Primary pancreatic cystic neoplasms revisited. Part I: serous cystic neoplasms

Primary pancreatic cystic neoplasms have been recognized increasingly during the two recent decades and include mainly serous cystic neoplasms, mucinous cystic neoplasms, and intraductal papillary mucinous neoplasms. Serous cystic neoplasms represent about 30% of all cystic neoplasms of the pancreas and are characterized by their microcystic appearance (on imaging, macroscopically, and microscopically) and their benign biologic behavior. Modern diagnostic methodology allows the preoperative diagnosis with an acceptable accuracy. Currently, indications for resection of serous cystic neoplasms of the pancreas include the presence of symptoms, size > 4 cm (because these ‘large’ neoplasms have a more rapid growth rate and probably will soon become symptomatic), and any uncertainty about the diagnosis of a serous versus a mucinous cystic neoplasm. Resection should also be considered for lesions in the body/tail of the pancreas. Conservative treatment is a reasonable option in selected patients (for example in the presence of small, asymptomatic lesions in the pancreatic head, especially in the frail or elderly patient).     

Primary pancreatic cystic neoplasms revisited. Part III. Intraductal papillary mucinous neoplasms

Intraductal papillary mucinous neoplasms (IPMNs) represent about 25% of all primary pancreatic cystic neoplasms and are increasingly recognized during the last two decades. They are characterized by intraductal proliferation of neoplastic mucinous cells forming papillary projections into the pancreatic ductal system, which is typically dilated and contains globules of mucus. IPMNs may be multifocal and have malignant potential. Modern imaging is essential in establishing preoperative diagnosis and in differentiating different subtypes of IPMNs (i.e., main-duct vs. branch-type disease). Endoscopic retrograde or magnetic resonance cholangiopancreatography accurately delineate the morphologic changes of the pancreatic ductal system. Endoscopic ultrasonography (usually used in conjunction with image-guided FNA and analysis of the aspirated material) is commonly used for differential diagnosis of IPMNs from other pancreatic cystic lesions. Surgical resection (usually anatomic pancreatectomy, depending on the location of the disease) is the treatment of choice. Total pancreatectomy may occasionally be required in selected patients, but is associated with formidable long-term morbidity. A conservative approach has recently been proposed for carefully selected patients with branch-duct IPMNs. Recurrences following surgical resection can be observed, especially in patients with multifocal disease or in the presence of underlying malignancy.     

Primary pancreatic cystic neoplasms revisited: part II. Mucinous cystic neoplasms

Mucinous cystic neoplasms (MCNs) of the pancreas represent one of the most common primary pancreatic cystic neoplasms, accounting for approximately half of these cases. MCNs are observed almost exclusively in women, and most commonly are located in the body/tail of the pancreas. In contrast to SCNs, MCNs have malignant potential. Proliferative changes (hyperplasia with or without atypia, borderline changes, non-invasive or carcinomas in-situ, and invasive carcinomas) can often be observed within the same neoplasm. Several risk factors for the presence of underlying malignancy within an MCN have recently been recognized. Cross-sectional imaging is of key importance for the diagnostic evaluation of patients with a cystic pancreatic lesion. Cyst fluid examination (cytology, biochemical/genetic analysis) is possible by using fine needle aspiration of the MCN, usually under endoscopic guidance, and may provide useful information for the differential diagnosis. Since MCNs have malignant potential, surgical resection is the treatment of choice.     

Diagnostic imaging of cystic pancreatic neoplasms

Cystic pancreatic neoplasms are being diagnosed with growing frequency due to improving imaging technologies and increasing clinician awareness. Distinguishing cystic neoplasms from pseudocysts and discriminating among the various cystic neoplasms is essential to appropriate management. The backbone of diagnosis of these tumors continues to be cross-sectional imaging by CT and MRI. Despite refinements in technology and significant progress in characterizing these lesions, the overall accuracy of CT and MR is limited. EUS, especially as means of FNA, will have an increasing role in the evaluation of selected cases as experience grows. No radiologic investigation can reliably distinguish cystic neoplasms from pseudocysts nor differentiate among cystic neoplasms in all cases. For uncertain lesions, surgeons should favor either careful observation with serial imaging or surgical resection.     

