Colorectal cancer is the third leading cause of cancer-related death, and its incidence is rising in the younger patient population. In the past decade, research has unveiled several processes (underlying tumorigenesis, many of which involve interactions between tumor cells and the surrounding tissue or tumor microenvironment (TME). Interactions between components of the TME are mediated at a sub-microscopic level. However, the endpoint of those interactions results in morphologic changes which can be readily assessed at microscopic examination of biopsy and resection specimens. Among these morphologic changes, alteration to the tumor stroma is a new, important determinant of colorectal cancer progression. Different methodologies to estimate the proportion of tumor stroma relative to tumor cells, or tumor stroma ratio (TSR), have been developed. Subsequent validation has supported the prognostic value, reproducibility and feasibility of TSR in various subgroups of colorectal cancer. In this manuscript, we review the literature surrounding TME in colorectal cancer, with a focus on tumor stroma ratio.

No abstract

320, recurrent admissions with sepsis, and recent colonoscopy showing evidence of proctitis (biopsy proven), the patient was diagnosed with sdPSC with overlap of autoimmune cholangiopathy. The sdPSC was treated with a cadaveric liver transplant, and upon explant, the patient's liver showed chronic obstructive cholangiopathy. His postoperative course was notable for persistently elevated bilirubin of which half was indirect. Upon ERCP, the liver showed a mild anastomotic stricture and tortuous duct which was treated with a stent. However, the stent was removed because of lack of frank stricture. The patient was started on a prednisone taper with tacrolimus. The patient is currently doing well post-transplant on low dose tacrolimus and mycophenolate. Discussion: Clinical presentation of sdPSC often consists of pruritis, jaundice, and acute cholangitis from cholestasis, and fatigue, liver failure and hepatosplenomegaly from liver cirrhosis. Notably, the patient presented with hepatomegaly, and jaundice. With this presentation, PSC, sdPSC, and benign recurrent intrahepatic cholestasis (BRIC) were all possible diagnoses. Unremarkable MRCP imaging highlighted the unlikeliness of PSC, and liver biopsy showed bridging fibrosis which excluded BRIC. Clinical diagnosis of sdPSC is difficult and a high degree of clinical suspicion is needed. The cause for Small Duct Primary Sclerosing Cholangitis is unknown, but there is an association with irritable bowel disease, presence of HLA-B8 and HLA-DR3 and autoimmune disease like hyper IgM.

Accurate classification of well-differentiated hepatocellular neoplasms can be challenging especially in core biopsies. Prostatespecific membrane antigen (PSMA) has been shown to highlight tumor-associated neovasculature in many nonprostatic solid tumors including hepatocellular carcinoma (HCC). Archived 164 hepatectomies and explants with 68 HCCs, 31 hepatocellular adenoma (HA), 24 dysplastic nodules (DN), and 42 metastases were retrieved, and pathologic parameters were evaluated. Sensitivity, specificity, accuracy, positive, and negative predictive values for correct diagnosis of HCC were calculated for PSMA and CD34 immunostains in tissue sections and HCC tissue microarrays. PSMA positivity was defined as capillarized sinusoidal/tumor-associated vessel staining involving ≥ 5% of the tumor area. In all, 55/68 (80.9%) HCC and 37/ 42 (88.1%) of liver metastasis were PSMA positive. PSMA was negative in HA, DN, and background liver (100% specificity). CD34 had a 98.5% sensitivity but a 65.5% specificity in identifying HCC. PSMA sensitivity remained high in the HCC tissue microarray (89.7%). PSMA was more accurate than CD34 (95.5% vs. 69.7%) in distinguishing grade 1 HCC from HA and high-grade DN while retaining high sensitivity (80%). The degree of PSMA positivity in HCC was greater in older, male, and human immunodeficiency virus patients (P < 0.05). No associations were found between PSMA staining and other tumor parameters (P > 0.05). PSMA is a marker of neoangiogenesis with increased expression in both primary and metastatic hepatic malignancies. Neovascular PSMA expression is more specific and accurate than CD34 for differentiating HCC from benign and precursor hepatic lesions. Diagnostic and therapeutic utility of PSMA radioligands in malignant liver neoplasms warrant further clinical investigations.

No abstract