carcinomas

Little is known about CD117 prevalence and clinicopathological implications in pulmonary large-cell neuroendocrine carcinoma. We studied CD117 immunoreactivity in surgical specimens from 39 large-cell neuroendocrine carcinomas of stages I–III and 27 limited-disease small-cell carcinomas, 56 typical and atypical carcinoids of the lung, and 10 neuroendocrine tumorlets, including the membrane and cytoplasmic immunostaining patterns. Membrane CD117 immunoreactivity in 5% or more tumor cells was documented in 30 (77%) large-cell neuroendocrine carcinomas and 18 (67%) small-cell carcinomas and 4 (7%) carcinoids, whereas cytoplasmic labeling was seen in 17 (44%) large-cell neuroendocrine carcinomas, 19 (70%) small-cell carcinomas, and 3 (5%) carcinoids. None of the neuroendocrine cells of the normal bronchial epithelium and of 10 tumorlets showed any CD117 immunoreactivity. Cytoplasmic immunostaining was more prevalent in small-cell carcinomas, whereas membrane labeling did not differ between the two types of high-grade carcinomas. Downregulation of CD117 by neoadjuvant chemotherapy was seen in large-cell neuroendocrine carcinomas but not small-cell carcinomas. Multiple linear regression analysis demonstrated a marginal association between cytoplasmic CD117 immunoreactivity and regional lymph node metastasis in small-cell carcinomas but not large-cell neuroendocrine carcinomas. There was no association between CD117 immunoreactivity and survival in either small-cell carcinoma or large-cell neuroendocrine carcinoma patients.