Histopathological evaluation of minor salivary gland papillary-cystic tumours: focus on genetic alterations in sialadenoma papilliferum and intraductal papillary mucinous neoplasm.

AIMS: Minor salivary gland tumours showing a predominant papillary-cystic structure are rare, and constitute a mixture of various types of neoplasm; thus, the histopathological assessment of these tumours poses a significant diagnostic challenge. We aimed to delineate the histological characteristics of these tumours and further mutational aspects with a particular focus on sialadenoma papilliferum (SP) and intraductal papillary mucinous neoplasm (IPMN). METHODS AND RESULTS: We retrieved 28 papillary-cystic tumours of the minor salivary glands, and performed histological re-evaluation and mutation analyses of several key oncogenes. The histological classifications were as follows: SP (n = 10), SP-like intraductal papillary tumour (SP-IPT) (n = 2), IPMN (n = 9), intraductal papilloma, cystadenoma, and cystadenocarcinoma (two, three and two respectively). Whereas SP typically consisted of a combination of exophytic squamous epithelium and endophytic intraductal papillary infoldings, SP-IPT lacked the exophytic component. SP and SP-IPT frequently harboured BRAF V600E mutations (75.0%), which were identified in both squamous and ductal components. IPMN was characterised by a well-demarcated cystic lesion filled exclusively with a papillary proliferation of mucinous cells and a high rate of AKT1 E17K mutations (88.9%). Intraductal papillomas were unilocular cystic lesions with intraluminal papillary growth of bland columnar cells. In contrast, both cystadenomas and cystadenocarcinomas showed a multicystic appearance with a papillary configuration. Cystadenocarcinomas invaded the surrounding tissue and were composed of markedly atypical tumour cells. CONCLUSION: The appropriate interpretation of histological findings and specific genetic alterations (e.g. BRAF V600E and AKT1 E17K in SP and IPMN) would be useful for the correct diagnosis of minor salivary gland papillary-cystic tumours.

Acinar cell cystadenoma of the pancreas: a benign neoplasm or non-neoplastic ballooning of acinar and ductal epithelium?

Acinar cell cystadenoma (ACA) of the pancreas was initially described as a non-neoplastic cyst of the pancreas and, at that time, referred to as "acinar cystic transformation." In subsequent studies, these lesions were given the designation of "-oma," despite the relative lack of evidence supporting a neoplastic process. To characterize these lesions further, we examined the clinical, pathologic, and immunohistochemical features of 8 ACAs. The majority of patients were female (7 of 8, 88%) and ranged in age from 18 to 57 years (mean, 43 y). Grossly, the cysts involved the head (n=5), body (n=1), or the entire pancreas (n=2). ACAs were either multilocular (n=4) or unilocular (n=4) and ranged in size from 1.8 to 15 cm (mean, 6.8 cm). Histologically, multilocular ACAs were lined by patches of acinar and ductal epithelium. Immunolabeling, including double-labeling for cytokeratin 19 and chymotrypsin, highlighted the patchy pattern of the ductal and acinar cells lining the cysts. In some areas, the cysts with patches of acinar and ductal differentiation formed larger locules with incomplete septa as they appeared to fuse with other cysts. In contrast, the unilocular cases were lined by 1 to 2 cell layers of acinar cells with little intervening ductal epithelium. Nuclear atypia, mitotic figures, necrosis, infiltrative growth, and associated invasive carcinoma were absent in all cases. In addition, we assessed the clonal versus polyclonal nature of ACAs, occurring in women, using X-chromosome inactivation analysis of the human androgen receptor (AR) gene. Five of 7 cases were informative and demonstrated a random X-chromosome inactivation pattern. Clinical follow-up information was available for all patients, and follow-up ranged from 10 months to 7.8 years (mean, 3.6 y), with no evidence of recurrence or malignant transformation. We hypothesize that early lesions are marked by acinar dilatation that expands into and incorporates smaller ductules and later larger ducts. As the cysts increase in size, they fuse forming larger cysts. Later lesions demonstrate a unilocular cyst lined by predominantly acinar epithelium with scattered ductal cells. The term cystadenoma, with its neoplastic connotation, does not seem to accurately reflect the histologic, immunohistochemical, or molecular features of these lesions. We suggest readopting the term "acinar cystic transformation" until the non-neoplastic versus neoplastic origin of these lesions can be resolved.