胰腺囊性肿瘤的临床及免疫组化分析

目的胰腺囊性肿瘤分类和分型与临床特征的关系。以期提高对该组肿瘤的认识。方法对手术切除的40例胰腺囊性肿瘤的临床病理和影像资料，进行临床、病理、及免疫组化法分析，根据WHO胰腺肿瘤分类标准将其分类。结果在40例囊性肿瘤中，浆液性肿瘤12例（30．0％），黏液性肿瘤10例（25．0％），导管内乳头状黏液性肿瘤7例（17．5％），实性假乳头性肿瘤9例（22．5％），导管腺癌囊性变1例，胰腺内分泌肿瘤囊性变1例。免疫组化检测无特异性标记物可以完全区分各类型，常有交叉和重叠。结论各类胰腺囊肿性病变在临床症状、影像学表现、组织形态及免疫表型上均无特异性，需综合判断，才能作出正确诊断，指导临床治疗。     

c-Ki-ras point mutations in ductectatic-type mucinous cystic neoplasms of the pancreas

Ductectatic-type mucinous cystic neoplasms of the pancreas constitute a recently recognized new human pancreatic tumor entity. Examination for the presence of point mutations at codon 12 of K-ras by oligonucleotide hybridization in 5 adenomas and 3 carcinomas revealed alteration in 3 and 2, respectively. In 4 of these positive cases, the transition was GGT----GAT (Gly----Asp) with the remaining one, found in a cancer, being GGT----GTT (Gly----Val). In two carcinoma cases, the same point mutation was detected both in the carcinoma area and in a coexisting adenoma component. Thus K-ras point mutation appears to be associated with this particular type of neoplasm in the same manner as observed for typical exocrine pancreas carcinomas. Our study also indicates the possible existence of an adenoma-carcinoma sequence in the evolution of this type of neoplasm and we suggest that K-ras activation may be an important event in the phase of adenoma development.     

Potential pitfalls in the management of primary pancreatic cystic neoplasms

Primary pancreatic cystic neoplasms (PCN) have been increasingly recognized over the last 2 decades, mainly as a result of the widespread use of modern imaging techniques in patients with abdominal complaints. Biological behavior and management greatly differ between subgroups of PCN. Accurate preoperative diagnosis is required to select the optimal management strategy for each individual patient with PCN. An in-depth knowledge of the biological, imaging, macroscopic/microscopic features, and laboratory findings of each subtype of PCN is required on the part of the clinician, in order to select a cost-effective diagnostic evaluation of the patient. Clinical judgment is also required on the part of the surgeon to select the optimal procedure and to avoid severe pitfalls in the surgical management of these neoplasms.     

胰腺囊性肿瘤诊疗及进展

胰腺囊性肿瘤(PCNs)是少见肿瘤,发病原因尚不明确,不良生活习惯（吸烟、饮酒、重咖啡、高脂高蛋白饮食等）、慢性胰腺炎、环境污染因素及遗传因素等是潜在致病因素。PCNs分为浆液性囊性肿瘤（SCN）、黏液性囊性肿瘤（MCN）、胰腺导管内乳头状黏液肿瘤(IPMN)和实性假乳头状瘤（SPN）四种类型。发病症状常不典型,早期诊断难。PCNs具有典型影像特点,单个影像检查技术对PCNs的准确性和局限性不同,CT检查在胰腺病变中仍是最基本、最主要的检查方式。MRI对于小的囊性病灶比CT更有优势。超声内镜（EUS）充分结合了内镜和超声检查的优势,与CT、MRI检查相辅相成,同时还可进行细针穿刺取病理及囊液分析。尽管PCNs大部分为良性,但只要达到切除标准,均应推荐患者进行手术治疗,严格遵循PCNs诊治流程,制订个体化PCNs治疗策略,使患者利益最大化。     

胰腺黏液性囊性肿瘤的诊治进展

胰腺囊性肿瘤是一种比较少见的胰腺肿瘤,主要包括黏液性囊性肿瘤、浆液性囊性肿瘤、导管内乳头状黏液瘤。其中,胰腺黏液性囊性肿瘤是常见的原发性胰腺囊性肿瘤之一,由于它是一种具有潜在恶性的肿瘤,故术前诊断具有重要意义。近年来,随着现代影像技术如 CT、MRI 及 EUS 等的提高和完善,术前胰腺黏液性囊性肿瘤的诊断率比以往已有大大提高,但在治疗方面仍然没有统一的指南或规范。本文着重对胰腺黏液性囊性肿瘤的诊断、治疗进展做一综述。     

