Jingmei Lin

Distinct clinicohistologic features of inflammatory bowel disease-associated colorectal adenocarcinoma: in comparison with sporadic microsatellite-stable and Lynch syndrome-related colorectal adenocarcinoma.

Long-standing inflammatory bowel disease (IBD), either ulcerative colitis or Crohn disease, is associated with a high risk of developing colorectal adenocarcinoma (CAC). However, histomorphology of IBD-associated CAC has not been thoroughly examined, and it is unclear whether and how these patients should be screened for Lynch syndrome (LS). We evaluated the demographic and morphologic features of 108 IBD-associated CACs, including ulcerative colitis-associated (n=95) and Crohn disease-associated CACs (n=13), against 93 control cases of sporadic microsatellite-stable (MSS) CAC, 20 cases of sporadic microsatellite instability high (MSI-H) CAC, and 23 CAC cases of LS. The mean age of patients with IBD-associated CAC was 50 years, which was lower compared with the mean age of 63.7 years of the sporadic MSS controls and 76.5 years of the sporadic MSI-H group but not statistically different from that of the LS patients. Synchronous CACs were noted in 20.4% of the IBD patients and 13% of LS patients but in only 2.1% of the sporadic MSS controls and in none of the MSI-H patients. Right-sided CACs were significantly less frequent in the IBD group than in sporadic MSS controls, MSI-H group, and LS patients (P<0.05 for all). In contrast to sporadic MSS CAC, IBD-associated CACs are characterized by lack of tumor necrosis, Crohn-like reaction, tumor histologic heterogeneity, the presence of mucin, and signet ring cell differentiation and tumor well differentiation. The histomorphologic similarity among IBD-associated and MSI-H tumors, either sporadic MSI-H or LS-related, is independent of MSI status. The young age of patients with IBD-associated CAC and the morphological similarities among IBD-associated, sporadic MSI-H, and LS-related CAC suggest that an age-based and morphology-based strategy before the screening test for LS may be less effective in IBD patients than in the non-IBD population.

Is the presence of 6 or fewer crypt apoptotic bodies sufficient for diagnosis of graft versus host disease? A decade of experience at a single institution.

Histopathology assessment is crucial for the diagnosis of graft versus host disease (GVHD), as the presence of crypt apoptosis is the cardinal criterion required. However, crypt apoptosis is not limited to GVHD; it also occurs in other conditions such as infection, drug reaction, or inflammatory reactions unrelated to GVHD. To better determine whether the presence of 6 or fewer apoptotic bodies is sufficient for the diagnosis of GVHD, we retrospectively reviewed 78 colon biopsies from 66 patients who received either hematopoietic stem cell (HSCT) or cord blood cell transplantation and whose colon biopsies exhibited apoptotic bodies. Among them, 41 cases contained 6 or fewer apoptotic bodies in the colon biopsy. These biopsies were compared with 141 colon biopsy controls that showed no significant pathologic changes as well as 16 colon biopsies with cytomegalovirus colitis from patients without a history of bone marrow transplantation. Among the 41 cases reviewed, 7 patients had coexisting GVHD in other organs (skin or liver). However, gastrointestinal symptoms of at least 4 HSCT patients whose colon biopsies contained 6 or fewer apoptotic bodies completely resolved in the absence of further intervention for GVHD. The discrepancy between pathologic findings and the clinical course may be due to confounding factors, such as infection or medication-induced injury. Our data suggest that identifying 6 or fewer crypt apoptotic bodies in colon biopsies from HSCT patients is worth reporting in order to alert the clinicians of the possibility of GVHD but not sufficient to render a diagnosis on the pathologic grounds alone. The colon biopsies containing 6 or fewer apoptotic bodies represent a heterogenous group. We suggest this group to be classified as indeterminate for GVHD, instead of diagnosing GVHD outright. Synthesis of all clinical, endoscopic, and pathologic information, including the status of infection, coexisting GVHD involvement in the other organs, and medication, is essential for confirmation of the diagnosis of GVHD.

EUS‐guided FNA cytology of pancreatic neuroendocrine tumour (PanNET): a retrospective study of 132 cases over an 18‐year period in a single institution

To determine the diagnostic accuracy and pitfalls of endoscopic ultrasound (EUS)‐guided fine needle aspiration (FNA) cytology of pancreatic neuroendocrine tumour (PanNET).

IgG4-related sclerosing cholangitis in the absence of autoimmune pancreatitis mimicking extrahepatic cholangiocarcinoma.