Pancreatic cystic tumours: when to resect, when to observe.

BACKGROUND AND OBJECTIVES: In recent years there has been an increase in the diagnosis of cystic tumors of the pancreas. In this setting, difficult diagnostic problems and different therapeutic management can be proposed. MATERIAL AND METHODS: A review of the literature and authors experience were undertaken. RESULTS: Cystic tumors of the pancreas include different neoplasms with a different biological behaviour. While most serous cystadenomas (SCAs) can be managed nonoperatively, patients with mucinous cystic neoplasms (MCNs), solid pseudopapillary tumors (SPTs), main-duct intraductal papillary mucinous neoplasms (IPMNs) should undergo surgical resection. Branch-duct IPMNs can be observed with radiological and clinical follow-up when asymptomatic, < 3 cm in size and without radiologic features of malignancy (i.e. nodules). CONCLUSIONS: Cystic tumors of the pancreas are common. Differential diagnosis among the different tumor-types is of paramount importance for appropriate management. Nonoperative management seems appropriate for most SCAs and for well-selected branch-duct IPMNs.

Apocrine cystadenoma and apocrine hidrocystoma: examination of 21 cases with emphasis on nomenclature according to proliferative features.

BACKGROUND: Apocrine cystadenoma (AC) and apocrine hidrocystoma (AH) have been used interchangeably in the literature to designate cystic lesions of apocrine glands. METHODS: We reviewed 21 cases with biopsies of apocrine cystic lesions diagnosed as AH or AC stained by hematoxylin and eosin. The following histological characteristics were recorded: (a) number of cysts, (b) predominant architectural growth pattern of cyst wall, (c) tumor circumscription, (d) nuclear atypia, (e) mitotic activity, counted per 1 mm2 and (f) Ki-67 staining pattern. RESULTS: Our findings clearly show that there is a non-proliferative group and a proliferative group among the lesions. In the non-proliferative group, one may see some structures that resemble papillary projections but lack a fibrous core. In the proliferative group, we found true papillae, and this change was associated with atypia, mitotic activity and increased Ki-67 staining. CONCLUSIONS: Apocrine cystic lesions with true papillary projections should be referred to as AC rather than AH, to emphasize the proliferative adenomatous growth and depicted by their frequency of cytological atypia and high mitotic activity. Furthermore, we suggest complete excision of AC that are proliferative tumors.

Tubular adenoma and syringocystadenoma papilliferum: a reappraisal of their relationship. An interobserver study of a series, by a panel of dermatopathologists.

Tubular adenoma (TA) and syringocystadenoma papilliferum (SCAP) may show histopathological overlap, with some lesions having features of both neoplasms (SCAP + TA). TA has been recently suggested to represent a carcinoma. Four observers blindly assessed 67 cases of TA, SCAP, and their lookalikes (poroma, apocrine adenoma, apocrine carcinoma; all lesions focally featuring a pseudopapillary pattern), and classified the lesions into one of four categories: (1) TA, (2) SCAP, (3) SCAP + TA, and (4) others. Lesions were also classified as benign or malignant. In only 29 cases was there unanimous agreement among the four observers, who classified 22 lesions as TA, three as SCAP, and four cases as others. Of the 38 cases where there was interobserver diagnostic variation, in 30, the diagnosis varied between TA or SCAP or SCAP + TA; the remainder fell in the others category. Analysis of the factors leading to interobserver variability indicated that diagnostic problems occurred when there were any of the following: epidermal acanthosis, papillomatosis, connection of the neoplastic tubules to the overlying epidermis and/or follicular infundibula, and plasma cell infiltration. These features accounted for the morphological overlap between TA and SCAP. All observers agreed that the lesions were benign; the only apocrine carcinoma included was recognized as such by all observers. From the study, it was concluded that TA may arise in the deep dermis without any epidermal connection, or, in other cases, it may be more superficially located with or without an epidermal connection. It may be reasonably inferred that, possibly as a response to infection, there may be accompanying plasma cells and variable acanthosis and papillomatosis, such that the appearances are those of "pure" SCAP, or lesions may have features "intermediate" or overlapping between TA and SCAP.