胰腺囊性肿瘤222例临床诊治分析

目的 总结本中心收治的胰腺囊性肿瘤（PCN）的诊治情况及预后,为PCN的临床处理提供一定依据。方法 回顾性分析2005年1月至2016年10月南京鼓楼医院收治的PCN病例,分析各类PCN的临床特征、超声内镜下表现、治疗方式及预后情况。结果 本研究共纳入222例PCN病例,包括94例导管内乳头状黏液瘤（IPMN）,58例黏液性囊性肿瘤（MCN）,43例浆液性囊性肿瘤（SCN）及27例实性假乳头状肿瘤（SPN）。各型PCN患者的男女比例1∶1.55,平均年龄为（56.0±15.7）岁,大部分PCN患者（64.0％,142／222）在就诊时有临床表现,其中以腹痛最常见（47.3％,105／222）。各型PCN术后病理提示分别有7例IPMN（16.3％,7／43）和5例MCN（9.1％,5／55）为恶性（伴浸润性癌或重度异型增生）,而SCN和SPN术后病理均为良性（P=0.027）。未手术的PCN患者中,分别有4例IPMN（8.3％,4／48）和2例SPN（66.7％,2／3）在随访过程中发生癌变。获随访的188例PCN患者的5年生存率为86.0％。124例PCN患者术后的5年生存率为90.0%,SCN、MCN和SPN的术后5年生存率分别为100.0％、92.1％和938％,而IPMN仅为74.0％,差异有统计学意义（P=0.003）。结论 PCN好发于中年女性,大部分患者就诊时有临床症状,最常表现为腹痛。MCN、IPMN和SPN具有恶变倾向,应在符合手术条件的情况下行手术切除;而SCN则可采取保守治疗。各类PCN预后差异显著,IPMN预后最差,MCN、SCN及SPN术后预后均较好。     

Cystic neoplasms of the pancreas: a heterogeneous disorder.

Cystic neoplasms of the pancreas are rare tumors with a relatively better prognosis as compared to other pancreatic cancers. They may be mistaken for pseudocysts. Seventeen patients who underwent surgical resection were analyzed. Seventy percent of the patients were females and 76.7% of the tumors were located in the tail of the pancreas. Preoperative diagnosis was made on the basis of ultrasonography and/or computed tomography findings in 60% of patients. Retrospective review of the imaging modalities revealed one or more findings suggestive of cystic neoplasms in 90% of the patients. These included multiloculated cysts, thickened cyst wall, intracystic mass or calcifications, and presence of liver metastasis. All the tumors were completely or partly excised. The final histopathological diagnosis was microcystic adenoma in 2, mucinous cyst adenoma in 1, papillary cystic neoplasm in 3, cystic neuroendocrine tumor in 5, and cystadenocarcinoma in 6. Of the 17 patients, 10 had malignant tumors. Seven patients with benign tumors and 3 patients with malignant tumors are disease free 12-30 months after resection. Cystic neoplasm must always be considered as a possibility when dealing with cystic lesions of the pancreas and a careful evaluation of ultrasonography and computed tomographic scan may give a clue to the diagnosis.     

Characterization of gene expression in mucinous cystic neoplasms of the pancreas using oligonucleotide microarrays

Mucinous cystic neoplasms (MCNs) of the pancreas are uncommon neoplasms usually located in the body or tail of the pancreas and usually in females (>90% of cases). Clinically, they are often misdiagnosed as non-neoplastic pseudocysts leading to failed opportunities for curative resection. To better understand the biology of MCNs and to identify markers of the disease, we performed global gene expression profiling of MCNs using oligonucleotide microarrays. Using laser capture microdissection applied to frozen sections, RNA was extracted from the neoplastic epithelium of MCNs, from the adjacent 'ovarian-type' stroma of MCNs, from histologically normal pancreatic ductal epithelium, from pancreatic acinar tissue and from fibrous stroma in pancreata affected by chronic pancreatitis. Each RNA sample was subjected to two rounds of linear amplification followed by hybridization with U133A gene chips (Affymetrix). The expression patterns of selected genes were confirmed by quantitative RT-PCR and by immunohistochemistry using tissue microarrays containing 19 resected MCNs. A total of 114 known genes were overexpressed in the neoplastic epithelium compared to normal pancreatic ductal epithelium (>3-fold) including S100P, PSCA, c-myc, STK6/STK15, cathepsin E and pepsinogen C. Activation of the Notch pathway in the epithelial component of MCNs was evident by the demonstration of overexpression of Jagged1 and the downstream Notch pathway member Hes1. In the 'ovarian-type' stroma, several genes involved in estrogen metabolism were overexpressed including STAR and ESR1 genes. Some of the genes identified as overexpressed in these neoplasms may be useful as markers that can distinguish MCNs from non-neoplastic pancreatic cystic lesions.     