Abstract Aims. IgG4-related sclerosing cholangitis in extrahepatic bile ducts in the absence of autoimmune pancreatitis (AIP) is rare and is poorly studied. Herein, we present the clinicopathological features of four cases of IgG4-related sclerosing cholangitis. Methods and results. The clinicopathological features of IgG4-related sclerosing cholangitis were compared with those of IgG4-related sclerosing cholangitis with AIP (n = 7), extrahepatic cholangiocarcinoma (n = 29), primary sclerosing cholangitis (n = 40), and secondary sclerosing cholangitis (n = 12). Several histomorphologic features distinguish IgG4-related sclerosing cholangitis, including a marked degree of bile duct injury, a higher percentage of lymphoid follicle formation, a higher percentage of perineuritis, and a more diffuse and dense lymphoplasmacytic infiltrate. All four cases of IgG4-related sclerosing cholangitis occurred exclusively in males. Of these cases, none had IgG4 serology checked preoperatively, and all had a preoperative diagnosis of extrahepatic cholangiocarcinoma. Clinical follow-up was available in 2 patients with a mean time of 11 months. Follow-up confirmed the benign course of the disease as the patients showed no evidence of relapse. IgG4-related conditions, including sclerosing cholecystitis and retroperitoneal fibrosis, were noted in three patients. Conclusions. IgG4-related sclerosing cholangitis in the absence of AIP presents as a distinct and under-recognized disease that mimics extrahepatic cholangiocarcinoma clinically. Awareness of this entity is essential to avoid erroneously diagnosing malignancy. The current threshold of 10 IgG4-positive plasma cells/high-power field (HPF) in the biopsy is not specific enough to exclude cholangiocarcinoma. Therefore, we suggest the diagnostic cut-off to be 50 IgG4-positive plasma cells/HPF in the biopsy.

Differential Expression of miR-31 between Inflammatory Bowel Disease and Microscopic Colitis

BACKGROUND Idiopathic inflammatory bowel disease (IBD) and microscopic colitis (MC) are distinct entities. However, patients with intermittent episodes of IBD and MC that are encountered in a clinical setting puzzle clinicians and pathologists. This study examined whether microRNA assisted in the classification of IBD and MC. DESIGN Small RNA was extracted from formalin-fixed, paraffin-embedded (FFPE) colon tissue and qRT-PCR was performed from cohorts of normal control (n=38), ulcerative colitis (n=36), Crohns disease (n=26), collagenous colitis (n=36), lymphocytic colitis (n=30), and patients with intermittent features of IBD and MC (n=6). RESULTS Differential expression of miR-31 distinguished IBD (ulcerative colitis and Crohns disease) from MC (collagenous colitis and lymphocytic colitis), confirming the specificity of miR-31 expression in IBD (P=0.00001). In addition, expression of miR-31 was increased in collagenous colitis compared to that of lymphocytic colitis (P=0.010). Among 6 patients with alternating episodes of IBD and MC, one patient had matching miR-31 expression in different phases (lymphocytic colitis to ulcerative colitis, and then back to collagenous colitis). The other 5 patients had MC-like expression patterns in both MC and IBD episodes. CONCLUSION In summary, IBD and MC have distinct miR-31 expression pattern. Therefore, miR-31 might be used as a biomarker to distinguish between IBD and MC in FFPE colonic tissue. In addition, miR-31 is differentially expressed in colonic tissue between lymphocytic colitis and collagenous colitis, suggesting them of separate disease processes. Finally, patients with alternating IBD and MC episodes represent a diverse group. Among them, the majority demonstrates MC-like miR-31 expression pattern in MC phases, which seems unlikely to support the speculation of MC as an inactive form of IBD. Although the mechanisms deserve further investigation, microRNA is a potentially useful biomarker to differentiate IBD and MC.

CD123 is a useful immunohistochemical marker to facilitate diagnosis of acute graft-versus-host disease in colon.

The efficacy of hematopoietic stem cell transplantation (HSCT) is greatly hampered by graft-versus-host disease (GVHD) and opportunistic infection; the gastrointestinal tract is one of the main target organs involved by GVHD and opportunistic infectious agents. The presence of crypt apoptosis is the major criterion for the histologic diagnosis of GVHD; however, it can also be seen in infection, especially cytomegalovirus (CMV) colitis. Therefore, the definitive histopathologic diagnosis of GVHD in gastrointestinal tract can be challenging or impossible without reliable ancillary markers. We studied the expression of CD123 and C4d in 38 colonic biopsies from patients with HSCT with acute GVHD and 14 colon biopsies from patients with CMV colitis without history of HSCT. CD123 expression was significantly increased in the acute GVHD group compared with the CMV group (65.8% versus 14.3%; P < .05) with increasing sensitivity in higher-grade GVHD (grades 1-2, 60%; grades 3-4, 72.2%). However, there was no significant difference in C4d deposition between the acute GVHD and CMV groups (68.4% versus 42.9%; P > .05). We further applied CD123 immunostaining to upper gastrointestinal (n = 23) and colonic biopsies (n = 24) in patients with HSCT without evidence of acute GVHD or infection and 11 biopsies from patients who had used mycophenolate. The negative staining of CD123 in all these cases further supports the specificity of CD123 in acute GVHD. In summary, CD123 might be a useful ancillary marker to aid in separating infection from GVHD in patients with HSCT.