Borderline ovarian tumors: diverse contemporary viewpoints on terminology and diagnostic criteria with illustrative images.

The National Cancer Institute sponsored a Borderline Ovarian Tumor Workshop held in August 2003 in Bethesda, MD. This report was developed from discussions at the Workshop. The participants acknowledged several areas of disagreement on basic terminology issues and agreed that a glossary with example images would help clarify many commonly misunderstood issues. This report defines terminology used in the pathological description of borderline tumors and their variants, and illustrates examples of each of the most common entities. It also addresses controversial aspects of the definitions and issues involving specimen handling and reporting. For those issues where there is disagreement, the terminology and diagnostic approaches reflecting the differing views are presented.

CT and MRI findings of cystadenofibromas of the ovary.

The aim of this study was to assess imaging findings on CT or MR images of histologically proven ovarian cystadenofibromas. In the period 1995-2001, 32 histologically proven ovarian cystadenofibromas were identified in 28 women. Of the 32 ovarian cystadenofibromas, 16 tumors were purely cystic and the remaining 16 were complex cystic on CT or MR images. Solid components of 16 complex cystic tumors were seen as nodular ( n=8) or trabecular ( n=9) solid areas. One tumor had both nodular and trabecular solid components. Among 16 complex cystic tumors, 14 had thick or irregular septa; thus, half of ovarian cystadenofibromas had morphological imaging features of malignancy on CT or MR images. On histology, solid components in the cystic tumors were correlated with fibrous stromas that occasionally made a false-positive result for malignancy on imaging.

A decomposition model to track gene expression signatures: preview on observer-independent classification of ovarian cancer.

MOTIVATION: A number of algorithms and analytical models have been employed to reduce the multidimensional complexity of DNA array data and attempt to extract some meaningful interpretation of the results. These include clustering, principal components analysis, self-organizing maps, and support vector machine analysis. Each method assumes an implicit model for the data, many of which separate genes into distinct clusters defined by similar expression profiles in the samples tested. A point of concern is that many genes may be involved in a number of distinct behaviours, and should therefore be modelled to fit into as many separate clusters as detected in the multidimensional gene expression space. The analysis of gene expression data using a decomposition model that is independent of the observer involved would be highly beneficial to improve standard and reproducible classification of clinical and research samples. RESULTS: We present a variational independent component analysis (ICA) method for reducing high dimensional DNA array data to a smaller set of latent variables, each associated with a gene signature. We present the results of applying the method to data from an ovarian cancer study, revealing a number of tissue type-specific and tissue type-independent gene signatures present in varying amounts among the samples surveyed. The observer independent results of such molecular analysis of biological samples could help identify patients who would benefit from different treatment strategies. We further explore the application of the model to similar high-throughput studies.

Intraductal papillary-mucinous tumor of the pancreas: a historical review of the nomenclature and recent controversy.

A number of studies on mucin-producing cystic neoplasm of the pancreas have been reported since the first report of the tumor in 1982. There has been some controversy about nomenclatures and clinicopathologic entities of mucin-producing cystic tumor, mucinous cystic tumor, and intraductal papillary tumor of the pancreas. In 1996 and 1997, new classifications of pancreatic neoplasms were published by the World Health Organization (WHO) and Armed Forces Institute of Pathology (AFIP). According to the new WHO and AFIP classifications, mucin-producing cystic neoplasm of the pancreas corresponds mainly to intraductal papillary-mucinous tumor and mucinous cystic tumor of the pancreas. and these two diseases are independent conditions. Intraductal papillary-mucinous tumor is regarded as a unique clinical entity, but controversy remains about the term and clinicopathologic entity. Some confusion and problems remain betweeen the two lesions. In this review, we review their historical background, terminology, WHO and AFIP classification, and problems with classification.