Cystic neoplasms of the pancreas with mucin-production.

AIM: To compare the clinico-pathological features of intraductal papillary mucinous cystic tumours (IPMT) and mucinous cystic tumours (MCT) of the pancreas. METHODS: Eighteen patients with IPMT and 18 with MCT who underwent surgical resection between 1990 and 2004 were retrospectively reviewed. Their clinico-pathological features were compared using univariate analysis. Statistical analyses of potential predictive factors of malignancy for each of these two groups were also conducted. RESULTS: Patients with IPMT were found to be older (64+/-10 vs 43+/-18 years, p<0.001) and were predominantly male (male:female ratio, 5:4 vs 1:17, p=0.003) as compared to patients with MCT. MCTs were found in the body-tail region (100%) whereas IPMTs were more evenly distributed (50% in the head) (p=0.001). Pathologically, IPMT was distinct from MCT in terms of size (3.8+/-3.2 vs 9.1+/-4.4 cm, p=0.001), association with secondary pancreatitis (50 vs 0%, p=0.011), communication with the pancreatic duct (94 vs 0%, p<0.001), presence of a dilated main pancreatic duct (61 vs 0%, p<0.001) and the presence of ovarian-type stroma (0 vs 44%, p=0.003). CONCLUSION: IPMT and MCT are distinct clinico-pathological entities. This distinction is important as management and outcome of these entities may differ.     

Intraductal papillary mucinous neoplasms of the pancreas.

BACKGROUND/AIMS: Intraductal papillary mucinous neoplasms (IPMNs) are neoplasms of the pancreatic duct epithelium characterized by intraductal papillary growth and thick mucin secretion. Quantities of mucin fill the main and/or branches of pancreatic ducts and cause ductal dilatation. This review encompasses IPMNs, including symptoms, diagnosis, management, and prognosis. METHODS: A Pubmed database search was performed. All abstracts were reviewed and all articles in which cases of IPMNs could be identified were further scrutinized. Further references were extracted by cross-referencing. RESULTS: Only one-third of all patients are symptomatic. According to the site of involvement, IPMNs are classified into three types: main duct type, branch duct type, and combined type. Most branch type IPMNs are benign, while the other two types are frequently malignant. The presence of large mural nodules increases the possibility of malignancy in all types. Presence of a large branch type IPMN and marked dilatation of the main duct indicate the existence of adenoma at least. Synchronous or metachronous malignancies may be developed in various organs. Endoscopic retrograde cholangiopancreatography, endoscopic ultrasonography, and intraductal ultrasonography clearly demonstrate ductal dilatation and mural nodules, while magnetic resonance pancreatography best visualizes the entire outline of IPMNs. CONCLUSIONS: Prognosis is excellent after complete resection of benign and non-invasive malignant IPMNs. The extent of pancreatic resection and the intraoperative management of resection margins remain controversial. Total pancreatectomy should be reserved for patients with resectable but extensive IPMNs involving the whole pancreas; its benefits, however, must be balanced against operative and postoperative risks. Regular monitoring for disease recurrence is important after surgery.     

Primary pancreatic lymphomas: a cytopathologic analysis of a rare malignancy

BACKGROUND: Primary pancreatic lymphomas (PPL) are extremely rare. Clinically, PPL usually present with symptoms of carcinoma of the pancreatic head. An accurate cytopathologic diagnosis by fine-needle aspiration (FNA) is imperative because the primary treatment is nonsurgical, based on a combination of chemotherapy and radiation therapy. METHODS: Eight cases of PPL were identified from the pathology files of The Johns Hopkins Hospital over a 14-year period (1989-2003). All cases were diagnosed on FNA performed under radiologic guidance. Needle rinses were used to perform flow cytometric (FC) analysis. No tissue studies were performed after the FNA diagnosis was made. RESULTS: A strong male predominance (male-to-female ratio of 7:1) was noted. The patients ranged in age from 35-75 years (mean age, 55 years). The tumors varied in size from 2-14 cm, as evaluated on the radiologic scans (mean dimension of 8.0 cm). Abdominal pain was the most common presenting symptom (six patients) followed by jaundice, acute pancreatitis, small bowel obstruction, and diarrhea. The cytomorphologic features included hypercellularity with discohesive cells with round nuclei, often prominent nucleoli, mitoses, and karyorrhexis. By FC analysis, all eight cases demonstrated a monoclonal pattern of immunoglobulin light chain expression. The patients were treated with either chemotherapy alone or in conjunction with radiation therapy or stem cell transplantation. CONCLUSIONS: PPL is an extremely rare pathologic entity. FNA coupled with FC analysis appears to be highly accurate in the diagnosis of PPL and is the sole diagnostic modality used clinically. Based on cytomorphology, the main differential diagnoses of PPL involve secondary lymphoma, pancreatic endocrine neoplasm, and florid chronic pancreatitis. An accurate FNA diagnosis of PPL is critical for timely, nonsurgical management and obviates the need for an exploratory laparotomy.     

