Invasive stratified mucin-producing carcinoma of the colorectum: expanding the morphologic spectrum of large bowel cancer.

BACKGROUND: Invasive stratified mucin-producing carcinoma is a recently recognized adenocarcinoma with distinctive features. It was first described in the cervix but similar tumors have since been reported in the penis, anus and prostate. In the gastrointestinal tract, the phenomenon of epithelial stratification has an interesting embryologic morphogenesis. Gastrointestinal mucosa starts off as nascent columnar epithelium that is subsequently patterned to confer regional specific functions. However, in disease states, normal architectural patterning can be disrupted by aberrant differentiation. Given this background and the phenotypic plasticity of neoplastic cells, we were interested in ascertaining whether invasive stratified mucin-producing carcinoma occurs in the colorectum. METHODS: This was a retrospective study of all 584 cases of colorectal carcinoma accessioned at our institution over a 2-year period (January 2021- December 2022). Cases were analyzed to determine which fulfilled the criteria for invasive stratified mucin-producing carcinoma. RESULTS: There were 9 cases of colorectal invasive stratified mucin-producing carcinoma-one pure form and 8 mixed. They showed the classic colorectal (CK20 + , CDX2 + , CK7-) immunostaining profile but, based on various morphologic criteria, they could be distinguished from conventional adenocarcinoma NOS, mucinous, signet ring cell, medullary, goblet cell and undifferentiated carcinomas. About half the cases were MLH1/PMS2 deficient and BRAF &/or PIK3CA mutated, which aligns with the hypermutated phenotype. CONCLUSIONS: Colorectal invasive stratified mucin-producing carcinoma appears to be a real entity, best recognized in its early stages. It appears to be a high-grade carcinoma. With tumor progression, it evolves into a mucinous adenocarcinoma with a proclivity towards signet ring cells. In summary, the study of this tumor, particularly in its early stages, provides useful clues to further understanding the biology and progression of large bowel cancer. Further studies are required to learn more about this tumor.

Pancreatic Neuroendocrine Tumors Complicated by Sinistral Portal Hypertension: Insights into Pathogenesis.

Purpose: To investigate the association between pancreatic neuroendocrine tumors (panNETs) and sinistral portal hypertension (SPH) and provide insights into the pathogenesis. Methods: A retrospective review of panNETs was conducted from our institution for 12 years. Medical imaging findings were analyzed to determine any association with splenic vein thrombosis (SVT) at diagnosis. The cases were further selected based on the criteria for SPH, namely, (1) presence of SVT, (2) gastric varices, (3) patent portal vein, and (4) normal liver function tests. Results: There were 61 patients with panNETs and 8 (8/61) had SVT and gastric varices at diagnosis. Four (4/8) met the strict criteria for SPH while the other four had more conventional portal hypertension. The four with SPH had large tumors located in the tail with splenic vein invasion and three of four presented with bleeding gastric varices. All four patients underwent surgical resection. Mean follow-up was 8.5 years and the hematemesis never recurred. The other four patients (four of eight) with gastric varices had unresectable disease and all died after a mean survival of 29 months. Conclusion: PanNETs appear to be more commonly associated with SVT and SPH compared with other tumors. This could be related to their relatively indolent nature and their intrinsic vascularity. From a surgical viewpoint, the decision to operate depends on many factors including but not limited to the size/stage, grade, and functionality of the tumor and comorbidities. These considerations notwithstanding, the association between panNETs and SPH suggests that there is benefit in timely resection of panNETs located in the tail.

Role of fine-needle aspiration in the surgical management of pancreatic neuroendocrine tumors: utility and limitations in light of the new World Health Organization classification.

CONTEXT: Pancreatic neuroendocrine tumors (Panc-NETs) are rare and tend to get overshadowed by their more prevalent and aggressive ductal adenocarcinoma counterparts. The biological behavior of PancNETs is unpredictable, and thus management is controversial. However, the new World Health Organization classification has significantly contributed to the prognostic stratification of these patients. Concurrently, there have been advances in surgical techniques for benign or low-grade pancreatic tumors. These procedures include minimally invasive and parenchyma-sparing operations such as laparoscopy and enucleation. OBJECTIVE: To report on the utility and limitations of fine-needle aspiration in the preoperative evaluation and management of PancNETs. DESIGN: This was a retrospective review of our institutional tumor database from 2002 to 2012. There were 25 cases of PancNETs that were localized and staged by medical imaging and diagnosed by fine-needle aspiration. RESULTS: Fourteen patients underwent laparotomy, with some requiring only limited surgery; 4 had laparoscopic resections; 4 were serially observed without surgical intervention; and another 3 were inoperable. After a mean follow-up of 37 months, more than half of the patients had no evidence of disease, including most of those who underwent minimally invasive surgery. CONCLUSIONS: Fine-needle aspiration is a useful diagnostic adjunct to medical imaging in the preoperative evaluation and management of PancNETs. However, there are limitations with regard to grading PancNETs using this technique.

Preliminary observations on expression of transforming growth factors beta1 and beta3 in equine full-thickness skin wounds healing normally or with exuberant granulation tissue.

OBJECTIVE: To determine whether transforming growth factor (TGF)-beta1 and -beta3 expression differs between equine limb wounds healing normally and those healing with experimentally induced exuberant granulation tissue (EGT). STUDY DESIGN: Six wounds were created on the lateral aspect of both metacarpi of each horse; one forelimb was untreated, and the other was bandaged to stimulate the development of EGT. Sequential wound biopsies allowed comparison of growth factor expression between the two types of wound. ANIMALS: Four horses (2 to 4 years of age; 350 to 420 kg). METHODS: Wounds were assessed grossly, histologically, and by enzyme-linked immunosorbent assay (ELISA) for TGF-beta1 and -beta3 expression at 12 and 24 hours and 2, 5, 10, and 14 days postoperatively. RESULTS: Bandaged wounds developed EGT. In all wounds, TGF-beta1 peaked early and remained elevated at 14 days. Peak TGF-beta1 concentration was higher in wounds with EGT, but not significantly so. Expression of TGF-beta3 differed from TGF-beta1, with peak TGF-beta3 concentrations being delayed. Concentrations of TGF-beta3 were higher in wounds healing normally, but this difference was not significant. CONCLUSIONS: During both normal and exuberant wound repair, the expression of TGF-beta1 occurred earlier than TGF-beta3 expression. Wounds healing with EGT tended to have higher concentrations of fibrogenic TGF-beta1 and lower concentrations of antifibrotic TGF-beta3 than wounds healing normally, although these differences were not statistically significant. CLINICAL RELEVANCE: This study suggests that the production of EGT in bandaged wounds may be related to increased expression of fibrogenic TGF-beta1 and decreased expression of antifibrotic TGF-beta3. Further investigation of the roles of TGF-beta1 and -beta3 may be important in understanding the molecular control of EGT in horses.