Macrocystic serous adenoma of the pancreas

Macrocystic serous adenoma of the pancreas (MSAP) is a rare neoplasm. Its preoperative diagnosis by physical examination and imaging studies is challenging, if not impossible. In recent years, a few cases of MSAP with correct cytodiagnosis by transabdominal fine-needle aspiration (TFNA) have been documented. This paper reports two cases of MSAP that were successfully diagnosed by TFNA cytology. Two adult women presented with epigastric discomfort. Abdominal imaging studies revealed a large pancreatic cystic lesion in both cases. TFNAs of the pancreatic lesions were subsequently performed and revealed a clear serous fluid containing small monolayered sheets of benign cuboidal epithelial cells with scant, clear or granular cytoplasm, vesicular nuclei and micronucleoli. The cell cytoplasm stained positively with periodic acid-Schiff (PAS) and negatively with PAS with prior digestion with diastase (PASD). The cytological findings in both cases were similar and suggested a serous cystadenoma. The two pancreatic lesions were removed by Whipple's operation. They showed features of a macrocystic serous adenoma of the pancreas that were characterized by a small number of large cystic cavities lined by a single layer of non-mucus secreting, PAS-positive and PASD-negative cuboidal epithelial cells. By electron microscopy, the epithelial lining cells showed short and aborted apical microvilli, well-formed desmosomes and a large amount of intracytoplasmic glycogen, suggesting a centroacinar ductal cell origin.     

Mucin histochemistry of ovarian mucinous cystadenomas expressing gastrointestinal characteristics

Fifty-four cases of ovarian mucinous cystadenoma, including twa cases containing ciliated cells representing the müllerian epithelial origin, one case admixed with serous adenoma component and six cases associated with mature teratoma, were examined for the demonstration of gastrointestinal characteristics using periodic acid-Schiff, alcian blue, galac-tose oxidase-Schiff, paradoxycal concanavalin A (ConA), Grimelius and Fontana-Masson stains. Of 41 endocervical-type mucinous cystadenomas not associated with teratoma, 34 cases (83%) showed ConA positivity, expressing gastrointestinal characteristics. As both cases with ciliated cells and the case with serous adenoma component exhibited ConA positivity, the ovarian surface epithelium is supposed to undergo mucinous metaplasia possessing gastrointestinal characteristics. As to the histogenesis of the ovarian mucinous tumors, the metaplasia theory is suggested.     

Neurohormonal peptide immunoreactive cells in mucinous cystadenomas and cystadenocarcinomas of the ovary

Summary In 144 benign mucinous cystadenomas of the ovary, 33 mucinous cystadenomas of borderline malignancy and 64 mucinous cystadenocarcinomas, the incidence of tumours containing argyrophil (and probably endocrine) cells was 18%, 33%, and 53%, respectively. The results of a semiquantitative assessment of the number of argyrophil cells in each individual tumour indicates that the greatest numbers occurred in the cystadenocarcinomas. As, however, the tumour cell density was larger in the cystadenocarcinomas than in the cystadenomas, and as the argyrophil cells often had a patchy distribution in the tumour epithelium, the incidence figures are unreliable. In addition, visualization of the argyrophil cells depends on an adequate fixation which is difficult to achieve in the routine processing of large tumour specimens.Many argyrophil cells in the cystadenocarcinomas displayed immunoreactivity with antisera raised against gastro-entero-pancreatic (GEP) neurohormonal peptides. In ten such tumours immunohistochemical evidence was obtained for the presence of the following neurohormonal peptides in the tumour cells: somatostatin, glucagon, gastrin/CCK, neurotensin, and enkephalin. Four of these ten cystadenocarcinomas were multihormonal, in that three contained two cell populations storing GEP neurohormonal peptides, and one tumour even three such populations. In the benign cystadenomas, however, no immunoreactive tumour cells were found. In those of borderline type, only two harboured immunoreactive cells. In both cases the tumour cells stored gastrin/CCK.The general appearance of the epithelium in the mucinous tumours — a continuous single-cell layer of mucin-producing cells intermingled with argyrophil cells of open type — and the spectrum of neurohormonal peptides observed, indicate an origin from the foregut endoderm.This investigation was supported by grants from the Swedish Medical Research Council (Projects No. 4X-4499 and 12X-718), the Swedish Cancer Society (Project No. 805), the Cancer Research Fund of Malmö General Hospital, and the Medical Faculty at the University of Lund     