Clinico-pathological features of cystic pancreatic endocrine neoplasms and a comparison with their solid counterparts.

AIM: Pancreatic endocrine neoplasms (PENs) may occasionally manifest as cystic lesions of the pancreas. The aim of this study is to report our experience with cystic PENs and to compare their clinico-pathological features with their solid counterparts. MATERIALS AND METHODS: From 1990 to 2004, 38 patients with PENs were reviewed. Six of these tumours appeared on radiological imaging as a cystic lesion of the pancreas. RESULTS: Of the 38 patients with a PEN, 21 of the patients were female and with a median age of 54.5 (range, 33-83) years. Sixteen patients had functional endocrine tumours of which insulinoma was the most common. The six patients with cystic PEN had a median age of 55.5 (range, 41-70) years and half were female. Cystic PENs were significantly larger [48 (range, 25-170) mm vs 19 (range, 3-120) mm, P = 0.013] and were less likely to be benign (0 vs 50%, P = 0.017) compared to their solid counterparts. There was no difference between cystic and solid PENs in terms of age, sex, presence of symptoms, proportion of functioning tumours and location of tumours within the pancreas. CONCLUSION: Cystic PENs share many clinico-pathological features with solid PENs. These differ only in the cystic appearance and tend to be of a larger size. Hence, these findings suggest that cystic and solid PENs are unlikely to be distinct pathological entities but are likely to be morphological variants of the same entity.     

Malignant papillary cystic tumor of the pancreas.

An example of the rare papillary cystic tumor of the pancreas was diagnosed cytologically by aspiration of the primary neoplasm. Subsequently, it metastasized, proving its low-grade malignant behavior. Diagnostic cytomorphologic features included abundant straight and branched papillary tissue fragments, and uniform, pale nuclei with folds or grooves. Although the primary tumor had a typical histologic appearance, metastases demonstrated increased nuclear pleomorphism and hyperchromasia, bizarre tumor giant cells, and an increased mitotic rate. Vimentin was diffusely positive, whereas neuron-specific enolase and somatostatin were focally and weakly reactive. Neurosecretory and zymogen granules were absent ultrastructurally. By flow cytometric study, the tumor was aneuploid (DNA Index = 1.3).     

Primary neoplasms of the small bowel.

Primary neoplasms of the small bowel are unusual and constitute 1-5% of all gastrointestinal tract neoplasms. Preoperative diagnostic difficulties, frequent dissemination at the time of the diagnosis, and poor prognosis are characteristic of this pathology. During a period of 26 years we treated 61 patients with tumors of the small bowel, 44 malignant and 18 benign (1 patient had both). The most common symptoms were abdominal pain (62%), weight loss (41%), and gastro-intestinal bleeding (31%). More than half of the patients were treated as emergencies and among the remaining, the most useful diagnostic test was the small intestinal barium study. Seventeen patients were operated on for intestinal obstruction, 6 of them due to intussusception of the tumor, while 8 other patients presented with perforation and 7 with massive gastrointestinal bleeding. Leiomyoma was the most frequent benign lesion. Among malignancies lymphoma was encountered in 38.6%, followed by adenocarcinoma (29.6%) and leiomyosarcoma (22.8%). Lymphoma was predominant among Sephardic Jews. Curative procedures were attempted in all but one of the benign cases and in 21 of the malignant cases. At the time of surgery metastases were present in 23 patients. The postoperative mortality was high (20% and 14% in the benign and malignant groups, respectively) most probably due to the high incidence of emergency surgery in a high risk population. The prognosis of the malignant tumors was poor with a 5-year survival of 18%. Their disappointing course seems to be related to late diagnosis because of nonspecific symptoms and difficulty in bringing the tumor to the fore. Hopefully, a greater awareness will lead to an earlier diagnosis and improve the prognosis.