Fine Needle Aspiration of Oncocytic Variants of Pancreatic Neuroendocrine Tumor: A Report of Three Misdiagnosed Cases

Objectives: An oncocytic variant of pancreatic neuroendocrine tumors (PanNET) is exceedingly rare. Here we report cytomorphological features of the oncocytic variant of PanNET and discuss how to avoid diagnostic pitfalls. Study Design: A computerized search of our laboratory information system was performed over an 18-year period to identify all cytology and surgical pathology cases where a diagnosis of PanNET was made or considered in the differential diagnosis. Three cases of the oncocytic variant of PanNET were identified. Results: Endoscopic ultrasound-guided fine needle aspiration (FNA) smears showed cohesive clusters of large atypical cells with abundant eosinophilic granular cytoplasm, anisonucleosis, nuclear enlargement and overlapping, prominent nucleoli, and a relatively smooth nuclear membrane. Nuclei were round to oval with finely granular chromatin. Additional features included rare isolated cells and glandular formation. Some of these morphological features, such as anisonucleosis, nuclear enlargement, and overlapping, prominent nucleoli, are also commonly seen in the pancreatic adenocarcinoma. All these cases were misclassified by FNA as adenocarcinoma (2 cases) or suspicious for carcinoma (1 case) and were histologically confirmed to be oncocytic variants of PanNET. Conclusions: Useful salient features of the oncocytic variant of PanNET include abundant eosinophilic granular cytoplasm, finely granular chromatin, and relatively smooth nuclear membrane. The awareness of this variant will help to avoid misdiagnosis.

Crohn's disease-like reaction predicts favorable prognosis in colitis-associated colorectal cancer.

Background: Idiopathic inflammatory bowel disease is associated with an increased risk of developing colorectal cancer. Colitis-associated colorectal cancer (CAC) has unique histomorphology features; however, whether histomorphology is predictive of survival in CAC, independent of overall clinical tumor stage, remains unknown. The aim of this study is to determine if clinicodemographics and tumor histomorphologic features are prognostic in patients with CAC. Methods: A cohort of CAC patients were identified from the Pathology Database at Cleveland Clinic; slides were reviewed and other relevant data were collected by retrospective review of medical records. Results: Univariate analysis demonstrated that poor differentiation, N stage (N1/N2 versus N0), M stage (M1 versus M0), Tumor, Node, Metastasis (TNM) stage (III/IV versus I/II), positive margin, and Crohns–like reaction were significantly associated with both overall survival (OS) and progression-free survival (PFS) in CAC. Additionally, the presence of >2 tumor-infiltrating lymphocytes/high-power field was found to be significantly associated with longer PFS. Multivariate analysis confirmed that high TNM stage (III/IV versus I/II) was associated with shorter OS and PFS (hazard ratio 2.7, 95% confidence interval [CI]: 1.1–6.7, P = 0.04; 4.84 [95% CI: 2.0–11.5], P < 0.001, respectively), and positive margin status was associated with shorter OS (hazard ratio 4.0 [95% CI: 1.0–15.7], P = 0.05), whereas the presence of Crohn’s–like reaction was associated with longer OS and PFS (hazard ratio 0.3 [95% CI: 0.12–0.79], P = 0.02; 0.25 [95% CI: 0.11–0.58], P = 0.001, respectively). Conclusions: In CAC, high tumor clinical stage and positive margin predict worse survival but Crohn’s disease–like reaction is associated with longer OS and PFS.

Hürthle Cell Neoplasms Diagnosed by Fine Needle Aspiration Are Not Associated with an Increased Risk of Malignancy

Objectives: The aim of this study is to determine the risk of neoplasm and malignancy in thyroid fine needle aspiration (FNA) diagnosed as atypia of undetermined significance with Hürthle cell change (AUS-H) or Hürthle cell neoplasm (HCN). Study Design: A computerized search of our laboratory information system was performed to identify all thyroid FNA and correlating surgical pathology diagnoses including Hürthle cell or oncocyte in the diagnostic nomenclature. The risks of neoplasm and malignancy were calculated for AUS-H and HCN categories separately. Results: For the 29 AUS-H cases, the follow-up histology demonstrated 15 benign lesions, 4 follicular adenomas, 7 Hürthle cell adenomas, 1 papillary microcarcinoma (PMC), 1 follicular carcinoma and 1 Hürthle cell carcinoma. For the 93 HCN cases, the follow-up histology demonstrated 28 benign lesions, 9 follicular adenomas, 32 Hürthle cell adenomas, 2 PMCs, 2 papillary thyroid carcinomas, 6 follicular carcinomas and 14 Hürthle cell carcinomas. Conclusions: The risks of neoplasm and malignancy were 62 and 7% for the AUS-H category and 73 and 24% for the HCN category, respectively. The risk of malignancy for the AUS-H patients is within the 5- to 15-percent range suggested by the Bethesda System for Reporting Thyroid Cytology and within the 15- to 30-percent range suggested for follicular neoplasms.

Fine needle aspiration evaluation of pancreatic lymphoma: A retrospective study of 25 cases in a single institution

Accurate diagnosis of pancreatic lymphoma is crucial for clinical management. We evaluate the role of fine‐needle aspiration (FNA) in the diagnosis of pancreatic lymphoma with the aid of flow cytometry and/or immunohistochemistry on the cell block.