Malignant transformation of mucinous ovarian cystadenomas of intestinal epithelial type

We studied 116 benign and 18 borderline malignant mucinous ovarian cystadenomas. Their epithelial lining was compared with normal epithelium of the uterine cervix and that of the small and large intestines, by both light and electron microscopy as well as histochemically. This morphological and histochemical analysis enabled us to subdivide mucinous cystadenomas into cervical, mixed and intestinal epithelial types. The epithelial cells of intestinal type tumours exhibited histochemical reactions very similar to, or identical with, those found in both immature and mature cells of intestinal mucosa. Malignant transformation was found in intestinal type mucinous cystadenomas only. Ultrastructural investigations of six neoplasms (four of intestinal and two of cervical epithelium type) confirmed the results found with the light microscope.     

Invasive mucinous cystic neoplasms of the pancreas

Mucinous cystic neoplasms (MCN) and intraductal papillary mucinous neoplasms (IPMN) of the pancreas both appear to have been included and intermixed in some early reports of pancreatic cystic neoplasms. Recognition of their distinguishing features evolved during the last decade of the twentieth century. One legacy of the early period is the statement that mucinous cystic neoplasms sometimes progress to invasive colloid carcinoma. It is now recognized that colloid carcinomas characteristically arise from IPMN. We set out to see if we could find MCN that invaded as colloid carcinomas and found no examples in MCN collected in two academic medical centers. We then sought to expand the number of MCN by evaluating series from additional centers. This yielded no examples of colloid carcinomas associated with 291 MCN, however one MCN exhibited a minor component with colloid (non-cystic mucinous) growth pattern within the fibrous wall of the neoplasm. The expression of CDX2, a marker of intestinal differentiation that is found in colloid carcinomas was examined by immunostaining in the original MCN series and in the MCN with the intratumoral colloid growth pattern. Focal expression of CDX2 was found in 22 of 43 MCN including the MCN that exhibited the intratumoral colloid growth pattern. Overall, the data suggest that MCN rarely, if ever, invade as colloid carcinoma but the expression of CDX2 by some MCN and the observation of intratumoral colloid growth pattern in one MCN seems to leave open the possibility that MCN might rarely invade as colloid carcinoma.     

Benign pulmonary lesions that may be misdiagnosed as malignant

Five benign pulmonary lesions that may be misdiagnosed as malignant tumors are reviewed. In three lesions, diagnostic problems arise when a spindle cell component is dominant and obscures other characteristic histologic features. In the inflammatory pseudotumor, correct diagnosis relies on recognition of the benign cytology of the spindle cells and identifying a typical admixture of plasma cell-rich inflammatory cells. For spindle cell carcinoids, useful diagnostic features are the organoid pattern, benign cytology, and neuroendocrine differentiation features of the spindle cells. Localized pleural mesothelioma (fibroma) is composed of benign spindle cells in a fibrocollagenous background; mesothelial differentiation is not present by ultrastructural or immunocytochemical analysis. In sclerosing hemangioma, a complex histology may suggest a number of malignancies. Observation of solid and papillary areas of benign tumor cells, as well as sclerosis of vessel walls and intervening areas, will allow correct diagnosis. Pseudolymphoma, a nodular benign lymphoid infiltrate, is distinguished by its polymorphous and polyclonal composition and numerous germinal centers.     