[Mucosecretory and papillary intraductal tumors of the pancreas: clinicopathological considerations and radiological aspects including computed tomography symptomatology]. / Tumeurs intracanalaires mucosecretantes et papillaires du pancreas: considerations clinico-pathologiques et aspects radiologiques comprenant la semiologie tomodensitometrique.

Intraductal papillary-mucinous tumor of the pancreas (IPMT) is an uncommon entity, defined as an intraductal papillary proliferation of mucin-producing epithelial cells. Since the original description of the disease by Ohhashi in 1982, the definition and the classification of the disease has remained confused until the recently published classification of the World Health Organisation (WHO). The purpose of this article is therefore to report the clinico-pathological features of IPMT according to the WHO classification, to illustrate the radiological features especially the computed tomographic signs and to discute of the treatment.

Cistadenoma mucinoso del páncreas: reporte e historia natural de un caso / Mucinous cistoadenoma of the pancreas: report and natural history of a case

Se reporta el caso de una paciente de 51 años de edad en quien se diagnosticó y resecó un quiste localizado en la cola del páncreas. Los síntomas iniciales fueron de dolor abdominal inespecífico por el que había sufrido dos intervenciones quirúrgicas del abdomen superior, en las que el quiste no fue detectado. Exámenes por imágenes descubrieron una masa quística que fue mal interpretado como pseudoquiste y tratado por endoscopista con drenaje transgástrico que no alteró su curso. Esta masa continuó creciendo con el consecuente aumento del dolor y malestar en hipocondrio izquierdo, hasta su remoción definitiva 2 años después de diagnosticada. El estudio histológico confirmó un cistadenoma mucinoso sin evidencia de malignidad. La evolución fue satisfactoria

[Pathological observation on the new classification and features of ovarian tumors].

Cases were presented to describe the clinical manifestations, histological features, and diagnostic criteria about the current classification of ovarian tumors. They included peritoneal serous borderline tumor, endocervical-like the intestinal-type mucinous borderline tumor, transitional cell carcinoma of ovarian surface epithelial-stromal tumors and juvenile granulosa cell tumor, sclerosing stromal tumor, hepatoid yolk sac tumor, and primary mucinous carcinoid tumor of non-surface epithelial ovarian tumors. Cases were also presented for discussing the significance of structures and features of some ovarian tumors which have been reevaluated and newly classified. For instance, tumor cell of granulosa cell tumor gives vimentin expression, but is unable to express cytokeratin in all the cases detected with monoclonal antibody of CK-2. Based on the clinical manifestations, exact locating site in the ovary, as well as the histology and histochemistry features, it is possible to identify the stromal luteoma, leydig cell tumor, and non-specific steroid cell tumor respectively in the family of steroid cell tumors. Additionally, the diagnostic significance of the occurrence of basal membrane-like substance and intestinal cells in some yolk sac tumors is also discussed.

Spectrum of cystic tumors of the pancreas.

The pathologic and clinical classification, as well as the behavior, of cystic tumors of the pancreas has been the subject of controversy. We retrospectively reviewed 50 patients with a diagnosis of cystic tumor of the pancreas observed at The Johns Hopkins Hospital from 1984 to 1991. These tumors were classified into three broad groups: I, cystadenoma; II, cystadenocarcinoma; and III, adenocarcinoma with mucin production or an associated cyst. The three groups did not differ with respect to age or sex. The most common clinical presentation was abdominal pain. Symptoms and signs among the three groups were similar except that patients with cystadenomas were less likely (p less than 0.05) to be jaundiced and more likely (p less than 0.05) to be asymptomatic. Radiologic findings on computerized tomography, cholangiography, and arteriography also overlapped, making precise preoperative determination of tumor type difficult. Operative classification was also often not possible. The resectability rate (Group I, 91%; Group II, 67%; Group III, 53%) and 5-year survival rate (Group I, 90%; Group II, 72%; Group III, 14%) correlated with careful pathologic determination. Cystic tumors of the pancreas represent a spectrum of disease ranging from benign cystadenoma to adenocarcinoma masquerading as cystadenocarcinoma. We recommend resection whenever possible, even when preoperative evaluation suggests benign disease.

