Shaoxiong Chen

Assessing breast tumor margin by multispectral photoacoustic tomography

An unmet need exists in high-speed and highly-sensitive intraoperative assessment of breast cancer margin during conservation surgical procedures. Here, we demonstrate a multispectral photoacoustic tomography system for breast tumor margin assessment using fat and hemoglobin as contrasts. This system provides ~3 mm tissue depth and ~125 μm axial resolution. The results agreed with the histological findings. A high sensitivity in margin assessment was accomplished, which opens a compelling way to intraoperative margin assessment.

Abrogating cholesterol esterification suppresses growth and metastasis of pancreatic cancer

Cancer cells are known to execute reprogramed metabolism of glucose, amino acids and lipids. Here, we report a significant role of cholesterol metabolism in cancer metastasis. By using label-free Raman spectromicroscopy, we found an aberrant accumulation of cholesteryl ester in human pancreatic cancer specimens and cell lines, mediated by acyl-CoA cholesterol acyltransferase-1 (ACAT-1) enzyme. Expression of ACAT-1 showed a correlation with poor patient survival. Abrogation of cholesterol esterification, either by an ACAT-1 inhibitor or by shRNA knockdown, significantly suppressed tumor growth and metastasis in an orthotopic mouse model of pancreatic cancer. Mechanically, ACAT-1 inhibition increased intracellular free cholesterol level, which was associated with elevated endoplasmic reticulum stress and caused apoptosis. Collectively, our results demonstrate a new strategy for treating metastatic pancreatic cancer by inhibiting cholesterol esterification.

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).

Utilization of cell-transferred cytologic smears in detection of EGFR and KRAS mutation on adenocarcinoma of lung

Cell-transfer technique has been proven useful for performing immunocytochemistry on fine-needle aspiration smears. However, its utility for EGFR and KRAS molecular testing has not been validated. Molecular testing was performed using the cell-transfer technique on both Papanicolaou-stained ethanol-fixed and Hema 3-stained air-dried smears from 32 fine-needle aspiration samples that had diagnoses of adenocarcinoma of the lung, and then was compared to the results of the corresponding formalin-fixed paraffin-embedded tissues. The molecular testing was successfully performed on 32 of 32 ethanol-fixed and 31 of 32 air-dried samples. The molecular results on ethanol-fixed and air-dried smears showed 100% agreement. There is 100% (32/32) agreement for the EGFR and 97% (31/32) agreement for the KRAS between the cell-transfer technique and formalin-fixed paraffin-embedded tissues. One discrepant case was due to low percentage of tumor cells on the smears. Cell-transfer technique is a reliable alternative method for EGFR and KRAS testing if the cell blocks lack adequate cellularity.

Percutaneous biopsy of the renal mass: FNA or core needle biopsy?

In recent years, there have been increasing indications for percutaneous renal biopsy. Fine‐needle aspiration (FNA), with or without core needle biopsy (CB), has been used increasingly in the management of renal tumors at the study institution.

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.

Detection of BRAF Mutations on Direct Smears of Thyroid Fine-Needle Aspirates Through Cell Transfer Technique

OBJECTIVES To determine the utility of the cell transfer technique (CTT) for BRAF molecular testing on thyroid fine-needle aspiration (FNA) specimens. METHODS Polymerase chain reaction (PCR)-based BRAF molecular testing was performed on tissues obtained through CTT from both air-dried and ethanol-fixed direct smears of thyroid FNA specimens and then compared with the corresponding thyroidectomy formalin-fixed, paraffin-embedded (FFPE) tissues on 30 cases. RESULTS BRAF testing was successfully performed on 29 of 30 air-dried CTT, 27 of 30 ethanol-fixed CTT, and 27 of 30 FFPE tissues. The results exhibited 11, 13, and 13 BRAF mutations and 18, 14, and 14 wild types for the air-dried CTT, the ethanol-fixed CTT, and the FFPE tissues, respectively. The concordance rate was 96% between air-dried and ethanol-fixed CTT tissues, 88% between air-dried CTT and FFPE tissues, and 92% between ethanol-fixed CTT and FFPE tissues. CONCLUSIONS PCR-based BRAF mutational testing can be reliably performed on the direct smears of the thyroid FNA specimens through the application of CTT.

Histologic and clinical follow-up of thyroid fine-needle aspirates in pediatric patients

Although fine‐needle aspiration (FNA) has an important role in evaluating thyroid nodules in adults, there is little published information regarding its utility in the pediatric population.

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.