Memory deficits following nucleus basalis magnocellularis lesions may be mediated through limbic, but not neocortical, targets

In order to test the contribution of the target areas of the nucleus basalis magnocellularis to the mediation of item and order recognition memory for spatial locations, one set of rats received lesions of the dorsolateral frontal cortex, parietal cortex, or basolateral amygdala after training in an order recognition memory task, whereas another set of animals received lesions of the nucleus basalis magnocellularis or basolateral amygdala in an item recognition memory task. Animals with basolateral amygdala lesions displayed a deficit for order recognition memory, but no deficit for item recognition memory, a pattern equivalent to that found for animals with nucleus basalis magnocellularis lesions. In contrast, animals with dorsolateral frontal cortex displayed no deficit, and animals with parietal cortex lesions displayed only a partial deficit for order recognition memory, results that differ from those found for animals with nucleus basalis magnocellularis lesions. It appears that the nucleus basalis magnocellularis influences item and order recognition memory for lists of spatial locations primarily through projections to limbic but not neocortical targets.     

Benign lesions of the gastrointestinal tract that may be misdiagnosed as malignant tumors

Benign lesions of the gastrointestinal tract (GIT) that may be misdiagnosed as malignant tumors are described and illustrated in this review. The clinicopathologic features that are important for the accurate diagnosis of each lesion are presented in detail. The entities chosen for discussion include inflammatory pseudotumors (IPT), pseudosarcomatous granulation tissue in GI polyps, pseudocarcinomatous invasion in GI polyps, and GI ulcers induced by radiation and chemotherapy.     

Progressive genomic alterations in intraductal papillary mucinous tumours of the pancreas and morphologically similar lesions of the pancreatic ducts

Intraductal papillary mucinous tumours (IPMTs) of the pancreas are rare neoplasms characterized by a prominent intraductal component, and by malignant potential. Little data exists concerning numerical chromosome aberrations in IPMTs. The biological significance of mucinous epithelial changes (mucinous hyperplasia) in small branching ducts adjacent to IPMTs also remains unclear. From a series of 12 IPMTs, we investigated by interphase cytogenetics 22 foci with mucinous hyperplasia, 27 foci with borderline lesions, and 11 samples with either intraductal (CIS) or invasive carcinoma. Chromosome 6 loss was detected in areas with mucinous hyperplasia (36.3%), borderline lesions (96.3%), and CIS/invasive carcinoma (100%). Similar losses, indicating clonal progression, were found for chromosome 17 (18.2%, 81.5%, and 100%), and for chromosome 18 (0%, 18.5%, and 100%). Quantitative analysis showed a significant intraductal expansion of cell clones harbouring these numerical aberrations within the spectrum of IPMTs. Mucinous epithelial changes in 11 resection samples with chronic pancreatitis showed monosomy 6 (36%) and monosomy 17 (27%). Conversely, areas with low-grade pancreatic intraepithelial neoplasia (PanIN-1), obtained from eight surgical specimens with ductal adenocarcinoma, showed monosomies for chromosome 6, 17, and 18 (100%, 87%, and 50%, respectively). We conclude that monosomies, as defined by FISH analysis, are frequent in both IPMTs and mucinous hyperplasia of pancreatic ducts adjacent to IPMTs. Monosomy 6 may represent an early event in the stepwise accumulation of genomic mutations necessary for the neoplastic transformation of pancreatic duct epithelia, whereas loss of chromosome 18 may be implicated in the progression of borderline to malignant IPMT. The detection of complex chromosomal aberrations in mucinous epithelial changes, and the quantitative expansion of monosomic cell clones in pancreatic ducts, provide evidence for a continuum between hyperplastic and dysplastic epithelial changes.     

Macrocystic serous cystadenoma of the pancreas: a morphologic variant differing from microcystic adenoma.

The term "microcystic adenoma" of the pancreas has gained nearly universal acceptance among pathologists owing to the characteristic gross and microscopic features of this tumor. The possible existence of macrocystic variants of serous cystadenoma has been largely ignored in the literature. We report five cases of macrocystic serous cystadenoma of the pancreas, two of which were of the unilocular type. These tumors exhibited distinctly different macroscopic features from microcystic adenoma, which created diagnostic difficulties for both the radiologist and pathologist. Computed tomography scans on all five cases were thought to represent either mucinous cystic neoplasms or pseudocysts and the tumors were misclassified in two of three cases on which intraoperative frozen sections were performed. In our opinion, microcystic and macrocystic serous tumors represent morphologic variants of the same benign pancreatic neoplasm and we suggest that the term "serous cystadenoma" be used to encompass all variants of this benign neoplasm.     