[A classification study of ovarian mucinous cystadenoma using fuzzy mathematics].

Ovarian mucinous cystadenomas (OMCA) are classified into three groups: benign, borderline and malignant. During diagnosis, pathologists often feel puzzled. Quantitative or semiquantitative computer-aided diagnosis is also defective. By using fuzzy mathematics, 129 cases (134 tumors) were studied. At first, they were classified objectively by fuzzy cluster analysis, and the results were used as the basis of study and the judicial criteria of methods. Using these data, an equation of fuzzy synthetical judgement was established. Then these cases were diagnosed again by the equation. The conforming rate was 96.27% (129/134). For comparison, from these data pluralistic concept regression equation was acquired by the computer, then these cases were diagnosed again by the equation, and the conforming rate was 94.03% (126/134). The difficulties in classification of OMCA are analysed and their causes are discussed. Compared with other methods, the merits and demerits of this new method are emphasized.

Neoplasias quísticas del páncreas / Cystic neoplasms of the pancreas

El 15% de las lesiones quísticas del páncreas son neoplásticas. Se reconocen tres tipos de neoplasias quísticas del páncreas: Adenoma microquístico seroso, Neoplasia mucinosa quística y tumor quístico papilar. El primero, llamado también cistoadenoma rico en glicógeno, es el más frecuente y es siempre benigno. La neoplasia mucinosa quística tiene un alto potencial de malignidad. 34% de displasias y 46% de malignidad (cistoadenocarcinoma). El tumor quístico papilar es habitualmente benigno y sólo ocasionalmente se maligniza (cistoadenocarcinoma de células acinares). Enfrentado el cirujano a una neoplasia quística del páncreas, debe tratar de reconocer el tipo de tumor, pues ello determina en gran parte, el tratamiento a seguir

Cystic neoplasms and true cysts of the pancreas.

As the spectrum of pancreatic cysts evolves, sped by the increasing utilization of CT scanning, it becomes apparent that the surgeon must gain information preoperatively about the family history, as well as the personal history of the patient. The presence of cysts in the liver or kidney should be sought. The relation of the lesion to the duodenum and biliary tract needs to be defined. The possibility that the "cyst" represents necrosis of a primary adenocarcinoma of the pancreatic duct should be considered prior to laparotomy. At the time of operation, biopsy of the cyst wall and frozen-section study are fundamental to a decision whether resection or drainage is the treatment of choice. Resection is generally the treatment of the cystic neoplasms, drainage the treatment of pseudocysts. The failure of the surgeon to distinguish between the two groups may be catastrophic. The true cysts and cystic neoplasms of the pancreas are rare lesions. The clinical and radiologic characteristics, the pathologic features, and the natural history of these lesions are not fully documented. Therefore, when they are encountered, the clinician who will carefully document their characteristics can make a contribution to our knowledge.

[Cystic pancreas adenoma. On the clinical relevance of histologic typing]. / Zystisches Pankreasadenom. Zur klinischen Relevanz einer histologischen Typisierung.

Although pancreatic cystadenomas are rare neoplasms, they are found today in rising frequencies due to improvement of diagnostic tools. There exist two types of cystadenoma: microcystic serous cystadenoma and mucinous cystadenoma. Usually, histological distinction from cystadenocarcinoma is readily made, but it may be difficult in the case of the mucinous variant. This subtype is supposed to be potentially malignant, whereas microcystic serous cystadenoma is always benign. In order to elucidate the characteristics of both variants, 5 own cases are reported in this article.