The increasing use of radiological imaging has led to greater detection of small and asymptomatic cystic lesions of the pancreas. Most are resectable, but not all are neoplastic. This review provides an update on the histopathology, immunohistochemistry, molecular biology, pathogenesis and management of cystic neoplasms of the exocrine pancreas. These include the serous, the mucinous cystic, the intraductal papillary mucinous and the solid pseudopapillary neoplasms. Recently reported variants are described and very rare cystic variants of other pancreatic epithelial and mesenchymal neoplasms are briefly mentioned.

S100A8 and its dimerization partner S100A9 are emerging as important chemokines in cancer. We previously reported that Smad4-negative pancreatic tumors contain fewer stromal S100A8-positive monocytes than their Smad4-positive counterparts. Here, we studied S100A8/A9-expressing cells in colorectal tumors relating their presence to clinicopathological parameters and Smad4 status. Two-dimensional gel electrophoresis (n = 12) revealed variation in the levels of S100A8 protein in colorectal cancer tumors, whereas immunohistochemical analysis (n = 313) showed variation in the numbers of stromal S100A8-positive and S100A9-positive cells. Loss of Smad4 expression was observed in 42/304 (14%) colorectal tumors and was associated with reduced numbers of S100A8-positive (P = 0.03) but not S100A9-positive stromal cells (P = 0.26). High S100A9 cell counts were associated with large tumor sizes (P = 0.0006) and poor differentiation grade (P = 0.036). However, neither S100A8 nor S100A9 cell counts predicted poor survival, except for patients with Smad4-negative tumors (P = 0.02). To address the impact of environmental S100A8/A9 chemokines on tumor cells, we examined the effects of exogenously added S100A8 and S100A9 proteins on cellular migration and proliferation of colorectal and pancreatic cancer cells. S100A8 and S100A9 enhanced migration and proliferation in Smad4-positive and Smad4-negative cancer cells. However, transient depletion of Smad4 resulted in loss of responsiveness to exogenous S100A8, but not S100A9. S100A8 and S100A9 activated Smad4 signaling as evidenced by phosphorylation of Smad2/3; blockade of the receptor for the advanced glycation end products inhibited this response. In conclusion, Smad4 loss alters the tumor's interaction with stromal myeloid cells and the tumor cells' response to the stromal chemokine, S100A8.

In a large cohort of patients with a poor prognosis, HSP27 is an independent marker of poor outcome in rectal cancer; its expression is not altered by neoadjuvant radiotherapy. This finding requires validation in an independent similar cohort of patients with rectal cancer. HSP27 levels merit evaluation as a stratification factor for treatment of rectal cancer.

Pancreatic hamartoma is a rare benign lesion and may be mistaken for a malignancy, as demonstrated by two cases. The first case was a 29-year-old man who presented with a 7-month history of intermittent upper abdominal pain, nausea and vomiting and a 15-kg weight loss. CT and MRI revealed a mass in the head of the pancreas. The second case was a 62-year-old man who presented with a 2-year history of intermittent abdominal pain, vomiting and a 25-kg weight loss. Although positron emission tomography was normal, CT revealed thickening of the duodenal wall and endoluminal ultrasonography revealed a tumour in the head of the pancreas. Both patients recovered from uneventful Kausch-Whipple pancreatoduodenectomy (in the first patient, it was pylorus-preserving), and in each case the histological diagnosis was hamartoma. Pancreatic hamartoma can present with vague, non-specific symptoms which, despite modern diagnostic tools, can be difficult to diagnose. Surgical resection with histopathological examination is required to confirm the diagnosis.

Skin biopsies from 117 cases of acute and 23 cases of lupoid leishmaniasis were studied. Of the 117 acute cases, anergic macrophage response were seen in 44, diffuse necrosis in 9 and focalized necrosis in 11 biopsies; the remaining 53 biopsies showed scanty or no parasites with a few to abundant epithelioid cells probably representing post necrotic changes before complete healing of the lesions. The 23 biopsies of lupoid leishmaniasis showed rather well organized epithelioid granulomata surrounded by lymphocytes, inconspicuous plasma cells, no amastigotes and no necrosis. Lupoid cases showed strong delayed hypersensitivity with leishmanin and low serum antibody titres. It appears that the lesions of urban cutaneous leishmaniasis spend a long time in the anergic phase. Partial destruction of parasites by activated macrophages together with gradual elevation of antibody levels prepares the appropriate antigen-antibody ratio for optimum development of necrosis at PI3 leading to effective elimination of parasites. Plasma cells appear to be important in the induction of necrosis and inhibition of epithelioid granulomata. A significant inverse relationship has been found between plasma cells and epitheloid cells. The delayed hypersensitivity observed in lupoid leishmaniasis is probably the result of a poor humoral response evidenced by inconspicuous plasma cells and low serum antibody titres.