From Benign IPMN Hyperplasia Adenoma and IDA

Arrangement

Benign IPMN (hyperplasia/adenoma) is papillary-sheet-palisading and cohesive (fig. 1a). Noninvasive IPMC shows small papillary-cohesive clusters that are often accompanied by outer protrusions of cells (fig. 1b). IDA is in sheet-tubular-solid form and loose (fig. 1c). As for arrangement of noninvasive

Fig. 2. Nuclei of benign IPMN (hyperplasia), noninvasive IPMC and IDA. a Benign IPMN has small nuclei but no hyperchromatin. Pancreatic ductal brushing, Papanicolaou stain. X400. b Noninvasive IPMC shows regular small nuclei, although larger than those of benign IPMN, at about 10 ^m in diameter without anisonucleosis (the standard makes neu-trocytes including cytoplasm 10 ^m, and each nucleus is measured from the proportion). Euchromatin shows severe atypia. Scrap smear, Papanicolaou stain. X400. c IDAP has a combination of large nuclei (>15 ^m in diameter) and hyperchromatin with prominent anisonucleosis. Scrap smear, Papanicolaou stain. X400. Arrows show neutrocytes.

Fig. 2. Nuclei of benign IPMN (hyperplasia), noninvasive IPMC and IDA. a Benign IPMN has small nuclei but no hyperchromatin. Pancreatic ductal brushing, Papanicolaou stain. X400. b Noninvasive IPMC shows regular small nuclei, although larger than those of benign IPMN, at about 10 ^m in diameter without anisonucleosis (the standard makes neu-trocytes including cytoplasm 10 ^m, and each nucleus is measured from the proportion). Euchromatin shows severe atypia. Scrap smear, Papanicolaou stain. X400. c IDAP has a combination of large nuclei (>15 ^m in diameter) and hyperchromatin with prominent anisonucleosis. Scrap smear, Papanicolaou stain. X400. Arrows show neutrocytes.

IPMC (1989-2001) [8, 14-18], there has been only a description of non-looseness [17]. Conversely, IDA has been reported as loose clusters [4, 19] and lacking cohesiveness [4, 19]. The papillary arrangement appears to be part of the basic histologic morphology of IPMT [7, 14], but not of IDA. These findings correspond with a report that higher grade adenocarcinomas tend to show non-cohesive clusters, whereas well-differentiated adenocarcinomas frequently exhibit cohesive and well-demarcated groups, resembling those in benign ductal fragments [20]. Consequently, cases with small papillary-cohesive clusters are classed as noninvasive IPMC.

Nuclei

Benign IPMN (hyperplasia/adenoma) has small, regular sized nuclei and no hyperchromatin (fig. 2a). Noninvasive IPMC shows small, regular nuclei, about 10 |xm in diameter (the standard makes neutrocytes including cytoplasm 10 |xm, and each nucleus is measured from this proportion), and euchromatin suggesting malignancy (fig. 2b). IDA has a combination of large nuclear size (>15 |xm at the short diameter) and hyperchromatin (fig. 2c). Namely, small, regular nuclei are observed in benign IPMN and noninvasive IPMC, but not in IDA [4] Conversely, a combination of large nuclei (>15 |xm at the shortest diameter) and hyperchromatin (defining malignancy) is observed only in IDAP, but not in benign IPMN and noninvasive IPMC [4]. Euchromatin (suggesting malignancy) is common in noninvasive IPMC, but rare in IDA and not seen in benign IPMN [4]. Uneven chromatin distribution is common in noninvasive IPMC [4, 8, 17, 18] and IDA [4, 19-21], but is absent or rare in IPMN [4]. Coarsely granular chromatin (this is more advanced irregular chromatin distribution and is conclusive for malignancy) is rarely observed in noninvasive IPMC [4, 17, 18], and is common in IDA [4, 19, 20], but not in IPMN [4]. Prominent nucleoli have been reported in noninvasive IPMC [4, 8, 17, 18] and IDA [5, 19-21]. For these reasons, noninvasive IPMC seem to have been reported as being undistinguishable from IDA. Consequently, cases with small malignant nuclei with euchromatin and without anisonucleosis are suggested to be noninvasive IPMC.

Cytoplasm

Benign IPMN (hyperplasia/adenoma) (fig. 3 a) and noninvasive IPMC (fig. 3b) have clearly defined cytoplasmic borders and small regular-sized cytoplasms. IDA has prominent anisocytosis, and poorly defined cytoplasmic borders (fig. 3c). A mixture of goblet cells is cytologically observed in benign IPMN (fig. 4a) and noninvasive IPMC (fig. 4b). This emphasizes the polyclonal-like finding. In contrast, these are cytologically hardly found in IDA (fig. 4c) [4]. IDA cells are monoclonal-like. In histological microscopic photographs, a polyclonal aspect is also recognized in IPMN [13, 22] and IPMC [7, 23], but not in IDA. Several researchers have classified IPMN into clear-, dark-, and compact-cell types based on cytoplasm condensation, epithelial form and expression pattern of MUC1, MUC2 and MUC5AC [24, 25]. Other researchers have also proposed that the papillae of IPMN could be divided into two types: intestinal and pancreatobiliary [26, 27]. In our experience [4], goblet cells are usually found in noninvasive IPMC. Consequently, cases with clearly defined cytoplasmic boundaries, a mixture of goblet cells and a polyclonal aspect suggest benign IPMN and noninvasive IPMC.

Conclusion

For all practical purposes, if a case with a clinically detected mucin-pro-ducing pancreatic tumor exhibits small papillary-cohesive clusters, only the features of mainly small (about 10 |xm) regular malignant nuclei, euchromatin, clearly defined cell borders, a mixture of goblet cells and a polyclonal aspect, are more strongly suggestive of noninvasive IPMC.

Fig. 3. Cytoplasmic border of benign IPMN (hyperplasia), noninvasive IPMC and IDA. a Benign IPMN (vinyl tube aspiration of the main duct of the resected pancreas, Papanicolaou stain, X400) and b noninvasive IPMC (scrap smear, Papanicolaou stain, X400) have columnar cytoplasm and a clearly defined cytoplasmic border. c IDAP are amorphous with a poorly defined cytoplasmic border, and have prominent anisocytosis. Scrap smear, Papanicolaou stain. X400.

Fig. 3. Cytoplasmic border of benign IPMN (hyperplasia), noninvasive IPMC and IDA. a Benign IPMN (vinyl tube aspiration of the main duct of the resected pancreas, Papanicolaou stain, X400) and b noninvasive IPMC (scrap smear, Papanicolaou stain, X400) have columnar cytoplasm and a clearly defined cytoplasmic border. c IDAP are amorphous with a poorly defined cytoplasmic border, and have prominent anisocytosis. Scrap smear, Papanicolaou stain. X400.

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