Senescence in intraductal papillary mucinous neoplasm of the pancreas

Intraductal papillary mucinous neoplasm of the pancreas is attracting attention as a precursor lesion of the invasive ductal adenocarcinoma, whereas it has been reported that some intraductal papillary mucinous neoplasms do not display progression to malignancy and remain almost unchanged in size and morphology. Recent studies have reported that oncogene-induced senescence has been observed in neoplasms, especially in premalignant lesions, and that it can play an important role in preventing malignant progression. To clarify the presence of senescence in intraductal papillary mucinous neoplasms, we analyzed the expression of several markers of senescence. The intraductal papillary mucinous neoplasms evaluated in this study were classified into 4 groups according to the degree of dysplasia. Senescence-associated β-galactosidase activity and senescence-associated heterochromatin foci formation were investigated in 33 cases of intraductal papillary mucinous neoplasms and 6 normal controls. Immunohistochemical analysis of p16(INK4a) and p15(INK4b) was performed in 158 cases of intraductal papillary mucinous neoplasms and 10 normal controls. In the normal controls, neither senescence-associated β-galactosidase activity nor senescence-associated heterochromatin foci formation was observed. Most of the normal epithelia were negative for either p16(INK4a) or p15(INK4b). For all 4 markers, the percentages of positive cases reached a peak in intraductal papillary mucinous neoplasm with low-grade dysplasia and showed significant decreasing trends in the transition from intraductal papillary mucinous neoplasm with low-grade dysplasia to intraductal papillary mucinous neoplasm with an associated invasive carcinoma. Our results indicate that senescence is induced in the early stage of intraductal papillary mucinous neoplasm and gradually attenuated according to the progression. It is suggested that senescence plays a role in preventing malignant progression of intraductal papillary mucinous neoplasm.     

Cystic lesions of the pancreas

In contrast to the relatively uniform pathology and the unyielding dismal outcome associated with infiltrating ductal adenocarcinoma of the pancreas, cystic lesions have a broad spectrum of gross and microscopic pathologies, and a range of clinical outcomes. The common cystic lesions of the pancreas are reviewed with emphasis on practical tips for distinguishing between the main entities.     

Cystic lesion mimicking intraductal papillary mucinous tumor arising in heterotopic pancreas of the stomach and synchronous intraductal papillary mucinous adenocarcinoma of the pancreas

This article presents the study of a 66-year-old man with an asymptomatic pancreatic mass detected incidentally 4 months earlier. A magnetic resonance imaging scan revealed 2 distinct cystic masses in the pancreas and the gastric antrum. Microscopically, the pancreatic lesion showed dilated cysts containing papillary structures lined by mucinous epithelium, which showed a loss of polarity, an increased nucleus-to-cytoplasm ratio, a prominent nucleolus, and high proliferation on immunostaining for Ki-67. The gastric lesion was composed of heterotopic pancreatic tissue surrounding a large dilated cyst that was lined with mucinous epithelium and contained a few intraluminal papillae.     

Macrocystic serous cystadenocarcinoma of the pancreas: the first report of a new pattern of pancreatic carcinoma

Cystic pancreatic neoplasms are rare and include mucinous and microcystic cystadenoma (carcinomas) and the recently described macrocystic adenoma. Their accurate diagnosis is difficult by radiology, and histopathology remains the modality of choice. The case of a 42-year-old woman presenting with a gradually enlarging abdominal mass is reported. Imaging studies revealed a large unilocular cystic lesion in the pancreas. An exploratory laparotomy was done with excision of the cyst along with pancreas. Numerous microscopic sections revealed a serous neoplasm with atypical nuclear features and focal invasion of the cyst wall. A final pathological diagnosis of macrocystic serous cystadenocarcinoma of the pancreas was made. The patient has been doing well two years after surgery. This is the first case of a macrocystic serous cystadenocarcinoma of the pancreas, highlighting the need for extensive sampling of all cystic lesions of the pancreas in order to reach a correct diagnosis.